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10,509,178
ACCEPTED
Security element and method for production thereof
The invention relates to an object, in particular a security element for security papers, bank notes, identity card or the like, as well as a security paper and a document of value with such a security element. Furthermore, the invention relates to a method for producing the object, in particular the security element or the security paper and the document of value with such a security element. The method in particular serves for manufacturing a precious-metal-coloured, preferably gold-coloured coating on a substrate.
1. Method for producing a security element or transfer element for securing documents of value or for protecting products, comprising the step of vapor depositing a substrate with a multicomponent evaporating material, which is transformed into the vapor phase by means of electron beam or resistance heating, characterized in that the evaporized evaporating material deposits as a precious-metal-coloured coating on the substrate. 2. Method according to claim 1, wherein the precious-metal-coloured coating is gold-coloured. 3. Method according to claim 1, wherein the evaporating material consists of individual components in separate crucibles. 4. Method according to claim 1, wherein the evaporating material is an alloy. 5. Method according to claim 1, wherein the evaporating material comprises one or several metals from the group containing copper (Cu), aluminum (Al), tin (Sn) and silver (Ag). 6. Method according to claim 1, wherein the evaporating material comprises Al/Cu or Sn/Cu or Ag/Cu or Ag/Sn/Cu. 7. Method according to claim 1, wherein the coating comprises 5 to 15 weight per cent aluminum and 85 to 95 weight per cent copper. 8. Method according to claim 1, wherein the evaporating material comprises at least one foreign metal. 9. Method according to claim 8, wherein the foreign metal is chosen from the group of iron, manganese, vanadium, chromium, cobalt, silicon, magnesium, zinc or titanium. 10. Method according to claim 1, wherein on the substrate are deposited different precious-metal-coloured coatings. 11. Method according to claim 1, wherein the substrate is a plastic film. 12. Method according to claim 1, wherein the coating is deposited in a layer thickness of 50 to 100 nm. 13. Method according to claim 1, wherein before the coating process diffraction structures are embossed into the substrate. 14. Method according to claim 1, wherein after the coating process the substrate is cut in a strip-shaped or ribbon-shaped fashion. 15. Method according to claim 1, wherein at least one of the layer thickness of the coating is determined by means of transmission measuring, and the composition of the coating is determined by means of reflection measuring, and at least one of possibly existing deviations in layer thickness and composition from the desired value are corrected by means of at least one of heating power and path speed with which the substrate to be coated is moved. 16. Method according to claim 1, wherein the coating is removed from the substrate and broken into small plates, which, optionally, can be processed into printing ink. 17. Security element or transfer element for securing documents of value or for protecting products, produced according to claim 1. 18. Security element or transfer element for securing documents of value or for protecting products with a substrate on which at least one coating made of a precious-metal-coloured alloy is present. 19. Security element or transfer element according to claim 18, wherein the alloy is gold-coloured. 20. Security element or transfer element according to claim 18, wherein the alloy comprises copper. 21. Security element or transfer element according to claim 18, wherein the alloy comprises at least one of aluminum, tin and silver. 22. Security element or transfer element according to claim 18, wherein the alloy comprises 8 weight per cent aluminum and 92 weight per cent copper. 23. Security element or transfer element according to claim 18, wherein the alloy comprises at least one foreign metal. 24. Security element or transfer element according to claim 23, wherein the foreign metal is chosen from the group of iron, manganese, vanadium, chromium, cobalt, silicon, magnesium, zinc or titanium. 25. Security element or transfer element according to claim 18, wherein the substrate is a plastic film. 26. Security element or transfer element according to claim 18, wherein the coating has a layer thickness of 50 to 100 nm. 27. Security element or transfer element according to claim 18, wherein the coating is at least partially overlaid with diffraction structures. 28. Security element or transfer element according to claim 27, wherein the diffraction structures are embossed in the substrate. 29. Security element according to claim 1, wherein the security element is a self-supporting label. 30. Security element according to claim 1, wherein the security element is a security thread. 31. Security paper for producing documents of value or document of value, characterized in that it has at least one security element according to claim 1. 32. Security paper or document of value according to claim 31, wherein the security element is a security thread and embedded at least partially in the security paper. 33. Security paper or document of value according to claim 31, wherein the security element is a transfer element, which is applied to the surface of the security paper. 34. A method for protecting goods from forgery comprising incorporating therewith a security element or transfer element according to claim 17. 35. A method for protecting goods from forgery comprising incorporating therewith a security paper or document of value according to claim 31. 36. Printing ink produced according to claim 16.
This application is a National Phase of International Application Serial No. PCT/EP03/03147, filed Mar. 26, 2003. FIELD OF THE INVENTION The invention relates to an object, in particular a security element for security papers, bank notes, identity card or the like, as well as a security paper and a document of value with such a security element. Furthermore, the invention relates to a method for producing the object, in particular the security element or the security paper and the document of value with such a security element. The method in particular serves for manufacturing a precious-metal-coloured, preferably gold-coloured coating on a substrate. BACKGROUND OF THE INVENTION When producing documents of value, which within the framework of the present invention means bank notes, check forms, shares, identification documents, credit cards, flight tickets and other deeds and documents as well as labels, seals, packaging and other elements for protecting products, it is particularly important to make arrangements against tampering and/or to take measures that permit the detection of the authenticity. Apart from the features which can be detected or used when testing is made by machines, there also exist features, which can be applied to such documents by everybody without technical auxiliary means and without any particular specialist knowledge for an unambiguous detection of the authenticity. One possibility to equip a security element, such as a security thread, with visually easily recognizable elements is described in EP 0 330 733 B1, in which a security thread is provided with gaps in an opaque layer, and which contains colouring and/or luminescent substances in the gaps. This security thread is embedded in security papers as a so called “window security thread”, i.e. it is woven in the paper during the sheet formation of the security paper, so that in regular distances it is freely accessible at the surface of the paper and fully embedded only in the intermediate areas. So as to increase the optical strikingness of a security element and to emphasize the value of the object to be protected, the security elements often are equipped with silver or gold colour tones. One possibility to obtain a gold-coloured coating is to vapor-deposit thin gold layers onto well reflecting grounds, such as e.g. aluminum or silver. But due to the high costs of the source material and the great technical efforts required to manufacture very regular layers, profitability is not given. Alternatively, also gold bronzes have been applied by means of vapor deposition with evaporation boat or sputtering. When vapor-depositing with evaporation boat a wire is continuously fed into a hot boat. When the boat is hot enough the just fed piece of wire immediately evaporizes and completely transitions into the vapor phase. A substrate located thereabove is coated with just that composition of this piece of wire. Within the boats, however, little lakes are often formed out of the molten wire, which e.g. consists of a certain alloy. From these lakes the individual components of the alloy evaporate at different rates due to different vapor pressures, the proportion of ingredients therefore being changed in the deposited material and thus on the substrate. The initially set colour tone thus continuously changes across the coating length and width of the item to be vapor-deposited during the vapor deposition process. Furthermore, also the sputtering technique is used. Here metal clusters are knocked off from a fixed target in the plasma, which condense on the substrate disposed thereabove. The composition of the coating can be kept relatively constantly, but sputtering is a very time intensive technique and thus of very low productivity. SUMMARY OF THE INVENTION The invention is therefore based on the problem of providing a method for producing precious-metal coloured coatings, as well as objects coated by means of such a method, in particular security elements and documents of value with such security elements. The method shall produce a constant colour tone of the coating, in particular in a profitable manner. The coated objects shall have, compared to prior art, an increased forgery-proofness, e.g. due to their optically striking appearance. According to the invention by means of an electron beam or a resistance-heated crucible, while generating a multicomponent vapor, evaporating material is evaporated, which produces a precious-metal-coloured multicomponent coating on a substrate. Electron-beam vapor deposition or vapor deposition by means of resistance-heated crucible are vacuum coating methods, with the help of which very thin, regular coatings can be applied. With electron-beam vapor deposition evaporating material located in a crucible is heated by means of an electron beam. With that vapor is generated, which condensates on the substrate guided thereabove. Instead of via the electron beam the evaporating material can also be supplied with energy via resistance heating of the crucible. The evaporating material can be liquid, as e.g. a molten metal, and is located in a crucible. Also subliming materials can be evaporated. The evaporation can take place out of a crucible, the evaporating material in this case being e.g. a multicomponent system such as an alloy. Or the evaporating material can consist of single components, which are located in separate crucibles. Each crucible is heated by one or several electron beams or by resistance heating. The crucibles are disposed in such a way, that the vapor lobes overlap each other above the crucibles. The heating power of the individual crucibles here is adjusted in such a way that a multicomponent coating, e.g. an alloy of the desired composition, is deposited on the substrate. BRIEF DESCRIPTION OF THE DRAWINGS The following figures are schematic diagrams and do not necessarily correspond to the dimensions and proportions present in reality. FIG. 1 shows an inventive document of value, FIG. 2 shows a cross section of the inventive document of value along the line A-A and FIG. 3a, 3b show a schematic structure of a vapor deposition apparatus. FIG. 1 shows an inventive document of value in a top view. The shown example is a bank note 1. This bank note has a strip-shaped security element 2, which extends across the whole width of the bank note 1. The whole surface of the security element 2 facing the viewer appears gold-coloured. The security element shown in FIG. 1 is a diffractive security element, which consists of an embossed plastic layer and at least one gold-coloured layer 3 produced according to example 1. FIG. 2 shows a cross section along the line A-A in FIG. 1. Here the plastic layer 4 can be seen, where the diffraction structure is placed in. Thereabove and directly adjoining the inventive gold-coloured coating 3 is disposed, into which a gap 6 is worked. The gaps can be any characters, alphanumeric characters, patterns, logos or the like. The security element shown in FIG. 2 can be for example a security thread. The security thread preferably consists of a transparent carrier film 4, on which the gold-coloured coating 3 is disposed. FIG. 3a schematically shows an experimental set-up, where in crucible 7 is contained a Cu/Al-alloy 8. By means of an electron beam 9 the alloy is caused to melt and while supplied with further energy to evaporate. Above the crucible a vapor lobe 10 is formed having a certain Cu/Al-composition. In this vapor lobe 10 is placed a film 12 guided on a chill roll 11, and on the film 12 a Cu/Al-alloy of the desired composition is deposited. FIG. 3b shows a process management alternative to that shown in FIG. 3a. The evaporating material here is composed of two single components located in separate crucibles, namely Cu 13 in crucible 14 and Al 15 in crucible 16. The single components are molten and evaporated by means of electron beam 9, so that above the crucibles two vapor lobes 17, 18 are formed, which overlap each other in area 19. Due to this overlapping the vapor phase has a certain Cu/Al-composition. As described in FIG. 3a a film 12 guided on a chill roll 11 is placed in the vapor phase, so that an alloy of Cu and Al in the desired composition can be deposited. DETAILED DESCRIPTION OF THE INVENTION Since the components of the evaporating material in general are substances with different evaporation rates, which depend e.g. on the process temperature and the vapor pressures of the individual components, great demands have to be made on the method. So as to coat a substrate with a certain composition, the vapor phase has to contain the individual components in the desired quantity ratio. But it has to be taken into account that the quantity ratios, e.g. within a molten alloy, usually deviate from the quantity ratios within the vapor phase, which is due to the different vapor pressures of the components, and thus have to be appropriately adjusted. In the molten mass the proportion of components with a high vapor pressure usually has to be lower, whereas the concentration of components with a lower vapor pressure usually have to be present to a higher degree, so as to obtain the desired quantity ratio in the vapor phase. The composition of the molten mass is chosen in such a way, that at a certain temperature the desired composition, which is to be deposited on the substrate, is present in the vapor. Furthermore, the composition of the evaporating material will continuously change during the vapor deposition process due to the different evaporating rates of the individual components. This effect can be compensated either by feeding certain components of the evaporating material or by using large volumes of molten mass. Preferably, the volumes of molten mass are chosen in such large amounts that one coating cycle can be carried out without feeding any further evaporating material. The vapor deposition of an alloy with a certain composition and a defined layer thickness preferably is controlled via a regulation mechanism, with the help of which the vapor-deposited layer is measured in transmitted light and/or reflected light, possibly at several points across the path width of the vapor-deposited substrate. For measuring the transmission and/or reflection optical devices known to persons skilled in the art are used. With transmission measuring the optical density of the deposited layer is measured and thus indirectly the thickness of the layer. If the vapor-deposited layer thickness varies from the preset value, it can be influenced by changing the path speed with which the substrate to be vapor-deposited is moved, and/or by the evaporation rate of the substance to be vapor-deposited. The evaporation rate here can be controlled via the energy of the electron beam or the heating power. If the layer thickness for example is higher than desired, the amount of vapor-deposited substance per area unit can be decreased by increasing the path speed. Alternatively or additionally, the evaporation rate can also be reduced e.g. by lowering the heating power or by lowering the energy of the electron beam. With reflection measuring the colour of the deposited layer is spectrally measured and with that the composition of a multicomponent evaporating material is indirectly determined. Usually for that purpose white light is irradiated, the reflected light spectrally analysed and described with the help of colour coordinates, e.g. according to the Munsell system or the CIE system. The colour coordinates of the vapor-deposited layer are compared to a desired value defined beforehand, which corresponds to a certain composition of the evaporating material, so that from a possible deviation a deviation in the composition can be concluded and, if so, countermeasures can be taken. The regulation here is effected via changing the evaporation rate of the individual components in the multicomponent evaporating material, e.g. by increasing or decreasing the electron beam energy or the heating power. When carrying out the regulation mechanism the following variations are thinkable. In the following preferred embodiments are described, where two crucibles each contain one alloy component, the invention, however, not being restricted to these variations. Variation A: The heating power in crucible 1, which preferably contains the main component of the alloy, is firmly set. The heating power is measured in such a way, that the result is, as experience has shown, a metal deposition of regular thickness across the whole width of the film that usually amounts to one to two meters. The amount of the alloy main component contained in crucible 1 here is dimensioned in such a way, that changes in the total heating power (sum of heating power in crucible 1 and crucible 2) has no effect on the layer thickness of the deposited evaporating material. Measuring the transmission for determining the layer thickness is therefore not necessary. But while the film is coated, the colour coordinates of the vapor-deposited layer are measured in reflected light, possibly at several points across the path width, and compared to a desired value defined beforehand. The deviations of one or several coordinates are then used to regulate the heating power in crucible 2. If crucible 2 is of a trough-shaped design, beside the heating power in crucible 2 possibly also the lateral distribution of the heating power above the length of the trough can be regulated. Variation B: As in variation A the heating power in crucible 1, which preferably contains the main component of the alloy, is firmly set, so that, as experience has shown, a metal deposition of regular thickness across the width of the film is obtained. While the film is coated, the optical density of the vapor-deposited layer is measured in transmitted light, possibly at several points across the path width. If values have been determined at different points of the path width, the average value of the optical density is calculated and compared to a given desired value for the layer thickness. In case of deviations the path speed, with which the film to be coated is moved, is regulated accordingly. For regulating the heating power in crucible 2 the same method as in Variation A is used. Variation C: Here the evaporation rate in crucible 1 as well as in crucible 2 is regulated at a constant path speed, with which the substrate to be vapor-deposited is moved forward. The evaporation rates here again are controlled via the heating power or the energy of the electron beam. The regulation of the evaporation rates here is influenced via the transmission measuring of the optical density of the deposited layer as well as by means of reflection measuring for determining the colour coordinates. So as to produce a constant layer thickness and thus a constant total amount of deposited material, the total heating power in crucible 1 and 2 preferably is of a constant value. For producing a constant alloy composition the relation of the heating power in crucible 1 to that in crucible 2 is preferably adjusted in a constant manner. The evaporating material preferably is a multicomponent system, such as compounds, mixtures or alloys, which produces a precious-metal coloured tone after being deposited onto the substrate. Within the terms of the invention, “precious-metal coloured” means every colour tone which contains silver- and/or gold-coloured portions. Consequently, depending on the composition of the evaporating material, the colour scale of the coating does not only contain the pure silver or gold tones. The color scale of silver tones ranges from a silver tone enriched with a white content to silver tones with light to dark grey or even black content. The colour scale of gold tones ranges from light gold, nickel, gold to dark gold and bronze. Additionally, by taking the respective measures also e.g. precious-metal coloured tones with tinges of yellow, green, red and brown can be produced. Preferably, “precious-metal coloured” means gold-coloured, and gold-coloured here comprises any thinkable gold tone. Preferably the evaporating material is an alloy, in particular gold bronze, “Gold bronze” within the terms of the invention means all the copper base alloys, in particular alloys which comprise copper and aluminum. Further preferred alloys are alloys comprising copper and tin, alloys comprising copper and silver or alloys comprising copper, tin and silver. Preferably the alloys deposited on the substrate comprise 95 to 75 weight per cent, particularly preferred 95 to 85 weight per cent, and in particular preferred 92 weight per cent copper. In an embodiment particularly preferred the alloy comprises 5 to 15 weight per cent aluminum and 95 to 85 weight per cent copper. The layer vapor-deposited onto the substrate preferably is composed of 8 weight per cent aluminum and 92 weight per cent copper, so that the result is a gold-coloured tone. For producing further colour tones, such as e.g. precious-metal tones, in particular gold tones, with tinges of yellow, green, red and brown, there exists the possibility of adding portions of foreign metal to the alloys. Suitable foreign metals are e.g. iron, manganese, vanadium, chromium, nickel, cobalt, silicon, magnesium, zinc or titanium. Preferably the portions of foreign metals amount to 5 weight per cent referred to the evaporating material deposited onto the substrate. Of course there also exists the possibility of producing colour tones of a more silvery appearance e.g. by increasing the aluminum portion. The respective composition of the evaporating material for producing the desired colour tones on the substrate can be ascertained by a person skilled in the art by respective preliminary experiments. The layer thickness of the vapor-deposited layer on the substrate preferably amounts to at least 20 nm up to a maximum of 200 nm, in particular layer thicknesses of 50 up to 150 nm are preferred. Of course layer thicknesses of less than 20 nm, for example layers of a thickness of a few μm can also be used. The multicomponent coating produced according to the invention can be distinguished from those coatings that are produced by methods according to prior art, such as e.g. sputtering or vapor deposition with evaporation boat, by different crystalline structure parameters, such as particle size, refractive index and conductivity. The analysis here can be more or less elaborate depending on the parameter taken into account, but lies within the range of knowledge of a person skilled in the art. The possibility of producing several gold-coloured tones also provides the option to equip a security element with several colour tones. The inventive security element, however, has at least one precious-metal-coloured coating. The optical impression rendered by such a security element can be imitated, if at all, only with great efforts, in particular if different-coloured coatings are applied in complicated patterns. The security element can be a security thread which consists of a self-supporting plastic film to which the precious-metal coloured coatings are applied. This security thread can at least partially be placed in a security paper or security document. But it is also thinkable to form the security element in a ribbon-shaped or label-shaped fashion and to fasten it to the surface of the security paper or document of value. Alternatively, the security element can also have the form of a transfer element. This variation is particularly advantageous, if the security element is disposed completely on the surface of the security paper or document of value. In this case the layer structure of the security element is prepared on a carrier film, usually a plastic film, and then transferred in the desired outline contours to the security paper or document of value by means of a hot stamping method. If the security element is disposed on the surface of the security paper or the document of value, it can have any outline structure, such as for example round, oval, star-shaped, rectangular, trapezoidal or strip-shaped outline contours. But the use of the inventive security element is not restricted to the sector of security documents. The inventive security element can also be advantageously used in the sector of product protection for protecting any goods from forgery. For that purpose the security element can have antitheft elements as well, such as for example a coil or a chip. The same applies to the security paper or document of value that is provided with such a security element. The substrate to be vapor-deposited preferably is a plastic film, preferably made of PET (polyethylene terephthalate), POP (polyphenylene oxide), PEN (polyethylene naphthalate) or PC (polycarbonate). Additionally, the plastic film of the security element can be provided with diffraction structures in the form of a relief structure. The diffraction structures can be any diffractive structures such as holograms or grating structures (e.g. Kinegram®, pixelgram) or the like. Usually these diffraction structures are embossed in the plastic film. As a further optically striking feature also gaps can be worked into the inventive coating, preferably with the help of a washing method as described in WO 99/13157 to which explicit reference is made herein. Here the security elements are prepared as a security film, which has several advantages of the security element. The basic material is a self-supporting, preferably transparent plastic film. This plastic film in the case of security threads or labels corresponds to the inventive plastic layer of the security element. If the security elements are dissolved out from an embossed film, the plastic film forms the carrier material of this transfer material, to which the plastic layer is applied in the form of a lacquer layer. In this lacquer layer or, in case of security threads or labels, in this plastic film diffraction structures can be embossed. The inventive plastic layer of the security element is printed in the form of the future gaps, preferably by gravure printing. For this a printing ink with a high pigment content is used, which forms a pored and raised applied ink layer. Then the coating is vapor-deposited to the printed plastic layer. As a last stage finally the applied ink layer and the inventive coating on top of it are removed by washing out with a liquid, possibly combined with mechanical action. Preferably a water-soluble printing ink is used, so that water can be used as a liquid. With that this method is very environmentally friendly and does not require any particular protective measures. The washing out can be supported by mechanical means, such as a rotating roll, brush or ultrasound. The use of etching techniques is in a considerable manner more elaborate, but in principle also possible. Here at first the inventive coating is deposited onto the plastic layer and then the whole surface, except for the areas to be removed, is printed with a protective lacquer layer. The whole security element layer structure is then guided through an etching bath, in which the areas not covered are dissolved from the plastic layer. If for different coatings different etching bathes are necessary, the covering process or the process of dipping into the etching bath has to be repeated with diverse etching solutions. Between the different etching bathes neutralization and cleaning bathes have to be provided, so that the chemicals of the different bathes are not rendered impure. Other methods are also thinkable, such as e.g. mechanical removal of the inventive coating or producing the breaches by means of laser scriber, electron beam erosion or other removal processes. The substrates vapor-deposited according to the invention can be further processed by e.g. mechanically scraping the vapor-deposited layer from the substrate, so that fine small plates are produced. These small plates preferably can be worked into printing ink and as such be used for security elements. The inventive coating method has the advantage that therewith in an extremely economic way, i.e. cost and time saving, precious-metal-coloured coatings can be produced, which compared to prior art are of an extremely regular design in view of colour tone and layer thickness. Due to their optically striking coating the security elements and documents of value produced according to the invention have a forgery-proofness increased accordingly, since they are recognizable without any further auxiliary means. Further embodiments and advantages of the inventive method, security element or security paper and document of value are explained with reference to the example and the figures. EXAMPLE 1 In a electron-beam vapor deposition plant films made of PET, alternatively made of POP, PC or PEN, of a width of 1000 mm are coated with a layer thickness of approximately 55 nm made of 8 weight per cent aluminum and 92 weight per cent copper. The evaporation is effected out of a crucible, the volumetric capacity of which is of at least such a large amount that one coating cycle can be carried out without feeding further material. The evaporating material, an aluminum/copper alloy, is heated with an electron gun. Since copper has a higher vapor pressure than aluminum in the molten mass, in the vapor the copper proportion is higher than compared to the molten mass. On a substrate moved through the vapor thus a copper-coloured film would be deposited. As to avoid this problem, the proportion of aluminum is increased relatively to that of copper in the molten mass. For that reason 80% copper and 20% aluminum are used in the molten mass, which has a silvery. colour tone. But the vapor above the molten mass has a copper aluminum proportion, which leads to gold-coloured deposits on a substrate having the above-mentioned aluminum/copper proportion (8/92). During longer vapor deposition periods the mixture ratio changes in favour of aluminum due to the higher evaporating rate of copper. This effect can be compensated either by feeding further copper or by using large volumes of molten mass. When using large amounts of molten mass the mixture ratio during a coating cycle changes only slightly and the colour tone of the vapor-deposited layer remains regular. EXAMPLE 2 This embodiment corresponds to that described in example 1 and differs from example 1 in that the evaporating material is caused to melt and evaporate not by means of an electron beam, but by means of a resistance-heated crucible.
<SOH> BACKGROUND OF THE INVENTION <EOH>When producing documents of value, which within the framework of the present invention means bank notes, check forms, shares, identification documents, credit cards, flight tickets and other deeds and documents as well as labels, seals, packaging and other elements for protecting products, it is particularly important to make arrangements against tampering and/or to take measures that permit the detection of the authenticity. Apart from the features which can be detected or used when testing is made by machines, there also exist features, which can be applied to such documents by everybody without technical auxiliary means and without any particular specialist knowledge for an unambiguous detection of the authenticity. One possibility to equip a security element, such as a security thread, with visually easily recognizable elements is described in EP 0 330 733 B1, in which a security thread is provided with gaps in an opaque layer, and which contains colouring and/or luminescent substances in the gaps. This security thread is embedded in security papers as a so called “window security thread”, i.e. it is woven in the paper during the sheet formation of the security paper, so that in regular distances it is freely accessible at the surface of the paper and fully embedded only in the intermediate areas. So as to increase the optical strikingness of a security element and to emphasize the value of the object to be protected, the security elements often are equipped with silver or gold colour tones. One possibility to obtain a gold-coloured coating is to vapor-deposit thin gold layers onto well reflecting grounds, such as e.g. aluminum or silver. But due to the high costs of the source material and the great technical efforts required to manufacture very regular layers, profitability is not given. Alternatively, also gold bronzes have been applied by means of vapor deposition with evaporation boat or sputtering. When vapor-depositing with evaporation boat a wire is continuously fed into a hot boat. When the boat is hot enough the just fed piece of wire immediately evaporizes and completely transitions into the vapor phase. A substrate located thereabove is coated with just that composition of this piece of wire. Within the boats, however, little lakes are often formed out of the molten wire, which e.g. consists of a certain alloy. From these lakes the individual components of the alloy evaporate at different rates due to different vapor pressures, the proportion of ingredients therefore being changed in the deposited material and thus on the substrate. The initially set colour tone thus continuously changes across the coating length and width of the item to be vapor-deposited during the vapor deposition process. Furthermore, also the sputtering technique is used. Here metal clusters are knocked off from a fixed target in the plasma, which condense on the substrate disposed thereabove. The composition of the coating can be kept relatively constantly, but sputtering is a very time intensive technique and thus of very low productivity.
<SOH> SUMMARY OF THE INVENTION <EOH>The invention is therefore based on the problem of providing a method for producing precious-metal coloured coatings, as well as objects coated by means of such a method, in particular security elements and documents of value with such security elements. The method shall produce a constant colour tone of the coating, in particular in a profitable manner. The coated objects shall have, compared to prior art, an increased forgery-proofness, e.g. due to their optically striking appearance. According to the invention by means of an electron beam or a resistance-heated crucible, while generating a multicomponent vapor, evaporating material is evaporated, which produces a precious-metal-coloured multicomponent coating on a substrate. Electron-beam vapor deposition or vapor deposition by means of resistance-heated crucible are vacuum coating methods, with the help of which very thin, regular coatings can be applied. With electron-beam vapor deposition evaporating material located in a crucible is heated by means of an electron beam. With that vapor is generated, which condensates on the substrate guided thereabove. Instead of via the electron beam the evaporating material can also be supplied with energy via resistance heating of the crucible. The evaporating material can be liquid, as e.g. a molten metal, and is located in a crucible. Also subliming materials can be evaporated. The evaporation can take place out of a crucible, the evaporating material in this case being e.g. a multicomponent system such as an alloy. Or the evaporating material can consist of single components, which are located in separate crucibles. Each crucible is heated by one or several electron beams or by resistance heating. The crucibles are disposed in such a way, that the vapor lobes overlap each other above the crucibles. The heating power of the individual crucibles here is adjusted in such a way that a multicomponent coating, e.g. an alloy of the desired composition, is deposited on the substrate.
20040927
20100119
20050818
63048.0
0
SHEWAREGED, BETELHEM
SECURITY ELEMENT AND METHOD FOR PRODUCTION THEREOF
UNDISCOUNTED
0
ACCEPTED
2,004
10,509,390
ACCEPTED
Organic electroluminescence element
An organic electroluminescence device of a long emission life is obtained by stacking an anode, a hole transport layer comprising an organic compound, a light emitting layer comprising an organic compound, an electron transport layer comprising an organic compound, and a cathode, in which the light emitting layer comprises an organic host material of an aluminum chelating complex of a specific structure and a phosphorescent organic guest material.
1. An organic electroluminescence device comprising: an anode; a hole transport layer comprising an organic compound; a light emitting layer having an organic compound; an electron transport layer having an organic compound; and a cathode which are stacked, characterized in that the light emitting layer includes an organic host material represented by the following structural formula (1): and a phosphorescent organic guest material. 2. An organic electroluminescence device according to claim 1, wherein a hole injection layer is provided between the anode and the hole transportation. 3. An organic electroluminescence device according to claim 1 or claim 2, wherein an electron injection layer is provided between the cathode and the electron transport layer. 4. An organic electroluminescence device according to any one of claims 1 to 3, wherein the phosphorescent organic guest material comprises a porphyrin compound represented by the following structural formula (2): (in the structural formula (2), Q represents —N═ or —C(R)═, M represents a metal, a metal oxide, or a metal halide, R represents hydrogen, alkyl, aralkyl, aryl or alkalyl, or a halogenated substituent thereof, T1 and T2 each represents hydrogen or alkyl, or jointly represent a completed unsaturated six-membered ring including a halogen substituent, the six-membered ring is formed of carbon, sulfur and nitrogen ring atoms, and the alkyl moiety contains 1 to 6 carbon atoms). 5. An organic electroluminescence device according to claim 4, wherein M in the phosphorescent organic guest material is platinum. 6. An organic electroluminescence device according to any one of claims 1 to 3, wherein the phosphorescent organic guest material comprises a compound represented by the following structural formula (3): (in the structural formula (3), M represents a metal, R1 to R8 each independently includes a hydrogen atom, alkyl group, oxy group, amino group or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R8 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less carbon atoms, and further, R1 together with R2, R2 together with R3, R3 together with R4, R5 together with R6, R6 together with R7, or R7 together with R8 can form a condensed benzo ring). 7. An organic electroluminescence device according to claim 6, wherein M in the phosphorescent organic guest material is iridium. 8. An organic electroluminescence device according to any one of claims 1 to 3, wherein the phosphorescent organic guest material comprises a compound represented by the following structural formula (4): (in the structural formula (4), M represents a metal, R1 to R6 each independently includes a hydrogen atom, alkyl group, oxy group, amino group or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R6 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less carbon atoms and, further, R1 together with R2, R3 together with R4, R4 together with R5, or R5 together with R6 can form a condensed benzo ring). 9. An organic electroluminescence device according to claim 8, wherein M in the phosphorescent organic guest material is iridium. 10. An organic electroluminescence device according to any one of claims 1 to 3, wherein the phosphorescent organic guest material comprises a compound represented by the following structural formula (5): (in the structural formula (5), M represents a metal, X1 and X2 each independently represents an oxygen atom or a sulfur atom, R1 to R11 each independently includes a hydrogen atom, alkyl group, oxy group, amino group, or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R11 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less carbon atoms and, further, R1 together with R2, R2 together with R3, R3 together with R4, R5 together with R6, R6 together with R7, R7 together with R8, or R8 together with R9 can form a condensed benzo ring). 11. An organic electroluminescence device according to claim 10, wherein M for the phosphorescent organic guest material is iridium. 12. An organic electroluminescence device according to any one of claims 1 to 3, where in phosphorescent organic guest material comprises a compound represented by the following structural formula (6): (in the structural formula (6), M represents a metal, X1 and X2 each independently represents an oxygen atom or a sulfur atom, R1 to R9 each independently includes a hydrogen atom, alkyl group, oxy group, amino group or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R9 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less of carbon atoms and, further, R1 together with R2, R3 together with R4, R4 together with R5, R5 together with R6, R7 together with R8, R8 together with R9, R9 together with R10, or R10 together with R11 can form a condensed benzo ring). 13. An organic electroluminescence device according to claim 12, wherein M in the phosphorescent organic guest material is iridium. 14. A material for an organic electric field light emitting device material which is a compound represented by the following structural material (1):
TECHNICAL FIELD The present invention relates to an organic electroluminescence device (hereinafter referred to as an organic EL device) utilizing electroluminescence of an organic compound that emits light by current injection, and having a light emitting layer in which the substance is formed in a layered state. BACKGROUND ART In general, each of organic EL devices using an organic material and constituting a display panel has a structure in that an anode as a transparent electrode, plural organic material layers including an organic light emitting layer and a cathode comprising a metal electrode are successively layered each as a thin film on a glass substrate as a display surface. In addition to the organic light emitting layer, the organic material layer includes a layer comprising a material having a hole transportability such as a hole injection layer and a hole transport layer, and a layer comprising a material having electron transportability such as an electron transport layer and an electron injection layer, and an organic EL device of a constitution provided with them has also been proposed. The electron injection layer also contains an in organic compound. When an electric field is applied to an organic EL device of a stacked body of an organic light emitting layer and an electron or hole transport layer, holes are injected from the anode and electrons are injected from the cathode. The organic EL divide utilizes emission of light that is emitted when the electrons and the holes are recombined in the organic light emitting layer to form exciters and they are returned to the ground state. For making the luminous efficiency higher and stably driving the device, a dye is sometimes doped as a guest material to the light emitting layer. In recent years, in addition to the fluorescence material, use of a phosphorescence material for the light emitting layer has also been proposed, since it is considered that the probability for the occurrence of singlet exciters and triplet exciters after recombination of electrons and holes in the light emitting layer of the organic EL device is 1:3 and it is considered that a device also utilizing phosphorescence caused by the triplet exciters can attain the luminous efficiency three to four times as high as the device using fluorescence caused by the singlet exciters. On the other hand, for reducing the power consumption improvement of the luminous efficiency and improvement of the driving stability of the organic EL device, it has been proposed to provide a hole blocking layer between the organic light emitting layer and the cathode for restricting the movement of the holes from the organic light emitting layer. By efficient accumulation of the holes in the light emitting layer by the hole blocking layer, the recombination probability with electrons can be improved to attain higher luminous efficiency. As the hole blocking material, it has been reported that phenanthroline derivatives and triazole derivatives are effective (refer to JP-A No. 8-109373 and JP-A No. 10-233284). In existent organic EL devices utilizing phosphorescence emission, hole transporting materials capable of transporting holes have been used for the light emitting layer host material and materials having higher ionizing potential energy (Ip) than the post material of the light emitting layer such as phenanthroline derivatives, for example, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, i.e., BCP or aluminum chelate complex, for example, ((1,1′-biphenyl)-4-olato)bis(2-methyl-8-quinolinolato NI, 08) aluminum, i.e., BAlq are used as the hole blocking layer in the layer adjacent cathode of the light emitting layer. In a case of using BCP for the hole blocking layer, while the emission characteristics at the initial stage are favorable, it involves a drawback that the driving life is extremely short. At present, materials having sufficiently high Ip and excellent in durability have not been known. BAlq is excellent in durability but has a drawback of poor hole blocking ability since Ip is not sufficiently high. Accordingly, in a case of using BAlq as the hole blocking layer and tris(8-hydroxyquinolateo N1, 08) aluminum, i.e., Alq3 as the electron transport layer, the electron transport layer emits light. In the organic electroluminescence device utilizing red phosphorescence emission, the emission of Alq3 (green) results in deterioration of chromaticity (orange instead of red). While it is effective to provide a light emitting layer of an organic phosphorescence material and a hole blocking layer for increasing the luminous efficiency of the organic EL device, it is necessary to further prolong the life of the device. It has been demanded for an organic EL device of high luminance efficiency that is continuously driven to emit light at high luminance with small quantity of current. DISCLOSURE OF THE INVENTION It is an object of the present invention to provide an organic EL device capable of prolonging the life. An organic electroluminescence device according to the invention is an organic electroluminescence device obtained by stacking an anode, a hole transport layer comprising an organic compound, a light emitting layer comprising an organic compound, an electron transport layer comprising an organic compound and a cathode characterized in that the light emitting layer comprises an organic host material represented by the following structural formula (1): and a phosphorescent organic guest material. The electroluminescence device according to the invention is characterized in that a hole injection layer is provided between the anode and the hole transportation. The electroluminescence device according to the invention is characterized in that an electron injection layer is provided between the cathode and the electron transport layer. The organic electroluminescence device according to the invention is characterized in that the phosphorescent organic guest material comprises a porphyrin compound represented by the following structural formula (2): (in the structural formula (2), Q represents —N═ or —C(R)═, M represents a metal, a metal oxide or a metal halide, R represents hydrogen, alkyl, aralkyl, aryl or alkalyl, or a halogenated substituent thereof, T1 and T2 each represents hydrogen or alkyl, or jointly represent a completed unsaturated six-membered ring including a halogen substituent, the six-membered ring is formed of carbon, sulfur and nitrogen ring atoms, and the alkyl moiety contains 1 to 6 carbon atoms). The organic electroluminescence device according to the invention is characterized in that M in the phosphorescent organic guest material is platinum. The organic electroluminescence device according to the invention is characterized in that the phosphorescent organic guest material comprises a compound represented by the following structural formula (3): (in the structural formula (3), M represents a metal, R1 to R8 each independently includes a hydrogen atom, alkyl group, oxy group, amino group or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R8 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less carbon atom and, further, R1 together with R2, R2 together with R3, R3 together with R4, R5 together with R6, R6 together with R7, or R7 together with R8 can form a condensed benzo ring). The organic electroluminescence device according to the invention is characterized in that M for the phosphorescent organic guest material is iridium. The organic electroluminescence device according to the invention is characterized in that the phosphorescent organic guest material comprises a compound represented by the following structural formula (4): (in the structural formula (4), M represents a metal, R1 to R6 each independently includes a hydrogen atom, alkyl group, oxy group, amino group, or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R6 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less of carbon atoms and, further, R1 together with R2, R3 together with R4, R4 together with R5, or R5 together with R6 can form a condensed benzo ring). The organic electroluminescence device according to the invention is characterized in that M in the phosphorescent organic guest material is iridium. The organic electroluminescence device according to the invention is characterized in that the phosphorescent organic guest material comprises a compound represented by the following structural formula (5): (in the structural formula (5), M represents a metal, X1 and X2 each independently represents an oxygen atom or a sulfur atom, R1 to R11 each independently includes a hydrogen atom, alkyl group, oxy group, amino group, or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R11 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less carbon atoms and, further, R1 together with R2, R2 together with R3, R3 together with R4, R5 together with R6 or R6 together with R7, R7 together with R8, R8 together with R9, or R10 together with R11 can form a condensed benzo ring). The organic electroluminescence device according to the invention is characterized in that M for the phosphorescent organic guest material is iridium. The organic electroluminescence device according to the invention is characterized in that the phosphorescent organic guest material comprises a compound represented by the following structural formula (6): (in the structural formula (6), M represents a metal, X1 and X2 each independently represents an oxygen atom or a sulfur atom, R1 to R9 each independently includes a hydrogen atom, alkyl group, oxy group, amino group or a hydrocarbon group having at least one carbon atom in the substituent, the number of carbon atoms is 1 to 10 in each of the hydrocarbon moieties, further, R1 to R9 can be selected independently from cyano, halogen, and α-haloalkyl, α-haloalkoxy, amide, sulfonyl, carbonyl, carbonyloxy and oxycarbonyl substituents containing 10 or less of carbon atoms and, further, R1 together with R2, R3 together with R4, R4 together with R5, R5 together with R6, R7 together with R8, or R8 together with R9 can form a condensed benzo ring). The organic electroluminescence device according to the invention is characterized in that M for the phosphorescent organic guest material is iridium. BRIEF EXPLANATION OF THE DRAWINGS FIG. 1 is a structural view showing an organic EL device according to the present invention. FIG. 2 is a structural view showing an organic EL device according to the invention. FIG. 3 is a structural view showing an organic EL device according to the invention. FIG. 4 is a graph showing characteristics for deterioration of luminance and driving voltage of the organic EL device in Example 1 according to the invention. FIG. 5 is a graph showing the voltage-luminance characteristics of the organic EL device in Example 2 according to the invention. FIG. 6 is a graph showing the current-luminance characteristics of the organic EL device in Example 2 according to the invention. FIG. 7 is a graph showing characteristics for deterioration of luminance and driving voltage of the organic EL device in Example 2 according to the invention. DISCLOSURE OF INVENTION Embodiments of the present invention are to be described with reference to the drawings. An organic EL device according to the invention comprises, as shown in FIG. 1, at least an anode 2, a hole transport layer 3, a light emitting layer 4, an electron transport layer 6 and a cathode 7, which is obtained by stacking, on a transparent substrate 1 for example made of glass, a transparent anode 2, a hole transport layer 3 comprising an organic compound, a light emitting layer 4 comprising an organic compound, an electron transport layer 6 comprising an organic compound and a metal cathode 7 made, for example, of a material with low work function. In the organic EL device according to the invention, the light emitting layer 4 is an organic material having an electron transportability doped with an organic host material represented by the following structural formula (1): and a phosphorescent material as an organic guest material. In the light emitting layer 4, the organic guest material is preferably doped such that a kind of material is doped at a ratio of from 4 to 10% by weight based on the entire kinds of materials. An example of a specific organic EL element includes a constitution of using ITO for the anode, 4,4-bis(N-(naphthyl)-N-phenyl-amino)biphenyl, i.e., NPB (Ip=5.4 eV), for the hole transport layer, an organic host material represented by the structural formula (1) for the light emitting layer, Alq3 for the electron transport layer and an aluminum for the cathode. The glass transition temperature of the compound of the structural formula (1) is 113° C. which is higher by about 15° C. than that of BAlq as the known compound having a similar structure. This enables further stabilization for the electrical and physical characteristics of the thin film in the organic EL device, high storability at high temperature and suppression for the degradation of luminance during continuous driving. Further, the ligand of the compound of the structural formula (1) has a longer conjugation system compared with biphenol as the ligand for BAlq and the electron transportability is improved as well. Accordingly, the compound of the structural formula (1) is effective as a material for the organic electric field light emitting material. In addition to the structure described above, another organic EL device structure also includes as shown in FIG. 2, a structure in which an electron injection layer 7a made of Li2O, etc. is stacked and deposited as a thin film between the electron transport layer 6 ad the cathode 7. In addition to the structure described above, a further organic EL device structure also includes as shown in FIG. 3, a structure in which a hole injection 3a such as made of a porphyrin compound, for example, copper phthalocyanine (CuPc) stacked and deposited as a thin film between the anode 2 and the hole transport layer 3. For the cathode 1, a material comprising a metal of a small work function, for example, aluminum, magnesium, indium, silver or an alloy for each of them and having a thickness of about 100 to 5000 Angstrom can be used. Further, for the anode 2, a conductive material of large work function, for example, indium tin oxide (hereinafter referred to as ITO) and having a thickness of about 1000 to 3000 angstrom or gold having a thickness of about 800 to 1500 angstrom can be used. In a case of using gold for the electrode material, the electrode is in a semi-transparent state. It may suffice that one of the cathode and the anode is transparent or semi-transparent. In the embodiment, the ingredient contained in the hole transport layer 3 is a substance having a hole transportability, for example, represented by the following formulae (7) to (32). In the embodiment, the ingredient contained in the electron transport layer 6 can be selected from the materials represented, for example, by the following formulae (33) to (51). In the formulae described above, Bu represents a butyl group and t-Bu represents a tertiary butyl group. Further, the organic material having the electron transportability also includes aluminum chelate complexes represented by the following formulae (52) to (87). Further, the organic material having the electron transportability usable for the electron transport layer 6 can also be selected from phenanthroline derivatives represented by the following formulae (88) to (96): The phosphorescent organic guest material for use in light emitting layer 4 can also be selected from the compounds shown by the structural formulae (2) to (6), for example, own by the following formulae (97) to (106): EXAMPLE 1 Plural organic EL devices were manufactured as samples specifically and light emitting characteristics thereof were evaluated. For the samples, copper phthalocyanine (CuPc) was used as the hole injection layer, NPB was used as the hole transport layer and Alq3 was used as the electron transport layer. In common with the samples, thin films of the respective materials were stacked successively on a glass substrate formed with an anode made of ITO with a film thickness of 1100 Å by vacuum vapor deposition at a vacuum degree of 5.0×10−6 Torr. At first, in sample 1, CuPc was deposited as a film to 250 Å thickness on a ITO cathode at a vapor deposition rate of 3 Å/sec, to form a hole injection layer. Then, NPB was deposited as a film to 550 Å thickness on a CuPc hole injection layer at a vapor deposition rate of 3 Å/sec to form a hole transport layer. Then, on the NPB hole transport layer, an organic host material of the structural formula (1) and an organic guest material XT emitting red phosphorous among the compounds shown by the structural formula (6) were co-deposited from different vapor deposition sources to 475 Å thickness to form a light emitting layer. In this process, the concentration of the organic guest material XT in the light emitting layer was 7 wt %. Then, on the mixed light emitting layer, Alq3 was vapor deposited to 300 Å thickness at a vapor deposition rate of 3 Å/sec to form an electron transport layer. Further, on the Alq3 electron transport layer, lithium oxide (Li2O) was vapor deposited as an electron injection layer to 10 Å at a vapor deposition rate of 0.1 Å/sec and, further thereon, aluminum (Al) was stacked as the cathode to 1000 Å at 10 Å/sec, to manufacture an organic light emitting device of the example. As a comparative example, a device of comparative example identical with that of Example 1 was also manufactured except for using BAlq for the organic host material in the mixed light emitting layer. FIG. 1 shows change of degradation of luminance and driving voltage when Example 1 and Comparative Example were driven continuously at a constant current of 5.5 mA/cm2 from the initial luminance of 340 cd/m2. In the device of Example 1, the luminance half-decay period was extended compared with the comparative example and the luminance life was excellent. Change of the driving voltage (increase) is one of parameters showing the degradation of the material along with continuous driving. Light emitting characteristics of the devices of Example 1 and the comparative example in a storage test at 100° C. were evaluated. Table 1 and Table 2 show the change of chromaticity, luminance and voltage relative to lapse of time in a case of driving the devices of Example 1 and Comparative Example at 5.5 mA/cm2 respectively. TABLE 1 Lapse of time Chromaticity diagram Luminance Driving voltage (hours) ClEx ClEy (cd/m2) (V) 0 0.676 0.321 326 8.41 63 0.676 0.323 322 7.70 159 0.673 0.324 292 7.24 324 0.672 0.325 239 7.09 500 0.667 0.328 197 6.86 TABLE 2 Lapse of time Chromaticity diagram Luminance Driving voltage (hours) ClEx ClEy (cd/m2) (V) 0 0.678 0.321 337 9.20 63 0.677 0.323 269 6.93 159 0.576 0.386 66 6.51 324 0.528 0.416 63 6.79 500 0.525 0.423 65 6.92 When the organic El device of the example was stored under the circumstance at 100° C., the luminance was lowered by 40% relative to the initial value at lapse of 500 hrs. Further, change of the chromaticity was also observed scarcely in the example. On the contrary, for the lowering of the luminance of the device of the comparative example, the luminance was lowered by 80% relative to the initial value at lapse of 160 hrs at 100° C. Further, change of chromaticity was observed and the emission color changed from red to yellow. The glass transition temperature Tg of the structural formula (1) of the organic host material is 113° C. and the glass transition temperature Tg of BAlq is 99° C. It is considered that since the organic host material of the light emitting layer of the example had higher Tg than that of the comparative example and the physical and electrical characteristics of the thin film in the organic EL device were stable, the degradation of luminance during continuous driving was suppressed and the driving life was improved compared with the device of the comparative example. Further, since the organic host material shown by the structural formula (1) had a ligand of longer conjugation system compared with BAlq used in the comparative example, it is excellent in the electron transportability. The organic EL device using the organic host material shown by the structural material (1) as the light emitting layer had more preferred current luminance characteristics than those of the device using BAlq as the light emitting layer and suffered from less lowering of efficiency, particularly, in a higher luminance region exceeding 300 cd/m2. EXAMPLE 2 A devices was manufactured quite in the same manner as Example 1 except for using 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphinePlatinum (II) (so-called PtOEP), instead of the organic guest material XT, as the phosphorescent organic guest material under the identical condition. Fore the devices of Example 2 and the comparative example, Table 3 shows the light emitting characteristics during continuous driving at a constant current of 2.5 mA/cm2, FIG. 5 shows voltage-luminance characteristics, and FIG. 6 shows current-luminance characteristics, respectively. The device of Example 2 using the material of the structural formula (1) of the invention for the host material in the light emitting layer had more satisfactory voltage-luminance characteristics and current characteristics compared with the device of the comparative example. That is, the device of high efficiency and low driving voltage could be obtained by using the material shown by the structural formula (1) as the host material of the light emitting layer. TABLE 3 Chromaticity Quantum diagram Luminance efficiency Driving ClEx ClEy (cd/m2) (%) voltage (V) Example 2 0.695 0.294 43 5.35 8.85 Comp. Example 0.709 0.283 38 4.89 9.66 FIG. 7 shows the change of degradation of luminance and driving voltage during continuous driving at a constant current of 7.5 mA/cm2. At the lapse of 300 hrs, both the device of Example 2 and the device of the comparative example maintained 95% or more of the initial luminance. For the driving voltage, it increased by 6.4% at the lapse of time of 300 hrs in the device of the comparative example, whereas it was suppressed to 3.5% in the device of Example 2. As has been described above, according to the present invention, since the organic host material of an aluminum chelate complex of the specified structure shown by the structural formula (1) is used as the main ingredient of the light emitting layer in the organic EL device having the light emitting layer using the phosphorescent material for the organic guest material, it is excellent in heat resistance and can attain a long driving life while maintaining favorable light emitting characteristics.
<SOH> BACKGROUND ART <EOH>In general, each of organic EL devices using an organic material and constituting a display panel has a structure in that an anode as a transparent electrode, plural organic material layers including an organic light emitting layer and a cathode comprising a metal electrode are successively layered each as a thin film on a glass substrate as a display surface. In addition to the organic light emitting layer, the organic material layer includes a layer comprising a material having a hole transportability such as a hole injection layer and a hole transport layer, and a layer comprising a material having electron transportability such as an electron transport layer and an electron injection layer, and an organic EL device of a constitution provided with them has also been proposed. The electron injection layer also contains an in organic compound. When an electric field is applied to an organic EL device of a stacked body of an organic light emitting layer and an electron or hole transport layer, holes are injected from the anode and electrons are injected from the cathode. The organic EL divide utilizes emission of light that is emitted when the electrons and the holes are recombined in the organic light emitting layer to form exciters and they are returned to the ground state. For making the luminous efficiency higher and stably driving the device, a dye is sometimes doped as a guest material to the light emitting layer. In recent years, in addition to the fluorescence material, use of a phosphorescence material for the light emitting layer has also been proposed, since it is considered that the probability for the occurrence of singlet exciters and triplet exciters after recombination of electrons and holes in the light emitting layer of the organic EL device is 1:3 and it is considered that a device also utilizing phosphorescence caused by the triplet exciters can attain the luminous efficiency three to four times as high as the device using fluorescence caused by the singlet exciters. On the other hand, for reducing the power consumption improvement of the luminous efficiency and improvement of the driving stability of the organic EL device, it has been proposed to provide a hole blocking layer between the organic light emitting layer and the cathode for restricting the movement of the holes from the organic light emitting layer. By efficient accumulation of the holes in the light emitting layer by the hole blocking layer, the recombination probability with electrons can be improved to attain higher luminous efficiency. As the hole blocking material, it has been reported that phenanthroline derivatives and triazole derivatives are effective (refer to JP-A No. 8-109373 and JP-A No. 10-233284). In existent organic EL devices utilizing phosphorescence emission, hole transporting materials capable of transporting holes have been used for the light emitting layer host material and materials having higher ionizing potential energy (Ip) than the post material of the light emitting layer such as phenanthroline derivatives, for example, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, i.e., BCP or aluminum chelate complex, for example, ((1,1′-biphenyl)-4-olato)bis(2-methyl-8-quinolinolato NI, 08) aluminum, i.e., BAlq are used as the hole blocking layer in the layer adjacent cathode of the light emitting layer. In a case of using BCP for the hole blocking layer, while the emission characteristics at the initial stage are favorable, it involves a drawback that the driving life is extremely short. At present, materials having sufficiently high Ip and excellent in durability have not been known. BAlq is excellent in durability but has a drawback of poor hole blocking ability since Ip is not sufficiently high. Accordingly, in a case of using BAlq as the hole blocking layer and tris(8-hydroxyquinolateo N1, 08) aluminum, i.e., Alq3 as the electron transport layer, the electron transport layer emits light. In the organic electroluminescence device utilizing red phosphorescence emission, the emission of Alq3 (green) results in deterioration of chromaticity (orange instead of red). While it is effective to provide a light emitting layer of an organic phosphorescence material and a hole blocking layer for increasing the luminous efficiency of the organic EL device, it is necessary to further prolong the life of the device. It has been demanded for an organic EL device of high luminance efficiency that is continuously driven to emit light at high luminance with small quantity of current.
20050628
20100824
20051020
58157.0
0
YAMNITZKY, MARIE ROSE
ORGANIC ELECTROLUMINESCENCE DEVICE
UNDISCOUNTED
0
ACCEPTED
2,005
10,509,401
ACCEPTED
Method for attaching two surfaces to each other using a bioadhesive polyphenolic protein and periodate ions
The present invention pertains to a method for attaching two surfaces to each other or coating a surface by providing a bioadhesive composition consisting of an aqueous solution of a bioadhesive polyphenolic protein derived from a byssus-forming mussel, and mixing said bioadhesive composition with a preparation comprising non-enzymatic oxidising periodate ions so that the concentration of periodate ions is at least 1.80 mmol/g in the final composition before applying the mixture to at least one of two surfaces to be attached to each other or coated or applying said composition and said periodate ions without any specific order, to at least one of two surfaces to be attached to each other or the surface to be coated, thereby mixing the bioadhesive composition and the periodate ions. The surfaces are then joined (if necessary) and left for sufficiently long time for curing to occur. The invention can be provided as a kit of parts comprising the MAP-solution, a preparation comprising the periodate ions and optionally a device to apply the compositions of the invention to surfaces that are to be attached to each other or coated.
1. Method for attaching two surfaces to each other comprising the steps of a) providing a bioadhesive composition consisting of an aqueous solution of a bioadhesive polyphenolic protein, which protein comprises 30-300 amino acids and consists essentially of tandemly linked peptide repeats comprising 3-15 amino acid residues, wherein at least 3% and preferably 6-30% of thee amino acid residues of said bioadhesive polyphenolic protein are DOPA; b) providing a preparation comprising periodate ions; c) mixing said bioadhesive composition and preparation comprising periodate ions so that the periodate ions constitute at least 0.465 mmol/g of the final composition; d) (i) applying the mixture to at least one of two surfaces to be attached to each other, or (ii) applying said composition and said preparation comprising periodate ions without any specific order, to at least one of two surfaces to be attached to each other, thereby mixing the bioadhesive composition and preparation comprising periodate ions; e) joining said surfaces to each other; and f) leaving said surfaces for a sufficiently long time for curing to occur. 2. Method for coating a surface comprising the steps of a) providing a bioadhesive composition consisting of an aqueous solution of a bioadhesive polyphenolic protein, which protein comprises 30-300 amino acids and consists essentially of tandemly linked peptide repeats comprising 3-15 amino acid residues, wherein at least 3% and preferably 6-30% of thee amino acid residues of said bioadhesive polyphenolic protein are DOPA; b) providing a preparation comprising periodate ions; c) (i) mixing said bioadhesive composition and preparation comprising periodate ions so that the periodate ions constitute at least 0.465 mmol/g of the final composition; d) (i) applying the mixture to the surface to be coated, or (ii) applying said composition and said preparation comprising periodate ions without any specific order, to the surface to be coated, thereby mixing the bioadhesive composition and preparation comprising periodate ions; and e) leaving said surface for a sufficiently long time for curing to occur. 3. Method according to claim 1 or claim 2, wherein the concentration of periodate ions in the final composition is at least 1.90 mmol/g. 4. Method according to claim 1 or claim 2, wherein the concentration of periodate ions in the final composition is at least 2.00 mmol/g. 5. Method according to anyone of the preceeding claims, wherein the concentration of the bioadhesive polyphenolic protein in the bioadhesive composition is in the range of 10-50 mg/ml. 6. Method according to anyone of the preceeding claims, wherein at least one of the surfaces to be attached or the surface to be coated is a biological surface. 7. Method according to anyone of the preceeding claims, wherein at least one of the surfaces to be attached or the surface to be coated is a non-biological surface. 8. Kit for attaching two surfaces to each other or coating a surface comprising a) a bioadhesive composition consisting of an aqueous solution of a bioadhesive polyphenolic protein, which protein comprises 30-300 amino acids and consists essentially of tandemly linked peptide repeats comprising 3-15 amino acid residues, wherein at least 3% and preferably 6-30% of thee amino acid residues of said bioadhesive polyphenolic protein are DOPA; b) a preparation comprising periodate ions; and c) written instructions showing how to use the kit in accordance with the method of anyone of claims 1-7. 9. Kit accoding to claim 8 further comprising (a) device(s) for applying a specified amount of the solution of the bioadhesive protein and the preparation comprising periodate ions to at least one of the surfaces that are to be attached to each other or to the surface that is to be coated.
The present invention pertains to a method for attaching two surfaces to each other or coating a surface, comprising the steps of providing a bioadhesive composition consisting of a bioadhesive polyphenolic protein derived from a byssus-forming mussel, mixing the bioadhesive protein with a high amount of non-enzymatic oxidising periodate ions before or simultaneously as applying the composition to the surfaces which are to be attached to each other or the surface to be coated. The surfaces are then joined and left for a sufficiently long time to allow curing to occur alternatively the surface coated by the composition is left for a sufficiently long time to allow curing to occur. The invention can be provided as a kit of parts comprising the bioadhesive protein solution and a preparation comprising a periodate salt. BACKGROUND OF THE INVENTION Attachment of different structures is crucial in a wide variety of processes. However, this is frequently associated with problems of different nature depending on what structures are to be attached. Areas that are particularly troublesome are adhesion in the medical field, and attachment of components of very small size, such as in the micro- and nano-techniques. In the medical field, examples of when adhesives have to be used to adhere biological material include repair of lacerated or otherwise damaged organs, especially broken bones and detached retinas and corneas. Dental procedures also often require adhesion of parts to each other, such as during repair of caries, permanent sealants and periodontal surgery. It is very important in biomedical applications of an adhesive and coating composition to use bio-acceptable and biodegradable components, which furthermore should not per se or due to contamination induce any inflammation or toxic reactions. In addition, the adhesive has to be able to attach structures to each other in a wet environment. In the electronic industry, a particular problem today is that the components that are to be attached to each other often are of very small size, and the amount of adhesive that is possible to use is very small. Adhesives that provide high adhesive strength even with minor amounts of adhesive are therefore required. Also for non-medical uses, an adhesive that is non-irritating, non-allergenic, non-toxic and environmentally friendly is preferred, in contrast to what many of the adhesives commonly used today usually are. Polyphenolic proteins, preferentially isolated from mussels, are known to act as adhesives. Examples of such proteins can be found in e.g. U.S. Pat. No. 4,585,585. Their wide use as adhesives has been hampered by problems related to the purification and characterisation of the adhesive proteins in sufficient amounts. Also, mostly when using the polyphenolic proteins as adhesives the pH has had to be raised to neutral or slightly basic (commonly to from 5.5 to 7.5) in order to facilitate oxidation and curing of the protein. However, this curing is slow and results in poor adhesive strength and therefore oxidisers, fillers and cross-linking agents are commonly added to decrease the curing time and obtain a stronger adhesive. Mussel adhesive protein (MAP) is formed in a gland in the foot of byssus-forming mussels, such as the common blue mussel (Mytilus edulis). The molecular weight of MAP from Mytilis edulis is about 130.000 Dalton and it has been disclosed to consist of 75-80 closely related repeated peptide sequences. The protein is further characterised by its many epidermal growth factor like repeats. It has an unusual high proportion of hydroxy-containing amino acids such as hydroxyproline, serine, threonine, tyrosin, and the uncommon amino acid 3,4-dihydroxy-L-phenylalanine (Dopa) as well as lysine. It may be isolated either from natural sources or produced biotechnologically. U.S. Pat. No. 5,015,677 as well as U.S. Pat. No. 4,585,585 disclose that MAP has very strong adhesive properties after oxidation and polymerisation, e.g. by the activity of the enzyme tyrosinase, or after treatment with bifunctional reagents. MAP is previously known to be useful as an adhesive composition e.g. for ophthalmic purposes. Robin et al., Refractive and Corneal Surgery, vol. 5, p. 302-306, and Robin et al., Arch. Ophthalmol., vol. 106, p. 973-977, both disclose MAP-based adhesives comprising an enzyme polymiser. U.S. Pat. No. 5,015,677 also describes a MAP-based adhesive containing a cross-linking agent and optionally a filler substance and a surfactant. Preferred cross-linking agents according to U.S. Pat. No. 5,015,677 are enzymatic oxidising agents, such as catechol oxidase and tyrosinase, but sometimes also chemical cross-linking agents, such as glutaraldehyde and formaldehyde can be used. Examples of fillers are proteins, such as casein, collagen and albumin, and polymers comprising carbohydrate moieties, such as chitosan and hyaluronan. U.S. Pat. No. 5,030,230 also relates to a bioadhesive comprising MAP, mushroom tyrosinase (cross-linker), SDS (sodium dodecyl sulfate, a surfactant) and collagen (filler). The bioadhesive is used to adhere a cornea prosthesis to the eye wall. EP-A-343 424 describes the use of a mussel adhesive protein to adhere a tissue, cell or another nucleic acid containing sample to a substrate during nucleic acid hybridisation conditions, wherein the mussel adhesive protein, despite the harsh conditions encountered during the hybridisation, provided adherence. U.S. Pat. No. 5,817,470 describes the use of mussel adhesive protein to immobilise a ligand to a solid support for enzyme-linked immunoassay. Mussel adhesive protein has also been used in cosmetic compositions to enhance adherence to nails and skin (WO 88/05654). A major problem associated with known MAP-based bioadhesive compositions, despite the superior properties of MAP per se, is that some constituents, in particular the presently used cross-linking agents, can harm and/or irritate living tissue and cause toxic and immunological reactions. Chemical crosslinking agents, such as glutaraldehyde and formaldehyde, are generally toxic to humans and animals, and it is highly inappropriate to add such agents to a sensitive tissue, such as the eye. Enzymes, such as catechol oxidase and tyrosinase, are proteins, and proteins are generally recognised as potential allergens, especially in case they originate from a species other than the patient. Because of their oxidising and hydrolysing abilities, they can also harm sensitive tissue. Therefore, there is still a need for new adhesive compositions, both for medical and other applications, that provide strong adhesion with small amounts of adhesive, that are simple to use and that do not cause toxic and allergic reactions. SUMMARY OF THE INVENTION The present invention pertains to a method for attaching two surfaces to each other or coating a surface, comprising the steps of providing a bioadhesive composition consisting of a bioadhesive polyphenolic protein derived from a byssus-forming mussel, mixing the bioadhesive protein with a preparation comprising periodate ions, so that the final concentration of periodate ions in the final composition is at least 1.80 mmol/g final composition, before applying the composition to the surfaces which are to be attached to each other or the surface to be coated. The surfaces are then joined and left for a sufficiently long time to allow curing to occur or the coated surface is left to cure for a sufficiently long time. The invention can be provided as a kit of parts comprising the bioadhesive protein solution and a preparation of periodate ions. Since the provided compositions are non-toxic and presumably non-allergenic the invention is especially suitable for use in medical applications for adherence or coating of biological tissues. Also, since very strong adhesive strengths are provided using the compositions of the present invention, it is also particularly useful for applications where only minute amounts of adhesives can be used, including non-biological surfaces. The invention can be provided in the form of a kit of parts comprising the MAP-solution and a preparation of periodate ions. Definitions As disclosed herein, the terms “polyphenolic protein”, “mussel adhesive protein” or “MAP” relates to a bioadhesive protein derived from byssus-forming mussels or which is recombinantly produced. Examples of such mussels are mussels of the genera Mytilus, Geukensia, Aulacomya, Phragmatopoma, Dreissenia and Brachiodontes. Suitable proteins have been disclosed in a plurality of publications, e.g. U.S. Pat. No. 5,015,677, U.S. Pat. No. 5,242,808, U.S. Pat. No. 4,585,585, U.S. Pat. No. 5,202,236, U.S. Pat. No. 5,149,657, U.S. Pat. No. 5,410,023, WO 97/34016, and U.S. Pat. No. 5,574,134, Vreeland et al., J. Physiol., 34: 1-8, and Yu et al., Macromolecules, 31: 4739-4745. They comprise about 30-300 amino acid residues and essentially consist of tandemly linked peptide units comprising 3-15 amino acid residues, optionally separated by a junction sequence of 0-10 amino acids. A characteristic feature of such proteins is a comparatively high amount of positively charged lysine residues, and in particular the unusual amino acid DOPA (L-3,4-dihydroxyphenylalanine). A polyphenolic protein suitable for use in the present invention has an amino acid sequence in which at least 3% and preferably 6-30% of the amino acid residues are DOPA. A few examples of typical peptide units are given below. However, it is important to note that the amino acid sequences of these proteins are variable and that the scope of the present invention is not limited to the exemplified subsequences below, as the skilled person realises that bioadhesive polyphenolic proteins from different sources, including recombinantly produced, can be regarded as equivalent: a) Val-Gly-Gly-DOPA-Gly-DOPA-Gly-Ala-Lys b) Ala-Lys-Pro-Ser-Tyr-diHyp-Hyp-Thr-DOPA-Lys c) Thr-Gly-DOPA-Gly-Pro-Gly-DOPA-Lys d) Ala-Gly-DOPA-Gly-Gly-Leu-Lys e) Gly-Pro-DOPA-Val-Pro-Asp-Gly-Pro-Tyr-Asp-Lys f) Gly-Lys-Pro-Ser-Pro-DOPA-Asp-Pro-Gly-DOPA-Lys g) Gly-DOPA-Lys h) Thr-Gly-DOPA-Ser-Ala-Gly-DOPA-Lys i) Gln-Thr-Gly-DOPA-Val-Pro-Gly-DOPA-Lys j) Gln-Thr-Gly-DOPA-Asp-Pro-Gly-Tyr-Lys k) Gln-Thr-Gly-DOPA-Leu-Pro-Gly-DOPA-Lys The term “surface” is to be interpreted broadly and may comprise virtually any surface. The choice of surface is not critical to the present invention. Examples of surfaces for which the invention are specially suitable for include non-biological surfaces such as glass, plastic, ceramic and metallic surfaces etc., and biological surfaces, comprising wood and different tissues such as skin, bone, teeth, the eye, cartilage, etc. By “sufficiently long time” is meant a time period long enough to allow curing of the bioadhesive composition. Curing is often immediate and typically the time period required for curing is from 5 sec to one hour. By “preparation comprising periodate ions” is meant a non-enzymatic, oxidising preparation comprising periodate ions from any salt comprising such periodate ions, such as NaIO4, KIO4, RuIO4 etc. The preparation can be an aqueous solution comprising the periodate salt or a preparation comprising the solid salt. DETAILED DESCRIPTION OF THE INVENTION The object of the present invention is to provide an adhesive composition to be used for attaching two surfaces to each other or coating a surface. The compositions provided in the invention can in principle be used to attach any surfaces to each other or to coat any surface. However, the compositions according to the present invention are particularly useful when adhesive or coating compositions are needed that are non-toxic, non-irritating or non-allergenic, or that can be used in wet environments. Also the compositions of the present invention are useful when a strong adhesion even with small amounts of adhesive, are required. Further advantages with the compositions provided in the present invention are their water solubility, the avoidance of organic solvents commonly used in adhesive or coating compositions, that they are biologically produced and harmless to the environment. The only mandatory components of the present invention is the polyphenolic protein and periodate ions. Previously when polyphenolic proteins have been used, it has been considered necessary to add additional components, such as fillers and oxidising agents, in order to achieve strong enough adhesive strength and the pH is commonly raised to neutral or slightly basic. The present inventor has shown that a very strong adhesion, comparable to the adhesive strength provided using the commonly used MAP compositions, can be provided simply using a solution of the MAP protein and mixing said MAP protein with preparation of periodate ions so that the concentration of periodate ions in the final composition is at least 1.80 mmol/g. The periodate ions can be provided via a preparation of an aqueous solution comprising any suitable salt comprising such ions, such as NaIO4, KIO4, RuIO4 etc., alone or in different combinations and ratios. Alternatively, the preparation comprising the periodate salt(s) can be dissolved directly in the MAP-solution. Preferably, the MAP concentration of the present invention is above 10 mg/ml. More preferably the concentration of the MAP-solution is above 20 mg/ml. Typically the concentration is between 20 and 50 mg/ml. One preferred object of the present invention is to provide an adhesive or coating composition for medical applications, e.g. for attaching biological and/or non-biological components to biological structures, an object for which the MAP protein in itself is well suited, since it is non-toxic and biodegradable. However, the enzymatic oxidising agents commonly added to MAP compositions in order to obtain cross-linking and oxidation can lead to irritation and allergic reactions and those MAP compositions are therefore not optimal for medical applications. Due to the lack of such components in the present invention, the compositions of the present invention are particularly suitable for attachment of biological surfaces to each other or to biological or non-biological components. For the above reasons the compositions of the present invention are also particularly useful for coating of materials used in medical applications or biological tissues. Due to the very high adhesive strength provided with very small amounts of the compositions of the present invention, one preferred field of application for which the compositions are particularly suitable for attachment of non-biological surfaces such as glass, plastic, ceramic and metallic surfaces. This is particularly useful within the electronic micro- and nano-techniques, optics, etc. for adhesion or coating of, for example, biosensors, microchips, solar cells, mobile phones, etc., since for these applications only minute amounts of adhesive can be used. The compositions of the present invention are also suitable for coating of non-biological surfaces. The adhesive compositions of the present invention are also useful for attachment of cells, enzymes, antibodies and other biological specimen to surfaces. According to one aspect of the invention the solution of MAP is mixed with a preparation comprising periodate ions so that the final concentration of periodate ions in the composition is at least 1.80 mmol/g final composition. The mixture is then applied to at least one of the surfaces to be attached to each other or to the surface to be coated. Alternatively, the MAP-solution and the preparation comprising periodate ions are separately applied, without any specific order, to at least one of the surfaces, which are to be attached to each other, or a surface to be coated. The MAP-solution can also be applied to one of the surfaces that are to be attached to each other while the preparation comprising periodate ions is applied to the other. If two surfaces are to be attached to each other they are then joined. Finally the attached or coated surfaces are left for a sufficiently long time to allow curing. The time necessary for curing will for example depend on the surfaces attached or coated, and the amount and the composition of the adhesive. Often, however, the curing is immediate and a time period of 5 sec to one hour is typically sufficient for curing to occur. Preferably the final concentration of periodate ions in the bioadhesive composion according to the present invention is at least 1.90 mmol/g final composition, and more preferably at least 2.00 mmol/g final composition. 40% by weight of NaIO4 in the final bioadhesive composition equals 1.86 mmol/g in the final composition. However, good adhesive strengths can also be achieved with down to 10% by weight of NaIO4. The present invention can be provided as a kit of parts useful in a method for attaching surfaces to each other or coating surfaces, comprising the MAP-solution, a solid or liquid preparation comprising the periodate ions and optionally at least one device, such as a syringe, to apply the compositions to the surfaces that are to be attached or coated. Preferred preparations and concentrations of periodate ions, concentration ranges of the MAP-solution, curing times and surfaces to attached or coated for use of this kit are as described above. EXAMPLE 1 In order to determine the adhesive strength using the compositions of the present invention, the adhesive strength between glass plates and biological tissue (muscle from cattle and pig) was determined. The MAP-solution (in 0.01 M citric acid) from Biopolymer Products of Sweden AB, Alings{dot over (a)}s, Sweden) was applied to a glass plate (75×25×2 mm), whereafter the non-enzymatic oxidising agent NaIO4 was applied to the glass plate and carefully mixed with the MAP-solution on the glass plate, before the biological tissue (approximately of the size 40×15×4 mm) was placed on the glass plate and fixed with a clip. The lower amount of NaIO4 (3-6% by weight of final composition, see Table 1-3) was used for comparison. The sample was thereafter allowed to cure under water (35° C.) for 5 min or 1 hour (see Table 1 and 2) or under dry conditions at room temperature for 1 min (see Table 3). To measure the adhesive strength after curing, the clip was removed from the sample and the sample was attached to a spring balance via the glass plate. The biological tissue was then pulled until it detached from the glass plate and the force needed for this was determined (Table 1-3). The adhesive area between the glass plate and the biological tissue was ca 0.3-0.4 cm2 on average, but varied from 0.1-0.8 cm2. As can be seen in Table 1-3, a substantial increase in adhesive strength is obtained, when the very high amount of non-enzymatic oxidising periodate ions according to the present invention, is used. TABLE 1 Adhesive strength between glass plate and biological tissue with curing for 5 min under water at 35° C. MAP NaIO4 NaIO4 % NaIO4 in final Adhesive Concentration MAP Concentration Amount composition (by strength Sample (mg/ml) Amount (μg) (M) (μl) weight) (g) 1 20 60 0.01 2 6 90 2 20 60 0.1 2 42 150 TABLE 2 Adhesive strength between glass plate and biological tissue with curing for 1 hour under water at 35° C. MAP NaIO4 NaIO4 % NaIO4 in final Adhesive Concentration MAP Concentration Amount composition (by strength Sample (mg/ml) Amount (μg) (M) (μl) weight) (g) 1 23 69 0.01 2 3 120 2 24 60 0.1 2 42 185 TABLE 3 Adhesive strength between glass plate and biological tissue with curing for 1 min under dry conditions at room temperature. MAP NaIO4 NaIO4 % NaIO4 in final Adhesive Concentration MAP Concentration Amount composition (by strength Sample (mg/ml) Amount (μg) (M) (μl) weight) (g) 1 24 60 0.01 1.5 5 25 2 22 66 0.1 3 49 110 3 24 60 0.5 1.5 73 125 4 22 66 0.5 3 83 110 EXAMPLE 2 The adhesive strength obtained by employing the compositions of the present invention was compared with the strength obtained by using a common epoxy adhesive. Two glass plates were attached to each other using either a MAP-solution and a high amount of the non-enzymatic oxidising agent NaIO4. The MAP-solution (in 0.01 M citric acid), from Biopolymer Products of Sweden AB, Alings{dot over (a)}s, Sweden) was applied to a glass plate (75×25×2 mm), whereafter the non-enzymatic oxidising agent NaIO4 was applied to the glass plate and carefully mixed with the MAP-solution on the glass plate, before placing a second glass plate onto the first one and fixing the glass plates to each other with a clip. The adhesive area between the glass plates covered was on average 0.5-0.7 cm2 (with a variation from 0.3-1.0 cm2). The samples were allowed to cure at room temperature for 72 hours before determining the shear strength (see Table 4). For comparison the adhesive strength between glass plates by employing common epoxy adhesive (Bostic AB, Helsingborg, Sweden) (10 mg) was determined. For the determination of shear strength the grip length was 75 mm and the cross head speed was 3.0 mm/min. The adhesive strength obtained using the compositions the present invention resulted in very strong adhesive strengths. As a comparison, the adhesive strength obtained employing ca 250 times more of a common epoxy glue is included (see Table 4). Therefore very strong adhesive strengths can be obtained with very small amounts of adhesive when using the compositions of the present invention. TABLE 4 Adhesive strength between glass plates with curing for 72 hours under dry conditions at room temperature. % NaIO4 in final MAP NaIO4 NaIO4 composition Epxoy glue Concentration MAP Concentration Amount (by Amount Adhesive Sample (mg/ml) Amount (μg) (M) (μl) weight) (mg) strength (N) 1 20 40 0.1 1.5 44 — 141 2 20 40 0.1 1.5 44 119 3 — — — — — 10 380
<SOH> BACKGROUND OF THE INVENTION <EOH>Attachment of different structures is crucial in a wide variety of processes. However, this is frequently associated with problems of different nature depending on what structures are to be attached. Areas that are particularly troublesome are adhesion in the medical field, and attachment of components of very small size, such as in the micro- and nano-techniques. In the medical field, examples of when adhesives have to be used to adhere biological material include repair of lacerated or otherwise damaged organs, especially broken bones and detached retinas and corneas. Dental procedures also often require adhesion of parts to each other, such as during repair of caries, permanent sealants and periodontal surgery. It is very important in biomedical applications of an adhesive and coating composition to use bio-acceptable and biodegradable components, which furthermore should not per se or due to contamination induce any inflammation or toxic reactions. In addition, the adhesive has to be able to attach structures to each other in a wet environment. In the electronic industry, a particular problem today is that the components that are to be attached to each other often are of very small size, and the amount of adhesive that is possible to use is very small. Adhesives that provide high adhesive strength even with minor amounts of adhesive are therefore required. Also for non-medical uses, an adhesive that is non-irritating, non-allergenic, non-toxic and environmentally friendly is preferred, in contrast to what many of the adhesives commonly used today usually are. Polyphenolic proteins, preferentially isolated from mussels, are known to act as adhesives. Examples of such proteins can be found in e.g. U.S. Pat. No. 4,585,585. Their wide use as adhesives has been hampered by problems related to the purification and characterisation of the adhesive proteins in sufficient amounts. Also, mostly when using the polyphenolic proteins as adhesives the pH has had to be raised to neutral or slightly basic (commonly to from 5.5 to 7.5) in order to facilitate oxidation and curing of the protein. However, this curing is slow and results in poor adhesive strength and therefore oxidisers, fillers and cross-linking agents are commonly added to decrease the curing time and obtain a stronger adhesive. Mussel adhesive protein (MAP) is formed in a gland in the foot of byssus-forming mussels, such as the common blue mussel ( Mytilus edulis ). The molecular weight of MAP from Mytilis edulis is about 130.000 Dalton and it has been disclosed to consist of 75-80 closely related repeated peptide sequences. The protein is further characterised by its many epidermal growth factor like repeats. It has an unusual high proportion of hydroxy-containing amino acids such as hydroxyproline, serine, threonine, tyrosin, and the uncommon amino acid 3,4-dihydroxy-L-phenylalanine (Dopa) as well as lysine. It may be isolated either from natural sources or produced biotechnologically. U.S. Pat. No. 5,015,677 as well as U.S. Pat. No. 4,585,585 disclose that MAP has very strong adhesive properties after oxidation and polymerisation, e.g. by the activity of the enzyme tyrosinase, or after treatment with bifunctional reagents. MAP is previously known to be useful as an adhesive composition e.g. for ophthalmic purposes. Robin et al., Refractive and Corneal Surgery, vol. 5, p. 302-306, and Robin et al., Arch. Ophthalmol., vol. 106, p. 973-977, both disclose MAP-based adhesives comprising an enzyme polymiser. U.S. Pat. No. 5,015,677 also describes a MAP-based adhesive containing a cross-linking agent and optionally a filler substance and a surfactant. Preferred cross-linking agents according to U.S. Pat. No. 5,015,677 are enzymatic oxidising agents, such as catechol oxidase and tyrosinase, but sometimes also chemical cross-linking agents, such as glutaraldehyde and formaldehyde can be used. Examples of fillers are proteins, such as casein, collagen and albumin, and polymers comprising carbohydrate moieties, such as chitosan and hyaluronan. U.S. Pat. No. 5,030,230 also relates to a bioadhesive comprising MAP, mushroom tyrosinase (cross-linker), SDS (sodium dodecyl sulfate, a surfactant) and collagen (filler). The bioadhesive is used to adhere a cornea prosthesis to the eye wall. EP-A-343 424 describes the use of a mussel adhesive protein to adhere a tissue, cell or another nucleic acid containing sample to a substrate during nucleic acid hybridisation conditions, wherein the mussel adhesive protein, despite the harsh conditions encountered during the hybridisation, provided adherence. U.S. Pat. No. 5,817,470 describes the use of mussel adhesive protein to immobilise a ligand to a solid support for enzyme-linked immunoassay. Mussel adhesive protein has also been used in cosmetic compositions to enhance adherence to nails and skin (WO 88/05654). A major problem associated with known MAP-based bioadhesive compositions, despite the superior properties of MAP per se, is that some constituents, in particular the presently used cross-linking agents, can harm and/or irritate living tissue and cause toxic and immunological reactions. Chemical crosslinking agents, such as glutaraldehyde and formaldehyde, are generally toxic to humans and animals, and it is highly inappropriate to add such agents to a sensitive tissue, such as the eye. Enzymes, such as catechol oxidase and tyrosinase, are proteins, and proteins are generally recognised as potential allergens, especially in case they originate from a species other than the patient. Because of their oxidising and hydrolysing abilities, they can also harm sensitive tissue. Therefore, there is still a need for new adhesive compositions, both for medical and other applications, that provide strong adhesion with small amounts of adhesive, that are simple to use and that do not cause toxic and allergic reactions.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention pertains to a method for attaching two surfaces to each other or coating a surface, comprising the steps of providing a bioadhesive composition consisting of a bioadhesive polyphenolic protein derived from a byssus-forming mussel, mixing the bioadhesive protein with a preparation comprising periodate ions, so that the final concentration of periodate ions in the final composition is at least 1.80 mmol/g final composition, before applying the composition to the surfaces which are to be attached to each other or the surface to be coated. The surfaces are then joined and left for a sufficiently long time to allow curing to occur or the coated surface is left to cure for a sufficiently long time. The invention can be provided as a kit of parts comprising the bioadhesive protein solution and a preparation of periodate ions. Since the provided compositions are non-toxic and presumably non-allergenic the invention is especially suitable for use in medical applications for adherence or coating of biological tissues. Also, since very strong adhesive strengths are provided using the compositions of the present invention, it is also particularly useful for applications where only minute amounts of adhesives can be used, including non-biological surfaces. The invention can be provided in the form of a kit of parts comprising the MAP-solution and a preparation of periodate ions. Definitions As disclosed herein, the terms “polyphenolic protein”, “mussel adhesive protein” or “MAP” relates to a bioadhesive protein derived from byssus-forming mussels or which is recombinantly produced. Examples of such mussels are mussels of the genera Mytilus, Geukensia, Aulacomya, Phragmatopoma, Dreissenia and Brachiodontes . Suitable proteins have been disclosed in a plurality of publications, e.g. U.S. Pat. No. 5,015,677, U.S. Pat. No. 5,242,808, U.S. Pat. No. 4,585,585, U.S. Pat. No. 5,202,236, U.S. Pat. No. 5,149,657, U.S. Pat. No. 5,410,023, WO 97/34016, and U.S. Pat. No. 5,574,134, Vreeland et al., J. Physiol., 34: 1-8, and Yu et al., Macromolecules, 31: 4739-4745. They comprise about 30-300 amino acid residues and essentially consist of tandemly linked peptide units comprising 3-15 amino acid residues, optionally separated by a junction sequence of 0-10 amino acids. A characteristic feature of such proteins is a comparatively high amount of positively charged lysine residues, and in particular the unusual amino acid DOPA (L-3,4-dihydroxyphenylalanine). A polyphenolic protein suitable for use in the present invention has an amino acid sequence in which at least 3% and preferably 6-30% of the amino acid residues are DOPA. A few examples of typical peptide units are given below. However, it is important to note that the amino acid sequences of these proteins are variable and that the scope of the present invention is not limited to the exemplified subsequences below, as the skilled person realises that bioadhesive polyphenolic proteins from different sources, including recombinantly produced, can be regarded as equivalent: a) Val-Gly-Gly-DOPA-Gly-DOPA-Gly-Ala-Lys b) Ala-Lys-Pro-Ser-Tyr-diHyp-Hyp-Thr-DOPA-Lys c) Thr-Gly-DOPA-Gly-Pro-Gly-DOPA-Lys d) Ala-Gly-DOPA-Gly-Gly-Leu-Lys e) Gly-Pro-DOPA-Val-Pro-Asp-Gly-Pro-Tyr-Asp-Lys f) Gly-Lys-Pro-Ser-Pro-DOPA-Asp-Pro-Gly-DOPA-Lys g) Gly-DOPA-Lys h) Thr-Gly-DOPA-Ser-Ala-Gly-DOPA-Lys i) Gln-Thr-Gly-DOPA-Val-Pro-Gly-DOPA-Lys j) Gln-Thr-Gly-DOPA-Asp-Pro-Gly-Tyr-Lys k) Gln-Thr-Gly-DOPA-Leu-Pro-Gly-DOPA-Lys The term “surface” is to be interpreted broadly and may comprise virtually any surface. The choice of surface is not critical to the present invention. Examples of surfaces for which the invention are specially suitable for include non-biological surfaces such as glass, plastic, ceramic and metallic surfaces etc., and biological surfaces, comprising wood and different tissues such as skin, bone, teeth, the eye, cartilage, etc. By “sufficiently long time” is meant a time period long enough to allow curing of the bioadhesive composition. Curing is often immediate and typically the time period required for curing is from 5 sec to one hour. By “preparation comprising periodate ions” is meant a non-enzymatic, oxidising preparation comprising periodate ions from any salt comprising such periodate ions, such as NaIO 4 , KIO 4 , RuIO 4 etc. The preparation can be an aqueous solution comprising the periodate salt or a preparation comprising the solid salt.
20040924
20070306
20051013
70026.0
0
MONDESI, ROBERT B
METHOD FOR ATTACHING TWO SURFACES TO EACH OTHER USING A BIOADHESIVE POLYPHENOLIC PROTEIN AND PERIODATE IONS
SMALL
0
ACCEPTED
2,004
10,509,549
ACCEPTED
Kappa-opioid receptor agonist comprising 2-phenylbenzothiazoline derivative
The present invention provides κ opioid receptor agonists comprising 2-phenylbenzothiazoline derivatives. The present invention relates to κ opioid receptor agonists comprising compounds or salts thereof having the chemical structure represented by the general formula [I]. Namely, it is important for exhibition of the κ opioid receptor agonist actions to have an alkyl group having an amino group at a phenyl group of 2-phenylbenzothiazoline as a substituent and to have an acyl group at a nitrogen atom of 2-phenylbenzothiazoline, wherein R is alkyl having the amino group as the substituent; and R1 is acyl.
1. A κ opioid receptor agonist comprising a compound having a chemical structure represented by the following general formula [I] as a basic skeleton or a salt thereof, wherein R is alkyl having an amino group as a substituent; and R1 is acyl. 2. A κ opioid receptor agonist comprising a compound represented by the following general formula [II] or a salt thereof, wherein R1 is acyl; R2 and R3, the same or different, are hydrogen, halogen, alkyl, cycloalkyl, aryl, hydroxyl or esters thereof, alkoxy, aryloxy, carboxyl or esters thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, cyano or nitro, wherein the alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylamino or arylamino can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, carboxyl or an ester thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, cyano or nitro; R4 and R5, the same or different, are hydrogen, alkyl, cycloalkyl, aryl, hydroxyl or esters thereof, alkoxy, aryloxy or acyl, wherein the alkyl, cycloalkyl, aryl, alkoxy, aryloxy or acyl can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, carboxyl or an ester thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, mercapto, alkylthio, arylthio, cyano, nitro or a heterocycle, and further the alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylamino, arylamino, alkylthio, arylthio or heterocycle can be substituted by aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, alkoxyalkoxy or carboxyl or an ester thereof; R4 and R5 can be bonded each other to form a heterocycle, the heterocycle can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy or carboxyl or an ester thereof, and further the alkyl, cycloalkyl, aryl, alkoxy or aryloxy can be substituted by aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, alkoxyalkoxy or carboxyl or an ester thereof; and A1 is alkylene. 3. The κ opioid receptor agonist as claimed in claim 2, which comprises a compound or a salt thereof, wherein R2 and R3, the same or different, are hydrogen, halogen, alkyl or alkoxy, wherein the alkyl can be substituted by halogen in the general formula [II]. 4. The κ opioid receptor agonist as claimed in claim 2, which comprises a compound or a salt thereof, wherein R4 and R5, the same or different, are hydrogen, alkyl, cycloalkyl, hydroxyl or esters thereof or alkoxy, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, carboxyl or an ester thereof, mercapto, alkylthio or a heterocycle, and further the alkyl or alkoxy can be substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkoxy in the general formula [II]. 5. The κ opioid receptor agonist as claimed in claim 2, which comprises a compound or a salt thereof, wherein R4 and R5 can be bonded each other to form a pyrrolidine ring or a piperidine ring, wherein the pyrrolidine ring or piperidine ring can be substituted by alkyl, hydroxyl or an ester thereof, alkoxy or carboxyl or an ester thereof, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy in the general formula [II]. 6. The κ opioid receptor agonist as claimed in claim 2, which comprises a compound or a salt thereof, wherein R1 is acyl, R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen, R3 is halogen or alkoxy, R4 is hydrogen, alkyl or cycloalkyl, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R4 and R5 can be bonded each other to form a pyrrolidine ring or a piperidine ring, wherein the pyrrolidine ring or piperidine ring can be substituted by alkyl, hydroxyl or an ester thereof, alkoxy or carboxyl or an ester thereof, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R5 is alkyl, hydroxyl or an ester thereof or alkoxy, wherein the alkyl can be substituted by cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, carboxyl or an ester thereof, mercapto, alkylthio or a heterocycle, and further the alkoxy can be substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkoxy, and A1 is alkylene in the general formula [II]. 7. The κ opioid receptor agonist as claimed in claim 2, which comprises a compound or a salt thereof, wherein R1 is acyl, R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen, R3 is halogen or alkoxy, R4 is alkyl or cycloalkyl, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy, R4 and R5 can be bonded each other to form a pyrrolidine ring, wherein the pyrrolidine ring can be substituted by alkyl, hydroxyl or an ester thereof or alkoxy, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R5 is alkyl, hydroxyl or an ester thereof or alkoxy, wherein the alkyl can be substituted by hydroxyl or an ester thereof, alkoxy, mercapto or alkylthio, and further the alkoxy can be substituted by alkoxy or alkoxyalkoxy, and A1 is alkylene in the general formula [II]. 8. A κ opioid receptor agonist comprising a compound or a salt thereof selected from the group consisting of 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-(2-methylpropyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-((2S)-2-hydroxymethylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-((3S)-hydroxyazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(thiophen-2-ylmethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N,N-diisopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(hydroxyethyl)-N-methylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxymethyloxyethyl))-amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-(2-methoxyethoxy-methoxy)ethyl) amino)propoxy)-5-methoxyphenyl]benzothiazoline 2-[2-(3-(N-(2-Acetoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-phenylcarboxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-cyclohexyl-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline and (+)-3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline. 9. An analgesic or an antipruritic comprising the κ opioid receptor agonist as claimed in claims 1 to 8 as active ingredient. 10. The analgesic as claimed in claim 9, wherein pain is derived from a rheumatic disease. 11. A compound or a salt thereof represented by the following general formula [III], wherein R1 is acyl: R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen; R3 is halogen or alkoxy; R4 is alkyl or cycloalkyl, wherein the alkyl can be substituted by cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy; R4 and R5 can be bonded each other to form a pyrrolidine ring substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkyl; R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6; R6 is hydroxyl or an ester thereof, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, mercapto or alkylthio; and A1 and A2, the same or different, are alkylene, provided that when R4 and R5 are bonded each other to form the pyrrolidine ring substituted by hydroxyl or the ester thereof, R2 is halogen, when R4 and R5 are bonded each other to form the pyrrolidine ring substituted by alkoxyalkyl, R2 is hydrogen, when R6 is hydroxyl or the ester thereof, R4 is isopropyl. 12. The compound or a salt thereof as claimed in claim 11, wherein R1 is acyl, R2 is hydrogen, R3 is alkoxy, R4 is alkyl, R4 and R5 can be bonded each other to form a pyrrolidine ring substituted by alkoxy or alkoxyalkyl, R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6, R6 is alkoxy, alkoxyalkoxy or alkoxyalkoxyalkoxy, and A1 and A2, the same or different, are alkylene in the general formula [III]. 13. The compound or a salt thereof as claimed in claim 11, wherein R1 is acyl, R2 is halogen, R3 is alkoxy, R4 is alkyl, R4 and R5 can be bonded each other to form a pyrrolidine substituted by hydroxyl or an ester thereof or alkoxy, R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6, R6 is alkoxy, alkoxyalkoxy or alkoxyalkoxyalkoxy, and A1 and A2, the same or different, are alkylene in the general formula [III]. 14. The compound or a salt thereof as claimed in claim 11, wherein R1 is acyl, R2 is hydrogen or halogen, R3 is alkoxy, R4 is isopropyl, R5 is -A2-R6, R6 is hydroxyl or an ester thereof, and A1 and A2, the same or different, are alkylene in the general formula [III]. 15. A compound or a salt thereof selected from the group consisting of 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-(N-(2-methoxymethyloxy-ethyl))amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-(2-methoxyethoxy-methoxy)ethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline 2-[2-(3-(N-(2-Acetoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline and 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-phenylcarboxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline.
TECHNICAL FIELD The present invention relates to κ opioid receptor agonists comprising 2-phenylbenzothiazoline derivatives or salts thereof and novel 2-phenylbenzothiazoline derivatives or salts thereof. The κ opioid receptor agonists of the present invention are particularly useful as therapeutic agents for pain, pruritus and the like. BACKGROUND ART Pain plays a physiologically important role as a warning reaction to know danger. On the other hand, pain is also a significant cause to lower quality of lives (QOL) of patients. Pain accompanying almost all diseases typified by rheumatic diseases is one of causes of dysfunction. Accordingly, it is medically very important to control pain (Experimental Medicine, 18 (17), 2332-2337 (2000) and J. Pharm. Soc., 120 (12), 1291-1307 (2000)). Narcotic analgesics such as morphine and nonnarcotic analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), indometacin and diclofenac sodium, are widely used now as drugs which control pain. However, while the narcotic analgesics have strong analgesic actions, they have side effects such as drug dependence, and their use are strictly limited accordingly. On the other hand, NSAIDs are very useful as therapeutic agents for pain derived from synthesis of inflammatory mediators such as prostaglandin but have no strong analgesic actions unlike the narcotic analgesics. In recent years, μ (mu), κ (kappa) and δ (delta) receptors have been proposed as subtypes of the opioid receptors, and it has been clarified that the side effects such as drug dependence of morphine are exhibited through the μ opioid receptor. Further, it has been found that analgesic actions are exhibited through any of the μ opioid receptor, the κ opioid receptor and the δ opioid receptor. These findings suggest a possibility that drugs which selectively act on the κ opioid receptor and the δ opioid receptor can be analgesics which solve problems of drugs which act on the μ opioid receptor. Compounds reported to serve as drugs which selectively act on the κ opioid receptor are compounds having a phenylacetic amide skeleton represented by U50488H, compounds having a benzodiazepine skeleton represented by Thifuadom, compounds having a phenothiazine skeleton represented by Apadoline, compounds having a 4,5-epoxymorphinan skeleton represented by TRK-820 and the like (“All of opioid”, published by Mikusu Co., Ltd., p. 222-229 (1999)). It is known that pain is weaken by activating the κ opioid receptor, and it was reported that a κ opioid receptor agonist is useful as an analgesic (“All of opioid”, published by Mikusu Co., Ltd., p. 25-36 (1999)). Further, it was also reported that the κ opioid receptor agonist has an antipruritic action (WO 98/23290). On the other hand, Japanese Laid-open Patent Publication Nos. 46079/1983, 67276/1984, 139679/1985 and 221679/1987 reported that 2-phenylbenzothiazoline derivatives have calcium antagonism and platelet aggregation actions and are useful as therapeutic agents for cardiovascular diseases such as hypertension, thrombosis, angina and arrhythmia. However, actions of these 2-phenylbenzothiazoline derivatives on the κ opioid receptor are not known, much less it is impossible to presume which derivatives thereof act as agonists or antagonists at all. Their analgesic actions and antipruritic actions are not reported at all, either. It is very interesting subjects to find new pharmacological actions of the known 2-phenylbenzothiazoline derivatives, which are useful as pharmaceuticals, and further to synthesize novel 2-phenylbenzothiazoline derivatives, which are their analogs, and to find useful pharmacological actions thereof. DISCLOSURE OF THE INVENTION Conducting intensive study in order to find new pharmacological actions of 2-phenylbenzothiazoline derivatives, the present inventors found that 2-phenylbenzothiazoline derivatives have excellent agonist actions on a human κ opioid receptor and are useful as therapeutic agents for pain and pruritus. Further, the present inventors prepared many novel 2-phenylbenzothiazoline derivatives wherein new various substituents such as hydroxyl, alkoxy and -A2-R6 were introduced to a nitrogen atom of an aminoalkylene group and found that these derivatives also have the κ opioid receptor agonist actions. Thus the present invention has been accomplished. The present invention relates to κ opioid receptor agonists comprising compounds having the chemical structure represented by the general formula [I] as a basic skeleton or salts thereof. To exhibit κ opioid receptor agonist actions, it is important to have an alkyl group having an amino group as a substituent at a phenyl group of 2-phenylbenzothiazoline and to have an acyl group at a nitrogen atom of 2-phenylbenzothiazoline. [wherein R is alkyl having the amino group as the substituent; and R1 is acyl.] More specifically, the present invention relates to κ opioid receptor agonists comprising compounds represented by the general formula [II] or salts thereof. [wherein R1 is acyl; R2 and R3, the same or different, are hydrogen, halogen, alkyl, cycloalkyl, aryl, hydroxyl or esters thereof, alkoxy, aryloxy, carboxyl or esters thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, cyano or nitro, wherein the alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylamino or arylamino can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, carboxyl or an ester thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, cyano or nitro; R4 and R5, the same or different, are hydrogen, alkyl, cycloalkyl, aryl, hydroxyl or esters thereof, alkoxy, aryloxy or acyl, wherein the alkyl, cycloalkyl, aryl, alkoxy, aryloxy or acyl can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, carboxyl or an ester thereof, alkylcarbonyl, arylcarbonyl, amino, alkylamino, arylamino, mercapto, alkylthio, arylthio, cyano, nitro or a heterocycle, and further the alkyl, cycloalkyl, aryl, alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylamino, arylamino, alkylthio, arylthio or heterocycle can be substituted by aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, alkoxyalkoxy or carboxyl or an ester thereof; R4 and R5 can be bonded each other to form a heterocycle, the heterocycle can be substituted by halogen, alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, aryloxy or carboxyl or an ester thereof, and further the alkyl, cycloalkyl, aryl, alkoxy or aryloxy can be substituted by aryl, hydroxyl or an ester thereof, alkoxy, aryloxy, alkoxyalkoxy or carboxyl or an ester thereof; and A1 is alkylene.] Compounds represented by the general formula [III] are novel compounds which are unknown in literatures among the compounds represented by the general formulae [I] and [II]. [wherein R1 is acyl: R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen; R3 is halogen or alkoxy; R4 is alkyl or cycloalkyl, wherein the alkyl can be substituted by cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy; R4 and R5 can be bonded each other to form a pyrrolidine ring substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkyl; R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6; R6 is hydroxyl or an ester thereof, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, mercapto or alkylthio; and A1 and A2, the same or different, are alkylene. Provided that when R4 and R5 are bonded each other to form the pyrrolidine ring substituted by hydroxyl or the ester thereof, R2 is halogen, when R4 and R5 are bonded each other to form the pyrrolidine ring substituted by alkoxyalkyl, R2 is hydrogen, when R6 is hydroxyl or the ester thereof, R4 is isopropyl.] The respective groups defined above are described in detail below. The alkyl having the amino group as the substituent is alkyl having a substituted or unsubstituted amino group as the substituent and is more specifically a group represented by the following general formula [II]. The alkyl is straight-chain or branched alkyl having one to six carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl or n-hexyl. The acyl is a partial structure such as hydrocarbonyl, alkylcarbonyl or arylcarbonyl of substituted or unsubstituted carboxylic acids and is acyl having one to 12 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl valeryl, isovaleryl, pivaloyl, monochloroacetyl, trichloroacetyl, trifluoroacetyl or benzoyl. The halogen is fluorine, chlorine, bromine or iodine. The cycloalkyl is cyclic cycloalkyl having three to eight carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. The aryl is a monocyclic aromatic hydrocarbon group such as phenyl, tolyl, xylyl or mesityl and a condensed-ring aromatic hydrocarbon group such as indenyl, naphthyl, phenanthryl, anthryl or pyrenyl. The alkoxy is straight-chain or branched alkoxy having one to six carbon atoms such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, isopentoxy or n-hexyloxy. The heterocycle is a saturated or unsaturated monocyclic or condensed polycyclic heterocycle having one to four the same or different nitrogen atom(s), oxygen atom(s) or sulfur atom(s) in its ring. Specific examples of saturated monocyclic heterocycles are pyrrolidine, piperidine, homopiperidine, piperazine and the like having a nitrogen atom in its ring; tetrahydrofuran, tetrahydropyran and the like having an oxygen atom in its ring; tetrahydrothiophene and tetrahydrothiopione and the like having a sulfur atom in its ring; morpholine and the like having a nitrogen atom and an oxygen atom in its ring; and thiomorpholine and the like having a nitrogen atom and a sulfur atom in its ring. The saturated monocyclic heterocycle can be condensed with a benzene ring or the like to form a condensed polycyclic heterocycle such as tetrahydroquinoline or tetrahydroisoquinoline. Specific examples of unsaturated monocyclic heterocycles are pyridine, pyrimidine, pyrrole, imidazole and the like having a nitrogen atom in its ring; furan and the like having an oxygen in its ring; thiophene and the like having a sulfur atom in its ring; oxazole and the like having a nitrogen atom and an oxygen atom in its ring; and thiazole and the like having a nitrogen atom and a sulfur atom in its ring. The unsaturated monocyclic heterocycle can be condensed with a benzene ring or the like to form a condensed polycyclic heterocycle such as indole, quinoline, phenanthridine, benzimidazole, benzoxazole or benzothiazole. The alkylene is straight-chain or branched alkylene having one to six carbon atoms such as methylene, ethylene, trimethlene, tetramethylene, pentamethylene, hexamethylene, methylmethylene, dimethylmethylene, ethylmethylene, propylmethylene, isopropylmethylene, butylmethylene, isobutylmethylene, s-butylmethylene, tert-butylmethylene, dimethylethylene, ethylethylene, propylethylene, isopropylethylene or methyltrimethylene. The compounds represented by the general formula [I], more specifically the compounds represented by the general formula [II] are hereinafter referred to as “the present compounds” as far as there is no proviso. The ester of hydroxyl is an ester with an alkylcarboxylic acid, an arylcarboxylic acid or the like. Examples of alkylcarboxylic acids are acetic acid, propionic acid, butyric acid, valeric acid, 2,2-dimethylpropanoic acid and the like, and examples of arylcarboxylic acids are benzoic acid, toluic acid and the like. The ester of carboxyl is an ester with an alkyl alcohol, an aryl alcohol or the like. Examples of alkyl alcohols are methanol, ethanol, propanol, butanol and the like, and examples of aryl alcohols are phenol, cresol, naphthol and the like. When the present compound has carboxyl as a substituent, the carboxyl can form an amide with an alkylamine, an arylamine or the like. Examples of alkylamines are methylamine, ethylamine, ethylmethylamine, dimethylamine, diethylamine and the like. Examples of arylamines are aniline, diphenylamine, ethylphenylamine and the like. Hydroxyl, mercapto, amino, alkylamino, arylamino or a nitrogen atom of the heterocycle can be protected with a protecting group in the present compounds. The protecting group of hydroxyl is a protecting group which is widely used as the protecting group of hydroxyl such as substituted or unsubstituted alkyl such as benzyloxymethyl, allyl, benzyl, p-methoxybenzyl, trityl, tetrahydropyranyl or tetrahydrofuranyl; substituted or unsubstituted ester such as methoxycarbonyl, ethoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, benzyloxycarbonyl or p-methoxybenzyloxycarbonyl; or saturated or unsaturated silyl such as trimethylsilyl, triethylsilyl, triisopropylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl. The protecting group of mercapto is a protecting group which is widely used as the protecting group of mercapto such as substituted or unsubstituted alkyl such as methoxymethyl, isobutoxymethyl, benzylthiomethyl, phenylthiomethyl, benzyl, p-methoxybenzyl, tert-butyl, trityl or tetrahydropyranyl; substituted or unsubstituted acyl such as acetyl, propionyl, butylyl, pivaloyl, benzoyl or tenoyl; substituted or unsubstituted ester such as methoxycarbonyl, tert-butoxycarbonyl or benzyloxycarbonyl; or substituted thio such as ethylthio, tert-butylthio or phenylthio. The protecting group of amino, alkylamino, arylamino or the nitrogen atom of the heterocycle is a protecting group which is widely used as the protecting group of amino, alkylamino, arylamino or the nitrogen atom of the heterocycle such as substituted or unsubstituted alkyl such as allyl, benzyl, trityl, (4-methoxyphenyl)diphenylmethyl or diphenylmethyl; substituted or unsubstituted acyl such as formyl, acetyl, trichloroacetyl, trifluoroacetyl, picolinoyl or benzoyl; ester such as methoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, benzyloxycarbonyl, diphenylmethoxycarbonyl or phenoxycarbonyl; or substituted or unsubstituted sulfonyl such as methanesulfonyl, benzenesulfonyl, toluenesulfonyl or 2,4,6-trimethylbenzenesulfonyl. The “salts” in the present invention can be any pharmaceutically acceptable salts and are exemplified by salts with an inorganic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid or phosphoric acid, salts with an organic acid such as acetic acid, fumaric acid, maleic acid, succinic acid, citric acid, tartaric acid, adipic acid, lactic acid, methanesulfonic acid, trifluoromethanesulfonic acid or p-toluenesulfonic acid, salts with an alkali metal such as lithium, sodium or potassium, salts with an alkaline earth metal such as calcium or magnesium, and quaternary salts with ammonia, methyl iodide or the like. When there are geometrical isomers or optical isomers in the present compounds, these isomers are also included in the scope of the present invention. Further, the present compounds can be in the form of hydrates or solvates. Preferred examples of the present invention are the following. (1) κ opioid receptor agonist comprising compounds or salts thereof as active ingredients wherein the respective groups defined in the general formula [II] are selected from the following groups or combinations thereof, 1) R2 and R3, the same or different, are hydrogen, halogen, alkyl or alkoxy, wherein the alkyl can be substituted by halogen. 2) R4 and R5, the same or different, are hydrogen, alkyl, cycloalkyl, hydroxyl or esters thereof or alkoxy, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, carboxyl or an ester thereof, mercapto, alkylthio or a heterocycle, and further the alkyl or alkoxy can be substituted by hydroxyl or an ester thereof, alkoxy or alkoxyalkoxy. 3) R4 and R5 can be bonded each other to form a pyrrolidine ring or a piperidine ring, wherein the pyrrolidine ring or piperidine ring can be substituted by alkyl, hydroxyl or an ester thereof, alkoxy or carboxyl or an ester thereof, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy. κ opioid receptor agonists comprising compounds or salts thereof wherein the respective groups defined by the general formula [II] are the following groups are more preferable, R1 is acyl, R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen, R3 is halogen or alkoxy, R4 is hydrogen, alkyl or cycloalkyl, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R4 and R5 can be bonded each other to form a pyrrolidine ring or a piperidine ring, wherein the pyrrolidine ring or piperidine ring can be substituted by alkyl, hydroxyl or an ester thereof, alkoxy or carboxyl or an ester thereof, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R5 is alkyl, hydroxyl or an ester thereof or alkoxy, wherein the alkyl can be substituted by cycloalkyl, aryl, hydroxyl or an ester thereof, alkoxy, carboxyl or an ester thereof, mercapto, alkylthio or a heterocycle, and further the alkoxy can be substituted by hydroxyl, alkoxy or alkoxyalkoxy, and A1 is alkylene. κ opioid receptor agonists comprising compounds or salts thereof wherein the respective groups defined by the general formula [II] are the following groups are particularly preferable, R1 is acyl, R2 is hydrogen, halogen or alkyl, wherein the alkyl can be substituted by halogen, R3 is halogen or alkoxy, R4 is alkyl or cycloalkyl, wherein the alkyl can be substituted by alkyl, cycloalkyl, aryl, hydroxyl or an ester thereof or alkoxy, R4 and R5 can be bonded each other to form a pyrrolidine ring, wherein the pyrrolidine ring can be substituted by alkyl, hydroxyl or an ester thereof or alkoxy, and further the alkyl can be substituted by hydroxyl or an ester thereof or alkoxy, R5 is alkyl, hydroxyl or an ester thereof or alkoxy, wherein the alkyl can be substituted by hydroxyl or an ester thereof, alkoxy, mercapto or alkylthio, and further the alkoxy can be substituted by alkoxy or alkoxyalkoxy, and A1 is alkylene. Particularly preferred specific examples in the present invention are κ opioid receptor agonists comprising the following compounds and salts thereof. 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-(2-methylpropyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-((2S)-2-hydroxymethylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-((3S)-hydroxyazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(thiophen-2-ylmethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropyl-amino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N,N-diisopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-methylamino)-propoxy)-5′-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxymethyloxy-ethyl) amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-(2-methoxyethoxy-methoxy)ethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline 2-[2-(3-(N-(2-Acetoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-phenylcarboxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-cyclohexyl-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Preferred examples of compounds represented by the formula [III] are the following. (1) Compounds or salts thereof wherein the respective groups defined by the general formula [III] are the following groups, R1 is acyl, R2 is hydrogen, R3 is alkoxy, R4 is alkyl, R4 and R5 can be bonded each other to form a pyrrolidine ring substituted by alkoxy or alkoxyalkyl, R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6, R6 is alkoxy, alkoxyalkoxy or alkoxyalkoxyalkoxy, and A1 and A2, the same or different, are alkylene. (2) Compounds or salts thereof wherein the respective groups defined by the general formula [III] are the following groups, R1 is acyl, R2 is halogen, R3 is alkoxy, R4 is alkyl, R4 and R5 can be bonded each other to form a pyrrolidine ring substituted by hydroxyl or an ester thereof or alkoxy, R5 is hydroxyl or an ester thereof, alkoxy or -A2-R6, R6 is alkoxy, alkoxyalkoxy or alkoxyalkoxyalkoxy, and A1 and A2, the same or different, are alkylene. (3) Compounds or salts thereof wherein the respective groups defined by the general formula [III] are the following groups, R1 is acyl, R2 is hydrogen or halogen, R3 is alkoxy, R4 is isopropyl, R5 is -A2-R6, R6 is hydroxyl or an ester thereof, and A1 and A2, the same or different, are alkylene. Particularly preferred specific examples of compounds represented by the formula [III] are the following compounds and salts thereof. 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline (+)-3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-(N-(2-methoxymethyloxy-ethyl) amino)propoxy)-5-methoxyphenyl]benzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-(2-methoxyethoxy-methoxy) ethyl)amino)prop oxy)-5-methoxyphenyl]benzothiazoline 2-[2-(3-(N-(2-Acetoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-phenylcarboxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline The present compounds can be prepared on the basis of the description of Japanese Laid-open Patent Publication Nos. 46079/1983, 67276/1984, 139679/1985 and 221679/1987. Processes for preparing novel compounds of the present invention will be described below. These compounds can be prepared not only through the following processes for preparation but also through widely-used various processes for preparation. Detailed processes for preparing the present compounds will be described in later Examples (section of Preparation of Present Compounds). The present compound [II] can be synthesized according to synthetic route 1. Namely, compound [IV] is reacted with alkyl halide [V] in an organic solvent such as dimethylformamide (DMF) in the presence of a base such as sodium hydride in the range of 0° to 80° C. for 30 minutes to 24 hours to synthesize compound [VI], and then compound [VI] is reacted with amine derivative [VII] in an organic solvent such as DMF in the presence of a base such as potassium carbonate in the range of room temperature to 80° C. for 30 minutes to 24 hours to give the present compound [II]. Compound [IV] can be synthesized according to synthetic route 2. Namely, aminothiophenol derivative [VIII] is reacted with aldehyde derivative [IX] in an organic solvent such as toluene at room temperature to 80° C. for 30 minutes to 24 hours, and then a nitrogen of a benzothiazoline ring is acylated with R1 introduction active substance [X]such as N-acetylimizazole to give compound [IV]. Compound [IV] can be optically resolved according to synthetic route 3 to synthesize respective optically active substances. Namely, compound [IV] is condensed by dehydration with carboxylic acid derivative [XI] in an organic solvent such as DMF in the presence of a catalyst such as dimethylaminopyridine using a condensing agent such as dicyclohexylcarbodiimide to give compound [XII], and then the obtained compound [XII] is fractionally crystallized using a solvent such as ethanol to give optically active substances [XII-A] and [XII-B], which are diastereomers. Further, optically active substances [XII-A] and [XII-B] are hydrolyzed with alkali respectively to give optically active substance [IV-A] exhibiting plus optical rotation and optically active substance [IV-B] exhibiting minus optical rotation. Compounds [VI-A] and [VI-B], which are optical isomers, can be obtained by using these compounds [IV-A] and [IV-B] as the starting materials of the process represented by the synthetic route 1, and compounds represented by the formulae [II-A] and [II-B], which are optically active substances, can be obtained respectively by reacting the compounds [VI-A] and [VI-B] with the amine derivative represented by the formula. Carboxylic acid derivative [XI] to be used in the above synthetic route can be synthesized by synthetic route 4. Namely, optically active aminothiol derivative [XIII] is reacted with benzaldehyde in a solvent such as water at 0° C. to room temperature for one to 24 hours, and then the resulting crystals are treated in a solvent such as water in the presence of acetic anhydride or the like at room temperature to 80° C. for 30 minutes to 12 hours to give carboxylic acid derivative [XI]. Amine derivative [VII] to be used in the above synthetic route 1 can be synthesized according to the process described in literatures (Japanese Laid-open Patent Publication No. 344821/2000, Tetrahedron 1996, 52, (10), 3473-86, J. Med. Chem. 1973, 16, 736-9 and J. Am. Chem. Soc. 1946, 68, 1582) and synthetic routes 5, 6, 7, 8 and 9. Namely, in synthetic route 5, compound [XIV] is reacted with alkyl halide [XV] in an organic solvent such as DMF in the presence of a base such as potassium carbonate at room temperature to 80° C. for 30 minutes to 24 hours to give amine derivative [VII]. Synthetic Route 5 In synthetic route 6, compound [XVI] is reacted with dibutyl dicarbonate in an organic solvent such as tetrahydrofuran at 0° C. to room temperature for 30 minutes to 24 hours, the resulting compound [XVII] is reacted with alkyl halide in an organic solvent such as DMF in the presence of a base such as sodium hydride at 0° C. to room temperature for 30 minutes to 24 hours, and then the resulting compound [XVIII] is deprotected with reagent such as a solution of hydrogen chloride in ethyl acetate to give amine derivative [VII]. In synthetic route 7, compound [XIX] is reacted with compound [XX] in an organic solvnt such as DMF in the presence of a base such as potassium carbonate at room temperature to 80° C. for 30 minutes to 24 hours to give amine derivative [VII]. In synthetic route 8, amine derivative [XIX] is reacted with aldehyde derivative [XXI] in an organic solvent such as benzene in the presence of anhydrous sodium sulfate at room temperature to 60° C. for one to 24 hours, and the reaction product is reduced with a reducing agent such as sodium borohydride to give amine derivative [VII]. In synthetic route 9, amine derivative [XIX] is reacted with carbonyl compound [XXII] in an organic solvent such as methylene chloride in the presence of a base such as N-methylmorpholine at 0° C. to room temperature for 30 minutes to 24 hours, and then the resulting amide compound [XXIII] is reacted with a reducing agent such as lithium aluminum hydride in an organic solvent such as diethyl ether at 0° to 40° C. for 30 minutes to 24 hours to give amine derivative [VII]. The present compound [II] can be synthesized according to synthetic route 10 other than synthetic route 2. Namely, compound [IV] is reacted with alcohol derivative [XXIV] in an organic solvent such as tetrahydrofuran in the presence of a condensing agent such as triphenylphosphine and diisopropyl azodicarboxylate at 0° to 40° C. for 30 minutes to 24 hours to give the compound [II]. The present compound [II] can be synthesized according to synthetic route 11 other than synthetic route 2. Namely, compound [XXV] (compound included in compound [III] synthesized in synthetic route 1) is reacted with acyl halide [XXVI] or alkyl halide [XXVII] in an organic solvent such as methylene chloride in the presence of a base such as pyridine at 0° to 40° C. for 30 minutes to 24 hours to give the compound [II]. The present compound [II] can be synthesized according to synthetic route 12 other than synthetic route 2. Namely, compound [XXVIII] (compound included in compound [III] synthesized in synthetic route 1) is reacted with alkyl halide [XXIX] in an organic solvent such as DMF in the presence of potassium carbonate at room temperature to 80° C. for 30 minutes to 24 hours to give the compound [II]. The present compounds prepared by the above synthetic routes can be converted into the above-mentioned salts using widely-used techniques. In order to find new pharmacological actions of the present compounds, agonist activity tests of the present compounds on a κ opioid receptor in a GTP binding activity measurement system were carried out, and effects of the present compounds in the tests were evaluated. Details will be described in later Example (section of pharmacological tests). The present compounds were found to have excellent κ opioid receptor agonist activities (actions). Further, antinociceptive action tests by a mouse acetic acid writhing method were carried out in order to confirm that the present compounds having the κ opioid receptor agonist actions have analgesic effects. As a result, the present compounds were found to have excellent analgesic effects. As mentioned above, it was reported that the agonist action on the κ opioid receptor is closely related to the analgesic actions and antipruritic actions, and the present compounds are expected to serve as drugs which can control pain and pruritus due to various diseases such as rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematodus, osteoarthritis, gout and rheumatic fever. The present compounds can be administered orally or parenterally. Examples of dosage forms are a tablet, a capsule, granule, powder, an injection, an ophthalmic solution. The preparations can be prepared by the usual methods. For example, oral preparations such as a tablet, a capsule, granule and powder can be prepared by optionally adding an excipient such as lactose, mannitol, starch, crystalline cellulose, light silicic acid anhydride, calcium carbonate or calcium hydrogenphosphate, a lubricant such as stearic acid, magnesium stearate or talc, a binder such as starch, hydroxypropylcellulose, hydroxypropylmethylcellulose or polyvinylpyrrolidone, a disintegrator such as carboxymethylcellulose, low substituted hydroxypropylcellulose or calcium citrate, a coating agent such as hydroxypropylmethylcallulose, macrogol or a silicone resin, a stabilizer such as ethyl p-hydroxybenzoate or benzyl alcohol, or a corrigent such as a sweetening agent, a sour agent or a perfume. Parenteral preparations such as an injection and an ophthalmic solution can be prepared by optionally adding an isotonic agent such as sodium chloride or concentrated glycerin, a buffer such as sodium phosphate or sodium acetate, a surfactant such as polyoxyethylene sorbitan monoolate, polyoxy 40 stearate or polyoxyethylene hydrogenated castor oil, a stabilizer such as sodium citrate or disodium edetate or a preservative such as benzalkonium chloride or paraben. The dosage of the present compound can be appropriately selected depending on symptoms, age, dosage form or the like. For example, in the case of oral preparations, the usually daily dosage is 0.1 to 5,000 mg, preferably 1 to 1,000 mg, which can be given in a single dose or several divided doses. BEST MODE FOR CARRYING OUT THE INVENTION Examples of preparations and formulations of the present compounds and results of pharmacological tests are shown below. These examples do not limit the scope of the present invention, but are intended to make the present invention more clearly understandable. REFERENCE EXAMPLE 1 3-Acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 1-1) A solution of 2-hydroxy-5-methoxybenzaldehyde (65.0 g, 427 mmol) in toluene (59 ml) and methanol (7 ml) was added to a solution of 2-amino-5-chlorothiophenol (67.7 g, 427 mmol) in toluene (117 ml) and methanol (13 ml) under a nitrogen stream at room temperature, and the mixture was stirred at 50° to 70° C. for 40 minutes. The temperature was returned to room temperature, and then N-acetylimidazole (100 g, 908 mmol) and toluene (65 ml) were added thereto successively. The whole was stirred at room temperature overnight, then chloroform (2,000 ml) and 1 N hydrochloric acid (650 ml×2) were added to the reaction mixture, and the whole was extracted. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution (650 ml×2) and saturated brine (650 ml) successively, dehydrated with anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was suspended in chloroform (650 ml), and the suspension was allowed to stand at room temperature overnight. The precipitated crystals were filtered off to give 76.1 g (53%) of the target compound. IR (KBr) 3296, 3072, 1636, 1502, 1456, 1444, 1374, 1320, 1272, 1195, 1037, 799 cm−1 REFERENCE EXAMPLE 2 3-Acetyl-2-(2-hydroxy-5-methoxyphenyl)-5-trifluoromethylbenzothiazoline (Reference Compound No. 2-1) The target compound (2.2 g, 47%) was obtained from 2-amino-4-trifluoromethylthiophenol (3.3 g) by a method similar to Reference Example 1. IR (KBr) 3362, 1660, 1506, 1429, 1332 cm−1 REFERENCE EXAMPLE 3 3-Acetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 3-1) The target compound (92.9 g, 77%) was obtained from 2-aminothiophenol (50.0 g) by a method similar to Reference Example 1. REFERENCE EXAMPLE 4 3-Acetyl-5-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 4-1) A solution of 2-hydroxy-5-methoxybenzaldehyde (10.0 g, 65.7 mmol) in methanol (20 ml) was added to a solution of 2-amino-4-chlorothiophenol (10.5 g, 65.7 mmol) in methanol (20 ml) under a nitrogen stream at room temperature, the mixture was stirred at room temperature for 50 minutes, and then the precipitated crystals were filtered off. Acetic anhydride (20 ml, 212 mmol) was added to the obtained crystals, the mixture was stirred at room temperature overnight, and then the reaction mixture was concentrated under reduced pressure. Methanol (60 ml), water (10 ml) and potassium carbonate (5.0 g) were added to the residue, the whole was stirred at room temperature overnight, and then the reaction mixture was concentrated under reduced pressure. Ethyl acetate (300 ml) and 1 N-hydrochloric acid (200 ml) were added to the residue, and the whole was extracted. The organic layer was washed with saturated brine (150 ml), dehydrated with anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=3/1) to give 7.7 g (60%) of the target compound. IR (neat) 3307, 2953, 1650, 1505, 1464, 1434, 1409, 1383, 1284, 1042, 809, 756 cm−1 REFERENCE EXAMPLE 5 (+)-3-Acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 5-1) (a) (2R,4R)-3-Acetyl-2-phenyl-4-thiazolidinecarboxylic Acid (Reference Compound No. 5-1a) A solution of sodium hydroxide (91.2 g, 2.28 mol) in water (1,500 ml) and a solution of benzaldehyde (232 ml) in methanol (1,500 ml) were added successively to a solution of L-cysteine (400 g, 2.28 mol) in water (1,500 ml) at room temperature, and the mixture was stirred for 15 minutes. The mixture was allowed to stand at room temperature overnight, and then the precipitated crystals were filtered off and dried. Acetic anhydride (1,000 ml, 11.4 mol) was added dropwise to a solution of the obtained crystals in water (1,200 ml) at 60° C. over 25 minutes. The mixture was stirred at the temperature for 15 minutes, and then the reaction mixture was allowed to stand under ice-cooling overnight. The precipitated crystals were filtered off and dried to give 261.2 g (46%) of the target compound. IR (KBr) 1717, 1603, 1419, 1281, 1236, 1214 cm−1 (b) (2S,4S)-3-Acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic Acid (Reference Compound No. 5-1b) A solution of benzaldehyde (102 ml, 1.01 mol) in ethanol (300 ml) was added to a solution of D-penicillamine (150 g, 1.01 mol) in water (900 ml) at room temperature. The mixture was stirred at room temperature for 15 minutes and under ice-cooling for 1.5 hours, and then the precipitated crystals were filtered off and dried. Acetic anhydride (480 ml, 5.05 mol) was added dropwise to a solution of the obtained crystals in water (700 ml) at 60° C. over 15 minutes. The mixture was stirred at the temperature for 15 minutes, then at room temperature for 15 minutes and under ice-cooling for 1.5 hours, and the precipitated crystals were filtered off and dried to give 252.3 g (89%) of the target compound. IR (neat) 3392, 2920, 1730, 1618, 1411, 1196, 1178, 732 cm−1 (c) (+)-3-Acetyl-2-[2-((2R,4R)-3-acetyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobenzothiazoline (Reference Compound No. 5-1c) (2R,4R)-3-Acetyl-2-phenyl-4-thiazolidinecarboxylic acid (5.87 g, 2.34 mmol) and N,N-dimethylaminopyridine (290 mg, 2.34 mol) were added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (5.24 g, 1.56 mmol) in anhydrous DMF (60 ml) at room temperature. After ice-cooling, dicyclohexylcarbodiimide (3.54 g, 1.71 mmol) was added thereto, and the mixture was stirred under ice-cooling for one hour and at room temperature for two hours. After ice-cooling, water (1 ml) was added to the reaction mixture, the whole was stirred at room temperature and then concentrated under reduced pressure, and chloroform (30 ml) was added to the residue. The resulting insoluble matter was filtered out, water (120 ml) was added to the mother liquor, and the whole was extracted with chloroform (50 ml). The organic layer was washed with a 10% aqueous citric acid solution (120 ml), a saturated aqueous sodium hydrogencarbonate solution (120 ml) and saturated brine (100 ml) successively, and dehydrated with anhydrous magnesium sulfate. Chloroform was evaporated under reduced pressure, chloroform (15 ml) was added to the residue, the resulting insoluble matter was filtered out, and the mother liquor was concentrated under reduced pressure. Ethanol (600 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. The precipitated crystals were filtered off and dried to give 3.87 g (43%) of the target compound. IR (KBr) 3425, 1765, 1673, 1654, 1576, 1492, 1463 1142 cm−1 (d-1) (+)-3-Acetyl-2-[2-((2S,4S)-3-acetyl-5,5-dimethyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobenzothiazoline (Reference Compound No. 5-1d-1) A solution of (2S,4S)-3-acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid (102 g, 0.38 mol) in anhydrous DMF (500 ml) was added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (127 g, 0.38 mol) in anhydrous DMF (500 ml) at room temperature. N,N-Dimethylaminopyridine (5.58 g, 45.7 mmol) was added thereto under a nitrogen atmosphere at room temperature with stirring. After ice-cooling, diethyl azodicarboxylate (87 g, 0.50 mol) was added thereto, and then the mixture was stirred under ice-cooling for 15 minutes, at room temperature for one hour and further at an internal temperature of about 40° C. for three days. The reaction mixture was concentrated under reduced pressure, a 10% aqueous citric acid solution (1,000 ml) was added to the residue, and the whole was extracted with ethyl acetate (1,000 ml). The organic layer was washed with water (1,000 ml) and saturated brine (1,000 ml) successively and dehydrated with magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, a mixed solvent (ethanol/diisopropyl ether=200 ml/1,000 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. One precipitated diastereomer was filtered out, and the mother liquor was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give 78.0 g (43%) of the target compound. IR (neat) 3009, 1679, 1650, 1495, 1464, 1380, 1322, 1176, 1140, 757 cm−1 (d-2) (+)-3-Acetyl-2-[2-((2S,4S)-3-acetyl-5,5-dimethyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobenzothiazoline (Reference Compound No. 5-1d) (2S,4S)-3-Acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid (6.2 g, 22.2 mmol) was added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (5 g, 14.9 mmol) in anhydrous DMF (20 ml) at room temperature. N,N-Dimethylaminopyrdine (270 mg, 2.21 mmol) was added thereto under a nitrogen atmosphere at room temperature with stirring. After ice-cooling, dicyclohexylcarbodiimide (3.1 g, 15.0 mmol) was added thereto, the mixture was stirred under ice-cooling for 15 minutes and at room temperature for three days, then ethyl acetate (100 ml) and water (100 ml) were added to the reaction mixture, and the whole was stirred at room temperature. The precipitated insoluble matter was filtered out, and the mother liquor was washed with a 10% citric acid solution (100 ml), water (100 ml) and saturated brine (100 ml) successively and dehydrated with anhydrous magnesium sulfate. Ethyl aceate was evaporated under reduced pressure, ethanol (50 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. One precipitated diastereomer was filtered out, the mother liquor was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give 4.2 g (47%) of the target compound. (e) (+)-3-Acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)-benzothiazoline (Reference Compound No. 5-1) A 1 N aqueous sodium hydroxide solution (970 ml) was added dropwise to a solution of (+)-3-acetyl-2-[2-((2S,4S)-3-acetyl-5,5-dimethy-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobanzothiazoline (193 g, 0.32 mol) in DMF (2,000 ml) under ice-cooling, and the mixture was stirred for 30 minutes. 1 N Hydrochloric acid was added to the reaction mixture at the temperature to acidify it, and the whole was extracted with ethyl acetate (4,000 ml). The organic layer was washed with saturated brine (4,000 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, chloroform (400 ml) was added to the residue, and the precipitated crystals were filtered off and dried to give 55.9 g of the target compound. The mother liquor was concentrated under reduced pressure, and the same operation was repeated to give 79.5 g (74%) of the target compound finally. IR (neat) 3068, 1644, 1466, 1384, 1277, 1257, 1196, 1091, 808 cm−1 REFERENCE EXAMPLE 6 (+)-3-Acetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 6-1) (a) (+)-3-Acetyl-2-[2-((2R,4R)-3-acetyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]benzothiazoline (Reference Compound No. 6-1a) The target compound (20.0 g, 83%) was obtained from 3-acetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (27.4 g) by a method similar to Reference Example 5 (c). IR (KBr) 3039, 2933, 1765, 1674, 1657, 1587, 1491, 1465 cm−1 (b) (+)-3-Acetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 6-1) The target compound (10.6 g, 95%0) was obtained from (+)-3-acetyl-2-[2-((2R,4R)-3-acetyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]benzothiazoline (19.9 g) by a method similar to Reference Example 5 (e). REFERENCE EXAMPLE 7 (−)-3-Acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (Reference Compound No. 7-1) (a) (−)-3-Acetyl-2-[2-((2S,4S)-3-acetyl-5,5-dimethyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobenzothiazoline (Reference Compound No. 7-1a) A solution of (2S,4S)-3-acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid [compound described in Reference Example 4 (b)] (102 g, 0.38 mol) in anhydrous DMF (500 ml) was added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)-benzothiazoline (127 g, 0.38 mol) in anhydrous DMF (500 ml) at room temperature. N,N-Dimethylaminopyridine (5.58 g, 45.7 mmol) was added thereto under a nitrogen atmosphere at room temperature with stirring. After ice-cooling, diethyl azodicarboxylate (87 g, 0.50 mol) was added thereto. The mixture was stirred under ice-cooling for 15 minutes, at room temperature for one hour and further at an internal temperature of about 40° C. for three days. The reaction mixture was concentrated under reduced pressure, a 10% aqueous citric acid solution (1,000 ml) was added to the residue, and the whole was extracted with ethyl acetate (1,000 ml). The organic layer was washed with water (1,000 ml) and saturated brine (1,000 ml) successively and dehydrated with magnesium sulfate, and ethyl acetate was evaporated under reduced pressure. A mixed solvent (ethanol/diisopropyl ether=200 ml/1000 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. The precipitated crystals were filtered off and dried to give 34.7 g of the target compound. The mother liquor was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give further 43.8 g of the target compound (total 43%). IR (neat) 3008, 1680, 1654, 1494, 1464, 1383, 1139, 755 cm−1 (b) (−)-3-Acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)-benzothiazoline (Reference Compound No. 7-1) The target compound (33.7 g, 77%) was obtained from (−)-3-acetyl-2-[2-((2S,4S)-3-acetyl-5,5-dimethyl-2-phenylthiazolidin-4-ylcarbonyloxy)-5-methoxyphenyl]-6-chlorobenzothiazolidine (78.3 g) by a method similar to Reference Example 4 (e). IR (KBr) 3068, 1643, 1509, 1467, 1385, 1350, 1277, 1196, 1092, 808 cm−1 REFERENCE EXAMPLE 8 3-Acetyl-2-[2-(3-bromopropoxy)-5-methoxyphenyl]benzothiazoline (Reference Compound No. 8-1) Potassium carbonate (27.5 g, 19.9 mmol) and 1,3-dibromopropane (105 ml, 1.03 mol) were added to a solution of 3-acetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (30.0 g, 8.93 mmol) in 2-propanol (200 ml). The mixture was refluxed for two hours and cooled to room temperature, then water (300 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (500 ml) twice. The ethyl acetate layer was washed with saturated brine (100 ml) twice, dehydrated with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=2/1). Diisopropyl ether was added to the obtained oily matter, and the mixture was refluxed to dissolve the oily matter. The solution was allowed to stand, and then the precipitated crystals were filtered off to give 32.1 g (76%) of the target compound. IR (KBr) 2952, 1672, 1591, 1576, 1499, 1468, 1379, 1278, 1210 cm−1 REFERENCE EXAMPLE 9 3-Acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (Reference Compound No. 9-1) A solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)-benzothiazoline (4.68 g, 14.4 mol) in DMF (15 ml) and 1-bromo-3-chloropropane (4.2 ml, 167 mmol) were added to a solution of 60% sodium hydride (680 mg, 17.0 mmol) in DMF (15 ml) successively under a nitrogen atmosphere under ice-cooling. The mixture was stirred at 50° C. for one hour, and then the reaction mixture was allowed to stand to room temperature. A saturated aqueous ammonium chloride solution (5 ml) and water (50 ml) were added to the reaction mixture, and the whole was extracted with ethyl acetate (50 ml) twice. The ethyl acetate layer was washed with saturated brine (30 ml) twice, dehydrated with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Methanol was added to the obtained oily matter, and the oily matter was dissolved by heating. The solution was allowed to stand, and then the precipitated crystals were filtered off to give 5.39 g (94%) of the target compound. IR (KBr) 2912, 1676, 1458, 1373, 1281, 1206, 1026 cm−1 REFERENCE EXAMPLE 10 3-Acetyl-6-chloro-2-[2-(2-bromoethoxy)-5-methoxyphenyl]-benzothiazoline (Reference Compound No. 10-1) The target compound (2.2 g, 67%) was obtained from 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (2.5 g) by a method similar to Reference Example 7. IR (KBr) 1666, 1574, 1498, 1464, 1377, 1216 cm−1 REFERENCE EXAMPLE 11 3-Acetyl-5-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (Reference Compound No. 11-1) The target compound (3.3 g, 78%) was obtained from 3-acetyl-5-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (3.5 g) by a method similar to Reference Example 7. IR (KBr) 2930, 1677, 1463, 1380, 1281, 1211, 1031, 806 cm−1 REFERENCE EXAMPLE 12 3-Acetyl-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline (Reference Compound No. 12-1) The target compound (1.9 g, 89%) was obtained from 3-acetyl-2-(2-hydroxy-5-methoxyphenyl)-5-trifluoromethylbenzothiazoline (1.8 g) by a method similar to Reference Example 7. IR (KBr) 2962, 1680, 1600, 1500, 1431, 1388, 1323 cm−1 REFERENCE EXAMPLE 13 3-Acetyl-6-chloro-2-[2-(1-methyl-3-p-toluenesulfonyloxypropoxy)-5-methoxyphenyl]benzothiazoline (Reference Compound No. 13-1) (a) 3-p-Toluenesulfonyloxy-1-methyl-1-propanol (Reference Compound No. 13-1a) Pyridine (9.0 ml, 111 mmol) was added to a solution of 1,3-butanediol (5.07 g, 56.3 mmol) in anhydrous methylene chloride (20 ml) at room temperature. After ice-cooling, p-toluenesulfonyl chloride (15.9 g, 83.4 mmol) was added thereto, the mixture was stirred at room temperature overnight, then water (60 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (100 ml). The ethyl acetate layer was washed with 1 N hydrochloric acid (30 ml) and saturated brine (30 ml) successively and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=3/1) to give 7.72 g (57%) of the target compound. IR (neat) 3543, 3413, 2970, 2929, 1598, 1356, 1176, 948 cm−1 (b) 3-Acetyl-6-chloro-2-[2-(1-methyl-3-p-toluenesulfonyloxypropoxy)-5-methoxyphenyl]benzothiazoline (Reference Compound No. 13-1) A solution of diisopropyl azodicarboxylate (1.54 g, 7.61 mmol) in anhydrous tetrahydrofuran (10 ml) was added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (2.56 g, 7.62 mmol), triphenylphosphine (2.00 g, 7.61 mmol) and 3-p-toluenesulfonyloxy-1-methylpropanol (1.86 g, 7.61 mmol) in anhydrous tetrahydrofuran (10 ml) at room temperature, and the mixture was stirred for four hours. The reaction mixture was concentrated, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=4/1) to give 1.58 g (37%) of the target compound. REFERENCE EXAMPLE 14 (+)-3-Acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (Reference Compound No. 14-1) 1-Bromo-3-chloropropane (106 ml, 1.07 mol) was added to a solution of 60% sodium hydride (4.50 g, 0.11 mol) in anhydrous DMF (100 ml) under ice-cooling. Next, a solution of (+)-3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (36.0 g, 0.11 mol) in anhydrous DMF (200 ml) was added dropwise thereto. After dropping, the mixture was further stirred for one hour, then water was added to the reaction mixture, and the whole was extracted with ethyl acetate (1,000 ml). The organic layer was washed with saturated brine (1,000 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, then methanol (300 ml) was added to the residue, and the mixture was stirred under ice-cooling. The precipitated crystals were filtered off and dried to give 29.0 g (66%) of the target compound. IR (KBr) 2940, 2835, 1871, 1755, 1671, 1576, 1497, 1464, 1347 cm−1 REFERENCE EXAMPLE 15 (−)-3-Acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (Reference Compound No. 15-1) The target compound (44.0 g, quantitatively) was obtained from (−)-3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (33.7 g) by a method similar to Reference Example 12. IR (neat) 2961, 2938, 1679, 1498, 1465, 1210, 1048, 810 cm−1 REFERENCE EXAMPLE 16 (+)-3-Acetyl-2-[2-(3-chloropropoxy)-5-methoxyphenyl]benzothiazoline (Reference Compound No. 16-1) The target compound (3.1 g, 82%) was obtained from (+)-3-aetyl-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (3.0 g) by a method similar to Reference Example 12. IR (neat) 2959, 2834, 1675, 1578, 1497, 1466, 1379, 1277, 1210, 1048, 750 cm−1 REFERENCE EXAMPLE 17 2-(Cyclohexylmethylamino)ethanol hydrochloride (Reference Compound No. 17-1) Sodium iodide (11.4 g, 76.2 mmol) was added to a solution of bromomethylcyclohexane (4.50 g, 25.4 mmol) and ethanolamine (7.76 g, 127 mmol) in ethanol (60 ml) at room temperature, and the mixture was refluxed for 18 hours. The temperature was returned to room temperature, and then diethyl ether (50 ml) and a saturated aqueous ammonium chloride solution (80 ml) were added to the reaction mixture. The aqueous layer was basified with a 4 N aqueous sodium hydroxide solution, and the whole was extracted with chloroform (100 ml). The chloroform layer was washed with saturated brine and dehydrated with anhydrous sodium sulfate. Chloroform was evaporated under reduced pressure, and a 4 N solution (10 ml) of hydrogen chloride in dioxane was added to the obtained oily matter at room temperature. The precipitated crystals were filtered off and washed with diethyl ether to give 3.85 g (78%) of the target compound. IR (KBr) 3317, 3060, 2926, 2851, 1564, 1448, 1430, 1079, 1040 cm−1 Similarly 2-(Cyclopropylmethylamino)ethanol Hydrochloride (Reference Compound No. 17-2) Yield: 45% IR (neat) 3358, 2957, 2794, 1592, 1452, 1077, 1029 cm−1 2-(1-Ethylpropylamino)ethanol Hydrochloride (Reference Compound No. 17-3) Yield: 60% IR (neat) 3346, 2971, 1591, 1459, 1075 cm−1 REFERENCE EXAMPLE 18 N-Benzyl-2-(methylthio)ethylamine Hydrochloride (Reference Compound No. 18-1) The target compound (1.3 g, 21%) was obtained from 2-(methythio)ethylamine (4.0 g) and benzyl bromide (5.0 g) by a method similar to Reference Example 15. IR (KBr) 2940, 2792, 2424, 1440, 1439, 746, 702 cm−1 REFERENCE EXAMPLE 19 N-(2-Methoxyethyl)cyclopropylmethylamine Hydrochloride (Reference Compound No. 19-1) The target compound (1.5 g, 41%) was obtained from 2-methoxyethylamine (3.3 g) and (bromomethyl)cyclopropane (3.0 g) by a method similar to Reference Example 15. IR (neat) 2949, 2794, 1587, 1453, 1122, 1033 cm−1 REFERENCE EXAMPLE 20 N-(2-Ethoxyethyl)isopropylamine (Reference Compound No. 20-1) The target compound (70.7 g, 51%) was obtained from 2-ethoxyethylamine (93.8 g) and isopropyl bromide (142 g) by a method similar to Reference Example 15. IR (neat) 2970, 2933, 2869, 2616, 1469, 1444, 1380 cm−1 REFERENCE EXAMPLE 21 N-(2-Benzyloxyethyl)isopropylamine Hydrochloride (Reference Compound No. 21-1) (a) 2-(N-tert-Butoxycarbonyl-N-isopropylamino)ethanol (Reference Compound No. 21-1a) A solution of dibutyl dicarbonate (25.0 g, 116 mmol) in tetrahydrofuran (40 ml) was added to a solution of 2-(isopropylamino)ethanol (10.0 g, 96.9 mmol) in tetrahydrofuran (60 ml) under ice-cooling. The mixture was stirred at room temperature for 3.5 hours, then a 10% aqueous citric acid solution (500 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (500 ml). The organic layer was washed with saturated brine (500 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give 24.0 g (quantitatively) of the target compound. IR (neat) 3438, 1694, 1052 cm−1 (b) N-(2-Benzyloxyethyl)-N-(tert-butoxycarbonyl)isopropylamine (Reference Compound No. 21-1b) A solution of 2-(N-tert-butoxycarbonyl-N-isopropylamino)-ethanol (3.00 g, 14.8 mmol) and benzyl bromide (2.6 ml, 22.1 mmol) in anhydrous tetrahydrofuran (30 ml) was added to a solution of 60% sodium hydride (885 mg, 22.1 mmol) in anhydrous tetrahydrofuran (20 ml) under ice-cooling, and the mixture was stirred at 60° C. for four hours. Water (100 ml) was added to the reaction mixture under ice-cooling, the temperature was returned to room temperature, and the whole was extracted with ethyl acetate (100 ml). The organic layer was washed with saturated brine (100 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=4/1) to give 1.30 g (30%) of the target compound. IR (neat) 1693, 1166, 1126, 736, 697 cm−1 (c) N-(2-Benzyloxyethyl)isopropylamine Hydrochloride (Reference Compound No. 21-1)= A 4 N solution (3 ml) of hydrogen chloride in ethyl acetate was added to a solution of N-(2-benzyloxyethyl)-N-(tert-butoxycarbonyl)-isopropylamine (1.20 g, 4.09 mmol) in ethyl acetate (3 ml) under ice-cooling. The mixture was stirred at room temperature for five hours, and the reaction mixture was concentrated under reduced pressure. The obtained solid was filtered off with hexane to give 728 mg (77%) of the target compound. IR (KBr) 2750-2600, 1127, 731, 696 cm−1 REFERENCE EXAMPLE 22 N-(2-Methoxybenzyl)isopropylamine Hydrochloride (Reference Compound No. 22-1) Isopropylamine (2.0 ml, 24 mmol) and anhydrous sodium sulfate (6.00 g, 42 mmol) were added to a solution of 2-methoxybenzaldehyde (3.14 g, 23 mmol) in benzene (6 ml) at room temperature. The mixture was stirred at room temperature overnight, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. Methanol (30 ml) was added to the obtained oily matter, and then sodium borohydride (0.87 g, 23 mmol) was added thereto under ice-cooling. The mixture was stirred at room temperature for four hours, saturated brine (15 ml) and water (30 ml) were added to the reaction mixture, and the whole was extracted with ethyl acetate (100 ml). The organic layer was washed with saturated brine (20 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, ethanol (25 ml) was added to the obtained oily matter, and then 6 N hydrochloric acid (10 ml) was added thereto at room temperature. The reaction mixture was concentrated under reduced pressure, diethyl ether was added to the obtained oily matter, and the resulting crystals were filtered off and washed with ethyl acetate to give 3.00 g (60%) of the target compound. IR (KBr) 3300-2000, 1606, 1587, 1500, 1465, 1444, 1256 cm−1 Similarly N-(1,3-Thiazol-2-ylmethyl)isopropylamine Hydrochloride (Reference Compound No. 22-2) Yield: 89% IR (KBr) 3352, 2973, 2683, 2554, 2413, 1946, 1693, 1572, 1476, 1388, 1296, 1150, 886, 781 cm−1 Similarly N-(Furan-2-ylmethyl)-N-isopropylamine Hydrochloride (Reference Compound No. 22-3) IR (KBr) 2952, 2774, 2573, 2426, 1587, 1447, 1156, 937, 760 cm−1 Similarly N-(Thiophen-2-ylmethyl)-N-isopropylamine Hydrochloride (Reference Compound No. 22-4) IR (KBr) 2943, 2727, 2680, 2458, 1594, 1232, 986, 735 cm−1 REFERENCE EXAMPLE 23 N-Isopropyl-3-cyclohexyl-1-propylamine Hydrochloride (Reference Compound No. 23-1) (a) N-Isopropyl-3-cyclohexylpropanamide (Reference Compound No. 23-1a) Thionyl chloride (6.0 ml, 82 mmol) was added to a solution of 3-cyclohexanepropanoic acid (5.00 g, 32 mmol) in chloroform (50 ml) at room temperature, and a small amount of dimethylformamide was added dropwise to the solution. The mixture was stirred at room temperature for four hours, and the reaction mixture was concentrated under reduced pressure. A solution of isopropylamine (1.70 g, 29 mmol) in methylene chloride (25 ml) and N-methylmorpholine (4.5 ml, 40 mmol) were added to a solution of the obtained oily matter in methylene chloride (25 ml) under ice-cooling. The mixture was stirred at room temperature overnight, water (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (120 ml). The organic layer was washed with a 1 N hydrochloric acid (50 ml), a 0.1 N aqueous sodium hydroxide solution (50 ml) and saturated brine (20 ml) successively and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure to give 6.00 g (95%) of the target compound. IR (KBr) 3304, 2923, 2851, 1637, 1547, 1449 cm−1 (b) N-Isopropyl-3-cyclohexyl-1-propylamine Hydrochloride (Reference Compound No. 23-1) A solution of N-isopropyl-3-cyclohexylpropanamide (5.60 g, 29 mmol) in diethyl ether (50 ml) was added dropwise to a solution of lithium aluminum hydride (1.40 g, 38 mmol) in diethyl ether (75 ml) under ice-cooling. The mixture was stirred at room temperature for 2.5 hours, then water (1.3 ml), a 4 N aqueous sodium hydroxide solution (1.3 ml) and water (3.9 ml) were added to the reaction mixture successively under ice-cooling, and the whole was stirred at room temperature overnight. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. 2 N hydrochloric acid (28 ml) was added to a solution of the obtained oily matter in ethanol (100 ml) at room temperature, and the whole was concentrated under reduced pressure. Ethanol and diethyl ether were added to the obtained oily matter, and the resulting insoluble matter was filtered off. The filtrate was concentrated under reduced pressure, and the obtained oily matter was treated in the same manner to filter off the insoluble matter. The obtained insoluble matters were combined and washed with ethyl acetate to give 1.20 g (19%) of the target compound. IR (KBr) 3100-2530, 1449 cm−1 EXAMPLE 1 3-Acetyl-2-[2-(3-(N-hydroxy-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-1) Potassium carbonate (590 mg, 4.25 mmol) and sodium iodide (530 mg, 3.54 mmol) were added to a solution of 3-acetyl-2-[2-(3-bromopropoxy)-5-methoxyphenyl]benzothiazoline (497 mg, 1.18 mmol) and N-methylhydroxylamine hydrochloride (209 mg, 2.36 mmol) in anhydrous DMF (6 ml) at room temperature. The mixture was stirred at 60° to 70° C. for three hours and then cooled to room temperature, water (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (70 ml). The organic layer was washed with water twice and saturated brine successively and dehydrated with anhydrous sodium sulfate, ethyl acetate was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=2/1). Ethyl acetate (2 ml) was added to the obtained oily matter, and a 4 N solution (5 ml) of hydrogen chloride in ethyl acetate was added thereto with stirring under ice cooling. The mixture was stirred at the temperature for five minutes, and the solvent was evaporated under reduced pressure. Hexane and ethyl acetate was added to the obtained oily matter, the mixture was stirred, and the precipitated solid was filtered off and dried under reduced pressure to give 331 mg (66%) of the target compound. IR (KBr) 3416, 1672, 1499, 1466, 1381, 1209, 1041, 750 cm−1 Similarly 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-2) Yield: quantitatively IR (neat) 3325, 2957, 2604, 1669, 1497, 1466, 1382, 1280, 1211, 1061, 752 cm−1 3-Acetyl-2-[2-(3-(N,N-bis(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-3) Yield: 91% IR (KBr) 3331, 2958, 2586, 1664, 1498, 1467, 1369, 1318, 1279, 1244, 1213, 1049, 754 cm−1 3-Acetyl-2-[2-(3-(N-benzyl-N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-4) Yield: 94% IR (neat) 3308, 2955, 2596, 1671, 1497, 1466, 1382, 1280, 1242, 1211, 1046, 751 cm−1 3-Acetyl-2-[2-(3-(N-(cyclohexylmethyl)-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-5) Yield: 76% IR (neat) 3305, 2930, 2601, 1672, 1497, 1466, 1382, 1279, 1211, 1052, 754 cm−1 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-(3-phenylpropyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-6) Yield: 56% IR (neat) 3306, 2952, 2588, 1672, 1497, 1466, 1280, 1243, 1211, 1048, 751 cm−1 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-(2-phenyloxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-7) Yield: 53% IR (neat) 3306, 2955, 2582, 1668, 1598, 1497, 1466, 1430, 1382, 1280, 1211, 1049, 752 cm−1 3-Acetyl-2-[2-(3-(N-(cyclopropylmethyl)-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-8) Yield: 73% IR (neat) 3306, 2957, 2589, 1667, 1498, 1467, 1383, 1280, 1211, 1045, 754 cm−1 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-9) Yield: 78% IR (neat) 3307, 2955, 2835, 1668, 1497, 1466, 1383, 1280, 1211, 1055, 752 cm−1 3-Acetyl-2-[2-(3-(N-methylamino)propoxy)-5-methoxyphenyl]-benzothiazoline Hydrochloride (Compound No. 1-10) Yield: 43% IR (neat) 3416, 2958, 2723, 1672, 1577, 1499, 1465, 1429, 1381, 1323, 1280, 1242, 1210, 1040, cm−1 3-Acetyl-2-[2-(3-(N-(ethoxycarbonylmethyl)-N-methylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-11) Yield: 80% IR (neat) 3400, 2941, 2460, 1748, 1673, 1497, 1467, 1381, 1279, 1211, 1048, 752 cm−1 3-Acetyl-2-[2-(3-(N-(aminocarbonylmethyl)-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-12) Yield: 85% IR (neat) 3324, 3152, 3010, 2958, 1685-1680, 1498, 1466, 1382, 1324, 1279, 1243, 1211, 1047, 751 cm−1 3-Acetyl-2-[2-(3-(N-(N,N-dimethylaminocarbonylmethyl)-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-13) Yield: 97% IR (neat) 2938, 1664, 1498, 1465, 1382, 1279, 1211, 1046, 751 cm−1 3-Acetyl-2-[2-(3-(N-methoxy-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-14) Yield: 59% IR (KBr) 2948, 2300, 1684, 1500, 1464, 1384, 1284, 1212, 1038, 1013, 750 cm−1 3-Acetyl-2-[2-(3-(N-(2-(N,N-dimethylamino)ethyl)-N-methylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-15) Yield: 59% IR (KBr) 2961, 2623, 1668, 1466, 1381, 1279, 1242, 1210, 1040, 750 cm−1 3-Acetyl-2-[2-(3-(N,N-dipentylamino)propoxy)-5-methoxyphenyl]-benzothiazoline Hydrochloride (Compound No. 1-16) Yield: 91% IR (neat) 2957, 2594, 1672, 1497, 1466, 1382, 1324, 1280, 1243, 1210, 1046, 752 cm−1 3-Acetyl-2-[2-(3-(N-benzyl-N-(2-methylthioethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-17) Yield: 43% IR (neat) 2952, 2455, 1672, 1497, 1466, 1381, 1280, 1211, 1044, 750 cm−1 3-Acetyl-2-[2-(3-(N-(benzyloxycarbonylmethyl)-N-methylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 1-18) Yield: 50% IR (neat) 2581, 1749, 1673, 1279, 1211, 807, 751, 699 cm−1 3-Acetyl-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 1-19) Yield: 67% IR (KBr) 3187, 2864, 1681, 1574, 1500, 1465, 1379, 1217 cm−1 EXAMPLE 2 3-Acetyl-2-[2-(2-(N-(ethoxycarbonylmethyl)-N-methylamino)ethoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 2-1) The target compound (261 mg, 44%) was obtained from 3-acetyl-2-[2-(3-bromoethoxy)-5-methoxyphenyl]benzothiazoline (500 mg) by a method similar to Example 1. IR (neat) 2577, 1748, 1673, 1282, 1211, 1106, 809, 752 cm−1 EXAMPLE 3 3-Acetyl-6-chloro-2-[2-(3-(N-(2-methoxyethyl)-N-n-propylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-1) Potassium carbonate (229 mg, 1.64 mmol) and sodium iodide (493 mg, 3.27 mmol) were added to a solution of 3-acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]benzothiazoline (451 mg, 1.09 mmol) and N-(2-methoxyethyl)-n-propylamine (259 mg, 2.18 mmol) in anhydrous dimethylformamide at room temperature. The mixture was stirred at 60° to 70° C. for 3.5 hours, and then the reaction mixture was cooled to room temperature. Water (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (70 ml). The organic layer was washed with water twice and saturated brine successively and dehydrated with anhydrous sodium sulfate, ethyl acetate was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: ethyl acetate). Chloroform (2 ml) was added to the obtained oily matter, and a 4 N solution (5 ml) of hydrogen chloride in ethyl acetate was added thereto with stirring under ice-cooling. The mixture was stirred at the temperature for five minutes, and the solvent was evaporated under reduced pressure. Ethyl ether and ethyl acetate were added to the obtained oily matter, and the precipitated solid was filtered off and dried under reduced pressure to give 349 mg (60%) of the target compound. IR (KBr) 2937, 2460, 1684, 1501, 1464, 1378, 1215, 1041, 811 cm−1 Similarly 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-2) Yield: 66% IR (KBr) 3288, 2605, 1684, 1420, 1380, 1217, 1056, 811, 745 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-cyclopropylmethyl)-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-3) Yield: 60% IR (neat) 3307, 2955, 2593, 1674, 1498, 1464, 1378, 1210, 1059, 810, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-cyclohexyl-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-4) Yield: 48% IR (KBr) 3297, 2596, 1685, 1214, 1060, 1043, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-5) Yield: 48% IR (KBr) 3306, 2648, 1684, 1217, 1094, 1040, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(1-ethylpropyl)-N-(2-hydroxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-6) Yield: 30% IR (KBr) 3288, 2971, 1683, 1497, 1464, 1378, 1282, 1212, 1061, 810 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(3-hydroxypropyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-7) Yield: 48% IR (KBr) 3388, 1684, 1216, 1056, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxy-2-methylpropyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-8) Yield: 63% IR (neat) 3305, 2973, 2834, 1674, 1497, 1464, 1378, 1281, 1210, 1057, 810, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-9) Yield: 46% IR (KBr) 3368, 2952, 2831, 1684, 1500, 1464, 1378, 1217, 1042, 814 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-n-propylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-10) Yield: 78% IR(neat) 3312, 2963, 2619, 1672, 1497, 1463, 1377, 1210, 1045, 810, 751 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-(2-methylpropyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-11) Yield: 61% IR (KBr) 3308, 2600, 1684, 1213, 1094, 1057, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-((2S)-2-hydroxymethylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-12) Yield: 60% IR (KBr) 3346, 2600-2500, 1684, 1215, 1041, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-((2S)-2-methoxymethylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-13) Yield: 64% IR (KBr) 3424, 2600-2400, 1676, 1210, 1094, 1044, 810 cm−1 3-Acetyl-6-chloro-2-[2-(3-((3S)-hydroxyazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-14) Yield: 92% IR (neat) 3306, 2956, 2594, 1673, 1498, 1463, 1378, 1211, 1044, 810, 755 cm−1 3-Acetyl-6-chloro-2-[2-(3-((2S)-methoxycarbonylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-15) Yield: 82% IR (KBr) 2545, 1747, 1678, 1236, 1210, 1044, 810 cm−1 3-Acetyl-2-[2-(3-(N-n-butyl-N-(2-hydroxyethyl)amino)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 3-16) Yield: 95% IR (neat) 3306, 2960, 2604, 1673, 1498, 1464, 1378, 1210, 1058, 810, 755 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-cyclopentyl-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-17) Yield: 49% IR (neat) 3306, 2957, 2594, 1675, 1497, 1464, 1377, 1282, 1210, 1046, 810, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxy-1-(hydroxymethyl)ethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-18) Yield: 72% IR (KBr) 3315, 2950, 1680, 1500, 1464, 1377, 1211, 1043, 809 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-cyclopropyl-N-(2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-19) Yield: 87% IR (neat) 3326, 2956, 2579, 2485, 1674, 1498, 1464, 1378, 1211, 1042, 810, 755 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(1,1-dimethyl-2-hydroxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-20) Yield: 82% IR (KBr) 3210, 2958, 2865, 1679, 1501, 1463, 1378, 1298, 1211, 1049, 808 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-(3-methylbutyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-21) Yield: 80% IR (neat) 3304, 2958, 2596, 1676, 1498, 1464, 1378, 1281, 1210, 1094, 810, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-((1S)-2-hydroxy-1-isopropylethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-22) Yield: 72% IR (neat) 3334, 2458, 1673, 1211, 1058, 1045, 810 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-23) Yield: 88% IR (KBr) 2943, 2643, 1673, 1573, 1498, 1464, 1378 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 3-24) Yield: 79% IR (KBr) 3418, 2943, 2643, 1673, 1573, 1498, 1464, 1378 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-25) Yield: 81% IR (neat) 2466, 1673, 1210, 1116, 1045, 810 cm−1 3-Acetyl-2-[2-(3-(N-benzyl-N-isopropylamino)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 3-26) Yield: 89% IR (neat) 2942, 2498, 1674, 1497, 1464, 1377, 1210, 1045, 810, 752 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-cyclohexyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-27) Yield: 57% IR (neat) 2939, 2487, 1674, 1497, 1464, 1377, 1210, 1052, 810, 752 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-28) Yield: 71% IR (KBr) 2964, 2776, 2450, 1680, 1499, 1462, 1377, 1211, 1054, 811 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isobutyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-29) Yield: 79% IR (neat) 2592, 1674, 1210, 1117, 1043, 810 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-30) Yield: 81% IR (neat) 2600-2400, 1674, 1210, 1114, 1046, 810 cm−1 3-Acetyl-2-[2-(3-(N-(2-benzyloxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 3-31) Yield: 73% IR (neat) 2500-2400, 1674, 1210, 1106, 1046, 810, 751, 700 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(3-cyclohexylpropyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-32) Yield: 61% IR (KBr) 2922, 2608, 1676, 1498, 1464, 1378, 1210 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-33) IR (neat) 2600-2400(b), 1675, 1210, 1108, 1046, 810 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(cyclopropylmethyl)-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-34) Yield: 73% IR (neat) 2936, 2588, 1676, 1499, 1464, 1377, 1210, 1040, 810 cm−1 3-Acetyl-2-[2-(3-(N,N-bis(2-ethoxyethyl)amino)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 3-35) Yield: 99% IR (neat) 2973, 2878, 2459, 1674, 1498, 1464, 1378, 1210, 1118, 1047, 810, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxybenzyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-36) Yield: 45% IR (neat) 2941, 2506, 1675, 1605, 1590, 1498, 1464, 1378, 1282, 1050, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(pyridyl-2-ylmethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-37) Yield: 64% IR (neat) 2961, 2457, 2062, 1674, 1618, 1497, 1464, 1379, 1282, 1212, 1056, 754 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-38) Yield: 67% IR (neat) 2943, 2495, 1675, 1574, 1498, 1464, 1378, 1211, 810, 751 cm−1 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(1,3-thiazol-2-ylmethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 3-39) Yield: 38% IR (neat) 2941, 2496, 1668, 1574, 1498, 1465, 1378, 1282, 1210, 1054, 809 cm−1 EXAMPLE 4 3-Acetyl-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline (Compound No. 4-1) The target compound (231 mg, 53%) was obtained from 3-acetyl-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline (400 mg) by a method similar to Example 3. IR (KBr) 3200, 2972, 1675, 1596, 1501 cm−1 Similarly 3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-5-trifluoromethylbenzothiazoline Hydrochloride (Compound No. 4-2) Yield: 50% IR (KBr) 3338, 2970, 2632, 1680, 1595, 1499, 1430, 1323 cm−1 EXAMPLE 5 3-Acetyl-5-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 5-1) The target compound (376 mg, 58%) was obtained from 3-acetyl-5-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (551 mg) by a method similar to Example 3. IR (neat) 2944, 2834, 1680, 1497, 1463, 1408, 1379, 1282, 1211, 754 cm−1 Similarly 3-Acetyl-5-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 5-2) Yield: 87% IR (neat) 2937, 2619, 2494, 1682, 1497, 1463, 1408, 1380, 1323, 1282, 1240, 1106, 1043, 754 cm−1 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 5-3) Yield: 92% IR (neat) 3304, 2953, 2624, 1678, 1498, 1463, 1380, 1282, 1211, 1055, 754 cm−1 3-Acetyl-5-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-n-propylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 5-4) Yield: 65% IR (KBr) 3347, 2965, 2624, 1680, 1499, 1464, 1379, 1283, 1211, 1053, 807 cm−1 EXAMPLE 6 3-Acetyl-6-chloro-2-[2-(2-(N-hydroxy-N-isopropylamino)ethoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 6-1) The target compound (234 mg, 59%) was obtained from 3-acetyl-6-chloro-2-[2-(2-bromoethoxy)-5-methoxyphenyl]-benzothiazoline (400 mg) by a method similar to Example 3. IR (KBr) 3233, 2971, 1679, 1592, 1574, 1495, 1463, 1378, 1210, 1052, 810, 756 cm−1 3-Acetyl-6-chloro-2-[2-(2-(N-(2-hydroxyethyl)-N-isopropylamino)-ethoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 6-2) Yield: 76% IR (neat) 3306, 2951, 2614, 1676 cm−1 3-Acetyl-6-chloro-2-[2-(2-(N-((1S)-2-hydroxy-1-isopropylethyl)amino)-ethoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 6-3) Yield: 75% IR (neat) 3322, 2800-2600, 1674, 1210, 1095, 810 cm−1 EXAMPLE 7 3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 7-1) The target compound (397 mg, 28%) was obtained from 3-acetyl-6-chloro-2-[2-(1-methyl-3-p-toluenesulfonyloxypropoxy)-5-methoxyphenyl]benzothiazoline (1.70 g) by a method similar to Example 3. IR (KBr) 3280, 2975, 2935, 2835, 1679, 1573, 1494, 1465, 1377, 1210, 810, 756 cm−1 Similarly 3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-1-methylpropoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 7-2) Yield: 40% IR (neat) 3317, 2975, 2630, 1677, 1574, 1495, 1465, 11377, 1209, 1040, 810 cm−1 EXAMPLE 8 3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 8-1) The target compound (474 mg, 81%) was obtained from 3-acetyl-2-[2-(3-chloropropoxy)-5-methoxyphenyl]benzothiazoline (500 mg) by a method similar to Example 3. IR (neat) 2934, 2834, 2454, 1674, 1577, 1498, 1466, 1380, 1279, 1210, 1116, 1044, 751 cm−1 Similarly 3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 8-2) Yield: 76% IR (neat) 2968, 2871, 2479, 1674, 1592, 1577, 1497, 1466 1322 cm−1 EXAMPLE 9 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-1) The target compound (1.53 g, 80%) was obtained from (+)-3-acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (1.50 g) by a method similar to Example 3. IR (KBr) 2938, 2835, 2607, 2495, 1677, 1499, 1465 cm−1 Similarly (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-2) Yield: 78% IR (neat) 3307, 2939, 2609, 1687, 1497, 1465, 1376, 1211, 1061, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-3) Yield: 49% IR (neat) 2973, 2940, 2881, 2602, 2479, 1675, 1592, 1574, 1498, 1464 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(thiophen-2-ylmethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-4) Yield: 14% IR (neat) 2937, 2478, 1675, 1499, 1464, 1377, 1238, 1043, 809, 711 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(furan-2-ylmethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-5) Yield: 62% IR (neat) 2970, 2471, 1677, 1499, 1465, 1347, 1210, 1043, 809, 747 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-((2S)-2-hydroxymethylazolan-1-yl)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-6) Yield: 36% IR (neat) 3331, 2951, 2619, 1674, 1465, 1348, 1239, 1043, 810 cm−1 (+)-3-Acetyl-2-[2-(3-((2S)-2-aminocarbonylazolan-1-yl)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 9-7) Yield: 60% IR (neat) 3376, 2958, 1681, 1577, 1465, 1378, 1211, 1044, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-((2S)-2-methoxycarbonylazolan-1-yl)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-8) Yield: 71% IR (neat) 2955, 2855, 2554, 1747, 1679, 1574, 1465, 1348, 1210, 1045, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-((2S)-2-methoxymethylazolan-1-yl)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-9) Yield: 70% IR (neat) 2940, 2836, 2610, 1676, 1574, 1465, 1348, 1238, 1041, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-ethyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-10) Yield: 19% IR (KBr) 2962, 2640, 2492, 1677, 1500, 1465, 1377, 1210, 1045, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N,N-diisopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-11) Yield: 10% IR (KBr) 2964, 2653, 1679, 1499, 1465, 1377, 1210, 1047, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-methylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-12) Yield: 74% IR (neat) 2965, 1681, 1498, 1465, 1376, 1211, 1047, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-((2S)-2-dimethylaminocarbonylazolan-1-yl)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-13) Yield: 67% IR (KBr) 2954, 1656, 1574, 1464, 1379, 1159, 1042, 809 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxy-2-methylpropyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-14) Yield: 35% IR (KBr) 3331, 2957, 2639, 1676, 1499, 1465, 1379, 1210, 1056, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-15) Yield: 16% IR (KBr) 3347, 2942, 1678, 1499, 1465, 1378, 1210, 1044, 810 cm−1 (+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-methylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 9-16) Yield: 51% IR (KBr) 3319, 2957, 2633, 1676, 1500, 1465, 1377, 1210, 1050, 810 cm−1 EXAMPLE 10 (−)-3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 10-1) The target compound (790 mg, 56%) was obtained from (−)-3-acetyl-6-chloro-2-[2-(3-chloropropoxy)-5-methoxyphenyl]-benzothiazoline (1.09 g) by a method similar to Example 3. IR (neat) 2939, 2487, 1675, 1498, 1464, 1210, 1116, 1042, 810 cm−1 Similarly (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 10-2) Yield: 60% IR (KBr) 3294, 2936, 2591, 1688, 1497, 1465, 1374, 1283, 1211, 1061, 810 cm−1 (−)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 10-3) Yield: 61% IR (neat) 2973, 2936, 2881, 2617, 2486, 1717, 1676, 1592, 1573, 1498, 1464 cm−1 EXAMPLE 11 (+)-3-Acetyl-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 11-1) The target compound (677 mg, 52%) was obtained from (+)-3-acetyl-2-[2-(3-chloropropoxy)-5-methoxyphenyl]benzothiazoline (966 mg) by a method similar to Example 3. IR (neat) 2968, 2611, 1967, 1675, 1592, 1577, 1497, 1466, 1380, 1278, 1210, 1160, 1107, 1046, 750 cm−1 Similarly (+)-3-Acetyl-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 11-2) Yield: 95% IR (neat) 2968, 2611, 1967, 1675, 1592, 1577, 1497, 1466, 1380, 1211, 1117, 1046, 751 cm−1 (+)-3-Acetyl-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 11-3) Yield: 37% IR (neat) 3321, 2963, 2621, 1672, 1592, 1497, 1382, 1211, 1047, 752 cm−1 EXAMPLE 12 3-Acetyl-2-[2-(3-(N,N-diethylamino)propoxy)-5-methoxyphenyl]-benzothiazoline Hydrochloride (Compound No. 12-1) A solution of diisopropyl azodicarboxylate (470 mg, 2.32 mmol) in anhydrous tetrahydrofuran (1 ml) and a solution of 3-dimethylamino-1-propanol (0.35 ml, 2.32 mmol) in anhydrous tetrahydrofuran (1 ml) were added to a solution of 3-acetyl-2-(3-hydroxy-5-methoxyphenyl)benzothiazoline (700 mg, 2.32 mmol) and triphenylphosphine (609 mg, 2.32 mmol) in anhydrous tetrahydrofuran (4 ml) successively at room temperature, and the mixture was stirred for two days. The reaction mixture was concentrated, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: ethyl acetate/methanol=20/1). Ethyl acetate (2 ml) was added to the obtained oily matter, and a 4 N solution (5 ml) of hydrogen chloride in ethyl acetate was added thereto with stirring under ice-cooling. The mixture was stirred at the temperature for 10 minutes, and the solvent was evaporated under reduced pressure to give 775 mg (74%) of the target compound. IR (neat) 2944, 2581, 2468, 1672, 1498, 1466, 1382, 1279, 1244, 1210, 1044, 752 cm−1 3-Acetyl-2-[2-(2-(dimethylamino)ethoxy)-5-methoxyphenyl]-benzothiazoline Hydrochloride (Compound No. 12-2) Yield: 62% IR (KBr) 2967, 2370, 1676, 1496, 1464, 1382, 1351, 1283, 1210, 1030, 754 cm−1 EXAMPLE 13 3-Acetyl-5-chloro-2-[2-(3-(dimethylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 13-1) The target compound (407 mg, 50%) was obtained from 3-acetyl-5-chloro-2-(3-hydroxy-5-methoxyphenyl)benzothiazoline (600 mg) by a method similar to Example 7. IR (KBr) 2961, 2572, 2510, 2449, 1683, 1496, 1464, 1376, 1315, 1211, 1042, 842 cm−1 EXAMPLE 14 3-Acetyl-6-chloro-2-[2-(3-(N-ethoxycarbonylmethyl-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 14-1) Potassium carbonate (299 mg, 2.16 mmol) and ethyl bromoacetate (0.13 ml, 1.13 mmol) were added to a solution of 3-acetyl-6-chloro-2-[2-(3-(N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (compound described in Example 3) (474 mg, 1.08 mmol) in anhydrous dimethylformamide at room temperature. The mixture was stirred at room temperature for 1.5 hours, water (30 ml) was added to the reaction mixture, and the whole was extracted with diethyl ether (50 ml). The organic layer was washed with water twice and saturated brine successively and dehydrated with anhydrous magnesium sulfate. Diethyl ether was evaporated under reduced pressure, and the obtained oily matter was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1). Methanol (2 ml) was added to the obtained oily matter, and a 10% solution (5 ml) of hydrogen chloride in methanol was added thereto with stirring under ice-cooling. The mixture was stirred at the temperature for five minutes, and the solvent was evaporatd under reduced pressure to give 542 mg (90%) of the target compound. IR (neat) 3406, 2942, 2458, 1747, 1674, 1498, 1464, 1378, 1210, 1042, 810, 753 cm−1 EXAMPLE 15 2-[2-(3-(N-(2-Acetoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline Hydrochloride (Compound No. 15-1) Acetic anhydride (0.26 ml, 2.91 mmol) was added to a solution of 3-acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline hydrochloride (300 mg, 0.58 mmol) in pyridine (0.47 ml, 5.80 mmol) under ice-cooling, and then the mixture was stirred at room temperature for two hours. A saturated aqueous sodium hydrogencarbonate solution (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (50 ml). The ethyl acetate layer was washed with saturated brine (50 ml) and dehydrated with anhydrous magnesium sulfate, and ethyl acetate was evaporated under reduced pressure. The obtained oily matter was dissolved in ethyl acetate (1 ml), and then a 4 N solution (0.5 ml) of hydrogen chloride in ethyl acetate. The mixture was concentrated under reduced pressure to give 277 mg (92%) of the target compound. IR (neat) 2604, 1745, 1676, 1211, 1050, 810 cm−1 EXAMPLE 16 3-Acetyl-6-chloro-2-[2-(3-((2S)-2-acetoxymethylazolan-1-yl)-propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 16-1) The target compound (556 mg, 95%) was obtained from 3-acetyl-6-chloro-2-[2-(3-((2S)-2-hydroxymethylazolan-1-yl)propoxy)-5-methoxyphenyl]benzothiazoline (500 mg) by a method similar to Example 15. IR (KBr) 2594, 1745, 1676, 1210, 1045, 810 cm−1 EXAMPLE 17 2-[2-(3-(N-Acetoxy-N-isopropylamino)propoxy)-5-methoxyphenyl]-3-acetyl-6-chlorobenzothiazoline p-toluenesulfonate (Compound No. 17-1) The target compound (266 mg, 60%) was obtained from 3-acetyl-6-chloro-2-[2-(3-(N-hydroxy-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline (300 mg) by a method similar to Example 15. IR (KBr) 3700-2000, 1805, 1722, 1679, 1573, 1499, 1464 cm−1 EXAMPLE 18 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-phenylcarboxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 18-1) Benzoyl chloride (0.20 ml, 1.20 mmol) was added to a solution of 3-acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline hydrochloride (300 mg, 0.58 mmol) and pyridine (0.39 ml, 4.70 mmol) in methylene chloride (0.5 ml) under ice-cooling. The mixture was stirred at the temperature for two hours, then a saturated aqueous sodium hydrogencarbonate solution (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (50 ml). The ethyl acetate layer was washed with a 10% aqueous citric acid solution (50 ml) and dehydrated with anhydrous magnesium sulfate, and ethyl acetate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: ethyl acetate/methanol=10/1). The obtained oily matter was dissolved in ethyl acetate (1 ml), and a 4 N solution (0.5 ml) of hydrogen chloride in ethyl acetate was added thereto under ice-cooling. The mixture was concentrated under reduced pressure to give 211 mg (62%) of the target compound. IR (neat) 2456, 1721, 1674, 1272, 1210, 1110, 1044, 810, 754, 712 cm−1 Similarly 3-Acetyl-2-[2-(3-(N-(2-tert-butylcarbonyloxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]-6-chlorobenzothiazoline Hydrochloride (Compound No. 18-2) Yield: quantitatively IR (neat) 2494, 1730, 1678, 1465, 1282, 1158, 1045, 811 cm−1 EXAMPLE 19 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyacetoxyethyl)-amino)propoxy)-5-methoxyphenyl]benzothiazoline Hydrochloride (Compound No. 19-1) Methoxyacetyl chloride (0.08 ml, 0.87 mmol) was added to a solution of 3-acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline hydrochloride (300 mg, 0.58 mmol) in triethylamine (0.41 ml, 2.90 mmol) and methylene chloride (1.0 ml) under ice-cooling. The mixture was stirred at room temperature for two hours, then water (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (50 ml). The ethyl acetate layer was washed with saturated brine (50 ml) and dehydrated with anhydrous magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (mobile phase: chloroform/methanol=50/1). The obtained oily matter was dissolved in ethyl acetate (1 ml), and then a 4 N solution (0.2 ml) of hydrogen chloride in ethyl acetate was added thereto under ice-cooling. The mixture was concentrated under reduced pressure to give 340 mg (quantitatively) of the target compound. IR (neat) 2477, 1757, 1676, 1281, 1127, 1043, 810 cm−1 EXAMPLE 20 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-(N-(2-methoxymethyloxy-ethyl))amino)propoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 20-1) N,N-Diisopropylethylamine (0.18 ml, 1.01 mmol) and chlorodimethyl ether (0.05 ml, 0.55 mmol) were added to a solution of 3-acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)-propoxy)-5-methoxyphenyl]benzothiazoline hydrochloride (235 mg, 0.46 mmol) in methylene chloride (2.0 ml) under ice-cooling. The mixture was stirred at room temperature for 3.5 hours, then a saturated aqueous sodium hydrogencarbonate solution (50 ml) was added to the reaction mixture, and the whole was extracted with ethyl acetate (50 ml). The ethyl acetate layer was washed with saturated brine (50 ml) and dehydrated with anhydrous magnesium sulfate, and ethyl acetate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: chloroform/methanol=20/1) to give 124 mg (52%) of the target compound. IR (neat) 1682, 1234, 1151, 1108, 1043, 810 cm−1 Similarly 3-Acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-(2-methoxyethoxymethoxy)-ethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline (Compound No. 20-2) Yield: 71% IR (neat) 1681, 1210, 1161, 1044, 810 cm−1 Formulation Examples General formulation examples of the present compound are shown below. 1) Tablet Formulation 1 in 100 mg Present compound 1 mg Lactose 66.4 mg Cornstarch 20 mg Calcium carboxymethylcellulose 6 mg Hydroxypropylcellulose 4 mg Magnesium stearate 0.6 mg Tablets according to the formulation as above are coated with 2 mg/tablet of a coating agent (an ordinary coating agent such as hydroxypropylmethylcellulose, macrogol or silicone resin) to obtain desired coated tablets. (The same is applied to tablets mentioned below.) Desired tablets can be obtained by appropriately changing the amounts of the present compound and the additives. 2) Capsule Formulation 1 in 150 mg Present compound 5 mg Lactose 145 mg Desired capsules can be obtained by appropriately changing the mixing ratio of the present compound to lactose. Pharmacological Tests 1. κ Opioid Receptor Agonist Activity Tests in GTP Binding Activity Measurement System Jinmin Zhu et al. reported a method of evaluating agonist activities of drugs on a κ opioid receptor wherein guanosine 5′-triphosphate (GTP) radiolabelled with a human κ opioid receptor is used in J. Pharmaco. Exp. Ter., 282, 676-684 (1997). κ opioid receptor agonist activities (actions) of test compounds were evaluated according to the method described in the above-mentioned literature. Preparation of Incubation Buffer N-2-Hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES, 4.77 g), magnesium chloride hexahydrate (2.03 g), sodium chloride (5.84 g), disodium ethylenediaminediacetate (EDTA•2Na, 0.37 g), DL-dithiothreitol (DTT, 0.15 g) and bovine serum albumin (BSA, 1.0 g) were dissolved in ultrapure water, pH was adjusted to 7.4 with sodium hydroxide, and further ultrapure water was added to the mixture so that a total amount was one liter to prepare a incubation buffer. Preparation of 10% Dimethyl Sulfoxide-Incubation Buffer Nine volume of the incubation buffer was added to one volume of dimethyl sulfoxide (DMSO) to prepare a 10% DMSO-incubation buffer. Preparation of 50 mM Tris-hydrochloric Acid Buffer Tris(hydroxymethyl)aminomethane hydrochloride (TRIZA-HCl, 66.1 g) and Tris(hydroxymethyl)aminomethane (TRIZA-Base, 9.7 g) were dissolved in ultrapure water so that a total amount was 10 liters to prepare a 50 mM Tris-hydrochloric acid buffer (pH 7.4). Preparation of κ Receptor Membrane Preparation Solution A human κ opioid receptor membrane preparation (100 unit/ml) was diluted 60 times with the incubation buffer under ice-cold to prepare a human κ opioid receptor membrane preparation solution. The membrane preparation solution was preserved under ice-cold. Preparation of Test Compound Solution A test compound was dissolved in 100% DMSO to prepare a 10−3 M test compound solution, and then the incubation buffer was added to the 10−3 M test compound solution to prepare a 10−4 M test compound solution. Next, the 10% dimethyl sulfoxide-incubation buffer was added to the 10−4 M test compound solution to prepare a 10−5 M, 10−6 M, 10−7 M, 10−8 M or 10−9 M test compound solution. Preparation of Positive Control Drug ((−)-U-50488) Solution A drug (−)-U50488 (J. Pharmacol. Exp. Ther., 224, 7-12 (1983)), which is known as a κ opioid receptor agonist, was used as a positive control drug in the tests. (−)-U-50488 was dissolved in 100% DMSO to prepare a 10−3 M positive control drug solution, and then the incubation buffer was added to the 10−3 M positive control drug solution to prepare a 10−4 M positive control drug solution. Next, the 10% DMSO-incubation buffer was added to the 10−4 M positive control drug solution to prepare a 10−6 M positive control drug solution. Preparation of Guanosine 5′-Diphosphate (GDP) Solution GDP was dissolved in ultrapure water to prepare a 10−3 M GDP solution, and the incubation buffer was added to the 10−3 M GDP solution to prepare a 10−5 M GDP solution. Preparation of Radiolabelled Reagent 10−3 M [35S]GTPγS was diluted with the incubation buffer to prepare 10−9 M radiolabelled reagent. Test Method 1. The incubation buffer (50 μl), the 10−5 M GDP solution (50 μl), the human κ opioid receptor membrane preparation solution (300 μl), the test compound solution and the 10−9 M radiolabelled reagent (50 μl) were put into a glass tube, and then the mixture was incubated at 30° C. for 60 minutes. 2. The 50 mM Tris-hydrochloric acid buffer (pH 7.4) was added to the mixture to stop the reaction, the reaction mixture was suction-filtered with a GF/B filter, and then the residue on the GF/B filter was washed with the 50 mM Tris-hydrochloric acid buffer (3 ml) three times. 3. The GF/B filter was air-dried, and then the residue on the GF/B filter was taken out with an antomatic dispenser and transfered into a vial. 4. Scintisol EX-H (5 ml) was introduced into the vial to prepare a sample solution, and then radioactivity in the sample solution was measured with a liquid scintillation counter for one minute. The radioactivity was expressed in “cpm” (counts per minute). Calculation Formula of κ Opioid Receptor Agonist Activity Each agonist activity of the test compound on the κ opioid receptor was expressed in [35S]GTPγS binding % when [35S]GTPγS binding of 10−6 M (−)-U50488 was 100%. Namely, [35S]GTPγS binding was calculated according to the following equation. [35S]GTPγS binding %=[[35S]GTPγS binding of test compound (cpm)−[35S]GTPγS binding of solvent (cpm)]/[35S]GTPγS binding of positive control drug (10−6 M (−)-U50488) (cpm)−[35S]GTPγS binding of solvent (cpm)]×100 Test Results Table 1 shows [35S]GTPγS binding (κ opioid receptor agonist) activities (%) when test compounds (compound Nos. 3-2,3-11, 3-12, 3-14, 3-25, 3-33, 3-38, 4-2, 5-3, 7-2, 8-1, 9-1, 9-2, 9-3, 9-4, 9-5, 9-10, 9-11, 9-12, 9-16, 10-1, 10-2, 10-3, 11-1, 11-3, 20-1 and 20-2) were used of which concentration was 10−9 M respectively, as examples of test results. TABLE 1 Test compound [35S]GTP γ S binding % Compound No. 3-2 66.5 Compound No. 3-11 53.7 Compound No. 3-12 75.6 Compound No. 3-14 59.8 Compound No. 3-25 67.9 Compound No. 3-33 75.8 Compound No. 3-38 58.4 Compound No. 4-2 65.1 Compound No. 5-3 51.2 Compound No. 7-2 62.9 Compound No. 8-1 103.0 Compound No. 9-1 93.2 Compound No. 9-2 103.9 Compound No. 9-3 117.5 Compound No. 9-4 72.1 Compound No. 9-5 132.5 Compound No. 9-10 116.8 Compound No. 9-11 55.0 Compound No. 9-12 107.9 Compound No. 9-16 57.2 Compound No. 10-1 50.5 Compound No. 10-2 65.8 Compound No. 10-3 55.7 Compound No. 11-1 66.8 Compound No. 11-3 85.1 Compound No. 20-1 65.1 Compound No. 20-2 50.5 (The values in Table 1 are the average of duplicate once tests.) As shown in Table 1, the present compounds exhibit excellent κ opioid receptor agonist activities (actions). 2. Antinociceptive Action Tests by Mouse Acetic Acid Writhing Method A mouse acetic acid writhing method by Anderson et al. (Fed. Proc., 18, 412 (1985)) is widely used as a method of evaluating analgesic effects of drugs. Accordingly, antinociceptive action tests of test compounds were carried out using the mouse acetic acid writhing method, and analgesic effects of the test compounds were evaluated. Preparation of 0.7% Acetic Acid Solution Physiological saline was added to 99.7% acetic acid to prepare a 0.7% acetic acid solution. Experimental Method Twenty minutes after oral administration of the test compound (30 mg/kg), the 0.7% acetic acid solution was administered intraperitoneally in a rate of 0.1 ml per 10 g of mouse weight. Next, times of writhing exhibited 10 to 20 minutes after administering acetic acid were counted to measure its antinociceptive action. Inhibition rates were calculated according to the following equation. The antinociceptive action of the test compound was expressed in an inhibition rate to writhing numbers of a vehicle group. Inhibition rate (%)=[1−(writhing numbers of drug administration group/writhing numbers of vehicle group)]×100 Test Results Table 2 shows antinociceptive actions (inhibition rates (%) to writhing times of the vehicle group) of the test compounds (compound Nos. 3-2, 3-25, 3-33, 5-3, 7-2, 9-1 ,9-2, 9-12, 9-3, 11-1, 20-1 and 20-2) as examples of test results. TABLE 2 Test compound Inhibition rate (%) Compound No. 3-2 76.1 Compound No. 3-25 91.0 Compound No. 3-33 99.5 Compound No. 5-3 51.6 Compound No. 7-2 70.0 Compound No. 9-1 97.7 Compound No. 9-2 81.2 Compound No. 9-12 57.8 Compound No. 9-3 100.0 Compound No. 11-1 98.3 Compound No. 20-1 94.8 Compound No. 20-2 81.7 (The values in Table 2 are the average of seven samples.) As shown in the above Table 2, the present compounds exhibit excellent antinociceptive actions in the antinociceptive action tests using the mouse acetic acid writhing method. Industrial Applicability 2-Phenylbenzothiazoline derivative or salts thereof (present compounds) have excellent κ opioid receptor agonist activities and antinociceptive actions. Accordingly, the present compounds are particularly useful as therapeutic agents for pain, pruritus and the like.
<SOH> BACKGROUND ART <EOH>Pain plays a physiologically important role as a warning reaction to know danger. On the other hand, pain is also a significant cause to lower quality of lives (QOL) of patients. Pain accompanying almost all diseases typified by rheumatic diseases is one of causes of dysfunction. Accordingly, it is medically very important to control pain (Experimental Medicine, 18 (17), 2332-2337 (2000) and J. Pharm. Soc., 120 (12), 1291-1307 (2000)). Narcotic analgesics such as morphine and nonnarcotic analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), indometacin and diclofenac sodium, are widely used now as drugs which control pain. However, while the narcotic analgesics have strong analgesic actions, they have side effects such as drug dependence, and their use are strictly limited accordingly. On the other hand, NSAIDs are very useful as therapeutic agents for pain derived from synthesis of inflammatory mediators such as prostaglandin but have no strong analgesic actions unlike the narcotic analgesics. In recent years, μ (mu), κ (kappa) and δ (delta) receptors have been proposed as subtypes of the opioid receptors, and it has been clarified that the side effects such as drug dependence of morphine are exhibited through the μ opioid receptor. Further, it has been found that analgesic actions are exhibited through any of the μ opioid receptor, the κ opioid receptor and the δ opioid receptor. These findings suggest a possibility that drugs which selectively act on the κ opioid receptor and the δ opioid receptor can be analgesics which solve problems of drugs which act on the μ opioid receptor. Compounds reported to serve as drugs which selectively act on the κ opioid receptor are compounds having a phenylacetic amide skeleton represented by U50488H, compounds having a benzodiazepine skeleton represented by Thifuadom, compounds having a phenothiazine skeleton represented by Apadoline, compounds having a 4,5-epoxymorphinan skeleton represented by TRK-820 and the like (“All of opioid”, published by Mikusu Co., Ltd., p. 222-229 (1999)). It is known that pain is weaken by activating the κ opioid receptor, and it was reported that a κ opioid receptor agonist is useful as an analgesic (“All of opioid”, published by Mikusu Co., Ltd., p. 25-36 (1999)). Further, it was also reported that the κ opioid receptor agonist has an antipruritic action (WO 98/23290). On the other hand, Japanese Laid-open Patent Publication Nos. 46079/1983, 67276/1984, 139679/1985 and 221679/1987 reported that 2-phenylbenzothiazoline derivatives have calcium antagonism and platelet aggregation actions and are useful as therapeutic agents for cardiovascular diseases such as hypertension, thrombosis, angina and arrhythmia. However, actions of these 2-phenylbenzothiazoline derivatives on the κ opioid receptor are not known, much less it is impossible to presume which derivatives thereof act as agonists or antagonists at all. Their analgesic actions and antipruritic actions are not reported at all, either. It is very interesting subjects to find new pharmacological actions of the known 2-phenylbenzothiazoline derivatives, which are useful as pharmaceuticals, and further to synthesize novel 2-phenylbenzothiazoline derivatives, which are their analogs, and to find useful pharmacological actions thereof.
20040928
20060926
20050526
99230.0
0
POWERS, FIONA
KAPPA-OPIOID RECEPTOR AGONIST COMPRISING 2-PHENYLBENZOTHIAZOLINE DERIVATIVE
UNDISCOUNTED
0
ACCEPTED
2,004
10,509,622
ACCEPTED
Novel oxidase
There is disclosed an oxidase gene useful for the diagnosis of RA and the screening of a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis. Also, an inspection method useful as a diagnosis method for RA is disclosed. Additionally, there is disclosed a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis, using the aforementioned novel oxidase gene. Also disclosed is a method for producing a pharmaceutical composition for the treatment of RA and/or the treatment of osteoarthritis which comprises an inhibitor of the aforementioned oxidase, which is obtainable by the aforementioned screening method, as an active ingredient.
1. (1) A polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2, and which is expressed specifically in rheumatoid arthritis patients, or (2) a polypeptide which comprises an amino acid sequence in which from 1 to several amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted, and which is expressed specifically in rheumatoid arthritis patients. 2. A polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2. 3. A polynucleotide coding for the polypeptide according to claim 1 or claim 2. 4. An expression vector comprising the polynucleotide according to claim 3. 5. A cell transformed with the expression vector according to claim 4. 6. A method for inspecting rheumatoid arthritis, comprising (1) a step of measuring an expression level in a subject of i) a gene comprising the nucleotide sequence according to claim 3, or ii) a gene comprising a nucleotide sequence of a polynucleotide coding for a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients, and (2) a step of comparing it with an expression level of the gene in a healthy person. 7. A rheumatoid arthritis inspection kit which comprises forward and reverse primers designed to specifically amplify i) a gene comprising the nucleotide sequence according to claim 3, or ii) a gene comprising a nucleotide sequence of a polynucleotide coding for a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients. 8. A method for screening a substance capable of inhibiting activity of a polypeptide, comprising (1) a step of allowing a substance to be tested to contact with a cell expressing the polypeptide according to claim 1 or claim 2 or a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients, (2) a step of analyzing whether or not activity of the polypeptide is inhibited, and (3) a step of selecting a substance capable of inhibiting activity of the polypeptide. 9. The screening method according to claim 8, wherein the substance which inhibits the activity of the polypeptide according to claim 1 or claim 2, or of a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients is a substance for the treatment of rheumatoid arthritis and/or a substance for the treatment of osteoarthritis. 10. A method for producing a pharmaceutical composition for the treatment of RA and/or the treatment of osteoarthritis, comprising a step of carrying out screening with the use of the screening method according to claim 8 or claim 9, and a step of formation using a substance obtained by the screening.
TECHNICAL FIELD This invention relates to a polypeptide as a novel oxidase, a polynucleotide coding for the polypeptide, a vector comprising the polynucleotide, a transformed cell comprising the vector, an inspection method useful for diagnosing rheumatoid arthritis (to be referred to as RA) and a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis. BACKGROUND OF THE INVENTION Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an enzyme which forms an reactive oxygen species (to be referred to as ROS) by receiving an electron from NADPH and finally delivering it to an oxygen molecule. Physiologically, the aforementioned enzyme mainly existing in phagocytes is taking an important role in a defense system in a living body against invasion of foreign bodies such as microorganisms, which is sterilization of them by forming ROS and the like. However, it is known that excess formation of ROS by the enzyme causes digestion of protein and DNA and the damage to membranes by lipid peroxide and thereby becomes the cause of disorders of cells and tissues and furthermore of various diseases including inflammatory diseases, vascular diseases, neurodegenerative diseases, cancers, heart diseases and the like (cf. non-patent reference 1 and non-patent reference 2). However, since expression of the NADPH oxidase which forms ROS is systemically distributed, there is a possibility of causing side effects when this is considered as a target of drug discovery. On the other hand, an NADPH oxidase family, NOX1, distributing in non-phagocytic cells has been identified by the recent studies, and it has been reported that ROS is tissue-specifically formed in cells other than phagocyte (cf. non-patent reference 3). It has been reported that NOX1 is present in the large intestine in a large amount and causes cell proliferation and upregulation of various genes, suggesting that it is concerned in various diseases in the large intestine. There are various reports on the amino acid sequences having high homology with NOX1 and nucleotide sequences coding for the sequences. These are registered at data bases as accession numbers AF166328 (GENPEPT), AJ438989 (GENPEPT), HSA438989 (GENBANK), AF127763 (GENPEPT), AF166327 (GENPEPT), Q9YSS8 (SWISSPROT) and Q9WV87 (SWISSPROT), and reported in the non-patent reference 4, patent reference 1 and patent reference 2. The molecules are described in these references as factors which exist and function in the large intestine and are useful for the diagnosis of large bowel cancer, development of a therapeutic agent for large bowel cancer and the like. A sequence having high homology with NOX1 is described in the patent reference 3 which describes that the sequence is concerned in the production of active oxygen and useful for the treatment of diseases related to abnormal cell growth such as cancers and prostatic hypertrophy. RA is a chronic inflammatory disease of unknown origin, which has the mainlocus of lesion in the synovial tissue and causes flare, swelling, heat sensation, pain, movement restriction and destruction of joints. Overproduction of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α) and the like, nitric oxide (NO), prostaglandins (PGs) and the like is known in the synovial tissue of RA (cf. non-patent reference 5). In recent years, a therapeutic method aimed at IL-1, IL-6 or TNF-α has been developed using a monoclonal antibody and a soluble receptor, and its efficacy is drawing attention (cf. non-patent reference 6). However, there is a group of patients in which complete remission cannot be introduced by the conventional therapeutic method which uses a therapeutic target molecule as the mechanism (cf. non-patent reference 7). Accordingly, identification of a new therapeutic target molecule different from the already known reports is expected. It is known that ROS activates NFκB which is a transcription factor that expresses and induces various molecules, via oxidation-reduction control (cf. non-patent reference 8). Among the molecules of which expression is induced by NFκB, TNFα known as an inflammatory cytokine is also broadly acknowledged in the clinical field as the target of anti-RA agents (cf. non-patent reference 9), and COX-2 known as a prostaglandin synthesizing enzyme is also broadly acknowledged in the clinical field as the target of agents for treating RA and osteoarthritis (cf. non-patent reference 10). On the other hand, standards on the classification of RA have been defined from an American university (cf. non-patent reference 11). However, since these standards are merely landmarks and disease condition patterns thereof are various, it has been considered that diagnosis of RA, particularly quantitative and convenient diagnosis thereof, is difficult to carry out. A quantitative and convenient diagnosis method for RA has been expected. (Patent reference 1) International publication WO 02/06515 pamphlet (Patent reference 2) International publication Wo 01/96390 pamphlet (Patent reference 3) International publication WO 00/28031 pamphlet (Non-patent reference 1) Trends in Pharmacological Science, (USA), 2000, vol. 21, pp. 119-120 (Non-patent reference 2) Federation of European Biochemical Society, (Germany), 1991, vol. 281, pp. 9-19 (Non-patent reference 3) Nature, (England), 1999, vol. 401, pp. 79-82 (Non-patent reference 4) Science, (USA), 2000, vol. 287, p. 138 (Non-patent reference 5) The Journal of Experimental Medicine, (USA), 1991, vol. 173, pp. 569-574 (Non-patent reference 6) Current Pharmaceutical Biotechnology, (USA), 2000, vol. 1, pp. 217-233 (Non-patent reference 7) Nature Reviews Immunology, (England), 2002, vol. 2, pp. 364-371 (Non-patent reference 8) The Journal of Biological Chemistry, (USA), 1993, vol. 268, pp. 11380-11388 (Non-patent reference 9) Arthritis & Rheumatism, (USA), 1999, vol. 36, pp. 1681-1690 (Non-patent reference 10) Arthritis & Rheumatism, (USA), 1998, vol. 41, pp. 1591-1602 (Non-patent reference 11) “Medicine”, edited by J. Axford, (USA), Blackwell Science, 1996, pp. 3.18-3.22 DISCLOSURE OF THE INVENTION The inventor of the present invention have conducted intensive studies and as a result succeeded in obtaining complete length sequence of a gene of a novel oxidase (to be referred to as NOX1-b) from synovial cells derived from a human RA patient. Also, it was found that the NOX1-b gene is not expressed in synovial cells derived from healthy persons but expressed specifically in synovial cells derived from RA patients to make an inspection method useful as a diagnosis method for RA possible by the use of NOX1-b-specific polymerase chain reaction (PCR) primers. Additionally, a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis was constructed by using the NOX1-b gene. It was revealed that expression of COX-2 known as a target of the treating agents for RA and osteoarthritis, and of TNFα known as a target of the treating agents for RA is significantly accelerated in cells expressing NOX1-b, in comparison with cells in which NOX1-b is not expressed, and that the expression acceleration of COX-2 and TNF-α is inhibited by an NOX1-b inhibitor. As a result of these findings, the present invention has been accomplished by providing a novel oxidase NOX1-b, an inspection method useful for the diagnosis of RA and a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis. That is, the present invention relates to (1) (i) A polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2, and which is expressed specifically in rheumatoid arthritis patients, or (ii) a polypeptide which comprises an amino acid sequence in which from 1 to several amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted, and which is expressed specifically in rheumatoid arthritis patients. (2) A polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2. (3) A polynucleotide coding for the polypeptide according to (1) or (2). (4) An expression vector comprising the polynucleotide according to (3). (5) A cell transformed with the expression vector according to (4). (6) A method for inspecting RA, comprising (i) a step of measuring an expression level in a subject of i) a gene comprising the nucleotide sequence according to (3), or ii) a gene comprising a nucleotide sequence of a polynucleotide coding for a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients, and (ii) a step of comparing it with an expression level of the gene in a healthy person. (7) A rheumatoid arthritis inspection kit which comprises forward and reverse primers designed to specifically amplify (i) a gene comprising the nucleotide sequence according to (3), or (ii) a gene comprising a nucleotide sequence of a polynucleotide coding for a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients. (8) A method for screening a substance capable of inhibiting activity of a polypeptide, comprising (i) a step of allowing a substance to be tested to contact with a cell expressing the polypeptide according to (1) or (2) or a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients, (ii) a step of analyzing whether or not activity of the polypeptide is inhibited, and (iii) a step of selecting a substance capable of inhibiting activity of the polypeptide. (9) The screening method according to (8), wherein the substance which inhibits the activity of the polypeptide according to (1) or (2), or of a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients is a substance for the treatment of rheumatoid arthritis and/or a substance for the treatment of osteoarthritis. (10) A method for producing a pharmaceutical composition for the treatment of RA and/or the treatment of osteoarthritis, comprising a step of carrying out screening with the use of the screening method according to (8) or (9), and a step of formation using a substance obtained by the screening. Although there are no reports on sequences identical to the NOX1-b complete length amino acid sequence comprising SEQ ID NO:2 and a nucleotide sequence coding for the sequence, there are various reports on amino acid sequences having high homology therewith and nucleotide sequences coding for the sequences. A sequence in which 1 amino acid or 1 base is different from the NOX1-b sequence of the present invention is registered at the databases GENPEPT and GENBANK as a accession number AF166328. Also, sequences in which 2 amino acids or 4 bases are different from the NOX1-b sequence of the present invention are registered at the databases of GENPEPT and GENBANK as accession numbers AJ438989 and HSA438989, respectively. However, there is no description in any one of them suggesting that proteins comprising these sequences are expressed in the synovial cells of RA patients and become the target of the treatment of RA. Proteins having high homology with the polypeptide of the present invention (49 amino acids are inserted between the 432nd and 433rd positions of SEQ ID NO:2) have been registered at the data base of GENPEPT as accession numbers AF127763 and AF166327, and at the data base of SWISSPROT as accession numbers Q9Y5S8 and Q9WV87, respectively, and reported in “Science, 287, 138 (2000)”, “Nature, 401, 79 (1999)” and WO 02/06515. In addition, a protein having high homology with the polypeptide of the present invention (16 amino acids are inserted between the 80th and 81st positions of SEQ ID NO:2, and 49 amino acids are inserted between the 432nd and 433rd positions) has been reported in WO 01/96390. However, the molecule is described in these references as a factor which exists and functions in the large intestine and is useful for the diagnosis of large bowel cancer, development of a therapeutic agent for large bowel cancer and the like, while its relation to RA is not described therein. A protein having high homology with the polypeptide of the present invention (49 amino acids are inserted between the 432nd and 433rd positions of SEQ ID NO:2) has been reported in WO 00/28031, and it is described that the sequence is concerned with the formation of reactive oxygen. It is described that the aforementioned protein is specifically and frequently expressed in the large intestine and useful for the treatment of diseases in which abnormal cell growth is concerned, such as cancers and prostatic hypertrophy. Although it is necessary to diagnose RA by synovial membrane, expression of the aforementioned protein in synovial tissue was not confirmed in the international publication pamphlet, and whether or not it is specifically expressed in RA patients is not verified, too. Additionally, whether or not the aforementioned protein accelerates expression of TNF-α and COX-2 as the cause of RA is not verified too, and there is no information that the protein is useful for the inspection of RA and as a target of the treatment of RA. Thus, the fact that the polypeptide of the present invention is not present in the healthy person-derived synovial cells but specifically present in the RA patient-derived synovial cells and the polypeptide of the present invention becomes a target of the treatment of RA is a knowledge found for the first time by the inventor of the present invention, and the method for inspecting RA using the same and the method for screening a substance for the treatment of RA are inventions carried out for the first time by the inventor of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows increase in the expression of NOX1-b mRNA in RA patient-derived synovial cells. FIG. 2 shows ROS producing activity of NOX1-b and inhibition by DPI. FIG. 3 shows increase in the expression of COX-2 mRNA and inhibition by DPI in NOX1-b expressing cells. FIG. 4 shows increase in the expression of TNF-α mRNA and inhibition by DPI in NOX1-b expressing cells. BEST MODE FOR CARRYING OUT THE INVENTION According to the present invention, “RA” is used as” the abbreviation of “rheumatoid arthritis”. Conventionally, Japanese translation of RA was “Mansei kansetsu riumachi(chronic rheumatoid arthritis)”, but it was announced by The Japan Rheumatism Association in 2002 that the Japanese version of RA is changed from “Mansei kansetsu riumachi(chronic rheumatoid arthritis)” to “Kansetsu riumachi(rheumatoid arthritis)”, so that the terminology was changed accordingly in this specification. <Polypeptide and Polynucleotide of the Invention> In the polypeptide of the present invention, (1) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2; and (2) a polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2, and which is expressed specifically in RA patients, or a polypeptide which comprises an amino acid sequence in which from 1 to several amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted, and which is expressed specifically in RA patients; (to be called functionally equivalent variant hereinafter) are included. As the “functionally equivalent variant of the present invention”, “a polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2, and which is expressed specifically in RA patients”, or “a polypeptide which comprises an amino acid sequence in which from 1 to 10, preferably from 1 to 7 and more preferably from 1 to 5, amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted, and which is expressed specifically in RA patients” is desirable. The polypeptides of the present invention have been described in the foregoing, the polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2 and the functionally equivalent variant of the present invention are generally referred to as “the polypeptide of the present invention” hereinafter. Among the “polypeptides of the present invention”, a protein which is a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2 is called “NOX1-b protein”. As the polypeptide of the present invention, “a polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2” and “a polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2, and which is expressed specifically in RA patients, or a polypeptide which comprises an amino acid sequence in which from 1 to 10, preferably from 1 to 7 and more preferably from 1 to 5, amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted, and which is specifically expressed in RA patients” are desirable, and “a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2” is more desirable. Additionally, the polynucleotide of the present invention may be any nucleotide sequence coding for the NOX1-b protein represented by the amino acid sequence described in SEQ ID NO:2 or a functionally equivalent variant thereof. Preferred is a polynucleotide having a nucleotide sequence coding for the amino acid sequence described in SEQ ID NO:2, and more preferred is the nucleotide sequence described in SEQ ID NO:1. The production method of the polynucleotide of the present invention is not particularly limited, but for example includes (1) a method using PCR, (2) a method using an usual genetic engineering technique (namely a method for selecting a transformant containing an amino acid sequence of interest from transformants which is transformed with a cDNA library) or (3) a chemical synthesis method and the like. Each of the production methods can be carried out in the same manner as described in WO 01/34785 in which invention of a novel enzyme is disclosed. However, the “novel protein of the invention” according to the aforementioned patent application specification is interpreted as a polypeptide of the present invention (e.g., NOX1-b protein), and the “gene of the invention” as a polynucleotide of the present invention (e.g., NOX1-b). Illustratively, according to the method which using PCR, the polynucleotide of the present invention can be produced, for example, by the procedure described in the a) First production method in 1) Production method of protein gene in “Mode for Carrying Out the Invention” of the aforementioned patent reference. Firstly, mRNA is extracted from a cell or tissue having the ability to produce the protein of the present invention, such as a human RA patient-derived synovial membrane. Next, a first strand cDNA can be synthesized by a reverse transcriptase reaction using the mRNA in the presence of a random primer or an oligo(dT) primer. The polynucleotide of the present invention or a part thereof is obtainable by subjecting the thus obtained first strand cDNA to a polymerase chain reaction (PCR) using two primers interposing a partial region of the objective gene. More illustratively, the objective gene is amplified, for example, by the method described in Example 1 using the sequences represented by SEQ ID NO:5 and SEQ ID NO:6 as the primers. Subsequently, by confirming whether or not the thus amplified gene is expressed specifically in RA patients for example by the method described in Example 4, the gene which is RA patient-specifically expressed in comparison with a healthy parson can be selected as the polynucleotide of the present invention. According to the method using a usual genetic engineering technique, the polynucleotide of the present invention can be produced, for example, by the procedure described in the b) Second production method in 1) Production method of protein gene in “Mode for Carrying Out the Invention” of the aforementioned patent reference. According to the method using a chemical synthesis method, the polynucleotide of the present invention can be produced, for example, by the methods described in the c) Third production method and d) Fourth production method in 1) Production method of protein gene in “Mode for Carrying Out the Invention” of the aforementioned patent reference. The methods for producing the expression vector, host cell and protein of the present invention can be carried out, for example, by the methods described in 2) Production methods of the vector of the present invention, the host cell of the present invention and the recombinant protein of the present invention in “Mode for Carrying Out the Invention” of the aforementioned patent reference. More illustratively, the expression vector of the present invention can be produced by the method described in Example 2 using a mammalian cell expression vector pcDNA3.1/HisB, and the host cell and protein of the present invention by the method described in Example 3 in which an NIH3T3 cell is transfected using a transfection reagent. Since the polynucleotide of the present invention can be used by itself as a hybridization probe in the following RA inspection method, it is useful for the inspection of RA. Additionally, the polynucleotide of the present invention can be used in preparing an antibody capable of specifically recognizing the polynucleotide of the present invention and as a control in detecting and/or determining its expression level. Inspection Method of RA/kit for RA Inspection As is described in the following, since it was found that NOX1-b was not expressed in samples derived from healthy persons, but NOX1-b was specifically expressed in samples derived from RA patients, the RA disease can be detected by using the expression. Illustratively, an embodiment containing the following steps can be exemplified. Namely, [1] a step in which measuring the expression level in a subject of (1) a gene comprising the nucleotide sequence of the polynucleotide of the present invention (namely, a gene comprising a nucleotide sequence of a polynucleotide coding for i) a polypeptide which comprises the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients, ii) a polypeptide which comprises an amino acid sequence in which from 1 to several amino acids of the amino acid sequence represented by SEQ ID NO:2 are deleted and/or inserted and which is expressed specifically in RA patients, or iii) a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2), or (2) a gene comprising a nucleotide sequence of a polynucleotide coding for a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients and [2] a step in which the result is compared with the expression level of the aforementioned gene in a healthy person. The “polypeptide which comprises an amino acid sequence having 90% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is specifically expressed in RA patients” according to the aforementioned (2) is called as “homologous polypeptide according to the present invention”. Although the homologous polypeptide according to the present invention is not particularly limited, so far as it is “a polypeptide which comprises an amino acid sequence having 95% or more of homology with the amino acid sequence represented by SEQ ID NO:2 and which is expressed specifically in RA patients”, a polypeptide which comprises an amino acid sequence preferably having 97% or more, more preferably 99% or more, of the homology is desirable. In this connection, the aforementioned “homology” according to this specification means the Identities value obtained by the BLAST (Basic local alignment search tool; Altschul, S. F. et al., J. Mol. Biol., 215, 403-410, 1990) retrieval. With regard to the parameters in this case, “blastp” is used as the “program name”, the “Gap insertion Cost value” by “0”, the “Gap elongation Cost value” by “0”, and “BLOSUM62” as the “Matrix”, respectively as the pair-wise alignment parameters. The homologous polypeptide according to the present invention can be produced by the same method for the production of the polypeptide of the present invention. The polypeptide of the present invention and the homologous polypeptide according to the present invention are generally referred to as the polypeptide for screening of the present invention. As the polypeptide for screening of the present invention, a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2 is particularly desirable. The gene expression level according to the RA inspection method of the present invention include transcription of the gene into mRNA and its translation into protein. Accordingly, the RA inspection method by the present invention is carried out based on the comparison of the expression level of mRNA which corresponds to a polynucleotide coding for the polypeptide for screening of the present invention (e.g., NOX1-b gene), or the expression level of a protein encoded by the gene. The method for measuring expression level of a gene (e.g., NOX1-B gene) in the step [1] can be carried out in accordance with a conventionally known gene analyzing method. For example, a hybridization technique in which a nucleic acid capable of hybridizing with the NOX1-b gene is used as the probe, a gene amplification technique in which DNA fragments capable of hybridizing with the NOX1-b gene are used as the primers, and the like can be used. Illustratively, it can be measured using a synovial cell-derived nucleic acid, such as mRNA or the like, obtained from a subject. With regard to the measurement of mRNA, it can be measured by a gene amplification reaction method using primers designed in such a manner that they can specifically amplify a polynucleotide coding for the polypeptide for screening of the present invention (e.g., NOX1-b sequence). Although the gene amplification reaction method is not particularly limited, a PCR method, an nucleic acid amplification method using a RNA polymerase and the like can be employed. More illustratively, it can be carried out by the method described in Example 4. The primers to be used in the RA inspection method, or the primers to be contained in the kit for RA inspection of the present invention, are not particularly limited as far as they can specifically amplify a polynucleotide coding for the polypeptide for screening of the present invention (e.g., NOX1-b sequence), and they can be designed based on a polynucleotide coding for the polypeptide for screening of the present invention (e.g., NOX1-b nucleotide sequence). Preferred are the oligonucleotides described in SEQ ID NO:5 and SEQ ID NO:6. The RA inspection which uses a hybridization technique can be carried out, for example, by using a northern hybridization, a dot blotting, a DNA micro-array method and the like. It can also be carried out using gene amplification technique such as a RT-PCR. According to the RT-PCR method, it is possible to carry out more quantitative analysis of the expression of a gene comprising a polynucleotide coding for the polypeptide for screening of the present invention (e.g., NOX1-b gene), by using a PCR amplification monitoring (real time PCR) method in the gene amplification process. For example, ABI PRISM 7700 (Applied Biosystems) can be used as PCR amplification monitoring method. Additionally, as the method in the step [1] for measuring the expression level of a gene containing the nucleotide sequence of a polynucleotide coding for the polypeptide for screening of the present invention, it is possible to employ a method in which the expression level is measured by detecting a protein comprising the polypeptide for screening of the present invention, preferably the NOX1-b protein. As such an inspection method, for example, it is able to use western blotting, immunoprecipitation, ELISA or the like, using a cell extract of synovial cells derived from a subject and using an antibody capable of binding to a protein comprising the polypeptide for screening of the present invention, preferably an NOX1-b protein and more preferably an antibody capable of specifically binding to NOX1-b. The comparing method of the step [2] is not particularly limited, as far as the expression level obtained in the step [1] is compared with an expression level in a healthy person, and the comparison can be carried out, for example, by the method described in Example 4. The RA inspection kit of the present invention contains at least forward and reverse primers designed in such a manner that it can specifically amplify a polynucleotide coding for the polypeptide for screening of the present invention. The forward and reverse primers include such as primers represented by the nucleotide sequences described in SEQ ID NO:5 and SEQ ID NO:6. Examples of other reagents which can be contained in the RA inspection kit of the present invention include those reagents such as those which are necessary for carrying out PCR (e.g., Taq polymerase, a nucleotide substrate, a buffer solution and the like). Screening Method of the Invention In the screening method of the present invention, a method for screening a substance capable of inhibiting activity of the polypeptide for screening of the present invention and a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis are included. (1) A method for screening a substance capable of inhibiting activity of the polypeptide for screening of the present invention The method for screening a substance capable of inhibiting activity of the polypeptide for screening of the present invention is not particularly limited so far as it contains the following steps (i) to (iii): (i) a step of allowing a substance to be tested to contact with a cell expressing the polypeptide for screening of the present invention, (ii) a step of analyzing whether or not activity of the aforementioned polypeptide is inhibited, and (iii) a step of selecting a substance capable of inhibiting activity of the aforementioned polypeptide. A substance capable of inhibiting activity of the polypeptide for screening of the present invention can be screened preferably by the method described in Example 5. (2) A method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis As described in the column of Technical Field, TNF-α known as an inflammatory cytokine is also broadly acknowledged in the clinical field as the target of treating agents for RA, and COX-2 known as a prostaglandin synthesizing enzyme is also broadly acknowledged in the clinical field as the target of the agents for treating RA and osteoarthritis. Accordingly, a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis can be screened by selecting a substance which reduces expression of TNF-α or COX-2. As is shown in the following Examples, it was revealed that expression of COX-2 and expression of TNF-α are significantly accelerated in a cell which expresses NOX1-b which is one of the polypeptides of the present invention (Example 6 and Example 7). Additionally, since these COX-2 expression induction and TNF-α expression induction were inhibited by DPI which is an NOX1-b inhibitor, it was considered that expression of COX-2 and TNF-α was induced via a redox control by ROS derived from NOX1-b which is one of the polypeptides of the present invention. Based on a new knowledge found by the inventor of the present invention that the upregulation of COX-2 and/or TNF-α is inhibited through the inhibition of activity of the polypeptide of the present invention, it was considered that a substance capable of inhibiting activity of the polypeptide for screening of the present invention has the treating effect for RA. That is, a method for screening a substance capable of inhibiting activity of the polypeptide for screening of the present invention can be used as a method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis. The method for screening a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis is not particularly limited so far as it contains the following steps (i) to (iii): (i) a step of allowing a substance to be tested to contact with a cell expressing the polypeptide for screening of the present invention, (ii) a step of analyzing whether or not activity of the aforementioned polypeptide is inhibited, and (iii) a step of selecting which a substance capable of inhibiting activity of the aforementioned polypeptide. Whether or not the substance obtained by the aforementioned screening method is a useful substance as the treating substance of RA can be judged by subjecting it to a conventionally known evaluation system of the treating agents of RA, or by subjecting to a modified evaluation system thereof. For example, confirming the RA-treating action can be carried out by a method which uses a collagen-induced arthritis model mouse (Fiona H. Duris et al., Immunol. Immunopathol., 73, 11-18, 1994). Also, by subjecting the substance obtained by the aforementioned screening method to a conventionally known evaluation system of treating agents of osteoarthritis, whether or not it is an useful substance as a substance for the treatment of osteoarthritis can be judged. Based on the difference in the method to be used for analyzing (measuring or detecting) activity of the polypeptide for screening of the present invention, the screening method of the present invention includes, for example, (a) a chemical-biochemical method, (b) a chemiluminescence method, (c) an electron spin resonance (ESR) method and the like. Each screening method is described in the following. (a) Chemical-Biochemical Method A substance capable of inhibiting activity of the polypeptide for screening of the present invention and a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis can be screened using a chemical-biochemical method. As the chemical-biochemical method includes, for example, (i) a screening method which uses a cytochrome C reduction method, (ii) a-screening method which uses reduction of nitroblue tetrazolium (NBT) and (iii) a screening method which uses reduction of a water-soluble tetrazolium salt. Detection by the cytochrome C reduction method uses an effect that oxidized cytochrome C changes to reduced counterpart having strong absorption at 550 nm when the former is reduced (J. M. MacCord and I. Fridovich, J. Biol. Chem., 244, 6049 (1969)). The NBT reduction method uses an effect that NBT forms water-insoluble blue formazan (absorption maximum 560 nm) when it is reduced by O2− (C. Beauchamp and I. Fridovich, Anal. Biochem., 44, 276 (1971)). Cells expressing the polypeptide for screening of the present invention are prepared. A substance to be tested is added thereto, an appropriate amount of a probe (e.g., cytochrome C) is further added thereto, and the mixture is incubated for a predetermined time. After the reaction, absorbance at 550 nm is measured. In case that conversion into the reduced form is inhibited when the substance to be tested is added, it can be judged that the aforementioned substance to be tested is a substance which inhibits activity of the polypeptide for screening of the present invention. It is desirable to carry out the screening method which uses a cytochrome C reduction method, as one of these methods, under the conditions described in Example 5. Regarding the substance which inhibits activity of the polypeptide for screening of the present invention, it is desirable to select a substance of 10 μM or less, preferably 1 μM or less, more preferably 0.1 μM or less. (b) Chemiluminescence Method Examples of the chemiluminescence method include (i) a screening method which uses a Vargula hilgendorfii luciferin derivative and (ii) a screening method which uses a luminol method. The Vargula hilgendorfii luciferin derivative forms an exited carbonyl compound by reacting with O2− in an aqueous solution of about neutral range and generates strong luminescence at 380 nm when the latter is reaching a ground state, so that the phenomenon is used (Goto, T: Pure Appl. Chem., Vol. 17, 421-441, 1968). The detection by a luminol method uses a phenomenon that it forms an aminophthalic acid dianion (exited state) by undergoing oxidation by HOCl, K3Fe(CN)6, K2S2O8, Fe2+ salt, Co3+ or the like in the presence of O2− or H2O2 in an alkaline aqueous solution and generates luminescence when the latter is reaching a ground state (Roswell, D. F. et al., Method in Enzymology, Vol. 15, 409-423, 1972). Cells expressing the polypeptide for screening of the present invention are prepared. A substance to be tested is added thereto and an appropriate amount of a probe (e.g., a Vargula hilgendorfii luciferin derivative) is further added thereto, and the mixture is allowed to undergo the reaction for a predetermined time. After the reaction, luminescence at 380 nm is measured. In case that the luminescence is inhibited when the substance to be tested is added, it can be judged that the aforementioned substance to be tested is a substance which inhibits activity of the polypeptide for screening of the present invention. With regard to the substance which inhibits activity of the polypeptide for screening of the present invention, it is desirable to select a substance of 10 μM or less, preferably 1 μM or less and more preferably 0.1 μM or less. (c) Electron Spin Resonance (ESR) Method The ESR signal of O2− can be indirectly measured by the use of the spin-trap method. That is, the ESR method uses a process in which a radical species having a short life span is allowed to react with a trapping agent, and ESR spectrum of the thus formed stable radical is analyzed. The currently used spin-trapping agent having most high general purpose performance is 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (Y. Noda, K. Anzai, A. Mori, M. Kohno, M. Shinmei and L. Packer, Biochem. Mol. Biol. Int., 42, 35 (1997)). Cells expressing the polypeptide for screening of the present invention are prepared. A substance to be tested is added thereto, an appropriate amount of a spin-trapping agent (e.g., DMPO) is further added thereto, and the mixture is allowed to react for a predetermined time. After the reaction, spectral analysis of the radical-added product is carried out. In case that signal of the radical-added product is inhibited when the substance to be tested is added, it can be judged that the aforementioned substance to be tested is a substance which inhibits activity of the polypeptide for screening of the present invention. With regard to the substance which inhibits activity of the polypeptide for screening of the present invention, it is desirable to select a substance of 10 μM or less, preferably 1 μM or less and more preferably 0.1 μM or less. Since the compound to be tested as the subject to be selected by the screening method of the present invention is not particularly limited, for example, various conventionally known compounds (including peptides) registered in chemical files, a group of compounds obtained by the combinatorial chemistry techniques (Terrett, N. K. et al., Tetrahedron, 51, 8135-8137, 1995) and a group of random peptides prepared by applying the phage display method (Felici, F. et al., J. Mol. Biol., 222, 301-310, 1991) and the like can be used. Also, natural components derived from microorganisms, plants, marine organisms or animals (e.g., culture supernatants or tissue extracts) and the like can also be used as the subject of the screening. Additionally, compounds (including peptides) obtained by chemically or biologically modifying the compounds (including peptides) selected by the screening method of the present invention can also be used. Method for Producing a Medicinal Composition for the Treatment of RA and/or the Treatment of Osteoarthritis In the present invention, a method for producing a medicinal composition for the treatment of RA and/or the treatment of osteoarthritis, comprising a step in which screening is carried out by using the screening method of the present invention and a step in which a substance obtained by the aforementioned screening is made into a pharmaceutical preparation. The pharmaceutical preparation which comprises a substance obtained by the screening method of the present invention as the active ingredient can be prepared using generally used pharmaceutical carriers, fillers and/or other additives. Examples of its administration include oral administration through such as tablets, pills, capsules, granules, fine subtilaes, powders and solutions for oral use, or parenteral administration through such as injections for intravenous injection, intramuscular injection and intraarticular injection, suppositories, percutaneous administration preparations, transmucosal administration preparations and the like. In the case of peptides which are digested in the stomach, parenteral administration such as intravenous injection is particularly desirable. In the solid composition for oral administration, one or more active substances are mixed with at least one inert diluent such as lactose, mannitol, glucose, microcrystalline cellulose, hydroxypropylcellulose, starch, polyvinyl pyrrolidone, aluminum magnesium silicate or the like. In accordance with the usual method, the aforementioned composition may contain other additives than the inert diluent, such as a lubricant, a disintegrating agent, a stabilizing agent and a solubilizing or solubilization assisting agent. If necessary, tablets or pills may be subjected to sugar coating or coated with a film of a gastric or enteric substance. The liquid composition for oral administration includes, for example, emulsions, solutions, suspensions, syrups, elixirs and the like and contains a generally used inert diluent such as purified water or ethanol. In addition to the inert diluent, the aforementioned composition may also includes other additives such as a moistening agent, a suspending agent, a sweetener, an aromatic and antiseptic. The injections for parenteral administration includes aseptic aqueous or non-aqueous solutions, suspensions and emulsions. Examples of the diluent for use in the aqueous solutions and suspensions include distilled water for injection and physiological saline. Examples of the diluent for use in the non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, a plant oil (e.g., olive oil), an alcohol (e.g., ethanol), polysorbate 80 and the like. The aforementioned composition may further contains a moistening agent, an emulsifying agent, a dispersing agent, a stabilizing agent, a solubilizing or solubilization assisting agent, an antiseptic and the like. The aforementioned compositions can be sterilized by filtration through a bacteria retaining filter, blending of a germicide or irradiation. Alternatively, it can also be used by firstly making into a sterile solid composition and dissolving it in sterile water or a sterile medium for injection prior to its use. The clinical dose can be optionally decided by taking into consideration strength of the activity of the active ingredient, namely the substance obtained by the screening method of the present invention, symptoms, age and sex of the subject to be administered and the like. For example, in the case of oral administration, the dose is usually approximately from 0.1 to 100 mg, preferably from 0.1 to 50 mg, per day per adult (as 60 kg in body weight). In the case of parenteral administration, it is from 0.01 to 50 mg, preferably from 0.01 to 10 mg, per day in the form of injections. EXAMPLES The following describes the present invention in detail based on examples, but the present invention is not limited by the examples. In this connection, unless otherwise noted, experiments were carried out in accordance with the conventionally known method (Sambrook, J. et al., “Molecular Cloning—A Laboratory Manual”, Cold Spring Harbor Laboratory, NY, 1989) such as gene manipulation experimentation manuals and manuals attached to reagents and the like. Example 1 Preparation of a Novel Oxidase NOX1-b and Determination of Complete Length Open Reading Frame (ORF) Using an RNA extraction kit (RNAeasy Protect Mini Kit) manufactured by Qiagen, mRNA was purified from an RA patient-derived synovial cell (HS-RA) manufactured by Toyobo and converted into cDNA using SUPERSCRIPT II (SUPERSCRIPT First-Strand Synthesis System for RT-PCR) (Gibco-BRL), and the thus obtained homemade cDNA was used as the template. Oligo DNA fragments coding for the outside of NOX1 ORF, represented by SEQ ID NO:3 and SEQ ID NO:4, were synthesized, and a PCR reaction of 94° C. for 1 minute and 35 cycles consisting of 94° C. for 30 seconds, 55° C. for 30 seconds and 68° C. for 3 minutes, was carried out using a DNA polymerase (PLATINUM™ Taq DNA polymerase; mfd. by Invitrogen). The cDNA obtained by the reaction was inserted into a cloning vector (TA cloning kit; mfd. by Invitrogen) (NOX1 vector) and analyzed by the dideoxy terminator method using ABI3700 DNA Sequencer (mfd. by Applied Biosystems) to determine the ORF sequence. This gene was named NOX1-b. Complete length nucleotide sequence of the gene is shown in SEQ ID NO:1, and its deduced amino acid sequence in SEQ ID NO:2. The ORF sequence of NOX1-b encoded a novel protein in which from the 433rd position to the 481st position of NOX1 (GenBank accession number: AF127763) are spliced out. Example 2 Cloning of NOX1-b Complete Length ORF and Construction of Protein Expression Plasmid The NOX1-b vector prepared in Example 1 was digested with EcoRI and XhoI and inserted into the EcoRI and XhoI sites of a protein expression vector (pcDNA3.1/HisB; mfd. by Invitrogen), thereby completing a complete length protein expression plasmid pcDNA3.1/HisB-NOX1-b. Example 3 Expression of HisB.NOX1-b in Animal Cell Strain NIH3T3 cells (mfd. by Dainippon Pharmaceutical) were spread on a 10 cm plate at a density of 1×106 cells and cultured for 12 hours, and then the expression plasmid pcDNA3.1/HisB-NOX1-b prepared in Example 2 and the vacant vector pcDNA3.1/HisB were introduced into the NIH3T3 cells using a transfection reagent (FuGENE™ 6 Transfection Reagent; mfd. by Roche) in accordance with the instructions attached thereto. After 12 to 16 hours of the plasmid introduction, the medium was replaced by a serum-free medium and then the culturing was continued for 48 hours to 60 hours. The introduced cells were washed with PBS and then recovered with an SDS sample buffer (S.B). The presence of the subject protein in the S.B was confirmed by a western blotting using an antibody which recognizes a C-terminal sequence common to the NOX1 protein and NOX1-b protein as an epitope (rabbit anti-MOX antibody; mfd. by Santa Cruz). That is, the thus recovered aforementioned S.B was subjected to an SDS/4%—20% acrylamide gel (mfd. by Daiichi Pure Chemicals) electrophoresis (under reduction condition) and then transferred on a PVDF membrane (mfd. by Millipore) using a blotting device. After the transfer, the PVDF membrane was blocked by adding Block Ace (mfd. by Dainippon Pharmaceutical) and then allowed to react with a biotinylated rabbit anti-IgG antibody (M2; mfd. by Sigma) and a horseradish peroxidase-labeled streptavidin (mfd. by Amersham Pharmacia) in that order. After the reaction, expression of the subject protein was verified using an ECL western blotting detection system (mfd. by Amersham Pharmacia). A band of 52±0.5 kD in molecular weight was detected in the sample obtained from the cells introduced with pcDNA3.1/HisB.NOX1-b, but the band was not detected in the sample obtained from the vacant vector-introduced cells, so that it was found that HisB.NOX1-b is expressed in the cells introduced with pcDNA3.1/HisB.NOX1-b. Example 4 Expression Increase of NOX1-b mRNA in RA Patient-Derived Synovial Cells Using the mRNA extraction method shown in Example 1, a homemade cDNA was prepared from healthy person-derived synovial cells (Cell System-SS cells) manufactured by Dainippon Pharmaceutical. By synthesizing probe primers coding for the NOX1-b-specific sequences represented by SEQ ID NO:5 and SEQ ID NO:6, a semi-quantitative RT-PCT reaction of 94° C. for 1 minute and 45 cycles consisting of 94° C. for 10 seconds, 55° C. for 20 seconds and 72° C. for 30 seconds, was carried out on each of RA patient- and healthy person-derived samples (prepared by diluting each template cDNA at 1, 1/10 and 1/100 times dilution ratios), using a DNA polymerase (r Taq DNA polymerase; mfd. by Toyobo). The primer sequence represented by SEQ ID NO:5 is a nucleotide sequence coding for a connecting region from which NOX1 was spliced out, namely the region where the 432nd position and the 482nd position of the NOX1 protein are connected, so that this is a sequence which does not recognize NOX1. Accordingly, the PCR products by SEQ ID NO:5 and SEQ ID NO:6 are NOX1-b-specific. When the PCR reactants were subjected to an agarose gel electrophoresis and the DNA fragments were detected by ethidium bromide (EtBr) staining, a band having a size considered to be that of NOX1-b was found in the RA patient-derived sample, but was not able to be found in the sample of healthy person. On the other hand, in the control PCR reaction of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) carried out using the primers represented by SEQ ID NO:7 and SEQ ID NO:8, the same band was found by the EtBr staining in both of the RA patient- and healthy person-derived samples (FIG. 1A). Additionally, the RT-PCR reaction was carried out on each of RA patient- and healthy person-derived samples in the same manner as in the above using probe primers coding for conventionally known NOX1-specific sequences represented by SEQ ID NO:13 and SEQ ID NO:6, and the results were compared with the data obtained by the use of the NOX1-b-specific probe primers. As a result, different from the case of NOX1-b, a band having a size considered to be that of NOX1 was found not only in the RA patient-derived samples but also in the healthy person-derived samples. In addition, changes in the band quantity of NOX1 stained by EtBr were not found in the RA patient-derived samples and healthy person-derived samples (FIG. 1B). Based on these results, it was revealed that expression of NOX1-b is significantly accelerated in the RA patient-derived synovial cells in comparison with the case of healthy person. It was also found that inspection of RA diagnosis can be carried out by the method described in this example. Example 5 ROS Producing Activity of NOX1-b Using the NOX1-b expressing cells shown in Example 3, the ROS productivity was measured by a cytochrome C reduction method. In order to measure ROS by the cytochrome C reduction method, vacant vector expressing cells and NOX1-b expressing cells were respectively dispensed in 0.5×106 cells/100 μl/well portions into a 96 well multi-well plate for cell culture (to be referred to as multi-well plate). About 12 hours thereafter, 4.62 mg/ml of cytochrome C was added and mixed in 100 μl/well portions under respective conditions, and then the multi-well plate was set on a plate reader to periodically measurement of absorbance at 550 nm. Integrated values after 1 hour thereof are shown in FIG. 2. As a result, it was revealed that the NOX1-b expressing cells have significant ROS producing activity in comparison with the vacant vector expressing cells. Additionslly, it was found that the activity is considerably inhibited when 1 μM of diphenylene iodonium chloride (to be referred to as DPI) known as an NADPH oxidase inhibitor is added 30 minutes before the addition of cytochrome C (FIG. 2). Based on these results, it was revealed that NOX1-b has ROS producing activity, and the activity is inhibited by DPI. A substance capable of inhibiting the activity of NOX1-b can be screened by the measuring method of the example. Example 6 Upregulation of COX-2 mRNA in NOX1-b Expressing Cells Using the mRNA extraction method shown in Example 1, respective cDNA samples were prepared from the vacant vector expressing cells and NOX1-b expressing cells. By synthesizing probe primers coding for the COX-2-specific sequences represented by SEQ ID NO:9 and SEQ ID NO:10, an RT-PCT reaction of 94° C. for 1 minute and 45 cycles consisting of 94° C. for 10 seconds, 55° C. for 20 seconds and 72° C. for 30 seconds, was carried out on each of the vacant vector expressing cell- and NOX1-b expressing cells-derived samples using a DNA polymerase (r Taq DNA polymerase; mfd. by Toyobo). When the PCR reactants were subjected to an agarose gel electrophoresis and the DNA fragments were detected by EtBr staining, it was confirmed that a band having a size considered to be that of COX-2 is considerably increased in the NOX1-b-derived samples in comparison with the case of vacant vector-derived samples (FIG. 3). On the other hand, in the control PCR reaction of G3PDH carried out using the primers represented by SEQ ID NO:7 and SEQ ID NO:8, the same band was found by the EtBr staining in both of the vacant vector expressing cell- and NOX1-b expressing cell-derived samples (FIG. 3). Accordingly, it was revealed that expression of COX-2 is significantly accelerated in the NOX1-b expressing cells in comparison with the vacant vector expressing cells. When DPI which is the NOX1-b inhibitor was added to the NOX1-b expressing cells to a final concentration of 1 μM and RT-PCR similar to the above was carried out 3 hours thereafter using the sample which was prepared by mRNA extraction method, it was revealed that induction of COX-2 expression by NOX1-b expression is inhibited by DPI (FIG. 3). Since the induction of COX-2 expression was inhibited by DPI, it was considered that expression of COX-2 was induced via the oxidation-reduction control by an NOX1-b-derived ROS. Example 7 Expression Increase of TNFα mRNA in NOX1-b Expressing Cells Probe primers coding for the TNF-α-specific sequences represented by SEQ ID NO:11 and SEQ ID NO:12 were synthesized. On each of the cDNA samples prepared in Example 6 and using a DNA polymerase (r Taq DNA polymerase; mfd. by Toyobo), RT-PCR reaction of 94° C. for 1 minute, 45 cycles of consisting of 94° C. for 10 seconds and 55° C. for 20 seconds and 72° C. for 30 seconds, was carried out. When the PCR reactants were subjected to an agarose gel electrophoresis and the DNA fragments were detected by ethidium bromide (EtBr) staining, a band having a size considered to be that of TNF-α was found in the NOX-1b expressing cell-derived sample, but was not able to be found in the vacant vector expressing cell-derived sample. On the other hand, in the control PCR reaction of G3PDH carried out using the primers represented by SEQ ID NO:7 and SEQ ID NO:8, the same band was found by the EtBr staining in both of the vacant vector expressing cell- and NOX1-b expressing cell-derived samples. Additionally, it was revealed that the induction of TNF-A expression is inhibited when the NOX1-b-derived cells are pretreated for 3 hours with 1 μM of DPI which is the NOX1-b inhibitor (FIG. 4). Accordingly, it was revealed that expression of TNF-α is significantly accelerated in the NOX1-b expressing cells in comparison with the case of vacant vector expressing cells. In addition, since the induction of TNF-α expression is inhibited by DPI, it is considered that the induction is carried out via the oxidation-reduction control by an NOX1-b-derived ROS. Industrial Applicability It was revealed that the polynucleotide of the present invention can be used as an index of RA diagnosis, because its expression acceleration reflects the pathology. It became possible to carry out inspection of the RA diagnosis, by using the expression of the polynucleotide of the present invention and of the polypeptide of the present invention encoded by the polynucleotide as indexes. Additionally, the present invention provides a novel oxidase which is expressed specifically in RA patient-derived synovial cells, and it is expected that PCR using the specific primer sequences can be applied to the inspection of diagnosis of RA. The screening method of the present invention is useful for the screening of a substance for the treatment of RA and/or a substance for the treatment of osteoarthritis. Thus, although the present invention has been described in the foregoing based on specified embodiments, its modifications and improvements obvious to those skilled in the art are included in the scope of the present invention.
<SOH> BACKGROUND OF THE INVENTION <EOH>Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an enzyme which forms an reactive oxygen species (to be referred to as ROS) by receiving an electron from NADPH and finally delivering it to an oxygen molecule. Physiologically, the aforementioned enzyme mainly existing in phagocytes is taking an important role in a defense system in a living body against invasion of foreign bodies such as microorganisms, which is sterilization of them by forming ROS and the like. However, it is known that excess formation of ROS by the enzyme causes digestion of protein and DNA and the damage to membranes by lipid peroxide and thereby becomes the cause of disorders of cells and tissues and furthermore of various diseases including inflammatory diseases, vascular diseases, neurodegenerative diseases, cancers, heart diseases and the like (cf. non-patent reference 1 and non-patent reference 2). However, since expression of the NADPH oxidase which forms ROS is systemically distributed, there is a possibility of causing side effects when this is considered as a target of drug discovery. On the other hand, an NADPH oxidase family, NOX1, distributing in non-phagocytic cells has been identified by the recent studies, and it has been reported that ROS is tissue-specifically formed in cells other than phagocyte (cf. non-patent reference 3). It has been reported that NOX1 is present in the large intestine in a large amount and causes cell proliferation and upregulation of various genes, suggesting that it is concerned in various diseases in the large intestine. There are various reports on the amino acid sequences having high homology with NOX1 and nucleotide sequences coding for the sequences. These are registered at data bases as accession numbers AF166328 (GENPEPT), AJ438989 (GENPEPT), HSA438989 (GENBANK), AF127763 (GENPEPT), AF166327 (GENPEPT), Q9YSS8 (SWISSPROT) and Q9WV87 (SWISSPROT), and reported in the non-patent reference 4, patent reference 1 and patent reference 2. The molecules are described in these references as factors which exist and function in the large intestine and are useful for the diagnosis of large bowel cancer, development of a therapeutic agent for large bowel cancer and the like. A sequence having high homology with NOX1 is described in the patent reference 3 which describes that the sequence is concerned in the production of active oxygen and useful for the treatment of diseases related to abnormal cell growth such as cancers and prostatic hypertrophy. RA is a chronic inflammatory disease of unknown origin, which has the mainlocus of lesion in the synovial tissue and causes flare, swelling, heat sensation, pain, movement restriction and destruction of joints. Overproduction of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α) and the like, nitric oxide (NO), prostaglandins (PGs) and the like is known in the synovial tissue of RA (cf. non-patent reference 5). In recent years, a therapeutic method aimed at IL-1, IL-6 or TNF-α has been developed using a monoclonal antibody and a soluble receptor, and its efficacy is drawing attention (cf. non-patent reference 6). However, there is a group of patients in which complete remission cannot be introduced by the conventional therapeutic method which uses a therapeutic target molecule as the mechanism (cf. non-patent reference 7). Accordingly, identification of a new therapeutic target molecule different from the already known reports is expected. It is known that ROS activates NFκB which is a transcription factor that expresses and induces various molecules, via oxidation-reduction control (cf. non-patent reference 8). Among the molecules of which expression is induced by NFκB, TNFα known as an inflammatory cytokine is also broadly acknowledged in the clinical field as the target of anti-RA agents (cf. non-patent reference 9), and COX-2 known as a prostaglandin synthesizing enzyme is also broadly acknowledged in the clinical field as the target of agents for treating RA and osteoarthritis (cf. non-patent reference 10). On the other hand, standards on the classification of RA have been defined from an American university (cf. non-patent reference 11). However, since these standards are merely landmarks and disease condition patterns thereof are various, it has been considered that diagnosis of RA, particularly quantitative and convenient diagnosis thereof, is difficult to carry out. A quantitative and convenient diagnosis method for RA has been expected. (Patent reference 1) International publication WO 02/06515 pamphlet (Patent reference 2) International publication Wo 01/96390 pamphlet (Patent reference 3) International publication WO 00/28031 pamphlet (Non-patent reference 1) Trends in Pharmacological Science , (USA), 2000, vol. 21, pp. 119-120 (Non-patent reference 2) Federation of European Biochemical Society, (Germany), 1991, vol. 281, pp. 9-19 (Non-patent reference 3) Nature , (England), 1999, vol. 401, pp. 79-82 (Non-patent reference 4) Science, (USA), 2000, vol. 287, p. 138 (Non-patent reference 5) The Journal of Experimental Medicine, (USA), 1991, vol. 173, pp. 569-574 (Non-patent reference 6) Current Pharmaceutical Biotechnology , (USA), 2000, vol. 1, pp. 217-233 (Non-patent reference 7) Nature Reviews Immunology , (England), 2002, vol. 2, pp. 364-371 (Non-patent reference 8) The Journal of Biological Chemistry , (USA), 1993, vol. 268, pp. 11380-11388 (Non-patent reference 9) Arthritis & Rheumatism , (USA), 1999, vol. 36, pp. 1681-1690 (Non-patent reference 10) Arthritis & Rheumatism , (USA), 1998, vol. 41, pp. 1591-1602 (Non-patent reference 11) “ Medicine ”, edited by J. Axford, (USA), Blackwell Science, 1996, pp. 3.18-3.22
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 shows increase in the expression of NOX1-b mRNA in RA patient-derived synovial cells. FIG. 2 shows ROS producing activity of NOX1-b and inhibition by DPI. FIG. 3 shows increase in the expression of COX-2 mRNA and inhibition by DPI in NOX1-b expressing cells. FIG. 4 shows increase in the expression of TNF-α mRNA and inhibition by DPI in NOX1-b expressing cells. detailed-description description="Detailed Description" end="lead"?
20040929
20070306
20050609
86169.0
0
CHOWDHURY, IQBAL HOSSAIN
NOVEL OXIDASE
UNDISCOUNTED
0
ACCEPTED
2,004
10,509,928
ACCEPTED
Clip for fire detector wire
A clip assembly (111) having a clamp member (115) with opposing fingers (121 and 123) configured to form a channel, and an insert member (129) that holds the fire detector wire (128) is disclosed. The insert member (128) is made of, coated with, or treated with an anti-friction material. The insert member includes end flanges (133, 135) that retain the insert member between the opposing fingers. The fire detector wire is installed into the insert member, and the insert member is then snapped into the channel formed by the opposing fingers of the clamp member.
1. A clip for mounting a fire detector wire to a structure comprising: a clip member comprising: a base portion adapted for mounting to the structure; at least two mounting apertures passing through the base portion; and a clamp portion upraised from the base portion having opposing spring action finger members; an anti-friction insert member adapted to carry the fire detector wire comprising: an elongated shaft portion; an axial central channel for receiving the fire detector wire; a longitudinal slot for allowing access to the central channel; and a flange on each end of the elongated shaft; wherein the insert member is configured to be releasably clamped between the finger members, the flanges preventing axial movement of the insert member relative to the finger members. 2. The clip according to claim 1, wherein the spring action finger members include opposing curves that define a channel configured to clampingly receive the insert member. 3. The clip according to claim 1, wherein the insert member is made of polytetrafluoroethylene. 4. The clip according to claim 1, further comprising: a lubricant disposed between the base portion and the structure.
TECHNICAL FIELD The present invention relates to mounting clips. In particular, the present invention relates to mounting clips for fire detector wires in aircraft. DESCRIPTION OF THE PRIOR ART Fire detector wires have been in used in aircraft for many years. They are installed in aircraft at selected locations to produce warning signals when fires break out or when temperatures exceed predetermined limits. These fire detector wires typically consist of two non-insulated electrical conductors in a sealed tube filled with a dielectric material or a gaseous material. If the temperature of the fire detector wire exceeds a predetermined temperature limit, the dielectric material breaks down, causing the non-insulated electrical conductors to short circuit. This short circuit is detected and a corresponding signal is sent to the cockpit to alert the pilot that the temperature in the vicinity of the fire detector wire has exceeded the predetermined limit. Any damage to the sealed tube of the fire detector wire can result in a loss of the dielectric material or the gaseous material and failure of the fire detector wire. These fire detector wires are typically mounted to the aircraft structure with mounting clips. The purpose of the mounting clips is to prevent the fire detector wire from coming into direct contact with the aircraft structure. These mounting clips usually include a flat base portion and an upraised clamp portion. The mounting clip is installed onto the aircraft by fastening the base portion to the aircraft structure at a selected location. Then the fire detector wire is snapped into the clamp portion. One of these mounting clips is shown in FIGS. 1A and 1B in the drawings. A prior-art clip 11 includes a flat base portion 13 and an upraised clamp portion 15. Base portion 13 includes a single mounting aperture 17 through which a fastener (not shown) passes to secure clip 11 to a structure 19 of an aircraft. Clamp portion 15 includes a plurality of opposing fingers 21, 23, and 25 that act as springs and form a channel 27 for receiving a fire detector wire (not shown). Clip 11 typically includes a surface lubricant to protect against fretting between base portion 13 and structure 19. Other prior-art fire detector mounting clips involve loop-type clamps and hinges. These clips require complicated moving parts that must be fastened after the fire detector wire is installed. This can be a very labor intensive task, as the clips are often Installed in hard to reach places. On some of these clips, the clamping portions may be lined with rubber or plastic sleeves. These loop-type clips are very expensive and typically stand much higher than the finger-type clips. All of these prior-art clips for fire detector wires have significant problems. For those with only one mounting aperture, the clips tend to rotate when subjected to vibration. This causes crimping and chafing of the fire detector wire. In addition, because there is not sufficient anti-friction protection between the opposing fingers and the fire detector wire, chafing of the fire detector wire can take place when the clip is subjected to vibration. For those with closed loops and hinges, they stand too high and involve too much time and labor to install. Thus, many shortcomings remain in the area of mounting systems for fire detector wires in aircraft. SUMMARY OF THE INVENTION There is a need for a clip for a fire detector wire in an aircraft that does not rotate when subjected to vibration, and that provides sufficient means of preventing crimping and chafing of the fire detector wire. Therefore, it is an object of the present invention to provide a clip for a fire detector wire in an aircraft that does not rotate when subjected to vibration, and that provides sufficient means of preventing crimping and chafing of the fire detector wire. These objects are achieved by providing a clip assembly having a clamp member with opposing fingers configured to form a channel, and an insert member that holds the fire detector wire. The insert member is made of, coated with, or treated with an anti-friction material. The insert member includes end flanges that retain the insert member between the opposing fingers. The fire detector wire is installed into the insert member, and the insert member is then snapped into the channel formed by the opposing fingers of the clamp member. The present invention provides significant benefits and advantages, including: (1) the clip does nor rotate relative to the aircraft structure when subjected to vibration, thereby preventing crimping and chafing of the fire detector wire; (2) the anti-friction insert member prevents chafing of the fire detector wire; (3) the end flanges of the insert member retain the insert member in the proper position between the opposing fingers of the clamp member; and (4) once the insert member is installed into the clap member, no further fastening or adjustment is required. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 A is a top view of a prior-art clip for a fire detector clip. FIG. 1 B is a front view of the prior-art clip of FIG. 1 A. FIG. 2 is an assembled perspective view of the clip for fire detector wire according to the present invention. FIG. 3 is a top view of the clip member of the clip of FIG. 2. FIG. 4 is a front view of the clip member of FIG. 3. FIG. 5 is a right side view of the clip member of FIG. 3. FIG. 6 is a front view of the insert member of the clip of FIG. 2. FIG. 7 is an end view of the insert member of FIG. 6. DESCRIPTION OF THE PREFERRED EMBODIMENT The present invention is a clip assembly for retaining a fire detector wire. The clip assembly of the present invention is shown In assembled form FIG. 2 and comprises a clip member 111 as shown In FIGS. 3-5, and an insert member 129 as shown in FIGS. 6 and 7. Although the present Invention will be described with respect to an aircraft application, it should be understood that the clip assembly of the present invention may be used in any vehicle or structure in which it is desirable to install a fire detector wire. Referring now to FIG. 2 and FIGS. 3-5 in the drawings, clip member 111 is illustrated. Clip member 111 Includes a flat base portion 113 and an upraised clamp portion 115. Base portion 113 includes at least two mounting apertures 117 through which are passed conventional fasteners (not shown) for securing clip member 111 to an aircraft structure 119. The presence of at least two mounting apertures 117 prevents clip member 11 from rotating relative to structure 119. Base portion 113 transitions into a clamp portion 115 that includes a plurality of upraised finger members 121, 123, and 125. Finger members 121, 123, and 125 extend up from base portion 113 at a selected angle A from structure 119. In the preferred embodiment, angle A is about 25°. Finger members 121, 123, and 125 extend up in a co-planar fashion for a short distance, and then finger members 121 and 123 transition into downward facing curves, while finger member 125 transitions into an opposing upward facing curve. These opposing curves form a channel 127 that is configured to releasably receive insert member 129. Opposing finger members 121, 123, and 125 act as springs to secure insert member 129 in place. Although channel 127 does not have a completely circular cross section, channel 127 has a minimum clearance C. This configuration ensures that a fire detector wire 128, which is secured within insert member 129, does not come into direct contact with structure 119. Clip member 111 is preferably manufactured from a metallic material with sufficient elastic properties to perform the desired spring functions. In the preferred embodiment, at least base portion 113 is coated with, or otherwise treated, with a lubricant to prevent fretting between base portion 113 and structure 119. Referring now to FIG. 2 and FIGS. 6 and 7 in the drawings, insert member 129 is illustrated in a front view and an end view, respectively. Insert member includes an elongated shaft portion 131 that terminates with flanges 133 and 135 on the opposing ends. Insert member 129 includes an axial central channel 137 that extends along the entire length of insert member 129. Although central channel 137 is shown having a circular cross-sectional geometry, it should be understood that the geometric cross-sectional shape of central channel may be other than circular to accommodate the cross-sectional shape of fire detector wire 128. A longitudinal slot 139 extends along the entire length of insert member 129, and allows access to central channel 137. Fire detector wire 128 is inserted into slot 139 and pressed into central channel 137. In the preferred embodiment, the width T of slot 139 is smaller than the diameter of central channel 137. This configuration facilitates the securing of fire detector wire 128 within central channel 137. Shaft portion has a length L between flanges 133 and 135 that is dimensioned to correspond to a width W between the outside edges of finger members 121 and 123. This ensures that flanges 133 and 135 remain on the outside of finger members 121 and 123, and that insert member 129 does not move axially while held in place between finger members 121, 123, and 125. In addition, shaft portion has an outside diameter D between flanges 133 and 135 that Is dimensioned to correspond to clearance C between the curves formed by finger members 121, 123, and 125, such that a small compressive load is exerted upon insert member 129 by finger members 121, 123, and 125. In the preferred embodiment, insert member 129 is made of polytetrafluoroethylene. However, it should be understood that in alternate embodiments other suitable anti-friction materials may be used, or insert member 129 may be manufactured from other materials, covered with, coated with, or otherwise treated with polytetrafluoroethylene or any other suitable anti-friction material. In operation, clip member 111 is secured to structure 119 by passing conventional fasteners through mounting apertures 117. Then, fire detector wire 128 is inserted through slot 139 into central channel 137 of insert member 129. Insert member 129 and fire detector wire 128 are then snapped into channel 127 of clip member 111. No other clamping, fastening, hinging, or adjusting is required. The multiple fasteners prevent clip member 111 from rotating relative to structure 119 due to vibration of the aircraft. This prevents crimping and chafing of fire detector wire 128. Insert member 129 is held in place by flanges 133 and 135. This further prevents chafing of fire detector wire 128. The present invention provides significant benefits and advantages, including: (1) the clip does nor rotate relative to the aircraft structure when subjected to vibration, thereby preventing crimping and chafing of the fire detector wire; (2) the anti-friction insert member prevents chafing of the fire detector wire; and (3) the end flanges of the insert member retain the insert member in the proper position between the opposing fingers of the clamp member. It is apparent that an invention with significant advantages has been described and illustrated. Although the present invention is shown in a limited number of forms, it is not limited to just these forms, but is amenable to various changes and modifications without departing from the spirit thereof.
<SOH> TECHNICAL FIELD <EOH>The present invention relates to mounting clips. In particular, the present invention relates to mounting clips for fire detector wires in aircraft.
<SOH> SUMMARY OF THE INVENTION <EOH>There is a need for a clip for a fire detector wire in an aircraft that does not rotate when subjected to vibration, and that provides sufficient means of preventing crimping and chafing of the fire detector wire. Therefore, it is an object of the present invention to provide a clip for a fire detector wire in an aircraft that does not rotate when subjected to vibration, and that provides sufficient means of preventing crimping and chafing of the fire detector wire. These objects are achieved by providing a clip assembly having a clamp member with opposing fingers configured to form a channel, and an insert member that holds the fire detector wire. The insert member is made of, coated with, or treated with an anti-friction material. The insert member includes end flanges that retain the insert member between the opposing fingers. The fire detector wire is installed into the insert member, and the insert member is then snapped into the channel formed by the opposing fingers of the clamp member. The present invention provides significant benefits and advantages, including: (1) the clip does nor rotate relative to the aircraft structure when subjected to vibration, thereby preventing crimping and chafing of the fire detector wire; (2) the anti-friction insert member prevents chafing of the fire detector wire; (3) the end flanges of the insert member retain the insert member in the proper position between the opposing fingers of the clamp member; and (4) once the insert member is installed into the clap member, no further fastening or adjustment is required.
20041001
20111220
20050609
63483.0
0
WOOD, KIMBERLY T
CLIP FOR FIRE DETECTOR WIRE
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,211
ACCEPTED
Thermoplastic composition comprising an aromatic polycarbonate and/or a polyester with improved mould release behaviour
The invention relates to a thermoplastic composition comprising (a) an aromatic polycarbonate and/or a polyester, and (b) an effective amount of a mould release agent containing (b1) a fatty acid ester of an aliphatic polyol having 2-6 hydroxy groups and an aliphatic C10-C36 carboxylic acid; and (b2) a saturated alpha-olefin oligomer of at least one C6-C18 alpha-olefin; the mass ratio of components (b1) and (b2) being from 1/9 to 9/1. With this thermoplastic composition a very regular injection moulding processing is possible, with lower release forces needed during demoulding of parts, and with shorter total moulding cycle-times. The invention further concerns the use of the thermoplastic composition according to the invention for injection moulding of articles and to moulded articles thus obtained.
1. Thermoplastic composition comprising (a) an aromatic polycarbonate or a blend of aromatic polycarbonate and polyester, in which the polycarbonate forms the continuous phase, and (b) a mould release agent, wherein the composition comprises 0.01-3 mass % of a mould release agent that contains (b1) a fatty acid ester of an aliphatic polyol having 2-6 hydroxy groups and an aliphatic C10-C36 carboxylic; and (b2) a saturated alpha-olefin oligomer of at least one C6-C18 alpha-olefin; with a mass ratio of components (b1) and (b2) of from 1/9 to 9/1. 2. Thermoplastic composition according to claim 1, wherein (a) is bisphenol A polycarbonate. 3. Thermoplastic composition according to claim 1, wherein the polyol in component (b1) has 3-4 hydroxy groups. 4. Thermoplastic composition according to claim 1, wherein the carboxylic acid in component (b1) is a C16-C22 fatty acid. 5. Thermoplastic composition according to claim 1, wherein component (b1) comprises pentaerythritol tetrastearate. 6. Thermoplastic composition according to claim 1, wherein component (b2) has a molar mass of about 400-800 g/mol. 7. Thermoplastic composition according to claim 1, wherein component (b2) is an oligomer of a C8-C12 poly-alpha-olefin. 8. Thermoplastic composition according to claim 1, wherein component (b2) is an oligomer of a C10 poly-alpha-olefin. 9. Thermoplastic composition according to claim 1, wherein the mass ratio of components (b1) and (b2) is from 1/6 to 6/1. 10. Thermoplastic composition according to claim 1, wherein the amount of mould release agent (b) is about 0.25-0.75 mass %. 11. Use of the thermoplastic composition according to claim 1 for injection moulding of articles. 12. Moulded articles made from the thermoplastic composition according to claim 1. 13. A method for making an injection molded article comprising injection molding a thermoplastic composition as set forth in claim 1.
The invention relates to a thermoplastic composition comprising (a) an aromatic polycarbonate and/or a polyester, and (b) a mould release agent. The invention further concerns the use of the thermoplastic composition according to the invention for injection moulding of articles and to moulded articles thus obtained. Such a thermoplastic composition is known from U.S. Pat. No. 4,626,566. In this patent publication a composition is disclosed that comprises an aromatic polycarbonate in an admixture with a mould release effective amount of a hydrogenated alpha-olefin oligomer fluid, preferably about 0.01-1 mass %. This composition is described to show better mould release behaviour than conventional agents, like pentaerythritol tetrastearate; that is lower ejection forces suffice to remove a moulded part from the opened mould of an injection moulding machine. Effective mould release behaviour is a key property for a thermoplastic composition to enable efficient and economic processing into formed articles via injection moulding. Normally a mould release agent (MRA) needs to be added to a composition to enable such processing behaviour. In order to function effectively as a MRA, such agent or compound must be stable at the processing conditions so that it will not loose its effectiveness and/or cause discoloration, and must not chemically interact with the polymers and other components of the composition, or otherwise adversely affect the composition. In case of transparent or translucent polymers, the MRA should not deteriorate transparency. During injection moulding, the MRA should not form deposits on the surface of the mould, nor should it after moulding migrate to the surface of the part to such extent that it becomes visible on the surface, often called blooming. Identification of inert yet more effective release agents remains therefore a continuous subject of attention. A disadvantage of the known thermoplastic composition described in U.S. Pat. No. 4,626,566 is, that it does not show problem-free mould release behaviour in every type of mould, especially not in moulds for relatively large parts or for parts with walls having little draft, causing irregular processing or high release forces, possibly resulting in distortion of an ejected part. Another disadvantage is that during demoulding of parts a squeaking noise may be made. It is therefore an object of the present invention to provide a thermoplastic composition that shows a more regular processing behaviour, with lower release forces during demoulding of parts. This object is achieved according to the invention with a thermoplastic composition that comprises 0.01-3 mass % of a mould release agent that contains (b1) a fatty acid ester of an aliphatic polyol having 2-6 hydroxy groups and an aliphatic C10-C36 carboxylic acid; and (b2) a saturated alpha-olefin oligomer of at least one C6-C18 alpha-olefin; with a mass ratio of components (b1) and (b2) of from 1/9 to 9/1. The thermoplastic composition according to the invention enables a very regular injection moulding processing, with lower release forces needed during demoulding of parts. A further advantage is that virtually no additional sounds, like squeaking, are made during processing. A still further advantage is that the total moulding cycle-time for a given part can be reduced, contributing to a more economic process. Furthermore, no slip-stick effects are observed during demoulding, leading to very smooth surfaces of moulded parts. It is rather surprising to find that these specific compounds form a synergetic combination showing such advantageous properties of a thermoplastic composition, since use of both compounds as release agents per se is known, even from one publication: in U.S. Pat. No. 4,626,566 pentaerythritol tetrastearate is used in comparative experiments. It is true that in U.S. Pat. No. 4,626,566 a general remark is made that the composition comprising alpha-olefin oligomer may further comprise lubricants such as the synthetic and naturally occurring polyol esters, but the combination according to the present invention is not specifically disclosed, nor is it suggested that such combination would show any synergetic effect as described in the present invention. U.S. Pat. No. 5,717,021 teaches to add 0.1-8 mass % of an aliphatic C4-C16 polyalpha olefin oligomer to a polycarbonate composition to improve its melt flow characteristics, which composition may further comprise a mould release agent. Specifically disclosed, however, are only compositions containing 0.15 mass % of pentaerythritol tetrastearate and 0.5-6 mass % of a polybutene copolymer of isobutylene and butene; whereas mould release behaviour is not addressed. The thermoplastic composition according to the invention comprises an aromatic polycarbonate and/or a polyester. In principle, any known aromatic polycarbonate may be used. Suitable aromatic polycarbonates in this composition are polycarbonates made from at least one dihydric phenol and a carbonate precursor, for example by using an interfacial polymerisation process. Suitable dihydric phenols that may be applied are compounds with one or more aromatic rings containing two hydroxyl groups, each directly attached to a carbon atom of an aromatic ring. Examples of such compounds include 4,4′-dihydroxybiphenyl, 2,2-bis(4-hydroxyphenyl)propane (bisphenol-A), 2,2-bis(4-hydroxy-3-methylphenyl)propane, 2,2-bis-(3-chloro-4-hydroxyphenyl)-propane, 2,2-bis-(3,5-dimethyl-4-hydroxyphenyl)-propane, 2,4-bis-(4-hydroxyphenyl)-2-methylbutane, 2,4-bis-(3,5-dimethyl-4-hydroxyphenyl)-2-methylbutane, 4,4-bis(4-hydroxyphenyl)heptane, bis-(3,5-dimethyl-4-hydroxyphenyl)-methane, 1,1-bis-(4-hydroxyphenyl)-cyclohexane, 1,1-bis-(3,5-dimethyl-4-hydroxyphenyl)-cyclohexane, 2,2-(3,5,3′,5′-tetrachloro-4,4′-dihydroxybiphenyl)propane, 2,2-(3,5,3′,5′-tetrabromo-4,4′-dihydroxybiphenyl)propane, (3,3′-dichloro-4,4′-dihydroxyphenyl)methane, bis-(3,5-dimethyl-4-hydroxyphenyl)-sulfone, bis-4-hydroxyphenylsulfone, bis-4-hydroxyphenylsulfide. The carbonate precursor can be a carbonyl halogenide, a halogen formiate or a carbonate ester. Examples of carbonyl halogenides include carbonyl chloride and carbonyl bromide. Examples of suitable halogen formiates are bis-halogen formiates of dihydric phenols like hydrochinon or of glycols like ethylene glycol. Examples of suitable carbonate esters include biphenyl carbonate, di(chlorophenyl)carbonate, di(bromophenyl)carbonate, di(alkylphenyl)carbonate, phenyltolyl carbonate and mixtures thereof. Although other carbonate precursors may be used as well, carbonylhalogenides and especially carbonylchloride, better known as phosgene, are preferred. The aromatic polycarbonates in the composition according to the invention may be produced from said compounds with known methods of preparation. In general, also a catalyst, an acid acceptor, and a compound for controlling the molar mass of the polycarbonate are used. Examples of a catalyst that may be used include tertiary amines like triethyl amine, tripropyl amine and N,N-dimethyl aniline, quaternary ammonium compounds like tetraethylammonium bromide en quaternary phosphonium compounds such as methyltriphenyl phosphoniumbromide. Examples of suitable acid acceptors include organic compounds like pyridine, triethyl amine, dimethyl aniline. Examples of inorganic acid acceptors are hydroxides, carbonates, bicarbonates and phosphates of an alkali- or earthalkali metal. Examples of compounds that can be used for controlling the molecular mass include monohydric phenols like phenol, p-alkylphenols, para-bromophenol and secundary amines. Within the definition of polycarbonate are also copolycarbonates made from at least two dihydric phenols and copolyester-carbonates, that are copolymers made from a dihydric phenol, a dicarboxylic acid and a carbonate precursor. Such aromatic polycarbonates, and their preparation and properties have been extensively described in for example Encycl. Polym. Sci. Eng., 11, p. 648-718 (Wiley, New York, 1988); or in Kunststoff Handbuch, 3/1, p. 117-297 (Hanser Verlag, Muenchen, 1992). In a special embodiment, the composition according to the invention contains a polycarbonate made from bisphenol-A and phosgene, and optionally minor amounts of other compounds with one, two, or more reactive groups, the latter compounds as comonomers, for example to affect the melt viscosity of the polymer. Such polymers, often referred to as bisphenol-A polycarbonate, or even simply polycarbonate (PC), are commercially available and are advantageously used as a construction material. The thermoplastic composition according to the invention may also comprise a polyester. In principle, all current thermoplastic polyesters and copolyesters can be used as the thermoplastic polyester in the composition according to the invention. Examples of such polyesters include essentially linear polyesters made via a condensation reaction of at least one dicarboxylic acid (diacid), or an ester-forming derivative thereof, and at least one dihydric alcohol (diol). The diacid and diol may both be either aliphatic or aromatic, but especially aromatic and partly aromatic polyesters are of interest as thermoplastic moulding materials in view of their high softening points and hydrolytic stability. Aromatic polyesters, also referred to as polyarylates, have essentially all ester linkages attached to aromatic rings. They may be semi-crystalline and even show liquid crystalline behaviour, or amorphous. Partly aromatic polyesters, obtained from at least one aromatic dicarboxylic acid (diacid), or an ester-forming derivative thereof, and at least one aliphatic diol are the preferred polyesters for the present invention. Examples of suitable aromatic dicarboxylic acids include terephthalic acid, 1,4-naphthalenedicarboxylic acid, or 4,4′-biphenyldicarboxylic acid. Suitable aliphatic diols are alkylene diols, especially those containing 2-6 C-atoms, preferably 2-4 C-atoms. Examples thereof include ethylene glycol, propylene diols and butylene diols. Preferably ethylene glycol, 1,3-propylene diol or 1,4-butylene diol are used, more preferably 1,4-butylene diol. Suitable partly aromatic polyesters are polyalkylene terephthalates, for example polyethylene terephthalate (PET), polypropylene terephthalate (PPT), or polybutylene terephthalate (PBT); polyalkylene naphthalates, for example polyethylene naphthalate (PEN), polybutylene naphthalate (PBN); polyalkylene dibenzoates, for example polyethylene bibenzoate; and blends or copolyesters hereof. Preferably, PET, PBT, PEN and PBN are used, more preferably PBT and PET, because of their commercial availability and advantageous combination of processing and performance properties. Such partly aromatic polyesters may optionally also contain a minor amount of units derived from other dicarboxylic acids, for example isophthalic acid, or other diols like cyclohexanedimethanol, which generally lowers the melting point of the polyester. The amount of other diacids or diols is preferably limited, unless it is desired to reduce the semi-crystalline character of the polyester. A special group of partly aromatic polyesters are so-called segmented or block copolyesters which, in addition to polyester segments from the above group of partly aromatic polyesters, called hard segments, also contain so-called soft segments. Such soft segments are derived from a flexible polymer; that is a substantially amorphous polymer with a low glass-transition temperature (Tg) and low stiffness, having reactive end-groups, preferably two hydroxyl groups. Preferably the T9 is below 0° C., more preferably below −20, and most preferably below −40° C. In principle various different polymers can be used as soft segment, suitable examples are aliphatic polyethers, aliphatic polyesters, or aliphatic polycarbonates. The molar mass of the soft segments may vary within a wide range, but is preferably chosen between 400 and 6000 g/mol. These block copolyesters, especially polyether esters, are useful as thermoplastic elastomers. Above mentioned thermoplastic polyesters, their preparation and properties are extensively described in for example “Encyclopedia of Polymer Science and Engineering”, Vol. 12, p. 1-75 and p217-256; John Wiley & Sons (1988), and in “Ullmann's Encyclopedia of Industrial Chemistry”, Vol. A21, p. 227-251; VCH Publishers Inc (1992); and in the references mentioned therein. The thermoplastic composition according to the invention may also comprise a blend of aromatic polycarbonate and polyester. In such blend both the polycarbonate and/or the polyester can be the major component; that is form a continuous phase or matrix. The ration between the polycarbonate and the polyester may vary between wide limits, e.g. from 1/9 to 9/1. The advantage of these blends is that an optimum combination of properties may be obtained. Preferably, the composition comprises a blend of bisphenol-A polycarbonate and polybutylene terephthalate. The composition according to the invention comprises an effective amount of (b1) a fatty acid ester of an aliphatic polyol having 2-6 hydroxy groups and an aliphatic C10-C38 carboxylic acid, and (b2) a saturated alpha-olefin oligomer of at least one C6-C18 alpha-olefin as mould release agent. An effective amount is understood to be any amount that reduces the force needed to eject an article from a mould and to obtain an article without distinct surface defects or distortions, as compared to a situation wherein no MRA is used. The composition according to the invention contains at least one fatty acid ester of an aliphatic polyol having 2-6 hydroxy groups and an aliphatic C10-C36 carboxylic acid as component (b1). Such compounds are well known, as are methods for their preparation. These compounds are monomeric polyesters made by reacting a polyol and a fatty acid. All or only part of the hydroxyl groups in the polyol may be esterified, depending on the molar ratio of fatty acid to hydroxyl groups. Preferably, the composition contains a fatty acid ester that has still some hydroxyl-functionality, since these compounds are found to be more effective. Both the aliphatic polyol and aliphatic carboxylic acid may be linear or branched. Preferably, the polyol and the carboxylic acid are fully saturated, because such compounds show better thermal stability. Examples of suitable aliphatic polyols (polyhydric alcohols) having 2-6 hydroxy groups include alkylene glycols, like ethylene glycol, propylene glycol, neopentyl glycol; polyglycols like diethylene glycol; glycerol, trimethylolethane, trimethylolpropane, ditrimethylolpropane, pentaerythritol, sorbitol, or mannitol. Mixtures of these compounds may also be used. Preferably, the polyol in component (b1) has 3-4 hydroxy groups. Examples thereof include glycerol, trimethylolethane, trimethylolpropane, ditrimethylolpropane, and pentaerythritol. Compounds (b1) derived herefrom show good compatibility with the polymer in the composition. Examples of suitable aliphatic C10-C36 carboxylic acid include capric acid, lauric acid, palmitic acid, stearic acid, behenic acid and montanic acid. Mixtures of these compounds may also be used. Preferably, the carboxylic acid contains 12-30; more preferably 14-28 carbon atoms. Most preferably the carboxylic acid in component (b1) is a C16-C22 fatty acid, because then an optimum balance is reached between compatibility of the fatty acid ester with the polymer and component (b2) in the composition and release performance. Very good results are obtained with esters of stearic acids, for example with compositions comprising glycerol monostearate, glycerol tristearate, and especially pentaerythritol tetrastearate as component (b1). Such compounds are commercially available from various sources. The composition according to the invention contains at least one saturated alpha-olefin oligomer of at least one C6-C18 alpha-olefin as component (b2). Such compounds and their preparation are known in the art. The compounds can for example be made by catalytic oligomerisation of an alpha-olefin, followed by hydrogenation to remove unsaturation. Such compounds are of oily or waxy nature, and show good fluidity over a wide temperature range. The compound is generally a mixture of oligomers of different degrees of polymerisation, branching and isomerisation, depending on their preparation. Suitable products generally have a molar mass (meant is number averaged molar mass, Mn, unless indicated otherwise) from about 250 up to several thousands. In view of their viscosity, alpha-olefin oligomers with a molar mass below about 1000 g/mol are preferred, more preferably the molar mass is about 400-800 g/mol, most preferably the molar mass is about 450-650 g/mol. This provides a better balance of material handling and release behaviour of the thermoplastic composition. The saturated alpha-olefin oligomer may be derived from a number of different alpha-olefins of mixtures thereof, but preferably component (b2) is an oligomer of a C8-C12 or even a C9-C11 poly-alpha-olefin, in order to optimise compatibility and release behaviour. Excellent results are obtained with a composition comprising as component (b2) oligomers of a C10 poly-alpha-olefin. Such compounds are for example commercially available from BP Chemicals under the trade name Durasyn®. The mass ratio between the two components (b1) and (b2) in the thermoplastic composition according to the invention can in principle vary between wide limits to show improved mould release behaviour. Preferably, the mass ratio of components (b1) and (b2) is from 1/9 to 9/1, to markedly reduce slip-stick effects. Lower ejection forces are especially obtained, when the mass ratio of components (b1) and (b2) is from 1/6 to 6/1, from 1/4 to 4/1, more preferably from 1/3 to 3/1, even more preferably from 2/3 to 3/2. Also a combination of any of the upper and lower ranges may be applied. Very good overall processing and demoulding behaviour was found for compositions wherein the mass ratio of components (b1) and (b2) is about 1/1. The composition according to the invention comprises an effective amount of the above described components as mould release agent. Generally, an amount of from about 0.01 mass % is needed to have any effect. Using more than about 3 mass % adds in general little to release performance, but may have negative effects on other properties or processing behaviour. Preferably, the amount of mould release agent (b) is about 0.05-2 mass %, more preferably 0,1-1 mass %, even more preferably 0,25-0,75 and still more preferably about 0,4-0,6 mass % to optimise processing and demoulding behaviour. A thermoplastic composition comprising bisphenol-A polycarbonate as (a) and 0.4-0.6 mass % of a 2/3 to 3/2 mixture of pentaerythritol tetrastearate and a C10 alpha-olefin oligomer as (b) shows remarkably good processing and mould release behaviour even when being processed into large complicated products. An additional advantage of the mould release system according to the invention is that it does not deteriorate optical transparency of a polycarbonate composition. The thermoplastic composition according to the invention generally contains at least one polycarbonate and/or at least one polyester polymer as a major component; which is forming a continuous or matrix phase of the composition. The composition may comprise from 99.99 to 30 mass % of at least one of said polymers, preferably at least 40, more preferably at least 50 mass %. The composition may further comprise up to 70 mass %, preferably up to 60 or 50 mass % of one or more other polymers, e.g. as impact-modifiers, filler materials and reinforcing agents, and/or flame retarding compounds. Examples of other polymers that may be comprised in the composition according to the invention are known to the skilled person, and include polyolefins like ethylene (co)polymers and ethylene-propylene elastomers, optionally modified or functionalised to improve compatibility with polyesters; styrenic copolymers, like (modified) styrene-butadiene block-copolymers (SBS, SEBS), styrene-acrylonitril copolymers (SAN), or acrylonitrile-butadiene-styrene copolymers (ABS); acrylonitrile-ethylene-propylene-styrene copolymers (AES); acrylonitrile-acrylic elastomer-styrene copolymers (AAS); (meth)acrylic copolymers, like ethylene-alkyl(meth)acrylate copolymers, or terpolymers further comprising glycidyl(meth)acrylates. Polyester-based compositions preferably comprise at least one of the latter terpolymers as impact-modifier, optionally in combination with non-functional or non-reactive copolymers. In a preferred embodiment, a polycarbonate-based composition further contains SAN and/or ABS copolymers. Such a PC/ABS composition, comprising the release agent according to the invention was found to show markedly improved mould release behaviour. Examples of suitable filler materials include various mineral particles, like mica, talcum, clay and the like. Suitable reinforcing agents include, for example, glass fibres, carbon fibres and mineral fibres. Glass fibres are preferred, and are generally provided with a suitable sizing agent As flame retarding compounds any compound known to be effective in polycarbonate and/or polyester compositions may be applied, both halogenated and halogen-free compounds. Preferably, the composition comprises a halogen-free flame retarding compound, like a phosphorous-containing compound. Preferred compounds include phosphoric esters, like triphenylphosphate (TPP); resorcinol bis(diphenylphosphate) (RDP), bisphenol A bis(diphenylphosphate) (BDP) or substituted derivatives or oligomers of these; or metal-phosphinates, optionally in combination with nitrogen-compounds. The composition may further comprise any customary additives, like heat- and UV-stabilisers, anti-oxidants, other processing aids, nucleating agents, colorants and anti-dripping agents, generally in minor amounts of up to several mass % each. The composition according to the invention can be obtained by mixing or blending the various components applying known techniques. The mixing may be a ‘dry’ blending operation, wherein the various components are mixed below the melt-processing temperatures of the polycarbonate and/or polyester; or a melt-blending process, wherein the components, optionally pre-blended, are mixed at suitable melt-processing temperatures, e.g. in a single- or twin-screw extruder. Also a combination of dry- and melt-blending techniques can be applied. The invention also relates to the use of the thermoplastic composition according to the invention for injection moulding of articles, since these novel compositions show advantageous properties during injection moulding operation; that is a very stable operation, easy mould release without slip-stick effects, and shorter overall moulding cycles. The invention further concerns moulded articles made from the thermoplastic composition according to the invention, especially via an injection moulding process. Such moulded articles can be made with less surface defects originating from demoulding operation, like streakes or scratches, and can be produced with shorter moulding cycle-time, thus at lower cost. The invention will now be further illustrated with the following examples and comparative experiments. Materials Following materials were used: PC a bisphenol-A polycarbonate with Limiting Viscosity Number of 46 ml/g (as determined on a solution is dichloromethane at 25° C.; ISO 16828/4); available as Xantar® 19 R (DSM Engineering Plastics, NL); PETS pentaerythritol tetrastearate (actual degree of esterification about 88%); available as Loxiol® EP 861 (Cognis, DE); GMS glycerol monosterate; available as Loxiol® EP12 (Cognis, DE); PAO1 saturated alpha-olefin oligomer of 1-decene, Mn about 450 g/mol; Durasyn 164 (BPChemicals, BE); PAO2 saturated alpha-olefin oligomer of 1-decene, Mn about 570 g/mol; Durasyn 166 (BPChemicals, BE). Injection moulding Mould release performance of different compositions was evaluated during injection moulding of a cylindrical beaker (of diameter 60 mm, height 70 mm and wall thickness of 1.8 mm) with a demoulding angle of 0° on an Engel 80 machine. Temperature settings of the cylinder were 280-290° C. (from hopper to nozzle), resulting in a melt temperature of 305° C. and the mould was kept at a constant temperature of 80° C. The mould was equipped with ejector pins, of which one was connected to a Kistler type 9021A force transducer. After initially discarding about 25 shots, demoulding forces were automatically registered and monitored during moulding of at least 75 subsequent shots. From shot numbers 1, 30 and 75 a detailed force registration with time was made. The average release force is calculated as the average value of the maximum in the demoulding force registered during 75 shots. Comparative Experiment A. A composition comprising PC, 0.3 mass % of PETS, and 0.2 mass % of GMS was made by melt mixing the components on a ZSK25 twin-screw extruder, and drying the obtained granules. Mould release performance was evaluated as indicated above; the results are summarized in Table 1. In FIG. 1 the detailed force registration is presented for shot number 75. Shown is the release force (as measured with the Kistler element) as a function of time. Comparative Experiments B and C. Similar to comparative experiment A, compositions were made and tested; except that in B the composition contains 0.6 mass % of PAO1 as MRA; and in C 0.6 mass % of PAO2 is used. Results are given in Table 1. In FIG. 2 the detailed force registration for shot number 75 of Comp exp. B is presented. The oscillation in the registered force represents the slip-stick behaviour also observed visually: the part is not ejected in a smooth single movement. Visually examining the surface of the part also reveals a wave-like pattern. EXAMPLE 1 Analogous to the other experiments, a composition was made with the following combination as MRA: 0.15 mass % of PETS, 0.1 mass % of GMS and 0.3 mass % of PAO1. The results are presented in Table 1 and FIG. 3 (representing the detailed force registration for shot number 75). Note the very smooth curve and the low maximum force value. The surface quality of moulded parts was found to be excellent. EXAMPLE 2 For testing on semi-industrial scale a composition comprising PC, 0.3 mass % of PETS and 0.3 mass % of PAO2 was made by melt mixing the components on a ZSK70 twin-screw extruder, and drying the obtained granules. The composition was processed into a tray-like part of approximately 57*57*8 cm, with walls showing very little draft, using an Engel 3002 (800 tons) injection moulding machine at standard temperature settings. The part had a mass of about 2.2 kg. Processing appeared to be very smooth and stable, and no demoulding problems were encountered. By further optimising processing settings, the total cycle-time per shot could be reduced from 100 s to 80 s (i.e. a reduction of about 20%). The moulded part had excellent transparency and was virtually free from surface defects. Comparative Experiments D and E Analogous to Example 2 compositions containing 0.6 mass % of PAO2 and PETS, respectively, were made and subsequently processed into the same part. In both cases release problems and irregular processing were encountered. During demoulding of a part made from composition D, a squeaking sound was made. Stable processing appeared only possible, when total cycle-time was significantly increased. TABLE 1 Average release MRA force (N) observations Comp. Exp. A 0.3 PETS 1300 Constant release force; 0.2 GMS No slip-stick effect Comp. Exp. B 0.6 PAO1 2100 Increasing from 2000 to 2100 N; Slip-stick effect Comp. Exp. C 0.6 PAO2 1750 Increasing from 1600 to 1900 N; Slip-stick effect Example 1 0.15 PETS 1000 Constant release force; 0.1 GMS no slip-stick effect 0.3 PAO1 Example 2 0.3 PETS n.d. Problem-free processing; 0.3 PAO2 Excellent surface quality Comp. Exp. D 0.6 PAO2 n.d. Troublesome demoulding; squeaking Comp. Exp. E 0.6 PETS n.d. Troublesome demoulding; irregular From these experiments it can be concluded that a thermoplastic composition comprising polycarbonate and a MRA containing both a fatty acid ester and a saturated alpha-olefin oligomer, shows significantly better demoulding behaviour during injection moulding than compositions containing only one of said compounds: a very stable moulding process, no slip-stick behaviour, no unpleasant squeaking noises, and lower release forces during ejection of a part. At similar concentration, the present MRA according to the invention shows a synergetic effect over each of its components. The obtained moulded parts also showed better surface quality, due to the absence of demoulding-related surface defects.
20050504
20081104
20051020
76533.0
0
YOON, TAE H
THERMOPLASTIC COMPOSITION COMPRISING AN AROMATIC POLYCARBONATE AND/OR A POLYESTER WITH IMPROVED MOULD RELEASE BEHAVIOUR
UNDISCOUNTED
0
ACCEPTED
2,005
10,510,229
ACCEPTED
Antigen-presenting complex-binding compositions and uses thereof
A composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen is disclosed.
1-140. (canceled) 141. A method of killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, the method comprising exposing the target cell to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, thereby killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. 142. The method of claim 141, wherein said composition-of-matter further comprises a toxin attached to said antibody or antibody fragment. 143. The method of claim 142, wherein said toxin is Pseudomonas exotoxin A or a portion thereof. 144. The method of claim 141, further comprising the step of obtaining the target cell from an individual. 145. The method of claim 141, wherein said exposing the cell to said composition-of-matter is effected by administering said composition-of-matter to an individual. 146. The method of claim 141, wherein the target cell is infected with the pathogen. 147. The method of claim 141, wherein the target cell is a T-lymphocyte or an antigen presenting cell. 148. The method of claim 141, wherein said antigen presenting cell is a B cell or a dendritic cell. 149. The method of claim 141, wherein said antibody fragment is a single chain Fv. 150. The method of claim 141, wherein said antigen-binding region includes an amino acid sequence selected from the group consisting of SEQ ID NOs: 14 to 97. 151. The method of claim 141, wherein said binding of said antibody or antibody fragment to said antigen-presenting portion of said complex is characterized by an affinity having a dissociation constant selected from the range consisting of 1×10−2 molar to 5×10−16 molar. 152. The method of claim 141, wherein said human antigen-presenting molecule is a major histocompatibility complex molecule. 153. The method of claim 152, wherein said major histocompatibility complex molecule is a major histocompatibility complex class I molecule. 154. The method of claim 153, wherein said major histocompatibility complex class I molecule is an HLA-A2 molecule. 155. The method of claim 141, wherein said pathogen is a viral pathogen. 156. The method of claim 155, wherein said viral pathogen is a retrovirus. 157. The method of claim 156, wherein said retrovirus is human T lymphotropic virus-1. 158. The method of claim 141, wherein said antigen derived from a pathogen is restricted by the antigen-presenting molecule. 159. The method of claim 141, wherein said antigen derived from a pathogen is a polypeptide. 160. The method of claim 159, wherein said polypeptide is a segment of a Tax protein, or a polypeptide having an amino acid sequence as set forth in SEQ ID NO: 3. 161-195. (canceled)
FIELD AND BACKGROUND OF THE INVENTION The present invention relates to compositions-of-matter capable of specifically binding particular antigen-presenting molecule (APM):antigen complexes. More particularly, the present invention relates to compositions-of-matter capable of specifically binding a particular human APM:pathogen-derived antigen complex. Diseases caused by pathogens, such as viruses, mycoplasmas, bacteria, fungi, and protozoans, account for a vast number of diseases, including highly debilitating/lethal diseases, affecting all human individuals at numerous instances during their lifetime. For example, diseases caused by retroviruses are associated with various immunological, neurological, and neoplastic disorders. For example, diseases caused by lymphotropic retroviruses, such as acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV), or the closely related human T-cell lymphotropic virus (HTLV), a causative agent of various lethal pathologies (for general references, refer, for example to: Johnson J M. et al., 2001. Int J Exp Pathol. 82:135-47; and Bangham C R., 2000. J Clin Pathol. 53:581-6), account for lethal disease epidemics of devastating human and economic impact. However, satisfactory methods of diagnosing, characterizing, and treating many kinds of pathogen-associated diseases such as diseases associated with lymphotropic viruses such as HIV or HTLV are unavailable. HTLV-1 was the first human retrovirus identified (Poiesz B. J. et al., 1980. Proc Natl Acad Sci USA. 77:7415-7419). It infects both CD4+ and CD8+ T-lymphocytes and is associated with a variety of diseases, including adult T-lymphocyte leukemia/lymphoma (ATLL; Yoshida M. et al., 1982. Proc Natl Acad Sci USA. 79:2031-2035) and a non neoplasic inflammatory neurological syndrome called human T lymphotropic type I (HTLV-1)-associated myelopathy/tropical virus spastic paraparesis (HAM/TSP; Osame M. et al., 1986. Lancet 1:1031-1032; reviewed in Ribas J G. and Melo G C., 2002. Rev Soc Bras Med Trop. 35:377-84; and Plumelle Y., 1999. Med Hypotheses. 52:595-604). Other diseases linked to HTLV-1 infection on the basis of seroepidemiological studies include Sjogren's syndrome, inflammatory arthropathies, polymyositis, and pneumopathies (Coscoy L. et al., 1998. Virology 248: 332-341). The HTLV protein Tax seems to play a major role in the pathogenesis of HTLV-1 associated diseases. Tax protein is known to stimulate the transcription of viral and cellular genes such as the genes coding for interleukin-2 (IL-2) and other cytokines, interleukin-2 receptor (IL-2R), proto-oncogenes, c-jun and c-fos, and major histocompatibility complex (MHC) molecules (Yoshida M., 1993. Trends Microbiol. 1:131-135). The transforming potential of Tax has been demonstrated in different experimental systems. It has been shown that rodent fibroblastic cell lines expressing Tax form colonies in soft agar and tumors in nude mice (Tanaka A. et al., 1990. Proc Natl Acad Sci USA. 87:1071-1075). Also, Tax transforms primary fibroblasts in cooperation with the Ras protein (Pozzatti R. et al., 1990. Mol Cell Biol. 10:413-417), and immortalizes primary T-lymphocytes in the presence of IL-2 (Grassmann R. et al., 1989. Proc Natl Acad Sci USA. 86:3351-3355). Transgenic mice carrying the tax gene develop different types of tumors (Grossman W. J. et al., 1995. Proc Natl Acad Sci USA. 92:1057-1061). Tax binds directly to DNA but acts in cooperation with several cellular transcription factors, but the role of these different interactions in the cell transformation mediated by Tax is still unclear (Coscoy L. et al., 1998. Virology 248: 332-341). HAM/TSP is a progressive chronic demyelinating disorder affecting the white matter of the central nervous system (CNS) and the spinal cord. The disease affects approximately twice as many females as males, and typically the time of disease onset occurs during the fourth decade of life. The disease causes numerous highly debilitating symptoms, with common early symptoms and signs including gait disturbance and weakness and stiffness of the lower limbs. The disease affects the lower extremities to a much greater degree than upper extremities, spasticity may be moderate to severe, and lower back pain commonly occurs. Disease progression is associated with bowel and bladder dysfunction, and sensory loss and dysesthesia. Patients examined via magnetic resonance imaging may exhibit nonspecific lesions in the brain as well as spinal cord atrophy. Immune manifestations associated with HAM/TSP include inflammatory infiltrates in the central nervous system consisting predominantly of monocytes, and large numbers of CD8+ T-cells which are primarily reactive with peptides of the HTLV-1 Tax protein. The frequency of such T-cells in the peripheral blood and cerebrospinal fluid (CSF) has been shown to be proportional to the amount of HTLV-1 proviral load and the levels of HTLV-1 tax mRNA expression. It has further been shown that in patients carrying the HLA-A2 allele, the immune response is dominated by CD8+ T-lymphocytes that recognize the Tax11-19 peptide (Bieganowska K. et al., 1999. J Immunol. 162:1765-1771; Nagai, M. et al., 2001. J Inf Dis. 183:197-205). Thus, immunological determinants, such as the Tax11-19 peptide and antigenic mimics thereof, shared by thymus, brain and HTLV-1 are thought to direct lymphocytic neurotropism and demyelinization in nervous tissues. It is thought that the specificity of thoracic spinal cord involvement could be linked to shared thymic and thoracic spinal cord determinants, genetically peculiar to HAM/TSP patients. In a first stage, disease onset may be dependent on CD4+ T-lymphocytes specific for such determinants, reactivated in response to HTLV-1 infection, and that demyelinization during this stage could potentially be initiated as a result of stoppage in the synthesis of myelin following alteration of expression of oligodendrocytic and neuronal adhesion molecules. The second stage of the disease, involving chronic inflammatory manifestations, may depend on CD8+ T-lymphocytes specific for viral peptides, but also on CD8+ T-lymphocytes specific for peptides generated as a result of proteolysis of myelin layer, and other central nervous system proteins. While, at best, therapy of HAM/TSP with corticosteroids, and IFN-gamma may result transient responses, similarly to numerous diseases associated with lymphotropic viruses there is currently no effective treatment for HAM/TSP, nor does the state of the art currently enable optimal prediction, diagnosis, staging, monitoring, and prognosis of the disease in patients. The immune system employs two types of immune responses to provide antigen specific protection from pathogens; humoral immune responses, and cellular immune, responses, which involve specific recognition of pathogen antigens via antibodies and T-lymphocytes, respectively. T-lymphocytes, by virtue of being the antigen specific effectors of cellular immunity, play a central and direct role in the body's defense against diseases mediated by intracellular pathogens, such as viruses, intracellular bacteria, mycoplasmas, and intracellular parasites, by directly cytolysing cells infected by such pathogens. However, helper T-lymphocytes also play a critical role in humoral immune responses against non intracellular pathogens by providing T-cell help to B lymphocytes in the form of interleukin secretion to stimulate production of antibodies specific for antigens of such pathogens. The specificity of T-lymphocyte responses is conferred by, and activated through T-cell receptors (TCRs). T-cell receptors are antigen specific receptors clonally distributed on individual T-lymphocytes whose repertoire of antigenic specificity is generated via somatic gene rearrangement mechanisms analogously to those involved in generating the antibody gene repertoire. T-cell receptors are composed of a heterodimer of transmembrane molecules, the main type being composed of an alpha-beta dimer and a smaller subset of a gamma-delta dimer. T-lymphocyte receptor subunits comprise a transmembrane constant region and a variable region in the extracellular domain, similarly to immunoglobulins, and signal transduction triggered by TCRs is indirectly mediated via CD3/zeta, an associated multi-subunit complex comprising signal transducing subunits. The two main classes of T-lymphocytes, helper T-lymphocytes and cytotoxic T-lymphocytes (CTLs), are distinguished by expression of the surface markers CD4 and CD8, respectively. As described hereinabove, the main function of helper T-lymphocytes is to secrete cytokines, such as IL-2, promoting activation and proliferation of CTLs and B lymphocytes, and the function of CTLs is to induce apoptotic death of cells displaying immunogenic antigens. T-lymphocyte receptors, unlike antibodies, do not recognize native antigens but rather recognize cell-surface displayed complexes comprising an intracellularly processed fragment of a protein or lipid antigen in association with a specialized antigen-presenting molecule (APM): major histocompatibility complex (MHC) for presentation of peptide antigens; and CD1 for presentation of lipid antigens, and to a lesser extent, peptide antigens. Peptide antigens displayed by MHC molecules and lipid antigens displayed by CD1 molecules have characteristic chemical structures are referred to as MHC-restricted peptides and CD1 restricted lipids, respectively. Major histocompatibility complex molecules are highly polymorphic, comprising more than 40 common alleles for each individual gene. “Classical” MHC molecules are divided into two main types, class I and class II, having distinct functions in immunity. Major histocompatibility complex class I molecules are expressed on the surface of virtually all cells in the body and are dimeric molecules composed of a transmembrane heavy chain, comprising the peptide antigen binding cleft, and a smaller extracellular chain termed β2-microglobulin. MHC class I molecules present 9- to 11-amino acid residue peptides derived from the degradation of cytosolic proteins by the proteasome a multi-unit structure in the cytoplasm, (Niedermann G., 2002. Curr Top Microbiol Immunol. 268:91-136; for processing of bacterial antigens, refer to Wick M J, and Ljunggren H G., 1999. Immunol Rev. 172:153-62). Cleaved peptides are transported into the lumen of the endoplasmic reticulum (ER) by TAP where they are bound to the groove of the assembled class I molecule, and the resultant MHC:antigen complex is transported to the cell membrane to enable antigen presentation to T-lymphocytes (Yewdell J W., 2001. Trends Cell Biol. 11:294-7; Yewdell J W. and Bennink J R., 2001. Curr Opin Immunol. 13:13-8). Major histocompatibility complex class II molecules are expressed on a restricted subset of specialized antigen-presenting cells (APCs) involved in T-lymphocyte maturation and priming. Such APCs in particular include dendritic cells and macrophages, cell types which internalize, process and display antigens sampled from the extracellular environment. Unlike MHC class I molecules, MHC class II molecules are composed of an alpha-beta transmembrane dimer whose antigen binding cleft can accommodate peptides of about 10 to 30, or more, amino acid residues. The antigen presenting molecule CD1, whose main function, as described hereinabove, is presentation of lipid antigens, is a heterodimer comprising a transmembrane heavy chain paired with beta2-microglobulin, similarly to MHC class I, and is mainly expressed on professional APCs, similarly to MHC class II (Sugita M. and Brenner M B., 2000. Semin Immunol. 12:511). CD1:antigen complexes are specifically recognized by TCRs expressed on CD4−CD8− T-lymphocytes and NKT lymphocytes and play a significant role in microbial immunity, tumor immunology, and autoimmunity. The cells of the body are thus scanned by T-lymphocytes during immune surveillance or during maturation of T-lymphocytes for their intracellular protein or lipid content in the form of such APM:antigen complexes. One strategy which has been proposed to enable optimal diagnosis, characterization, and treatment of diseases, such as HAM/TSP, associated with an infection by a pathogen involves using molecules capable of specifically binding APM:antigen complexes composed of a particular combination of APM and an antigen derived from such a pathogen. Such molecules, for example, could be conjugated to functional moieties, such as detectable moieties or toxins, and the resultant conjugates could be used to detect such complexes or cells displaying such complexes, or to kill cells displaying such complexes. Hence, such conjugates could be used to diagnose/characterize and treat a pathogen infection in an individual, respectively. Alternately, molecules capable of specifically binding such complexes could be used to bind such complexes on cells so as to block activation of T-lymphocytes bearing. TCRs specific for such complexes. Such molecules could further be used, for example, to isolate such complexes, or cells displaying such complexes, such as cells infected with a pathogen, or APCs exposed to a pathogen-derived antigen. Several prior art approaches have been described involving molecules capable of binding particular APM:antigen complexes. One approach involves using TCRs or derivatives thereof specific for particular MHC:peptide complexes in attempts to provide reagents capable of specifically binding such complexes. Another approach involves using antibodies or derivatives thereof specific for particular mouse MHC:peptide complexes in attempts to provide reagents capable of specifically binding such complexes (Aharoni, R. et al., 1991. Nature 351:147-150; Andersen, P. S. et al., 1996. Proc. Natl. Acad. Sci. U.S.A 93:1820-1824; Dadaglio, G. et al., 1997. Immunity 6:727-738; Day, P. M. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:8064-8069; Krogsgaard, M. et al., 2000. J. Exp. Med. 191:1395-1412; Murphy, D. B. et al., 1989. Nature 338:765-768; Porgador, A. et al., 1997. Immunity 6:715-726; Reiter, Y. et al., Proc. Natl. Acad. Sci. U.S.A. 94:4631-4636; Zhong, G. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:13856-13861; Zhong, G. et al., 1997. J. Exp. Med. 186:673-682). A further approach involves utilizing antibodies or derivatives thereof specific for the human MHC class I molecule HLA-A1 in complex with an HLA-A1 restricted peptide derived from the melanoma specific tumor associated antigen melanoma associated antigen (MAGE)-A1 in attempts to provide reagents capable of specifically binding such a complex (Chames, P. et al., 2000. Proc. Natl. Acad. Sci. U.S.A. 97:7969-7974). An additional approach involves employing antibodies or derivatives thereof specific for the human MHC class I molecule HLA-A2 in complex with an HLA-A2 restricted peptide derived from the melanoma specific tumor associated antigen gp100 in attempts to provide reagents capable of specifically binding such a complex (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426). Yet another approach involves using antibodies or derivatives thereof specific for human MHC class I molecule HLA-A2 in complex with an HLA-A2 restricted peptide derived from human telomerase catalytic subunit (hTERT) in attempts to provide reagents capable of specifically binding such a complex (Lev, A. et al., 2002. Cancer Res. 62:3184-3194). However, all of the aforementioned prior art approaches suffer from significant disadvantages: (i) approaches involving the use TCRs or portions thereof as compounds capable of specifically binding particular MHC:peptide complexes are suboptimal due to the relatively low intrinsic binding affinity of TCRs for such complexes; (ii) approaches involving the use of antibodies or portions thereof specific for MHC:peptide complexes comprising non-human MHC are not suitable for human application; and (iii) approaches involving antibodies or portions thereof specific for MHC:non-pathogen-derived antigen complexes are not suitable for specifically binding complexes comprising pathogen-derived antigens. Thus, all prior art approaches have failed to provide an adequate solution for providing molecules capable of specifically binding with high specificity and affinity a particular human APM:pathogen-derived antigen complex. There is thus a Widely recognized need for, and it would be highly advantageous to have, molecules devoid of the above limitation. SUMMARY OF THE INVENTION According to one aspect of the present invention there is provided a method of detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, the method comprising: (a) exposing the antigen-presenting portion of the complex to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (b) detecting the antibody or antibody fragment of the conjugate, thereby detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the complex is displayed or expressed by a target cell, and step (a) is effected by exposing the target to the composition-of-matter. According to still further features in the described preferred embodiments the method of detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen further comprises: (c) obtaining the target cell from an individual. According to another aspect of the present invention there is provided a method of detecting in a biological sample an antigen-presenting portion of a complex composed of an antigen-presenting molecule and an antigen, the method comprising: (a) attaching the biological sample to a surface; (b) exposing the biological sample to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (c) detecting the antibody or antibody fragment of the conjugate, thereby detecting in a biological sample an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen. According to further features in preferred embodiments of the invention described below, the he method of detecting in a biological sample an antigen-presenting portion of a complex composed of an antigen-presenting molecule and an antigen further comprises: (d) obtaining the biological sample from an individual. According to still further features in the described preferred embodiments, step (b) is effected by administering the composition-of-matter to an individual. According to still further features in the described preferred embodiments, the antigen is derived from a pathogen. According to still further features in the described preferred embodiments, the biological sample is infected with the pathogen. According to still further features in the described preferred embodiments, the biological sample is a cell sample or a tissue sample. According to yet another aspect of the present invention there is provided a method of diagnosing an infection by a pathogen in an individual, the method comprising: (a) exposing a target cell of the individual to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from the pathogen, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (b) detecting the antibody or antibody fragment of the conjugate, thereby diagnosing an infection by a pathogen in an individual. According to further features in preferred embodiments of the invention described below, the method of diagnosing an infection by a pathogen in an individual further comprises: (c) obtaining the target cell from the individual. According to still further features in the described preferred embodiments, step (a) is effected by administering the composition-of-matter to the individual. According to still further features in the described preferred embodiments, the composition-of-matter further comprises a detectable moiety attached to the antibody or antibody fragment, and detecting the antibody or antibody fragment of the conjugate is effected by detecting the detectable moiety attached to the antibody or antibody fragment of the conjugate. According to still another aspect of the present invention there is provided a method of killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, the method comprising exposing the target cell to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, thereby killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the method of killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen further comprises the step of obtaining the target cell from an individual. According to still further features in the described preferred embodiments, exposing the target cell to the composition-of-matter is effected by administering the composition-of-matter to an individual. According to still further features in the described preferred embodiments, the target cell is infected with the pathogen. According to still further features in the described preferred embodiments, the target cell is a T-lymphocyte or an antigen presenting cell. According to still further features in the described preferred embodiments, the antigen presenting cell is a B cell or a dendritic cell. According to a further aspect of the present invention there is provided a method of treating a disease associated with a pathogen in an individual, the method comprising administering to the individual a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient, a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from the pathogen, thereby treating a disease associated with a pathogen in an individual. According to a yet a further aspect of the present invention there is provided an isolated polynucleotide comprising a first nucleic acid sequence encoding an antibody fragment, the antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the isolated polynucleotide further comprises a second nucleic acid sequence encoding a polypeptide selected from the group consisting of a coat protein of a virus, a detectable moiety, and a toxin. According to still further features in the described preferred embodiments, the second nucleic acid sequence is translationally fused with the first nucleic acid sequence. According to still a further aspect of the present invention there is provided a nucleic acid construct comprising the isolated polynucleotide and a promoter sequence for directing transcription of the isolated polynucleotide in a host cell. According to further features in preferred embodiments of the invention described below, the promoter sequence is a T7 promoter sequence. According to still further features in the described preferred embodiments, the promoter sequence is capable of driving expression of the nucleic acid sequence in a prokaryote. According to still further features in the described preferred embodiments, the promoter sequence is capable of driving inducible expression of the nucleic acid sequence. According to an additional aspect of the present invention there is provided a host cell comprising the nucleic acid construct. According to further features in preferred embodiments of the invention described below, the host cell is a prokaryotic cell. According to still further features in the described preferred embodiments, the prokaryotic cell is an E. coli cell. According to yet an additional aspect of the present invention there is provided a virus comprising the nucleic acid construct. According to still an additional aspect of the present invention there is provided a virus comprising a coat protein fused to an antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the virus is a filamentous phage and the coat protein is pIII. According to another aspect of the present invention there is provided a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to yet another aspect of the present invention there is provided a pharmaceutical compositions comprising as an active ingredient the composition-of-matter and a pharmaceutically acceptable carrier. According to still another aspect of the present invention there is provided a composition-of-matter comprising a multimeric form of an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to a further aspect of the present invention there is provided a pharmaceutical composition comprising as an active ingredient the composition-of-matter comprising a multimeric form of an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, and a pharmaceutically acceptable carrier. According to, further features in preferred embodiments of the invention described below, the antibody is a monoclonal antibody. According to still further features in the described preferred embodiments, the antibody fragment is a monoclonal antibody fragment. According to still further features in the described preferred embodiments, the antibody fragment is selected from the group consisting of an Fd fragment, an Fab, and a single chain Fv. According to still further features in the described preferred embodiments, the antigen-binding region includes an amino acid sequence selected from the group consisting of SEQ ID NOs: 14 to 97. According to still further features in the described preferred embodiments, the antibody or antibody fragment, or a part of the antibody or antibody fragment is of human origin. According to still further features in the described preferred embodiments, the part of the antibody or antibody fragment is a portion of a constant region of the antibody or antibody fragment, or a constant region of the antibody or antibody fragment. According to still further features in the described preferred embodiments, the binding of the antibody or antibody fragment to the antigen-presenting portion of the complex is characterized by an affinity having a dissociation constant selected from the range consisting of 1×10−2 molar to 5×10−16 molar. According to still further features in the described, preferred embodiments, the composition-of-matter further comprises a toxin or detectable moiety attached to the antibody or antibody fragment. According to still further features in the described preferred embodiments, the detectable moiety is selected from the group consisting of a recognition sequence of a biotin protein ligase, a biotin molecule, a streptavidin molecule, a fluorophore, an enzyme, and a polyhistidine tag. According to still further features in the described preferred embodiments, the biotin protein ligase is BirA. According to still further features in the described preferred embodiments, the fluorophore is phycoerythrin. According to still further features in the described preferred embodiments, the enzyme is horseradish peroxidase. According to still further features in the described preferred embodiments, the toxin is Pseudomonas exotoxin A or a portion thereof. According to still further features in the described preferred embodiments, the portion of Pseudomonas exotoxin A is a translocation domain and/or an ADP ribosylation domain. According to still further features in the described preferred embodiments, the human antigen-presenting molecule is a major histocompatibility complex molecule. According to still further features in the described preferred embodiments, the major histocompatibility complex molecule is a major histocompatibility complex class I molecule. According to still further features in the described preferred embodiments, the major-histocompatibility complex class I molecule is an HLA-A2 molecule. According to still further features in the described preferred embodiments, the human antigen-presenting molecule is a single chain antigen-presenting molecule. According to still further features in the described preferred embodiments, the pathogen is a viral pathogen. According to still further features in the described preferred embodiments, the viral pathogen is a retrovirus. According to still further features in the described preferred embodiments, the retrovirus is human T lymphotropic virus-1. According to still further features in the described preferred embodiments, the antigen derived from a pathogen is restricted by the antigen-presenting molecule. According to still further features in the described preferred embodiments, the antigen derived from a pathogen is a polypeptide. According to still further features in the described preferred embodiments, the polypeptide is a segment of a Tax protein, or a polypeptide having an amino acid sequence as set forth in SEQ ID NO: 3. The present invention successfully addresses the shortcomings of the presently known configurations by providing a composition-of-matter comprising an antibody or antibody fragment capable of binding with optimal specificity/affinity a human APM:pathogen-derived antigen complex. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. BRIEF DESCRIPTION OF THE DRAWINGS The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. In the drawings: FIG. 1 is a histogram depicting specific binding of recombinant Fab-phage clones to HLA-A2:Tax11-19 complex, as determined by ELISA. TAX—HLA-A2:Tax11-19 complex, gp100-154—HLA-A2:G9-154 peptide complex, MUC1-D6—HLA-A2:MUC1-D6 peptide complex, MART 27—HLA-A2:MART 27 peptide complex. FIGS. 2a-c are photographs depicting Western immunoblotting assays of expression and purification of Fab's selected for specific binding to HLA-A2:Tax11-19 complex. Shown are SDS-PAGE analyses of purified Fab protein after metal affinity chromatography, inclusion bodies from BL21 cultures expressing Fab T3F2 light chain and Fd fragment, and purified in vitro refolded non-reduced (NR) and reduced (R) Fab T3F2 (FIGS. 2a-c, respectively). M—molecular weight markers. FIGS. 3a-c are histograms depicting specific binding of soluble purified Fab's T3D4, T3E3, and T3F2, respectively, to immobilized HLA-A2:Tax11-19 complex, but not to HLA-A2:control peptide complexes, as determined by ELISA. FIGS. 4a-b are data plots depicting the binding characteristics of Fab's T3E3 and T3F2, respectively, as determined by titration ELISA using single chain HLA-A2:Tax11-19 complex as binding target. FIG. 4c is a competitive binding analysis data plot depicting the ability of purified Fab T3F2 to inhibit the binding of [125]iodine labeled Fab T3F2 to immobilized HLA-A2:Tax complex. The apparent binding affinity of the recombinant Fab was determined as the concentration of competitor (soluble purified Fab) required for 50 percent inhibition of the binding of the [125]iodine labeled tracer. FIGS. 5a-f are flow cytometry histograms depicting specific detection of HLA-A2:Tax11-19 complex on the surface of APCs. RMAS-HHD, JY, and human dendritic (DC) cells (FIGS. 5a-b, 5c-d, and 5e-f, respectively) were loaded with Tax11-19 peptide or negative control melanoma gp100-derived peptide G9-154, as described in the experimental procedures. Peptide-loaded cells were then incubated with the soluble purified HLA-A2:Tax11-19 complex specific Fab's T3E3 (FIGS. 5a, 5c, and 5e) or T3F2 (FIGS. 5b, 5d, and 5f). Note specific staining of cells loaded with Tax11-19 but not negative control peptide. Control unloaded cells are shown in black trace. Control assays were performed using the 10 different negative control HLA-A2 restricted peptides listed under Materials and Methods. FIGS. 6a-c are flow cytometry histograms depicting specific detection of HLA-A2:Tax11-19 complex on the surface of antigen-presenting cells (APCs) using Fab T3F2 tetramer. RMAS-HHD, JY, or HLA-A2 positive mature dendritic cells (FIGS. 6a-c, respectively) were pulsed with Tax11-19 peptide. Peptide pulsed cells were then incubated with phycoerythrin conjugated T3F2 tetramer or monomer, as indicated. Fab monomer binding was detected using phycoerythrin conjugated anti human Fab antibody. Control unloaded cells stained with the T3F2 tetramer are shown. FIGS. 7a-d depict specific detection of cell surface displayed HLA-A2:Tax11-19 complex by T3F2 after naturally occurring active intracellular processing. FIGS. 7a-b are flow cytometry histograms depicting specific detection of HLA-A2:Tax11-19 complex on the surface of HLA-A2 positive JY cells, but not HLA-A2 negative APD cells, respectively. Cells were transfected with pcDNA control vector or with pcDNA containing the intact full length Tax gene (pcTAX), and 12 to 24 hours following transfection, cells were stained by flow cytometry using Fab T3F2 or the negative control Fab G2D12 specific for HLA-A2:G9-154 complex. FIG. 7c is a bar graph depicting the efficiency of Tax gene transduction into JY and APD cells, as monitored by transfection of the pcDNA vector carrying the GFP gene. FIG. 7d is a flow cytometry histogram depicting staining of HLA-A2 positive RSCD4 and HLA-A2 negative HUT102 cells (which are lines of human CD4 positive T-cells infected with HTLV-1) with phycoerythrin conjugated Fab T3F2 tetramer, or negative control G2D12, as indicated. FIGS. 8a-b depict quantitation of the number of HLA-A2:Tax11-19 complexes on the surface of Tax11-19 peptide pulsed cells. JY APCs were pulsed with various concentrations of Tax11-19 peptide and surface display of HLA-A2-Tax11-19 peptide complex on the cells was analyzed by flow cytometry using phycoerythrin conjugated T3F2 Fab. FIG. 8a is a bar graph depicting the calculated number of complexes per cell with various concentration of peptide. The level of fluorescence intensity on stained cells was quantitated flow cytometrically using calibration beads conjugated to graded numbers of phycoerythrin molecules (QuantiBRITE PE beads, Becton-Dickinson). FIG. 8b is a flow cytometry histogram depicting fluorescence intensity as a function of Tax11-19 peptide concentration. FIGS. 8c-d depict high-sensitivity quantitative detection of HLA-A2:Tax11-19 complex on the surface JY APCs transfected with the Tax gene mixed at different ratios within a non-transfected cell population. The mixed population was stained with Fab T3F2 and detection sensitivity was monitored by single-color flow cytometry. FIG. 8c is a set of overlapping flow cytometry histograms shown in large-scale (left panel) or zoomed (right panel) depicting quantitative detection of transfected cells mixed into populations of non-transfected cells at the various ratios, as indicated. FIG. 8d is a data table depicting sensitivity of detection of HLA-A2:Tax11-19 complex as a function of the percentage of transfected cells admixed within a population of non-transfected cells, on the basis of a transfection efficiency of 62.1 percent. Note detection of HLA-A2:Tax11-19 complex-displaying cells present in a population of non-transfected cells in a proportion as low as 1 percent. FIGS. 9a-f are photomicrographs depicting immunohistochemical detection of HLA-A2:Tax11-19 complex by Fab T3F2 following intracellular processing. FIGS. 9a-b depict ×60 and ×40 original magnification views, respectively, of Tax transfected JY cells stained with Fab T3F2. FIG. 9c depicts control non transfected JY cells stained with Fab T3F2. FIG. 9d depicts staining of Tax transfected JY cells with negative control Fab G2D12 specific for HLA-A2:G9-154 complex. FIGS. 9e-f depict HLA-A2 negative cells transfected for expression of Tax or not transfected, respectively, stained with T3F2. Cells were adsorbed onto poly-L-lysine coated glass slips 12 to 24 hours following transfection, and stained with Fab T3F2. As a negative control Fab G2D12 was used. FIG. 10 is a data plot depicting specific and efficient killing of target cells displaying a specific human MHC:viral peptide complex by a fusion protein consisting of an anti specific human MHC:viral peptide complex Fab conjugated to a toxin. A cytotoxicity assay was performed using T3F2-PE38 KDEL fusion protein, consisting of anti HLA-A2:Tax11-19 complex Fab fused to the PE38 KDEL truncated form of pseudomonas exotoxin A. To assay cytolysis by the fusion protein, JY cells loaded with Tax11-19 peptide, loaded with control HLA-A2 restricted peptides, or not peptide loaded were incubated with T3F2-PE38 KDEL. Note specific and efficient T3F2-PE38 KDEL mediated killing of cells loaded with Tax11-19 peptide, but not of control JY cells loaded control peptide, or of JY cells not peptide loaded. DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is of compositions-of-matter capable of specifically binding particular antigen-presenting molecule (APM):antigen complexes, and to methods of using such compositions-of-matter to detect, characterize or kill/damage cells/tissues expressing/displaying such complexes. In particular, the present invention can be used to optimally detect, characterize or kill/damage human cells/tissues displaying/expressing a particular human APM:pathogen-derived antigen complex, such as cells/tissues infected with a pathogen, or antigen-presenting cells (APCs) exposed to the pathogen, or an antigen thereof. As such the compositions-of-matter of the present invention can be used, for example, to optimally diagnose, characterize, and treat a pathogen infection in a human. Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. Molecules capable of binding with optimal specificity/affinity a particular human APM:pathogen-derived antigen complex would be of significant and unique utility since they would enable optimal diagnosis, characterization, and treatment of pathogen infections in humans. Various molecules capable of binding specific APM:antigen complexes have been described by the prior art. For example, one approach involves using antibodies or derivatives thereof specific for mouse MHC:peptide complexes in attempts to provide compounds capable of specifically binding such murine complexes. Another approach involves using antibodies or derivatives thereof specific for human MHC:tumor-associated antigen (TAA) peptide complexes in attempts to provide compounds capable of specifically binding such human tumor antigen-presenting complexes. A further approach involves using antibodies or derivatives thereof specific for human MHC:telomerase-derived peptide complexes in attempts to provide compounds capable of specifically binding such human telomerase antigen-presenting complexes. However, all such prior art approaches suffer from significant drawbacks. Prior art approaches involving molecules capable of specifically binding complexes comprising non-human APMs do not have utility for human applications, and prior art approaches involving compositions-of-matter capable of specifically binding complexes comprising non-pathogen-derived antigens do not have utility for applications requiring molecules capable of specifically binding complexes comprising pathogen-derived antigens, such as diagnosis, characterization, and treatment of pathogen infections in humans. Thus, the prior art has failed to provide molecules capable of binding particular human APM:pathogen-derived antigen complexes with optimal specificity and affinity. While reducing the present invention to practice molecules capable of binding particular human APM:pathogen-derived antigen complexes with optimal specificity and affinity were unexpectedly uncovered. Such a capacity is unique relative to all prior art molecules capable of binding particular APM:antigen complexes. It was also unexpectedly uncovered that attaching such molecules to a detectable moiety or toxin could be used, respectively, to detect/characterize, or kill/damage with optimal efficiency/specificity cells/tissues displaying such complexes. Such capacities are also unique relative to all prior art molecules capable of binding particular APM:antigen complexes. Thus, in sharp contrast to prior art molecules capable of binding particular APM:antigen complexes, the molecules of the present invention can be used to detect, or characterize with optimal specificity and sensitivity, or kill with optimal efficiency and specificity human cells/tissues infected with a pathogen, or antigen-presenting cells exposed to a pathogen, or an antigen thereof. Thus, according to one aspect of the present invention there is provided a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of an APM and an antigen derived from a pathogen. The composition-of-matter is optimal for use in essentially any application benefiting from a reagent having the capacity to specifically bind the antigen-presenting portion of a complex composed of a particular APM and a particular antigen derived from a pathogen which is restricted by such an APM (referred to hereinafter as “complex” or “the complex”). Such applications particularly include those involving: (i) specific detection of the antigen-presenting portion of the complex, in particular for diagnosing a disease associated with the pathogen; (ii) killing/damaging cells/tissues displaying/expressing the antigen-presenting portion of the complex (referred to herein as “target cells/tissues”), including pathogen-infected cells or APCs exposed to an antigen of the pathogen; and (iii) blocking binding of the antigen-presenting portion of the complex to a cognate T-cell receptor (TCR); and (iv) and isolating the complex or a cell displaying/expressing the complex. As used herein, the term “antibody” refers to a substantially whole or intact antibody molecule. As used herein, the phrase “antibody fragment” refers to molecule comprising a portion or portions of an antibody capable of specifically binding an antigenic determinant or epitope, such as the antigen-presenting portion of the complex. As used herein, the phrase “antigen-binding region”, when relating to the antibody or antibody fragment, refers to a portion of the antibody or antibody or antibody fragment (typically a variable portion) capable of specifically binding a particular antigenic determinant or epitope, or particular set of antigenic determinants or epitopes. As used herein, the term “APM” refers to an antigen-presenting molecule such as an MHC molecule, a CD1 molecule, and a molecule structurally and/or functionally analogous to an MHC or CD1 molecule. A specific APM is typically capable, of binding any of a particular set of distinct antigens so as to form an antigen-presenting complex therewith which can be specifically bound by a variable portion of a TCR. Antigen-presenting molecules forming complexes whose antigen-presenting portions comprise antigenic determinants or epitopes which can be specifically bound by the antibody or antibody fragment comprised in the composition-of-matter are described in further detail hereinbelow. As used herein, the term “antigen” refers to a molecule or portion thereof (typically a peptide or a lipid), where such a molecule or portion thereof is capable of specifically binding an antigen-binding groove of an APM. Such an antigen is commonly referred to in the art as being “restricted” by such an APM. A typical antigen, such as a pathogen-derived antigen, is typically generated in a human cell by intracellular processing of a larger molecule derived from the pathogen. Such cells typically include a cell infected with the pathogen—in particular an intracellular pathogen, or an APC exposed to an antigen derived from the pathogen. The antigen generally has a characteristic dimension and/or chemical composition—for example, a characteristic amino acid length and set of anchor residues, respectively, in the case of a peptide antigen—enabling it to specifically bind the antigen-binding groove of a particular APM so as to form an APM:antigen complex therewith having an antigen presenting portion capable of specifically binding a variable region of a cognate TCR. As used herein, the phrase “antigen-presenting portion”, when relating to the complex, refers to any portion of the complex which can be specifically bound by the antibody or antibody fragment, such that the antibody or antibody fragment is effectively incapable of specifically binding: (i) the APM of the complex not bound to the antigen of the complex; (ii) an APM:antigen complex composed of the APM of the complex and an antigen other than that of the complex; or (iii) an APM:antigen complex composed of an APM other than that of the complex and any antigen restricted by such an APM, including the antigen of the complex. As mentioned hereinabove, the antigen-presenting portion of the complex is typically a portion of the complex capable of specifically binding a cognate TCR variable region. Antigen-presenting portions of complexes which can be specifically bound by the antibody or antibody fragment comprised in the composition-of-matter of the present invention are described in further detail hereinbelow. As used herein, the term peptide refers to a polypeptide composed of 50 amino acid residues or less. Depending on the application and purpose, the composition-of-matter may comprise an antibody or an antibody fragment. Preferably, the composition-of-matter comprises an antibody fragment. Antibody fragments, various types of which are described in further detail hereinbelow, have the advantage of generally being smaller than an antibody while retaining essentially a substantially identical binding specificity of a whole antibody comprising the immunoglobulin variable regions of the antibody fragment. Thus, a composition-of-matter of the present invention comprising an antibody fragment will be generally smaller than one comprising an antibody, and will thereby generally have superior biodistribution, and diffusion properties (for example, systemically in-vivo, or in isolated tissues) than the latter. A smaller composition-of-matter will have the additional advantage of being less likely to include moieties capable of causing steric hindrance inhibiting binding of the antibody or antibody fragment comprised in the composition-of-matter to the antigen-presenting portion of the complex. Also, the absence of some or all of an antibody constant region (referred to herein as “constant region”), such as an Fc region, from a composition-of-matter of the present invention comprising an antibody fragment lacking such an Fc region will be advantageous for applications involving exposure of the composition-of-matter to a molecule capable of specifically binding such a constant region and in which such binding is undesirable. Typically this may involve an undesired binding of an Fc region comprised in a composition-of-matter of the present invention exposed to a cognate Fc receptor, or an Fc-binding complement component (for example, complement component C1q, present in serum). Fc receptors are displayed on the surface of numerous immune cell types, including: professional APCs, such as dendritic cells; B lymphocytes; and granulocytes such as neutrophils, basophils, eosinophils, monocytes, macrophages, and mast cells. In particular, the absence of a functional constant region, such as the Fc region, from the composition-of-matter will be particularly advantageous in applications in which the composition-of-matter is exposed to a specific ligand of a constant region, such as a cognate Fc receptor or an Fc binding complement component, capable of activating an undesired immune response, such as an Fc receptor-mediated immune cell activation or complement component-mediated complement cascade, respectively, via interaction with the constant region. It will be appreciated by the ordinarily skilled artisan that in various contexts, the aforementioned Fc receptor-displaying cell types will function as APCs displaying/expressing the complex. Hence a composition-of-matter of the present invention comprising an antibody fragment lacking an Fc region may be advantageous for preventing undesired binding of the antibody or antibody fragment by Fc receptors displayed by such cells, or for preventing consequent activation of such cells. Alternately, an antibody or antibody fragment of the present invention comprising such a functional constant region may be advantageous in applications in which such an immune response is desirable. This will be particularly desirable in applications involving use of the composition-of-matter to kill/damage target cells/tissues, as described in further detail hereinbelow. A composition-of-matter of the present invention comprising an antibody or an antibody fragment including a constant region, such as an Fc region, which may be conveniently attached to a functional moiety will also be advantageous for applications in which such attachment is desirable. Furthermore, the use of a composition-of-matter of the present invention comprising an antibody fragment will be advantageous relative to one employing a whole antibody when employing recombinantly producing the antibody or antibody fragment due to antibody fragments being more economical and efficient to synthesize due to their smaller size relative to whole antibodies. Depending on the application and purpose, the composition-of-matter may advantageously comprise an antibody or antibody fragment having any of various structural and/or functional characteristics. In particular, according to the teachings of the present invention, the composition-of-matter may advantageously comprise: (i) a monoclonal or polyclonal antibody or antibody fragment; (ii) a monomeric or multimeric form of antibody or antibody fragment; (iii) an antibody or antibody fragment of any of various configurations or types (such as those described hereinbelow); (iv) an antibody or antibody fragment, or portion thereof, originating from any of various mammalian species; (v) an antibody or antibody fragment attached to any of various functional moieties; (vi) an antibody or antibody fragment capable of specifically binding any of various particular complexes; and/or (vii) an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of the complex with a desired affinity. As mentioned hereinabove, depending on the application and purpose, the antibody or antibody fragment may be polyclonal or monoclonal. As used herein, a composition-of-matter of the present invention comprising a “polyclonal” or “monoclonal” antibody or antibody fragment is a population of molecules of the composition-of-matter comprising a polyclonal or monoclonal population of the antibody or antibody fragment, respectively. As used herein, a composition-of-matter of the present invention comprising a “polyclonal” or “monoclonal” antibody or antibody fragment is a population of composition-of-matter molecules of the present invention each comprising a monoclonal antibody or antibody fragment or a population thereof. Methods of generating monoclonal or polyclonal antibodies or antibody fragments are described hereinbelow. Preferably, according to the teachings of the present invention, the antibody or antibody fragment is monoclonal. For applications benefiting from optimal reproducibility, standardization, or precision, such as analytical applications, as described in further detail hereinbelow, a composition-of-matter comprising a monoclonal antibody or antibody fragment will generally be superior to one comprising a polyclonal antibody or antibody fragment directed at the antigen-presenting portion of the same complex. A monoclonal antibody or antibody fragment will be particularly advantageous in instances where the antibody or antibody fragment has been characterized as having a desired binding affinity/specificity for the antigen-presenting portion of the complex. A composition-of-matter of the present invention comprising such an antibody or antibody fragment will thus be optimal for an application, as will generally be the case, benefiting from a composition-of-matter comprising an antibody or antibody fragment capable of binding the antigen-presenting portion of the complex with the highest affinity/specificity possible. As is described and demonstrated in the Examples section below, a composition-of-matter comprising a monoclonal antibody fragment can be used to optimally practice various aspects of the present invention, including applications involving specific detection of the complex, or killing/damaging of target cells/tissues. Alternately, for applications wherein a composition-of-matter capable of binding one or more complexes with a spectrum of, or with various distinct affinities/specificities is desirable, a composition-of-matter of the present invention comprising a polyclonal antibody or antibody fragment will be advantageous. In any case, where no monoclonal antibody or antibody fragment having a desired binding affinity/specificity for the antigen-presenting portion of the complex is available, a composition-of-matter comprising a polyclonal antibody or antibody fragment will nevertheless often be adequate since the heterogeneity of a polyclonal antibody or antibody fragment mixture will often include one or more antibodies or antibody fragments having an adequate binding affinity/specificity for the antigen-presenting portion of the complex. As mentioned hereinabove, depending on the application and purpose, the antibody fragment may be any of various configurations or types. Suitable antibody fragments include a complementarity-determining region (CDR) of an immunoglobulin light chain (referred to herein as “light chain”), a CDR of an immunoglobulin heavy chain (referred to herein as “heavy chain”), a variable region of a light chain, a variable region of a heavy chain, a light chain, a heavy chain, an Fd fragment, an Fv, a single chain Fv, an Fab, an Fab′, and an F(ab′)2. Antibody fragments among the aforementioned antibody fragments which comprise whole or essentially whole variable regions of both light and heavy chains are defined as follows: (i) Fv, a fragment of an antibody molecule consisting of the light chain variable domain (VL) and the heavy chain variable domain (VH) expressed as two chains (typically obtained via genetic engineering of immunoglobulin genes); (ii) single chain Fv (also referred to in the art as “scFv”), a single chain molecule including the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker (a single-chain Fv is typically obtained via genetic engineering of immunoglobulin genes and polypeptide linker-encoding DNA); (iii) Fab, a fragment of an antibody molecule containing essentially a monovalent antigen-binding portion of an antibody generally obtained by suitably treating the antibody with the enzyme papain to yield the intact light chain and the heavy chain Fd fragment (the Fd fragment consists of the variable and CH1 domains of the heavy chain); (iv) Fab′, a fragment of an antibody molecule containing a monovalent antigen binding portion of an antibody typically obtained by suitably treating the antibody molecule with the enzyme pepsin, followed by reduction of the resultant F(ab′)2 fragment (two Fab′ fragments are obtained per antibody molecule); and (v) F(ab′)2, a fragment of an antibody molecule containing a monovalent antigen-binding portion of an antibody molecule typically obtained by suitably treating the antibody molecule with the enzyme pepsin (i.e., an F(ab′)2 consists of two Fab's connected by a pair of disulfide bonds). Depending on the application and purpose, the antibody fragment is preferably an Fab, or a single chain Fv. As is described and illustrated in the Examples section which follows, and as described in further detail below, a composition-of-matter of the present invention comprising an Fab may be employed to effectively practice the present invention, in particular aspects thereof involving using the composition-of-matter to detect the antigen-presenting portion of the complex. As is described and illustrated in the Examples section which follows, and as described in further detail below, a composition-of-matter of the present invention comprising a single chain Fv may be utilized to effectively practice the present invention, in particular aspects thereof involving utilizing the composition-of-matter to kill/damage target cells/tissues. It will be appreciated by the ordinarily skilled artisan that, due to an Fab′ being essentially similar in structure to an Fab, a composition-of-matter of the present invention comprising an Fab′ may be employed interchangeably with one comprising an Fab, where such Fab′ and Fab comprise essentially the same heavy and light chain variable regions. For applications, as will usually be the case, benefiting from a composition-of-matter of the present invention comprising an antibody fragment capable of binding the antigen-presenting portion of the complex with the highest possible affinity, a composition-of-matter of the present invention comprising an F(ab′)2 may be advantageously employed over one comprising a monovalent antibody fragment, such as an Fab, an Fab′ or a single chain Fv, due to the divalent binding of an F(ab′)2 to the antigen-presenting portion of the complex relative to the monovalent binding of such a monovalent antibody fragment. As mentioned hereinabove, depending on the application and purpose, the antibody or antibody fragment may originate from any of various mammalian species. Preferably, the antibody or antibody fragment is of human origin. An antibody or antibody fragment of human origin may be derived as described further hereinbelow, or as described in the Examples section which follows. A composition-of-matter of the present invention comprising an antibody or antibody fragment of human origin will generally be preferable for applications involving administration of the composition-of-matter to an individual. For example, such an antibody or antibody fragment will generally tend to be better tolerated immunologically than one of non human origin since non variable portions of non human antibodies will tend to trigger xenogeneic immune responses more potent than the allogeneic immune responses triggered by human antibodies which will typically be allogeneic with the individual. It will be preferable to minimize such immune responses since these will tend to shorten the half-life, and hence the effectiveness, of the composition-of-matter in the individual. Furthermore, such immune responses may be pathogenic to the individual, for example by triggering harmful inflammatory reactions. As used herein, the term “individual”, refers to a human. Alternately, an antibody or antibody fragment of human origin, or a humanized antibody, will also be advantageous for applications in which a functional physiological effect, for example an immune response against a target cell, activated by a constant region of the antibody or antibody fragment in the individual is desired. Such applications particularly include those in which the functional interaction between a functional portion of the antibody or antibody fragment, such as an Fc region, with a molecule such as an Fc receptor or an Fc-binding complement component, is optimal when such a functional portion is, similarly to the Fc region, of human origin. Depending on the application and purpose, a composition-of-matter of the present invention comprising an antibody or antibody fragment including a constant region, or a portion thereof, of any of various isotypes may be employed. Preferably, the isotype is selected so as to enable or inhibit a desired physiological effect, or to inhibit an undesired specific binding of the composition-of-matter via the constant region or portion thereof. For example, for inducing antibody-dependent cell mediated cytotoxicity (ADCC) by a natural killer (NK) cell, the isotype will preferably be IgG; for inducing ADCC by a mast cell/basophil, the isotype will preferably be IgE; and for inducing ADCC by an eosinophil, the isotype will preferably be IgE or IgA. For inducing a complement cascade the composition-of-matter will preferably comprise an antibody or antibody fragment comprising a constant region or portion thereof capable of initiating the cascade. For example, the antibody or antibody fragment may advantageously comprise a Cgamma2 domain of IgG or Cmu3 domain of IgM to trigger a C1q-mediated complement cascade. Conversely, for avoiding an immune response, such as the aforementioned one, or for avoiding a specific binding via the constant region or portion thereof, the composition-of-matter will preferably not comprise a constant region, or a portion thereof, of the relevant isotype. As mentioned hereinabove, depending on the application and purpose, the antibody or antibody fragment may be attached to any of various functional moieties. An antibody or antibody fragment, such as that of the present invention, attached to a functional moiety may be referred to in the art as an “immunoconjugate”. Preferably, the functional moiety is a detectable moiety or a toxin. An antibody or antibody fragment attached to a toxin may be referred to in the art as an immunotoxin. As is described and demonstrated in further detail hereinbelow, a detectable moiety or a toxin may be particularly advantageously employed in applications of the present invention involving use of the composition-of-matter to detect the antigen-presenting portion of the complex, or to kill/damage target cells/tissues, respectively. The composition-of-matter may comprise an antibody or antibody fragment attached to any of numerous types of detectable moieties, depending on the application and purpose. For applications involving using the composition-of-matter to detect the antigen-presenting portion of the complex, the detectable moiety attached to the antibody or antibody fragment is preferably a reporter moiety enabling specific detection of the antigen-presenting portion of the complex bound by the antibody or antibody fragment of the composition-of-matter. While various types of reporter moieties may be utilized to detect the antigen-presenting portion of the complex, depending on the application and purpose, the reporter moiety is preferably a fluorophore or an enzyme. Alternately, the reporter moiety may be a radioisotope, such as [125]iodine, as is described and illustrated in the Examples section below. A fluorophore may be advantageously employed as a detection moiety enabling detection of the antigen-presenting portion of the complex via any of numerous fluorescence detection methods. Depending on the application and purpose, such fluorescence detection methods include, but are not limited to, fluorescence activated flow cytometry (FACS), immunofluorescence confocal microscopy, fluorescence in-situ hybridization (FISH), fluorescence resonance energy transfer (FRET), and the like. Various types of fluorophores, depending on the application and purpose, may be employed to detect the antigen-presenting portion of the complex. Examples of suitable fluorophores include, but are not limited to, phycoerythrin (PE), fluorescein isothiocyanate (FITC), Cy-chrome, rhodamine, green fluorescent protein (GFP), blue fluorescent protein (BFP), Texas red, PE-Cy5, and the like. Preferably, the fluorophore is phycoerythrin. As is described and illustrated in the Examples section below, a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to a fluorophore, such as phycoerythrin, can be used to optimally detect the antigen-presenting portion of the complex using various immunofluorescence-based detection methods. Ample guidance regarding fluorophore selection, methods of linking fluorophores to various types of molecules, such as an antibody or antibody fragment of the present invention, and methods of using such conjugates to detect molecules which are capable of being specifically bound by antibodies or antibody fragments comprised in such immunoconjugates is available in the literature of the art [for example, refer to: Richard P. Haugland, “Molecular Probes: Handbook of Fluorescent Probes and Research Chemicals 1992-1994”, 5th ed., Molecular Probes, Inc. (1994); U.S. Pat. No. 6,037,137 to Oncoimmunin Inc.; Hermanson, “Bioconjugate Techniques”, Academic Press New York, N.Y. (1995); Kay M. et al., 1995. Biochemistry 34:293; Stubbs et al., 1996. Biochemistry 35:937; Gakamsky D. et al., “Evaluating Receptor Stoichiometry by Fluorescence Resonance Energy Transfer,” in “Receptors: A Practical Approach,” 2nd ed., Stanford C. and Horton R. (eds.), Oxford University Press, UK. (2001); U.S. Pat. No. 6,350,466 to Targesome, Inc.]. While various methodologies may be employed to detect the antigen-presenting portion of the complex using a fluorophore, such detection is preferably effected as described and demonstrated in the Examples section below. Alternately, an enzyme may be advantageously utilized as the detectable moiety to enable detection of the antigen-presenting portion of the complex via any of various enzyme-based detection methods. Examples of such methods include, but are not limited to, enzyme linked immunosorbent assay (ELISA; for example, to detect the antigen-presenting portion of the complex in a solution), enzyme-linked chemiluminescence assay (for example, to detect the complex in an electrophoretically separated protein mixture), and enzyme-linked immunohistochemical assay (for example, to detect the complex in a fixed tissue). Numerous types of enzymes may be employed to detect the antigen-presenting portion of the complex, depending on the application and purpose. Examples of suitable enzymes include, but are not limited to, horseradish peroxidase (HPR), beta-galactosidase, and alkaline phosphatase (AP). Preferably, the enzyme is horseradish peroxidase. As is described in the Examples section which follows, a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to an enzyme such as horseradish peroxidase can be used to effectively detect the antigen-presenting portion of the complex, such as via ELISA, or enzyme-linked immunohistochemical assay. Ample guidance for practicing such enzyme-based detection methods is provided in the literature of the art (for example, refer to: Khatkhatay M I. and Desai M., 1999. J Immunoassay 20:151-83; Wisdom G B., 1994. Methods Mol. Biol. 32:433-40; Ishikawa E. et al., 1983. J Immunoassay 4:209-327; Oellerich M., 1980. J Clin Chem Clin Biochem. 18:197-208; Schuurs A H. and van Weemen B K., 1980. J Immunoassay 1:229-49). While various methodologies may be employed to detect the antigen-presenting portion of the complex using an enzyme, such detection is preferably effected as described in the Examples section below. The functional moiety may be attached to the antibody or antibody fragment in various ways, depending on the context, application and purpose. A polypeptidic functional moiety, in particular a polypeptidic toxin, may be advantageously attached to the antibody or antibody fragment via standard recombinant techniques broadly practiced in the art (for Example, refer to Sambrook et al., infra, and associated references, listed in the Examples section which follows). While various methodologies may be employed, attaching a polypeptidic functional moiety to the antibody or antibody fragment is preferably effected as described and illustrated in the Examples section below. A functional moiety may also be attached to the antibody or antibody fragment using standard chemical synthesis techniques widely practiced in the art [for example, refer to the extensive guidelines provided by The American Chemical Society (for example at: http://www.chemistry.org/portal/Chemistry)]. One of ordinary skill in the art, such as a chemist, will possess the required expertise for suitably practicing such chemical synthesis techniques. Alternatively, a functional moiety may be attached to the antibody or antibody fragment by attaching an affinity tag-coupled antibody or antibody fragment of the present invention to the functional moiety conjugated to a specific ligand of the affinity tag. Various types of affinity tags may be employed to attach the antibody or antibody fragment to the functional moiety. Preferably, the affinity tag is a biotin molecule, more preferably a streptavidin molecule. A biotin or streptavidin affinity tag can be used to optimally enable attachment of a streptavidin-conjugated or a biotin-conjugated functional moiety, respectively, to the antibody or antibody fragment due to the capability of streptavidin and biotin to bind to each other with the highest non covalent binding affinity known to man (i.e., with a Kd of about 10−14 to 10−15). A biotin affinity tag may be highly advantageous for applications benefiting from, as will oftentimes be the case, a composition-of-matter of the present invention comprising a multimeric form of the antibody or antibody fragment, which may be optimally formed by conjugating multiple biotin-attached antibodies or antibody fragments of the present invention to a streptavidin molecule, as described in further detail below. As used herein the term “about” refers to plus or minus 10 percent. Various methods, widely practiced in the art, may be employed to attach a streptavidin or biotin molecule to a molecule such as the antibody or antibody fragment to a functional moiety. For example, a biotin molecule may be advantageously attached to an antibody or antibody fragment of the present invention attached to a recognition sequence of a biotin protein ligase. Such a recognition sequence is a specific polypeptide sequence serving as a specific biotinylation substrate for the biotin protein ligase enzyme. Ample guidance for biotinylating a target polypeptide such as an antibody fragment using a recognition sequence of a biotin protein ligase, such as the recognition sequence of the biotin protein ligase BirA, is provided in the literature of the art (for example, refer to: Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532). Preferably, such biotinylation of the antibody or antibody fragment is effected as described and illustrated in the Examples section below. Alternately, various widely practiced methods may be employed to attach a streptavidin molecule to an antibody fragment, such as a single chain Fv (for example refer to Cloutier S M. et al., 2000. Molecular Immunology 37:1067-1077; Dubel S. et al., 1995. J Immunol Methods 178:201; Huston J S. et al., 1991. Methods in Enzymology 203:46; Kipriyanov S M. et al., 1995. Hum Antibodies Hybridomas 6:93; Kipriyanov S M. et al., 1996. Protein Engineering 9:203; Pearce L A. et al., 1997. Biochem Molec Biol Intl 42:1179-1188). Functional moieties, such as fluorophores, conjugated to streptavidin are commercially available from essentially all major suppliers of immunofluorescence flow cytometry reagents (for example, Pharmingen or Becton-Dickinson). Standard recombinant DNA chemical techniques are preferably employed to produce a fusion protein comprising streptavidin fused to a polypeptidic functional moiety. Standard chemical synthesis techniques may also be employed to form the streptavidin-functional moiety conjugate. Extensive literature is available providing guidance for the expression, purification and uses of streptavidin or streptavidin-derived molecules (Wu S C. et al., 2002. Protein Expression and Purification 24:348-356; Gallizia A. et al., 1998. Protein Expression and Purification 14:192-196), fusion proteins comprising streptavidin or streptavidin-derived molecules (Sano T. and Cantor C R., 2000. Methods Enzymol. 326:305-11), and modified streptavidin or streptavidin-derived molecules (see, for example: Sano T. et al., 1993. Journal of Biological Chemistry 270:28204-28209), including for streptavidin or streptavidin-derived molecules whose gene sequence has been optimized for expression in E. coli (Thompson L D. and Weber P C., 1993. Gene 136:243-6). The use of a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to a functional moiety for various purposes other than detection of the antigen-presenting portion of the complex, or killing/damaging target cells/tissues is also envisaged by the present invention. In particular, a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to an affinity tag, or any substance, particle, virus or cell displaying/expressing such a composition-of-matter, can be conveniently isolated or purified using an affinity purification method employing as a capture ligand a specific ligand of the affinity tag. Preferably, for such purposes, the affinity tag is a polyhistidine tag, and the purification method is effected using nickel as the specific ligand of the affinity tag. A histidine tag is a peptide typically consisting of 4 to 8 histidine amino acid residues. Preferably a histidine tag composed of 6 histidine residues, commonly referred to as a hexahistidine tag in the art, is employed. Such histidine tags specifically bind nickel-containing substrates. Ample guidance regarding the use of histidine tags is available in the literature of the art (for example, refer to Sheibani N., 1999. Prep Biochem Biotechnol. 29:77). Purification of molecules comprising histidine tags is routinely effected using nickel-based affinity purification techniques. An alternate suitable capture ligand for histidine tags is the anti histidine tag single-chain antibody 3D5 (Kaufmann, M. et al., 2002. J Mol. Biol. 318, 135-47). While various techniques may be employed, purifying a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to a histidine tag is preferably effected as described and illustrated in the Examples section which follows. The composition-of-matter may be purified using any of various suitable standard and widely employed affinity chromatography techniques. Ample guidance for practicing such techniques is provided in the literature of the art [for example, refer to: Wilchek M. and Chaiken I., 2000. Methods Mol Biol 147, 1-6; Jack G W., 1994. Mol Biotechnol 1, 59-86; Narayanan S R., 1994. Journal of Chromatography A 658, 237-258; Nisnevitch M. and Firer M A., 2001. J Biochem Biophys Methods 49, 467-80; Janson J C. and Kristiansen T. in “Packings and Stationary Phases in Chromatography Techniques”, Unger K K. (ed), Marcel Dekker, New York, pp. 747 (1990); Clonis Y D: HPLC of Macromolecules: A Practical Approach, IRL Press, Oxford, pp. 157 (1989); Nilsson J. et al., 1997. Protein Expr Purif. 11:1-16]. Various affinity tags, other than those described hereinabove, may also be employed to attach the functional moiety to the antibody or antibody fragment or to purify a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to an affinity tag, or any substance, particle, virus or cell displaying/expressing such a composition-of-matter. Such affinity tags include, but are not limited to, a streptavidin tag (Strep-tag), an epitope tag (a moiety, usually peptidic, which can be specifically bound with high affinity by a specific monoclonal antibody), a maltose-binding protein (MBP) tag, and a chitin-binding domain (CBD) tag. Examples of epitope tags include an 11-mer Herpes simplex virus glycoprotein D peptide, and an 11-mer N-terminal bacteriophage t7 peptide, being commercially known as HSVTag and t7Tag, respectively (Novagen, Madison, Wis., USA), and 10- or 9-amino acid c-myc or Haemophilus influenza hemagglutinin (HA) peptides, which are recognized by the variable regions of monoclonal antibodies 9E10 and 12Ca5, respectively. A Strep-tag is a peptide having the capacity to specifically bind streptavidin. Ample guidance regarding the use of Strep-tags is provided in the literature of the art (see, for example: Schmidt, T G M. and Skerra, A. 1993. Protein Eng. 6:109; Schmidt T G M. et al., 1996. Journal of Molecular Biology 255:753-766; Skerra A. and Schmidt T G M., 1999. Biomolecular Engineering 16:79-86; Sano T. and Cantor C R. 2000. Methods Enzymol. 326, 305-11; and Sano T. et al., 1998. Journal of Chromatography B 715:85-91). A suitable maltose-binding domain tag is malE-encoded maltose-binding protein which has the capacity to specifically bind a substrate including amylose such as, for example, an amylose-based affinity purification column. Ample guidance regarding the use of maltose-binding protein as an affinity tag is provided in the literature of the art (see, for example: Guan M. et al., 2002. Protein Expr Purif. 26:229-34; Cattoli F and Sarti G C, 2002. Biotechnol Prog. 18:94-100). A suitable chitin-binding domain tag is B. circulans cbd-encoded chitin binding domain which has the capacity to specifically bind chitin. Ample guidance regarding the use of maltose-binding protein as an affinity tag is provided in the literature of the art (see, for example: Humphries H E et al., 2002. Protein Expr Purif. 26:243-8; and Chong S. et al., 1997. Gene 192:271-81). Thus, the functional moiety may be attached to the antibody or antibody fragment via any of the aforementioned various affinity tags, depending on the application and purpose. As mentioned hereinabove, the functional moiety attached to the antibody or antibody fragment may be a toxin. For applications of the composition-of-matter involving killing/damaging of target cells/tissues, the toxin is preferably capable of killing/damaging the target cells/tissues when conjugated thereto as a consequence of specific binding of the antibody or antibody fragment to the antigen-presenting portion of the complex. Any of various toxins may be attached to the antibody or antibody fragment, to thereby generate an immunotoxin suitable, for example, to kill/damage target cells/tissues using a composition-of-matter comprising such an immunotoxin. Preferably, the toxin is Pseudomonas exotoxin A, more preferably a portion thereof comprising the translocation domain and/or an ADP ribosylation domain. Preferably, the portion comprising the translocation domain and/or an ADP ribosylation domain is the toxin PE38 KDEL. Generation of an immunotoxin comprising PE38 KDEL as a toxin moiety is preferably effected as described and illustrated in the Examples section below. Ample guidanice for generating such an immunotoxin is provided in the literature of the art (for example, refer to: Brinkmann U. et al., 1991. Proc. Natl. Acad. Sci. U.S.A. 88:8616-20; and Brinkmann U., 2000. In-vivo 14:21-7). Other types of toxins which may be attached to the antibody or antibody fragment, depending on the application and purpose, in particular to kill/damage a target cell, include, but are not limited to, various bacterial toxins, plant toxins, chemotherapeutic agents, and radioisotopes, respectively. Examples of toxins commonly used to generate immunotoxins include ricin and Pseudomonas exotoxin A-derived PE40 toxin. Alternately, immunotoxins may be generated with toxins such as diphtheria toxin, pertussis toxin, or cholera toxin. Ample guidance for selecting, generating and using immunotoxins is provided in the literature of the art (for example, refer to: Knechtle S J. 2001, Philos Trans R Soc Lond B Biol: Sci. 356:681-9; Hall W A., 2001. Methods Mol. Biol. 166:139-54; Brinkmann U., 2000. In-vivo 14:21-7; Haggerty H G. et al., 1999. Toxicol Pathol. 27:87-94; Chaplin J W., 1999. Med Hypotheses 52:133-46; Wu M., 1997. Br J Cancer. 75:1347-55; Hall W A. 1996, Neurosurg Clin N Am. 7:537-46; Pasqualucci L. et al., 1995. Haematologica 80:546-56; Siegall C B., 1995. Semin Cancer Biol. 6:289-95; Grossbard M L. et al., Clin Immunol Immunopathol. 76:107-14; Ghetie M A and Vitetta E S., 1994. Curr Opin Immunol. 6:707-14; Grossbard M L and Nadler L M., 1994. Semin Hematol. 31:88-97; Frankel A E., 1993. Oncology (Huntingt) 7:69-78; Pai L H. and Pastan I., 1993. JAMA. 269:78-81; Boon, T. and van der Bruggen, P., 1996. J. Exp. Med. 183:725-729; Renkvist, N. et al., 2001. Cancer Immunol Immunother. 50:3-15; Rosenberg, S. A., 2001. Nature 411:380-384; and U.S. Pat. No. 5,677,274). As mentioned hereinabove, depending on the application and purpose, the composition-of-matter may advantageously comprise a monomeric or multimeric form of the antibody or antibody fragment. A composition-of-matter of the present invention comprising a multimeric form of the antibody or antibody fragment will generally bind the antigen-presenting portion of the complex with higher avidity, and thereby with higher affinity, than one comprising a monomeric form of the antibody or antibody fragment. Hence, a composition-of-matter of the present invention comprising a multimeric form of the antibody or antibody fragment may be advantageous for applications benefiting from, as will usually be the case, a reagent capable of specifically binding the antigen-presenting portion of the complex with the highest affinity possible. As is described and illustrated in the Examples section below, a composition-of-matter of the present invention comprising a multimeric form of an antibody or antibody fragment may be advantageously employed to effectively practice the method of the present invention, in particular with respect to applications involving using the composition-of-matter to specifically detect the antigen-presenting portion of the complex. Various methods may be employed to generate a composition-of-matter of the present invention comprising a multimeric form of the antibody or antibody fragment. Preferably, the multimeric form of the antibody or antibody fragment is generated by binding a plurality of antibodies or antibody fragments attached to an affinity tag to a multimerizing molecule capable of specifically and simultaneously binding such a plurality of affinity tags. Alternately, the multimeric form of the antibody or antibody fragment may be generated by attaching a plurality of antibodies or antibody fragments of the present invention to a moiety capable of automultimerizing, so as to thereby multimerize such a plurality of antibodies or antibody fragments. Any of various types of multimerizing molecule/affinity tag combinations may be employed to generate the multimeric form of the antibody or antibody fragment of the present invention. Preferably, such a combination consists of a biotin affinity tag, and a streptavidin multimerizing molecule, which, as described hereinabove, bind to each other with the highest affinity known to man, and hence will normally generate an optimally stable multimeric form of an antibody or antibody fragment of the present invention. For certain applications a composition-of-matter of the present invention comprising a monomeric form of the antibody or antibody fragment may be advantageous. Such a composition-of-matter, due to its relatively small size may be advantageous for applications, such as in-vivo applications, benefiting from optimal biodistribution and/or diffusion thereof. As is described and illustrated in the Examples section which follows, a composition-of-matter of the present invention comprising a monomeric form of an antibody or antibody fragment of the present invention may be advantageously utilized, for example, in applications where such an antibody or antibody fragment is attached to a toxin to kill/damage target cells. Preferably, the composition-of-matter comprises an antibody or antibody fragment capable of specifically binding a complex in which the APM is an MHC class I molecule and the antigen is an MHC class I-restricted antigen (referred to herein as “MHC class I:antigen complex”). Alternately, the composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex in which the APM is an MHC class II molecule and the antigen is an MHC class II-restricted antigen (“MHC class II:antigen complex”), or the APM is a CD1 molecule and the antigen is a CD1 molecule and the antigen is a CD1-restricted antigen (“CD1:antigen complex”). The composition-of-matter may also comprise an antibody or antibody fragment capable of specifically binding a complex structurally and/or functionally analogous to an APM:antigen complex such as one of the aforementioned MHC- or CD1-based complexes. The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of any of various particular MHC class II:antigen complexes. For example, the antigen-presenting portion of an MHC class II:antigen complex having as an APM an HLA-DP, HLA-DQ or HLA-DR molecule. A composition-of-matter of the present invention may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex composed of an MHC class II molecule and any of various MHC class II-restricted antigens, which are generally peptides about 10 to 30 amino acid residues in length. Such peptides generally have particular chemical compositions enabling their specific binding to a particular MHC class II molecule (for example, refer to: Fairchild P J., 1998. J Pept Sci. 4:182; Rammensee H G., 1995. Curr Opin Immunol. 7:85; Sinigaglia F. and Hammer J., 1994. APMIS. 102:241; and Hobohm U. and Meyerhans A., 1993. Eur J. Immunol. 23:1271). The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of any of various particular CD1:antigen complexes. For example, the antigen-presenting portion of a CD1:antigen complex having as an APM a CD1a, CD1b, CD1c or CD1d molecule. A composition-of-matter of the present invention may comprise an antibody or antibody-fragment capable of specifically binding the antigen-presenting portion of a complex composed of a CD1 molecule and any of various CD1-restricted antigens, which may be either peptides or more typically lipids. For example: CD1b and CD1c molecules both have the capacity to specifically associate with CD1b- or CD1-c-restricted lipoarabinomannan, mycolic acid, or glucose monomycolate antigens; CD1c has the capacity to specifically associate with CD1c-restricted polyisoprenyl glycolipid antigens; and CD1d has the capacity to specifically associate with CD1d-restricted glycophosphatidylinositol (GPI) anchor lipid and glycosylceramide lipid antigens. The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of any of various particular MHC class I:antigen complexes, for example, an MHC class I:antigen complex having as an MHC class I APM an HLA-A, HLA-B, or HLA-C molecule (referred to herein as “HLA-A:antigen complex”, “HLA-B:antigen complex”, or “HLA-A:antigen complex”, respectively). While the composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex in which the APM is any of various HLA-A molecules, the composition-of-matter is preferably capable of binding the antigen-presenting portion of one in which the HLA-A molecule is HLA-A2, most preferably HLA-A2.1 (alternately termed “HLA-A*201”). As is described and illustrated in Examples section below, a composition-of-matter of the present invention comprising an antibody or antibody fragment capable of specifically binding a complex having an HLA-A2 molecule as APM can be used to effectively practice various embodiments of the present invention. A composition-of-matter of the present invention may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex composed of an MHC class I molecule and any of various MHC class I-restricted antigens, which are typically peptides about 9 to 11 amino acid residues in length. Such peptides generally have particular chemical compositions enabling their specific binding to a particular MHC class I molecule (for example, refer to: Bianco A. et al., 1998. J Pept Sci. 4:471; Fairchild P J., 1998. J Pept Sci. 4:182; Falk K. and Rotzschke O., 1993. Semin Immunol. 5:81; Rammensee H G., 1995. Curr Opin Immunol. 7:85; and Hobohm U. and Meyerhans A., 1993. Eur J Immunol. 23:1271). As described hereinabove, the composition-of-matter of the present invention comprises an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a particular complex composed of a human APM and an antigen derived from a pathogen. While the composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a particular complex comprising an APM-restricted antigen derived from essentially any type of pathogen, the pathogen is preferably an intracellular pathogen. Alternately, the pathogen may a non-intracellular pathogen, such as a bacterium, a fungus, a protozoan, a mycobacterium, a helminth, and the like. The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex comprising an APM-restricted antigen derived from any of various intracellular pathogens, including a virus, a mycobacterium, a bacterium (such as, for example, Listeria monocytogenes), and a protozoan (such as, for example, Leishmania or Trypanosoma). Preferably the antibody or antibody fragment is capable of specifically binding the antigen-presenting portion of a complex comprising an APM-restricted antigen derived from a viral pathogen. Examples of such viral pathogens include retroviruses, circoviruses, parvoviruses, papovaviruses, adenoviruses, herpesviruses, iridoviruses, poxviruses, hepadnaviruses, picornaviruses, caliciviruses, togaviruses, flaviviruses, reoviruses, orthomyxoviruses, paramyxoviruses, rhabdoviruses, bunyaviruses, coronaviruses, arenaviruses, and filoviruses. While the composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex comprising as APM-restricted antigen an antigen derived from any of various retroviruses, the retrovirus is preferably human T lymphotropic virus-1 (HTLV-1; also referred to as human T-cell leukemia virus in the art). Alternately, the retrovirus may be, for example, HTLV-2, a human immunodeficiency virus (HIV) causing acquired immunodeficiency syndrome (AIDS) such as HIV-1 or HIV-2, or the like. The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex comprising any of various antigens derived from HTLV-1. Preferably, a composition-of-matter of the present invention comprising an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex comprising as APM-restricted antigen derived from HTLV-1, an antigen derived from Tax protein. The composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a complex comprising as APM-restricted antigen any of various Tax protein-derived antigens, and having an antigen binding region comprising any of various amino acid sequences. Preferably, the antibody or antibody fragment comprises an antibody or antibody fragment: (i) capable of specifically binding the antigen-presenting portion of a complex comprising as Tax protein-derived APM-restricted antigen a peptide comprising amino acid residues 11 to 19 of Tax protein, a peptide having the amino acid sequence set forth in SEQ ID NO: 3, or preferably both; (ii) having an antigen-binding region including a maximal number of amino acid sequences corresponding to one selected from: the group of amino acid sequences set forth in SEQ ID NOs: 14 to 97; or (iii) preferably both. As is described and illustrated in the Examples section below, a composition-of-matter of the present invention comprising an antibody or antibody fragment: (i) capable of specifically binding a complex having as APM-restricted antigen a peptide comprising amino acid residues 11 to 19 of Tax protein having the amino acid sequence set forth in SEQ ID NO: 3; and (ii) having an antigen-binding region including amino acid sequences corresponding to those set forth in SEQ ID NOs: 14 to 97 can be used to effectively practice various embodiments of the present invention involving using the composition-of-matter for detecting the antigen-presenting portion of the complex, or killing target cells/tissues. It will, be appreciated that a cell infected with a pathogen, and an APC exposed to the pathogen, or an antigen thereof, may express distinct complexes comprising different APMs and/or different antigens derived from the pathogen, and that hence, the composition-of-matter may be advantageously selected so as to selectively bind one or the other of such cell types. This may be advantageously applied in numerous applications of the present invention, such as, for example, when using the composition-of-matter, as described hereinbelow, to treat a disease associated with a pathogen in an individual by selectively killing/damaging cells infected with the pathogen displaying one particular complex of an APM and an antigen derived from the pathogen without killing/damaging benign or beneficial APCs displaying a different complex of an APM and an antigen derived from the pathogen. As mentioned hereinabove, depending on the application and purpose, the antibody or antibody fragment may be selected capable of binding the antigen-presenting portion of the complex with a desired affinity. Preferably, the desired affinity is as high as possible. A composition-of-matter of the present invention comprising an antibody or antibody fragment having as high as possible a binding affinity for the antigen-presenting portion of the complex will generally enable optimally stable conjugation of a functional moiety to the antigen-presenting portion of the complex, and thereby detection of the antigen-presenting portion of the complex with optimal sensitivity, or killing/damaging of target cells/tissues with, optimal efficiency. Preferably, the affinity is characterized by a dissociation constant (Kd) selected from the range of 1×10−2 molar to 5×10−3 molar, more preferably 5×10−3 molar to 5×10−4 molar, more preferably 5×10−4 molar to 5×10−5 molar, more preferably 5×10−5 molar to 5×10−6 molar, more preferably 5×10−6 molar to 5×10−7 molar, more preferably 5×10−7 molar to 5×10−8 molar, more preferably 5×10−8 molar to 5×10−9 molar, more preferably 5×10−9 molar to 5×10−10 molar, more preferably 5×10−10 molar to 5×10−11 molar, more preferably 5×10−11 molar to 5×10−12 molar, more preferably 5×10−12 molar to 5×10−13 molar, more preferably 5×10−13 molar to 5×10−14 molar, more preferably 5×10−14 molar to 5×10−15 molar, and most preferably 5×10−15 molar to 5×10−16. As is illustrated in the Examples section below, an antibody or antibody fragment capable of binding the antigen-presenting portion of a complex with an affinity characterized by a dissociation constant of about 10−9 molar can be generated using the protocol set forth therein. As is described and illustrated in the Examples section which follows, a composition-of-matter of the present invention comprising an antibody or antibody fragment having a binding affinity for the antigen-presenting portion of the complex characterized by a dissociation constant of about 10−9 molar can be used to effectively practice various embodiments of the present invention, including those involving using the composition-of-matter for detecting the antigen-presenting portion of the complex, or for killing/damaging target cells/tissues. Various methods may be employed to obtain the antibody or antibody fragment capable of specifically binding the antigen-presenting portion of the complex. Preferably, the antibody or antibody fragment is obtained by screening a combinatorial antibody or antibody fragment display library for an element of the library displaying an antibody or antibody fragment capable of binding the antigen-presenting portion of the complex conjugated to a substrate with the desired affinity. Preferably, where the antibody or antibody fragment is an Fab, this may be advantageously effected by screening an Fab-phage library on substrate-immobilized single-chain MHC:peptide complex, preferably as described in the Examples section below. Ample guidance for identifying an antibody or antibody fragment capable of specifically binding the complex is provided in the literature of the art (for example, for generation of a human-derived antibody or antibody fragment refer, for example, to: Chames, P. et al., 2000. Proc. Natl. Acad. Sci. U.S.A. 97:7969-7974; Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426; and Lev, A. et al., 2002. Cancer Res. 62:3184-3194; for generation of a non human-derived antibody or antibody fragment refer, for example, to: Aharoni, R. et al., 1991. Nature 351:147-150; Andersen, P. S. et al., 1996. Proc. Natl. Acad. Sci. U.S. A 93:1820-1824; Dadaglio, G. et al., 1997. Immunity 6:727-738; Day, P. M. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:8064-8069; Krogsgaard, M. et al., 2000. J. Exp. Med. 191:1395-1412; Murphy, D. B. et al., 1989. Nature 338:765-768; Porgador, A. et al., 1997. Immunity 6:715-726; Reiter, Y. et al., Proc. Natl. Acad. Sci. U.S.A. 94:4631-4636; Zhong, G. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:13856-13861; Zhong, G. et al., 1997. J. Exp. Med. 186:673-682; Orlandi D. R. et al., 1989. Proc Natl Acad Sci USA. 86:3833-3837; for a general reference, refer to Winter G. et al., 1991. Nature 349:293-299). Further guidance for generating the antibody or antibody fragment comprised in the composition-of-matter of the present invention is provided hereinbelow. It will be appreciated by the ordinarily skilled artisan that generating an antibody or antibody fragment of a desired affinity, for example one characterized by a dissociation constant as high as 10−12 for a desired antigenic determinant can be achieved using common art techniques. The composition-of-matter may be used per se or it can be formulated as an active ingredient in a pharmaceutical composition. Thus, as described hereinabove, the present invention provides, and may be practiced, depending on the application and purpose using, a composition-of-matter comprising: (i) a monoclonal or polyclonal antibody or antibody fragment; (ii) a monomeric or multimeric form of an antibody or antibody fragment; (iii) an antibody or antibody fragment characterized by any of various configurations; (iv) an antibody or antibody fragment or a portion thereof derived from any of various mammalian species; (v) an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of any of various specific human APM:pathogen-derived antigen complexes; and/or (vi) an antibody or antibody fragment capable of specifically binding the antigen-presenting portion of a particular human APM:pathogen-derived antigen complex with a desired affinity. While further reducing the present invention to practice, genetic sequences encoding an antibody fragment of the present invention were isolated. Thus, according to another aspect of the present invention there is provided an isolated polynucleotide comprising a nucleic acid sequence encoding an antibody fragment of the present invention. Depending on the application and purpose, the isolated polynucleotide preferably further comprises a nucleic acid sequence encoding a coat protein of a virus, a detectable moiety, and a toxin. Preferably, in order to enable generation of a chimeric polypeptide comprising the antibody fragment fused to the coat protein of the virus, the detectable moiety or the toxin, the nucleic acid sequence encoding the polypeptide is translationally fused with that encoding the antibody fragment. Nucleic acid sequences encoding polypeptides may be translationally fused in a polynucleotide by cloning the structural sequences of such nucleic acid sequences in-frame relative to each other in the polynucleotide without intervening transcriptional/translational stop codons, or any other sequences, present between such structural sequences capable of preventing production of a chimeric polypeptide comprising the polypeptides encoded by such structural sequences. An antibody fragment attached to a coat protein of a virus can be used to generate a virus displaying the antibody fragment by virtue of the antibody fragment being fused to the coat protein of the virus. Generating such a virus may be effected as described in further detail hereinbelow, and in the Examples section which follows. While various methods may be used to generate the isolated polynucleotide, the isolated polynucleotide is preferably generated as described in the Examples section, below. As is described and illustrated in the Examples section below, an isolated polynucleotide of the present invention can be used to generate an antibody fragment or conjugate thereof with a coat protein of a virus, a detectable moiety, and/or a toxin suitable for generating the composition-of-matter of the present invention. While reducing the present invention to practice nucleic acid constructs capable of expressing the polynucleotide of the present invention were isolated or generated. Thus, the present invention provides a nucleic acid construct comprising the isolated polynucleotide of the present invention and a promoter sequence for directing transcription thereof in a host cell. While various promoter sequences may be employed capable of directing transcription of the isolated polynucleotide in various types of host cell, depending on the application and purpose, the promoter sequence is preferably capable of directing transcription thereof in a prokaryote. The promoter sequence may be capable of directing transcription of the polynucleotide in any of various suitable prokaryotes. Preferably, the prokaryote is E. coli. In order to enable regulatable transcription of the nucleic acid sequence in the host cell, the promoter sequence is preferably further capable of directing inducible transcription of the nucleic acid sequence in the host cell. Various types of promoter sequences capable of directing transcription or inducible transcription of the polynucleotide in the host cell, such as a suitable E. coli cell may be employed. Preferably, the promoter sequence is a T7 promoter sequence. It will be appreciated by the skilled artisan that a construct of the present invention comprising a T7 promoter sequence for directing transcription of the polynucleotide can be used to efficiently inducibly express in a suitable E. coli host cell the antibody fragment of the present invention, or a conjugate thereof with a coat protein of a virus, detectable moiety, and/or toxin. Preferably, the nucleic acid construct is isolated or assembled, and is used to inducibly produce the antibody fragment of the present invention in a host cell as is described and demonstrated in the Examples section below. As described hereinabove, the nucleic acid construct may be expressed in various types of host cells. For example, the nucleic acid construct may be advantageously expressed in a eukaryotic host cell, such as a mammalian cell or a plant cell. Methods of expressing nucleic acid constructs encoding antibody fragments in eukaryotic cells are widely practiced by the ordinarily skilled artisan. Plant cells expressing the nucleic acid construct can be used to generate plants expressing the nucleic acid construct, thereby enabling inexpensive and facile production of large quantities of antibody which can be harvested, processed and stored using existant infrastructure. Expression of the nucleic acid construct of the present invention in plants can be used to produce plants expressing various forms of the composition-of-matter of the present invention, including immunoconjugates such as immunotoxins. Ample guidance for expressing nucleic acid constructs encoding antibody fragments, such as nucleic acid constructs encoding immunotoxins, in plant cells, and thereby in plants, is provided in the literature of the art (for example, refer to: Peeters K. et al., 2001. Vaccine: 19:2756-61; De Jaeger G. et al., 2000. Plant Mol. Biol. 43:419-28; Fischer R. et al., 2000. J Biol Regul Homeost Agents. 14:83-92; Fischer R. et al., 1999. Biotechnol Appl Biochem. 30:101-8; and Russell D A., 1999. Curr Top Microbiol Immunol. 240:119-38). While reducing the present invention to practice, viruses comprising the nucleic acid construct of the present invention, and a coat protein fused to an antibody fragment of the present invention were isolated or generated. Thus, the present invention provides a virus comprising the nucleic acid construct of the present invention and/or a coat protein fused to an antibody fragment of the present invention. The virus of the present invention can be used in various applications, such as, for example, for selecting an antibody fragment of the present invention having a desired binding affinity/specificity for the antigen-presenting portion of the complex. Alternately, such a virus may be used for propagating the antibody fragment or the nucleic acid construct. Preferably, such propagation is effected by using the virus to infect a host cell. Any of various types of viruses comprising an antibody fragment of the present invention fused to any of various types of coat protein may be used. Preferably, the virus is a filamentous phage and the coat protein is pIII. While various methods may be employed to obtain and utilize the virus, it is preferably obtained and utilized as described and demonstrated in the Examples section which follows. While reducing the present invention to practice, host cells comprising the nucleic acid construct were generated and used to produce antibody fragments of the present invention. Thus, the present invention provides a host cell comprising the nucleic acid construct. While the host cell may be advantageously used in various applications, it is preferably used to produce the antibody fragment, as mentioned hereinabove. Alternately, the host cell may be used to propagate the nucleic acid construct. Various types of host cell may be used to practice the present invention, depending on the application and purpose. Preferably, the host cell is a prokaryotic cell. Alternately, the host cell may be a mammalian cell (please refer to the antibody/antibody fragment production guidelines herein for description of suitable mammalian cells, and methods of their use). While any of various types of prokaryotic host cells may be utilized, the prokaryotic cell is preferably an E. coli cell. While various methods may be employed to obtain and utilize the E. coli host cell, for example, to produce the antibody or antibody fragment, it is preferably obtained and utilized as described and demonstrated in the Examples section which follows. While reducing the present invention to practice the capacity of the composition-of-matter to enable specific detection of the antigen-presenting portion of a particular human APM:pathogen-derived antigen complex was demonstrated. Thus, according to another aspect of the present invention there is provided a method of detecting the antigen-presenting portion of the complex. The method is effected by exposing the antigen-presenting portion of the complex to a composition-of-matter of the present invention to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody, fragment comprised in the composition-of-matter. Once the conjugate is formed, the method further comprises detecting the antibody or antibody fragment of the conjugate so as to thereby detect the antigen-presenting portion of the complex. The method according to this aspect of the present invention can be used to detect the antigen-presenting portion of the complex in any of various contexts and applications. In particular, as described hereinbelow, the method can be used to diagnose an infection by a pathogen in an individual. Depending on the application and purpose, various methods may be utilized to expose the antigen-presenting portion of the complex to the composition-of-matter, according to the teachings of the present invention. When using the method for detecting the antigen-presenting portion of a complex displayed/expressed by target cells/tissues, or of a complex immobilized on a surface, the antigen-presenting portion of the complex is preferably exposed to the composition-of-matter by exposing the target cells/tissues, or the surface-immobilized antigen-presenting portion of the complex, respectively, to the composition-of-matter. For certain applications, the biological sample may be advantageously obtained from an individual prior to contacting the composition-of-matter with the biological sample. Alternately, the composition-of-matter may be contacted with the biological sample by administering the composition-of-matter to the individual. As described hereinabove, once the composition-of-matter and the antigen-presenting portion of the complex exposed to the composition-of-matter form the conjugate, the method further comprises detecting the antibody or antibody fragment of the conjugate so as to thereby detect the antigen-presenting portion of the complex. While various methods may be employed to detect the antibody or antibody fragment of the antigen-presenting portion of the complex, the antigen-presenting portion of the complex is preferably detected by using a composition-of-matter of the present invention comprising an antibody or antibody fragment attached a detectable moiety, and detecting the antibody or antibody fragment by detecting the detectable moiety attached thereto. As described hereinabove, various detectable moieties may be used to detect the antigen-presenting portion of the complex in the context of various detection assays, depending on the application and purpose. Preferably, the method according to this aspect of the present invention is used to detect the antigen-presenting portion of a complex in a biological sample. Alternately, the method may be used to detect the antigen-presenting portion of a complex immobilized on a non-cellular surface, such as an the surface of an ELISA plate. While the method may be used to detect the antigen-presenting portion of the complex in essentially any type of biological sample, it is preferably applied to detect the antigen-presenting portion of a complex displayed/expressed by target cells/tissues. Preferably, the target cells are pathogen infected cells displaying the complex, or APCs displaying the complex, such as professional APCs, dendritic cells, B lymphocytes, granulocytes, neutrophils, basophils, eosinophils, monocytes, macrophages, and mast cells. It will be appreciated that since, as described hereinabove, the composition-of-matter may comprise an antibody or antibody fragment capable of specifically binding a complex comprising as, APM-restricted antigen an antigen derived from essentially any pathogen, the method according to this aspect of the present invention can be used to detect a complex comprising as APM-restricted antigen, an antigen derived from essentially any pathogen. Preferably, the method is used to detect target cells displaying/expressing a particular complex comprising as APM-restricted antigen, an HTLV-1-derived antigen Preferably, the method according to this aspect of the present invention is effected as described in the Examples section which follows. As is demonstrated in the Examples section below, practicing the method according to the protocol set forth therein can be used in numerous contexts to detect with optimal specificity and sensitivity cells displaying a particular complex comprising as APM-restricted antigen, an HTLV-1-derived antigen, or such a complex immobilized on a non cellular surface. Thus, the method according to this aspect of the present invention may be used to effectively and potently diagnose and characterize an infection by a pathogen in an individual. It will be appreciated that since, as described hereinabove, this aspect of method of the present invention can be used to detect essentially any complex in essentially any context with optimal specificity and/or sensitivity, the method according to this aspect of the present invention can be used to optimally diagnose and characterize essentially any infection associated with essentially any pathogen. For example, as described in the Examples section below, the method according to this aspect of the present invention can be used to optimally detect an APM:retrovirus-derived antigen. Thus, the method can be used to optimally detect in an individual an infection by a retrovirus. Retrovirus are associated with a wide variety of diseases including an array of malignancies, immunodeficiencies (notably AIDS), and neurological disorders, and syndromes as seemingly diverse as arthritis, osteopetrosis, and anemia. Thus, the method according to this aspect of the present invention can be used, for example, to optimally diagnose essentially all such diseases in an individual. Preferably, the method according to this aspect of the present invention is used to diagnose an HTLV-1 infection, or a disease associated with such infection, in an individual, since, as described and demonstrated, in the Examples section which follows, the method according to this aspect of the present invention can be used to detect with optimal sensitivity and specificity a target cell displaying a complex comprising as APM-restricted antigen, an HTLV-1-derived antigen. Diseases associated with HTLV-1 infection which may diagnosed and characterized using this according to this aspect of the present invention include adult T-lymphocyte leukemia/lymphoma (ATLL; Yoshida M. et al., 1982. Proc Natl Acad Sci USA. 79:2031-2035), Sjogren's syndrome, inflammatory arthropathies, polymyositis, and pneumopathies (Coscoy L. et al., 1998. Virology 248: 332-341). Most preferably, this aspect of the present invention can be used for diagnosis and characterization of HTLV-1 associated myelopathy/tropical virus spastic paraparesis (HAM/TSP; Osame M. et al., 1986. Lancet 1:1031-1032), as is described in Example 2 of the Examples section which follows. While reducing the present invention to practice, the capacity of the composition-of-matter of the present invention to enable killing/damaging of target cells was demonstrated. Thus, according to a further aspect of the present invention there is provided a method of killing or damaging target cells. According to the teachings of the present invention, the method is effected by exposing the target cells to the composition-of-matter of the present invention. The method may be effected so as to kill various types of target cells in various ways, depending on the application and purpose. Preferably, the method is effected by exposing target cells to a composition-of-matter of the present invention comprising an antibody or antibody fragment attached to a toxin, so as to thereby kill/damage the target cells via the toxin. Alternately, in an in-vivo context or an in-vitro equivalent thereof, the method may be effected by exposing target cells to a composition-of-matter of the present invention comprising an antibody or antibody fragment including an Fc region, or portion thereof, capable of specifically binding a molecule capable of initiating an immune response, such as a complement cascade or ADCC, directed against target cells bound by such an antibody or antibody fragment, as described hereinabove. While the method according to this aspect of the present invention can be used for killing/damaging target cells in any of various contexts and applications, it is preferably employed to kill/damage target cells so as to treat a disease associated with a pathogen in an individual. It will be appreciated that the method may also be used to kill/damage target cells in-vitro or in-vivo in an animal model, in particular to test and/or optimize killing/damaging of target cells using the composition-of-matter. Such testing and/or optimizing killing/damaging of target cells using the composition-of-matter may be advantageously applied towards optimizing treatment of the disease in the individual using the composition-of-matter. When using the method according to this aspect of the present invention for optimizing use of the composition-of-matter to kill/damage target cells for treating the disease, the method may be advantageously effected by obtaining the target cells from the individual. One of ordinary skill in the art, such as a physician, will possess the necessary expertise to obtain target cells from an individual. Various types of target cells may be obtained from the individual for optimizing use of the composition-of-matter to kill/damage target cells. Preferably, such target cells are cells infected with the pathogen since such cells will be of particular utility for optimizing killing of target cells infected with the pathogen, and hence for optimizing treatment of the disease in the individual. It will be appreciated that since, as described hereinabove, the composition-of-matter may comprise an antibody or antibody fragment capable of binding with optimal specificity and affinity a complex comprising as APM-restricted antigen an antigen derived from essentially any pathogen, the method according to this aspect of the present invention can be used to kill/damage cells displaying/expressing a complex comprising as APM-restricted antigen, an antigen derived from essentially any pathogen with optimal efficiency and specificity. Preferably, the method is used to kill/damage target cells displaying/expressing a particular complex comprising as APM-restricted antigen, an HTLV-1-derived antigen Preferably the method according to this aspect of the present invention is effected as described in the Examples section which follows. As is demonstrated in the Examples section below, practicing the method according to the protocol set forth therein can be used to kill with optimal efficiency and specificity cells displaying a particular complex comprising as APM-restricted antigen, an H-TLV-1-derived antigen. Thus, the present invention provides a method of treating a disease associated with a pathogen in an individual. The method is effected by administering to the individual a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient a composition-of-matter of the present invention comprising as APM-derived antigen, an antigen derived from the pathogen. As described in detail hereinbelow, the pharmaceutical composition may be administered in various ways. As described hereinabove, the method according to this aspect of the present invention is preferably effected using a composition-of-matter comprising an immunotoxin. Ample guidance for treating a disease using an immunotoxin is provided in the literature of the art (for example, for general references refer to: Knechtle S J. 2001, Philos Trans R Soc Lond B Biol Sci. 356:681-93; Kreitman R J., 2001. Methods Mol. Biol. 166:111-23; Brinkmann U., 2000. in-vivo 14:21-7; Ghetie M A and Vitetta E S., 1994. Curr Opin Immunol. 6:707-14; Wu M., 1997. Br J Cancer. 75:1347-55; Hall W A. 1996, Neurosurg Clin N Am. 7:537-46; Boon, T. and van der Bruggen, P., 1996. J. Exp. Med. 183:725-729; Renkvist, N. et al., 2001. Cancer Immunol Immunother. 50:3-15; Rosenberg, S. A., 2001. Nature 411:380-384; and U.S. Pat. No. 5,677,274; for treatment of acquired immunodeficiency syndrome (AIDS), refer, for example, to Chaplin J W., 1999. Med Hypotheses 52:133-46; for treatment of brain tumors, refer, for example, to Hall W A., 2001. Methods Mol. Biol. 166:139-54; for treatment of hematological malignancies, refer, for example to: Pasqualucci L. et al., 1995. Haematologica 80:546-56; Grossbard M L. et al.,. Clin Immunol Immunopathol. 76:107-14; and Grossbard M L and Nadler L M., 1994. Semin Hematol. 31:88-97; for treatment of carcinomas, refer, for example, to Siegall C B., 1995. Semin Cancer Biol. 6:289-95; for treatment of cancer, refer, for example, to: Frankel A E., 1993. Oncology (Huntingt) 7:69-78; and Pai L H. and Pastan I., 1993. JAMA. 269:78-81). The method can be used to treat various types of diseases associated with a pathogen using various methodologies taught by the present invention. Preferably, the method is used to treat a disease associated with a pathogen by killing/damaging pathogen infected cells. This may be advantageously performed where the pathogenesis of the disease derives predominantly from the pathogen infected, cells. Alternately, the method may be used to treat the disease, where the disease involves a pathogenic immune response directed against pathogen-infected cells by pathogenic T-lymphocytes activated by pathogenic APCs displaying/expressing a complex comprising as APM-restricted antigen, an antigen derived from the pathogen. This is preferably effected, as described hereinabove, by using the composition-of-matter to kill/damage such pathogenic APCs. Alternately, the pathogenic immune response mediated by such pathogenic APCs may be inhibited as described hereinabove, by using a composition-of-matter of the present invention comprising an antibody or antibody fragment capable of specifically binding the pathogenic complex so as to thereby block activation of the pathogenic T-lymphocytes via engagement of the TCRs thereof by the complex. It will be appreciated that since, as described hereinabove, this aspect of method of the present invention can be used to kill with optimal efficiency and specificity cells displaying/expressing essentially any particular complex, the method according to this aspect of the present invention can be used to optimally treat essentially any infection associated with essentially any pathogen in an individual. For example, as described in the Examples section below, the method according to this aspect of the present invention can be used to kill/damage with optimal efficiency and specificity cells displaying a complex comprising as APM-restricted antigen, an antigen derived from a retrovirus. Thus, the method can be used to optimally treat, for example, an infection associated with a retrovirus in an individual Thus, the method according to this aspect of the present invention can be used, for example, to optimally treat the broad range of diseases associated with a retroviral infection described hereinabove. Preferably, the method according to this aspect of the present invention is used to treat an HTLV-1 infection in an individual, since, as described and demonstrated in the Examples section which follows, the method according to this aspect of the present invention can be used to kill with optimal efficiency and specificity target cells displaying a complex comprising as APM-restricted antigen, an HTLV-1-derived antigen. As described hereinabove, the antibody or antibody fragment of the present invention may be generated in numerous ways. A monoclonal or polyclonal antibody or antibody fragment of the present invention may be generated via methods employing induction of in-vivo production of antibody or antibody fragment molecules, or culturing of antibody- or antibody fragment producing cell lines. Ample guidance for practicing such methods is provided in the literature, of the art [for example, refer to Harlow and Lane, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory, New York, (1988)]. Cell culture-based methods of generating antibodies include the hybridoma technique, the human B-cell hybridoma technique, and the Epstein-Barr virus (EBV)-hybridoma technique (Kohler G. et al., 1975. Nature 256:495-497; Kozbor D. et al., 1985. J. Immunol. Methods 81:31-42; Cote R J. et al., 1983. Proc Natl Acad Sci USA. 80:2026-2030; Cole S P. et al., 1984. Mol. Cell. Biol. 62:109-120). Generating an antibody or antibody or antibody fragment of the present invention in-vivo may be advantageously effected by repeated injection of a target antigen (e.g., one comprising the antigen-presenting portion of the complex) into a mammal in the presence of adjuvants according to a schedule which boosts production of antibodies in the serum. In cases wherein the target antigen is too small to elicit an adequate immunogenic response (referred to as a “hapten” in the art), the hapten can be coupled to an antigenically neutral carrier such as keyhole limpet hemocyanin (KLH) or serum albumin [e.g., bovine serum albumin (BSA)] carriers (for example, refer to: U.S. Pat. Nos. 5,189,178 and 5,239,078). Coupling a hapten to a carrier can be effected using various methods well known in the art. For example, direct coupling to amino groups can be effected and optionally followed by reduction of the imino linkage formed. Alternatively, the carrier can be coupled using condensing agents such as dicyclohexyl carbodiimide or other carbodiimide dehydrating agents. Linker compounds can also be used to effect the coupling both homobifunctional and heterobifunctional linkers are available from Pierce Chemical Company, Rockford, Ill. The resulting immunogenic complex can then be injected into suitable mammalian subjects such as mice, rabbits, and the like. Following in-vivo generation of an antibody, its serum titer in the host mammal can readily be measured using immunoassay procedures which are well known in the art. Such a polyclonal antibody containing anti-serum may be utilized as such, following purification thereof to generate a pure polyclonal or monoclonal antibody preparation. Such an anti-serum or purified antibody preparation may also be modified in various ways, depending on the application and purpose, prior to use. Genetic sequences encoding an antibody isolated from such an anti-serum may be determined using standard art techniques, and used to recombinantly produce the antibody or a modification thereof, such as an antibody fragment. An antibody fragment of the present invention can be obtained using various methods well known in the art. For example, such an antibody fragment can be prepared by proteolytic hydrolysis of a parental antibody or by recombinant expression in E. coli or mammalian cells (e.g., Chinese hamster ovary cell culture or other protein expression systems) of DNA encoding the fragment. An F(ab′)2 antibody fragment can be produced by enzymatic cleavage of a parental antibody with pepsin to provide a 5S fragment. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages to produce a 3.5S monovalent Fab′ antibody fragment. Enzymatic cleavage of a parental antibody with pepsin can be used to directly produce two monovalent Fab′ fragments and an Fc fragment. Ample guidance for practicing such methods is provided in the literature of the art (for example, refer to: Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647; Porter R R., 1959. Biochem J. 73:119-126). As described hereinabove, an Fv is composed of paired heavy chain variable and light chain variable domains. This association may be noncovalent (for example, refer to Inbar et al., 1972. Proc. Natl. Acad. Sci. U.S.A. 69:2659-62). Alternatively, as described hereinabove the variable domains can be linked to generate a single chain Fv by an intermolecular disulfide bond, or such chains may be covalently cross-linked using chemicals such as glutaraldehyde. A single chain Fv may advantageously prepared by constructing a structural gene comprising DNA sequences encoding the heavy chain variable domain and the light chain variable domain connected by an oligonucleotide encoding a peptide linker. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli which will then synthesize such a single chain Fv. Ample guidance for practicing such methods of producing a single chain Fv is provided in the literature of the art (for example, refer to: Whitlow and Filpula, 1991. Methods 2:97-105; Bird et al., 1988. Science 242:423-426; Pack et al., 1993. Bio/Technology 11:1271-77; and Ladner et al., U.S. Pat. No. 4,946,778). Other methods of cleaving an antibody, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragment bind to the target antigen that is recognized by the intact antibody. A polypeptide comprising a complementarity determining region (CDR) peptide of an antibody can be obtained via recombinant techniques using genetic sequences encoding such a CDR, for example, by RT-PCR of mRNA of an antibody-producing cell. Ample guidance for practicing such methods is provided in the literature of the art (for example, refer to Larrick and Fry, 1991. Methods 2:106-10). It will be appreciated that for human therapy or diagnostics, a humanized antibody or antibody fragment may be advantageously used. Humanized non human (e.g., murine) antibodies are genetically engineered chimeric antibodies or antibody fragments having—preferably minimal—portions derived from non human antibodies. Humanized antibodies include antibodies in which complementary determining regions of a human antibody (recipient antibody) are replaced by residues from a complementarity determining region of a non human species (donor antibody) such as mouse, rat or rabbit having the desired functionality. In some instances, Fv framework residues of the human antibody are replaced by corresponding non human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported complementarity determining region or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the complementarity determining regions correspond to those of a non human antibody and all or substantially all, of the framework regions correspond to those of a relevant human consensus sequence. Humanized antibodies optimally also include at least a portion of an antibody constant region, such as an Fc region, typically derived from a human antibody (see, for example, Jones et al., 1986. Nature 321:522-525; Riechmann et al., 1988. Nature 332:323-329; and Presta, 1992. Curr. Op. Struct. Biol. 2:593-596). Methods for humanizing non human antibodies or antibody fragments are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non human. These non human amino acid residues are often referred to as imported residues which are typically taken from an imported variable domain. Humanization can be essentially performed as described (see, for example: Jones et al., 1986. Nature 321:522-525; Riechmann et al., 1988. Nature 332:323-327; Verhoeyen et al., 1988. Science 239:1534-1536; U.S. Pat. No. 4,816,567) by substituting human complementarity determining regions with corresponding rodent complementarity determining regions. Accordingly, such humanized antibodies are chimeric antibodies, wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non human species. In practice, humanized antibodies may be typically human antibodies in which some complementarity determining region residues and possibly some framework residues are substituted by residues from analogous sites in rodent antibodies. Human antibodies or antibody fragments can also be produced using various techniques known in the art, including phage display libraries [see, for example, Hoogenboom and Winter, 1991. J. Mol. Biol. 227:381; Marks et al., 1991. J. Mol. Biol. 222:581; Cole et al., “Monoclonal Antibodies and Cancer Therapy”, Alan R. Liss, pp. 77 (1985); Boerner et al., 1991. J. Immunol. 147:86-95). Humanized antibodies can also be made by introducing sequences encoding human immunoglobulin loci into transgenic animals, e.g., into mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon antigenic challenge, human antibody production is observed in such animals which closely resembles that seen in humans in all respects, including gene rearrangement, chain assembly, and antibody repertoire. Ample guidance for practicing such an approach is provided in the literature of the art (for example, refer to: U.S. Pat. Nos. 5,545,807, 5,545,806, 5,569,825, 5,625,126, 5,633,425, and 5,661,016; Marks et al., 1992. Bio/Technology 10:779-783; Lonberg et al., 1994. Nature 368:856-859; Morrison, 1994. Nature 368:812-13; Fishwild et al., 1996. Nature Biotechnology 14:845-51; Neuberger, 1996. Nature Biotechnology 14:826; Lonberg and Huszar, 1995. Intern. Rev. Immunol. 13:65-93). Once an antibody or antibody or antibody fragment is obtained, it may be advantageously tested for specific binding to the antigen-presenting portion of the complex, for example via ELISA, using surface-immobilized target complex, as described in further detail hereinbelow, and in the Examples section which follows. Following confirmation of specific binding of the antibody or antibody fragment to the antigen-presenting portion of the complex, various methods may be employed to modify the antibody or antibody fragment to display the desired binding affinity for the antigen-presenting portion of the complex. Such methods include those based on affinity maturation (for example, refer to: Chowdhury, P. S., and Pastan, I., 1999. Nat. Biotechnol. 17:568-72). As described hereinabove, the present invention can be used to treat a disease associated with an infection by a pathogen in an individual by administering a pharmaceutical composition comprising as an active ingredient a composition-of-matter of the present invention. As used herein a “pharmaceutical composition” refers to a preparation of one or more of the active ingredients described herein with other chemical components such as physiologically suitable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of active ingredients to an organism. Herein the term “active ingredients” refers to the composition-of-matter accountable for the biological effect. Hereinafter, the phrases “physiologically acceptable carrier” and “pharmaceutically acceptable carrier” which may be interchangeably used refer to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered active ingredients. An adjuvant is included under these phrases. Herein the term “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. Techniques for formulation and administration of drugs may be found in “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., latest edition, which is incorporated herein by reference. Suitable routes of administration may, for example, include oral, rectal, transmucosal, especially transnasal, intestinal or parenteral delivery, including intramuscular, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections. Alternately, one may administer the pharmaceutical composition in a local rather than systemic manner, for example, via injection of the pharmaceutical composition directly into a tissue region of a patient. Pharmaceutical compositions of the present invention may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations which, can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. For injection, the active ingredients of the pharmaceutical composition may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art. For oral administration, the pharmaceutical composition can be formulated readily by combining the active ingredients with pharmaceutically acceptable carriers well known in the art. Such carriers enable the pharmaceutical composition to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for oral ingestion by a patient. Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethylcellulose, sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Alternately, for oral administration, the pharmaceutical composition may comprise an edible part of a plant containing, for example the immunotoxin of the present invention, as described hereinabove. Hence an individual may consume such an immunotoxin in the form of a plant food endogenously expressing the immunotoxin. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active ingredient doses. Pharmaceutical compositions which can be used orally, include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active ingredients may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner. For administration by nasal inhalation, the active ingredients for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from a pressurized pack or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g. gelatin for use in a dispenser may be formulated containing a powder mix of the active ingredients and a suitable powder base such as lactose or starch. The pharmaceutical composition described herein may be formulated for parenteral administration, e.g., by bolus, injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multidose containers with optionally, an added preservative. The compositions may be suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Pharmaceutical compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form. Additionally, suspensions of the active ingredients may be prepared as appropriate oily or water based injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acids esters such as ethyl oleate, triglycerides or liposomes. Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the active ingredients to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredients may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water based solution, before use. The pharmaceutical composition of the present invention may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides. Pharmaceutical compositions suitable for use in context of the present invention include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients (nucleic acid construct) effective to prevent, alleviate or ameliorate symptoms of a disorder (e.g., ischemia) or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. For any preparation used in the methods of the invention, the therapeutically effective amount or dose can be estimated initially from in vitro and cell culture assays. For example, a dose can be formulated in animal models to achieve a desired concentration or titer. Such information can be used to more accurately determine useful doses in humans. Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl, et al., 1975, in “The Pharmacological Basis of Therapeutics”, Ch. 1 p. 1). Dosage amount and interval may be adjusted individually to provide plasma or brain levels of the active ingredients sufficient to exert a desired therapeutic effect (minimal effective concentration, MEC). The MEC will vary for each preparation, but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. Detection assays can be used to determine plasma concentrations. Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved. The amount of a composition to be administered will, of course, be dependent on the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc. Compositions of the present invention may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the active ingredients. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration. Such notice, for example, may be of labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a preparation of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition, as if further detailed above. It is expected that during the life of this patent many relevant medical diagnostic techniques will be developed and the scope of the phrase “method of detecting” is intended to include all such new technologies a priori. Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples. EXAMPLES Reference is now made to the following examples, which together with the above descriptions, illustrate the invention in a non limiting fashion. Generally, the nomenclature used herein and the laboratory procedures utilized in the present invention include molecular, biochemical, microbiological and recombinant DNA techniques. Such techniques are thoroughly explained in the literature. See, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988); Watson et al., “Recombinant DNA”, Scientific American Books, New York; Birren et al. (eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, Cold Spring Harbor Laboratory Press, New York (1998); methodologies as set forth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and 5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis, J. E., ed. (1994); “Current Protocols in Immunology” Volumes I-III Coligan J. E., ed. (1994); Stites et al. (eds), “Basic and Clinical Immunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994); Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W. H. Freeman and Co., New York (1980); available immunoassays are extensively described in the patent and scientific literature, see, for example, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578; 3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533; 3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521; “Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “Nucleic Acid Hybridization” Hames, B. D., and Higgins S. J., eds. (1985); “Transcription and Translation” Hames, B. D., and Higgins S. J., eds. (1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “Immobilized Cells and Enzymes” IRL Press, (1986); “A Practical Guide to Molecular Cloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317, Academic Press; “PCR Protocols: A Guide To Methods And Applications”, Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategies for Protein Purification and Characterization—A Laboratory Course Manual” CSHL Press (1996); all of which are incorporated by reference as if fully set forth herein. Other general references are provided throughout this document. The procedures therein are believed to be well known in the art and are provided for the convenience of the reader. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. Example 1 Generation of Reagents Capable of Binding with Optimal Affinity and Specificity Particular Human APM:Pathogen-Derived Antigen Complexes Applicable Towards Optimal Diagnosis, Characterization, and Treatment of Human Pathogen Infections Diseases associated with a pathogen infection, such as a viral infection, include numerous debilitating or lethal diseases of major medical and economic impact, including influenza, the common cold, and acquired immunodeficiency syndrome (AIDS). One theoretically potent approach which has been proposed for diagnosing, characterizing, and treating such pathogen mediated diseases involves using compounds capable of binding specific human antigen-presenting molecule (APM):pathogen-derived peptide complexes. Such compounds could be used to identify and characterize pathogen infected cells/tissues, or APCs exposed to viral antigens with optimal specificity, to deliver cytotoxic agents with optimal selectivity and efficiency to pathogen infected cells, and to serve as uniquely potent tools for studying pathogen mediated pathogenesis involving viral antigen presentation. However, all prior art approaches of generating compounds capable of specifically binding such complexes have failed to provide compounds capable of binding with optimal affinity/specificity human APM:pathogen-derived antigen complexes. While reducing the present invention to practice, the present inventors have unexpectedly uncovered such compounds, as follows. Materials and Methods: Cell lines and antibodies: RMA-S-HHD is a TAP2 deficient murine cell line which expresses HLA-A2.1/Db-beta2-microglobulin single-chain (Pascolo, S. et al., 1997. J. Exp. Med. 185:2043-2051). JY is a TAP and HLA-A2 positive EBV transformed B lymphoblast cell line. APD is an HLA-A2 negative/HLA-A1 positive B cell line. HUT 102 and RSCD4 are HLA-A2 negative and positive, HTLV-1 infected human CD4 positive T-lymphocyte cell lines, respectively. G2D12 is an anti HLA-A2:G9-154 complex Fab used as a negative control (peptide G9-154 is derived from the melanoma specific gp100 protein). Monoclonal antibodies w6/32 and BB7.2 specifically bind correctly folded, peptide bound HLA (pan HLA), and HLA-A2, respectively. Production of biotinylated soluble HL4-A2:Tax11-19 complex: Soluble biotinylated HLA-A2:Tax11-19 complex was generated as previously described (Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532). Briefly, a construct was assembled for expression of single chain MHC fusion protein containing HLA-A2.1 (alternately termed HLA-A*201) fused to beta2-microglobulin, the BirA recognition sequence for site specific biotinylation at the C-terminus, and a hexahistidine tag fused to the CH1 domain of the Fd chain. In this single chain fusion protein, HLA-A2 and beta2-microglobulin are fused via a flexible peptide linker. For expression of this single chain E. coli, transformants were generated using the construct, inclusion bodies containing the fusion protein were isolated from the periplasmic fraction of transformants by nickel affinity chromatography, and the fusion protein from inclusion bodies was refolded in-vitro in the presence of a 5 to 10 fold molar excess of HLA-A2 restricted peptide so as to generate soluble, correctly folded and assembled HLA-A2:Tax11-19 complexes. Correctly folded HLA-A2:Tax11-19 complex was isolated and purified by anion exchange Q-Sepharose chromatography (Pharmacia) followed by site specific biotinylation using the BirA enzyme (Avidity, Denver, Colo.), as previously described (Altman J. D. et al., 1996. Science 274:94-96). The homogeneity and purity of the HLA-A2:Tax11-19 complex were analyzed by various biochemical means including SDS-PAGE, size exclusion chromatography, and enzyme linked immunosorbent assay (ELISA), as previously described (Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532). Selection of Fab-phages capable of specifically binding HL4-A2:Tax11-19 complex: Selection of Fab-phages (Fab-phages) on surface immobilized biotinylated MHC:peptide complex was performed as previously described (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426; Lev, A. et al., 2002. Cancer Res. 62:3184-3194). Briefly, a large human Fab library containing 3.7×1010 different Fab clones (de Haard, H. J. et al., 1999. J. Biol. Chem. 274:18218-18230) was used for the selection. Aliquots of 1013 phages were pre incubated with 200 microliters of streptavidin coated paramagnetic beads (Dynal, Oslo) to deplete streptavidin binders. The remaining phages were then panned using decreasing amounts of surface immobilized biotinylated HLA-A2:Tax11-19 complex as binding target (500 nanomolar for the first round, and 100 nanomolar for the following rounds). Bound phages were eluted with 100 millimolar triethylamine, and the eluate was neutralized with 1 molar Tris.HCl pH 7.4. Neutralized phages were then used to infect E. coli TG1 cells (OD600=0.5) by incubation for 30 minutes at 37 degrees centigrade. The diversity of the selected antibodies was determined by DNA fingerprinting. The Fab DNA of different clones was PCR amplified using the primers pUC-reverse [5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO: 1)]and fd-tet-seq24 [5′-TTTGTCGTCTTTCCAGACGTTAGT-3′ (SEQ ID NO: 2)] followed by digestion with BstNI (New England Biolabs, U.S.A.) by incubation for 2 hours at 60 degrees centigrade. Reaction products were analyzed by agarose gel electrophoresis. Expression and purification of soluble recombinant Fab's: Fab's were expressed and purified as previously described (Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532). Briefly, cultures of TG1 or BL21 cells transformed with constructs for expression of Fab's under the control of isopropyl beta-D-thiogalactoside (IPTG) inducible regulatory sequences were grown to OD600=0.8 to 1.0. Cultures were induced to express recombinant Fab by addition of 1 millimolar IPTG and further culturing for 3 to 4 hours at 30 degrees centigrade. Periplasmic content was released using B-PER solution (Pierce), and applied onto a pre-washed TALON column (Clontech). Bound Fab was eluted from the column using 0.5 ml of 100 millimolar imidazole dissolved in phosphate buffered saline solution, and dialyzed twice against phosphate buffered saline solution by overnight incubations at 4 degrees centigrade to remove residual imidazole. ELISA of Fab-phage clones and purified Fab's: The binding specificities of individual Fab-phage clones and soluble Fab's for HLA-A2:Tax11-19 complex were determined by ELISA using biotinylated HLA-A2:Tax11-19 complex as binding target. ELISA plates (Falcon) were coated overnight with BSA-biotin (1 microgram/well). Coated plates were washed and incubated for 1 hour at room temperature with streptavidin (1 microgram/well). After extensive washing, the plates were incubated for 1 hour at room temperature with 0.5 microgram of HLA-A2:Tax-11-19 complex. The plates were blocked for 30 minutes at room temperature with 2 percent skim to milk-phosphate buffered saline solution, and were subsequently incubated for 1 hour at room temperature with about 109 phage clones per well, or with various concentrations of soluble purified Fab. The plates were washed and incubated with horseradish peroxidase conjugated anti human Fab antibody for soluble Fab, or with horseradish peroxidase conjugated anti M13 phage antibody for Fab-phages. Detection was performed using TMB reagent (Sigma). The amino acid sequences of the Tax11-19 target peptide and of HLA-A2 restricted negative control peptides used for screening the Fab-phage clones or purified Fab's are shown in Table 1. TABLE 1 HLA-A2 restricted peptides used for screening Fab-phage clones or purified soluble Fab's. Sequence Protein Peptide position LLFGYPVYV (SEQ ID NO: 3) TAX 11-19 LLLTVLTVV (SEQ ID NO: 4) MUC1-D6 13-21 NLTISDVSV (SEQ ID NO: 5) MUC1-A7 130-138 NLVPMVATV (SEQ ID NO: 6) CMV-pp65 495-503 SVRDRLARL (SEQ ID NO: 7) EBNA-3A 596-604 ILAKFLHWL (SEQ ID NO: 8) hTERT 540-548 RLVDDFLLV (SEQ ID NO: 9) hTERT 865-873 IMDQVPFSV (SEQ ID NO: 10) Gp100 209-217 YLEPGPVTV (SEQ ID NO: 11) GplOO 280-288 KTWGQVWQV (SEQ ID NO: 12) GplOO 154-162 EAAGIGILTV (SEQ ID NO: 13) MART 26-35 Production of fluorescent Fab T3F2 tetramer: The genes encoding the light and heavy chains of Fab, T3F2 were cloned separately into a pET expression vector for T7-promoter regulated expression of cloned inserts. The light chain gene was engineered as a fusion protein including the BirA recognition sequence for site specific biotinylation at the carboxy terminus (T3F2 light-BirA). These constructs were expressed separately in E. coli BL21 cells and upon induction with IPTG, intracellular inclusion bodies containing large amounts of the recombinant protein were generated. Inclusion bodies containing the T3F2 chains were purified, solubilized, reduced, and refolded in-vivo at a 1:1 ratio in a redox shuffling buffer system containing 0.1 molar Tris.HCl, 0.5 molar arginine, and 90 micromolar oxidized glutathione at pH 8.0. Correctly folded Fab was then isolated and purified by anion exchange MonoQ chromatography (Pharmacia). The Fab peak fractions were concentrated using Centricon-30 (Amicon) to 1 milligram per milliliter and the buffer was exchanged to 10 millimolar Tris.HCl pH 8.0. Biotinylation was performed using the BirA enzyme (Avidity, Denver, Colo.), as previously described (Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532; Altman J. D. et al., 1996. Science 274:94-96). Excess biotin was removed from biotinylated Fab using a G-25 desalting column. Phycoerythrin labeled streptavidin (Jackson-Immunoresearch) was added at a molar ratio of 1:4 to produce fluorescent tetramers of the biotinylated Fab. Flow Cytometry: The B cell line RMA-S-HHD transformant expressing HLA-A2-beta2-microglobulin, the EBV transformed HLA-A2 positive JY cells, mature human HLA-M positive dendritic cells, and the HLA-A2 negative B cell line APD-70 were used to determine the reactivity: of the recombinant Fab's with cell surface expressed HLA-A2:Tax11-19 complex. Peptide pulsing was performed as indicated. Briefly, about 106 cells were washed twice with serum-free RPMI and incubated overnight at 26 degrees centigrade or 37 degrees centigrade, respectively, in medium containing 1 to 50 micromolar of the peptide. The RMA-S-HHD cells were subsequently incubated at 37 degrees centigrade for 2 to 3 hours to stabilize cell surface expression of HLA-A2:Tax11-19 complex. Alternatively, 20×106 JY or APD cells were transfected with 20 micrograms of the eukaryotic expression vector pcDNA 3.1 (Invitrogen) encoding the TAX protein cDNA (pcTAX). The cDNA was a kind gift of Drs. M. Yutsudo (Osaka University) and T. Oka, (Okayama University). Twelve to twenty four hours after transfection, cells were incubated for 60 to 90 minutes at 4 degrees centigrade with recombinant Fab (20 microgram per milliliter) in a volume of 100 microliters. After incubation, the primarily labeled cells were washed three times, and incubated with 1 microgram of anti human Fab antibody (Jackson-Immunoresearch). The secondarily labeled cells were then washed three times, and resuspended in ice cold phosphate buffered saline solution. All subsequent washes and incubations were performed under ice cold conditions. The cells were analyzed using a FACStar flow cytometer (Becton Dickinson) and the results were analyzed using WINANOMOLARDI software (Trotter J., http://facs.scripps.edu). Flow cytometric analysis of peptide loaded cells was performed as previously described (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426; Lev, A. et al., 2002. Cancer Res. 62:3184-3194). Competition binding assays: Flexible ELISA plates were coated with BSA-biotin and 10 micrograms of HLA-A2:Tax11-19 complex in a volume of 100 microliters were immobilized, as previously described (Lev, A. et al., 2002. Cancer Res. 62:3184-3194; Cohen, C J. et al., 2002. Cancer Res. 62:5835-5844). Binding of soluble purified Fab was performed via a competitive binding analysis in which the ability of purified Fab to inhibit the binding of [125]iodine-Fab to specific surface immobilized HLA-A2:Tax11-19 complex was examined. Recombinant Fab was radiolabeled with [125]iodine using the Bolton-Hunter reagent. The radiolabeled Fab was added to the wells as a tracer (3×105 to 5×105 counts per minute per well) in the presence of increasing concentrations of unlabeled Fab as competitor. Binding assays were performed by incubation at room temperature for 1 hour in phosphate buffered saline solution. After incubation, plates were washed 5 times with phosphate buffered saline solution and bound radioactivity was determined using a gamma counter. The apparent affinity of Fab was determined by extrapolating the concentration of competitor necessary to achieve 50 percent inhibition of binding of [125]iodine labeled Fab to the immobilized HLA-A2:Tax11-19 complex. Non specific binding was determined by adding a 20- to 40-fold excess of unlabeled Fab. Enzyme-linked immunohistochemical analysis of specific human MHC:viral peptide complexes: JY or APD cells were transfected with pcTAX vector, as described above. After 24 hours, transfected cells were incubated with 20 micrograms of horseradish peroxidase (HRP) labeled T3F2 Fab tetramer for 1 hour on ice in RMPI supplemented with 10 percent FCS. The cell suspension was applied onto glass slides precoated with 0.1 percent poly-L-lysine (Sigma), as previously described [Harlow, E., and Lane, D. in: “Antibodies: A Laboratory Manual”. Cold Spring Harbor, Cold Spring Harbor Laboratory Press (1988)], and the slides were incubated for 1 hour at room temperature. Following incubation, the slides were washed three times with phosphate buffered saline solution, and incubated with a DAB+ solution (Dako) for 1 minute followed by washing with phosphate buffered saline solution to remove excess staining reagent. Expression and purification of soluble recombinant anti HLA-A2:Tax11-19 complex immunotoxin: The DNA sequences encoding the heavy and light chain variable domains of T3F2 were recovered from Fab-phage clone by PCR amplification and subcloned using the NcoI-NotI fragment into bacterial expression vector pIB-NN, for expression of T3F2-PE38, a single chain immunotoxin consisting of the toxin PE38 KDEL fused to a single chain Fv of T3F2 via the carboxy terminus of the light chain variable region. Toxin PE38 KDEL consists of the translocation and ADP-ribosylation domains of Pseudomonas exotoxin A. Expression in BL21 IDE3 cells, refolding from inclusion bodies, and purification of the T3F2-PE38 was performed as previously described (Brinkmann U. et al., 1991. Proc. Natl. Acad. Sci. U.S.A. 88:8616-20). Experimental Results: Generation of anti HLA-A2:Tax11-19 complex antibodies: The immune response in HTLV-1 infected patients carrying the MHC class I allele HLA-A2 is primarily directed against the HLA-A2 restricted Tax protein-derived Tax11-19 peptide by clonal expansion of HTLV-1 reactive CD8 positive T-lymphocytes. Recombinant HLA-A2:Tax11-19 complex was generated using a previously described single chain MHC-beta2-microglobulin fusion protein expression construct (Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532). Using this construct, the extracellular domains of HLA-A2 are fused to beta2-microglobulin using a flexible 15 amino acid long peptide linker. The HLA-A2:Tax11-19 complex was produced by in-vitro refolding of inclusion bodies in the presence of Tax11-19 peptide. The refolded HLA-A2:Tax11-19 complex was found to be very pure, homogenous, and monomeric, as determined by SDS-PAGE and size-exclusion chromatography analyses (data not shown). Recombinant HLA-A2:Tax11-19 complex generated by this strategy has been previously characterized in detail with respect to its biochemical, biophysical, and biological properties, and was found to be correctly folded and functional [Denkberg, G. et al., 2000. Eur. J. Immunol. 30:3522-3532; Harlow, E., and Lane, D. in: “Antibodies: A Laboratory Manual”. Cold Spring Harbor: Cold Spring Harbor Laboratory Press (1988)]. For selection of antibodies capable of specifically binding a specific MHC:peptide complex, a large Fab-phage library consisting of a repertoire of 3.7×1010 recombinant human Fab's (de Haard, H. J. et al., 1999. J. Biol. Chem. 274:18218-18230) was used. Due to exposure of the Fab's to streptavidin coated plates during selection, the library was first depleted of streptavidin binders, and subsequently used for panning soluble recombinant HLA-A2:Tax11-19 complex. A 1,300 fold enrichment in phage titer was observed after three rounds of panning (Table 2). The specificity of the selected Fab-phages was determined by a differential ELISA using streptavidin coated wells incubated with biotinylated HLA-A2 in complex with either the Tax11-19 peptide or negative control HLA-A2 restricted peptides. Phage clones analyzed following the third round of selection exhibited two types of binding patterns toward the HLA-A2:Tax11-19 complex; one class of antibodies consisted of pan MHC binders which cannot differentiate between the various specific MHC:peptide complexes; the second type consisted of antibodies that specifically bound the HLA-A2:Tax11-19 complex. The ELISA screen revealed that 87 percent of randomly selected clones (78/90) screened from the third round of panning appeared to specifically bind the HLA-A2:Tax11-19 complex. TABLE 2 Screening of Fab-phages for anti HLA-A2:Tax11-19 complex Fab's. Fraction Phage Phage Ratio Fold MHC:peptide MHC:peptide No. of Cycle input (I) output (O) (O/I) enrichment complex binders complex binders Fab's 1 7.2 × 1012 9.6 × 105 1.3 × 10−7 — — — — 2 5.8 × 1013 1.1 × 107 1.9 × 10−7 1.5 15/90 (17%) 10/90 (11%) 6 3 5.2 × 1013 8.7 × 109 1.7 × 10−4 1,300 78/90 (87%) 56/90 (62%) 14 However, an unexpectedly high percentage of Fab's, 62 percent (56/90), were fully Tax11-19 peptide dependent for binding and specific for HLA-A2:Tax11-19 complex when tested as Fab-phages in ELISAs using various HLA-A2:control peptide complexes as binding targets. As shown in Table 2, 62 percent of the clones bound only to the HLA-A2:Tax11-19 complex and not to negative control complexes containing other HLA-A2 restricted peptides. Such clones thus exhibited an MHC restricted peptide specific binding similar to T-cell receptors (TCRs). These apparent HLA-A2:Tax11-19 complex specific clones remained specific for HLA-A2:Tax11-19 complex in a secondary screening using HLA-A2 complexed with other HLA-A2 restricted peptides (listed under Materials and Methods). FIG. 1 shows a representative analysis of four Fab clones which reacted only with the HLA-A2:Tax11-19 complex and not with HLA-A2:negative control peptide complexes displaying melanoma gp100 and MART-1-derived epitopes, and the MUC1-derived D6 epitope. The diversity pattern of the peptide specific clones (from round two or three) was examined by DNA fingerprint analysis. Twenty different restriction patterns (6 for clones isolated from the second round of panning, and 14 different patterns after the third round of selection) were found, indicating successful selection of several different Fab's capable of specifically binding HLA-A2:Tax11-19 complex. DNA sequencing analysis confirmed these observations. The variable heavy and variable light chain complementarity determining region sequences of 14 clones specific for HLA-A2:Tax11-19 complex are shown in Table 3. TABLE 3 Amino acid sequences of complementarity determining regions of Fab's specifically binding HLA-A2:Tax11-19complex Fab Chain* CDR1 CDR2 CDR3 T3E3 H SYTIS GIIPIFGTANYAQKFQG DTDSSGYYGAVDY (SEQ ID NO: 14) (SEQ ID NO: 15) (SEQ ID NO: 16) L RASQSVGSYLA DASHRAT QQRSNWPPMYT (SEQ ID NO: 17) (SEQ ID NO: 18) (SEQ ID NO: 19) T3F2 H SYGMH VISYDGSNKYYADSVKG DFDYGDSYYYYGMDV (SEQ ID NO: 20) (SEQ ID NO: 21) (SEQ ID NO: 22) L RSSQSLLHSNGY LGSNRAS MQALQTPRT (SEQ ID NO: 23) (SEQ ID NO: 24) (SEQ ID NO: 25) T3D4 H NYGIN WISAYNGDTKYAQRLQD GDSTVGYEYLQY (SEQ ID NO: 26) (SEQ ID NO: 27) (SEQ ID NO: 28) L QASQGIGKYLN VASSLQS QQTSSFPPT (SEQ ID NO: 29) (SEQ ID NO: 30) (SEQ ID NO: 31) T3D3 H SYAIS RIIPILGIANYAQKFQG QGGDYSNYYYYMDV (SEQ ID NO: 32) (SEQ ID NO: 33) (SEQ ID NO: 34) L RASQSVSSYLA DASNRAT QHRFNWPVT (SEQ ID NO: 35) (SEQ ID NO: 36) (SEQ ID NO: 37) T3D1 H SYGMH VISYDGSNKYYADSVKG DQTYYGSGSPRGGLDY (SEQ ID NO: 38) (SEQ ID NO: 39) (SEQ ID NO: 40) L TGSSGSIANNYVQ EDDQRPS QSYDNSNSFVV (SEQ ID NO: 41) (SEQ ID NO: 42) (SEQ ID NO: 43) T2B12 H SNSAAWN RTYYRSKWYNDYVSVKS GPYDTTGPWGNWFDP (SEQ ID NO: 44) (SEQ ID NO: 45) (SEQ ID NO: 46) L RASQSVSSDLA GASYRAT QQYGSSPRT (SEQ ID NO: 47) (SEQ ID NO: 48) (SEQ ID NO: 49) T2G7 H SYGMH VISYDGSNKYYADSVKG DFDYGDSYYYYGMDV (SEQ ID NO: 50) (SEQ ID NO: 51) (SEQ ID NO: 52) L RSSQSLLHSNGYNYLD LGSNRAS MQALQTPRT (SEQ ID NO: 53) (SEQ ID NO: 54) (SEQ ID NO: 55) T2H9 H SYAMS AISGSGGSTYYADSVKG DSLAGATGTDFDY (SEQ ID NO: 56) (SEQ ID NO: 57) (SEQ ID NO: 58) L RASQTVTANYLA DASVRAT QQYGSSPIT (SEQ ID NO: 59) (SEQ ID NO: 60) (SEQ ID NO: 61) T3A2 H SYAMS GISGSGGSTYYADSVKG DFDYGGNSGSLFDY (SEQ ID NO: 62) (SEQ ID NO: 63) (SEQ ID NO: 64) L GASESVGGNYLA DASTRAT QHYGSSPSTY (SEQ ID NO: 65) (SEQ ID NO: 66) (SEQ ID NO: 67) T3A4 H SSNWWS EIYHSGSTNYNPSLKS HSYDYLWGTYRFDY (SEQ ID NO: 68) (SEQ ID NO: 69) (SEQ ID NO: 70) L RASQDIGTWLA AATTLES QQARSLPYT (SEQ ID NO: 71) (SEQ ID NO: 72) (SEQ ID NO: 73) T3B5 H NYGIN WISAYNGDTKYAQRLQD GDSTVGYEYLQY (SEQ ID NO: 74) (SEQ ID NO: 75) (SEQ ID NO: 76) L QASQGIGKYLN VASSLQS QQTSSFPPT (SEQ ID NO: 77) (SEQ ID NO: 78) (SEQ ID NO: 79) T4B7 H SYGMH VISYDGSNKYYADSVKG DYNGYGDYVLGY (SEQ ID NO: 80) (SEQ ID NO: 81) (SEQ ID NO: 82) L RASQSVSSYLA DASNRAT QQRSNWASYT (SEQ ID NO: 83) (SEQ ID NO: 84) (SEQ ID NO: 85) T4D10 H SYYMH IINPSGGSTSYAQKFQG DRGGGYDVSPYGMDV (SEQ ID NO: 86) (SEQ ID NO: 87) (SEQ ID NO: 88) L RASQSISSYLN AASNLQT QQTYSLPT (SEQ ID NO: 89) (SEQ ID NO: 90) (SEQ ID NO: 91) T4B12 H SYAIS GIIPIPGITNYAQKFQG RVGYYYGMDV (SEQ ID NO: 92) (SEQ ID NO: 93) (SEQ ID NO: 94) L AGSGGDIASNFVQ EENRRPS QSYDGSAW (SEQ ID NO: 95) (SEQ ID NO: 96) (SEQ ID NO: 97) *H - heavy chain, L - light chain Specificity and affinity of anti HLA-A2:Tax11-19 complex Fab's: Using E. coli BL21 or TG1 cells, soluble Fab's from 3 phage clones exhibiting the most specific binding pattern to HLA-A2:Tax11-19 complex (analyzed above, FIG. 1) were produced. SDS-PAGE analysis of Fab's purified from the periplasmic fraction of E. coli transformants by nickel affinity chromatography revealed homogenous, pure Fab's with the expected molecular weight of 50 kDa (FIG. 2a). Quantities of 2 to 4 milligrams of pure Fab was obtained from 1 liter of bacterial shake flask culture. For further manipulation; i.e. to increase the avidity of monomeric Fab's, the Fab's were also produced by in-vitro refolding. The light chain and Fd fragment (truncated portion of the heavy chain consisting of the variable region and the CH1 domain of the constant region) were subcloned into pET based expression vectors for T7 promoter regulated expression of cloned inserts, and upon induction with IPTG, large amounts of recombinant protein accumulated as intracellular inclusion bodies (FIG. 2b). Upon in-vitro redox shuffling refolding, purified monomeric Fab's were obtained in high yield (4 to 6 milligrams of purified Fab was obtained from two 1 liter shake flask cultures, each expressing the Fab light or Fd fragment; FIG. 2c). The fine specificity of the soluble Fab's for HLA-A2:Tax11-19 complex was analyzed by ELISA using biotinylated HLA-A2:Tax11-19 complex immobilized to BSA-streptavidin coated wells. The BSA-streptavidin-biotin spacer enables the correct folding of the complex, which may be distorted by direct binding to plastic. To verify correct folding of the bound complex and its stability during binding assays, the ability of the bound complex to react with the conformation specific monoclonal antibody w6/32 which exclusively recognizes correctly folded, peptide complexed HLA was monitored. FIGS. 3a-c show specific binding of soluble Fab's T3D4, T3E3, and T3F2, respectively, to HLA-A2:Tax11-19 complex, but not to 10 control HLA-A2:peptide complexes containing viral epitopes derived from CMV or EBV, and a variety of tumor associated epitopes such as telomerase epitopes (540, 865), melanoma gp100 and MART-1-derived epitopes (154,209,280 and MART, respectively), and the MUC1-derived epitopes A7 and D6 (see experimental procedures for list of peptides). Thus, these anti specific MHC:peptide complex Fab's exhibit the binding characteristics and fine specificity of a TCR. In control experiments, the Fab's did not recognize the Tax11-19 peptide alone when immobilized on the plate, nor immobilized streptavidin or other protein antigens such as BSA, IgG, RNase, or chymotrypsin (data not shown). The binding affinity properties of two of the soluble Fab's were tested using a saturation ELISA assay using addition of increasing amounts of Fab's to biotinylated HLA-A2:Tax11-19 bound to streptavidin coated plates. As shown in FIGS. 4a-b, the binding of Fab's T3E3 and T3F2, respectively, was dose dependent and saturable. Extrapolating the 50 percent binding signal of either fragment revealed that their affinity was in the nanomolar range. Finally, the apparent binding affinity of the Fab's for HLA-A2:Tax11-19 complex was determined using a competition binding assay in which the binding of [125]iodine labeled Fab was competed with increasing concentrations of unlabeled Fab's. These binding studies (FIG. 4c) revealed an apparent binding affinity of approximately 25 to 30 nanomolar for the T3F2 antibody. Similar results were observed for the T3E3 antibody (not shown). Detection of HLA-A2:Tax11-19 complex on peptide pulsed antigen-presenting cells (APCs): To demonstrate that the isolated Fab's can specifically bind HLA-A2:Tax11-19 complex not only in the recombinant soluble form but also in the native form, as expressed on the cell surface, murine TAP2 deficient RMA-S cells transfected with the human HLA-A2 gene in a single chain format (Pascolo, S. et al., 1997. J. Exp. Med. 185:2043-2051) (HLA-A2.1/Db-beta2-microglobulin single chain, RMA-S-HHD cells). The Tax11-19 peptide and HLA-A2 restricted control peptides were loaded on RMA-S-HHD cells and the ability of the selected Fab's to bind to peptide loaded cells was monitored by flow cytometry. Peptide induced MHC stabilization of the TAP2 mutant RMA-S-HHD cells was demonstrated by reactivity of monoclonal antibodies w6/32 (HLA conformation dependent) and BB7.2 (HLA-A2 specific) with peptide loaded but not unloaded cells (data not shown). Fab's T3E3 and T3F2 reacted only with Tax11-19 peptide loaded RMA-S-HHD cells but not with cells loaded with the gp100 derived G9-154 peptide (FIGS. 5a-b, respectively). Similar results were observed using flow cytometric analysis using 10 other HLA-A2 restricted control peptides (data not shown). Cells, of the TAP and HLA-A2 positive EBV transformed B lymphoblast cell line JY were also used as APCs. The cells were incubated with Tax11-19 peptide, and HLA-A2 restricted control peptides, and following incubation the cells were washed and incubated with the Fab's. The T3E3 or T3F2-Fab's were found to bind only to JY cells incubated with the Tax11-19 peptide against which they were selected but not to HLA-A2 restricted control peptides-(FIGS. 5c-d, respectively). As a control, peptide loaded HLA-A2 negative/HLA-A1 positive APD B cells were also used. No binding of the Fab's to these cells was observed (data not shown). Fab's T3E3 and T3F2 were also tested for binding to peptide pulsed mature HLA-A2 positive dendritic cells. As shown in FIGS. 5e-f, respectively, the T3E3 and T3F2 Fab's recognized HLA-A2 positive dendritic cells pulsed with Tax11-19 peptide but not with a control gp100-derived peptide. The Fab's were modified for detection of MHC:peptide complex on the surface of cells. Since the density of a particular endogenous HLA:peptide complex on cells is expected to be low compared to that of peptide pulsed APCs, the avidity of Fab T3F2 was increased by making Fab tetramers, which are directly tagged with a fluorescent probe. This approach was used previously to increase the binding avidity of MHC:peptide complexes to TCRs or to increase the sensitivity of recombinant antibody molecules (Cloutier, S. M. et al., 2000. Mol. Immunol. 37:1067-1077). Another advantage of using fluorescently labeled tetramers is that only a single staining step is required whereas monomeric unlabeled Fab's require a fluorescently labeled secondary antibody. The Fab tetramers generated with fluorescently labeled streptavidin were thus used to measure the expression of HLA-A2:Tax11-19 complex on the surface of peptide pulsed APCs. As shown in FIGS. 6a-c, the intensity of the binding as measured by flow cytometry with peptide pulsed RMA-S-HHD (FIG. 6a), JY cells (FIG. 6b), and human dendritic cells (FIG. 6c), was dramatically increased by two logs compared to the staining intensity with the T3F2 Fab monomer. Unexpectedly, the staining pattern of the mature HLA-A2 positive dendritic cells was found to be scattered over a wide range of fluorescence intensities, indicating for the first time that dendritic cell populations display heterogeneous levels of specific MHC:peptide complexes at the cell surface. Such results therefore indicate the potency of the Fab's such as those described herein for studying the biology of specific MHC:peptide complex presentation by APCs. In particular, these results demonstrate the ability of the Fab's to detect cell surface displayed HLA-A2:Tax11-19 complex. Cell surface detection of HLA-A2:Tax11-19 complex formed by intracellular antigen processing: To examine the ability of the Fab's to detect HLA-A2:Tax11-19 complex produced by physiological antigen processing, the HTLV-1 Tax gene was transfected Pinto HLA-A2 positive and negative JY or APD cells, respectively. Twenty four hours following transfection, the reactivity of T3F2 to cell surface displayed HLA-A2:Tax11-19 complex was tested by flow cytometry. The analysis was performed using the high avidity tetrameric Fab T3F2. Positive staining above control could be clearly seen only with HLA-A2 positive JY cells transfected with the Tax gene but not with HLA-A2 negative cells transfected with the Tax gene (FIGS. 7a-b, respectively). Negative control Fab G2D12 specific for HLA-A2:G9-154 complex did not react with the Tax transfected JY cells (FIG. 7a). The Tax11-19 peptide specific, MHC restricted pattern of reactivity by T3F2 was not due to differences in transfection efficiency, or HLA expression of JY and APD cells. As determined via control experiments employing transfection of green fluorescent protein (GFP) into these cells, the percentage of transfected cells with both cell lines using the same transfection protocol used for expression of Fab was similar (FIG. 7c), and the staining intensity of these cells with w6/32, a pan MHC monoclonal antibody, was similar (data not shown). These results indicate that the Fab's are capable of detecting HLA-A2:Tax11-19 complex formed by intracellular antigen processing. The use of Fab T3F2 for detecting HLA-A2:Tax11-19 complex on virus infected cells was attempted. To this end, HLA-A2 negative HUT 102 and HLA-A2 positive RSCD4 cells (human CD4 positive T-lymphocyte cell lines infected with HTLV-1) were used. As shown in FIG. 7d, a significant staining with Fab T3F2 was observed on RSCD4 but not on HUT 102 cells, indicating that the Fab is capable of detecting the specific HLA-A2:Tax11-19 complex on the surface of virus infected cells. Unexpectedly, the staining pattern revealed two cell subpopulations having moderate or high reactivity, respectively, with the Fab, which may indicate variability in the expression of the HLA-A2:Tax11-19 complex within subpopulations of RSCD4 HTLV-1 infected cells. Similar variability was observed in staining experiments with an anti Tax protein antibody (not shown). Negative control Fab G2D12 specific for HLA-A2:G9-154 complex did not stain RSCD4 cells (FIG. 7d). These results underscore the utility of anti specific MHC:peptide complex Fab's, in particular that of the above described anti HLA-A2:Tax11-19 complex fragments, for the study of antigen presentation on APCs as well as virus infected cells. High sensitivity detection and direct quantitation of surface expressed HLA-A2:Tax11-19 complex on APCs and virus infected cells: The data presented above demonstrate the high specificity of the HLA-A2:Tax11-19 complex specific Fab's as well as their ability to detect naturally processed Tax11-19 peptide complexed with HLA-A2. The sensitivity of specific MHC:peptide recognition by the Fab's in-vitro was tested by staining with Fab T3F2 was tested over a broad range of Tax11-19 peptide concentrations. As shown in FIGS. 8a-b, titration of peptide pulsed JY cells using graded concentrations of Tax11-19 peptide demonstrated staining intensity dependent on the concentration of the peptide used for pulsing, and that the Fab was capable of detecting HLA-A2-Tax11-19 complex when pulsing Tax11-19 peptide at a concentration in the low nanomolar range. The staining intensity of peptide pulsed JY cells observed with T3F2 Fab was estimated by comparison to calibration beads displaying graded numbers of phycoerythrin molecules. This comparison enabled determination of the number of HLA-A2:Tax11-19 complexes displayed on the surface of cells that are pulsed with various concentrations of the Tax11-19 peptide (FIG. 8a and Table 2). Specific detection of as few as 100 HLA-A2-Tax11-19 complexes per cell was achieved (using 6 nanomolar Tax11-19 peptide pulsing) and reached saturation at about 1.1× to 1.2×105 complexes per cell when pulsing with 25 to 50 micromolar Tax11-19 peptide. These results therefore demonstrate that the sensitivity of specific MHC:peptide complex detection by T3F2 Fab is in the same range as the minimal concentration peptide needed to elicit measurable cytokine secretion (IL-2 or IFN-gamma) from T-lymphocyte hybridomas or target T-lymphocyte lysis by CD8 positive cytotoxic T-lymphocyte lines (Reis e Sousa, C., and Germain, R. N., 1995. J. Exp. Med. 182:841-851; Reis e Sousa, C. et al., 1996. J. Exp. Med. 184:149-157). A major problem hampering the study of MHC dependent antigen presentation is the unavailability of adequate methods for quantifying surface expression levels on individual cells of specific MHC:peptide complexes produced by intracellular antigen processing. Using flow cytometric analysis of cell surface display of HLA-A2:Tax11-14 complex using Fab T3F2 and comparison of the fluorescence intensity of T3F2 stained cells with that of calibration beads displaying graded numbers of phycoerythrin sites, it was possible to quantitate the number of specific HLA-A2:Tax11-19 complexes on the cell surface (Table 4). Namely, JY cells pulsed with 1.5 micromolar Tax11-19 peptide displayed on their surface 5×103 complexes per cell, while JY cells transfected with the Tax gene displayed on their surface, after intracellular antigen processing, 1×104 complexes per cell. The latter result is in complete agreement with recent quantitation of murine H-2kb bound to the ovalbumin peptide SIINFEKL after recombinant Vaccinia virus infection of cells in-vitro using an anti specific mouse MHC:peptide complex antibody (Porgador, A. et al., 1997. Immunity 6:715-726). As shown in FIG. 7d and Table 4, direct detection of HLA-A2:Tax11-19 complex on HTLV-1 infected cells enabled quantification of the number of complexes displayed on these cells. This analysis, using calibration beads, revealed that virus infected RSCD4 cells display on their surface about 3×104 HLA-A2:Tax11-19 complexes per cell. As demonstrated in FIG. 7d, Fab T3F2 recognized two subpopulations of HTLV-1 infected RSCD4 cells with high and moderate reactivity. The highly reactive cells express on their surface 3×1 HLA-A2:Tax11-19 complexes while the cell population with low to moderate staining intensity expresses several hundred HLA-A2:Tax11-19 complexes. These results clearly demonstrate the power of such anti specific MHC:peptide complex Fab's to quantitate specific MHC:peptide complex expression on each cell in a population. TABLE 4 Quantitation of the number of HLA-A2:Tax11-19 complexes on the surface of APCs and HTLV-1-infected cells Cells Mean number of sites per cell* JY (50 mM peptide pulsed) 120,132 ± 16,934 JY (1.5 mM peptide pulsed) 5,150 ± 691 JY (Tax-transfected) 12,746 ± 2,877 RSCD4 (CD4 positive T-cells, High: HTLV-1-infected) 32,820 ± 4,910 Low: 456 ± 72 Background** 32 ± 13 *The fluorescence intensity of stained cells in each experiment was compared with fluorescence intensities of calibration beads with known numbers of phycoerythrin (PE) molecules per bead (QuantiBRITE PE beads, Becton-Dickinson) and the number of sites for each experiment was determined. The mean number of non specific sites was determined by the intensity of staining of cells that are HLA-A2 positive # but not infected with HTLV-1, HLA-A2 negative cells infected with HTLV-1, or APCs not transfected with the Tax gene. The number of specific sites for each experiment was then calculated for each experiment. The deviation in number of sites depend on the sensitivity of detection and the physiological status of the cells in each individual determination. **The background number of sites was determined as described, using SK-BR3 (HLA-A2 negative/HUT102), FM3D (HLA-A2 positive), and JY (HLA-A2 positive) cells not transfected with the Tax gene as controls. Detection of cells displaying HLA-A2:Tax11-19 complex in a heterogeneous cell population: At present, there are no reagents available for detecting and phenotyping individual cells displaying specific MHC:peptide complexes in mixed cell populations. Such reagents would have great utility, for example, for detecting or staging tumorigenic cells, or for studying antigen presentation in lymphoid tissues within heterogeneous cell populations. The anti specific MHC:peptide complex Fab's described above would be ideally suited to conduct such analyses. To simulate a heterogeneous population of cells in which only a small fraction expresses a specific MHC:peptide complex, Tax transfected and control non transfected JY cells were mixed in various ratios, and the reactivity of T3F2 Fab to such cells was analyzed by flow cytometry. As shown in FIG. 8c, single color flow cytometric analysis using T3F2 Fab allows accurate identification of the admixed Tax transfected JY cells that express on their surface HLA-A2:Tax11-19 complex generated by intracellular antigen processing. T3F2 Fab was shown to be able to detect Tax transfected JY cells in a proportion as low as 1 percent within a population of non transfected cells (FIGS. 8c-d), as demonstrated by the ability to detect 0.5 percent of positive cells (calculated from a maximal 61.2 percent transfection efficiency of JY cells; FIG. 8d). These results demonstrate the ease with which anti specific MHC:peptide complex, Fab's can reveal a cell subpopulation bearing a specific endogenously generated MHC:peptide complex. Immunohistochemical detection of cells displaying HLA-A2:Tax11-19 complex generated by intracellular antigen processing: Another major potential use for anti specific MHC:peptide complex antibodies is in situ immunohistochemical analysis of specific MHC:peptide complexes in tissues. As a first step to assess this potential, the capacity of T3F2 Fab to detect in situ HLA-A2:Tax11-19 complex displayed on JY cells by intracellular antigen processing was determined. Tax transfected JY cells were subjected to single step immunohistochemical analysis using horseradish peroxidase conjugated T3F2 Fab. As shown in FIGS. 9a-f, these experiments showed the capacity of the Fab to strongly and specifically stain Tax transfected (FIGS. 9a-b) but not control non transfected JY cells (FIG. 9c). Negative control Fab G2D 12 specific for HLA-A2:G9-154 complex did not exhibit any significant immune reactivity on Tax transfected JY cells (FIG. 9d). Further evidence for the specific, MHC restricted reactivity of Fab T3F2 in these in situ immunohistochemistry experiments is provided by the lack of reactivity of the Fab with Tax transfected (FIG. 9e) and non transfected (FIG. 9f) HLA-A2 negative/HLA-A1 positive APD cells. These data demonstrate the capacity of the T3F2 Fab to specifically detect HLA-A2:Tax11-19 complex generated by intracellular antigen processing in situ on cells and potentially in tissue sections. To the present inventors' knowledge, this is the first demonstration of in situ detection of a specific human MHC:peptide complex. Specific cytolysis of cells displaying HLA-A2:Tax11-19 complex by T3F2-PE38 immunotoxin: The capacity of an anti specific human MHC:viral peptide complex immunotoxin to cytolyse cells displaying such a complex was determined by testing the capacity of T3F2-PE38 to kill/damage peptide loaded APCs. The killing assay was performed by loading JY cells with Tax11-19 peptide, or control HLA-A2 restricted peptides, including the gp100-derived G9-209 peptide. As shown in FIG. 10, T3F2-PE38 was capable of killing JY cells loaded with Tax11-19 peptide with an IC50 of 2,500 nanograms per milliliter. No T3F2-PE38 mediated cytolysis of JY cells loaded with control HLA-A2 restricted peptides, or of cells not loaded with peptide occurred. Thus, the capacity to specifically and efficiently kill/damage target cells displaying a specific human MHC:viral peptide complex using cytotoxic conjugates targeted using an antibody specific for such a complex was demonstrated for the first time. Discussion: The above described results demonstrate for the first time generation of recombinant antibody-derived molecules, such as Fab's, capable of specifically binding specific human MHC:pathogen-derived peptide complexes, such as MHC:viral peptide complexes, and of cytotoxic conjugates including such molecules to specifically kill/damage cells displaying, such complexes. Until now, anti specific MHC:pathogen-derived peptide complex antibodies have been generated against murine forms of such complexes only (Andersen, P. S. et al., 1996. Proc. Natl. Acad. Sci. U.S.A 93:1820-1824; Day, P. M. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:8064-8069; Porgadot, A. et al., 1997. Immunity 6:715-726; Reiter, Y. et al., Proc. Natl. Acad. Sci. U.S.A. 94:4631-4636). These novel molecules exhibit high affinity, high specificity binding to specific human MHC:pathogen-derived peptide complexes, and hence display TCR like specificity for such complexes. However, in contrast to the inherently low affinity of TCRs for MHC:peptide complexes, these molecules display the high affinity antigen binding characteristics of antibodies, while retaining TCR specificity. By virtue of such characteristics such molecules have very promising utility in the numerous diagnostic, therapeutic and scientific applications which would benefit from the capacity to specifically label or target specific human MHC:pathogen-derived peptide complexes such as those comprising viral peptides. Crucial features of these Fab's were identified, including the capacity to: (a) bind with high sensitivity and specificity particular human MHC:pathogen-derived peptide complexes, such as HLA-A2:Tax11-19 complex, expressed or displayed by cells which are infected with a pathogen such as HTLV-1, peptide loaded, in suspension, and/or surface immobilized using immunohistochemical techniques; and (b) the capacity to deliver molecules, such as toxins, to cells displaying a specific human MHC:pathogen-derived peptide complex, such as HLA-A2:Tax11-19 complex. An important feature of these molecules is their capacity to detect specific human MHC:pathogen-derived peptide complexes at surface densities near the threshold limit required for triggering signaling via the TCR. Studies from other laboratories using a monoclonal antibody specific for mouse MHC class I (H-2Kb) in complex with an ovalbumin peptide indicated that the lower limit of sensitivity of flow cytometry detection is in the range of 100 to 500 specific MHC:peptide complexes per cell using single step or sandwich staining techniques (Porgador, A. et al., 1997. Immunity 6:715-726). The data presented herein for anti specific human MHC:pathogen-derived peptide Fab's are in good agreement with these numbers since the HLA-A2:Tax11-19 complex specific Fab was able to detect in a reproducible manner as few as 100 complexes per cell. These numbers agree with several estimates of the threshold number of specific MHC:peptide complexes on APCs required to elicit effector responses from T-lymphocytes, such as cytokine secretion (Demotz, S. et al., 1990. Science 249:1028-1030; Harding, C.V., and Unanue, E. R., 1990. Nature 346:574-576), and are about 10 fold greater than what may be required for cytotoxic T-lymphocyte mediated cell lysis (Christinck E R. et al., 1991. Nature 352:67-70; Sykulev Y. et al., 1996. Immunity 4:565-71). Using flow cytometry, it was possible to use an anti specific human MHC:pathogen-derived peptide complex Fab to detect such complexes on cells pulsed with peptide concentrations being similar to those required to trigger cytokine secretion by T-lymphocyte hybridoma or cytotoxic T-lymphocyte lines, and being within a few fold of concentrations required for sensitizing target T-lymphocytes for lysis in a short term assay by APCs (Porgadok, A. et al., 1997. Immunity 6:715-726). The presently described data indicate that when applied to dissociated cell populations using flow cytometry, the Fab's can detect specific human MHC:pathogen-derived peptide complexes at densities approaching those required for activating T-lymphocytes. Hence these molecules are suitable reagents for evaluating specific human MHC:pathogen-derived peptide complex expression at low but physiologically relevant levels. This principle was applied here to mixtures of the parental JY APCs and its Tax gene transfected derivative. The latter intracellularly processes Tax antigens and displays the relevant HLA-A2:Tax11-19 complex at the cell surface, as demonstrated by positive staining of Tax transfected but not control cells using T3F2 Fab. Even when using T3F2 Fab in a single step staining for flow cytometry, it was possible to readily identify Tax transfected cells admixed with non transfected JY cells in a proportion as low as 1 percent. The extreme ease with which precise quantitation of cell surface expressed specific human MHC:pathogen-derived peptide complexes can be accomplished using this approach also makes it an invaluable tool for analyzing antigen processing and presentation. Increasingly, such analyzes are aimed at determining quantitative differences in antigen display resulting from use of distinct forms of an antigen, of various antigen delivery methods, or of cells deficient in some known or suspected component of the antigen processing machinery. Without reagents such as the presently described anti specific human MHC:viral peptide complex Fab's, the quantitation of cell surface levels of specific human MHC:pathogen-derived peptide complexes relies on biochemical isolation of antigenic peptides. This is an expensive and laborious process subject to numerous experimental artifacts and cannot distinguish between intracellular pools of loaded molecules and those on the cell surface accessible to TCRs. In the data presented here, anti HLA-A2:Tax11-19 complex Fab's enabled quantitation of such complexes generated by intracellular antigen processing on the surface of cells transfected with the Tax gene or on HTLV-1 infected cells. This analysis demonstrated that intracellular antigen processing in Tax transfected cells led to a display of about 104 specific MHC:peptide complexes per cell. Comparison with total HLA-A2 staining showed that nearly 90 percent of the HLA-A2 molecules were occupied with a single-peptide species (not shown). These data agree with previous studies in which the number of H-2Kb:ovalbumin-derived peptide complexes on the surface of cells following infection with recombinant Vaccinia virus encoding the peptide was analyzed in a variety of contexts (Porgador, A. et al., 1997. Immunity 6:715-726). These data also agree with results from studies investigating the occupancy of MHC class I molecules by peptides derived from virally encoded proteins displayed by infected cells (Antón, L. C. et al., 1997. J. Immunol. 158:2535-42). Such occupancy estimates were obtained by analysis of stabilization of newly synthesized MHC class I heavy chain-beta2-microglobulin complexes, or by elution of peptides from expressed MHC class I molecules and reconstruction experiments to determine the peptide concentration in the eluates. The ability of Fab T3F2 to detect the heterogeneity of HLA-A2:Tax11-19 complex expression levels in a population of virally infected cells was shown. Such novel and striking data highlight the potential utility of such antibodies for studying specific human MHC:pathogen-derived peptide complex expression in contexts such as diagnosis of infection with a pathogen. Immunohistochemical staining with T3F2 Fab permitted in situ detection of HLA-A2:Tax11-19 complex generated by intracellular antigen processing on the surface of Tax transfected JY cells. Staining of background HLA display levels with the Fab was insignificant under these conditions because neither non transfected cells nor HLA-A2 negative cells transfected with Tax exhibited positive staining. Such data represent the first immunohistochemical visualization of a specific human MHC:peptide complex on immobilized biological samples. Such an approach could be applied to confocal immunofluorescence microscopy, which, using anti specific human MHC:pathogen-derived peptide complex antibodies, would permit analysis of the intracellular site(s) of assembly and trafficking of such complexes. In situ localization of APCs displaying or expressing specific human MHC:pathogen-derived peptide complexes would be especially valuable in characterizing the intercellular interactions between APCs and T-lymphocytes involved in initiation, propagation, and maintenance of anti viral T-lymphocyte immune responses. Multicolor histochemistry could be used to reveal not only the type and location of viral APCs but also the phenotype of interacting anti viral T-lymphocytes, including the set of cytokines elicited. The fact that 62 percent of the HLA-A2:Tax 11-19 complex binding Fab's were peptide specific and MHC restricted was unexpected since these antibodies were selected from a non immune repertoire considered not to be biased toward such specificity. The fact that it was possible to isolate from the same phage library recombinant Fab's capable of specifically binding a large variety of specific MHC:peptide complexes comprising various cancer associated or viral HLA-A2 restricted peptides (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426; Lev, A. et al., 2002. Cancer Res. 62:3184-3194) indicates that the capacity to isolate anti MHC:Tax11-19 complex antibodies from such a library was not Tax or peptide related. It is possible that one particular antibody family or antibody V gene segment could have an intrinsic propensity to bind HLA-A2 molecules, and that the high frequency could be explained by a high abundance of such antibodies in the non immune library. However, the sequences of the selected clones are derived from many different antibody families and germline segments, without any biases visible in the complementarity determining regions (CDRs) either (Table 3). The high frequency and high, affinities for some of the antibodies isolated herein suggest that these molecules may be present at a high frequency in the antibody repertoires from the B cell donors of the phage library, however an in-vivo role for such antibodies remains unclear. Whatever the reason for this high frequency of Fab's to bind specific MHC:peptide complexes may be, it appears that this phage based approach can be successfully applied to identify recombinant antibodies capable of specifically binding to a large variety of specific human MHC:pathogen-derived peptide complexes. Thus, it may now be possible to elucidate the role of pathogen-derived antigens not only from the perspective of the T-lymphocyte, using MHC:pathogen-derived peptide complex based TCR detection reagents such as tetrameric single chain MHC:pathogen-derived peptide complexes, but also from the perspective of pathogen-derived APCs and diseased cells, using the novel antibody type described herein. A further application for anti specific human MHC:pathogen-derived peptide complex antibodies is in structure function studies of specific interactions between such complexes and cognate TCRs. By mutating particular residues in the MHC restricted pathogen-derived peptide and testing the influence of these mutations on the binding of the Fab's and peptide specific T-lymphocyte clones, it may be possible to obtain important data regarding the structure function relationship and the different nature of the recognition process between such Fab's and the native TCR (Stryhn A. et al., 1996. Proc. Natl. Acad. Sci. U.S.A. 93:10338-10342). Conclusion: By virtue of the capacity of the presently described Fab's to specifically bind with optimal affinity and specificity particular human APM:pathogen-derived antigen complexes, such reagents are uniquely suitable and optimal relative to all prior art compounds for: (a) identification, and characterization of cells/tissues expressing or displaying such complexes; (b) specific killing of cells displaying such complexes by targeting cytotoxic drugs or radionuclides to pathogen infected cells analogously to previously described methodologies (Boon, T. and van der Bruggen, P., 1996. J. Exp. Med. 183:725-729; Renkvist, N. et al., 2001. Cancer Immunol. Immunother. 50:3-15; Rosenberg, S. A., 2001. Nature 411:380-384); (c) confocal microscopic visualization and characterization of the intracellular localization and trafficking of such complexes; (d) tracking of cells displaying such complexes in real-time via confocal microscopy and in-vivo; and (e) modulation of immune responses by blocking interactions between specific human APM:pathogen-derived antigen complexes and cognate TCRs, analogously to previously described methodologies practiced by the present inventors (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426; Lev, A. et al., 2002. Cancer Res. 62:3184-3194). For example, the presently described reagents could be used to control pathogenic T-lymphocyte mediated anti pathogen immune responses without the risk of antigen administration to an infected individual, and without the loss of function of an entire MHC allele, as would be the case with prior art anti MHC antibodies. Thus, the presently described compounds are uniquely and optimally suitable for diagnosing, characterizing and treating diseases in humans caused by pathogens such as viruses, and for studying aspects of such diseases involving antigen presentation. Example 2 Optimal Prediction, Diagnosis, Staging, Monitoring and Prognosis of a Pathogen-Associated Disease Using a Detection Reagent Specific for a Complex of a Human Antigen-Presenting Molecule and a Pathogen-Derived Antigen Background: As described above, there are currently no satisfactory treatment methods, nor does the state of the art enable optimal prediction, diagnosis, staging, monitoring and prognosis for diseases associated with HTLV-1 infection, such as HAM/TSP, int human patients. The pathogenesis of such diseases is associated with lymphocyte mediated autoimmune responses primarily directed against peptides of the HTLV-1 Tax protein. Hence, an optimal strategy for diagnosing, staging and characterizing patients having such a disease would be to obtain and employ a detection reagent capable of specifically detecting a complex of an antigen-presenting molecule (APM) and a Tax-derived peptide antigen displayed by cells infected with HTLV-1. It will be appreciated that the optimal diagnosis, staging and monitoring capacity which could be afforded by such a reagent would in turn enable the optimal development of therapy for such a disease. While various molecules capable of binding particular APM:antigen complexes have been proposed in the prior art, none have been shown to be capable of detecting a complex of a human antigen-presenting molecule and a pathogen-derived antigen, and hence of enabling characterization of a pathogen-induced disease. As described below, the present inventors have devised for the first time relative to the prior art a method of utilizing a detection reagent specific for a complex of a human APM and an HTLV-1 Tax peptide for optimally characterizing an HTLV-1-associated disease, such as HAM/TSP, in a human, thereby overcoming the limitations of the prior art. Materials and Methods: Harvesting of peripheral blood and cerebrospinal fluid lymphocytes: Peripheral blood is harvested via routine blood collection and cerebrospinal fluid (CSF) is harvested via lumbar puncture from HLA-A2 positive HAM/TSP patients. Peripheral blood mononuclear cells (PBMCs) are isolated from the harvested peripheral blood by centrifugation over a Ficoll cushion following hypotonic erythrocyte lysis. CD4+, CD4+CD25+, and CD8+ T-cell subsets are isolated from the harvested blood and CSF via magnetic cell sorting using MACS beads. Flow cytometric analysis of HLA-A2:Tax11-19 complexes on peripheral blood and cerebrospinal fluid T-cell subsets from HAM/TSP patients: The isolated CD4+, CD4+CD25+ and CD8+ T-cell subsets are analyzed for surface expression of HLA-A2:Tax11-19 peptide complex via flow cytometry, performed essentially as described above in Example 1, using as complex detection reagent phycoerythrin-conjugated T3F2 Fab tetramer (refer to Example 1, above). Alternately, CD4+, CD4+CD25+ and CD8+ T-cell subsets from the harvested blood and from the harvested CSF are analyzed for surface expression of HLA-A2:Tax11-19 complex via multicolor flow cytometry, essentially as previously described (Kivisakk P. et al., 2003. Proc. Natl. Acad. Sci. U.S.A. 100:8389-8394), using as detection reagents phycoerythrin-conjugated T3F2 Fab tetramer with: FITC-conjugated anti-human CD4 antibody; FITC-conjugated anti-human CD8 antibody; or FITC-conjugated anti-human CD4 antibody and PE-Cy5-conjugated anti-human CD25 antibody. As described in Example 1 above, Tax11-19 peptide-loaded or gp100-derived G9-154 peptide-loaded HLA-A2-positive RMAS-HHD cells are employed as positive and negative controls, respectively, for surface expression of the HLA-A2:Tax11-19 complex. Analysis of HTLV-1 proviral DNA load, and HTLV-1 tax mRNA load in lymphocytes: Analysis of HTLV-1 proviral DNA load is performed via PCR, essentially as previously described (Thorstensson R. et al., Transfusion 42:780-91; Coste J., 2000. Transfus Clin Biol. 7 Suppl 1:11s-17s; Nakamura S. and Nakayama T., 1997. Nippon Rinsho. 55:833-8; Kazanji M. et al., 2000. J. Virol. 74:4860-7). Analysis of HTLV-1 tax mRNA load is performed via RT-PCR essentially as previously described (Kazanji M., 2000. AIDS Res Hum Retroviruses 16:1741-6; Higashiyama Y. et al. 1994. Clin Exp Immunol. 96:193-201; Kazanji M. et al., 2000. J Virol. 74:4860-7). Determination of HAM/TSP disease severity: Disease severity in HAM/TSP patients is measured according to expanded disability status scale, essentially as previously described (EDSS; Kurtzke J., 1983. Neurology 33:1444-1452). Results: Profiles of HLA-A2:Tax11-19 complex surface expression on CD4+, CD4+CD25+ and CD8+ T-cell subsets isolated from peripheral blood and CSF of HAM/TSP patients are determined with high sensitivity via flow cytometry. CD4+, CD8+, and CD4+CD25+cells are found to specifically display HLA-A2:Tax11-19 complex surface expression. The highest levels of surface complex expression are detected in CD4+CD25+cells, in accordance with such T-cells being the major reservoir of HTLV-1 provirus. Correlations are analyzed and determined between levels of HLA-A2:Tax11-19 complex expression on CD8+, CD4+, and CD4+CD25+cells with HTLV-1 proviral DNA load, HTLV-1 tax mRNA load, and HTLV-1 Tax-specific CD8+ T-cell frequencies. Correlation of surface expression levels of the complex on the various cell T-cell subsets with disease severity is analyzed and determined. Levels of HLA-A2:Tax11-19 complex surface expression on CD4+CD25+T-lymphocytes are found to correlate with disease severity. Conclusion: The anti-APM:antigen complex antibodies of the present invention can be used for enabling optimal prediction, diagnosis, staging, monitoring and prognosis of a pathogen-associated disease such as an HTLV-1 associated disease, thereby overcoming numerous limitations of the prior art. In particular, the anti-HLA-A2:Tax11-19 complex antibodies of the present invention can be used for enabling optimal prediction, diagnosis, staging, monitoring and prognosis of HAM/TSP in humans, thereby overcoming numerous limitations of the prior art. It will be appreciated that such antibodies enable optimal elucidation of the pathogenesis of HTLV-1 associated diseases, enable optimal development of therapy for such diseases, and can be employed as therapeutic agents to treat such diseases according to the presently disclosed teachings. It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents, patent applications and sequences identified by their accession numbers mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent, patent application or sequence identified by its accession number was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.
<SOH> FIELD AND BACKGROUND OF THE INVENTION <EOH>The present invention relates to compositions-of-matter capable of specifically binding particular antigen-presenting molecule (APM):antigen complexes. More particularly, the present invention relates to compositions-of-matter capable of specifically binding a particular human APM:pathogen-derived antigen complex. Diseases caused by pathogens, such as viruses, mycoplasmas, bacteria, fungi, and protozoans, account for a vast number of diseases, including highly debilitating/lethal diseases, affecting all human individuals at numerous instances during their lifetime. For example, diseases caused by retroviruses are associated with various immunological, neurological, and neoplastic disorders. For example, diseases caused by lymphotropic retroviruses, such as acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV), or the closely related human T-cell lymphotropic virus (HTLV), a causative agent of various lethal pathologies (for general references, refer, for example to: Johnson J M. et al., 2001. Int J Exp Pathol. 82:135-47; and Bangham C R., 2000. J Clin Pathol. 53:581-6), account for lethal disease epidemics of devastating human and economic impact. However, satisfactory methods of diagnosing, characterizing, and treating many kinds of pathogen-associated diseases such as diseases associated with lymphotropic viruses such as HIV or HTLV are unavailable. HTLV-1 was the first human retrovirus identified (Poiesz B. J. et al., 1980. Proc Natl Acad Sci USA. 77:7415-7419). It infects both CD4+ and CD8+ T-lymphocytes and is associated with a variety of diseases, including adult T-lymphocyte leukemia/lymphoma (ATLL; Yoshida M. et al., 1982. Proc Natl Acad Sci USA. 79:2031-2035) and a non neoplasic inflammatory neurological syndrome called human T lymphotropic type I (HTLV-1)-associated myelopathy/tropical virus spastic paraparesis (HAM/TSP; Osame M. et al., 1986. Lancet 1:1031-1032; reviewed in Ribas J G. and Melo G C., 2002. Rev Soc Bras Med Trop. 35:377-84; and Plumelle Y., 1999. Med Hypotheses. 52:595-604). Other diseases linked to HTLV-1 infection on the basis of seroepidemiological studies include Sjogren's syndrome, inflammatory arthropathies, polymyositis, and pneumopathies (Coscoy L. et al., 1998. Virology 248: 332-341). The HTLV protein Tax seems to play a major role in the pathogenesis of HTLV-1 associated diseases. Tax protein is known to stimulate the transcription of viral and cellular genes such as the genes coding for interleukin-2 (IL-2) and other cytokines, interleukin-2 receptor (IL-2R), proto-oncogenes, c-jun and c-fos, and major histocompatibility complex (MHC) molecules (Yoshida M., 1993. Trends Microbiol. 1:131-135). The transforming potential of Tax has been demonstrated in different experimental systems. It has been shown that rodent fibroblastic cell lines expressing Tax form colonies in soft agar and tumors in nude mice (Tanaka A. et al., 1990. Proc Natl Acad Sci USA. 87:1071-1075). Also, Tax transforms primary fibroblasts in cooperation with the Ras protein (Pozzatti R. et al., 1990. Mol Cell Biol. 10:413-417), and immortalizes primary T-lymphocytes in the presence of IL-2 (Grassmann R. et al., 1989. Proc Natl Acad Sci USA. 86:3351-3355). Transgenic mice carrying the tax gene develop different types of tumors (Grossman W. J. et al., 1995. Proc Natl Acad Sci USA. 92:1057-1061). Tax binds directly to DNA but acts in cooperation with several cellular transcription factors, but the role of these different interactions in the cell transformation mediated by Tax is still unclear (Coscoy L. et al., 1998. Virology 248: 332-341). HAM/TSP is a progressive chronic demyelinating disorder affecting the white matter of the central nervous system (CNS) and the spinal cord. The disease affects approximately twice as many females as males, and typically the time of disease onset occurs during the fourth decade of life. The disease causes numerous highly debilitating symptoms, with common early symptoms and signs including gait disturbance and weakness and stiffness of the lower limbs. The disease affects the lower extremities to a much greater degree than upper extremities, spasticity may be moderate to severe, and lower back pain commonly occurs. Disease progression is associated with bowel and bladder dysfunction, and sensory loss and dysesthesia. Patients examined via magnetic resonance imaging may exhibit nonspecific lesions in the brain as well as spinal cord atrophy. Immune manifestations associated with HAM/TSP include inflammatory infiltrates in the central nervous system consisting predominantly of monocytes, and large numbers of CD8+ T-cells which are primarily reactive with peptides of the HTLV-1 Tax protein. The frequency of such T-cells in the peripheral blood and cerebrospinal fluid (CSF) has been shown to be proportional to the amount of HTLV-1 proviral load and the levels of HTLV-1 tax mRNA expression. It has further been shown that in patients carrying the HLA-A2 allele, the immune response is dominated by CD8+ T-lymphocytes that recognize the Tax 11-19 peptide (Bieganowska K. et al., 1999. J Immunol. 162:1765-1771; Nagai, M. et al., 2001. J Inf Dis. 183:197-205). Thus, immunological determinants, such as the Tax 11-19 peptide and antigenic mimics thereof, shared by thymus, brain and HTLV-1 are thought to direct lymphocytic neurotropism and demyelinization in nervous tissues. It is thought that the specificity of thoracic spinal cord involvement could be linked to shared thymic and thoracic spinal cord determinants, genetically peculiar to HAM/TSP patients. In a first stage, disease onset may be dependent on CD4+ T-lymphocytes specific for such determinants, reactivated in response to HTLV-1 infection, and that demyelinization during this stage could potentially be initiated as a result of stoppage in the synthesis of myelin following alteration of expression of oligodendrocytic and neuronal adhesion molecules. The second stage of the disease, involving chronic inflammatory manifestations, may depend on CD8+ T-lymphocytes specific for viral peptides, but also on CD8+ T-lymphocytes specific for peptides generated as a result of proteolysis of myelin layer, and other central nervous system proteins. While, at best, therapy of HAM/TSP with corticosteroids, and IFN-gamma may result transient responses, similarly to numerous diseases associated with lymphotropic viruses there is currently no effective treatment for HAM/TSP, nor does the state of the art currently enable optimal prediction, diagnosis, staging, monitoring, and prognosis of the disease in patients. The immune system employs two types of immune responses to provide antigen specific protection from pathogens; humoral immune responses, and cellular immune, responses, which involve specific recognition of pathogen antigens via antibodies and T-lymphocytes, respectively. T-lymphocytes, by virtue of being the antigen specific effectors of cellular immunity, play a central and direct role in the body's defense against diseases mediated by intracellular pathogens, such as viruses, intracellular bacteria, mycoplasmas, and intracellular parasites, by directly cytolysing cells infected by such pathogens. However, helper T-lymphocytes also play a critical role in humoral immune responses against non intracellular pathogens by providing T-cell help to B lymphocytes in the form of interleukin secretion to stimulate production of antibodies specific for antigens of such pathogens. The specificity of T-lymphocyte responses is conferred by, and activated through T-cell receptors (TCRs). T-cell receptors are antigen specific receptors clonally distributed on individual T-lymphocytes whose repertoire of antigenic specificity is generated via somatic gene rearrangement mechanisms analogously to those involved in generating the antibody gene repertoire. T-cell receptors are composed of a heterodimer of transmembrane molecules, the main type being composed of an alpha-beta dimer and a smaller subset of a gamma-delta dimer. T-lymphocyte receptor subunits comprise a transmembrane constant region and a variable region in the extracellular domain, similarly to immunoglobulins, and signal transduction triggered by TCRs is indirectly mediated via CD3/zeta, an associated multi-subunit complex comprising signal transducing subunits. The two main classes of T-lymphocytes, helper T-lymphocytes and cytotoxic T-lymphocytes (CTLs), are distinguished by expression of the surface markers CD4 and CD8, respectively. As described hereinabove, the main function of helper T-lymphocytes is to secrete cytokines, such as IL-2, promoting activation and proliferation of CTLs and B lymphocytes, and the function of CTLs is to induce apoptotic death of cells displaying immunogenic antigens. T-lymphocyte receptors, unlike antibodies, do not recognize native antigens but rather recognize cell-surface displayed complexes comprising an intracellularly processed fragment of a protein or lipid antigen in association with a specialized antigen-presenting molecule (APM): major histocompatibility complex (MHC) for presentation of peptide antigens; and CD1 for presentation of lipid antigens, and to a lesser extent, peptide antigens. Peptide antigens displayed by MHC molecules and lipid antigens displayed by CD1 molecules have characteristic chemical structures are referred to as MHC-restricted peptides and CD1 restricted lipids, respectively. Major histocompatibility complex molecules are highly polymorphic, comprising more than 40 common alleles for each individual gene. “Classical” MHC molecules are divided into two main types, class I and class II, having distinct functions in immunity. Major histocompatibility complex class I molecules are expressed on the surface of virtually all cells in the body and are dimeric molecules composed of a transmembrane heavy chain, comprising the peptide antigen binding cleft, and a smaller extracellular chain termed β 2 -microglobulin. MHC class I molecules present 9- to 11-amino acid residue peptides derived from the degradation of cytosolic proteins by the proteasome a multi-unit structure in the cytoplasm, (Niedermann G., 2002. Curr Top Microbiol Immunol. 268:91-136; for processing of bacterial antigens, refer to Wick M J, and Ljunggren H G., 1999. Immunol Rev. 172:153-62). Cleaved peptides are transported into the lumen of the endoplasmic reticulum (ER) by TAP where they are bound to the groove of the assembled class I molecule, and the resultant MHC:antigen complex is transported to the cell membrane to enable antigen presentation to T-lymphocytes (Yewdell J W., 2001. Trends Cell Biol. 11:294-7; Yewdell J W. and Bennink J R., 2001. Curr Opin Immunol. 13:13-8). Major histocompatibility complex class II molecules are expressed on a restricted subset of specialized antigen-presenting cells (APCs) involved in T-lymphocyte maturation and priming. Such APCs in particular include dendritic cells and macrophages, cell types which internalize, process and display antigens sampled from the extracellular environment. Unlike MHC class I molecules, MHC class II molecules are composed of an alpha-beta transmembrane dimer whose antigen binding cleft can accommodate peptides of about 10 to 30, or more, amino acid residues. The antigen presenting molecule CD1, whose main function, as described hereinabove, is presentation of lipid antigens, is a heterodimer comprising a transmembrane heavy chain paired with beta 2 -microglobulin, similarly to MHC class I, and is mainly expressed on professional APCs, similarly to MHC class II (Sugita M. and Brenner M B., 2000. Semin Immunol. 12:511). CD1:antigen complexes are specifically recognized by TCRs expressed on CD4 − CD8 − T-lymphocytes and NKT lymphocytes and play a significant role in microbial immunity, tumor immunology, and autoimmunity. The cells of the body are thus scanned by T-lymphocytes during immune surveillance or during maturation of T-lymphocytes for their intracellular protein or lipid content in the form of such APM:antigen complexes. One strategy which has been proposed to enable optimal diagnosis, characterization, and treatment of diseases, such as HAM/TSP, associated with an infection by a pathogen involves using molecules capable of specifically binding APM:antigen complexes composed of a particular combination of APM and an antigen derived from such a pathogen. Such molecules, for example, could be conjugated to functional moieties, such as detectable moieties or toxins, and the resultant conjugates could be used to detect such complexes or cells displaying such complexes, or to kill cells displaying such complexes. Hence, such conjugates could be used to diagnose/characterize and treat a pathogen infection in an individual, respectively. Alternately, molecules capable of specifically binding such complexes could be used to bind such complexes on cells so as to block activation of T-lymphocytes bearing. TCRs specific for such complexes. Such molecules could further be used, for example, to isolate such complexes, or cells displaying such complexes, such as cells infected with a pathogen, or APCs exposed to a pathogen-derived antigen. Several prior art approaches have been described involving molecules capable of binding particular APM:antigen complexes. One approach involves using TCRs or derivatives thereof specific for particular MHC:peptide complexes in attempts to provide reagents capable of specifically binding such complexes. Another approach involves using antibodies or derivatives thereof specific for particular mouse MHC:peptide complexes in attempts to provide reagents capable of specifically binding such complexes (Aharoni, R. et al., 1991. Nature 351:147-150; Andersen, P. S. et al., 1996. Proc. Natl. Acad. Sci. U.S.A 93:1820-1824; Dadaglio, G. et al., 1997. Immunity 6:727-738; Day, P. M. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:8064-8069; Krogsgaard, M. et al., 2000. J. Exp. Med. 191:1395-1412; Murphy, D. B. et al., 1989. Nature 338:765-768; Porgador, A. et al., 1997. Immunity 6:715-726; Reiter, Y. et al., Proc. Natl. Acad. Sci. U.S.A. 94:4631-4636; Zhong, G. et al., 1997. Proc. Natl. Acad. Sci. U.S.A. 94:13856-13861; Zhong, G. et al., 1997. J. Exp. Med. 186:673-682). A further approach involves utilizing antibodies or derivatives thereof specific for the human MHC class I molecule HLA-A1 in complex with an HLA-A1 restricted peptide derived from the melanoma specific tumor associated antigen melanoma associated antigen (MAGE)-A1 in attempts to provide reagents capable of specifically binding such a complex (Chames, P. et al., 2000. Proc. Natl. Acad. Sci. U.S.A. 97:7969-7974). An additional approach involves employing antibodies or derivatives thereof specific for the human MHC class I molecule HLA-A2 in complex with an HLA-A2 restricted peptide derived from the melanoma specific tumor associated antigen gp100 in attempts to provide reagents capable of specifically binding such a complex (Denkberg, G. et al., 2002. Proc. Natl. Acad. Sci. U.S.A. 99:9421-9426). Yet another approach involves using antibodies or derivatives thereof specific for human MHC class I molecule HLA-A2 in complex with an HLA-A2 restricted peptide derived from human telomerase catalytic subunit (hTERT) in attempts to provide reagents capable of specifically binding such a complex (Lev, A. et al., 2002. Cancer Res. 62:3184-3194). However, all of the aforementioned prior art approaches suffer from significant disadvantages: (i) approaches involving the use TCRs or portions thereof as compounds capable of specifically binding particular MHC:peptide complexes are suboptimal due to the relatively low intrinsic binding affinity of TCRs for such complexes; (ii) approaches involving the use of antibodies or portions thereof specific for MHC:peptide complexes comprising non-human MHC are not suitable for human application; and (iii) approaches involving antibodies or portions thereof specific for MHC:non-pathogen-derived antigen complexes are not suitable for specifically binding complexes comprising pathogen-derived antigens. Thus, all prior art approaches have failed to provide an adequate solution for providing molecules capable of specifically binding with high specificity and affinity a particular human APM:pathogen-derived antigen complex. There is thus a Widely recognized need for, and it would be highly advantageous to have, molecules devoid of the above limitation.
<SOH> SUMMARY OF THE INVENTION <EOH>According to one aspect of the present invention there is provided a method of detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, the method comprising: (a) exposing the antigen-presenting portion of the complex to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (b) detecting the antibody or antibody fragment of the conjugate, thereby detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the complex is displayed or expressed by a target cell, and step (a) is effected by exposing the target to the composition-of-matter. According to still further features in the described preferred embodiments the method of detecting an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen further comprises: (c) obtaining the target cell from an individual. According to another aspect of the present invention there is provided a method of detecting in a biological sample an antigen-presenting portion of a complex composed of an antigen-presenting molecule and an antigen, the method comprising: (a) attaching the biological sample to a surface; (b) exposing the biological sample to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (c) detecting the antibody or antibody fragment of the conjugate, thereby detecting in a biological sample an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen. According to further features in preferred embodiments of the invention described below, the he method of detecting in a biological sample an antigen-presenting portion of a complex composed of an antigen-presenting molecule and an antigen further comprises: (d) obtaining the biological sample from an individual. According to still further features in the described preferred embodiments, step (b) is effected by administering the composition-of-matter to an individual. According to still further features in the described preferred embodiments, the antigen is derived from a pathogen. According to still further features in the described preferred embodiments, the biological sample is infected with the pathogen. According to still further features in the described preferred embodiments, the biological sample is a cell sample or a tissue sample. According to yet another aspect of the present invention there is provided a method of diagnosing an infection by a pathogen in an individual, the method comprising: (a) exposing a target cell of the individual to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from the pathogen, to thereby obtain a conjugate of the antigen-presenting portion of the complex and the antibody or antibody fragment; and (b) detecting the antibody or antibody fragment of the conjugate, thereby diagnosing an infection by a pathogen in an individual. According to further features in preferred embodiments of the invention described below, the method of diagnosing an infection by a pathogen in an individual further comprises: (c) obtaining the target cell from the individual. According to still further features in the described preferred embodiments, step (a) is effected by administering the composition-of-matter to the individual. According to still further features in the described preferred embodiments, the composition-of-matter further comprises a detectable moiety attached to the antibody or antibody fragment, and detecting the antibody or antibody fragment of the conjugate is effected by detecting the detectable moiety attached to the antibody or antibody fragment of the conjugate. According to still another aspect of the present invention there is provided a method of killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, the method comprising exposing the target cell to a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding the antigen-presenting portion of the complex, thereby killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the method of killing or damaging a target cell expressing or displaying an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen further comprises the step of obtaining the target cell from an individual. According to still further features in the described preferred embodiments, exposing the target cell to the composition-of-matter is effected by administering the composition-of-matter to an individual. According to still further features in the described preferred embodiments, the target cell is infected with the pathogen. According to still further features in the described preferred embodiments, the target cell is a T-lymphocyte or an antigen presenting cell. According to still further features in the described preferred embodiments, the antigen presenting cell is a B cell or a dendritic cell. According to a further aspect of the present invention there is provided a method of treating a disease associated with a pathogen in an individual, the method comprising administering to the individual a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient, a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from the pathogen, thereby treating a disease associated with a pathogen in an individual. According to a yet a further aspect of the present invention there is provided an isolated polynucleotide comprising a first nucleic acid sequence encoding an antibody fragment, the antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the isolated polynucleotide further comprises a second nucleic acid sequence encoding a polypeptide selected from the group consisting of a coat protein of a virus, a detectable moiety, and a toxin. According to still further features in the described preferred embodiments, the second nucleic acid sequence is translationally fused with the first nucleic acid sequence. According to still a further aspect of the present invention there is provided a nucleic acid construct comprising the isolated polynucleotide and a promoter sequence for directing transcription of the isolated polynucleotide in a host cell. According to further features in preferred embodiments of the invention described below, the promoter sequence is a T7 promoter sequence. According to still further features in the described preferred embodiments, the promoter sequence is capable of driving expression of the nucleic acid sequence in a prokaryote. According to still further features in the described preferred embodiments, the promoter sequence is capable of driving inducible expression of the nucleic acid sequence. According to an additional aspect of the present invention there is provided a host cell comprising the nucleic acid construct. According to further features in preferred embodiments of the invention described below, the host cell is a prokaryotic cell. According to still further features in the described preferred embodiments, the prokaryotic cell is an E. coli cell. According to yet an additional aspect of the present invention there is provided a virus comprising the nucleic acid construct. According to still an additional aspect of the present invention there is provided a virus comprising a coat protein fused to an antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to further features in preferred embodiments of the invention described below, the virus is a filamentous phage and the coat protein is pIII. According to another aspect of the present invention there is provided a composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to yet another aspect of the present invention there is provided a pharmaceutical compositions comprising as an active ingredient the composition-of-matter and a pharmaceutically acceptable carrier. According to still another aspect of the present invention there is provided a composition-of-matter comprising a multimeric form of an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen. According to a further aspect of the present invention there is provided a pharmaceutical composition comprising as an active ingredient the composition-of-matter comprising a multimeric form of an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen, and a pharmaceutically acceptable carrier. According to, further features in preferred embodiments of the invention described below, the antibody is a monoclonal antibody. According to still further features in the described preferred embodiments, the antibody fragment is a monoclonal antibody fragment. According to still further features in the described preferred embodiments, the antibody fragment is selected from the group consisting of an Fd fragment, an Fab, and a single chain Fv. According to still further features in the described preferred embodiments, the antigen-binding region includes an amino acid sequence selected from the group consisting of SEQ ID NOs: 14 to 97. According to still further features in the described preferred embodiments, the antibody or antibody fragment, or a part of the antibody or antibody fragment is of human origin. According to still further features in the described preferred embodiments, the part of the antibody or antibody fragment is a portion of a constant region of the antibody or antibody fragment, or a constant region of the antibody or antibody fragment. According to still further features in the described preferred embodiments, the binding of the antibody or antibody fragment to the antigen-presenting portion of the complex is characterized by an affinity having a dissociation constant selected from the range consisting of 1×10 −2 molar to 5×10 −16 molar. According to still further features in the described, preferred embodiments, the composition-of-matter further comprises a toxin or detectable moiety attached to the antibody or antibody fragment. According to still further features in the described preferred embodiments, the detectable moiety is selected from the group consisting of a recognition sequence of a biotin protein ligase, a biotin molecule, a streptavidin molecule, a fluorophore, an enzyme, and a polyhistidine tag. According to still further features in the described preferred embodiments, the biotin protein ligase is BirA. According to still further features in the described preferred embodiments, the fluorophore is phycoerythrin. According to still further features in the described preferred embodiments, the enzyme is horseradish peroxidase. According to still further features in the described preferred embodiments, the toxin is Pseudomonas exotoxin A or a portion thereof. According to still further features in the described preferred embodiments, the portion of Pseudomonas exotoxin A is a translocation domain and/or an ADP ribosylation domain. According to still further features in the described preferred embodiments, the human antigen-presenting molecule is a major histocompatibility complex molecule. According to still further features in the described preferred embodiments, the major histocompatibility complex molecule is a major histocompatibility complex class I molecule. According to still further features in the described preferred embodiments, the major-histocompatibility complex class I molecule is an HLA-A2 molecule. According to still further features in the described preferred embodiments, the human antigen-presenting molecule is a single chain antigen-presenting molecule. According to still further features in the described preferred embodiments, the pathogen is a viral pathogen. According to still further features in the described preferred embodiments, the viral pathogen is a retrovirus. According to still further features in the described preferred embodiments, the retrovirus is human T lymphotropic virus-1. According to still further features in the described preferred embodiments, the antigen derived from a pathogen is restricted by the antigen-presenting molecule. According to still further features in the described preferred embodiments, the antigen derived from a pathogen is a polypeptide. According to still further features in the described preferred embodiments, the polypeptide is a segment of a Tax protein, or a polypeptide having an amino acid sequence as set forth in SEQ ID NO: 3. The present invention successfully addresses the shortcomings of the presently known configurations by providing a composition-of-matter comprising an antibody or antibody fragment capable of binding with optimal specificity/affinity a human APM:pathogen-derived antigen complex. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
20041013
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20060420
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LUCAS, ZACHARIAH
ANTIGEN-PRESENTING COMPLEX-BINDING COMPOSITIONS AND USES THEREOF
SMALL
1
CONT-ACCEPTED
A61K
2,004
10,510,401
ACCEPTED
Method and composition for the prevention or retarding of staling and its effect during the baking process of bakery products
The present invention is related to a method for the prevention or retarding of staling during the baking process of bakery products which comprises the step of adding a sufficiently effective amount of at least one intermediate thermostable and/or thermostable serine protease in the bakery products. The present invention further relates to an improver for the prevention or retarding of staling during the baking process of bakery products, which comprises at least one intermediate thermostable and/or thermostable serine protease.
1. A method for the prevention or retarding of staling during the baking process of bakery products which comprises the step of adding a sufficiently effective amount of at least one intermediate thermostable and/or thermostable serine protease in said bakery products. 2. The method according to claim 1, wherein the intermediate thermostable and/or thermostable serine protease has a temperature activity optimum higher than 60° C. 3. The method according to the claim 1, wherein the ratio between the protease activity at optimum temperature and the protease activity at 25° C. is higher than 10. 4. The method according to claim 1 wherein the intermediate thermostable and/or thermostable serine protease is obtained by extraction from naturally-occurring eukaryotic or prokaryotic organisms, by synthesis or by genetic engineering. 5. The method according to claim 1 wherein the intermediate thermostable and/or thermostable serine protease is a neutral protease. 6. The method according to claim 1 wherein said protease is selected from the group consisting of aqualysin I, aqualysin II, thermitase and keratinase. 7. The method according to claim 1 wherein the thermostable serine protease is a Taq protease isolated from Thermus aquaticus LMG 8924, a keratinase, isolated from Bacillus licheniformis LMG 7561 and/or a thermitase isolated from Thermoactinomyces vulgaris. 8. The method according to claim 1, further comprising the step of adding another anti-staling additive selected from the group consisting of thermostable α-amylase, β-amylase, intermediate thermostable maltogenic amylase, lipase, glycolsyltransferases, pullulanases and emulsifiers. 9. The method according to claim 1 wherein the bakery product is selected from the group consisting of bread, soft rolls, bagels, donuts, Danish pastry, hamburger rolls, pizza, pita bread and cakes. 10. An improver for the prevention or retarding of staling during the baking process of bakery products, wherein said improver it comprises at least one intermediate thermostable or thermostable serine protease. 11. The improver as in claim 10, wherein the protease has a temperature activity optimum higher than 60° C. 12. The improver as in claim 10, wherein the ratio between the protease activity at optimum temperature and the protease activity at 25° C. is higher than 10. 13. The improver as in claim 10 wherein said protease is obtained by extraction from naturally occurring eukaryotic or prokaryotic organisms, by synthesis or by genetic engineering 14. The improver as in claim 10 wherein said protease is a Taq protease, a keratinase and/or a thermitase. 15. The improver as in claim 10 wherein said protease is selected from the group consisting of aqualysin I, aqualysin II, keratinase and thermitase. 16. The improver according to claim 10, wherein the thermostable serine protease is a Taq protease isolated from Thermus aquaticus LMG 8924, a keratinase isolated from Bacillus licheniformis LMG 7561 and/or a thermitase isolated from Thermoactinomyces vulgaris. 17. The improver as in claim 10 further comprising another anti-staling additive selected from the group consisting of thermostable α-amylase, β-amylase, intermediate thermostable maltogenic amylase, lipase, glycolsyltransferases, pullulanases and emulsifiers. 18. The improver as in claim 10 wherein said improver is a bread improver. 19. (canceled) 20. (canceled) 21. (canceled) 22. (canceled) 23. The method of claim 2, wherein the intermediate thermostable and/or thermostable serine protease has a temperature activity optimum higher than 70° C. 24. The method of claim 2, wherein the intermediate thermostable and/or thermostable serine protease has a temperature activity optimum higher than 75° C. 25. The method of claim 3, wherein the ratio between the protease activity at optimum temperature and the protease activity at 25° C. is higher than 15. 26. The method of claim 1, wherein the intermediate thermostable and/or thermostable serine protease is an alkaline protease. 27. The method of claim 8, wherein said emulsifiers are selected from the group consisting of monoglycerides, diglycerides and stearoyllactylates. 28. The improver of claim 11, wherein said protease has a temperature activity optimum higher that 70° C. 29. The improver of claim 11, wherein said protease has a temperature activity optimum higher that 75° C. 30. The improver of claim 12, wherein the ratio between the protease activity at optimum temperature and the protease activity at 25° C. is higher than 15. 31. The improver of claim 17, wherein said emulsifiers are selected from the group consisting of monoglycerides, diglycerides and stearoyllactylates.
FIELD OF THE INVENTION The present invention concerns a method and a composition for the prevention or retarding of staling and associated effects during the baking process of bakery products which comprise at least one intermediate thermostable and/or thermostable serine protease. BACKGROUND OF THE INVENTION The consumers prefer to buy fresh bread and they want it to remain fresh for a long time. Retarding the staling has always been a challenge to producers of bakery ingredients. The fact that the production of bread is more and more centralised and farther away from the distribution points puts an even larger pressure on the development of additives and ingredients to maintain the softness of bread. Also soft rolls, hamburger, buns and pastry products are subject to staling and a loss of softness. There are a number of ingredients known to retard the staling of bread and soft bakery products. Fat and emulsifiers such as distilled monoglycerides and stearoyllactylates are already used since decades. Mono-, di- and polysaccharides have a positive influence on water retention and binding. Water loss is often associated with staling and the saccharides have positive influence on the mouthfeel of baked products and thus diminish the perception of staling. Amylases are known to have a beneficial effect on staling and starch retrogradation. Bread staling is a complex phenomenon. It is perceived as a softening of the crust, a hardening of the crumb and the disappearance of fresh bread flavour. The hardening of the crumb is not only due to a loss of water during storage as was already demonstrated by Boussingault in ((1852) Ann. Chim. Phys. 3, 36, 490). It is the result of a number of physico-chemical processes. Over the years, researchers have tried to unravel these processes and developed different theories. In the early days, bread firming was attributed solely to the retrogradation of starch (Katz, J. R. (1930) Z. Phys. Chem., 150, 37-59). It was shown by X-ray diffraction that the starch in bread is forming a micro-crystalline structure during storage. Later it was shown that the water soluble starch fraction diminished during bread staling (Schoch et al. (1947) Cereal Chem., 24, 231-249), which concludes that during baking starch granules absorb water. The linear amylose chains become soluble and diffuse to the water phase. In time more and more amylose is present in the water phase. So the amylose is partially leached out of the swollen starch granules. The branched amylopectine remains in the granules. The leaching process is limited by the available water. During cooling the amylose retrogrades very quickly and forms a gel. The retrogradation of amylopectine is believed to involve primarily association of its outer branches and requires a longer time than does the retrogradation of amylose, giving it prominence in the staling process, which occurs over time after the product has cooled, aggregate more slowly, due to stereochemical interferences. The amylopectine formed intramolecular bonds. The prominent role of starch in staling of bread is further illustrated by the use of carbohydrases to diminish or to slow down the staling of baked products. It was shown (Conn J. F. et al. (1950) Cereal Chem., 27, 191-205) that amylases from bacterial or fungal origin slow down the rate of staling of bread and result in a less firm crumb structure. The addition of thermostable alfa-amylases or beta-amylases is most effective. However this also results in a gummy and sticky crumb. The document EP0412607 discloses the use of a thermostable alfa-1,6-endoglucanase or an alfa-1,4-exoglucanase to reduce staling; EP0234858 discloses the use of a thermostable maltogenic beta-amylase to retain the crumb softness. However, it is still not clear whether the anti-staling effect is due to the dextrins produced or to the modification of the amylose and amylopectine and the consequent reduced tendency to crystallise. Also the influence of emulsifiers as glycerolmonostearate and sodiumstearoyllactylate seems to confirm the role of starch in bread crumb firming (Schuster G. (1985) Emulgatoren für Lebensmittel—Springer Verlag 323-329). It is the interaction between these emulsifiers and the starch which results in a changed starch conformation that accounts for the observed reduction of staling. As there was not always a good correlation between starch structure and staling (Zobel H. F. et al (1959) Cereal Chem., 36, 441), other flour constituents were also investigated. The role of flour proteins in the crumb firming process has been studied but it was found that they were less important than starch (Cluskey, J. E. (1959) Cereal Chem., 36, 236-246.), (Dragsdorf, R. D. et al. (1980) Cereal Chem., 57, 310-314) studied the water migration between starch and gluten during bread storage. These authors concluded that due to a change in the cristallinity of the starch, it adsorbed more water, so the water migrates from the gluten to the starch and so less free water is available. In later study (Martin et al. (1991) Cereal Chem., 68(5), 498-503 and 503-507), it appears that the high molecular weight dextrins do not have an antifirming effect on bread crumb. Instead, the high DP dextrins may entangle and/or form a hydrogen bond with protein fibrils, thus effectively cross-linking the gluten. Consequently, the firming rate is increased. It is stated that in weaker flours the gluten interacts stronger with the starch granules. This results in bread crumb that firms faster. However better gluten quality and stronger flour also result in higher loaf volume and thus in a softer crumb. Axford et al. (1968) cited in Faridi, H. (1985) Rheology of wheat products, AACC, p. 263-264) showed that the loaf specific volume was a major factor in measuring both the rate and the extent of firming. So the role of gluten in bread firming remains still questionable and few attempts have been made to slow down firming based on gluten modification. Proteases have a long history of use in the baking sector. They are mostly used by the baker to reduce mechanical dough development requirements of unusually strong or tough gluten. They lower the viscosity and increase the extensibility of the dough. In the end product they improve the texture compressibility, the loaf volume and the bread colour. Also the flavour can be enhanced by production of certain peptides. The proteases mellow the gluten enzymatically rather than mechanically. They reduce the consistency of the dough, decreasing the farinograph value. The proteases most used in baking are from Aspergillus oryzae and Bacillus subtilis. The neutral bacterial proteases are by far more active on gluten than the alkaline proteases. Papain, bromelain and ficin are thiol-proteases extracted from papaya, pineapple and figs. Especially papain is very reactive towards gluten proteins. Bacterial proteases and papain, especially neutral proteases, are used in cookies, breadsticks and crackers where a pronounced slackening of the dough is wanted. However, in breadmaking, a more mild hydrolysis of fungal proteases is preferred. Proteases also have major disadvantages. The action of the proteases is not limited in time, it continues after mixing and weakens the dough structure in time. This phenomenon increases the risk of weakening the dough and increases the stickiness of the dough. Sometimes their action is even enhanced by the pH drop during fermentation. The use of proteases in baking requires strict control of the bulk fermentation and proofing conditions of the dough. The proteases are inactivated during baking (Kruger, J. E. (1987) Enzymes and their role in cereal technology AACC 290-304). Especially neutral Bacillus proteases and papain should be dosed very carefully as overdoses slacken the dough too much. This may result in dough collapse before ovening or a lower bread volume and a more open crumb structure. Especially in Europe, where the flours are weaker than in the US or Canada, the risk of overdosing protease is very present. Furthermore, proteases also increase stickiness because by the hydrolytic action water is released from the gluten (Schwimmer, S. (1981) Source book of food enzymology-AVI Publishing, 583-584). This means that in practice proteases are not much used in breadmaking in Europe. The document EP021179 discloses the use of an alfa-amylase preparation in which the protease (inactivated) was used in combination with emulsifiers to inhibit staling. Conforti et al. (1996) FSTA, 96(12), M0190 Abstract of presentation) added an enzyme mixture comprising bacterial amylase, fungal amylase and fungal protease to fat substituted muffins. The control fat containing muffin was more tender. The enzyme treatment decreased the staling rate. This is not surprising in view of the presence of amylases. Lipase is also known to soften bread crumb and to somewhat reduce the firming rate of bread crumb (WO 94/04035 example 2). Fungal proteases are sensitive to high temperatures. Their potency of protein hydrolysis in a moderate to high temperature range of about 50° C. or higher is normally poor. Some bacterial neutral and alkaline proteases are resistant to higher heat treatments. Till now reports on bacteria-derived proteases with heat resistance that can retain good peptidase activity, for example, in a high temperature range of about 60° C. have been scarce. The document EP1186658 discloses such enzyme produced by a bacterium of the genus Bacillus subtilis, more specifically an M2-4 strain. The disclosed enzyme mixture, however, completely looses its activity at a temperature of about 70° C. Neutral thermostable proteases from Bacillus, which may be tolerant to oxidising agents, are preferred in detergent formulations. Also alkaline thermostable proteases from Bacillus are used in washing and detergent formulations. Papain is very heat stable and requires a prolonged heating at 90-100° C. for deactivation. Bromelain is less stable and can be deactivated at around 70° C. Other heat stable proteases are produced by Bacillus licheniformis NS70 (Chemical Abstracts, 127, 4144 CA), Bacillus licheniformis MIR 29 (Chemical Abstracts, 116, 146805 CA), Bacillus stearothermophilus (Chemical Abstracts, 124, 224587 CA), Nocardiopsis (Chemical Abstracts, 114, 162444 CA) and Thermobacteroides (Chemical Abstracts, 116, 146805 CA). This is not an exhaustive list, but it illustrates the importance of the thermostable serine proteases and their application, mostly in detergents. No reference is made to baking and anti-staling properties. Lipase is also known to soften bread crumb and to somewhat reduce the firming rate of bread crumb (WO 94/04035 example 2). Fungal proteases are sensitive to high temperatures. Some bacterial neutral and alkaline proteases are resistant to higher heat treatments. Neutral thermostable proteases from Bacillus, which may be tolerant to oxidising agents, are preferred in detergent formulations. Also alkaline thermostable proteases from Bacillus are used in washing and detergent formulations. Papain is very heat stable and requires a prolonged heating at 90-100° C. for deactivation. Bromelain is less stable and can be deactivated at around 70° C. Other heat stable proteases are produced by Bacillus licheniformis NS70 (Chemical Abstracts, 127, 4144 CA), Bacillus licheniformis MIR 29 (Chemical Abstracts, 116, 146805 CA), Bacillus stearothermophilus (Chemical Abstracts, 124, 224587 CA), Nocardiopsis (Chemical Abstracts, 114, 162444 CA) and Thermobacteroides (Chemical Abstracts, 116, 146805 CA). This is not an exhaustive list, but it illustrates the importance of the thermostable serine proteases and their application, mostly in detergents. No reference is made to baking and anti-staling properties. Papain is a proteolytically active constituent in the latex of the tropical papaya fruit. The crude dried latex contains a mixture of at least four cysteine proteinases. Thermolysin is an extracellular, metalloendopeptidase secreted by the gram-positive thermophilic bacterium Bacillus thermoproteolyticus. STATE OF THE ART Keratinase is a protease which is active on keratin, a scleroprotein existing as a constituent in mammalian epidermis, hair, wool, nails and feathers. Practical applications of the enzyme are as ingredient in depilatory compositions; as dehairing aid of hides in leather manufacture, the breaking down of keratin and reconstitution into textile fabrics. No application of said enzyme in the food industry is known. Thermus aquaticus is a hyperthermophile belonging to the Archea. The well known “Taq polymerase”™ is isolated from this organism. Pyrococcus furiosus is another representative from this group. Thermostable proteases were isolated from these organisms. Thermitase is an extracellular endopeptidase from Thermoactinomyces vulgaris. Because of its relatively low cleaving specificity towards peptide bonds, thermitase has many applications. It is suitable for producing partially hydrolysed proteins for health and other special diets. SUMMARY OF THE INVENTION A first aspect of the present invention is related to a method for the prevention or retarding of staling and associated effects during the baking process of bakery products, said method comprising the step of adding a sufficiently effective amount of at least one thermostable protease to the ingredients of said bakery products. Preferably said proteases are neutral or alkaline proteases, most preferably alkaline proteases. Preferably, the intermediate thermostable and/or thermostable serine protease has its optimal temperature activity higher than 60° C., preferably higher than 70° C., more preferably higher than 75° C. or even higher than 80° C. The preferred intermediate thermostable and/or thermostable serine protease used in the method according to the invention presents a ratio between the protease activity at optimum temperature and the protease activity at 25° C., higher than 10, preferably higher than 15. As such the enzyme will preferably be active during the baking process and preferably not during the rising process. Such intermediate thermostable and/or thermostable serine protease can be obtained by extraction from naturally occurring eukaryotic or prokaryotic organisms, by synthesis or by genetic engineering by a method well-known to a person skilled in the art. The preferred intermediate thermostable and/or thermostable thermostable serine protease is Taq protease which can be advantageously isolated from the strain Thermus aquaticus (LMG8924) or is keratinase, preferably isolated from Bacillus licheniformis (LMG7561) or is thermitase isolated from Thermoactinomyces vulgaris. These three proteinases all belong to the class of the serine peptidases. Papain (belonging to the class of cysteine peptidases) and thermolysin (belonging to the class of metallopeptidases) were also included in the baking trials performed but were not able to reduce staling and/or had undesirable side effects and/or negative effects on the baking process and the resulting products. In the method according to the invention, use of the intermediate thermostable and/or thermostable serine protease can be combined with another enzyme, such as a thermostable α-amylase, β-amylase, intermediate thermostable maltogenic amylase, lipase, glycolsyltransferases or pullulanases. The thermostable protease can also be added to a non-enzymetic additive such as an emulsifier (monoglyceride, diglyceride and/or stearoyllactylades). Other suitable emulsifiers may also be added to said intermediate thermostable and/or thermostable serine protease during the baking process. Synergistic or cumulative effects are present. Therefore, the method according to the invention will result in improved bakery products which are preferably selected from the group consisting of bread, soft rolls, bagels, donuts, danish pastry, hamburger rolls, pizza, pita bread and cakes. Another aspect of the present invention is related to an anti-staling composition for bakery products comprising at least one thermostable protease. Another embodiment of the present invention is an improver composition, more specifically a bread improver composition, comprising at least one intermediate thermostable and/or thermostable serine protease and the usual active ingredients of an improver composition. An improver composition is a well-known concept amongst bakers. It is a mixture of active ingredients such as enzymes and emulsifiers, which are mixed with the usual ingredients for making bread, such as flour and water. A further embodiment of the present invention is related to the use of said intermediate thermostable and/or thermostable protease, especially a keratinase of the invention in the food industry and more specifically in bakery products. DETAILED DESCRIPTION OF THE INVENTION The invention relates to the use of an intermediate thermostable and/or thermostable serine protease in baked goods. Preferably, these serine proteases are alkaline proteases but they can also be neutral proteases. The enzyme preparation has a pronounced effect on crumb softness and on retarding the staling of baked products. The enzyme preparation is characterised by the fact that it has no adverse effect on dough rheology, on the crumb structure and on the volume of the resulting bread. The enzyme has a low activity at a temperature of 25° C. to 40° C. meaning that they will have no to low activity during dough resting and/or rising. The enzyme has a temperature optimum of 60° C.-80° C. or higher. The enzyme is or is not inactivated during the baking process. The intermediate thermostable and/or thermostable serine proteases according to the present invention are characterised by having a positive effect as anti-staling agents. This effect is especially noticeable in combination with other anti-staling enzymes. As examples of other anti-staling enzymes the person skilled in the art may select thermostable amylases from Bacillus licheniformis or Bacillus stearothermophilus and thermostable maltogenic amylases (i.e. Novamyl® from Novozymes). Their effect is also additive to the anti-staling effect of mono- en diglycerides, stearoyllactylates and other emulsifiers used in baking. The intermediate thermostable and/or thermostable serine proteases of the invention can be used in bread, soft rolls, bagels, donuts, danish pastry, hamburger rolls, pizza and pita bread, cake and other baked products where staling and inhibition thereof is an quality issue. The intermediate thermostable and/or thermostable serine protease of the invention can be produced by prokaryotes (bacteria) and eukaryotes (fungi, Archea, animals, plants etc) and/or can be produced by genetic engineering or even by synthesis with any technique known in the art. Basically the most important characteristics of the proteases that are used in this invention are: 1) Their thermostability: At a pH where the enzyme is stable they have a temperature optimum that is higher than 60° C., preferably higher than 70° C. and even more preferable higher than 75° C., higher than 80° C. or 85° C. 2) The ratio between the activity at optimum temperature and at 25° C. is at least higher than 10 and preferable higher than 15. 3) They belong to the group of the serine proteases. Preferably, the proteases of the invention do not loose their activity at temperatures higher than 60° C., preferably higher than 70° C., 75° C., 80° C. or even 85° C. The enzymes of the present invention may still be active at the very high internal temperatures that are reached within a product during baking (at least about 75° C. for yeast leavened baked food and at least about 90° C.-95° C. for chemically leavened baked food, when fully baked). Within the optimum range of temperature, the temperature may range anywhere from about 60° C. to 61° C., 62° C., 63° C., . . . 84° C., 85° C., . . . 89° C., 90° C., . . . 94° C., 95° C. with all integers included therein. The enzyme of the invention is preferably a keratinase, a Taq protease and/or a thermitase. The keratinase is preferably produced by Bacillus licheniformis (example B. licheniformis LMG 7561). The Taq protease is preferably produced by Thermus aquaticus (example Thermus aquaticus LMG 8924). The thermitase is preferably produced by Thermoactinomyces vulgaris. The proteases may be obtained from the respective micro-organisms by use of any suitable technique. For instance, the protease preparation may be obtained by fermentation of a micro-organism and subsequent isolation of the protease containing preparation from the resulting broth by methods known in the art such as centrifugation and ultrafiltration. The proteases may also be obtained by cloning the DNA sequence coding for a suitable protease in a host organism, expressing the protease intra- or extra-cellular and collecting the produced enzyme. Preferably, the protease is present in a form that allows exact and/or more or less exact dosing. Dosing can be difficult when the proteases are part of a complex natural mixture comprising more than one type of enzymes. In such case, the enclosure of one or more purification steps might be needed. The proteases may also be obtained by directed evolution or gene shuffling of thermostable or non-thermostable serine proteases or enzymes. As long as they have peptide cleaving activity, they are considered to be proteases in the scope of this invention. Surprisingly, the inventors found that the use of a protease which had no perceivable action on the dough rheology had a pronounced effect on the softness and retardation of the crumb hardness. There was no adverse effect on the crumb elasticity or no increase of the crumb stickiness as compared to a control. The effect was additive to known anti-staling agents (such as -amylases) and permits the development of bread and other soft bakery products with a prolonged shelf life. The choice of the protease is very important. The protease should exert no adverse effect during mixing and the subsequent proofing. Otherwise the dosage that can be administered is to low to diminish the staling rate and to maintain a good crumb elasticity. The higher the temperature optimum of the enzyme, the lower the negative effect on the crumb structure and on the dough rheology. The present invention will be described hereafter in detail in the following non-limiting examples and in reference to the enclosed figures. SHORT DESCRIPTION OF THE FIGURES The FIG. 1 represents the protease temperature optimum expressed in function of the relative activity (%) at pH 7.0, in a buffered solution of 0.1 M phosphate for aqualysin I (♦0 , full line) and keratinase (●, dotted line). The FIG. 2 represents the retarding effect of the addition of Taq protease (0 U: ♦, 800 U:) upon staling of bread in the absence and presence of Novamyl® (0-8 g/100 kg flour). The FIG. 3 shows the improved effect on retarding bread staling following the addition of keratinase (0 U: ♦, 800 U:) in bread in the absence or presence of Novamyl® (0-8 g/100 kg flour). The FIG. 4 shows the temperature optimum of thermitase, expressed in function of its relative activity (%) at pH 7.0, in a buffered solution of 0.1 M phosphate. The FIG. 5 shows the thermal stability of thermitase, expressed in function of its relative activity DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION One of the preferred serine proteases used, is obtained from the strain Bacillus licheniformis LMG 7561 and has keratinase activity. By amino acid similarity and phenylmethylsulfonyl fluoride inhibition, the keratinase was demonstrated to be a serine protease. The keratinase in question is obtained by culturing the strain Bacillus licheniformis LMG 7561 on the following medium: 0.5 g/l NH4Cl, 0.5 g/l NaCl, 0.3 g/l K2HPO4, 0.4 g/l KH2PO4, 0.1 g/l MgCl2.6H2O, 2 g/l citric acid, 0.1 g/l yeast extract and 10 g/l feather meal. The medium is adjusted to pH 6.5 with phosphoric acid. No pH control is imposed. Incubation is done at 45° C. with aeration (P2 60%, 1.25 vvm) during 40 hours after which the medium is collected for further concentration. The supernatant is then concentrated by membrane ultrafiltration (molecular cut off: 5,000 Da). The crude keratinase solution obtained that way is stored frozen until used in baking tests. The keratinase solution obtained that way displays maximum activity at a temperature of 60° C. and a pH of 8.0. In the pH range of 7 to 9 more than 85% of the maximum activity was measured. There isn't almost any loss of enzyme activity while heating the solution an hour at 60° C. Heating the enzyme at 70° C. during 14 min reduces the activity with 50%. The activity was measured on keratin. For standard measurements, 4 g of keratin were dissolved in 100 ml sodium hydroxide. After dissolution the pH is adjusted slowly to 8.0 with 3.2 M phosphoric acid. Distilled water is added to a final volume of 200 ml. 5 ml of the substrate solution is pre-incubated at 60° C. 1 ml of enzyme solution is added and incubated at 60° C. Then 5 ml of 14% TCA (TriChloroAcetic acid) is added to the incubated enzyme solution. Mixed for 60 minutes. The solution is filtered and the absorbance is measured at 275 nm relative to a blank solution (enzyme added after the TCA addition). The ⁢ ⁢ activity ⁢ ⁢ is ⁢ expressed ⁢ ⁢ as ⁢ ⁢ KU ⁢ / ⁢ ml = ( A275 ⁢ ⁢ nm ⁢ ⁢ Enzyme - A275 ⁢ ⁢ nm ⁢ ⁢ Blanc ) * 11 0.0075 * 30 The fermentation contained 300 to 1500 KU/ml. For baking purposes the activity was expressed as mU/ml based on the protazym tablet determination. The KU were only used to demonstrate the presence of the keratinase. The Taq protease in question is obtained by culturing the strain Thermus aquaticus LMG 8924 on the following medium: 1 g/l tryptone; 1 g/l yeast extract; 100 ml/l salt solution and 900 ml distilled water. The pH is adjusted to 8.2 with 1 M NaOH prior to sterilisation 121° C. for 15 minutes. The salt solution has the following composition: 1 g/l nitriloacetic acid 0.6 g/l CaSO4.2H2O; 1 g/l MgSO4.7H2O; 80 mg/l NaCl, 1.03 g/l KNO3; 6.89 g/l NaNO3; 2.8 g/l Na2HPO4.12H2O; 10 ml/l FeCl3.6H2O solution (47 mg/100 ml); 10 ml/l Trace element solution and 1 l distilled water. The Trace element solution has the following composition: 0.5 ml/l H2SO4; 1.7 g/l MnSO4.H2O; 0.5 g/l ZnSO4.7H2O; 0.5 g/l H3BO3; 25 mg/l CuSO4.5H2O; 25 mg/l Na2MoO4.2H2O; 46 mg/l CoCl2. 6H2O and 1 l distilled water. Incubation is done at 60° C. with aeration (pO2 60%, 4 vvm) during 24 hours after which the medium is collected for further concentration. Thermus aquaticus LMG 8924 produced at least two kinds of extracellular proteases. One of the extracellular proteases was called aqualysin I, and is an alkaline protease which was secreted linearly from the early stationary phase until the time the cells ceased to grow. The optimum temperature of the proteolytic activity was between 70 and 80° C. The other was called aqualysin II and is a neutral protease, the production of which appeared from day 4 and the concentration of this protease continued linearly for 5 days. The maximum activity was obtained at 95° C. (the highest temperature tested). The fermentation extract was used after 1 day of fermentation for the baking tests. As the fermentation was stopped after 1 day, the protease present is the aqualysin I. Aqualysin I is strongly inhibited by the microbial serine protease inhibitors and can be classified as an alkaline serine protease. The supernatant is then concentrated by membrane ultrafiltration (molecular cut off: 10,000 Da). The crude Taq protease solution obtained that way is stored frozen until used in baking tests. The Taq protease solution obtained that way displays maximum activity at a temperature of 80° C. There isn't almost any loss of enzyme activity while heating the solution an hour at 80° C. Heating the enzyme at 90° C. during 10 min reduces the activity with 60%. The protease activity was measured on azurine-crosslinked casein (AZCL-casein). It is prepared by dyeing and crosslinking casein to produce a material which hydrates in water but is water insoluble. Hydrolysis by proteases produces water soluble dyed fragments, and the rate of release of these (increase in absorbance at 590 nm) can be related directly to enzyme activity (Protazyme AK Tablets, Megazyme, Ireland). A protazyme AK tablet is incubated in 100 mM Na2HPO4.2H2O; pH 7.0 at 60° C. for 5 min. An aliquot of enzyme (1.0 ml) is added and the reaction is allowed to continue for exactly 10 min. The reaction is terminated by the addition of tri-sodium phosphate (10 ml, 2% w/v, pH 12.3). The tube is allowed to stand for approx. 2 min at room temperature and the contents are filtered. The absorbance of the filtrate is measured at 590 nm against a substrate blank. The activity is expressed as mU/ml=(34.2*(AbS590enzyme−Abs590 blank)+0.6)/dilution In the case of the thermophilic microorganism, Thermoactinomyces vulgaris, it is known that during the logarithmic phase of multiplication several proteolytic enzymes are secreted into the surrounding medium. Among the up to five proteolytic components of the culture filtrate one protease dominates amounting 70 to 80% of the total activity, termed thermitase. Thermitase is an extracellular, thermostable serine proteinase. The pH profile shows a broad optimum between pH 7.5 and 9.5. The enzyme demonstrates maximal stability in the pH range of 6.4 to 7.6 with increasing instability beyond pH 8.0 and below 5.75, especially at elevated temperatures and longer time periods. Depending on the size of the substrate, thermitase shows maximum activity at temperatures ranging from 65° C. (gelatin), 70° C. (protamine) to 85° C. (azocasein). The temperature optimum is most pronounced with the biggest substrate (azocasein): activity at 85° C. is 12 times over the activity shown at 25° C. Thermitase in question is obtained by culturing the strain Thermoactinomyces vulgaris NRRL b-1617 in a culture medium with the following composition: wheat starch (20 g/l), bacteriological pepton (5 g/l), yeast extract (3 g/l) and malt extract (3 g/l) in destilled water. Incubation is done at 45° C. with an aeration of 12 l/min and a rotation of 200 rpm. The supernatant was collected after 24 h of incubation. Because of the fact that the culture supernatant contained a lot of α-amylase activity, a first purification step was performed to separate the protease activity from the α-amylase activity to perform baking trials. The supernatant was concentrated by membrane ultrafiltration (molecular cut off: 10,000 Da). Thermitase was purified by column chromatography on a S-sepharose column (Pharmacia). The column was equilibrated with 500 mM Na-acetate buffer (pH 4.5) and afterwards with 10 mM Na-acetate buffer (pH 4.5) and 5 mM CaCl2. The α-amylase activity didn't bind on the column and thermitase was eluted with 10 mM Na-acetate buffer (pH 4.5), 5 mM CaCl2 and 1 M NaCl. The eluted fraction was dialysed against 10 mM Na-acetate buffer (pH 4.5) and 5 mM CaCl2 and used to perform baking trials. Side-activities like -amylase activity was measured by the Phadebas Amylase Test™ (Pharmacia & Upjohn). The substrate is a water-insoluble cross-linked starch polymer carrying a blue dye. It is hydrolysed by -amylase to form water-soluble blue fragments. The absorbance of the blue solution is a function of the -amylase activity in the sample. Xylanase side-activity was measured by the xylazyme Method™ (Megazyme). The substrate employed is azurine-crosslinked xylan. This substrate is prepared by dyeing and crosslinking highly purified xylan (from birchwood) to produce a material which hydrates in water but is water insoluble. Hydrolysis by endo-(1,4)- -D-xylanase produces water soluble dyed fragments, and the rate of release of these (increase in absorbance at 590 nm) can be related directly to enzyme activity. The Taq protease solution obtained didn't show any -amylase or xylanase side activity. The keratinase solution obtained had no xylanase activity and contained less than 8 U/ml α-amylase activity as measured by Phadebas test. The thermitase solution obtained after the purification process didn't show any α-amylase or xylanase side activity. The baking tests were performed in 1 kg bread. The basic recipe was (in grams): Flour (Duo): 1500 Water: 840 Fresh Yeast (Bruggeman, Belgium): 75 Sodium Chloride: 30 Partially hydrogenated palm oil: 21 Distilled monoglycerides: 3 Saccharose 6 Ascorbic acid: 0.06 The following breadmaking process was used: The ingredients were mixed for 2′ at low and 6′ at high speed in a Diosna SP24 mixer. The final dough temperature was 29° C. After bulk fermentation for 20′ at 25° C., 600 g dough pieces were made up using the Euro 200S (Bertrand-Electrolux Baking) set at R8/L19 and moulded. The dough pieces are proofed at 35° C. for 50′ at 95% relative humidity. Then the breads are baked at 230° C. in a MIWE CONDO (Micheal Wenz—Arnstein—Germany) oven with steam (0.1 L before and 0.2 L after ovening the breads). It is obvious to one skilled in the art that same end results can be obtained by using equipment of other suppliers. The softness of the bread was measured by a TA-XT2 texture analyser (Stable Micro Systems UK). The bread was sliced and the force to obtain a 25% deformation of 4 slices of 1 cm was measured. This is called the hardness. The hardness is measured at day 1 and day 6 after baking. The difference between the two measure forces is “the loss of softness”: Loss of softness=deformation force at day 6−deformation force at day 1 It is a relative measure. The absolute values have no meaning as such but should be compared to a reference for interpretation. The elasticity is the difference between the aforementioned force and the force after 20 sec of relaxation. When the elasticity is lower than in the reference bread, this means that the crumb becomes less resilient. The crumb, when compressed does not regain its original shape. This means that during slicing or handling the crumb structure may be lost irreversibly. It is important that by using an added enzyme there is no loss of elasticity compared to a control bread. Addition of the enzymes of the present invention to the bread dough did not change the proof time, loaf moisture and specific load volume. The initial moisture content of bread varied slightly, but all the loaves lost approximately the same amount of moisture during six days of storage at room temperature. EXAMPLES Example 1 Tag Protease A bread has been baked according to the aforementioned method with addition of Taq protease (eventually in the presence of different doses of Novamyl®10 000 BG from Novozymes (Denmark)). Doses are expressed on 100 kg of flour weight used in the baking test. The following table 1 expresses the loss in softness between day 1 and day 6 after baking as defined previously. TABLE 1 Softness Novamyl ® 800 U Taq 0 U Taq g/100 kg protease protease 0 140 209 2.5 128 152 5 96 118 8 68 105 The example shows that the use of Taq protease will retard staling in bread. A combination of Taq protease with an intermediate thermostable maltogenic amylase (e.g. Novamyl®, commercial enzyme of Novozymes) will retard staling in bread significantly. So there is a synergistic effect between the thermostable serine proteases and -amylases. This effect becomes more pronounced at higher doses of Novamyl® (see FIG. 2). Table 2 shows that the elasticity of the bread crumb is hardly affected by the use of the Taq protease. TABLE 2 Elasticity Novamyl ® 800 U Taq 0 U Tag g/100 kg protease protease 0 61.5 61.9 2.5 63.1 63.4 5 63.0 64.2 8 63.4 64.9 Example 2 Keratinase A bread baked according to the aforementioned method with the addition of keratinase (eventually in the presence of Novamyl® 10 000 BG from Novozymes (Denmark)). Doses in the following table 3 are expressed on 100 kg of flour weight used in the baking test. The table expresses the loss in softness between day 1 and day 6 after baking as defined previously. TABLE 3 Softness Novamyl ® 800 U g/100 kg keratinase 0 U keratinase 0 121 209 2.5 95 126 5 64 111 8 50 59 It is clear from this experiment that adding the thermostable serine protease keratinase has a pronounced effect on softness. There is a cumulative effect with thermostable maltogenic amylases as Novamyl® (see FIG. 3). It was verified that the small quantity of amylase present in the preparation had no impact on softness and the relaxation ratio by testing this amylase separately. Table 4 also shows that there is no adverse effect on the relaxation ratio when this protease is used. TABLE 4 Elasticity Novamyl ® 800 U g/100 kg keratinase 0 U keratinase 0 62.6 63.6 2.5 64.3 65.0 5 65.5 65.8 8 65.4 65.8 Example 3 Thermitase A bread baked according to the aforementioned method with the addition of thermitase (eventually in combination with Novamyl® 10 000 EG from Novozymes (Denmark)). Doses in the following table 5 are expressed on 100 kg flour weight used in the baking test. Table 5 expresses the loss in softness between day 1 and day 6 after baking as defined previously. TABLE 5 Softness Novamyl ® 10.500 U g/100 kg Thermitase 0 U Thermitase 0 140 197 2.5 87 107 5 65 102 8 62 68 It is obvious from this experiment that adding the thermostable serine protease thermitase has a pronounced effect on softness. There is also a cumulative effect with thermostable maltogenic amylases as Novamyl®. After purification of thermitase there was no alfa-amylase present in the preparation that could have an impact on softness and the relaxation ratio. Table 6 shows that there is also no adverse effect on the relaxation ratio when this protease is used. TABLE 6 Elasticity Novamyl ® 10500 U g/100 kg Thermitase 0 U Thermitase 0 62 64 2.5 64 65 5 64.6 66.3 8 64.4 66.2 The thermitase optimum relative activity (%) of protease at pH 7.0, in a buffered solution of 0.1 M phosphate and the thermal stability (expressed in function or the relative stability at a given temperature) are given in FIGS. 4 and 5 respectively. Treatment with Taq protease, keratinase and/or or thermitase alone, as mixture and/or together with thermostable amylases (e.g. Novamyl®) significantly affects bread softness. The enzyme treated bread was softer, when Taq protease, keratinase and/or thermitase were added. The examples illustrate that thermostable serine proteases according to the present invention increase shelf live of baked products as far as softness and staling are concerned. Example 4 Effect of Keratinase, Thermitase and Taq Protease on the Crumb Structure and the Sensory Characteristics of Bread The above-mentioned intermediate thermostable and/or thermostable serine proteases according to the present invention did not have a negative effect on the crumb structure, whereas other non-thermostable proteases or proteases belonging to another group of proteases like papain (cysteine peptidase) or thermolysin (metallopeptidase) did. Use of for instance papain or thermolysin resulted in the crumb structure becoming more open, dependent of the doses that were used. There was also no effect on the volume of the baked products by using the thermostable serine proteases of the invention. Crust colour, character of crust, colour of crumb, aroma and taste of bread did not change significantly with the addition of keratinase, Taq protease and/or thermitase. Example 5 Application of Tag Protease in Cake Recipe: Mix Satin Creme Cake: 1000 g Eggs: 350 g Oil: 300 g Water: 225 g Method: Mixer: Hobart Instrument: Padle Speed: 1 min speed 1 and 2 min speed 2 than Adding oil and water, 1 min speed 1, scrape Down and 2 min speed 1 Batter weight: 300 g Temperature: 180° C. Time: 45 min Doses in the following table 7 are expressed on 100 kg of flour weight used in the baking test. Table 7 expresses the loss in softness measured after 4 days, 1 week, 2 weeks and 3 weeks after baking. TABLE 7 Softness 0 U Taq 600 U Taq 1200 U Taq protease protease protease 4 days 396 321 237 1 week 492 379 298 2 weeks 542 457 268 4 weeks 687 441 308
<SOH> BACKGROUND OF THE INVENTION <EOH>The consumers prefer to buy fresh bread and they want it to remain fresh for a long time. Retarding the staling has always been a challenge to producers of bakery ingredients. The fact that the production of bread is more and more centralised and farther away from the distribution points puts an even larger pressure on the development of additives and ingredients to maintain the softness of bread. Also soft rolls, hamburger, buns and pastry products are subject to staling and a loss of softness. There are a number of ingredients known to retard the staling of bread and soft bakery products. Fat and emulsifiers such as distilled monoglycerides and stearoyllactylates are already used since decades. Mono-, di- and polysaccharides have a positive influence on water retention and binding. Water loss is often associated with staling and the saccharides have positive influence on the mouthfeel of baked products and thus diminish the perception of staling. Amylases are known to have a beneficial effect on staling and starch retrogradation. Bread staling is a complex phenomenon. It is perceived as a softening of the crust, a hardening of the crumb and the disappearance of fresh bread flavour. The hardening of the crumb is not only due to a loss of water during storage as was already demonstrated by Boussingault in ((1852) Ann. Chim. Phys. 3, 36, 490). It is the result of a number of physico-chemical processes. Over the years, researchers have tried to unravel these processes and developed different theories. In the early days, bread firming was attributed solely to the retrogradation of starch (Katz, J. R. (1930) Z. Phys. Chem., 150, 37-59). It was shown by X-ray diffraction that the starch in bread is forming a micro-crystalline structure during storage. Later it was shown that the water soluble starch fraction diminished during bread staling (Schoch et al. (1947) Cereal Chem., 24, 231-249), which concludes that during baking starch granules absorb water. The linear amylose chains become soluble and diffuse to the water phase. In time more and more amylose is present in the water phase. So the amylose is partially leached out of the swollen starch granules. The branched amylopectine remains in the granules. The leaching process is limited by the available water. During cooling the amylose retrogrades very quickly and forms a gel. The retrogradation of amylopectine is believed to involve primarily association of its outer branches and requires a longer time than does the retrogradation of amylose, giving it prominence in the staling process, which occurs over time after the product has cooled, aggregate more slowly, due to stereochemical interferences. The amylopectine formed intramolecular bonds. The prominent role of starch in staling of bread is further illustrated by the use of carbohydrases to diminish or to slow down the staling of baked products. It was shown (Conn J. F. et al. (1950) Cereal Chem., 27, 191-205) that amylases from bacterial or fungal origin slow down the rate of staling of bread and result in a less firm crumb structure. The addition of thermostable alfa-amylases or beta-amylases is most effective. However this also results in a gummy and sticky crumb. The document EP0412607 discloses the use of a thermostable alfa-1,6-endoglucanase or an alfa-1,4-exoglucanase to reduce staling; EP0234858 discloses the use of a thermostable maltogenic beta-amylase to retain the crumb softness. However, it is still not clear whether the anti-staling effect is due to the dextrins produced or to the modification of the amylose and amylopectine and the consequent reduced tendency to crystallise. Also the influence of emulsifiers as glycerolmonostearate and sodiumstearoyllactylate seems to confirm the role of starch in bread crumb firming (Schuster G. (1985) Emulgatoren für Lebensmittel—Springer Verlag 323-329). It is the interaction between these emulsifiers and the starch which results in a changed starch conformation that accounts for the observed reduction of staling. As there was not always a good correlation between starch structure and staling (Zobel H. F. et al (1959) Cereal Chem., 36, 441), other flour constituents were also investigated. The role of flour proteins in the crumb firming process has been studied but it was found that they were less important than starch (Cluskey, J. E. (1959) Cereal Chem., 36, 236-246.), (Dragsdorf, R. D. et al. (1980) Cereal Chem., 57, 310-314) studied the water migration between starch and gluten during bread storage. These authors concluded that due to a change in the cristallinity of the starch, it adsorbed more water, so the water migrates from the gluten to the starch and so less free water is available. In later study (Martin et al. (1991) Cereal Chem., 68(5), 498-503 and 503-507), it appears that the high molecular weight dextrins do not have an antifirming effect on bread crumb. Instead, the high DP dextrins may entangle and/or form a hydrogen bond with protein fibrils, thus effectively cross-linking the gluten. Consequently, the firming rate is increased. It is stated that in weaker flours the gluten interacts stronger with the starch granules. This results in bread crumb that firms faster. However better gluten quality and stronger flour also result in higher loaf volume and thus in a softer crumb. Axford et al. (1968) cited in Faridi, H. (1985) Rheology of wheat products, AACC, p. 263-264) showed that the loaf specific volume was a major factor in measuring both the rate and the extent of firming. So the role of gluten in bread firming remains still questionable and few attempts have been made to slow down firming based on gluten modification. Proteases have a long history of use in the baking sector. They are mostly used by the baker to reduce mechanical dough development requirements of unusually strong or tough gluten. They lower the viscosity and increase the extensibility of the dough. In the end product they improve the texture compressibility, the loaf volume and the bread colour. Also the flavour can be enhanced by production of certain peptides. The proteases mellow the gluten enzymatically rather than mechanically. They reduce the consistency of the dough, decreasing the farinograph value. The proteases most used in baking are from Aspergillus oryzae and Bacillus subtilis . The neutral bacterial proteases are by far more active on gluten than the alkaline proteases. Papain, bromelain and ficin are thiol-proteases extracted from papaya, pineapple and figs. Especially papain is very reactive towards gluten proteins. Bacterial proteases and papain, especially neutral proteases, are used in cookies, breadsticks and crackers where a pronounced slackening of the dough is wanted. However, in breadmaking, a more mild hydrolysis of fungal proteases is preferred. Proteases also have major disadvantages. The action of the proteases is not limited in time, it continues after mixing and weakens the dough structure in time. This phenomenon increases the risk of weakening the dough and increases the stickiness of the dough. Sometimes their action is even enhanced by the pH drop during fermentation. The use of proteases in baking requires strict control of the bulk fermentation and proofing conditions of the dough. The proteases are inactivated during baking (Kruger, J. E. (1987) Enzymes and their role in cereal technology AACC 290-304). Especially neutral Bacillus proteases and papain should be dosed very carefully as overdoses slacken the dough too much. This may result in dough collapse before ovening or a lower bread volume and a more open crumb structure. Especially in Europe, where the flours are weaker than in the US or Canada, the risk of overdosing protease is very present. Furthermore, proteases also increase stickiness because by the hydrolytic action water is released from the gluten (Schwimmer, S. (1981) Source book of food enzymology-AVI Publishing, 583-584). This means that in practice proteases are not much used in breadmaking in Europe. The document EP021179 discloses the use of an alfa-amylase preparation in which the protease (inactivated) was used in combination with emulsifiers to inhibit staling. Conforti et al. (1996) FSTA, 96(12), M0190 Abstract of presentation) added an enzyme mixture comprising bacterial amylase, fungal amylase and fungal protease to fat substituted muffins. The control fat containing muffin was more tender. The enzyme treatment decreased the staling rate. This is not surprising in view of the presence of amylases. Lipase is also known to soften bread crumb and to somewhat reduce the firming rate of bread crumb (WO 94/04035 example 2). Fungal proteases are sensitive to high temperatures. Their potency of protein hydrolysis in a moderate to high temperature range of about 50° C. or higher is normally poor. Some bacterial neutral and alkaline proteases are resistant to higher heat treatments. Till now reports on bacteria-derived proteases with heat resistance that can retain good peptidase activity, for example, in a high temperature range of about 60° C. have been scarce. The document EP1186658 discloses such enzyme produced by a bacterium of the genus Bacillus subtilis , more specifically an M2-4 strain. The disclosed enzyme mixture, however, completely looses its activity at a temperature of about 70° C. Neutral thermostable proteases from Bacillus , which may be tolerant to oxidising agents, are preferred in detergent formulations. Also alkaline thermostable proteases from Bacillus are used in washing and detergent formulations. Papain is very heat stable and requires a prolonged heating at 90-100° C. for deactivation. Bromelain is less stable and can be deactivated at around 70° C. Other heat stable proteases are produced by Bacillus licheniformis NS70 (Chemical Abstracts, 127, 4144 CA), Bacillus licheniformis MIR 29 (Chemical Abstracts, 116, 146805 CA), Bacillus stearothermophilus (Chemical Abstracts, 124, 224587 CA), Nocardiopsis (Chemical Abstracts, 114, 162444 CA) and Thermobacteroides (Chemical Abstracts, 116, 146805 CA). This is not an exhaustive list, but it illustrates the importance of the thermostable serine proteases and their application, mostly in detergents. No reference is made to baking and anti-staling properties. Lipase is also known to soften bread crumb and to somewhat reduce the firming rate of bread crumb (WO 94/04035 example 2). Fungal proteases are sensitive to high temperatures. Some bacterial neutral and alkaline proteases are resistant to higher heat treatments. Neutral thermostable proteases from Bacillus , which may be tolerant to oxidising agents, are preferred in detergent formulations. Also alkaline thermostable proteases from Bacillus are used in washing and detergent formulations. Papain is very heat stable and requires a prolonged heating at 90-100° C. for deactivation. Bromelain is less stable and can be deactivated at around 70° C. Other heat stable proteases are produced by Bacillus licheniformis NS70 (Chemical Abstracts, 127, 4144 CA), Bacillus licheniformis MIR 29 (Chemical Abstracts, 116, 146805 CA), Bacillus stearothermophilus (Chemical Abstracts, 124, 224587 CA), Nocardiopsis (Chemical Abstracts, 114, 162444 CA) and Thermobacteroides (Chemical Abstracts, 116, 146805 CA). This is not an exhaustive list, but it illustrates the importance of the thermostable serine proteases and their application, mostly in detergents. No reference is made to baking and anti-staling properties. Papain is a proteolytically active constituent in the latex of the tropical papaya fruit. The crude dried latex contains a mixture of at least four cysteine proteinases. Thermolysin is an extracellular, metalloendopeptidase secreted by the gram-positive thermophilic bacterium Bacillus thermoproteolyticus.
<SOH> SUMMARY OF THE INVENTION <EOH>A first aspect of the present invention is related to a method for the prevention or retarding of staling and associated effects during the baking process of bakery products, said method comprising the step of adding a sufficiently effective amount of at least one thermostable protease to the ingredients of said bakery products. Preferably said proteases are neutral or alkaline proteases, most preferably alkaline proteases. Preferably, the intermediate thermostable and/or thermostable serine protease has its optimal temperature activity higher than 60° C., preferably higher than 70° C., more preferably higher than 75° C. or even higher than 80° C. The preferred intermediate thermostable and/or thermostable serine protease used in the method according to the invention presents a ratio between the protease activity at optimum temperature and the protease activity at 25° C., higher than 10, preferably higher than 15. As such the enzyme will preferably be active during the baking process and preferably not during the rising process. Such intermediate thermostable and/or thermostable serine protease can be obtained by extraction from naturally occurring eukaryotic or prokaryotic organisms, by synthesis or by genetic engineering by a method well-known to a person skilled in the art. The preferred intermediate thermostable and/or thermostable thermostable serine protease is Taq protease which can be advantageously isolated from the strain Thermus aquaticus (LMG8924) or is keratinase, preferably isolated from Bacillus licheniformis (LMG7561) or is thermitase isolated from Thermoactinomyces vulgaris. These three proteinases all belong to the class of the serine peptidases. Papain (belonging to the class of cysteine peptidases) and thermolysin (belonging to the class of metallopeptidases) were also included in the baking trials performed but were not able to reduce staling and/or had undesirable side effects and/or negative effects on the baking process and the resulting products. In the method according to the invention, use of the intermediate thermostable and/or thermostable serine protease can be combined with another enzyme, such as a thermostable α-amylase, β-amylase, intermediate thermostable maltogenic amylase, lipase, glycolsyltransferases or pullulanases. The thermostable protease can also be added to a non-enzymetic additive such as an emulsifier (monoglyceride, diglyceride and/or stearoyllactylades). Other suitable emulsifiers may also be added to said intermediate thermostable and/or thermostable serine protease during the baking process. Synergistic or cumulative effects are present. Therefore, the method according to the invention will result in improved bakery products which are preferably selected from the group consisting of bread, soft rolls, bagels, donuts, danish pastry, hamburger rolls, pizza, pita bread and cakes. Another aspect of the present invention is related to an anti-staling composition for bakery products comprising at least one thermostable protease. Another embodiment of the present invention is an improver composition, more specifically a bread improver composition, comprising at least one intermediate thermostable and/or thermostable serine protease and the usual active ingredients of an improver composition. An improver composition is a well-known concept amongst bakers. It is a mixture of active ingredients such as enzymes and emulsifiers, which are mixed with the usual ingredients for making bread, such as flour and water. A further embodiment of the present invention is related to the use of said intermediate thermostable and/or thermostable protease, especially a keratinase of the invention in the food industry and more specifically in bakery products.
20050512
20161004
20051117
66452.0
0
BADR, HAMID R
Method and composition for the prevention or retarding of staling of bakery products
UNDISCOUNTED
0
ACCEPTED
2,005
10,510,458
ACCEPTED
Curable foam elasomeric compositions
A two-part curable foaming composition comprising: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed.
1. A two-part curable foaming composition comprising: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water, and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed. 2. The two-part curable foaming composition of claim 1, wherein the elastomeric foam is formed under temperatures greater than ambient. 3. The two-part curable foaming composition of claim 1, wherein the first and/or second part further comprise a lubricous agent. 4. The two-part curable foaming composition of claim 1, wherein said lubricous agent comprises a silicone/polyether surfactant. 5. The two-part curable foaming composition of claim 3, wherein the surfactant creates a surface of the elastomeric foam. 6. The two-part curable foaming composition of claim 1, wherein the nitrogen-containing compound is a primary or secondary amine. 7. The two-part curable foaming composition of claim 1, wherein said catalyst is a strong Lewis base. 8. The two-part curable foaming composition of claim 1, wherein said catalyst is an amine condensation catalyst. 9. The two-part curable foaming composition of claim 1, wherein the catalyst is selected form the group consisting of 1,8-diazobicyclo (5,4,0)-undec-5-ene (DBU); dibutylamine; quinuclidine, 1,4-diazabicyclo(2,2,2) octane, and combinations thereof. 10. The two-part curable foaming composition of claim 1, wherein the alkoxysilyl capped prepolymer comprises the reaction product of a isocyanoalkylenetrialkoxy silane with a polyether diol. 11. The two-part curable foaming composition of claim 1, wherein the alkoxysilyl capped prepolymer comprises a trimethoxysilyl capped diurethane polyether. 12. The two-part curable foaming composition of claim 1, wherein the polyether diol comprises polypropylene oxide diol. 13. The two-part curable foaming composition of claim 1, wherein the foaming composition further comprises fillers, plasticizers, catalysts, stabilizer, lubricants, surfactants and combinations thereof. 14. An elastomeric foam comprising the reaction product of: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed. 15. A moisture curable foaming composition comprising an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen, and water. 16. A sound and vibration dampening composition comprising the foam of claim 1. 17. A composite structure comprising first and second substrates and an elastomeric foam positioned therebetween, said elastomeric foam comprising the reaction product of an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen, water, and a catalyst which accelerates both foaming and cross-linking through the alkoxysilyl groups. 18. A method of filling the gap between two substrate surfaces comprising: (A) Providing a two-part curable foaming composition comprising: (a) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (b) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed. (B) Combining the parts in the gap between the substrates; and (C) Permitting the composition to form a cured foam therebetween. 19. A method of making a noise and vibration dampening seal between surfaces comprising the steps of: introducing between the surfaces a composition comprising a mixture of: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed; permitting the composition to form a cured foam. 20. A method of manufacturing a self-lubricating, foaming composition, comprising: (A) providing a curable composition comprising an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen for reaction with the polyhydrogen siloxane, water and a catalyst which accelerates both foaming and cross-linking through the alkoxysilyl group; (B) providing to the curable composition a silicone/polyether surfactant; (C) dispensing the composition onto a substrate surface; (D) exposing the composition to conditions favorable to generating a cured foam; and (E) permitting the surfactant to migrate to the surface to provide a lubricious surface. 21. The method of claim 20, further comprising joining a second substrate surface to the lubricious surface of the cured foam. 22. The composition of claim 1, further comprising aminoalkyltrimethoxy silane. 23. The method of claim 20, further comprising adding aminopropyltrimethoxysilane to said curable composition. 24. A two-part curable foaming composition comprising: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen and which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (ii) water; wherein after mixing together the first and second parts a cured elastomeric foam is formed. 25. A two-part curable foaming composition which provides a lubricous surface comprising: (A) A first part comprising: (i) an alkoxysilyl capped prepolymer; and (ii) a polyhydrogen siloxane; (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; and (B) A second part comprising: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; provided that at least one of the parts contain a catalyst and a lubricant and wherein after mixing together the first and second parts a cured elastomeric foam is formed.
FIELD OF THE INVENTION The present invention relates to two-part curable foaming compositions which are particularly useful for sealing, adhesive applications, gap filling, noise reduction and vibration dampening. More particularly, the compositions of the present invention relate to elastomeric compositions which undergo condensation curing and which release hydrogen during the cure process to result in a cured elastomeric foam as an end product. BACKGROUND OF RELATED TECHNOLOGY Elastomeric foaming compositions have been developed for a variety of purposes. For example, the resiliency of elastomeric foamed compositions have advantages as noise and vibration dampening materials. Additionally, gaps can be filled by the expansion of the composition as it foams and eventually thermosets its shape during final cure. Additionally, foaming elastomeric compositions have been used in thermal insulation and electrical applications as well as flame resistant barrier applications. Many commercially available products are known and promoted for these purposes. For example, U.S. Pat. No. 4,808,634 discloses a curable foaming silicone composition containing a vinyl polysiloxane, a hydride polysiloxane, a hydroxyl source selected from organic alcohol or organic alcohol in combination with water or hydroxylated organosiloxane, from 1 to about 250 ppm of platinum catalyst and a ketoximine compound effective to lower the foam density. Foam is created through the reaction of the hydride polysiloxane with the hydroxy source to liberate hydrogen gas. The platinum catalyst is necessary for cure and the ketoximine is recited as a critical element in the composition for reducing the density of the resultant foam. U.S. Pat. No. 5,358,975 also relates to organosiloxane elastomeric foams. The '975 patent incorporates a triorganosiloxy end-blocked polydiorgano siloxane, an organohydrogen siloxane, a platinum catalyst, an a, β, ω-diol and a resinous copolymer containing siloxy vinyl groups. The combination of the specific diols and the resinous copolymer are recited as providing reduced density foams. Foaming is produced as a result of the reaction of the polyhydrogen siloxane and the alcohol which liberate hydrogen gas. Numerous patents disclose the addition of blowing agents to effectuate foams. For example, see U.S. Pat. Nos. 6,110,982 and 5,373,027. U.S. Pat. No. 6,207,730 B1 discloses an epoxy composition to which is added thermoplastic shell microspheres for inhibition of seepage of the epoxy through porous substrates. The microspheres may encapsulate a gas. U.S. Pat. No. 6,277,898 B1 discloses epoxy resins useful as photocurable paints which use chemical or mechanical expansion agents to create foams. U.S. Pat. No. 5,356,940 discloses a fine pored silicone foam which is formed by mixing a vinyl silicone, an organo-platinum catalyst, fumed silica, and water as a first part, with a second part which includes a silicone polymer having at least two double bonds per molecule, finned silica and polydimethylhydrogensiloxane. The two components are mixed and the reaction is subsequently pressurized, using air or nitrogen, so that the pressurized gas is present in the mixture in a dissolved form. Subsequently, the reaction mixture is heated and the dissolved gas is released, thereby forming a fine pored silicone foam. U.S. Pat. No. 5,900,430 discloses silicone foaming compositions which contain an organopolysiloxane containing a specified amount of an alkenyl group and/or a hydroxyl group, an organohydrogenpolysiloxane, a compound having an active hydrogen, such as an alcohol, a platinum catalyst and an acetylenic alcohol compound. Foaming occurs during the cure process by the reaction of the compound having an active hydrogen group, i.e., an alcohol, with the organohydrogenpolysiloxane compound to release hydrogen gas. U.S. Pat. No. 5,246,973 discloses a foamable silicone composition that evolves neither toxic gas or hydrogen. The foamable silicone composition comprises a thermosetting liquid silicone and 0.1 to 30 parts by weight of a thermally expansible hollow plastic micro particles. The thermosetting liquid silicone is a diorganopolysiloxane component containing alkenyl groups. An organopolysiloxane that contains at least two silicon-bonded hydrogen atoms in each polymer and a platinum metal catalyst are also included. The inclusion of the hollow plastic micro particle functions as a blowing or foaming agent that causes the composition to yield the foam. U.S. Pat. No. 5,061,736 discloses foamable silicone compositions useful as fire-resistant joint-sealing members. The compositions disclosed contain a diorganopolysiloxane, a finely divided reinforcing silica filler, a powder of a ferrite such as a divalent metallic element such as manganese, copper, nickel, from 10 to 70 parts by weight of a finely divided inorganic material, such as mica or glass powders, finely divided platinum metal, a curing agent for silicone rubbers such as a peroxide or condensation catalyst, and the blowing agent is a composition which produces a foaming gas when exposed to elevated temperature, such as nitrogen, carbon dioxide, azobisiobutyronitrile. The blowing agent is present in the range of about 1 to 10 parts by weight. U.S. Pat. No. 6,003,274 discloses a reinforcement web for a hollow structural member having layer of expandable foam dispersed on its principal surfaces. The foam is a resin-based material containing a blowing agent. U.S. Pat. Nos. 5,575,526 and 6,092,864 also disclose laminates which have support members or beams bonded together with a structural foam layer. A synthetic structural resin is combined with a cell-forming agent (blowing agent) and hollow microspheres to produce the structural foam layer. U.S. Pat. No. 6,218,442 B1 discloses a corrosion-resistant foam formulation which includes one or more thermosettable synthetic resins, one or more curatives, one or more blowing agents and one or more organic titanates or zirconates. The disclosed synthetic resins include epoxies. Notwithstanding the state of the art, there is a continued need for curable foaming compositions which do not require the addition of blowing agents for creation of the foam, but rather rely on the in situ formation of hydrogen gas which is liberated during the curing process. SUMMARY OF THE INVENTION The present invention produces curable foaming elastomeric compositions which produce an elastomeric foam in situ without the addition of blowing agents. The compositions of the present invention rely on the reaction of water and polyhydrogensiloxane crosslinking agent in the presence of a catalytic amount of one or more amines to react and liberate hydrogen gas which results in the formation of a closed celled foam as the composition undergoes condensation curing. In one aspect of the invention there is provided a two-part curable foaming composition including: (A) A first part including (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed. The reaction product of this composition provides the cured elastomeric foam. In another aspect of the invention there is provided an elastomeric foam which includes the reaction product of a first part including an alkoxysilyl capped prepolymer and a polyhydrogen siloxane; and a second part including a nitrogen-containing compound having an active hydrogen, water and a catalyst. In yet another aspect of the invention there is provided a moisture curable foaming composition which includes an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen for reaction with the polyhydrogen siloxane and which nitrogen-containing compound accelerates cross-linking of the alkoxysilyl groups, and water. In yet another aspect of the invention there is provided a sound and vibration dampening composition made from the aforementioned compositions. In yet another aspect of the invention there is provided a composite structure including first and second substrates and an elastomeric foam positioned therebetween. The elastomeric foam includes the reaction product of an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound haying an active hydrogen, water and a catalyst which accelerates both foam formation and cross-linking through the alkoxysilyl group. It is contemplated that the nitrogen containing compound having an active hydrogen may also be a compound which accelerates both the foam formation and cross-linking of the alkoxysilyl group, eliminating the need for a separate catalyst. Ordinarily, primary and secondary amines having an active hydrogen do not provide the combination of rapid cure and foam formation without additional catalyst. In yet another aspect of the invention there is provided a method of filling the gap between two substrate surfaces including providing a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and where upon mixing together the first and second parts a cured elastomeric foam is formed; and permitting the composition to form a cured foam therebetween. In yet another aspect of the invention there is provided a method of making a noise and vibration dampening seal between surfaces including the steps of introducing a composition between the surfaces which includes A two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed; and permitting the composition to form a cured foam. In yet another aspect of the invention there is provided a method of manufacturing a self-lubricating, foaming composition, including providing a curable composition including an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen for reaction with the polyhydrogen siloxane, a catalyst for accelerating foam formation and cross-linking through the alkoxysilyl group and water; providing to the curable composition a silicone/polyether surfactant; dispensing the composition onto a substrate surface; exposing the composition to conditions favorable to generating a cured foam; and permitting the surfactant to migrate to the surface to provide a lubricious surface. In a further aspect of the invention there is provided a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen and which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (ii) water; wherein after mixing together the first and second parts a cured elastomeric foam is formed. In a further aspect of the invention there is provided a two-part curable foaming composition which provides a lubricous surface including: a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; provided that at least one of the parts contain a catalyst and a lubricant and wherein after mixing together the first and second parts a cured elastomeric foam is formed. The compositions of the present invention are capable of room temperature cure desirably, temperatures greater than ambient are used to achieve more rapid cure times. DETAILED DESCRIPTION OF THE INVENTION The present invention provides for two-part curable foaming compositions which include a variety of thermosetting compositions as the structural component. The thermosetting resins are formed from polymer materials which may have a variety of different types of polymeric backbones and which are end-capped with alkoxysilyl-groups in order to undergo condensation curing. Desirably these materials are elastomeric in nature to provide the design and properties of vibration and sound dampening. In general, such alkoxysilyl end-capped thermosetting compositions include those described in U.S. Pat. No. 5,663,269, which is incorporated herein by reference. Generally, these materials are prepolymers which can be further reacted to form fully cured materials. In particular, such alkoxysilyl end-capped compositions include those of the formula: wherein: A may be a siloxy repeating group which may contain a heteroatom-containing group, such as a N, S or O containing group either as a linkage in the repeating siloxy group or as a group pendent to the siloxy group; an alkylene or alkylene oxide group, such as ethylene or propylene oxide; a polyester, polyester/urethane group; a polyether or polyether/urethane group; an epoxy group; or a copolymer of any of the above combinations and admixtures of these materials are also useful; R1, R2, R3 and R4 may be identical or different and are monovalent hydrocarbon radicals having up to 10 carbon atoms (C1-10) or halo or cyano substituted hydrocarbon radicals; R3 may also be OR4 or a monovalent heterohydrocarbon radical having up to 10 carbon atoms (C1-10) wherein the hetero atoms are selected from O, N and S; R4 may be alkyl(C1-10), preferably methyl, ethyl or isopropyl; R4 may also be CH2CH2OCH3; and n is an integer, desirably from 1 to 12,000. Particularly useful alkoxylsilyl end-capped prepolymers include those having the formula: wherein R is a hydrocarbon diradical which may include heteroatom groups; A is a C1-30 linear or branched, substituted or unsubstituted aliphatic group or an aromatic-containing group; R4 is methyl; R5 is a substituted or unsubstituted C1-24 alkyl or aryl group; R4 may also be the same as R5 provided A includes a carboxy, carbamate, carbonate, ureido or urethane group; R6 is an C1-24 alkyl, alkylene or aryl group, a (meth)arcryloxyalkyl group or R8 is C1-4 diradical hydrocarbon; R7 is an alkenyl group; R6 may also be R4O or R5O. Desirably, R is a polymer selected from the group consisting of polyesters, polyethers, polyolefins, polyurethanes, polysiloxanes, poly(meth)acrylates, polyepoxides and combinations thereof. The polyhydrogen siloxane useful in the present invention includes those having the formula: wherein at least two of R9, R10 and R11 are H; otherwise R9, R10 and R11 can be the same or different and can be a substituted or unsubstituted hydrocarbon radical from C1-20 such hydrocarbon radicals including those as previously defined for formula I above; thus the SiH group may be terminal, pendent or both; R12 can also be a substituted or unsubstituted hydrocarbon radical from C1-20 such hydrocarbon radicals including those as previously defined for formula I above, and desirably is an alkyl group such as methyl; x is an integer from 10 to 1,000; and y is an integer from 1 to 20. Desirably R groups which are not H are methyl. The polyhydrogen siloxane is desirably present in amounts sufficient to achieve the desired amount of crosslinking and generate a sufficient amount of foam. Desirably, amounts of about 0.1 to about 10% by weight of the composition are useful. The aforementioned alkoxysilyl end-capped prepolymeric materials and the polyhydrogen siloxane compound are generally combined as a first part, e.g., Part A, of the two-part curable foaming compositions. Desirably, the alkoxysilyl end-capped material is present in amounts of about 20 to about 80% by weight of the first part and about 10% to about 70% by weight of the total composition, i.e., the combined first (A) and second (B) parts. The second part (B) of the present invention includes a nitrogen-containing component, which has an active nitrogen present for reaction with the polyhydrogen siloxane and subsequent production and release of hydrogen gas. The release of hydrogen gas during cure results in the formation of a cured foam. Additionally, the second part includes water which is necessary to effectuate the condensation cure of the two-part composition. Desirably, either the first part or the second part, or both parts include a catalyst which accelerates the foam formation and cross-linking through the alkoxysilyl groups. The catalyst is generally a distinct component from the nitrogen-containing compound having an active hydrogen, although it is contemplated that a single compound may serve both for hydrogen donation, i.e., production of hydrogen gas, and for cross-linking through the alkoxysilyl groups. The nitrogen-containing component is generally a primary or secondary amine and may be chosen from a wide number of compounds. For example, suitable amines include, but are not limited to, primary amines represented by the formula R13NH2, secondary amines represented by the formula R132NH, and tertiary amines represented by the formula R133N, wherein each R13 is independently selected from the group consisting of alkyl, aryl, alkaryl, or aralkyl radicals, preferably, C1-10 alkyl, C6-10 aryl, C7-15 alkaryl, and C7-15 aralkyl radicals. Non-limiting examples of suitable amine co-activators include tri-n-butylamine, dimethyl-p-toluidine, dimethyl-o-toluidine, diethyl-p-toluidine, and di-2-hydroxyethyl-p-toluidine. Similarly, the nature of the primary or secondary amine is not critical for purposes of this invention, i.e., aliphatic or aromatic amines can be used. For example, primary aliphatic amines such as ethyl, n-butyl, n-propyl, iso-propyl, n-hexyl and t-butyl amines conveniently can be used. Also primary aromatic amines, such as aniline, p-toluidine, o- or p-naphthalamine, xylidene, benzylamine or p-benzylaniline can be used. While the primary amines are preferred amines for use in preparing the condensation products disclosed herein, aliphatic or aromatic secondary amines also can be used. Typically examples of acceptable secondary amines are diethylamine, dipropylamine, diisopropylamine, diphenylamine, N-phenyl benzylamine and N-allylaniline. Amine-aldehyde condensation products are also useful as the nitrogen-containing compound. Typical examples of aldehyde-amine condensation products which are useful in the invention disclosed herein are the following: formaldehyde-p-benzyl aniline; acetaldehyde-benzylamine; crotonaldehyde-butylamine; cinnamic aldehyde-aniline; cinnamic aldehyde-butylamine; 2-phenylpropionaldehyde-butylamine; butyraldehyde-butyl-amine; butyraldehydreaniline; hydrocinnamaldehyde-butylamine; naphthaldehyde-o-toluidine; and heptaldehyde-N-allylaniline. Additional useful amine compounds include dicyandiamide, diethylenetriamine, triethylenetetramine, diethylaminopropylamine, m-xylenediamine, diaminodiphenylamine, isophoronediamine, menthenediamine, polyamides, and combinations thereof. Useful aliphatic cycloaliphatic amines include 2,2′-dimethyl-4,4′-methylene-bis(cyclohexylamine) (Ancamine 2049). Useful aromatic amines include 4,4′-diaminodiphenyl sulfone (Ancamine S and Ancamine SP). A blend of aromatic and aliphatic amines (i.e., Ancamine 2038) is also useful. Dissociable amine salts are also useful. Various imidazoles are also useful as the nitrogen-containing compound in the present invention provided they have an active hydrogen. For example, useful compounds include, without limitation, 1-(2-cyanomethyl)-2-ethyl-α-4-methylimidazole and 2-phenyl-4,5-dihydroxymethyl imidazole; imidazole, isoimidazole, 2-methyl imidazole, 2-ethyl-4-methylimidazole, 2,4-dimethylimidazole, butylimidazole, 2-heptadecenyl-4-methylimidazole, 2-undecenylimidazole, 1-vinyl-2-methylimidazole, 2-n-heptadecylimidazole, 2-undecylimidazole, 2-heptadecylimidazole, 1-benzyl-2-methylimidazole, 1-propyl-2-methylimidazole, 1-cyanoethyl-2-methylimidazole, 1-cyanoethyl-1-cyanoethyl-2-undecylimidazole, 1-cyanoethyl-2-phenylimidazole, 1-guanaminoethyl-2-methylimidazole, addition products of an imidazole and trimellitic acid, addition products of an imidazole and 2-n-heptadecyl-4-methylimidazole, phenylimidazole, benzylimidazole, 2-methyl-4,5-diphenylimidazole, 2,3,5-triphenylimidazole, 2-styrylimidazole, 1-(dodecyl benzyl)-2-methylimidazole, 2-(2-hydroxyl-4-t-butylphenyl)-4,5-diphenylimidazole, 2-(2-methoxyphenyl)-4,5-diphenylimidazole, 2-(3-hydroxyphenyl)-4,5-diphenylimidazole, 2-(p-dimethylaminophenyl)-4,5-diphenylimidazole, 2-(2-hydroxyphenyl)-4,5-diphenylimidazole, di(4,5-diphenyl-2-imidazole)-benzene-1,4,2-naphthyl-4,5-diphenylimidazole, 1-benzyl-2-methylimidazole, 2-p-methoxystyrylimidazole, and combinations thereof. The nitrogen-containing component is generally present in amounts of about 0.1% to about 10% by weight of the second part (B) of the two-part composition and desirably in amounts of about 0.05% to about 2% by weight of the total composition (A+B). Water is present in amounts of about 0.1% to about 10% by weight of the second part (B) of the two-part composition and desirably in amounts of about 0.05% to about 5.0% by weight of the total composition (A+B). Due to the presence of water in the formulation, the CTV can be chosen and adjusted to a wide variety of depths. Whereas high CTV is often a difficult property to achieve in some condensation curing polymers, it is an advantage of the present inventon to be able to do so. The catalyst, which may be in either or both of the parts, is one which will accelerate both the formation of the film, i.e., the formation of hydrogen gas and also one which accelerates cross-linking through the alkoxysilyl groups. Desirably, the catalyst is present in the second part (B). Desirably the catalyst is one which is considered a strong Lewis base. The catalyst is preset in amounts of about 0.05 to about 3% by weight of the total composition. Examples of catalysts include 1,8-diazobicyclo(5,5,0)undec-7-ene, quinuclidine and 1,4-diazobicyclo(2,2,2)octane. A lubricous additive is also desirably incorporated into the composition. This additive provides a lubricous surface to the reaction product of the composition. Generally, the lubricous additive migrates to the surface of the composition during and/or after cure. Desirably, the additive is a liquid. A liquid which is partially soluble in the composition. More desirably, the additive is a surfactant which is compatible with the composition for providing a lubricous surface. The additive is optionally present in amounts of up to about 20% by weight of the total composition. The two-part curable foaming compositions of the present invention desirably include the following constituents: CONSTITUENT WEIGHT % Part A Alkoxysilyl Capped Prepolymer 20-80 Polyhydrogen Siloxane 0.1-0.5 Filler 25-60 Plasticizer 15-20 Lubricous Additive 0-20 Part B Active Hydrogen-Containing Amine 0.05-2.0 Compound Filler 50-80 Plasticizer 0-40 Water 0.1-10 Catalyst 0.05-3.0 Lubricous Additive 0-30 Other moisture cure catalysts may also be employed in the present invention. Such catalysts would ordinarily be present in Part B as opposed to Part A containing the reactive silicone prepolymer, for stability purposes. Nonlimiting examples of useful moisture cure catalysts include from about 0.1 to about 5% by weight and desirably about 0.25 to about 2.5% by weight of at least one compound of a metal which is typically selected from among titanium, tin, zirconium and mixtures thereof. Tetraisopropoxytitanate, tetrabutoxytitanate, dibutyltindilaurate and dibutyltindiacetate are specific examples. U.S. Pat. No. 4,111,890 lists numerous others that are useful. EXAMPLES The following compositions represented by Tables 1-11 were prepared in accordance with the present invention. Parts A and B were mixed together using a static mixer and heated at 100° C. A cured elastomeric foam resulted in approximately 10 minutes. The foaming occurred within seconds of the parts being mixed. Within 24 hours of cure, surface lubricity was present due to the lubricant present in the composition. Each of the compositions were cured on acrylic coated polycarbonate automotive parts. The cure-through-volume (CTV) of the compositions varied from about ⅛″ to ¼″ in thickness (depth). The tensile peel strength of each of the inventive compositions was tested. All test pieces exhibited 100% cohesive failure, which was the desired result. The substrate surface was fully covered by the composition subsequent to peel, showing excellent adhesion. Additionally, the compositions exhibited properties useful for sound and vibration dampening. Example 1 A two-part curable foaming composition of the present invention was prepared as set forth below. To form Part A, the trimethoxysilyl capped prepolymer component was mixed with the calcium carbonate filler until the liquid prepolymer fully wet the mixture. This mixture was then heated to 110° C. and a full vacuum was pulled on the mixture. The heating and vacuum was performed for one hour, sufficient time to dry the calcium carbonate. To the mixture was then added the remainder of Part A constituents, TINUVIN 327, TINUVIN 765, the polyether/silicone surfactant, and the polyhydrogensiloxane. The mixture was mixed for ten minutes and de-aerated. TABLE 1 CONSTITUENT Weight % In part A Tri-methoxysilyl capped polypropylene oxide 38.0 Niax L-1602 (Polyether/Silicone Copolymer 28.0 surfactant) Calcium Carbonate 31.6 Methyl Hydrogen Polysiloxane 1.2 (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.4 piperidinyl) sebacate (TINUVIN 765) 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.8 chlorobenzotriazole (TINUVIN 327) Part B was then added to Part A by first adding the plasticizers and fillers (butylbenzylthalate, calcium carbonate, and carbon black) until the liquid wet these components. Water and the nitrogen-containing curatives were then added and the entire mixture was mixed for twenty minutes. TABLE 2 CONSTITUENT Weight % In Part B Butyl Benzyl Phthalate 25.0 Calcium Carbonate 72.2 Carbon Black 0.6 Dibutylamine 0.6 Tap water 0.6 1,8,-Diazaobicyclo(5,4,0) 1.0 undec-7-ene The results of mixing components A and B together was a rapidly curing, foaming elastomeric material which exhibited excellent noise reduction, vibration dampening, and gap filling ability. Table 3 below is representative of the overall mixed composition, i.e., Parts A and B mixed together, of this composition. TABLE 3 CONSTITUENT Weight % Butyl Benzyl Phthalate 12.5 Niax Silicone L-1602 14.0 Calcium Carbonate 51.9 Trimethoxysilyl capped polypropylene oxide 19 Carbon Black 0.3 Methyl Hydrogen Polysiloxane 0.6 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.4 chlorobenzotriazole (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.2 piperidinyl) sebacate Dibutylamine 0.3 Water 0.3 1,8-Diazobicyclo(5,4,0) undec-7-ene 0.5 Example 2 TABLE 4 CONSTITUENT Weight % In part A Tri-methoxysilyl capped polypropylene oxide 60.0 Niax L-1602 (Polyether/Silicone Copolymer 16.0 surfactant) Calcium Carbonate 21.8 Methyl Hydrogen Polysiloxane 1.0 (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.4 piperidinyl) sebacate (TINUVIN 765) 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.8 chlorobenzotriazole (TINUVIN 327) Part B was then added to Part A by first adding the plasticizers and fillers (butylbenzylthalate, calcium carbonate, and carbon black) until the liquid wet these components. Water and the nitrogen-containing curatives were then added and the entire mixture was mixed for twenty minutes. TABLE 5 CONSTITUENT Weight % In Part B Butyl Benzyl Phthalate 18.0 Niax L-1602 8.0 (Polyether/Silicone Copolymer surfactant) Calcium Carbonate 71.8 Carbon Black 0.3 Dibutylamine 0.6 Tap water 0.6 1,8-Diazaobicyclo(5,4,0) 0.7 undec-7-ene After 10 minutes at 100° C. and 2 hours at room temperature, the foam was found to be uniform and have a Shore hardness of 30. The surface slowly became increasing lubricous and after 24 hours had excellent surface lubricity. Example 3 TABLE 6 CONSTITUENT Weight % In part A Tri-methoxysilyl capped polypropylene oxide 38.0 Niax L-1602 (Polyether/Silicone Copolymer 24.0 surfactant) Calcium Carbonate 35.8 Methyl Hydrogen Polysiloxane 1.0 (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.4 piperidinyl) sebacate (TINUVIN 765) 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.8 chlorobenzotriazole (TINUVIN 327) Part B was then added to Part A by first adding the plasticizers and fillers (butylbenzylthalate, calcium carbonate, and carbon black) until the liquid wet these components. Water and the nitrogen-containing curatives were then added and the entire mixture was mixed for twenty minutes. TABLE 7 CONSTITUENT Weight % In Part B Butyl Benzyl Phthalate 26.0 Calcium Carbonate 71.2 Carbon Black 0.6 Dibutylamine 0.6 Tap water 0.6 1,8-Diazaobicyclo(5,4,0) 1.0 undec-7-ene After 10 minutes at 100° C. and 2 hours at room temperature, the foam was found to be uniform and have a Shore hardness of 40. The surface slowly became increasing lubricous and after 24 hours had excellent surface lubricity. Example 4 TABLE 8 CONSTITUENT Weight % In part A Tri-methoxysilyl capped polypropylene oxide 38.0 Niax L-1602 (Polyether/Silicone Copolymer 15.0 surfactant) Calcium Carbonate 44.6 Methyl Hydrogen Polysiloxane 1.2 (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.4 piperidinyl) sebacate (TINUVIN 765) 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.8 chlorobenzotriazole (TINUVIN 327) Part B was then added to Part A by first adding the plasticizers and fillers (butylbenzylthalate, calcium carbonate, and carbon black) until the liquid wet these components. Water and the nitrogen-containing curatives were then added and the entire mixture was mixed for twenty minutes. TABLE 9 CONSTITUENT Weight % In Part B Butyl Benzyl Phthalate 10.0 Niax L-1602 15.0 (Polyether/Silicone Copolymer surfactant) Calcium Carbonate 72.0 Carbon Black 0.6 Dibutylamine 0.6 Tap water 0.6 1,8-Diazaobicyclo(5,4,0) 1.2 undec-7-ene After 10 minutes at 100° C. and 2 hours at room temperature, the foam was found to be uniform and have a Shore hardness of 55. The surface slowly became increasing lubricous and after 24 hours had excellent surface lubricity Example 5 TABLE 10 CONSTITUENT Weight % In part A Tri-methoxysilyl capped polypropylene oxide 38.0 Niax L-1602 (Polyether/Silicone Copolymer 18.0 surfactant) Calcium Carbonate 41.2 Methyl Hydrogen Polysiloxane 1.6 (Bis) and (Methyl)-(1,2,2,6,6-Pentamethyl-4- 0.4 piperidinyl) sebacate (TINUVIN 765) 2-(3,5-Di-(tert)-butyl-2hydroxyphenyl)-4- 0.8 chlorobenzotriazole (TINUVIN 327) Part B was then added to Part A by first adding the plasticizers and fillers (butylbenzylthalate, calcium carbonate, and carbon black) until the liquid wet these components. Water and the nitrogen-containing curatives were then added and the entire mixture was mixed for twenty minutes. TABLE 11 CONSTITUENT Weight % In Part B Niax L-1602 25.0 (Polyether/Silicone Copolymer surfactant) Calcium Carbonate 71.8 Carbon Black 0.6 Dibutylamine 0.6 Tap water 0.6 1,8-Diazaobicyclo(5,4,0) 1.4 undec-7-ene After 10 minutes at 100° C. and 2 hours at room temperature, the foam was found to be uniform and have a Shore hardness of 45. The surface slowly became increasing lubricous and after 24 hours had excellent surface lubricity
<SOH> BACKGROUND OF RELATED TECHNOLOGY <EOH>Elastomeric foaming compositions have been developed for a variety of purposes. For example, the resiliency of elastomeric foamed compositions have advantages as noise and vibration dampening materials. Additionally, gaps can be filled by the expansion of the composition as it foams and eventually thermosets its shape during final cure. Additionally, foaming elastomeric compositions have been used in thermal insulation and electrical applications as well as flame resistant barrier applications. Many commercially available products are known and promoted for these purposes. For example, U.S. Pat. No. 4,808,634 discloses a curable foaming silicone composition containing a vinyl polysiloxane, a hydride polysiloxane, a hydroxyl source selected from organic alcohol or organic alcohol in combination with water or hydroxylated organosiloxane, from 1 to about 250 ppm of platinum catalyst and a ketoximine compound effective to lower the foam density. Foam is created through the reaction of the hydride polysiloxane with the hydroxy source to liberate hydrogen gas. The platinum catalyst is necessary for cure and the ketoximine is recited as a critical element in the composition for reducing the density of the resultant foam. U.S. Pat. No. 5,358,975 also relates to organosiloxane elastomeric foams. The '975 patent incorporates a triorganosiloxy end-blocked polydiorgano siloxane, an organohydrogen siloxane, a platinum catalyst, an a, β, ω-diol and a resinous copolymer containing siloxy vinyl groups. The combination of the specific diols and the resinous copolymer are recited as providing reduced density foams. Foaming is produced as a result of the reaction of the polyhydrogen siloxane and the alcohol which liberate hydrogen gas. Numerous patents disclose the addition of blowing agents to effectuate foams. For example, see U.S. Pat. Nos. 6,110,982 and 5,373,027. U.S. Pat. No. 6,207,730 B1 discloses an epoxy composition to which is added thermoplastic shell microspheres for inhibition of seepage of the epoxy through porous substrates. The microspheres may encapsulate a gas. U.S. Pat. No. 6,277,898 B1 discloses epoxy resins useful as photocurable paints which use chemical or mechanical expansion agents to create foams. U.S. Pat. No. 5,356,940 discloses a fine pored silicone foam which is formed by mixing a vinyl silicone, an organo-platinum catalyst, fumed silica, and water as a first part, with a second part which includes a silicone polymer having at least two double bonds per molecule, finned silica and polydimethylhydrogensiloxane. The two components are mixed and the reaction is subsequently pressurized, using air or nitrogen, so that the pressurized gas is present in the mixture in a dissolved form. Subsequently, the reaction mixture is heated and the dissolved gas is released, thereby forming a fine pored silicone foam. U.S. Pat. No. 5,900,430 discloses silicone foaming compositions which contain an organopolysiloxane containing a specified amount of an alkenyl group and/or a hydroxyl group, an organohydrogenpolysiloxane, a compound having an active hydrogen, such as an alcohol, a platinum catalyst and an acetylenic alcohol compound. Foaming occurs during the cure process by the reaction of the compound having an active hydrogen group, i.e., an alcohol, with the organohydrogenpolysiloxane compound to release hydrogen gas. U.S. Pat. No. 5,246,973 discloses a foamable silicone composition that evolves neither toxic gas or hydrogen. The foamable silicone composition comprises a thermosetting liquid silicone and 0.1 to 30 parts by weight of a thermally expansible hollow plastic micro particles. The thermosetting liquid silicone is a diorganopolysiloxane component containing alkenyl groups. An organopolysiloxane that contains at least two silicon-bonded hydrogen atoms in each polymer and a platinum metal catalyst are also included. The inclusion of the hollow plastic micro particle functions as a blowing or foaming agent that causes the composition to yield the foam. U.S. Pat. No. 5,061,736 discloses foamable silicone compositions useful as fire-resistant joint-sealing members. The compositions disclosed contain a diorganopolysiloxane, a finely divided reinforcing silica filler, a powder of a ferrite such as a divalent metallic element such as manganese, copper, nickel, from 10 to 70 parts by weight of a finely divided inorganic material, such as mica or glass powders, finely divided platinum metal, a curing agent for silicone rubbers such as a peroxide or condensation catalyst, and the blowing agent is a composition which produces a foaming gas when exposed to elevated temperature, such as nitrogen, carbon dioxide, azobisiobutyronitrile. The blowing agent is present in the range of about 1 to 10 parts by weight. U.S. Pat. No. 6,003,274 discloses a reinforcement web for a hollow structural member having layer of expandable foam dispersed on its principal surfaces. The foam is a resin-based material containing a blowing agent. U.S. Pat. Nos. 5,575,526 and 6,092,864 also disclose laminates which have support members or beams bonded together with a structural foam layer. A synthetic structural resin is combined with a cell-forming agent (blowing agent) and hollow microspheres to produce the structural foam layer. U.S. Pat. No. 6,218,442 B1 discloses a corrosion-resistant foam formulation which includes one or more thermosettable synthetic resins, one or more curatives, one or more blowing agents and one or more organic titanates or zirconates. The disclosed synthetic resins include epoxies. Notwithstanding the state of the art, there is a continued need for curable foaming compositions which do not require the addition of blowing agents for creation of the foam, but rather rely on the in situ formation of hydrogen gas which is liberated during the curing process.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention produces curable foaming elastomeric compositions which produce an elastomeric foam in situ without the addition of blowing agents. The compositions of the present invention rely on the reaction of water and polyhydrogensiloxane crosslinking agent in the presence of a catalytic amount of one or more amines to react and liberate hydrogen gas which results in the formation of a closed celled foam as the composition undergoes condensation curing. In one aspect of the invention there is provided a two-part curable foaming composition including: (A) A first part including (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed. The reaction product of this composition provides the cured elastomeric foam. In another aspect of the invention there is provided an elastomeric foam which includes the reaction product of a first part including an alkoxysilyl capped prepolymer and a polyhydrogen siloxane; and a second part including a nitrogen-containing compound having an active hydrogen, water and a catalyst. In yet another aspect of the invention there is provided a moisture curable foaming composition which includes an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen for reaction with the polyhydrogen siloxane and which nitrogen-containing compound accelerates cross-linking of the alkoxysilyl groups, and water. In yet another aspect of the invention there is provided a sound and vibration dampening composition made from the aforementioned compositions. In yet another aspect of the invention there is provided a composite structure including first and second substrates and an elastomeric foam positioned therebetween. The elastomeric foam includes the reaction product of an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound haying an active hydrogen, water and a catalyst which accelerates both foam formation and cross-linking through the alkoxysilyl group. It is contemplated that the nitrogen containing compound having an active hydrogen may also be a compound which accelerates both the foam formation and cross-linking of the alkoxysilyl group, eliminating the need for a separate catalyst. Ordinarily, primary and secondary amines having an active hydrogen do not provide the combination of rapid cure and foam formation without additional catalyst. In yet another aspect of the invention there is provided a method of filling the gap between two substrate surfaces including providing a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and where upon mixing together the first and second parts a cured elastomeric foam is formed; and permitting the composition to form a cured foam therebetween. In yet another aspect of the invention there is provided a method of making a noise and vibration dampening seal between surfaces including the steps of introducing a composition between the surfaces which includes A two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; provided that at least one of the parts contain a catalyst and wherein after mixing together the first and second parts a cured elastomeric foam is formed; and permitting the composition to form a cured foam. In yet another aspect of the invention there is provided a method of manufacturing a self-lubricating, foaming composition, including providing a curable composition including an alkoxysilyl capped prepolymer, a polyhydrogen siloxane, a nitrogen-containing compound having an active hydrogen for reaction with the polyhydrogen siloxane, a catalyst for accelerating foam formation and cross-linking through the alkoxysilyl group and water; providing to the curable composition a silicone/polyether surfactant; dispensing the composition onto a substrate surface; exposing the composition to conditions favorable to generating a cured foam; and permitting the surfactant to migrate to the surface to provide a lubricious surface. In a further aspect of the invention there is provided a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen and which accelerates both foaming and cross-linking through said alkoxysilyl groups; and (ii) water; wherein after mixing together the first and second parts a cured elastomeric foam is formed. In a further aspect of the invention there is provided a two-part curable foaming composition which provides a lubricous surface including: a two-part curable foaming composition including: (A) a first part including: (i) an alkoxysilyl capped prepolymer; (ii) a polyhydrogen siloxane; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; and (B) a second part including: (i) a nitrogen-containing compound having an active hydrogen; (ii) water; and (iii) optionally a catalyst which accelerates both foaming and cross-linking through said alkoxysilyl groups; (iv) optionally, a lubricant; provided that at least one of the parts contain a catalyst and a lubricant and wherein after mixing together the first and second parts a cured elastomeric foam is formed. The compositions of the present invention are capable of room temperature cure desirably, temperatures greater than ambient are used to achieve more rapid cure times. detailed-description description="Detailed Description" end="lead"?
20050815
20100309
20060119
64723.0
C08G7700
0
ZEMEL, IRINA SOPJIA
CURABLE FOAM ELASTOMERIC COMPOSITIONS
UNDISCOUNTED
0
ACCEPTED
C08G
2,005
10,510,550
ACCEPTED
High integrity polyester strapping
Polyester strapping made from polyester and less than 3% by weight of a polyolefn additive exhibits improved resistance to longitudinal splitting when the strapping is later placed under tension in packaging reinforcement applications. The polyolefin improves the longitudinal split resistance of the strapping without facilitating unwanted longitudinal stretch of the polyester strapping when under tension. The polyolefin additive may be combined with other conventional additives, or may be used alone in order to minimize costs.
1. Strapping, comprising: more than 92% by weight polyester; and less than 8% by weight of additives comprising one or more polyolefins and optional additional additives; wherein the one or more polyolefins constitute less than 3% by weight of the strapping. 2. The strapping of claim 1, comprising: 97.2-99.8% by weight of the polyester; and 0.2-2.8% by weight of the one or more polyolefins. 3. The strapping of claim 1, comprising: 98.0-99.6% by weight of the polyester; and 0.4-2.0% by weight of the one or more polyolefins. 4. The strapping of claim 1, comprising: 98.5-99.5% by weight of the polyester; and 0.5-1.5% by weight of the one or more polyolefins. 5. The strapping of claim 1, wherein the polyester comprises polyethylene terephthalate. 6. The strapping of claim 1, wherein the polyester comprises polybutylene terephthalate. 7. The strapping of claim 1, wherein the polyester comprises polyethylene naphthalate. 8. The strapping of claim 1, wherein the polyester comprises polyethylene isophthalate. 9. The strapping of claim 1, wherein the polyester has an intrinsic viscosity of about 0.7-1.2 deciliters/gram. 10. The strapping of claim 1, wherein the polyolefin comprises linear low density polyethylene. 11. The strapping of claim 1, wherein the polyolefin comprises branched low density polyethylene. 12. The strapping of claim 1, wherein the polyolefin comprises high density polyethylene. 13. The strapping of claim 1, wherein the polyolefin comprises polypropylene. 14. The strapping of claim 1, wherein at least some of the polyolefin is chemically grafted with a polar monomer. 15. The strapping of claim 1, wherein the polyolefin is chemically unmodified. 16. The strapping of claim 1, wherein the additives comprise an elastomeric material. 17. The strapping material of claim 16, wherein the elastomeric material comprises a styrene block copolymer. 18. Strapping having a width of about 0.5-3 cm and a thickness of about 0.03-0.20 cm, consisting essentially of polyester and one or more polyolefins. 19. Strapping having a width of about 0.5-3 cm and a thickness of about 0.03-0.20 cm, comprising polyester and less than 3% by weight of one or more polyolefins. 20. The strapping of claim 19, uniaxially oriented in a longitudinal direction of the strapping. 21. The strapping of claim 19, having a width of about 1-2.5 cm and a thickness of about 0.05-0.15 cm. 22. The strapping of claim 19, having a width of about 1.25-2 cm and a thickness of about 0.08-0.10 cm. 23. The strapping of claim 19, wherein the polyolefin comprises linear low density polyethylene. 24. The strapping of claim 19, further comprising an elastomeric additive. 25. The strapping of claim 19, wherein the polyolefin comprises a chemically modified polyolefin. 26. Strapping which has been uniaxially oriented by stretching in a longitudinal direction, having a width of about 0.5-3 cm and a thickness of about 0.03-0.20 cm, comprising polyester and linear low density polyethylene. 27. The strapping material of claim 26, having a uniaxially oriented length which is about 3-7 times an initial, unstretched length. 28. The strapping material of claim 26, having a uniaxially oriented length which is about 4-6 times an initial, unstretched length.
FIELD OF THE INVENTION This invention relates to improved polyester strapping useful for binding pallets, bales, large boxes and the like. In particular, the invention relates to polyester strapping having improved resistance to splitting in the longitudinal direction, while under tension, and improved weldability. BACKGROUND OF THE INVENTION Strapping made of metal or high strength plastic has long been used to secure the packaging of heavy boxes, pallets loaded with bricks and other heavy objects, large textile bales, and other packaging applications which require high strength reinforcement. Common materials used for the strapping include metal, polyester and polypropylene. Metal strapping is quite strong, but is also relatively expensive. Polypropylene strapping is less expensive, but may stretch longitudinally and loosen when under high tension. Polyester strapping is less expensive than metal strapping, is very strong, and is not easily stretched. For this reason, polyester strapping is useful in a wide variety of reinforcing applications. Polyester strapping is commonly produced by forming continuous strips of polyester using a spinneret or other extrusion die, and molecularly orienting the strips in the longitudinal direction under conditions of heat and tension. The molecular orientation increases the strength of the strapping in the longitudinal direction. However, as the polyester molecules become more aligned in the longitudinal (machine) direction, they become less entangled in the lateral (transverse) direction. As a result, the increased strength of the strapping in the longitudinal direction resulting from the orientation, comes at the expense of reduced strength in the lateral direction. When the polyester strapping is pulled tight in the longitudinal direction during use, the resulting necking and bending stresses in the lateral direction may render the polyester strapping more susceptible to split in the longitudinal direction along a substantial length, ranging from a few centimeters to one meter or more. Various attempts have been made to reduce the longitudinal splitting of polyester strapping by adding elastomeric ingredients or subjecting the strap to specialized processing, for instance, as described in U.S. Pat. No. 6,210,769. To date, these attempts have not resulted in a practical, cost effective technology to reduce split. SUMMARY OF THE INVENTION The present invention is directed to polyester strapping which contains polyester and less than 3% by weight of a polyolefin additive selected from reactive or non-reactive linear low density polyethylene, branched low density polyethylene, high density polyethylene, polypropylene and combinations of the materials. The polyolefin can be used alone or in combination with other (e.g., conventional) additives, provided that the total additive concentration is less than 8% by weight, and the amount of polyester is more than 92% by weight of the polyester strapping. Some of the other suitable additives are listed below. The polyester strapping of the invention has been shown to exhibit increased resistance to longitudinal splitting. Because the polyolefin additive is used in amounts of less than 3% by weight, it does not significantly affect the high strength and low stretchability of the polyester strapping in the longitudinal direction. The present invention is also directed to a process for making polyester strapping according to the composition of the invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view of a process for making polyester strapping according to the invention. FIG. 2 is a schematic view of an extruder feed throat arrangement useful in the process of the invention. DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS The present invention is directed to polyester strapping having improved integrity, and a process for making it. The polyester strapping is composed primarily of a polyester. Desirably, the polyester is selected from polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polyethylene isophthalate, and copolymers and combinations thereof. Preferably, the polyester is polyethylene terephthalate. The polyester may have an intrinsic viscosity of about 0.7-1.2 measured using the Goodyear Solution IV test method. The test is equivalent to ASTM D-2857 for Dilute Solution Viscosity of Polymers. The polyester constitutes more than 92% by weight of the polyester strapping. The polyester desirably constitutes more than 94%, more desirably more than 97% by weight of the polyester strapping, for instance, from 97.2-99.8% by weight of the polyester strapping. For example, the polyester may constitute from 98.0-99.6% by weight of the polyester strapping, for instance from 98.5-99.5% by weight of the polyester strapping. The polyester strapping also includes a polyolefin additive selected from linear low density polyethylene, branched low density polyethylene, high density polyethylene, polypropylene, and combinations thereof. The polyolefin may be reactive or non-reactive. Polyolefins are generally non-reactive, but can be rendered reactive by chemical modification (grafting) with a polar monomer as described below. The term “low density polyethylene” refers to homopolymers of ethylene and copolymers of ethylene with up to 25% by weight of a C3 to C20 alpha-olefin comonomer, which have a density in the range of 0.860 to 0.935 grams/cm3. Desirably, the density is between 0.900-0.930 grams/cm3, preferably between 0.910-0.925 grams/cm3. The term “linear low density polyethylene” refers to low density polyethylene copolymers as described above, whose main polymer chain is essentially linear with not more than 5 long chain branches per 1000 ethylene units. Long chain branches are defined as including carbon chains having longer than 10 carbon units. Depending on the density of the linear low density polyethylene, the comonomer may constitute from 3-25% by weight of the polymer, with lower comonomer contents generally representing linear polymers at the higher end of the density range. Examples of preferred comonomers are butylene, hexene and octene. The linear low density polyethylene may have a melt index of about 0.5-12 grams/10 min, suitably about 1-3 grams/10 min, measured using ASTM D1238 at 190° C. with a load of 2.16 kg. The term “branched low density polyethylene” refers to low density polyethylene homopolymers and copolymers as described above, having more than 5 long chain branches per 1000 ethylene units. The branched low density polyethylene may have the same melt index ranges described for linear low density polyethylene. The term “high density polyethylene” refers to polyethylene homopolymers and ethylene-alpha olefin copolymers having densities in excess of 0.935 grams/cm3, typically about 0.945-0.960 grams/cm3. The high density polyethylene may have the same melt index ranges described for linear low density polyethylene. The term “polypropylene” includes propylene homopolymers and propylene-alpha olefin copolymers containing up to 7% by weight of a C2 or C4-C10 alpha-olefin comonomer. The term does not include propylene-ethylene rubbers or similar materials having higher comonomer contents. Polypropylenes typically have densities of about 0.875-0.900 grams/cm3. The polypropylene may have a melt flow rate of about 1-20 grams/10 min, suitably about 2-10 grams/10 min, measured using ASTM D1238 at a temperature of 230° C. and a load of 2.16 kg. The polyolefin additive constitutes less than 3% by weight of the polyester strapping, for instance, from 0.2-2.8% by weight of the polyester strapping. For example, the polyolefin additive may constitute from 0.4-2.0% by weight of the polyester strapping, for instance from 0.5-1.5% by weight of the polyester strapping. The preferred additive is linear low density polyethylene. Suitable linear low density polyethylenes include ESCORENE® 1001.32 and 1002.32 ethylene-alpha olefin copolymers sold by the Exxon-Mobil Chemical Co. These polymers have melt indices of 1.0 and 2.0 grams/10 min., respectively, densities of about 0.918 grams/cm3, a butene comonomer, and can be added in the amounts described above. In many applications, the polyolefin will perform quite well in reducing or eliminating longitudinal splitting of the polyester strapping. In order to minimize cost, it is desired to employ the polyolefin in an unmodified form, as the only additive to the polyester. However, it is also within the scope of the invention to maximize the longitudinal split resistance and improve the weldability of the strapping in some of the most difficult applications by a) chemically modifying some of the polyolefin additive to make it reactive with the polyester, and/or b) combining the polyolefin with one or more conventional additives. Chemical modification of the polyethylene may be accomplished by grafting the polyolefin with about 0.1-3.0% by weight, desirably about 1.0-2.0% by weight of a polar monomer, based on the weight of the polyolefin, to produce a chemically modified (i.e., grafted) polyolefin. The chemical modification may be accomplished using conventional techniques, with the aid of heat in an extruder or other high temperature reactor, or with the aid of a catalyst in a solution reactor. Suitable polar monomers include maleic anhydride, maleic acid, acrylic acid and the like. When a chemically modified polyolefin is employed, it is desirably mixed with unmodified polyolefin in an amount of about 5-50% by weight modified polyolefin and 50-95% by weight unmodified polyolefin, preferably about 10-25% by weight modified polyolefin and 75-90% by weight unmodified polyolefin. In this embodiment, because both of the additive components are polyolefins, the total amount of chemically modified and unmodified polyolefins should be within the ranges stated above based on the weight of the polyester strapping. For instance, the total amount of polyolefin additives is less than 3% by weight of the polyester strapping, suitably 0.2-2.8% by weight, for example 0.4-2.0% by weight, for instance 0.5-1.5% by weight. Commercially available chemically modified polyethylenes are sold by Mitsui Petrochemical Co. under the trade name ADMER®, by Mitsui Petrochemical Co. under the trade name TAFMER®, by E.I. DuPont DeNemours & Co. under the trade name CXA®, and by Uniroyal Co. under the trade name CROMPTON®. Commercially available chemically modified polypropylenes include maleic anhydride-grafted polypropylene sold by Mitsui Petrochemical Co. under the trade name ADMER®, by Uniroyal Co. under the trade name CROMPTON®, and by E.I. DuPont DeNemours & Co. under the trade names CXA® and FUSABOND®. Alternatively, the polyolefin additive may be combined with a conventional elastomeric material additive. Elastomeric additives include propylene-ethylene copolymer rubbers (containing 40-80% by weight propylene and 20-60% by weight ethylene), propylene-ethylene-diene elastomers, styrene-butadiene elastomers, styrene-ethylene-propylene elastomers, styrene-ethylene-butene-styrene elastomers, and the like. When the elastomeric additives are employed, the total amount of polyolefin and elastomer additives should constitute less than 8% by weight of the polyester strapping, suitably less than 6% by weight of the polyester strapping. The elastomeric material may be used in an amount needed to provide the polyester strapping with optimum longitudinal split resistance without unduly reducing the longitudinal stretching resistance of the polyester strapping. One suitable family of elastomeric additives includes styrene-(ethylene-butylene)-styrene, styrene-butudiene-styrene, styrene-(ethylene-propylene)-styrene, and styrene-isoprene-styrene block copolymers sold by Kraton Polymers LLC under the trade name KRATON®. Styrene-based elastomeric additives, which can suitably added at about 0.5-2.0% by weight of the polyester strapping, include polystyrene alone or combined with styrene-butadiene compounds, as well as styrene-butylene copolymers, high impact polystyrene (e.g. polystyrene combined with butadiene rubber), and combinations thereof. Examples include MC6800 high impact polystyrene from Chevron Phillips Chemical Co., Polystyrene 147F from BASF, STYROLUX and STYROFLEX styrene-butadiene block copolymers from BASF. In most instances, the total amount of polyolefin and other additives should not exceed 6% by weight of the polyester strapping, and the amount of polyolefin will be less than 3% by weight of the strapping. The polyester strapping of the invention may have a width of about 0.5 cm to 3.0 cm, desirably about 1 cm to about 2.5 cm, preferably about 1.25 cm to about 2.0 cm. The polyester strapping may have a thickness of about 0.03 cm to about 0.20 cm, desirably about 0.05 cm to about 0.15 cm, preferably about 0.08 cm to about 0.10 cm. The surface of the strapping may be plain and smooth, or may be embossed or printed with a suitable pattern or design. Depending on the end use application, each piece of strapping may have a length ranging from about 0.5 meter to 3 meters or more. The polyester strapping typically includes polyester molecules which have been oriented in the longitudinal direction of the strapping. Typically, the orientation is accomplished by heating a precursor strapping to a temperature which is above the softening point and below the melting point of the polyester, and stretching the precursor strapping to about 3-7 times its initial length, desirably to about 4-6 times its initial length. A suitable stretching temperature for polyethylene terephthalate is about 130-170° C., desirably about 140-160° C. FIG. 1 schematically illustrates a process 10 for preparing polyester strapping according to the invention. Referring to FIG. 1, an extruder feed throat system 12 is used to feed polyester pellets and pellets of the polyolefin additive into an extruder 14. The details of the feed throat system will be discussed below with respect to FIG. 2. The extruder 14 melts the polyester and low density polyethylene, and mixes them together. The temperature inside the extruder is typically set at about 260-290° C., desirably about 275° C. For optimal extrusion performance and product properties, the polyester should have an intrinsic viscosity at 285° C. of about 0.70-1.20 deciliters per gram, desirably 0.73-1.10 deciliters per gram, measured using conventional techniques indicated above. The polyolefin additive should have a melt index or melt flow rate within the ranges indicated above. Other additives, if used, may have a wide variety of melt index and melt flow rates, measured by conventional methods. The extruder 14 may be a single screw or twin screw extruder, configured for the melting, mixing and conveying of polyester. The extruder 14 conveys the polyester composition to a die 16, where the composition is extruded in the form of a strand 18, or a plurality of strands, into a water bath 20. In alternative embodiments, the die 16 maybe replaced with a plurality of dies, arranged in parallel, with each die 16 extruding one or more strands 18 into the water bath 20. The strand or strands 18 are typically rectangular in shape, corresponding to the shape of rectangular slot openings present in the face of the die. The water bath 20 is used to rapidly quench the strand, in order to minimize the crystallization of the polyester. After being quenched, each strand 18 enters and passes through a first roller assembly 22, an oven 24, and a second roller assembly 26, which are collectively used for longitudinally orienting the strand 18. The first roller assembly 22 includes a plurality of nip rollers 28, at least some of which are heated. The nip rollers 28 turn at a first surface velocity, with each roller turning in a direction which conveys the strand 18 forward. The strand 18 winds around and between the nip rollers 28, and is preheated before passing through the oven 24, and to the second roller assembly 26. The second roller assembly 26 includes a plurality of nip rollers 30, at least some of which are heated. The nip rollers 30 turn at a second surface velocity which is faster than the first surface velocity of the nip rollers 28, causing longitudinal orientation of each strand 18 through the oven 24 and between the second set of nip rollers 30. The first nip rollers 28, oven 24 and second nip rollers 30 are set to temperatures which facilitate heating and longitudinal orientation of each strand 18. Each strand 18 is typically longitudinally oriented by stretching to a length which is about 3-7 times its initial, unstretched length, desirably about 4-6 times its initial, unstretched length. Typically, about 80% of the stretching will take place in the oven 24, and about 20% of the stretching will take place in the second nip roller assembly 26. For instance, where it is desired to stretch a strand 18 to five times its initial length, the second nip rollers 30 will be set to turn at a second surface velocity which is five times as fast as the first surface velocity of the first nip rollers 28. The strand 18 will be stretched to about four times its initial, unstretched length in the oven 24, and slightly further, to about five times its initial, unstretched length, after leaving the oven 24. After leaving the second nip roller assembly 26, each strand 18 is subjected to an annealing process which includes a third nip roller assembly 32, a second oven 34, and a fourth nip roller assembly 36. The third nip roller assembly 32 includes a third set of nip rollers 38, at least some of which are heated, which turn at a third surface velocity which is desirably about the same as the second surface velocity of the second nip rollers 30. The fourth nip roller assembly 36 includes a fourth set of nip rollers 40, which may or may not be heated, and which turn at a fourth surface velocity that is slightly less than the third surface velocity of the third set of nip rollers 38. The fourth surface velocity may be about 90% to less than 100% of the third surface velocity, and can be about 95% of the third surface velocity. The third nip rollers 38, oven 34 and fourth nip rollers 40 are set to temperatures which facilitate slight longitudinal direction annealing (shrinkage) of each strand 18, for example to about 95% of its previously stretched length. The resulting polyester strapping, formed from the polyester and polyolefin additive, is cooled and wound for storage and subsequent use. The polyester strapping has improved longitudinal split resistance due to the presence of the polyolefin additive. Other processes may also be used to make the polyester strapping including, for instance, a sheet extrusion process. In a sheet extrusion process, the polyester and additive composition is formed into a sheet. The extruded sheet is molecularly oriented in the longitudinal (machine) direction and sometimes in the lateral (transverse) direction. The oriented sheet is then cut into strapping having the desired width. FIG. 2 illustrates one embodiment of an extruder feed throat arrangement 12 designed for extruder 14. The polyester pellets 48 are heated to about 175-180° C. and dried, and are fed to the feed throat using a metering device 50 at a predetermined rate. The polyolefin pellets 54 are fed from one side of the feed throat using a separate metering device 52. A bed 60 of polymer pellets is maintained at the bottom of the hopper 12, when extruder 14 is full. It is desirable to prevent the polyolefin pellets from melting and sticking to the side of the feed throat 12, which would prevent them from reaching the extruder 14. To accomplish this, a deflector plate 56 is positioned above the region where the polyolefin pellets enter the feed throat 12. The deflector plate 56 prevents the hot polyester pellets from directly contacting the polyolefin as it is being fed. Furthermore, the polyolefin pellets are fed into a jacketed channel 58 which can be continuously cooled using water or another cooling fluid. The jacketed channel 58 extends all the way to the extruder 14. The jacketed channel 58 prevents the polyolefin pellets from being heated to a softening or sticking temperature, and prevents the polyester pellets from contacting the polyolefin pellets, until after both polymers have entered the extruder 14. Alternatively, the polyolefin pellets may be added directly to the polyester stream at the feed throat, or melted and added directly to the extruder. While the embodiments of the invention described herein are presently preferred, various modifications and improvements can be made without departing from the spirit and scope of the invention. The scope of the invention is defined by the appended claims, and all changes that fall within the meaning and range of equivalents are intended to be embraced therein.
<SOH> BACKGROUND OF THE INVENTION <EOH>Strapping made of metal or high strength plastic has long been used to secure the packaging of heavy boxes, pallets loaded with bricks and other heavy objects, large textile bales, and other packaging applications which require high strength reinforcement. Common materials used for the strapping include metal, polyester and polypropylene. Metal strapping is quite strong, but is also relatively expensive. Polypropylene strapping is less expensive, but may stretch longitudinally and loosen when under high tension. Polyester strapping is less expensive than metal strapping, is very strong, and is not easily stretched. For this reason, polyester strapping is useful in a wide variety of reinforcing applications. Polyester strapping is commonly produced by forming continuous strips of polyester using a spinneret or other extrusion die, and molecularly orienting the strips in the longitudinal direction under conditions of heat and tension. The molecular orientation increases the strength of the strapping in the longitudinal direction. However, as the polyester molecules become more aligned in the longitudinal (machine) direction, they become less entangled in the lateral (transverse) direction. As a result, the increased strength of the strapping in the longitudinal direction resulting from the orientation, comes at the expense of reduced strength in the lateral direction. When the polyester strapping is pulled tight in the longitudinal direction during use, the resulting necking and bending stresses in the lateral direction may render the polyester strapping more susceptible to split in the longitudinal direction along a substantial length, ranging from a few centimeters to one meter or more. Various attempts have been made to reduce the longitudinal splitting of polyester strapping by adding elastomeric ingredients or subjecting the strap to specialized processing, for instance, as described in U.S. Pat. No. 6,210,769. To date, these attempts have not resulted in a practical, cost effective technology to reduce split.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to polyester strapping which contains polyester and less than 3% by weight of a polyolefin additive selected from reactive or non-reactive linear low density polyethylene, branched low density polyethylene, high density polyethylene, polypropylene and combinations of the materials. The polyolefin can be used alone or in combination with other (e.g., conventional) additives, provided that the total additive concentration is less than 8% by weight, and the amount of polyester is more than 92% by weight of the polyester strapping. Some of the other suitable additives are listed below. The polyester strapping of the invention has been shown to exhibit increased resistance to longitudinal splitting. Because the polyolefin additive is used in amounts of less than 3% by weight, it does not significantly affect the high strength and low stretchability of the polyester strapping in the longitudinal direction. The present invention is also directed to a process for making polyester strapping according to the composition of the invention.
20050609
20091201
20051027
93731.0
2
FERGUSON, LAWRENCE D
HIGH INTEGRITY POLYESTER STRAPPING
UNDISCOUNTED
0
ACCEPTED
2,005
10,510,651
ACCEPTED
Wireless enabled memory module
A wireless-enabled memory module provides host devices access to a memory via a standard memory expansion interface and further incorporates embedded processing capability and a wireless network capability. The wireless-enabled memory module can be used in any host device providing a compatible memory card controller and interface. Host devices so equipped become wireless-memory enabled devices and can provide memory access to any other remote device enabled for compatible wireless communications. It is thereby possible for a remote device to access the memory content of the memory module and cause transfers of either full-size or scaled versions of the content to the remote device through a first network, and optionally further transfer the content from the remote device through a second network to the Internet in the form of an e-mail message or MMS attachment.
1. A removable module for coupling to a digital host and a wireless network, the coupling to the host being via an expansion port of the host, the wireless network having at least one remote wireless device, the module comprising: a host-to-module interconnect for removable coupling with the host; a host-to-module interface controller coupled to the host-to-module interconnect; wireless transceiver circuitry for coupling with the wireless network; a memory controller; an embedded non-volatile memory coupled to the memory controller; and a control sub-system coupled to the host-to-module interface controller, the wireless transceiver circuitry, and the memory controller, the control sub-system managing the transfer of data between the embedded non-volatile memory and the wireless network. 2. A removable module for operative coupling to a digital host, a removable memory, and a wireless network, the coupling to the host being via an expansion port of the host, the wireless network having at least one remote wireless device, the module comprising: a host-to-module interconnect for removable coupling with the host; a host-to-module interface controller coupled to the host-to-module interconnect; wireless transceiver circuitry for coupling with the wireless network; a removable memory controller; a slot for receiving and coupling the removable memory to the removable memory controller; and a control sub-system coupled to the host-to-module interface controller, the wireless transceiver circuitry, and the removable memory controller, the control sub-system managing the transfer of data between the removable memory and the wireless network. 3. The removable module of claim 1, wherein the host-to-module interconnect and the host-to-module interface controller are implemented in accordance with the CompactFlash standard. 4. The removable module of claim 2, wherein the host-to-module interconnect and the host-to-module interface controller are implemented in accordance with the CompactFlash standard. 5. The removable module of claim 1, wherein the host-to-module interconnect and the host-to-module interface controller are implemented in accordance with the Secure Digital (SD) standard. 6. The removable module of claim 2, wherein the host-to-module interconnect and the host-to-module interface controller are implemented in accordance with the Secure Digital (SD) standard. 7. The removable module of claim 1, wherein the host-to-module interface controller, the memory controller, and the control sub-system are all on a single ASIC. 8. The removable module of claim 2, wherein the host-to-module interface controller, the removable memory controller, and the control sub-system are all on a single ASIC. 9. The removable module of claim 1, further including media scaling circuitry. 10. The removable module of claim 2, further including media scaling circuitry. 11. The removable module of claim 1, wherein the wireless transceiver circuitry is implemented in accordance with the BlueTooth standard. 12. The removable module of claim 2, wherein the wireless transceiver circuitry is implemented in accordance with the BlueTooth standard. 13. The removable module of claim 9, wherein the media scaling circuitry selectively produces a version of a requested portion of the embedded non-volatile memory content that is scaled to a selected one of a plurality of available scaling factors. 14. The removable module of claim 10, wherein the media scaling circuitry selectively produces a version of a requested portion of the removable memory content that is scaled to a selected one of a plurality of available scaling factors. 15. The removable module of claim 13, wherein the plurality of scaling factors includes a thumbnail scaling factor. 16. The removable module of claim 14, wherein the plurality of scaling factors includes a thumbnail scaling factor. 17. The removable module of claim 13, wherein the plurality of scaling factors includes at least a small and a large scaling factor. 18. The removable module of claim 14, wherein the plurality of scaling factors includes at least a small and a large scaling factor. 19. A method of transferring data, the method comprising: providing a host with an expansion port; coupling a removable module to the expansion port, the removable module having a host-to-module interconnect for removable coupling with the host, a host-to-module interface controller coupled to the host-to-module interconnect, a control sub-system coupled to the host-to-module interface controller, wireless transceiver circuitry coupled to the control sub-system, and a memory controller coupled to the control sub-system; coupling a non-volatile memory to the memory controller; providing a remote wireless-enabled device, the remote device having a user interface and being capable of communicating over a first wireless network to the removable module; accessing the non-volatile memory through the user interface of the remote device; and transferring selected data between the remote device and the non-volatile memory. 20. The method of claim 19, wherein the host is a digital camera. 21-85. (canceled)
SUMMARY A wireless-enabled memory module (WEMM) in accordance with the invention provides devices access to a memory via a standard memory interface and further incorporates embedded processing capability and a wireless network capability. This card can be used in any host device providing a compatible memory card controller and interface. Host devices equipped with a WEMM become wireless-memory enabled devices (WMED). WEMMs and WMEDs can communicate with any other remote device enabled for compatible wireless communications. Remote devices so enabled are referred to herein as Remote Wireless-enabled Devices (RWED). The wireless network capability and embedded processing of the WEMM provides RWEDs (such as a mobile phone, PDA, or PC) read and write access to the contents of the memory in the WEMM via a wireless connection, such as a BlueTooth connection in an illustrative embodiment. As an implementation option, the memory of the WEMM may be embedded, may be a removable flash memory card, or both. The RWED can use this wireless access provided by the WEMM to perform selective data transfers between the WEMM's memory and internal storage within the RWED. Additionally, by e-mail or MMS attachments sent via an additional network, the RWED may act as an intermediary to transfer data (in either direction) between the WEMM's memory and the Internet. For example, a BlueTooth-enabled mobile phone user could access a WEMM that is inserted in a digital camera host. The user could send a friend one or more photos as an e-mail message. The e-mail would result in the transfer of some or all of the stored images from the camera host over the BlueTooth connection to the remote mobile phone, and then to the Internet via the mobile phone network. Similarly, received attachments may be stored to the WEMM. As a further implementation option, the embedded processing on the WEMM may include a media-scaling engine that can scale the contents to different sizes before transmission over the wireless connection. This enables the user to browse the memory contents in thumbnail form quickly and easily from the remote device. It also permits the user to retrieve a version of the selected content that has been scaled appropriately for the bandwidth capabilities of the BlueTooth connection or mobile network. In a preferred embodiment, the media-scaling engine is implemented using signal processing hardware. However, some or all of its functionality may be also implemented via firmware in the processor sub-system. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a block diagram of a wireless-enabled memory module (WEMM) 1000, physically and electrically compatible with the Compact Flash expansion module standard, and in accordance with the present invention. FIG. 2 is a diagram of a system 2000, in accordance with the present invention, illustrating how data on a host device 2100 equipped with a WEMM 1000 may be transmitted over a variety of networks (including 2300, 2500, and 2700). FIG. 3 is a block diagram of a WED 3000, physically and electrically compatible with the Secure Digital expansion module standard, and in accordance with the present invention. FIGS. 4A and 4B depict further illustrative embodiments or the present invention, 4000 and 4300 respectively, in which power is supplied to the WEMM either from a customer Portable Server or from an onboard Power Source. DETAILED DESCRIPTION Table 1 identifies and expands the abbreviations used in FIG. 1. TABLE 1 Associated ID No. Abbreviation(s) Expanded Name 1000 W.E.M.M. Wireless Enabled Memory Module 1100 R.S.D.F.M. Removable Secure Digital Flash Memory 1200 E.F.M. Embedded Flash Memory 1300 M.S.E. Media Scaling Engine 1400 F.M.C. Flash Memory Controller 1500 B.R. Bluetooth Radio 1600 P.S.S. Processor Sub-System 1610 C.P.U. Processor 1620 W.RAM Working RAM 1630 FW Firmware 1635 W.S. Web Server 1700 C.F.I.C CompactFlash Interface Controller 1800 C.F.E.C. CompactFlash Expansion Connector In the illustrative embodiment of FIG. 1, the WEMM 1000 and interface (1700, 1710, and 1800) to the host are compatible with the Compact Flash industry standard. The WEMM's memory includes both embedded flash memory 1200 and removable flash memory 1100 compatible with the Secure Digital (SD) industry standard. The wireless network is a Wireless Personal Area Network (WPAN) compatible with the Bluetooth industry standard. As will be appreciated by those skilled in the art, the specifics of each implementation will dictate the particular requirements of the wireless interface. In an illustrative embodiment intended primarily for use with mobile phones, a low-speed, low-cost, Bluetooth interface 1500 is used. In another illustrative embodiment intended primarily for use with computing devices, such as PCs, a higher-speed, higher-cost, Bluetooth interface is used. The higher speed interface will reduce the time required to transfer a given file and will make the transfer of larger multimedia objects (e.g. higher resolution images and higher quality music) more practical. It will be appreciated by those skilled in the art that the baseband functions of the radio may be stored in the WEMM's integral firmware and performed via the WEMM's integral processor. Note that the WEMM 1000 constitutes a first-level removable module and the removable flash memory 1100 constitutes a second-level removable module. It will be appreciated by those skilled in the art that there are a number of choices for each of these miniature-form-factor standard interfaces. Thus the WEMM 1000 is not restricted to the CF standard, and the removable flash memory 1100 is not restricted to the SD standard. A first system application of the WEMM is the wireless transfer of digital photos between a camera and a mobile phone, for associated transfer via the mobile phone network. There is a large installed base of digital cameras that use standard removable memory cards, but do not have I/O expandability or wireless network functionality. These cameras can be augmented with a wireless-enabled memory module, in accordance with the present invention, to send photos via a mobile phone or any other compatibly enabled wireless communications device. Table 2 identifies and expands the abbreviations used in FIG. 2. TABLE 2 Associated ID No. Abbreviation(s) Expanded Name 2000 (none) (none) 2100 W.M.E.D. (H.D.) Wireless Memory Enabled Device (Host Device) 2200 R.W.E.D. (WX1AN/ Remote Wireless Enabled Device WX2AN D.R.D.) (WX1AN/WX2AN Dual Remote Device) 2300 WX1AN W.L. WX1AN Link 2400 WX2AN W.L. WX2AN Link 2500 WX2AN SYS WX2AN System 2600 G.W. Gateway 2700 INET Internet A general application for the invention is the illustrative system 2000 of FIG. 2. FIG. 2 illustrates a host device having no native integral wireless capability (such as a camera or a portable audio device) into which a WEMM 1000 is inserted. The resulting combination being a WMED 2100 as previously defined. A WMED communicates with an RWED (e.g. mobile phone) having at least one wireless interface. In FIG. 2, the WMED 2100 communicates with the RWED 2200 over a WX1AN 2300 (a wireless area network of a first type), such as the BlueTooth Wireless Personal Area Network (WPAN) standard. To illustrate a more general system, the RWED 2200 of FIG. 2 is a Dual WX1AN/WX2AN device (i.e., it has two wireless interfaces), such as a mobile phone or wireless-enabled PDA. In many applications, the WMED 2100 and its associated user interface will be unaware of the capabilities of the WEMM 1000 and offer no means to control it. In an illustrative embodiment, the WX1AN 2300 connection enables the RWED 2200 to access the content within the memory of the WEMM 1000 through a browser-server relationship. The server functionality 1635, which has an associated implementation of the WAP-over-BlueTooth protocol, is stored in the WEMM's integral firmware 1630 and is performed via the WEMM's integral processor 1610. (WAP is the Wireless Application Protocol.) Thus the user interface to the WEMM 1000 is accomplished via an embedded WAP/Web server 1635 within the WEMM 1000 communicating with a WAP browser on the RWED 2200. The RWED browser-based interface allows the user to: Browse the contents of the memory (as discussed below, either/both of 1100 or/and 1200) in the WEMM, viewing thumbnail size versions created by an embedded media scaling engine 1300; Send a multimedia object (e.g., a photograph), optionally scaled to one of a number of sizes via the scaling engine, as an MMS (Multimedia Message Service, a multimedia extension of SMS) or email attachment via a cell phone; and Load a received attachment into the WEMM for storage or for use (e.g., viewing on a camera). In an alternate embodiment, the user interface makes use of the knowledge of the memory controller of the last file written to allow short cuts, such as “send the last photograph taken”. In an alternate embodiment, the remote device implements a custom user interface created with the SmartPhone2002 or J2ME Java engines instead of the generic WAP browser. The Dual WX1AN/WX2AN RWED 2200 is in turn connected to a WX2AN system 2500 (a wireless area network of a second type), such as the GSM Wireless Wide Area Network (WWAN) standard, which in turn connects through a Gateway 2600 to the Internet 2700. The RWED 2200 can then retrieve content from the memory (either/both of 1100 or/and 1200) in the WEMM 1000 via the WX1AN 2300 and send it (for example in e-mail or MMS form) via the WX2AN 2500 through a Gateway 2600 to the Internet 2700. To accommodate the lower-speed interfaces that may be employed, either between the WEMM 1000 and the remote device 2200, or between the remote device 2200 and its WXAN 2500, the WEMM additionally includes processing functionality to scale the size of an individual media item that is sent to the remote device. When the user wishes to browse the content of the memory in the WEMM from the remote device, the WEMM 1000 would send “thumbnail” scaled versions through the BlueTooth connection 2300, for quick browsing. When a media item is selected, it can be sent to the remote device 2200 in one of a number of larger scaling levels, depending on the wireless bandwidths involved. In an illustrative embodiment using a low-speed Bluetooth interface, camera owners will be able to send postcard versions of snapshots via a mobile phone, using cameras that do not have integral wireless network capability. The invention thus will enable and expand the market for sending and receiving snapshots over wireless networks. In an illustrative embodiment using a high-speed Bluetooth interface, large high-resolution files may be transferred between a camera equipped with the wireless-enabled memory module and a PC. The invention thus will enable and expand the market for PC-based digital photography, including storage, backup, and archiving of digital photographs. Other system applications of the wireless-enabled memory module enable other devices to communicate via a mobile phone or to computing devices such as PCs. An example is transfer of MP3 files between an MP3 player and a mobile phone, for associated transfer via the mobile phone network, by equipping the MP3 player with a wireless-enabled memory module having a low-speed Bluetooth implementation. Another example is transfer of large music files between an audio device (e.g. a home entertainment system) and a PC, by equipping the audio device with a wireless-enabled memory module having a high-speed Bluetooth implementation. As an implementation option, the memory capability of the WEMM 1000 is implemented using an embedded fixed size memory 1200, a removable memory 1100 (for example a removable SD memory device), or both. In an illustrative embodiment, the removable memory is a second-level module and the wireless-enabled memory module is a first-level module, such as those disclosed by U.S. Pat. No. 6,353,870, CLOSED CASE REMOVABLE EXPANSION CARD HAVING INTERCONNECT AND ADAPTER CIRCUITRY FOR BOTH I/O AND REMOVEABLE MEMORY. Table 3 identifies and expands the abbreviations used in FIG. 3. TABLE 3 Associated ID No. Abbreviation(s) Expanded Name 1200 E.F.M. Embedded Flash Memory 1300 M.S.E. Media Scaling Engine 1400 F.M.C. Flash Memory Controller 1500 B.R. Bluetooth Radio 1600 P.S.S. Processor Sub-System 1610 C.P.U. Processor 1620 W.RAM Working RAM 1630 FW Firmware 1635 W.S. Web Server 3000 W.E.M.M. Wireless Enabled Memory Module 3100 CNTLIO Control & I/O ASIC 3110 S.D.I.C. Secure Digital Interface Controller 3200 S.D.E.C. Secure Digital expansion connector An alternative embodiment is shown in FIG. 3, a block diagram of a WEMM 3000 according to the invention as implemented in an SD form factor. A custom ASIC 3100, as shown, could be optionally implemented, including e.g., the microprocessor 1600, memory interface 3110, media scaling engine 1300 and memory controller 1400 all on one chip. In an illustrative embodiment, the WEMM 3000 processing capability includes the ability to rescale the media objects, including JPEG images and MP3 audio stored in the modules memory on the fly. This allows the WAP/Web interface to provide thumbnail images and highly compressed audio versions of the contents of the WEMM 3000 and to rescale media objects, including photos and audio recordings, to an appropriate size and quality for transmission over the wireless network. Media objects (images and audio) are sent as an email message either via the phone's built in email capability or using an embedded SMTP/PPP stack over the phone's IP network connection (e.g. GPRS). In another embodiment, the images may be sent as an MMS message. Two alternative embodiments, illustrated in FIGS. 4A and 4B, show how a WEMM (4200 in FIG. 4A, 4300 in FIG. 4B) can be used separately from the host device, when the host device does not require access to the memory. FIG. 4A shows an embodiment of a combination 4000 in which a special “holder” 4100 containing a power source 4110 is used in place of the full-function host, acting as a portable storage server and providing power to the WEMM 4200. Alternatively, FIG. 4B illustrates an embodiment in which a WEMM 4300 itself incorporates a power source 4360. Table 4 identifies and expands the abbreviations used in FIGS. 4A and 4B. TABLE 4 Associated ID No. Abbreviation(s) Expanded Name 4000 (none) (none) 4100 P.S. Portable Server 4110 WEMM PWR Wireless Enabled Memory Module Power Source 4200 W.E.M.M. Wireless Enabled Memory Module 4220 B.R. Bluetooth Radio 4230 F.K. F-key(s) 4240 E.F.M. Embedded Flash Memory 4250 CTLIO Control & I/O ASIC 4300 W.E.M.M. Wireless Enabled Memory Module 4320 B.R. Bluetooth Radio 4330 F.K. F-key(s) 4340 E.F.M. Embedded Flash Memory 4350 CTLIO Control & I/O ASIC 4360 PWR Power Source FIGS. 4A and 4B also illustrate that the WEMM has at least one Function-key (F-key, i.e. a button with an associated configurable function). The F-key(s) are identified as 4230 in FIG. 4A and as 4330 in FIG. 4B. Example key functions include (a) e-mailing the last-taken photo to a pre-configured address, and (b) transferring the last-taken photo to the mobile phone in preparation for manual addressing and sending. CONCLUSION Although the present invention has been described using particular illustrative embodiments, it will be understood that many variations in construction, arrangement and use are possible consistent with the teachings and within the scope of the invention. Functionally equivalent techniques known to those skilled in the art may be employed instead of those illustrated to implement various components or sub-systems. It is also understood that many design functional aspects may be carried out in either hardware (i.e., generally dedicated circuitry) or software (i.e., via some manner of programmed controller or processor), as a function of implementation dependent design constraints and the technology trends of faster processing (which facilitates migration of functions previously in hardware into software) and higher integration density (which facilitates migration of functions previously in software into hardware). All such variations in design comprise insubstantial changes over the teachings conveyed by the illustrative embodiments. The names given to interconnect and logic are illustrative, and should not be construed as limiting the invention. It is also understood that the invention has broad applicability to other applications, and is not limited to the particular application or industry of the illustrated embodiments. The present invention is thus to be construed as including all possible modifications and variations encompassed within the scope of the appended claims.
<SOH> SUMMARY <EOH>A wireless-enabled memory module (WEMM) in accordance with the invention provides devices access to a memory via a standard memory interface and further incorporates embedded processing capability and a wireless network capability. This card can be used in any host device providing a compatible memory card controller and interface. Host devices equipped with a WEMM become wireless-memory enabled devices (WMED). WEMMs and WMEDs can communicate with any other remote device enabled for compatible wireless communications. Remote devices so enabled are referred to herein as Remote Wireless-enabled Devices (RWED). The wireless network capability and embedded processing of the WEMM provides RWEDs (such as a mobile phone, PDA, or PC) read and write access to the contents of the memory in the WEMM via a wireless connection, such as a BlueTooth connection in an illustrative embodiment. As an implementation option, the memory of the WEMM may be embedded, may be a removable flash memory card, or both. The RWED can use this wireless access provided by the WEMM to perform selective data transfers between the WEMM's memory and internal storage within the RWED. Additionally, by e-mail or MMS attachments sent via an additional network, the RWED may act as an intermediary to transfer data (in either direction) between the WEMM's memory and the Internet. For example, a BlueTooth-enabled mobile phone user could access a WEMM that is inserted in a digital camera host. The user could send a friend one or more photos as an e-mail message. The e-mail would result in the transfer of some or all of the stored images from the camera host over the BlueTooth connection to the remote mobile phone, and then to the Internet via the mobile phone network. Similarly, received attachments may be stored to the WEMM. As a further implementation option, the embedded processing on the WEMM may include a media-scaling engine that can scale the contents to different sizes before transmission over the wireless connection. This enables the user to browse the memory contents in thumbnail form quickly and easily from the remote device. It also permits the user to retrieve a version of the selected content that has been scaled appropriately for the bandwidth capabilities of the BlueTooth connection or mobile network. In a preferred embodiment, the media-scaling engine is implemented using signal processing hardware. However, some or all of its functionality may be also implemented via firmware in the processor sub-system.
20041008
20081021
20060316
64682.0
H04J308
1
ZEWDU, MELESS NMN
WIRELESS ENABLED MEMORY MODULE
SMALL
0
ACCEPTED
H04J
2,004
10,510,693
ACCEPTED
Electric driven tool device
The invention relates to an electric driven tool device, especially an electric hand-held tool device, comprising an asynchronous electric motor (2) or a brush-less synchronous electric motor and a computer-controlled motor control device (8). The invention is characterized by a frequency converter (4) which can be controlled by the motor control device, whereby a motor (drive) voltage can be applied to the motor (2), and with a current detector (10) which co-operates with the motor control device (8) and detects the motor current. The motor control device (8) is embodied in such a manner that, in a first phase of the motor operation, the frequency of the motor current is maintained in a constant manner up to a limiting current I(grenz) and, in a second phase of the motor operation, at loads above the load at which the motor current reaches the limiting current I(grenz), the frequency of the motor current is lowered in such a manner that the motor current is maintained at a constant value.
1-18. (canceled) 19. An electric tool device, the device comprising: an electromotor, said electromotor being one of asynchronous or brush-less synchronous; a motor control means, said motor control means having computer control; a frequency converter which can be controlled by said motor control means for applying a drive voltage to said motor; and a current detector which detects a motor current and which communicates with said motor control means, wherein said motor control means is designed such that, in a first phase of motor operation at motor currents of up to a limit current I(limit), the voltage applied to said motor and the frequency of the motor current are kept constant and, in a second phase of motor operation at loads above that load at which the motor current reaches the limit current I(limit), the voltage applied to said motor is kept constant and the frequency of the motor current is reduced to such an extent that the motor current is kept at a constant value. 20. The electric tool device of claim 19, wherein the device is a manual electric tool device. 21. The electric tool device of claim 19, wherein said motor control means is designed such that the motor current is kept at the constant value I(limit) during the second phase. 22. The electric tool device of claim 19, wherein said motor control means is designed such that the voltage applied to said motor is kept at a same value during the first and second phases. 23. The electric tool device of claim 19, wherein said current detector comprises a shunt resistance. 24. The electric tool device of claim 19, further comprising a housing in which said frequency converter and said motor control means are disposed. 25. The electric tool device of claim 19, wherein said limit current I(limit) is selected between 4A and 20A. 26. The electric tool device of claim 15, wherein said limit current I(limit) is selected between 10A and 15A. 27. The electric tool device of claim 19, wherein said frequency converter and said motor control means are formed on a common plate or are disposed in a closed electronic housing. 28. The electric tool device of claim 19, wherein said motor control means is designed such that, during a third phase of motor operation in which the motor current cannot be kept constant merely by reducing the frequency of the motor current, the motor voltage is also lowered. 29. The electric tool device of claim 28, wherein said motor control means is designed such that, when a motor voltage U(limit) has been reached during the third phase, said motor is switched off. 30. The electric tool device of claim 28, wherein said motor control means is designed such that, when a motor voltage U(limit) has been reached during the third phase, instead of switching off said motor, a residual excitation is applied to said motor to ensure that said motor automatically starts again after elimination of the load. 31. A method for operating an electric tool device or a manual electric tool device, the device comprising an asynchronous electromotor or a brush-less synchronous electromotor and with a computer-controlled motor control means, the method comprising the steps of: a) during a first phase of motor operation under low load at motor currents up to a limit current I(limit), a voltage applied to the motor and a frequency of motor current is kept constant; and b) during a second phase of motor operation at loads above that load at which the motor current reaches the limit current I(limit), the voltage applied to the motor is kept constant and the frequency of the motor current is reduced such that the motor current is kept at a constant value. 32. The method of claim 31, wherein the motor current is kept at the constant value I(limit) during the second phase. 33. The method of claim 31, wherein the voltage applied to the motor is kept at a constant value during the second phase. 34. The method of claim 31, wherein the voltage applied to the motor is kept constant during the first and second phases. 35. The method of claim 34, wherein the motor voltage is kept at a same value during the first and second phases. 36. The method of claim 31, wherein the limit current I(limit) is selected between 10A and 20A. 37. The method of claim 36, wherein the limit current is between 10A and 15A. 38. The method of claim 31, wherein, during a third phase of motor operation in which the motor current cannot be kept constant merely by reducing the frequency of the motor current, the motor voltage is also reduced in response to further increasing load. 39. The method of claim 38, wherein, when a motor voltage U(limit) has been reached during the third phase, the motor is switched off. 40. The method of claim 38, wherein, when a motor voltage U(limit) has been reached during the third phase, instead of switching off the motor, a residual excitation is applied to the motor to ensure that the motor automatically starts again after elimination of the load.
The invention concerns an electric driven tool device, in particular, a manual electric tool device, comprising an asynchronous electromotor or a brush-less synchronous electromotor, and a computer-controlled motor control means, i.e. with an, in particular, microprocessor-controlled control electronics. Manual electric driven tool devices are mainly driven by electromotors having a current converter or commutator with carbon brushes. In particular, so-called universal motors are used. Carbon brushes are subject to constant wear and must be replaced after some time. Commutator motors of this type have almost linear performance characteristics up to a certain load. At higher loads, the motor rotational speed decreases and the motor current increases. There are also manual electric tool devices having a controlled commutator motor. The motor rotational speed is thereby kept constant with increasing load mostly via phase section control, such as e.g. in the electric tool device distributed by the applicant under the trade name “Vario-Constamatik”. If the load of the motor exceeds a certain value, control via the control electronics is not possible, inevitably producing uncontrolled motor characteristics. In so-called semi-stationary electric tool devices, such as e.g. circular saw benches, reciprocating table type planers, strip straightening machines etc. an asynchronous electromotor or a synchronous electromotor are conventionally used which are operated at the constant frequency of the motor drive voltage. The frequency used is, in particular, the mains frequency, in Europe 50 Hertz and in the U.S.A. 60 Hertz. DE 298 09 768 U1 discloses a semi-stationary electric tool device in the form of a circular saw bench, comprising an asynchronous electromotor or a synchronous electromotor, which is operated at a higher, constant frequency of 300 to 400 Hertz compared to the mains frequency by using a frequency converter. The rotational speed of the motor is therefore correspondingly higher and a downstream reducing gear is disposed in the drive motor. DE 198 16 684 A1 discloses a manual electric tool device comprising an electromotor without carbon brushes. The device unit contains the drive motor and the electric components of the electromotor control, which are directly required for control thereof and has a separate external current supply unit. It is the underlying purpose of the invention to produce an electric tool device which has linear performance characteristics similar to those of a commutator motor comprising carbon brushes but without the need for a commutator carbon brush system, which is susceptible to wear. The motor control device should function without expensive sensors, such as e.g. tachometer sensors or Hall sensors. This object is achieved in a manual electric tool device of the above-mentioned type, which is characterized by a frequency converter, which can be controlled by the motor control means for applying a motor (drive) voltage to the motor, and with a current detector which detects the motor current and cooperates with the motor control device, wherein the motor control means is designed such that in a first phase of motor operation at motor currents up to a limit current I(limit), the frequency of the motor current is kept constant and in a second phase of motor operation at loads above that load at which the motor current reaches the limit current I(limit), the frequency of the motor current is reduced such that the motor current is kept at a constant value. The above-mentioned term “limit current” I(limit) designates a drive current strength below the tilting point, i.e. below that current strength at which the electromotor stops. The limit current is preferably selected to be 5 to 15% less than the tilting point current. For powerful electromotors, the limit current I(limit) may be between 15 and 20 A and for weak electromotors 4-8 A. The drive motor is operated at a constant frequency F up to a certain load which corresponds to the limit current I(limit). This produces an almost horizontal motor characteristic dependence if the motor rotational speed N is plotted in dependence on the load or the torque M produced by the motor. As the load increases, i.e. the torque M increases and the motor rotational speed N decreases only slightly due to the so-called slip of the electromotor. This first operating region corresponds, in principle, to the normal characteristic dependence of an uncontrolled synchronous or asynchronous electromotor at loads at sufficient separation from the so-called tilting point. On the other hand, this region of the characteristic dependence also corresponds approximately to the characteristic dependence of a universal motor (series-characteristic motor) having a commutator carbon brush system and regulated via phase section control. If the load or the torque exerted by the electromotor corresponds to a certain value I(limit) of the motor current, the drive motor is operated using the motor control means with a variable frequency such that the motor current I remains constant. The term motor current mentioned above designates the motor drive current which flows through the stator windings of the motor. In this second load region, a certain value of the motor current I is controlled by changing the frequency. In a preferred further development of the electric tool device, the motor control means is designed such that the motor current is kept at the constant value I(limit) during this second phase. In a further preferred embodiment of the invention, the motor control means is designed such that the voltage applied to the motor (motor drive voltage) is also kept at a constant value during this second phase. The motor control means is preferably designed such that the voltage applied to the motor is kept at a constant, in particular, same value during the first and second phases. To perform the above-mentioned control process, it has proven to be advantageous if the current detector comprises a shunt resistance which can preferably be used directly via a voltage tap as a current measuring means. It has also proven to be advantageous, in dependence on the design of the required motor performance, if the value of the limit current I(limit) is selected to be between 4 and 20 amperes, in particular between 10 and 15 amperes. It is also suitable if the frequency converter, the motor control means, and the current detector which detects the motor current are designed on a common plate and/or disposed in a closed electronic housing and can be built in the form of one single construction unit. In a further particularly important embodiment of the invention, the motor control means is designed such that, during a third motor operation phase in which the motor current can no longer be kept constant merely by reducing the motor current frequency with further increasing load, the motor voltage is also reduced. If the above-described motor control meets its limit during the second phase in response to further increasing load, further reduction of the frequency can no longer keep the motor current constant and the motor encounters its control limits. A further development of the invention proposes to change, i.e. reduce the frequency and also the motor voltage. In consequence thereof, the motor rotational speed decreases considerably and the user quickly notices that the motor is overloaded and can correspondingly decrease the load to thereby prevent tilting of the motor. In a further design of this inventive concept, the motor control may be designed such that when a motor voltage U(limit) has been reached during the third phase, the motor is switched off. Instead of switching off the motor, a residual excitation can be applied to the motor to ensure that the motor can restart automatically after elimination of the load to thereby resume normal control operation. The invention also concerns a method for operating a manual electric tool device comprising an asynchronous electromotor or a brush-less synchronous electromotor and a computer-controlled motor control means comprising the features of claim 12. Preferred embodiments of this inventive method can be extracted from claims 13 through 19. Use of the inventive electric tool device and performance of the inventive method for operating an electric tool device may produce motor performance characteristics to which a user of electric tool devices with a carbon brush commutator system, so-called universal motors, is accustomed, without using such a commutator carbon brush system which is susceptible to wear. On the other hand, it has proven to be advantageous that despite use of asynchronous electromotors or brush-less synchronous electromotors, the “tilting” of the motor, which is common per se, can be prevented. The motor is always driven at a point of operation which is optimum for the instantaneous load through selection of the optimum frequency. Further features, details and advantages of the invention can be extracted from the following claims and the drawing and subsequent description of a preferred embodiment of the invention. FIG. 1 shows a schematic view of the circuit of an inventive manual electric tool device; FIG. 2 shows a motor diagram plotting the motor rotational speed N versus the motor torque M. FIG. 1 schematically shows the basic construction of the motor control of an inventive electric tool device. The motor 2, an asynchronous electromotor or a brush-less synchronous electromotor, is connected to a frequency converter 4 fed via a mains voltage, from which it receives the motor supply or motor excitation voltage. The frequency converter 4 is connected to the normal mains supply 6 with e.g. 230V/50 Hz. A micro-processor operated motor control means 8 is also provided which controls the frequency converter 4 and provides the specifications for the frequency of the motor drive voltage and for the value of the motor drive voltage, to the frequency converter 4. A current detector 10 is moreover provided in a respective control line between the frequency converter 4 and electromotor 2. It may preferably be a shunt resistance 12 for generating a value corresponding to the motor current via electronic tap switches (known per se and not shown), which can be fed to the motor control means 8 as an initial value. The frequency converter 4, the motor control means 8 and the current value detector 10 with circuit (not shown) are disposed or housed as a construction unit in an electronic housing which is protected from moisture. FIG. 2 shows a motor diagram, in which the motor rotational speed N is shown as a function of the motor torque M, i.e. as function of the load on the electromotor. The frequency of the motor excitation voltage and the value of this voltage are kept constant up to a limit current I(limit). The electromotor is operated with approximately constant torque N in the region designated with I. As the motor current increases due to increasing load past the limit value I(limit), the frequency of the motor drive voltage is controlled through the motor control means such that the motor current I remains constant, preferably at the limit value I(limit) which is between 10 and 20A, in particular between 10 and 15A and preferably e.g., for a right angle grinder motor, at 12 to 14 A. With increasing load, the frequency of the motor excitation voltage applied to the motor via the frequency converter and therefore also the motor rotational speed M decrease. One therefore obtains approximately the characteristics of a commutator motor outside of the region which can be controlled. The inventive electric tool device will behave in a manner familiar to the users of devices having universal motors, i.e. the rotational speed of the motor decreases noticeably with increasing load. This region is designated with II in FIG. 2. If the load continues to increase, the control limit is reached at the end of the region II, and the motor current can no longer be kept constant merely through reduction of the frequency of the motor excitation voltage. In a further development of the invention, the frequency and also the voltage are reduced to be able to keep the motor current I at the same level. In the region of the motor diagram designated with III, the characteristic curve drops drastically, i.e. the motor rotational speed N decreases considerably with load, such that a user easily recognizes that the motor rotates in the overloaded state and can appropriately reduce the load. This control in the region III prevents tilting of the motor. When a limit voltage U(limit) has been reached, the motor is switched off for safety reasons, since the motor current could otherwise no longer be kept constant. Alternatively, a low residual voltage can be maintained such that when the load is removed, the motor can slowly restart operation and automatically return to the region which can be controlled.
20041008
20070911
20050728
95619.0
0
SMITH, TYRONE W
ELECTRIC DRIVEN TOOL DEVICE
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,725
ACCEPTED
Reflection element of exposure light and production method therefor, mask, exposure system, and production method of semiconductor device
A reflector for extreme ultraviolet light, its manufacture method, a phase shift mask, an exposure apparatus and a semiconductor manufacture method, capable of making the wavelength dependency of a reflectance via a plurality of reflection surfaces be coincident with an center wavelength of exposure light of exposure light and retaining a sufficient energy reaching a subject to be exposed. The reflector for exposure light to be used for exposure of a subject to be exposed in a lithography process of manufacturing a semiconductor device is configured to have a multi-layer film structure made by repetitively stacking a plurality of layers in the same order. The periodical length of the repetitive stack unit of the multi-layer film structure is set in such a manner that the center of full width at half maximum of the reflectance via a predetermined number of reflectors becomes coincident with the center wavelength of extreme ultraviolet light to be reflected (S102).
1. A reflector for exposure light, characterized in that: said reflector for exposure light has a multi-layer film structure that a plurality of layers are repetitively stacked in the same order; a periodical length of a repetitive stack unit of said multi-layer film structure is set so that a center of full width at half maximum of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of said exposure light to be reflected, and said reflector for exposure light is used when said exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device. 2. A reflector for exposure light according to claim 1; characterized in that: in addition to said periodical length of said repetitive stack unit of said multi-layer film structure, a film thickness ratio between a plurality of layers constituting said repetitive stack unit is set so that said center of full width at half maximum of said reflectance via said predetermined number of reflectors becomes coincident with said center wavelength of exposure light to be reflected. 3. A reflector for exposure light according to claim 1; wherein said exposure light is any one of extreme ultraviolet light, ultraviolet light, an electron beam, an X-ray, a charged particle ray, a radial ray, or a visible light. 4. A reflector for exposure light according to claim 1; wherein said multi-layer film structure is made by stacking constituted of Si and Mo in the same order. 5. A reflector for exposure light according to claim 4; wherein said multi-layer film structure is stacked on a glass substrate comprising SiO2 from said glass surface toward the surface of said reflector. 6. A method of manufacturing a reflector for exposure light, characterized in that; a multi-layer film structure made by repetitively stacking a plurality of layers in the same order is formed by setting a periodical length of a repetitive stack unit of said multi-layer film structure and a film thickness ratio between a plurality of layers constituting said repetitive stack unit in such a manner that a center of full width at half maximum of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. 7. A method of manufacturing a reflector for exposure light according to claim 6; wherein said exposure light is any one of extreme ultraviolet light, ultraviolet light, an electron beam, an X-ray, a charged particle ray, a radial ray, or a visible light. 8. A method of manufacturing a reflector for exposure light according to claim 6; wherein said multi-layer film structure is made by stacking constituted of Si and Mo in the same order. 9. A method of manufacturing a reflector for exposure light according to claim 8; wherein said multi-layer film structure is stacked on a glass substrate comprising SiO2 from said glass surface toward the surface of said reflector. 10. A mask used when exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device, said mask characterized by; including a reflector portion having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order and an absorption film portion covering the reflector portion with a predetermined pattern; wherein said mask is structured so that there is a phase difference between reflection light of exposure light from said reflector portion and reflection light of said exposure light from said absorption film portion, and that in said reflection portion a periodical length of a repetitive stack unit of said multi-layer film structure and a film thickness ratio between the plurality of layers constituting said repetitive stack unit are set so that a center of full width at half maximum of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. 11. A mask according to claim 10, wherein said mask is a phase shift mask. 12. A mask according to claim 10; wherein said exposure light is any one of extreme ultraviolet light, ultraviolet light, an electron beam, an X-ray, a charged particle ray, a radial ray, or a visible light. 13. A mask according to claim 10; wherein said multi-layer film structure is made by stacking constituted of Si and Mo in the same order. 14. A mask according to claim 12; wherein said multi-layer film structure is stacked on a glass substrate comprising SiO2 from said glass surface toward the surface of said reflector. 15. A mask according to claim 10; wherein said buffer layer comprises Ru (ruthenium). 16. A mask according to claim 15; wherein a light reflection surface side of said reflector is covered with TaN (tantalum nitride) 17. An exposure apparatus used when exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device, characterized by: including a predetermined number of reflectors for exposure light, said reflector having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order; wherein in said reflector for exposure light a periodical length of a repetitive stack unit of said multi-layer film structure and a film thickness ratio between the plurality of layers constituting said repetitive stack unit are set so that a center of full width at half maximum of a reflectance via said predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. 18. An exposure apparatus according to claim 17; wherein said exposure light is any one of extreme ultraviolet light, ultraviolet light, an electron beam, an X-ray, a charged particle ray, a radial ray, or a visible light. 19. A semiconductor device manufacture method characterized by: including a reflector portion having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order and an absorption film portion covering the reflector portion with a predetermined pattern; wherein exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device; by using a mask structured so that there is a phase difference between reflection light of exposure light from said reflector portion and reflection light of said exposure light from said absorption film portion, and that in said reflection portion a periodical length of a repetitive stack unit of said multi-layer film structure and a film thickness ratio of said plurality of layers constituting said repetitive stack unit are set so that a center of full width at half maximum of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. 20. A semiconductor device manufacture method according to claim 19; wherein said exposure light is any one of extreme ultraviolet light, ultraviolet light, an electron beam, an X-ray, a charged particle ray, a radial ray, or a visible light.
TECHNICAL FIELD The present invention relates to a reflector for exposure light having a function of reflecting exposure light, such as mask blanks of exposure masks and reflection mirrors, the reflector being used when a circuit pattern is transferred by exposure light to a subject to be exposed such as a wafer in a lithograph process of manufacturing a semiconductor device, and to a reflector manufacture method. The present invention also relates to a mask having a function of reflecting exposure light. The present invention also relates to an exposure apparatus constituted of exposure light reflectors. The present invention also relates to a semiconductor device manufacture method using an exposure light mask. BACKGROUND ART Recent fine semiconductor devices require to minimize a pattern width (line width), a pitch between patterns and the like of a circuit pattern to be formed on a wafer and or a resist pattern for forming the circuit pattern and the like. This minimization request can be dealt with by shortening the wavelength of ultraviolet light to be used as exposure light to resist. As miniaturization of semiconductor devices progresses more, the wavelength of ultraviolet light to be used as exposure light is shortened to, for example, a wavelength of 365 nm for semiconductor devices under a 350 nm design rule, a wavelength of 248 nm for semiconductor devices under a 250 nm and 180 nm design rule, and a wavelength of 193 nm for semiconductor devices under a 130 nm and 100 nm design rule, ultraviolet light having a wavelength of 157 nm being now in use. It is know that a resolution relative to a wavelength is generally expressed by the Rayleigh's equation w=k1×(λ/NA) where w is a minimum width pattern to be resolved, NA is a numerical aperture of a lens in a projection optical system, λ is a wavelength of exposure light and k1 is a process constant. The process constant is determined mainly by the performance of resist, selection of ultra resolution techniques and the like. It is known that k1 can be selected to be about 0.35 if optimum resist and ultra resolution techniques are used. According to the ultra resolution techniques, ±first order refraction light of light transmitted through a mask and refracted by a mask light shielding pattern is selectively used to obtain a pattern smaller than the wavelength. It can be known from the Rayleigh's equation that the minimum pattern width capable of being dealt with if a wavelength of, for example, 157 nm is used, is w=61 nm by using a lens with NA=0.9. Namely, if a pattern width narrower than 61 nm is to be obtained, it is necessary to use ultraviolet light having a wavelength shorter than 157 nm. From this reason, studies have been made recently to use light having a wavelength of 13.5 nm called extreme ultraviolet (EUV; Extreme Ultra Violet) light as ultraviolet light having a wavelength shorter than 157 nm. Since there is light transmission material such as CaF2 (calcium fluoride) and SiO2 (silicon dioxide) for ultraviolet light having a wavelength of 157 nm or longer, it is possible to form a mask and an optical system capable of transmitting the ultraviolet light. However, for the extreme ultraviolet light having a wavelength of 13.5 nm, material capable of transmitting the extreme ultraviolet light at a desired thickness does not exist. Therefore, if the extreme ultraviolet light having a wavelength of 13.5 nm is used, not a mask and an optical system of a light transmission type, but a mask and an optical system of a light reflection type is required to be used. If a mask and an optical system of the light reflection type are used, light reflected from a mask surface is required to be guided to a projection optical system without being interfered with light incident upon the mask. It is therefore essential that light incident upon the mask is required to be oblique at an angle φ relative to the normal to the mask surface. This angle is determined from the numerical aperture NA of a lens in a projection optical system, a mask multiplication m and a size σ of an illumination light source. Specifically, in an exposure apparatus with NA=0.3 and σ=0.8, light is incident upon a mask, having a solid angle of 3.44±2.75 degrees. If a mask having a reduction factor of 4 relative to a wafer is used and an exposure apparatus has NA=0.25 and σ=0.7, light is incident upon the mask, having a solid angle of 3.58±2.51 degrees. As a reflection type mask for use with oblique incidence light, a mask blank is known which reflects extreme ultraviolet light and has an absorption film covering the mask blank with a predetermined pattern and absorbing extreme ultraviolet light and a buffer film interposed between the mask blank and absorption film. The mask blank has the structure that an Si (silicon) layer and an Mo (molybdenum) layer are alternately stacked, and the repetition number of stacks is generally 40 layers. Since the absorption film for extreme ultraviolet light covers the mask blank with a predetermined pattern, incidence light is selectively reflected in accordance with a circuit pattern to be formed, a resist pattern or the like. The buffer film is formed, as an etching stopper when the absorption film is formed, or in order to avoid damages to be caused when defects are removed after the absorption mask is formed. As described above, a conventional mask blank has generally 40 layers as the repetition number of stacks of the Si layer and Mo layer. A reflectance of Si is 0.9993-0.00182645i and a reflectance of Mo is 0.9211-0.00643543i, where i is an imaginary unit. It is known that a proper ratio r of a Mo layer thickness to a total thickness of the Si layer and Mo layer is Mo layer thickness/(Si layer thickness+Mo layer thickness)=0.4. Therefore, in a conventional mask blank, if the wavelength λ of extreme ultraviolet light to be used for exposure is 13.5 nm, the total thickness of the Si layer and Mo layer is (λ/2)/(0.9993×0.6+0.9211×0.4)=6.973 nm, a thickness of the Si layer is 6.9730×0.6=4.184, and a thickness of an Mo layer is 6.9730×0.4=2.789 nm. FIG. 1 shows a reflectance of the mask blank having 40 layers of the stack of the Si layer and Mo layer described above. In the example shown in FIG. 1, the reflectance is at an incidence angle of 4.84 degrees. The incidence angle is defined as an angle relative to the normal to the surface of the mask blank. The structure that the Si layer and Mo layer are alternately stacked is used not only for a mask blank of the reflection type but also for a reflection mirror constituting a reflection type optical system in quite a similar manner. Namely, the reflection mirror for extreme ultraviolet light has generally 40 layers as the repetition number of stacks of the Si layer and Mo layer, and the reflectance shown in FIG. 1 is obtained by properly setting the thicknesses of the Si layer and Mo layer when the wavelength of extreme ultraviolet light is 13.5 nm. Extreme ultraviolet light generally propagates via a plurality of reflection surfaces from a light source of an exposure apparatus to resist coated on a wafer, for example, six mirror reflection surfaces of an illumination optical system, six mirror reflection surfaces of a projection optical system and one reflection surface of a mask, thirteen surfaces in total. Extreme ultraviolet light emitted from the light source is attenuated upon reflection at a reflection surface. If this attenuation is large, sufficient energy cannot reach the resist coated on the wafer and there is a fear that pattern formation and the like cannot be performed properly. If extreme ultraviolet light propagates via a plurality of reflection surfaces, the energy reaching the resist coated on a wafer can be estimated from a reflectance at each of the plurality of reflection surfaces and a light source intensity. A reflectance R via a plurality of reflection planes is given by the following equation (1) if the light propagates via thirteen reflection surfaces in total. RTE is a reflectance of a TE wave per one reflection surface and RTM is a reflectance of a TM wave per one reflection surface. R={(RTE+RTM)/2}13 (1) A reflectance R of thirteen surfaces in total was obtained by using the equation (1) when the mask blank and reflection mirrors having the reflectance shown in FIG. 1 are used. The reflectance R is as shown in FIG. 4. It can be seen from the example shown in FIG. 4 that the center of the half width of a spectrum of the reflectance R is not coincident with 13.5 nm which is the center wavelength of exposure light of extreme ultraviolet light. Namely, even if the center of FWHM (Full Width at Half Maximum) of a reflectance per one reflection surface is coincident with the center wavelength of exposure light (refer to FIG. 1), the center of FWHM of the reflectance R via thirteen reflection surfaces in total is not necessarily coincident with the center wavelength of exposure light and the wavelength dependency may deviate from the center wavelength of exposure light. This results from that the peak wavelength for the reflectance per one reflection surface is not coincident with 13.5 nm which is the center wavelength of exposure light of extreme ultraviolet light. As above, if the wavelength dependency of the reflectance via a plurality of reflection surfaces deviates from the center wavelength of exposure light of extreme ultraviolet light, attenuation at the center wavelength of exposure light, i.e., attenuation of a light source intensity of the light source, becomes large. Therefore, sufficient energy will not reach at an exposure light wavelength suitable for resist coated on a wafer, and the probability that pattern formation and the like cannot be performed properly becomes very high. It is therefore an object of the present invention to provide a reflector for exposure light which can retain a sufficient energy reaching a subject to be exposed, by making the wavelength dependency of a reflectance via a plurality of reflection surfaces be coincident with the center wavelength of exposure light of exposure light such as extreme ultraviolet light. In a lithography process for manufacturing a semiconductor device, a number (a variety) of exposure masks is used in some cases. Further, if there are a plurality of exposure apparatuses and manufacture is executed at a plurality of factories, a plurality of exposure masks are often used even for the same product and even in the same process. In such cases, it is fairly conceivable that thicknesses of films and the like constituting each of a plurality of exposure masks have a manufacture variation. The manufacture variation of this type, i.e., a thickness variation of films and the like constituting each exposure mask, causes a deviation of the center of FWHM of the reflectance relative to extreme ultraviolet light, which may result in a reduction in arrival energy at an exposure light wavelength suitable for resist coated on a wafer. It is therefore desired to remove the variation as much as possible. However, for example, when the productivity of mask blanks is considered, it is not realistic to limit the film thickness and the like too severely. It is therefore an object of the present invention to provide a reflector for exposure light, its manufacture method, a mask, an exposure apparatus and a semiconductor device manufacture method, which can retain a sufficient energy reaching a subject to be exposed, by making the wavelength dependency of a reflectance via a plurality of reflection surfaces be coincident with the center wavelength of exposure light of exposure light such as extreme ultraviolet light. DISCLOSURE OF THE INVENTION The present invention is a reflector for exposure light devised in order to achieve the above-described objects. The reflector for exposure light is characterized in that it has a multi-layer film structure that a plurality of layers are repetitively stacked in the same order, that a periodical length of a repetitive stack unit of the multi-layer film structure is set so that a center of FWHM of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected, and that the reflector is used when the exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device. In addition to the periodical length of the repetitive stack unit of the multi-layer film structure, a film thickness ratio between a plurality of layers constituting the repetitive stack unit may also be set so that the center of FWHM of the reflectance via the predetermined number of reflectors becomes coincident with the center wavelength of exposure light to be reflected. The present invention is a method of manufacturing a reflector for exposure light devised in order to achieve the above-described object. Namely, the method is characterized in that a multi-layer film structure made by repetitively stacking a plurality of layers in the same order is formed by setting a periodical length of a repetitive stack unit of the multi-layer film structure and a film thickness ratio between a plurality of layers constituting the repetitive stack unit in such a manner that a center of FWHM of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. The present invention is a mask devised in order to achieve the above-described object and used when exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device. The mask is characterized by including a reflector portion having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order and an absorption film portion covering the reflector portion with a predetermined pattern, wherein the mask is structured so that there is a phase difference between reflection light of exposure light from the reflector portion and reflection light of the exposure light from the absorption film portion, and that in the reflection portion a periodical length of a repetitive stack unit of the multi-layer film structure and a film thickness ratio between the plurality of layers constituting the repetitive stack unit are set so that a center of FWHM of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. The present invention is an exposure apparatus devised in order to achieve the above-described object and used when exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device. The exposure apparatus is characterized by including a predetermined number of reflectors for exposure light, the reflector having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order, wherein in the reflector for exposure light a periodical length of a repetitive stack unit of the multi-layer film structure and a film thickness ratio between the plurality of layers constituting the repetitive stack unit are set so that a center of FWHM of a reflectance via the predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. The present invention is a semiconductor device manufacture method devised in order to achieve the above-described object. The semiconductor device manufacture method is characterized by including a reflector portion having a multi-layer film structure made by repetitively stacking a plurality of layers in the same order and an absorption film portion covering the reflector portion with a predetermined pattern, wherein exposure light is exposed to a subject to be exposed in a lithography process for manufacture of a semiconductor device, by using a mask structured so that there is a phase difference between reflection light of exposure light from the reflector portion and reflection light of the exposure light from the absorption film portion, and that in the reflection portion a periodical length of a repetitive stack unit of the multi-layer film structure and a film thickness ratio of the plurality of layers constituting the repetitive stack unit are set so that a center of FWHM of a reflectance via a predetermined number of reflectors becomes coincident with a center wavelength of exposure light to be reflected. According to the above-described reflector for exposure light, the periodical length of the repetitive stack unit of the multi-layer film structure is set so that the center of FWHM of the reflectance via a predetermined number of reflectors becomes coincident with the center wavelength of exposure light to be reflected. Therefore, the reflectance of exposure light via the predetermined number of reflectors is coincident with the center wavelength of the exposure light. Accordingly, attenuation of the exposure light intensity can be prevented from becoming large even if the exposure light propagates via the predetermined number of reflectors, and it is possible to retain sufficient arrival energy when exposure to the subject to be exposed is executed. Further, according to the above-described reflector for exposure light, its manufacture method, mask, exposure apparatus and semiconductor device manufacture method, the periodical length of the repetitive stack unit of the multi-layer film structure and the film thickness ratio among a plurality of layers constituting the repetitive stack unit are set so that the center of FWHM of the reflectance via a predetermined number of reflectors becomes coincident with the center wavelength of exposure light to be reflected. Namely, by setting also the film thickness ratio between a plurality of layers, the center of FWHM of the reflectance becomes coincident with the center wavelength of exposure light even if the total film thickness of the multi-layer film structure is shifted. Accordingly, an allowable variation width of the total film thickness of the multi-layer film structure can be broadened. Even in this case, attenuation of the exposure light intensity can be prevented from becoming large, and it is possible to retain sufficient arrival energy when exposure to the subject to be exposed is executed. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is an illustrative diagram showing an example of reflectances when a single reflector is used for extreme ultraviolet light, and more specifically a diagram showing reflectances by one reflector surface of a multi-layer film structure made by stacking 40 layers of Si 4.184 nm/Mo 2.789 nm at a periodical length 6.973 nm of a film thickness. FIG. 2 is a cross sectional side view showing an example of the outline structure of a reflector for exposure light according to the present invention. FIG. 3 is a perspective view showing an example of the outline structure of a mask according to the present invention. FIG. 4 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a plurality of reflectors, and more specifically a diagram showing reflectances by thirteen reflector surfaces each constituted of a multi-layer film structure made by stacking 40 layers of Si 4.184 nm/Mo 2.789 nm at a periodical length 6.973 nm of a film thickness. FIG. 5 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a single reflector according to the present invention, and more specifically a diagram showing reflectances by a single reflector surface constituted of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 6 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a plurality of reflectors according to the present invention, and more specifically a diagram showing reflectances by thirteen reflector surfaces each constituted of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 7 is a flow chart illustrating an example of a manufacture procedure for a reflector to be used with extreme ultraviolet light according to the present invention. FIG. 8 is an illustrative diagram showing an example of the results of relative energies reaching wafers when there is a film thickness variation of respective layers constituting a multi-layer film structure. FIG. 9 is an illustrative diagram showing an example of reflectances by a single reflector when there is a variation of total film thicknesses of multi-layer film structures, and more specifically a diagram showing reflectances Rmask of thinner and thicker cases of the total film thickness dtotal=278 nm of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 10 is an illustrative diagram showing an example of reflectances by a plurality of reflectors when there is a variation of total film thicknesses of multi-layer film structures, and more specifically a diagram showing reflectances Rtotal by twelve multi-layer film mirrors each having a total thickness dtotal=278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and via one mask blank having the multi-layer film structure and a variation of total film thicknesses dtotal. FIG. 11 is an illustrative diagram showing an example of relative energies reaching wafers when there is a variation of total thicknesses of multi-layer film structures, and more specifically a diagram showing relative energies Erelative via the propagation route of twelve multi-layer film mirrors each having a total thickness dtotal=278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and one mask blank having the multi-layer film structure and a variation of the total film thicknesses dtotal. FIG. 12 is an illustrative diagram showing an example of the relation between a periodical length of a film thickness and an optimum r value of a multi-layer film structure. FIG. 13 is an illustrative diagram showing an example of reflectances by a single reflector for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showi reflectances Rmask by one reflector surface of a multi-layer film structure having an optimum combination of a total film thickness dtotal and a Γ value and made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 14 is an illustrative diagram showing an example of reflectances by a plurality of reflectors for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showing reflectances Rtotal by twelve multi-layer film mirrors each having a total thickness dtotal=278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and by one mask blank having an optimum Γ value. FIG. 15 is an illustrative diagram showing an example of relative energies reaching wafers via a plurality of reflectors for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showing relative energies Erelative via the propagation route of twelve multi-layer film mirrors each having a total thickness dtotal=278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and one mask blank having an optimum Γ value. FIG. 16 is an illustrative diagram showing an example of the results obtained by plotting allowable variation values of a total film thickness as a function of a relative energy, for both the cases wherein a Γ value is optimized and not optimized. FIG. 17 is an illustrative diagram showing an example of TE wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 18 is an illustrative diagram showing an example of TM wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 19 is an illustrative diagram showing an example of TE wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 20 is an illustrative diagram showing an example of TM wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 21 is an illustrative diagram showing an example of reflectance ratio distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 22 is an illustrative diagram showing an example of reflectance ratio distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 23 is a schematic diagram showing an example of the outline structure of an exposure apparatus. BEST MODE FOR CARRYING OUT THE INVENTION With reference to the drawings, description will be made on a reflector for extreme ultraviolet light and its manufacture method, a phase shift mask and an exposure apparatus according to the invention. It is obvious that the present invention is not limited to preferred embodiments to be described below. First, an example of an exposure apparatus will be described. The exposure apparatus described herein is used for exposing a subject (resist on a wafer) to extreme ultraviolet light in a manufacture process for semiconductor devices, particularly in a lithography process of transferring a circuit pattern of a semiconductor device from an exposure mask to a wafer. More in detail, the route from a light source for irradiating extreme ultraviolet light having a center wavelength of 13.5 nm to resist on a wafer which is a subject to be exposed, is structured so that extreme ultraviolet light propagates via thirteen reflection surfaces in total, twelve mirror reflection surfaces of an optical system and one reflection surface of an exposure mask. Next, description will be made on a reflector for extreme ultraviolet light to be used by this exposure apparatus, i.e., a reflector for extreme ultraviolet light according to the present invention. The reflector for extreme ultraviolet light described herein is used as a reflection mirror constituting a mirror reflection surface of an optical system or a mask blank constituting a reflection surface of an exposure mask. More in detail, as shown in FIG. 2, the reflector has a multi-layer film structure made by repetitively stacking 40 layers each constituted of an Si layer 2 and an Mo layer 3 in the same order of Mo/Si/Mo/Si, . . . , Mo/Si from a low expansion glass 1 of, for example, SiO2 (silicon dioxide) or the like toward the reflector surface (front surface). The reflector 4 having the multi-layer film structure of this type may be formed by ion beam sputtering. More specifically, the Si layer 2 and Mo layer 3 are formed at predetermined film forming speeds by using, for example, an ion beam sputtering system. In order to configure a reflection type exposure mask by using the reflector 4, as shown in FIG. 3 an absorption film 6 made of extreme ultraviolet light absorbing material such as TaN (tantalum nitride) is formed on the reflector 4, with a buffer film 5 made of Ru (ruthenium) or the like being interposed therebetween. Namely, a light reflection surface side of the reflector 4 is covered with the absorption film 6 having a predetermined pattern so that incidence light can be selectively reflected in correspondence with a circuit pattern, resist pattern or the like to be formed. If a reflection mirror is to be configured, the light reflection surface of the reflector is used as it is to reflect incidence light. For example, as the optical conditions, a center wavelength (exposure wavelength) of extreme ultraviolet light as incidence light is set to 13.5 nm, and as the exposure conditions, NA=0.25 and σ=0.70. As already described, since the reflector having the multi-layer film structure of this type has an Si reflectance of 0.9993-0.00182645i, an Mo reflectance of 0.9211-0.00643543i and an extreme ultraviolet light wavelength λ of 13.5 nm, generally a ratio Γ of a thickness of the Mo layer to a total thickness of the Si layer and Mo layer is set to 0.4, a total thickness of the Si layer and Mo layer is set to (λ/2)/(0.9993×0.6+0.9211×0.4)=6.973 nm, a thickness of the Si layer is set to 6.9730×0.6=4.184 nm and a thickness of the Mo layer is set to 6.9730×0.4=2.789 nm. However, with the reflector having the multi-layer film structure constructed as above, as shown in FIG. 1, although the center of FWHM of the reflectance by a single reflector is coincident with the center wavelength of exposure light, the peak wavelength is shifted from the center wavelength of exposure light. Therefore, as shown in FIG. 4, the wavelength dependency of the reflectance R via the propagation route of thirteen reflection surfaces in total may shift from the center wavelength of exposure light because the center of FWHM is not always coincident with the center wavelength of exposure light. The reflector 4 having the multi-layer film structure described in this preferred embodiment is designed to have a periodical length of a film thickness of a repetitive stack unit of the Si layer 2 and Mo layer 3, different from a conventional design, in order to make the reflectance become coincident with the center wavelength of exposure light so that sufficient energy reaching resist can be retained even if the propagation route via thirteen reflection surfaces in total is used. Namely, with the reflector 4 described in the preferred embodiment, the periodical length of the repetitive stack unit of the multi-layer film structure is set so that the center of FWHM of the reflectance via the thirteen reflection surfaces in total becomes coincident with the center wavelength of extreme ultraviolet light. More specifically, a shift is considered between the peak wavelength of the reflectance by a single reflector and the center wavelength of exposure light. A correction corresponding to this shift amount is added to the value of the wavelength λ of extreme ultraviolet light and the total thickness of the Si layer 2 and Mo layer 3 is identified by an equation of (λ/2)/(0.9997×0.6+0.9221×0.4) while the value of the film thickness ratio Γ is maintained at 0.4. In this manner, the reflector 4 described in this embodiment has the structure that the total thickness of the Si layer 2 and Mo layer 3, i.e., a periodical length of the repetitive stack unit, is 6.95 nm. In this case, since Γ=0.4, a film thickness of one Si layer 2 is 4.17 nm and a film thickness of one Mo layer 3 is 2.78 nm. The reflector 4 structured as above has a reflectance spectrum by a single reflector wherein as shown in FIG. 5 the center of FWHM is not coincident width the center wavelength of exposure light. However, for the reflectance R via thirteen reflection surfaces in total, as shown in FIG. 6 the center of FWHM is coincident with the center wavelength of exposure light. This may be ascribed to that since the periodical length of a film thickness of the repetitive stack unit of the multi-layer film structure, i.e., the optical periodical length, is different from a conventional length, the wavelengths strengthening through interference by the multi-layer film structure are also different so that the peak wavelength of the reflectance shifts. Description will be made on a manufacture procedure for the reflector 4 having this structure. FIG. 7 is a flow chart illustrating an example of a reflector manufacture procedure. As illustrated in this drawing, when the reflector 4 is manufactured, first a reflectance spectrum is obtained at the route corresponding to the number of reflectors 4 mounted on the exposure apparatus, particularly, thirteen reflection surfaces in total (Step 101, hereinafter Step is abbreviated to “S”). The reflectance spectrum may be actually measured by forming a sample of the reflector or may be obtained by utilizing simulation techniques. After the reflectance spectrum is obtained, it is judged whether the center of FWHM of the reflectance spectrum is coincident with the center wavelength of exposure light of extreme ultraviolet light (S102). If this judgement result indicates that both are not coincident, the periodical length of a film thickness of the Si layer 2 and Mo layer 3 of the multi-layer film structure is changed so as to make both become coincident (setting is performed again), and thereafter the reflectance spectrum is again obtained at the route of thirteen reflection surfaces in total (S101). These processes are repeated until both become coincident. It can be considered that the film thicknesses of the Si layer 2 and Mo layer 3 of the multi-layer film structure are set to have desired values by properly adjusting the film forming speeds, for example, of sputtering. If the exposure apparatus, particularly an optical system formed by reflection mirrors, is structured by using the reflectors 4 formed in the above-described manner (e.g., reflector having a periodical length of a film thickness of 6.95 nm and Γ of 0.4), the reflectance R becomes coincident with the center wavelength of exposure light even at the route that extreme ultraviolet light propagates via thirteen reflection surfaces in total between the light source for extreme ultraviolet light and the resist on a wafer. It is therefore possible to suppress a large attenuation of the intensity of extreme ultraviolet light and retain a sufficient energy for resist exposure. Of the reflector 4 used by the exposure apparatus, a mask blank constituting an exposure mask among others is frequently changed with a circuit pattern to be transferred. Therefore, an individual difference is inevitable, namely, a film thickness variation of multi-layer film structures of mask blanks is inevitable. The film thickness variation of multi-layer film structures is mainly classified into two variations, variations of respective thicknesses dSi of Si layers 2 and respective thicknesses dMo of Mo layers 3 and a variation of total film thicknesses dtotal after 40 layers are stacked. This relation is represented by the following equation (2): d total = ∑ j 40 ⁢ ⁢ djSi + ∑ j 40 ⁢ ⁢ djMo ( 2 ) wherein the variations of respective thicknesses dSi of Si layers 2 and respective thicknesses dMo of Mo layers 3 do not influence greatly the intensity reduction by reflection of extreme ultraviolet light if the variation of total film thicknesses dtotal is restricted in a desired range. This can be confirmed by calculating the reflectance Rtotal, for example, via the route of thirteen reflection surfaces of the exposure apparatus including twelve reflection mirrors structured to have a periodical length of a film thickness of 6.95 nm and Γ=0.4 and one mask blank having a film thickness variation, by using the following equation (3) and a reflectance R12 via twelve reflection mirrors and a reflectance Rmask of the mask blank having a film thickness variation. Rtotal=R12×Rmask (3) More specifically, the mask blanks having variations of dSi and dMo are used, and the energies reaching resist on a wafer at standard deviations 3σ=0.5 nm and 3σ=1.0 nm are compared with the energy at 3σ=0.0 nm. More in detail, the energy E(3σ=0.5)=∫Rtotal dλ at 3σ=0.5 nm and the energy E(3σ=1.0)=∫Rtotal dλ at 3σ=1.0 nm are obtained, and these energies are compared with the energy E(3σ=0)=∫Rtotal dλ at 3σ=0.0 nm. These comparisons are performed by using the following equations (4) and (5): Erelative=E(3σ=0.5)/E(3σ=0) (4) Erelative=E(3σ=1.0)/E(3σ=0) (5) The comparison results of reaching energies at three types of variations (variations A to C) obtained by using the equations (4) and (5) are shown in FIG. 8. In this case, if Erelative≧0.95 is used as the judgement criterion based on the rule of thumb, as apparent from the example shown in the drawing, the energy reaching degree does not pose any problem at 3σ=0.5 nm, and any problem occurs even at 3σ=1.0 nm for the two types of variations (variations A and B). With respect to these results, in the actual mask blank manufacture process, it is possible to control the variation width narrower than that at 3σ=0.5. If these results are considered synthetically, it can be said that these variations do not pose any problem even if there are variations of the film thickness dSi of Si layer 2 and the film thicknesses dMo of Mo layers 3. As different from the variations of the film thicknesses dSi and dMo of the layers, the variation of the total film thicknesses dtotal greatly influences the intensity reduction of extreme ultraviolet light by reflection. This can be ascribed to that, for example, in the case of a multi-layer film structure having Γ=0.4, even if the center of FWHM of the reflectance spectrum is made coincident with the center wavelength of exposure light of extreme ultraviolet light as described previously, the center of FWHM shifts to the shorter wavelength side from the center wavelength of exposure light if the total film thicknesses dtotal of the multi-layer film structure have a variation and become thinner than a desired value, whereas the center of FWHM shifts to the longer wavelength side from the center wavelength of exposure light if the total film thickness becomes thicker than the desired value. FIG. 9 shows reflectances Rmask at variations from −3 nm to +3 nm of the total film thicknesses dtotal of multi-layer film structures wherein, for example, Γ is 0.4, the film thickness of the Si layer 2 is 4.17 nm, the film thickness of the Mo layer 3 is 2.78 nm and the periodical length of the repetitive stack unit is 6.95 nm. It can be seen from the example shown in the drawing that the center of FWHM of the reflectance Rmask shifts to the shorter or longer wavelength side of the center wavelength of exposure light in accordance with the variation of the total film thicknesses dtotal. As different from the variations of the film thicknesses dSi and dMo of the layers, the variation of the total film thicknesses dtotal is required that a variation width thereof is restricted in a predetermined constant allowable range. A variation width of the total film thickness dtotal can be obtained as in the following for multi-layer film structures having, for example, Γ of 0.4. First, basing upon the results shown in FIG. 9, the reflectances Rtotal via thirteen surfaces in total relative to the variations of the total film thicknesses dtotal are obtained. The results are shown in FIG. 10. The energies reaching resist on a wafer are obtained from the results shown in FIG. 10 and compared each other. More specifically, for example, the total film thickness dtotal is changed from −3 nm to +3 nm and the reaching energies E(Δdtotal=−3)=∫Rtotal dλ, E(Δdtotal=−2)=∫Rtotal dλ, E(Δdtotal=−1)=∫Rtotal dλ, E(Δdtotal=+1)=∫Rtotal dλ, E(Δdtotal=+2)=∫Rtotal dλ, E(Δdtotal=+3)=∫Rtotal dλ are obtained and compared with the reaching energy E(Δdtotal=0)=∫Rtotal dλ with no variation. Namely, the relative energies reaching the wafer at the variations of the dtotal are obtained, including Erelative=E(Δdtotal=−3)/E(Δdtotal=0), Erelative=E(Δdtotal=−2)/E(Δdtotal=0), E(Δdtotal=−1)/E(Δdtotal=0), Erelative=E(Δdtotal=0)/E(Δdtotal=0), Erelative=E(Δdtotal=+1)/E(Δdtotal=0), Erelative=E(Δdtotal=+2)/E(Δdtotal=0), and E(Δdtotal=+3)/E(Δdtotal=0). The comparison results of the energies Erelative obtained in this manner are shown in FIG. 11. The allowable range of the variation of dtotal can be obtained from the comparison results of the energies Erelative relative to Δdtotal. Namely, if Erelative≧0.95 based on the rule of thumb is used as the judgement criterion, it can be seen also from the results shown in FIG. 11 that the allowable variation of dtotal is in the range from −2.195 nm to +2.755 nm and in the range width of 4.95 nm. In other words, for multi-layer film structures having Γ of 0.4, a variation of 1.78% is allowable for the reference value dtotal=278 nm. However, if the productivity of, for example, a mask blank, is considered, it is needless to say that the allowable variation of dtotal is desired to have a broad width. In this context, multi-layer film structures are not configured to make the variation of the total film thicknesses dtotal falls in the allowable range while Γ is fixed to a constant value, but the allowable range of the variation of dtotal can be broadened by selecting an optimum Γ value together with the above-described periodical length of the film thickness of the multi-layer film structure. Detailed description will be made on selecting an optimum Γ value. For example, the relation between the periodical length of the film thickness and an optimum Γ of a multi-layer film structure is given, for example, as shown in FIG. 12. More specifically, if the periodical length of a film thickness is 6.88 nm, Γ=0.25 (in this case, the total film thickness dtotal=275.2 nm, the film thickness of one Si layer=5.1600 nm and the film thickness of one Mo layer=1.7200 nm); if the periodical length of a film thickness is 6.90 nm, Γ=0.30 (in this case, the total film thickness dtotal=276.0 nm, the film thickness of one Si layer=4.8300 and the film thickness of one Mo layer=2.0700 nm), Γ=0.25 (in this case, the total film thickness dtotal=275.2 nm, the film thickness of one Si layer=5.1600 nm and the film thickness of one Mo layer=1.7200 nm); if the periodical length of a film thickness is 6.90 nm, Γ=0.30 (in this case, the total film thickness dtotal=276.0 nm, the film thickness of one Si layer=4.8300 nm and the film thickness of one Mo layer=2.0700 nm); if the periodical length of a film thickness is 6.92 nm; Γ=0.35 (in this case, the total film thickness dtotal=276.8 nm, the film thickness of one Si layer=4.4980 nm and the film thickness of one Mo layer=2.4220 nm); if the periodical length of a film thickness is 6.95 nm, Γ=0.40 (in this case, the total film thickness dtotal=278.0 nm, the film thickness of one Si layer=4.1700 nm and the film thickness of one Mo layer=2.7800 nm); if the periodical length of a film thickness is 6.98 nm, Γ=0.45 (in this case, the total film thickness dtotal=279.2 nm, the film thickness of one Si layer=3.8390 nm and the film thickness of one Mo layer=3.1410 nm); if the periodical length of a film thickness is 7.01 nm, Γ=0.50 (in this case, the total film thickness dtotal=280.4 nm, the film thickness of one Si layer=3.5050 nm and the film thickness of one Mo layer=3.5050 nm); if the periodical length of a film thickness is 7.03 nm, Γ=0.55 (in this case, the total film thickness dtotal=281.2 nm, the film thickness of one Si layer=3.1635 nm and the film thickness of one Mo layer=3.8665 nm); and if the periodical length of a film thickness is 7.05 nm, Γ=0.60 (in this case, the total film thickness dtotal=282.0 nm, the film thickness of one Si layer=2.8200 nm and the film thickness of one Mo layer=4.2300 nm). FIG. 13 shows reflectances by a single multi-layer film structure, i.e., by a single reflection surface when optimum Γ values are selected. It can be understood from the example shown in the drawing that even if the total thickness dtotal shifts, the wavelength giving the peak intensity will not be changed by optimizing a combination of the periodical length of a film thickness and Γ value. FIG. 14 shows reflectances Rtotal via thirteen surfaces in total when optimum Γ values are selected. It can be understood from the example shown in the drawing that the half value center of the reflectance is always coincident with the center wavelength of exposure light at 13.5 nm. The energies reaching resist on a wafer are obtained from the results shown in FIG. 14 and they are compared each other. Specifically, the reaching energies when the optimum Γ values are selected are obtained, including E(Γ=0.25)=∫Rtotal dλ, E(Γ=0.30)=∫Rtotal dλ, E(Γ=0.35)=∫Rtotal dλ, E(Γ=0.40)=∫Rtotal dλ, E(Γ=0.45)=∫Rtotal dλ, E(Γ=0.50)=∫Rtotal dλ, E(Γ=0.55)=∫Rtotal dλ, and E(Γ=0.60)=∫Rtotal dλ, and compared with E(Γ=0.40)=∫Rtotal dλ used as a reference. Namely, the relative energies reaching the wafer at the variations of dtotal are obtained, including Erelative=E(Γ=0.25)/E(Γ=0.40), E(Γ=0.30)/E(Γ=0.40), E(Γ=0.35)/E(Γ=0.40), E(Γ=0.40)/E(Γ=0.40), E(Γ=0.45)/E(Γ=0.40), E(Γ=0.50)/E(Γ=0.40), E(Γ=0.55)/E(Γ=0.40), and E(Γ=0.60)/E(Γ=0.40). The comparison results of Erelative obtained in this manner are shown in FIG. 15. The allowable range of the variation of dtotal can be obtained from the comparison results of Erelative obtained in this manner. Namely, if Erelative≧0.95 based on the rule of thumb is used as the judgement criterion, it can be seen also from the results shown in FIG. 15 that the allowable variation of dtotal is in the range from −2.220 nm to +3.585 nm and in the range width of 5.805 nm. This means that a variation of 2.09% is allowable for the reference value dtotal=278 nm. Namely, if the multi-layer film structure is configured not by fixing Γ to a constant value but by selecting an optimum Γ value together with the periodical length of a film thickness, the allowable variation value of the total thickness dtotal of the multi-layer film structure increases. FIG. 16 shows the results obtained by plotting the allowable variation values of the total film thickness dtotal as a function of Erelative in both cases when the Γ value is optimized and not optimized. It can be seen also from the example shown in the drawing that if the Γ value is optimized, the allowable variation value increases more than if the Γ value is not optimized, and that in the same variation range, a lager energy can be obtained than if the Γ value is not optimized. It can be considered from this that of the reflectors 4 used by the exposure apparatus, the mask blank constituting the exposure mask among others is manufactured by selecting the optimum Γ value together with the periodical length of a film thickness. Namely, in the mask blank manufacture process, if dtotal is shifted from the dtotal reference value of 278 nm at Γ=0.40, the film forming conditions are selected from FIG. 12 so as to obtain an optimum relation between the Γ value and dtotal. More specifically, as shown in FIG. 7, after the exposure apparatus is configured having twelve reflection surfaces of the reflection mirrors having the periodical length of a film thickness set in the manner already described (S103), a mask blank used for the exposure apparatus is manufactured (S104). Before this manufacture, first the total film thickness dtotal of the multi-layer film structure is obtained (S105). The total film thickness dtotal may be actually measured by forming a sample of the mask blank or may be obtained by utilizing simulation techniques. It is assumed that the multi-layer film structure has Γ of 0.40. After the total film thickness dtotal is obtained, the periodical length of the film thickness at the total film thickness dtotal is obtained (S106) to judge whether the periodical length of the film thickness is shifted from a predetermined reference value, e.g., the reference value of 278 nm at Γ=0.40. If it is shifted from the reference value, the Γ value is optimized to change the periodical length of the film thickness and Γ value (to perform setting again) and thereafter the above-described Steps are repeated. Namely, in manufacturing a mask blank, in addition to the periodical length of the repetitive stack unit of the multi-layer film structure, the Γ value, which is the film thickness ratio between the Si layer and Mo layer constituting the repetitive stack unit, is also set in such a manner that the center of FWHM of the reflectance Rtotal via thirteen surfaces in total becomes coincident with the center wavelength of extreme ultraviolet light (refer to FIG. 14) to configure the multi-layer film structure. As the exposure mask is constituted of the mask blank obtained in this manner, the allowable variation width of the total film thickness dtotal can be broadened. It can therefore be expected that the productivity of mask blanks (exposure masks) is improved so that it is possible to realize the improvement on a manufacture efficiency of semiconductor devices, the reduction of a manufacture cost and the like. Furthermore, also in this case, since it is possible to suppress the intensity of extreme ultraviolet light from being attenuated considerably, a sufficient reaching energy for exposure to resist can be retained and it is possible to avoid beforehand the manufacture quality and the like of semiconductor devices from being degraded. In this description, although optimization of the Γ value is used by way of example when a mask blank is manufactured, it is obvious that the Γ value is optimized when a reflection mirror is manufactured. Namely, the optimization of the Γ value described in the embodiment is applicable to all types of reflectors for extreme ultraviolet light. Therefore, remarkable effects can be obtained relative to the film thickness variation of, for example, a half tone phase shift mask blank, by optimizing the Γ value. Description will be made on application of the optimization of a Γ value of a half tone phase shift mask blank. As an example of a half tone phase shift, a mask blank of a multi-layer film structure for reflecting extreme ultraviolet light is used on which a TaN film of extreme ultraviolet light absorbing material is formed with a Ru film being interposed therebetween. This half tone phase shift mask provides a phase shift mask function by setting a phase difference of 180 degrees between light reflected from the reflection surface of the mask blank and light reflected from the surface of the TaN film. For example, the film thicknesses giving a phase difference of 180 degrees are 13 nm for the R film and 30 nm for the TaN film. FIGS. 17 and 18 show the wavelength dependency of a phase difference when the Γ value is not optimized relative to the variation of the total film thicknesses dtotal of mask blanks of the above-described half tone phase shift mask. FIG. 17 is a diagram showing the phase difference distribution of TE waves, and FIG. 18 is a diagram showing the phase difference distribution of TM waves. It can be seen from the examples shown in these drawings that the phase difference range is from 167 degrees to 184 degrees if the Γ value is not optimized. In contrast, FIGS. 19 and 20 show the wavelength dependency of a phase difference when the Γ value is optimized relative to the variation of the total film thicknesses dtotal of mask blanks of the half tone phase shift mask. FIG. 19 is a diagram showing the phase difference distribution of TE waves, and FIG. 20 is a diagram showing the phase difference distribution of TM waves. It can be seen from the examples shown in these drawings that the phase difference distribution width is improved from 167 degrees to 183 degrees if the Γ value is optimized. Namely, by optimizing the Γ value, the phase difference distribution width is improved by about 6%. FIG. 21 shows a ratio Tratio=T(Ru+TaN)/Tblank of a reflectance T(R+TaN) of the R film and TaN film when the Γ value is not optimized relative to the variation of the total film thicknesses dtotal of mask blanks to a reflectance Tblank of mask blanks. This ratio Tratio is desired to have a small distribution, similar to the phase difference distribution. In contrast, FIG. 22 shows the ratio Tratio when the Γ value is optimized. From the comparison of these examples shown in the drawings, it can be seen that the wavelength dependency of the reflectance ratio becomes small by optimizing the Γ value. Namely, as the optimization of the Γ value is applied to the blank of the half tone phase shift mask, a phase shift mask can be realized wherein not only the variation width of the total film thickness dtotal is broadened, but also the phase difference distribution and reflectance ratio distribution are small. In the above description, although the exposure apparatus constituted of thirteen reflection surfaces in total is used by way of example, the invention is also applicable to exposure of different types. FIG. 23 is a diagram showing an example of the outline structure of another exposure apparatus. In an exposure apparatus 10 in the example shown in the drawing, exposure light output from a light source 11 of extreme ultraviolet light is separated by a beam splitter 12, narrowed to a proper angle by a prism unit 13 and passes through a fly eye lens 14 to form modified illumination or annular illumination to be described later. This light is reflected by (or transmitted through) a mask pattern of a reticle 16 via an illumination lens system 15, converged by a focussing lens system 17, and becomes obliquely incident illumination for resist coated on a wafer 18. Instead of using the beam splitter 12 and prism unit 13, the modified illumination or half tone annular illumination may be formed by using a filter which transmits an amount of light equal to or larger than some degree through a light source center and its nearby area. Further, if a mercury lamp is used as the light source 3 shown in FIG. 2, an exposure apparatus with an i-line stepper can be realized. The invention is not limited to this, but other types of exposure apparatuses may also be used such as a g-line stepper, a KrF excimer laser stepper and an ArF excimer laser stepper. The exposure beam is not limited only to extreme ultraviolet light but other beams may be used such as ultraviolet light, an electron beam, an X-ray, a radial ray, a charged particle ray and a light ray, with which the present invention can be properly reduced in practice. For example, one of electron beam exposure techniques is low energy electron proximity projection lithography (LEEPL). LEEPL uses a stencil mask made of a membrane having a thickness of several hundreds nm and formed with holes corresponding to a device pattern. A mask is disposed just above a wafer at a distance of several tens, m between the mask and wafer. The pattern area of the mask is scanned with an electron beam at several tens keV to transfer the pattern to the wafer (T. Utsumi, Journal of Vacuum Science and Technology B17, 2897 (1999)). In this manner, an electron beam emitted from a low acceleration electron gun passes through an aperture, is changed to a parallel beam by a condenser lens, and passes through a deflector to be irradiated on a wafer via the mask. Also in this case, by using a mask described in the present invention, it becomes possible to properly deal with a micro fine pattern width and pattern pitch of a transfer image so that the present invention can contribute to the improvement on the performance of semiconductor devices. There is a method of supporting a small segment membrane by a beam structure (grid structure). This is used by a mask of SCALPEL (scattering with angular limitation in projection electron-beam lithography), PREVAIL (projection exposure with variable axis immersion lenses) and an EB stepper (for example, L. R. Harriott, Journal of Vacuum Science nd Technology B15, 2130 (1997); H. C. Pfeiffer, Japanese Journal of Applied Physics 34, 6658 (1995)). With SCALPEL, an electron beam emitted from a low acceleration electron gun passed through an aperture, is changed to a parallel beam by a condenser lens, and passes through a deflector to be irradiated to a wafer via a mask. With PREVAIL, a condenser lens, a reticle, a first projection lens, a crossover aperture, a second projection lens, a sample, a lens under the sample are sequentially arranged from an electron source side to transfer a reticle pattern to the sample. Also in these cases, by using a mask described in the present invention, it becomes possible to properly deal with a micro fine pattern width and pattern pitch of a transfer image so that the present invention can contribute to the improvement on the performance of semiconductor devices. Even if not only extreme ultraviolet light, but also ultraviolet light, an electron beam, an X-ray, a radial ray, a charged particle ray or a light ray is used as the exposure beam, a line width variation and a pattern position misalignment after exposure to a wafer can be minimized by applying the present invention. Therefore, it becomes possible to properly deal with a micro fine pattern width and pattern pitch of a transfer image so that the present invention can contribute to the improvement on the performance of semiconductor devices. Industrial Applicability As described above, according to a reflector for extreme ultraviolet light, its manufacture method, a phase shift mask, an exposure apparatus and a semiconductor manufacture method of the present invention, the wavelength dependency of a reflectance via a plurality of reflection surfaces can be made coincident with the center wavelength of exposure light of extreme ultraviolet light. Accordingly, it is possible to retain a sufficient reaching energy for exposure of a subject to be exposed. Further, if an optimum r value is selected, the allowable variation width of a film thickness of the reflector can be broadened so that a sufficient energy reaching an exposure subject can be retained without degrading the productivity and the like of reflectors.
<SOH> BACKGROUND ART <EOH>Recent fine semiconductor devices require to minimize a pattern width (line width), a pitch between patterns and the like of a circuit pattern to be formed on a wafer and or a resist pattern for forming the circuit pattern and the like. This minimization request can be dealt with by shortening the wavelength of ultraviolet light to be used as exposure light to resist. As miniaturization of semiconductor devices progresses more, the wavelength of ultraviolet light to be used as exposure light is shortened to, for example, a wavelength of 365 nm for semiconductor devices under a 350 nm design rule, a wavelength of 248 nm for semiconductor devices under a 250 nm and 180 nm design rule, and a wavelength of 193 nm for semiconductor devices under a 130 nm and 100 nm design rule, ultraviolet light having a wavelength of 157 nm being now in use. It is know that a resolution relative to a wavelength is generally expressed by the Rayleigh's equation w=k1×(λ/NA) where w is a minimum width pattern to be resolved, NA is a numerical aperture of a lens in a projection optical system, λ is a wavelength of exposure light and k1 is a process constant. The process constant is determined mainly by the performance of resist, selection of ultra resolution techniques and the like. It is known that k1 can be selected to be about 0.35 if optimum resist and ultra resolution techniques are used. According to the ultra resolution techniques, ±first order refraction light of light transmitted through a mask and refracted by a mask light shielding pattern is selectively used to obtain a pattern smaller than the wavelength. It can be known from the Rayleigh's equation that the minimum pattern width capable of being dealt with if a wavelength of, for example, 157 nm is used, is w=61 nm by using a lens with NA=0.9. Namely, if a pattern width narrower than 61 nm is to be obtained, it is necessary to use ultraviolet light having a wavelength shorter than 157 nm. From this reason, studies have been made recently to use light having a wavelength of 13.5 nm called extreme ultraviolet (EUV; Extreme Ultra Violet) light as ultraviolet light having a wavelength shorter than 157 nm. Since there is light transmission material such as CaF 2 (calcium fluoride) and SiO 2 (silicon dioxide) for ultraviolet light having a wavelength of 157 nm or longer, it is possible to form a mask and an optical system capable of transmitting the ultraviolet light. However, for the extreme ultraviolet light having a wavelength of 13.5 nm, material capable of transmitting the extreme ultraviolet light at a desired thickness does not exist. Therefore, if the extreme ultraviolet light having a wavelength of 13.5 nm is used, not a mask and an optical system of a light transmission type, but a mask and an optical system of a light reflection type is required to be used. If a mask and an optical system of the light reflection type are used, light reflected from a mask surface is required to be guided to a projection optical system without being interfered with light incident upon the mask. It is therefore essential that light incident upon the mask is required to be oblique at an angle φ relative to the normal to the mask surface. This angle is determined from the numerical aperture NA of a lens in a projection optical system, a mask multiplication m and a size σ of an illumination light source. Specifically, in an exposure apparatus with NA=0.3 and σ=0.8, light is incident upon a mask, having a solid angle of 3.44±2.75 degrees. If a mask having a reduction factor of 4 relative to a wafer is used and an exposure apparatus has NA=0.25 and σ=0.7, light is incident upon the mask, having a solid angle of 3.58±2.51 degrees. As a reflection type mask for use with oblique incidence light, a mask blank is known which reflects extreme ultraviolet light and has an absorption film covering the mask blank with a predetermined pattern and absorbing extreme ultraviolet light and a buffer film interposed between the mask blank and absorption film. The mask blank has the structure that an Si (silicon) layer and an Mo (molybdenum) layer are alternately stacked, and the repetition number of stacks is generally 40 layers. Since the absorption film for extreme ultraviolet light covers the mask blank with a predetermined pattern, incidence light is selectively reflected in accordance with a circuit pattern to be formed, a resist pattern or the like. The buffer film is formed, as an etching stopper when the absorption film is formed, or in order to avoid damages to be caused when defects are removed after the absorption mask is formed. As described above, a conventional mask blank has generally 40 layers as the repetition number of stacks of the Si layer and Mo layer. A reflectance of Si is 0.9993-0.00182645i and a reflectance of Mo is 0.9211-0.00643543i, where i is an imaginary unit. It is known that a proper ratio r of a Mo layer thickness to a total thickness of the Si layer and Mo layer is Mo layer thickness/(Si layer thickness+Mo layer thickness)=0.4. Therefore, in a conventional mask blank, if the wavelength λ of extreme ultraviolet light to be used for exposure is 13.5 nm, the total thickness of the Si layer and Mo layer is (λ/2)/(0.9993×0.6+0.9211×0.4)=6.973 nm, a thickness of the Si layer is 6.9730×0.6=4.184, and a thickness of an Mo layer is 6.9730×0.4=2.789 nm. FIG. 1 shows a reflectance of the mask blank having 40 layers of the stack of the Si layer and Mo layer described above. In the example shown in FIG. 1 , the reflectance is at an incidence angle of 4.84 degrees. The incidence angle is defined as an angle relative to the normal to the surface of the mask blank. The structure that the Si layer and Mo layer are alternately stacked is used not only for a mask blank of the reflection type but also for a reflection mirror constituting a reflection type optical system in quite a similar manner. Namely, the reflection mirror for extreme ultraviolet light has generally 40 layers as the repetition number of stacks of the Si layer and Mo layer, and the reflectance shown in FIG. 1 is obtained by properly setting the thicknesses of the Si layer and Mo layer when the wavelength of extreme ultraviolet light is 13.5 nm. Extreme ultraviolet light generally propagates via a plurality of reflection surfaces from a light source of an exposure apparatus to resist coated on a wafer, for example, six mirror reflection surfaces of an illumination optical system, six mirror reflection surfaces of a projection optical system and one reflection surface of a mask, thirteen surfaces in total. Extreme ultraviolet light emitted from the light source is attenuated upon reflection at a reflection surface. If this attenuation is large, sufficient energy cannot reach the resist coated on the wafer and there is a fear that pattern formation and the like cannot be performed properly. If extreme ultraviolet light propagates via a plurality of reflection surfaces, the energy reaching the resist coated on a wafer can be estimated from a reflectance at each of the plurality of reflection surfaces and a light source intensity. A reflectance R via a plurality of reflection planes is given by the following equation (1) if the light propagates via thirteen reflection surfaces in total. R TE is a reflectance of a TE wave per one reflection surface and R TM is a reflectance of a TM wave per one reflection surface. in-line-formulae description="In-line Formulae" end="lead"? R ={( R TE +R TM )/2} 13 (1) in-line-formulae description="In-line Formulae" end="tail"? A reflectance R of thirteen surfaces in total was obtained by using the equation (1) when the mask blank and reflection mirrors having the reflectance shown in FIG. 1 are used. The reflectance R is as shown in FIG. 4 . It can be seen from the example shown in FIG. 4 that the center of the half width of a spectrum of the reflectance R is not coincident with 13.5 nm which is the center wavelength of exposure light of extreme ultraviolet light. Namely, even if the center of FWHM (Full Width at Half Maximum) of a reflectance per one reflection surface is coincident with the center wavelength of exposure light (refer to FIG. 1 ), the center of FWHM of the reflectance R via thirteen reflection surfaces in total is not necessarily coincident with the center wavelength of exposure light and the wavelength dependency may deviate from the center wavelength of exposure light. This results from that the peak wavelength for the reflectance per one reflection surface is not coincident with 13.5 nm which is the center wavelength of exposure light of extreme ultraviolet light. As above, if the wavelength dependency of the reflectance via a plurality of reflection surfaces deviates from the center wavelength of exposure light of extreme ultraviolet light, attenuation at the center wavelength of exposure light, i.e., attenuation of a light source intensity of the light source, becomes large. Therefore, sufficient energy will not reach at an exposure light wavelength suitable for resist coated on a wafer, and the probability that pattern formation and the like cannot be performed properly becomes very high. It is therefore an object of the present invention to provide a reflector for exposure light which can retain a sufficient energy reaching a subject to be exposed, by making the wavelength dependency of a reflectance via a plurality of reflection surfaces be coincident with the center wavelength of exposure light of exposure light such as extreme ultraviolet light. In a lithography process for manufacturing a semiconductor device, a number (a variety) of exposure masks is used in some cases. Further, if there are a plurality of exposure apparatuses and manufacture is executed at a plurality of factories, a plurality of exposure masks are often used even for the same product and even in the same process. In such cases, it is fairly conceivable that thicknesses of films and the like constituting each of a plurality of exposure masks have a manufacture variation. The manufacture variation of this type, i.e., a thickness variation of films and the like constituting each exposure mask, causes a deviation of the center of FWHM of the reflectance relative to extreme ultraviolet light, which may result in a reduction in arrival energy at an exposure light wavelength suitable for resist coated on a wafer. It is therefore desired to remove the variation as much as possible. However, for example, when the productivity of mask blanks is considered, it is not realistic to limit the film thickness and the like too severely. It is therefore an object of the present invention to provide a reflector for exposure light, its manufacture method, a mask, an exposure apparatus and a semiconductor device manufacture method, which can retain a sufficient energy reaching a subject to be exposed, by making the wavelength dependency of a reflectance via a plurality of reflection surfaces be coincident with the center wavelength of exposure light of exposure light such as extreme ultraviolet light.
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is an illustrative diagram showing an example of reflectances when a single reflector is used for extreme ultraviolet light, and more specifically a diagram showing reflectances by one reflector surface of a multi-layer film structure made by stacking 40 layers of Si 4.184 nm/Mo 2.789 nm at a periodical length 6.973 nm of a film thickness. FIG. 2 is a cross sectional side view showing an example of the outline structure of a reflector for exposure light according to the present invention. FIG. 3 is a perspective view showing an example of the outline structure of a mask according to the present invention. FIG. 4 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a plurality of reflectors, and more specifically a diagram showing reflectances by thirteen reflector surfaces each constituted of a multi-layer film structure made by stacking 40 layers of Si 4.184 nm/Mo 2.789 nm at a periodical length 6.973 nm of a film thickness. FIG. 5 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a single reflector according to the present invention, and more specifically a diagram showing reflectances by a single reflector surface constituted of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 6 is an illustrative diagram showing an example of reflectances when extreme ultraviolet light propagates via a plurality of reflectors according to the present invention, and more specifically a diagram showing reflectances by thirteen reflector surfaces each constituted of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 7 is a flow chart illustrating an example of a manufacture procedure for a reflector to be used with extreme ultraviolet light according to the present invention. FIG. 8 is an illustrative diagram showing an example of the results of relative energies reaching wafers when there is a film thickness variation of respective layers constituting a multi-layer film structure. FIG. 9 is an illustrative diagram showing an example of reflectances by a single reflector when there is a variation of total film thicknesses of multi-layer film structures, and more specifically a diagram showing reflectances R mask of thinner and thicker cases of the total film thickness d total =278 nm of a multi-layer film structure made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 10 is an illustrative diagram showing an example of reflectances by a plurality of reflectors when there is a variation of total film thicknesses of multi-layer film structures, and more specifically a diagram showing reflectances R total by twelve multi-layer film mirrors each having a total thickness d total =278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and via one mask blank having the multi-layer film structure and a variation of total film thicknesses d total . FIG. 11 is an illustrative diagram showing an example of relative energies reaching wafers when there is a variation of total thicknesses of multi-layer film structures, and more specifically a diagram showing relative energies E relative via the propagation route of twelve multi-layer film mirrors each having a total thickness d total =278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and one mask blank having the multi-layer film structure and a variation of the total film thicknesses d total . FIG. 12 is an illustrative diagram showing an example of the relation between a periodical length of a film thickness and an optimum r value of a multi-layer film structure. FIG. 13 is an illustrative diagram showing an example of reflectances by a single reflector for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showi reflectances R mask by one reflector surface of a multi-layer film structure having an optimum combination of a total film thickness d total and a Γ value and made by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness. FIG. 14 is an illustrative diagram showing an example of reflectances by a plurality of reflectors for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showing reflectances R total by twelve multi-layer film mirrors each having a total thickness d total =278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and by one mask blank having an optimum Γ value. FIG. 15 is an illustrative diagram showing an example of relative energies reaching wafers via a plurality of reflectors for extreme ultraviolet light having an optimum Γ value according to the present invention, and more specifically a diagram showing relative energies E relative via the propagation route of twelve multi-layer film mirrors each having a total thickness d total =278 nm and manufactured by stacking 40 layers of Si 4.17 nm/Mo 2.78 nm at a periodical length 6.95 nm of a film thickness and one mask blank having an optimum Γ value. FIG. 16 is an illustrative diagram showing an example of the results obtained by plotting allowable variation values of a total film thickness as a function of a relative energy, for both the cases wherein a Γ value is optimized and not optimized. FIG. 17 is an illustrative diagram showing an example of TE wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 18 is an illustrative diagram showing an example of TM wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 19 is an illustrative diagram showing an example of TE wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 20 is an illustrative diagram showing an example of TM wave phase difference distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 21 is an illustrative diagram showing an example of reflectance ratio distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is not optimized. FIG. 22 is an illustrative diagram showing an example of reflectance ratio distributions of a half tone phase shift mask at respective wavelengths, relative to a variation of total film thicknesses when a Γ value is optimized. FIG. 23 is a schematic diagram showing an example of the outline structure of an exposure apparatus. detailed-description description="Detailed Description" end="lead"?
20041008
20070130
20050714
70153.0
0
ASSAF, FAYEZ G
Reflector for exposure light and its manufacture method, mask, exposure apparatus and semiconductor device manufacture method
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,777
ACCEPTED
Automated tissue engineering system
The invention provides systems, modules, bioreactor and methods for the automated culture, proliferation, differentiation, production and maintenance of tissue engineered products. In one aspect is an automated tissue engineering system comprising a housing, at least one bioreactor supported by the housing, the bioreactor facilitating physiological cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources. A fluid containment system is supported by the housing and is in fluid communication with the bioreactor. One or more sensors are associated with one or more of the housing, bioreactor or fluid containment system for monitoring parameters related to the physiological cellular functions and/or generation of tissue constructs; and a microprocessor linked to one or more of the sensors. The systems, methods and products of the invention find use in various clinical and laboratory settings.
1-137. (canceled) 138. An automated tissue engineering system comprising; a housing; at least one bioreactor supported by said housing, said bioreactor facilitating physiological cellular functions and/ or the generation of one or more tissue constructs from cell and/or tissue sources; a fluid containment system supported by said housing and in fluid communication with said bioreactor, one or more sensors associated with one or more of said housing, bioreactor or fluid containment system for monitoring parameters related to said physiological cellular functions and/or generation of tissue constructs; and a microprocessor linked to one or more of said sensors. 139. The system of claim 138, wherein said bioreactor comprises a bioreactor housing; one or more inlet ports and one or more outlet ports for media flow; and at least one chamber defined within said bioreactor housing for receiving a variety of cells and/or tissues. 140. The system of claim 139, wherein said bioreactor housing comprises a lid, said one or more inlet ports and outlet ports being provided within said bioreactor housing and/or said lid. 141. The system of claim 138, wherein said chamber is selected from the group consisting of a tissue digestion chamber, culture/proliferation chamber, differentiation/tissue formation chamber and combinations thereof. 142. The system of claim 139, wherein two or more chambers are provided operably connected within said bioreactor. 143. The system of claim 139, wherein said chamber houses one or more substrates and/or scaffolds. 144. The system of claim 143, wherein said substrate is a contained suspension of micro-carrier. 145. The system of claims 139, wherein said chamber contains a plurality of zones. 146. The system of claim 145, wherein said plurality of zones may each accommodate a scaffold and/or substrate. 147. The system of claim 142, wherein at least one of said two or more chambers and said bioreactors are one of at least independently operable and co-operatively operable. 148. The system of claim 142, wherein at least one of said chambers and bioreactors are operably connected to provide for the exchange of one or more of fluids, cells and tissues between at least one of said chambers and said bioreactors. 149. The system of claim 148, wherein at least one of said chambers and said bioreactor are connected via at least one of a passageway, tubing, connector, valve, pump, filter, fluid access port, in-line gas exchange membrane, in-line sensor and void in a separation wall. 150. The system of claim 138, wherein said bioreactor is removably accomodated with said fluid containment system via said inlet port and said outlet port. 151. An automated tissue engineering system comprising; a housing; at least one tissue engineering module removably accommodated within said housing, said tissue engineering module comprising a support structure that holds at least one bioreactor, said bioreactor facilitating at least one of cell culture and tissue engineering functions, a fluid containment system in fluid communication with said bioreactor, and one or more sensors for monitoring parameters related to at least one of said cell culture and tissue engineering functions; and a microprocessor disposed in said housing and linked to said tissue engineering module, said microprocessor controlling the operation of said tissue engineering module. 152. The tissue engineering system of claim 151, wherein said bioreactor comprises a bioreactor housing having one or more inlet ports and one or more outlet ports for media flow; and at least one chamber defined within said bioreactor housing for receiving at least one of said cells and tissues and facilitating said cell culture and tissue engineering functions. 153. The tissue engineering system of claim 152, wherein said chamber houses one or more substrates and/or scaffolds. 154. The tissue engineering system of claim 152, wherein at least one of, said two or more chambers, and said bioreactors are at least one of independently operable and cooperatively operable. 155. The tissue engineering system of claim 151, wherein at least one of said chambers and said bioreactors are operably connected to provide for the exchange of at least one of said fluids, cells and tissues between at least one of said chambers and said bioreactors. 156. The tissue engineering system of claim 153, wherein said chamber contains a plurality of zones to contain a plurality of substrates and/ or scaffolds. 157. The tissue engineering system of claim 151, wherein said fluid containment system comprises a plurality of flexible reservoirs connected by flexible tubing for supplying and retrieving fluid to and from said bioreactor. 158. The tissue engineering system of claim 151, wherein said housing comprises one or more environmental sensors and an environmental control unit to maintain said environmental conditions within one or more of said housing, tissue engineering module, bioreactor, fluid containment system, and said flexible reservoirs. 159. The tissue engineering system of claim 151, wherein said housing has at least one insertion slot for insertion of said tissue engineering module via at least one set of guides for receiving said support structure. 160. The tissue engineering system of claim 159, wherein said insertion slot and said guides are vertically or horizontally orientated with respect to said housing. 161. The tissue engineering system of claim 159, wherein said insertion slot has a movable door and a locking mechanism. 162. The tissue engineering system of claim 151, wherein said system additionally comprises a user interface in operation with said microprocessor, said user interface providing for the entry of user inputs to said microprocessor and/or the output of system status. 163. The tissue engineering system of claim 162, further comprising a data system to permit input, output, recording, transfer and storage of information. 164. The tissue engineering system of claim 163, further comprising a computer and communications link. 165. The tissue engineering system of claim 151, wherein said microprocessor performs quality control assessments of said cell culture and tissue engineering functions. 166. The tissue engineering system of claim 151, wherein said tissue engineering module additionally comprises one or more microprocessors that are in operable connection with said microprocessor disposed in said housing. 167. A portable and sterilizable tissue engineering module, the module comprising; a structural support holding at least one bioreactor, said bioreactor facilitating cell culture and tissue engineering functions; a fluid containment system in fluid communication with said bioreactor; and one or more sensors for monitoring parameters related to said cell culture and tissue engineering functions. 168. The tissue engineering module of claim 167, wherein said bioreactor comprises: a bioreactor housing having one or more inlet ports and one or more outlet ports for media flow; and at least one chamber defined within said bioreactor housing for receiving at least one of said cells and tissues and facilitating said cell culture and tissue engineering functions. 169. The tissue engineering module of claim 168, wherein said chamber houses one or more substrates and/or scaffolds. 170. The tissue engineering module of claim 168, wherein two or more chambers are provided operably connected within said bioreactor. 171. The tissue engineering module of claim 167, wherein two or more bioreactors are operably connected. 172. The tissue engineering module of claim 170, wherein at least one of said two or more chambers, and said bioreactors are independently operable and/or co-operatively operable. 173. The tissue engineering module of claim 172, wherein said module comprises a first bioreactor, a second bioreactor and a third bioreactor, said first bioreactor containing a tissue digestion chamber, said second bioreactor containing a culture/ proliferation chamber, said third bioreactor containing a differentiation/tissue formation chamber, and wherein said first, second and third bioreactors are operatively connected. 174. The tissue engineering module of claim 170, wherein said chambers and/or bioreactors are operably connected to provide for the exchange of fluids, cells and/or tissues between said chambers and/or bioreactors. 175. The tissue engineering module of claim 168, wherein said chamber contains a plurality of zones to contain a plurality of substrates and/or scaffolds. 176. The tissue engineering module of claim 167, wherein said fluid containment system comprises a plurality of flexible reservoirs connected by flexible tubing for supplying and retrieving fluid to and from said bioreactor. 177. The tissue engineering module of claim 176, wherein at least one of said flexible reservoir and said tubing is provided with fluid access ports for the loading or removal of material from said fluid containment system. 178. The tissue engineering module of claim 167, wherein a plurality of fluid flow control valves are provided in operable connection with fluid containment system to control the flow of fluid with said fluid containment system and said bioreactor. 179. The tissue engineering module of claim 178, wherein said module additionally comprises one or more pump units in connection with said fluid containment system for the pumping of fluid throughout said fluid containment system. 180. The tissue engineering module of claim 167, wherein a fluid flow plate is mounted or provided integral to said structural support, said fluid flow plate being operationally connected to said fluid control valves to direct fluid flow within and between said fluid containment system and said bioreactor. 181. The tissue engineering module of claim 167, wherein said tissue engineering module additionally comprises a heating and mixing chamber to heat and mix fluids flowing to said bioreactor. 182. The tissue engineering module of claim 167, wherein one or more gas exchange membranes are provided within one of or between said fluid containment system and bioreactor, said gas exchange membranes permitting the transfer of gaseous products into or out of fluid flowing to or resident in said bioreactor. 183. The tissue engineering module of claim 167, wherein said module additionally comprises a thermoelectric element in operable connection with said bioreactor. 184. The tissue engineering module of claim 167, wherein said module additionally comprises one or more microprocessors in operable connection with said sensors. 185. The tissue engineering module of claim 167, wherein said module additionally comprises one or more access ports, said access ports being operatively linked with at least one of said bioreactor and said fluid containment system, said access ports providing for sterile loading or removal of cells, fluids, cell and tissue culture media, growth factors, pharmaceutical agents, quality control reagents, quality control samples and other materials. 186. The tissue engineering module of claim 185, wherein said access ports are operatively linked to a syringe manifold integrated with said structural support. 187. The tissue engineering module of claim 167, wherein said bioreactor is integrally mounted to said structural support. 188. The tissue engineering module of claim 167, wherein said bioreactor is detachable from said structural support. 189. The tissue engineering module of claim 167, wherein a camera is provided for visual inspection within said bioreactor. 190. The tissue engineering module of claim 167, wherein said module additionally comprises an identifying element. 191. The tissue engineering module of claim 167, wherein said module is sterilizable before use and disposable after use. 192. A bioreactor for facilitating and supporting cellular functions and/or the generation of tissue constructs, said bioreactor comprising; a bioreactor housing; one or more inlet ports and one or more outlet ports for media flow; at least one chamber defined within said bioreactor housing for facilitating and supporting cellular functions and/or the generation of one or more tissue constructs from cell and/ or tissue sources; and one or more sensors for monitoring parameters related to said cellular functions and/or generation of tissue constructs within said at least one chamber. 193. The bioreactor of claim 192, wherein said bioreactor housing comprises a lid, said lid. 194. The bioreactor of claim 192, wherein said bioreactor comprises a single culture/proliferation chamber having at least one of a culture/proliferation scaffold and a substrate supported therein. 195. The bioreactor of claim 192, wherein said bioreactor comprises a culture/proliferation chamber connected to a downstream differentiation/tissue formation chamber, said culture/proliferation chamber having at least one of a proliferation scaffold and a substrate supported therein, said differentiation/ tissue formation chamber having an implantable differentiation scaffold supported therein. 196. The bioreactor of claim 192, wherein a connecting passageway is provided between said culture/proliferation chamber and said differentiation/tissue formation chamber, said connecting passageway facilitating movement of cells released from said proliferation scaffold and/or substrate to said differentiation scaffold. 197. The bioreactor of claim 196, further comprising a digestion chamber for the digestion of tissue biopsy material, said digestion chamber being upstream of said culture/proliferation chamber. 198. The bioreactor of claim 195, wherein one or more filters are provided at a location selected from upstream of said proliferation scaffold, upstream of said differentiation scaffold, upstream to said outlet port and combinations thereof. 199. The bioreactor of claim 196, wherein said differentiation/tissue formation chamber contains a plurality of zones to contain a plurality of differentiation scaffolds and/ or substrates. 200. The bioreactor of claim 192, wherein said bioreactor has a sampling port that is operatively connected to one or more of said chambers. 201. The bioreactor of claim 192, wherein a gas exchange membrane forms part of said chamber. 202. The bioreactor of claim 192, wherein said bioreactor is removably accomodated with a fluid containment system via said inlet port and said outlet port. 203. The bioreactor of claim 192, wherein a mixing diaphragm forms part of said chamber and is operably connected to at least one of a mixing actuator and a mixing drive. 204. The bioreactor of claim 203, wherein said mixing diaphragm is incorporated within said bioreactor. 205. The bioreactor of claim 192, wherein said bioreactor is operatively connected to at least one of an impact actuator and an impact drive. 206. The bioreactor of claim 192, wherein said chamber further supports physiological stimulation of resident cells and/or tissues. 207. The bioreactor of claim 192, further comprising a micro-loading diaphragm in operable connection with at least one of a micro-loading actuator and a micro-loading drive. 208. The bioreactor of claim 206, wherein said stimulation is performed by supplying an electric field. 209. The bioreactor of claim 192, wherein said bioreactor is operationally accommodated within a tissue engineering module comprising a fluid containment system affixed to a structural support and in fluid communication with said bioreactor, and wherein said fluid containment system comprises a plurality of flexible reservoirs connected by flexible tubing for supplying and retrieving fluid to and from said bioreactor. 210. The bioreactor of claim 209, wherein said tissue engineering module is accommodated within a housing of an automated tissue engineering system, said system comprising a microprocessor for operation with said module and wherein said microprocessor controls the functioning of said module. 211. The bioreactor of claim 192, wherein said bioreactor additionally comprises an optical probe. 212. The bioreactor of claim 192, wherein said bioreactor is sterilizable before use and disposable after use. 213. A method for the automated digestion of a tissue biopsy, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; providing tissue digestion enzymes within said bioreactor; and monitoring and maintaining digestion conditions within said bioreactor for a sufficient period of time for a desired level of tissue digestion. 214. A method for the automated proliferation of cells, said method comprising; seeding cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell proliferation. 215. A method for the automated differentiation of cells, said method comprising; seeding cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell differentiation. 216. A method for the production of a tissue construct, said method comprising; seeding cells onto a scaffold supported within a bioreactor, said bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor, and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for said cells to express extracellular matrix that provides structural support for the tissue construct. 217. An automated method for digesting a tissue biopsy to provide primary cells, including precursor cells, and further proliferating and differentiating the cells to enable the formation of a tissue implant, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; providing tissue digestion enzymes; monitoring and maintaining suitable digestion conditions within said bioreactor for a sufficient period of time to obtain disassociated cells; seeding the disassociated cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or, more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor, monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain the desired level of cell proliferation and expansion; releasing the expanded cells from the proliferation substrate or scaffold; seeding the expanded cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor, and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain a tissue implant. 218. A method for providing a skeletal implant, the method comprising; seeding osteogenic and/ or osteoprogenitor cells onto a porous scaffold of a bone biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the osteogenic and/ or osteoprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a tissue implant for orthopedic applications. 219. A method for providing a cartilage implant, the method comprising; seeding chondrogenic and/or chondroprogenitor cells onto a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor for assessment by a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the chondrogenic and/or chondroprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a cartilage implant. 220. A method for providing an implant for reestablishing the inner nucleus of a spinal disc, the method comprising; seeding nucleus pulposus cells within a scaffold a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow proliferation and/or differentiation of the nucleus pulposus cells and the expression of extracellular matrix components characteristic of the nucleus pulposus. 221. A method for washing cells, said method comprising: loading a cell suspension containing one or more undesired chemicals into a chamber, continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to said cells but permeable to said undesired chemicals to provide a washed cell suspension; and collecting the washed cell suspension. 222. A method for enrichment of cells, said method comprising: loading a cell suspension containing excessive cell suspension volume into a chamber; continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to the cells but allowing the excessive cell suspension volume to be removed and collected.
FIELD OF THE INVENTION This invention relates to devices, methods and systems for the automated culture, proliferation, differentiation, production and maintenance of tissue engineered products. Such systems, methods and products find use in various clinical and laboratory settings. BACKGROUND OF THE INVENTION Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. The disclosures of these references are hereby incorporated by reference into the present disclosure. During the past several years, researchers have developed and used different cell culture and tissue engineering techniques for the culture and production of various types of cellular implants. Such systems are described for example in U.S. Pat. Nos. 5,041,138, 5,842,477, 5,882,929, 5,891,455, 5,902,741, 5,994,129, 6,048,721 and 6,228,635. Bioreactor systems have also been developed for the culture of cells and cellular implants and are described for example in U.S. Pat. Nos. 5,688,687, 5,728,581, 5,827,729 and 6,121,042. The aforementioned methods and systems generally employ conventional laboratory culturing techniques using standard culture equipment for cell seeding of selected cell populations onto scaffolds. As such, the generated implants simply comprise proliferated cell populations grown on a type of biopolymer support where any manipulation of the cellular environment is limited to endogenous cell production of cytokines present in any standard cell culture, and application of shear and/or physical stresses due to circulation of cell culture media and physical manipulation of the support onto which the cells are seeded. The systems do not address nor are they capable of generating a tissue implant that comprises proliferated and differentiated cells representative of developing tissues in vivo and further integrated within a selected scaffold that can be successfully integrated in vivo. Moreover, known methods and systems are not capable of multi-functionally carrying out all of the steps of biopsy tissue digestion to yield disassociated cells, subsequent cell seeding on a proliferation substrate, cell number expansion, controlled differentiation, tissue formation and production of a tissue implant within a single automated tissue engineering system. This is primarily because known culture systems are not sophisticated in that they are not capable of automatically evaluating and manipulating the changing environment surrounding the developing implant such that cells progressively proliferate and differentiate into a desired implant. Furthermore, conventional culture methods and systems are labor intensive and suffer from the drawbacks of contamination and varying degrees of culturing success due to human error and lack of continual performance evaluation. Conventional culture systems require that most of the initial steps in the preparation of cells for seeding (i.e. tissue digestion, cell selection) is performed manually which is time consuming, unreliable in terms of the quality of the tissue produced, and prone to culture contamination problems. The systems are incapable of supporting the automated preparation of tissue engineered implants from primary or precursor cells due to inherent design limitations that restrict the cell and tissue culture process, the inability to adequately monitor and modify the environment to support tissue development, and the absence of techniques to enable the implementation of effective quality control measures. Thus, there remains a real and unmet need for an improved system for in vitro and ex vivo tissue engineering that can consistently meet the operational requirements associated with the different steps in the development and production of tissue engineered implants. Of particular importance is the ability to create functional tissue constructs where the cells present are active, differentiated and already expressing extracellular matrix. This involves more than, and is strikingly different to, the simple simulation of the mature in vivo environment present at the host site. This is because the preparation of functional de novo tissue fundamentally requires that the cells progress through a series of developmental stages as part of an ex vivo sequence. In order to address both clinical and research requirements, new devices, methods and systems have been developed that obviate several of the disadvantages and limitations of conventional ex vivo culturing techniques and systems. SUMMARY OF THE INVENTION The present invention is directed to a user-friendly automated system for cell culture and tissue engineering that can be used in a variety of clinical and research settings for both human and veterinary applications. As used herein, “tissue engineering” may be defined as “the application of principles and methods of engineering and life sciences toward fundamental understanding and development of biological substitutes to restore, maintain and improve tissue functions”. This definition is intended to include procedures where the biological substitutes are cells or combinations of different cells that may be implanted on a substrate or scaffold formed of biocompatible materials to form a tissue, in particular an implantable tissue construct. Furthermore, it is noted that the cells involved in the tissue engineering processes may be autologous, allogenic or xenogenic. The tissue engineering system of the present invention is designed to perform all activities under sterile operating conditions. The system is fully automated, portable, multifunctional in operation and performs/provides one or more of the following: sterile reception/storage of tissue biopsy; automated monitoring of digestion process digestion of biopsy tissue to yield disassociated cells; cell sorting and selection, including safe waste collection; cell seeding on or within a proliferation substrate or scaffold proliferation of cells to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of implantable tissue. The tissue engineering system of the present invention may be pre-programmed to perform each of the above noted steps, individually, sequentially or in certain predetermined partial sequences as desired and required. Furthermore, each of these steps, or any combination thereof, are accomplished within one or more bioreactors on a tissue engineering module. In operation, the tissue engineering system is pre-programmed and automatically controlled thus requiring minimal user intervention and, as a result, enhances the efficiency and reproducibility of the cell culture and/or tissue engineering process while minimizing the risks of contamination. The tissue engineering system of the invention and components thereof are operable under conditions of microgravity and/or zero gravity where such system and components are used for space research. The system of the present invention is designed such that primary or precursor cells can be isolated from a donor tissue for further propagation, differentiation and production of a tissue implant. Alternatively, cell lines may also be used either alone or in combination with other cell sources. In accordance with the invention, is an automated tissue engineering system, the system comprising a housing that supports at least one bioreactor that facilitates physiological cellular functions and the generation of tissue constructs from cell and tissue sources. The housing also supports a fluid containment system that is in fluid communication with the bioreactor. Associated with the housing and/or the bioreactor are sensors that monitor physiological parameters of fluid provided in the fluid containment system. A microprocessor disposed within the housing is linked to the bioreactor and the fluid containment system and functions to control their functioning. The microprocessor may also independently control environmental conditions within the system. In accordance with another aspect of the invention there is provided a system for cell and tissue engineering comprising portable, sterile tissue engineering modules having one or more bioreactors which provide the basis for tissue digestion, cell seeding on a proliferation substrate, cell proliferation, cell seeding on a differentiation scaffold, cell differentiation, and tissue formation with subsequent maturation into functional tissue for implantation. The bioreactor is operatively connected with a media flow and reservoir system for the delivery of reagents and the collection of waste fluids in a non-reflux manner. The bioreactor and/or the media flow system optionally include gas exchange components that utilize semi-permeable membranes to allow the transfer of gaseous products thereby controlling levels of dissolved gases in the media. The tissue engineering module operatively interacts with a central microprocessor controlled base unit that automatically monitors the progression of the cell culture or tissue engineering process and adjusts the environmental conditions to meet the requirements of the different stages of cell culture and tissue development within the bioreactor. Deviations from ideal conditions are sensed by a variety of sensors present within the bioreactor and the signals generated are monitored by the central microprocessor. As such, changes in environmental conditions such as but not limited to pH, temperature and dissolved gases can be automatically monitored and altered as required. In addition, the status of cell proliferation is indirectly assessed by detection of metabolic turnover as a function of time (e.g. pH, O2, CO2, lactic acid and glucose consumption). Further to the control of processing conditions by the central microprocessor, the tissue engineering module itself may optionally include a secondary onboard microprocessor that operates in unison with the central microprocessor. The tissue engineering module microprocessor expands the data processing capabilities of the tissue engineering system by performing specific functions directly onboard the tissue engineering module, thereby minimizing the demands on the central microprocessor. Various growth factors, cytokines, experimental agents, pharmaceuticals, chemicals, culture fluids and any combinations thereof may be loaded and stored within any of the reservoirs located on the tissue engineering module and automatically transferred to the one or more bioreactors according to a pre-programmed sequence or as required by the developing tissue implant. The individual tissue engineering modules are removable from the system for transport without compromising the sterility of the tissue engineered constructs present within the bioreactor. Such removal does not affect the processing of any other modules present within the tissue engineering system. Furthermore, the tissue engineering module may be considered to be disposable following the completion of a tissue engineering sequence, as this practice prevents contamination arising from prior use. In various embodiments of the invention, the device and system can be used to digest tissues obtained by surgical biopsy. In another embodiment, cells can be filtered and a particular population selected and isolated. In another embodiment, digested cells can be proliferated to expand the population of the cells. In still a further embodiment, cells can be seeded and cultivated on a desired scaffold or substrate (also referred to as a matrix). In yet a further embodiment, cells can be differentiated on and/or throughout a desired scaffold or substrate until suitable tissue formation is obtained. In yet a further embodiment, the tissue may be stimulated to promote tissue maturity. In yet another embodiment, a tissue implant is produced that is suitable for reconstructive surgery. In still a further embodiment, cell sampling can be done at each stage of cellular proliferation and developmental progression in a sterile manner without adverse effects on the culture itself. Each of the aforementioned embodiments can be done alone or sequentially as desired. Tracking of such processing events can be performed by the central microprocessor and/or the module-based microprocessor for incorporation into quality control records. In one aspect, the tissue engineering system optionally uses a synthetic biomaterial compound, Skelite™, described in Applicant's U.S. Pat. No. 6,323,146 (the contents of which are herein incorporated by reference) to enhance biological performance. Briefly, Skelite™ is an isolated bioresorbable biomaterial compound comprising calcium, oxygen and phosphorous, wherein a portion of at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 0.6 Angstroms. In one embodiment, Skelite™ may be used to enhance cell proliferation through its use as a coating on the walls of the bioreactor, as a thin film on the proliferation substrate, or as a three-dimensional and thereby high surface area proliferation scaffold The use of Skelite™ in the proliferation stage may be demonstrated to: increase the rate of proliferation; increase the cell yield following the proliferation step; reduce the surface area required for a target cell yield; reduce the problematic tendency of cell phenotype dedifferentiation during proliferation; and enhance the binding of growth factors to the proliferation substrate. In a further embodiment, Skelite™ may be used as a resorbable scaffold to enhance the differentiation of cells and the subsequent formation of tissue constructs. The use of Skelite™ in the differentiation stage may be demonstrated to: increase productivity by improving the reliability of the differentiation stage; increase the integrity and hence biological viability of the tissue construct; allow flexibility in construct configuration based on various scaffold formats; allow the stages of proliferation, differentiation and tissue formation to occur on a common substrate; enhance the binding of growth factors to the differentiation scaffold; and improve tissue construct handling properties during surgical implantation. In another aspect, the present invention provides a method and system for the preparation of tissue constructs through the automated steps of digestion, proliferation, seeding and differentiation of primary or precursor cells that originate from a patient thus eliminating immunological and disease transmission issues. An implant may be formed from the controlled cultivation of various cell types, including but not limited to chondrocytes, stromal cells, osteoblasts, nerve cells, epithelial cells stem cells and mixtures thereof. The system of the invention in an embodiment, incorporates one or more detachable, portable, and independently operable tissue engineering modules that support one or more bioreactors, media reservoirs and fluid/media flow system. Each module, and hence the bioreactor(s), is under the automated control of a central microprocessor. The module and associated bioreactor(s) may be configured for various specialized applications such as, but not limited to: sterile reception/storage of tissue biopsy; automated mixing and delivery of digestion reagents; automated monitoring of digestion process; digestion of biopsy tissue to yield disassociated cells; cell sorting and selection, including safe waste collection; cell washing and cell collection; cell seeding on or within a proliferation substrate or scaffold; automated mixing and delivery of proliferation reagents; proliferation of cells to expand cell populations; automated monitoring of cell conditions, including detection of confluence; controlled cell release from the proliferation substrate or scaffold; repeated proliferation steps on selected surface area sizes to increase cell numbers; channeling of cell population toward one or more tissue engineering scaffolds or matrices; cell seeding on or within the tissue engineering scaffold or matrix; automated mixing and delivery of differentiation reagents; automatic monitoring of cell/tissue culture conditions; cell differentiation to allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of cells and/or implantable tissue. When two or more bioreactors, are provided within the system either supported directly within the housing of the system or supported on a tissue engineering module insertable into the housing, the bioreactors may be provided connected in series and individually operable and controlled by the microprocessor or alternatively, may be operated and controlled independently depending on the user's programming of the microprocessor and the desired result to be achieved. Furthermore, when two or more bioreactors are provided within the system, the bioreactors and internal chambers may be connected such that there is an exchange of cells and/or tissues from bioreactor to bioreactor. The bioreactor can be manufactured in various sizes and configurations as required to support varying numbers and sizes of proliferation and differentiation scaffolds or substrates. The bioreactor may be incorporated as part of the structural components of the tissue engineering module. Alternately, the bioreactor may be detachable as a separate component to the remaining components of tissue engineering module. If present as a discrete component, the bioreactor may be packaged separately in a sterile package and joined to the tissue engineering module using sterile access techniques at the time of use. Furthermore, the sterile access techniques enable the bioreactor to be detached from the module, upon completion of the tissue engineering process, for easy transport to the operating room in preparation for the retrieval of a newly formed implantable tissue construct. The bioreactor and/or the tissue engineering module may be rotated or agitated within the overall tissue engineering system via control actuators. Rotation may enable the beneficial use of gravity to effect specific bioprocessing sequences such as sedimentation-based cell seeding and fluid exchange within the bioreactor. The tissue engineering module may be bar coded or provided with a memory chip for rapid and accurate tracking both within the tissue engineering system and externally as part of the clinical or experimental environment. Such tracking technology as incorporated within the tissue engineering device also enables electronic tracking via clinic-based information systems for patient records. This ensures that the tissue engineering module and hence the associated cells or tissue implants are properly coded to ensure administration to the correct patient and that the process is recorded for hospital billing purposes. The module and/or bioreactor may also utilize a bar code and/or memory chip in a similar manner for rapid and accurate patient and sample tracking. According to an aspect of the present invention is an automated tissue engineering system comprising; a housing; at least one bioreactor supported by said housing, said bioreactor facilitating physiological cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources; a fluid containment system supported by said housing and in fluid communication with said bioreactor, one or more sensors associated with one or more of said housing, bioreactor or fluid containment system for monitoring parameters related to said physiological cellular functions and/or generation of tissue constructs; and a microprocessor linked to one or more of said sensors. According to another aspect of the present invention is an automated tissue engineering system comprising; a housing; at least one tissue engineering module removably accomodated within said housing, said tissue engineering module comprising a support structure that holds at least one bioreactor, said bioreactor facilitating physiological cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources, a fluid containment system in fluid communication with said bioreactor, and one or more sensors for monitoring parameters related to said cell culture and/or tissue engineering functions; and a microprocessor disposed in said housing and linked to said tissue engineering module, said microprocessor controlling the operation of said tissue engineering module. According to a further aspect of the invention is portable and sterilizable tissue engineering module, the module comprising; a structural support holding at least one bioreactor, said bioreactor facilitating cell culture and tissue engineering functions; a fluid containment system in fluid communication with said bioreactor, and one or more sensors for monitoring parameters related to said cell culture and tissue engineering functions. In aspects of this embodiment, the bioreactor comprises a bioreactor housing having one or more inlet ports and one or more outlet ports for media flow and at least one chamber defined within said bioreactor housing for receiving cells and/or tissues and facilitating said cell culture and tissue engineering functions. The chamber may be selected from the group consisting of a cell culture/proliferation chamber, cell differentiation/tissue formation chamber, tissue digestion chamber and combinations thereof. Furthermore, the chamber houses one or more substrates and/or scaffolds. In embodiments of the invention, two or more chambers may be provided operably connected within the bioreactor and be operably connected. Alternatively, the two or more bioreactors may be independently operable or co-operatively operable. In still further aspects, the chambers and/or bioreactors are operably connected to provide for the exchange of fluids, cells and/or tissues between the chambers and/or bioreactors. The scaffold for use in the present invention is selected from the group consisting of a porous scaffold, a porous scaffold with gradient porosity, a porous reticulate scaffold, a fiberous scaffold, a membrane encircled scaffold and combinations thereof. Chambers may also be further subdivided into zones. For example, a differentiation/tissue formation chamber may be provided with a plurality of zones to contain several scaffolds. Funnels or similar passageways may be provided between chambers within a bioreactor. Furthermore, one or more filters may be provided at any location within a bioreactor. According to still another aspect of the present invention is a bioreactor that provides an environment for cell culture and/or tissue engineering functions selected from the group consisting of storage of tissue biopsy, digestion of tissue biopsy, cell sorting, cell washing, cell concentrating, cell seeding, cell proliferation, cell differentiation, cell storage, cell transport, tissue formation, implant formation, storage of implantable tissue, transport of implantable tissue and combinations thereof. According to still another aspect of the present invention is a bioreactor for facilitating and supporting cellular functions and generation of implantable tissue constructs, said bioreactor comprising; a bioreactor housing; one or more inlet ports and one or more outlet ports for media flow; at least one chamber defined within said bioreactor housing for facilitating and supporting cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources; and one or more sensors for monitoring parameters related to said cellular functions and/or generation of tissue constructs within said at least one chamber. In embodiments of the invention, the bioreactor housing comprises a lid, where the lid may be a detachable lid or integral with the bioreactor housing. Cells and tissues may be selected from bone, cartilage, related bone and cartilage precursor cells and combinations thereof. More specifically, cells suitable for use in the bioreactor, module and system of the invention are selected from but not limited to the group consisting of embryonic stem cells, adult stem cells, osteoblastic cells, pre-osteoblastic cells, chondrocytes, nucleus pulposus cells, pre-chondrocytes, skeletal progenitor cells derived from bone, bone marrow or blood, including stem cells, and combinations thereof. The cells or tissues may be of an autologous, allogenic, or xenogenic origin relative to the recipient of an implant formed by the cell culture and tissue engineering functions of the invention. According to another aspect of the invention is a tissue implant produced within a bioreactor of the present invention. According to yet another aspect of the present invention is a tissue implant produced by the tissue engineering system of the present invention. According to another aspect of the present invention is a tissue engineered implantable construct for repair of bone trauma wherein the implant comprises a porous scaffold of a bone biomaterial in combination with active bone cells and tissue engineered mineralized matrix. According to another aspect of the present invention is a tissue engineered implant comprising: a cartilage zone comprising tissue engineered cartilage that is devoid of any mineral-based scaffold; a bone biomaterial zone comprising a porous scaffold; and an interfacial zone between said cartilage zone and said bone biomaterial zone. The cartilage zone promotes lateral integration with the host cartilage while the bone biomaterial zone promotes lateral and vertical integration with the subchondral bone plate when implanted in vivo. The interfacial zone provides the structural union between the cartilage zone and the bone biomaterial zone. The cartilage zone may additionally incorporate a secondary non-mineral scaffold that assists with the formation of tissue engineered cartilage and allows for the development of a shaped surface profile in keeping with the particular anatomical characteristics present at the site of implantation. According to another aspect of the present invention is a method for digesting a tissue biopsy, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor providing tissue digestion enzymes; and monitoring and maintaining suitable digestion conditions within said bioreactor for a sufficient period of time for a desired level of tissue digestion. According to another aspect of the present invention is a method for the proliferation of cells, said method comprising; seeding cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell proliferation. According to another aspect of the present invention is a method for the differentiation of cells, said method comprising; seeding cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell differentiation. According to another aspect of the present invention is a method for digesting a tissue biopsy to provide primary cells, including precursor cells such as stem cells, and then proliferating and differentiating the cells to enable the formation of a tissue implant, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect and relay physiological conditions within said bioreactor to a microprocessor; providing tissue digestion enzymes; monitoring and maintaining suitable digestion conditions within said bioreactor for a sufficient period of time to obtain disassociated cells; seeding the disassociated cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain the desired level of cell proliferation and expansion; releasing the expanded cells from the proliferation substrate or scaffold; seeding the expanded cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect and relay physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain a tissue implant. According to another aspect of the present invention is a method for providing a skeletal implant, the method comprising; seeding osteogenic and/or osteoprogenitor cells onto a porous scaffold of a bone biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the osteogenic and/or osteoprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a tissue implant for orthopedic applications. According to still another aspect of the invention is a method for providing a cartilage implant, the method comprising; seeding chondrogenic and/or chondroprogenitor cells onto a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor, and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the chondrogenic and/or chondroprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a cartilage implant. According to still another aspect of the invention is a method for washing cells, the method comprising: loading a cell suspension containing one or more undesired chemicals into a chamber; continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to said cells but permeable to said undesired chemicals to provide a washed cell suspension; and collecting the washed cell suspension. According to yet another aspect of the invention is a method for enrichment of cells, the method comprising: loading a cell suspension containing excessive cell suspension volume into a chamber; continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to the cells but allowing the excessive cell suspension volume to be removed and collected. According to yet another aspect of the invention is a method for providing an implant for re-establishing the inner nucleus of a spinal disc, the method comprising; seeding nucleus pulposus cells within a scaffold a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow proliferation and/or differentiation of the nucleus pulposus cells and the expression of extracellular matrix components characteristic of the nucleus pulposus. According to still a further aspect of the present invention is a method for the preparation of quality assessment samples for use in clinical tissue engineering, said method comprising; parallel preparation of primary and secondary implants using the system of the invention as described herein, where the primary implant is for implantation and one or more secondary implants are for testing purposes to infer the calibre of the primary implant. The tissue engineering system of the present invention in various embodiments is under the control of one or more microprocessors that may be preprogrammed in order that the user can select a specific type of environment (or sequence of environments) within the bioreactor such as tissue digestion, cell proliferation, cell differentiation and/or tissue construct formation. This eliminates operator intervention and reduces the possibility of inadvertent contamination. The tissue engineering system of the invention can be provided as a “kit”. In this manner the device, tissue engineering module(s), bioreactor(s) and various components thereof can be packaged and sold together along with instructions and quality control techniques. The system of the present invention is ideal for clinical use in hospitals, and in particular surgical settings where due to trauma and/or disease, a tissue-engineered implant is desired. Using the present system, tissue engineered implantable constructs can be safely prepared from autologous tissue obtained via patient biopsy, allogenic cells or xenogenic cells. The specifications of such tissue engineered implantable constructs can be matched to the type, size and condition of the implantation site. Furthermore, the implant as generated by the present system contains active cells that promote integration with the host thereby improving patient recovery. In practice, using an autologous cell model, a tissue biopsy can be obtained from the patient and placed directly into the bioreactor present on the tissue engineering module while in the operating room. A specific bioreactor design is selected depending on the type and size of the tissue construct desired. At the completion of the tissue engineering process, the tissue construct produced can be transported still contained in the sterile bioreactor to the operating room for implantation back into the patient. The system is ideal for providing “customized” autologous tissue implants in a safe and therapeutically effective manner. The system and methods of the present invention are not limited to providing automated cell culture techniques. The tissue engineering system described moves well beyond the cell expansion used in cell therapy. The tissue engineering system may be used to create functional tissue constructs where the cells present are active, differentiated and already expressing extracellular matrix. Consequently, the tissue constructs so produced are in a high state of development and thereby accelerate the rate and improve the quality of tissue repair at the implant site. The system of the invention is also suitable for pharmacological research. Specifically, the system finds use in the area of drug development. New potential drugs and molecules can be tested on cells and tissues to determine effects on cellular events and tissue development. Such testing can be done on a patient's own cells/tissues to assess and possibly avoid adverse side effects prior to administration. Alternatively, specialized cell lines or tissues can be used with the system as a key tool in the drug discovery process. The system can be programmed to monitor and assess various physiological conditions of the cells/tissues present within the bioreactor and thus provide a fast indication of the biological effects of a selected drug or molecule. The system may also be used for research and development studies where conventional tissue engineering techniques are difficult to use and practice, and/or in conditions requiring extensive diagnostic recording. For example, microgravity studies involving tissue engineering are difficult to conduct due to the unique properties of this environment. Traditional cell and tissue culture techniques are simply not viable in this environment due to fluid containment issues and the absence of gravity-based transport of cells. The system and methods of the invention are easily adaptable to the microgravity environment as the system is completely sealed to prevent fluid loss and the migration of cells as part of the tissue engineering process can be achieved by controlled fluid flow. Other features and advantages of the present invention will become apparent from the following detailed description, examples and drawings. It should be understood, however, that the detailed description, specific examples and drawings while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from said detailed description. BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be further understood from the following description with reference to the figures, in which: FIG. 1 illustrates a general methodology for clinical tissue engineering as applied to the example of cartilage repair using autologous chondrocytes; FIG. 2 shows an integrated tissue engineering device of the present invention; FIG. 3 shows a further embodiment of the tissue engineering device of FIG. 2; FIG. 4 shows a further embodiment of the tissue engineering device of FIG. 2; FIG. 5 shows a cut-away view of the tissue engineering device of FIG. 2 illustrating some of the internal components and a tissue engineering module for insertion into the device; FIG. 6 shows an enlarged cut-away view of the tissue engineering device of FIG. 2 illustrating an inserted tissue engineering module; FIG. 7 shows an enlarged perspective view of the tissue engineering module and interface with components of the device housing; FIG. 7(a) shows an enlarged perspective view of the bioreactor and pump unit; FIG. 7(b) shows an enlarged perspective view of the pump unit and the associated pump tubing; FIG. 8 shows a perspective view of the reverse side of the tissue engineering module of FIG. 7 and the internal configuration of the flow plate that attaches thereto; FIG. 9 shows an enlarged perspective view of the mixing and micro-loading components associated with the instrumented bioreactor design; FIG. 10 shows the basic tissue engineering fluid flow schematic; FIG. 11 shows a further embodiment of the basic tissue engineering fluid flow schematic; FIG. 12 shows alternate bioreactor, proliferation substrate or scaffold, differentiation scaffold and process monitoring designs, as applicable to different tissue engineering scenarios; FIG. 13 shows an enlarged perspective view of the bioreactor of the tissue engineering module, illustrating the internal configuration of the bioreactor and the flow path of fluids; FIG. 14 shows a further embodiment of the bioreactor of the tissue engineering module, illustrating the internal configuration of the bioreactor; FIG. 15 shows a rotatable bioreactor design; FIG. 16 shows the sterile sampling embodiment of the tissue engineering module; FIG. 17 shows a further embodiment of the tissue engineering fluid flow schematic; FIG. 18 shows yet a further embodiment of the tissue engineering fluid flow schematic; and FIG. 19 shows a bioreactor design suitable for tissue digestion and cell collection; FIG. 20 shows a bioreactor design suitable for cell proliferation; FIG. 21 shows a bioreactor design suitable for cell differentiation and tissue construct formation; FIG. 22 shows yet a further embodiment of the tissue engineering fluid flow schematic; and FIG. 23 shows a further embodiment of the tissue engineering module with separate bioreactors for tissue digestion/cell collection, cell proliferation, and cell differentiation/tissue formation. DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to an integrated, automated tissue engineering device for the ex vivo processing of cells, particularly autologous cells, to enable cell proliferation, cell differentiation and tissue formation in an efficient and consistent manner requiring minimal human intervention. The tissue constructs developed within the device may be integrated into a host to assist in tissue reconstruction procedures and subsequent patient recovery. Furthermore, the invention provides automated methods for tissue engineering using a variety of cells from a number of different sources (for example autologous cells obtained via patient biopsy, allogenic cells or xenogenic cells). Furthermore, the cells may be precursor cells, primary cells, cells from an immortal cell line and combinations thereof. The general methodology and principle for clinical tissue engineering incorporating the tissue engineering system and methods of the present invention is illustrated in FIG. 1, using autologous cartilage tissue engineering as a representative example. In such example, cells (i.e. chondrocytes) are obtained from a surgical biopsy of a patient and either manually or automatically seeded onto a suitable substrate or scaffold (i.e. a Skelite™ support). The chondrocytes and the support are present within the bioreactor portion of an automated tissue engineering module, with the module forming part of a clinical base station of the tissue engineering system. A central microprocessor is present within the tissue engineering system and controls and customizes the internal environment of the bioreactor, and hence facilitates tissue growth therein, resulting in the stimulation of cell growth within and onto the support to generate an implant. Sensors within the bioreactor provide feedback to the microprocessor to ensure that the cells are seeded, expanded and differentiated in a desired and controlled manner to provide an autologous tissue implant. Once the implant is generated, it is removed from the bioreactor for surgical implantation into the patient. The present system provides an advantageous way to provide autologous tissue engineered implants in a sterile, safe, convenient and efficacious manner. Furthermore, the ability to prepare tissue engineered implants in a clinical setting allows considerable flexibility in the locations for undertaking the tissue engineering process. While the system can be used in a centralized location, the design and operation of the system enables clinical use at regional centers. Such widespread availability precludes the transportation of biological material to and from centralized cell/tissue processing facilities, thereby improving the cost effectiveness and efficiency of the tissue engineering process while avoiding shipment, tracking and regulatory complications. In accordance with an embodiment of the present invention is a tissue engineering system as shown in FIG. 2 and generally indicated with reference numeral 100. The system 100 (may alternatively be referred to as a device) comprises a housing 102 having an insertion slot 104 for receiving a tissue engineering module. The insertion slot 104 has a movable door 106 and a locking mechanism 108. A user interface 110 such as a touch screen, key pad or combination of both is provided for control of system operation and for the display of system status. A data storage system 112 is present which permits the recording of information via a variety of mediums known to those of skill in the art (i.e. ZIP, CDROM, diskette, flashcard). A computer/communications link 114 provides the capability to upload new software, modify control parameters using an external computer, download data as well as troubleshoot and test the device. This link also permits the system to be connected to electronic information systems present at the clinic. The system 100 is powered with a power input 116. FIG. 3 shows a further embodiment of the system 100 having several bay doors 106 to accommodate several tissue engineering modules. FIG. 4 shows a further embodiment of the system 100 having bay doors 106 orientated in a horizontal manner to allow for the preferential orientation of the tissue engineering module relative to the gravity vector. FIG. 5 shows the internal configuration of the system 100 represented in FIGS. 2 and 3 with the vertical orientation of the bay doors for vertical insertion of a tissue engineering module. A tissue engineering module 118 is shown for insertion within the insertion slot 104 of the bay door 106. The tissue engineering module 118 slides into the system housing 102 via a guide rail system 120. Upon insertion, the module 118 engages with one or more pump units 122 (i.e. peristaltic, piston, diaphragm or rotary), electrical connectors 124 (i.e. DIN, AMP, PCB, breadboard socket), and valve actuators 126 (i.e. servo motor, linear drive, linear actuator). Any suitable guide system to allow the module to be inserted properly into the system may be contemplated as is understood by one of skill in the art. As better seen in FIG. 6, where the tissue engineering module 118 is inserted into the housing 102, a series of valve actuators 126 interface with valves (shown in more detail in FIGS. 7 and 7a) on the module to provide flow control. The electrical connectors 124 provide electrical connection between the module 118 and a central microprocessor unit (CPU) 128 via an electronic back-plane 130. The CPU 128 controls the operational sequence, the transport of fluids and gases, the management of process data, the monitoring of system status, the user interface, and the external data communication port. The CPU 128 provides control through electrical links with active and passive electrical components present on the back-plane 130 and each of the inserted tissue engineering modules 118. Temperature sensors 132 (i.e. thermocouple, RTD or thermistor), gas sensors 134 (i.e. O2 and CO2) and an environment control unit (ECU) 136 are controlled by the CPU 128 to maintain the environment (i.e. temperature and gas atmosphere) within the housing 102 using standard methods known to those skilled in the art. The environment can be adjusted to meet the requirements of the tissue engineering process, including storage of reagents at refrigeration temperature (i.e. 4° C.), the simulation of nominal body temperature (i.e. 37° C.), and the availability of gaseous mixtures for transport into and out of the module 118 in the event that the module is equipped with gas exchange components (i.e. membranes). Gaseous conditions are monitored by the gas sensors 134 located within the housing 102 and the data is sent to the CPU 128 via the electronic back-plane 130. Gas input(s) to the ECU can be via gas supply inlet 140 provided within the housing 102 configured with standard fittings. In other embodiments, gases may be housed within the ECU. Gases for use within the device include but are not limited to oxygen, carbon dioxide, nitrogen and mixtures thereof. In order to adequately contain such gases within the housing 102, the bay door 106 is configured to provide for a hermetic seal when closed. The housing 102 is insulated with insulating material 142 such as styrofoam, aerogel, fiberglass and the like to allow for the efficient regulation of internal temperatures (i.e. 4° C. to 37° C.). While the tissue engineering system of the present invention is generally shown to comprise a boxed shaped housing, it is understood by one of skill in the art that the housing may be made of various configurations so long as it may accommodate the components as described herein. For example, this includes but is not limited to open configurations that may not require a top and/or side portions. The tissue engineering module 118 is illustrated in more detail in FIGS. 7-9. The tissue engineering module 118 comprises a rigid structural spine 200 to which is affixed a bioreactor 202. The bioreactor 202 comprises a bioreactor housing that has a lid 204 and may be customized with respect to the substrate(s) or scaffold(s) contained therein to enable tissue digestion, cell culture, cell proliferation, cell differentiation, tissue implant formation and combinations thereof. The bioreactor lid may be detachable or alternatively made integral to the bioreactor housing. The bioreactor 202 may be separately detachable and disposable relative to the structural spine 200. To enable such detachment, the bioreactor 202 and the structural spine 200 may use fluid disconnect fittings that include the provision for self sealing of input and output lines to avoid loss of fluids and to prevent contamination of the contents of the bioreactor. The entire tissue engineering module may be considered to be disposable following the completion of a tissue engineering sequence, as this practice prevents contamination arising from prior use. Alternately, only selected components of the module 118 may be considered as disposable due to contact with fluids, leaving non-contamination prone components available for re-use. As seen in FIGS. 7, 7a and 7b, a fluid containment system 206 is affixed onto the structural spine 200 of the tissue engineering module 118. The fluid containment system 206 is comprised of a sterile series of flexible reservoirs 208 and flexible tubing 210 for supplying and retrieving types of tissue and cell culture fluids and pharmaceuticals to and from the bioreactor 202. The reservoirs 208 may be of varying configuration and number as required and may contain different types of cell and tissue culture media, growth factors, pharmaceutical agents and may also contain waste media and/or media samples from the bioreactor 202. Fluids are loaded or removed from the fluid containment system 206 via a series of fluid access ports 212. Tubing 210 is present to provide fluid connection between the various reservoirs 208 and the fluid control components, such as the fluid flow control valves 214. The fluid flow control valves 214 are opened and closed by valve actuators 126. Similarly, the pump unit 122 interfaces with disposable pump components present on the module. These pump components may be pistons, diaphragms, rotary elements or peristaltic tubing 218, provided that the operation of these components does not generate harsh conditions, such as excessive shear stress, that compromise cell viability during the transfer of cell suspensions. The pump unit 122 and the valve actuators 126 reside within the housing 102. Alternately, the actuators and pump unit may form part of the tissue engineering module, however, this may result in disposal of these components following patient use. Fluid is transferred out of the reservoirs 208 by the programmed action of the pump unit 122 on the pump tubing 218. Fluid travels from a flexible fluid reservoir 208 to a fluid valve 214 via tubing 210. A fluid flow plate 220 (as shown in FIG. 8) directs fluid flow between different flow control valves 214 and the pump tubing 218 of the pump unit 122. Fluid is returned to a selected empty reservoir 208 for storage. A flexible printed circuit board (PCB) 222 provides the electronic interface for electronic components (i.e. sensors) present on the structural spine 200 and/or the bioreactor 202. In the event that a sensor indicates that a monitored parameter (e.g., pH) is outside acceptable levels, the CPU triggers a control intervention such as replacing the media within the bioreactor. The tissue engineering module may optionally include a microprocessor 224 to enable data processing and data storage directly on the module. This information may transferred to the central CPU 128 while the module is inserted into the housing 102 and retained in electronic memory for later access once the module is removed. In addition to the data stored via the microprocessor or memory chip resident on the tissue engineering module, the module may also optionally include a bar code 226, magnetic strip 228, electronic memory (not shown) and/or ID label 230 to facilitate administrative tracking within the clinic. As seen in FIG. 8, the fluid flow plate 220 is secured to the 25 structural spine 200 of the tissue engineering module 118. The technique for attachment of the fluid flow plate may be, but is not limited to, a press fit, snap fit, ultrasonic weld, solvent bond and the like, recognizing that the technique adopted must allow for sealing of the assembly to avoid loss of fluids and to prevent contamination. As shown in the disassembled view in FIG. 8a, the fluid flow plate 220 has an integral fluid pathway 232 to provide a means for directing flow associated with the actuation of the fluid valves 214. New flow paths may be accommodated via revisions to the pathway present on the flow plate 220. In one embodiment, the fluid plate 220 may be integrally formed into the structural spine 200 to form a single component. A fluid heating and mixing chamber 234 is included to ensure fluids that are directed to the bioreactor are at the correct temperature and are adequately mixed so as to not disrupt the biological processes underway in the bioreactor. Furthermore, a thermoelectric element 236 is present on the tissue engineering module 118 to vary the temperature within the bioreactor 202 compared with the operational temperature of the module, as defined by the operation of the ECU 136. Such a temperature change may be necessary to simulate nominal physiological conditions within the bioreactor, while the remaining components of the tissue engineering module, particularly the reagents and/or samples, are at a reduced temperature (i.e. refrigeration) to maintain physical, chemical and/or biological viability. Power and control of the thermoelectric element is performed by the CPU 128. In addition to sensors present on the bioreactor, a sensor 238 present on the tissue engineering module provides feedback to the CPU 128. The sensor and thermoelectric connections are made via the electrical cabling 240 and connector 124. FIG. 9 shows the mixing and micro-loading aspects of the tissue engineering module 118. The bioreactor 202 has a mixing drive 260 operably connected with a mixing actuator 262 and to the mixing diaphragm 264. The mixing diaphragm is incorporated as part of the bioreactor 202 or the bioreactor lid 204, as shown. In operation, the mixing drive 260 in combination with the mixing actuator 262 provide translation or pulsing of the mixing diaphragm to effect controlled mixing of the contents of the bioreactor 202. Ideally, the nature of the mixing is such to avoid high fluid shear that could compromise the physical integrity of cells present within the bioreactor. For certain tissue engineering protocols, moderate levels of fluid shear are actually beneficial for the successful development of tissue constructs. In addition to the mixing components, an impact drive 266 and impact actuator 268 are present. These components serve to apply a controlled impact to the bioreactor assembly at the conclusion of the proliferation sequence to assist with the release of cells from a proliferation substrate or scaffold resident within the bioreactor. Also provided is a micro-loading drive 270 in operable connection with a micro-loading actuator 272 and micro-loading diaphragm 274. The micro-loading diaphragm 274 is incorporated as part of the bioreactor 202 or the bioreactor lid 204, as shown. The location and orientation of the micro-loading diaphragm is such to enable intimate contact with the substrate or scaffold and any associated cells or tissues present in the bioreactor 202. The application of micro-loads is known to be advantageous for certain tissue engineering protocols. The mixing drive 260, impact drive 266, and micro-loading drive 270 may be any of a series of electromechanical devices such as solenoids, linear drives, rotational drives, or piezo electric components. Furthermore, it is possible for the mixing drive 260, impact drive 266, micro-loading drive 270, and the related actuators to be mounted on the housing 200. Alternatively, the drives and actuators may be mounted on the tissue engineering module or the bioreactor provided that the design of the drives is consistent with the disposable nature of the tissue engineering module. In addition to the provision of mechanical stimulation, the bioreactor may also be configured to introduce electrical and/or chemical stimulation of the tissue construct. In particular, electric fields may be generated in the region of the bioreactor to enhance cell transport and/or tissue formation. Methods of generation of electric fields are known to those of skill in the art and include but are not limited to the provision of electric coils. FIG. 10 illustrates a basic fluid flow schematic for the tissue engineering module 118 in which there is a single cell or tissue culture chamber present within the bioreactor 202, (refer to descriptions of FIGS. 12 and 17 for further information on the multi-chamber bioreactors). The flow path links the bioreactor 202 to reservoirs 208 that supply fluid and collect waste. The fluid access ports 212 may be used to load reagents or remove samples or waste fluid. Flow is generated by the operation of pump unit 122 with flow direction defined by actuation of specific flow control valves 214. Perfusion to the bioreactor can be either continuous or pulsatile, provided that the associated flow does not result in high fluid shear in regions containing cells, as such conditions could damage the cells or an emerging tissue construct. A recirculation loop 280 is provided to allow the fluid contents of the bioreactor to be either monitored or modified by external components, such as an in-line gas exchange membrane 282, without necessitating the delivery of new fluid from the fluid reservoirs 208. Components of the tissue engineering module 118 dedicated to storing fluids, (i.e. reservoirs 208), are kept refrigerated at approximately 4° C. to facilitate storage of fluids that would otherwise degrade at the elevated temperatures used to simulate body temperature (i.e. 37° C.). According to a preprogrammed routine, the CPU 128 controls the operation of fluid valve(s) 214 to allow fluid stored in a reservoir 208 to be delivered via the pump unit 122 into a heating and mixing chamber 234 prior to entry into the bioreactor chamber 300 (shown in detail in FIGS. 13, 14 and 15). Fluids are supplied to the bioreactor via the inlet port 302 and removed via outlet port 304. To simulate normal body temperatures for optimal cell and tissue culture performance, the bioreactor 202, the pump unit 122 and the heating and mixing chamber 234 are maintained at approximately 37° C. by the operation of a thermoelectric element 236. It will be obvious to one skilled in the art that alternate thermal regulation devices may be used to obtain the desired thermal profiles for the tissue engineering module 118. FIG. 11 illustrates a variation on the basic fluid flow schematic where the fluid flow control valves are substituted for multiple pump units 122. This configuration provides enhanced operational redundancy and a reduced component count. Operation of such a system requires that any dormant pump unit prevents unregulated pass-through flow, as such an occurrence would compromise the controlled delivery of fluids. FIGS. 12a-12d illustrate various bioreactor configurations and alternate formats for the substrates and scaffolds used for the proliferation and differentiation steps involved in the operation of the tissue engineering system. FIG. 12a shows a series of interchangeable bioreactor designs that address different bioprocessing scenarios. The Type I scenario is indicative of a basic single chamber 300 within a bioreactor 202 that accommodates a proliferation scaffold or substrate 310, or a differentiation scaffold or substrate (not shown) and is ideally suited to either proliferation or differentiation. Cells are either manually seeded onto the scaffold 310 or automatically delivered via the fluid pathway of the tissue engineering module. The Type II scenario involves a multi-chamber bioreactor that provides for the use of a scaffold 310 (or substrate) for proliferation of the cell population and an implantable differentiation scaffold 312 that promotes the formation of a tissue construct. The culture/proliferation chamber 300 is connected to the differentiation/tissue formation chamber 306 via a funnel 314. The funnel serves to channel the cells released from the proliferation scaffold 310 into the implantable differentiation scaffold 312. The use of a filter 316 in several locations within the bioreactor serves to regulate the size of the cells or cell aggregates that can freely pass from one chamber to the next. A filter 316a is present upstream of the proliferation scaffold with the purpose of regulating the incoming cell population for the cell expansion step. Another filter 316b is present upstream of the differentiation scaffold again to control the cell population entering this step of the tissue engineering sequence. In addition, there is a further filter 316c over the outlet port 304 to prevent the loss of cells from the differentiation/tissue formation chamber during operations involving fluid transfer through the bioreactor. The filter 316 can be a filter membrane or mesh or similar type filtering material as is known to those of skill in the art. The Type III scenario combines tissue digestion with subsequent proliferation, differentiation and tissue construct formation. In this scenario, a tissue biopsy 320 is loaded into a digestion chamber 322 present within the bioreactor 202. Digestion of the tissue biopsy occurs through the delivery of digestion enzymes into the bioreactor from one of the fluid reservoirs 208 present on the tissue engineering module. Disassociated cells exit the digestion chamber 322 under the influence of gravity sedimentation and/or fluid flow through the culture/proliferation chamber 300, and subsequently collect on the proliferation scaffold 310. Transfer of tissue aggregates out of the digestion chamber 322 is precluded by the presence of a filter membrane/mesh 316a in the flow path between the digestion chamber 322 and the culture/proliferation chamber 300. Following proliferation, the cells are released and transferred to the implantable differentiation scaffold 312 via the cell funnel 314. Again, membrane/mesh filters are present both upstream 316b and downstream 316c of the implantable differentiation scaffold 312 to ensure that the correct cell population are seeded on the scaffold and that cells are not inadvertently lost to waste during fluid transfer operations. In the preceding scenarios, various configurations of the proliferation substrate 310 or scaffold are possible, as illustrated for example in FIG. 12b. For example, one configuration is a porous scaffold 310a having a relatively even pore gradient. A pore gradient scaffold 310b is a porous scaffold having a pore gradient where the pore size decreases as cells travel through the scaffold. This promotes a more homogeneous distribution of cells throughout the scaffold at the conclusion of the cell seeding process. A pore gradient scaffold with reversed orientation 310c may be used. Alternatively, a fiber filter scaffold 310d, may be used which is a fibrous matrix typical of organic compounds such as collagen. It is also possible to utilize a contained suspension of micro-carriers (e.g. Cytodex™) as the proliferation substrate. Furthermore, the bioreactor may have an optical probe 324 (shown in conjunction with the porous scaffold 310a) supported by the CPU 128 to enable the inspection of the cell seeding process occurring within the proliferation scaffold and to further assess the proliferation events, particularly progress toward attaining a confluent cell layer. As with proliferation, there are a variety of implantable differentiation scaffolds 312 that may be formed in differing configuration and of diverse materials (i.e. inorganic mineral-based scaffolds such calcium phosphate, organic biopolymer scaffolds such as collagen, etc.) and employed in the tissue engineering process. FIG. 12c illustrates a multi-zone differentiation/tissue formation chamber 306 that comprises up to three implantable differentiation scaffolds 312, all of which may simultaneously proceed toward tissue construct formation. This allows for the preparation of different sizes of implantable tissue and for the use of alternate implantable differentiation scaffolds to assess and maximize tissue yield. For example, scaffold 312a is a porous reticulate formed from a bone biomaterial such as Skelite™ for use in bone and cartilage applications where the tissue construct requires hard tissue anchoring within bone. The scaffold 312a may be further enhanced through the use of a scaffold membrane/mesh 326 that encircles the implant to create a membrane encircled scaffold 312b such that the loss of cells out of the scaffold 312a during the cell seeding process is minimized, thereby making the tissue engineering process more efficient. The membrane may preferably only partially encircle the scaffold or alternatively, more fully encircle the scaffold. While the primary purpose of the scaffold membrane/mesh 326 is to contain the cells on and within the implantable differentiation scaffold 312, careful selection of the properties of the scaffold membrane/mesh 326 as is understood by one of skill in the art either allows or limits the passage of specific molecular entities that may have a marked influence on the tissue engineering process at the cellular level. A further embodiment is a gradient porosity and membrane encircled scaffold 312c that combines the advantages of the scaffold membrane/mesh 326 with a pore gradient. The gradient is configured to deliberately cause the cells to collect on the top surface with only minimal propagation into the scaffold. A degree of porosity in the surface is considered advantageous for tissue stability and for the supply of nutrients to the developing tissue via the scaffold surface. This approach results in the development of a bipolar tissue construct with distinct stratified zones. The top zone is essentially comprised of de novo tissue. The bottom zone is essentially free of cells or tissue and remains as an open porous scaffold. The middle interfacial zone represents the structurally stable transition between the open scaffold and the de novo tissue layer. Such a bipolar tissue construct is ideal for the repair of focal defects in articular cartilage as the top layer is tissue engineered cartilage that provides for lateral integration with the host cartilage, while the bottom layer provides for lateral and axial integration with the subchondral bone. Integration of the bottom layer with the surrounding subchondral bone may be further enhanced by the application of bone marrow to the open scaffold at the time of surgical implantation. In cartilage repair applications, it is important that the mineral-based scaffold does not extend to the articular surface, as this may compromise joint function. Accordingly, a secondary non-mineral scaffold (not shown in the figures) may be employed in the top zone of de novo cartilage to assist with the formation of tissue constructs of sufficient size to treat large cartilage lesions (i.e. up to 10 cm2 in diameter and 2-3 mm in thickness). Furthermore, the secondary scaffold can be configured to generate shaped constructs that have articular surface profiles that more closely match the particular anatomical characteristics present at the site of implantation. Candidate materials for the secondary scaffold are synthetic biopolymers (e.g. PGA, PLA) or natural biopolymers (e.g. alginate, agarose, fibrin, collagen, hyaluronic acid). These secondary scaffolds may be in the form of hydrogels or three-dimensional preformed scaffolds. Alternate techniques for the preparation of bipolar tissue constructs are possible within the tissue engineering system. The implantable differentiation scaffold 312 may be partially infiltrated with a bioresorbable polymer that limits cell seeding to certain regions of the scaffold. This creates a preferential zone of new tissue formation during the preparation of the tissue construct. Upon implantation, the polymer is resorbed thereby leaving voids in the porous scaffold that promote anchorage within the host tissue. A further configuration involves an implantable scaffold with relatively open porosity that is positioned away from the exit of the differentiation/tissue formation chamber. During cell seeding, this open space provides for the collection of cells that migrate through the open scaffold. As cells are accumulated within the differentiation/tissue formation chamber, both the open space and a portion of the scaffold become infiltrated with cells and thereby create a preferential zone of new tissue formation. The resulting tissue construct comprises a de novo tissue zone that is devoid of the scaffold, a middle transition zone or interfacial zone containing both de novo tissue and the scaffold, and a region of the porous scaffold that is open and essentially free of cells or tissue. FIG. 12d illustrates a bioreactor monitoring scheme whereby sensors 216 (i.e. temperature, pH, dissolved gases, etc) are integrated into the lid 204 of the bioreactor 202 to provide feedback to the CPU 128 of the progress of the tissue engineering process. In addition, a CCD camera 330 may be employed to monitor the optical properties of the proliferation scaffold 310 (or substrate) for evidence of impending confluence (e.g. optical density and/or light scattering as a function of cell density) such that cell release is timed to maximize the cell yield from the proliferation step. FIG. 13 better shows the flow path and fluid circulation within the bioreactor 202. The bioreactor 202 is shown to have an inlet port 302, an outlet port 304 and an internal cavity defining a basic chamber 300. Fluid flows from the fluid flow plate 220 into the bioreactor 202 via the inlet port 302 and exits through the outlet port 304. The bioreactor lid 204 attaches to the bioreactor 202. A variety of different mounting hardware may be used to hold the bioreactor lid 204 and bioreactor 202 together. The chamber 300 may be designed to accommodate one or more substrates or scaffolds 310. Furthermore, the bioreactor 202 may be subdivided into separate chambers that permit the steps of tissue digestion, proliferation, differentiation, and tissue formation. Each chamber may be configured with inlet and outlet ports that are independently controlled via flow control valves for greater control over the tissue engineering sequence. Circulation of fluid is effected by the activation of one or more flow control valves 214 and the pump unit 122, based on control signals from the CPU 128. Depending upon the specific valves activated, operation of the pump unit 122 moves fluid from one of the fluid reservoirs 208 into the bioreactor 202 or permits recirculation of the fluid within the bioreactor. For biological processes that require stable dissolved gas concentrations, recirculation is advantageous as it enables the fluid to be passed across a membrane that facilitates gas exchange. The nature of the exchange is based on the dissolved concentrations in the bioreactor versus the external conditions established by the ECU 136. The bioreactor lid 204 is shown to have a sampling port 332 and sensor probes 216 that are operably connected to the interior chamber of the bioreactor. Alternatively, the sampling port may be provided elsewhere on the bioreactor housing. The sampling port allows the removal or addition of materials into and out from the bioreactor. The sampling port may be replaced or augmented with a gas exchange membrane as required. FIG. 14 illustrates a multi chamber bioreactor 202 with the bioreactor lid 204 removed for clarity. The inlet port 302 is connected to a tissue digestion chamber 322. The configuration of the tissue digestion chamber 322 permits a patient biopsy to be loaded into the bioreactor for subsequent automated digestion to yield disassociated cells. The circulation path within the digestion chamber promotes the gentle agitation of the biopsy to prevent stagnant areas that could potentially lead to excessive exposure of the biopsy tissue to circulating digestion enzymes. Furthermore, the inlet and/or outlet of the digestion chamber may house a filter membrane/mesh 316 (not shown) of varying porosity to provide for cell sorting and to preclude the release of partially digested tissue aggregates. The bioreactor contains a second chamber 300 that accommodates a proliferation substrate or scaffold 310 for receiving cells for proliferation. The proliferation scaffold may be formed in various geometries that support both two-dimensional and three-dimensional proliferation, and may be comprised of various biocompatible materials that promote cell proliferation, such as calcium phosphate biomaterials (for example Skelite™), biopolymers, or natural matrices (for example collagen). Cells delivered from the tissue digestion chamber 322, or via the optional cell inoculation port 334, become dispersed on or within the proliferation substrate or scaffold 310 and proliferate, thereby increasing the cell population for subsequent cell differentiation and tissue formation. Note that the process may be terminated following proliferation if the goal is to only expand the cell population without further differentiation. An implantable differentiation scaffold 312 is present within a differentiation/tissue formation chamber 306 at the base of the bioreactor 202. As with the proliferation scaffold 310, the implantable differentiation scaffold 312 may be formed in different geometries and may be composed of a variety of biocompatible materials that are properly selected to meet the biological requirements of the implant site, (for example Skelite™ is an ideal candidate implant for skeletal sites). In operation, cells are released from the proliferation substrate or scaffold 310 through an automated sequence, such as the delivery of enzymes (for example trypsin) and the timed application of impact to the bioreactor via the impact drive 266 (not shown). The cell suspension migrates under the controlled flow conditions present in the bioreactor into the implantable scaffold 312 via the cell funnel 314, whereupon the cells become resident and initiate the differentiation and tissue formation sequence. Upon conclusion of this sequence, the tissue so formed may be removed from the bioreactor for subsequent implantation. One skilled in the art would understand that the particular embodiment of the bioreactor of FIG. 14 is only a representative design example. The bioreactor, in general, can be configured in various ways with respect to overall shape, size and internal configuration without adverse effect on function. For example, a gas exchange membrane 336 present on the bioreactor may be a separate and discrete component that is connected in-line with one or more fluid delivery tubes 210 or the flow plate 220 of the tissue engineering module 118. Furthermore, the chambers of the bioreactor may be isolated from each other via control valves to avoid the necessity for all fluids to pass through all chambers. When required the passageways between chambers may be opened to effect the transfer of fluids and cell suspensions. An example of such a variation that enables increased flexibility in bioprocessing conditions and sequences is illustrated in FIG. 17. An alternate configuration to enable controlled exposure of the implantable differentiation scaffold 312 to the contents of the bioreactor is the use of a shuttle 318 that isolates the implantable scaffold until cell seeding is required as part of the differentiation step. To enable cell seeding, the shuttle 318 moves the implantable scaffold into the fluid flow from a protected location within the bioreactor. Various configurations of the shuttle are possible, including rotation-based movement or the use of a removable barrier that isolates the implantable scaffold until cell seeding is required. FIG. 15 illustrates a rotational bioreactor design that takes advantage of the orientation of the gravity vector to effect cell transport by sedimentation at different stages in the tissue engineering process. Note that while this figure illustrates rotation of the bioreactor, the technical objective may be equally attained by rotation of the tissue engineering module or indeed by rotation of the entire housing 102. As shown in FIG. 15, the bioreactor 202 is attached to a rotational shaft 350 which is affixed to the structural spine 200 of the tissue engineering module 118. This provides a mechanism for the rotation of the bioreactor 202 in order that cell seeding via sedimentation can occur on to selected proliferation surfaces within the culture/proliferation chamber 300. The proliferation surfaces of the bioreactor may be optionally coated with biomaterials that enhance proliferation (for example Skelite™), or a dedicated proliferation substrate or scaffold may be inserted into the chamber 300 to provide this role. As an alternative to the use of the digestion chamber 322, a second inoculation port 352 is provided at the side of the bioreactor 202 to enable direct cell seeding. Cells may be initially seeded on a proliferation surface 354 which is relatively small (FIG. 15a). Based on elapsed proliferation time or the detection of confluence, the cells may be automatically released and the bioreactor rotated via the rotational shaft 350 such that the cells released from the proliferation surface 354 will sediment on to the increased area of surface 356 (FIG. 15b), allowing further proliferation. At the completion of the secondary proliferation step, the expanded cells are released and the bioreactor is again rotated to permit seeding of the implantable scaffold 312 (FIG. 15c). Thus the rotational shaft 350 and associated flexible tubes 358 allow the bioreactor 202 to be rotated as required to maximize the use of gravity sedimentation in sequential proliferation stages. It is within the scope of the present invention to use the rotational shaft in a manner to agitate or shake the bioreactor where such conditions are desirable. Referring now to FIG. 16, the tissue engineering module 118 may be adapted to include techniques for the sterile sampling of suspended cells, tissue culture fluids, and/or waste products. In this embodiment, a syringe manifold 400 and sterile offloading ports 402 are integrated into the structural spine 200 of the tissue engineering module 118. Microbore tubing 406 links the syringe manifold to the bioreactor 202 via the sampling port 332. Syringes 404 are connected to offloading ports 402 at the manifold 400 to enable the collection and removal of fluid samples or cell suspensions for subsequent analysis without compromising the operation, integrity or sterility of the tissue engineering process. An alternate sampling technique is also provided whereby a fusible bioreactor sampling line 408 is connected to the bioreactor lid 204. As this line is physically linked to the interior of the bioreactor and is in close proximity to the biological events underway therein, the line contains fluid of substantially the same composition as that present within the bioreactor. Consequently, a representative sample of the bioreactor fluid may be obtained by fusing the ends of the sampling line and then removing the line from the tissue engineering module for subsequent analysis. It will be obvious to one skilled in the art that such a fusible line can be used as the basis for a sampling technique through the automatic operation of sealing components within the housing 102. FIG. 17 illustrates a more complex fluid flow schematic for the tissue engineering module 118 in which the different requirements for digestion, proliferation and differentiation are accommodated by separate bioreactor chambers. These chambers may be present within a series of discrete bioreactors or combined within a single bioreactor that maintains separate control over the conditions in each chamber. A tissue digestion chamber 322 is present that accommodates a tissue biopsy 320. A proliferation chamber 300 is present that is configured to accept cells from the digestion chamber 322 and allows seeding of a proliferation substrate or scaffold 310. A differentiation/tissue formation chamber 306 is also present that is configured to accept the expanded cell numbers from the proliferation chamber 300 and allows seeding of an implantable scaffold 312. Tissue engineering reagents (i.e. media, enzyme solutions, washing solutions, etc.) are loaded in fluid reservoirs 208a-208e. Waste products are collected in fluid reservoir 208f, which can be manually aspirated for sampling purposes using access port 212f. Additional fluid reservoirs may form part of the fluid reservoir system 206 and be accommodated on the tissue engineering module as required for different tissue engineering processes. Fluid flow through the system is directed by the operation of fluid pumps 122a-122k, flow control valves 214a-214c, and uni directional flow valves 410a-410c (i.e. fluid flow check valves). Furthermore, pumps 212a-212k are configured to operate as active pumps or passive valves (open/closed), according to control inputs from a central microprocessor. Filters 316a-316d are used to selectively control the movement of cell suspensions within the system and to limit the passage of cell aggregates during washing and transition stages of the tissue engineering process. Levels of dissolved gasses in the media are maintained via the in-line gas exchange membranes 282a and 282b. Optional syringes 404a and 404b are present to allow cell collection or media sampling via sterile offloading ports 402a and 402b. In operation, a tissue biopsy 320 is inserted into the tissue digestion chamber 322 between filters 316a and 316b. A digestion medium containing enzymes is pumped into the tissue digestion chamber 322 from the fluid reservoir system 206 to initiate the digestion process. Digestion may be enhanced by gentle agitation of the digestion medium within the digestion chamber via a mixing diaphragm to maximize reagent exposure to the biopsy. The digestion medium may be continuously or periodically re-circulated via pump 122g. During recirculation, the fluid flow is directed into the bottom of the digest chamber, against the gravity vector, in order to suspend and tumble the tissue biopsy, thereby maximizing the effectiveness of the digestion process. Filter 316a prevents migration of cells and cell aggregates into the fluid pathway. The recirculation path includes the in-line gas exchange membrane 282a which provides for consistent levels of dissolved gases in the digestion medium. Introduction of a washing solution, contained in the fluid reservoir system 206, into the bottom of the digestion chamber 322 flushes the digestion chamber and effectively washes the digestion medium from both the disassociated cells and any residual cell aggregates. Following a single or multiple washing procedures, the application of reverse flow transfers the cell suspension to either the proliferation chamber 300 or the optional syringe 404a for external inspection or analysis. The transfer of partially digested tissue out of the digestion chamber is precluded by filter 316b that is sized to allow passage of disassociated cells and retention of cell aggregates. Cells generated from the biopsy digestion process or available via direct loading of a cell suspension are seeded through fluid flow and/or gravity sedimentation onto a proliferation substrate or scaffold 310 present within the proliferation chamber 300. Following a quiescent period to allow attachment of the cells to the proliferation substrate or scaffold 310 (for the example of attachment dependent cells), a proliferation medium is introduced into the proliferation chamber 300 from the fluid reservoir system 206. This medium is periodically replaced with fresh proliferation medium from the reservoir system 206 at specific times during the proliferation phase. In between the medium replacement steps, the fluid within the proliferation chamber is continuously or periodically recirculated under the control of pumps 122g, 122h and 122i, plus control valves 214a and 214b. The fluid delivery and recirculation paths include the inline gas exchange membrane 282a which provides for consistent levels of dissolved gases in the proliferation medium. During a medium replacement step, the supply of fresh medium from the fluid reservoir system 206 is balanced by the removal of fluid to the waste reservoir 208f via pump 122f. Thus, through a combination of periodic medium replacement steps and controlled recirculation, the tissue engineering system maintains optimal conditions within the proliferation chamber throughout the proliferation process. Once the cell culture approaches confluence, the media within the proliferation chamber 300 is evacuated into the waste reservoir 208f by pump 122f. In this process, the removal of fluid from the proliferation chamber is balanced by incoming sterile air delivered via a sterile filter port on the proliferation chamber (not shown) or by incoming PBS wash solution from the fluid reservoir system 206. The cells are washed extensively by two consecutive washing steps with the PBS wash solution to remove residual proliferation medium. The cells are subsequently released from the proliferation substrate or scaffold 310 through an automated sequence, such as the delivery of enzymes (for example trypsin) and the timed application of impact to the bioreactor via an impact drive. Following cell release, the enzymatic process may be stopped by the delivery of media containing serum that inhibits enzyme activity. In order to collect the cells for eventual seeding on to the implantable scaffold 312 within the differentiation/tissue formation chamber 306, the cell suspension is transferred from the proliferation chamber 300 to the filter 316c. The filter 316c prevents the passage of cells but allows the media to continue via valve 214b to the waste reservoir 208f under the control of pump 122f. The collected cells are then released from the filter 316c by the application of reverse flow and are delivered to either the differentiation/tissue formation chamber 306 or the optional syringe 404b for external inspection or analysis. Cell seeding on to the implantable differentiation scaffold 312 is achieved by transferring the cells from the filter 316c to the top surface of the scaffold via pump 122j. The loss of cells away from the scaffold is minimized by the optional use of a scaffold membrane or mesh 326. Following cell seeding, fresh differentiation media may be introduced into the differentiation/tissue formation chamber 306 through a secondary input by the operation of pump 122k. This secondary input is located away from that region of the implantable scaffold that is seeded with cells so as to minimize the potential for damaging sheer stresses that could compromise the formation of cell aggregates. The differentiation medium is periodically replaced with fresh differentiation medium from the reservoir system 206 at specific times during the differentiation phase. In between the medium replacement steps, the fluid within the differentiation/tissue formation chamber is continuously or periodically recirculated under the control of pumps 122j or 122k, plus control valve 214b. The path for the delivery of both fresh differentiation medium and recirculated medium includes the in-line gas exchange membrane 282b which provides for consistent levels of dissolved gases in the differentiation medium. During a medium replacement step, the supply of fresh medium from the fluid reservoir system 206 is balanced by the removal of fluid to the waste reservoir 208f via pump 122f. Environmental conditions within the differentiation/tissue formation chamber are monitored and controlled for the period necessary for the successful formation of the tissue construct, at which time the differentiation/tissue formation chamber of the bioreactor is opened and the construct retrieved for subsequent clinical or research use. FIG. 18 illustrates a variation on the fluid flow schematic of FIG. 17 where the proliferation scaffold or substrate 310 within the proliferation chamber 300 is replaced with a planar proliferation substrate of relatively large surface area. The orientation of the substrate is such that cell sedimentation under gravity evenly distributes the cells over the proliferation surface. Provided that the correct orientation of the proliferation chamber is maintained, the proliferation substrate may be in the form of a rigid polymer culture plate or a flexible wall container. FIG. 19 shows a tissue digestion bioreactor 500 that contains a tissue digestion chamber 322 of an appropriate size to accommodate one or more tissue samples such as a tissue biopsy 320. The bioreactor 500 consists of four primary components: a bioreactor base 502 that substantially forms the tissue digestion chamber 322, a removable bioreactor lid 504, port filter 316b, and optional port filter 316a (not shown). The bioreactor lid 504 provides for a media port 506 with an optional port filter 316a (not shown) and an air outlet port 508. The bioreactor base 500 accommodates filter 316b that allows passage of disassociated cells out of the tissue digestion chamber 322, via media port 510, and retention of tissue aggregates and biopsy debris. Following insertion of the tissue biopsy 320, the bioreactor is filled under automated control with an enzyme solution through port 506 or port 510. The addition of enzyme solution to the tissue digestion chamber 322 is balanced by air escaping through port 508. Biopsy digestion takes place under continuous or intermittent recirculation of the enzyme solution, thereby keeping the released cells in suspension and maximizing the exposure of the biopsy to the enzyme reagents. During recirculation, the enzyme solution enters the bioreactor through port 510 and leaves via port 506. This creates a fluid flow path in a direction opposite to the gravity vector such that the biopsy is suspended and tumbled to maximize the effectiveness of the enzyme reagents. Digestion may be enhanced by gentle agitation of the digestion medium within the digestion chamber via a mixing diaphragm (not shown). Port 508 may be closed during any recirculation steps, as air bubbles present in the fluid flow system are trapped in the upper half of the bioreactor, above the inlet 512 of port 506. Upon completion of the digestion sequence, the application of reverse flow of either air or medium through port 506 transfers the disassociated cells through port 510 to either a proliferation chamber or a cell collection vessel. FIG. 20 shows a proliferation bioreactor 520 that provides for a proliferation chamber 300. The bottom of the proliferation chamber consists of proliferation substrate 310 suitable for cell attachment and growth. To adjust or maintain the levels of dissolved gases in the medium, a gas permeable membrane (not shown) may be incorporated to the top surface of the proliferation chamber that allows the transport of gases such as oxygen and CO2. Separation walls 522 divide the internal space of the proliferation chamber into a channel system that forces medium to follow a predefined pathway from the inlet port 524 to the outlet port 526. The design of the proliferation bioreactor design has several important operational features. Relatively uniform cell seeding can be obtained by the infusion of a cell suspension through the channel system. Furthermore, the channel configuration ensures that media flow is well distributed over the whole proliferation surface, thereby reducing potential low-flow regions that may compromise local cell vitality due to reduced nutritional supply or waste product removal. At the conclusion of the proliferation sequence, continuous or intermittent recirculation of an appropriate enzyme solution through the channel system induces uniform cell detachment due to the effect of the enzyme reaction and the low-level sheer stresses generated by the fluid flow. Accordingly, cell harvest is achieved without the need for mechanical shaking or rotation of the proliferation chamber. FIG. 21 shows a differentiation bioreactor 530 designed to promote cell differentiation and subsequent tissue construct formation. The bioreactor consists of four primary components: a bioreactor base 532 that substantially forms a differentiation/tissue formation chamber 306, a removable bioreactor lid 534, a permeable membrane tube 326, and a differentiation scaffold 312. The permeable membrane tube 326 tightly encircles the scaffold reticulate to form a tissue growth compartment 536 above the scaffold. The tissue growth compartment may extend within the scaffold according to the pore size of the scaffold and the placement of the scaffold within the membrane tube. The membrane tube is also affixed to the inlet 540 of port 542, such that the membrane is physically located centrally within the differentiation/tissue formation chamber 306. This divides the bioreactor into two independent compartments, a cell and tissue growth compartment 536 and an outer cell-free medium compartment 538, all within the overall differentiation/tissue formation chamber 306. The pore size of the membrane tube is selected on the basis of being impermeable for cells but permeable for nutrients, waste products, growth factors, etc., within the culture medium. If desired, membrane pore size can be chosen in a manner to exclude molecules of a certain molecular weight from passing through the membrane. The bioreactor lid 534 has two air outlets ports 542 and 544, and one media inlet port 546. The bioreactor base 532 accommodates two further ports 548 and 550. The inlet port 546 is required for loading a cell suspension into the tissue growth compartment 536 and for the perfusion of the emerging tissue construct with culture medium. During the delivery of the cell suspension into the empty tissue growth compartment, entrapped air is allowed to exit through port 542. In a similar fashion, the outer cell free compartment 538 is loaded with media via port 548 or port 550 and entrapped air may escape via port 544. The design of the differentiation bioreactor allows direct perfusion of the tissue construct through media delivery to port 546 or indirect media supply to the surrounding cell free compartment 538 via port 548. Typically, ports 542 and 544 are closed during perfusion and port 550 serves as a media outlet; however, various alternate media supply scenarios are possible based on specific tissue engineering requirements. An important aspect of the media perfusion strategy is that the permeable membrane 326, which forms part of the tissue growth compartment, allows fresh culture medium to permeate into the tissue growth compartment without any loss of cells away from the scaffold. Furthermore, nutrition is provided to the cells from essentially all directions without restrictions from any impermeable bioreactor walls. FIG. 22 illustrates a further embodiment of the fluid flow schematic in which the bioreactors of FIGS. 19-21 may be employed. A tissue digestion chamber 322 is present that accommodates a tissue biopsy. A proliferation chamber 300 is present that is configured to accept cells from the digestion chamber 322 and allows seeding of a proliferation substrate. A bubble trap 560 removes air bubbles from the input line to the proliferation chamber and therefore prevents these bubbles from entering the proliferation chamber 300 and potentially compromising localized cell populations. A reservoir 562 is present to accept the expanded cell numbers from the proliferation chamber 300 and to serve as a temporary holding container during a cell washing and cell concentration procedure performed with the aid of a cross flow filtration module 564. A differentiation/tissue formation chamber 306 is also present that is configured to accept the cells from reservoir 562 after the washing and concentration step and allows seeding of an implantable scaffold 312. Tissue engineering reagents (i.e. media, enzyme solutions, washing solutions, etc.) are stored in fluid reservoirs 208a-208e. Waste products are collected in fluid reservoir 208f. Fluid flow through the system is directed by the operation of fluid pumps 122a and 122b, flow control valves 214a-214v according to control inputs from a central microprocessor. Air filters 566a-566c allow the transfer of air into or out of the system as required during operation without compromising system sterility. Furthermore, in-line gas exchange membranes (not shown) may be deployed at various locations within the fluid flow paths to facilitate the control of dissolved gases in the culture medium. In operation, a tissue biopsy 320 is inserted into the tissue digestion chamber 322. A digestion medium containing enzymes is pumped into the tissue digestion chamber 322 from a fluid reservoir 208 to initiate the digestion process. The digestion medium may be continuously or periodically re-circulated via pump 122a, thereby keeping the released cells in suspension and maximizing reagent exposure to the biopsy. Introduction of a proliferation culture medium from one of the fluid reservoirs 208 into the top of the digestion chamber 322 transfers the cell suspension to the proliferation chamber 300 and simultaneously dilutes the enzyme solution to a concentration that is tolerable for cell proliferation in the in the proliferation chamber 300. The transfer of partially digested tissue out of the digestion chamber is precluded by port filter 316b that is sized to allow passage of disassociated cells and retention of cell aggregates. Cells generated from the biopsy digestion process are homogeneously distributed throughout the proliferation chamber 300 either by the recirculation of the cell suspension via the activation of valves 214h, 214J, 214l and the pump 122a, or by the automated application of gentle shaking of the proliferation bioreactor. Following a quiescent period to allow attachment of the cells to the proliferation substrate, the proliferation medium is periodically or continuously replaced with fresh proliferation medium from one of the fluid reservoirs 208. During a medium replacement step, the supply of fresh medium from the fluid reservoir system 208 is balanced by the removal of fluid to the waste reservoir 208f via valve 214i. Once the cell culture approaches confluence, the media within the proliferation chamber 300 is evacuated into the waste reservoir 208f. In this process, the removal of fluid from the proliferation chamber is balanced by incoming sterile air delivered via a sterile filter 566a or by incoming PBS wash solution from one of the fluid reservoirs 208. The cells are subsequently released from the proliferation substrate through an automated sequence, such as the delivery of enzymes (for example trypsin) and the timed recirculation of the cell suspension or the timed application of impact or agitation to the bioreactor via an impact drive. In order to remove the enzymes and to collect the cells in a relatively small volume of medium for subsequent transfer to the cell differentiation chamber 306, the cell suspension is transferred from the proliferation chamber 300 to the reservoir 562. The cell suspension is then continuously recirculated via valves 214m, 214j, 214q and pump 122a through the cross-flow filtration module 564. The membrane in the cross flow filtration module 564 prevents the loss of cells but allows a certain percentage of media (permeate) to be removed via valve 214o to the waste reservoir 208f. The consequence is a reduction of the suspension volume and/or dilution of any enzymes present, provided the removal of permeate is compensated by the supply of fresh medium from one of the fluid reservoirs 208. The continuous flow reduces the potential for cells to become entrapped within the membrane of the cross-flow module 564. Cell seeding on to the implantable differentiation scaffold 312 is achieved by transferring the washed cells from the reservoir 562 to the top surface of the scaffold via the valves 214m, 214j, 214p, and pump 122a. The loss of cells away from the scaffold is minimized by the optional use of a scaffold membrane or mesh 326. Following cell seeding, fresh differentiation media may be introduced into the differentiation/tissue formation chamber 306 through the operation of pump 122b. The differentiation medium is periodically or continuously replaced with fresh differentiation medium from the reservoir system. During a medium replacement step, the supply of fresh medium from one of the fluid reservoirs 208 is balanced by the removal of fluid to the waste reservoir 208f via valve 214u. In between the medium replacement steps, the fluid within the differentiation/tissue formation chamber is continuously or periodically recirculated under the control of pump 122b, valve 214t, and either valve 214r for perfusion through the tissue construct or valve 214s for delivery outside the scaffold membrane 326. This secondary fluid delivery path outside the scaffold membrane is located away from that region of the implantable scaffold that is seeded with cells so as to minimize the potential for damaging sheer stresses that could compromise the formation of cell aggregates. As with the previous embodiments of the fluid flow schematic, environmental conditions within the differentiation/tissue formation chamber are monitored and controlled for the period necessary for the successful formation of the tissue construct, at which time the differentiation/tissue formation chamber of the bioreactor is opened and the construct retrieved for subsequent clinical or research use. FIG. 23 illustrates an embodiment of the invention where the tissue engineering module as described herein comprises three bioreactors. FIG. 23 illustrates the combined use of the tissue digestion bioreactor of FIG. 19 having an internal tissue digestion chamber 322, with the proliferation bioreactor of FIG. 20 having a proliferation chamber 300, and the differentiation bioreactor of FIG. 21 having a differentiation chamber 306. These bioreactors are operably connected on a tissue engineering module to provide for the automated steps involved in the sequence of tissue digestion, cell proliferation, cell differentiation, and tissue formation. It is understood by one of skill in the art that the automated tissue engineering system may comprise one or more bioreactors as supported to a housing either by a structural support or by equivalent means. When comprising two or more bioreactors, the bioreactors may be operatively connected or alternatively, independently operable and/or co-operatively operable. Furthermore, each bioreactor may comprise a different internal chambers or the same type of chambers. In a further embodiment, the chambers and/or bioreactors are operably connected to provide for the exchange of fluids, cells and/or tissues between the chambers and/or the bioreactors. The automated tissue engineering system of the invention is easy to prepare for use. The following sequence is a representative example for the preparation of a cartilage implant based on the use of the tissue engineering system of the present invention for the repair of focal defects in articular cartilage. For this application, the stages of tissue digestion, cell proliferation and cell differentiation/tissue formation are required. The three stages of the tissue engineering process may be accomplished by way of a single bioreactor with multiple chambers or three separate and discrete bioreactors, as shown in FIGS. 17, 18 and 22. Prior to initiating the tissue engineering sequence, the following reagent compositions are loaded into the reservoirs 208a through 208e in the tissue engineering module via the reservoir injection ports 212. Reagent A is utilized for the digestion of chondrocytes derived from small human articular cartilage biopsies. Reagents B, D and E are utilized for cell proliferation. Reagent C is utilized for differentiation and tissue construct formation. Reagent A—Digestion Medium: DMEM/F-12, 5% FCS or autologous serum, 1 μg/ml Insulin, 50 μg/ml Ascorbic Acid, 100 IU/100 μg/ml Pen/Strep, 2.5% Hepes Buffer, 0.1% (1 mg/ml) Pronase and 0.025% (0.25 mg/ml) Collagenase, pH 7.4 Reagent B—Proliferation Medium: DMEM/F-12, 10% FCS or autologous serum, 10 μg/ml Ascorbic Acid, 100 IU/100 μg/ml Pen/Strep, 2.5% Hepes Buffer, pH 7.4 Reagent C—Differentiation Medium: DMEM/F-12, 10% FCS or autologous serum, 1 μg/ml Insulin, 50 μg/ml ascorbic acid, 100 IU/100 μg/ml Pen/Strep, 2.5% Hepes Buffer, pH 7.4 Reagent D—PBS Wash Solution: 137 mM NaCl, 3.7 mM KCl, 8 mM Na2HPO4*2H2O, 1.5 mM KH2PO4, in H2O, pH 7.4 Reagent E—Cell Release Solution: 1× Trypsin solution The above reagents are nominally stable for periods up to several weeks when stored at 4° C. on the tissue engineering module within the system enclosure. Enzymes may be stored lyophilized within the tissue engineering module and hydrated at the time of use. This allows custom enzyme tailoring to the specific tissue engineering application. A human cartilage biopsy (100-500 mg) is obtained through an arthroscopic surgery from a non-load bearing area on the upper medial femoral condyle. Prior to loading the biopsy into the digestion chamber, the biopsy is weighed and the mass recorded for subsequent data entry into the programming sequence for the base unit. Following mass determination, the biopsy is placed within the digestion chamber and the bioreactor is closed ready for the tissue engineering module to be inserted into the base unit of the tissue engineering system. Once the tissue engineering module is installed, the CPU of the base unit is then programmed via the user interface according to the size of the biopsy and the tissue engineering sequence desired. On initiation of the programmed automated sequence, pronase/collagenase digestion of the biopsy is commenced by an infusion of Reagent A into the digestion chamber of the bioreactor through the activation of the required flow valves and the operation of the fluid delivery pump. Digestion is performed at 37° C. over a 16 hour period under continuous or intermittent recirculation of Reagent A to keep cells in suspension and to to maximize reagent exposure to the biopsy. This may be followed by two consecutive washing steps in Reagent D. At the end of this digestion sequence, approximately 200,000 to 500,000 cells per 100 mg of biopsy tissue are obtained. At this point a sample of the digested cells may be retrieved via the sampling port in order to assess cell number and vitality. This biological assessment is typically assessed outside the system by way of a hemocytometer after staining with trypan blue. Under the automated control of the base unit, the disassociated cells are delivered on to the proliferation substrate or scaffold present in the proliferation chamber of the bioreactor in order to establish a cell seeding density between 2000 cells/cm2 and 15000 cells/cm2. To effect continued proliferation toward confluence, Reagent B is supplied from a reservoir on the tissue engineering module according to a preprogrammed flow profile. The temperature and pH of the medium are monitored to detect deviations from 37° C. and pH 7.4, respectively. In addition, the status of cell proliferation is indirectly assessed by detection of metabolic turnover as a function of time (e.g. pH, O2, CO2, lactic acid and glucose consumption). The level of confluence is further supported by optical monitoring via CCD camera linked to the proliferation probe embedded within the proliferation chamber. Once impending confluence is determined either empirically or by way of sensor-based monitoring, the cells are washed extensively by two consecutive washing steps with Reagent D to remove all culture medium. Detachment of propagated cells from the proliferation substrate or scaffold is initiated by the transfer of Reagent E from a reservoir within the tissue engineering module into the proliferation chamber. This trypsin solution is present for 5 minutes within the bioreactor whereupon the reaction is stopped by the automatic addition of Reagent B which contains FCS or autologous serum that inhibits enzyme activity. Cell release from the proliferation substrate or scaffold is further enhanced by the application of low frequency impact to the bioreactor via the impact drive or recirculation of the trypsin solution. Once released, a cell washing and filtration step is performed in order to remove the trypsin and to concentrate the cell suspension for subsequent transfer on to the scaffold present in the differentiation/tissue formation bioreactor. For this application, a bipolar configuration is ideal as this provides for cartilage layer at the articular surface that is connected to a porous scaffold layer, formed of a bone biomaterial such as Skelite™, for integration with the subchondral bone. The preparation of the bipolar construct may be achieved through one of several alternate procedures. The differentiation scaffold may be formed with a pore density gradient that preferentially traps cells at one end creating a region of high cell concentration which promotes the formation of the cartilage layer. Alternately, the scaffold may be previously coated on one end with fibrin gel to preclude cell attachment and cartilage matrix formation in this region. With either approach, the loss of cells away from the scaffold is minimized by the optional use of an encircling membrane or mesh. The flow rate for cell delivery is low to ensure fluid shear does not damage the proliferated cell population. Following the completion of the cell seeding step, fluid flow through the differentiation/tissue formation chamber is stopped to enable the formation of cell aggregates, as this is known to be crucial in terms of successful differentiation. Following this important step, perfusion of Reagent C is performed over the period necessary for tissue formation and maturation in order to optimally supply cells with nutrients and to remove waste products. After this culture period, the cells will have produced extracellular matrix that is substantially identical to that of native human articular cartilage. The properties of the tissue formed can be confirmed by independent external biochemical methods such as collagen typing via SDS-PAGE and gene expression. As a final step in the process, the tissue engineering system provides notification by way of the user interface that the sequence is complete and the tissue engineering module may be removed to harvest the implant. The tissue engineering module or a detachable form of the bioreactor may be transported to the operating room whereupon the bioreactor lid is removed in a sterile field and the implant retrieved for surgical use. It should be noted that the system of the invention is not limited to a particular type of cell or tissue. For example, a skeletal implant may be prepared for use in the reconstruction of bone defects. In this application, bone marrow could be used as the source of the primary and/or precursor cells required for the tissue engineering process. Accordingly, there is no requirement to perform tissue digestion; hence, the bioreactor may be of the type that only supports proliferation and differentiation. Depending on the available cell population and the required size of the implant, even proliferation may not be required. In this case, the configuration of the bioreactor may be directed to the single stage of cell differentiation and ongoing tissue formation. The final tissue construct would be comprised of an implantable scaffold, which may be composed of a bone biomaterial such as Skelite™, with active bone cells lining the open pores of the scaffold and actively laying down new mineralized matrix (osteoid). Such an implant would be quickly integrated at the implant site thereby accelerating the recovery process. As a further example of the flexibility of the system, tissue engineered blood vessels may be prepared using culture expanded endothelial cells seeded onto flexible scaffolds of a tubular geometry in the final differentiation stage. The integrated tissue engineering system of the present invention has several advantages compared to methods and systems of the prior art. In particular, the turnkey operation of the device enables complex tissue engineering procedures to be performed under automated control in the clinic, thereby precluding the need to transport cells to centralized facilities for biological processing. The system is simple to use and obviates the existing time consuming and expensive human tissue culture procedures which often lead to implant contamination and failure. The tissue engineering modules and associated subsystem assemblies may be customized for the type of cell or tissue to be cultured and may be fabricated from any suitable biocompatible and sterilization tolerant material. The entire tissue engineering module or specific components thereof are replaceable and may be considered disposable. The tissue engineering module may be provided in a single-use sterile package that simplifies system set-up and operation in clinical settings. It is understood by those skilled in the art that the tissue engineering module and device of the present invention can be fabricated in various sizes, shapes and orientation. The device can be fabricated to incorporate a single tissue engineering module or multiple modules in vertical or horizontal formats. Accordingly, the subassemblies can be made to correspond to the spatial format selected for the tissue engineering device. As such, different types of tissue engineering can be simultaneously conducted in a single device with each tissue engineering sequence being automatically monitored and controlled on an individual basis. It is also within the scope of the invention to have a plurality of automated tissue engineering systems operating and networked under the control of a remote computer. Although preferred embodiments of the invention have been described herein in detail, it will be understood by those skilled in the art that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. The disclosures of these references are hereby incorporated by reference into the present disclosure. During the past several years, researchers have developed and used different cell culture and tissue engineering techniques for the culture and production of various types of cellular implants. Such systems are described for example in U.S. Pat. Nos. 5,041,138, 5,842,477, 5,882,929, 5,891,455, 5,902,741, 5,994,129, 6,048,721 and 6,228,635. Bioreactor systems have also been developed for the culture of cells and cellular implants and are described for example in U.S. Pat. Nos. 5,688,687, 5,728,581, 5,827,729 and 6,121,042. The aforementioned methods and systems generally employ conventional laboratory culturing techniques using standard culture equipment for cell seeding of selected cell populations onto scaffolds. As such, the generated implants simply comprise proliferated cell populations grown on a type of biopolymer support where any manipulation of the cellular environment is limited to endogenous cell production of cytokines present in any standard cell culture, and application of shear and/or physical stresses due to circulation of cell culture media and physical manipulation of the support onto which the cells are seeded. The systems do not address nor are they capable of generating a tissue implant that comprises proliferated and differentiated cells representative of developing tissues in vivo and further integrated within a selected scaffold that can be successfully integrated in vivo. Moreover, known methods and systems are not capable of multi-functionally carrying out all of the steps of biopsy tissue digestion to yield disassociated cells, subsequent cell seeding on a proliferation substrate, cell number expansion, controlled differentiation, tissue formation and production of a tissue implant within a single automated tissue engineering system. This is primarily because known culture systems are not sophisticated in that they are not capable of automatically evaluating and manipulating the changing environment surrounding the developing implant such that cells progressively proliferate and differentiate into a desired implant. Furthermore, conventional culture methods and systems are labor intensive and suffer from the drawbacks of contamination and varying degrees of culturing success due to human error and lack of continual performance evaluation. Conventional culture systems require that most of the initial steps in the preparation of cells for seeding (i.e. tissue digestion, cell selection) is performed manually which is time consuming, unreliable in terms of the quality of the tissue produced, and prone to culture contamination problems. The systems are incapable of supporting the automated preparation of tissue engineered implants from primary or precursor cells due to inherent design limitations that restrict the cell and tissue culture process, the inability to adequately monitor and modify the environment to support tissue development, and the absence of techniques to enable the implementation of effective quality control measures. Thus, there remains a real and unmet need for an improved system for in vitro and ex vivo tissue engineering that can consistently meet the operational requirements associated with the different steps in the development and production of tissue engineered implants. Of particular importance is the ability to create functional tissue constructs where the cells present are active, differentiated and already expressing extracellular matrix. This involves more than, and is strikingly different to, the simple simulation of the mature in vivo environment present at the host site. This is because the preparation of functional de novo tissue fundamentally requires that the cells progress through a series of developmental stages as part of an ex vivo sequence. In order to address both clinical and research requirements, new devices, methods and systems have been developed that obviate several of the disadvantages and limitations of conventional ex vivo culturing techniques and systems.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to a user-friendly automated system for cell culture and tissue engineering that can be used in a variety of clinical and research settings for both human and veterinary applications. As used herein, “tissue engineering” may be defined as “the application of principles and methods of engineering and life sciences toward fundamental understanding and development of biological substitutes to restore, maintain and improve tissue functions”. This definition is intended to include procedures where the biological substitutes are cells or combinations of different cells that may be implanted on a substrate or scaffold formed of biocompatible materials to form a tissue, in particular an implantable tissue construct. Furthermore, it is noted that the cells involved in the tissue engineering processes may be autologous, allogenic or xenogenic. The tissue engineering system of the present invention is designed to perform all activities under sterile operating conditions. The system is fully automated, portable, multifunctional in operation and performs/provides one or more of the following: sterile reception/storage of tissue biopsy; automated monitoring of digestion process digestion of biopsy tissue to yield disassociated cells; cell sorting and selection, including safe waste collection; cell seeding on or within a proliferation substrate or scaffold proliferation of cells to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of implantable tissue. The tissue engineering system of the present invention may be pre-programmed to perform each of the above noted steps, individually, sequentially or in certain predetermined partial sequences as desired and required. Furthermore, each of these steps, or any combination thereof, are accomplished within one or more bioreactors on a tissue engineering module. In operation, the tissue engineering system is pre-programmed and automatically controlled thus requiring minimal user intervention and, as a result, enhances the efficiency and reproducibility of the cell culture and/or tissue engineering process while minimizing the risks of contamination. The tissue engineering system of the invention and components thereof are operable under conditions of microgravity and/or zero gravity where such system and components are used for space research. The system of the present invention is designed such that primary or precursor cells can be isolated from a donor tissue for further propagation, differentiation and production of a tissue implant. Alternatively, cell lines may also be used either alone or in combination with other cell sources. In accordance with the invention, is an automated tissue engineering system, the system comprising a housing that supports at least one bioreactor that facilitates physiological cellular functions and the generation of tissue constructs from cell and tissue sources. The housing also supports a fluid containment system that is in fluid communication with the bioreactor. Associated with the housing and/or the bioreactor are sensors that monitor physiological parameters of fluid provided in the fluid containment system. A microprocessor disposed within the housing is linked to the bioreactor and the fluid containment system and functions to control their functioning. The microprocessor may also independently control environmental conditions within the system. In accordance with another aspect of the invention there is provided a system for cell and tissue engineering comprising portable, sterile tissue engineering modules having one or more bioreactors which provide the basis for tissue digestion, cell seeding on a proliferation substrate, cell proliferation, cell seeding on a differentiation scaffold, cell differentiation, and tissue formation with subsequent maturation into functional tissue for implantation. The bioreactor is operatively connected with a media flow and reservoir system for the delivery of reagents and the collection of waste fluids in a non-reflux manner. The bioreactor and/or the media flow system optionally include gas exchange components that utilize semi-permeable membranes to allow the transfer of gaseous products thereby controlling levels of dissolved gases in the media. The tissue engineering module operatively interacts with a central microprocessor controlled base unit that automatically monitors the progression of the cell culture or tissue engineering process and adjusts the environmental conditions to meet the requirements of the different stages of cell culture and tissue development within the bioreactor. Deviations from ideal conditions are sensed by a variety of sensors present within the bioreactor and the signals generated are monitored by the central microprocessor. As such, changes in environmental conditions such as but not limited to pH, temperature and dissolved gases can be automatically monitored and altered as required. In addition, the status of cell proliferation is indirectly assessed by detection of metabolic turnover as a function of time (e.g. pH, O 2 , CO 2 , lactic acid and glucose consumption). Further to the control of processing conditions by the central microprocessor, the tissue engineering module itself may optionally include a secondary onboard microprocessor that operates in unison with the central microprocessor. The tissue engineering module microprocessor expands the data processing capabilities of the tissue engineering system by performing specific functions directly onboard the tissue engineering module, thereby minimizing the demands on the central microprocessor. Various growth factors, cytokines, experimental agents, pharmaceuticals, chemicals, culture fluids and any combinations thereof may be loaded and stored within any of the reservoirs located on the tissue engineering module and automatically transferred to the one or more bioreactors according to a pre-programmed sequence or as required by the developing tissue implant. The individual tissue engineering modules are removable from the system for transport without compromising the sterility of the tissue engineered constructs present within the bioreactor. Such removal does not affect the processing of any other modules present within the tissue engineering system. Furthermore, the tissue engineering module may be considered to be disposable following the completion of a tissue engineering sequence, as this practice prevents contamination arising from prior use. In various embodiments of the invention, the device and system can be used to digest tissues obtained by surgical biopsy. In another embodiment, cells can be filtered and a particular population selected and isolated. In another embodiment, digested cells can be proliferated to expand the population of the cells. In still a further embodiment, cells can be seeded and cultivated on a desired scaffold or substrate (also referred to as a matrix). In yet a further embodiment, cells can be differentiated on and/or throughout a desired scaffold or substrate until suitable tissue formation is obtained. In yet a further embodiment, the tissue may be stimulated to promote tissue maturity. In yet another embodiment, a tissue implant is produced that is suitable for reconstructive surgery. In still a further embodiment, cell sampling can be done at each stage of cellular proliferation and developmental progression in a sterile manner without adverse effects on the culture itself. Each of the aforementioned embodiments can be done alone or sequentially as desired. Tracking of such processing events can be performed by the central microprocessor and/or the module-based microprocessor for incorporation into quality control records. In one aspect, the tissue engineering system optionally uses a synthetic biomaterial compound, Skelite™, described in Applicant's U.S. Pat. No. 6 , 323 , 146 (the contents of which are herein incorporated by reference) to enhance biological performance. Briefly, Skelite™ is an isolated bioresorbable biomaterial compound comprising calcium, oxygen and phosphorous, wherein a portion of at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 0.6 Angstroms. In one embodiment, Skelite™ may be used to enhance cell proliferation through its use as a coating on the walls of the bioreactor, as a thin film on the proliferation substrate, or as a three-dimensional and thereby high surface area proliferation scaffold The use of Skelite™ in the proliferation stage may be demonstrated to: increase the rate of proliferation; increase the cell yield following the proliferation step; reduce the surface area required for a target cell yield; reduce the problematic tendency of cell phenotype dedifferentiation during proliferation; and enhance the binding of growth factors to the proliferation substrate. In a further embodiment, Skelite™ may be used as a resorbable scaffold to enhance the differentiation of cells and the subsequent formation of tissue constructs. The use of Skelite™ in the differentiation stage may be demonstrated to: increase productivity by improving the reliability of the differentiation stage; increase the integrity and hence biological viability of the tissue construct; allow flexibility in construct configuration based on various scaffold formats; allow the stages of proliferation, differentiation and tissue formation to occur on a common substrate; enhance the binding of growth factors to the differentiation scaffold; and improve tissue construct handling properties during surgical implantation. In another aspect, the present invention provides a method and system for the preparation of tissue constructs through the automated steps of digestion, proliferation, seeding and differentiation of primary or precursor cells that originate from a patient thus eliminating immunological and disease transmission issues. An implant may be formed from the controlled cultivation of various cell types, including but not limited to chondrocytes, stromal cells, osteoblasts, nerve cells, epithelial cells stem cells and mixtures thereof. The system of the invention in an embodiment, incorporates one or more detachable, portable, and independently operable tissue engineering modules that support one or more bioreactors, media reservoirs and fluid/media flow system. Each module, and hence the bioreactor(s), is under the automated control of a central microprocessor. The module and associated bioreactor(s) may be configured for various specialized applications such as, but not limited to: sterile reception/storage of tissue biopsy; automated mixing and delivery of digestion reagents; automated monitoring of digestion process; digestion of biopsy tissue to yield disassociated cells; cell sorting and selection, including safe waste collection; cell washing and cell collection; cell seeding on or within a proliferation substrate or scaffold; automated mixing and delivery of proliferation reagents; proliferation of cells to expand cell populations; automated monitoring of cell conditions, including detection of confluence; controlled cell release from the proliferation substrate or scaffold; repeated proliferation steps on selected surface area sizes to increase cell numbers; channeling of cell population toward one or more tissue engineering scaffolds or matrices; cell seeding on or within the tissue engineering scaffold or matrix; automated mixing and delivery of differentiation reagents; automatic monitoring of cell/tissue culture conditions; cell differentiation to allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of cells and/or implantable tissue. When two or more bioreactors, are provided within the system either supported directly within the housing of the system or supported on a tissue engineering module insertable into the housing, the bioreactors may be provided connected in series and individually operable and controlled by the microprocessor or alternatively, may be operated and controlled independently depending on the user's programming of the microprocessor and the desired result to be achieved. Furthermore, when two or more bioreactors are provided within the system, the bioreactors and internal chambers may be connected such that there is an exchange of cells and/or tissues from bioreactor to bioreactor. The bioreactor can be manufactured in various sizes and configurations as required to support varying numbers and sizes of proliferation and differentiation scaffolds or substrates. The bioreactor may be incorporated as part of the structural components of the tissue engineering module. Alternately, the bioreactor may be detachable as a separate component to the remaining components of tissue engineering module. If present as a discrete component, the bioreactor may be packaged separately in a sterile package and joined to the tissue engineering module using sterile access techniques at the time of use. Furthermore, the sterile access techniques enable the bioreactor to be detached from the module, upon completion of the tissue engineering process, for easy transport to the operating room in preparation for the retrieval of a newly formed implantable tissue construct. The bioreactor and/or the tissue engineering module may be rotated or agitated within the overall tissue engineering system via control actuators. Rotation may enable the beneficial use of gravity to effect specific bioprocessing sequences such as sedimentation-based cell seeding and fluid exchange within the bioreactor. The tissue engineering module may be bar coded or provided with a memory chip for rapid and accurate tracking both within the tissue engineering system and externally as part of the clinical or experimental environment. Such tracking technology as incorporated within the tissue engineering device also enables electronic tracking via clinic-based information systems for patient records. This ensures that the tissue engineering module and hence the associated cells or tissue implants are properly coded to ensure administration to the correct patient and that the process is recorded for hospital billing purposes. The module and/or bioreactor may also utilize a bar code and/or memory chip in a similar manner for rapid and accurate patient and sample tracking. According to an aspect of the present invention is an automated tissue engineering system comprising; a housing; at least one bioreactor supported by said housing, said bioreactor facilitating physiological cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources; a fluid containment system supported by said housing and in fluid communication with said bioreactor, one or more sensors associated with one or more of said housing, bioreactor or fluid containment system for monitoring parameters related to said physiological cellular functions and/or generation of tissue constructs; and a microprocessor linked to one or more of said sensors. According to another aspect of the present invention is an automated tissue engineering system comprising; a housing; at least one tissue engineering module removably accomodated within said housing, said tissue engineering module comprising a support structure that holds at least one bioreactor, said bioreactor facilitating physiological cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources, a fluid containment system in fluid communication with said bioreactor, and one or more sensors for monitoring parameters related to said cell culture and/or tissue engineering functions; and a microprocessor disposed in said housing and linked to said tissue engineering module, said microprocessor controlling the operation of said tissue engineering module. According to a further aspect of the invention is portable and sterilizable tissue engineering module, the module comprising; a structural support holding at least one bioreactor, said bioreactor facilitating cell culture and tissue engineering functions; a fluid containment system in fluid communication with said bioreactor, and one or more sensors for monitoring parameters related to said cell culture and tissue engineering functions. In aspects of this embodiment, the bioreactor comprises a bioreactor housing having one or more inlet ports and one or more outlet ports for media flow and at least one chamber defined within said bioreactor housing for receiving cells and/or tissues and facilitating said cell culture and tissue engineering functions. The chamber may be selected from the group consisting of a cell culture/proliferation chamber, cell differentiation/tissue formation chamber, tissue digestion chamber and combinations thereof. Furthermore, the chamber houses one or more substrates and/or scaffolds. In embodiments of the invention, two or more chambers may be provided operably connected within the bioreactor and be operably connected. Alternatively, the two or more bioreactors may be independently operable or co-operatively operable. In still further aspects, the chambers and/or bioreactors are operably connected to provide for the exchange of fluids, cells and/or tissues between the chambers and/or bioreactors. The scaffold for use in the present invention is selected from the group consisting of a porous scaffold, a porous scaffold with gradient porosity, a porous reticulate scaffold, a fiberous scaffold, a membrane encircled scaffold and combinations thereof. Chambers may also be further subdivided into zones. For example, a differentiation/tissue formation chamber may be provided with a plurality of zones to contain several scaffolds. Funnels or similar passageways may be provided between chambers within a bioreactor. Furthermore, one or more filters may be provided at any location within a bioreactor. According to still another aspect of the present invention is a bioreactor that provides an environment for cell culture and/or tissue engineering functions selected from the group consisting of storage of tissue biopsy, digestion of tissue biopsy, cell sorting, cell washing, cell concentrating, cell seeding, cell proliferation, cell differentiation, cell storage, cell transport, tissue formation, implant formation, storage of implantable tissue, transport of implantable tissue and combinations thereof. According to still another aspect of the present invention is a bioreactor for facilitating and supporting cellular functions and generation of implantable tissue constructs, said bioreactor comprising; a bioreactor housing; one or more inlet ports and one or more outlet ports for media flow; at least one chamber defined within said bioreactor housing for facilitating and supporting cellular functions and/or the generation of one or more tissue constructs from cell and/or tissue sources; and one or more sensors for monitoring parameters related to said cellular functions and/or generation of tissue constructs within said at least one chamber. In embodiments of the invention, the bioreactor housing comprises a lid, where the lid may be a detachable lid or integral with the bioreactor housing. Cells and tissues may be selected from bone, cartilage, related bone and cartilage precursor cells and combinations thereof. More specifically, cells suitable for use in the bioreactor, module and system of the invention are selected from but not limited to the group consisting of embryonic stem cells, adult stem cells, osteoblastic cells, pre-osteoblastic cells, chondrocytes, nucleus pulposus cells, pre-chondrocytes, skeletal progenitor cells derived from bone, bone marrow or blood, including stem cells, and combinations thereof. The cells or tissues may be of an autologous, allogenic, or xenogenic origin relative to the recipient of an implant formed by the cell culture and tissue engineering functions of the invention. According to another aspect of the invention is a tissue implant produced within a bioreactor of the present invention. According to yet another aspect of the present invention is a tissue implant produced by the tissue engineering system of the present invention. According to another aspect of the present invention is a tissue engineered implantable construct for repair of bone trauma wherein the implant comprises a porous scaffold of a bone biomaterial in combination with active bone cells and tissue engineered mineralized matrix. According to another aspect of the present invention is a tissue engineered implant comprising: a cartilage zone comprising tissue engineered cartilage that is devoid of any mineral-based scaffold; a bone biomaterial zone comprising a porous scaffold; and an interfacial zone between said cartilage zone and said bone biomaterial zone. The cartilage zone promotes lateral integration with the host cartilage while the bone biomaterial zone promotes lateral and vertical integration with the subchondral bone plate when implanted in vivo. The interfacial zone provides the structural union between the cartilage zone and the bone biomaterial zone. The cartilage zone may additionally incorporate a secondary non-mineral scaffold that assists with the formation of tissue engineered cartilage and allows for the development of a shaped surface profile in keeping with the particular anatomical characteristics present at the site of implantation. According to another aspect of the present invention is a method for digesting a tissue biopsy, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor providing tissue digestion enzymes; and monitoring and maintaining suitable digestion conditions within said bioreactor for a sufficient period of time for a desired level of tissue digestion. According to another aspect of the present invention is a method for the proliferation of cells, said method comprising; seeding cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell proliferation. According to another aspect of the present invention is a method for the differentiation of cells, said method comprising; seeding cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time for a desired level of cell differentiation. According to another aspect of the present invention is a method for digesting a tissue biopsy to provide primary cells, including precursor cells such as stem cells, and then proliferating and differentiating the cells to enable the formation of a tissue implant, the method comprising; loading a tissue biopsy within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect and relay physiological conditions within said bioreactor to a microprocessor; providing tissue digestion enzymes; monitoring and maintaining suitable digestion conditions within said bioreactor for a sufficient period of time to obtain disassociated cells; seeding the disassociated cells onto a proliferation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain the desired level of cell proliferation and expansion; releasing the expanded cells from the proliferation substrate or scaffold; seeding the expanded cells onto a differentiation substrate or scaffold supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect and relay physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable culturing conditions within said bioreactor for a sufficient period of time to obtain a tissue implant. According to another aspect of the present invention is a method for providing a skeletal implant, the method comprising; seeding osteogenic and/or osteoprogenitor cells onto a porous scaffold of a bone biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the osteogenic and/or osteoprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a tissue implant for orthopedic applications. According to still another aspect of the invention is a method for providing a cartilage implant, the method comprising; seeding chondrogenic and/or chondroprogenitor cells onto a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor, and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow the chondrogenic and/or chondroprogenitor cells to proliferate and/or differentiate throughout the scaffold to provide a cartilage implant. According to still another aspect of the invention is a method for washing cells, the method comprising: loading a cell suspension containing one or more undesired chemicals into a chamber; continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to said cells but permeable to said undesired chemicals to provide a washed cell suspension; and collecting the washed cell suspension. According to yet another aspect of the invention is a method for enrichment of cells, the method comprising: loading a cell suspension containing excessive cell suspension volume into a chamber; continuously recirculating the cell suspension from the chamber through a cross-flow filtration module that comprises a membrane impermeable to the cells but allowing the excessive cell suspension volume to be removed and collected. According to yet another aspect of the invention is a method for providing an implant for re-establishing the inner nucleus of a spinal disc, the method comprising; seeding nucleus pulposus cells within a scaffold a porous scaffold of a biomaterial supported within a bioreactor connected with a media reservoir and flow system, said bioreactor having one or more sensors to detect physiological conditions within said bioreactor to a microprocessor; and monitoring and maintaining suitable conditions within said bioreactor for a sufficient period of time to allow proliferation and/or differentiation of the nucleus pulposus cells and the expression of extracellular matrix components characteristic of the nucleus pulposus. According to still a further aspect of the present invention is a method for the preparation of quality assessment samples for use in clinical tissue engineering, said method comprising; parallel preparation of primary and secondary implants using the system of the invention as described herein, where the primary implant is for implantation and one or more secondary implants are for testing purposes to infer the calibre of the primary implant. The tissue engineering system of the present invention in various embodiments is under the control of one or more microprocessors that may be preprogrammed in order that the user can select a specific type of environment (or sequence of environments) within the bioreactor such as tissue digestion, cell proliferation, cell differentiation and/or tissue construct formation. This eliminates operator intervention and reduces the possibility of inadvertent contamination. The tissue engineering system of the invention can be provided as a “kit”. In this manner the device, tissue engineering module(s), bioreactor(s) and various components thereof can be packaged and sold together along with instructions and quality control techniques. The system of the present invention is ideal for clinical use in hospitals, and in particular surgical settings where due to trauma and/or disease, a tissue-engineered implant is desired. Using the present system, tissue engineered implantable constructs can be safely prepared from autologous tissue obtained via patient biopsy, allogenic cells or xenogenic cells. The specifications of such tissue engineered implantable constructs can be matched to the type, size and condition of the implantation site. Furthermore, the implant as generated by the present system contains active cells that promote integration with the host thereby improving patient recovery. In practice, using an autologous cell model, a tissue biopsy can be obtained from the patient and placed directly into the bioreactor present on the tissue engineering module while in the operating room. A specific bioreactor design is selected depending on the type and size of the tissue construct desired. At the completion of the tissue engineering process, the tissue construct produced can be transported still contained in the sterile bioreactor to the operating room for implantation back into the patient. The system is ideal for providing “customized” autologous tissue implants in a safe and therapeutically effective manner. The system and methods of the present invention are not limited to providing automated cell culture techniques. The tissue engineering system described moves well beyond the cell expansion used in cell therapy. The tissue engineering system may be used to create functional tissue constructs where the cells present are active, differentiated and already expressing extracellular matrix. Consequently, the tissue constructs so produced are in a high state of development and thereby accelerate the rate and improve the quality of tissue repair at the implant site. The system of the invention is also suitable for pharmacological research. Specifically, the system finds use in the area of drug development. New potential drugs and molecules can be tested on cells and tissues to determine effects on cellular events and tissue development. Such testing can be done on a patient's own cells/tissues to assess and possibly avoid adverse side effects prior to administration. Alternatively, specialized cell lines or tissues can be used with the system as a key tool in the drug discovery process. The system can be programmed to monitor and assess various physiological conditions of the cells/tissues present within the bioreactor and thus provide a fast indication of the biological effects of a selected drug or molecule. The system may also be used for research and development studies where conventional tissue engineering techniques are difficult to use and practice, and/or in conditions requiring extensive diagnostic recording. For example, microgravity studies involving tissue engineering are difficult to conduct due to the unique properties of this environment. Traditional cell and tissue culture techniques are simply not viable in this environment due to fluid containment issues and the absence of gravity-based transport of cells. The system and methods of the invention are easily adaptable to the microgravity environment as the system is completely sealed to prevent fluid loss and the migration of cells as part of the tissue engineering process can be achieved by controlled fluid flow. Other features and advantages of the present invention will become apparent from the following detailed description, examples and drawings. It should be understood, however, that the detailed description, specific examples and drawings while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from said detailed description.
20050929
20130723
20060629
64592.0
C12N508
1
UNDERDAHL, THANE E
AUTOMATED TISSUE ENGINEERING SYSTEM
UNDISCOUNTED
0
ACCEPTED
C12N
2,005
10,510,841
ACCEPTED
Nf-kb inhibitors
The present invention provides novel compounds and methods for using them to treat diseases with aminothiophene inhibitors of IKK-β phosphorylation of IκB. In so doing these aminothiophene inhibitors block pathological activation of transcription factor NF-κB in which diseases excessive activation of NF-κB is implicated.
1. A compound of formula (I): wherein: R1 represents NR4R5; R2 represents CONH2 or SO2NH2; R3 is selected from the group consisting of halogen, C1-4alkyl, NH2, CF3, OCF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl, (CH2)qNR7R8, O—(CH2)qNR7R8, (CH2)q-aryl, O—(CH2)q-aryl, (CH2)q-heteroaryl, O—(CH2)q-heteroaryl, (CH2)q-heteroalkyl, O—(CH2)q-heteroalkyl and NO2; R4 represents H or C1-4alkyl; R5 represents H or CONHR6; R6 is selected from the group consisting of hydrogen, alkyl and aryl; R7 represents C1-4alkyl; R8 represents C1-4alkyl; m is 0, 1, 2 or 3; n is 0, 1, 2, or 3; p is 1, 2 or 3; and q is 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof. 2. A compound of formula (Ia): wherein: R1 represents NR4R5; R2 represents CONH2; R3 is selected from the group consisting of halogen, C1-4alkyl, NH2, CF3, OCF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl, (CH2)qNR7R8, O—(CH2)qNR7R8, (CH2)q-aryl, O—(CH2)q-aryl, (CH2)q-heteroaryl, O—(CH2)q-heteroaryl, (CH2)q-heteroalkyl, O—(CH2)q-heteroalkyl and NO2; R4 represents H; R5 represents CONHR6; R6 represents H; R7 represents C1-4alkyl; R8 represents C1-4alkyl; m is 0; n is 1 or 2; p is 1, or 2; and q is 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof. 3. A compound according to claim 1 wherein the compound is selected from the group consisting of: 2-Amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide; 2-Ureido-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-4H-indeno[1,2b]thiophene-3-carboxylic acid amide; 2-Amino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-8-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 8-Methoxy-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; and 7-Bromo-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; or a pharmaceutially acceptable salt thereof. 4. A method of treating a disease characterized by pathological NF-κB activation comprising inhibiting the pathological activation by administering to a patient in need thereof an effective amount of a compound according to claim 1. 5. A method according to claim 3 wherein the disease is an inflammatory or tissue repair disorder. 6. A method according to claim 4 wherein the disease is selected from the group consisting of inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis, osteoporosis and fibrotic diseases, dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage, autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including aquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome, and Ataxia Telangiestasia. 7. A method according to claim 3 wherein said disease is dermatosis. 8. A method according to claim 3 wherein the disease is selected from the group consisting of: psoriasis, atopic dermatitis, and UV-induced skin damage. 9. A method according to claim 3 wherein he disease is selected from the group consisting of autoimmune diseases; tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, osteoarthritis, osteoporosis, and Ataxia Telangiestasia. 10. A method according to claim 3 wherein said disease is an autoimmune disease. 11. A method according to claim 3 wherein the autoimmune disease is systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, or alkylosing spondylitis, diabetes 12. A method according to any one of claim 1 wherein the disease is cancer and or cachexia. 13. A method according to claim 3 wherein the cancer is Hodgkins disease. 14. A method according to claim 3 wherein the disease is inflammation associated with infection and certain viral infections, including acquired immune deficiency syndrome (AIDS). 15. A method according to claim 3 wherein the disease is AIDS. 16. A method according to claim 3 wherein the disease is adult respiratory distress syndrome. 17. A method according to claim 3 wherein there is dual inhibition of NF-κB and checkpoint kinase.
FIELD OF THE INVENTION This invention relates in general to a method of inhibiting pathological activation of the transcription factor NF-κB (nuclear factor-KB) using aminothiophene compounds. Such methods are particularly useful for treating diseases in which activation of NF-κB is implicated. More specifically, these methods may be used for inhibiting IKK-β (IκB kinase-β, also known as IKK-2) phosphorylation of IκB (inhibitory protein κB)-which prevents subsequent degradation and activation of NF-κB dimers. Such methods are useful in the treatment of a variety of diseases associated with NF-κB activation including inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis; osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage; autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome, Ataxia Telangiestasia. BACKGROUND OF THE INVENTION Recent advances in scientific understanding of the mediators involved in acute and chronic inflammatory diseases and cancer have led to new strategies in the search for effective therapeutics. Traditional approaches include direct target intervention such as the use of specific antibodies, receptor antagonists, or enzyme inhibitors. Recent breakthroughs in the elucidation of regulatory mechanisms involved in the transcription and translation of a variety of mediators have led to increased interest in therapeutic approaches directed at the level of gene transcription. Nuclear factor κB (NF-κB) belongs to a family of closely related dimeric transcription factor complexes composed of various combinations of the Rel/NF-κB family of polypeptides. The family consists of five individual gene products in mammals, RelA (p65), NF-κB1 (p50/p105), NF-κB2 (p49/p100), c-Rel, and RelB, all of which can form hetero- or homodimers. These proteins share a highly homologous 300 amino acid “Rel homology domain” which contains the DNA binding and dimerization domains. At the extreme C-terminus of the Rel homology domain is a nuclear translocation sequence important in the transport of NF-κB from the cytoplasm to the nucleus. In addition, p65 and cRel possess potent transactivation domains at their C-terminal ends. The activity of NF-κB is regulated by its interaction with a member of the inhibitor IκB family of proteins. This interaction effectively blocks the nuclear localization sequence on the NF-κB proteins, thus preventing migration of the dimer to the nucleus. A wide variety of stimuli activate NF-κB through what are likely to be multiple signal transduction pathways. Included are bacterial products (LPS), some viruses (HIV-1, HTLV-1), inflammatory cytokines (TNFα, IL-1), environmental and oxidative stress and DNA damaging agents. Apparently common to all stimuli however, is the phosphorylation and subsequent degradation of Iκ. IκB is phosphorylated on two N-terminal serines by the recently identified IκB kinases (IKK-α and IKK-β). Site-directed mutagenesis studies indicate that these phosphorylations are critical for the subsequent activation of NF-κB in that once phosphorylated the protein is flagged for degradation via the ubiquitin-proteasome pathway. Free from IκB, the active NF-κB complexes are able to translocate to the nucleus where they bind in a selective manner to preferred gene-specific enhancer sequences. Included in the genes regulated by NF-κB are a number of cytokines and chemokines, cell adhesion molecules, acute phase proteins, immunoregulatory proteins, eicosanoid metabolizing enzymes and anti-apoptotic genes. It is well-known that NF-κB plays a key role in the regulated expression of a large number of pro-inflammatory mediators including cytokines such as TNF, IL-1β, IL-6 and IL-8, cell adhesion molecules, such as ICAM and VCAM, and inducible nitric oxide synthase (iNOS). Such mediators are known to play a role in the recruitment of leukocytes at sites of inflammation and in the case of iNOS, may lead to organ destruction in some inflammatory and autoimmune diseases. The importance of NF-κB in inflammatory disorders is further strengthened by studies of airway inflammation including asthma, in which NF-κB has been shown to be activated. This activation may underlie the increased cytokine production and leukocyte infiltration characteristic of these disorders. In addition, inhaled steroids are known to reduce airway hyperresponsiveness and suppress the inflammatory response in asthmatic airways. In light of the recent findings with regard to glucocorticoid inhibition of NF-κB, one may speculate that these effects are mediated through an inhibition of NF-κB. Further evidence for a role of NF-κB in inflammatory disorders comes from studies of rheumatoid synovium. Although NF-κB is normally present as an inactive cytoplasmic complex, recent immunohistochemical studies have indicated that NF-κB is present in the nuclei, and hence active, in the cells comprising rheumatoid synovium. Furthermore, NF-κB has been shown to be activated in human synovial cells in response to stimulation with TNF-α or IL-1β. Such a distribution may be the underlying mechanism for the increased cytokine and eicosanoid production characteristic of this tissue. See Roshak, A. K., et al., J. Biol. Chem., 271, 31496-31501 (1996). Expression of IKK-β has been shown in synoviocytes of rheumatoid arthritis patients and gene transfer studies have demonstrated the central role of IKK-β in stimulated inflammatory mediator production in these cells. See Aupperele et al. J. Immunology 1999. 163: 427-433 and Aupperle et al. J. Immunology 2001; 166: 2705-11. More recently, the intra-articular administration of a wild type IKK-β adenoviral construct was shown to cause paw swelling while intra-articular administration of dominant-negative IKK-β inhibited adjuvant-induced arthritis in rat. See Tak et al. Arthritis and Rheumatism 2001; 44: 1897-1907. The NF-κB/Rel and IκB proteins are also likely to play a key role in neoplastic transformation and metastasis. Family members are associated with cell transformation in vitro and in vivo as a result of overexpression, gene amplification, gene rearrangements or translocations. In addition, rearrangement and/or amplification of the genes encoding these proteins are seen in 20-25% of certain human lymphoid tumors. Further, NF-κB is activated by oncogenic ras, the most common defect in human tumors and blockade of NF-κB activation inhibits ras mediated cell transformation. In addition, a role for NF-κB in the regulation of apoptosis has been reported, strengthening the role of this transcription factor in the regulation of tumor cell proliferation. TNF, ionizing radiation and DNA damaging agents have all been shown to activate NF-κB which in turn leads to the upregulated expression of several anti-apoptotic proteins. Conversely, inhibition of NF-κB has been shown to enhance apoptotic-killing by these agents in several tumor cell types. As this likely represents a major mechanism of tumor cell resistance to chemotherapy, inhibitors of NF-κB activation may be useful chemotherapeutic agents as either single agents or adjunct therapy. Recent reports have implicated NF-κB as an inhibitor of skeletal cell differentiation as well as a regulator of cytokine-induced muscle wasting (Guttridge et al. Science; 2000; 289: 2363-2365.) further supporting the potential of NF-κB inhibitors as novel cancer therapies. Several NF-κB inhibitors are described in C. Wahl, et al. J. Clin. Invest. 101(5), 1163-1174 (1998), R. W. Sullivan, et al. J. Med. Chem. 41, 413-419 (1998), J. W. Pierce, et al. J. Biol. Chem. 272, 21096-21103 (1997). The marine natural product hymenialdisine is known to inhibit NF-κB. Roshak, A., et al., JPET, 283, 955-961 (1997). Breton, J. J and Chabot-Fletcher, M. C., JPET, 282, 459-466 (1997). Additionally, patent applications have been filed on aminothiophene inhibitors of the IKK-2, see Callahan, et al., WO 2002030353; Baxter, et al., WO 2001058890, Faull, et al., WO 2003010158; Griffiths, et al., WO2003010163; Fancelli, et al., WO 200198290; imidazole inhibitors of IKK-2, see Callahan, et al., WO 200230423; anilinophenylpyrimidine inhibitors of IKK-2, see Kois, et al., WO 2002046171; β-carboline inhbitors of IKK-2, see Ritzeler, et al., WO 2001068648, Ritzeler, et al., EP 1134221; Nielsch, et al. DE 19807993; Ritzeler, et al., EP 1209158; indole inhibitors of IKK-2, see Ritzeler, et al., WO 2001030774; benzimidazole inhibitors of the IKK-2, see Ritzeler, et al., DE 19928424; Ritzeler et al, WO 2001000610; aminopyridine inhibitors of IKK-2, see Lowinger, et al, WO2002024679; Murata, et al, WO 2002024693; Murata, et al., WO2002044153; pyrazolaquinazoline inhibitors of IKK-2, see Beaulieu, et al., WO2002028860; Burke et al, WO2002060386, Burke, et al. U.S. 20030022898; quinoline inhibitors of IKK-2, Browner, et al., WO2002041843, Browner, et al., U.S. 20020161004 and pyridylcyanoguanidine inhibitors of IKK-2, see Bjorkling, et al., WO 2002094813, Binderup et al, WO 2002094322 and Madsen, et al., WO 200294265. The natural products staurosporine, quercetin, K252a and K252b have been shown to be IKK-2 inhibitors, see Peet, G. W. and Li, J. J. Biol. Chem., 274, 32655-32661 (1999) and Wisniewski, D., et al., Analytical Biochem. 274, 220-228 (1999). Synthetic inhibitors of IKK-2 have also been described, see Burke, et al. J. Biol. Chem., 278, 1450-1456 (2003) and Murata, et al., Bioorg. Med. Chem. Lett., 13, 913-198 (2003) have described IKK-2 inhibitors. U.S. Pat. No. 3,963,750 describes the preparation of certain aminothiophenes. SUMMARY OF THE INVENTION The present invention involves novel compounds and novel methods of inhibiting the activation transcription factor NF-κB using the present compounds. An object of the present invention is to provide a method for treating diseases which may be therapeutically modified by altering the activity of transcription factor NF-κB. Accordingly, in the first aspect, this invention provides a pharmaceutical composition comprising a compound according to Formula I. In another aspect, this invention provides a method of treating diseases in which the disease pathology may be therapeutically modified by inhibiting phosphorylation and subsequent degradation of IκB by IKK-β. In still another aspect, this invention provides a method of treating diseases in which the disease pathology may be therapeutically modified by inhibiting pathological activation of NF-κB. In a particular aspect, this invention provides methods for treating a variety of diseases associated with NF-κB activation including inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis, osteoporosis and fibrotic diseases, dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage; autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome and Ataxia Telangiestasia. DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention are selected from Formula (I) herein below: wherein: R1 represents NR4R5; R2 represents CONH2 or SO2NH2; R3 is selected from the group consisting of halogen, C1-4alkyl, NH2, CF3, OCF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl, (CH2)qNR7R8, O—(CH2)qNR7R8, (CH2)q-aryl, O—(CH2)q-aryl, (CH2)q-heteroaryl, O—(CH2)q-heteroaryl, (CH2)q-heteroalkyl, O—(CH2)q-heteroalkyl and NO2; R4 represents H or C1-4alkyl; R5 represents H or CONHR6; R6 is selected from the group consisting of hydrogen, alkyl and aryl; R7 represents C1-4alkyl; R8 represents C1-4-alkyl; m is 0, 1, 2 or 3; n is 0, 1, 2, or 3; p is 1, 2 or 3; and q is 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof. Preferred: wherein: R1 represents NR4R5; R2 represents CONH2; R3 is selected from the group consisting of halogen, C1-4alkyl, NH2, CF3, OCF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl, (CH2)qNR7R8, O—(CH2)qNR7R8, (CH2)q-aryl, O—(CH2)q-aryl, (CH2)q-heteroaryl, O—(CH2)q-heteroaryl, (CH2)q-heteroalkyl, O—(CH2)q-heteroalkyl and NO2; R4 represents H; R5 represents CONHR6; R6 represents H; R7 represents C1-4alkyl; R8 represents C1-4alkyl; m is 0; n is 1 or 2; p is 1, or 2; and q is 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof. The present invention includes all hydrates, solvates, complexes and prodrugs of the compounds of this invention. Prodrugs are any covalently bonded compounds, which release the active parent, drug according to Formula I in vivo. If a chiral center or another form of an isomeric center is present in a compound of the present invention, all forms of such isomer or isomers, including enantiomers and diastereomers, are intended to be covered herein. Inventive compounds containing a chiral center may be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture may be separated using well-known techniques and an individual enantiomer may be used alone. In cases in which compounds have unsaturated carbon-carbon double bonds, both the cis (Z) and trans (E) isomers are within the scope of this invention. In cases wherein compounds may exist in tautomeric forms, such as keto-enol tautomers, each tautomeric form is contemplated as being included within this invention whether existing in equilibrium or predominantly in one form. This invention provides methods for treating a variety of diseases associated with NF-κB activation including inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage; autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome, and Ataxia Telangiestasia. Preferred compounds useful in the present invention include: 2-Amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide; 2-Ureido-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-4H-indeno[1,2b]thiophene-3-carboxylic acid amide; 2-Amino4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-8-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 8-Methoxy-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Amino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; 2-Acetylamino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; and 7-Bromo-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide; or a pharmaceutially acceptable salt thereof. The meaning of any substituent at any one occurrence in Formula I or any subformula thereof is independent of its meaning, or any other substituent's meaning, at any other occurrence, unless specified otherwise. As used herein, “alkyl” refers to an optionally substituted hydrocarbon group joined by single carbon-carbon bonds and having 1-6 carbon atoms joined together. The alkyl hydrocarbon group may be linear, branched or cyclic, saturated or unsaturated. Substituents on optionally substituted alkyl are selected from the group consisting of aryl, OH, O-alkyl, CO, halogen, CF3, and OCF3. As used herein, “aryl” refers to an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to two conjugated or fused ring systems. Aryl includes carbocyclic aryl, and biaryl groups, all of which may be optionally substituted. Substituents are selected from the group consisting of halogen, C1-4 alkyl, NH2, OCF3, CF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl and NO2. As used herein, “heteroaryl” refers to an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to two conjugated or fused ring systems and 1-3 heteroatoms selected from O, S and N. Heteroaryl includes carbocyclic heteroarylaryl, aryl-heteroaryl and biheteroarylaryl groups, all of which may be optionally substituted. Preferred aryl include phenyl and naphthyl. More preferred aryl include phenyl. Preferred substituents are selected from the group consisting of halogen, C1-4 alkyl, NH2, OCF3, CF3, O-alkyl, S-alkyl, CN, CHO, SO2-alkyl and NO2. Examples of heteroaryl rings included pyrrole, furan, thiophene, indole, isoindole, benzofuran, isobenzofuran, benzothiphene, pyridine, quinoline, isoquinoline, quinolizine, pyrazole, imidazole, isoxazole, oxazole, isothiazole, thiazole, pyridazine, pyrimidine, and pyrazine. As used herein, “heteroalkyl” refers to an optionally substituted ring not having conjugated pi electron system containing up 1-3 heteroatoms selected from O, S and N. Examples of heteroalkyl rings are piperidine, piperazine, morpholine, tetrahydrofuran, tetrahydopyran, and tetrahydrothiophene. As used herein “halogen” refers to include F, Cl, Br, and I. All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth. The general preparation of the aminothiophene analogs is shown in Schemes 1 and 2. Morpholine is added to a stirred solution of cyanoacetamide, sulfur, and cyclic ketone in absolute ethanol. The resulting solution is stirred at room temperature or up to 60° C. overnight. The solvent is then removed under vacuo and the residue is taken up into ethyl acetate, washed by water and brine, dried over anhydrous magesium sulfate, filtered and concentrated under vacuo to give a dark brown solid. The product is then usually purified by chromatography to give the desired product. This invention provides a pharmaceutical composition, which comprises a compound according to Formula I and a pharmaceutically acceptable carrier, diluent or excipient. Accordingly, the compounds of Formula I may be used in the manufacture of a medicament. Pharmaceutical compositions of the compounds of Formula I prepared as hereinbefore described may be formulated as solutions or lyophilized powders for parenteral administration. Powders may be reconstituted by addition of a suitable diluent or other pharmaceutically acceptable carrier prior to use. The liquid formulation may be a buffered, isotonic, aqueous solution. Examples of suitable diluents are normal isotonic saline solution, standard 5% dextrose in water or buffered sodium or ammonium acetate solution. Such formulation is especially suitable for parenteral administration, but may also be used for oral administration or contained in a metered dose inhaler or nebulizer for insufflation. It may be desirable to add excipients such as polyvinylpyrrolidone, gelatin, hydroxy cellulose, acacia, polyethylene glycol, mannitol, sodium chloride or sodium citrate. Alternately, these compounds may be encapsulated, tableted or prepared in an emulsion or syrup for oral administration. Pharmaceutically acceptable solid or liquid carriers may be added to enhance or stabilize the composition, or to facilitate preparation of the composition. Solid carriers include starch, lactose, calcium sulfate dihydrate, terra alba, magnesium stearate or stearic acid, talc, pectin, acacia, agar or gelatin. Liquid carriers include syrup, peanut oil, olive oil, saline and water. The carrier may also include a sustained release material such as glyceryl monostearate or glyceryl distearate, alone or with a wax. The amount of solid carrier varies but, preferably, will be between about 20 mg to about 1 g per dosage unit. The pharmaceutical preparations are made following the conventional techniques of pharmacy involving milling, mixing, granulating, and compressing, when necessary, for tablet forms; or milling, mixing and filling for hard gelatin capsule forms. When a liquid carrier is used, the preparation will be in the form of a syrup, elixir, emulsion or an aqueous or non-aqueous suspension. Such a liquid formulation may be administered directly p.o. or filled into a soft gelatin capsule. Typical compositions for inhalation are in the form of a dry powder, solution, suspension or emulsion. Administration may for example be by dry powder inhaler (such as unit dose or multi-dose inhaler, e.g. as described in U.S. Pat. No. 5,590,645 or by nebulisation or in the form of a pressurized aerosol. Dry powder compositions typically employ a carrier such as lactose, trehalose or starch. Compositions for nebulisation typically employ water as vehicle. Pressurized aerosols typically employ a propellant such as dichlorodifluoromethane, trichlorofluoromethane or, more preferably, 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane or mixtures thereof. Pressurized aerosol formulations may be in the form of a solution (perhaps employing a solubilising agent such as ethanol) or a suspension which may be excipient free or employ excipients including surfactants and/or co-solvents (e.g. ethanol). In dry powder compositions and suspension aerosol compositions the active ingredient will preferably be of a size suitable for inhalation (typically having mass median diameter (MMD) less than 20 microns e.g. 1-10 especially 1-5 microns). Size reduction of the active ingredient may be necessary e.g. by micronisation. Pressurized aerosol compositions will generally be filled into canisters fitted with a valve, especially a metering valve. Canisters may optionally be coated with a plastics material e.g. a fluorocarbon polymer as described in WO96/32150. Canisters will be fitted into an actuator adapted for buccal delivery. Typical compositions for nasal delivery include those mentioned above for inhalation and further include non-pressurized compositions in the form of a solution or suspension in an inert vehicle such as water optionally in combination with conventional excipients such as buffers, anti-microbials, tonicity modifying agents and viscosity modifying agents which may be administered by nasal pump. For rectal administration, the compounds of this invention may also be combined with excipients such as cocoa butter, glycerin, gelatin or polyethylene glycols and molded into a suppository. The methods of the present invention include topical, inhaled and intracolonic administration of the compounds of Formula I. By topical administration is meant non-systemic administration, including the application of a compound of the invention externally to the epidermis, to the buccal cavity and instillation of such a compound into the ear, eye and nose, wherein the compound does not significantly enter the blood stream. By systemic administration is meant oral, intravenous, intraperitoneal and intramuscular administration. The amount of a compound of the invention (hereinafter referred to as the active ingredient) required for therapeutic or prophylactic effect upon topical administration will, of course, vary with the compound chosen, the nature and severity of the condition being treated and the animal undergoing treatment, and is ultimately at the discretion of the physician. While it is possible for an active ingredient to be administered alone as the raw chemical, it is preferable to present it as a pharmaceutical formulation. The active ingredient may comprise, for topical administration, from 0.01 to 5.0 wt % of the formulation. The topical formulations of the present invention, both for veterinary and for human medical use, comprise an active ingredient together with one or more acceptable carriers therefor and optionally any other therapeutic ingredients. The carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin to the site of where treatment is required such as: liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose. Drops according to the present invention may comprise sterile aqueous or oily solutions or suspensions and may be prepared by dissolving the active ingredient in a suitable aqueous solution of a bactericidal and/or fungicidal agent and/or any other suitable preservative, and preferably including a surface active agent. The resulting solution may then be clarified by filtration, transferred to a suitable container, which is then sealed and sterilized by autoclaving, or maintaining at 90-100 C for half an hour. Alternatively, the solution may be sterilized by filtration and transferred to the container by an aseptic technique. Examples of bactericidal and fungicidal agents suitable for inclusion in the drops are phenylmercuric nitrate or acetate (0.002%), benzalkonium chloride (0.01%) and chlorhexidine acetate (0.01%). Suitable solvents for the preparation of an oily solution include glycerol, diluted alcohol and propylene glycol. Lotions according to the present invention include those suitable for application to the skin or eye. An eye lotion may comprise a sterile aqueous solution optionally containing a bactericide and may be prepared by methods similar to those for the preparation of drops. Lotions or liniments for application to the skin may also include an agent to hasten drying and to cool the skin, such as an alcohol or acetone, and/or a moisturizer such as glycerol or an oil such as castor oil or arachis oil. Creams, ointments or pastes according to the present invention are semi-solid formulations of the active ingredient for external application. They may be made by mixing the active ingredient in finely divided or powdered form, alone or in solution or suspension in an aqueous or non-aqueous fluid, with the aid of suitable machinery, with a greasy or non-greasy basis. The basis may comprise hydrocarbons such as hard, soft or liquid paraffin, glycerol, beeswax, a metallic soap, a mucilage, an oil of natural origin such as almond, corn, arachis, castor or olive oil, wool fat or its derivatives, or a fatty acid such as stearic or oleic acid together with an alcohol such as propylene glycol or macrogols. The formulation may incorporate any suitable surface active agent such as an anionic, cationic or non-ionic surface active agent such as sorbitan esters or polyoxyethylene derivatives thereof. Suspending agents such as natural gums, cellulose derivatives or in organic materials such as silicaceous silicas, and other ingredients such as lanolin, may also be included. The compounds of Formula I are useful as inhibitors of the IKK-beta kinase phosphorylation of IκB and as such are inhibitors of NF-κB activation. The present method utilizes compositions and formulations of said compounds, including pharmaceutical compositions and formulations of said compounds. The present invention particularly provides methods of treatment of diseases associated with inappropriate NF-κB activation, which methods comprise administering to an animal, particularly a mammal, most particularly a human in need thereof one or more compounds of Formula I. The present invention particularly provides methods for treating inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage, autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including aquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome and Ataxia Telangiestasia. For acute therapy, parenteral administration of one or more compounds of Formula I is useful. An intravenous infusion of the compound in 5% dextrose in water or normal saline, or a similar formulation with suitable excipients, is most effective, although an intramuscular bolus injection is also useful. Typically, the parenteral dose will be about 0.01 to about 50 mg/kg; preferably between 0.1 and 20 mg/kg, in a manner to maintain the concentration of drug in the plasma at a concentration effective to inhibit IKK-beta and therefore activation of NF-κB. The compounds are administered one to four times daily at a level to achieve a total daily dose of about 0.4 to about 80 mg/kg/day. The precise amount of a compound used in the present method which is therapeutically effective, and the route by which such compound is best administered, is readily determined by one of ordinary skill in the art by comparing the blood level of the agent to the concentration required to have a therapeutic effect. The compounds of Formula I may also be administered orally to the patient, in a manner such that the concentration of drug is sufficient to inhibit IKK-beta and therefore activation of NF-κB or to achieve any other therapeutic indication as disclosed herein. Typically, a pharmaceutical composition containing the compound is administered at an oral dose of between about 0.1 to about 50 mg/kg in a manner consistent with the condition of the patient. Preferably the oral dose would be about 0.5 to about 20 mg/kg. The compounds of Formula I may also be administered topically to the patient, in a manner such that the concentration of drug is sufficient to inhibit IKK-beta and therefore activation of NF-κB or to achieve any other therapeutic indication as disclosed herein. Typically, a pharmaceutical composition containing the compound is administered in a topical formulation of between about 0.01% to about 5% w/w. No unacceptable toxicological effects are expected when compounds of the present invention are administered in accordance with the present invention. The ability of the compounds described herein to inhibit the activation of NF-κB is clearly evidenced in their ability to inhibit the phosphorylation of the N-terminal fragment of IκB-α by IKK-β(see Table 1 for examples). These compounds also block the degradation of IκB-α and the nuclear translocation of NF-κB in human monocyctes and other mammalian cells upon activation of the cells with a pro-inflammatory stimulii (e.g., TNF-α, LPS, etc.). In addition these compounds inhibit pro-inflammatory mediator production from LPS-stimulated human monocytes and stimulated human primary synovial fibroblasts. The utility of the present NF-κB inhibitors in the therapy of diseases is premised on the importance of NF-κB activation in a variety of diseases. NF-κB plays a key role in the regulated expression of a large number of pro-inflammatory mediators including cytokines such as TNF, IL-1β, IL-6 and IL-8 (Mukaida et al., 1990; Liberman and Baltimore, 1990; Matsusaka et al., 1993), cell adhesion molecules, such as ICAM and VCAM (Marui et al., 1993; Kawai et al., 1995; Ledebur and Parks, 1995), and inducible nitric oxide synthase (iNOS) (Xie et al., 1994; Adcock et al., 1994). (Full reference citations are at the end of this section). Such mediators are known to play a role in the recruitment of leukocytes at sites of inflammation and in the case of iNOS, may lead to organ destruction in some inflammatory and autoimmune diseases (McCartney-Francis et al., 1993; Kleemann et al., 1993. Evidence for an important role of NF-κB in inflammatory disorders is obtained in studies of asthmatic patients. Bronchial biopsies taken from mild atopic asthmatics show significant increases in the number of cells in the submucosa staining for activated NF-κB, total NF-κB, and NF-κB-regulated cytokines such as GM-CSF and TNFα compared to biopsies from normal non-atopic controls (Wilson et al., 1998). Furthermore, the percentage of vessels expressing NF-κB immunoreactivity is increased as is IL-8 immunoreactivity in the epithelium of the biopsy specimens (Wilson et al., 1998). As such, inhibition of IL-8 production through the inhibition of NF-κB, as has been demonstrated by these compounds would be predicted be beneficial in airway inflammation. Recent studies suggest that NF-κB may also play a critical role in the pathogenesis of inflammatory bowel disease (IBD). Activated NF-κB is seen in colonic biopsy specimens from Chron's disease and ulcerative colitis patients (Ardite et al., 1998; Rogler et al., 1998; Schreiber et al., 1998). Activation is evident in the inflamed mucosa but not in uninflamed mucosa (Ardite et al., 1998; Rogler et al., 1998) and is associated with increased IL-8 mRNA expression in the same sites (Ardite et al., 1998). Furthermore, corticosteroid treatment strongly inhibits intestinal NF-κB activation and reduces colonic inflammation (Ardite et al., 1998; Schreiber et al., 1998). Again, inhibition of IL-8 production through the inhibition of NF-κB, as has been demonstrated by these compounds would be predicted be beneficial in inflammatory bowel disease. Animal models of gastrointestinal inflammation provide further support for NF-κB as a key regulator of colonic inflammation. Increased NF-κB activity is observed in the lamina propria macrophages in 2,4,6,-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice with p65 being a major component of the activated complexes (Neurath et al., 1996; Neurath and Pettersson, 1997). Local administration of p65 antisense abrogates the signs of established colitis in the treated animals with no signs of toxicity (Neurath et al., 1996; Neurath and Pettersson, 1997). As such, one would predict that small molecule inhibitors of NF-κB would be useful in the treatment of IBD. Further evidence for a role of NF-κB in inflammatory disorders comes from studies of rheumatoid synovium. Although NF-κB is normally present as an inactive cytoplasmic complex, recent immunohistochemical studies have indicated that NF-κB is present in the nuclei, and hence active, in the cells comprising human rheumatoid synovium (Handel et al., 1995; Marok et al., 1996; Sioud et al., 1998) and in animal models of the disease (Tsao et al., 1997). The staining is associated with type A synoviocytes and vascular endothelium (Marok et al., 1996). Furthermore, constitutive activation of NF-κB is seen in cultured synoviocytes (Roshak et al., 1996; Miyazawa et al., 1998) and in synovial cell cultures stimulated with IL-1β or TNFα (Roshak et al., 1996; Fujisawa et al., 1996; Roshak et al., 1997). Thus, the activation of NF-κB may underlie the increased cytokine production and leukocyte infiltration characteristic of inflamed synovium. The ability of these compounds to inhibit NF-κB and thereby inhibit the production of pro-inflammatory mediators (e.g. cytokines and prostanoids) by these cells would be predicted to yield benefit in rheumatoid arthritis. Biological Assays: The compounds of this invention may be tested in one of several biological assays to determine the concentration of compound, which is required to have a given pharmacological effect. NF-κB activity may also be measured in an electrophoretic mobility shift assay (EMSA) to assess the presence of NF-κB protein in the nucleus. The cells of interest are cultured to a density of 1×106/mL. The cells are harvested by centrifugation, washed in PBS without Ca2+ and Mg2+ and resuspended in PBS with Ca2+ and Mg2+ at 1×107 cells/mL. To examine the effect of compound on the activation of NF-κB, the cell suspensions are treated with various concentrations of drug or vehicle (DMSO, 0.1%) for 30 min. at 37° C. prior to stimulation with TNF-α (5.0 ng/mL) for an additional 15 min. Cellular and nuclear extracts are prepared follows. Briefly, at the end of the incubation period the cells (1×107 cells) are washed 2× in PBS without Ca2+ and Mg2+. The resulting cell pellets are resuspended in 20 uL of Buffer A (10 mM Hepes (pH 7.9), 10 mM KCl, 1.5 mM MgCl2, 0.5 mM dithiothreitol (DTT) and 0.1% NP-40) and incubated on ice for 10 min. The nuclei are pelleted by microcentrifugation at 3500 rpm for 10 min at 4° C. The resulting supernatant was collected as the cellular extract and the nuclear pellet was resuspended in 15 uL Buffer C (20 mM Hepes (pH 7.9), 0.42 M NaCl, 1.5 mM MgCl2, 25% glycerol, 0.2 mM EDTA, 0.5 mM DTT, and 0.5 mM phenylmethylsulphonyl fluoride (PMSF)). The suspensions are mixed gently for 20 min at 4° C. then microcentrifuged at 14,000 rpm for 10 min at 4° C. The supernatant is collected and diluted to 60 uL with Buffer D (20 mM Hepes (pH 7.9), 50 mM KCl, 20% glycerol, 0.2 mM EDTA, 0.5 mM DTT, and 0.5 mM PMSF). All samples are stored at −80° C. until analyzed. The protein concentration of the extracts is determined according to the method of Bradford (Bradford, 1976) with BioRad reagents. The effect of compounds on transcription factor activation is assessed in an electrophoretic mobility shift assay (EMSA) using nuclear extracts from treated cells as described above. The double stranded NF-κB consensus oligonucleotides (5′-AGTTGAGGGGACTTTCCCAGGC-3′) are labelled with T4 polynucleotide kinase and [g-32P]ATP. The binding mixture (25 uL) contains 10 mM Hepes-NaOH (pH 7.9), 4 mM Tris-HCl (pH 7.9), 60 mM KCl, 1 mM EDTA, 1 mM dithiothreitol, 10% glycerol, 0.3 mg/mL bovine serum albumin, and 1 ug poly(dI-dC)•poly(dI-dC). The binding mixtures (10 ug nuclear extract protein) are incubated for 20 min at room temperature with 0.5 ng of 32P-labelled oligonucleotide (50,000-100,000 cpm) in the presence or absence of unlabeled competitor after which the mixture is loaded on a 4% polyacrylamide gel prepared in 1× Tris borate/EDTA and electrophoresed at 200 V for 2 h. Following electrophoresis the gels are dried and exposed to film for detection of the binding reaction. The effect of compounds on the phosphorylation of IκB may be monitored in a Western blot. Cellular extracts are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on 10% gels (BioRad, Hercules, Calif.) and the proteins transferred to nitrocellulose sheets (Hybond™-ECL, Amersham Corp., Arlington Heights, Ill.). Immunoblot assays are performed using a polyclonal rabbit antibody directed against IκBα or IκBβ followed with a peroxidase-conjugated donkey anti-rabbit secondary antibody (Amersham Corp., Arlington Heights, Ill.). Immunoreactive bands are detected using the Enchanced Chemiluminescence (ECL) assay system (Amersham Corp., Arlington Heights, Ill.). Assays for IκB kinases were conducted as follows: IKK-α was expressed as a hexa-histidine tagged protein in baculovirus-infected insect cells and purified over a Ni-NTA affinity column. Kinase activity was assayed using 50 ng of purified protein in assay buffer (20 mM Hepes, pH 7.7, 2 mM MgCl2, 1 mM MnCl2, 10 mM β-glycerophosphate, 10 mM NaF, 10 mM PNPP, 0.3 mM Na3VO4, 1 mM benzamidine, 2 μM PMSF, 10 μg/ml aprotinin, 1 ug/mL leupeptin, 1 ug/mL pepstatin, 1 mM DTT) containing various concentrations of compound or DMSO vehicle and ATP as indicated (Pharmacia Biotech Inc., Piscataway, N.J.). The reaction was started by the addition of 200 ng IκB-GST (Santa Cruz Biotechnology, Inc., Santa Cruz, Calif.), in a total volume of 50 uL. The reaction was allowed to proceed for 1 h. at 30° C. after which the reaction was terminated by the addition of EDTA to a final concentration of 20 mM. Kinase activity was determined by dissociation-enhanced lanthanide fluorescence immunoassay (Wallac Oy, Turku, Finland) using a phospho-IκB-α (Ser32) antibody (New England Biolabs, Inc., Beverly, Mass.) and an Eu3+-labelled anti-rabbit IgG (Wallac Oy, Turku, Finland). The plates were read in a VICTOR 1420 Multilabel Counter (Wallac), using a standard europium protocol (excitation 340 nm, emission 615 nm; fluorescence measured for 400 μs after a 400 usec delay). Data are expressed as fluorescence (cps) units. IKK-β was expressed as a GST-tagged protein, and its activity was assessed in a 96-well scintillation proximity assay (SPA). Briefly, IKK-β was diluted in assay buffer as described above (20 nM final), with various concentrations of compound or DMSO vehicle, 240 nM ATP and 200 nCi [γ-33P]-ATP (10 mCi/mL, 2000 Ci/mmol; NEN Life Science Products, Boston, Mass.). The reaction was started with the addition of a biotinylated peptide comprising amino acids 15-46 of IκB-A (American Peptide) to a final concentration of 2.4 μM, in a total volume of 50 uL. The sample incubated for one hour a 30° C., followed by the addition of 150 uL of stop buffer (PBS w/o Ca2+, Mg 2+, 0.1% Triton X-100 (v/v), 10 mM EDTA) containing 0.2 mg streptavidin-coated SPA PVT beads (Amersham Pharmacia Biotech, Piscataway, N.J.). The sample was mixed, incubated for 10 min. at room temperature, centrifuged (1000×g, 2 minutes), and measured on a Hewlett-Packard TopCount. In addition, IKK-β or IKK-α activity is measured by phosphorylation of recombinant GST-IkappaBalpha using time-resolved fluorescence resonance energy transfer (TR-FRET) in 384-well microtitre plates. Briefly IKK-βor IKK-α is diluted in assay buffer (50 mM HEPES pH 7.4 containing 10 mM magnesium chloride, 1 mM CHAPS, 1 mM DTT and 0.01% w/v BSA) to 5 nM final concentration. This is added to various concentrations of compound or DMSO vehicle and the reaction started by addition of 25 nM GST-IkappaBalpha and 1 μM ATP in assay buffer to a volume of 30 uL. After incubation for 30 min at ambient temperature the reaction was stopped by addition of 50 mM pH 7.4 EDTA (15 uL). Detection of phophorylated product was achieved by addition of a LANCE europium chelate labelled specific anti-phosphoserine monoclonal antibody at 0.5 nM final concentration (Cell signalling Technology via Perkin Elmer) and allophycocyanin labelled anti-GST antibody at 10 nM final concentration (Prozyme) to give a final volume of 60 μl. After a further incubation at ambient temperature of a least 30 min the signal was read on a Perkin Elmer Discovery fluorimeter. The effect of IKK-β inhibitors on primary synovial fibroblast mediator production was assesses as follows: Primary cultures of human RSF were obtained by enzymatic digestion of synovium obtained from adult patients with rheumatoid arthritis as previously described (Roshak et al., 1996b). Cells were cultured in Earl's Minimal Essential Medium (EMEM) which contained 10% fetal bovine serum (FBS), 100 units/ml penicillin and 100 μg/ml streptomycin (GIBCO, Grand Island, N.Y.), at 37° C. and 5% CO2. Cultures were used at passages 4 through 9 in order to obtain a more uniform type B fibroblast population. For some studies, fibroblasts were plated at 5×104 cells/mL in 16 mm (diameter) 24 well plates (Costar, Cambridge, Mass.). Cells (70-80% confluence) were exposed to IL-10 (1 ng/mL) (Genzyme, Cambridge, Mass.) for the designated time. Drugs in DMSO vehicle (1%) were added to the cell cultures 15 minutes prior to the addition of IL-1. Studies were conducted 3-4 times using synovial cells from different donors. RSF cellular extracts were prepared from cells treated as described above. Briefly, human RSF were removed by trypsin/EDTA, washed, and harvested by centrifugation. Cellular extracts were prepared as previously described (Dignam et al., 1983; Osborn, et al., 1989). Briefly, at the end of the incubation period the cells (1×107 cells) were washed 2× in PBS without Ca2+ and Mg2+. The resulting cell pellets were resuspended in 20 uL of Buffer A (10 mM Hepes (pH 7.9), 10 mM KCl, 1.5 mM MgCl2, 0.5 mM. Effect of IKK-β inhibition on human monocyte stimulated eicosanoid and cytokine production was assessed as follows: Monocytes were isolated from heparinized whole blood by double gradient centrifugation as previously described. Isolated monocyte enriched PBMCs were then adhered to 24 well culture plates at 2×106 cells/mL in RPMI 1640 10% FBS (Hyclone, Logan, Utah) for 2 h. to further enrich the monocyte population. The media was then removed, cells washed once with RPMI 1640, and 1 mL RPMI 1640 10% FBS was added to the wells. Test compounds are added to the wells with a final vehicle concentration of 0.05% DMSO. Monocytes were activated by the addition of 200 ng/mL endotoxin (LPS; E. coli serotype 026:B6)(Sigma, St. Louis, Mo.) and incubated for 24 hrs. Cell-free supemates were analyzed by ELISA for TNF-α (EIA developed at SB), PGE2 (Cayman Chemical, Ann Arbor, Mich.), and IL-8 and IL-6 Biosource International, Camarillo, Calif.). Viability of the cells was determined by trypan blue exclusion. Effect of IKK-β inhibitors on phorbol ester-induced inflammation was assessed as follows: The inflammatory response induced by the cutaneous application of phorbol ester (PMA) to the external pinnae of Balb/c mice has proven to be a useful model to examine multifactorial inflammatory cell infiltration and inflammatory alteration of epidermis. The intense inflammatory lesion is dominated by neutrophil infiltration, which can be easily quantified by measurement tissue concentration myeloperoxidase, an azuriphilic granular enzyme present in neutrophils. In addition, the overall intensity of the inflammatory response can be measured by determination of ear thickness. Balb/c mice (n=6/group) were administered drug treatment or vehicle followed by PMA (4 ug/ear). The mice were sacrificed 4 h. later, the ear thickness determined and NF-κB activation was monitored by IκBα western or EMSA analysis. Effect of IKK-β inhibitors on rat carrageenan-induced paw edema was assessed as follows: Male Lewis rats (Charles River-Raleigh, N.C.) were housed and allowed free access to food and water, and weighed between 200-275 g for each experiment. Compound or vehicle (0.5% Tragacanth (p.o.) or 10% DMSO, 5% DMA, 30% Cremophor(i.p.)) was administered 30 minutes to 1 hour prior to the carrageenan injection. Edema was induced by injection of 1% carrageenan in sterile dH2O (0.05 ml/paw) into the plantar surface of the right hindpaw. Paw thickness was measured prior to administration of compound or vehicle, and again at 3 hours, to determine change in paw volume. Rats were euthanized by CO2 inhalation and the right hindfoot was removed, immediately frozen in liquid nitrogen and stored at −80C for analysis. To determine the effects of an IKK-2 inhibitor in the mouse collagen-induced arthritis (CIA) model, 12 male DBA/1 mice (20-22 grams) per treatment group were immunized on day 0 with a total of 100 uL of complete Freund's adjuvant (CFA) containing 200 ug of bovine type II collagen. On day 21 mice were boosted with 100 uL of phosphate buffered saline (PBS) containing 200 ug of bovine type II collagen (the 100 uL of collagen/CFA or collagen/PBS was injected subcutaneously into the tail). The IKK-2 inhibitor in vehicle, or vehicle alone, was administered intraperitoneally, twice daily, from days 1 through 40 (disease symptoms are evident beginning on days 25-28). Two additional treatment groups included the positive control etanercept (Enbrel) (4 mg/kg, intraperitoneally, every other day), and the etanercept vehicle (PBS). Mice were scored daily, through day 50, for clinical symptoms (see below), and paw thicknesses were measured. In addition to the 12 mice per treatment group that were scored throughout the experiment, at several time points during the course of disease satellite mice (3-5 per treatment group) treated as described above were utilized to measure cytokine/chemokine levels and p65 levels in the paw, the ex vivo antigen recall response by draining lymph node cells/splenocytes, and histological changes in the joint. Induction of arthritis AIA is induced by a single injection of 0.75 mg of Mycobacterium butyricum (Difco, Detroit, Mich.) suspended in paraffin oil into the base of the tail of male Lewis rats aged 6-8 weeks (160-180 g). Hindpaw volumes are measured by a water displacement method on day 16 and/or day 20. Test compounds were homogenized in a suitable vehicle and administered by a suitable route. Control animals are administered vehicles alone. Two dosing protocols are genrally used: prophylactic dosing, which is initiated on the day of adjuvant injection and therapeutic administration, initiated on day 10 once inflammation has been established. Clinical Scoring Each paw was assigned a score ranging from 0-4, based on the following criteria: 0=no inflammation 1=single swollen digit 2=several swollen digits, mild paw swelling 3=several swollen digits, moderate paw swelling 4=all digits swollen, severe paw swelling EXAMPLES AND EXPERIMENTAL General Nuclear magnetic resonance spectra were recorded at either 250, 300 or 400 MHz using, respectively, a Bruker AM 250, Bruker ARX 300 or Bruker AC 400 spectrometer. CDCl3 is deuteriochloroform, DMSO-d6 is hexadeuteriodimethylsulfoxide, and CD3OD is tetradeuteriomethanol. Chemical shifts are reported in parts per million (d) downfield from the internal standard tetramethylsilane. Abbreviations for NMR data are as follows: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, dd=doublet of doublets, dt=doublet of triplets, app=apparent, br=broad. J indicates the NMR coupling constant measured in Hertz. Continuous wave infrared (IR) spectra were recorded on a Perkin-Elmer 683 infrared spectrometer, and Fourier transform infrared (FTIR) spectra were recorded on a Nicolet Impact 400 D infrared spectrometer. IR and FTIR spectra were recorded in transmission mode, and band positions are reported in inverse wavenumbers (cm−1). Mass spectra were taken on either VG 70 FE, PE Syx API III, or VG ZAB HF instruments, using fast atom bombardment (FAB) or electrospray (ES) ionization techniques. Elemental analyses were obtained using a Perkin-Elmer 240C elemental analyzer. Melting points were taken on a Thomas-Hoover melting point apparatus and are uncorrected. All temperatures are reported in degrees Celsius. Analtech Silica Gel GF and E. Merck Silica Gel 60 F-254 thin layer plates were used for thin layer chromatography. Both flash and gravity chromatography were carried out on E. Merck Kieselgel 60 (230-400 mesh) silica gel. Where indicated, certain of the materials were purchased from the Aldrich Chemical Co., Milwaukee, Wis., TCI America, Portland, Oreg. All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth. The above description fully discloses the invention including preferred embodiments thereof. Modifications and improvements of the embodiments specifically disclosed herein are within the scope of the following claims. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Therefore the Examples herein are to be construed as merely illustrative and not a limitation of the scope of the present invention in any way. The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows. Example 1 2-Amino-4H-indeno[1,2-b]thiophene-3-carboxylic Acid Amide Trifluoroacetate Morpholine (1 mL) was added dropwise to a stirred solution of cyanoacetamide (0.84 g, 0.01 mol), sulfur (0.36, 0.012 mol), and 2-indanone (1.32 g, 0.01 mmol) in absolute ethanol (5 mL). The resulting solution was stirred at 60° C. overnight. The solvent was then removed under vacuo and the residue was taken up into ethyl acetate (10 mL), washed by water (2×10 mL) and brine (10 mL), dried over anhydrous magesium sulfate, filtered and concentrated under vacuo to give a dark brown solid. The product was then purified on Gilson preparative HPLC (YMC HPLC column 50×20 mm I.D., s-5 μm, 120 Å; gradient elution, 0.1% TFA in acetonitrile:0.1% aqueous TFA, 10:90 to 90:10, 10 min) to give the title compound as a brown solid (100 mg, 0.435 mmol, 4.3% yield). ESMS m/z: 231 [M+H]+. Example 2 2-Ureido-4H-indeno[1,2-b]thiophene-3-carboxylic Acid Amide Chlorosulfonyl isocyanate (0.025 g, 0.17 mL) was added dropwise to a stirred solution of 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide trifluoroacetate (0.040 g, 0.17 mmol) in dry dichloromethane (2 mL). The resulting reaction mixture was stirred under nitrogen for 30 min. Water (0.5 mL) was then added to the reaction mixture and the reaction mixture was allowed to stir an additional 10 minutes before the solvent was removed under vacuo. The residue was then purified on Gilson preparative HPLC (YMC HPLC column 50×20 mm I.D., s-5 μm, 120 Å; gradient elution, 0.1% TFA in acetonitrile: 0.1% aqueous TFA, 10:90 to 90:10, 10 min) to give title compound as brown solid (0.020 g, 0.435 mmol, 43.5% yield). ESMS m/z: 274 [M+H]+. Example 3 2-Acetylamino-4H-indeno[1,2-b]thiophene-3-carboxylic Acid Amide Acetyl chloride (0.039 g, 0.5 mmol) was added dropwise to a stirred solution of 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide(0.115 g, 0.5 mmol) in dry pyridine (3 mL) at room temperature. The resulting reaction mixture was stirred under nitrogen for 2 h. Ethyl ether (20 mL) was then added to the reaction mixture. The reaction mixture was allowed to stir an additional 10 minutes. The reaction mixture was then filtered, washed with excess ethyl ether, air dried to give the title compound as light brown solid (0.082 g, 0.435 mmol, 60.3% yield). ESMS m/z: 273 [M+H]+. Example 4 2-Amino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 1 except that 2-indanone was replaced with beta-tetralone to give the above title compound as brown solid. ESMS m/z: 245 [M+H]+. Example 5 2-Acetylamino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 3 except that 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide to give the above title compound as brown solid. ESMS m/z: 287 [M+H]+. Example 6 2-Ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 2 except 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide to give the above title compound as brown solid. ESMS m/z: 288 [M+H]+. Example 7 2-Amino-8-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide Trifluoroacetate The title compound was prepared by the same procedure as Example 1 except that 2-indanone was replaced with 7-methoxy-2-tetralone to give the above title compound as light grey solid ESMS m/z: 275 [M+H]+. Example 8 8-Methoxy-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 2 except 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-8-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3 carboxylic acid amide trifluoroacetate to give the above title compound as brown solid. ESMS m/z: 318 [M+H]+. Example 9 2-Amino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide Morpholine (0.57 mL) was added dropwise to a stirred solution of cyanoacetamide (0.48 g, 5.7 mmol), sulfur (0.20, 6.24 mmol), and 6-methoxy-2-tetralone (1.00 g, 5.7 mmol) in absolute ethanol (3 mL). The resulting solution was stirred at 70° C. overnight. The solvent was then removed under vacuo and the residue was taken up into ethyl acetate (10 mL), washed by water (2×10 mL) and brine (10 mL), dried over anhydrous magesium sulfate, filtered and concentrated under vacuo to give a dark brown oil. The residul oil was purified by flash chromaograph (silic gel, 75% ethyl acetate/hexane) to give the title compound as light grey solid (0.12 g, 0.437 mmol, 7.6% yield). ESMS m/z: 275 [M+H]+. Example 10 2-Acetylamino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboylic Acid Amide The title compound was prepared by the same procedure as Example 3 except that 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-7-methoxy-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide to give the above title compound as light grey solid. ESMS m/z: 317 [M+H]+. Example 11 2-Amino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 9 except 6-methoxy-2-tetralone was replaced with 6-bromo-2-tetralone to give the above title compound as light grey solid. ESMS m/z: 324 [M+H]+. Example 12 2-Acetylamino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 3 except that 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide to give the above title compound as light grey solid. ESMS m/z: 366 [M+H]+. Example 13 7-Bromo-2-ureido-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic Acid Amide The title compound was prepared by the same procedure as Example 2 except 2-amino-4H-indeno[1,2-b]thiophene-3-carboxylic acid amide was replaced with 2-amino-7-bromo-4,5-dihydro-naphtho[1,2-b]thiophene-3-carboxylic acid amide trifluoroacetate to give the above title compound as brown solid. ESMS m/z: 367 [M+H]+.
<SOH> BACKGROUND OF THE INVENTION <EOH>Recent advances in scientific understanding of the mediators involved in acute and chronic inflammatory diseases and cancer have led to new strategies in the search for effective therapeutics. Traditional approaches include direct target intervention such as the use of specific antibodies, receptor antagonists, or enzyme inhibitors. Recent breakthroughs in the elucidation of regulatory mechanisms involved in the transcription and translation of a variety of mediators have led to increased interest in therapeutic approaches directed at the level of gene transcription. Nuclear factor κB (NF-κB) belongs to a family of closely related dimeric transcription factor complexes composed of various combinations of the Rel/NF-κB family of polypeptides. The family consists of five individual gene products in mammals, RelA (p65), NF-κB1 (p50/p105), NF-κB2 (p49/p100), c-Rel, and RelB, all of which can form hetero- or homodimers. These proteins share a highly homologous 300 amino acid “Rel homology domain” which contains the DNA binding and dimerization domains. At the extreme C-terminus of the Rel homology domain is a nuclear translocation sequence important in the transport of NF-κB from the cytoplasm to the nucleus. In addition, p65 and cRel possess potent transactivation domains at their C-terminal ends. The activity of NF-κB is regulated by its interaction with a member of the inhibitor IκB family of proteins. This interaction effectively blocks the nuclear localization sequence on the NF-κB proteins, thus preventing migration of the dimer to the nucleus. A wide variety of stimuli activate NF-κB through what are likely to be multiple signal transduction pathways. Included are bacterial products (LPS), some viruses (HIV-1, HTLV-1), inflammatory cytokines (TNFα, IL-1), environmental and oxidative stress and DNA damaging agents. Apparently common to all stimuli however, is the phosphorylation and subsequent degradation of Iκ. IκB is phosphorylated on two N-terminal serines by the recently identified IκB kinases (IKK-α and IKK-β). Site-directed mutagenesis studies indicate that these phosphorylations are critical for the subsequent activation of NF-κB in that once phosphorylated the protein is flagged for degradation via the ubiquitin-proteasome pathway. Free from IκB, the active NF-κB complexes are able to translocate to the nucleus where they bind in a selective manner to preferred gene-specific enhancer sequences. Included in the genes regulated by NF-κB are a number of cytokines and chemokines, cell adhesion molecules, acute phase proteins, immunoregulatory proteins, eicosanoid metabolizing enzymes and anti-apoptotic genes. It is well-known that NF-κB plays a key role in the regulated expression of a large number of pro-inflammatory mediators including cytokines such as TNF, IL-1β, IL-6 and IL-8, cell adhesion molecules, such as ICAM and VCAM, and inducible nitric oxide synthase (iNOS). Such mediators are known to play a role in the recruitment of leukocytes at sites of inflammation and in the case of iNOS, may lead to organ destruction in some inflammatory and autoimmune diseases. The importance of NF-κB in inflammatory disorders is further strengthened by studies of airway inflammation including asthma, in which NF-κB has been shown to be activated. This activation may underlie the increased cytokine production and leukocyte infiltration characteristic of these disorders. In addition, inhaled steroids are known to reduce airway hyperresponsiveness and suppress the inflammatory response in asthmatic airways. In light of the recent findings with regard to glucocorticoid inhibition of NF-κB, one may speculate that these effects are mediated through an inhibition of NF-κB. Further evidence for a role of NF-κB in inflammatory disorders comes from studies of rheumatoid synovium. Although NF-κB is normally present as an inactive cytoplasmic complex, recent immunohistochemical studies have indicated that NF-κB is present in the nuclei, and hence active, in the cells comprising rheumatoid synovium. Furthermore, NF-κB has been shown to be activated in human synovial cells in response to stimulation with TNF-α or IL-1β. Such a distribution may be the underlying mechanism for the increased cytokine and eicosanoid production characteristic of this tissue. See Roshak, A. K., et al., J. Biol. Chem., 271, 31496-31501 (1996). Expression of IKK-β has been shown in synoviocytes of rheumatoid arthritis patients and gene transfer studies have demonstrated the central role of IKK-β in stimulated inflammatory mediator production in these cells. See Aupperele et al. J. Immunology 1999. 163: 427-433 and Aupperle et al. J. Immunology 2001; 166: 2705-11. More recently, the intra-articular administration of a wild type IKK-β adenoviral construct was shown to cause paw swelling while intra-articular administration of dominant-negative IKK-β inhibited adjuvant-induced arthritis in rat. See Tak et al. Arthritis and Rheumatism 2001; 44: 1897-1907. The NF-κB/Rel and IκB proteins are also likely to play a key role in neoplastic transformation and metastasis. Family members are associated with cell transformation in vitro and in vivo as a result of overexpression, gene amplification, gene rearrangements or translocations. In addition, rearrangement and/or amplification of the genes encoding these proteins are seen in 20-25% of certain human lymphoid tumors. Further, NF-κB is activated by oncogenic ras, the most common defect in human tumors and blockade of NF-κB activation inhibits ras mediated cell transformation. In addition, a role for NF-κB in the regulation of apoptosis has been reported, strengthening the role of this transcription factor in the regulation of tumor cell proliferation. TNF, ionizing radiation and DNA damaging agents have all been shown to activate NF-κB which in turn leads to the upregulated expression of several anti-apoptotic proteins. Conversely, inhibition of NF-κB has been shown to enhance apoptotic-killing by these agents in several tumor cell types. As this likely represents a major mechanism of tumor cell resistance to chemotherapy, inhibitors of NF-κB activation may be useful chemotherapeutic agents as either single agents or adjunct therapy. Recent reports have implicated NF-κB as an inhibitor of skeletal cell differentiation as well as a regulator of cytokine-induced muscle wasting (Guttridge et al. Science; 2000; 289: 2363-2365.) further supporting the potential of NF-κB inhibitors as novel cancer therapies. Several NF-κB inhibitors are described in C. Wahl, et al. J. Clin. Invest. 101(5), 1163-1174 (1998), R. W. Sullivan, et al. J. Med. Chem. 41, 413-419 (1998), J. W. Pierce, et al. J. Biol. Chem. 272, 21096-21103 (1997). The marine natural product hymenialdisine is known to inhibit NF-κB. Roshak, A., et al., JPET, 283, 955-961 (1997). Breton, J. J and Chabot-Fletcher, M. C., JPET, 282, 459-466 (1997). Additionally, patent applications have been filed on aminothiophene inhibitors of the IKK-2, see Callahan, et al., WO 2002030353; Baxter, et al., WO 2001058890, Faull, et al., WO 2003010158; Griffiths, et al., WO2003010163; Fancelli, et al., WO 200198290; imidazole inhibitors of IKK-2, see Callahan, et al., WO 200230423; anilinophenylpyrimidine inhibitors of IKK-2, see Kois, et al., WO 2002046171; β-carboline inhbitors of IKK-2, see Ritzeler, et al., WO 2001068648, Ritzeler, et al., EP 1134221; Nielsch, et al. DE 19807993; Ritzeler, et al., EP 1209158; indole inhibitors of IKK-2, see Ritzeler, et al., WO 2001030774; benzimidazole inhibitors of the IKK-2, see Ritzeler, et al., DE 19928424; Ritzeler et al, WO 2001000610; aminopyridine inhibitors of IKK-2, see Lowinger, et al, WO2002024679; Murata, et al, WO 2002024693; Murata, et al., WO2002044153; pyrazolaquinazoline inhibitors of IKK-2, see Beaulieu, et al., WO2002028860; Burke et al, WO2002060386, Burke, et al. U.S. 20030022898; quinoline inhibitors of IKK-2, Browner, et al., WO2002041843, Browner, et al., U.S. 20020161004 and pyridylcyanoguanidine inhibitors of IKK-2, see Bjorkling, et al., WO 2002094813, Binderup et al, WO 2002094322 and Madsen, et al., WO 200294265. The natural products staurosporine, quercetin, K252a and K252b have been shown to be IKK-2 inhibitors, see Peet, G. W. and Li, J. J. Biol. Chem., 274, 32655-32661 (1999) and Wisniewski, D., et al., Analytical Biochem. 274, 220-228 (1999). Synthetic inhibitors of IKK-2 have also been described, see Burke, et al. J. Biol. Chem., 278, 1450-1456 (2003) and Murata, et al., Bioorg. Med. Chem. Lett., 13, 913-198 (2003) have described IKK-2 inhibitors. U.S. Pat. No. 3,963,750 describes the preparation of certain aminothiophenes.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention involves novel compounds and novel methods of inhibiting the activation transcription factor NF-κB using the present compounds. An object of the present invention is to provide a method for treating diseases which may be therapeutically modified by altering the activity of transcription factor NF-κB. Accordingly, in the first aspect, this invention provides a pharmaceutical composition comprising a compound according to Formula I. In another aspect, this invention provides a method of treating diseases in which the disease pathology may be therapeutically modified by inhibiting phosphorylation and subsequent degradation of IκB by IKK-β. In still another aspect, this invention provides a method of treating diseases in which the disease pathology may be therapeutically modified by inhibiting pathological activation of NF-κB. In a particular aspect, this invention provides methods for treating a variety of diseases associated with NF-κB activation including inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease) osteoarthritis, osteoporosis and fibrotic diseases, dermatosis, including psoriasis, atopic dermatitis and ultraviolet radiation (UV)-induced skin damage; autoimmune diseases including systemic lupus eythematosus, multiple sclerosis, psoriatic arthritis, alkylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, including Hodgkins disease, cachexia, inflammation associated with infection and certain viral infections, including acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome and Ataxia Telangiestasia. detailed-description description="Detailed Description" end="lead"?
20041008
20070227
20050728
90265.0
0
LAMBKIN, DEBORAH C
NF-KB INHIBITORS
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,874
ACCEPTED
Method of manufacturing an electronic device, and electronic device
The invention relates to a method of manufacturing a semiconductor device (10), whereby an electric element (11) is attached on or above a carrier plate (4) which comprises a first layer (5) of a first material and a second layer (2) of a second material which differs from the first, which is electrically conducting, which has a smaller thickness than the first layer (5), and in which a cavity (6) is formed that extends at least to the first layer (5). The element (11) is electrically connected to parts (2) of the carrier plate (4) at first connection regions (1), and an encapsulation is deposited around the element (11) and in the cavity (6). Then so much of the first layer (5) of the carrier plate (4) is removed that the cavity (6) is reached, whereby second connection conductors (2) are formed from the remaining portion of the carrier plate (4). According to the invention, at least one further cavity (7) is formed in a portion of the carrier plate (4) surrounded by the cavity (6) before the encapsulation (3) is deposited, which further cavity (7) becomes at least substantially filled with a portion of the encapsulation (3) during the deposition thereof and, within the second connection regions (2), separates a portion (2A) thereof from the remaining portion (2B) thereof, the smallest dimension of the portion (2A) being chosen to be smaller than the smallest dimension of the remaining portion (2B) of each second connection region (2). The portion (2A) may thus be readily provided with solder (8A) having a smaller thickness than the solder (8B) in the remaining portion of the second connection region (2). This is an advantage, for example in the case of surface mounting of the device (10). Preferably, the first connection regions (1) are connected to the portion (2A) of the connection region (2).
1. A method of manufacturing an electronic device which comprises an electric element provided with first connection regions and with an electrically insulating envelope, which method comprises the steps of: providing a recess in a first surface of a carrier plate, said plate comprising in that order a first layer of a first material and a second layer of a second, electrically conducting material different from the first material, which recess extends from the first surface through the second layer at least to the first layer; providing the electric element on or above the surface of the carrier plate; electrically connecting the first connection regions to portions of the second layer lying within the recess; surrounding the electric element by means of the insulating envelope which fills up the recess in the carrier plate at least substantially; and removing the carrier plate from a second surface of the carrier plate, which second surface faces away from the first surface, to at least an extent such that the recess filled by a portion of the envelope is reached, whereby second connection regions are formed by the portions of the second layer lying within the recess, characterized in that the recess extends into the first layer, such that underetching takes place in the first layer with respect to the second layer under formation of a cavity, which cavity is filled up by the insulating envelope. 2. A method as claimed in claim 1, characterized in that, before the envelope is provided, at least one further recess is provided in a portion of the carrier plate surrounded by the recess, which further recess is largely filled with a portion of the envelope during the application thereof, and which further recess is positioned within each second connection region such that a portion thereof is delimited from the remaining portion of the second connection region, the smallest dimension of said portion being chosen to be smaller than the smallest dimension of the remaining portion of the second connection region, and so much of the carrier plate is removed that also said further recess is reached. 3. A method as claimed in claim 1, characterized in that a solder particle is provided on at least a portion of each second connection region after so much of the carrier plate has been removed that the recess and the further recess have been reached and the second connection regions have been formed. 4. A method as claimed in claim 3, characterized in that the solder particle is melted after its application such that each second connection region is wetted in its entirety, and such that the height of the solder in said portion of each second connection region is smaller than it is of the solder in the remaining portion of each second connection region after solidification of the solder owing to its cooling down. 5. A method as claimed in claim 2, characterized in that the first connection regions are connected to said portions of the second connection regions. 6. A method as claimed in claim 2, characterized in that the recess and the further recess are formed in one and the same process step. 7. A method as claimed in claim 2, characterized in that the further recess is made in the form of one or several recesses in the carrier plate which are positioned within each second connection region under formation such that they together with part of the inner edge of the recess surround a portion of each second connection region, of which portion the smallest dimension is smaller than the smallest dimension of the remaining portion of each second connection region. 8. A method as claimed in claim 2, characterized in that the ratio of the smallest dimension of the portion to that of the remaining portion of the second connection region is preferably chosen to be smaller than 1/2, more preferably between 1/3 and 1/6. 9. A method as claimed in any one of the preceding claims, characterized in that aluminum is chosen for the material of the first layer of the carrier plate, and copper is chosen for the material of the second layer of the carrier plate. 10. A semiconductor device comprising an electric element provided with first connection regions, further comprising second connection regions with a first side and with a second side facing away therefrom, which second connection regions are each provided at the first side with an electrical connection to the first connection regions and can be provided at the second side with electrical connection pieces for placement on a substrate, which electric element is surrounded by an electrically insulating envelope which extends at least to the second connection region, characterized in that the envelope extends to the second side of each second connection region such that the second connection region is accessible in a recess of the envelope for being placed on the substrate. 11. A semiconductor device as claimed in claim 10 and provided with second connection regions of varying size, whereon, when solder bumps are used as the electrical connection pieces, said bumps will have a height which is dependent on the size of the respective second connection regions.
The invention relates to a method of manufacturing an electronic device which comprises an electric element provided with first connection regions and with an electrically insulating envelope, which method comprises the steps of providing a recess in a first surface of a carrier plate, said plate comprising in that order a first layer of a first material and a second layer of a second, electrically conducting material different from the first material, which recess extends from the first surface through the second layer at least to the first layer; providing the electric element on or above the surface of the carrier plate; electrically connecting the first connection regions to portions of the second layer lying within the recess; surrounding the electric element by means of the insulating envelope which fills the recess in the carrier plate at least substantially; and removing the carrier plate from a second surface of the carrier plate, which second surface faces away from the first surface, to at least an extent such that the recess filled by a portion of the envelope is reached, whereby second connection regions are formed by the portions of the second layer lying within the recess. The invention also relates to a semiconductor device comprising an electric element provided with first connection regions, further comprising second connection regions with a first side and with a second side facing away therefrom, which second connection regions are provided at the first side with an electrical connection to the first connection regions and can be provided at the second side with electrical connection pieces for placement on a substrate, which electric element is surrounded by an electrically insulating envelope which extends at least to the second connection regions. Such a method is particularly suitable for the inexpensive manufacture of semiconductor devices among other items. The electric element therein is an electric element, such as a (semi-)discrete transistor or diode, an integrated circuit, a memory circuit, etc. The devices manufactured by such a method may also be particularly compact, which renders possible the ever advancing miniaturization required in many applications. Such a method and such a semiconductor device are known from European patent EP 1 160 858 A2. It is described therein how a semiconductor IC (=Integrated Circuit) can be enveloped in a compact manner. The IC is fastened on or above a carrier plate. The first connection regions of the IC are connected to parts of the carrier plate either directly or via an electrically conducting wire. The carrier plate comprises two metal layers in succession, of which the upper layer adjoining the IC has a smaller thickness than the lower layer. The carrier plate is provided with a recess which extends from the surface of the second layer into the first layer and which surrounds portions of the carrier plate from which the second connection regions of the enveloped IC will be formed. After the IC has been provided on or above the carrier plate, an electrically insulating (and passivating) envelope is provided around the IC and against the carrier plate. The recess is largely filled up with part of the envelope thereby. Then as large as possible a portion of the carrier plate is removed, in particular a major portion of the first layer thereof, such that the recess filled with a portion of the envelope is reached. The second connection regions of the enveloped IC are formed thereby from (remaining) portions of the carrier plate. The IC is then ready, for example, for final surface mounting or for fastening to a lead frame. A disadvantage of the known method is that the solder provided as solder bumps on the second connection regions for final mounting will flow out over the entire connection region with a comparatively small and substantially homogeneous thickness after the necessary heating, and will thus remain present also after solidification. This may be avoided through the provision of a solder-repelling layer on the second connection regions, which layer is provided with openings by means of photolithography, in which openings the solder bumps are provided. This, however, makes the method more complicated. This is because said photolithography step has to take place during the assembling process, i.e. after the enveloping step. Such assembling processes, however, are often carried out in factories in which lithographic equipment is not present. In addition, a lithographic step requires an accuracy and time duration which are not available during assembling. An alternative reduction in size of the second connection regions does not provide a solution either, because this will cause the electrical and thermal quality of the connection of the IC to the outer world to deteriorate. This is also not desirable. It is accordingly a first object of the invention to provide a method which does not have the above disadvantage, or at least to a lesser degree, and which is yet simple and accordingly inexpensive. According to the invention, a method of the kind mentioned in the opening paragraph is for this purpose characterized in that the recess extends into the first layer, such that underetching takes place in the first layer with respect to the second layer under formation of a cavity, which cavity is filled up by the insulating envelope. Etching down into the first layer creates a cavity below the second layer. This cavity is filled up by the insulating envelope. The edges of the second connection regions are provided thereby with a protective layer consisting of the insulating envelope. When the carrier plate is removed from the second surface, this protective layer will come to the surface. The second connection regions lie recessed with respect to said surface. The method according to the invention has among its advantages that no lithographic step is necessary any more after enveloping; the second connection regions are in fact patterned into contact surfaces by means of the envelope. The properties of the electrically insulating envelope, which often comprises a synthetic resin such as an epoxy resin or a thermoplastic material, are such that solder is repelled thereby. The solder that is subsequently applied to the second connection regions thus remains restricted to the contact surfaces. It is a further advantage of the method according to the invention that the second layer may be kept thin, in particular in comparison with the first layer. This has the result that second connection regions can be positioned at a smaller mutual distance than was possible in the prior art. Finally, a major advantage of a method according to the invention is that it is comparatively simple and does not require an additional step. In a favorable embodiment of the method, before the envelope is provided, at least one further recess is provided in a portion of the carrier plate surrounded by the recess, which further recess is substantially filled with a portion of the envelope during the provision thereof. Said further recess is positioned within the respective second connection region such that a portion thereof is delimited from the remaining portion of the second connection region, the smallest dimension of said portion being chosen to be smaller than the smallest dimension of the remaining portion of the second connection region. When the carrier plate is removed, so much of the carrier plate is removed that also the further recess is reached. Each second connection region formed is thus locally interrupted by a portion of the envelope present there. The properties of the electrically insulating envelope, which often comprises a synthetic resin such as an epoxy resin or a thermoplastic material, are such that solder is repelled thereby. It is true that the solder bump when provided at one side of the interruption of the second connection region will flow out during melting over the entire remaining portion of the second connection region, but after solidification it will remain present with a greater thickness in that portion of the connection region whose smallest dimension is greatest. Such a local elevation of the solder is particularly favorable, for example, for final surface mounting of the semiconductor device. In addition, the electrical and thermal properties of the connection of the electric element to the outer world remain excellent because the surface of the total second connection region is hardly made smaller by the local interruption thereof, while also the electrical and thermal quality of the interconnection between the (two) parts of the second connection region thus formed remains excellent. This is very important, in particular in the case of comparatively compact semiconductor devices, even if the absolute power dissipation thereof is not great, because the power density increases in such devices. In a preferred embodiment of a method according to the invention, therefore, a solder particle is provided on at least a portion of each second connection region after so much of the carrier plate has been removed that the recess and further recess have been reached and the second connection regions have been formed. Preferably, the solder particle is melted after its application such that each second connection region is wetted in its entirety, and such that the height of the solder in said portion of each second connection region is smaller than it is in the remaining portion of each second connection region after solidification of the solder owing to cooling-down. In a major embodiment, the first connection regions are connected to said portions of the second connection regions. As a result, the connection between the first and the second connection region is not broken again or mechanically loaded during final mounting of the finished device by means of the thicker solder of the remaining portion of each second connection region. Preferably, furthermore, the recess and the further recess are simultaneously formed in one and the same process step. The method according to the invention is not more complicated or more expensive than the known method in that case. The use of an adapted mask suffices for achieving the desired result. Preferably, the further recess is formed as one or several recesses in the carrier plate which are positioned within the respective second connection region to be formed such that they, together with a portion of the inner edge of the recess, delimit a portion of each second connection region whose smallest dimension is smaller than the smallest dimension of the remaining portion thereof. The ratio of the smallest dimension of the portion to that of the remaining portion of the second connection region is preferably chosen to be smaller than 1/2, and more preferably between 1/3 and 1/6. Very favorable results were obtained when aluminum was chosen for the material of the first layer of the carrier plate and copper for the material of the second layer of the carrier plate. These materials, and in particular copper, have good electrical and thermal properties and in addition can be very well, even selectively etched with respect to one another, for example in a wet-chemical etchant. The removal of the major portion of the carrier plate may also very well be effected by means of CMP (=Chemical Mechanical Polishing). Good results were obtained when the thickness of the first layer of the carrier plate was chosen to lie between 10 and 300 μm, and preferably at approximately 30 μm, and the thickness of the second layer was chosen to lie between 2 and 20 μm, preferably at 10 μm. It is advantageous to remove the first layer of the carrier plate in its entirety after the envelope has been provided. A very good etchant for aluminum—besides a possible use of CMP—is formed by hot sodium lye. The method according to the invention is particularly suitable for the manufacture of semiconductor devices with discrete or semi-discrete electric elements such as used, for example, in mobile telephones. The invention also relates to semiconductor devices obtained by a method according to the invention. It is a second object of the invention to provide a semiconductor device of the kind mentioned in the second paragraph which can be manufactured in an inexpensive manner and in which the second connection regions are effective protected. This second object is achieved in that the envelope extends to the second side of the second connection regions such that the second connection regions are accessible in a recess of the envelope for being placed on the substrate. The second connection regions in the semiconductor device according to the invention lie in a recess of the envelope, i.e. recessed with respect to the surface of the semiconductor device. The semiconductor device thus complies with the requirements for placement on a substrate, while no additional layers are necessary for this. The electrical connection in the semiconductor device is preferably formed by bumps, but it may alternatively be realized with solder, bonding wires, or anisotropically conducting glue. It is furthermore possible to realize the connection in a contactless manner, for example by capacitive coupling, in particular for electric elements in which the number of incoming and outgoing signals and the power dissipation are comparatively limited, such as those used for identification purposes. The connection pieces for placement on a substrate are preferably solder bumps. Alternatively, anisotropically conducting glues or other connection pieces may be used. In a favorable embodiment, the device is provided with second connection regions of varying size on which the solder bumps, when applied as electrical connection pieces, will have a height which is dependent on the size of the respective second connection region. The use of solder bumps of varying heights is found to be a very desirable characteristic of an envelope in practice. This may be realized in a simple manner in the device according to the invention thanks to the repelling action of the envelope with respect to solder. The invention will now be explained in more detail with reference to an embodiment and the drawing, in which FIG. 1 diagrammatically and in perspective view shows a semiconductor device manufactured by a method according to the invention, FIG. 2 shows the device of FIG. 1 in a diagrammatic cross-sectional view taken on the line II-II in the thickness direction, and FIGS. 3 to 9 show the device of FIG. 1 in consecutive stages of manufacture by an embodiment of a method according to the invention in a diagrammatic cross-sectional view taken on the line 11-11 in the thickness direction. The Figures are not true to scale, and some dimensions have been particularly exaggerated for greater clarity. Corresponding regions or components have been given the same reference numerals as much as possible. FIG. 1 is a diagrammatic perspective view of a semiconductor device manufactured by a method according to the invention. FIG. 2 also shows the device of FIG. 1, in a diagrammatic cross-sectional view taken on the line II-II in the thickness direction. FIGS. 2 to 5 are diagrammatic cross-sectional views taken on the line II-II in the thickness direction in FIG. 1 of the device of FIG. 1 in consecutive stages of its manufacture by means of an embodiment of a method according to the invention. The device 10 comprises an electric element 11 (see FIG. 2) which is provided with a plurality, three in this case, of first connection regions 1, two of which are depicted in FIG. 2, and which is surrounded by an envelope 3, made of epoxy material in this case. A second connection region 2 for each first connection region 1 is present on the envelope 3 and is connected thereto by means of solder 12. The electric element 11 in this example comprises a bipolar transistor 11 and is accordingly provided with three second connection regions 2, as can be seen at the upper side. Said regions are provided with solder 8. The second connection regions 2 are surrounded by portions 6 of the envelope 3, and portions 7 of the envelope 3 lie within the second connection regions 2. The solder 8 extends over each entire second connection region 2, but it has a greater thickness locally (see FIG. 2). Since portions 2A of the second connection regions 2 are delimited from the remaining portion 2B of the second connection regions 2 by portions 7 of the envelope 3 and by a portion of the inner edge of the portions 6 of the envelope 3, a solder bump 8 placed in the second connection region 2 has indeed wetted the entire second connection region 2 after melting but, after solidification of the solder 8, the thickness of the portion 8A of the solder 8 lying on the portion 2A will be smaller than the thickness of the portion 8B of the solder 8 lying on the remaining portion 2B. This is also because the smallest dimension of the portion 2A is smaller than the smallest dimension of the remaining portion of the second connection region. This difference in thickness of the solder 8 is favorable for surface mounting of the device 10. FIGS. 3 to 9 are diagrammatic cross-sectional views taken on the line II-II in the thickness direction in FIG. 1 showing the device of FIG. 1 in consecutive stages of manufacture by an embodiment of a method according to the invention. The method starts, see FIG. 3, with a carrier plate 4 which comprises a first layer, of aluminum in this case and 30 μm thick. A second layer 2 of an electrically conducting material, copper in this case, and with a thickness smaller than that of the first layer 5, 10 μm in this case, is present thereon. In this assembly, see FIG. 4, the beginning of a recess 6 and of a further recess 7, i.e. two further, round recesses 7, are formed by means of photolithography and etching. The etchant used may be, for example, ferrichloride which etches copper more or less selectively with respect to aluminum. Subsequently, see FIG. 5, the formation of the recess 6 and of the further recess 7 is continued in that the first layer 5 of the carrier plate 4 is etched. Aluminum may be selectively etched with respect to copper, for example, by means of sodium lye. In this manner the aluminum of the first layer 5 is underetched with respect to the portions 2A, 2B of the copper layer 2. Subsequently, see FIG. 6, an electric element 11, a bipolar transistor 11 in this case, is fastened on or above, in this case on the carrier plate 4. This is done here by means of solder 12, with which the electric element 11 is fastened by its connection regions 11 to the portions 2A, 2B of the carrier plate 4. The electric element 11 may be fastened to the carrier plate 4 in an alternative manner, for example by means of an electrically insulating glue. The connection regions 1 of the element 11 are then preferably turned so as to face away from the carrier plate 4 and are electrically connected to the portions 2A, 2B of the carrier plate 4 by means of conductive wires. After this, see FIG. 7, the device 10 is placed in a mold (not shown) and an envelope 3 comprising an epoxy resin material in this case, is provided around the element 11 and pressed against the carrier plate 4 by means of injection molding. The recess 6 and the further recess 7 are thus filled with portions 6, 7 of the envelope 3. Subsequently, see FIG. 8, a major portion of the carrier plate 4 is removed, by means of CMP (=Chemical Mechanical Polishing) in this case. This continues until the recess 6 and further recess 7 filled with portions of the envelope 3 have been reached. In the present example, the final remnants of the first layer 5 still present between the portions 6 and 7 of the envelope 3 are then removed in an etching process, for example by means of the selective etchant for aluminum mentioned above. Thus, according to the invention, a smaller portion 2A—at least as regards the smallest dimension—is delimited within each second connection region 2 from the larger remaining portion 2B of each second connection region. The delimitation of the portion 2A is formed on the one hand by the inner edge of the portion 6 of the envelope 3 surrounding the second connection region 2, and on the other hand by the portions 7, two portions here, of the envelope 3 formed within the second connection region 2. After the solder bump 8, see FIG. 9, has been placed on the portion 2B of the second connection region 2, for example, and has been melted, the solder 8 will flow out over the entire second connection region 2 before it solidifies again owing to cooling down, but the thickness of the solder 8A in the portion 2A of the second connection region 2 will be smaller than in the portion 2B thereof. The electrical and thermal qualities of the portions 2A, 2B are substantially the same here as in the case in which the portions 7 of the envelope 3 are not present within each second connection region 2. This is true in particular thanks to the fact that the portions 6 and 7 of the envelope 3 extend partly above the second connection region 2, so that the surface area thereof is not or at least substantially not reduced. The result is a particularly compact semiconductor device 10 which is highly suitable for surface mounting and which also has very favorable thermal and electrical properties. It is of particular advantage here that the first connection regions 1 of the element 1 in this example are connected to the portion 2A of the second connection region 2, where the solder thickness is smallest. It is noted that FIG. 9 shows the same assembly as FIG. 2, but FIG. 9 has been rotated through 180° in the plane of drawing with respect to FIG. 2. This is connected with the manufacture of the device 10 described with reference to FIGS. 3 to 9, which makes such a representation logical. The following should be noted with respect to the dimensions of the device 10 whose manufacture was described above. The dimensions of the electric element 11 are 350×350 μm2. Its thickness is approximately 200 μm. The entire device 10 measures 1000×800×230 μm3. The fact that the entire device 10 is larger than the element 11 has the advantage that the device can be positioned more easily by means of a placement machine, for example during final mounting. The thickness of the solder 8A is, for example, 30 μm, and that of the solder 8B 150 μm. The smallest dimensions of the portion 2A and of the remaining portion 2B of each second connection region 2 are approximately 30 and 180 μm, respectively. These are the dimensions measured along the line II-II in FIG. 1 in the present example. The portion 2A, furthermore, is approximately square, and the greatest dimension of the remaining portion 2B of each second connection region is approximately 600 μm. The invention is not limited to a method as described for the embodiment, since many variations and modifications are possible to those skilled in the art within the scope of the invention. Thus devices may be manufactured with different geometries and/or different dimensions. It is also possible to use alternative materials, especially for the carrier plate. It is further noted that a large number of devices can be manufactured simultaneously by the method according to the invention, although the manufacture of a single device only is described and depicted for the embodiment. Individual semiconductor devices may then be obtained by mechanical separation techniques such as sawing, cutting, or breaking. In an attractive modification, another recess is formed between two adjoining devices in the carrier plate. When the envelope is provided over the element in the form of a drop of liquid, this liquid will wet the carrier plate and the element up to the edge of the other recess. The liquid may then be cured. When the carrier plate is removed, the individual devices will then automatically become separated. Besides semiconductor devices with a discrete element, as in the example, smaller, semi-discrete ICs, for example comprising 1 to 100 active and/or passive elements, may alternatively be manufactured. An application to larger, more complicated ICs is also advantageously possible. Another advantageous possibility is to use a filter or one or several passive elements as the electric element. It is finally noted that the second connection region may be given a geometry other than that shown in the examples. Thus both the portion and the remaining portion of said region may have approximately a circular geometry, the circles being interconnected by one or several narrower portions. It will be obvious that in this case the smallest dimension both of the portion and of the remaining portion of the second connection region will be equal to the diameter of the respective portion and remaining portion of the second connection region. The further recesses need not be round, as in the example, but may have some other geometry.
20041008
20060530
20050707
69888.0
0
TOLEDO, FERNANDO L
METHOD OF MANUFACTURING AN ELECTRONIC DEVICE, AND ELECTRONIC DEVICE
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,894
ACCEPTED
Control circuit
A digital control circuit enables/disables the feedback of serial transmissions of an UART receive signal when the G-LINK output port is short circuited in a particular operational mode. In a conventional operational mode, the digital control circuit monitors the state of the UART's Tx output and during an UART transmission, the Rx line normally is used for data feedback to set to a high state and eliminate unnecessary or unwarranted UART interrupts generated by the G-LINK circuit. The digital control circuit thus enables the G-LINK signal feedback to the UART when required, thereby maintaining a functionality to identify the unit's operational mode and allows the serial ports of the G-LINK to be configured and utilized during conventional operational modes.
1. A circuit arrangement comprising: a first circuit having an output line and an input line; a second circuit having an input line for receiving signals from the output line of the first circuit, an output line for transmitting signals to the input line of the first circuit; and a control circuit for controlling signals transmitted from the second circuit output line to the first circuit input line. 2. The circuit arrangement of claim 1 wherein the control circuit controls signals transmitted from the second circuit output line to the first circuit input line in accordance with signals transmitted at the output line of the first circuit. 3. The circuit arrangement of claim 2 wherein the control circuit inhibits the signals transmitted from the second circuit output line to the first circuit input line when the first circuit is transmitting signals at the output line of the first circuit. 4. The circuit arrangement of claim 2, wherein the control circuit keeps the input line of the first circuit at a high state when the first circuit is transmitting signals at the output line. 5. The circuit arrangement of claim 2 wherein the first circuit is a selected one of Universal Asynchronous Receiver/Transmitter (UART) and Universal Synchronous/Asynchronous Receiver/Transmitter (USART). 6. The circuit arrangement of claim 5, wherein the second circuit is a G-Link circuit. 7. The circuit arrangement of claim 2 wherein the second circuit further comprises a bi-directional line. 8. The circuit arrangement of claim 7, wherein short-circuiting the bidirectional line initiates a demonstration mode. 9. The circuit arrangement of claim 8 wherein the shorting circuiting is a short circuit to ground. 10. The circuit arrangement of claim 1 wherein the first circuit generates an interrupt signal if the first circuit receives the signals transmitted from the second circuit. 11. The circuit arrangement of claim 1, wherein signals transmitted from the first circuit at the output line control an external pager module through the second circuit for connecting to a pager service. 12. The circuit arrangement of claim 1, wherein the second circuit further comprises a second input line for receiving IR signals transmitted from an IR blaster sources, the second circuit transmits at the output line the IR signals for remotely controlling an external device. 13. The circuit arrangement of claim 1, wherein the second circuit provides feedback between the output line of the first circuit and the input line of the first circuit. 14. The circuit arrangement of claim 1 wherein the control circuit controls signals transmitted from the second circuit output line to the first circuit input line according to a mode of operation. 15. A method for controlling communication from a serial interface circuit to a receiver-transmitter circuit in a system under control of a CPU and an operating system, the method comprising the steps of: detecting a mode of operation of the system; if the mode is a first mode, allowing the serial interface circuit to transmit signals to the receiver-transmitter circuit; and if the mode is a second mode, detecting whether the receiver-transmitter circuit is transmitting signals to the serial circuit, if the receiver-transmitter is transmitting, prohibiting the serial interface circuit to transmit signals to the receiver-transmitter. 16. The circuit arrangement of claim 15 wherein the receiver-transmitter circuit is a selected one of Universal Asynchronous Receiver/Transmitter (UART) and Universal Synchronous/Asynchronous Receiver/Transmitter (USART). 17. The circuit arrangement of claim 15, wherein the serial interface circuit is a G-Link circuit. 18. The circuit arrangement of claim 15 wherein the serial interface circuit further comprises a bi-directional line. 19. The circuit arrangement of claim 18, wherein short-circuiting the bidirectional line initiates a demonstration mode. 20. The circuit arrangement of claim 19 wherein the shorting circuiting is a short circuit to ground.
Priority is claimed from U.S. provisional patent application 60/371,983 filed Apr. 12, 2002. FIELD OF THE INVENTION The present invention relates to control circuits in television set-top boxes, and more particularly, to a feedback control circuit. BACKGROUND In order to achieve high-speed packet transmission, a gigabit rate transmit/receive chip set (transceiver) must be employed. One such transceiver is a device sold by the Hewlett Packard Company headquartered in Palo Alto, Calif., USA, which makes and sells a transmitter designated as the HDMP-1022 transmitter and a receiver designated as the HDMP-1024 receiver. The HDMP-1022 transmitter and HDMP-1024 receiver chip set is described in detail in a 40-page Preliminary Technical Data sheet dated August 1996, distributed by Hewlett Packard and, at present, has been available on its Internet website. This data sheet shows how the HDMP-1022 transmitter and the HDMP-1024 receiver can be utilized as a gigabit, or G-LINKT™ controller, to provide transmit and receive G-LINK serial interface operations. The G-LINK of the present invention is an upgraded G-LINK II. An application of a G-LINK controller is shown in FIG. 1, which can be used in a set-top box. In the figure, a G-LINK circuit 10 serves as a serial interface circuit for coupling a conventional universal asynchronous receiver-transmitter (UART) circuit 12 to a G-LINK serial port 14 for a plurality of purposes, such as providing the UART 12 with a signal path and controls for converting from full duplex to half duplex communication to and from the G-LINK serial port 14. In addition, the G-LINK circuit 10 may relay infrared (IR) signals received from IR blaster source 20 via data line 21 for the G-LINK serial port 14 to drive an IR blaster (not shown). All the components in FIG. 1 are controllable by an operating system (not shown) and the UART 12 is defined as a COM port. As such, when the UART 12 receives a signal, it generates an interrupt signal to be processed by the operating system. In one mode of operation such as in a configuration test mode wherein the configuration of the system is tested, the G-LINK circuit 10 forwards a test signal from the G-LINK serial port 14 to the UART 12. Under this mode of operation, the UART 12 should receive the test signal and generate interrupts accordingly. However, in another mode of operation, such as in a demonstration mode wherein a user is educated on the use and capabilities of the system, the G-LINK circuit 10 unnecessarily transmits signals it receives from the UART 12 back to the UART 12. This unnecessary feedback causes the UART 12 to generate unnecessary interrupts to be served by the operating system. The processing of these unnecessary interrupts may degrade the performance of the set-top box. Thus, there is a need to control the communication between the G-LINK circuit and the UART 12. SUMMARY OF THE INVENTION According to the principles of the invention, a digital control circuit (DCC) enables/disables signals transmitted from a second circuit (such as a G-LINK circuit) to an input/output device (such as an universal asynchronous receiver/transmitter (UART)). In addition to transmitting signals to the input/output device, the second circuit also receives signals transmitted from the input/output device. The DCC may control the signals transmitted from the second circuit according to the signals transmitted by the input/output device to the second circuit. For example, when the input/output device is transmitting signals to the second circuit, the DCC inhibits signals transmitted from the second circuit to the input/output device. This way, the input/output device does not receive any signals from the second device and thus does not generate interrupts to a central processing unit (CPU). In one embodiment, the second circuit is a G-LINK circuit having a bi-directional line coupled to a G-LINK port, and the input/output device is a UART. When the G-LINK port is short-circuited in a particular operational mode, the DCC prevents signal transmissions from the G-LINK circuit to the UART. In another operational mode, the DCC monitors the state of the UART's output and during UART transmission, the DCC sets a high state on the receive line of the UART, indicating no incoming signals and thus preventing unnecessary or unwarranted UART interrupts from being generated by signals coming from the G-LINK circuit. In yet another operation mode, the DCC allows free flow of signals to be transmitted from the G-LINK circuit to the UART. The DCC thus enables the G-LINK signal feedback to the UART when required. BRIEF DESCRIPTION OF THE DRAWINGS The teachings of the present invention can be readily understood by considering the following detailed description in conjunction with the accompanying drawings, in which: FIG. 1 depicts a prior art circuit arrangement using a G-LINK circuit, a G-LINK serial port, a UART, and an IR blaster source in a set-top box; FIG. 2 depicts a circuit arrangement according to the principles of the invention for controlling communications between the G-LINK circuit transmit line and the UART receive line; FIGS. 3A and 3B illustrate an exemplary digital control circuit used in the circuit arrangement shown in FIG. 2 and the setup arrangements for different modes of operation; FIG. 4 illustrates a flowchart showing the steps for entering the demonstration mode under the control of the CPU and the operating system; and FIG. 5 illustrates a flowchart for a method for controlling transmission from a serial interface circuit to a receiver-transmitter circuit according to the mode of operation. To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. DETAILED DESCRIPTION FIG. 2 illustrates an exemplary circuit arrangement according to the principles of the invention. A G-LINK circuit 10 serves as a serial interface circuit for coupling a conventional universal asynchronous receiver-transmitter (UART) circuit 12, e.g., a portion of a TL811 integrated circuit made by TeraLogic Inc. headquartered in Mountain View Calif., USA, to a G-LINK serial port 14 for a plurality of purposes, e.g., to provide the UART 12 with a signal path and controls for converting from full duplex to half duplex communication to and from G-LINK serial port 14, or to provide a signal path directly from the UART 12 to the G-LINK serial port 14 for full duplex communications, for further design improvements or for troubleshooting purposes. A digital control circuit (DCC) 22 is disposed between an output line (GLNK_Rx 18) of the G-LINK circuit 10 and a receive (input) line (UART_Rx 23) of the UART 12 for controlling the signals transmitted from the G-LINK circuit 10 to the UART 12 according to the activity present at GLNK_Tx 16 (the output line of the UART 12 or the input line of G-LINK circuit 10) and other factors discussed below. Additionally, the present arrangement is used for the G-LINK serial port 14 to drive an infrared (IR) blaster (not shown) in response to an IR blaster source 20 via an IR blaster data line 21 coupled to G-LINK circuit 10 as shown in FIG. 2. The IR blaster is an infrared light emitting diode (LED), disposed outside of the set-top box, for controlling an external device (not shown) which can be remotely controllable by IR signals, e.g., a VCR, television receiver, DVD player, etc. The use of an IR blaster for such a purpose is known to those skilled in the art. The IR blaster source 20 is driven by a complex programmable logic device (CPLD) (not shown) and is discussed more fully below. The circuit arrangement in FIG. 2 can also be used in a manner where paging control commands can be transmitted from the UART 12 to G-LINK serial port via the G-LINK circuit 14 for controlling an external pager module to establish a connection with a paging service provider. This circuit arrangement has been used in the ATC311 high definition televisions provided by Thomson Inc., Indianapolis, Ind., USA. The invention is particularly suitable for use in a set-top box (not shown) for a television receiver (not shown). Only those portions of the set-top box and/or the television receiver necessary for understanding the present invention are further discussed below. For example, the set-top box has an operating system, which in the present case is Windows CE™, a product of the Microsoft Corp. headquartered in Redmond Wash., USA, and a central processing unit (CPU) (not shown) both of which control the UART 12, the G-LINK circuit 10 and the DCC 22 discussed below. When the UART 12 receives a signal, the UART 12 generates an interrupt signal, which normally requires the operating system to jump to an interrupt handler to process the interrupt. Other input/output or receiver-transmitter devices such a universal synchronous/asynchronous transmitter-receiver (USART) may be used in this circuit arrangement as well. The circuit arrangement in FIG. 2 operates under several modes of operation. In a configuration test mode of operation, the DCC 22 allows all the signals transmitted from the G-LINK circuit 10 to be delivered to the UART 12. In a demonstration mode, the DCC 22 disables any signals transmitted from the G-LINK circuit 10 to the UART 12. The operating system should not place the set-top box in the demonstration mode unless the operating system detects that the G-LINK serial port 14 is short-circuited, which is an indication from a user that the user wants the set-top box to enter the demonstration mode. When the G-LINK serial port 14 is short-circuited, the G-LINK circuit 10 generally returns any signals that it receives from the UART 12. Thus, to detect whether the G-LINK serial port is short-circuited, the operating system may place the set-top box in the configuration test mode, send a test signal to the G-LINK circuit 10 through the UART 12, and wait to see if the test signal returns from the UART 12. If the test signal returns, the operating system determines that the G-LINK serial port has been short-circuited and may proceed to place the set-top box in the demonstration mode. Short-circuiting the G-LINK serial port 14 can be achieved by shorting the plug, thereby shorting the data signal line to ground. When the G-LINK serial port 14 is not short-circuited, the set-top box normally is operating under a default mode, in which a tester by using test equipment is able to send debug messages from the UART 12 to G_LINK serial port 14. Under the default mode of operation, the G-LINK circuit 10 sends back signals it receives from the UART 12, which is unnecessary. To eliminate or mask interrupts generated by these returned signals, the DCC 22 monitors the state of the UART output line GLNK_Tx 16 and during UART 12 transmission, the UART receive line UART_Rx 23, is set to a high state, indicating to the UART 12 that no signals have been received and blocking the signals coming from the G-LINK circuit 10. When the G-LINK serial port 14 is not short-circuited, the operating system may also place the set-top box in an IR blaster mode. Under this mode, the G-LINK circuit 10 generally sends signals to the UART 12. These signals are unnecessary. As such, the DCC 22 disables any signals transmitted from the G-LINK circuit 10 via GLNK_Rx 18 to the UART 12, again eliminating unnecessary interrupts. The DCC hardware logic and control registers are shown in FIG. 3A. The table of FIG. 3B shows the logical behavior for the DCC 22 for each control register's setting and corresponding data inputs. In FIGS. 3A and 3B, GLNK_Rx, GLNK_Tx, and UART_Rx represent logic (signal) states at GLNK_Rx 18, GLNK_Tx 16, and UART_Rx 23, respectively. FIG. 3A shows that DCC 22 comprises five devices U1 through U5. U1 24 is a sequentially clocked flip-flop functioning as a latch, U2 26 and U3 28 comprise common low level logic gates, and U4 30 and U5 32 are common signal multiplexers. The DCC 22 takes the following inputs to generate UART_Rx: GLNK_Tx, GLNK_Rx, register 4 bit 3, register 6 bit 2, and register 6 bit 4. Registers 4 and 6 are included in a complex programmable logic device (CPLD) (not shown) and are set by the operating system. In the following discussion, a logic value of 1 (high) generally means that no signals are transmitted. For example, when GLNK_Tx has a logic value of 1, it generally means that the GLNK_Tx 16 line is idle, i.e., not transmitting or receiving. U4 30 and U5 32 multiplexers provide the G-LINK circuit 10 with three systems level operating modes. The simplest mode is the demonstration mode (setup number 5 or mode 3 in FIG. 3B) where the output of U5 32 is at a logic high level—UART_Rx has a logic value of 1, i.e., the UART_Rx 23 line is idle and thus the UART 12 does not receive any signal. This mode is actuated when U5 32 has a control signal from the CPLD with register 6 bit 4 being set to a logic level 1 as shown in the table of FIG. 3B. When register 6 bit 4 is set to a logic low level, the DCC 22 operates in one of the other two modes, or one of setup numbers 1-4. The output of U5 32 directly depends on the output of U4 30 according to FIG. 3B. U4 multiplexer is controlled by the logic level of CPLD register 6 bit 2. When the logic level of CPLD register 6 bit 2 is high, the DCC 22 operates under the configuration test mode or mode 2. In this case, the output of U4 30 is just the signals coming from GLNK_Rx 18. See FIG. 3A. As such, the output signals at UART_Rx 23 are the same as those coming from GLNK_Rx 18. Thus, the DCC 22 enables the free flow of signals transmitted from the G-LINK circuit 10 to the UART 12. This is necessary because the test signals are generally transmitted through the G-LINK serial port 14 to the UART 12 to be processed by the operating system. When CPLD register 6, bit 2 is set to a logic low level, the DCC 22 operates under mode 1. The output of U4 30 directly depends on the output of U3 28, which is a NAND gate having three inputs: CPLD register 14 bit 3, the signals coming from GLNK_Tx and the output signals from U2 26. U2 26 is an inverter for inverting signals coming from GLNK_Rx 18. A signal from GLNK_Tx 16 is latched at U1 24 when the signal from the GLNK_Rx 18 is transitioning from a logic value of 1 to 0. This latched state of G-LINK-Tx 16 eliminates false logic transitions at the output of U3 28 that may be due to phase or timing differences in the G-LINK_Rx 18 and G-LINK_Tx 16 signals. Under mode 1, when CPLD register 14 bit 3 is set to a logic value of 1, the DCC 22 is in default operating condition. The DCC in this default operating condition checks whether the UART 12 is transmitting signals to the G-LINK circuit 10. If the UART 12 is not transmitting, the DCC 22 enables signals transmitted from the G-LINK circuit 10 to the UART 12. Otherwise, if the UART 12 is transmitting, the DCC 22 disables the signals transmitted from the G-LINK circuit 10. In FIGS. 3A and 3B, when the signals from GLNK_Tx 16 have a logic value of 1 (no signals), the output of U3 28 is the output of U2 26 or the signals coming from GLNK_Rx 18. In effect, the signals at UART_RX 23 are the same as those coming in at GLNK_Rx 18. On the other hand, if signals from GLNK_Tx 16 have a logic value of 0 (the UART 12 is transmitting), the output of U3 28 has a logic value of 1. In effect, the signals at UART_Rx 23 are held at a logic value of 1, disabling the transmission from the G-LINK circuit 10 to the UART 12. Under mode 1, if CPLD register 14 bit 3 is set to a logic value of 0, the IR blaster is active, i.e., the G-LINK circuit 10 is receiving IR signals from the IR blaster source 20 and transmitting the IR signals to an external IR blaster via the G-LINK serial port 14. Under this situation, the output of U3 28 has a logic value of 1, which causes the signals at UART_Rx 23 to have a logic value of 1 as well, disabling the transmission from the G-LINK circuit 10 to the UART 12. It should be understood that the specific level signals from the CPLD and signal levels stated in FIG. 3B are specific to the operating system used and associated circuitry, are exemplary and are presented to convey an understanding of the operation to one skilled in the art. The CPLD and its respective registers form no part of the present invention. When a shorting plug is inserted into the G-LINK serial port 14, this short-circuiting of the output is sensed and the system is placed in the demonstration mode wherein the user is educated on the use and capabilities of the system. It is of course understood that equivalents of a shorting plug can be used, e.g., a front panel switch. This mode is typically utilized in a retail store for actuating a demonstration mode, and conforms to setup 5 of FIG. 3B. The operation of the demonstration mode forms no part of the present invention. FIG. 4 shows a flowchart of entering the demonstration mode of operation under the control of the CPU and the operating system. When a user short-circuits the G-LINK serial port 14, the user is instructing the set-top box to enter the demonstration mode. At 402 the UART is configured as a COM port, an option provided for by the operating system. In the exemplary embodiment, the CPLD registers (not shown) are set at 404, where both bits 2 and 4 of the CPLD register 6 are set to zero, i.e., the set-top box is either in default or IR blaster mode. The process continues through link 406 to node 408 for a determination of whether the IR blaster is active. In this embodiment and as shown in FIG. 3B, if register 14 bit 3 is zero, then the IR blaster mode is active. If the IR blaster mode is active, there is a return to link 406. If “no”, there is a determination at 410 of whether the operating system wants to test for whether the G-LINK serial port 14 is short-circuited (shown as “Test for DEMO PIN?”) for providing a demonstration, as discussed above. If “no”, there is a return to link 406. If “yes,” the CPLD registers are reset at 412, setting bit 2 of CPLD register 6 to logic 1 and bit 4 to a logic 0. This setting places the circuit arrangement in FIG. 3A in the configuration test mode. At 414, the operating system determines whether the UART 12 input line, UART_Rx 23 is at a logic zero, indicating that there is signals coming into the UART 12. As discussed above, when the serial port 14 is short-circuited, the G-LINK circuit 10 sends back any signals it receives from the UART 12. Thus, when the operating system receives a signal it previously sent, the operating system determines that the G-LINK serial port 14 is short-circuited. If the decision block 414 returns “yes”, the CPLD is again reset at 416 to place the circuit arrangement in FIG. 3A in the demonstration mode. As shown in FIG. 3B, to set the circuit arrangement in the demonstrative mode, bit 2 of register 2 is set to logic 0 and bit 4 is set to logic 1. The process then returns to link 406. If “no,” the process returns to 404, setting the circuit arrangement back to either the default or the IR blaster alive mode. FIG. 5 illustrates a method for controlling transmission from a serial interface circuit such as the G-LINK circuit 10 in FIG. 2 to a receiver-transmitter circuit such as the UART 12 in FIG. 2 in a system according to the mode of operation. At 510, the mode of the operation of the system is detected. The mode is determined at 520. If the mode is a first mode such as the configuration test mode shown in FIG. 3B, allow the serial interface circuit to transmit signals to the receiver-transmitter circuit at 530. If the mode is in a second mode such as the default mode shown in FIG. 3B, determine whether the receiver-transmitter circuit is transmitting signals to the serial interface circuit at 540. If the receiver-transmitter circuit is transmitting, prohibit the serial interface circuit to transmit signals to the receiver-transmitter at 550. Otherwise, if the receiver-transmitter is not transmitting, allow the serial interface circuit to transmit signals to the receiver-transmitter circuit. As shown in FIG. 3A, the serial interface circuit may also include a bidirectional line for interfacing with a serial port (such as the G-LINK serial port 14). The examples given herein are presented to enable those skilled in the art to more clearly understand and practice the instant invention. The examples should not be considered as limitations upon the scope of the invention, but as merely being illustrative and representative of the use of the invention. Numerous modifications and alternative embodiments of the invention will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode of carrying out the invention and is not intended to illustrate all possible forms thereof. It is also understood that the words used are words of description, rather than limitation, and that details of the structure may be varied substantially without departing from the spirit of the invention and the exclusive use of all modifications which come within the scope of the appended claims is reserved.
<SOH> BACKGROUND <EOH>In order to achieve high-speed packet transmission, a gigabit rate transmit/receive chip set (transceiver) must be employed. One such transceiver is a device sold by the Hewlett Packard Company headquartered in Palo Alto, Calif., USA, which makes and sells a transmitter designated as the HDMP-1022 transmitter and a receiver designated as the HDMP- 1024 receiver. The HDMP-1022 transmitter and HDMP-1024 receiver chip set is described in detail in a 40-page Preliminary Technical Data sheet dated August 1996, distributed by Hewlett Packard and, at present, has been available on its Internet website. This data sheet shows how the HDMP-1022 transmitter and the HDMP-1024 receiver can be utilized as a gigabit, or G-LINKT™ controller, to provide transmit and receive G-LINK serial interface operations. The G-LINK of the present invention is an upgraded G-LINK II. An application of a G-LINK controller is shown in FIG. 1 , which can be used in a set-top box. In the figure, a G-LINK circuit 10 serves as a serial interface circuit for coupling a conventional universal asynchronous receiver-transmitter (UART) circuit 12 to a G-LINK serial port 14 for a plurality of purposes, such as providing the UART 12 with a signal path and controls for converting from full duplex to half duplex communication to and from the G-LINK serial port 14 . In addition, the G-LINK circuit 10 may relay infrared (IR) signals received from IR blaster source 20 via data line 21 for the G-LINK serial port 14 to drive an IR blaster (not shown). All the components in FIG. 1 are controllable by an operating system (not shown) and the UART 12 is defined as a COM port. As such, when the UART 12 receives a signal, it generates an interrupt signal to be processed by the operating system. In one mode of operation such as in a configuration test mode wherein the configuration of the system is tested, the G-LINK circuit 10 forwards a test signal from the G-LINK serial port 14 to the UART 12 . Under this mode of operation, the UART 12 should receive the test signal and generate interrupts accordingly. However, in another mode of operation, such as in a demonstration mode wherein a user is educated on the use and capabilities of the system, the G-LINK circuit 10 unnecessarily transmits signals it receives from the UART 12 back to the UART 12 . This unnecessary feedback causes the UART 12 to generate unnecessary interrupts to be served by the operating system. The processing of these unnecessary interrupts may degrade the performance of the set-top box. Thus, there is a need to control the communication between the G-LINK circuit and the UART 12 .
<SOH> SUMMARY OF THE INVENTION <EOH>According to the principles of the invention, a digital control circuit (DCC) enables/disables signals transmitted from a second circuit (such as a G-LINK circuit) to an input/output device (such as an universal asynchronous receiver/transmitter (UART)). In addition to transmitting signals to the input/output device, the second circuit also receives signals transmitted from the input/output device. The DCC may control the signals transmitted from the second circuit according to the signals transmitted by the input/output device to the second circuit. For example, when the input/output device is transmitting signals to the second circuit, the DCC inhibits signals transmitted from the second circuit to the input/output device. This way, the input/output device does not receive any signals from the second device and thus does not generate interrupts to a central processing unit (CPU). In one embodiment, the second circuit is a G-LINK circuit having a bi-directional line coupled to a G-LINK port, and the input/output device is a UART. When the G-LINK port is short-circuited in a particular operational mode, the DCC prevents signal transmissions from the G-LINK circuit to the UART. In another operational mode, the DCC monitors the state of the UART's output and during UART transmission, the DCC sets a high state on the receive line of the UART, indicating no incoming signals and thus preventing unnecessary or unwarranted UART interrupts from being generated by signals coming from the G-LINK circuit. In yet another operation mode, the DCC allows free flow of signals to be transmitted from the G-LINK circuit to the UART. The DCC thus enables the G-LINK signal feedback to the UART when required.
20041008
20080909
20050804
60016.0
0
FLORES, LEON
DIGITAL CONTROL CIRCUIT FOR SERIAL UART TRANSMISSIONS
UNDISCOUNTED
0
ACCEPTED
2,004
10,510,895
ACCEPTED
Hard surface cleaning compositions
The present invention is directed to a pourable acidic hard surface cleaning and/or disinfecting composition which contains suspended inclusions which appear as visibly discernible, discrete particulate materials, preferably where said discrete particulate materials are based on alginates.
1. A hard surface cleaning and/or disinfecting composition which comprises: an acid constituent; at least one anionic surfactant; suspended inclusions which appear as visibly discernible, discrete particulate materials; a thickener constituent; optionally, at least one further detersive surfactant selected from nonionic, amphoteric and zwitterionic surfactants; optionally, at least one organic solvent; optionally, one or more constituents for improving the aesthetic or functional features of the inventive compositions; and; water. 2. The composition according to claim 1 whererin the acid constituent contains an acid selected from the group consisting of: citric acid, sorbic acid, acetic acid, boric acid, formic acid, maleic acid, adipic acid, lactic acid, malic acid, malonic acid, glycolic acid, and mixtures thereof. 3. The composition according to claim 2 wherein the acid constituent comprises citric acid. 4. The composition according to claim 1 wherein the composition comprises an organic solvent. 5. The composition according to claim 4 wherein the organic solvent is selected from alcohols, glycols, water miscible ethers, water miscible glycol ethers, monalkylether esters, and mixtures thereof. 6. The composition according to claim 5 wherein the organic solvent is selected from alcohols, water miscible glycol ethers and mixtures thereof. 7. The composition according to claim 5 wherein the organic solvent is an alcohol. 8. The composition according to claim 1 wherein the compositions exclude added organic solvents. 9. The composition according to claim 1 wherein the compositions exclude organic solvents. 10. The composition according to claim 1 wherein the pH is from about 1 to about 5. 11. The composition according to claim 1 wherein the pH is from about 1 to about 4. 12. The composition according to claim 1 wherein the pH is from about 1 to about 3. 13. The composition according to claim 1 wherein the anionic surfactant is a sulfate. 14. A hard surface cleaning and/or disinfecting composition according to claim 1 wherein said composition exhibits antimicrobial efficacy against at least one of the following organisms: Staphylococcus aureus (gram positive type pathogenic bacteria) (ATCC 6538), Salmonella choleraesuis (gram negative type pathogenic bacteria) (ATCC 10708), Escheria coli (gram negative type pathogenic bacteria) (ATCC 11229) and Pseudomonas aeruginosa (ATCC 15442) of not more than 1/60 according to the AOAC Use-Dilution Test Method. 15. A method of treating a hard surface comprising applying an effective amount of a composition according to claim 1 to the surface in need of treatment. 16. The composition according to claim 1 wherein the suspended inclusions which appear as visibly discernible, discrete particulate materials are based on alginate materials.
The present invention relates to pourable disinfecting hard surface cleaning compositions. More particularly the present invention relates to thickened lavatory cleaning compositions which provide a cleaning and disinfecting effect to hard surfaces, and which include visibly discernible inclusions. Cleaning compositions which also provide a disinfecting or sanitizing effect are commercially important products. Such compositions enjoy a wide field of utility in assisting in the removal of stains and grime from surfaces, especially those characterized as useful with “hard surfaces”. Hard surfaces are those which are frequently encountered in lavatories such as lavatory fixtures such as toilets, shower stalls, bathtubs, bidets, sinks, etc., as well as countertops, walls, floors, etc. Two types of commonly encountered stains in lavatories include “hard water” stains and “soap scum” stains. Such hard surfaces, and such stains, may also be found in different environments as well, including kitchens, hospitals, etc. Various formulations in compositions of cleaning agents have been produced and are known to the art which cleaning agents are generally suited for one type of stain but not necessarily for both classes of stains. For example, it is known to the art that highly acidic cleaning agents comprising strong acids, such as hydrochloric acids, are useful in the removal of hard water stains. However, the presence of strong acids is known to be an irritant to the skin and further offers the potential of toxicological danger. Other classes of cleaning compositions and formulations are known to be useful upon soap scum stains, however, generally such compositions comprise an organic and/or inorganic acid, one or more synthetic detergents from commonly recognized classes such as those described in U.S. Pat. No. 5,061,393; U.S. Pat. No. 5,008,030; U.S. Pat. No. 4,759,867; U.S. Pat. No. 5,192,460; U.S. Pat. No. 5,039,441. Generally, the compositions described in these patents are claimed to be effective in the removal of soap scum stains from such hard surfaces and may find further limited use in other classes of stains. However, the formulations of most of the compositions within the aforementioned patents generally have relatively high amounts of acids (organic and/or inorganic) which raises toxicological concerns, and further none of the above patents provide any disinfecting properties. While many disinfecting hard surface cleaning compositions are known to the art, there is nonetheless a need for further improved compositions in the art. According to the one aspect of the invention, there is provided a pourablehard surface cleaning and/or disinfecting composition which comprises (preferably consists essentially of): an acid constituent; at least one anionic surfactant; suspended inclusions which appear as visibly discernible, discrete particulate materials, preferably where said discrete particulate materials are based on alginates; a thickener constituent; optionally, at least one further detersive surfactant selected from nonionic, amphoteric and zwitterionic surfactants; optionally, but desirably at least one organic solvent; optionally, one or more constituents for improving the aesthetic or functional features of the inventive compositions; and; water. Particularly preferred compositions according to the invention are acidic in character, are effective in the removal of both soap scum stains and hard water stains, and which compositions provide an effective sanitizing effect to hard surfaces. In further aspects of the invention there are provided processes for the production of the aforesaid compositions. It is yet a further object of the invention to provide a readily pourable cleaning composition which features the benefits described above. It is a further object of the invention to provide a process for the simultaneous cleaning and sanitization of hard surfaces, which process comprises the step of: providing a composition as outlined above, and applying an effective amount to a hard surface requiring such treatment. The present inventive compositions necessarily comprise an acid constituent which be a water soluble inorganic acid, or a water soluble organic acids. By way of non-limiting example useful inorganic acids include hydrochloric acid, phosphoric acid, sulfuric acid acid. With respect to water soluble organic acids, generally include at least one carbon atom, and include at least one carboxyl group (—COOH) in its structure. Preferred are water soluble organic acids which contain from 1 to about 6 carbon atoms, and at least one carboxyl group as noted. Particularly preferred amongst such organic acids are: formic acid, citric acid, sorbic acid, acetic acid, boric acid, maleic acid, adipic acid, lactic acid, malic acid, malonic acid, glycolic acid, and mixtures thereof. According to certain preferred embodiments however, the acid constituent is a combination of citric acid in combination with at least one further acid selected from the group consisting of sorbic acid, acetic acid, boric acid, formic acid, maleic acid, adipic acid, lactic acid, formic acid, malic acid, malonic acid, and glycolic acid. Most preferably, the acid constituent is a combination of citric acid with lactic acid, glycolic acid or malic acid. As the inventive compositions are necessarily acidic in nature (pH<7.0) there should be sufficient acid present in the composition such that the pH of the composition is desirably less than 6, preferably from about 5.0 to about 1.0, more preferably from about 4.0 to about 1.0, and even more preferably from about 3.0 to about 1.0. Of course mixtures of two or more acids may be used, and the acid constituent may be present in any effective amount. Desirably however, the acid constituents is present in an amount not in excess of 20% wt. based on the total weight of the compositions; preferably the acid constituent is present in an amount of from about 0.05-20% wt., more preferably from about 0.5-20% wt., and most preferably is present in an amount of from about 1% wt. to about 15% wt. The acid constituent of the inventive formulations provide free acidity within the cleaning composition, which free acid reacts with the fatty acid metal salts which are comprised within soap scum stains releasing the metal ions and freeing the fatty acid, which facilitates the removal of these undesired stains from hard surfaces. These acids also sequester the resulting free metal ions which are released from the soap scum stains. Also where the acids are selected to feature disinfecting properties, they concomitantly provide antimicrobial activity necessary to disinfect the cleaned surface. The compositions of the present invention necessarily includes at least anionic surfactant. Generally any anionic surfactant material may be used in the inventive compositions. By way of non-limiting example, particularly suitable anionic surfactants include: alkali metal salts, ammonium salts, amine salts, or aminoalcohol salts of one or more of the following compounds (linear and secondary): alcohol sulfates and sulfonates, alcohol phosphates and phosphonates, alkyl sulfates, alkyl ether sulfates, sulfate esters of an alkylphenoxy polyoxyethylene ethanol, alkyl monoglyceride sulfates, alkyl sulfonates, olefin sulfonates, paraffin sulfonates, beta-alkoxy alkane sulfonates, alkylamidoether sulfates, alkylaryl polyether sulfates, monoglyceride sulfates, alkyl ether sulfonates, ethoxylated alkyl sulfonates, alkylaryl sulfonates, alkyl benzene sulfonates, alkylamide sulfonates, alkyl monoglyceride sulfonates, alkyl carboxylates, alkyl sulfoacetates, alkyl ether carboxylates, alkyl alkoxy carboxylates having 1 to 5 moles of ethylene oxide, alkyl sulfosuccinates, alkyl ether sulfosuccinates, alkylamide sulfosuccinates, alkyl sulfosuccinamates, octoxynol or nonoxynol phosphates, alkyl phosphates, alkyl ether phosphates, taurates, N-acyl taurates, fatty taurides, fatty acid amide polyoxyethylene sulfates, isethionates, acyl isethionates, and sarcosinates, acyl sarcosinates, or mixtures thereof. Generally, the alkyl or acyl radical in these various compounds comprise a carbon chain containing 12 to 20 carbon atoms. Preferred anionic surfactants useful in forming the compositions of the invention include alkyl sulfates which may be represented by the following general formula: wherein R is an straight chain or branched alkyl chain having from about 8 to about 18 carbon atoms, saturated or unsaturated, and the longest linear portion of the alkyl chain is 15 carbon atoms or less on the average, M is a cation which makes the compound water soluble especially an alkali metal such as sodium, or is ammonium or substituted ammonium cation, and x is from 0 to about 4. Of these, most preferred are the non-ethoxylated C12-C15 primary and secondary alkyl sulfates. Exemplary commercially available alkyl sulfates include one or more of those available under the tradenames RHODAPON® (ex. Rhône-Poulenc Co.) as well as STEPANOL® (ex. Stepan Chemical Co.). Exemplary alkyl sulfates which is preferred for use is a sodium lauryl sulfate surfactant presently commercially available as RHODAPON® LCP (ex. Rhône-Poulenc Co.), as well as a further sodium lauryl sulfate surfactant composition which is presently commercially available as STEPANOL® WAC (ex. Stepan Chemical Co.). Particularly preferred anionic surfactants useful in forming the compositions of the invention include alkyl sulfonate anionic surfactants which may be represented according to the following general formula: wherein R is an straight chain or branched alkyl chain having from about 8 to about 18 carbon atoms, saturated or unsaturated, and the longest linear portion of the alkyl chain is 15 carbon atoms or less on the average, M is a cation which makes the compound water soluble especially an alkali metal such as sodium, or is ammonium or substituted ammonium cation, and x is from 0 to about 4. Most preferred are the C12-C15 primary and secondary alkyl sulfates. Exemplary, commercially available alkane sulfonate surfactants include one or more of those available under the tradename HOSTAPUR® (ex. Clariant). An exemplary and particularly alkane sulfonate which is preferred for use is a secondary sodium alkane sulfonate surfactant presently commercially available as HOSTAPUR® SAS from Hoechst Celanese. The anionic surfactant is present in the compositions of the present invention in an amount of from about 0.1 to about 20% by weight, more preferably is present in an amount of from about 0.1-20% wt., and most preferably is present in an amount of from about 1% wt. to about 20% wt. As a further necessary constituent, the inventive compositions comprise a thickener constituent. Thickeners useful in the present invention to achieve this viscosity are selected from the group consisting of cellulose, alkyl celluloses, alkoxy celluloses, hydroxy alkyl celluloses, alkyl hydroxy alkyl celluloses, carboxy alkyl celluloses, carboxy alkyl hydroxy alkyl celluloses, xanthan gum, gellan gum and mixtures thereof. Examples of the cellulose derivatives include ethyl cellulose, hydroxy ethyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxy propyl methyl cellulose, and ethyl hydroxy ethyl cellulose. Preferably, the thickener is a mixture of hydroxy ethyl cellulose and xanthan gum or is a mixture of xantham gum and gellan gum. Further specific preferred thickeners and combinations of thickeners are described in the Examples. The amount of thickener present in the composition may be any amount which is effective in suspending the suspended inclusions as hereinafter described. Desirably the composition of the present of invention is thickened to a viscosity range of from about 100 to about 2000 centipoise, preferably to a viscosity of from about 750 to about 1500 centipoise, more preferably is in the range of about 800-1200 centipoise measured at room temperature, on aRVT Brookfield viscometer, spindle #2, at 60 rpm. Generally good thickening has been observed when the total amount of the thickeners are present in amount from about 0.1 to about 5% by weight, more preferably from about 0.1 to about 4% by weight, and most preferably from about 0.1% wt. to about 1% wt. Preferably other thickening materials, particularly those based on synthetic polymers such as acrylic acid copolymers, e.g. Carbopol® materials, as well as those based on clays, and those based on cellulose including modified celluloses are absent from the inventive compositions. As a necessary constituent, the inventive compositions include suspended inclusions. These suspend inclusions appear as visibly discernible, discrete particulate materials to the consumer of the inventive compositions. These suspended inclusions desirably appear as small discrete visible particles suspended within the composition, particularly by a consumer having normal “20/20” vision. It is to be understood however that not all of the particulate materials present in the inventive composition need be visibly discernible as a portion of the particulate materials may be smaller than the visible threshold of the consumer having normal vision. It is nonetheless required that at least a substantial portion of the particulate materials present in the inventive composition need be visibly discernible as discrete particles. Desirably the particulate materials are supplied to have an average particle size in the range of about 50 μm to about 1000 μm, preferably in the range of about 350 μm to about 1000 μm, most preferably in the range of about 450 μm to about 650 μm, and especially preferably in the range of about 575 μm to about 625 μm. Desirably the average particle size of these particulate materials represents that at least 85% of the particles, more preferably at least 90%, still more preferably at least 92%, and most preferably at least 90% of the particles present are within a specified range. The suspended inclusions present in the inventive compositions are most desirably based on alginates although other visibly discernible, discrete particulate materials may be used as well, or in the place of alginate based materials. However the preferred suspended inclusions are based on alginates. Alginate based particulate materials used for the suspended inclusions in the inventive compositions may be formed from an alginate or salts of alginic acid such as potassium alginate, calcium alginate or sodium alginate salts, and advantageously may be conveniently harvested from naturally occurring seaweed especially of the species Laminaria wherein the sodium alginate form predominates. Alginates typically consist of sequences of α-L-guluronic acid and β-D-mannuronic acid which may be present in the alginate in various differing ratios. The term “beads” conveniently describes the geometry of the alginate based particulate materials as when these are formed form an aqueous slurry containing an alginate such as sodium alginate with one or more further constituents and then expelled to form individual particles or droplets, the coalescing aqueous slurry may form generally spherical particles, hence the term “beads”. Of course, other processes for the formation of alginate based suspended inclusions are also contemplated as being useful in conjunction with the present invention such as processes wherein the alginate optionally containing one or more further constituents is comminuted by other methods, such as milling, grinding or other known art technique. In such instances the comminuted alginate based suspended inclusions may not necessarily form generally spherical particles but may form individual particles of irregular geometry. In such an instance the largest dimension of such individual particles of irregular geometry are used as the basis for determining the average particle size of the In a preferred embodiment the alginate beads are based on calcium alginates as the calcium salts of alginates are insoluble or poorly soluble in water, and thus are particularly desirable in the present inventive compositions which are substantially aqueous. The calcium salts of alginates used to form the alginate based particulate materials preferably exhibit little swelling or collapse when incorporated in the present inventive composition. The alginate based particulate materials may contain from about 0.5% wt. to 100% wt. of an alginate or alginate salt, although quite frequently the amount of alginate in the alginate based particulate materials are much less, generally on from about 0.5% wt. to about 10% wt., more preferably from about 0.5% wt. to about 5% wt. Such alginate based particulate materials may be conveniently referred to as “alginate beads”. Such alginate beads may be formed by a variety of known art processes including those described in the background section of PCT/US95/08313 to Thomas et al., as well as in U.S. Pat. No. 6,467,699 B1, the contents of which are incorporated by reference. Alternately such alginate based particulate materials may be commercially purchased from various suppliers, including geniaLab BioTechnologie (Braunschwig, Germany). As noted the composition of the alginate based particulate materials may include only a small proportion of an alginate or alginate salt, and may include one or more further non-alginate materials especially one or more inorganic materials such as titanium dioxide which improves the opacity, hence the visibility of the beads, as well as one or more coloring agents such as pigments such as ultramarine blue, said coloring agents which also improve the aesthetic appearance of the beads. Other further non-alginate materials not recited herein may also be include in the composition of the alginate based particulate materials. The alginate based particulate materials may be composed of a major proportion of water which is entrained within the structure of the discrete alginate based particulates and due to the highly porous character of alginates when in an aqueous compositions 80% wt., and usually 90% wt. or even greater of the mass of the discrete alginate based particulates may be water with the remaining balance to 100% wt. being the alginate or alginate salt, and one or more further non-alginate materials. Conveniently such alginate based particulate materials may be prepared, stored and sold as a slurry of discrete alginate based particulates in an aqueous-based carrier composition which may contain a minor amount of one or more further additives such as one or more salts especially chloride salts such as calcium chloride, as well as a preservative for inhibiting the growth of undesirable microorganisms in the slurry containing the discrete alginate based particulates. Preferred commercially available alginate based particulate material comprise from about 0.5% wt. to about 5% wt. of a calcium alginate, a pigment present in an amount up to about 0.01% wt., from about 0.1% wt. to about 5% wt. of TiO2 and the remaining balance of the mass of the alginate based particulate material comprised of a 2% calcium chloride solution in water which may also con an a minor amount, approx. 2% of calcium chloride. Such alginate based particulate material can be separated from the aqueous-based carrier composition by means of a fine sieve or other means for decanting the aqueous-based carrier composition from the alginate based particulate materials. By the term “suspended” when referring to inclusions, is to be understood that when the formed inventive compositions are manually shaken and then allowed to return to a quiescent state, such as by permitting them to stand on a tabletop or other surface at room temperature (approx. 20° C.) for 48 hours, the majority of the inclusions do not drop more than 7%, preferably do not drop more than 5%, most preferably do not drop more than 2% of their original distance from the bottom of the container in which the inventive composition is present when they have returned to a quiescent state following manual shaking. By “majority of inclusions” is meant to convey that at least 90% of, preferably at least 95% and most preferably at least 97% of the inclusions physically present in the compositions. This is a particularly attractive and characteristic feature of preferred embodiments of inventive compositions, as the suspended inclusions do not appear to move perceptibly over long periods of time. Desirably, at least 90% of, preferably at least 95% and most preferably at least 97% of the inclusions physically present in the compositions do not drop more than 5%, most preferably do not drop more than 2% of their original distance from the bottom of the container in which the inventive composition is present when they have returned to a quiescent state following manual shaking when measured after 72 hours, more preferably when measured after 168 hours, still more preferably when measured after 10 days, yet more preferably after 14 days when left in a quiescent state at room temperature. In certain particularly preferred embodiments of the invention at least 90% of, preferably at least 95% and most preferably at least 97% of the inclusions physically present in the compositions do not drop more than 5%, after 3 weeks and especially after 4 weeks when retained in a quiescent state at room temperature. Although optional, the compositions according to the present invention may include one or more further detersive surfactants particularly those selected from amongst further nonionic, amphoteric and zwitterionic surfactants, particularly those which may provide a detersive effect to the compositions. Generally any nonionic surfactant material may be used in the inventive compositions. Practically any hydrophobic compound having a carboxy, hydroxy, amido, or amino group with a free hydrogen attached to the nitrogen can be condensed with an alkylene oxide, especially ethylene oxide or with the polyhydration product thereof, a polyalkylene glycol, especially polyethylene glycol, to form a water soluble or water dispersible nonionic surfactant compound. By way of non-limiting example, particularly examples of suitable nonionic surfactants which may be used in the present invention include the following: One class of useful nonionic surfactants include polyalkylene oxide condensates of alkyl phenols. These compounds include the condensation products of alkyl phenols having an alkyl group containing from about 6 to 12 carbon atoms in either a straight chain or branched chain configuration with an alkylene oxide, especially an ethylene oxide, the ethylene oxide being present in an amount equal to 5 to 25 moles of ethylene oxide per mole of alkyl phenol. The alkyl substituent in such compounds can be derived, for example, from polymerized propylene, diisobutylene and the like. Examples of compounds of this type include nonyl phenol condensed with about 9.5 moles of ethylene oxide per mole of nonyl phenol; dodecylphenol condensed with about 12 moles of ethylene oxide per mole of phenol; dinonyl phenol condensed with about 15 moles of ethylene oxide per mole of phenol and diisooctyl phenol condensed with about 15 moles of ethylene oxide per mole of phenol. A further class of useful nonionic surfactants include the condensation products of aliphatic alcohols with from about 1 to about 60 moles of an alkylene oxide, especially an ethylene oxide. The alkyl chain of the aliphatic alcohol can either be straight or branched, primary or secondary, and generally contains from about 8 to about 22 carbon atoms. Examples of such ethoxylated alcohols include the condensation product of myristyl alcohol condensed with about 10 moles of ethylene oxide per mole of alcohol and the condensation product of about 9 moles of ethylene oxide with coconut alcohol (a mixture of fatty alcohols with alkyl chains varying in length from about 10 to 14 carbon atoms). Other examples are those C6-C11 straight-chain alcohols which are ethoxylated with from about 3 to about 6 moles of ethylene oxide. Their derivation is well known in the art. Examples include Alfonic® 810-4.5, which is described in product literature from Sasol as a C8-10 having an average molecular weight of 356, an ethylene oxide content of about 4.85 moles (about 60 wt. %), and an HLB of about 12; Alfonic® 810-2, which is described in product literature as a C8-C10 having an average molecular weight of 242, an ethylene oxide content of about 2.1 moles (about 40 wt. %), and an HLB of about 12; and Alfonic® 610-3.5, which is described in product literature as having an average molecular weight of 276, an ethylene oxide content of about 3.1 moles (about 50 wt. %), and an HLB of 10. Other examples of alcohol ethoxylates are C10 oxo-alcohol ethoxylates available from BASF under the Lutensol® ON tradename. They are available in grades containing from about 3 to about 11 moles of ethylene oxide (available under the names Lutensol® ON 30; Lutensol® ON 50; Lutensol® ON 60; Lutensol® ON 65; Lutensol® ON 66; Lutensol® ON 70; Lutensol® ON 80; and Lutensol®ON 110). Other examples of ethoxylated alcohols include the Neodol® 91 series non-ionic surfactants available from Shell Chemical Company which are described as C9-C11 ethoxylated alcohols. The Neodol®91 series non-ionic surfactants of interest include Neodol®91-2.5, Neodol®91-6, and Neodol® 91-8. Neodol® 91-2.5 has been described as having about 2.5 ethoxy groups per molecule; Neodol 91-6 has been described as having about 6 ethoxy groups per molecule; and Neodol 91-8 has been described as having about 8 ethoxy groups per molecule. Further examples of ethoxylated alcohols include the Rhodasurf® DA series non-ionic surfactants available from Rhodia which are described to be branched isodecyl alcohol ethoxylates. Rhodasurf® DA-530 has been described as having 4 moles of ethoxylation and an HLB of 10.5; Rhodasurf® DA-630 has been described as having 6 moles of ethoxylation with an HLB of 12.5; and Rhodasurf® DA-639 is a 90% solution of DA-630. Further examples of ethoxylated alcohols include those from Tomah Products (Milton, Wis.) under the Tomadol® tradename with the formula RO(CH2CH2O)nH where R is the primary linear alcohol and n is the total number of moles of ethylene oxide. The ethoxylated alcohol series from Tomah include 91-2.5; 91-6; 91-8—where R is linear C9/C10/C11 and n is 2.5, 6, or 8; 1-3; 1-5; 1-7; 1-73B; 1-9; where R is linear C11 and n is 3, 5, 7 or 9; 23-1; 23-3; 23-5; 23-6.5—where R is linear C12/C13 and n is 1, 3, 5, or 6.5; 25-3; 25-7; 25-9; 25-12—where R is linear C12/C13/C14/C15 and n is 3, 7, 9, or 12; and 45-7; 45-13—where R is linear C14/C15 and n is 7 or 13. A further class of useful nonionic surfactants include primary and secondary linear and branched alcohol ethoxylates, such as those based on C6-C18 alcohols which further include an average of from 2 to 80 moles of ethoxylation per mol of alcohol. These examples include the Genapol® UD (ex. Clariant, Muttenz, Switzerland) described under the tradenames Genapol® UD 030, C11-oxo-alcohol polyglycol ether with 3 EO; Genapol® UD, 050 C11-oxo-alcohol polyglycol ether with 5 EO; Genapol® UD 070, C11-oxo-alcohol polyglycol ether with 7 EO; Genapol® UD 080, C11-oxo-alcohol polyglycol ether with 8 EO; Genapol® UD 088, C11-oxo-alcohol polyglycol ether with 8 EO; and Genapol® UD 110, C11-oxo-alcohol polyglycol ether with 11 EO. A further class of useful nonionic surfactants include those surfactants having a formula RO(CH2CH2O)nH wherein R is a mixture of linear, even carbon-number hydrocarbon chains ranging from C12H25 to C16H33 and n represents the number of repeating units and is a number of from about 1 to about 12. Surfactants of this formula are presently marketed under the Genapol® tradename (ex. Clariant), which surfactants include the “26-L” series of the general formula RO(CH2CH2O)nH wherein R is a mixture of linear, even carbon-number hydrocarbon chains ranging from C12H25 to C16H33 and n represents the number of repeating units and is a number of from 1 to about 12, such as 26-L-1, 26-L-1.6, 26-L-2, 26-L-3, 26-L-5, 26-L-45, 26-L-50, 26-L-60, 26-L-60N, 26-L-75, 26-L-80, 26-L-98N, and the 24-L series, derived from synthetic sources and typically contain about 55% C12 and 45% C14 alcohols, such as 24-L-3, 24-L-45, 24-L-50, 24-L-60, 24-L-60N, 24-L-75, 24-L-92, and 24-L-98N, all sold under the Genapol® tradename. A further class of useful nonionic surfactants include alkoxy block copolymers, and in particular, compounds based on ethoxy/propoxy block copolymers. Polymeric alkylene oxide block copolymers include nonionic surfactants in which the major portion of the molecule is made up of block polymeric C2-C4 alkylene oxides. Such nonionic surfactants, while preferably built up from an alkylene oxide chain starting group, and can have as a starting nucleus almost any active hydrogen containing group including, without limitation, amides, phenols, thiols and secondary alcohols. One group of such useful nonionic surfactants containing the characteristic alkylene oxide blocks are those which may be generally represented by the formula (A): HO-(EO)x(PO)y(EO)z—H (A) where EO represents ethylene oxide, PO represents propylene oxide, y equals at least 15, (EO)x+y equals 20 to 50% of the total weight of said compounds, and, the total molecular weight is preferably in the range of about 2000 to 15,000. These surfactants are available under the PLURONIC (ex. BASF) or Emulgen (ex. Kao.) A further group of such useful nonionic surfactants containing the characteristic alkylene oxide blocks are those can be represented by the formula (B): R-(EO,PO)a(EO,PO)b—H (B) wherein R is an alkyl, aryl or aralkyl group, where the R group contains 1 to 20 carbon atoms, the weight percent of EO is within the range of 0 to 45% in one of the blocks a, b, and within the range of 60 to 100% in the other of the blocks a, b, and the total number of moles of combined EO and PO is in the range of 6 to 125 moles, with 1 to 50 moles in the PO rich block and 5 to 100 moles in the EO rich block. Specific nonionic surfactants which in general are encompassed by Formula B include butoxy derivatives of propylene oxide/ethylene oxide block polymers having molecular weights within the range of about 2000-5000. Still further examples of useful nonionic surfactants include those which can be represented by formula (C) as follows: RO—(BO)n(EO)x—H (C) wherein EO represents ethylene oxide, BO represents butylene oxide, R is an alkyl group containing 1 to 20 carbon atoms, n is about 5-15 and x is about 5-15. Yet further useful nonionic surfactants include those which may be represented by the following formula (D): HO-(EO)x(BO)n(EO)y—H (D) wherein EO represents ethylene oxide, BO represents butylene oxide, n is about 5-15, preferably about 15, x is about 5-15, preferably about 15, and y is about 5-15, preferably about 15. Still further exemplary useful nonionic block copolymer surfactants include ethoxylated derivatives of propoxylated ethylene diamine, which may be represented by the following formula: where (EO) represents ethoxy, (PO) represents propoxy, the amount of (PO)x is such as to provide a molecular weight prior to ethoxylation of about 300 to 7500, and the amount of (EO)y is such as to provide about 20% to 90% of the total weight of said compound. Further useful non-ionic surfactants which may be used in the inventive compositions include those presently marketed under the trade name Pluronics® (ex. BASF). The compounds are formed by condensing ethylene oxide with a hydrophobic base formed by the condensation of propylene oxide with propylene glycol. The molecular weight of the hydrophobic portion of the molecule is of the order of 950 to 4,000 and preferably 200 to 2,500. The addition of polyoxyethylene radicals of the hydrophobic portion tends to increase the solubility of the molecule as a whole so as to make the surfactant water-soluble. The molecular weight of the block polymers varies from 1,000 to 15,000 and the polyethylene oxide content may comprise 20% to 80% by weight. Preferably, these surfactants are in liquid form and particularly satisfactory surfactants are available as those marketed as Pluronics® L62 and Pluronics® L64. Alkylmonoglyocosides and alkylpolyglycosides which find use in the present inventive compositions include known nonionic surfactants which are alkaline and electrolyte stable. Alkylmonoglycosides and alkylpolyglycosides are prepared generally by reacting a monosaccharide, or a compound hydrolyzable to a monosaccharide with an alcohol such as a fatty alcohol in an acid medium. Various glycoside and polyglycoside compounds including alkoxylated glycosides and processes for making them are disclosed in U.S. Pat. Nos. 2,974,134; 3,219,656; 3,598,865; 3,640,998; 3,707,535, 3,772,269; 3,839,318; 3,974,138; 4,223,129 and 4,528,106 the contents of which are incorporated by reference. One exemplary group of such useful alkylpolyglycosides include those according to the formula: R2O—(CnH2nO)r-(Z)x wherein: R2 is a hydrophobic group selected from alkyl groups, alkylphenyl groups, hydroxyalkylphenyl groups as well as mixtures thereof, wherein the alkyl groups may be straight chained or branched, and which contain from about 8 to about 18 carbon atoms, n has a value of 2-8, especially a value of 2 or 3; r is an integer from 0 to 10, but is preferably 0, Z is derived from glucose; and, x is a value from about 1 to 8, preferably from about 1.5 to 5. Preferably the alkylpolyglycosides are nonionic fatty alkylpolyglucosides which contain a straight chain or branched chain C8-C15 alkyl group, and have an average of from about 1 to 5 glucose units per fatty alkylpolyglucoside molecule. More preferably, the nonionic fatty alkylpolyglucosides which contain straight chain or branched C8-C15 alkyl group, and have an average of from about 1 to about 2 glucose units per fatty alkylpolyglucoside molecule. A further exemplary group of alkyl glycoside surfactants suitable for use in the practice of this invention may be presented by the following formula (A): RO—(R1O)y-(G)x-Zb (A) wherein: R is a monovalent organic radical containing from about 6 to about 30, preferably from about 8 to 18 carbon atoms, R1 is a divalent hydrocarbon radical containing from about 2 to about 4 carbon atoms, y is a number which has an average value from about 0 to about 1 and is preferably 0, G is a moiety derived from a reducing saccharide containing 5 or 6 carbon atoms; and, x is a number having an average value from about 1 to 5 (preferably from 1.1 to 2); Z is O2M1 O(CH2), CO2M1, OSO3M1, or O(CH2)SO3M1; R2 is (CH2)CO2 M1 or CH═CHCO2M1; (with the proviso that Z can be O2M1 only if Z is in place of a primary hydroxyl group in which the primary hydroxyl-bearing carbon atom, —CH2OH, is oxidized to form a group) b is a number of from 0 to 3x+1 preferably an average of from 0.5 to 2 per glycosal group; p is 1 to 10, M1 is H+ or an organic or inorganic counterion, particularly cations such as, for example, an alkali metal cation, ammonium cation, monoethanolamine cation or calcium cation. As defined in Formula (A) above, R is generally the residue of a fatty alcohol having from about 8 to 30 and preferably 8 to 18 carbon atoms. Examples of such alkylglycosides as described above include, for example APG 325 CS Glycoside®) which is described as being a 50% C9-C11 alkyl polyglycoside, also commonly referred to as D-glucopyranoside, (commercially available from Henkel KGaA) and Glucopon® 625 CS which is described as being a 50% C10-C16 alkyl polyglycoside, also commonly referred to as a D-glucopyranoside, (ex. Henkel). Further nonionic surfactants which may be included in the inventive compositions include alkoxylated alkanolamides, preferably C8-C24 alkyl di(C2-C3 alkanol amides), as represented by the following formula: R5—CO—NH—R6—OH wherein R5 is a branched or straight chain C8-C24 alkyl radical, preferably a C10-C16 alkyl radical and more preferably a C12-C14 alkyl radical, and R6 is a C1-C4 alkyl radical, preferably an ethyl radical. The inventive compositions may also include a nonionic amine oxide constituent. Exemplary amine oxides include: (A) Alkyl di(lower alkyl)amine oxides in which the alkyl group has about 10-20, and preferably 12-16 carbon atoms, and can be straight or branched chain, saturated or unsaturated. The lower alkyl groups include between 1 and 7 carbon atoms. Examples include lauryl dimethyl amine oxide, myristyl dimethyl amine oxide, and those in which the alkyl group is a mixture of different amine oxide, dimethyl cocoamine oxide, dimethyl(hydrogenated tallow)amine oxide, and myristyl/palmityl dimethyl amine oxide; (B) Alkyl di(hydroxy lower alkyl)amine oxides in which the alkyl group has about 10-20, and preferably 12-16 carbon atoms, and can be straight or branched chain, saturated or unsaturated. Examples are bis(2-hydroxyethyl) cocoamine oxide, bis(2-hydroxyethyl) tallowamine oxide; and bis(2-hydroxyethyl)stearylamine oxide; (C) Alkylamidopropyl di(lower alkyl)amine oxides in which the alkyl group has about 10-20, and preferably 12-16 carbon atoms, and can be straight or branched chain, saturated or unsaturated. Examples are cocoamidopropyl dimethyl amine oxide and tallowamidopropyl dimethyl amine oxide; and (D) Alkylmorpholine oxides in which the alkyl group has about 10-20, and preferably 12-16 carbon atoms, and can be straight or branched chain, saturated or unsaturated. Preferably the amine oxide constituent is an alkyl di(lower alkyl)amine oxide as denoted above and which may be represented by the following structure: wherein each: R1 is a straight chained C1-C4 alkyl group, preferably both R1 are methyl groups; and, R2 is a straight chained C8-C18 alkyl group, preferably is C10-C14 alkyl group, most preferably is a C1-2 alkyl group. Each of the alkyl groups may be linear or branched, but most preferably are linear. Most preferably the amine oxide constituent is lauryl dimethyl amine oxide. Technical grade mixtures of two or more amine oxides may be used, wherein amine oxides of varying chains of the R2 group are present. Preferably, the amine oxides used in the present invention include R2 groups which comprise at least 50% wt., preferably at least 60% wt. Of C12 alkyl groups and at least 25% wt. of C14 alkyl groups, with not more than 15% wt. of C16, C18 or higher alkyl groups as the R2 group. Of course the nonionic surfactant constituent, when present, my comprise two or more nonionic surfactants. In certain preferred embodiments the inventive compositions comprise at least one nonionic surfactant. When present, any nonionic surfactants present in the compositions of the present invention are desirably included in an amount of from about 0.01% wt. to about 20% wt., more preferably is present in an amount of from about 0.1-20% wt., and most preferably is present in an amount of from about 1 to about 10% wt. The compositions according to the invention may optionally further comprise an alkyl ethoxylated carboxylate surfactant. In particular, the alkyl ethoxylated carboxylate comprises compounds and mixtures of compounds which may be represented by the formula: R1(OC2H4)n—OCH2COO−M+ wherein R1 is a C4-C18 alkyl, n is from about 3 to about 20, and M is hydrogen, a solubilizing metal, preferably an alkali metal such as sodium or potassium, or ammonium or lower alkanolammonium, such as triethanolammonium, monoethanolammonium, or diisopropanolammonium. The lower alkanol of such alkanolammonium will normally be of 2 to 4 carbon atoms and is preferably ethanol. Preferably, R1 is a C12-C15 alkyl, n is from about 7 to about 13, and M is an alkali metal counterion. Examples of alkyl ethoxylated carboxylates contemplated to be useful in the present invention include, but are not necessarily limited to, sodium buteth-3 carboxylate, sodium hexeth-4 carboxylate, sodium laureth-5 carboxylate, sodium laureth-6 carboxylate, sodium laureth-8 carboxylate, sodium laureth-11 carboxylate, sodium laureth-13 carboxylate, sodium trideceth-3 carboxylate, sodium trideceth-6 carboxylate, sodium trideceth-7 carboxylate, sodium trideceth-19 carboxylate, sodium capryleth-4 carboxylate, sodium capryleth-6 carboxylate, sodium capryleth-9 carboxylate, sodium capryleth-13 carboxylate, sodium ceteth-13 carboxylate, sodium C12-15 pareth-6 carboxylate, sodium C12-15 pareth-7 carboxylate, sodium C14-15 pareth-8 carboxylate, isosteareth-6 carboxylate as well as the acid form. Sodiumlaureth-8 carboxylate, sodium laureth-13 carboxylate, pareth-25-7 carboxylic acid are preferred. A particularly preferred sodium laureth-13 carboxylate can be obtained from Clariant Corp. under the trade name Sandopan® LS-24. When present, any alkyl ethoxylated carboxylate surfactant present in the compositions of the present invention are desirably included in an amount of from about 0.1 to about 20% by weight, more preferably is present in an amount of from about 0.1-20% wt., and most preferably is present in an amount of from about 1 to about 10% wt. By way of non-limiting example exemplary amphoteric surfactants include one or more water-soluble betaine surfactants which may be represented by the general formula: wherein R1 is an alkyl group containing from 8 to 18 carbon atoms, or the amido radical which may be represented by the following general formula: wherein R is an alkyl group having from 8 to 18 carbon atoms, a is an integer having a value of from 1 to 4 inclusive, and R2 is a C1-C4 alkylene group. Examples of such water-soluble betaine surfactants include dodecyl dimethyl betaine, as well as cocoamidopropylbetaine. When present, any amphoteric surfactants present in the compositions of the present invention are desirably included in an amount of from about 0.1 to about 20% by weight, more preferably is present in an amount of from about 0.1-20% wt., and most preferably is present in an amount of from about 1 to about 10% wt. Most desirably, the total amount of detersive surfactants present in the inventive compositions, inclusive of the necessary anionic surfactants and any further optional surfactants does not exceed about 20% wt., more preferably does not exceed about 15% wt. Optionally, but in many cases desirably, the inventive compositions comprise one or more organic solvents. By way of non-limiting example exemplary useful organic solvents which may be included in the inventive compositions include those which are at least partially water-miscible such as alcohols (e.g., low molecular weight alcohols, such as, for example, ethanol, propanol, isopropanol, and the like), glycols (such as, for example, ethylene glycol, propylene glycol, hexylene glycol, and the like), water-miscible ethers (e.g. diethylene glycol diethylether, diethylene glycol dimethylether, propylene glycol dimethylether), water-miscible glycol ether (e.g. propylene glycol monomethylether, propylene glycol mono ethylether, propylene glycol monopropylether, propylene glycol monobutylether, ethylene glycol monobutylether, dipropylene glycol monomethylether, diethyleneglycol monobutylether), lower esters of monoalkylethers of ethylene glycol or propylene glycol (e.g. propylene glycol monomethyl ether acetate), and mixtures thereof. Glycol ethers having the general structure Ra—Rb—OH, wherein Ra is an alkoxy of 1 to 20 carbon atoms, or aryloxy of at least 6 carbon atoms, and Rb is an ether condensate of propylene glycol and/or ethylene glycol having from one to ten glycol monomer units. Of course, mixtures of two or more organic solvents may be used in the organic solvent constituent. When present, the organic solvent constituent may be present in amounts of from about 0.1 to about 20% by weight, more preferably is present in an amount of from about 0.1-110% wt., and most preferably is present in an amount of from about 1 to about 10% wt. According to certain particularly preferred embodiments, the inventive compositions exclude added organic solvents, particularly those described immediately above. It is recognized that organic solvents may be present as carriers for certain other constituents essential to the present invention, and these may be present; generally the total amount of such organic solvents, if present, is less than about than 0.1% wt., more preferably less than 0.05% wt. and most preferably comprise no organic solvents as described above. While optional, the compositions of the invention may further include an oxidizing agent, which is preferably a peroxyhydrate or other agent which releases hydrogen peroxide in aqueous solution. Such materials are per se, known to the art. Such peroxyhydrates are to be understood as to encompass hydrogen peroxide as well as any material or compound which in an aqueous composition yields hydrogen peroxide. Examples of such materials and compounds include without limitation: alkali metal peroxides including sodium peroxide and potassium peroxide, alkali perborate monohydrates, alkali metal perborate tetrahydrates, alkali metal persulfate, alkali metal percarbonates, alkali metal peroxyhydrate, alkali metal peroxydihydrates, and alkali metal carbonates especially where such alkali metals are sodium or potassium. Further useful are various peroxydihydrate, and organic peroxyhydrates such as urea peroxide. Desirably the oxidizing agent is hydrogen peroxide. Desirably the oxidizing agent, especially the preferred hydrogen peroxide is present in the inventive compositions in an amount of from about 0.01% wt. to about 10.0% wt., based on the total weight of the composition of which it forms a part. Minor amounts of stabilizers such as one or more organic phosphonates, stannates, pyrophosphates, as well as citric acid as well as citric acid salts may be included and are considered as part of the oxidizing agent. The inclusion of one or more such stabilizers aids in reducing the decomposition of the hydrogen peroxide due to the presence of metal ions and or adverse pH levels in the inventive compositions. The compositions of the present invention can also optionally comprise one or more further constituents which are directed to improving the aesthetic or functional features of the inventive compositions. By way of non-limiting example such further constituents include one or more coloring agents, fragrances and fragrance solubilizers, viscosity modifying agents, other surfactants, pH adjusting agents and pH buffers including organic and inorganic salts, optical brighteners, opacifying agents, hydrotropes, antifoaming agents, enzymes, anti-spotting agents, anti-oxidants, preservatives, and anti-corrosion agents. When one or more of the optional constituents is added, i.e., fragrance and/or coloring agents, the esthetic and consumer appeal of the product is often favorably improved. The use and selection of these optional constituents is well known to those of ordinary skill in the art. When present, the one or more optional constituents present in the inventive compositions do not exceed about 20% wt., preferably do not exceed 15% wt., and most preferably do not exceed 10% wt. Certain optional constituents which are nonetheless desirably present in the inventive compositions are pH adjusting agents and especially pH buffers. Such pH buffers include many materials which are known to the art and which are conventionally used in hard surface cleaning and/or hard surface disinfecting compositions. By way of non-limiting example pH adjusting agents include phosphorus containing compounds, monovalent and polyvalent salts such as of silicates, carbonates, and borates, certain acids and bases, tartrates and certain acetates. Further exemplary pH adjusting agents include mineral acids, basic compositions, and organic acids, which are typically required in only minor amounts. By way of further non-limiting example pH buffering compositions include the alkali metal phosphates, polyphosphates, pyrophosphates, triphosphates, tetraphosphates, silicates, metasilicates, polysilicates, carbonates, hydroxides, and mixtures of the same. Certain salts, such as the alkaline earth phosphates, carbonates, hydroxides, can also function as buffers. It may also be suitable to use as buffers such materials as aluminosilicates (zeolites), borates, aluminates and certain organic materials such as gluconates, succinates, maleates, and their alkali metal salts. When present, the pH adjusting agent, especially the pH buffers are present in an amount effective in order to maintain the pH of the inventive composition within a target pH range. As the compositions are largely aqueous in nature, and comprises as the balance of the composition water in to order to provide to 100% by weight of the compositions of the invention. The water may be tap water, but is preferably distilled and is most preferably deionized water. If the water is tap water, it is preferably substantially free of any undesirable impurities such as organics or inorganics, especially minerals salts which are present in hard water which may thus undesirably interfere with the operation of the constituents present in the aqueous compositions according to the invention. The inventive compositions provide certain technical benefits when used on hard surfaces, particularly: satisfactory removal of hard water stains, satisfactory removal of soap scum stains, and satisfactory disinfection or sanitization of hard surfaces. In preferred embodiments, the compositions are readily pourable and are be desirably provided as a ready to use pourable product in a manually squeezable (manually deformable) bottle. In use, the consumer generally applies an effective amount of the composition and within a few moments thereafter, wipes off the treated area with a rag, towel, brush or sponge, usually a disposable paper towel or sponge. In certain applications, however, especially where undesirable stain deposits are heavy, the composition according to the invention may be left on the stained area until it has effectively loosened the stain deposits after which it may then be wiped off, rinsed off, or otherwise removed. For particularly heavy deposits of such undesired stains, multiple applications may also be used. A particularly advantageous feature of the inventive compositions is that as the suspended inclusions are visibly discrete and visibly discernible to the consumer, these same inclusions are visible to the consumer on hard surfaces to which the inventive compositions have been applied. This permits for ready visual inspection of the coverage of the hard surface by an inventive composition immediately after application of the composition by a consumer. Such provides not only an attractive attribute to commercial products based on such compositions but also provides a visual indicator to the consumer of thorough coverage and contact with hard surfaces. This visual indicator provides an important means whereby the consumer may visually inspect a surface, particularly a surface wherein the presence of undesired microorganisms is suspected, to ensure that thorough coverage and contact with said hard surface is realized. As is known, physical contact between the inventive composition and undesired microorganisms is required in order to the inventive compositions to provide a disinfecting effect. An important technical characteristic lies in rheology of the inventive compositions. The compositions may be described as being rheopectic at lower shear rates, an especially upon standing in quiescent state, but are thixotropic at higher shear rates. Such dual properties are very advantageous, as when the compositions are at rest in a container, e.g., upon standing, their rheopectic behavior provides for the stable suspension of the inclusions described herein. When it is desired to dispense the compositions from a container especially through the nozzle of a bottle, the thixotropic characteristics of the compositions permit for their dispensing through the nozzle of such a bottle. Ideally, after being dispensed from such a squeezable bottle onto a surface, especially an inclined surface the compositions return to a quiescent state and once again display a rheopectic behavior. Furthermore, as at least some of the suspended inclusions are delivered from the composition and onto the surface, these inclusions are present on the surface and provide a useful indicator as to the coverage of the dispensed composition onto the surface. The inventive compositions are desirably provided as a ready to use product which may be directly applied to a hard surface. By way of example, hard surfaces suitable for coating with the polymer include surfaces composed of refractory materials such as: glazed and unglazed tile, brick, porcelain, ceramics as well as stone including marble, granite, and other stones surfaces; glass; metals; plastics e.g. polyester, vinyl; fiberglass, Formica®, Corian® and other hard surfaces known to the industry. Hard surfaces which are to be particularly denoted are lavatory fixtures such as shower stalls, bathtubs and bathing appliances (racks, curtains, shower doors, shower bars) toilets, bidets, wall and flooring surfaces especially those which include refractory materials and the like. Further hard surfaces which are to be denoted are those associated with kitchen environments and other environments associated with food preparation, including cabinets and countertop surfaces as well as walls and floor surfaces especially those which include refractory materials, plastics, Formica®, Corian® and stone. Still further hard surfaces include those associated with medical facilities, e.g., hospitals, clinics as well as laboratories, e.g., medical testing laboratories. The compositions according to the invention are easily produced by any of a number of known art techniques. Conveniently, a part of the water is supplied to a suitable mixing vessel further provided with a stirrer or agitator, and while stirring, the remaining constituents are added to the mixing vessel, including any final amount of water needed to provide to 100% wt. of the inventive composition. The following examples below illustrate exemplary formulations and preferred formulations of the inventive composition. It is to be understood that these examples are presented by means of illustration only and that further useful formulations fall within the scope of this invention and the claims may be readily produced by one skilled in the art and not deviate from the scope and spirit of the invention. Throughout this specification and in the accompanying claims, weight percents of any constituent are to be understood as the weight percent of the active portion of the referenced constituent, unless otherwise indicated. EXAMPLES Exemplary formulations illustrating certain preferred embodiments of the inventive compositions and described in more detail in Table I below were formulated generally in accordance with the following protocol. Into a suitably sized vessel, a measured amount of water was provided after which the constituents were added in the following sequence: thickening agents, surfactant(s), acid and then the remaining constituents. Mixing, which generally lasted from 5 minutes to 120 minutes was maintained until the particular formulation appeared to be homogeneous. The exemplary compositions were readily pourable, and retained well mixed characteristics (i.e., stable mixtures) upon standing. The constituents may be added in any order. Examples of inventive formulations are shown in Table 1 below (unless otherwise stated, the components indicated are provided as “100% active”) wherein the amounts of the named constituents are indicated in % w/w. Deionized water was added in “quantum sufficient” to provide the balance to 100 parts by weight of the compositions. TABLE 1 Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7 Ex. 8 Ex. 9 Ex. 10 Ex. 11 Ex. 12 hydroxyethylcellulose 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 — xanthan gum 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.2 gellan gum — — — — — — — — — — — 0.05 sodium lauryl sulfate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 citric acid 4.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 formic acid — 2.0 — — — — — — — — — — malonic acid — — — — 2.0 — — — — — — — maleic acid — — — — — 2.0 — — — — — — adipic acid — — 2.0 — — — — — — — — — boric acid — — — 2.0 — — — — — — — — lactic acid — — — — — — — — — 2.3 — 2.0 glycolic acid — — — — — — — — — — 2.0 — malic acid — — — — — — 2.0 — — — — — acetic acid — — — — — — — 2.0 — — — — sorbic acid — — — — — — — — 2.0 — — — sodium hydroxide 0.5 0.77 0.34 0.34 0.34 0.34 0.34 0.34 0.34 0.28 0.34 0.34 dye 1 1 1 1 1 1 1 1 1 1 1 — fragrance 0.28 0.28 0.28 0.28 0.28 0.28 0.28 0.28 0.28 0.28 0.28 0.21 alginate beads 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.3 di water q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. The identity of the individual constituents indicated above is listed on the following table wherein is indicated the generic name, the commercial preparation used, the percent active weight (% w/w basis) of the compound identified by the generic name, and in some cases the supplier of the commercial preparation: TABLE 2 hydroxyethylcellulose CELLOSIZE QP-100MH (100%) (ex. Union Carbide, division of Dow Chemical) xanthan gum KELZAN ASXT (100%) (ex. Kelco) gellan gum KELCOGEL AFT (100%) (ex. Kelco) sodium lauryl sulfate Stepanol WAC (30%) (ex. Stepan Co.), except for Ex. 12 where Stepanol LCP (30%) a low cloud point sodium lauryl sulfate was used citric acid anhydrous citric acid (100%) (ex. ADM) formic acid formic acid (94%) malonic acid malonic acid (99%) maleic acid maleic acid (100%) adipic acid adipic acid (98%) boric acid boric acid (99.5%) lactic acid lactic acid (88%) glycolic acid glycolic acid (70%) (ex. DuPont) malic acid malic acid (100%) acetic acid acetic acid (100%) sorbic acid sorbic acid (100%) sodium hydroxide NaOH pellets, anhydrous (100%) dye 1% aqueous solution of a FD&C yellow dye fragrance proprietary composition alginate beads alginate based particulate material compsiring less than 5% wt of calcium alginate, less than 0.01% wt. of a pigment, less than 5% wt. of TiO2 and the balance to 100% wt. water drained from an aqueous carrier containing 2% calcium chloride in solution (ex. geniaLabs Biotechnologie, Germany) di water deionized water Certain of the compositions described on Table 1 above were tested to evaluate certain technical characteristics of the compositions. Evaluation of Composition Stability: Certain of the compositions described on Table 1 were evaluated to observe the stability of the alginate beads in the compositions following storage of the compositions under accelerated ageing testing, wherein the compositions were stored for 1 week at 49° C. The results are indicated in the following Table: TABLE 3 Ex. 1 stable Ex. 2 stable Ex. 3 swell Ex. 4 swell Ex. 5 swell Ex. 6 swell Ex. 7 stable Ex. 8 swell Ex. 9 swell Ex. 10 stable Ex. 11 stable A result of “stable” indicated that the suspended inclusions based on the alginate based particulate materials did not change in from their initial appearance at the conclusion of the test. A result of “swell” indicated that the suspended inclusions based on the alginate based particulate materials slightly to somewhat changed in from their initial appearance at the conclusion of the test. In all of the formulations however the alginate based particulate materials were stably suspended inclusions. Evaluation of Viscosity: The viscosity of the compositions were evaluated utilizing using an LVT-II Brookfield Viscometer, #2 spindle at 20 rpm and 20° C. The viscosity of all of the compositions according to Examples 1-11 was in the range of 1100-1500 cps. The viscosity of the composition according to Ex. 12 measured as noted above was 306 cps. Evaluation of Efficacy Against Hard Water Stains: A formulation according to the invention, namely the formulation described as “Ex. 10” on Table 1 was evaluated for its efficacy in removing hard water stains. Such hard water stains are also referred to as “limescale”. The test protocol was as follows: Five sample marble tiles, each measuring 5.75 inches by 2.88 inches by 0.37 inches were washed and dried for one hour in a laboratory oven at 80° C. The tiles were then weighed, and thereafter immersed in 900 ml. of the formulation according to Ex. 10 for 10 seconds, removed from the formulation and thereafter allowed to rest at room temperature (approx. 20° C.) on a laboratory bench. Thereafter the tiles were thoroughly rinsed with deionized water, manually dried using a laboratory wipe (Kimwipe®), and then again dried for one hour at 80° C. in a laboratory oven. Thereafter the tiles were removed, and allowed to cool to room temperature and reweighed. The results of this test, including average results for limescale removal and % weight loss are indicated in the following table. TABLE 4 sample initial limescale % wt. loss of tile # weight (g) final weight (g) removed (g) sample tile 1 294.0960 294.0490 0.0470 0.0160 2 293.4320 293.3760 0.0560 0.0191 3 295.4210 295.3680 0.0530 0.0179 4 298.8390 298.7870 0.0520 0.0174 5 304.0830 304.0290 0.0540 0.0178 0.0524 (avg.) 0.0176 (avg.) The results indicate the loss of carbonates (calcium carbonate, magnesium carbonates, etc.) from the marble compositions of the tiles, and demonstrate the efficacy of the inventive composition in the removal of inorganic carbonates, a major constituent in limescale. As a comparative example, the same test protocol as indicated above was repeated but using a commercially available bathroom cleaning product, “Lysol® Cling Toilet Bowl Cleaner—Country Scent” instead of the formulation according to Ex. 10. The results of this test are indicated in the following table. TABLE 4 (comparative example) sample initial limescale % wt. loss of tile # weight (g) final weight (g) removed (g) sample tile 6 295.8070 295.7960 0.0110 0.0037 7 296.8830 296.8690 0.0140 0.0047 8 291.8520 291.8400 0.0120 0.0041 9 300.3410 300.3370 0.0040 0.0013 10 299.4050 299.3920 0.0130 0.0043 0.0108 (avg.) 0.0036 (avg.) As can be seen by comparing the results of the foregoing tables, the sample tiles treated with the inventive composition exhibited good efficacy at removal of inorganic carbonates from the sample tiles, while the tiles treated with the prior art composition demonstrated much lower efficacy at removal of inorganic carbonates. Evaluation of Antimicrobial Efficacy: Several of the exemplary formulations described in more detail on Table 1 above were evaluated in order to evaluate their antimicrobial efficacy against Staphylococcus aureus (gram positive type pathogenic bacteria) (ATCC 6538), Salmonella choleraesuis (gram negative type pathogenic bacteria) (ATCC 10708), Escheria coli (gram negative type pathogenic bacteria) (ATCC 11229) and Pseudomonas aeruginosa (ATCC 15442). The testing was performed generally in accordance with the protocols outlined in “Use-Dilution Method”, Protocols 955.14, 955.15 and 964.02 described in Chapter 6 of “Official Methods of Analysis”, 16th Edition, of the Association of Official Analytical Chemists; “Germicidal and Detergent Sanitizing Action of Disinfectants”, 960.09 described in Chapter 6 of “Official Methods of Analysis”, 15th Edition, of the Association of Official Analytical Chemists; or American Society for Testing and Materials (ASTM) E 1054-91 the contents of which are herein incorporated by reference. This test is also commonly referred to as the “AOAC Use-Dilution Test Method”. Testing was performed on the inventive formulation described as “Ex. 10” described on Table 1, above at dilutions of 1 part formulation to 25 parts water. As is appreciated by the skilled practitioner in the art, the results of the AOAC Use-Dilution Test Method indicates the number of test substrates wherein the tested organism remains viable after contact for 10 minutes with at test disinfecting composition /total number of tested substrates (cylinders) evaluated in accordance with the AOAC Use-Dilution Test. Thus, a result of “0/60” indicates that of 60 test substrates bearing the test organism and contacted for 10 minutes in a test disinfecting composition, 0 test substrates had viable (live) test organisms at the conclusion of the test. Such a result is excellent, illustrating the excellent disinfecting efficacy of the tested composition. Results of the antimicrobial testing are indicated on the Table, below. The reported results indicate the number of test cylinders with live test organisms/number of test cylinders tested for each example formulation and organism tested. TABLE 5 Test Results Conclusion Staphylococcus aureus 1/60 Pass Salmonella choleraesuis 1/60 Pass Escheria coli 1/60 Pass Pseudomonas aeruginosa 1/60 Pass As may be seen from the results indicated above, the compositions according to the invention provide excellent cleaning benefits to hard surfaces, including hard surfaces with difficult to remove stains. These advantages are further supplemented by the excellent antimicrobial efficacy of these compositions against known bacteria commonly found in bathroom, kitchen and other environments. Such advantages clearly illustrate the superior characteristics of the compositions, the cleaning and antimicrobial benefits attending its use which is not before known to the art.
20050408
20070306
20050804
82199.0
0
BOYER, CHARLES I
HARD SURFACE CLEANING COMPOSITIONS COMPRISING ALIGINATE MATERIALS AND XANTHAN GUM
UNDISCOUNTED
0
ACCEPTED
2,005
10,511,105
ACCEPTED
Method and system for authenticating user of data transfer device
The invention relates to a method and system for authenticating a user of a data transfer device (such as a terminal in a wireless local area network, i.e. WLAN). The method comprises: setting up a data transfer connection from the data transfer device to a service access point. Next, identification data of the mobile subscriber (for example an MSISDN) are inputted to the service access point. This is followed by checking from the mobile communications system whether the mobile subscriber identification data contains an access right to the service access point. If a valid access right exists, a password is generated, then transmitted to a subscriber terminal (for example a GSM mobile phone) corresponding to the mobile subscriber identification data, and login from the data transfer device to the service access point takes place with the password transmitted to the subscriber terminal.
1. A method for authenticating a user of a data transfer device, comprising: setting up a data transfer connection from the data transfer device to a service access point; inputting identification data of a subscriber of a mobile communications system to the service access point; checking from the mobile communications system whether the mobile subscriber identification data contains an access right to the service access point; and, if a valid access right exists, generating a password, transmitting the password to a subscriber terminal corresponding to the mobile subscriber identification data, and logging in to the service access point from the data transfer device using the password transmitted to the subscriber terminal. 2. A method according to claim 1, wherein the mobile subscriber identification data consist of a mobile subscriber international ISDN number [[(MSISDN)]] MSISDN. 3. A method according to claim 1, wherein in connection with the check, a query is sent to the home location register of the mobile communications system. 4. A method according to claim 3, wherein the mobile subscriber identification data consist of the mobile subscriber international ISDN number, and with the query first the home location register of the mobile communications system is searched for the international mobile subscriber identity [[(IMSI)]] IMSI corresponding to the mobile subscriber international ISDN number and then with the international mobile subscriber identity the home location register of the mobile communications system is searched for the related subscriber data, where the access right is defined. 5. A method according to claim 1, wherein the password is transmitted to the subscriber terminal in a packet-switched message. 6. A method according to claim 1, wherein the password is transmitted to the subscriber terminal in a short message. 7. A method according to claim 1, wherein the data transfer connection between the data transfer device and the service access point is a radio link. 8. A method according to claim 7, wherein the radio link is implemented using a wireless local area network. 9. A method according to claim 7, wherein the radio link is implemented using a short-range radio transceiver. 10. A method according to claim 1, wherein the data transfer connection between the data transfer device and the service access point is wired. 11. A method according to claim 1, wherein the method further comprises: billing for the data transfer connection between the data transfer device and the service access point in a bill directed to the identification data of the mobile subscriber. 12. A method according to claim 1, wherein the data transfer connection initially set up between the data transfer device and the service access point is maintained until login. 13. A method according to claim 1, wherein the method further comprises: transmitting a second password from the service access point to the data transfer device over a data transfer connection, the second password being also used in connection with login. 14. A method according to claim 1, wherein the method further comprises: transmitting a confirmation identifier from the service access point to the data transfer device over a data transfer connection and transmitting the same confirmation identifier to the subscriber terminal together with the password, the password being only used if the received confirmation identifiers are the same. 15. A method according to claim 1, wherein the data transfer connection between the data transfer device and the service access point is set up when the subscriber terminal is roaming. 16. A method according to claim 15, wherein the method further comprises: informing the subscriber terminal that if the roaming by the subscriber terminal in the visited mobile communications system fulfils a predetermined criterion, the data transfer connection from the data transfer device to the service access point is provided at a lower charge than usual; and implementing the data transfer connection from the data transfer device to the service access point at a lower charge than usual if the predetermined criterion is met. 17. A method according to claim 16, wherein the method further comprises: receiving at the visited mobile communications system information from the subscriber terminal indicating that a lower charge data transfer connection to the service access point is preferred. 18. A method according to claim 17, wherein the method further comprises: receiving at the authentication server information from the visited mobile communications system indicating that the data transfer device of the user of the subscriber terminal will be provided with a lower charge data transfer connection to the service access point. 19. A method according to claim 16, wherein the predetermined criterion is met if the subscriber terminal contacts the visited mobile communications system and/or if the subscriber terminal continues roaming in the visited mobile communications system for a predetermined time. 20. A method according to claim 16, wherein to check whether the predetermined criterion is met, a periodic query is made to the home location register of the mobile subscriber's home mobile communications system. 21. A method according to claim 1, wherein the method further comprises: using the mobile subscriber identification data as a user ID in connection with login. 22. A method according to claim 1, wherein the method further comprises: transmitting a user ID to the subscriber terminal corresponding to the mobile subscriber identification data and using the transmitted user ID in connection with login. 23. A method according to claim 1, wherein the method further comprises: transmitting a user ID to the data transfer device over a data transfer connection and using the transmitted user ID in connection with login. 24. A system for authenticating a user of a data transfer device, comprising: a data transfer device, a service access point that can be linked to the data transfer device over a first data transfer connection, and an authentication server linked to the service access point over a second data transfer connection; wherein the service access point is configured to receive over the first data transmission connection identification data of a subscriber of a mobile communications system inputted from the data transfer device and to transmit the mobile subscriber identification data to the authentication server over the second data transfer connection; the authentication server is configured to check from the mobile communications system over a third data transfer connection whether the mobile subscriber identification data contains an access right to the service access point and, if a valid access right exists, to generate a password and transmit the password to a subscriber terminal corresponding to the identification data of the subscriber of the mobile communications system; and the data transfer device is configured to use the password transmitted to the subscriber terminal in connection with login to the service access point. 25. A system according to claim 24, wherein the identification data of the subscriber of the mobile communications system consist of the mobile subscriber international ISDN. 26. A system according to claim 24, wherein the authentication server is an Authentication, Authorization and Accounting AAA server. 27. A system according to claim 24, wherein for checking the access right to the service access point, the authentication server is configured to transmit a query to the home location register of the mobile communications system. 28. A system according to claim 27, wherein the identification data of the subscriber of the mobile communications system consist of the mobile subscriber international ISDN number, and the authentication server is configured to submit the query to first search the home location register of the mobile communications system for the international mobile subscriber identity corresponding to the mobile subscriber international ISDN number and then use the international mobile subscriber identity to search the home location register of the mobile communications system for the related subscriber data, where the access right is defined. 29. A system according to claim 24, wherein the authentication server is configured to transmit the password to the subscriber terminal in a packet-switched message. 30. A system according to claim 24, wherein the authentication server is configured to transmit the password to the subscriber terminal in a short message. 31. A system according to claim 24, wherein the first data transfer connection is a radio link. 32. A system according to claim 31, wherein the service access point is configured to implement the radio link using a wireless local area network. 33. A system according to claim 31, wherein the service access point comprises a short-range radio transceiver for implementing the radio link. 34. A system according to claim 24, wherein the first data transfer connection is wired. 35. A system according to claim 24, wherein the system further comprises an accounting server, which is configured to generate the billing data relating to the first data transfer connection and to transfer the data to the mobile communications system, in which the billing data are formed into a bill associated with the identification data of the subscriber of the mobile communications system. 36. A system according to claim 24, wherein the service access point is configured to maintain the first data transfer connection initially set up between the data transfer device and the service access point until login. 37. A system according to claim 24, wherein the authentication server is configured to transmit a second password from the service access point to the data transfer device over the first data transfer connection and the data transfer device is configured to also use the second password in connection with login. 38. A system according to claim 24, wherein the authentication server is configured to transmit a confirmation identifier via the service access point to the data transfer device over the first data transfer connection and to transmit the same confirmation identifier to the subscriber terminal together with the password. 39. A system according to claim 24, wherein the first data transfer connection is set up when the subscriber terminal is roaming. 40. A system according to claim 39, wherein the visited mobile communications system is configured to inform the subscriber terminal that if the roaming by the subscriber terminal in the visited mobile communications system fulfils a predetermined criterion, the data transfer connection from the data transfer device to the service access point is provided at a lower charge than usual, and the authentication server is configured to implement the data transfer connection from the data transfer device to the service access point at a lower charge than usual if the predetermined criterion is met. 41. A system according to claim 40, wherein the visited mobile communications system is configured to receive from the subscriber terminal information indicating that a data transfer connection to the service access point provided at a lower charge than usual is preferred. 42. A system according to claim 41, wherein the authentication server is configured to receive from the visited mobile communications system information indicating that the data transfer device of the user of the subscriber terminal will be provided with a data transfer connection to the service access point implemented at a lower charge than usual. 43. A system according to claim 40, wherein the predetermined criterion is met if the subscriber terminal contacts the visited mobile communications system and/or if the subscriber terminal continues roaming in the visited mobile communications system continues for a predetermined time. 44. A system according to claim 40, wherein to check whether the predetermined criterion is met, a periodic query is made to the home location register of the home mobile communications system of the subscriber terminal. 45. A system according to claim 24, wherein the data transfer device is configured to use the mobile subscriber identification data as the password to log in to the service access point. 46. A system according to claim 24, wherein the authentication server is configured to transmit a user ID to the subscriber terminal corresponding to the identification data of the subscriber of the mobile communications system and the data transfer device is configured to use the user ID transmitted to the subscriber terminal in connection with login to the service access point. 47. A system according to claim 24, wherein the authentication server is configured to transmit the user ID via the service access point to the data transfer device over the first data transfer connection and the data transfer device is configured to use the user ID transmitted to the data transfer device in connection with login to the service access point.
FIELD The invention relates to a method for authenticating a user of a data transfer device and to a system for authenticating a user of a data transfer device. BACKGROUND Prior art knows different methods for authenticating users of data transfer devices. One authentication method is based on the use of a SIM card (Subscriber Identity Module) placed in the data transfer device, the method requiring, however, a smart card reader in the data transfer device. Moreover, the solution is not easy to apply in situations where a data transfer service is to be used temporarily, maybe only once, on the data transfer service, because for that purpose a SIM card would have to be delivered to the data transfer device of the user. U.S. Pat. No. 6,112,078, which is incorporated herein as a reference, discloses a solution which does not include a SIM card and in which at least some of the authentication data are transmitted to a mobile station or a paging device which the user of the data transfer device has at his/her disposal. For reasons of data security, all the authentication data, for example the user ID and the password, are not sent over the same the transmission path. BRIEF DESCRIPTION It is an object of the invention to provide an improved method for authenticating a user of a data transfer device and an improved system for authenticating a user of a data transfer device. One aspect of the invention is a method for authenticating a user of a data transfer device, comprising: setting up a data transfer connection from the data transfer device to a service access point; inputting identification data of a subscriber of a mobile communications system to the service access point; checking from the mobile communications system whether the mobile subscriber identification data contains an access right to the service access point; and, if a valid access right exists, generating a password, transmitting the password to a subscriber terminal corresponding to the mobile subscriber identification data, and logging in to the service access point from the data transfer device using the password transmitted to the subscriber terminal. Another aspect of the invention is a system for authenticating a user of a data transfer device, comprising: a data transfer device, a service access point that can be linked to the data transfer device over a first data transfer connection, and an authentication server linked to the service access point over a second data transfer connection; the service access point is configured to receive over the first data transmission connection identification data of a subscriber of a mobile communications system inputted from the data transfer device and to transmit the mobile subscriber identification data to the authentication server over the second data transfer connection; the authentication server is configured to check from the mobile communications system over a third data transfer connection whether the mobile subscriber identification data contains an access right to the service access point, and, if a valid access right exists, to generate a password and transmit the password to a subscriber terminal corresponding to the identification data of the subscriber of the mobile communications system; and the data transfer device is configured to use the password transmitted to the subscriber terminal in connection with login to the service access point. The preferred embodiments of the invention are disclosed in the dependent claims. The invention is based on the idea that a data transfer device user is authenticated utilizing the identification data of a subscriber of a mobile communications system. A password, at least, is transmitted to a subscriber terminal corresponding to the mobile subscriber identification data. The mobile subscriber identification data shows that an access right to a desired service access point is provided. The method and system of the invention provide a number of advantages. The authentication of the data transfer device user does not require any additional equipment or software to be used in the data transfer device, but only access to a subscriber terminal, either through ownership or by borrowing, in a mobile communications system. The solution also functions when the subscriber terminal is roaming. In addition, the solution is convenient for an operator managing a service access point; provisioning does not require the delivery of a SIM card to the user, for example, and yet authentication is in a way based on an existing SIM card placed into a subscriber terminal. LIST OF FIGURES In the following the invention will be described in greater detail with reference to the preferred embodiments and the accompanying drawings, in which FIG. 1 is a schematic block diagram illustrating a system for authenticating a user of a data transfer device; FIG. 2 is a flow diagram illustrating a method for authenticating a user of a data transfer device; and FIG. 3 is a signal sequence diagram illustrating information transmitted between different network elements in connection with the authentication of a data transfer device user. DESCRIPTION OF EMBODIMENTS FIG. 1 shows a simplified example of a system for authenticating a user of a data transfer device 100 and also illustrates connections from the system to other necessary parts with which information is exchanged and which are used for implementing data transfer connections. There are four main parts that can be distinguished: devices 104 at the user's disposal; a data transfer network 118 serving the data transfer device 100, a visited mobile communications system 126 and a home mobile communications system 134. The data transfer network 118 comprises a Service Access Point (SAP) 110 that can be linked to the data transfer device 100 over a first data transfer connection 102. The service access point 110 forms what is known as an Access Zone (AZ, also known as a Hotspot) in an office, university campus area, hotel or airport, for example, where local area network connections are being offered to users. Users of portable computers, for example, can thus be provided with a fast broadband service via the access zone. In addition, the data transfer network 118 comprises an authentication server 114 connected to the service access point 110 over a second data transfer connection. According to an embodiment, the first data transfer connection 106 is a radio connection. The radio connection 106 can be implemented by configuring the service access point 110 to use a Wireless Local Area Network (WLAN) to implement the radio connection 106. In another embodiment the service access point 110 comprises a short-range radio transceiver for implementing the radio connection 106. The short-range radio transceiver may be, for example, a radio transceiver based on the Bluetooth® technology or a wireless local area network based on IEEE (The Institute of Electrical and Electronics Engineers, Inc.) 802.11 or 802.11b standard. The role of the service access point 110 is to function as a port through which the services of the data transfer network 118 are provided to the data transfer device 100. If the first data transfer connection 106 is implemented over a wireless local area network, the service access point 110 may be a service access point of the wireless local area network, such as a service access point of the type Nokia® A032 used in a wireless local area network and serving as a wireless Ethernet bridge to the local area network. In that case the service access point 110 comprises a radio module for implementing radio connections and the necessary equipment and software for encrypting the data on the radio connections. The service access point 110 may also comprise an external modem that allows a Dial-up Access to be implemented to an Internet Service Provider (ISP), in which case the service access point may comprise a firewall, for example one implemented on the basis of the NAT. (Network Address Translation) technology, for protecting the local network. In addition, the data transfer network 118 may comprise an Access Controller (AC) 112 between the service access point 110 and the authentication server 114, the controller serving as a gateway between the access zone and the Internet. It is thus possible to gain access from the data transfer network 118 through the access controller 112 to a WWW server (World-Wide Web) with which the data transfer device 100 can then exchange information after authentication. The access controller 112 may be a Nokia® P022 type access controller, for example, which is responsible for user authentication, realtime network monitoring and for collecting accounting data for billing. According to an embodiment, the authentication server 114 is an AAA server (Authentication, Authorization and Accounting), which means that the server is not only responsible for user authentication, i.e. for confirming the alleged identity of the user, but also for authorizing the use of the system and for accounting operations carried out for billing the use of the system. The authentication server 114 may apply an AAA protocol defined by the IETF (Internet Engineering Task Force), such as the Radius protocol (Remote Authentication Dial-In User Service, RADIUS) or the Diameter protocol. In the wireless local area network the authentication server 114 transfers authentication data and billing data between the data transfer network 118 and the mobile communications system 126, 134. According to an embodiment, the first data transfer connection 106 is wired. The data transfer connection may be implemented using any prior art network technology enabling bi-directional wired data transfer between the service access point 110 and the data transfer device 100. One example of this type of network technology is a wired local area network based on IEEE 802.3 standard, i.e. an Ethernet standard, and implemented using a coaxial cable or a twisted pair, for example. FIG. 1 shows parts of a visited mobile communications network 126 and a home mobile communications network 134, because according an embodiment the first data transfer connection 106 is implemented when the subscriber terminal 102 is roaming. Roaming functionality is a functional entity in Mobility Management (MM), which enables correct call routing when a user and his/her subscriber terminal 102 are roaming from one network to another, for example from a mobile communications system 134 managed by a national operator of the subscriber's home country to a foreign mobile communications system 126 managed by a foreign operator. Another possible embodiment is one where only the home mobile communications system 134 is needed, for example when the user remains in the home country. In the description below, the parts of the mobile communications systems 126, 134 shown in FIG. 1 are therefore, where applicable, in one and the same mobile communications system. The mobile communications system 126, 134 may be any prior art radio system that allows information to be transferred from a network part of the mobile communications system to a subscriber terminal 104 connected to the network part over a radio link 108. The following mobile communications systems can be mentioned as examples: second generation GSM (Global System for Mobile Communications), GSM-based GRPS (General Packet Radio System) that employs 2,5-generation EDGE technology (Enhanced Data Rates for Global Evolution) for increasing data transfer rate or the EGPRS (Enhanced GPRS) and the third-generation mobile communications system known at least by the names IMT-2000 (International Mobile Telecommunications 2000) and UMTS (Universal Mobile Telecommunications System). However, the embodiments are not restricted to these examples, but those skilled in the art will be able to apply the teachings of the invention also to other radio systems having similar characteristics. When necessary, additional information about the mobile communications system in question is available from specifications of the field, for example from those of the GSM system or the UMTS, and from the literature of the art, for example from Juha Korhonen: Introduction to 3G Mobile Communications. Artech House 2001. ISBN 1-58053-287-X. The service access point 110 is configured to receive over the first data transfer connection 106 the mobile subscriber identification data inputted from the data transfer device 100 and to transmit the mobile subscriber identification data over a second data transfer connection to the authentication server 114. According to an embodiment, the identification data of the subscriber of the mobile communications system 134 consist of a Mobile Subscriber International Integrated Services Digital Network Number (MSISDN), which identifies the subscriber globally and unambiguously because the MSISDN consists of three parts: country code, national network identifier and subscriber number. The authentication server 114 is configured to use a third data transfer connection to check from the mobile communications system 134 whether the subscriber identification data contains an access right to the service access point 110 and, if a valid access right exists, to generate a password and to transmit the password to the subscriber terminal 102 corresponding to the identification data of the subscriber of the mobile communications system 134. The authentication server 114 may also generate the necessary User Account, if one does not exist already. In connection with login to the service access point 110, the data transfer device 100 is configured to use the password delivered to the subscriber-terminal 102. The password that was generated may be a character string containing letters and/or numbers and/or different special characters, for example. The character string may be defined using ASCII codes (American Standard Code for Information Interchange), for example. Login may be performed using for example a WWW dialog or, in accordance with IEEE 802.1x standard, using the dial-in dialog of the operating system of the data transfer device. The data transfer device 100 is of a type enabling a bi-directional data transfer connection 106 to be set up to the service access point 110. The data transfer device may thus be for example a portable computer provided with an Ethernet card, a Bluetooth® transceiver, or a card implementing a wireless local area network which may comprise a short-range radio transceiver, for example. One example of a card implementing a local area network is a wireless local area network card of the Nokia® C110/C111-type, although it should be noted that the system for user authentication functions without the SIM card reader contained in the cards of this type. Another example is a radio card of the Nokia® D211-type, which functions in various modes for implementing a data transfer connection, such as: wireless local area network, GPRS and HSCSD (High Speed Circuit Switched Data). The subscriber terminal 102 is of a type that enables a wireless data transfer connection to be set up to the mobile communications system 126. In the UMTS, for example, the subscriber terminal 102 consists of two parts: Mobile Equipment (ME) and UMTS Subscriber Identity Module (USIM), i.e. a SIM card. The SIM card contains user data and, in particular, data associated with information security, for example an encryption algorithm. In the GSM, the subscriber terminal 102 naturally uses the SIM card of the GSM system. The subscriber terminal 102 contains at least one transceiver for setting up a radio connection 102 to a radio access network or base station system of the mobile communications system 126. FIG. 1 shows a base station 120 of the mobile communications system 126 to which the subscriber terminal 102 sets up the radio connection 108. One subscriber terminal 102 may contain at least two different subscriber identity modules. In addition, the subscriber terminal 102 contains an antenna, a user interface and a battery. Current subscriber terminals 102 take diverse forms; they may be vehicle-mounted or portable, for example. Subscriber terminals 102 have also been provided with characteristics better known from PC's or portable computers. One example of this type of subscriber terminal 102 is Nokia® Communicator®. In the example of FIG. 1, the devices 104 that are at the user's disposal, i.e. the data transfer device 100 and the subscriber terminal 102, are shown as separate devices, although according to one embodiment they may be located in one and the same physical device, for example in a Nokia® Communicator-type device, in which the characteristics required of the data transfer device 100 have been implemented by means of a wireless local area network card, and the characteristics of the subscriber terminal 102 by means of a mobile subscriber terminal incorporated in the device and a SIM card provided by a mobile operator. In this kind of combination device the processing of the information needed in authentication can be automated for example by transferring the password received at the subscriber terminal 102 automatically to the log-in dialog of the data transfer device 100. According to an embodiment, the authentication server 114 is configured to transmit the password to the subscriber terminal 102 in the form of a packet-switched message. In one embodiment the authentication server 114 is configured to transmit the password to the subscriber terminal 102 in a Short Message (SM). The short message can be implemented using a Short Message Service (SMS), for example. FIG. 1 shows a Short Message Service Centre (SMSC) 122 of the mobile communications system 126, through which centre the short messages are transferred and into which they may be stored if they cannot be delivered immediately to the receiver 102. In principle the short message service centre 122 is not a part of the mobile communications system 126, although it is often integrated into a Mobile Service Switching Centre (MSC). There are also other ways of transmitting a text message, for example by using the Multimedia Messaging Service (MMS). MMS is a new type of service in which the method of transmission corresponds to that of the SMS. An MMS message may, however, contain three different simultaneous elements: text, audio and image. According to an embodiment, the authentication server 114 is configured to check the access right to the service access point 110 by submitting a query to a home location register 130 of the mobile communications system 134. FIG. 1 only shows the base station 120 and the short message service centre 122 of the mobile communications system 126; the rest of the infrastructure is depicted by block 124. From the infrastructure of the visited mobile communications system 126 there is a data transfer connection 128, provided for example by means of signalling system no. 7 (SS7, ITU-T No. 7) of the ITU-T, the telecommunications standardization sector of the International Telecommunications Union, to the home mobile communications system 134, of which only the Home Location Register (HLR) 130 is shown, which contains the subscriber parameters of all subscribers of the mobile communications system 134 permanently stored therein. Since the home location register 130 is usually at the mobile services switching centre, block 130 in FIG. 1 also includes the switching centre. According to an embodiment mentioned earlier, the identification data of the subscriber of the mobile communications system 134 consist of the mobile subscriber international ISDN number. In that case the authentication server 114 may be configured to submit a query in which it first searches the home location register 130 of the mobile communications system 134 for the International Mobile Subscriber Identity (IMSI) corresponding to the mobile subscriber international ISDN number and then uses the international mobile subscriber identity to search the home location register 130 of the mobile communications system 134 for the related subscriber data, where the access right is defined. According to an embodiment, the system further comprises an accounting server 116, which is configured to generate the billing data relating to the first data transfer connection 106 and to transfer the data to the mobile communications system 134, in which the billing data are formed into a bill associated with the identification data of the subscriber of the mobile communications system 134. In the example of FIG. 1 we have a situation where the subscriber terminal 102 is within the area of the visited mobile communications system 126, in which case the billing data generated at the accounting server 116 are transferred to an accounting server 132 of the home mobile communications system 134. The billing data may be transferred using for example Charging Records (CDR) directed to the IMSI. According to an embodiment, the service access point 110 is configured to maintain the first data transfer connection 106 initially set up between the data transfer device 100 and the service access point 110 until login. In other words, in this embodiment the first data transfer connection 106 is not disconnected at any stage and therefore mere capture of a password by an unauthorized intruder does not create a major data security risk, because the intruder would also have be able to capture the first data transfer connection 106. The data transfer connection 106 uses an SSL protocol (Secure Sockets Layer), for example, for authenticating and encrypting TCP (Transmission Control Protocol) connections. Instead of the SSL, a protocol known as TLS (Transport Layer Security) can also be used. The encryption keys to be used may be derived from TLS authentication or simply from the password by means of strong password authentication protocols (such as the Secure Remote Password protocol or Encrypted Key Exchange protocol). According to an embodiment, the authentication server 114 is configured to transmit a second password via the service access point 110 to the data transfer device 100 over the first data transfer connection 106, the data transfer device 100 being configured to also use the second password at login, for example such that the two passwords placed one after the other form the required password. This embodiment ensures that the user offering the second password is the same as the one who used the data transfer device 100 to order the password to the subscriber terminal 102. According to an embodiment, the authentication server 114 is configured to transmit a confirmation identifier via the service access point 110 to the data transfer device 100 over the first data transfer connection 106 and to transmit the same confirmation identifier to the subscriber terminal 102 together with the password. This enables the user to compare the two confirmation identifiers received over different data transfer paths and to use the password only if the two confirmation identifiers are the same. With this embodiment the user is assured that the password came to the subscriber terminal 102 from the source 114 requested by the user with his/her data transfer device 100. According to an embodiment, the data transfer device 100 is configured to log in to the service access point 110 using the mobile subscriber identification data, for example the already mentioned mobile subscriber international ISDN or the international mobile subscriber identity, as a user ID, although the latter may be more difficult for the user to find out than the mobile subscriber international ISDN. An advantage of this embodiment is that the system does not need to transfer the user ID towards the user. However, embodiments in which the user ID is transferred from the system towards the user are also possible. In such cases the user ID does not need to be originally known by the user but it may be generated at the authentication server 114, for example. According to an embodiment, the authentication server 114 is configured to transmit the user ID to the subscriber terminal 102 corresponding to the identification data of the subscriber of the mobile communications system 134 and the data transfer device 100 is configured to use the user ID received at the subscriber terminal 102 to log in to the service access point 110. According to an embodiment, the authentication server 114 is configured to transmit the user ID from the service access point 110 to the data transfer device 100 over the first data transfer connection 106 and the data transfer device 100 is configured to use the user ID received at the data transfer device 100 to log in to the service access point 110. We have described above how the service access point 110, authentication server 114 and data transfer device 100 are to be configured to enable the system for authenticating the user of the data transfer device 100 to be implemented. The devices in question comprise control parts controlling their operation, the control parts being currently usually implemented as a processor with the related software, although different hardware implementations are also possible, for example a circuit consisting of separate logic components or one or more Application-specific Integrated Circuits (ASIC). Also a hybrid of these different implementations is possible. When selecting the method of implementing the configuration, a person skilled in the art will take into account for example the requirements set to the size and power consumption of the device, the required processing power, manufacturing costs and production volumes. With reference to the flow diagram of FIG. 2, the method for authenticating the user of the data transfer device will be described in the following. At the same time, reference is made to the signal sequence diagram of FIG. 3, which illustrates the information transmitted between different network elements in connection with the authentication of the data transfer device user. For the sake of clarity, the service access point 110 and the service access controller 112 are combined into a single element in FIG. 3, and internal elements of the visited mobile communications system 126 and the home mobile communications system are not shown. The execution of the method starts at 200, when the user wishes to use the service access point. At 202 a data transfer connection is first set up from the data transfer device to the service access point. According to an embodiment, the data transfer connection between the data transfer device and the service access point is a radio connection. According to an embodiment, the radio connection is implemented with a wireless local area network. According to another embodiment, the radio connection is implemented using a short-range radio transceiver. In another embodiment, the data transfer connection between the data transfer device and the service access point is wired. As regards these different methods of implementing the data transfer connection reference is made to the disclosure above. Next, at 204 the identification data of the mobile subscriber are inputted 204 to the service access point. According to an embodiment, the mobile subscriber identification data consist of the mobile subscriber international ISDN. As shown in FIG. 3, the MSISDN 300 is transmitted from the data transfer device 100 to the service access point/service access controller 110, 112. At 206 the access right of the subscriber identification data to the service access point is then checked from the mobile communications system. According to an embodiment, the checking is made by means of a query sent to the home location register of the mobile communications system. In the embodiment in which the mobile subscriber identification data consist of the mobile subscriber international ISDN, the query can be made as shown in FIG. 3 such that first the home location register of the mobile communications system 134 is searched for the international mobile subscriber identity (IMSI) corresponding to the mobile subscriber international ISDN by means of a MAP_SEND_IMSI message (MAP=Mobile Application Part protocol) 304, 306 and a REPLY 308, 310 received to the query and then, on the basis of the international mobile subscriber identity, the home location register of the mobile communications system 134 is searched for the subscriber data, which contains the access right definition, by means of a MAP_RESTORE_DATA message 312, 314 and a REPLY 316, 318 received to it. Since in the example of FIG. 3 the subscriber terminal 102 is within the area of the visited mobile communications system 126, the messages to and from the home mobile communications service 134 travel through the visited system. At 208 is then checked whether the mobile subscriber identification data has access right to the service access point. If there is no access right, or it is not valid, the routine proceeds to 210, which means that no service can be provided to the user through the service access point, and then to 220 where the execution of the method is terminated. If a valid access right exists, the routine proceeds from 208 to 212 where the password is generated. The routine then proceeds to 214 where the password is transmitted to the subscriber terminal corresponding to the mobile subscriber identification data. According to an embodiment, the password is transmitted to the subscriber terminal in a packet-switched message. According to another embodiment, the password is transmitted to the subscriber terminal 102 in a short message SMS 320, 322, 324, 326, as shown in FIG. 3, starting from the authentication server 114 and going through the visited mobile communications system 126, the home mobile communications system 134 and then again the visited mobile communications system 126. The embodiment can be modified as described earlier. Next, at 216 the service access point is logged in from the data transfer device using the password delivered to the subscriber terminal. In FIG. 3 this is illustrated in the form of a log-in dialog in which the user ID and the password are transmitted from the data transfer device 100 to the service access point/service access controller 110, 112 in a LOGIN message 328, which is further transmitted to the authentication server 114 in a LOGIN message 330 to which a REPLY message 332 is received at the service access point/service access controller 110, 112. Then at 218 the data transfer device user is able to use data transfer services via the service access point. A service is implemented by transferring SERVICE messages 334 to and from, as needed, the data transfer device 100 and the service access point/service access controller 110, 112. Finally when the user switches off the connection from the data transfer device to the service access point, the execution of the method is terminated at 220. According to an embodiment, the method further comprises: billing for the data transfer connection between the data transfer device and the service access point in a bill directed to the identification data of the mobile subscriber. As shown in FIG. 3, this may be carried out for example by transferring from the service access point/service access controller 110, 112 a CDR message 336, 338 containing billing data through the authentication server 114 to the home mobile communications system 134. According to an embodiment, the data transfer connection set up at the beginning between the data transfer device and the service access point is kept until login takes place. This provides the above described advantage of information security. According to an embodiment, the method further comprises: transmitting a second password from the service access point to the data transfer device over a data transfer connection and using also the second password at login. Also this embodiment enhances information security, as described above. According to an embodiment, the method further comprises: transmitting from the service access point a confirmation identifier to the data transfer device over the data transfer connection and transmitting the same confirmation identifier together with the password, the password being only used if the received confirmation identifiers are the same. This embodiment has also-been described above. According to an embodiment, the method further comprises: using the mobile subscriber identification data as a user ID when logging in. According to an embodiment, the method further comprises: transmitting the user ID to the subscriber terminal corresponding to the mobile subscriber identification data and using the transmitted user ID when logging in. According to an embodiment, the method further comprises: transmitting the user ID to the data transfer device over the data transfer connection and using the transmitted user ID when logging in. The method can be implemented using the system described above with reference to FIG. 1, although other environments are also possible. According to an embodiment, the visited mobile communications system 126 is configured to inform the subscriber terminal 102 that if a roaming of the subscriber terminal in the visited mobile communications system 126 fulfils a predetermined criterion, a lower charge than usual will be applied to the data transfer connection 106 from the data transfer device 100 to the service access point 110. In addition, the authentication server 114 is configured to implement the data transfer connection 106 from the data transfer device 100 to the service access point 110 at a lower charge than usual, if the predetermined criterion is met. At first the predetermined criterion may be that the subscriber terminal 102 contacts the visited mobile communications network 126 and later the criterion may be that the subscriber terminal 102 remains in the mobile communications system 126 it has selected. The purpose of this is to make the user of the roaming subscriber device 102 to prefer that the subscriber device 102 use specifically the mobile communications system 126 managed by the operator in question for the entire duration of the roaming. The use of the mobile communications system 126 generates income to the operator and thus allows the operator to offer the data transfer connection 106 to the service access point 110 at a lower charge, even free of charge in extreme cases, for the duration of the visit. Next, a method is described that can be used for implementing this kind of roaming that creates customer loyalty. The visited mobile communications system 126 is informed of a new subscriber terminal 102 by a location update performed by the subscriber terminal 102 upon its entry into the coverage area of the base station 120. Next, an SMS message (SMS=Short Message Service) is sent from the mobile communications system 126 to the subscriber terminal 102 to inform that if the user remains in this mobile communications system 126, the data transfer connection 106 will be provided free of charge, through a public wireless local area network, for example, to the service access point 110. In addition, the SMS message may contain instructions informing that if the user wishes to use this service, he/she should send a reply SMS message from his/her subscriber terminal 102 to a specific number. The reply SMS message should be blank or have a predetermined content, such as abbreviation “WLAN”. If the user is expected to reply with an SMS message, then upon receipt of the message, and otherwise immediately after having sent the message, the visited mobile communications system 126 informs the authentication server 114 that data transfer services may be provided free of charge to the user through the service access point 110. The reply SMS message expected of the user allows to avoid unnecessary loading of the system by users who are not interested in the service in question. The information to the authentication server 114 can be transmitted in an SMS message sent from the visited mobile communications system 126, for example. This requires that the authentication server functions as an SME (Short Message Entity) or is capable of receiving a MAP_MT_FORWARD_SHORT_MESSAGE message based on the MAP protocol. The information contains the identifier of the user, such as an MSISDN or IMSI. The authentication server 114 parses the contents of the SMS message and analyses the identifier of the user. The authentication server 114 is thus informed that data transfer services available from the data transfer network 118 may be provided free of charge to a specific user through the service access point 110. The authentication server 114 then creates a user ID for the user, such as an MSISDN or IMSI. In addition, a password is created. The user ID and the password may be delivered to the user as described above, although other suitable prior art methods for implementing authentication may possibly also be used. At the same time, it is possible to submit additional information to the user. The use provided free of charge may at first cover a predetermined period, for example fifteen minutes. The user ID is activated if the user uses it for logging in to the service access point 110. The contents of the user ID may include the following: user ID: +35840123456 password: qwertyiop time: 90 minutes created: 19102002;09:16:48 valid: 29102002;09:16:48 service quality: low billing: NULL time release of session: 900 seconds. The duration of the service provided free of charge to the user through the data transfer network 118 may be extended if the subscriber terminal 102 of the user continues roaming in the mobile communications system 126 for a predetermined period. A convenient way to check whether roaming continues is to send a period query to this effect, one or twice an hour, for example, to the home location register 130 of the home mobile communications system 134 of the subscriber terminal 102. The query may be implemented using a MAP_SEND_ROUTING_INFO_FOR_SM message of the MAP protocol, for example, which is replied by a SEND_ROU_FOR_SM message containing the PLMN address (Public Land Mobile Network) of the serving mobile services switching centre. If this address belongs to the same mobile communications system as the service access point, it is concluded that roaming continues. The session of the data transfer device 100 at the service access point 110 may be terminated either by the user or by the service access point, which switches off the connection when the time provided free of charge runs out. The user ID may be deleted from the authentication server 114 after a predetermined time, for example a month, or when it is detected that the user of the subscriber terminal 102 has terminated the roaming. In FIG. 2 the arrangement 201 of this kind of lower charge data transfer connection takes place before the described authentication. The procedure of block 206 is not necessarily needed if the authentication server has received information from the visited mobile communications system stating that a data transfer connection to the service access point may be provided at a lower charge than usual for the data transfer device of the user of the subscriber terminal. The predetermined criterion is met if the subscriber terminal contacts the visited mobile communications system and/or if the roaming by the subscriber terminal in the visited mobile communications system continues for a predetermined time. That the predetermined criterion is met can be checked by means of a period query made to the home location register of the home mobile communications system of the subscriber terminal; although the execution of the method shown in FIG. 2 may have been terminated at this point already, the user can be provided with a service at lower charge the next time he/she logs in from his/her data transfer device to the service access point. The procedures of blocks 201, 206, 212 and 214 do not necessarily have to be carried out in connection with a subsequent login, unless the operator wishes to change the password. Although the invention is described above with reference to an example based on the accompanying drawings, it is apparent that the invention is not restricted to it but may be varied in many ways within the scope of the inventive idea disclosed in the accompanying claims. It is to be noted, in particular, that the names of the network elements and the distribution of their functionalities may vary, because, after all, it is merely a question of the desired degree of integration of the network elements and the size of the data transfer network 118: in large networks a network element may be dedicated to specific tasks only, whereas in small networks one network element may carry out a plural number of functions, which in FIG. 1 are shown separately.
<SOH> BACKGROUND <EOH>Prior art knows different methods for authenticating users of data transfer devices. One authentication method is based on the use of a SIM card (Subscriber Identity Module) placed in the data transfer device, the method requiring, however, a smart card reader in the data transfer device. Moreover, the solution is not easy to apply in situations where a data transfer service is to be used temporarily, maybe only once, on the data transfer service, because for that purpose a SIM card would have to be delivered to the data transfer device of the user. U.S. Pat. No. 6,112,078, which is incorporated herein as a reference, discloses a solution which does not include a SIM card and in which at least some of the authentication data are transmitted to a mobile station or a paging device which the user of the data transfer device has at his/her disposal. For reasons of data security, all the authentication data, for example the user ID and the password, are not sent over the same the transmission path.
<SOH> BRIEF DESCRIPTION <EOH>It is an object of the invention to provide an improved method for authenticating a user of a data transfer device and an improved system for authenticating a user of a data transfer device. One aspect of the invention is a method for authenticating a user of a data transfer device, comprising: setting up a data transfer connection from the data transfer device to a service access point; inputting identification data of a subscriber of a mobile communications system to the service access point; checking from the mobile communications system whether the mobile subscriber identification data contains an access right to the service access point; and, if a valid access right exists, generating a password, transmitting the password to a subscriber terminal corresponding to the mobile subscriber identification data, and logging in to the service access point from the data transfer device using the password transmitted to the subscriber terminal. Another aspect of the invention is a system for authenticating a user of a data transfer device, comprising: a data transfer device, a service access point that can be linked to the data transfer device over a first data transfer connection, and an authentication server linked to the service access point over a second data transfer connection; the service access point is configured to receive over the first data transmission connection identification data of a subscriber of a mobile communications system inputted from the data transfer device and to transmit the mobile subscriber identification data to the authentication server over the second data transfer connection; the authentication server is configured to check from the mobile communications system over a third data transfer connection whether the mobile subscriber identification data contains an access right to the service access point, and, if a valid access right exists, to generate a password and transmit the password to a subscriber terminal corresponding to the identification data of the subscriber of the mobile communications system; and the data transfer device is configured to use the password transmitted to the subscriber terminal in connection with login to the service access point. The preferred embodiments of the invention are disclosed in the dependent claims. The invention is based on the idea that a data transfer device user is authenticated utilizing the identification data of a subscriber of a mobile communications system. A password, at least, is transmitted to a subscriber terminal corresponding to the mobile subscriber identification data. The mobile subscriber identification data shows that an access right to a desired service access point is provided. The method and system of the invention provide a number of advantages. The authentication of the data transfer device user does not require any additional equipment or software to be used in the data transfer device, but only access to a subscriber terminal, either through ownership or by borrowing, in a mobile communications system. The solution also functions when the subscriber terminal is roaming. In addition, the solution is convenient for an operator managing a service access point; provisioning does not require the delivery of a SIM card to the user, for example, and yet authentication is in a way based on an existing SIM card placed into a subscriber terminal.
20041014
20080701
20050811
90633.0
0
AJIBADE AKONAI, OLUMIDE
METHOD AND SYSTEM FOR AUTHENTICATING USER OF DATA TRANSFER DEVICE
UNDISCOUNTED
0
ACCEPTED
2,004
10,511,284
ACCEPTED
Human Papilloma Virus Detection With Dna Microarray
A method is provided of detecting the presence of HPV comprising the following steps: a. amplification and labelling part of the E1 HPV gene, in particular its 3′ end; b. hydrizing the labelled fragment to a solid support containing microarrays with various HPV specific capture probes; c. removing uncaptured labeled fragments; d. detecting captured detectable moiety indicating the presence of HPV sequence DNA in a sample. Further provided is a test kit for carrying out said detection method.
1. A method of detecting the presence of HPV in a sample comprising the following steps: amplifying and labeling part of the E1 HPV gene, wherein amplification is performed using at least two oligonucleotides selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:23, to thereby form a labeled fragment; hybridizing the labeled fragment to a solid support upon which a plurality of HPV E1-gene specific capture probes are immobilzed; removing uncaptured labeled fragments; and detecting the captured labeled fragment, wherein detection of the fragment indicates presence of HPV in the sample. 2. The method according to claim 1, wherein the HPV E1-gene specific capture probes are selected from the group consisting of SEQ ID NO:24 to SEQ ID NO:59, and wherein the HPV E1-gene specific capture probes are optionally immobilized on the support as synthesized oligonucleotides or are optionally built on the support by light-directed oligonucleotide synthesis. 3. The method according to claim 1 wherein the step of amplification and labeling further comprises amplifying and labeling an HPV gene other than the HPV E1 gene. 4. A kit comprising: a device suitable for carrying out the detection method according to the present invention as claimed in any one of claim 1, claim 2, or claim 3; at least two oligonucleotides selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:23; one or more solid supports containing HPV E1-gene specific capture probes selected from the group consisting of SEQ ID NO:24 to SEQ ID NO:59; and an optional reagent for signal enhancement. 5-9. (canceled) 10. The method of claim 1 wherein amplification is performed using at least four oligonucleotides thereby producing a second labeled fragment, and wherein the labeled fragment and the second labeled fragment belong to different ones of risk clusters selected from the group consisting of low-risk HPV type, high-risk HPV type, and remaining HPV type. 11. The method of claim 1 wherein amplification is performed using at least four oligonucleotides thereby producing a second labeled fragment, and wherein the labeled fragment and the second labeled fragment belong to the high-risk HPV type. 12. The method of claim 2 wherein the plurality of HPV E1-gene specific capture probes includes at least three of SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:45, SEQ ID NO:51, SEQ ID NO:54, and SEQ ID NO:55. 13. The method of claim 2 wherein the plurality of HPV E1-gene specific capture probes includes at least three of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:43, SEQ ID NO:44, and SEQ ID NO:49. 14. A method of detecting the presence of HPV in a sample comprising the following steps: amplifying and labeling part of the E1 HPV gene to thereby form a labeled fragment, wherein the amplification is performed such that the labeled fragment has a sequence capable of hybridizing with at least one of the plurality of HPV E1-gene specific capture probes; wherein the HPV E1-gene specific capture probes are selected from the group consisting of SEQ ID NO:24 to SEQ ID NO:59; hybridizing the labeled fragment to a solid support upon which at least two of the plurality of HPV E1-gene specific capture probes are immobilized; removing uncaptured labeled fragments; and detecting the captured labeled fragment, wherein detection of the fragment indicates presence of HPV in the sample. 15. The method of claim 14 wherein amplification is performed using at least four oligonucleotides thereby producing a second labeled fragment, and wherein the labeled fragment and the second labeled fragment belong to different ones of risk clusters selected from the group consisting of low-risk HPV type, high-risk HPV type, and remaining HPV type. 16. The method of claim 14 wherein the solid support comprises at least three of SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:45, SEQ ID NO:51, SEQ ID NO:54, and SEQ ID NO:55. 17. The method of claim 14 wherein the solid support comprises at least three of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:43, SEQ ID NO:44, and SEQ ID NO:49.
FIELD OF THE INVENTION The present invention is in the field of molecular biology and diagnostics, and relates in particular to an improved diagnostic procedure for the detection of Human Papilloma Virus (HPV) types using DNA microarray techniques. The diagnostic method is useful for the detection of any known HPV types, for example, in the early detection of (pre)neoplastic epithelial lesions in uterine cervix, and tumors of skin, head and neck and other sites. BACKGROUND OF THE INVENTION Cancer is the second overall leading cause of death, after ischemic heart disease, in the United States and Western Europe and despite recent advances in its treatment, there is, for most cancer types, no miracle cure on the horizon. Cancer causes approximately 25% of all deaths. The incidence continues to rise, probably reflecting the increasing average age of the population. The key to survival is early diagnosis and treatment. About two decades ago HPV was associated with human tumors. Since then it has been detected in tumors and (pre)neoplastic lesions of different sites such as uterine cervix, penis, skin, middle ear, anus, squamous cell tumours of the head and neck region (oral mucosa, tonsil, larynx, pharynx), lung, urinary bladder. More than 70 different types of HPV have been reported with different relations to the progression of a lesion. Some of the types have stronger association with the progression to malignant tumors than others e.g. type 16 and 18 are associated with high grade intraepithelial dysplasia of the cervix. These are called ‘high risk’ HPV types. The number of HR-HPV has been expanded the last years to e.g. 16, 18 45, 31, 33 check. Other types are mainly associated with benign tumors such type such as 1,2, 4, 5, and 6 with benign skin warts. HPV type 11 is frequently present in juvenile recurrent respiratory papillomas. Frequently in a series of cases of one histologic type of lesion different HPV types have been detected. Occasionally, multiple HPV types were found within one lesion (coinfection). In erythroplasia of Querat HPV type 8 was found in combination with other types of HPV [Wieland 2000]. In renal transplant recipients the number of keratotic lesions increases after several years. Also in these lesions a wide range of HPV types are recognized [De Jong-Tieben 2000]. In Epidermodysplasia Verruciformis HPV type 47 has been shown [Adachi 1996]. In Global nail dystrophy type 57 infection was found. [McCown 1999] Although several different types have been described, recently minor variations in DNA composition have been within one type. Because of the genetic diversity of HPV the use of type-specific amplification is impractical for epidemiologic studies, for which accurate typing is essential. Within the HPV region many gene sequences have been described both at the DNA and protein level such as E1, E2, E3, E4, E5, E6, E7, L1 and L2. Several methods use the one or more of the genes above such as PGMY LBA, SPF10 LiPA GP5+16+ combination Only one is using another E1 region than our invention does. Several methods exist for the detection of HPV in general as well as for typing. Many use the polymerase chain reaction (PCR) for amplification of part of the HPV genome. For the PCR type specific primers can be used. As an alternative primers are used that allow amplification of more than one types. In some HPV tests primers are intended to amplify all types (general primers). These primers can be degenerated to a limited extent. With this approach one or more combinations of primers intend to cover for all HPV types (Jacobs, et al. J Clin Microbiol 1997 35:791-795; Bauer, et al., JAMA 1991 265:472477). After PCR sequencing can be performed for HPV typing. An alternative approach is to hybridise the DNA fragments to a filter containing different areas with different DNA fragments. Each area contains then DNA corresponding to one type. However, cross hybridisations may occur. In theory all different HPV types may be amplified and sequenced individually, but depending on the amount of types and variations to be known this will be an increasing amount of work. Other approaches for the detection of HPV types are the use of restriction fragment length polymorphism analysis combined with an amplification technique, and another alternative for the detection of HPV is the use of an amplification technique in combination with single stranded conformational polymorphism (Mayrand, J Clin Microbiol 2000 38:3388-3393). Still other approaches are hybrid capture II and Ligase chain reaction (Yamazaki, et al., Int J Cancer 2001 94:222-227). Yet approaches is to detect HPV is by in situ hybridisation (AmorTegui, et al., 1990 23:301-306; Unger, et al., J Histo chem. Cytochem 1998 46:535-540; Lizard, et al., J Virol. Methods 1998 72:15-25)) or in situ PCR (Jean-Shiunn Shyu J Surg Oncol 2001 78:101-109). On one histologic slide or cytologic specimen HPV type specific DNA fragments are necessary to obtain a signal. Thus, in theory recognition of any HPV types at least a similar number of slides/specimens is required to examine one kind of biologic sample. This would be a very laborious procedure. Recent developments show after a PCR the use of a line probe or line blot assay to detect different types. Comparison of different line probes assays (PGMY LBA and SPF10 LiPA) reveals a difference in sensitivity for one assay: with PGMY LBA more HPV types 42, 56 and 59 and with SPF10 LiPA more HPV types 31 and 52 were detected [Van Doom 2002]. Also for the GP5+/6+ primers a reverse line blot assay has recently been described detecting 37 mucosal types [Van den Brule 2002 J Clin Microbiol 2002 40:779-787]. The concordance between different methods is moderate (Meyer et al. Dermatiology 2000 201:204-211; Vernon J Clin Mircobiol 2000 38:651-655). Recently, ‘chip’ technology has been developed (see, e.g., U.S. Pat. No. 5,445,934). The term ‘microarray’ or ‘chip’ technology as used herein, is meant to indicate analysis of many small spots to facilitate large scale nucleic acid analysis enabling the simultaneous analysis of thousands of DNA sequences. This technique is seen as an improvement on existing methods, which are largely based on gelelectrophoresis. For a review, see Nature Gen. (1999) 21 Suppl. 1. Line blot assay and microarray methods both use circumscribed areas containing specific DNA fragments. As will be known in the art, line blotting is usually performed on membranes (Gravitt, et al., J Clin Microbiol 1998 36:3020-3027, whereas microarray is usually performed on a solid support and may also be performed on smaller scale. The utility of DNA arrays for genetic analysis has been demonstrated in numerous applications including mutation detection, genotyping, physical mapping and gene-expression monitoring. The basic mechanism is hybridization between arrays of nucleotides and target nucleic acid. Recently, the Point-EXACCT method was transferred to DNA microarray format, where a glass support is homogeneously streptavidin-coated. This coating is used to spot biotinylated probe to the glass slide and to hybridize a single-stranded target DNA to this nucleic acid probe. For detection a second probe is added, or the single stranded DNA is already labeled. The use of streptavidin-coated slides for microarray analysis is disclosed in WO 02/44713 the contents of which are incorporated herein by reference. In conclusion, HPV types can be discerned with various laborious techniques. The present invention provides a further improvement of the microarray technique with coverage of any known HPV types on the array. SUMMARY OF THE INVENTION In one aspect of the invention, a combination of oligonucleotides is used, allowing amplification of a part of the E1 HPV gene. This part of the sequence has thus far not been used for HPV typing before. Especially preferred is the 3′ end of the E1 HPV gene, in particular a region between about 29 to about 188 nucleotides from the 3′ terminus of the E1 gene. The size of the whole gene varies from 1820 to 1964 nucleotides. In a further aspect of the invention the examination of integration of HPV in human DNA a combination of E1 region with another HPV region such as E6 or L1 is suitable. In a further aspect of the invention microarray is used for detection of the specific HPV type(s) after the amplification. In a further aspect of the invention the system allows rapid reading with absorption in regular light microscope suitable for detecting and typing HPV in one procedure. These and other aspects of the invention will be outlined in some more detail in the following description. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 depicts a schematic representation of HPV sequences containing regions with general primers sets. The schematic representation is modified from an image presented by Kleter, Utrecht, on 24 Jan. 2002. The position from the CWZ primers in the E1 region is distinctly different from other sites. FIG. 2 depicts a schematic representation of the microarray procedure. From a clinical sample or other sample DNA is extracted (A), amplified and labeled (B). parallel a micro array has been prepared containing all HPV subtypes (C). Labeled DNA is hybridized to the array (D). DNA and other components that are not attached are washed away. Remaining fragments are hybridized based on corresponding HPV sequences and visualized based on the presence of the label. Then the spots with label may be discerned from those without label and used for HPV type detection (E,F). FIG. 3 shows an example of HPV 16 detection in the fluorescence and absorption mode. Detection ctl>=positive control in triplicate. HPV 16>=spots with capture probes for HPV 16 in triplicate visualized as described in the procedure. Sensitivity>=signal of three different concentrations of HPV capture probes in triplicate. DETAILED DESCRIPTION OF THE INVENTION The present invention provides a significant improvement of the method of detecting HPV. A new combination of oligonucleotides for HPV detection is used for amplification and detection. The term amplification product denotes a specific fragment of double stranded DNA that arises in a process aimed at the multiplication of that fragment. All known methods for amplification are incorporated. The term HPV specific is used herein for the combination of primer sets and detection probe. The length of the detection probe may be too short to be specific for HPV in itself, if examine against all information in gene banks. However, after amplification with HPV specific probes the chance of detecting labeled DNA other than HPV is neglectable. The oligonucleotides for capturing may, therefore, not be unique. The term primer and probe as used herein denote oligonucleotides. Primer is used for the single stranded DNA fragment that is used for amplification. Probe is used for the single stranded DNA fragment that has a capture function on the solid support. The term “detection probe” as used herein emphasizes the capturing function. The term degenerate primer or probe denotes an oligonucleotide with at certain positions either a mixture of different nucleotides or a base analogue. The terms incubation of proteins and hybridisation of nucleic acids have similar components i.e. diffusion and binding of molecules to there specific targets. With diffusion, as used herein, the same process is meant for nucleic acids, proteins and other molecules interacting with a target on the solid support. The term visualization denotes any way that in a non-radioactive fashion a hybridization product with hapten can be visualized with any microscope system. The target on the solid support consists of solid part with attached i.e. immobilized one or more different kinds of molecules, such as nucleic acids, proteins, whole cells, sections of cells or tissues. The terms incubation chamber and hybridisation chamber, as used herein, are synonyms and are meant to indicate the three dimensional space above the target present on the solid support, where the solid support is an integral part of the incubation/hybridisation chamber. The terms ‘microarray’ or ‘chip’ technique or technology, as used herein, are synonyms and are meant to indicate analysis of a plurality of small spots of nucleic acids distributed on a small surface area to facilitate large scale nucleic acid analysis enabling the simultaneous analysis of thousands of DNA and/or RNA sequences. The terms are likewise applicable to the analysis of peptides or proteins in a similar way. The term incubation fluid is meant to indicate the fluid containing e.g. the substrate to be bound on the solid support. The term test fluid is meant to indicate the volume of any fluid component necessary for the experiment/test to be carried out with the flow through system. The terms immunohistochemistry and immunocytochemistry, are meant as synonyms, indicating the binding of antibodies to haptens, usually parts of tissues or cells present on the solid support, but also as used herein it is the visualization procedure after binding to the hapten. The terms low and high risk HPV denote a difference in association with the chance of development of malignancy. This has especially for the uterine cervix been described. For high risk is the chance of development of malignancy is higher than for the low risk HPV types. All reported HPV gene sequences in October 2000 (E1, E2, E4, E5, E6, E7, L1 and L2) (both at the DNA and protein level) were separately and systematically analyzed to select a region of the HPV genome that allowed subdivision of all HPV types into clusters of HPV types. Based on sequence homology at the protein and/or DNA level, several previously unassigned HPV types putatively can be assigned either as low risk or high risk HPV. The subdivision of all HPV types intended to make an as large as possible distinction between low and high risk mucosal types of HPV. The following criteria were used. Each cluster had to contain at least two regions with a relative high degree of DNA sequence homology between the different HPV types in that cluster to allow the formulation of ‘common’ PCR primers. In addition, these potential PCR primer location sites should differ as much as possible between different clusters to allow amplification of cluster-specific and/or risk-specific HPV types. Another criterium was that between the potential PCR-primer locations, sufficient heterogeneity between the DNA sequences is present to select DNA sequences that allow for discrimination between different HPV types. Based on these criteria, the HPV E1 gene was chosen for design of the assay. Subsequently, three major groups of HPV types were discrimated: i) high risk mucosal HPV types, ii) low risk mucosal HPV types and iii) the remaining HPV types. Six clusters were formulated. Cluster A contains all known low risk HPV types. Cluster E and F contain almost all high risk HPV types, clusters B and C contain the remaining HPV types and cluster D contains both high risk HPV types and some of the remaining HPV types. Examples of the primers for each cluster are shown in table 1. (SEQ ID NO: 1 etc.) with and without tag. The amplification of HPV E1 products is suitably performed with PCR or another method known those skilled in the art. Primers can be labeled, designed with a tag or not being labeled at all. In the latter two situations a second step is required to add a label to the amplification product. These techniques are also well known to a skilled person. It has now surprisingly been found that the microarray technology can be successfully applied for the detection of one or more HPV types within a sample, thus enabling to analyse clinical samples at a much larger scale of operation. The presence of one or more HPV types within a sample is usually recognized within one day. The oligonucleotide DNA array technique according to the present invention works with high concentrations of all products. Different spots are characterized by HPV specific probes. Once the principle is established, the concentrations are optimized step by step in order to allow higher efficiency of the HPV array analysis. The compositions of the primers and of the reagents used, are determined and optimized by routine experimentation. The detection mode may vary but the invention is practised conveniently with absorption microscopy and other modes such as fluorescence and laser scanning microscopy. Preferably, a fluorescence mode is used for reasons of quantitation, higher sensitivity, larger dynamic range, instead of extinction mode. The latter has the advantage that the outcome can be made visible with regular light microscopy. General Applications Using the HPV Array Detection Method of the Invention detection of HPV infection detection of single or multiple infections in the same analysis Specific Applications to detect recurrence after treatment of cervical cancer or dysplasia. to detect HPV infection in cervical screening to detect HPV in case of cervical cytology with atypical cells of undetermined significance (ASCUS cells) to detect high risk type HPV in cervical epithelial abnormalities to detect the presence or absence of HPV in the differential diagnosis of carcinoma of unknown origin. Certain embodiments of the present invention are further detailed and illustrated below. Generation of HPV Targets In a preferred embodiment the target HPV sequences are labeled in an asymmetrical PCR reaction after a regular HPV type specific PCR amplification. As tag several options exist which are well known to a person skilled in the art. 5′-digoxigenin-modified reverse oligonucleotide primers recognizing a tag are used in the asymmetrical PCR. The primer concentrations may vary. Suitable concentrations are 0.05 and 1 μM for forward and reverse primers, respectively. Variations in these conditions are well known to a person skilled in the art. In another embodiment other ways of amplification may be used as well. Examples are rolling circle PCR, nucleic acid sequence based amplification, transcription based mediated amplification. These are well known to a person skilled in the art. In an alternative embodiment as label other options exist such as biotin. The choice may depend on the way capture oligonucleotides are attached to the solid support (see below). In an alternative embodiment amplification products may be labeled internally using digoxigenin-11-dUTP replacing dTTP (or a mixture of the latter two nucleotides) in the amplification mixture of the PCR or other labels well known to a person skilled in the art. In yet another alternative embodiment amplification products can be labeled directly with a fluorescent group (e.g. Cy-dyes, Fluorescein, Rhodamine, Texas Red) using modified reverse primers (end-labeled) or modified nucleotides (internal labeling) in PCR. In other embodiments for labeling quantum dots, analogues allowing silver or gold type of staining reaction, nuclear analogues allowing infrared or interference based detection may be used. These are well known to a person skilled in the art. In another embodiment to prepare single stranded DNA amplification products may be labeled in one of the abovementioned ways using equal primer concentrations in the PCR reaction. In that case the double stranded DNA amplification products have to be denatured (e.g. by heat), quickly cooled on ice and used in the hybridization mixture. Other ways to prepare single stranded DNA after amplification may be used as well, These are well known to a person skilled in the art. In a preferred embodiment amplification products may before a second amplification be purified after a first amplification procedure. This approach may be used after an initial amplification without label to subsequently label the amplification product. Preparation of Microarrays In general capture olignucleotides can be attached on different ways to a solid support or may be synthesized directly on the solid support by light directed synthesis. In a preferred embodiment streptavidin coated slides are used as solid support for microarray analysis as disclosed in WO 02/44713, which is incorporated herein by reference. Streptavidin-coated microscope glass slides are used as a solid support in this microarray procedure. In another embodiment other ways to attach capture probes to the solid support may be used. Examples are: crosslinking the DNA to the aminated (silanized) slides by baking the array at 80° C. for 24 hrs. UV crosslinking may be used as an additional step (also for: Poly-L-lysine coated slides); other solid supports as Amino-silane coated slides, Acrylamide coated slides, Epoxy-activated slides, Aldehyde activated slides, NHS ester activated slides, Hydrogel epoxy activated slides, Isothiocyanate activated slides, Mercaptosilane activated slides, Nitrocellulose-coated glass slides, well known to a person skilled in the art. The concentration of 5′ biotin-modified oligonucleotides may vary but in a preferred embodiment the concentration may be (12 μM, in 3× SSC/1.5 M Betaine)[SSC; 1× (8.76 g/L NaCl, 4.41 g/L sodium citrate, pH 7.0]. Several robots exits for the positioning of already synthesized oligonucleotides to the solid support. These are known to a person skilled in the art. We use a SDDC-2 array spotting robot from Engineering Services Inc.(ESI, Toronto, ON, Canada) and Stealth micro spotting pins (SMP3, ArrayIt). These pins are assumed to deliver ˜0.6 nl volume at each spotting site, resulting in spots of ˜100 μm in diameter according to the manufacturer. In a preferred embodiment the spots on the slides were printed in triplicate for reasons quality control, but this may vary from one 10 or more. Spacing between the spots may vary depending on the software, but can be as small as 10 micron and be as large as with a dot spacing of 400 μm to more than 1 mm. In a preferred embodiment we use a relative humidity between 45-60% during spotting varied and the temperature kept at 22° C., but these conditions may vary. Spots containing a suspension of 5′ biotin-modified DNA oligonucleotides are being printed on streptavidin glass slides using a commercially available microarray robot (SDDC-2, ESI/Virtek). We use 12 μM solutions of the biotinylated oligonucleotides for spotting but have shown that 6-20 μM of oligonucleotides in spotting solutions gave similar results. In a preferred embodiment in the spotting buffer betaine may be added. The betaine concentration may vary but a concentration of 1.5 M to the 3× SSC is suitable. DNA spotting solutions we get clearly visible spots (by eye and by light microscopy) making this a point in the procedure to validate the quality of the array. After testing the quality of the array by this visual check, the betaine can be washed away for long term storage of the slides, without negative influence on the bound oligonucleotide, subsequent hybridization, or background after visualization. In another embodiment spotting buffers without betaine may be used. These are well known to a person skilled in the art. In a preferred embodiment 5′ biotin-modified oligonucleotides were used for printing on the array. A 16-atom spacer arm has been used to attach the biotin group to the oligonucleotides, whereas a 12-atom spacer arm was used in the attachment between the digoxigenin (DIG) and the penultimate 5′ terminal nucleotide. The spacer length may vary from 1 to 16 c-atoms. Based on previous experience with K-ras the probes for HPV were designed similar to K-ras i.e. the biotin label with a spacer was directly coupled to a 20 mer HPV specific fragment. Initial experiments were not successful. Subsequently, the HPV specific fragment was increased to a length of 40 nucleotides. This resulted in stronger signals, but also increase in cross reactivity. Therefore, An additional spacer was necessary between the oligonucleotide with the biotin spacer and the HPV specific fragment, in addition, the 40-mer HPV may be reduced in size with resulting improvement of quality since cross reactivity may be diminished. Primers and probes are presented in Table 1 below. TABLE 1 Oligonucleotide sequences related to amplification (cluster a-F) and capturing HPV 1-85 SEQ ID NO SEQUENCE USE Cluster 1 GTGCCAGGAW CAGTTGTTAG Amplification primer A 2 CAWKTGHATT TCAATDGC Amplification primer A 3 CAGTTGTTAG AACTKTATGA Amplification primer A 4 TCYTGYAAHG TCCAHGGYTC Amplification primer A 5 GAAATSVTTY TTYMRAAGGT Amplification primer B 6 TCCTGGCACR CATCTAAACG Amplification primer B 7 TTTBHAAATV CATTTCCAWT WGA Amplification primer D 8 TAAACGHTKR SAHAGNKTCT CCAT Amplification primer D 9 CCTTTTTCTC AAGGACGTGG Amplification primer E 10 CDTGGTSCAR ATTAGAYTTG Amplification primer F 11 GNHGGHACCA CBTGGTGG Amplification primer E + F 12 CITGGTICAI ATTAGAITTG Amplification primer F 13 GIIGGIACCA CITGGTGG Amplification primer E + F 14 TWGSIYTIIT IGATGAYGYI AC Amplification primer C 15 TIGSIYTIWT RGATGATGCI AC Amplification primer C 16 TIGSIYTIIT IGATGAYGYI AC Amplification primer C 17 GATTTCCAGC TTTGGTCAGT Amplification primer C 18 CCAMARCCTT TYAAARAAAG AIKYCCA Amplification primer C 19 SMAARYTTKI KRAAAAAASA IKTCCA Amplification primer C 20 TNGSNYTNHT DGATGAYGYN AC Amplification primer C 21 SSMMARYYTK HBRAARAAAS ABKYCCA Amplification primer C 22 CCAMARCCTT TYAAARAAAG AHKYCCA Amplification primer C 23 VMAARYTTKH KRAAAAAASA BKTCCA Amplification primer C 24 TTTTCTTTTC TTTTCAGAGG AGCAGGACGA CAATG Probe HPV2 25 TTTTCTTTTC TTTTCTGAAG ACGAGGAGGA CAATG Probe HPV3 26 TTTTCTTTTC TTTTCCCATT AAAGGTGTCC GAAGC Probe H2V6 27 TTTTCTTTTC TTTTCAGATG TGTCAAAAGC CAAAG Probe HPV7 28 TTTTCTTTTC TTTTCCGAGG AGGAGCATGG AAACC Probe HPV10 29 TTTTCTTTTC TTTTCCCATT AACTGTGTCA GAGAC Probe HPV11 30 TTTTCTTTTC TTTTCATTGA CAGTATCACA AGCTA Probe HPV13 31 TTTTCTTTTC TTTTCCAGAC CTACGTGACC ATATA Probe HPV16 32 TTTTCTTTTC TTTTCACATG GCATACAGAC ATTAA Probe HPV18 33 TTTTCTTTTC TTTTCGAGGA AAATGGAAAC CCTAG Probe HPV28 34 TTTTCTTTTC TTTTCTAGTA AACGACTTTG TGATC Probe HPV31 35 TTTTCTTTTC TTTTCAGCAC TGGAAATATC CAGGG Probe HPV32 36 TTTTCTTTTC TTTTCCTTTA TTGTATACAG CCAAA Probe HPV33 37 TTTTCTTTTC TTTTCAGTAA TGGAAATCCA CTATA Probe HPV34 38 TTTTCTTTTC TTTTCTAGCA CATGTTTGTC TGATC Probe H2V35 39 TTTTCTTTTC TTTTCAGAAT ACTATGAACA AGACA Probe HPV39 40 TTTTCTTTTC TTTTCAGATG TTTCAAAGGC TAAAG Probe HPV40 41 TTTTCTTTTC TTTTCAACAT TGGAAACATG TAGAG Probe HPV42 42 TTTTCTTTTC TTTTCGAAAT GTATACGATA TGAAT Probe HPV44 43 TTTTCTTTTC TTTTCACATG GTATTACCAA ACTAA Probe HPV45 44 TTTTCTTTTC TTTTCTTTTG TTTTACAAAG CAAAG Probe HPV52 45 TTTTCTTTTC TTTTCTTTAG CGCTGAACGA CAACG Probe HPV54 46 TTTTCTTTTC TTTTCTGTTA TTACACAAAG CAAAG Probe HPV55 47 TTTTCTTTTC TTTTCGTTTC TTTACAAGGA CGTGG Probe HPV56 48 TTTTCTTTTC TTTTCAGAGG ATCAGGAAGA CAATG Probe HPV57 49 TTTTCTTTTC TTTTCCTATA ATGTATACAG CCAGA Probe HPV58 50 TTTTCTTTTC TTTTCAGACA TTAATGAACA CATAA Probe HPV59 51 TTTTCTTTTC TTTTCAGAGG GATCTGATCA ACAGG Probe HPV61 52 TTTTCTTTTC TTTTCCTTTG TATTATAAAG CTAAA Probe HPV67 53 TTTTCTTTTC TTTTCAGTTT TTTTTCCACC ACTTG Probe HPV69 54 TTTTCTTTTC TTTTCAGAAC ATTATGAACA GGACA Probe HPV70 55 TTTTCTTTTC TTTTCAGAGG GACCTGACGA ACAGG Probe HPV72 56 TTTTCTTTTC TTTTCAGTAA TGGGAACCCA CTATA Probe HPV73 57 TTTTCTTTTC TTTTCTATAT GCACTAAATG ATGTA Probe HPV82 58 TTTTCTTTTC TTTTCTTTAG AATTGCATCA AGAGG Probe HPV83 59 TTTTCTTTTC TTTTCAACAT TACGAGACTG ATAGT Probe H2V85 In a preferred embodiment the 5′-Biotin-modified capture oligonucleotides have a length of 35 nucleotides. The 5′end of the oligonucleotide sequence starts with a 15-mer that contains a triple [TTTTC] repeat, followed by a stretch of HPV type-specific nucleotides. The length of the first part with repeats may vary from no repeat (i.e. 0 nucleotides) to more than 10 repeats. This part has a second spacer function and optimizes hybridization. In our hands the repeats is sufficient for a suitable signal. In addition, nucleotide composition may be other than TTTTC, but need to be selected in such a way that no cross hybridization occurs with other relevant DNA fragments in the assay. For one HPV specific capture probe the spacer length does not need to be constant, but may vary as well. In a preferred embodiment the HPV specific sequences have a length of 20 nucleotides. These were chosen from multisequence alignments after ordering and clustering all HPV E1 gene sequences and blasted against all collaborate NCBI nucleotide databases to check for their uniqueness among HPV strains (NCBI: national center for biotechnology information). Within the HPV-specific sequence of the capture oligonucleotides of two closely related types at least 1 but preferably 2 positions are unique to a HPV type. In another embodiment the length of the HPV specific 20 nucleotides may vary. This may be shorter, longer or combinations of different lengths may be used. In another embodiment the capture probes consist of 5′ modified peptide nucleic acids (PNA). These can be used for their high affinity binding. Also a combination of 5′ modified oligonucleotides and PNA may be present on the array. For purposes of recognition the where the spots are located on the slide we used marker oligonucleotides with a 5′ biotin-modified oligonucleotides of 40 nucleotides in length with a digoxigenin-modification at the penultimate 3′ terminal nucleotide. But the length of this marker oligonucleotide may vary and be longer or shorter. In another embodiment the oligonucleotide sequence may be complementary to the ones defined in the table. This holds for the primer and probes. Spotted arrays were kept in a dry and cold place (refrigerated) until use. Arrays have been stored for over 3 months and gave results similar to new arrays. Hybridization In a preferred embodiment the printed arrays are washed before hybridization in phosphate-buffered saline [PBS; 1× (0.21 g/L KH2PO4, 9 g/L NaCl, 0.73 g/L Na2HP)4*7H2O, pH 7.4)] containing 0.5 mL/L Tween 20 for 10 min to remove unbound materials. Other washing buffers are suitable as well known to a person skilled in the art. In a preferred embodiment disposable coverplates (Shandon) were used for all hybridizations, incubations, wash and immunochemical detection steps. Glass microscope slides fit in these coverplates and are held in a vertical position during the whole procedure. There is a 80 micron space on top of the slide when fixed in the coverplate (approximate volume of 80 μl) and the incubation mixture is being retained by capillary forces. Washing the slides is simply performed by adding PBS-T to the upper buffer reservoir (approximately 3 ml) and have it pass the array. In another embodiment other slide holders can be used or the slide can be incubated in horizontal fashion. In these situations the amount of hybridization fluid may vary. In a preferred embodiment the microarrays were prehybridized in a buffer containing 3.3× SSC/1.7 mM EDTA/17 mM Hepes/0.12% Tween 20 pH 7.3 for 5 min at RT and hybridized in the same solution with probe for 1 h at 22° C. The probe hybridization solution contained 40% v/v of the unpurified total PCR products of the asymmetrical PCR per hybridization in the same buffer, but this 40% ratio may vary. Hybridization incubation was performed for 1 h at RT (around 22° C.), but the time and temperature may vary. The hybridization mixture may a composition of different PCR reactions and the hybridization buffer. Or for different PCR reactions serial hybridization may be performed. In another embodiment other hybridization buffers and temperatures may be used. These are well known to a person skilled in the art. In a preferred embodiment washing after hybridization is performed to decrease cross-hybridization of target to mismatched capture oligonucleotides. Five subsequent washes of 5 min. each are performed at room temperature PBS-Tween 20 (0.05%); 2× SSC/0.1% SDS; 1× SSC/0.1% SDS; 0.1× SSC; 0.05× SSC. In another embodiment the wash procedure after hybridization may be performed at other, usually higher, temperatures. In a preferred embodiment the HPV array is designed with a visual control probe (VCP) containing biotine label on the 5′ end and a visualization hapten on the penultimate 3′ end. In fact this is an internal positive control for the visualization procedure and may also provide information about the position of the HPV specific probes and other negative control probes. The VCP may be spotted at various concentrations providing information about the dynamic range of the visualization procedure for each experiment. In another embodiment other control probes may be sued as well. These are well known to a person skilled in the art. Visualization Procedure In a preferred embodiment as a control for hybridization to the hybridization mixture an antisense Cy3-labeled oligonucleotide may be added, that recognizes the 15-nucleotide stretch preceding the HPV-specific sequence of the capture oligonucleotides. The length of this array may be longer dependent on the length of the second spacer or shorter. In another embodiment this antisense oligonucleotide may be added to the array after the Dig-detection and visualization, followed by a short PBS-T wash step. In a preferred embodiment the after hybridization and washing on the array remaining digoxigenin groups of the labeled PCR products were incubated by a 1:100 dilution of a mouse monoclonal antibody to digoxigenin (Anti-digoxigenin clone 1.71.256, Roche Molecular Biochemicals, Almere, The Netherlands) according to the manufacturers protocol, followed by a 45 min. incubation with a 1:20 dilution of alkaline phosphatase-conjugated rabbit anti-mouse immunoglobulins (DAKO, Amsterdam, The Netherlands). The Vector Blue alkaline phosphatase substrate kit (SK-5300, Vector Laboratories, Burlingame, Calif., USA) was used to detect alkaline phosphatase activity according to the manufacturer's instructions. Vector Blue produces a blue reaction product that can be seen using brightfield or fluorescent microscopy. Slides analysed with light microscopy (absorption mode) were mounted with an aqueous-based mounting medium Imsol Mount (Klinipath, Duiven, The Netherlands). Slides analysed with laser scanner (fluorescence mode) were washed twice for 5 min. in PBS containing 0.5 mL/L Tween 20, rinsed in water, washed for 3 min in ethanol 100% and air-dried in the dark. The Vector Blue reaction product is detected as a red fluorescence using a laser that excites at 635 m wavelength. The chemical substances mentioned above are not restrictive in any sense but examples of components that may be used for adequate result. In another embodiment other visualization chemistries can be used which are well known to a person skilled in the art. An example is the Vector Red alkaline phosphatase substrate kit (SK-5100), that may be used to give red spots in brightfield microscopy and green spots in fluorescence detection mode (at 532 nm excitation). Imaging and Data Analysis In a preferred embodiment slides with fluorescent mode were scanned with Microarray laserscanner Genepix 4000A and data analysis was performed with GenePix Pro 3.0 software from Axon Instruments Inc. (Foster City, Calif.). Scans show an image of the whole array without losing the overall image. This scanner uses a 532 nm laser to excite Cy3 and a 635 nm laser to excite Cy5. The green laser light of the 532 nm laser was also used to excite the reaction product of alkaline phosphatase and Vector Red and the light of the 635 nm laser was used to excite the reaction product of Vector Blue and alkaline phosphatase. Sixteen-bit TIFF images of 10 μm resolution were subtracted for local background intensity. The software does not normalize the data. The median of the feature intensities of three spots were used to calculate mean signal intensities for each DNA concentration spotted. Slides with absorption mode were also semiquantitatively analysed by regular light microscopy (using 25× total magnification). In another embodiment slides may be photographed with a CCD camera attached onto a light microscope. When using specific adaptors or low-magnification lenses, the whole array can be viewed and documented in one shot. Other commercially available systems may be used as well and may easily be determined by a person skilled in the art. In a preferred embodiment the array is visualized with conventional bright field microscopy. Thus the abovementioned scanners are not obligatory for analysis. This set up allows the use of the HPV array in any modem pathology laboratory that PCR and immunohistochemistry facilities. In another embodiment infrared, phase contrast or interference based methods may be sued for imaging. These are well known to a person skilled in the art. Although the present invention is herein described in certain typical embodiments, it will be understood that variations may be made without departing from the spirit of the invention. For example, the HPV DNA array according to the invention is typically described herein using alkaline phosphatase for detection with absorption microscopy. Evidently, for visualization purposes this enzyme may be replaced by a fluorescent substance or other known detectable group. This needs to be put in perspective of the usually microscopic detection system used. The test characteristics of the system may be dependent of the combination used. Such variations are evident to the man skilled in the art, are all encompassed within the scope of the present invention. The present disclosure is to be considered as in all respects illustrative and not restrictive, the scope of the invention being indicated by the appended Claims, and all changes which come within the meaning and range of equivalency are intended to be embraced therein.
<SOH> BACKGROUND OF THE INVENTION <EOH>Cancer is the second overall leading cause of death, after ischemic heart disease, in the United States and Western Europe and despite recent advances in its treatment, there is, for most cancer types, no miracle cure on the horizon. Cancer causes approximately 25% of all deaths. The incidence continues to rise, probably reflecting the increasing average age of the population. The key to survival is early diagnosis and treatment. About two decades ago HPV was associated with human tumors. Since then it has been detected in tumors and (pre)neoplastic lesions of different sites such as uterine cervix, penis, skin, middle ear, anus, squamous cell tumours of the head and neck region (oral mucosa, tonsil, larynx, pharynx), lung, urinary bladder. More than 70 different types of HPV have been reported with different relations to the progression of a lesion. Some of the types have stronger association with the progression to malignant tumors than others e.g. type 16 and 18 are associated with high grade intraepithelial dysplasia of the cervix. These are called ‘high risk’ HPV types. The number of HR-HPV has been expanded the last years to e.g. 16, 18 45, 31, 33 check. Other types are mainly associated with benign tumors such type such as 1,2, 4, 5, and 6 with benign skin warts. HPV type 11 is frequently present in juvenile recurrent respiratory papillomas. Frequently in a series of cases of one histologic type of lesion different HPV types have been detected. Occasionally, multiple HPV types were found within one lesion (coinfection). In erythroplasia of Querat HPV type 8 was found in combination with other types of HPV [Wieland 2000]. In renal transplant recipients the number of keratotic lesions increases after several years. Also in these lesions a wide range of HPV types are recognized [De Jong-Tieben 2000]. In Epidermodysplasia Verruciformis HPV type 47 has been shown [Adachi 1996]. In Global nail dystrophy type 57 infection was found. [McCown 1999] Although several different types have been described, recently minor variations in DNA composition have been within one type. Because of the genetic diversity of HPV the use of type-specific amplification is impractical for epidemiologic studies, for which accurate typing is essential. Within the HPV region many gene sequences have been described both at the DNA and protein level such as E1, E2, E3, E4, E5, E6, E7, L1 and L2. Several methods use the one or more of the genes above such as PGMY LBA, SPF 10 LiPA GP5+16+ combination Only one is using another E1 region than our invention does. Several methods exist for the detection of HPV in general as well as for typing. Many use the polymerase chain reaction (PCR) for amplification of part of the HPV genome. For the PCR type specific primers can be used. As an alternative primers are used that allow amplification of more than one types. In some HPV tests primers are intended to amplify all types (general primers). These primers can be degenerated to a limited extent. With this approach one or more combinations of primers intend to cover for all HPV types (Jacobs, et al. J Clin Microbiol 1997 35:791-795; Bauer, et al., JAMA 1991 265:472477). After PCR sequencing can be performed for HPV typing. An alternative approach is to hybridise the DNA fragments to a filter containing different areas with different DNA fragments. Each area contains then DNA corresponding to one type. However, cross hybridisations may occur. In theory all different HPV types may be amplified and sequenced individually, but depending on the amount of types and variations to be known this will be an increasing amount of work. Other approaches for the detection of HPV types are the use of restriction fragment length polymorphism analysis combined with an amplification technique, and another alternative for the detection of HPV is the use of an amplification technique in combination with single stranded conformational polymorphism (Mayrand, J Clin Microbiol 2000 38:3388-3393). Still other approaches are hybrid capture II and Ligase chain reaction (Yamazaki, et al., Int J Cancer 2001 94:222-227). Yet approaches is to detect HPV is by in situ hybridisation (AmorTegui, et al., 1990 23:301-306; Unger, et al., J Histo chem. Cytochem 1998 46:535-540; Lizard, et al., J Virol. Methods 1998 72:15-25)) or in situ PCR (Jean-Shiunn Shyu J Surg Oncol 2001 78:101-109). On one histologic slide or cytologic specimen HPV type specific DNA fragments are necessary to obtain a signal. Thus, in theory recognition of any HPV types at least a similar number of slides/specimens is required to examine one kind of biologic sample. This would be a very laborious procedure. Recent developments show after a PCR the use of a line probe or line blot assay to detect different types. Comparison of different line probes assays (PGMY LBA and SPF 10 LiPA) reveals a difference in sensitivity for one assay: with PGMY LBA more HPV types 42, 56 and 59 and with SPF 10 LiPA more HPV types 31 and 52 were detected [Van Doom 2002]. Also for the GP5+/6+ primers a reverse line blot assay has recently been described detecting 37 mucosal types [Van den Brule 2002 J Clin Microbiol 2002 40:779-787]. The concordance between different methods is moderate (Meyer et al. Dermatiology 2000 201:204-211; Vernon J Clin Mircobiol 2000 38:651-655). Recently, ‘chip’ technology has been developed (see, e.g., U.S. Pat. No. 5,445,934). The term ‘microarray’ or ‘chip’ technology as used herein, is meant to indicate analysis of many small spots to facilitate large scale nucleic acid analysis enabling the simultaneous analysis of thousands of DNA sequences. This technique is seen as an improvement on existing methods, which are largely based on gelelectrophoresis. For a review, see Nature Gen. (1999) 21 Suppl. 1. Line blot assay and microarray methods both use circumscribed areas containing specific DNA fragments. As will be known in the art, line blotting is usually performed on membranes (Gravitt, et al., J Clin Microbiol 1998 36:3020-3027, whereas microarray is usually performed on a solid support and may also be performed on smaller scale. The utility of DNA arrays for genetic analysis has been demonstrated in numerous applications including mutation detection, genotyping, physical mapping and gene-expression monitoring. The basic mechanism is hybridization between arrays of nucleotides and target nucleic acid. Recently, the Point-EXACCT method was transferred to DNA microarray format, where a glass support is homogeneously streptavidin-coated. This coating is used to spot biotinylated probe to the glass slide and to hybridize a single-stranded target DNA to this nucleic acid probe. For detection a second probe is added, or the single stranded DNA is already labeled. The use of streptavidin-coated slides for microarray analysis is disclosed in WO 02/44713 the contents of which are incorporated herein by reference. In conclusion, HPV types can be discerned with various laborious techniques. The present invention provides a further improvement of the microarray technique with coverage of any known HPV types on the array.
<SOH> SUMMARY OF THE INVENTION <EOH>In one aspect of the invention, a combination of oligonucleotides is used, allowing amplification of a part of the E1 HPV gene. This part of the sequence has thus far not been used for HPV typing before. Especially preferred is the 3′ end of the E1 HPV gene, in particular a region between about 29 to about 188 nucleotides from the 3′ terminus of the E1 gene. The size of the whole gene varies from 1820 to 1964 nucleotides. In a further aspect of the invention the examination of integration of HPV in human DNA a combination of E1 region with another HPV region such as E 6 or L1 is suitable. In a further aspect of the invention microarray is used for detection of the specific HPV type(s) after the amplification. In a further aspect of the invention the system allows rapid reading with absorption in regular light microscope suitable for detecting and typing HPV in one procedure. These and other aspects of the invention will be outlined in some more detail in the following description.
20050421
20090512
20080626
91865.0
C12Q170
0
WOOLWINE, SAMUEL C
HUMAN PAPILLOMA VIRUS DETECTION WITH DNA MICROARRAY
SMALL
0
ACCEPTED
C12Q
2,005
10,511,294
ACCEPTED
Adjustable-length tube, in particular for poles
An adjustable-length tube (10) for sticks, having an outer tube (12) and an inner tube (11) that can be inserted telescope-like into the outer tube (12) for adjusting the length of the tube, and having a spreading device (15) that is supported at the insertion end of the inner tube (11), the spreading device being able to clamp the inner tube (11) axially in the outer tube (12) and having a spreading element (16) that can be radially pressed apart and that is furnished with an inner cone (27), an interior element (17) that is provided with a reverse-oriented outer cone (22) and that is accommodated in the spreading element (16) so as to be axially movable, and an adjusting screw (18) that is axially oriented and is supported in a rotationally fixed manner on the inner tube (11), the adjusting screw having an operational connection to an internally threaded bore (21) in the interior element (17). So that an adjustable-length tube of this type responds to impact-like axial stresses by continuing to clamp rather than sliding or giving way, provision is made that the inner cone (27) of the spreading element (16) is situated such that it opens in the direction of the inner tube (11), and the spreading element (16) is supported between an inner limit stop (28) on the inner tube (11) and an exterior limit stop (26) on the free end of the adjusting screw (18) so as to be axially movable within narrow limits.
1-7. (canceled) 8. An adjustable-length pole, the pole comprising: at least one outer tube; an inner tube structured and dimensioned for insertion into said outer tube in a telescoping fashion for adjusting a length of the pole; an inner limit stop disposed at an end of said inner tube; an adjusting screw axially oriented within said outer tube and supported in a rotationally fixed manner on said end of said inner tube; an exterior limit stop disposed on a free end of said adjusting screw; a spreading element, said spreading element structured to be radially pressed apart, said spreading element having a bore defining an inner cone, said inner cone opening towards said end of said inner tube, said spreading element disposed between said inner limit stop and said exterior limit stop such that it can move axially within narrow limits; and an axially moveable interior element having an outer cone structured, dimensioned, and disposed for cooperation with said inner cone of said spreading element, said interior element having an internal threaded bore cooperating with said adjusting screw, wherein said spreading element and said interior element cooperate to form a spreading device supported at axially said end of said inner tube, said spreading device for clamping said inner tube within said outer tube. 9. The pole of claim 8, wherein the pole is a stick. 10. The adjustable-length pole of claim 8, wherein said spreading element is configured in a pot-like fashion, wherein a pot base is penetrated by a free end area of said adjusting screw, facing away from said inner tube. 11. The adjustable-length pole of claim 8, wherein said spreading element comprises a cylindrical shoulder having a smaller exterior diameter and facing said inner tube, said shoulder being axially guided at one area of said end of said inner tube. 12. The adjustable-length pole of claim 8, wherein said exterior limit stop is formed by a cap that is axially secured at said free end of said adjusting screw after said spreading element has been set in place. 13. The adjustable-length pole of claim 8, wherein said exterior limit stop is formed by a head that is molded onto said free end of said adjusting screw, with said spreading element having a peripheral slot that extends along an entire axial length of said spreading element. 14. The adjustable-length pole of claim 11, wherein said spreading device has a plug that accommodates said adjusting screw in an axial and rotationally fixed manner, said plug being supported axially and in a rotationally fixed manner in said inner tube and defining said inner limit stop, said plug having an axially protruding guide member cooperating with said cylindrical shoulder of said spreading element. 15. The adjustable-length pole of claim 8, wherein said interior element has one or more radially protruding fins, which are guided in axial slots of said spreading element.
The present invention relates to an adjustable-length tube, especially for sticks,1 in accordance with the preamble of claim 1. In an adjustable-length tube such as is known from DE 297 06 849 U1, the spreading element is provided with a tapering inner cone oriented towards the inner tube, whereas the corresponding interior element that is provided with the outer cone is displaced towards the inner tube by the adjusting screw so that the spreading device can grab hold. In this manner, although the result is a relatively parallel clamping over the entire axial length of the spreading element, nevertheless it has been found that in response to impact-like stresses on the stick tip from the handle-side of an adjustable-length stick, an axial displacement of the outer tube with respect to the inner tube cannot always be avoided and especially not when, in the twisting motion, insufficient force has been applied for purposes of clamping. Furthermore, from DE 297 08 829 U1, an adjustable-length tube is known, in which the interior element that is provided with the outer cone is formed by the forward free end of the adjusting screw, and the spreading element that is provided with the inner cone is moved axially on the adjusting screw. In this context, although the inner cone of the spreading element is opened towards the inner tube, nevertheless the same aforementioned disadvantages arise here if the spreading element is axially fixed in the spread-apart state. In this case as well, a relative motion between the outer tube and the spreading element can occur. The objective of the present invention is to create an adjustable-length tube, especially for sticks, of the species cited above, which, in response to impact-like axial stresses, continues to clamp rather than slide or give way. 1 Translator's note: The two reference patents cited on this page refer to “walking sticks and ski poles” but the present application only mentions “sticks” (Stoecke). I have translated the latter German word as “sticks” despite the fact that this word in English can have several other additional meanings (e.g., in sports, “hockey sticks”). The features indicated in claim 1 are put forward to achieve this objective in an adjustable-length tube, especially for sticks, of the aforementioned species. As a result of the features according to the present invention, it is achieved that in response to an aforementioned impact-like stress, the holding force between the spreading element, or inner tube, and the outer tube is increased, because as a result of the relative axial movability of the interior element and the spreading element, the former is able to penetrate further into the inner cone of the spreading element. Even in the case of a telescope mechanism that is tightened using too little torque, the result is essentially a further spreading, which in turn reinforces the clamping force in the direction of the stress, so that even in these cases a displacement or a relative motion is prevented. A jam-free guiding of the spreading element within the given axial movability is provided by the features as recited in claim 2 and/or 3. Advantageous embodiments with regard to the outer limit stop for the spreading element will become apparent from the features of claim 4 or those of claim 5. In the former case, the assembly of the spreading element takes place before the attachment of the outer limit stop, whereas in the latter case, with the limit stop already provided, the spreading element is configured such that it can be placed onto the adjusting screw and the interior element radially. One advantageous embodiment of the inner limit stop will become apparent from the features as recited in claim 6. The features as recited in claim 7 are put forward to achieve a rotationally fixed axial movability of the interior element with respect to the spreading element. Further details of the present invention can be derived from the following description, in which the present invention is described in greater detail and is explained on the basis of the exemplary embodiments depicted in the drawing. In the latter: FIG. 1 in a partial longitudinal cutaway and truncated view depicts an adjustable-length tube according to a first exemplary embodiment of the present invention, FIG. 2 depicts a partial longitudinal cutaway view, rotated 90° with respect to FIG. 1, of the first exemplary embodiment, FIG. 3 depicts a view along the line III-III of FIG. 2, FIG. 4 depicts a representation corresponding to FIG. 1, but in accordance with a second exemplary embodiment of the present invention, and FIG. 5 depicts a representation corresponding to FIG. 2, but in accordance with the second exemplary embodiment of the present invention. In the connecting segments of an adjustable-length tube 10, 110, depicted in the drawing in accordance with two exemplary embodiments, an inner tube 11, 111 is guided telescope-like in an outer tube 12,112. For this purpose, inner tube 11, 111, at its end 13, 113 that is facing outer tube 12, 112, is provided with a spreading device 15, 115, using which inner tube 11, 111 can be fixed at any position within the outer tube 12, 112 in a clamping manner. Spreading device 15, 115 has an exterior element in the form of a spreading element 16, 116, an interior element 17, 117, and an adjusting screw, or externally threaded rod 18, 118. Externally threaded rod 18, 118, which is arranged in the axial direction of tube 10, 110, is supported at its one end area in a rotationally fixed manner on insertion end 13, 113 of inner tube 11, 111. For this purpose, externally threaded rod 18, 118 is inserted, or screwed, into an end plug 19, 119, or is integrally configured on the latter, or the like, and is axially fixed and held in a rotationally fixed manner in the end plug using adhesive or the like. End plug 19, 119 is also axially fixed and supported in a rotationally fixed manner in inner tube 11, 111. Interior element 17, 117 by its axial central interior thread 21, 121 is screwed onto externally threaded rod 18, 118. Interior element 17, 117 is provided on its exterior side with a cone 22, 122, or it is configured in a conical manner. Outer cone 22, 122 tapers toward the free end of externally threaded rod 18, 118. Externally threaded rod 18, 118 penetrates internally threaded bore 21, 121 of interior element 17, 117 and is connected at its protruding free end in a rotationally fixed manner to an exterior limit stop 26, 126. Exterior-side spreading element 16, 116 on its spreadable main body 23, 123 has an inner cone, or interior taper 27, 127, whose slope corresponds to that of outer cone, or exterior taper 22, 122 of interior element 17, 117. According to the graphic depiction, interior element 17, 117 is accommodated without play in spreading element 16, 116, which is oriented in the contrary direction, outer cone 22, 122 being shorter than inner cone 27, 127. In accordance with the depicted arrangement, inner cone, or interior taper 27, 127 of spreading element 16, 116 opens towards inner tube 11, 111. By way of example, spreading element 16, 116 can be made of plastic, and interior element 17, 117 can be made of metal or plastic. Integral end plug 19, 119 is provided with an interior part 31, 131, which is supported in inner tube 11, 111 so as to be prevented from rotating or sliding, and a collar 32, 132, which lies on the annular end face of inner tube 11, 111. Protruding from collar 32, 132 is a guide piece 33, 133 for spreading element 16, 116, the guide piece having a smaller diameter than the latter. Spreading element 16, 116 is roughly pot shaped, pot base 36, 136 having a through bore 37, 137, which is penetrated by the free end area of adjusting screw 18, 118. Pot base 36, 136 is axially movable relative to adjusting screw 18, 118. Main body 23, 123 of spreading element 16, 116, which on the exterior periphery can be provided with one or more friction linings, can be coated therewith, or can be configured through its surface composition (for example, longitudinal ribs) so as to achieve an increased frictional force with respect to the interior periphery of outer tube 12, 112, has, on its end facing away from pot base 36, 136 and facing inner tube 11, 111, a cylindrical shoulder 38, 138, that is smaller in its exterior diameter, in which guide piece 33, 133 can engage at its end side. In this context, between guide piece 33, 133 and spreading element 16, 116, enough play is available, so that the latter can move unhindered both axially and radially. Therefore, spreading element 16, 116 is axially movable within narrow limits between outer limit stop 26, 126 on the free end of adjusting screw 18, 118 and an inner limit stop surface 28, 128, which is formed by the annular surface of collar 32, 132 around guide piece 33, 133. The distance between both limit stop surfaces 24, 124 and 28, 128 is somewhat greater than the axial length of spreading element 16, 116 between the exterior surface of pot base 36, 136 and the annular end face of cylindrical shoulder 38, 138. In the exemplary embodiment of FIGS. 1 through 3, exterior limit stop 26 is formed by a cap 26′, which is attached to the free end of adjusting screw 18, for example, by being screwed, pressed, glued, plastic-extruded, or attached in some other way. Cap 26′ has a radial edge 24, which can come into contact with spreading element 16. In the exemplary embodiment of FIGS. 4 and 5, exterior limit stop 126 is configured as a head 126′ that is formed on the free end of adjusting screw 118, interior annular surface 124 of the head constituting the limit stop surface for spreading element 116. Interior element 17, 117 on each of two diametrically opposite peripheral areas of outer cone 22, 122 has a fin 41, 42, and 141, 142, whose longitudinal end face runs parallel to the stick axis. Each fin 41, 42, and 141, 142 is axially guided in a correspondingly wide slot 43, 44, and 143, 144 of spreading element 16, 116. In this manner, when interior element 17, 117 moves axially relative to spreading element 16, 116, it cannot rotate with respect to the latter. Both slots 43, 44, and 143, 144 are provided essentially over the longitudinal extension of main body 23, 123 of spreading element 16, 116, i.e., they only penetrate into the area of cylindrical shoulder 38, 138 to an insignificant extent. In other words, this also means that the greatest radial dimension of diametrically opposite fins 41, 42, and 141, 142, is equal to the interior diameter of cylindrical shoulder 38, 138. As can be seen from FIG. 3, which essentially applies to both exemplary embodiments, spreading element 16, 116 is furnished on its exterior periphery with four notches 46 that are all axially and centrally symmetrical to each other, which run in the longitudinal direction and extend over virtually the entire length of main body 23, 123 of spreading element 16, 116. Generated in this manner are defined, peripheral clamping areas of spreading element 16, 116. In the exemplary embodiment of FIGS. 1 through 3, after spreading device 16 is fixed in inner tube 11, interior element 17 is screwed onto the free end of adjusting screw 18, and thereafter spreading element 16 is placed over adjusting screw 18. Subsequently, exterior limit stop 26 is attached at the protruding end of adjusting screw 18, after which the end of inner tube 11, which has been completed in this manner, can be inserted into outer tube 12. In the exemplary embodiment of FIGS. 4 and 5, in which adjusting screw 118 has molded head 126′ and in which interior element 117 is screwed from the other side of adjusting screw 118, before adjusting screw 118 has been fixedly joined to end plug 119, spreading element 116 (if it has not been threaded first) must subsequently be placed over adjusting screw 118 and interior element 117. For this purpose, spreading element 116 according to FIG. 5 has an axially continuous slot 148, at which spreading element 116 can be opened radially and placed over interior element 117 and adjusting screw 118. In the depicted exemplary embodiment, continuous slot 148 is partially identical with one of slots 143, 144, although it is narrower in the area that extends further. In response to the motion of clamping inner tube 111, 111 in outer tube 12, 112 using spreading device 15, 115, interior element 17, 117 is moved away from inner tube 11, 111 in the direction of arrow A by rotating inner tube 11, 111 and therefore adjusting screw 18, 118 to the right (in the case of a left-handed thread) or to the left (in the case of a right-handed thread) with respect to outer tube 12, 112, spreading element 16, 116 first being moved, or pushed, in the same direction up to exterior limit stop 26,126. Thereafter, in response to a further axial motion of interior element 17, 117, spreading element 16, 116 is spread apart radially in the direction of arrow A, so that the exterior circumference of spreading element 16, 116 under pressure contacts the interior circumference of outer tube 12, 112. In this state, the annular end face of cylindrical shoulder 38, 138 of spreading element 16, 116 has a specific, preestablished, slight distance a from inner limit stop surface 28, 128 of collar 32, 132. Then, inner tube 11, 111 being clamped in outer tube 12, 112 using a more or less high torque, if an impact-like axial stress is exerted from outer tube 12, 112, which is provided, for example, with a handle, onto inner tube 11, 111, which is provided with a stick tip, then due to the clamping fixation of spreading element 16, 116 in outer tube 12, 112, interior element 17, 117 can move axially. This means that interior element 17, 117 moves further into interior cone 27, 127 of spreading element 16, 116, which leads to a further spreading of spreading element 16, 116 and therefore to an increase in the holding force between interior tube 11, 111 and outer tube 12, 112.
20041015
20100601
20050922
59578.0
1
GARCIA, ERNESTO
ADJUSTABLE-LENGTH TUBE, IN PARTICULAR FOR POLES
SMALL
0
ACCEPTED
2,004
10,511,402
ACCEPTED
Nanoimprint resist
The invention relates to a method for microstructuring electronic components, which yields high resolutions (≦200 nm) at a good aspect ratio while being significantly less expensive than photolithographic methods. The inventive method comprises the following steps: i) a planar unhardened sol film of a nanocomposite composition according to claim 1 is produced; ii) a target substrate consisting of a bottom coat (b) and a support (c) is produced; iii) sol film material obtained in step i) is applied to the bottom coat (b) obtained in step ii) by means of a microstructured transfer embossing stamp; iv) the applied sol film material is hardened; v) the transfer embossing stamp is separated, whereby an embossed microstructure is obtained as a top coat (a). The method for producing a microstructured semiconductor material comprises the following additional steps: vi) the remaining layer of the nanocomposite sol film is plasma etched, preferably with CHF3/O2 plasma; vii) the bottom coat is plasma etched, preferably with O2 plasma; viii) the semiconductor material is etched or the semiconductor material is doped in the etched areas.
1. A microlithographic arrangement comprising a) a microstructured layer of a nanocomposite composition comprising a1) a polymerizable silane of the general formula (I) and/or (II) and/or condensates derived therefrom SiX4 (I) in which the radicals X are identical or different and are hydrolyzable groups or hydroxyl groups; R1aR2bSiX(4-a-b) (II) in which R1 is a nonhydrolyzable radical, R2 is a radical carrying a functional group, X has the above meaning and a and b have the value 0, 1, 2 or 3, the sum (a+b) having the value 1, 2 or 3, and a2) nanoscale particles selected from the group consisting of the oxides, sulfides, selenides, tellurides, halides, carbides, arsenides, antimonides, nitrides, phosphides, carbonates, carboxylates, phosphates, sulfates, silicates, titanates, zirconates, aluminates, stannates, plumbates and mixed oxides thereof, as a top coat; b) a bottom coat comprising an aromatics-containing polymer or copolymer containing novolaks, styrenes, (poly)hydroxystyrenes and/or (meth)acrylates; c) a substrate. 2. The microlithographic arrangement as claimed in claim 1, wherein the top coat a) is a sol film. 3. The microlithographic arrangement as claimed in claim 1 wherein the substrate c) is a semiconductor material. 4. The microlithographic arrangement as claimed in claim 1, wherein the nanocomposite composition contains from 1 to 50 percent by volume, preferably from 1 to 30 percent by volume, of nanoparticles. 5. The microlithographic arrangement as claimed in claim 1, where the nanoscale particles have been surface-modified with compounds selected from the group consisting of the carboxylic acids, carboxamides, carboxylic esters, amino acids, β-diketones, imides, quaternary ammonium salts of the general formula N+R10R20R3R40Y−, where the radicals R10 to R40 are identical or different and may be aliphatic, aromatic and/or cycloaliphatic groups and Y− is an inorganic or organic anion. 6. The microlithographic arrangement as claimed in claim 1, wherein the nanocomposite composition contains polymerizable monofunctional and/or bifunctional monomers, oligomers and/or polymers selected from the group consisting of (poly)acrylic acid, (poly)methacrylic acid, (poly)acrylates, (poly)methacrylates, (poly)acrylamides, (poly)methacrylamides, (poly)carbamides, (poly)olefins, (poly)styrene, (poly)amides, (poly)imides, (poly)vinyl compounds, (poly)esters, (poly)arylates, (poly)carbonates, (poly)ethers, (poly)etherketones, (poly)sulfones, (poly)epoxides, fluorine polymers, organo(poly)siloxanes, (poly)siloxanes and hetero(poly)siloxanes. 7. The microlithographic arrangement as claimed in claim 1, where the nanocomposite composition contains a fluorosilane of the formula (III) R3(X1)3Si (III) in which R3 is a partly fluorinated or perfluorinated C2-C20-alkyl and X1 is C1-C3-alkoxy, chlorine, methyl or ethyl. 8. The microlithographic arrangement as claimed in 1, wherein the nanocomposite composition contains a crosslinking initiator. 9. A method for the production for microlithographic arrangement as claimed in claim 1, comprising the steps: i) production of a planar uncured sol film of said nanocomposite; ii) production of a target substrate comprising a bottom coat b) and a support c); iii) transfer of sol film material from i) by means of a microstructured transfer imprint stamp to the bottom coat b) in ii); iv) curing of the transferred sol film material; v) removal of the transfer imprint stamp to give an imprinted microstructure as top coat a). 10. The method as claimed in claim 9, wherein the uncured sol film i) is applied to a planar starting substrate comprising a support and/or an adhesion-promoting film. 11. The method as claimed in claim 9, wherein the transfer imprint stamp comprises silicone, glass or silica glass. 12. The method as claimed in claim 9 wherein the transfer imprint stamp is pressed into the sol film i) for from 5 to 300 seconds, then removed and placed on the bottom coat b) in the course of from 10 to 300 seconds and pressed against b) for a time of from 10 to 300 seconds under a pressure of from 10 to 100 kPa. 13. The method as claimed in claim 9 wherein thermal curing or UV curing is carried out while the transfer imprint stamp is pressed against b). 14. A method for the production of a microstructured semiconductor material, comprising the steps i) to v) as claimed in claim 9, support c) being the semiconductor material to be structured, and the steps vi) plasma etching of the residual layer of the nanocomposite sol film, preferably with CHF3/O2 plasma, vii) plasma etching of the bottom coat, preferably with O2 plasma, viii) etching of the semiconductor material or doping of the semiconductor material in the etched areas.
The present invention is in the area of microlithography. The miniaturization of electronic components, for which a resolution down to the range of less than 1 μm is required, has been achieved substantially by photolithographic techniques. The limit of resolution is predetermined by the wavelength of the radiation used for reproducing the original, so that short-wave radiation, such as high-energy UV radiation, electron beams and X-rays, must be used. Owing to the occurrence of diffraction effects in the case of increasingly small structures, structuring by photolithography reaches its physical limits, which are about 150 nm. On the other hand, the increasingly high requirements with respect to resolution, wall slope and aspect ratio (ratio of height to resolution) result in a cost explosion in the case of the apparatuses required for photolithographic structuring, such as masks, mask aligners and steppers. In particular, owing to their price of several million US$, modern steppers are a considerable cost factor in microchip production. It was therefore the object of the present invention to develop a method for the microstructuring of electronic components which gives high resolutions (≦200 nm) in combination with a good aspect ratio but is substantially more economical than photolithographic methods. U.S. Pat. No. 5,772,905 describes a nanoimprint method which is based on a thermoplastic deformation of the resist, applied to the whole surface of a substrate, by a relief present on a rigid stamp. Thermoplastics (polymethyl methacrylate, PMMA) are used as a resist for hot stamping. Owing to conventional thickness variations of about 100 nm over the total wafer surface, it is not possible to structure 6, 8 and 12 inch wafers in one step with a rigid stamp. Thus, a complicated “step and repeat” method would have to be used, which, however, is unsuitable owing to the reheating of already structured neighboring areas. WO 99/22 849 discloses a microstructuring method which takes a different approach. There, a flexible polydimethylsiloxane stamp having the desired microstructure is placed on a flat, inorganic substrate. As a result of the capillary forces, a liquid is subsequently drawn into the structure. This is an aqueous TEOS solution. The solvent is removed by osmosis and a porous SiO2 structure remains behind. These layers are used predominantly in biomimetics (composites for teeth and bones). In U.S. Pat. No. 5,900,160, U.S. Pat. No. 5,925,259 and U.S. Pat. No. 5,817,242, a stamp is wet with a UV-curable resist (self-assembled monolayer, e.g. alkylsiloxane) and then pressed onto a smooth substrate. Analogously to a conventional stamp process, the structured resist material remains when the stamp is raised from the substrate surface. The resist materials used exhibit sufficient wetting with respect to the substrate but are not suitable for a lift-off method, nor do they have sufficient etch resistance. The structure dimensions are in the region of 1 μm and are thus more than 1 order of magnitude too large. These methods are all unsuitable for achieving the object according to the invention. It has been found that the abovementioned requirements can be met by a mechanical transfer stamping method if a specific nanocomposite composition is used as a transfer resist (nanoimprint resist). The present invention relates to the use of a nanocomposite composition, comprising a) a polymerizable silane of the general formula (I) and/or (II) and/or condensates derived therefrom SiX4 (I) in which the radicals X are identical or different and are hydrolyzable groups or hydroxyl group; R1aR2bSiX(4-a-b) (II) in which R1 is a nonhydrolyzable radical, R2 is a radical carrying a functional group, X has the above meaning and a and b have the value 0, 1, 2 or 3, the sum (a+b) having the value 1, 2 or 3, and b) nanoscale particles selected from the group consisting of the oxides, sulfides, selenides, tellurides, halides, carbides, arsenides, antimonides, nitrides, phosphides, carbonates, carboxylates, phosphates, sulfates, silicates., titanates, zirconates, aluminates, stannates, plumbates and mixed oxides thereof, as a resist for the microstructuring of semiconductor materials, flat screens, micromechanical components and sensors. In the above formulae, the hydrolyzable groups X are, for example, hydrogen or halogen, such as F, Cl, Br or I; alkoxy, preferably C1-6-alkoxy, such as, for example, methoxy, ethoxy, n-propoxy, isopropoxy and butoxy; aryloxy, preferably C6-10-aryloxy, such as, for example, phenoxy; acyloxy, such as, for example, acetoxy or propionyloxy; alkylcarbonyl, preferably C2-7-alkylcarbonyl, such as, for example, acetyl; amino, monoalkylamino or dialkylamino having preferably 1 to 12, in particular 1 to 6, carbon atoms in the alkyl group or groups. The nonhydrolyzable radical R1 is, for example, alkyl, preferably C1-6-alkyl, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, pentyl, hexyl or cyclohexyl; alkenyl, preferably C2-6-alkenyl, such as, for example, vinyl, 1-propenyl, 2-propenyl and butenyl; alkynyl, preferably C2-6-alkynyl, such as, for example, acetylenyl and propargyl; and aryl, preferably C6-10-aryl, such as, for example, phenyl and naphthyl.. Said radicals R1 and X can, if desired, have one or more conventional substituents, such as, for example, halogen or alkoxy. Specific examples of the functional groups of the radical R are epoxy, hydroxyl, ether, amino, monoalkylamino, dialkylamino, amido, carboxyl, mercapto, thioether, vinyl, acryloyloxy, methacryloyloxy, cyano, halogen, aldehyde, alkylcarbonyl, sulfo and phosphoric acid groups. These functional groups are preferably bonded to the silicon atom via alkylene, alkenylene or arylene bridge groups which may be interrupted by oxygen or sulfur atoms or —NH— groups. Said bridge groups are derived, for example, from the abovementioned alkyl, alkenyl or aryl radicals. The bridge groups of the radicals R2 preferably contain 1 to 18, in particular 1 to 8, carbon atoms. In the general formula (II), a preferably has the value 0, 1 or 2, b preferably has the value 1 or 2 and the sum (a+b) preferably has the value 1 or 2. Particularly preferred hydrolyzable silanes of the general formula (I) are tetraalkoxysilanes, such as tetraethoxysilane (TEOS) and tetramethoxysilane. Particularly preferred organosilanes of the general formula (II) are epoxysilanes, such as 3-glycidyloxypropyltrimethoxysilane (GPTS) or 3-glycidyloxypropyltriethoxysilane, and silanes having reactive polymerizable double bonds, such as, for example, acryloyloxypropyltrimethoxysilane or 3-methacryloyloxypropyltrimethoxysilane. Said silanes or the functional groups thereof are preferred because (after hydrolytic polycondensation is complete) they can be used for a polyaddition or polymerization reaction with, for example, the polymerizable mono- and/or bifunctional organic monomers, oligomers and/or polymers and/or react with reactive groups present on the surface of the nanoscale particles and can thus contribute to the immobilization (for example by incorporation into a network) of the nanoscale particles. The hydrolysis and polycondensation of the above compounds is carried out in a conventional manner, if desired in the presence of an acidic or basic condensation catalyst, such as HCl, HNO3 or NH3. Thus, hydrolysis and polycondensation can be effected, for example, under the (generally known) conditions of the sol-gel process. The volume fraction of the nanoscale particles in the nanocomposite composition is expediently from 1 to 50% by volume, preferably from 1 to 30% by volume and in particular from 5 to 20% by volume. The nanoscale particles usually have a particle size of from 1 to 200 nm, preferably from 2 to 50 nm and in particular from 5 to 20 nm. Nanoscale inorganic particles as such as known, for example from WO 96/31572, and are, for example, oxides, such as CaO, ZnO, CdO, SiO2, TiO2, ZrO2, CeO2, SnO2, PbO, Al2O3, In2O3 and La2O3; sulfides, such as CdS and ZnS; selenides, such as GaSe, CdSe or ZnSe; tellurides, such as ZnTe or CdTe; halides, such as NaCl, KCl, BaCl2, AgCl, AgBr, Agl, CuCl, CuBr, Cdl2 or Pbl2; carbides, such as CeC2; arsenides, such as AlAs, GaAs or CeAs; antimonides, such as InSb; nitrides, such as BN, AIN, Si3N4 or Ti3N4; phosphides, such as GaP, InP, Zn3P2 or Cd3P2; carbonates, such as Na2CO3, K2CO3, CaCO3, SrCO3 and BaCO3; carboxylates, e.g. acetates, such as CH3COONa and Pb(CH3COO)4; phosphates; sulfates; silicates; titanates; zirconates; aluminates; stannates; plumbates and corresponding mixed oxides whose composition preferably corresponds to the composition of conventional glasses having a low coefficient of thermal expansion, e.g. binary, tertiary or quaternary combinations of SiO2, TiO2, ZrO2 and Al2O3. Also suitable are, for example, mixed oxides having the perovskite structure, such as Ba TiO3 or PbTiO3. In addition, organically modified inorganic particles, such as, for example, particulate polymethylsiloxanes, methacryloyl-functionalized oxide particles and salts of methylphosphoric acid may be used. These nanoscale particles can be produced in a conventional manner, for example by flame hydrolysis, flame pyrolysis and plasma methods according to the literature mentioned in WO 96/31 572. Stabilized colloidal, nanodisperse sols of inorganic particles, such as, for example, silica sols from BAYER, SnO2— sols from Goldschmidt, TiO2 sols from MERCK, SiO2, ZrO2, Al2O3 and Sb2O3 sols from Nissan Chemicals or Aerosil dispersions from DEGUSSA, are particularly preferred. The nanoscale particles can be changed in their viscosity behavior by surface modification. Suitable surface modifiers, i.e. surface-modifying low molecular weight organic (=carbon-containing) compounds which have at least one functional group which can react and/or (at least) interact with groups present on the surface of the powder particles and with the polymer matrix, are in particular compounds having a molecular weight which is not higher than 500, preferably not higher than 350 and in particular not higher than 200. Such compounds are preferably liquid under standard temperature and pressure conditions and preferably have altogether not more than 15, in particular altogether not more than 10 and particularly preferably not more than 8 carbon atoms. The functional groups which these compounds must carry depend primarily on the surface groups of the nanoscale material used in each case and moreover on the desired interaction with the polymer matrix. Thus, an acid/base reaction according to Bronsted or Lewis can take place, for example, between the functional groups of the surface-modifying compound and the surface groups of the particles (including complex formation and adduct formation). An example of another suitable interaction is the dipole-dipole interaction. Examples of suitable functional groups are carboxyl groups, (primary, secondary, tertiary and quaternary) amino groups and C—H-acidic groups (e.g. β-diketones). A plurality of these groups may also be present simultaneously in a molecule (betaines, amino acids, EDTA). Accordingly, examples of preferred surface modifiers are saturated or unsaturated mono- and polycarboxylic acids (preferably monocarboxylic acids) having 1 to 12 carbon atoms (e.g. formic acid, acetic acid, propionic acid, butyric acid, pentanoic acid, hexanoic acid, acrylic acid, methacrylic acid, crotonic acid, citric acid, adipic acid, succinic acid, glutaric acid, oxalic acid, maleic acid and fumaric acid) and their esters (preferably C1-C4-alkyl esters) and amides, e.g. methyl methacrylate. Examples of further suitable surface modifiers are imides and quaternary ammonium salts of the formula N+R10R20R30R40Y− in which R10 to R40 are aliphatic, aromatic or cycloaliphatic groups which may differ from one another and which have preferably 1 to 12, in particular 1 to 6, carbon atoms and Y− is an inorganic or organic anion, e.g. Cl or acetate; mono- and polyamines, in particular those of the general formula R3-nNHn, in which n is 0, 1 or 2 and the radicals R, independently of one another, are alkyl groups having 1 to 12, in particular 1 to 6 and particularly preferably 1 to 4 carbon atoms, e.g. methyl, ethyl, n-propyl, isopropyl and butyl, and ethylenepolyamines, e.g. ethylenediamine, diethylenetriamine; amino acids; imines; β-dicarbonyl compounds having 4 to 12, in particular 5 to 8, carbon atoms, such as, for example, acetylacetone, 2,4-hexanedione, 3,5-heptanedione, acetoacetic acid and C1-C4-alkyl acetoacetates; and modified alcoholates in which some of the OR groups (R as defined above) are substituted by inert organic groups. For the electrostatic stabilization of the nanoscale particles, for example, the compounds known for this purpose, such as, for example, NaOH, NH3, KOH, Al(OH)3 or tetramethylammonium hydroxide, may also be used. The nanocomposite compositions used according to the invention may furthermore contain polymerizable monofunctional and/or bifunctional organic monomers, oligomers and/or polymers from the group consisting of (poly)acrylic acid, (poly)methacrylic acid, (poly)acrylates, (poly)methacrylates, (poly)acrylamides, (poly)methacrylamides, (poly)carbamides, (poly)olefins, (poly)styrene, (poly)amides, (poly)imides, (poly)vinyl compounds, (poly)esters, (poly)arylates, (poly)carbonates, (poly)ethers, (poly)etherketones, (poly)sulfones, (poly)epoxides, fluorine polymers, organo(poly)siloxanes, (poly)siloxanes and hetero(poly)siloxanes. Examples are (poly)vinyl chloride, (poly)vinyl alcohol, (poly)vinylbutyral, corresponding copolymers, e.g. poly(ethylene-vinyl acetate), polyethylene terepthalate, polyoxymethylene, polyethylene oxide or polyphenylene oxide, organopolysiloxanes or heteropolysiloxanes formed with metals and transition metals, as described, for example, in EP-A-36 648 and EP-A-223 067, and mixtures of two or more of these polymers, provided that they are compatible with one another. Instead of said polymers, their oligomers and/or precursors (monomers) may also be used. Among these polymers, polymers, such as polyacrylates, polymethacrylates (e.g. PMMA), glycidyl ethers, such as, for example, bisphenol A diglycidyl ether, and polyvinylbutyral, which are soluble in organic solvents are particularly preferred. The polymerizable monofunctional and/or bifunctional organic monomers, oligomers and/or polymers may be present in an amount of from 0 to 20 mol %, preferably from 0.1 to 15 mol %, in particular from 1 to 10 mol %, based on the polymerizable silane. A preferred nanocomposite composition furthermore contains a fluorosilane of the formula (III) R3(X1)3Si (III) in which R3 is a partly fluorinated or perfluorinated C2-C20-alkyl and X1 is C1-C3-alkoxy, methyl, ethyl or chlorine. Partly fluorinated alkyl is understood as meaning those alkyl radicals in which at least one hydrogen atom is replaced by a fluorine atom. Preferred radicals R3 are CF3CH2CH2, C2F5CH2CH2, C4F9CH2CH2, n-C6F13CH2CH2, n-C8F17CH2CH2, n-C10F21CH2CH2 and i-C3F7O-(CH2)3. Examples of fluorosilanes of the formula (III), which are also commercially available, are tridecafluoro-1,1,2,2-tetrahydrooctyl-1-triethoxysilane, CF3CH2CH2 SiCl2CH3, CF3CH2CH2 SiCl(CH3)2, CF3CH2CH2Si(CH3)(OCH3)2, i-C3F7O-(CH2)3SiCl2CH3, n-C6F13CH2CH2SiCl2CH3 and n-C6F13CH2CH2 SiCl(CH3)2. The fluorosilanes of the formula (III) may be present in an amount of from 0 to 3% by weight, preferably from 0.05 to 3% by weight, particularly preferably from 0.1 to 2.5% by weight, in particular from 0.2 to 2% by weight, based on the total weight of the nanocomposite composition. The presence of fluorosilanes is required in particular when a glass or silica glass stamp is used as the transfer imprint stamp. The nanocomposite composition expediently contains a polymerization, polyaddition and/or polycondensation catalyst which can thermally and/or photochemically induce crosslinking and curing (referred to collectively as “crosslinking initiator”). Photoinitiators used may be, for example, the commercially available initiators. Examples of these are Irgacure® 184 (1-hydroxycyclohexyl phenyl ketone), Irgacure® 500 (1-hydroxycyclohexyl phenyl ketone, benzophenone) and other photoinitiators of the Irgacure® type available from Ciba; Darocur® 1173, 1116, 1398, 1174 and 1020 (available from Merck), benzophenone, 2-chlorothioxanthone, 2-methylthioxanthone, 2-isopropylthioxanthone, benzoin, 4,4′-dimethoxybenzoin, benzoin ethyl ether, benzoin isopropyl ether, benzil dimethyl ketal, 1,1,1-trichloroacetophenone, diethoxyacetophenone and dibenzosuberone. Suitable thermal initiators are, inter alia, organic peroxides in the form of diacyl peroxides, peroxydicarbonates, alkyl peresters, dialkyl peroxides, perketals, ketone peroxides and alkyl hydroperoxides. Specific examples of such thermal initiators are dibenzoyl peroxide, tert-butyl perbenzoate and azobisisobutyronitrile. When used, the crosslinking initiator is usually employed in an amount of from 0.1 to 5, preferably from 0.5 to 3, % by weight, based on the nanocomposite composition. The invention furthermore relates to a microlithographic arrangement comprising a) a microstructured layer of a nanocomposite composition as a top coat; b) a bottom coat comprising an aromatics-containing (co)polymer containing novolaks, styrenes, (poly)hydroxystyrenes and/or (meth)acrylates; c) a substrate. The substrate is preferably a semiconductor material to be structured, e.g. a silicon wafer or indium tin oxide layers on glass. The bottom coat present thereon should have good adhesion both to the top coat a) and to the substrate and preferably has a layer thickness of from about 0.1 to 20 μm. The invention furthermore relates to a method for the production of such a microlithographic arrangement, comprising the steps: i) production of an uncured sol film of the nanocomposite composition described above; ii) production of a target substrate comprising bottom coat b) and substrate c); iii) transfer of sol film material from i) by means of a microstructured transfer imprint stamp to the bottom coat b) in ii); iv) curing of the transferred sol film material; v) removal of the transfer imprint stamp to give an imprinted microstructure as top coat a). The uncured sol film i) is expediently applied to a planar arrangement, comprising a support, e.g. glass, silica glass, plastic or silicon wafer, and/or an adhesion-promoting film. The adhesion-promoting film contains organic polymers which ensure good wetting with respect to the support and the nanocomposite sol film to be deposited thereon. The adhesion-promoting film may comprise, for example, an aromatics-containing polymer or copolymer, containing novolaks, styrenes, (poly)hydroxystyrenes and/or (meth)acrylates. The adhesion-promoting film can be applied to the support by known methods, such as, for example, spin coating. The nanocomposite composition according to the invention is then applied as a sol film to the adhesion-promoting film, expediently in a film thickness of from 0.5 to 1 μm, by known methods, such as, for example, spin coating, spray coating or roller coating. The sol film preferably has a viscosity of from 80 mPa s to 2 Pa s, preferably from 100 mPa s to 1 Pa s and particularly preferably from 200 mPa s to 600 mPa s. The nanocomposite composition can be applied either as such or preferably as a solution in an organic solvent. Examples of suitable solvents are alcohols, such as butanol, ketones, such as acetone, esters, such as ethyl acetate, ethers, such as tetrahydrofuran, and aliphatic, aromatic and halogenated hydrocarbons, such as hexane, benzene, toluene and chloroform. The nanocomposite composition can be prepared, for example, by dispersing the nanoscale particles in one of the abovementioned solvents and/or one of said polymerizable compounds, for example with stirring or by means of ultrasonics. The dispersion obtained is then mixed with the other components of the nanocomposite composition, if required with dilution with a solvent. The solvent used for dilution is either identical to the solvent used for the dispersion or miscible therewith. If the solvent used does not evaporate during the application of the nanocomposite sol film, it is expedient substantially to remove the solvent after application of the film by suitable measures, such as, for example, heating, since otherwise transfer of the sol film material by means of a transfer imprint stamp is problematic. The target substrate can be produced by the same methods. The bottom coat can have a composition which is the same as or similar to that of the above-described adhesion-promoting film of the starting substrate. After application of the nanocomposite sol and evaporation of the solvent in air, the fluorosilane molecules have accumulated at the surface, into which the glass or silica glass transfer imprint stamp is then pressed for from about 5 to 300 seconds, preferably from 10 to 60 seconds (immersion time). The transfer imprint stamp may also consist of silicone rubber. In this case, no fluorosilanes of the formula (III) are required. The fluorinated side chains of the fluorosilane molecules are in principle repelled by the hydrophilic surface of the glass or silica glass stamp and only weakly attracted by the surface of the adhesion-promoting film or of the substrate, and therefore diffuse in a concentration gradient. After said immersion time, the transfer imprint stamp is pulled out of the excess nanocomposite sol film. The adhesion of the sol film material in the 30 to 500 nm, preferably 100 to 200 nm, deep and broad microchannels of the stamp due to capillary forces and due to partial removal of the fluorosilane molecules from the (silica) glass surface is sufficiently great for it to be picked up by the stamp. If the immersion time is not reached, the transfer is incomplete. The transfer of the microstructure to the target substrate is effected by the air, preferably in the course of from 10 to 300 seconds. The fluorosilane accumulates at the interface with the air, so that the wetting of the stamp is very good and the sol does not contract to a drop in the transfer stamp. After the transfer stamp is placed on the bottom coat b) of the target substrate, the stamp is pressed against the bottom coat b) for a duration of from 10 to expediently 300 seconds, preferably from 20 to 50 seconds, in particular from 30 to 40 seconds, under a pressure of from 10 to 100 kPa. During this, the fluorosilane diffuses back in the direction of the (silica) glass surface, so that, after curing, the adhesion to the bottom coat is sufficiently good and that to the transfer stamp is sufficiently poor. The layer thickness of the transferred material is from 50 to 1 000 nm, preferably from 150 to 500 nm. If the same nanocomposite sol were to be used without fluorosilane and transferred by means of a silica glass stamp, no structure would be deposited on the target substrate. The sol remains completely in the stamp. While the transfer imprint stamp rests on the bottom coat, thermal curing or UV curing takes place. In the case of UV-transparent transfer stamps, curing by UV radiation is preferred. After heating to about 80 to 150° C. for from about 1 to 10 minutes and/or UV irradiation for from about 5 to 20 minutes, the transferred sol film material has cured and the transfer imprint stamp is removed to give an imprinted microstructure (top coat a). An investigation of this microstructured arrangement with the aid of a scanning electron microscope shows that not only the imprinted microstructure remains behind on the target substrate but also an unstructured residual layer of the nanocomposite sol film having a thickness of less than 30 nm. For subsequent use in microelectronics, it is necessary for the nanocomposite sol film and the bottom coat to have different etch resistance in order to achieve a steep wall slope and a high aspect ratio (ratio of height of the lands to distance between two lands). Thus, the nanocomposite composition used according to the invention can be etched with a CHF3/O2 gas mixture but not by an oxygen plasma. In the case of the bottom coat, the opposite is true. The present invention therefore also relates to a method for the production of a microstructured semiconductor material, comprising the abovementioned steps i) to v), support c) being the semiconductor material to be structured, and the steps vi) plasma etching of the residual layer of the nanocomposite sol film, preferably with CHF3/O2 plasma, vii) plasma etching of the bottom coat, preferably with O2 plasma, viii) doping of the semiconductor material in the etched areas, or etching of the semiconductor material. After the etching process, the resist coating can be removed by means of conventional solvents, such as, for example, tetramethylammonium hydroxide. Scanning electron micrographs show that, after the method according to the invention, nanostructures having an edge length of about 150 nm and a wall slope of about 90° are imprinted. EXAMPLES 1) Preparation of a Nanocomposite Composition 236.1 g (1 mol) of glycidyloxypropyltrimethoxysilane (GPTS) are refluxed with 27 g (1.5 mol) of water for 24 hours. Methanol formed is then stripped off on a rotary evaporator at 70° C. 345 g of tetrahexylammonium hydroxide-modified silica sol (SiO2 colloid, diameter about 10 nm, about 30% strength by weight in isopropanol, modified with 2.4 mg of tetrahexylammonium hydroxide solution (40% strength by weight in water) per g of silica sol) are added, with stirring, to the GPTS condensate thus prepared. The isopropanol is then removed in a rotary evaporator. In each case 1% by weight, based on the sol, of a cationic photoinitiator (UVI 6974, Union Carbide) and tridecafluoro-1,1,2,2-tetrahydrooctyl-1-triethoxysilane, and 22.3 g (0.0714 mol) of bisphenol A diglycidyl ether, are added to the solvent-free sol. The sol is diluted by adding isopropoxyethanol until a nanocomposite composition having a viscosity of about 300 mPa s is obtained. 2) Preparation of the Novolak for Starting Substrate and Target Substrate: 120 g of m-cresol, 60 g of p-cresol and 106.8 g of 37% strength by weight formalin are heated together with 4 g of oxalic acid dihydrate for 6 hours at 100° C. For the removal of water and unconverted cresol, formaldehyde and oxalic acid by distillation, the reaction mixture is heated to 200° C. and the pressure is reduced to 50 mbar. 172 g of novolak are obtained as a solid. 3) Production of the Starting Substrate: a) A 4 inch silicon wafer pretreated with hexamethyidisilazane is coated in a spin coater with a novolak solution (17.5 g of the novolak prepared above in 82.3 g of PGMEA). A softbake is then effected for 90 s at 110° C. and a hardbake for 90 s at 235° C., so that the resulting layer thickness is about 500 nm (adhesion-promoting layer). b) The nanocomposite composition prepared above is applied by spin coating (2 000 revolutions, 30 s) to the adhesion-promoting layer thus prepared. For removal of the solvent, the sol film is dried for 1 minute at about 25° C. without the sol film curing. The layer thickness of the nanocomposite sol film is about 500 nm. 4) Production of the Target Substrate: The target substrate is produced analogously to 3a). 5) Transfer and Imprinting of the Microstructure onto the Target Substrate: The imprinting apparatus is a computer-controlled test machine (Zwick 1446 model) which makes it possible to program loading and relief speeds and to maintain defined pressures over a specific time. The force transmission is effected via a shaft to which the imprinting stamp is fastened by means of a joint. This permits the exact orientation of the imprint structure relative to the substrate. A metal halide lamp (UV-S400 model from Panacol-Elosol GmbH, UV-A radiation 325-380 nm) serves for the photochemically initiated curing. A microstructured silica glass stamp (4×4 cm, structure depth 200 nm) is pressed under a force of 40 N into the uncured sol film of the starting substrate produced above. After a waiting time of 15 s, the stamp is pulled out of the excess sol film. The stamp now completely wet with sol film material is held in the air for 30 s, then placed on the target substrate produced above and pressed for 35 s with a force of 50 N onto the bottom coat, the transferred film being cured by the UV lamp. After an imprinting and exposure time of 5 minutes altogether, the stamp is removed and the cured microstructured sol film material is retained on the target substrate. A scanning electron micrograph of the coating shows that structures having a geometry of 150 nm×150 nm with a steep wall slope are reproduced. A residual layer thickness of 25 mm of sol film material is present between bottom coat and the transferred structures. 6) Etching Process The substrate was etched under the following conditions: 1) with CHF3/O2 (25:10), 300 W, 50 mmHg, RIE mode, anisotropic; for removal of the residual top coat; 2) with O2, 300 W, 50 mmHg, RIE mode, anisotropic; for removal of the bottom coat. Aspect ratio about 3.
20050503
20081007
20051013
75123.0
0
DAHIMENE, MAHMOUD
NANOIMPRINT RESIST
UNDISCOUNTED
0
ACCEPTED
2,005
10,511,654
ACCEPTED
Packet error signal generator
A software packet error system for a High Definition Television (HDTV) receiver. A data packet error signal is transferred from a forward error correcting Reed-Solomon decoder to a transport processor. In response to a segment sync signal, the transport processor generates an error signal which appears on a programmable output pin. The software packet error signal is synchronized with the outgoing data packet signal such that each data packet is bracketed or framed by its associating packet error signal. Precession of the start of the data packets forwarded on the transport but relative to the start of the data packets appearing at the output of the decoder occurs as a result of a training packet generated for every 312 data packets. The precession is reset at the beginning of every field and is predictable across the field duration with sufficient accuracy to make the software packet error mechanism feasible.
1. An apparatus for processing a received signal containing a datastream, comprising: a signal decoder, the signal decoder generating a first error signal in response to indecipherable data received by the decoder; and a transport processor, the transport processor receiving the first error signal, the transport processor generating a second error signal after receiving the first error signal. 2. The apparatus of claim 1, wherein the datastream comprises a modulated signal containing data packets. 3. The apparatus of claim 2, further comprising: a transport bus, the transport bus forwarding data packets to subsequent processing stages; and at least one synchronization signal, the transport processor generating the second error signal in response to receiving the synchronization signal. 4. The apparatus of claim 4, wherein the second error signal is forwarded to the transport bus so as to have a synchronized relationship to the data packets being forwarded via the transport bus. 5. The apparatus of claim 5, wherein the second error signal is formed as a series of logical high frames, each logical high frame being associated with a data packet. 6. The apparatus of claim 6, wherein the duration of each logical high frame of the second error signal has a duration greater than the data packet associated with the logical high frame. 7. The apparatus of claim 7, wherein each logical high frame of the second error signal begins at an earlier time than the data packet associated with the logical high frame. 8. The apparatus of claim 8, wherein each logical high frame of the second error signal ends at a later time than the data packet associated with the logical high frame. 9. The apparatus of claim 9, further comprising a demodulator, the demodulator deriving the synchronization signal from the received signal. 10. The apparatus of claim 1 wherein the transport processor is implemented as a microprocessor. 11. A system for generating an error signal based on an error encountered while processing a received signal which includes an image representative datastream containing data packets, comprising: a forward error detecting and correcting decoder which generates a first error signal; a synchronization signal derived from the received signal; a transport processor interconnected to receive the first error signal and the synchronization signal, the transport processor generating a second error signal in response to the first error signal and the synchronization signal. 12. The system of claim 11, further comprising a transport bus, the data packets being forwarded to subsequent processing stages via the transport bus. 13. The system of claim 12, wherein the second error signal is forwarded via the transport bus simultaneously with the data packets associated with the second error signal. 14. The system of claim 13, wherein the data packets are forwarded as a series of discrete spaced apart frames, the second error signal being adapted to indicate an error in a defective data packet by having a duration that spans the frame of the defective data packet. 15. The system of claim 14, wherein the second error signal assumes a logical low state when no error is present in a data packet. 16. The system of claim 15, wherein the forward error detecting and correcting decoder is a Reed-Solomon decoder. 17. The system of claim 11 wherein the transport processor is implemented as a microprocessor. 18. In a system for processing a received signal containing an image representative datastream containing data packets, a packet error signal generating method comprising the steps of: demodulating the received signal to produce a demodulated signal; error detecting the demodulated signal to produce a first error signal; forwarding the first error signal to a transport processor; forwarding a synchronization signal to the transport processor, thereby associating the first error signal with a particular data packet; and generating a second error signal in response to the synchronization signal being received by the transport processor. 19. A method according to claim 17, further comprising the step of generating the second error signal as a series of discrete frames, each frame having a duration greater than an associated data packet. 20. A method according to claim 18, further comprising the steps of: starting each discrete second error signal frame before an associated data packet begins; and stopping each discrete second error signal frame after an associated data packet ends. 21. A method according to claim 19, wherein the error detecting step comprises Reed-Solomon error detection and correction.
The present patent application is based on and claims priority from Provisional U.S. Patent Application No. 60/372,203 of the same title filed on Apr. 17, 2002. FIELD OF THE INVENTION This invention relates to generally to a method and apparatus for processing a high definition television (HDTV) signal, and more particularly to the generation of error signals by means of software rather than hardware. BACKGROUND OF THE INVENTION An example of a portion of a prior art HDTV system 21 is depicted in FIG. 1. In such a system, a terrestrial analog broadcast signal 1 is forwarded to an input network or front end that includes an RF tuning circuit 14 and an intermediate frequency processor 16 including a double conversion tuner for producing an IF passband output signal 2. The broadcast signal 1 is a carrier suppressed eight bit vestigial sideband (VSB) modulated signal as specified by the Grand Alliance for HDTV standards. Such a VSB signal is represented by a one dimensional data symbol constellation where only one axis contains data to be recovered by the receiver 21. The passband IF output signal 2 generated by IF unit 316 is converted to an oversampled digital symbol datastream by an analog to digital converter (ADC) 19. The output oversampled digital datastream 3 is demodulated to baseband by a digital demodulator and carrier recovery network 22. The recovery of data from modulated signals conveying digital information in symbol form usually requires that three functions be performed by receiver 21. First is timing recovery for symbol synchronization, second is carrier recovery (frequency demodulation to baseband), and finally channel equalization. Timing recovery is a process by which a receiver clock (timebase) is synchronized to a transmitter clock. This permits a received signal to be sampled at optimum points in time to reduce slicing or truncation errors associated with decision directed processing of received symbol values. Adaptive channel equalization is a process of compensating for the effects of changing conditions and disturbances on the signal transmission channel. This process typically employs filters that remove amplitude and phase distortions resulting from frequency dependent, time variable characteristics of the transmission channel, thereby improving symbol decision capability. Carrier recovery is a process by which a received RF signal, after being converted to a lower intermediate frequency passband (typically near baseband), is frequency shifted to baseband to permit recovery of the modulating baseband information. A small pilot signal at the suppressed carrier frequency is added to the transmitted signal 1 to assist in achieving carrier lock at the VSB receiver 21. The demodulation function performed by demodulator 22 is accomplished in response to the reference pilot carrier contained in signal 1. Unit 22 produces as an output a demodulated symbol datastream 4. ADC 19 oversamples the input 10.76 Million Symbols per second VSB symbol datastream 2 with a 21.52 MHz sampling clock (twice the received symbol rate), thereby providing an oversampled 21.52 Msamples/sec datastream with two samples per symbol. The advantage of using a two sample per symbol scheme as compared to one sample per symbol is the ability to use symbol timing recovery schemes such as the Gardner symbol timing recover method. Interconnected to ADC 19 and demodulator 22 is a segment sync and symbol clock recovery network 24. The network 24 detects and separates from random noise the repetitive data segment sync components of each data frame. The segment sync signals 6 are used to regenerate a properly phased 21.52 MHz clock which is used to control the datastream symbol sampling performed by ADC 19. A DC compensator 26 uses an adaptive tracking circuit to remove from the demodulated VSB signal 4 a DC offset component present in the pilot signal. Field sync detector 28 detects the field sync component by comparing every received data segment with an ideal field reference signal stored in the memory of the receiver 21. The field sync detector 28 also provides a training signal to channel equalizer 34. NTSC interference detection and filtering are performed by unit 5, an example of which is disclosed in U.S. Pat. No. 5,512,957, entitled METHOD AND APPARATUS FOR COMBATING CO-CHANNEL NTSC INTERFERENCE FOR DIGITAL TV TRANSMISSION, issued on Apr. 30, 1996, to Hulyalkar. Afterwards, the signal 7 is adaptively equalized by channel equalizer 34 which may operate in a combination of blind, training and decision directed modes. An example of an adaptive channel equalizer is disclosed in U.S. Pat. No. 6,490,007, entitled ADAPTIVE CHANNEL EQUALIZER, issued on Dec. 3, 2002 to Bouillet et al. The output datastream from NTSC filter 5 is converted to a one sample/symbol (10.76 Msymbol/sec) datastream prior to reaching equalizer 34. Equalizer 34 corrects channel distortions, but phase noise randomly rotates the symbol constellation. Phase tracking network 36 removes the residual phase and gain noise in the output signal received from equalizer 34, including phase noise which has not been removed by the preceding carrier recovery network 22 in response to the pilot signal. The phase corrected output signal 9 of tracking network 36 is then trellis decoded by unit 25, deinterleaved by unit 24, Reed-Solomon error corrected by unit 23 and descrambled by unit 27. The final step is to forward the decoded datastream 10 to audio, video and display processors 50. In the receiver 21, the output signal 11 of the Reed-Solomon decoder 23 includes data sent in packets for subsequent processing by the audio, visual and display processors 50. The data is accompanied by a data framing signal, a clock signal, and an error signal that indicates whether or not the decoder 23 detected an uncorrectable error in the data packet. Typically, the decoder unit 23 generates the error signal via circuitry within the decoder 23 dedicated to this purpose. However, if the error generating hardware does not work correctly, additional expense must be incurred by incorporating hardware in subsequent stages that will assist in the generation of the error detection signal. Ideally, a software based solution is needed which will eliminate the need for including redundant error detection circuitry in an HDTV receiver. BRIEF SUMMARY OF THE INVENTION The present invention utilizes a transport processor, implemented as a microprocessor to execute software instructions within an HDTV receiver to generate an error signal when the receiver demodulator detects an uncorrectable error within a data packet. A packet error signal is generated by the forward error correcting Reed-Solomon decoder residing within the demodulator integrated circuit package. The integrated circuit includes a programmable output pin which generates a software packet error signal that is synchronized with the outgoing data packets. The error signal has a duration greater than its associated data packet, and is programmed to begin before and end after its associated data packet. In this manner, the error signal completely brackets or frames the underlying data packet. The software packet error signal is made available to the microprocessor by utilizing a different timing scheme than the one used to advance data packets on the transport processor bus. Every 313th data packet is training data generated by the field sync detector for use by the adaptive channel equalizer. The training data packet is not sent to the transport processor. The missing 313th data packet creates a gap in the data stream that is concealed by adding a small increment of time to the gaps existing between the remaining 312 data packets that are eventually sent to the transport processor. This added time has the effect of causing the start time of the 312 data packets on the transport bus to begin earlier than the start time of the data packets appearing at the output of the Reed-Solomon decoder. This precession effect is reset at the beginning of each data field and is predictable across the duration of each data field. BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a block diagram of a portion of a prior art high definition television receiver; FIG. 2 is a block diagram of a portion of a high definition television receiver constructed according to the principles of the present invention.; FIG. 3 is a timing diagram depicting the synchronization of a data signal and a software packet error signal as utilized by the invention depicted in FIG. 2; FIG. 4 is a timing diagram depicting transmission of the software packet error signal according to the principles of the present invention; FIG. 5 is a microcode listing that permits implementation of the present invention; and FIG. 6 is a flow chart depicting the implementation and operation of the present invention. DETAILED DESCRIPTION OF THE INVENTION In FIG. 2 a portion of an HDTV receiver 12 is depicted. The phase corrected signal 13 from equalizer 21 is trellis decoded by unit 40, then deinterleaved by unit 42. Decoded and deinterleaved data packets from unit 40 are error detected and corrected by a forward error correcting (FEC) unit 44 such as a Reed-Solomon error detecting and decoding network. Error corrected packets from unit 44 are descrambled (derandomized) by unit 46. Transport processor 60 provides appropriate timing control and clock signals for other elements of the receiver 12 and also serves as a data communications link between the various networks that make up the receiver 12. In the illustrated embodiment, the transport processor 60 is implemented as a microprocessor 60 executing software instructions to operate in a manner described in more detail below. Error corrector 44 and microprocessor 60 cooperate to control the operation of equalizer 21. Afterwards, a decoded datastream is subjected to audio, video and display processing by unit 15. The packet error rate is a measurement performed within the FEC unit 44 based on well known FEC algorithms which are capable of determining when a packet contains more errors than can be corrected. The FEC generates a packet error signal 17 which is forwarded to microprocessor 60 via bus 18. Other synchronization signals such as the segment sync signal 20 and the field sync signal 29 are also sent to bus 18, and when the packet error signal 17 is sensed by microprocessor 60, the arrival of one of the other synchronization signals 20 or 29, for example, triggers the creation of a software packet error (SPE) which appears on programmable output pin 30. Referring also to FIG. 3, the SPE signal 31 is generated so as to be synchronized with the outgoing data packet signal 32. In particular, each error signal 33, for example, frames or brackets its associated data packet 35. The leading edge 37 of SPE 33 occurs earlier in time than the leading edge 38 of the associated data packet 38. Similarly, the trailing edge 39 of the SPE 33 occurs later in time than the trailing edge 41 of the data packet 35. This bracketing or framing characteristic of the SPE 31 is important because the error signal 17 available to microprocessor 60 uses a different timing scheme than the data packets 35 appearing on the transport bus 48. Every 313th data packet is in fact training data for the adaptive channel equalizer 21 and so is not forwarded to the transport bus 48. The missing 313th packet creates a gap in the sequence of data packets that is redistributed by the data deinterleaver 42 which adds an additional increment of time to the space 43 existing between each of the remaining 312 data packets which are actually forwarded to the transport bus 48. The time that is added to the gaps 43 has the effect of causing the leading edge 38 of each data packet 35 to appear on the transport bus 48 at a time that is earlier than the appearance of the same data packets at the output 45 of the Reed-Solomon decoder 44. This precession effect is reset at the beginning of each data field, and is predictable across the duration of the each field. The software packet error signal 31 associated with the current segment sync signal appearing on the derandomizer test bus 47 is sent at the same time as the data packet associated with the next segment is sent to the transport bus 48. In this manner, the microprocessor 60 receives the packet error signal at least one segment prior to the time that the packet error signal must be used. In other words, the packet error signal must advance from the derandomizer test bus 47 and be available for use on programmable output pin 30 at the arrival of the next segment sync signal 20 with sufficient time to encompass the beginning and end of the packet clock signal appearing on transport bus 48 and with enough margin to accommodate system clock rate variations. Each data packet clock pulse is delayed by a slightly larger amount than the preceding clock pulse with respect to the segment sync signal 20 in order to evenly distribute across the entire data field the sync gap caused by the missing training signal data packet. The microprocessor 60 monitors the segment count relative to the field sync signal 17 of Reed-Solomon decoder 44 and delays the transition of the software packet error signal 31 so that the transition occurs between packet enable signals appearing on the transport bus 48. At some point the timing scenario becomes that depicted in FIG. 4, i.e. the packet error signal F_ERR(0) is generated by waiting almost to the end 49 of the packet interval 51 before transitioning to the value 52 for the next packet 53. Unfortunately, the microprocessor 60 must consume processing time during this waiting period. A better approach is to skip outputting the F_ERR signal for one packet and reset the F_ERR output to occur shortly after the sync signal associated with subsequent packets. The error signal transition 54 thus occurs shortly after the sync signal 20 appears, as is the case with error signal F_ERR (1). The segment sync signal to skip must be selected properly to avoid misframing the outgoing packets. There will typically be more than one such segment sync signal which may be skipped. The timing protocol of packet error signal 31 with respect to the segment sync signal 20 is reset for the first packet occurring after the Reed-Solomon field sync signal 17. This causes the packet clock and the error signal 31 to maintain the timing relationship illustrated in FIG. 4. However, the demodulator field sync signal 29 drives the interrupt of microprocessor 60 and occurs 55 segment sync pulses prior to the field sync pulse 17 associated with decoder 44. In order to compensate for the 55 segment delay, the packet error signal 31 is not reset until 55 segment sync pulses have occurred following the demodulator field sync pulse 29. Since one segment sync signal 20 has been used instead as training data, only 312 segment sync signals 20 appear on the randomizer test bus 47. Assuming a clock speed of 10.76 MHz, the missing segment sync signal appears 13 microseconds prior to the demodulator field sync pulse 29. Since the packet error signal 31 generated in response to the missing segment does not correspond to a data packet being forwarded along the transport bus 48, this particular error signal must be discarded. This is accomplished by incrementing the read pointer in the field sync register of microprocessor 60. At the time this increment occurs, the write pointer is already one pulse ahead of the read pointer, as illustrated in FIG. 4, so the software packet error signal 31 remains available in advance of when it is needed to frame its associated data packet. Referring also to FIG. 5 and 6, the microcode listing used to implement the aforementioned functions can be inspected. Lines 001-069 address the manipulation of segment sync signal 20, while lines 070-076 deal with the field sync signal 29. At step 61, lines 001-004 perform initialization functions, such as clearing the interrupt status bit and updating the segment sync counter for the one microsecond timer. The actual software packet error generation steps begins at step 62 with lines 005-008, and include the restarting and resetting of the capture state machine and allowing the microprocessor 60 access to the random access memory. Lines 009-015 (step 63) take the captured software packet error signal 31 and set it up on the current data segment in order to gate the next outgoing data packet. This step includes obtaining the value of the SPE 31 which is contained in bit 15, storing it in a FIFO buffer, and incrementing the FIFO input pointer. At step 64, lines 016-022 monitor data packet traffic since the last field sync pulse 29 in order to correctly resync the microprocessor 60 enable pulse. Lines 023-026 (step 65) cause the SPE signal 31 to maintain is state until it is time to change state as depicted in FIG. 4. The calculated delay period is updated at step 66 with lines 027-033, where the delay is incremented once for every three data packets. For a clock frequency of 10.76 MHz, the delay loop is approximately 0.629 microseconds per loop, and the segment precession time of the outgoing data packets is approximately 0.2158 microseconds (0.629/0.2158 is approximately equal to 3). After completing step 66, lines 034-042 update the gate signal (step 67) in order to suppress the packet associated with a HIGH SPE signal 31. At step 68, lines 043-054 verify the consistency of the packet error count. Since the field sync signal pulse 29 occurs 55 segment sync pulses before the Reed-Solomon decoder 44 sync pulse, at step 69 the microcode lines 055-069 anticipate the occurrence of the decoder 44 sync pulse and resync at the appropriate time. At step 70 the field sync pulse 29 is monitored at lines 070-076, and the entire process is then restarted at step 61. While this process has been described with reference to particular frequencies, segment delays, and signal paths, etc., the present invention may be tailored to suit other configurations. Further, different protocols may be employed based on the absolute packet error rate or whether or not the packet error rate remains relatively unchanged over a predetermined period of time.
<SOH> BACKGROUND OF THE INVENTION <EOH>An example of a portion of a prior art HDTV system 21 is depicted in FIG. 1 . In such a system, a terrestrial analog broadcast signal 1 is forwarded to an input network or front end that includes an RF tuning circuit 14 and an intermediate frequency processor 16 including a double conversion tuner for producing an IF passband output signal 2 . The broadcast signal 1 is a carrier suppressed eight bit vestigial sideband (VSB) modulated signal as specified by the Grand Alliance for HDTV standards. Such a VSB signal is represented by a one dimensional data symbol constellation where only one axis contains data to be recovered by the receiver 21 . The passband IF output signal 2 generated by IF unit 316 is converted to an oversampled digital symbol datastream by an analog to digital converter (ADC) 19 . The output oversampled digital datastream 3 is demodulated to baseband by a digital demodulator and carrier recovery network 22 . The recovery of data from modulated signals conveying digital information in symbol form usually requires that three functions be performed by receiver 21 . First is timing recovery for symbol synchronization, second is carrier recovery (frequency demodulation to baseband), and finally channel equalization. Timing recovery is a process by which a receiver clock (timebase) is synchronized to a transmitter clock. This permits a received signal to be sampled at optimum points in time to reduce slicing or truncation errors associated with decision directed processing of received symbol values. Adaptive channel equalization is a process of compensating for the effects of changing conditions and disturbances on the signal transmission channel. This process typically employs filters that remove amplitude and phase distortions resulting from frequency dependent, time variable characteristics of the transmission channel, thereby improving symbol decision capability. Carrier recovery is a process by which a received RF signal, after being converted to a lower intermediate frequency passband (typically near baseband), is frequency shifted to baseband to permit recovery of the modulating baseband information. A small pilot signal at the suppressed carrier frequency is added to the transmitted signal 1 to assist in achieving carrier lock at the VSB receiver 21 . The demodulation function performed by demodulator 22 is accomplished in response to the reference pilot carrier contained in signal 1 . Unit 22 produces as an output a demodulated symbol datastream 4 . ADC 19 oversamples the input 10.76 Million Symbols per second VSB symbol datastream 2 with a 21.52 MHz sampling clock (twice the received symbol rate), thereby providing an oversampled 21.52 Msamples/sec datastream with two samples per symbol. The advantage of using a two sample per symbol scheme as compared to one sample per symbol is the ability to use symbol timing recovery schemes such as the Gardner symbol timing recover method. Interconnected to ADC 19 and demodulator 22 is a segment sync and symbol clock recovery network 24 . The network 24 detects and separates from random noise the repetitive data segment sync components of each data frame. The segment sync signals 6 are used to regenerate a properly phased 21.52 MHz clock which is used to control the datastream symbol sampling performed by ADC 19 . A DC compensator 26 uses an adaptive tracking circuit to remove from the demodulated VSB signal 4 a DC offset component present in the pilot signal. Field sync detector 28 detects the field sync component by comparing every received data segment with an ideal field reference signal stored in the memory of the receiver 21 . The field sync detector 28 also provides a training signal to channel equalizer 34 . NTSC interference detection and filtering are performed by unit 5 , an example of which is disclosed in U.S. Pat. No. 5,512,957, entitled METHOD AND APPARATUS FOR COMBATING CO-CHANNEL NTSC INTERFERENCE FOR DIGITAL TV TRANSMISSION, issued on Apr. 30, 1996, to Hulyalkar. Afterwards, the signal 7 is adaptively equalized by channel equalizer 34 which may operate in a combination of blind, training and decision directed modes. An example of an adaptive channel equalizer is disclosed in U.S. Pat. No. 6,490,007, entitled ADAPTIVE CHANNEL EQUALIZER, issued on Dec. 3, 2002 to Bouillet et al. The output datastream from NTSC filter 5 is converted to a one sample/symbol (10.76 Msymbol/sec) datastream prior to reaching equalizer 34 . Equalizer 34 corrects channel distortions, but phase noise randomly rotates the symbol constellation. Phase tracking network 36 removes the residual phase and gain noise in the output signal received from equalizer 34 , including phase noise which has not been removed by the preceding carrier recovery network 22 in response to the pilot signal. The phase corrected output signal 9 of tracking network 36 is then trellis decoded by unit 25 , deinterleaved by unit 24 , Reed-Solomon error corrected by unit 23 and descrambled by unit 27 . The final step is to forward the decoded datastream 10 to audio, video and display processors 50 . In the receiver 21 , the output signal 11 of the Reed-Solomon decoder 23 includes data sent in packets for subsequent processing by the audio, visual and display processors 50 . The data is accompanied by a data framing signal, a clock signal, and an error signal that indicates whether or not the decoder 23 detected an uncorrectable error in the data packet. Typically, the decoder unit 23 generates the error signal via circuitry within the decoder 23 dedicated to this purpose. However, if the error generating hardware does not work correctly, additional expense must be incurred by incorporating hardware in subsequent stages that will assist in the generation of the error detection signal. Ideally, a software based solution is needed which will eliminate the need for including redundant error detection circuitry in an HDTV receiver.
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>The present invention utilizes a transport processor, implemented as a microprocessor to execute software instructions within an HDTV receiver to generate an error signal when the receiver demodulator detects an uncorrectable error within a data packet. A packet error signal is generated by the forward error correcting Reed-Solomon decoder residing within the demodulator integrated circuit package. The integrated circuit includes a programmable output pin which generates a software packet error signal that is synchronized with the outgoing data packets. The error signal has a duration greater than its associated data packet, and is programmed to begin before and end after its associated data packet. In this manner, the error signal completely brackets or frames the underlying data packet. The software packet error signal is made available to the microprocessor by utilizing a different timing scheme than the one used to advance data packets on the transport processor bus. Every 313th data packet is training data generated by the field sync detector for use by the adaptive channel equalizer. The training data packet is not sent to the transport processor. The missing 313th data packet creates a gap in the data stream that is concealed by adding a small increment of time to the gaps existing between the remaining 312 data packets that are eventually sent to the transport processor. This added time has the effect of causing the start time of the 312 data packets on the transport bus to begin earlier than the start time of the data packets appearing at the output of the Reed-Solomon decoder. This precession effect is reset at the beginning of each data field and is predictable across the duration of each data field.
20041018
20101005
20051013
89616.0
0
WONG, ALLEN C
PACKET ERROR SIGNAL GENERATOR
UNDISCOUNTED
0
ACCEPTED
2,004
10,511,749
ACCEPTED
Plasma display panel manufacturing method
The present invention provides a method of manufacturing a PDP that prevents defects due to dust adhering to a photomask, for example, from occurring in a structure of the PDP. In photolithography, exposure is performed twice in a same process, and photomask (22) is moved within an allowable range of displacement in an exposure pattern, between a first and a second exposures. Photomask (22) is exposed twice in total before and after moving photomask (22). Region (21a), an unexposed region due to interruption of dust (22b) attached to photomask (22), can be suppressed, enabling pattern exposure on photosensitive Ag paste film (21) to be favorably performed.
1. A method of manufacturing a plasma display panel, in which a structure of the plasma display panel is formed with photolithography, wherein at least one of the structures of the plasma display panel is exposed twice in a process of forming the structure, and a photomask is moved within an allowable range of displacement in a exposure pattern, between a first and a second exposures. 2. A method of manufacturing a plasma display panel, in which a structure of the plasma display panel is formed with photolithography, wherein at least one of the structures of the plasma display panel is exposed twice in a process of forming the structure, and a photomask is moved by at least one cycle of periodicity included in a exposure pattern, and also within an allowable range of displacement at the position, between a first and a second exposures.
TECHNICAL FIELD The present invention relates to a manufacturing method for forming a structure of a plasma display panel (hereinafter, abbreviated as “PDP”) that is known as a large-screen, thin, and lightweight display apparatus. BACKGROUND ART A PDP displays images by exciting a phosphor substance with ultraviolet light generated by gas discharge for light emission. A PDP is roughly classified into the AC type and DC type by driving method, and the surface-discharge type and opposed-discharge type by discharging method. In terms of moving to finer-resolution, an increase in the screen size, and easiness in manufacturing owing to simplicity of the structure, a PDP nowadays prevails with a three-electrode structure and the surface-discharge type. A PDP is composed of a front panel and a back panel. The front panel has display electrodes including scanning electrodes and sustain electrodes; a dielectric layer covering the display electrodes; and a protective layer further covering the dielectric layer, on a substrate made of glass or the like. The back panel has a plurality of address electrodes orthogonal to the display electrodes, a dielectric layer covering the address electrodes, and partition walls on the dielectric layer. Arranging the front panel and the back panel facing each other forms a discharge cell at the intercept of the display electrode and the data electrode, where the discharge cell has a phosphor layer therein. Such a PDP offers high-speed display as compared with a liquid crystal panel. In addition, it features a wide viewing angle, easy upsizing, and a high-quality display owing to its self-luminous property, attracting attention among flat-panel displays. It is widely used in various applications, particularly for a display apparatus in a public place where many people gather, and for enjoying a large-screen image at home. In a PDP, at least one of a display electrode and address electrode requires a relatively high accuracy in its shape and allocation pitch. Therefore, so-called photolithography is used, where the whole surface of the substrate is coated with a conducting material such as a metallic material, containing a photosensitive material, which is exposed and developed using a photomask with an electrode pattern. A method for forming an electrode with a predetermined shape at a predetermined position of a substrate using photolithography is introduced in, for example, the 2001 FPD Technology Outlook (Electronic Journal, Co., Oct. 25, 2000, pp. 589-594, pp. 601-603, and pp. 604-607). However, in the above-mentioned photolithography, if undesired dust or the like adheres to the exposure part of the photomask used, the photosensitive material corresponding to the part is not exposed to light and is not polymerized. Consequently, the material is dissoluted when developing, preventing a desired pattern to be achieved. In other words, a so-called “dropout” occurs in the pattern, causing a break in a part of an electrode. A break in an electrode prevents supplying power to pixels on the downstream of the feed direction depending on a broken position. Such inconvenience and defects are fatal because they cause troubles in image display of a PDP. The above describes an example for an electrode. In a PDP, despite its large screen, a structure other than an electrode requires accuracy. Consequently, photolithography is used also to form a structure, such as a partition wall, other than an electrode. Such a case also causes the same problems in image display as in an electrode. Still, in the present invention, a structure of a PDP refers to that formed with photolithography, such as an electrode (e.g. address electrode and display electrode 6), a light-impervious layer, and partition wall 14. SUMMERY OF THE INVENTION The present invention, in a manufacturing method for forming a structure of a PDP with photolithography, aims at providing a manufacturing method that prevents defects from occurring in formed structures of the PDP. In order to achieve the above-mentioned objective, the method of manufacturing a PDP according to the present invention is to form a structure of the PDP using photolithography, where at least one of the above-mentioned structures of the PDP is exposed twice in its forming process, and the photomask is moved between the first and the second exposures within an allowable range of displacement in the exposure pattern. Further, the method of manufacturing a PDP according to the present invention is to form a structure of the PDP using photolithography, where at least one of the above-mentioned structures of the PDP is exposed twice in its forming process, and the photomask is moved between the first and the second exposures by at least one cycle of the periodicity included in the exposure pattern, and also within an allowable range of displacement in the exposure pattern at the position. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective sectional view showing an example of a general makeup of a PDF manufactured with a manufacturing method according to an embodiment of the present invention. FIGS. 2A through 2D illustrate a flow of a process to form an address electrode, which is a structure of a PDP according to the present invention. FIGS. 3A through 3C illustrate an example of how to move a photomask. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Hereinafter, a description is made for a method of manufacturing a PDP according to an embodiment of the present invention using drawings. First, a description is made for a structure of a PDP. FIG. 1 is a perspective sectional view showing an example of a general makeup of a PDP manufactured with a manufacturing method according to an embodiment of the present invention. Front panel 2 of PDP 1 has display electrode 6 including scanning electrode 4 and sustain electrode 5 formed on a main surface of substrate 3, which is smooth, transparent, and insulative, like glass, made with float process or the like; light-impervious layer 7 provided between display electrode 6 and another adjacent one; dielectric layer 8 covering display electrode 6 and light-impervious layer 7; and protective layer 9 further covering dielectric layer 8, containing MgO, for example. Scanning electrode 4 and sustain electrode 5 are structured so that bus electrodes 4b and 5b are laminated on transparent electrodes 4a and 5a, respectively, made of a highly-conductive material such as a metallic material, in order to reduce electrical resistance. Light-impervious layer 7 shields white light coming from a phosphor layer (described later) when non-emitting, effectively improving contrast. Back panel 10 has address electrode 12 formed on a main surface of substrate 11, which is smooth, transparent, and insulative, like glass, made with float process or the like, on the back surface; dielectric layer 13 covering the address electrode 12; partition wall 14 arranged at a position corresponding to between address electrode 12 and another adjacent one, on dielectric layer 13; and phosphor layers 15R, 15G, and 15B, between partition wall 14 and another adjacent one. Front panel 2 and back panel 10 are arranged facing each other across partition wall 14, so that display electrode 6 and address electrode 12 are orthogonal to each other, and the peripheries of front panel 2 and back panel 10 are sealed with a sealing member. In discharge space 16 formed between front panel 2 and back panel 10, a discharge gas (e.g. 5% of Ne—Xe) is encapsulated with a pressure of 66.5 kPa (500 Torr). The intercept of display electrode 6 and address electrode 12 in discharge space 16 works as discharge cell 17 (a unit of light-emitting region). Next, a description is made for a method of manufacturing PDP 1 referring to FIG. 1. In order to manufacture front panel 2, first form scanning electrode 4 and sustain electrode 5 on substrate 3, like stripes for example. Specifically, form a film, which is a material of transparent electrodes 4a and 5a, made of indium tin oxide (ITO) or the like, on substrate 3, using electronic beam evaporation technique, for example. Then pattern a resist on the ITO film so that the resist remains as the pattern for transparent electrodes 4a and 5a. After that, etch transparent electrodes 4a and 5a, which is a well-known method, and then exfoliate the resist to form transparent electrodes 4a and 5a. Still, SnO2 or the like also can be used as the transparent electrode material. Next, form bus electrodes 4b and 5b on transparent electrodes 4a and 5a. Specifically, use black pigment, glass frit (PbO—B2O3—SiO2 base, Bi2O3—B2O3—SiO2 base, etc.), polymerization initiator, photo-sclerotic monomer, and photosensitive black paste containing an organic solvent, for the materials of bus electrodes 4b and 5b. Then, after forming a black electrode film on the glass substrate with the photosensitive black paste, using screen printing or the like; dry it. Continuously, form a metal electrode film on the black electrode film, using screen printing or the like, with a conducting material containing Ag, glass frit (PbO—B2O3—SiO2 base, Bi2O3—B2O3—SiO2 base, etc.), polymerization initiator, photo-sclerotic monomer, photosensitive Ag paste containing an organic solvent; and dry it again. After that, make a pattern with photolithography, and bake it to form bus electrodes 4b and 5b. The above-mentioned manufacturing method allows forming display electrode 6 including scanning electrode 4 and sustain electrode 5. Next, form light-impervious layer 7. That is, after forming a film with a photosensitive black paste using screen printing or the like, make a pattern with photolithography, and then bake it. Here, light-impervious layer 7 may be formed concurrently with the base black layers of bus electrodes 4b and 5b. A forming method without using a paste may be exploited as long as the photosensitive paste is black. Still, light-impervious layer 7 may be formed before bus electrodes 4b and 5b are formed. Next, cover display electrode 6 and light-impervious layer 7 with dielectric layer 8, which is formed by applying a paste containing a lead-based glass material, using screen printing or the like. Then, bake the paste at a predetermined temperature for a predetermined time, at 560° C. for 20 minutes for example, to form dielectric layer 8 with a predetermined thickness, approximately 20 μm, for example. As a paste containing a lead-based glass material, a mixture of PbO (70 wt %), B2O3 (15 wt %), SiO2 (10 wt %), and Al2O3 (5 wt %); and an organic binder (e.g. alpha-terpineol with 10% ethycellulose dissoluted) is used. Here, the organic binder is an organic solvent with a resin dissoluted therein, where, besides ethycellulose, an acrylic resin can be used as the resin; and n-butylcarbitol, for example, can be used as the organic solvent. Moreover, a dispersing agent such as glyceryl trileate may be mixed in such an organic binder. Still, instead of screen printing using a paste, a molded, film-like dielectric precursor may be laminated and baked to form dielectric layer 8. Next, cover dielectric layer 8 with protective layer 9. Protective layer 9 includes MgO or the like, as its principal component. Form protective layer 9 so that it has a predetermined thickness, approximately 0.5 μm for example, with a film-forming process such as deposition or sputtering. Meanwhile, for back panel 10, address electrode 12 is formed on substrate 11, like stripes. Specifically, form a film with screen printing or the like, on substrate 11, using a photosensitive Ag paste for example, to be a material of address electrode 12; make a pattern with photolithography or the like; and bake it to form address electrode 12. Next, cover address electrode 12 with dielectric layer 13. After applying a paste containing a lead-based glass material, with screen printing or the like, bake the paste at a predetermined temperature for a predetermined time, at 560° C. for 20 minutes for example, to form dielectric layer 13 with a predetermined thickness, approximately 20 μm. Instead of screen-printing using a paste, a molded, film-like base dielectric layer precursor may be laminated and baked to form dielectric layer 13. Next, form partition wall 14 like stripes, for example. Form a film with a photosensitive paste having an aggregate such as Al2O3, and glass frit as it base resin, with a printing method, die coating, or the like; make a pattern with photolithography; and bake it to form partition wall 14. Alternatively, forming may be performed, after repeatedly applying a paste containing a lead-based glass material, with screen printing or the like, at a predetermined pitch, by baking it. Here, the gap between partition walls 14 is approximately 130 μm to 240 μm for a HDTV set with its screen size of 32 to 50 inches, for example. In the groove between partition wall 14 and another adjacent one, form phosphor layers 15R, 15G, and 15B composed of the respective phosphor particles red (R), green (G),and blue (B). In order to form these layers, apply a phosphor ink paste including phosphor particles with each color and an organic binder; and bake it at 400° C. to 590° C., for example, to burn out the organic binder. This forms phosphor layers 15R, 15G, and 15B with each phosphor particle binding. Lay front panel 2 and back panel 10 so that display electrode 6 on front panel 2 and address electrode 12 on back panel 10 are orthogonal to each other; insert a sealing member such as sealing glass to the peripheries of front panel 2 and back panel 10; and seal them with a hermetic seal layer (not illustrated) formed by baking it at approximately 450° C. and for 10 to 20 minutes, for example. Then, after once exhausting discharge space 16 with a high vacuum, 1.1*10−4 Pa for example, encapsulate a discharge gas (e.g. a He—Xe-based or Ne—Xe-based inert gas) with a predetermined pressure to produce PDP 1. While PDP 1 in this case has a large screen, a structure of PDP 1, such as display electrode 6, light-impervious layer 7, address electrode 12, and partition wall 14, requires accuracy in its shape and position; and thus photolithography is widely used for a method of forming such a structure. Hereinafter, a description is made for photolithography, namely a method of manufacturing a PDP according to the present invention, taking address electrode 12, namely a structure of PDP 1, for example, mainly about the exposure process, namely a feature of the present invention, using drawings. FIGS. 2A through 2D illustrate a general flow of the process to form address electrode 12, which is a structure of PDP1. First, as shown in FIG. 2A, apply a uniform coating of a photosensitive Ag paste with screen printing or the like, to form photosensitive Ag paste film 21 on substrate 11. Next, as shown in FIG. 2B, arrange photomask 22 including an exposure pattern for making address electrode 12 shown in FIG. 1 with photolithography, positioning at a predetermined position on substrate 11. In FIG. 2B, the unhatched area of photomask 22 is an open part, becoming exposure part 22a. In addition, in order to describe the features of the present invention, as a matter of convenience, an assumption has been made that undesired dust 22b remains attached to a part of photomask 22. Next, as shown in FIG. 2C, perform a first exposure on photosensitive Ag paste film 21 through photomask 22. Specifically, irradiate photomask 22 with ultraviolet light 23 from an extra-high-pressure mercury lamp. Here, if it is assumed that undesired dust 22b remains attached to open part 22a of photomask 22, region 21a, a position of photosensitive Ag paste film 21 corresponding to dust 22b, is not to be exposed to light. Next, move photomask 22 within an allowable range of displacement in the exposure pattern to perform a second exposure. That is, in the process of forming address electrodes, which are structures of PDP 1, perform an exposure process twice. Still, the above-mentioned allowable range of displacement in the exposure pattern is defined by accuracy both in shape and position of electrode 12 shown in FIG. 1. Next, an example of how to move photomask 22 is shown in FIGS. 3A through 3C with the positional relationship between open part 22a and dust 22b before and after moving photomask 22. FIG. 3A shows a method of the second exposure (shown by solid lines) in which a position slightly moved from that of photomask 22 in the first exposure (shown by broken lines) is exposed within an allowable range of displacement in the exposure pattern. Further, FIG. 3B shows a case, if address electrodes 12 are like stripes, where after a first exposure shown by broken lines is performed, a second exposure is performed as shown by solid lines. This is a method in which the width direction is within an allowable range of displacement in the exposure pattern in the second exposure, and the exposed position is moved in its direction of expansion (lengthwise in the pattern). In addition, generally, address electrode 12 shown in FIG. 1 is allocated with periodicity due to the makeup of a PDP, and thus as shown in FIG. 3C, a method may be adopted in which photomask 22 is moved by at least one cycle of the exposure pattern, as long as within an allowable range of displacement in the exposure pattern. Still, a structure of PDP 1 composes discharge cell 17, which becomes a pixel, and therefore the allocation pattern of a structure of PDP 1 usually has periodicity. Moving of photomask 22 shown in FIG. 2D is effective if dust 22b is assumed smaller than an allowable range of displacement in the exposure pattern. Meanwhile, the cases shown in FIG. 3B and FIG. 3C are effective if dust 22b is assumed greater than that. Here, FIG. 2D shows a state in which photomask 22 has been moved by one cycle to the left direction from the state of FIG. 2C, shown in FIG. 3C, looking straight at FIG. 2D from the front. That is, move photomask 22 within an allowable range of displacement in the exposure pattern to perform a second exposure. In this case, because undesired dust 22b was temporarily attached to the exposure part of photomask 22, even if region 21a, a position of photosensitive Ag paste film 21 corresponding to dust 22b, is not exposed in the first exposure, region 21a changes in the second exposure. Consequently, region 21a, not exposed in the first exposure, is to be exposed. In the second exposure, although region 21b, a region not exposed due to interruption of dust, newly occurs at a position displaced by one cycle of the exposure pattern, region 21b has been already exposed in the first exposure. In other words, if photomask 22 is moved, dust attaches at the same position of photosensitive Ag paste film 21 before and after moving with a very low probability. Therefore, as long as photomask 22 is exposed twice in total before and after moving photomask 22, an unexposed region due to interruption of dust 22b attached to photomask 22 can be prevented from occurring. That is, pattern exposure is favorably performed on photosensitive Ag paste film 21. Additionally, accuracy in the exposed pattern falls within the allowable range of error. Finally, developing photosensitive Ag paste film 21 exposed with the pattern of address electrode 12 in the above way, makes photosensitive Ag paste film 21 the pattern of address electrode 12; and baking it completes address electrode 12. Although the above description is made for address electrode 12 as an example of a structure of PDP 1, such a structure mentioned above refers to that formed with photolithography, such as display electrode 6, light-impervious layer 7, partition wall 14, and the like. Even for at least one of these structures, the above-mentioned effect can be achieved by applying the present invention in the forming process. INDUSTRIAL APPLICABILITY The present invention provides, in a method of forming a structure of a PDP with photolithography, a method of manufacturing a PDP and the PDP to be manufactured therewith that prevent defects, due to dust adhering to a photomask, for example, from occurring in the structure of the PDP, offering a high industrial applicability.
<SOH> BACKGROUND ART <EOH>A PDP displays images by exciting a phosphor substance with ultraviolet light generated by gas discharge for light emission. A PDP is roughly classified into the AC type and DC type by driving method, and the surface-discharge type and opposed-discharge type by discharging method. In terms of moving to finer-resolution, an increase in the screen size, and easiness in manufacturing owing to simplicity of the structure, a PDP nowadays prevails with a three-electrode structure and the surface-discharge type. A PDP is composed of a front panel and a back panel. The front panel has display electrodes including scanning electrodes and sustain electrodes; a dielectric layer covering the display electrodes; and a protective layer further covering the dielectric layer, on a substrate made of glass or the like. The back panel has a plurality of address electrodes orthogonal to the display electrodes, a dielectric layer covering the address electrodes, and partition walls on the dielectric layer. Arranging the front panel and the back panel facing each other forms a discharge cell at the intercept of the display electrode and the data electrode, where the discharge cell has a phosphor layer therein. Such a PDP offers high-speed display as compared with a liquid crystal panel. In addition, it features a wide viewing angle, easy upsizing, and a high-quality display owing to its self-luminous property, attracting attention among flat-panel displays. It is widely used in various applications, particularly for a display apparatus in a public place where many people gather, and for enjoying a large-screen image at home. In a PDP, at least one of a display electrode and address electrode requires a relatively high accuracy in its shape and allocation pitch. Therefore, so-called photolithography is used, where the whole surface of the substrate is coated with a conducting material such as a metallic material, containing a photosensitive material, which is exposed and developed using a photomask with an electrode pattern. A method for forming an electrode with a predetermined shape at a predetermined position of a substrate using photolithography is introduced in, for example, the 2001 FPD Technology Outlook (Electronic Journal, Co., Oct. 25, 2000, pp. 589-594, pp. 601-603, and pp. 604-607). However, in the above-mentioned photolithography, if undesired dust or the like adheres to the exposure part of the photomask used, the photosensitive material corresponding to the part is not exposed to light and is not polymerized. Consequently, the material is dissoluted when developing, preventing a desired pattern to be achieved. In other words, a so-called “dropout” occurs in the pattern, causing a break in a part of an electrode. A break in an electrode prevents supplying power to pixels on the downstream of the feed direction depending on a broken position. Such inconvenience and defects are fatal because they cause troubles in image display of a PDP. The above describes an example for an electrode. In a PDP, despite its large screen, a structure other than an electrode requires accuracy. Consequently, photolithography is used also to form a structure, such as a partition wall, other than an electrode. Such a case also causes the same problems in image display as in an electrode. Still, in the present invention, a structure of a PDP refers to that formed with photolithography, such as an electrode (e.g. address electrode and display electrode 6 ), a light-impervious layer, and partition wall 14 .
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a perspective sectional view showing an example of a general makeup of a PDF manufactured with a manufacturing method according to an embodiment of the present invention. FIGS. 2A through 2D illustrate a flow of a process to form an address electrode, which is a structure of a PDP according to the present invention. FIGS. 3A through 3C illustrate an example of how to move a photomask. detailed-description description="Detailed Description" end="lead"?
20041019
20110607
20050929
83509.0
0
RAYMOND, BRITTANY L
PLASMA DISPLAY PANEL MANUFACTURING METHOD
UNDISCOUNTED
0
ACCEPTED
2,004
10,511,867
ACCEPTED
Optical element, optical head, optical information recording/reproduction device, computer, video recording device, video reproduction device, server, and car navigation system
The present invention provides a first light source (21) that emits light of a first wavelength, that at least either records onto or reproduces information from an information recording medium (30), a light source (22) that emits light of a second wavelength that records onto or reproduces information from an information recording medium (33), a light source (23) that emits light of a third wavelength that records onto or reproduces information from an information recording medium (23), focusing means, an optical element (28) that passes light of the first wavelength and diffracts light of the second and third wavelengths, wherein the optical element (28) is an optical element in which grooves are formed in a substrate, wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves, and wherein the grooves are formed in two steps of depth d and depth 2d.
1. An optical element, comprising: a substrate in which grooves are formed; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is the refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in two steps of depth d and depth 2d. 2. An optical element, comprising: a substrate in which grooves are formed; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d. 3. The optical head according to claim 2, wherein the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order: depth 3d, depth d, depth 4d, depth 2d. 4. The optical element according to claim 1 or 2, wherein the grooves are formed in concentric ring-shapes. 5. The optical element according to claim 1 or 2, wherein the grooves are adjacent via a portion in which no grooves are formed, and the width of each step of the grooves is substantially the same as the width of the portion in which no grooves are formed. 6. An optical head, comprising: a first light source that emits light of a first wavelength that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 7. An optical head, comprising: a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 8. The optical head according to claim 7, wherein the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order depth 3d, depth d, depth 4d, depth 2d. 9. The optical head according to claim 6 or 7, wherein the second wavelength is 1.5 to 1.8 times the length of the first wavelength. 10. The optical head according to claim 6 or 7, wherein the grooves of the optical element are formed on a face that is close to the focusing means. 11. The optical head according to claim 6 or 7, wherein for light of the second wavelength that is diffracted by the optical element, the light that diverges is stronger than the light that converges with respect to incident light. 12. The optical head according to claim 6 or 7, wherein the optical element corrects the aberration to not more than 70 mλ when light of the second wavelength that is diffracted by the optical element is focused on an information surface of a second information recording medium. 13. An optical head comprising: a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 14. An optical head, comprising: a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 15. The optical head according to claim 14, wherein the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order depth 3d, depth d, depth 4d, depth 2d. 16. The optical head according to claim 13 or 14, wherein the second wavelength is 1.5 to 1.8 times the length of the first wavelength; and wherein the third wavelength is 1.8 to 2.2 times the length of the first wavelength. 17. The optical head according to claim 13 or 14, wherein, when a first region is a substantially circle-shaped region in the central vicinity of the first optical element, a second region is a substantially ring-shaped region that surrounds the first region, and a third region is a region on the outside of the second region, light of the first wavelength passes through the first, second and third region, light of the second wavelength passes through the first and second region, and light of the third wavelength passes through the first region. 18. The optical head according to claim 13 or 14, wherein for light of the second wavelength and third wavelength that are diffracted by the first optical element, the light that diverges is stronger than the light that converges with respect to incident light. 19. The optical head according to claim 13 or 14, further comprising: phase correcting means for correcting the aberration of light of the second wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the second wavelength is focused on the information surface of the second information recording medium, and for correcting the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the third wavelength is focused on the information surface of the third information recording medium; wherein the phase correcting means does not change the phase of light of the first wavelength; and wherein the phase correcting means is provided in the light path between the light sources and the optical information recording medium. 20. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium. 21. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; wherein the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in two steps of depth d and depth 2d. 22. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; wherein the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in three steps of depth d, depth 2d and depth 3d. 23. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; and wherein the first optical element and the second optical element are formed on a top and a rear of a single substrate. 24. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; and wherein the first optical element and the second optical element are formed on a top and a rear of a single substrate, and the face on which the second optical element is formed, of the two faces of the single substrate, is closer to the focusing means. 25. The optical head according to claim 13 or 14, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; and wherein the first and second optical elements correct the aberration of light of the second wavelength that is diffracted by the first and second optical elements to not more than 70 mλ when that light is focused onto the information surface of the second information recording medium; and correct the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when that light is focused on the information surface of the third information recording medium. 26. The optical head according to claim 13 or 14, wherein, when a distance between the surface of the first information recording medium on the focusing means side and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, a difference between the maximum value and the minimum value of WD1, WD2 and WD3 is smaller than the maximum value of the diameter of the focusing means. 27. The optical head according to claim 13 or 14, wherein, when a distance between the surface of the first information recording medium on the focusing means side and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, WD1, WD2 and WD3 are substantially equivalent. 28. The optical head according to claim 6, 7, 13 or 14, further comprising: a converter for converting a plurality of signals, which are received in parallel and are output from the photodetecting means into a serial signal. 29. The optical head according to claim 6, 7, 13 or 14, further comprising: a converter for converting a plurality of signals, which are received in parallel and are output from the photodetecting means, into a serial signal; wherein the serial signal is an electrical signal. 30. The optical head according to claim 6, 7, 13 or 14, further comprising: a first converter for converting a plurality of signals, which are output from the photodetecting means and received in parallel, into a serial signal; and a second converter for receiving the electric signal that is output from the first converter and for converting the electric signal into an optical signal. 31. An optical information recording and reproduction apparatus, comprising: an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength, further comprising: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 32. An optical information recording and reproduction apparatus, comprising: an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength, further comprising: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 33. The optical information recording and reproduction apparatus according to claim 32, wherein the grooves are lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order depth 3d, depth d, depth 4d, depth 2d. 34. An optical information recording and reproduction apparatus, comprising: an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; further comprising: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 35. An optical information recording and reproduction apparatus, comprising: an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; further comprising: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. 36. The optical information recording and reproduction apparatus according to claim 34 and 35, further comprising: a second optical element that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium. 37. An optical element, comprising: a substrate, in which steps are formed protruding from a flat surface thereof; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d; and wherein the height of the steps is an integer multiple of d. 38. The optical element according to claim 37, wherein the steps are formed in concentric ring-shapes. 39. An optical head, comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. 40. An optical head, comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the position of the second light source is set closer to the focusing means than a position at which the aberration at the information recording surface of the second information recording medium, when the optical element is not present, is at a minimum; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. 41. An optical head, comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the position of the second light source is set further from the focusing means than a position that is substantially midway between the position of that light source at which the aberration at the information recording surface of the second information recording medium when the optical element is not present is at a minimum, and the position of that light source at which light of the second wavelength that is incident on the focusing means is collimated light; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. 42. The optical head according to claim 39, 40 or 41, further comprising: tilting means for tilting the focusing means. 43. An optical head comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the second wavelength that is incident on the focusing means is collimated light; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. 44. The optical head according to claim 39, 40, 41 or 43, wherein the optical element corrects the aberration to not more than 70 mλ when light of the second wavelength is focused on the information recording surface of the second information recording media. 45. An optical head, comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; an optical element that passes light of the first wavelength and light of the third wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength, light of the second wavelength and light of the third wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expressions: 760 nm≦(n1−1)×d≦840 nm and −10 nm<λ1/(n1−1)·λ3/(n3−1)/2<10 nm. are satisfied when a refractive index of the optical element at the wavelength of 400 nm is n, the third wavelength is λ3 (nm), a refractive index of the optical element at the wavelength λ3 is n3, and a height (nm) of one step is d. 46. An optical head, comprising: a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; an optical element that passes light of the first wavelength and light of the third wavelength, and changes the phase of light of the second wavelength; a liquid crystal element that passes light of the first wavelength and light of the second wavelength, and diffracts light of the third wavelength; focusing means for focusing light of the first wavelength, light of the second wavelength and light of the third wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; wherein the expression: 700 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d; and wherein the liquid crystal element comprises: a substrate that has a relief-shaped hologram pattern; a first transparent electrode, which is formed on the relief-shaped hologram pattern; and a second transparent electrode that is arranged opposite the first transparent electrode to sandwich the liquid crystal; wherein the liquid crystal element passes light of the first wavelength and light of the second wavelength, and diffracts light of the third wavelength by controlling a voltage that is applied to the first transparent electrode and the second transparent electrode. 47. An optical information recording and reproduction apparatus, comprising: an optical head according to claim 39, 40, 41, 43, 45 or 46; and moving means for moving the information recording media and the optical head relative to each other. 48. A computer, comprising: an optical information recording and reproduction apparatus that includes an optical head according to claim 6, 7, 13, 14, 39, 40, 41, 43, 45 or 46, as an external storage device. 49. An image recording device, comprising: an optical information recording and reproduction apparatus that includes an optical head according to claim 6, 7, 13, 14, 39, 40, 41, 43, 45 or 46; which can at least record images from among recording images onto and reproducing images from an information recording medium. 50. An image reproduction device, comprising: an optical information recording and reproduction apparatus that includes an optical head according to claim 6, 7, 13, 14, 39, 40, 41, 43, 45 or 46; wherein it specializes in reproducing images from an information recording medium. 51. A server, comprising: an optical information recording and reproduction apparatus that includes an optical head according to claim 6, 7, 13, 14, 39, 40, 41, 43, 45 or 46, as an external storage device. 52. A car navigation system, comprising: an optical information recording and reproduction apparatus that includes an optical head according to claim 6, 7, 13, 14, 39, 40, 41, 43, 45 or 46, as an external storage device.
TECHNICAL FIELD The present invention relates to optical information recording and reproduction apparatuses, computers, image recording devices, image reproduction devices, servers and car navigation systems for performing information recording, reproduction or erasure of information on information recording media such as optical disks and optical cards, and to optical elements, optical heads and liquid crystal elements used in these devices. BACKGROUND ART Optical memory technology that uses optical disks as high-density, large-volume memory media gradually is being applied widely to and entering general use in digital audio disks, video disks, document file disks and also data files. To successfully achieve recording onto and reproduction of information from an optical disk with high reliability via a minutely narrowed light beam, there is a need for a focusing function forming a minute spot at the diffraction limit, focus control and tracking control of the optical system, and a pit signal (“information signal”) detection function. With recent advances in optical system design technology and the shortening of wavelengths of the semiconductor lasers serving as light sources, the development of optical disks containing volumes of memory at greater than conventional densities is progressing. As an approach to higher densities, increasing the optical disk side numerical aperture (NA) of a focusing optical system that minutely stops down a light beam onto an optical disk has been investigated. A problem that occurs at this time is that there is an increase in aberration caused by an inclination of the disk in relation to the light axis (what is known as “tilt”). When the NA is made large, the aberration caused by tilt increases. It is possible to prevent this by reducing the thickness (substrate thickness) of the transparent substrate of the optical disk. A Compact Disc (CD), which can be considered a first generation optical disk, is used with a light source emitting infrared light (a wavelength λ3 is 780 nm to 820 nm) and an objective lens with an NA of 0.45, and has a substrate thickness of approximately 1.2 mm. A Digital Versatile Disc (DVD), which can be considered a second generation optical disk, is used with a light source emitting red light (a wavelength λ2 is 630 nm to 680 nm) and an objective lens with an NA of 0.6, and has a substrate thickness of approximately 0.6 mm. And, a system has been proposed in which a third generation optical disk is used with a light source that emits blue light (a wavelength λ1 is 380 nm to 420 nm) and an objective lens with an NA of 0.85, the disk having a substrate thickness of 0.1 mm. It should be noted that in this specification, the substrate thickness means the thickness of the transparent substrate from the face at which a light beam is incident on the optical disk (or optical recording medium) to the information recording surface. Thus, the thickness of the substrate of optical disks becomes thinner with increasing recording density. From the standpoint of economics and the space occupied by the device, it is desirable that a single optical information recording and reproduction apparatus is capable of recording and reproducing optical disks of different substrate thickness and recording density. For this purpose, there is a need for an optical head device that is provided with a focusing optical system that is capable of focusing a light beam up to the diffraction limit onto optical disks of different substrate thicknesses. An example of a device that records and reproduces information from both DVD and CD optical disks (information recording media) is proposed in the Patent Document 1 described below. As a first conventional example, this content is described simply using FIGS. 58 to 60. FIG. 58 is a structural overview of an optical head 300. FIG. 58A shows the manner in which information is recorded onto or reproduced from a DVD and FIG. 58B shows the manner in which information is recorded onto or reproduced from a CD. It contains a red semiconductor laser 301 that emits light of a wavelength of 635 nm to 650 nm, and an infrared semiconductor laser 302 that emits light of a wavelength of 780 nm. When reproducing a DVD 308, which is a second information recording medium, the light emitted from the red semiconductor laser 301 passes through a wavelength selecting prism 303, and is converted to collimated light by a collimator lens 304. The light that was converted to collimated light is reflected by a beam splitter 305, passes through a dichroic hologram 306, is converted to convergent light by an objective lens 307, and is irradiated onto the DVD 308. The light that was reflected by the DVD 308 again passes through the objective lens 307 and the dichroic hologram 306, passes through the beam splitter 305, is converted to convergent light by a detecting lens 309, and is focused onto a photodetector 310. When reproducing a CD 311, which is a third information recording medium, the light emitted from the infrared semiconductor laser 302 is reflected by the wavelength selecting prism 303, and is converted to collimated light by a collimator lens 304. The light that was converted to collimated light is reflected by a beam splitter 305, is diffracted by the dichroic hologram 306, is converted to convergent light by an objective lens 307, and is irradiated onto the CD 311. The light that was reflected by the CD 311 again passes through the objective lens 307 and the dichroic hologram 306, passes through the beam splitter 305, is converted to convergent light by the detecting lens 309, and is focused onto the photodetector 310. Spherical aberration caused by the difference in substrate thickness of DVDs and CDs is corrected by the dichroic hologram 306. FIG. 59 is a cross-sectional view of the dichroic hologram 306. Grooves of depth d, 2d and 3d are arranged in that order on the surface of the dichroic hologram 306. The depth d is determined such that, d=λ1/(n1−1) where λ1 is the wavelength of the red semiconductor laser and n1 is the refractive index of the dichroic hologram 306 at the wavelength λ1. In this way, the transmittance of the light of wavelength λ1, increases without diffracting the light. Here, the wavelength of light emitted from the infrared semiconductor laser is λ2, and the refractive index of the dichroic hologram 306 at the wavelength λ2 is n2. FIG. 60A shows the wavefront after the light of wavelength λ2 has passed the dichroic hologram 306, in which, d×(n2−1)/λ2=0.75. In this case, a phase shift of 0.75 times the wavelength occurs per step. As phase shifts of greater than one can be ignored, FIG. 60B shows a wavefront that is re-written, based only on that portion to the right of the decimal point. This wavefront becomes first order diffraction light, which has a high diffraction efficiency at one side. Furthermore, in the non-Patent Document 1 described below an example is given of a device for reproducing information on CDs, DVDs and ultra high density optical disks. This is briefly explained using FIGS. 61 and 62 as a second conventional example. FIG. 61 is a structural overview showing an optical head. Collimated light emitted from an optical system 201 that contains a blue light source of wavelength λ1=405 nm passes through prisms 204, 205 and a phase plate 206, which will be explained later, is focused by an objective lens 207, and is irradiated onto an information recording surface of an optical disk 208 (an ultra high density optical disk) whose substrate thickness is 0.1 mm. The light that was reflected by the optical disk 208 returns back along the travel path and is detected by a photodetector of the optical system 201. The diverging light that is emitted by an optical system 202 that contains a source of red light of wavelength λ2=650 nm is reflected by the prism 204, passes through the prism 205 and the phase plate 206, is focused by the objective lens 207 and is irradiated onto an information recording surface of an optical disk 209 (DVD), whose substrate thickness is 0.6 mm. The light that was reflected from the optical disk 209 returns back along the travel path, and is detected by a photodetector of the optical system 202. The diverging light emitted by an optical system 203, which has a source of infrared light of a wavelength λ3=780 nm is reflected by the prism 205, passes through the phase plate 206, is focused by the objective lens 207, and is irradiated onto an information recording surface of an optical disk 210 (CD), whose substrate thickness is 1.2 mm. The light that was reflected by the optical disk 210 returns back along the travel path, and is detected by a photodetector of the optical system 203. The objective lens 207 is designed so as to handle substrate thicknesses of 0.1 mm, and spherical aberration occurs in CDs and DVDs because of the difference in substrate thickness. Correction of this spherical aberration occurs due to the degree of divergence of the diverging light that is emitted by the optical system 202 and optical system 203, and due to the phase plate 206. Different spherical aberration is generated when divergent light is incident on the objective lens, so it is possible to cancel out spherical aberration caused by the difference in substrate thickness by this new spherical aberration. The degree of divergence of the diverging light is set such that spherical aberration is a minimum. Spherical aberration caused by the diverging light cannot be completely corrected, and higher order spherical aberrations (principally fifth order spherical aberrations) remain. These fifth order spherical aberrations are corrected by the phase plate 206. FIG. 62 shows a surface (FIG. 62A) and a lateral view (FIG. 62B) of the phase plate 206. If the refractive index at the wavelength λ1 is defined as n1, and h=λ1/(n1−1), then the phase plate 206 is constituted by phase shift steps 206a of height h and height 3h. The height h generates a phase shift of 1λ (where λ is the wavelength that is used) in the light of wavelength λ1, however this does not affect the phase distribution and there is no impediment to recording or reproduction of the optical disk 208. On the other hand, if the refractive index of the phase plate 206 at the wavelength λ2 is n2, then a phase shift of the light of wavelength λ2 of h/λ2×(n2−1)=0.625 λ is generated. Furthermore, if the refractive index of the phase plate 206 at the wavelength λ3 is n3, then a phase shift of the light of wavelength λ3 of h/λ3×(n3−1)=0.52 λ is generated. In relation to DVDs and CDs, this wave shift is used to convert the wavefronts, and the remaining fifth order spherical aberrations are corrected. Moreover, the Patent Document 2 described below proposes a method for reproducing information using an objective lens that is capable of recording and reproducing ultra high density optical disks, and two objective lenses that are capable of reproducing CDs and DVDs. This is described briefly as a third conventional example, using FIG. 63. A lens holder 233 is provided with an objective lens 231 that is used when recording onto and replaying from ultra high density optical disks, an objective lens 232 that is used when reproducing DVDs and CDs, and drive coils 234, and is suspended by wires 236 from a fixed portion 237. A magnetic circuit is constituted by a magnet 238 and a yoke 239. An electromagnetic force is caused by the flow of electric current through the drive coil 234, and the objective lenses 231 and 232 are driven in the focusing direction and the tracking direction. In the third conventional example, which of the objective lenses 231 and 232 is used depends on the optical disk to be recorded and reproduced. Furthermore, as a technique for correcting chromatic aberration, a chromatic aberration correcting hologram is proposed in the Patent Document 3 described below, in which the cross-sectional shape of the optical element is saw tooth shaped, wherein light of a first wavelength λ1 is corrected using second order diffracted light, and light of a second wavelength λ2 is corrected using first order diffracted light. However, in the optical head of the first conventional example, when light is irradiated onto optical disks that have widely different substrate thicknesses, such as a substrate thickness of 1.2 mm and a substrate thickness of 0.1 mm, there is the problem that the distance between the disk and the objective lens changes significantly, the movable range of the actuator increases, and the head becomes large. Moreover, there is the problem that in order to detect the light that corresponds to the three types of light sources, the number of signal wires increases and the width of the flexible cable that connects the optical head and the optical disk drive is wider. Furthermore, in the optical disk device according to the second conventional example, since the light is incident on the objective lens as divergent light when reproducing CDs and DVDs, there is the problem that when the objective lens is driven in the tracking direction, a large coma aberration is generated and the optical disks cannot be favorably reproduced. Furthermore, in the optical disk device of the third conventional example, because the objective lenses 231 and 232 are lined up in a tangential direction (y direction) and the objective lens 231 is arranged such that it is positioned on a straight line in the tracking direction (x direction) that passes through a rotational center O of the optical disk, there is the problem that DVDs and CDs that use the objective lens 232 cannot use the differential push-pull (DPP) method or the three beam method, which are common tracking detection methods. This problem is described using FIG. 64. The DPP method or the three beam method use a main spot for reproduction, and two sub spots for tracking detection. A main spot 232a of the objective lens 232 shown in FIG. 63 is in a spot position 150a shown in FIG. 64. The subspots are in positions 150b and 150c, and are set at an optimal angle θ0 with respect to a reproduction track 153. The spots move in the x-direction in accordance with the seek operation of the optical head, and the spot positions change to 151a, 151b and 151c. Because the spot positions 150a and 151a are not on the straight line that passes through the axis of rotation O of the optical disks in the x-direction, the angle θ0 changes to θ1 due to the seek operation of the optical head. That is to say, in the configuration of the third conventional example, there is the problem that tracking control cannot be carried out reliably. Patent Document 1 JP H9-306018A Patent Document 2 JP H11-120587A Patent Document 3 JP 2001-60336 Non-Patent Document 1 Session We-C-05 of ISOM 2001 (p30 of the proceedings) DISCLOSURE OF INVENTION It is an object of the present invention to solve the foregoing conventional problems, and to provide optical elements, optical heads, optical information recording and reproduction apparatuses, computers, image recording devices, image reproduction devices, servers and navigation systems that can reliably record information onto and reproduce from a plurality of information recording media whose substrate thicknesses are different. In order to achieve this object, a first optical element of the present invention comprises a substrate in which grooves are formed; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in two steps of depth d and depth 2d. A second optical element of the present invention comprises a substrate in which grooves are formed; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d. A first optical head of the present invention comprises a first light source that emits light of a first wavelength that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A second optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A third optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A fourth optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A first optical information recording and reproduction apparatus of the present invention comprises an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength, and further comprises: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A second optical information recording and reproduction apparatus of the present invention comprises an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; focusing means for focusing light that is emitted from the first light source and from the second light source; an optical element that passes light of the first wavelength and diffracts light of the second wavelength; and photodetecting means for detecting light of the first wavelength and light of the second wavelength, and further comprises: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength and light of the second wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 (nm)≦(n−1)×d≦420 (nm) is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A third optical information recording and reproduction apparatus of the present invention comprises an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; and further comprises: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in two steps of depth d and depth 2d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A fourth optical information recording and reproduction apparatus of the present invention comprises an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; and further comprises: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the first optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; wherein the grooves are formed in four steps of depth d, depth 2d, depth 3d and depth 4d; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A third optical element of the present invention comprises a substrate, in which steps are formed protruding from a flat surface thereof; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d; and wherein the height of the steps is an integer multiple of d. A fifth optical head of the present invention comprises a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. A sixth optical head of the present invention comprises a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the position of the second light source is set closer to the focusing means than a position at which the aberration at the information recording surface of the second information recording medium, when the optical element is not present, is at a minimum. wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. A seventh optical head of the present invention comprises a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein the position of the second light source is set further from the focusing means than a position that is substantially midway between the position of that light source at which the aberration at the information recording surface of the second information recording medium when the optical element is not present is at a minimum, and the position of that light source at which light of the second wavelength that is incident on the focusing means is collimated light. wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. An eighth optical head of the present invention comprises a a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; an optical element that passes light of the first wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the second wavelength that is incident on the focusing means is collimated light; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expression: 380 nm≦(n−1)×d≦420 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d. A ninth optical head of the present invention comprises a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; an optical element that passes light of the first wavelength and light of the third wavelength, and converts the phase of light of the second wavelength; focusing means for focusing light of the first wavelength, light of the second wavelength and light of the third wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; and wherein the expressions: 760 nm≦(n1−1)×d≦840 nm and −10 nm<λ1/(n1−1)−λ3/(n3−1)/2<10 nm are satisfied when a refractive index of the optical element at the wavelength of 400 nm is n, the third wavelength is λ3 (nm), a refractive index of the optical element at the wavelength λ3 is n3, and a height (nm) of one step is d. A tenth optical head of the present invention comprises a first light source that emits light of a first wavelength that is in a range of 380 nm to 420 nm and that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; an optical element that passes light of the first wavelength and light of the third wavelength, and changes the phase of light of the second wavelength; a liquid crystal element that passes light of the first wavelength and light of the second wavelength, and diffracts light of the third wavelength; focusing means for focusing light of the first wavelength, light of the second wavelength and light of the third wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength, light of the second wavelength and light of the third wavelength; wherein the optical element is an optical element comprising a substrate, in which steps are formed protruding from a flat surface thereof; wherein the expression: 700 nm≦(n−1)×d≦840 nm is satisfied when a refractive index of the substrate at a wavelength of 400 nm is n, and a height (nm) of one step is d; and wherein the liquid crystal element comprises: a substrate that has a relief-shaped hologram pattern; a first transparent electrode, which is formed on the relief-shaped hologram pattern; and a second transparent electrode that is arranged opposite the first transparent electrode to sandwich the liquid crystal; wherein the liquid crystal element passes light of the first wavelength and light of the second wavelength, and diffracts light of the third wavelength by controlling a voltage that is applied to the first transparent electrode and the second transparent electrode. An eleventh optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; photodetecting means for detecting light of the first wavelength, light of the second wavelength, and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A twelfth optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; photodetecting means for detecting light of the first wavelength, light of the second wavelength, and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media; and wherein, when a distance between the surface of the first information recording medium on the focusing means side, and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side, and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side, and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, a difference between the maximum value and the minimum value of WD1, WD2 and WD3 is smaller than the maximum value of the diameter of the focusing means. A thirteenth optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; photodetecting means for detecting light of the first wavelength, light of the second wavelength, and light of the third wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media; and wherein, when a distance between the surface of the first information recording medium on the focusing means side, and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side, and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side, and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, WD1, WD2 and WD3 are substantially equivalent. A fourteenth optical head of the present invention comprises a light source that emits light that at least either records onto or reproduces information from an information recording medium; focusing means for focusing light that is emitted from the light source; and photodetecting means for detecting the light; wherein the light is focused by the focusing means and is irradiated onto the information recording media; wherein the detecting means detects the light that is at least either reflected or diffracted by the information recording media; and further comprises converter for converting a plurality of signals, which are received in parallel, that are output from the photodetecting means into a serial signal. A fifth optical information recording and reproduction apparatus comprises an optical head that includes; a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a third light source that emits light of a third wavelength, that at least either records onto or reproduces information from a third information recording medium; focusing means for focusing light that is emitted from the first light source, from the second light source and from the third light source; a first optical element that passes light of the first wavelength and diffracts light of the second wavelength and light of the third wavelength; and photodetecting means for detecting light of the first wavelength, light of the second wavelength, and light of the third wavelength, and further comprises: moving means for moving the information recording medium and the optical head relative to each other; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the optical element, after which they are focused by the focusing means and are irradiated onto the information recording media; and wherein the photodetecting means detects light that is at least either reflected or diffracted by the information recording media. A fifteenth optical head of the present invention comprises first focusing means and second focusing means for irradiating light onto the information recording medium; wherein the first focusing means and the second focusing means are lined up in the tracking direction; wherein the first focusing means is positioned on the inner circumference side of the information recording medium, and the second focusing means is positioned on the outer circumference side of the information recording medium; wherein the outside diameter of the first focusing means is less than the outside diameter of the second focusing means, and the second focusing means can reproduce information at the inner most circumference of the information recording medium when a rotating system, which rotates the information recording medium, and the optical head are in close proximity. A sixteenth optical head of the present invention is an optical head that at least either records onto or reproduces information from at least three information recording media that have different substrate thickness; wherein the optical head contains first focusing means and second focusing means for irradiating light onto the information recording medium; and wherein the first focusing means irradiates light onto a first information recording medium whose substrate thickness is most thick, and the second focusing means irradiates light onto the information recording media, excluding the first information recording medium. A seventeenth optical head of the present invention is an optical head that at least either records onto or reproduces information from a plurality of information recording media that have different substrate thickness, comprising: a plurality of focusing means that irradiate light onto the plurality of information recording medium; and a movable body that is capable of moving in the focus direction and in the tracking direction; wherein the focusing means that irradiates light onto the information recording medium whose substrate thickness is the thinnest is positioned substantially in the center of the movable body, and the plurality of focusing means are mounted on the movable body, lined up in the tracking direction. An eighteenth optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; a focusing means for focusing light of the first wavelength and light of the second wavelength onto the information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength, wherein light of the second wavelength is irradiated onto the first information recording medium to detect the tilt of the first information recording medium. A nineteenth optical head of the present invention comprises a first light source that emits light of a first wavelength, that at least either records onto or reproduces information from a first information recording medium; a second light source that emits light of a second wavelength, that at least either records onto or reproduces information from a second information recording medium; first focusing means for focusing light of the first wavelength onto the first information recording medium; second focusing means for focusing light of the second wavelength onto the second information recording medium; and detecting means for detecting light of the first wavelength and light of the second wavelength; wherein light of the second wavelength is irradiated onto the first information recording medium to detect the tilt of the first information recording medium. A liquid crystal element of the present invention comprises a substrate that has a relief-shaped hologram pattern; a first transparent electrode, which is formed on the relief-shaped hologram pattern; and a second transparent electrode that is arranged opposite the first transparent electrode to sandwich the liquid crystal; wherein it is possible to change between diffracting and passing for the light incident in the liquid crystal element by controlling a voltage that is applied to the first transparent electrode and the second transparent electrode. A sixth optical information recording and reproduction apparatus of the present invention comprises any of the fifth to tenth optical heads, or the fifteenth to nineteenth optical heads; and moving means for moving the information recording media and the optical head relative to each other. A computer of the present invention comprises an optical information recording and reproduction apparatus, which includes any of the optical heads, as an external storage device. An image recording device of the present invention comprises an optical information recording and reproduction apparatus that includes any of the optical heads, wherein it can at least record moving images from among recording moving images onto and reproducing moving images from an information recording medium. An image reproduction device of the present invention comprises an optical information recording and reproduction apparatus that includes any of the optical head, wherein it reproduces images from an information recording medium. A server of the present invention comprises an optical information recording and reproduction apparatus, which includes any of the optical heads, as an external storage device. A car navigation system of the present invention comprises an optical information recording and reproduction apparatus, which includes any of the optical heads, as an external storage device. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a structural diagram showing how a high density optical disk is recorded and reproduced according to the first embodiment of the present invention. FIG. 1B is a structural diagram showing how a DVD is recorded and reproduced according to the first embodiment of the present invention. FIG. 1C is a structural diagram showing how a CD is recorded and reproduced according to the first embodiment of the present invention. FIG. 2A is a view of an upper surface of a dichroic hologram used in the first embodiment of the present invention. FIG. 2B is a view of a rear surface of the dichroic hologram used in the first embodiment of the present invention. FIG. 3 is a cross-sectional view of the dichroic hologram used in the first embodiment of the present invention. FIG. 4A is a schematic view of wavefronts after light of wavelength λ2 has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 4B is a schematic diagram of the wavefronts that are calculated by ignoring the integer portions of the wavelength of the wavefronts in FIG. 4A. FIG. 5 is a conceptual diagram showing the diffraction efficiency of light that is diffracted by the dichroic hologram used in the first embodiment of the present invention. FIG. 6A is a schematic view of a wavefront of the light of wavelength λ3 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 6B is a schematic view of the wavefront of FIG. 6A that is calculated ignoring the integer portion of the wavelength. FIG. 7 is a cross-sectional view of a separate dichroic hologram to that used in the first embodiment of the present invention. FIG. 8A is a schematic view of a wavefront of the light of wavelength λ2 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 8B is a schematic view of the wavefront of FIG. 8A that is calculated ignoring the integer portion of the wavelength. FIG. 8C is a schematic view of a wavefront of the light of wavelength λ3 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 8D is a schematic view of the wavefront of FIG. 8C that is calculated ignoring the integer portion of the wavelength. FIG. 9A is a conceptual diagram showing the diffraction efficiency of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 9B is a conceptual diagram showing the transmittance of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 10 is a schematic view showing the principal directions of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 11 is a structural diagram of an optical disk drive according to the first embodiment of the present invention. FIG. 12A is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD1. FIG. 12B is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD2. FIG. 12C is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD3. FIG. 13A is a schematic view of a conventional optical disk drive when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WDa. FIG. 13B is a schematic view of the conventional optical disk drive when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WDb. FIG. 14A is a structural view of associated circuits of an optical head according to the first embodiment of the present invention. FIG. 14B is a structural view according to a separate example of associated circuits of the optical head according to the first embodiment of the present invention. FIG. 15 is an outline of a signal that is output from the associated circuit of the optical head according to the first embodiment of the present invention. FIG. 16A is a structural diagram of the manner in which a high density optical disk is recorded and reproduced in an optical system according to a second embodiment of the present invention. FIG. 16B is a structural view of the manner in which a DVD is recorded and reproduced in an optical system according to the second embodiment of the present invention. FIG. 17A is a view of an upper surface of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 17B is a view of a rear surface of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 18A is a structural diagram of a separate example of the manner in which a high density optical disk is recorded and reproduced in the optical system according to the second embodiment of the present invention. FIG. 18B is a structural diagram of a separate example of the manner in which a DVD is recorded and reproduced in the optical system according to the second embodiment of the present invention. FIG. 19A is a view of an upper surface of a separate example of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 19B is a view of a rear surface of a separate example of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 20A is a structural diagram of the manner in which a high density optical disk is recorded and reproduced in an optical system according to a third embodiment of the present invention. FIG. 20B is a structural diagram of the manner in which a DVD is recorded and reproduced in the optical system according to the third embodiment of the present invention. FIG. 20C is a structural diagram of the manner in which a CD is recorded and reproduced in the optical system according to the third embodiment of the present invention. FIG. 21A is a view of an upper surface of a dichroic hologram that is used in the third embodiment of the present invention. FIG. 21B is a view of a rear surface of the dichroic hologram that is used in the third embodiment of the present invention. FIG. 21C is a cross-sectional view of the dichroic hologram that is used in the third embodiment of the present invention. FIG. 22 is a cross-sectional view of the dichroic hologram according to the third embodiment of the present invention. FIG. 23A is a schematic view of a wavefront of the light of wavelength λ2 after it has passed through the dichroic hologram used in the third embodiment of the present invention. FIG. 23B is a schematic view of the wavefront of FIG. 23A that is calculated ignoring the integer portion of the wavelength. FIG. 24 is a conceptual diagram showing the diffraction efficiency of light that is diffracted by the dichroic hologram used in the third embodiment of the present invention. FIG. 25A is a schematic view of a wavefront of the light of wavelength λ3 after it has passed through the dichroic hologram used in the third embodiment of the present invention. FIG. 25B is a schematic view of the wavefront of FIG. 25A that is calculated ignoring the integer portion of the wavelength. FIG. 26 is a structural diagram of an optical head according to a fourth embodiment of the present invention. FIG. 27A is a structural overview of an objective lens drive apparatus according to the fourth embodiment of the present invention. FIG. 27B is a lateral view of the objective lens drive apparatus according to the fourth embodiment of the present invention. FIG. 28 is an overview showing the structure of an optical head according to a fifth embodiment of the present invention. FIG. 29A is a plan view of a phase plate according to the fifth embodiment of the present invention. FIG. 29B is a lateral view of the phase plate according to the fifth embodiment of the present invention. FIG. 30 is a diagram of wavefront aberration according to the fifth embodiment of the present invention. FIG. 31 is a structural diagram of an optical head according to a sixth embodiment of the present invention. FIG. 32A is a plan view of a phase plate according to the sixth embodiment of the present invention. FIG. 32B is a lateral view of the phase plate according to the sixth embodiment of the present invention. FIG. 33 is a diagram of the wavefront aberration according to the sixth embodiment of the present invention. FIG. 34 is a structural diagram of an optical head according to a seventh embodiment of the present invention. FIG. 35A is a plan view of a phase plate according to the seventh embodiment of the present invention. FIG. 35B is a lateral view of the phase plate according to the seventh embodiment of the present invention. FIG. 36 is a diagram of the wavefront aberration according to the seventh embodiment of the present invention. FIG. 37 is a structural diagram of an optical head according to an eighth embodiment of the present invention. FIG. 38 is a structural diagram of a mirror according to the eighth embodiment of the present invention. FIG. 39A is a plan view of a phase plate according to a ninth embodiment of the present invention. FIG. 39B is a lateral view of the phase plate according to the ninth embodiment of the present invention. FIG. 40 is a structural diagram of an optical head according to a tenth embodiment of the present invention. FIG. 41A is a plan view of a liquid crystal hologram according to the tenth embodiment of the present invention. FIG. 41B is a lateral view of the liquid crystal hologram according to the tenth embodiment of the present invention. FIG. 42A is a plan view of a phase plate according to the tenth embodiment of the present invention. FIG. 42B is a lateral view of the phase plate according to the tenth embodiment of the present invention. FIG. 43 is a structural diagram of an optical head according to an eleventh embodiment of the present invention. FIG. 44 is a structural diagram of an objective lens drive apparatus according to the eleventh embodiment of the present invention. FIG. 45 is a diagram used to describe the manner in which the objective lens is tilted. FIG. 46 is a diagram used to describe positions of three spots according to the eleventh embodiment of the present invention. FIG. 47 is a structural diagram of the optical head according to the eleventh embodiment of the present invention. FIG. 48 is a structural diagram of an optical head according to a twelfth embodiment of the present invention. FIG. 49A is a cross-sectional view of an objective lens according to the twelfth embodiment of the present invention. FIG. 49B is a view of a rear surface of the objective lens according to the twelfth embodiment of the present invention. FIG. 50 is a diagram used to describe tilt detection according to the twelfth embodiment of the present invention. FIG. 51 is a structural diagram of an optical head according to a thirteenth embodiment of the present invention. FIG. 52 is an overview of an optical disk drive that uses an optical head according to the present invention. FIG. 53 is an external view of a personal computer that uses the optical disk drive of the present invention. FIG. 54 is an external view of an optical disk recorder that uses the optical disk drive of the present invention. FIG. 55 is an external view of an optical disk player that uses the optical disk drive of the present invention. FIG. 56 is an external view of a server that uses the optical disk drive of the present invention. FIG. 57 is a car navigation system that uses the optical disk drive of the present invention. FIG. 58A is a structural diagram showing the manner in which a DVD is recorded and reproduced by an optical head according to a first conventional example. FIG. 58B is a structural diagram showing the manner in which a CD is recorded and reproduced by the optical head according to the first conventional example. FIG. 59 is a cross-sectional view of a dichroic hologram according to the first conventional example. FIG. 60A is a schematic view of a wavefront of the light of wavelength λ2 after it has passed through the dichroic hologram used in the first conventional example. FIG. 60B is a schematic view of the wavefront of FIG. 60A that is calculated ignoring the integer portion of the wavelength. FIG. 61 is a structural diagram of an optical head according to a second conventional example. FIG. 62A is a plan view of a phase plate according to the second conventional example. FIG. 62B is a lateral view of the phase plate according to the second conventional example. FIG. 63 is a structural diagram of an objective lens according to a third conventional example. FIG. 64 is a diagram that is used to explain the position of three spots according to the third conventional example. BEST MODE FOR CARRYING OUT THE INVENTION According to a first optical element of the present invention, since light of a wavelength 380 to 420 nm can pass with favorable efficiency, and light of a wavelength 630 to 680 nm can be diffracted with favorable efficiency, a wavefront of light of different wavelengths can be converted with little loss. Furthermore, manufacturing can be simplified, since it has two step grooves. According to a second optical element of the present invention, since light of a wavelength 380 to 420 nm can pass with favorable efficiency, and light of a wavelength 630 to 680 nm can be diffracted with favorable efficiency, a wavefront of light of different wavelengths can be converted with little loss. Furthermore, the efficiency of the light that is diffracted can be increased further, since it has four step grooves. In the second optical element it is preferable that the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order: depth 3d, depth d, depth 4d, depth 2d. The efficiency of the light that is diffracted can be increased further in this configuration. Furthermore, it is preferable that the grooves are formed in concentric ring-shapes. According to this configuration, light that has a flat wavefront that is incident on the optical element as collimated light can be converted to a converging wavefront or a diverging wavefront. Furthermore, it is also possible to add or remove spherical aberration at the same time. Furthermore, it is preferable that the grooves are adjacent via a portion in which no grooves are formed, and the width of each step of the grooves, is substantially the same as the width of the portion in which no grooves are formed. According to this configuration, manufacturing is simplified, and the efficiency of diffracted light can be increased. According to a first optical head of the present invention, a first light passes through the optical element with favorable efficiency and can record onto and reproduce from the first optical information medium, and a second light is diffracted by the optical element with favorable efficiency and can record onto and reproduce from the second optical information medium. Furthermore, manufacturing can be simplified, since it is a two step groove. According to a second optical head of the present invention, the first light passes through the optical element with favorable efficiency and can record onto and reproduce from the first optical information medium, and the second light is diffracted by the optical element with favorable efficiency and can record onto and reproduce from the second optical information medium. Furthermore, the efficiency of the light that is diffracted improves since the optical element has four step grooves. In the first and the second optical heads, it is preferable that the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order: depth 3d, depth d, depth 4d, depth 2d. The efficiency of the light that is diffracted can be increased further according to this configuration. Furthermore, it is preferable that the second wavelength is 1.5 to 1.8 times the length of the first wavelength. According to this configuration, the efficiency of the light that is diffracted can be increased further. Furthermore, it is preferable that the grooves of the optical element are formed on a face that is close to the focusing means. According to this configuration, by bringing the focusing means closer to the grooves face of the optical element, manufacturing can be simplified because groove interval can be large even when making similar wavefront. that contains the grooves, the efficiency of the light that is diffracted can be further increased. Furthermore, it is preferable that as for light of the second wavelength that is diffracted by the optical element, the light that diverges is stronger than the light that converges with respect to incident light. According to this configuration, since the focal length of the diffracted light can be extended, the working distance can be substantially fixed even when recording onto and reproducing from a disk whose substrate thickness is thick. Furthermore, it is preferable that the optical element corrects the aberration to not more than 70 mλ when light of the second wavelength that is diffracted by the optical element is focused on an information surface of a second information recording medium. According to this configuration, information can be recorded and reproduced reliably since the aberration of the diffracted light can be corrected to a sufficiently small amount when information is recorded onto and reproduced from the second information recording medium. According to a third optical head of the present invention, the structure is simplified since a single optical element converts the wavefront of the second light and the third light, whose aberration was corrected. Furthermore, since the third optical head is provided with grooves whose depth is in two steps, through which the first light passes with favorable efficiency, and the second light is diffracted with favorable efficiency, the wavefront of light of different wavelength can be converted with less losses. Moreover, manufacturing can be simplified, because it is a two step groove. According to a fourth optical head of the present invention, manufacturing can be simplified because a single optical element converts the wavefronts of the second light and the third light, whose aberrations were corrected. Furthermore, since the third optical head is provided with grooves whose depth is in four steps, the wavelength of light of different efficiencies can be converted with less loss because the first light passes with favorable efficiency, and the second light is diffracted with favorable efficiency. Moreover, the utilization efficiency of the light can be improved because it is a four step groove. In a third and a fourth optical head, it is preferable that the depth of the grooves is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order depth 3d, depth d, depth 4d, depth 2d. According to this configuration, the efficiency of the light that is diffracted can be increased further. Furthermore, it is preferable that the second wavelength is 1.5 to 1.8 times the length of the first wavelength, and that the third wavelength is 1.8 to 2.2 times the length of the first wavelength. According to this configuration, the utilization efficiency of the light can be increased further. Furthermore, it is preferable that when a first region is a substantially circle-shaped region in the central vicinity of the first optical element, a second region is a substantially ring-shaped region that surrounds the first region, and a third region is a region on the outside of the second region, light of the first wavelength passes through the first, second and third region, light of the second wavelength passes through the first and second region, and light of the third wavelength passes through the first region. According to this configuration, information can be reliably recorded and reproduced because the light of each wavelength is converted optimally wavefront using different regions of a single optical element. Furthermore, it is preferable that as for light of the second wavelength and third wavelength that are diffracted by the first optical element, the light that diverges is stronger than the light that converges with respect to incident light. According to this configuration, since the focal length of the diffracted light can be extended, the working distance can be substantially fixed even when recording onto and reproducing from a disk whose substrate thickness is thick. Furthermore, it is preferable that the third and fourth optical heads provide phase correcting means for correcting the aberration of light of the second wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the second wavelength is focused on the information surface of the second information recording medium, and for correcting the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the third wavelength is focused on the information surface of the third information recording medium, wherein the phase correcting means does not change the phase of light of the first wavelength, and wherein the phase correcting means is provided in the light path between the light sources and the optical information recording medium. According to this configuration, since aberration of the diffracted light can be corrected to a sufficiently small amount during recording and reproduction of the second information recording medium and the third information recording medium, information can be recorded and reproduced reliably. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be reliably recorded and reproduced because two optical elements are used for converting the wavefronts to correct the aberration of the second light and of the third light. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; wherein the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n1−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in two steps of depth d and depth 2d. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. Moreover manufacturing can be simplified, because it is a two step groove. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; wherein the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in three steps of depth d, depth 2d, depth 3d. According to this configuration the aberration can be corrected to an even smaller amount and the information can be reliably recorded and reproduced because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. Furthermore, the utilization efficiency of the light can be increased because the second optical element has three-step grooves. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength, wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; wherein the first optical element and the second optical element are formed on a top and a rear of a single substrate. According to this configuration, the single optical element can be provided with two functions, so that the configuration of the optical head is simplified. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength, wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; and wherein the first optical element and the second optical element are formed on a top and a rear of a single substrate, and the face on which the second optical element is formed, of the two faces of the single substrate, is closer to the focusing means. According to this configuration, manufacturing is facilitated because by causing the focusing means and a face of the grooves of the second optical element to come closer, the groove interval can be increased even when making similar wavefronts for the second information recording media, which requires a smaller groove interval. Furthermore, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength; wherein light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means, and irradiated onto the optical information recording medium; and wherein the first and second optical elements correct the aberration of light of the second wavelength that is diffracted by the first and the second optical elements to not more than 70 mλ when it is focused on the information surface of the second information recording medium, and correct the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when it is focused on the information surface of the third information recording medium. According to this configuration, information can be recorded and reproduced reliably because the aberration can be corrected to a sufficiently small amount when the diffracted light records onto and reproduces from the second information recording medium and the third information recording medium. Furthermore, it is preferable that when a distance between the surface of the first information recording medium on the focusing means side, and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side, and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side, and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, a difference between the maximum value and the minimum value of WD1, WD2 and WD3 is smaller than the maximum value of the diameter of the focusing means. According to this configuration, the height of the focusing means can be stabilized further and information can be recorded and reproduced with greater reliability, even when recording and reproducing information on different types of information recording media. Furthermore, it is preferable that when a distance between the surface of the first information recording medium on the focusing means side, and the tip of the focusing means on the side of the first information recording medium is WD1 when light of the first wavelength is irradiated onto the first information recording medium, and a distance between the surface of the second information recording medium on the focusing means side, and the tip of the focusing means on the side of the second information recording medium is WD2 when light of the second wavelength is irradiated onto the second information recording medium, and a distance between the surface of the third information recording medium on the focusing means side, and the tip of the focusing means on the side of the third information recording medium is WD3 when light of the third wavelength is irradiated onto the third information recording medium, WD1, WD2 and WD3 are substantially equivalent. According to this configuration, since the height of the focusing means is substantially the same, the optical head can be small. In any of the first to fourth optical heads, it is preferable that they further a comprise converter for converting a plurality of signals, which are received in parallel and are output from the photodetecting means, into a serial signal. According to this configuration, fabrication of the optical head can be facilitated because the number of signal lines that link the optical head and the drive can be reduced. It is also preferable that they further comprise a converter for converting a plurality of signals, which are received in parallel and are output from the photodetecting means, into a serial signal, wherein the serial signal is an electrical signal. According to this configuration, the signal is easier to manage. It is also preferable further to comprise a first converter for converting a plurality of signals, which are output from the photodetecting means and are received in parallel, into a serial signal; and a second converter for receiving the electric signal that is output from the first converter and for converting the electric signal into an optical signal. According to this configuration, there is no deterioration of even a high frequency signal because the signal is converted to an optical signal, and the signal can be output with less noise. According to a first optical information recording and reproduction apparatus of the present invention, a first information recording medium can be recorded and reproduced by passing a first light through an optical element with favorable efficiency, and a second information recording medium can be recorded and reproduced by diffracting a second light with favorable efficiency through the optical element. Furthermore, manufacturing can be simplified, since it has two step grooves. According to a second optical information recording and reproduction apparatus of the present invention, a first information recording medium can be recorded and reproduced by passing a first light with favorable efficiency through an optical element, and a second information recording medium can be recorded and reproduced by diffracting a second light with favorable efficiency through the optical element. Furthermore, the efficiency of the diffracted light is further improved because the optical element has four step grooves. It is preferable that the second optical element of the second optical recording and reproduction apparatus of the present invention comprises grooves whose depth is lined up in the order: depth 2d, depth 4d, depth d, depth 3d, or in the order depth 3d, depth d, depth 4d, depth 2d. According to this configuration, the efficiency of the diffracted light can be further improved. According to a third optical information recording and reproduction apparatus of the present invention, the structure is simplified because a single optical element can convert the wavefront of a second light and a third light to correct aberration. Furthermore, since the third optical information recording and reproduction apparatus provides grooves that have a depth of two steps, and the first light passes with favorable efficiency and the second light is diffracted with favorable efficiency, the wavefronts of light of different wavelength can be converted with little loss. Moreover, manufacturing can be simplified, since it has two step grooves. According to a fourth optical information recording and reproduction apparatus of the present invention, the structure is simplified because a single optical element can convert the wavefront of a second light and a third light to correct aberration. Furthermore, since the fourth optical information recording and reproduction apparatus provides grooves that have a depth of four steps, and the first light passes with favorable efficiency and the second light is diffracted with favorable efficiency, the wavefronts of light of different wavelength can be converted with little loss. Moreover, the efficiency of the diffracted light is further improved because the optical element has four step grooves. In the third and fourth optical information recording and reproduction apparatuses of the present invention, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength, and that light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means and irradiated onto the optical information recording medium. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. According to a third optical element of the present invention, light, the wavelength 380 to 420 nm can be passed with favorable efficiency, and the wavefront of light of wavelength 630 to 680 nm can be converted. In the third optical element of the present invention, it is preferable that the steps are formed in a concentric ring-shapes. According to this configuration, light that has a flat wavefront that is incident on the optical element as collimated light can be converted to a converging wavefront or a diverging wavefront. Furthermore, it is also possible to add or remove spherical aberration at the same time. According to a fifth optical head of the present invention, the wavelength 380 to 420 nm can be passed with favorable efficiency, and the wavefront of light of wavelength 630 to 680 nm can be converted. According to a sixth optical head of the present invention, loss of light with respect to ultra high density optical disks (the first information recording medium) and DVDs (the second information recording medium) can be suppressed using a simply constructed phase plate. According to a seventh optical head of the present invention, generation of coma aberration can be decreased even when the focusing means is moved in the tracking direction because the degree of divergence of the light that is incident on the focusing means is small. In any of the fifth to seventh optical heads, it is preferable further to provide tilting means for tilting the focusing means. In this configuration, coma aberration can be cancelled out. According to an eighth optical head of the present invention, a tilting apparatus for the focusing means is not necessary because the light that is incident on the focusing means is collimated light, and the optical head can be simplified. In any of the fifth to eighth optical heads of the present invention, it is preferable that the optical element corrects the aberration of light of the second wavelength when it is focused on the information recording surface of the second information recording medium to not more than 70 mλ. According to this configuration, the wavefront aberration is less than the Marshall standard 70 mλ, the optical head has a diffraction limit capability, and information can be recorded and reproduced favorably. According to a ninth optical head of the present invention, by providing an optical element that satisfies the expression, the wavefront of light of the second wavelength can be converted without substantially affecting the first light and the third light. According to a tenth optical head of the present invention, by providing a liquid crystal element, if the liquid crystal element is in the OFF state when the ultra high density optical disk (the first information recording medium) and the DVD (the second information recording medium) are used, then the light is not affected, and if the liquid crystal element is in the ON state when the CD (the third information recording medium) is used, then the wavefront of the light can be converted. According to an eleventh optical head of the present invention, a high density first information recording medium can be recorded and reproduced by a first light, a second information recording medium can be recorded and reproduced by a second light, and a third information recording medium can be recorded and reproduced by a third light. Furthermore, the structure is simplified because a single optical element converts the wavefronts to correct the aberration of the second light and the third light. In an eleventh optical head of the present invention, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength, and that light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means and irradiated onto the optical information recording medium. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. Furthermore, it is preferable that the second wavelength is 1.5 to 1.8 times the length of the first wavelength, and that the third wavelength is 1.8 to 2.2 times the length of the first wavelength. According to this configuration, the light utilization ratio can be increased further. Furthermore, it is preferable that when a first region is a substantially circle-shaped region in the central vicinity of the first optical element, a second region is a substantially ring-shaped region that surrounds the first region, and a third region is a region on the outside of the second region, light of the first wavelength passes through the first, second and third region, light of the second wavelength passes through the first and second region, and light of the third wavelength passes through the first region. According to this configuration, information can be recorded and reproduced reliably because the light of each wavelength is converted optimally wavefront using different regions of a single optical element. It is also preferable that as for light of the second wavelength and light of the third wavelength that is diffracted by the optical element, the light that diverges is stronger than the light that converges with respect to incident light. According to this configuration, since the focal length of the diffracted light can be extended, the working distance can be substantially fixed even when recording onto and reproducing from a disk whose substrate thickness is thick. It is also preferable that phase correcting means for correcting the aberration of light of the second wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the second wavelength is focused on the information surface of the second information recording medium, and for correcting the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when light of the third wavelength is focused on the information surface of the third information recording medium, is provided in the light path between the light sources and the optical information recording medium, wherein the phase correcting means does not change the phase of light of the first wavelength. According to this configuration, information can be recorded and reproduced reliably because diffracted light can correct the aberration to a sufficiently small amount when information is recorded and reproduced for the second information recording medium and the third information. It is also preferable that the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in two steps of depth d and depth 2d. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. Furthermore, manufacturing can be simplified, since it has two step grooves. It is also preferable that the second optical element is an optical element in which grooves are formed in a substrate; wherein the expression: 760 nm≦(n−1)×d≦840 nm is satisfied, where n is a refractive index of the substrate at a wavelength of 400 nm, and d (nm) is a depth per step of the grooves; and wherein the grooves are formed in three steps of depth d, depth 2d and depth 3d. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. Furthermore, the utilization efficiency of the light can be increased because the second optical element has three step grooves. It is also preferable that the first optical element and the second optical element are formed on a top and a rear of a single substrate. According to this configuration, the single optical element can be provided with two functions, so that the configuration of the optical head is simplified. It is also preferable that the first optical element and the second optical element are formed on a top and a rear of a single substrate, and that the face on which the second optical element is formed, of the two faces of the single substrate, is closer to the focusing means. According to this configuration, manufacturing is facilitated because by causing the focusing means and a face of the grooves of the second optical element to come closer, the groove interval can be increased even when making similar wavefronts for the second information recording media, which requires a smaller groove interval. It is also preferable that the first and second optical elements correct the aberration of light of the second wavelength that is diffracted by the first and the second optical elements to not more than 70 mλ when it is focused on the information surface of the second information recording medium, and correct the aberration of light of the third wavelength that is diffracted by the first optical element to not more than 70 mλ when it is focused on the information surface of the third information recording medium. According to this configuration, information can be recorded and reproduced reliably because the aberration can be corrected to a sufficiently small amount when the diffracted light records onto and reproduces from the second information recording medium and the third information recording medium. According to a twelfth optical head of the present invention, the height of the focusing means can be stabilized further and information can be recorded and reproduced with greater reliability, even when recording and reproducing information on different types of information recording media. According to a thirteenth optical head of the present invention, the height of the focusing means is substantially the same, and information can be recorded and reproduced with greater reliability, even when recording and reproducing information on different types of information recording media. According to a fourteenth optical head of the present invention, fabrication of the optical head can be facilitated because the number of signal lines that link the optical head and the drive can be reduced. In the fourteenth optical head of the present invention, it is preferable that the serial signal is an electrical signal. According to this configuration, the signal is easier to manage. Furthermore, it is preferable further to provide a second converter for receiving the electric signal that is output from the first converter and for converting the electric signal into an optical signal. According to this configuration, there is no deterioration of even a high frequency signal because the signal is converted to an optical signal, and the signal can be output with less noise. According to a fifth optical information recording and reproduction apparatus of the present invention, a high density first information recording medium can be recorded and reproduced by a first light, a second information recording medium can be recorded and reproduced by a second light, and a third information recording medium can be recorded and reproduced by a third light. Furthermore, the structure is simplified because a single optical element converts the wavefronts to correct the aberration of the second light and the third light. In the fifth optical information recording and reproduction apparatus of the present invention, it is preferable that a second optical element is further provided that passes light of the first wavelength and light of the third wavelength, and diffracts light of the second wavelength, and that light of the first wavelength, light of the second wavelength and light of the third wavelength pass through the two optical elements, after which they are focused by the focusing means and irradiated onto the optical information recording medium. According to this configuration, the aberration can be corrected to an even smaller amount and the information can be recorded and reproduced reliably because two optical elements are used to convert the wavefronts to correct the aberration of the second light and of the third light. According to a fifteenth optical head of the present invention, since the outside diameter of a first focusing means is small, a second optical means also can move to the most inner circumference position, and is capable of reading in the information at the innermost circumference position. According to a sixteenth optical head of the present invention, tilt sensing can be performed using a simple configuration by utilizing light of a wavelength that is not recording or reproducing information, such that it is not necessary to install a new tilt sensor, thus reducing costs. In the sixteenth optical head of the present invention, it is preferable that the first focusing means emits light onto the information recording medium whose substrate thickness is 1.2 mm, and second focusing means emits light onto the information recording media whose substrate thickness is 0.1 mm and 0.6 mm. It is also preferable that the first focusing means and the second focusing means are lined up in the tracking direction. According to this configuration, it is possible to use the DPP method or the three beam method, which are common tracking detection methods, and favorable tracking detection can be performed. According to a seventeenth optical head of the present invention, the tilt control can be prevented from interfering with the focus control, since the information recording medium on which it is preferable to perform tilt adjustment, whose substrate thickness is thinnest, is substantially in the center of a movable body. In the seventeenth optical head of the present invention, it is preferable to further provide tilting means that tilt the focusing means. According to an eighteenth and a nineteenth optical head of the present invention, tilt sensing can be performed using a simple configuration by utilizing light of a wavelength that is not recording or reproducing information, such that it is not necessary to install a new tilt sensor, thus reducing costs. In the eighteenth and nineteenth optical head of the present invention, it is preferable that the first wavelength is in the range 380 to 420 nm. Furthermore, in the nineteenth optical head, it is preferable that the first focusing means and the second focusing means are lined up in the tracking direction. According to this configuration, it is possible to use the DPP method or the three beam method, which are common tracking detection methods, and favorable tracking detection can be performed. It is also preferable that the second focusing means is provided with a region through which light of a second wavelength passes without being focused. According to this configuration, the tilt of the first information recording medium can be detected using the light that passes through this region. It is also preferable that the second focusing means is provided with a region through which light of the second wavelength is focused onto the first information recording medium. According to this configuration, the tilt of the first information recording medium can be detected using the light that passes through this region. It is also preferable that a holder on which the first focusing means and the second focusing means is mounted, is provided with a through hole through which light of the second wavelength passes. According to this configuration, the tilt of the first information recording medium can be detected using light that passes through the hole in the holder. According to a liquid crystal element of the present invention, it is possible to change between a light influencing setting, and a setting in which the wavefront of the light is converted, depending on the type of information recording media. According to a computer, an image recording apparatus, a moving image reproduction apparatus, a server and a car navigation system of the present invention, information can be recorded onto and reproduced from different types of optical disks reliably, and they can be used over a wide range of applications. Hereinafter, an embodiment of the present invention is described with reference to drawings. On each drawing given below, the same symbols are given to parts that perform the same action. First Embodiment FIG. 1 shows a structural view of an optical head 20 according to a first embodiment of the present invention. The optical head 20 is capable of at least either recording to or reproducing from (referred to below as “recording and reproduction”) an optical disk. FIG. 1A shows the recording and reproduction state of a high density optical disk whose substrate thickness is thin, FIG. 1B shows the recording and reproduction state of a DVD, and FIG. 1C shows the recording and reproduction state of a CD. The optical head 20 is provided with three types of light source; a blue semiconductor laser 21 (light source of a first wavelength) of a wavelength of approximately 400 nm (380 nm to 420 nm), a red semiconductor laser 22 (light source of a second wavelength) of a wavelength of 630 nm to 680 nm, and an infrared semiconductor laser 23 (light source of a third wavelength) of a wavelength of 780 nm to 820 nm. When recording and reproducing a high density optical disk 30 (FIG. 1A), light of a wavelength λ1 emitted from the blue semiconductor laser 21 passes through wavelength selecting prisms 24 and 25, and is converted to collimated light by a collimator lens 26. The light that was made parallel is reflected by a beam splitter 27, passes through a dichroic hologram (optical element) 28, is converted to convergent light by an objective lens (focusing means) 29 and is irradiated onto the high density optical disk (a first information recording medium) 30. The numerical aperture (NA) of the objective lens 29 is 0.85, and the substrate thickness of the high density optical disk is assumed to be 0.1 mm. The objective lens 29 is designed such that the aberration is at a minimum, that is to say, such that the standard deviation of the wavefront aberration is at a minimum when the blue light of wavelength λ1 is irradiated onto the disk of substrate thickness 0.1 mm. Furthermore, the dichroic hologram 28 is designed so as to allow the light of wavelength λ1 to pass through it without being affected. The light that was reflected by the high density optical disk 30, diffracted and modulated, passes again through the objective lens 29 and the dichroic hologram 28, passes through the beam splitter 27, is converted to convergent light by a detecting lens 31, and is incident on a photodetector (a photodetecting means) 32. The photodetector 32 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. When recording and reproducing a DVD 33 (a second information recording medium) (FIG. 1B), light of a wavelength λ2 emitted from the red semiconductor laser 22 is reflected by the wavelength selecting prism 24, passes through the wavelength selecting prism 25, and is converted to collimated light by the collimator lens 26. The light that was converted to collimated light is reflected by the beam splitter 27, is diffracted and wavefront converted by the dichroic hologram (optical element) 28, converted to converging light by the objective lens 29, and is irradiated onto the DVD 33. The numerical aperture (NA) of the light emitted from the objective lens 29 is limited to 0.6. The substrate thickness of the DVD 33 is 0.6 mm. The dichroic hologram 28 is designed such that when the red light of wavelength λ2 irradiates the disk of the substrate thickness 0.6 mm after passing through the objective lens 29, the standard deviation of the wavefront aberration is not more than 70 mλ. The light that was reflected by the DVD 33, diffracted and modulated, passes again through the objective lens 29 and the dichroic hologram 28, passes through the beam splitter 27, is converted to converging light by the detecting lens 31, and is incident on the photodetector 32. The photodetector 32 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. When recording and reproducing a CD 34 (third information recording medium) (FIG. 1C), light of a wavelength λ3 emitted from the infrared semiconductor laser 23 is reflected by the wavelength selecting prism 25, and is converted to collimated light by the collimator lens 26. The light that was converted to collimated light is reflected by the beam splitter 27, is diffracted and wavefront converted by the dichroic hologram (optical element) 28, is converted to converging light by the objective lens 29, and is irradiated onto the CD 34. The numerical aperture (NA) of the light emitted from the objective lens 29 is limited to 0.4. The substrate thickness of the CD 34 is 1.2 mm. The dichroic hologram 28 is designed such that when the infrared light of wavelength λ3 irradiates the disk of the substrate thickness 1.2 mm after passing through the objective lens 29, the standard deviation of the wavefront aberration is not more than 70 mλ. The light that was reflected by the CD 34, diffracted and modulated, passes again through the objective lens 29 and the dichroic hologram 28, passes through the beam splitter 27, is converted to converging light by the detecting lens 31 and is incident on the photodetector 32. The photodetector 32 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. FIG. 2A shows an upper surface pattern of the dichroic hologram, and FIG. 2B shows a rear surface pattern. The light that approaches the disk enters from the rear surface (first optical element) 40 and exits from an upper surface (second optical element) 41. Light of wavelength λ3, which is in a range of 780 nm to 820 nm, is diffracted in a region 42 of the rear surface 40, and a pattern is formed so as to provide a wavefront that is optimal to the CD 34 (such that the standard deviation of the wavefront aberration is not more than 70 mλ when focusing on the CD 34). The light of wavelength λ3 passes through the upper surface 41 without being affected. Furthermore, the light of wavelength λ2, which is in a range of 630 to 680 nm, is diffracted by the pattern in the region 42 of the rear surface 40, after which it is also diffracted by the pattern that is formed in a region 43 on the upper surface 41. The pattern within the region 43 is formed such that the light of wavelength λ2 that was diffracted by both upper and rear surfaces has an optimal wavelength for the DVD 33 (such that when focusing on DVD 33, the standard deviation of the wavefront aberration is not more than 70 mλ). Because the principal object of the upper surface 41 and the rear surface 40 is to apply power to the diffracted light and to correct spherical aberration, the pattern is concentric ring-shaped. Light in the vicinity of wavelength λ1=400 nm passes through both upper and rear surfaces without being affected. FIG. 3 shows an enlarged cross-section of the rear surface 40 of the dichroic hologram 28. The rear surface 40 of the dichroic hologram is engraved with grooves that have four types of depth (d to 4d). These grooves are configured in a repeating pattern of a group of grooves that are lined up as a single group in the order of 2d, 4d, d, 3d and no-groove portion. Here, depth d is: d=λ1/(n1−1) where n1 is the refractive index of a medium at the wavelength λ1, which is selected from within the range 380 to 420 nm. The phase shift in the light of wavelength λ1 that occurs due to the light path difference between the indented groove portion and the no-groove portion is an integer multiple of 2π by satisfying this relationship. That is to say, the light path length (n1−1)×d is equivalent to the wavelength λ1. Due to this, light of the blue semiconductor laser of wavelength λ1 passes through the dichroic hologram 28 unaffected (it is not diffracted). If the wavelength is fixed, the light path length expressed by (n1−1)×d has a unique value, and the effect that the light that is within the wavelength range 380 to 420 nm passes substantially through the dichroic hologram 28 can be obtained if the light path length is within a predetermined range. More specifically, it is preferable that the expression: 380 nm≦(n1−1)×d≦420 nm is satisfied when the standard wavelength, from the range 380 to 420 nm of wavelengths of λ1, is 400 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. On the other hand, light of wavelength λ2 of the red semiconductor laser has a modulated wavefront as shown in FIG. 4A. Because the light of wavelength λ2 that records and reproduces DVDs is in the range 630 nm to 680 nm, d is a depth that is equivalent to approximately 0.6 times the length of wavelength λ2. Consequently, 2d is 1.2λ, 3d is 1.8λ and 4d corresponds to 2.4λ. If each value is an integer multiple of λ then the phase shift of the light does not occur, so that with regards to the phase of the light, integer multiples of λ can be ignored. Thus, considering only the fractional parts smaller than the decimal point, d is 0.6λ, 2d is 0.2λ (1.2λ−1λ), 3d is 0.8λ (1.8λ−1λ), and 4d corresponds to 0.4λ (2.4λ−2λ). Consequently the grooves arranged in the order of 2d, 4d, d and 3d form wavefronts that have stepwise phase changes of 0.2λ, 0.4λ, 0.6λand 0.8λ with respect to the light of wavelength λ2 as shown in FIG. 4B. That is to say that with respect to the light of wavelength λ2, the grooves shown in FIG. 3 can be thought of as grooves that deepen in a stepwise manner in the direction from the 2d side to the 3d side, as shown in FIG. 4B. When grooves such as those shown in FIG. 3 are formed on the incident face side (a boundary at which the light propagates from a medium of low refractive index (such as air) to a one of a high refractive index (such as glass)) of an optical element, the intensity of light that is diffracted in a direction 1 (the direction from the groove depth 3d side toward the groove depth 2d side) of FIG. 3 is stronger than light that is diffracted in a direction 2 (the direction from the groove depth 2d side toward the groove depth 3d side). Here, FIG. 5 shows the relationship between the groove depth of a single step that is standardized with respect to the wavelength λ, and an efficiency R, which is the efficiency of incident light that is converted to first order diffracted light by a dichroic hologram such as that whose cross-section is shown in FIG. 3. When the depth that corresponds to a single step is 0.6 times λ, the diffraction efficiency is at its maximum, and it is possible to obtain a diffraction efficiency greater than 0.8. Furthermore, a wavefront of the light of wavelength λ3 of the infrared semiconductor laser is modulated as shown in FIG. 6A. Because λ3 is in a range of 780 nm to 820 nm for the purpose of recording and reproducing CDs, d is a depth equivalent to approximately 0.5 times the length of wavelength λ3. Consequently, 2d is 1.0λ, 3d is 1.5λ and 4d is equivalent to 2.0λ. As described previously, as the phase of the light, the integer multiple portions of λ can be ignored, so if only the portions smaller than the decimal point are considered, then d is 0.5λ, 2d is 0 (1.0λ−1λ), 3d is 0.5λ (1.5λ−1λ) and 4d is equivalent to 0 (2.0λ−2λ). Consequently, the grooves arranged in the order of 2d, 4d, d, 3d form wavefronts that have a two step phase of 0, 0, 0.5λ, 0.5λ, whose duty ratio is 3:2 with respect to light of wavelength λ3 as shown in FIG. 6B. In this case, according to FIG. 5, a diffraction efficiency of about 0.3 can be obtained when the depth corresponding to a single step is 0.5 times λ. FIG. 7 shows an enlarged cross-sectional view of the upper surface 41 of the dichroic hologram 28. The upper surface of the dichroic hologram 28 is engraved with grooves of three different depths (d to 3d). These grooves are configured as a single group in a repeating pattern of a group of grooves that are lined up in an order of d, 2d, 3d, and no-groove portion. Depth d is: d=2×λ1/(n1−1) when n1 is the refractive index of a medium at a wavelength λ1, which is selected from the range 380 to 420 nm. By satisfying this relationship, the phase shift in the light of wavelength λ1 that occurs due to the light path difference between the indented portion, which is the groove, and the no-groove portion is an integer multiple of 2π. Due to this, light of the blue semiconductor laser of wavelength λ1 passes through unaffected by the dichroic hologram 28 (it is not diffracted). In this case, the light path length, which is (n1−1)×d, is equivalent to two times the wavelength λ1. As described previously, if the light path length is within a predetermined range then it is possible to achieve the effect that light of a wavelength, which is in a range of 380 to 420 nm, can substantially pass through the dichroic hologram 28. More specifically, it is preferable that the expression: 760 nm≦(n1−1)×d≦840 nm is satisfied when the standard wavelength, from the range 380 to 420 nm of wavelengths of λ1, is 400 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. On the other hand, the light of wavelength λ2 of the red semiconductor laser has a modulated wavefront as shown in FIG. 8A. Because the light of wavelength λ2 that records and reproduces DVDs is in the range λ2=630 nm to 680 nm, d is a depth that corresponds to approximately 1.2 times the length of wavelength λ2. Consequently, 2d is 2.4λ and 3d is 3.6λ. As previously described, integer multiple portions of λ can be ignored for phases of the light, so if only the fractional parts smaller than the decimal point are considered, d is 0.2λ(1.2λ−λ), 2d is 0.4λ (2.4λ−2λ) and 3d is 0.6λ (3.6λ−3λ). Consequently the grooves arranged in the order of d, 2d, and 3d form wavefronts that have stepwise phase changes of 0.2λ, 0.4λ, and 0.6λ with respect to light of wavelength λ2 as shown in FIG. 8B. That is to say that, with respect to the light of wavelength λ2, the grooves shown in FIG. 7 can be considered as grooves that deepen in a stepwise manner in the direction from the d side to the 3d side, as shown in FIG. 8B. When grooves such as those shown in FIG. 7 are formed on the incident face side of an optical element (a boundary at which the light propagates from one of a high refractive index (such as glass) to a medium of low refractive index (such as air)), the intensity of light that is diffracted in a direction 1 (the direction from the groove depth 3d side toward the groove depth d side) of FIG. 7 is stronger than light that is diffracted in a direction 2 (the direction from the groove depth d side toward the groove depth 3d side). FIG. 9A shows the relationship between the groove depth of a single step that is standardized with respect to the wavelength λ, and an efficiency R, which is the efficiency of incident light that is converted to first order diffracted light by a dichroic hologram 28 such as is shown in FIG. 7. When the depth corresponding to a single step is 1.2 times λ, a diffraction efficiency higher than 0.65 can be obtained. Furthermore, the light of wavelength λ3 of the infrared semiconductor laser has a wavefront that is modulated as shown in FIG. 8C. Because λ3 is in a range of 780 nm to 820 nm for the purpose of recording and reproducing CDs, d is a depth equivalent to approximately 1.0 times the length of wavelength λ3. Consequently, 2d is 2.0λ and 3d is equivalent to 3.0λ. As described previously, as the phase of the light, the integer multiple portions of λ can be ignored, so if only the portions smaller than the decimal point are considered then all are equivalent to 0 as shown in FIG. 8d. Consequently, the light of wavelength λ3 is unaffected by the dichroic hologram 28 (it is not diffracted), and substantially passes through it. Here, FIG. 9B shows the relationship between the groove depth of a single step that is standardized with respect to the wavelength λ, and an efficiency R, which is the efficiency of incident light that is converted to zero order diffracted light by a dichroic hologram such as is shown in FIG. 7. When the depth corresponding to a single step is 1.0 times λ, it is possible to obtain a transmittance of approximately 0.9. In this way the light of wavelength λ1 at the rear surface (first optical element) 40 passes though the dichroic hologram 28 substantially without being affected, while the light of wavelength λ2 and wavelength λ3 are diffracted. Furthermore, at the upper surface (second optical element) 41, the light of wavelength λ1 and λ3 pass through and the light of wavelength λ2 is diffracted. Due to this, information can be recorded and reproduced reliably because light sources that have appropriate wavelengths for each of the three types of optical disks (information recording media) are used and light of low aberration can be focused on the information surface with excellent efficiency. Furthermore, the same effect also can be obtained when there are two types of optical disk. It should be noted that the dichroic hologram 28 used here has the first optical element and the second optical element formed on the upper surface 41 and the rear surface 40 as a single piece. However it is also possible to arrange a dichroic hologram such that the first optical element and the second optical element are formed on separate elements. In that case, their centers can be matched up to the optical axis by adjusting the position of both optical elements. Furthermore, it is preferable that the dichroic hologram 28 is fabricated from glass. If it is fabricated from resin, then it is preferable to use amorphous polyolefin based resins whose absorbtance is not more than 5%, and whose absorptance is preferably not more than 3%. This is due to the fact that light of a wavelength of not more than 420 nm has a strong chemical action, so there is a possibility that the resin may be damaged if an optical element of high absorptance is irradiated over a long period. It is relatively difficult to damage amorphous polyolefin based resins, even by irradiating with light of a wavelength less than 420 nm. Moreover, it is also possible to fabricate one of the optical elements on the surface of the objective lens. In this case, it is possible to increase the positional accuracy of the optical axis of the objective lens. Furthermore, the diffraction efficiency shown here is a value that is calculated when the widths of adjacent grooves of different depths are substantially equivalent. Furthermore, even if the grooves are lined up in a sequence that is completely opposite to the examples given here, the same effect can be obtained apart from a change in the direction in which the light is efficiently diffracted. Furthermore, it goes without saying that even if the start point of the way the grooves are lined up, and the way the grooves are described is changed, if the grooves are actually lined up in the same sequence, then the same effect can be obtained. Moreover, the wavelengths λ1 and λ2 satisfy the relationship 1.5≦λ2/λ1≦1.8, and the wavelengths λ1 and λ3 satisfy the relationship 1.8≦λ3/λ1≦2.2. Furthermore, as shown in FIG. 10, the light of wavelength λ2, which is diffracted by the dichroic hologram 28 is designed such that the diffraction efficiency of the light of wavelength λ2 that is diffracted from collimated light to diverging light (direction 1) by the dichroic hologram 28, is greater than the diffraction efficiency on the side in which it is diffracted to converging light (direction 2). More specifically, grooves such as are shown in FIG. 3 are arranged in a concentric ring shape on the incident face such that the direction 1 approaches the circumference, and the direction 2 approaches the center, and moreover, on the exit face side, grooves such as are shown in FIG. 7 are arranged in a concentric ring-shape such that the direction 1 approaches the circumference, and the direction 2 approaches the center. In this way, because the diffraction efficiency in the direction 1 is higher than the diffraction efficiency in the direction 2, the diffracted light is substantially converted to diverging light, and the dichroic hologram 28 acts as a concave lens. Thus, a focal length f of the focusing optical system, which is matched to the objective lens, lengthens and even DVDs, which at 0.6 have a thicker substrate than a substrate thickness of 0.1, can be operated at a relatively large working distance. It should be noted that there is no particular discussion here of methods for limiting the aperture of the light of wavelength λ2 or the light of wavelength λ3, however there is the method of vapor depositing a wavelength selecting filter onto the dichroic hologram 28 or the objective lens 29, or the method of providing a separate glass filter. Furthermore, it is also possible to control the aperture by providing an opening across the light path that is passed only by light of a single wavelength (in the region between the light source and the wavelength selecting prism). FIG. 11 shows an entire structural example of an optical disk drive 50 as an optical information recording and reproduction apparatus. An optical disk 51 is fixed by sandwiching between a turntable 52 and a damper 53, and is rotated by a motor (rotating system) 54, which is a moving means. An optical head 20 is mounted on a traverse (conveying system) 55, which is a moving means, and the point that is irradiated by light is capable of moving from the inner circumference of the optical disk 51 to the outer circumference. The control circuits 56 perform focus control, tracking control, traverse control and rotational control of the motor and the like based on signals received from the optical head 20. FIG. 12 shows the working distance when recording and reproducing each disk. The height of the side at which light is incident on the optical disk is determined by the position of the turntable 52. On the other hand, the relative height of fixing elements 60 on the actuator of the optical head 20 with respect to the turntable 52 is determined uniquely by the structure and the positional relationship of the traverse 55 and the motor 54. Furthermore, the position of a movable element 61 of the actuator that moves the objective lens 29 in the focus direction is determined by the position of the recording surface of the optical disk, and by back focus on the disk side of the objective lens 29, which is the focusing means. Back focus means the length between the tip of the focusing means to the point of convergence of the light rays. The tip of the focusing means more specifically that, of the intersections between the objective lens 29 and the optical axis, it is the intersection that is on the optical disk side. The working distance WD is WD=BF−t/n when the refractive index at the wavelength λ is n, the substrate thickness of the disk is t and the back focus is BF. For example, on a disk in which the substrate thickness is thick, and t/n is large, the working distance WD becomes small such that if the focusing means not designed such that the back focus BF can change in response to that change, then the working distance WD will vary greatly when there is a change in substrate thickness. FIG. 12 shows the working distance WD at a working distance WD1 (FIG. 12A), a working distance WD2 (FIG. 12B) and a working distance WD3 (FIG. 12C), depending on the type of optical disk, that is, depending on changes in the substrate thickness. A configuration according to a conventional example is shown in FIG. 13, showing the case in which a working distance changes greatly depending on the type of optical disk. When there is a large change in working distance due to the type of the optical disk, there is a large change in the relative distance between the fixing elements 60 of the actuator and the movable element 61. Because a working distance WDa in FIG. 13A is small, the movable element 61 is relatively higher than the upper side (disk side) of the fixing elements 60. However as in FIG. 13B, when the working distance WDb is large, the moving element 61 is relatively lower than the lower side (side furthest from the disk) of the fixing elements 60. Because regular optical disks droop on their inner and outer circumferential sides and have shake of disc in focusing direction when rotating, to a certain extent the fixing elements 60 cover the vertical movement range of the movable element 61. However, when there is a difference in working distance, there is a problem in that to absorb that difference, the size of the actuator increases, and the overall size of the optical head. increases. Furthermore, when the movable range is large, the movable element 61 tilts depending on the position of the movable element 61, and there is the problem that the optical system is susceptible to generating aberrations. The moveable range of the moveable element 61 also depends on the structure of the actuator, however it is preferable that it is less than the lateral direction width of the moveable element 61. This is because, if the lateral width is large, even if a height difference develops between left and right, then the tilting angle is small. However, if the lateral width is small, even with a minimal left and right height difference, the tilting angle becomes large. Consequently, the difference in working distance caused by disk type, that is to say, the movable range of the movable element 61 is preferably smaller than the lateral width of the movable element 61. In the example of FIG. 12, it is preferable that the maximum and minimum differences between WD1, WD2 and WD3, being the difference in working distance caused by disk type, are smaller than the lateral width of the movable element 61. In the case of the ultra high density optical disk, when NA=0.85, and the focal length f of the focusing means is 2.0 mm, the beam diameter is φ3.4 mm. Because the minimum value of the width of the movable element 61 is this beam width, in this case there is a need to set the difference between the maximum value and minimum value of the working distance to 3.4 mm at most. It should be noted that when considering the actual size of the actuator, the movement range of the actuator is at best 1 mm, so that it is preferable that the difference between the maximum working distance and minimum working distance is not more than half that at 0.5 mm. Moreover, in order not to substantially affect the size of the actuator, it is preferable that the difference between the maximum value and the minimum value of the working distance is not more than 0.2 mm. Of course, the most preferable state is the one in which the working distance is equivalent when recording onto and reproducing information from differing types of information recording media, and in which the difference between the maximum value and the minimum value is 0. In the present embodiment, since the back focus BF can be set optimally using the dichroic hologram 28 according to the disk that is recorded or reproduced, the WD can be substantially fixed during recording and reproduction of each disk. More specifically, in the example given previously, light from the blue semiconductor laser (wavelength λ1) is not diffracted by the dichroic hologram 28, and the diffraction efficiency of the light from the red semiconductor laser (wavelength λ2) is set to differ from the diffraction efficiency of the light from the infrared semiconductor laser (wavelength λ3). Thus, light of the blue semiconductor laser passes as is through the dichroic hologram 28, the degree of divergence of the light of the red semiconductor laser differs from the degree of divergence of the light of the infrared semiconductor laser, and it is possible to change the back focus depending on the light from each laser. That is to say, it is possible to design the dichroic hologram 28 so as to control the back focus depending on the type of disk, and it is possible to substantially fix the WD without consideration to the type of disk. If the WD can be substantially fixed in this way, then the size of the entire optical head can be reduced, and because the movable range of the movable element 61 can be reduced, it is possible to suppress the generation of aberrations caused by tilt of the movable element 61. FIG. 14 shows an example that unifies the signal output from the optical head of the present embodiment. An optical head 70 has the same optical structural elements as the optical head 20. It differs in the provision of a P/S (parallel/serial) converting circuit 71 (parallel/serial converter) that converts the output signal from the photodetector 32 that is received as a parallel signal into a serial signal. A P/S converting circuit 71 receives signals through a plurality of signal lines from the photodetector 32, time divides and lines them up serially, and outputs them as an output signal through a single signal line. As a method for this, there is the method of sequentially switching an analog switch in an internal portion of the P/S converting circuit based on the clock, which is a timing signal, and outputting the serial signal as an output signal. Furthermore, a method is also possible in which the signal that is obtained in parallel is subjected to analog/digital conversion (A/D conversion), stored in memory and then transmitted as digital data in a serial sequence. FIG. 15 shows an example of the signal in such a case. Synchronised with the clock as the timing signal, digital signals such as an RF signal, and FE+ signal, an FE− signal, a TE+ signal and a TE− signal and the like are transmitted. Thus, the number of signal lines between the optical head and the control circuits and the like of the optical disk drive can be reduced. In optical heads that record and reproduce CDs and DVDs as well as high density optical disks, approximately three times the usual amount of signal lines are necessary just to drive the semiconductor lasers, which are the light source. FIG. 14A shows an example in which the photodetector (photodetecting means) is shared, and as shown in FIG. 14B, also conceivable is a case in which the photodetector (photodetecting means) is not shared, and which has the photodetector (photodetecting means) 72 and a photodetector (photodetecting means) 73, and a case which contains three photodetectors. In these cases, there is a further increase in signal lines, the width of the flexible cable that connects the optical head and the drive is enlarged, and there is the problem of a loss of flexibility (the ease of bending) of the flexible cable. Furthermore, if the flexible cable is changed to a multilayer flexible circuit, then although the width of the flexible cable can be reduced, there is the problem of an increase in cost. If the optical head is an optical head 75 that is provided with a P/S converting circuit 74 for receiving signals in parallel from the photodetector 72 and the photodetector 73, and outputting them as serial signals such as is shown in FIG. 14B, then the number of signal lines can be greatly reduced. In the example of the optical head 75 in FIG. 14B, the signal from the P/S converting circuit 74 is converted to an optical signal by an LED (electrical/optical converter) 76 and is output to an optic fiber 77. In this case, it is possible to transmit a higher frequency signal than an electric signal yet with lower noise, and there is the advantage that these signals can be transmitted with sufficient accuracy and period of time even if there is an increase in the number of signals to be converted. It should be noted that the example in which the P/S converting circuit is utilized is not limited to optical heads in which light sources of three wavelengths are used, and the same effect can be obtained with optical heads containing light sources of one wavelength or two wavelengths. In these cases as well, if a plurality of signal lines are needed for tracking signals or focus signals, then the optical head can be consolidated into a single unit. Furthermore, if A/D conversion is performed within the optical head, then because paths that introduce noise can be shortened, this is also effective in raising the SN ratio of the signal. Second Embodiment An example of an optical head applied interchangeably to high density optical disks and DVDs is described as a second embodiment. FIG. 16 is a structural example of an optical head 80. As shown in FIG. 16A, a light of wavelength λ1 emitted from a blue semiconductor laser (a light source of a first wavelength) 21 passes through the wavelength selecting prism 24, and is converted to collimated light by the collimator lens 26. The light that was converted to collimated light is reflected by the beam splitter 27, passes through the dichroic hologram (optical element) 81, is focused by the objective lens (focusing means) 29 and is irradiated onto the high density optical disk (first information recording medium) 30. The numerical aperture (NA) of the objective lens is 0.85, and the substrate thickness of the high density optical disk 30 is assumed to be 0.1 mm. The objective lens 29 is designed such that spherical aberration is at a minimum when the blue light of wavelength λ1 is radiated onto a disk whose substrate thickness is 0.1 mm. Furthermore, the dichroic hologram 81 is designed so as to pass the light of wavelength λ1 without affecting it. The light that was reflected by the high density optical disk 30, diffracted and modified, again passes through the objective lens 29 and the dichroic hologram 81, passes through the beam splitter 27, is focused by the detecting lens and is incident on a photodetector (photodetecting means) 82. The photodetector 82 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. As shown in FIG. 16B, when recording and reproducing the DVD 33 (second information recording medium), the light of wavelength λ2 is emitted from the red semiconductor laser 22, is reflected by the wavelength selecting prism 24 and is converted to collimated light by the collimator lens 26. The light that was converted to collimated light is reflected by the beam splitter 27, is diffracted by the dichroic hologram 81 and wavefront converted, is focused by the objective lens 29 and is irradiated onto the DVD 33. Here, the numerical aperture (NA) of the light that is emitted from the objective lens is limited to 0.6. The substrate thickness of the DVD 33 is 0.6 mm. The dichroic hologram 81 is designed such that when the red light of wavelength λ2 that has passed through the objective lens 29 is irradiated on to the disk of substrate thickness of 0.6 mm, the standard deviation of wavefront aberration is not more than 70 mλ. The light that was reflected at the DVD 33, diffracted and modulated, again passes through the objective lens 29 and the dichroic hologram 81, passes through the beam splitter 27, is focused by the detecting lens 31, and is incident on the photodetector 82. The photodetector 82 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. FIG. 17 shows a pattern on the upper surface (the disk side) and the rear side (the side that is furthest from the disk) of the dichroic hologram 81. The light that approaches the disk passes through from the rear surface to the upper surface. No particular pattern is formed on the rear surface shown in FIG. 17B. On the upper surface that is shown in FIG. 17A, the light in the range of wavelength λ2=630 to 680 nm is diffracted by a pattern within a region 83. The pattern within the region 83 is formed such that the light of wavelength λ2 that was diffracted at the upper surface has a wavefront that is optimal for the DVD 33. Since the principal object is to apply power to the diffracted light and to correct spherical aberration, the pattern is concentric ring-shaped. Light in the vicinity of wavelength λ1=400 nm passes through both upper and lower surfaces without being affected. The cross-sectional form of the hologram that is formed on the upper surface of the dichroic hologram 81 is the same as the cross-sectional form of that which is formed on the rear surface 40 of the dichroic hologram 28 of the first embodiment. Accordingly, because high diffraction efficiencies can be obtained for the light of wavelength λ2 that is in the range 630 to 680 nm, satisfactory light utilization efficiency can be achieved. Consequently, since it is possible to use light sources whose respective wavelengths are appropriate to the types of optical disks (information recording media), namely high density optical disks 30 and DVDs 33, and to focus light with less aberrations onto the information surfaces at high efficiencies, information can be recorded and reproduced reliably. As in the present embodiment, by setting the surface of the dichroic hologram 81 on which the pattern is provided to be the face closest to the objective lens, it is possible to prevent the minimum pitch of the dichroic hologram 81 from becoming too small, thus facilitating fabrication of the dichroic hologram 81. Furthermore, because recording and reproduction of CDs is omitted from the present embodiment, not only is a light source for CDs unnecessary, but the shape of the dichroic hologram 81 is simplified, and since the variety of signals that the photodetector 82 detects is reduced, the photodetector is simpler than that of the first embodiment. Furthermore, FIG. 18 shows an optical head 84 that uses a dichroic hologram 85 in place of the dichroic hologram 81. FIG. 18A is a structural overview of the high density optical disk 30 during recording and reproduction, and FIG. 18B is a structural overview of the DVD 33 during recording and reproduction. FIG. 19 shows a pattern on an upper surface (disk side) and rear surface (side furthest from the disk) of the dichroic hologram 85. The upper surface of the dichroic hologram 85 that is shown in FIG. 19A has the same pattern that is formed on the upper surface of the dichroic hologram 81 shown in FIG. 17. A pattern, which is a hologram for correcting chromatic aberration in light of wavelength λ1, is formed in a region 87 on the rear surface of the dichroic hologram 85 shown in FIG. 19B. Holograms for correcting chromatic aberrations are explained in detail in the Patent Document 3 (JP 2001-60336A). In this specification, the cross-section of the optical element is saw tooth-shaped, and a method is described whereby second order diffracted light is used for correcting light of a first wavelength λ1, and first order diffracted light is used for correcting light of a second wavelength λ2. Aberration that occurs at the objective lens caused by wavelength offset of the light of wavelength λ1 is cancelled out by changes in the diffracting angle of the diffraction grating to correct chromatic aberration. Accordingly chromatic aberration can be corrected without the addition of new parts. Furthermore, an example of an optical head is described in the present embodiment. However, as in the structure in FIG. 11 of the first embodiment, by providing moving means such as a conveying system 55 or a rotating system 54, and a control circuit 56, the optical head can be used as an optical information recording and reproduction apparatus (optical disk drive). Third Embodiment A third embodiment shows an example of a head that records and reproduces information onto three types of optical disks using three types of light sources using an optical element that has a dichroic hologram on one face and a phase shift step on an opposite face. Furthermore, a dichroic hologram that has two types of groove depths is described. FIG. 20 is a structural overview of an optical head 90 according to the present embodiment. Parts that are the same as in the first and second embodiment are given the same symbols, and the description thereof is hereby omitted. The present embodiment differs from the first and second embodiments in the use of a dichroic hologram (optical element) 91, which has a phase shift step on its rear surface. A front view of the dichroic hologram 91 is shown in FIG. 21, while FIG. 21A shows an upper surface (disk side), FIG. 21B shows a rear surface (side furthest from the disk), and FIG. 21C is a cross-sectional view of FIG. 21B. As shown in FIG. 21A, grooves are formed as a dichroic hologram in a circle-shaped region 93 (first region) in the vicinity of the center of an upper surface 92, and in a ring-shaped region 94 (second region) that wraps around the region 93. No grooves are formed in a region 95 (third region) that is on the outer side of the region 94. On the other hand, as shown in FIG. 21B, a phase shift step (phase correcting means) 97 is formed on a rear surface 96. The light of wavelength λ1=380 nm to 420 nm passes as is through the dichroic hologram on the upper surface, but the light of wavelength λ2=630 nm to 680 nm and the light of wavelength λ3=780 nm to 820 nm is diffracted. The light of wavelength λ1 passes through the region 93 and the region 94 and one part of the region 95. The light of wavelength λ3 that reproduces the CD 34 passes through the rear surface 96, after which it irradiates only onto the region 93 of the upper surface 92. The pattern of the region 93 is designed such that when the light of wavelength λ3 that was diffracted is irradiated onto the CD 12 of t=1.2 mm, the standard deviation of the wavefront aberration is not more than 70 mλ. The phase shift step 97 of the rear surface 96 shown in FIG. 21B is a step that does not affect the light of wavelength λ1 and the light of wavelength λ3. The light of wavelength λ2 is phase modulated by the phase shift step 97 of the rear surface 96, and is irradiated onto the circle-shaped region 93 (first region) and the ring-shaped region 94 (second region) of the upper surface 92. The shape of the pattern in the ring-shaped region 94 and the phase shift step 97 (phase correcting means) is designed such that the standard deviation of the wavefront aberration is not more than 70 mλ when the light that was diffracted at the circle-shaped region 93 and the ring-shaped region 94 is irradiated onto the DVD 33 of t=0.6. FIG. 22 shows an enlarged cross-sectional view of the dichroic hologram 91. The surface of the dichroic hologram 91 is engraved with grooves that have two types of depths (d and 2d). Those grooves form sets of grooves lined up in the order d, 2d, no groove, and are formed as a repetition of those sets. Where a refractive index of a medium at wavelength λ1 that is within the range of 380 nm to 420 nm is n1, the depth d is expressed by: d=λ1/(n1−1). Accordingly, the light of wavelength λ1 from the blue light semiconductor laser passes through without any effect. Furthermore, as described in the first embodiment, if the light path length is within a predetermined range, then the effect that light within the wavelength range 380 nm to 420 nm substantially passes through the dichroic hologram can be obtained. Thus, it is preferable that the expression: 380 nm≦(n−1)×d≦420 nm is satisfied, where n is the refractive index of the substrate at a wavelength of 400. On the other hand, the wavefront of the light of wavelength λ2 of the red semiconductor laser is modulated as shown in FIG. 23A. Since the wavelength λ2 is in the range 630 nm to 680 nm for recording and reproduction of the DVD 33, d has a depth that corresponds to approximately 0.6 times the length of the wavelength λ2. Consequently, 2d corresponds to 1.2λ. Since the integer multiples of λ can be ignored in the phases of light, with consideration given only to the portion on the right of the decimal point, d corresponds to 0.6λ and 2d corresponds to 0.2λ. Consequently, grooves that are lined up in the order d, 2d form wavefronts having phases that change stepwise as 0.6λ and 0.2λ, as shown in FIG. 23B. FIG. 24 shows the relationship between a groove depth of a single step that is normalized by the wavelength λ, and the efficiency R of converting incident light to first order diffracted light at the dichroic hologram, such as is shown in FIG. 22. From FIG. 24, a diffraction efficiency in the order of 0.6 can be obtained when the depth of one step is 0.6 times λ. Furthermore, the wavefront of the light of wavelength λ3 of the infrared semiconductor laser is modulated as shown in FIG. 25A. Since the wavelength λ3 is in the range 780 nm to 820 nm for CD recording and reproduction, d has a depth that corresponds to approximately 0.5 times the length of wavelength λ3. Consequently, 2d corresponds to 1.0λ. Since the integer portions of λ can be ignored in the phases of light, with consideration given only to the part to the right of the decimal point, d corresponds to 0.5λ and 2d corresponds to 0. Consequently, grooves that are lined up in the order d, 2d, form wavefronts having two step phases are 0.5λ and 0 as shown in FIG. 25B, whose duty ratio is 1:2. Due to this, a diffraction ratio in the order of 0.3 can be obtained when the depth of one step is 0.5 times λ, as shown in FIG. 24. If the dichroic hologram 91 as shown in FIG. 21 is used, then the hologram pattern is only fabricated on one face, and since the rear surface is constituted by a phase shift step that has low light-intensity-loss, light utilization efficiency can be raised. Thus, since it is possible to use light sources having wavelengths that are appropriate to the three types of optical disks (information recording media) to focus low aberration light onto the information surface at high efficiency, information can be recorded and reproduced reliably. It should be noted that here, the dichroic hologram and the phase shift step are formed on the upper surface and rear surface of a single optical element. However it is also possible to arrange a member in which these are formed on separate optical elements. In this case, by tuning the position of both optical elements, it is possible to adjust their centers to the optical axis. Furthermore, the diffraction efficiency shown here is a value calculated when the width of adjacent grooves of various depths is substantially equivalent. Moreover, the relationship between the wavelengths λ1 and λ2 satisfies: 1.5≦λ2/λ1≦1.8, and the relationship between the wavelengths λ1 and λ3 satisfies: 1.8≦λ3/λ1≦2.2. The conventional example disclosed in Patent Document 1 (JP H9-306018A), is illustrated by an example that has three types of groove depths, which allows one wavelength to pass through and diffracts another wavelength. However, there is no mention of the fact that when the wavelengths of λ1 and λ2 have the relationship: 1.5≦λ2/λ1≦1.8, a dichroic hologram that has two types of groove depths, or a dichroic hologram that has four types of groove depths in which these groove depths are lined up in the order 2d, 4d, d, 3d, no groove, can increase the diffraction efficiency of light of wavelength λ2. This is subject matter that is first disclosed by the present invention. Furthermore, the fact that an appropriate diffraction ratio of light of the wavelength λ3 that has the relationship: 1.8≦λ3/λ1≦2.2. can be obtained with the aforementioned dichroic hologram is another original disclose of the present invention. It should be noted that it is also possible that the hologram that is grouped with the phase shift step is of the shape that has four types of groove depths that are shown in the first embodiment. Similarly, it is also possible to use a dichroic hologram of a form having two types of groove depths, as shown in the third embodiment, applied to the dichroic hologram of the first embodiment. It should be noted that for simplicity, the light sources here are separate, and the photodetector is shared, however a single light source such as a monolithic semiconductor laser also can be used as the lightsource, and the photodetectors also can be separate. Even with this configuration, the same effect can be demonstrated. Furthermore, a disk whose substrate thickness t=0.1 and numerical aperture is 0.8 has been assumed as the example of the high density optical disk. However it is not limited to this. Also, although the present embodiment has been described using the example of an optical head, by providing a moving means such as the traverse system 55 or the rotating system 54, and the control circuit 56, it can be used as the optical information recording and reproduction apparatus (optical disk drive), as shown in FIG. 11 of the first embodiment. Fourth Embodiment FIG. 26 shows a structural view of the optical head according to a fourth embodiment of the present invention. It differs from the optical head according to the second conventional example in that it is provided with an objective lens drive apparatus 44 that is capable of tilting the objective lens 11. FIG. 26 shows the manner in which an ultra high density optical disk 12, which has a substrate thickness of 0.1 mm and an optical disk (DVD) 13, which has a substrate thickness of 0.6 mm, are recorded and reproduced. In order to simplify the description, both disks are drawn overlapped in the same location. The optical head shown in this drawing is provided with a light source 1 that produces a wavelength 380 nm to 420 nm (wavelength λ1), and a module 2a. A photodetector and a light source of light of a wavelength 630 nm to 680 nm (wavelength λ2) are contained within the module 2a. During recording and reproduction of the ultra high density optical disk 12, the light of wavelength λ1 that is emitted from the light source 1 passes through prisms 4 and 6 and is converted to collimated light by a focusing lens 7. This collimated light is reflected by a mirror 8, passes through a phase plate 9, is focused by the objective lens 11 and is irradiated onto the ultra high density optical disk 12. The objective lens 11 given here has a numerical aperture (NA) of 0.85, and is designed such that aberration with respect to the optical disk 12 whose substrate thickness is 0.1 mm is at a minimum. Furthermore, a phase plate 206 contains the phase shift step 206a (FIG. 62) shown in the second conventional example, and is designed such that the light of wavelength λ1 passes through without being affected. The light that was reflected by the ultra high optical disk 12 passes again through the objective lens, is focused by the focusing lens 7, is reflected by the prism 6 and is incident on a detecting device 15. The detecting device 15 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. When recording onto and reproducing from the DVD 13, the light of wavelength λ2 that was emitted from the light source in the module 2a is reflected by the prism 4, passes through the prism 6, and is converted by the focusing lens 7 to diverging light that has an optimum degree of divergence. Then, by changing the position of the light source of the module 2a as given by A to D in the diagram, it is possible to alter the degree of divergence, or convert it to collimated light at the focusing lens 7. When there is no phase plate 206, if the position of the light source of module 2a is B, then the divergent light that passed through the focusing lens 7 passes through the objective lens 11, whose numerical aperture is limited to NA 0.6 and which is designed such that aberrations with respect to the optical disk 12 whose substrate thickness is 0.1 mm are at a minimum, to become diverging light whose standard deviation of wavefront aberration is at a minimum when emitted onto the DVD 13 whose substrate thickness is 0.6 mm. The diverging light is reflected by the mirror 8, its aberration is corrected by wavefront conversion by the phase plate 206, is focused by the objective lens 11 and irradiated onto the DVD 13. The NA of the light that is emitted from the objective lens 11 is limited to 0.6. The light that is reflected by the DVD 13 passes again through the objective lens 11 and the phase plate 206, is reflected by the mirror 8, is focused by the focusing lens 7, passes through the prism 6, is reflected by the prism 4 and is incident on the detecting device of the module 2a. The detecting device of the module 2a contains a plurality of photodetecting regions, and emits a signal in response to the amount of light that is received. If the light that is incident on the objective lens 11 is diverging, then when the objective lens is driven in the tracking direction, coma aberration occurs because the light is incident on the objective lens 11 at an incline. This first embodiment is provided with an objective lens drive apparatus 44 that is capable of tilting, and coma aberration that is caused due to driving the objective lens 11 in the tracking direction can be cancelled out by coma aberration that occurs by tilting the objective lens 11. FIG. 27 shows the objective lens drive apparatus 44 that is capable of tilting the objective lens 11. FIG. 27A is a structural diagram of the objective lens drive apparatus, and FIG. 27B schematically shows a lateral view. A lens holder 33 is provided with the objective lens 11 and drive coils 34a, 34b and 35, and these are suspended from a fixed portion 37 by wires 36. A magnetic circuit is constituted by the drive coils 34a, 34b and 35, and a magnet 38. The objective lens 11 is driven in the tracking direction (x direction) by passing an electric current through the drive coils 35, and is driven in the focus direction by passing an electric current in the same direction, and of the same value, through the drive coils 34a and 34b. And, by passing different electric currents through the electric coils 34a and 34b the objective lens 11 can be tilted in the φ direction as shown in FIG. 27B. Depending on the amount of tracking movement of the objective lens 11, coma aberration can be cancelled out by tilting the objective lens 11. Since a large coma aberration occurs when the objective lens is moved in the tracking direction in the second conventional example, accurate recording and reproduction is difficult. However according to the present embodiment, less aberrated light can be focused onto the information surface by tilting the objective lens, and information can be recorded and reproduced favorably. Fifth Embodiment FIG. 28 is a structural diagram showing an optical head according to a fifth embodiment of the present invention. It differs from the fourth embodiment in a phase plate 9, and in that the light source of the module 2a is in the position A. The position A of the light source of the module 2a is closer to the objective lens 11 than the position B, at which the standard deviation of the wavefront aberration of the light that is emitted from the module 2a is at a minimum. FIG. 29 shows the structure of the phase plate 9. FIG. 29A is a plan view of an upper surface (disk side), and FIG. 29B is a lateral view. A phase shift step 9a that is circular and that has a height d is configured on the phase plate 9. The height d is: d=2 λ1/(n1−1), whereby n1 is the refractive index of the phase plate 9 at the wavelength λ1. During recording onto and reproducing from the ultra high density optical disk 12, the light of wavelength λ1 is phase shifted by 2λ (where λ is the wavelength that is used) by the phase shift step 9a, however since this is an integer multiple of the wavelength, the wavefront of the light is not affected, and there is no light loss. That is to say, favorable jitter can be obtained during reproduction of the ultra high density optical disk 12 and sufficient peak intensity can be obtained when recording. In this case, if the wavelength λ that is used is determined, then the phase shift 2λ is also uniquely fixed. However if the phase shift 2λ is within a predetermined range with respect to a predetermined wavelength λ that is used, then an effect can be obtained whereby the wavefront of the light that has a wavelength within the range 380 to 420 nm is substantially unaffected at the phase plate 9. More specifically, the expression: 760 nm≦(n−1)×d≦840 nm can be satisfied when the wavelength standard is 400 nm, which is within the range of wavelength λ1 that is 380 to 420 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. On the other hand, during recording and reproduction of the DVD 13, a phase shift of d/λ2×(n2−1)=1.2λ is generated in the light of wavelength λ2 by the phase shift step 9a. Since integer multiples of the wavelength can be ignored for phases of the light, if consideration is given only to the portion to the right of the decimal point then d corresponds to 0.2λ. That is to say, the wavefront of the light of wavelength λ2 is converted. FIG. 30 shows a wavefront aberration in the case in which there is no phase plate 9 by a thin line, and the wavefront aberration in the case in which there is a phase plate 9 by a thick line. In the case in which there is no phase plate 9, the standard deviation of the wavefront aberration is 77 mλ, however in the case in which there is the phase plate 9, the standard deviation reduced to 51 mλ. This is the same as in the second conventional example. If the standard deviation of the wavefront aberration is lower than the Marshall Standard of 70 mλ, then the optical head has a diffraction limit capability, and information can be recorded and reproduced favorably. Thus, because the degree of divergence of the light of wavelength 2 is greater than that shown in the second conventional example, the present fifth embodiment can get by with fewer steps on the phase plate 9, and the configuration is greatly simplified. That is to say, fabrication of the phase plate is facilitated, light loss can be suppressed, and electrical power consumption of the light source can be reduced. Furthermore, if the light that is incident on the objective lens 11 is divergent light, then coma aberration occurs when the objective lens 44 is driven in the tracking direction. However by using the objective lens drive apparatus 44, which is capable of tilting and which was described in the fourth embodiment, if the objective lens 11 is tilted in response to the amount of tracking movement, coma aberration can be cancelled out. Thus, according to the present fifth embodiment, it is possible to suppress the loss of light to the ultra high density optical disk 12 and the DVD 13 using a phase plate of simple construction. Furthermore, since coma aberration can be corrected by tilting the objective lens 11, it is possible to focus light with less aberrations onto the information surface, and information can be recorded and reproduced favorably. It should be noted that for simplicity, the module 2a combines the light source and the detecting device in a single body. However the light source and the detecting device may also be separate bodies. Sixth Embodiment FIG. 31 shows a structural diagram of an optical head according to a sixth embodiment of the present invention. It differs from the fourth embodiment in the light source of the module 2a being in the position C, a phase plate 16, and in that a tilting apparatus for the objective lens 11 not being necessary. The position of the light source of the module 2a is at position C, which is substantially the mid point between position D and position B. That is to say, the position C is a position that is substantially midway between the position D, from which point the light of wavelength λ2 that passes through the focusing lens 7 is collimated light, and the position B, from which point the light of wavelength λ2 that passes through the focusing lens 7 passes through the objective lens 11, whose numerical aperture is limited to 0.6 and which is designed such that aberration of light is at a minimum with respect to the optical disk 12 whose substrate thickness is 0.1 mm, to have minimum wavefront aberration when irradiated onto the DVD whose substrate thickness is 0.6 mm. Since the degree of divergence of the diverging light that is incident on the objective lens 11 is less than when the light source of the module 2a is in position B, even if the objective lens 11 is driven in the tracking direction, the occurrence of coma aberration is negligible. That is, since there is no necessity to provide a tilting apparatus for tilting the objective lens 11, the system configuration can be simple. FIG. 32 shows a structure of a phase plate 16. FIG. 32A is a plan view of an upper surface (disk side), and FIG. 32B is a lateral view. A phase shift step 16a that provides concentric ring-shaped steps d, 2d, 3d and 4d, whose single step height is d, is configured on the phase plate 16. When the refractive index of the phase plate 16 at the wavelength λ1 is set to n1, the height d is determined by: d=2 λ1/(n1−1). Furthermore, as described in the fifth embodiment, if the phase shift is within a predetermined range, than an effect can be obtained whereby the wavefront of the light that has a wavelength that is within the range 380 to 420 nm is substantially unaffected at the phase plate. More specifically, the expression: 760 nm≦(n−1)×d≦840 nm can be satisfied when the wavelength standard is set to 400 nm, which is within the range of wavelength λ1 that is 380 to 420 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. During recording and reproducing of the ultra high density optical disk 12, the light of wavelength λ1 is phase shifted by 2λ by the height d, however since this is an integer multiple of the wavelength, the wavefront of the light is not affected, and there is no light loss. That is to say, a favorable jitter is obtained when reproducing from the ultra high density optical disk 12 and sufficient peak intensity can be obtained when recording. On the other hand, during recording and reproduction of the DVD 13, the height d generates a phase shift of d/λ2×(n2−1)=1.2 λ in the light of wavelength λ2. Since integer multiples of the wavelength can be ignored for phases of the light, if consideration is given only to the portion to the right of the decimal point, then d corresponds to 0.2λ. Similarly, heights 2d, 3d, and 4d correspond to phase shifts of 0.4λ, 0.6λ and 0.8λ. That is to say, the wavefront of the light of wavelength λ2 is converted. FIG. 33 shows a wavefront aberration in the case in which there is no phase plate 16 by a thin line, and the wavefront aberration in the case in which there is a phase plate 16 by a thick line. The width and height of the steps of the phase plate 16a are configured so as to correct the wavefront aberration of the thin line. Thus, while the standard deviation of the wavefront aberration is 490 mλ when there is no phase plate 16, it reduces to 58 mλ when the phase plate 16 is in place. If the standard deviation of the wavefront aberration is lower than the Marshall Standard of 70 mλ, then the optical head has a diffraction limit capability, and information can be recorded and reproduced favorably. Thus, since the coma aberration that is generated when the objective lens 11 is driven in the tracking direction can be suppressed according to the present embodiment, it is possible to omit the tilting apparatus of the objective lens 11, the optical head can be made straightforward, and the system configuration also simplified. Furthermore, because it is possible to focus light with less aberrations onto the information recording surfaces of the ultra high density optical disk 12 and the DVD 13, information can be recorded and reproduced favorably. It should be noted that that the present embodiment is described using an example in which the phase shift step has a height of 4d, however it is also possible to use heights of 5d, 6d or greater. Furthermore, even if the position of the light source of the module 2a is between C and D, if the configuration of the width and height of the phase shift step is changed so as to correct the wavefront aberration, then the same effect can be obtained. Furthermore, for simplicity the module 2a combines the light source and the photodetector in a single body, however the light source and the photodetector may also be separate bodies. Furthermore, although in the present embodiment, the coma aberration is suppressed to the extent that tilting the objective lens 11 is not necessary, however it is possible to add a tilt drive to the objective lens 11. By adding tilting, the tilt margin of the optical disk is enlarged, and even disks that are warped to a large extent can be favorably recorded and reproduced. Seventh Embodiment An optical head according to the seventh embodiment of the present invention is shown in FIG. 34. It differs from the sixth embodiment in that there is no module for the DVD 13, only a light source 2, and in that it has a phase shift step 17. The light source 2 is set in a position such that the light of wavelength λ2 that passes through the focusing lens 7 is collimated light. Thus, since the light that was reflected by the DVD 13 can be focused on the detecting device 15 it is possible to use the detecting device for both the ultra high density optical disk 12 and for the DVD 13. That is, the number of parts can be reduced, and a cost reduction achieved. Furthermore, since the light that is incident on the objective lens 11 is collimated light, there is no necessity for the tilting apparatus for the objective lens 11, the optical head is simplified, and coma aberration does not occur even when the objective lens 11 is driven in the tracking direction. FIG. 35 shows the structure of the phase plate 17. FIG. 35A is a plan view from an upper surface (disk side), and FIG. 35B is a lateral view. A phase shift step 17a that has concentric ring-shaped steps d, 2d, 3d and 4d, whose single step height is d, is configured on the phase plate 17. When the refractive index of the phase plate 17 at the wavelength λ1 is set to n1, the height d is determined by: d=2 λ1/(n1−1). The configuration in FIG. 35B has an increased number of steps in the radial direction than that of the structure in FIG. 32B of the sixth embodiment.However since the minimum width is in the order of 12 μm, it is easier to fabricate. During recording and reproduction of the ultra high density optical disk 12, the light of wavelength λ1 is phase shifted by 2λ by the height d, however since this is an integer multiple of the wavelength, the wavefront of the light is not affected, and there is no light loss. That is to say, a favorable jitter can be obtained during reproduction from the ultra high density optical disk 12 and sufficient peak intensity can be obtained when recording. Furthermore, as described in the fifth embodiment, if the phase shift 2λ is within a predetermined range, then an effect can be obtained whereby the wavefront of the light that has a wavelength within the range 380 to 420 nm is substantially unaffected at the phase plate. More specifically, the expression: 760 nm≦(n−1)×d≦840 nm can be satisfied when the wavelength standard is 400 nm, which is within the range of wavelength λ1 that is 380 to 420 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. On the other hand, during recording and reproduction of the DVD 13, the height d generates a phase shift of d/λ2×(n2−1)=1.2λ in the light of wavelength λ2. Since integer multiples of the wavelength can be ignored for phases of the light, when consideration is given only to the portion to the right of the decimal point, d corresponds to 0.2λ. Similarly, heights 2d, 3d, and 4d correspond to phase shifts of 0.4λ, 0.6λ and 0.8λ. That is to say, the wavefront of the light of wavelength λ2 is converted. FIG. 36 shows a wavefront aberration in the case in which there is no phase plate 17 by a thin line, and a wavefront aberration in the case in which there is a phase plate 17 by a thick line. The width and height of the steps of the phase plate 17 are configured so as to correct the wavefront aberration of the thin line. Thus, while the standard deviation of the wavefront aberration is 780 mλ when there is no phase plate 17, it reduces to 58 mλ when the phase plate 17 is in place. If the standard deviation of the wavefront aberration is lower than the Marshall Standard of 70 mλ, then the optical head has a diffraction limit capability, and information can be recorded and reproduced favorably. In this manner, by causing the light that is incident on the objective lens 11 to be collimated light according to the present embodiment, the necessity of the tilting apparatus for the objective lens 11 disappears, the optical head can be made more straightforward, and the system configuration also simplified. Furthermore, because it is possible to focus light with less aberrations onto the information recording surfaces of the ultra high density optical disk 12 and the DVD 13, information can be recorded and reproduced favorably. It should be noted that that the present embodiment is described using an example in which the phase shift step has a height of 4d, however it is also possible to use heights of 5d, 6d or greater. Eighth Embodiment An optical head according to the eighth embodiment is shown in FIG. 37. It differs from the seventh embodiment in the provision of a mirror 19, and a phase plate 18, but the configuration up to where the light that is emitted from the light source becomes collimated light, and the configuration in which the light that was reflected by the optical disk 12 is incident on the detecting device 15 are the same as in the seventh embodiment. As shown in FIG. 38, the mirror 19 has a flat reflecting surface 19a and a curved reflecting surface 19b, which has a radius of curvature R. The reflecting surface 19a is constituted by a dichroic film that totally reflects a light 1a of wavelength λ1 remain parallel with respect to the objective lens 11, while allowing a light 2b of wavelength λ2 to completely pass. Furthermore, the reflective surface 19b totally reflects and converts the light 2b of wavelength λ2 into diverging light that has a degree of convergence that is optimal for the objective lens 11. The phase shift steps of the phase plate 18 are set in response to the degree of divergence. For example, the degree of divergence and the phase plate 18 can be the same as in the sixth embodiment. Thus with such a configuration, since the coma aberration that occurs when the objective lens 11 is driven in the tracking direction can be suppressed to an insignificant amount, it is possible to focus light with less aberrations onto the information recording surfaces of the ultra high density optical disk 12 and the DVD 13, and information can be recorded and reproduced favorably. Furthermore, costs can be reduced since the detecting devices can be combined into one. Furthermore, since the number of steps is fewer, and the width of the steps is wider than in the seventh embodiment, manufacture is facilitated, fabrication to shape as designed is possible, and it is possible to reduce light loss. Ninth Embodiment A description of the ninth embodiment of the present invention uses FIG. 39. FIG. 39 shows a structural diagram of the phase plate 18. FIG. 39A is a lateral view, and FIG. 39B is a view of a rear surface. The phase plate 18 is constituted by a phase shift step 18a on an upper surface (disk side), and a chromatic aberration correction hologram 18b that has the power of a convex lens on the rear surface (side furthest from the disk). The chromatic aberration correction hologram 18b is disclosed in detail in the Patent Document 3 (JP 2001-60336A). This corrects chromatic aberration by canceling out the aberration that is caused at the objective lens by a shift in the wavelength of the light of wavelength λ1, by changing the diffraction angle of a diffraction grating. By configuring the phase plate 18 and the chromatic aberration correction hologram 18b as a single piece, it is possible to correct chromatic aberration without supplementing new parts. It should be noted that it is possible to obtain the same effect by configuring the chromatic aberration correction hologram into a single piece with the phase plates that are described in the fourth to eighth embodiments. Tenth Embodiment An optical head according to the tenth embodiment of the present invention is shown in FIG. 40. The ultra high density optical disk 12 whose substrate thickness is 0.1 mm, the optical disk (DVD) 13 whose substrate thickness is 0.6 mm and the optical disk (CD) 14 whose substrate thickness is 1.2 mm are shown in their recording and reproduction state, and for the purpose of simplifying the description, they are drawn overlapping in the same position. The optical head contains the light source 1 that emits light of a wavelength 380 nm to 420 nm (wavelength λ1), the light source 2 that emits light of a wavelength 630 nm to 680 nm (wavelength λ2) and the light source 3 that emits light of a wavelength 780 nm to 820 nm (wavelength λ3). During recording and reproduction of the ultra high density optical disk 12, the light of wavelength λ1 that is emitted from the light source 1 passes through the prisms 4, 5, and 6, and is converted to collimated light by the focusing lens 7. This collimated light is reflected by the mirror 8, passes through a liquid crystal hologram 10 and the phase plate 17, is focused by the objective lens 11, and is irradiated onto the ultra high density optical disk 12. Here, the objective lens 11 is designed to have an NA of 0.85, and to handle light of wavelength λ1 and a disk whose substrate thickness is 0.1 mm. Furthermore, the phase plate 17, as will be explained below, is designed to allow light of wavelength λ1 and λ3 to pass without being affected, and to convert the wavefront of the light of wavelength λ2. Furthermore, during recording and reproduction of the ultra high density optical disk, the liquid crystal hologram is in a state in which a voltage is not applied (OFF), and the light passes through without being affected. The light that was reflected by the ultra high density optical disk 12 passes again through the objective lens 11, the phase plate 17 and the liquid crystal hologram 10, and is reflected by the mirror 8. This reflected light is focused by the focusing lens 7, is reflected by the prism 6, and is incident on the detecting device 15. The detecting device 15 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. During recording and reproduction of the DVD 13, the light of wavelength λ2 that is emitted from the light source 2 is reflected by the prism 4, passes through the prisms 5 and 6, and is converted to collimated light by the focusing lens 7. This collimated light is reflected by the mirror 8, passes through the liquid crystal hologram 10, is wavefront converted by the phase plate 17, is focused by the objective lens 11, and is irradiated onto the DVD 13. Here, the NA of the light that is emitted from the objective lens 11 is limited to 0.6. Furthermore, the phase plate 17 is designed such that after passing through the objective lens 11, which is designed such that aberration with respect to the disk whose substrate thickness is 0.1 mm is at a minimum, when the collimated light of wavelength λ2 is irradiated onto the optical disk whose substrate thickness is 0.6 mm, the standard deviation of the wavefront aberration is not more than 70 mλ. Furthermore, during recording and reproduction of the DVD 13, the liquid crystal hologram is in the OFF condition, and the light of wavelength λ2 passes through without being affected. The light that was reflected by the DVD 13 passes again through the objective lens 11, the phase plate 17 and the liquid crystal hologram 10, and is reflected by the mirror 8. This reflected light is focused by the focusing lens 7, is reflected by the prism 6, and is incident on the detecting device 15. During recording and reproduction of the CD 14, the light of wavelength λ3 that was emitted from the light source 3 is reflected by the prism 5, passes through the prism 6, and is converted to collimated light by the focusing lens 7. This collimated light is reflected by the mirror 8, and is wavefront converted by the liquid crystal hologram 10. Moreover, it passes through the phase plate 17, is focused by the objective lens 11, and is irradiated onto the CD 14. Here, the NA of the light that is emitted by the objective lens 11 is limited to 0.45. Furthermore, the phase plate 17 allows the light of wavelength λ3 to pass without influence. Furthermore, during recording and reproduction of the CD 14, the liquid crystal hologram is in a condition in which an electric voltage is applied (ON), and is designed such that, the standard deviation of the wavefront aberration is not more than 70 mλ when the collimated light of wavelength λ3 is irradiated onto the optical disk whose substrate thickness is 1.2 mm after passing through the objective lens 11. The light that was reflected by the CD 14 again passes through the objective lens 11, the phase plate 17 and the liquid crystal hologram 10, is reflected by the mirror 8, is focused by the focusing lens 7, and is reflected by the prism 6 to be incident on the detecting device 15. The configuration of the phase plate 17 is the same as the structure in FIG. 35. That is to say the phase shift step 17a that has concentric ring-shaped steps d, 2d, 3d and 4d, whose single step height is d, is provided on the phase plate 17. When the refractive index of the phase plate 17 at wavelengths λ1 and λ3 is n1 and n3, the height d is: d=2 λ1 /(n1−1). The refractive indices n1 and n2 satisfy: −10 nm<λ1/(n1−1)−λ3/(n3−1)/2<10 nm. The wavefront of the light of wavelength λ2 can be converted substantially without influencing the light of wavelength λ1 and λ3 by appropriately selecting the wavelength that is used and the material of the phase plate. During recording and reproduction of the ultra high density optical disk 12, the light of wavelength λ1 is phase shifted 2λ by the height d, and during recording and reproduction of the CD 14, the phase shift of the light of wavelength λ3 by the height d is substantially λ. When using light of either wavelength λ1 or λ3, the phase shift is an integer multiple of the wavelength so the wavefront of the light is unaffected, and there is no loss of light. That is, favorable jitter can be obtained when replaying from the ultra high density optical disk 12 and the CD 14, and sufficient peak intensity can be obtained when recording. Furthermore, as shown in the fifth embodiment, if the phase shift 2λ is within a predetermined range, then an effect can be obtained whereby the wavefront of the light that has a wavelength within the range 380 to 420 nm is substantially unaffected at the phase plate. More specifically, the expression: 760 nm≦(n−1)×d≦840 nm can be satisfied when the wavelength standard is 400 nm, which is within the range of wavelength λ1 that is 380 to 420 nm, and n is the refractive index of the substrate at a wavelength of 400 nm. On the other hand, during recording and reproduction of the DVD 13, a phase shift of d/λ2×(n2−1)=1.2 λ is generated in the light of wavelength λ2. Since integer multiples of the wavelength can be ignored for phases of the light, when consideration is given only to the portion to the right of the decimal point, d corresponds to 0.2λ. Similarly, heights 2d, 3d, and 4d correspond to phase shifts of 0.4λ, 0.6λ and 0.8λ. That is to say, the wavefront of the light of wavelength λ2 is converted. For example, if the wavelength of the lights that are used is λ1=405 nm, λ2=650 nm and λ3=780 nm, then BK7, which is a common glass material, can be used as the material of the phase plate, and the height of one step of the phase shift step can be d=1.5292 μm. Since the refractive index of BK7 is n1=1.15297, n2=1.5141 and n3=1.5107, the phase shift per step for the lights of wavelength λ1, λ2 and λ3 are respectively 2λ, 1.2λ and λ. That is, when using the ultra high density optical disk 12 and the CD 14, the phase plate has no influence, and the wavefronts can be converted only when using the DVD 13. FIG. 36 shows a wavefront aberration in the case in which there is no phase plate 17 by a thin line, and the wavefront aberration in the case in which there is a phase plate 17 by a thick line. The width and height of the steps of the phase shift step 17a are configured so as to correct the wavefront aberration of the thin line. Thus, while the standard deviation of the wavefront aberration is 780 mλ when there is no phase plate 17, it reduces to 58 mλ when the phase plate 17 is in place. If the standard deviation of the wavefront aberration is lower than the Marshall Standard of 70 mλ, then the optical head has a diffraction limit capability, and information can be recorded and reproduced favorably. FIG. 41 shows the structure of the liquid crystal hologram 10. FIG. 41A is a plan view of an upper surface (disk side), and FIG. 41B is an enlarged cross-sectional view. A relief-shaped hologram pattern is provided on a substrate 10b whose refractive index is no, and a transparent electrode 10c is formed on that face. A liquid crystal 10a is sandwiched between transparent electrodes 10c and 10d. The refractive index of the liquid crystal 10a changes depending on the voltage across the transparent electrode 10c and 10d. It has a refractive index of ne when in the state in which there is an applied voltage (ON), and has a refractive index of no when in the state in which there is no applied voltage (OFF). In the OFF condition, the liquid crystal 10a and the substrate 10b have equivalent refractive indices. Although it is a simple flat plate in this case, a difference in the refractive indices is generated in the ON state, and a refractive effect is generated due to the hologram. A predetermined diffraction effect can be obtained by appropriately selecting the combination of the material of the substrate 10b and the material of the liquid crystal 10a. The hologram has aberrations so as to cancel out wavefront aberrations that are generated when the light of wavelength λ3 passes through the objective lens 11 and is irradiated onto the CD 14. That is, when using the ultra high density optical disk 12 and the DVD 13, if the hologram is turned to the OFF condition, then the lights are unaffected, and if the hologram is turned to the ON condition, then the wavefront of the light can be converted. Thus, according to the present embodiment, it is possible to focus light with less aberrations onto the information recording surfaces of the ultra high density optical disk 12, the DVD 13 and the CD 14, and information can be favorably recorded and reproduced. It should be noted that in the tenth embodiment of the present invention, a case is described in which the light of wavelength λ2 is converted to collimated light by the focusing lens 7. However it is also possible to use cases in which it is converted to diverging light, such as in the fifth and sixth embodiments. Furthermore, recording and reproduction of the CD 14 is described using the liquid crystal, however the phase shift step of the present invention is characterized in that it does not influence the CD 14, so it is possible to use any method known in the art to record and reproduce the CD 14. Furthermore, if the hologram pattern of the liquid crystal is configured to cancel out the wavefront aberration that is generated by the DVD 13, then it is possible to use the liquid crystal even during recording and reproduction of the DVD 13. Moreover, it is also possible to mount individual liquid crystal holograms for the CD 14 and the DVD 13. Furthermore, the height of the phase shift steps of the fifth to the tenth embodiments was d=2λ1/(n1−1). However if the present invention is limited to recording onto and reproducing from the ultra high density optical disk 12 and the DVD 13, then it is possible to realize the same phase shift even if the height is d=λ1/(n1−1). Furthermore, as described previously, if the phase shift is within a predetermined range, then an effect can be obtained whereby the wavefront of the light that has a wavelength within the range 380 to 420 nm is substantially unaffected at the phase plate. Due to this, when the refractive index at the standard wavelength of 400 nm is n, then it is also possible that the expression: 380 nm≦(n−1)×d≦420 nm is satisfied. In this case, since the height d generates a phase shift of 0.6λ in the light of wavelength λ2, d, 2d, 3d and 4d correspond to phase shifts of 0.6λ, 0.2λ, 0.8λ and 0.4λ. For example, the phase shift step 16a (FIG. 32) of the sixth embodiment becomes the same as the phase shift step 16b that is shown in FIG. 42. If done in this manner, since the height of the steps can be lowered, fabrication of the phase plate is facilitated and the manufacturing time can be shortened. Furthermore, since it is easier to fabricate the shape as designed, light loss is less and the effect of suppressing electrical power consumption can be obtained. Furthermore, the phase shift step can be formed easily by etching a glass substrate. Furthermore, it is also possible to form the phase shift step by molding glass or resin. Furthermore, it is also possible to form the phase shift step into a single piece with the objective lens. It should be noted that if using resin as the material for the phase shift step, because chemical changes are likely to occur when the wavelength is less than 420 nm, it is preferable that the light absorptance ratio is not more than 5%, and more preferably is not more than 3%. It is preferable to use amorphous polyolefins (such as Zonex or APEL), for example. Furthermore, a disk whose substrate thickness is 0.1 mm and whose NA is 0.85 was assumed as an example of the ultra high density optical disk, however it is not limited to this. Furthermore, no particular method is described for limiting the aperture of the light. However there are methods in which a wavelength selecting filter (not shown) is vapor deposited on the phase plate 17 or the objective lens 11, or in which a separate glass filter is provided. Furthermore, it is also possible to restrict the light by providing an aperture on the light path that is traveled only by light of each wavelength (between the light source and the prism). Eleventh Embodiment An optical head according to the eleventh embodiment of the present invention is shown in FIG. 43. This diagram shows the ultra high density optical disk 12 whose substrate thickness is 0.1 mm, the optical disk (DVD) 13 whose substrate thickness is 0.6 mm and the optical disk (CD) 14 whose substrate thickness is 1.2 mm. In order to simplify the description, these are drawn as overlapped in the same position. The optical head contains the light source 1 of wavelength 380 nm to 420 nm (λ1), the light source 2 of wavelength 630 nm to 680 nm (λ2) and the light source 3 of wavelength 780 nm to 820 nm (λ3). During recording and reproduction of the ultra high density optical disk 12, the light of wavelength λ1 that is emitted from the light source 1 passes through the prisms 4, 5, and 6, and is converted to collimated light by the focusing lens 7. This collimated light is reflected at a reflecting surface 67a of a dichroic mirror 20, passes through the phase plate 17, is focused by an objective lens 39 and is irradiated onto the ultra high density optical disk 12. Here, the reflecting surface 67a is constituted by a dichroic film that totally reflects the light of wavelength λ1 and λ2, and causes the light of wavelength λ3 to completely pass. The phase plate 17 is the same as the phase plate that was used in the seventh embodiment. Furthermore, the objective lenses 39 and 45, and the phase plate 17 are mounted in a lens holder 33. The light that was reflected by the ultra high density optical disk 12 passes again through the objective lens 39 and the phase plate 17, and is reflected by the reflecting surface 67a of the dichroic mirror 67. This reflected light is focused by the focusing lens 7, and is reflected by the prism 6 to be incident on the detecting device 15. The detecting device 15 contains a plurality of photodetecting regions, and outputs a signal in response to the amount of light that is received. During recording and reproduction of the DVD 13, the light of wavelength λ2 that is emitted from the light source 2 is reflected by the prism 4, passes through the prisms 5 and 6, and is converted to collimated light by the focusing lens 7. This collimated light is reflected by the reflecting surface 67a of the dichroic mirror 67, is wavefront converted by the phase plate 17, is focused by the objective lens 39 and is irradiated onto the DVD 13. The light that was reflected by the DVD 13 passes again through the objective lens 39 and the phase plate 17, and is reflected by the reflecting surface 67a of the dichroic mirror 67. This reflected light is focused by the focusing lens 7, and is reflected by the prism 6 to be incident on the detecting device 15. During recording and reproduction of the CD 14, the light of wavelength λ3 that was emitted from the light source 3 is reflected by the prism 5, passes through the prism 6 and is converted to collimated light by the focusing lens 7. This collimated light passes through the reflecting surface 67a of the dichroic mirror 67, is reflected at a reflecting surface 67b, is focused by an objective lens 45 and is irradiated onto the CD 14. The light that is reflected by the CD 14 passes again through the objective lens 45, is reflected by the reflecting surface 67b of the dichroic mirror 67, is focused by the focusing lens 7 and is reflected by the prism 6 to be incident on the detecting device 15. By using separate objective lenses 39 and 45, information can be recorded and reproduced from each of the ultra high density optical disk 12, the DVD 13 and the CD 14. An objective lens drive apparatus in which the objective lenses 39 and 45 are mounted in the lens holder 33 is described in detail using FIG. 44. The lens holder 33 contains the objective lens 39, which is used when recording onto and reproducing from the ultra high density optical disk 12 and the DVD 13, the objective lens 45, which is used when recording to and reproducing from the CD 14 and drive coils 34a, 34b and 35, and is suspended from the fixed portion 37 by the wires 36. A magnetic circuit is constituted by the drive coils 34a, 34b and 35, and a magnet 38. The objective lenses 39 and 45 are driven in the tracking direction (x direction) by passing an electric current through the drive coils 35, and are driven in the focus direction by passing an electric current in the same direction, and of the same value, through the drive coils 34a and 34b. And, by passing different electric currents through the electric coils 34a and 34b the objective lens 39 can be tilted in the φ direction as shown in FIG. 45. With this configuration, coma aberration caused by tilting of the optical disk can be corrected by tilting the objective lens 39. The present embodiment differs from the third embodiment in that the two objective lenses 39 and 45 are lined up in the tracking direction (x direction). FIG. 46 shows the condition of a spot of light that is irradiated onto the optical disk. The differential push-pull method (DPP) and the three beam method use a main spot for reproducing information, and two sub spots for tracking detection. The main spot 39a of the objective lens 39 shown in FIG. 44 is the spot in a position 57a shown in FIG. 46. The sub spots are in positions 57b and 57c and are set at an angle θ0 that is optimum for the play track 59a. In the three beam method, for example, the angle θ0 is set such that the sub spots 57b and 57c are positioned at ¼ Tp (where Tp is the track pitch of the optical disk). Furthermore, in the DPP method, the subspots 57b and 57c are set so as to be positioned at 1/2 Tp. These spots move in the x-direction in accordance with the seek operation of the optical head, and the positions of the spots become 58a, 58b and 58c. Since the spot positions 57a and 57b lie on a straight line that passes through the rotational center O of the optical disk in the x direction, even if the seek operation of the optical disk is performed, the angle at the play track 59b is kept at θ0. The spot of the objective lens 45 is also the same. Thus, according to the present embodiment, by lining up two objective lenses in the tracking direction it is possible to use the DPP method or the three beam method, which are common tracking methods, and favorable tracking detection can be carried out. Here, common objective lenses contain more or less coma aberration that is caused by manufacturing errors. In order to correct this, it is common practice to perform skew adjustment by tilting the optical axis of the objective lens with respect to the light that is incident on the objective lens. Skew adjustment is carried out by tilting the objective lens drive apparatus. As for the objective lens drive apparatus on which the two objective lenses are mounted, the objective lenses change position as a single body when the objective lens drive apparatus is tilted. Due to this, even if skew adjustment is performed on one objective lens, the other lens does not necessarily reach its optimum condition. Furthermore, it is necessary to raise the accuracy of the skew adjustment with increased optical disk recording density. In the present embodiment, by dedicating use of the objective lens 45 to the CD 14, which has the lowest recording density of the three optical disks, it is possible to separate the skew adjustment of the objective lens 39, omitting it with respect to the objective lens 45, and thus simplify the skew adjustment. That is to say, skew adjustment of the objective lens 39 is carried out, but dedicated skew adjustment is not necessary for the CD 14. With regard to the CD whose recording density is relatively low, since there is no particular necessity for accurate skew adjustment, even without an adjustment that tilts the objective lens drive apparatus, it is sufficient to have coarse adjustment in which the objective lens 45 is tilted with respect to the lens holder 33. Furthermore, since the CD uses a relatively long wavelength and a low NA, there is a large degree of freedom in the design of the objective lens 45. By removing sine conditions, it is possible to design an objective lens 45 such as this to suppress to a minimum the coma aberration that occurs when the objective lens 45 is tilted. If an objective lens 45 that is designed in such a way is used, then dedicated skew adjustment for the CD 14 can be omitted. It should be noted that a wire suspension-type objective lens drive apparatus was used in describing the present embodiment. However a similar effect of simplifying the skew adjustment can be obtained even if two objective lenses are mounted on an axially oscillating-type objective lens drive apparatus. Furthermore, since the CD 14 has a low NA, the outside diameter of the objective lens 45 can be designed to be smaller. That is, it is possible to arrange the objective lens 45 on the inner circumferential side of the optical disk of the objective lens 39. This is illustrated using FIG. 47. The objective lenses 39 and 45 are arranged lined up in the tracking direction on an optical head 62. The ultra high density optical disk 12 is fixed, sandwiched between a turntable 63 and a damper 64, and is rotated by a motor 65. The optical head 62 rides on a traverse 66, and is capable of moving (seek operation) from the inner circumference to the outer circumference of the optical disk 12. The optical head 62 and the motor 65 are in close proximity when the optical head 62 moves to the position of the information that is recorded at the most inner circumference of the optical disk 12. In this case, since the outer diameter of the objective lens 45 is small, the objective lens 39 can move to the inner most circumference position, and it is possible to read in information without problems. Furthermore, information on the inner most circumference also can be reproduced using the objective lens 45. Furthermore, since the objective lens 45 is shifted further from the central position of the lens holder 33 than the objective lens 39, as shown in FIG. 45, a movement in the focus direction ZT occurs when tilted. This causes the tilt control to interfere with the focus control, and is not preferable from the standpoint of control stability. On the other hand, since the objective lens 39 is positioned in the center (tilting center) of the lens holder 33, there is no substantial movement in the focus direction, and control interference does not occur. That is, with respect to the ultra high density optical disk 12 and the DVD 13, with which tilting is preferable, information can be recorded and reproduced reliably and favorably using tilt control by arranging the objective lens 39 in the center of the lens holder 33. Thus, according to the present embodiment, by arranging the objective lens 39 that is for the ultra high density optical disk 12 and the DVD 13 in the center of the lens holder, and arranging the objective lens 45 for the CD 14 on the inner peripheral side of the optical disk, many effects can be obtained, such as simplifying skew adjustment, allowing reproduction of data on the inner most circumference of the optical disks and making it possible to tilt the objective lens for the ultra high density optical disk and the DVD. It should be noted that if tilting is not necessary, then the drive coils 34a and 34b can be interchangeable. Furthermore, the present embodiment was explained using the phase plate 17. However a liquid crystal or a hologram can be used as long as it is a means that is capable of recording and reproducing the ultra high density optical disk 12 and the DVD 13. Furthermore, the present embodiment was explained using the case in which the objective lens 39 was used during recording and reproduction from the ultra high density optical disk and the DVD 13, and the objective lens 45 was used during recording and reproduction of the CD 14. However even if a dedicated objective lens is used for the ultra high density optical disk 12, and an objective lens is used for the DVD 13 and the CD 14, then the DPP method or the three beam method can be used, and a similar, or equivalent effect can be obtained. Furthermore, at this time, it goes without saying that it is also possible to record and reproduce just of one of either of the CD 14 or the DVD 13. Twelfth Embodiment An optical head according to the twelfth embodiment of the present invention is shown in FIG. 48. It differs from the eleventh embodiment, in an objective lens 68, and in that it contains a detecting device 69 that is for detecting the tilt of the optical disk. FIG. 48 shows the recording and reproducing state of the ultra high density optical disk 12, and shows the manner in which the ultra high density optical disk is tilted. The light of wavelength λ1 that is emitted from the light source 1 is focused by the objective lens 39, and is irradiated onto the ultra high density optical disk 12 to perform recording and reproduction. At the same time, the light of wavelength λ3 that is emitted from the light source 3 is incident on an objective lens 68, which is described later, and pass through remain collimated light only in a ring-shaped region, after which it is irradiated onto the ultra high density optical disk 12. The direction of light that is reflected from the ultra high density optical disk 12 that is tilted is changed, and is detected by the detecting device 69. In the diagram, the reflected light of the ring-shaped region is indicated by hatching. Here, a cross-sectional view of the objective lens 68 is shown in FIG. 49A, and as shown in FIG. 49B, a rear surface view (the opposite side to the disk) contains a ring-shaped region 77a for tilt detection. Collimated light that passes through the region 77a passes straight though, as is, without being focused. Light that passes through regions other than 77a is optimized for the CD 14. During recording and reproduction of the CD 14, there is a slight reduction in the amount of light, but this causes no problems with recording and reproduction. FIG. 50 shows the detecting device 69. The detecting device contains two detecting regions, and the ring-shaped light that is received moves in response to the amount of tilt of the ultra high density optical disk 12. The amount of tilt of the ultra high density optical disk 12 can be detected by a signal difference V1−V2 that is obtained at each of the detecting regions of the detecting device 69. Coma aberration is generated because of warping (tilt) of the optical disks, which generally occurs due to manufacturing errors or age or the like. And since high accuracy aberration properties are demanded along with increase in recording density, it is preferable to correct coma aberration by tilting the objective lens in order to favorably carry out recording and reproduction. If tilt detection is carried out according to the present embodiment, and tilting drive carried out by the objective lens drive mechanism that is capable of tilting that was described in the eleventh embodiment, then coma aberration can be corrected based on the tilt detection signal, and information can be recorded and reproduced favorably. Thus, according to an embodiment of the present invention, since light of another wavelength, which is not being used for recording or reproduction, is utilized, tilting can be detected by a simple configuration, there is no necessity to attach a new tilt sensor, and costs can be reduced. Furthermore, highly accurate tilt detection can be obtained since the tilt is detected in the vicinity of the spot that is recording and reproducing information. It should be noted that the present embodiment is described using the case in which the detecting region of the detecting device 69 is divided into two, however if it is divided into four, then it is possible to detect tilt in the radial and tangential directions. Furthermore, in the foregoing description, an example was given of detecting tilt of the ultra high density optical disk whose substrate thickness is 0.1 mm using the light for the CD 14. However the present embodiment is not limited to this, and it is also possible to detect the tilt of the DVD 13 using the light for the CD 14. Even in this case, since tilt detection is carried out using light of a wavelength that is not recording or reproducing information, the same effect can be obtained. Furthermore, in the present embodiment, some of the objective lens 68 was given to the region for tilt detection. However it is not limited to this, and the same effect can be obtained by opening a through hole (not shown) in the lens holder 33 that holds the objective lens 68 to pass light for tilt detection. Furthermore, for simplicity, the detecting device 15 for recording and reproduction, and the detecting device 69 for tilt detection are separate bodies. However they can also be a single piece. Thirteenth Embodiment An optical head according to the thirteenth embodiment of the present invention is shown in FIG. 51. This differs from the twelfth embodiment in the provision of an objective lens 79. FIG. 51 shows the manner in which the ultra high density optical disk 12 is recorded or reproduced, and the manner in which the ultra high density optical disk is tilted. The light of wavelength λ1 that is emitted from the light source 1 is focused by the objective lens 39 and irradiated onto the ultra high density optical disk 12 to carry out recording and reproduction. At the same time, the light of wavelength λ3 that is emitted from the light source 3 is incident on the objective lens 79 and is irradiated onto the ultra high density optical disk 12. Here, the objective lens 79 is designed such that aberration of light with respect to a substrate thickness of 0.1 mm is minimized by an inner circumference area 79a, and that aberration of light with respect to a substrate thickness of 1.2 mm (CD) is minimized by an outer circumference area 79b. During recording reproduction of the CD, recording and reproduction is performed using the spot created by the outer circumference region 79b. At this time, light of the inner circumference region is largely unfocused, and does not affect recording or reproduction. On the other hand, of the light that is incident on the ultra high density optical disk 12, although the spot of the light of the outer circumference region 79b is largely unfocused, the light of the inner circumference region 79a is focused in the vicinity of the recording surface. The light of the inner circumference region 79a that is reflected by the ultra high density optical disk is detected by the detecting device 15. In the diagram, reflected light of the inner circumference region 79a is shown by hatching. Since focus control is carried out with respect to the objective lens 79 during recording and reproduction of the ultra high density optical disk 12, if the ultra high density optical disk 12 tilts, then a focus shift will occur with respect to the objective lens 79. Using methods such as the astigmatization method or the knife edge method in the detecting device 15, if light in which a focus shift has occurred is detected, this can be used as a tilt detection signal. Coma aberration is generated because of warp in optical disks, which generally occurs due to, for example, manufacturing errors or age. And since high accuracy aberration properties are required with increasing recording density, in order to carry out recording and reproduction favorably, coma aberration preferably is corrected by tilting the objective lens. According to the present embodiment, by performing tilt detection using the detecting device 15 and by performing tilting drive using the tilt capable objective lens drive apparatus that was described in the eleventh embodiment, coma aberration can be corrected and information can be favorably recorded and reproduced. Thus, according to the present embodiment, since light of another wavelength that is not recording or reproducing, is utilized, tilting can be detected by a simple configuration, there is no necessity to attach a new tilt sensor, and costs can be reduced. Furthermore, highly accurate tilt detection can be obtained since the tilt is detected in the vicinity of the spot that is recording and reproducing information. It should be noted that in the present embodiment, an example is described in which tilt of the optical disk 12 whose substrate thickness is 0.1 mm is detected using light for the CD 14. However, it is not limited to this, and it is also possible to detect the tilt of the DVD 13 using the light for the CD 14. Even in this case, the same effect can be obtained because tilt is detected by utilizing light of a wavelength that is not recording and reproducing information. Fourteenth Embodiment FIG. 52 shows a complete structural example of an optical disk drive 89 as an optical information recording and reproduction apparatus. An optical disk 61 is fixed, sandwiched between the turntable 63 and the damper 64, and is rotated by the motor (rotating system) 65, which is a moving means. The optical head 62 that is described in any one of the fourth to thirteenth embodiments rides on the traverse (conveying system) 66, which is a moving means, and is set such that the light that is emitted can move from the inner circumference to the outer circumference of the optical disk. A control circuit 68 performs focus control, tracking control traverse control and motor rotation control based on the signal that is received from the optical head 62. Furthermore, it also reproduces information from the reproduction signal, and sends the recording signal to the optical head 62. Fifteenth Embodiment The fifteenth embodiment is an embodiment in which an optical head that was shown in the first to fourteenth embodiment is used in a computer. FIG. 53 shows a perspective view of the computer (personal computer) according to the present embodiment. In FIG. 53, a computer 100 is constituted by an optical disk drive (optical information recording and reproduction apparatus) 101, a keyboard 103 to input information, and a monitor 102 for displaying information. The optical disk drive 101 is provided with any of the optical heads described in the first to fourteenth embodiments. Since the computer 100 is provided with the optical disk drive 101 that includes any of the optical heads described in the first to fourteenth embodiments as an external recording device, information can be recorded and reproduced reliably for different types of optical disks, and it can be used over a wide range of applications. Furthermore, it is possible to make use of the high capacity of optical disks to back up the computer hard disk. Furthermore, by making use of the low cost and portability of the media (optical disk), and its interchangeability, in which its information can be read out on another optical disk drive, programs or data can be exchanged with other people, or can be for personal use. Furthermore, it can also handle pre-existing media such as DVDs or CDs. Sixteenth Embodiment The sixteenth embodiment is an embodiment in which an optical head shown in the first to fourteenth embodiments is used in an optical disk recorder (image recording device). FIG. 54 shows a perspective view of the optical disk recorder according to the present embodiment. An optical disk recorder 110 is used when connected to a monitor 111 that is for displaying images recorded on the optical disk recorder 110. Since the optical disk recorder 110 is provided with an optical disk drive that includes an optical head described in any of the first to fourteenth embodiments, information can be reliably recorded onto and reproduced from different types of optical disks, and it can be used over a wide range of applications. Furthermore, the optical disk recorder 110 records images onto the media, which then can be reproduced when desired. There is no necessity to rewind the optical disk like a tape after recording and after reproduction, and chasing playback, in which the start of a program can be reproduced while recording that program, and simultaneous recording/replaying, in which a pre-recorded program is reproduced while recording another program, are possible. Moreover, by making use of the low cost and portability of the media (optical disk), and its interchangeability, in which its information can be read out on another optical disk drive, programs or data can be exchanged with other people, or can be for personal use. Furthermore, it also can handle pre-existing media such as DVDs or CDs. It should be noted that the description here is of an optical disk recorder provided with only an optical disk drive, however an internal hard disk can also be provided, as can a video tape that has a recording and reproduction function. In this manner, temporary saving or backup of images is facilitated. Seventeenth Embodiment The seventeenth embodiment is an embodiment in which optical heads shown in the first to fourteenth embodiments are used in an optical disk player (image reproduction apparatus). FIG. 55 shows a perspective view of the optical disk player according to the present embodiment. An optical disk player 121 is provided with a liquid crystal monitor 120, and can display images that are recorded on an optical disk on the liquid crystal monitor. Since the disk player 121 has an internal optical disk drive that includes an optical head described in any of the first to fourteenth embodiments, information can be recorded onto and reproduced from different types of optical disks reliably, and it can be used over a wide range of applications. Furthermore, the optical disk player can reproduce images, which are recorded onto the media, when desired. There is no necessity to rewind the optical disk like a tape after reproduction, and images can be accessed and reproduced at a desired location. Furthermore, it also can handle pre-existing media such as DVDs or CDs. Eighteenth Embodiment The eighteenth embodiment is an embodiment in which an optical head shown in the first to fourteenth embodiments is used in a server. FIG. 56 is a perspective view of the server according to the present embodiment. A server 130 is provided with an optical disk drive 131, a monitor 133 for displaying information and a keyboard 134 to input information, and is connected to a network 135. Since the server 130 has an inbuilt optical disk drive that includes an optical head described in any of the first to fourteenth embodiments, information can be and reproduced from different types of optical disks reliably, and the server can be used over a wide range of applications. Furthermore, making use of the large capacity of optical disks, information (such as images, speech, moving images, HTML text and text documents) that is recorded on the optical disk is transmitted in response to a demand from the network 135. Furthermore, information that is sent from the network is recorded in the requested position. Furthermore, since it is also possible to reproduce information that is recorded on pre-existing media, such as CDs and DVDs, it is also possible to transmit that information. Nineteenth Embodiment The nineteenth embodiment is an embodiment in which an optical head shown in the first to fourteenth embodiments is used in a car navigation system. FIG. 57 shows a perspective view of the car navigation system according to the present embodiment. A car navigation system 140 has an internal optical disk drive that is connected to and is used with a liquid crystal monitor 141 that displays topographical and destination information. Since the car navigation system 140 is provided with an optical disk drive that includes an optical head described in any of the first to fourteenth embodiments, information can be recorded and reproduced from different types of optical disks reliably, and it can be used over a wide range of applications. Furthermore, the car navigation system 140 calculates its present position based on information from map information recorded on a medium, a geo-positioning system (GPS) or a gyroscope, a speedometer and an odometer, and displays that position on the liquid crystal monitor. Furthermore, if the destination is input, the system calculates the optimum route to the destination based on the map information and the road information, and displays this on the liquid crystal monitor. By using a large capacity optical disk to record the map information, it is possible to provide detailed road information covering a wide area on a single disk. Furthermore, information about restaurants, convenience stores and gasoline stands that are in the vicinity of the roads also can be provided simultaneously, contained on the optical disk. Moreover, with the passage of time, road information becomes old and inaccurate. However since optical disks are interchangeable, and the media is cheap, the latest information can be obtained by substitution with a disk containing the newest road information. Furthermore, since the car navigation system can handle the recording and reproduction of pre-existing media such as DVDs and CDs, it is possible to watch movies or listen to music inside the vehicle. INDUSTRIAL APPLICABILITY Since the present invention according to the embodiments above reliably can record and reproduce information from optical disks that have different substrate thicknesses such as high density optical disks whose substrate thickness is thin, and DVDs and CDs, it can be applied in computers, image recording devices, image reproducing devices, servers and car navigation systems.
<SOH> BACKGROUND ART <EOH>Optical memory technology that uses optical disks as high-density, large-volume memory media gradually is being applied widely to and entering general use in digital audio disks, video disks, document file disks and also data files. To successfully achieve recording onto and reproduction of information from an optical disk with high reliability via a minutely narrowed light beam, there is a need for a focusing function forming a minute spot at the diffraction limit, focus control and tracking control of the optical system, and a pit signal (“information signal”) detection function. With recent advances in optical system design technology and the shortening of wavelengths of the semiconductor lasers serving as light sources, the development of optical disks containing volumes of memory at greater than conventional densities is progressing. As an approach to higher densities, increasing the optical disk side numerical aperture (NA) of a focusing optical system that minutely stops down a light beam onto an optical disk has been investigated. A problem that occurs at this time is that there is an increase in aberration caused by an inclination of the disk in relation to the light axis (what is known as “tilt”). When the NA is made large, the aberration caused by tilt increases. It is possible to prevent this by reducing the thickness (substrate thickness) of the transparent substrate of the optical disk. A Compact Disc (CD), which can be considered a first generation optical disk, is used with a light source emitting infrared light (a wavelength λ 3 is 780 nm to 820 nm) and an objective lens with an NA of 0.45, and has a substrate thickness of approximately 1.2 mm. A Digital Versatile Disc (DVD), which can be considered a second generation optical disk, is used with a light source emitting red light (a wavelength λ 2 is 630 nm to 680 nm) and an objective lens with an NA of 0.6, and has a substrate thickness of approximately 0.6 mm. And, a system has been proposed in which a third generation optical disk is used with a light source that emits blue light (a wavelength λ 1 is 380 nm to 420 nm) and an objective lens with an NA of 0.85, the disk having a substrate thickness of 0.1 mm. It should be noted that in this specification, the substrate thickness means the thickness of the transparent substrate from the face at which a light beam is incident on the optical disk (or optical recording medium) to the information recording surface. Thus, the thickness of the substrate of optical disks becomes thinner with increasing recording density. From the standpoint of economics and the space occupied by the device, it is desirable that a single optical information recording and reproduction apparatus is capable of recording and reproducing optical disks of different substrate thickness and recording density. For this purpose, there is a need for an optical head device that is provided with a focusing optical system that is capable of focusing a light beam up to the diffraction limit onto optical disks of different substrate thicknesses. An example of a device that records and reproduces information from both DVD and CD optical disks (information recording media) is proposed in the Patent Document 1 described below. As a first conventional example, this content is described simply using FIGS. 58 to 60 . FIG. 58 is a structural overview of an optical head 300 . FIG. 58A shows the manner in which information is recorded onto or reproduced from a DVD and FIG. 58B shows the manner in which information is recorded onto or reproduced from a CD. It contains a red semiconductor laser 301 that emits light of a wavelength of 635 nm to 650 nm, and an infrared semiconductor laser 302 that emits light of a wavelength of 780 nm. When reproducing a DVD 308 , which is a second information recording medium, the light emitted from the red semiconductor laser 301 passes through a wavelength selecting prism 303 , and is converted to collimated light by a collimator lens 304 . The light that was converted to collimated light is reflected by a beam splitter 305 , passes through a dichroic hologram 306 , is converted to convergent light by an objective lens 307 , and is irradiated onto the DVD 308 . The light that was reflected by the DVD 308 again passes through the objective lens 307 and the dichroic hologram 306 , passes through the beam splitter 305 , is converted to convergent light by a detecting lens 309 , and is focused onto a photodetector 310 . When reproducing a CD 311 , which is a third information recording medium, the light emitted from the infrared semiconductor laser 302 is reflected by the wavelength selecting prism 303 , and is converted to collimated light by a collimator lens 304 . The light that was converted to collimated light is reflected by a beam splitter 305 , is diffracted by the dichroic hologram 306 , is converted to convergent light by an objective lens 307 , and is irradiated onto the CD 311 . The light that was reflected by the CD 311 again passes through the objective lens 307 and the dichroic hologram 306 , passes through the beam splitter 305 , is converted to convergent light by the detecting lens 309 , and is focused onto the photodetector 310 . Spherical aberration caused by the difference in substrate thickness of DVDs and CDs is corrected by the dichroic hologram 306 . FIG. 59 is a cross-sectional view of the dichroic hologram 306 . Grooves of depth d, 2 d and 3 d are arranged in that order on the surface of the dichroic hologram 306 . The depth d is determined such that, in-line-formulae description="In-line Formulae" end="lead"? d =λ 1 /( n 1 −1) in-line-formulae description="In-line Formulae" end="tail"? where λ 1 is the wavelength of the red semiconductor laser and n 1 is the refractive index of the dichroic hologram 306 at the wavelength λ 1 . In this way, the transmittance of the light of wavelength λ 1 , increases without diffracting the light. Here, the wavelength of light emitted from the infrared semiconductor laser is λ 2 , and the refractive index of the dichroic hologram 306 at the wavelength λ 2 is n 2 . FIG. 60A shows the wavefront after the light of wavelength λ 2 has passed the dichroic hologram 306 , in which, in-line-formulae description="In-line Formulae" end="lead"? d ×( n 2 −1)/λ 2 =0.75. in-line-formulae description="In-line Formulae" end="tail"? In this case, a phase shift of 0.75 times the wavelength occurs per step. As phase shifts of greater than one can be ignored, FIG. 60B shows a wavefront that is re-written, based only on that portion to the right of the decimal point. This wavefront becomes first order diffraction light, which has a high diffraction efficiency at one side. Furthermore, in the non-Patent Document 1 described below an example is given of a device for reproducing information on CDs, DVDs and ultra high density optical disks. This is briefly explained using FIGS. 61 and 62 as a second conventional example. FIG. 61 is a structural overview showing an optical head. Collimated light emitted from an optical system 201 that contains a blue light source of wavelength λ 1 =405 nm passes through prisms 204 , 205 and a phase plate 206 , which will be explained later, is focused by an objective lens 207 , and is irradiated onto an information recording surface of an optical disk 208 (an ultra high density optical disk) whose substrate thickness is 0.1 mm. The light that was reflected by the optical disk 208 returns back along the travel path and is detected by a photodetector of the optical system 201 . The diverging light that is emitted by an optical system 202 that contains a source of red light of wavelength λ 2 =650 nm is reflected by the prism 204 , passes through the prism 205 and the phase plate 206 , is focused by the objective lens 207 and is irradiated onto an information recording surface of an optical disk 209 (DVD), whose substrate thickness is 0.6 mm. The light that was reflected from the optical disk 209 returns back along the travel path, and is detected by a photodetector of the optical system 202 . The diverging light emitted by an optical system 203 , which has a source of infrared light of a wavelength λ 3 =780 nm is reflected by the prism 205 , passes through the phase plate 206 , is focused by the objective lens 207 , and is irradiated onto an information recording surface of an optical disk 210 (CD), whose substrate thickness is 1.2 mm. The light that was reflected by the optical disk 210 returns back along the travel path, and is detected by a photodetector of the optical system 203 . The objective lens 207 is designed so as to handle substrate thicknesses of 0.1 mm, and spherical aberration occurs in CDs and DVDs because of the difference in substrate thickness. Correction of this spherical aberration occurs due to the degree of divergence of the diverging light that is emitted by the optical system 202 and optical system 203 , and due to the phase plate 206 . Different spherical aberration is generated when divergent light is incident on the objective lens, so it is possible to cancel out spherical aberration caused by the difference in substrate thickness by this new spherical aberration. The degree of divergence of the diverging light is set such that spherical aberration is a minimum. Spherical aberration caused by the diverging light cannot be completely corrected, and higher order spherical aberrations (principally fifth order spherical aberrations) remain. These fifth order spherical aberrations are corrected by the phase plate 206 . FIG. 62 shows a surface ( FIG. 62A ) and a lateral view ( FIG. 62B ) of the phase plate 206 . If the refractive index at the wavelength λ 1 is defined as n 1 , and h=λ 1 /(n 1 −1), then the phase plate 206 is constituted by phase shift steps 206 a of height h and height 3 h. The height h generates a phase shift of 1λ (where λ is the wavelength that is used) in the light of wavelength λ 1 , however this does not affect the phase distribution and there is no impediment to recording or reproduction of the optical disk 208 . On the other hand, if the refractive index of the phase plate 206 at the wavelength λ 2 is n 2 , then a phase shift of the light of wavelength λ 2 of h/λ 2 ×(n 2 −1)=0.625 λ is generated. Furthermore, if the refractive index of the phase plate 206 at the wavelength λ 3 is n 3 , then a phase shift of the light of wavelength λ 3 of h/λ 3 ×(n 3 −1)=0.52 λ is generated. In relation to DVDs and CDs, this wave shift is used to convert the wavefronts, and the remaining fifth order spherical aberrations are corrected. Moreover, the Patent Document 2 described below proposes a method for reproducing information using an objective lens that is capable of recording and reproducing ultra high density optical disks, and two objective lenses that are capable of reproducing CDs and DVDs. This is described briefly as a third conventional example, using FIG. 63 . A lens holder 233 is provided with an objective lens 231 that is used when recording onto and replaying from ultra high density optical disks, an objective lens 232 that is used when reproducing DVDs and CDs, and drive coils 234 , and is suspended by wires 236 from a fixed portion 237 . A magnetic circuit is constituted by a magnet 238 and a yoke 239 . An electromagnetic force is caused by the flow of electric current through the drive coil 234 , and the objective lenses 231 and 232 are driven in the focusing direction and the tracking direction. In the third conventional example, which of the objective lenses 231 and 232 is used depends on the optical disk to be recorded and reproduced. Furthermore, as a technique for correcting chromatic aberration, a chromatic aberration correcting hologram is proposed in the Patent Document 3 described below, in which the cross-sectional shape of the optical element is saw tooth shaped, wherein light of a first wavelength λ 1 is corrected using second order diffracted light, and light of a second wavelength λ 2 is corrected using first order diffracted light. However, in the optical head of the first conventional example, when light is irradiated onto optical disks that have widely different substrate thicknesses, such as a substrate thickness of 1.2 mm and a substrate thickness of 0.1 mm, there is the problem that the distance between the disk and the objective lens changes significantly, the movable range of the actuator increases, and the head becomes large. Moreover, there is the problem that in order to detect the light that corresponds to the three types of light sources, the number of signal wires increases and the width of the flexible cable that connects the optical head and the optical disk drive is wider. Furthermore, in the optical disk device according to the second conventional example, since the light is incident on the objective lens as divergent light when reproducing CDs and DVDs, there is the problem that when the objective lens is driven in the tracking direction, a large coma aberration is generated and the optical disks cannot be favorably reproduced. Furthermore, in the optical disk device of the third conventional example, because the objective lenses 231 and 232 are lined up in a tangential direction (y direction) and the objective lens 231 is arranged such that it is positioned on a straight line in the tracking direction (x direction) that passes through a rotational center O of the optical disk, there is the problem that DVDs and CDs that use the objective lens 232 cannot use the differential push-pull (DPP) method or the three beam method, which are common tracking detection methods. This problem is described using FIG. 64 . The DPP method or the three beam method use a main spot for reproduction, and two sub spots for tracking detection. A main spot 232 a of the objective lens 232 shown in FIG. 63 is in a spot position 150 a shown in FIG. 64 . The subspots are in positions 150 b and 150 c , and are set at an optimal angle θ 0 with respect to a reproduction track 153 . The spots move in the x-direction in accordance with the seek operation of the optical head, and the spot positions change to 151 a , 151 b and 151 c . Because the spot positions 150 a and 151 a are not on the straight line that passes through the axis of rotation O of the optical disks in the x-direction, the angle θ 0 changes to θ 1 due to the seek operation of the optical head. That is to say, in the configuration of the third conventional example, there is the problem that tracking control cannot be carried out reliably. Patent Document 1 JP H9-306018A Patent Document 2 JP H11-120587A Patent Document 3 JP 2001-60336 Non-Patent Document 1 Session We-C-05 of ISOM 2001 (p30 of the proceedings)
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1A is a structural diagram showing how a high density optical disk is recorded and reproduced according to the first embodiment of the present invention. FIG. 1B is a structural diagram showing how a DVD is recorded and reproduced according to the first embodiment of the present invention. FIG. 1C is a structural diagram showing how a CD is recorded and reproduced according to the first embodiment of the present invention. FIG. 2A is a view of an upper surface of a dichroic hologram used in the first embodiment of the present invention. FIG. 2B is a view of a rear surface of the dichroic hologram used in the first embodiment of the present invention. FIG. 3 is a cross-sectional view of the dichroic hologram used in the first embodiment of the present invention. FIG. 4A is a schematic view of wavefronts after light of wavelength λ 2 has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 4B is a schematic diagram of the wavefronts that are calculated by ignoring the integer portions of the wavelength of the wavefronts in FIG. 4A . FIG. 5 is a conceptual diagram showing the diffraction efficiency of light that is diffracted by the dichroic hologram used in the first embodiment of the present invention. FIG. 6A is a schematic view of a wavefront of the light of wavelength λ 3 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 6B is a schematic view of the wavefront of FIG. 6A that is calculated ignoring the integer portion of the wavelength. FIG. 7 is a cross-sectional view of a separate dichroic hologram to that used in the first embodiment of the present invention. FIG. 8A is a schematic view of a wavefront of the light of wavelength λ 2 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 8B is a schematic view of the wavefront of FIG. 8A that is calculated ignoring the integer portion of the wavelength. FIG. 8C is a schematic view of a wavefront of the light of wavelength λ 3 after it has passed through the dichroic hologram used in the first embodiment of the present invention. FIG. 8D is a schematic view of the wavefront of FIG. 8C that is calculated ignoring the integer portion of the wavelength. FIG. 9A is a conceptual diagram showing the diffraction efficiency of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 9B is a conceptual diagram showing the transmittance of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 10 is a schematic view showing the principal directions of the light that is diffracted by the dichroic hologram that is used in the first embodiment of the present invention. FIG. 11 is a structural diagram of an optical disk drive according to the first embodiment of the present invention. FIG. 12A is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD 1 . FIG. 12B is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD 2 . FIG. 12C is a schematic view of the optical disk drive according to the first embodiment of the present invention when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WD 3 . FIG. 13A is a schematic view of a conventional optical disk drive when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WDa. FIG. 13B is a schematic view of the conventional optical disk drive when recording onto and reproducing information from a disk, when the distance between the disk and focusing means is WDb. FIG. 14A is a structural view of associated circuits of an optical head according to the first embodiment of the present invention. FIG. 14B is a structural view according to a separate example of associated circuits of the optical head according to the first embodiment of the present invention. FIG. 15 is an outline of a signal that is output from the associated circuit of the optical head according to the first embodiment of the present invention. FIG. 16A is a structural diagram of the manner in which a high density optical disk is recorded and reproduced in an optical system according to a second embodiment of the present invention. FIG. 16B is a structural view of the manner in which a DVD is recorded and reproduced in an optical system according to the second embodiment of the present invention. FIG. 17A is a view of an upper surface of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 17B is a view of a rear surface of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 18A is a structural diagram of a separate example of the manner in which a high density optical disk is recorded and reproduced in the optical system according to the second embodiment of the present invention. FIG. 18B is a structural diagram of a separate example of the manner in which a DVD is recorded and reproduced in the optical system according to the second embodiment of the present invention. FIG. 19A is a view of an upper surface of a separate example of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 19B is a view of a rear surface of a separate example of a dichroic hologram that is used in the second embodiment of the present invention. FIG. 20A is a structural diagram of the manner in which a high density optical disk is recorded and reproduced in an optical system according to a third embodiment of the present invention. FIG. 20B is a structural diagram of the manner in which a DVD is recorded and reproduced in the optical system according to the third embodiment of the present invention. FIG. 20C is a structural diagram of the manner in which a CD is recorded and reproduced in the optical system according to the third embodiment of the present invention. FIG. 21A is a view of an upper surface of a dichroic hologram that is used in the third embodiment of the present invention. FIG. 21B is a view of a rear surface of the dichroic hologram that is used in the third embodiment of the present invention. FIG. 21C is a cross-sectional view of the dichroic hologram that is used in the third embodiment of the present invention. FIG. 22 is a cross-sectional view of the dichroic hologram according to the third embodiment of the present invention. FIG. 23A is a schematic view of a wavefront of the light of wavelength λ 2 after it has passed through the dichroic hologram used in the third embodiment of the present invention. FIG. 23B is a schematic view of the wavefront of FIG. 23A that is calculated ignoring the integer portion of the wavelength. FIG. 24 is a conceptual diagram showing the diffraction efficiency of light that is diffracted by the dichroic hologram used in the third embodiment of the present invention. FIG. 25A is a schematic view of a wavefront of the light of wavelength λ 3 after it has passed through the dichroic hologram used in the third embodiment of the present invention. FIG. 25B is a schematic view of the wavefront of FIG. 25A that is calculated ignoring the integer portion of the wavelength. FIG. 26 is a structural diagram of an optical head according to a fourth embodiment of the present invention. FIG. 27A is a structural overview of an objective lens drive apparatus according to the fourth embodiment of the present invention. FIG. 27B is a lateral view of the objective lens drive apparatus according to the fourth embodiment of the present invention. FIG. 28 is an overview showing the structure of an optical head according to a fifth embodiment of the present invention. FIG. 29A is a plan view of a phase plate according to the fifth embodiment of the present invention. FIG. 29B is a lateral view of the phase plate according to the fifth embodiment of the present invention. FIG. 30 is a diagram of wavefront aberration according to the fifth embodiment of the present invention. FIG. 31 is a structural diagram of an optical head according to a sixth embodiment of the present invention. FIG. 32A is a plan view of a phase plate according to the sixth embodiment of the present invention. FIG. 32B is a lateral view of the phase plate according to the sixth embodiment of the present invention. FIG. 33 is a diagram of the wavefront aberration according to the sixth embodiment of the present invention. FIG. 34 is a structural diagram of an optical head according to a seventh embodiment of the present invention. FIG. 35A is a plan view of a phase plate according to the seventh embodiment of the present invention. FIG. 35B is a lateral view of the phase plate according to the seventh embodiment of the present invention. FIG. 36 is a diagram of the wavefront aberration according to the seventh embodiment of the present invention. FIG. 37 is a structural diagram of an optical head according to an eighth embodiment of the present invention. FIG. 38 is a structural diagram of a mirror according to the eighth embodiment of the present invention. FIG. 39A is a plan view of a phase plate according to a ninth embodiment of the present invention. FIG. 39B is a lateral view of the phase plate according to the ninth embodiment of the present invention. FIG. 40 is a structural diagram of an optical head according to a tenth embodiment of the present invention. FIG. 41A is a plan view of a liquid crystal hologram according to the tenth embodiment of the present invention. FIG. 41B is a lateral view of the liquid crystal hologram according to the tenth embodiment of the present invention. FIG. 42A is a plan view of a phase plate according to the tenth embodiment of the present invention. FIG. 42B is a lateral view of the phase plate according to the tenth embodiment of the present invention. FIG. 43 is a structural diagram of an optical head according to an eleventh embodiment of the present invention. FIG. 44 is a structural diagram of an objective lens drive apparatus according to the eleventh embodiment of the present invention. FIG. 45 is a diagram used to describe the manner in which the objective lens is tilted. FIG. 46 is a diagram used to describe positions of three spots according to the eleventh embodiment of the present invention. FIG. 47 is a structural diagram of the optical head according to the eleventh embodiment of the present invention. FIG. 48 is a structural diagram of an optical head according to a twelfth embodiment of the present invention. FIG. 49A is a cross-sectional view of an objective lens according to the twelfth embodiment of the present invention. FIG. 49B is a view of a rear surface of the objective lens according to the twelfth embodiment of the present invention. FIG. 50 is a diagram used to describe tilt detection according to the twelfth embodiment of the present invention. FIG. 51 is a structural diagram of an optical head according to a thirteenth embodiment of the present invention. FIG. 52 is an overview of an optical disk drive that uses an optical head according to the present invention. FIG. 53 is an external view of a personal computer that uses the optical disk drive of the present invention. FIG. 54 is an external view of an optical disk recorder that uses the optical disk drive of the present invention. FIG. 55 is an external view of an optical disk player that uses the optical disk drive of the present invention. FIG. 56 is an external view of a server that uses the optical disk drive of the present invention. FIG. 57 is a car navigation system that uses the optical disk drive of the present invention. FIG. 58A is a structural diagram showing the manner in which a DVD is recorded and reproduced by an optical head according to a first conventional example. FIG. 58B is a structural diagram showing the manner in which a CD is recorded and reproduced by the optical head according to the first conventional example. FIG. 59 is a cross-sectional view of a dichroic hologram according to the first conventional example. FIG. 60A is a schematic view of a wavefront of the light of wavelength λ 2 after it has passed through the dichroic hologram used in the first conventional example. FIG. 60B is a schematic view of the wavefront of FIG. 60A that is calculated ignoring the integer portion of the wavelength. FIG. 61 is a structural diagram of an optical head according to a second conventional example. FIG. 62A is a plan view of a phase plate according to the second conventional example. FIG. 62B is a lateral view of the phase plate according to the second conventional example. FIG. 63 is a structural diagram of an objective lens according to a third conventional example. FIG. 64 is a diagram that is used to explain the position of three spots according to the third conventional example. detailed-description description="Detailed Description" end="lead"?
20041018
20081216
20051027
86384.0
0
GIESY, ADAM
OPTICAL ELEMENT, OPTICAL HEAD, OPTICAL INFORMATION RECORDING/REPRODUCTION DEVICE, COMPUTER, VIDEO RECORDING DEVICE, VIDEO REPRODUCTION DEVICE, SERVER, AND CAR NAVIGATION SYSTEM
UNDISCOUNTED
0
ACCEPTED
2,004
10,511,881
ACCEPTED
Aluminum conductor composite core reinforced cable and method of manufacture
This invention relates to an aluminum conductor composite core reinforced cable (ACCC) and method of manufacture. An ACCC cable having a composite core surrounded by at least one layer of aluminum conductor. The composite core comprises at least one longitudinally oriented substantially continuous reinforced fiber type in a thermosetting resin matrix having an operating temperature capability within the range of about 90 to about 230° C., at least 50% fiber volume fraction, a tensile strength in the range of about 160 to about 240 Ksi, a modulus of elasticity in the range of about 7 to about 30 Msi and a thermal expansion coefficient in the range of about 0 to about 6×10−6 m/m/C. According to the invention, a B-stage forming process may be used to form the composite core at improved speeds over pultrusion processes wherein the speeds ranges from about 9 ft/min to about 50 ft/min.
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A composite core for an electrical cable comprising: an inner core consisting of advanced composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; and an outer core consisting of low modulus composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; wherein, said composite core comprises a core tensile strength of at least about 160 Ksi (1103 MPa). 104. A composite core as claimed in claim 103 wherein, the reinforced fiber types of the composite core are selected from the group consisting of carbon, Kevlar, basalt, glass, aramid, boron, liquid crystal fibers, high performance polyethylene and carbon nanofibers. 105. A composite core as claimed in claim 103 comprising a thermosetting resin having a neat resin fracture toughness at least about 0.87 INS-lb/in (0.96 MPa·m1/2). 106. A composite core as claimed in claim 103 wherein, at least one reinforced fiber type in the inner core comprises a modulus of elasticity in the range of about 22 (151 GPa) to 37 Msi (255 GPa) coupled with a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/° C. and a tensile strength of at least about 350 Ksi (2413 MPa) and at least one reinforced fiber type in the outer core comprises a tensile strength in the range of at least about 180 Ksi (1241 MPa) coupled with a coefficient of thermal expansion in the range of about 5×10−6 to about 10×10−6 m/m/C. 107. A composite core as claimed in claim 103 wherein, the composite material of the inner core and the outer core is selected to meet physical characteristics in the end composite core including a tensile strength of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 Msi (48 GPa) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/° C. 108. A composite core as claimed in claim 103 comprising a fiber/resin volume fraction in the range of at least about 50%. 109. A composite core as claimed in claim 103 comprising a fiber/resin ratio of at least about 62% by weight. 110. A composite core as claimed in claim 103 wherein, said composite core comprises a hybridized concentric core having an inner carbon fiber/thermosetting resin core and an outer glass fiber/thermosetting resin core. 111. A composite core as claimed in claim 103 wherein, said inner and outer cores form a concentric hybridized core. 112. A composite core as set forth in claim 103 wherein, said outer core and said inner core form a segmented concentric core. 113. A composite core as claimed in claim 103 wherein, at least one layer of a plurality of aluminum segments is wrapped around the core. 114. A composite core for an electrical cable comprising: two or more types of reinforced fiber types in a thermosetting resin matrix, said core-having at least 50% fiber volume fraction, wherein at least one fiber comprises a modulus of elasticity in the range of about 22 (151 GPa) to 37 Msi (255 GPa) coupled with a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/C and a tensile strength at least about 350 Ksi (2413 MPa) and at least one fiber comprises a coefficient of thermal expansion in the range of about 5×10−6 m/m/C to about 10×10−6 m/m/C and a tensile strength of at least about 180 Ksi (1241 MPa). 115. A composite core as claimed in claim 114 wherein, the reinforced fiber types of the composite core are selected from the group consisting of carbon, Kevlar, basalt, glass, aramid, boron, liquid crystal fibers, high performance polyethylene and carbon nanofibers. 116. A composite core as claimed in claim 114 comprising a thermosetting resin having a neat resin fracture toughness at least about 0.87 INS-lb/in (0.96 MPa·m1/2). 117. A composite core as claimed in claim 114 wherein, a proportion and type of fibers are selected to meet physical characteristics in the end composite core including a tensile strength in the range of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 (48 GPa) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/° C. 118. A composite core as claimed in claim 114 comprising a fiber/resin volume fraction in the range of at least about 50%. 119. A composite core as claimed in claim 114 comprising a fiber resin ratio of at least about 62% by weight. 120. A composite core as claimed in claim 114 wherein said composite core comprises a hybridized concentric core having an inner carbon/thermosetting resin layer and an outer glass fiber/thermosetting resin layer. 121. A composite core as claimed in claim 114 wherein, the core comprises an outer layer and an inner layer that form a concentric hybridized core. 122. A composite core as set forth in claim 114 wherein, the core comprises an outer layer and an inner layer that form a segmented concentric core. 123. A composite core as claimed in claim 114 wherein, at least one layer of a plurality of aluminum segments is wrapped around the core. 124. A composite core for an electrical cable comprising: one or more types of longitudinally oriented and substantially continuous reinforced fiber types in a thermosetting resin matrix, said core having a tensile strength of at least about 160 Ksi (1103 MPa) and a modulus of elasticity in the range of about 7 to about 30 Msi. 125. A composite core as claimed in claim 124 wherein, the reinforced fiber types of the composite core are selected from the group consisting of carbon, Kevlar, basalt, glass, aramid, boron, liquid crystal fibers, high performance polyethylene and carbon nanofibers. 126. A composite core as claimed in claim 124 comprising a thermosetting resin having a neat resin fracture toughness at-least about 0.87 INS-lb/in (0.96 MPa·m1/2). 127. A composite core as claimed in claim 124 wherein, the composite core comprises two or more fiber types wherein, at least one reinforced fiber type comprises a modulus of elasticity in the range of about 22 (151 GPa) to 37 Msi (255 GPa) coupled with a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/C and a tensile strength in the range of at least about 350 Ksi (2413 MPa) and at least one reinforced fiber type comprises a tensile strength in the range of at least about 180 Ksi (1241 MPa) coupled with a coefficient of thermal expansion in the range of about 5×10−6 to about 10×10−6 m/m/C. 128. A composite core as claimed in claim 124 comprising a fiber/resin volume fraction in the range of at least about 50%. 129. A composite core as claimed in claim 124 comprising a fiber resin ratio of at least about 62% by weight. 130. A composite core as claimed in claim 124 wherein said composite core comprises a hybridized concentric core having an inner carbon/thermosetting resin layer and an outer glass fiber/thermosetting resin layer. 131. A composite core as claimed in claim 124 wherein, said composite core comprises an inner layer and an outer layer wherein, said layers form a concentric hybridized core. 132. A composite core as set forth in claim 130 wherein, said composite core comprises an inner and an outer layer wherein, said layers form a segmented concentric core. 133. A composite core as claimed in claim 124 wherein, at least one layer of a plurality of aluminum segments is wrapped around the core. 134. A composite core for an electrical cable comprising a composite material, said core having a tensile strength of at least about 160 Ksi (1103 MPa) and an operating temperature of at least about 90° C. wherein, said core is sufficiently flexible to wind around at least a seven foot wheel diameter for transportation. 135. A composite core as claimed in claim 134 wherein, the reinforced fiber types of the composite core are selected from the group consisting of carbon, Kevlar, basalt, glass, aramid, boron, liquid crystal fibers, high performance polyethylene and carbon nanofibers. 136. A composite core as claimed in claim 134 comprising a thermosetting resin having a neat resin fracture toughness at least about 0.87 INS-lb/in (0.96 MPa·m1/2). 137. A composite core as claimed in claim 134 wherein, said composite material further comprises at least one reinforced fiber type comprising a modulus of elasticity in the range of about 22 (151 GPa) to 37 Msi (255 GPa) coupled with a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/° C. and a tensile strength in the range of at least about 350 Ksi (2413 MPa) and at least one reinforced fiber type comprising a tensile strength in the range of at least about 180 Ksi (1241 MPa) coupled with a coefficient of thermal expansion in the range of about 5×10−6 to about 10×10−6 m/m/PC. 138. A composite core as claimed in claim 134 wherein, the composite material comprises a number and type of fibers selected to meet physical characteristics in the end composite core including a tensile strength in the range of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 (48) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230 C and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/C. 139. A composite core as claimed in claim 134 wherein, said composite core comprises a hybridized concentric core having an inner carbon/thermosetting resin layer and an outer glass fiber/thermosetting resin layer. 140. A composite core as claimed in claim 134 wherein, said composite core comprises an inner layer and an outer layer wherein, said layers form a concentric hybridized core. 141. A composite core as set forth in claim 134 wherein said composite core comprises an outer layer and an inner layer that form a segmented concentric core. 142. A composite core as claimed in claim 134 wherein at least one layer of a plurality of aluminum segments is wrapped around the core. 143. A composite core for an electrical cable comprising: an inner core comprising a high grade carbon fiber comprising a tensile strength of at least 700 Ksi and a tensile modulus of at least 30 Msi in a thermosetting resin comprising a viscosity range of at least about 200 to about 1500 Centipoise at 20° C.; and an outer core comprising an E-glass fiber in a thermosetting resin comprising a viscosity range of at least about 200 to about 1500 Centipoise at 20° C.; wherein, the composite core comprises a tensile strength in the range of about 160 to 240 Ksi and a modulus of elasticity in the range of about 7 to about 30 Msi. 144. A composite core as claimed in claim 143 wherein the inner core and the outer core comprise a number and type of fibers selected to meet physical characteristics in the end composite core including a tensile strength in the range of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 (48) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/° C. 145. A composite core as claimed in claim 143 wherein, said inner and outer cores form a concentric hybridized core. 146. A composite core as set forth in claim 143 wherein, said outer core and said inner core form a segmented concentric core. 147. A composite core as claimed in claim 143 wherein at least one layer of a plurality of aluminum segments is wrapped around the core. 148. A composite core for an electrical cable comprising: an inner core comprising a carbon fiber and at least a portion of one or more fibers having mechanical properties in excess of glass fiber in a thermosetting resin; and an outer core comprising a glass fiber in a thermosetting resin. 149. The composite core as claimed in claim 148, wherein the fiber having mechanical properties in excess of glass fiber is basalt. 150. A composite core as claimed in claim 148 wherein, the inner and outer cores comprise a proportion and type of fibers selected to meet physical characteristics in the end composite core including a tensile strength in the range of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 (48 GPa) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/° C. 151. A composite core as claimed in claim 148 wherein, said inner and outer cores form a concentric hybridized core. 152. A composite core as set forth in claim 148 wherein, said outer core and said inner core form a segmented concentric core. 153. A composite core as claimed in claim 148 wherein, at least one layer of a plurality of aluminum segments is wrapped around the core. 154. An electrical cable comprising: a composite core further comprising: an inner core consisting of advanced composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; an outer core consisting of low modulus composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; and at least one layer of conductor surrounding said outer core; wherein, said composite core comprises a core tensile strength of at least about 166 Ksi (1103 MPa). 155. An electrical cable as claimed in claim 154 wherein, the reinforced fiber types of the composite core are selected from the group consisting of carbon, Kevlar, basalt, glass, aramid, boron, liquid crystal fibers, high performance polyethylene and carbon nanofibers. 156. An electrical cable as claimed in claim 154 wherein the composite core further comprises a thermosetting resin having a neat resin fracture toughness at least about 0.87 INS-lb/in (0.96 MPa·m1/2). 157. An electrical cable as claimed in claim 154 wherein, the composite core comprises at least one reinforced fiber type in the inner core comprising a modulus of elasticity in the range of about 22 (151 GPa) to 37 Msi (255 GPa) coupled with a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/° C. and a tensile strength of at least about 350 Ksi (2413 MPa) and at least one reinforced fiber type in the outer core comprising a tensile strength in the range of at least about 180 Ksi (1241 MPa) coupled with a coefficient of thermal expansion in the range of about 5×10−6 to about 10×10−6 m/m/C. 158. An electrical cable as claimed in claim 154 wherein, the composite material of the inner core and the outer core is selected to meet physical characteristics in the end composite core including a tensile strength of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 Msi (48 GPa) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient at least in the range of about 0 to about 6×10−6 m/m/° C. 159. An electrical cable as claimed in claim 154 wherein, the composite core comprises a fiber/resin volume fraction in the range of at least about 50%. 160. An electrical cable as claimed in claim 154 wherein, the composite core comprises a fiber/resin ratio of at least about 62% by weight. 161. An electrical cable as claimed in claim 154 wherein, said composite core comprises a hybridized concentric core having an inner carbon fiber/thermosetting resin core and an outer glass fiber/thermosetting resin core. 162. An electrical cable as claimed in claim 154 wherein, said inner and outer cores form a concentric hybridized core. 163. An electrical cable as set forth in claim 154 wherein, said outer core and said inner core form a segmented concentric core. 164. A method of transmitting electrical power comprising: using a cable comprising a composite core and at least one layer of aluminum conductor surrounding the composite core, the composite core further comprising: an inner core consisting of advanced composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; and an outer core consisting of low modulus composite material comprising at least one longitudinally oriented and substantially continuous reinforced fiber type in a thermosetting resin; wherein the composite core comprises a tensile strength in the range of at least about 160 Ksi (1103 MPa); and transmitting power across the composite cable. 165. Method of processing a composite core member comprising the steps of: providing a predetermined number and type of fiber tows; guiding the fiber tows through a wet-out process; using a B-stage oven and a series of a plurality of bushings to shape and compress said fiber tows; and curing the composite core member. 166. A method as set forth in claim 164 wherein, using a B-stage oven and a series of a plurality of bushings to shape and compress said fiber tows further comprises using a plurality of bushings having a plurality of passageways wherein, the orientation of passageways is determined by the desired cross section configuration of the composite core. 167. A method as set forth in claim 164 wherein the number and type of fiber tows are selected to meet physical characteristics in the end composite core including a tensile strength of at least 160 Ksi (1103 MPa), a modulus of elasticity in the range of at least about 7 (48) to about 30 Msi (206 GPa), an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient in the range of about 0 to about 6×10−6 m/m/° C. 168. A method as set forth in claim 164 wherein, the step of guiding the fiber tows through the wet-out process further comprises using a wet-out tank filled with resin and a pre-heating step prior to wet-out'to evaporate moisture in the fiber tows. 169. A method as set forth in claim 164 wherein, the wet-out process further comprises a tank filled with resin and a device to aid in wetting the fibers. 170. A method as set forth in claim 164 wherein, the wet out tank filled with resin comprises a series of wipers to remove excess resin from the fibers. 171. A method as set forth in claim 164 wherein, the step of using a B-stage oven and a series of a plurality of bushings to shape and compress said fiber tows further comprises using bushings having a plurality of passageways wherein, at least a portion of the passageways diminishes with consecutive bushings. 172. A method as set forth in claim 164 wherein, the step-of using a B-stage oven and a series of a plurality of bushings to shape and compress said fiber tows further comprises using bushings having a plurality of passageways wherein, at least a portion of the passageways diminishes with consecutive bushings and wherein, at least a portion of the position of the passageways changes with consecutive bushings. 173. A method as set forth in claim 164 wherein the step of shaping and compressing the fiber tows further comprises: guiding the fiber tows into a first B-stage temperature oven; guiding the fiber tows into a second B-stage temperature oven comprising a series of bushings wherein each bushing in the series comprises a plurality of passageways; guiding the fiber tows through the consecutive series of bushings and passageways; and using the bushings to form the composite core. 174. A method as set forth in claim 164 wherein the step of curing the composite core further comprises: guiding the composite core through a second B-stage temperature oven to a curing oven wherein the curing oven temperature is in the range of about 330 (165) to about 370 F (188 C); guiding the composite core from the curing oven to a cooling zone wherein the cooling zone is in the range of about 30 (−1) to about 100 F (37 C); guiding the composite core from the cooling zone to a post-cure oven wherein the temperature of the post-cure oven is in the range of about 330 (165) to about 370 F (188 C); and guiding the composite core from the post-cure oven through a cooling zone wherein the core is cooled by air in the range of about 170 (76) to about 180 F (82 C). 175. A method as set forth in claim 164 wherein the step of using a B-stage oven and a series of a plurality of bushings to shape and compress the fiber tows further comprises forming one or more segments to make the composite core. 176. A method as set forth in claim 164 wherein the step of guiding the fiber tows further comprises twisting the orientation of the fiber.
CLAIM FOR PRIORITY In relation to this International Application, applicants claim priority of earlier U.S. provisional application Ser. No. 60/374,879 filed in the United States Patent and Trademark Office on 23 Apr. 2002, the entire disclosure of which is incorporated by reference herein. TECHNICAL FIELD The present invention relates to an aluminum conductor composite core (ACCC) reinforced cable and method of manufacture. More particularly, to a cable for providing electrical power having a reinforced fiber thermosetting resin composite core surrounded by aluminum conductor capable of carrying increased ampacity at elevated temperatures. BACKGROUND OF INVENTION This invention relates to composite core members and aluminum conductor composite core (ACCC) reinforced cable products made therefrom. This invention further relates to a forming process for an aluminum conductor composite core reinforced cable (ACCC). In the traditional aluminum conductor steel reinforced cable (ACSR) the aluminum conductor transmits the power and the steel core is designed to carry the transfer load. In an ACCC cable, the steel core of the ACSR cable is replaced by a composite core comprising at least one reinforced fiber type in a thermosetting resin matrix. Replacing the steel core has many advantages. An ACCC cable can maintain operating temperatures in the range of about 90 to about 230° C. without corresponding sag induced in traditional ACSR cables. Moreover, to increase ampacity, an ACCC cable couples a higher modulus of elasticity with a lower coefficient of thermal expansion. This invention relates to an aluminum conductor composite core reinforced cable suitable for operation at high operating temperatures without being limited by current operating limitations inherent in other cables for providing electrical power wherein provision of electrical power includes both distribution and transmission cables. Typical ACSR cables can be operated at temperatures up to 100° C. on a continuous basis without any significant change in the conductor's physical properties related to a reduction in tensile strength. These temperature limits constrain the thermal rating of a typical 230-kV line, strung with 795 kcmil ACSR “Drake” conductor, to about 400 MVA, corresponding to a current of 1000 A. Conductor cables are constrained by the inherent physical characteristics of the components that limit ampacity. More specifically, the ampacity is a measure of the ability to send power through the cable wherein increased power causes an increase in the conductor's operating temperature. Excessive heat causes the cable to sag below permissible levels. Therefore, to increase the load carrying capacity of transmission cables, the cable itself must be designed using components having inherent properties that withstand increased ampacity without inducing excessive sag. Although ampacity gains can be obtained by increasing the conductor area that wraps the core of the transmission cable, increasing conductor weight increases the weight of the cable and contributes to sag. Moreover, the increased weight requires the cable to use increased tension in the cable support infrastructure. Such large load increases typically would require structure reinforcement or replacement, wherein such infrastructure modifications are typically not financially feasible. Thus, there is financial motivation to increase the load capacity on electrical transmission cables while using the existing transmission liens. European Patent Application No. EP116374A3 discloses a composite core comprised of a single type of reinforced glass fiber and thermoplastic resin. The object is to provide an electrical transmission cable which utilizes a reinforced plastic composite core as a load bearing element in the cable and to provide a method of carrying electrical current through an electrical transmission cable which utilizes an inner reinforced plastic core. The composite core fails in these objectives. A one fiber system comprising glass fiber does have the required stiffness to attract transfer load and keep the cable from sagging. Secondly, a composite core comprising glass fiber and thermoplastic resin does not meet the operating temperatures required for increased ampacity, namely, between 90 and 230° C. Composite cores designed using a carbon epoxy composite core also have inherent difficulties. The carbon epoxy core has very limited flexibility and is cost prohibitive. The cable product having a carbon epoxy core does not have sufficient flexibility to permit winding and transport. Moreover, the cost for carbon fibers are expensive compared to other available fibers. The cost for carbon fibers is in the range of $5 to $37 per pound compared to glass fibers in the range of $0.36 to $1.20 per pound. Accordingly, a composite core constructed of only carbon fibers is not financially feasible. Physical properties of composite cores are further limited by processing methods. Previous processing methods cannot achieve a high fiber/resin ratio by volume or weight. These processes do not allow for creation of a fiber rich core that will achieve the strength to compete with a steel core. Moreover, the processing speed of previous processing methods are limited by inherent characteristics of the process itself. For example, traditional pultrusion dies are approximately 36 inches, having a constant cross section. The result is increased friction between the composite and the die slowing processing time. The processing times in such systems for epoxy resins range within about 6 inches/minute to about 12 inches/minute, which is not economically feasible. Moreover, these processes do not allow for composite configuration and tuning during the process, wherein tuning comprises changing the fiber/resin ratio. It is therefore desirable to design economically feasible ACCC cables having at least one reinforced fiber type in a thermosetting resin matrix comprising inherent physical characteristics that facilitate increased ampacity without corresponding cable sag. It is further desirable to process composite cores using a process that allows configuration and tuning of the composite cores during processing and allows for processing at speeds in the range of about 9 ft/min 2.74(m/min) to 50 ft/min (15.24 m/min). SUMMARY OF THE INVENTION Increased ampacity can be achieved by using an aluminum conductor composite core (ACCC) reinforced cable. An ACCC reinforced cable is a high-temperature, low-sag conductor, which can be operated at temperatures above 100° C. while exhibiting stable tensile strength and creep elongation properties. It is further desirable to achieve practical temperature limits of up to 230° C. Using an ACCC reinforced cable, which has the same diameter as the original, at 180° C. also increases the line rating by 50% without any significant change in structure loads. If the replacement conductor has a lower thermal elongation rate than the original, then the support structures will not have to be raised or reinforced. In particular, replacing the core of distribution and transmission conductor cables with a composite strength member comprising fiber and resin with a relatively high modulus of elasticity and a relatively low coefficient of thermal expansion facilitates an increased conductor cable ampacity. It is further desirable to design composite cores having long term durability allowing the composite strength member to operate at least sixty years, and more preferably seventy years at the temperatures associated with the increased ampacity, about 90 to 230° C., without having to increase either the diameter of the composite core, or the outside diameter of the conductor. This in turn allows for more physical space to put more aluminum and for the mechanical and physical performance to be able to meet the sag limits without increased conductor weight. Further, the invention allows for formation of a composite core having a smaller core size. A smaller core size allows the conductor cable to accommodate an increased volume of aluminum wherein an ACCC cable has the same strength and weight characteristics as a conductor cable without a composite core. To achieve the desired ampacity gains, a composite core according to the invention may also combine fibers having a low modulus of elasticity with fibers having a high modulus of elasticity for increased stiffness of the core and a lower elongation percent. By combining fibers, a new property set including different modulus of elasticity, thermal expansion, density and cost is obtained. Sag versus temperature calculations show achievable ampacity gains when an advanced composite is combined with low modulus reinforced fibers having inherent physical properties within the same range as glassfiber. Composite cores according to the invention meet certain physical characteristics dependent upon the selection of reinforced fiber types and thermosetting resins with desired inherent physical properties. Composite cores according to the invention have substantially low thermal expansion coefficients, substantially high tensile strength, ability to withstand a substantially high range of operating temperatures, ability to withstand a low range of ambient temperatures, substantially high dielectric properties and sufficient flexibility to permit winding. In particular, composite cores according to the present invention have a tensile strength within the range of about 160 to about 240 Ksi, a modulus of elasticity within the range of about 7 to about 30 Msi, an operating temperature within the range of about 90 to about 230° C. and a thermal expansion coefficient within the range of about 0 to about 6×10−6 m/m/C. These ranges can be achieved by a single reinforced fiber type or a combination of reinforced fiber types. Theoretically, although the characteristics could be achieved by a single fiber type alone, from a practical point of view, most cores within the scope of this invention comprise two or more distinct reinforced fiber types. In addition, depending on the physical characteristics desired in the final composite core, the composite core accommodates variations in the relative amounts of fibers. Composite cores of the present invention can be formed by a B-stage forming process wherein fibers are wetted with resin and continuously pulled through a plurality of zones within the process. The B-stage forming process relates generally to the manufacture of composite core members and relates specifically to an improved apparatus and process for making resin impregnated fiber composite core members. More specifically, according to a preferred embodiment, a multi-phase B-stage process forms a composite core member from fiber and resin with superior strength, higher ampacity, lower electrical resistance and lighter weight than previous core members. The process enables formation of composite core members having a fiber to resin ratio that maximizes the strength of the composite, specifically flexural, compressive and tensile strength. In a further embodiment, the composite core member is wrapped with high conductivity aluminum resulting in an ACCC cable having high strength and high stiffness characteristics. BRIEF DESCRIPTION OF THE DRAWINGS These and other features of the invention are best understood by referring to the detailed description of the invention, read in light of the accompanying drawings, in which: FIG. 1 is a schematic diagram of a B-stage forming process used for forming reinforced fiber composite core members in accordance with the present invention. FIG. 2 is a schematic diagram of a bushing showing sufficiently spaced passageways for insertion of the fibers in a predetermined pattern to guide the fibers through the B-stage forming process in accordance with the present invention. FIG. 3 is a schematic view of the structure of a bushing, said view showing the passageways used to shape and compress the bundles of reinforced fibers in accordance with the present invention. FIG. 4 is schematic comparison of two different bushings showing a reduction in the passageways from one bushing to the next to shape and compact the fibers into bundles in forming the composite core in accordance with the present invention. FIG. 5 shows a cross-sectional view of thirty possible composite core cross-section geometries according to the invention. FIG. 6 is a multi-dimensional cross-sectional view of a plurality of bushings overlaid on top of one another showing the decreasing passageway size with respective bushings. FIG. 7 is a multi-phase schematic view of a plurality of bushings showing migration of the passageways and diminishing size of the passageways with each successive bushing in accordance with the invention. FIG. 8 is a cross sectional view of one embodiment of a composite core according to the invention. FIG. 9 is a schematic view of an oven process having cross circular air flow to keep the air temperature constant in accordance with the invention. FIG. 10 is a cross-sectional view of the heating element in the oven represented in FIG. 9 showing each heater in the heating element in accordance with the invention. FIG. 11 is a schematic view of one embodiment of an aluminum conductor composite core (ACCC) reinforced cable showing an inner advanced composite core and an outer low modulus core surrounded by two layers of aluminum conductor according to the invention. DETAILED DESCRIPTION OF THE INVENTION The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that the disclosure will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. The drawings are not necessarily drawn to scale but are configured to clearly illustrate the invention. The present invention relates to a reinforced composite core member made from reinforced fibers embedded in a high temperature resin for use in aluminum conductor composite core reinforced (ACCC) cables to provide for electrical power distribution wherein electrical power distribution includes distribution and transmission cables. FIG. 11 illustrates a typical embodiment of an ACCC reinforced cable 300. FIG. 11 illustrates an ACCC reinforced cable having a reinforced carbon fiber/epoxy resin composite inner core 302 and a reinforced glass fiber/epoxy resin composite outer core 304, surrounded by a first layer of aluminum conductor 306 wherein a plurality of trapezoidal shaped aluminum strands wrap around the composite core and having a second layer of aluminum conductor 308 wherein a plurality of trapezoidal shaped aluminum strands wrap around the first aluminum layer 306. Composite cores of the present invention comprise the following characteristics: at least one type of reinforced fiber, variable relative amounts of each reinforced fiber type, reinforced fiber types of substantially small diameter, reinforced fiber types of a substantially continuous length, composite cores having a high packing density, reinforced fiber tows having relative spacing within the packing density, a volume fraction at least 50%, a fiber weight fraction between about 60 and about 75%, adjustable volume fraction, substantially low thermal expansion coefficient, a substantially high tensile strength, ability to withstand a substantially high range of operating temperatures, ability to withstand substantially low ambient temperature, having the potential to customize composite core resin properties, substantially high dielectric properties, having the potential of a plurality of geometric cross section configurations, and sufficient flexibility to permit winding of continuous lengths of composite core. A composite core of the following invention has a tensile strength in the range of about 160 to about 240 Ksi, a modulus of elasticity in the range of about 7 to about 30 Msi, an operating temperature in the range of about 90 to about 230° C. and a thermal expansion coefficient in the range of about 0 to about 6×10−6 m/m/C. To achieve these physical characteristics, composite cores of the present invention can comprise one type of reinforced fiber having inherent physical properties to enable the composite core to meet the required physical specifications. From a practical point of view, most cables within the scope of this invention comprise at least two distinct reinforced fiber types. Combining two or more reinforced fibers into the composite core member offers substantial improvements in strength to weight ratio over materials commonly used for cable in an electrical power transmission system. Fibers may be selected from the group comprising, for example: carbon fibers—both HM and HS (pitch based), Kevlar fibers, basalt fibers, glass fibers, Aramid fibers, boron fibers, liquid crystal fibers, high performance polyethylene fibers and carbon nanofibers. Several types of carbon, boron, Kevlar and glass fibers are commercially available. Each fiber type has subtypes of varying characteristics that may be combined in various combinations in order to achieve a particular composite. It is noted that these are only examples of fibers that meet the specified characteristics of the invention, such that the invention is not limited to these fibers only. Other fibers meeting the required physical characteristics of the invention may be used. Composite cores of the present invention preferably comprise fiber tows having relatively small yield or K numbers. A fiber tow is an untwisted bundle of continuous microfibers wherein the composition of the tow is indicated by its yield or K number. For example, 12K tow has 12,000 individual microfibers. Ideally, microfibers wet out with resin such that the resin coats the circumference of each microfiber within the bundle or tow. Wetting may be affected by tow size, that is, the number of microfibers in the bundle, and individual microfiber size. Larger tows create more difficulty wetting around individual fibers in the bundle due to the number of fibers contained within the bundle whereas smaller fiber diameter increases the distribution of resin around each fiber within each fiber tow. Wetting and infiltration of the fiber tows in composite materials is of critical importance to performance of the resulting composite. Incomplete wetting results in flaws or dry spots within the fiber composite reducing strength and durability of the composite product. Fiber tows may also be selected in accordance with the size of fiber tow that the process can handle in order to enable forming a composite having optimal desired physical characteristics. One process for forming composite cores in accordance with the present invention is called B-stage forming process. Fiber tows of the present invention for carbon are selected preferably in the range of about 4K to about 50K and glass fiber tows are preferably selected in the range of about 800 to about 1200 yield. Individual reinforced fiber sizes in accordance with the present invention preferably are within the range of about 8 to about 15 μm for glass fibers and most preferably about 10 μm in diameter whereas carbon fibers are preferably in the range of about 5 to about 10 μm and most preferably about 7 μm in diameter. For other types of fibers a suitable size range is determined in accordance with the desired physical properties. The ranges are selected based on optimal wet-out characteristics and feasibility. For example, fibers less than about 5 μm are so small in diameter that they pose certain health risks to those that handle the fibers. On the other end, fibers approaching 25 μm in diameter are difficult to work with because they are stiffer and more brittle. Composite cores of the present invention comprise fiber tows that are substantially continuous in length. In practice, carbon fiber tows comprising the present invention are preferably between about 1000 and 300meters in length, depending on the size of the spool. However, glass fiber lengths can range up to 36 km depending on the size of the spool. Most preferably, fibers are selected in the range of 1000 to 33,000 meters. It is most preferable to select the longest fibers that the processing equipment will accommodate due to less splicing of fibers to form a continuous composite core in excess of 6000 feet. Fiber ends may be glued end-to-end forming a substantially continuous fiber tow length. Continuous towing orients the fibers longitudinally along the cable. Composite cores of the present invention comprise fibers having a high packing efficiency relative to other conductor cable cores. In particular, traditional steel conductor cables generally comprise several round steel wires. Due to the round shape of the wires, the wires cannot pack tightly together and can only achieve a packing efficiency of about 74%. The only way that a steel core could have 100% packing efficiency would be to have a solid steel rod as opposed to several round steel wires. This is not possible because the final cable would be to stiff and would not bend. In the present invention, individual fibers are oriented longitudinally, wherein each fiber is coated with resin. and cured forming a hybridized composite core member having 100% packing efficiency. Higher packing efficiency yields a composite strength that is greater for a given volume relative to other cables. In addition, higher packing efficiency allows for formation of a composite core of smaller diameter thereby increasing the amount of aluminum conductor material capable of wrapping around the composite conductor core. Composite cores of the present invention comprise reinforced fibers that are substantially heat resistant. Heat resistance enables an ACCC cable to transmit increased power due to the ability of the composite core to withstand higher operating temperatures. The fibers used in the present invention have the ability to withstand operating temperatures between the range of about 90 and about 230° C. Most preferably, the fibers in the present invention have the ability to withstand operating temperatures between the range of about 170 to 200° C. Moreover, fibers used in the present invention can preferably withstand an ambient temperature range between about −40 to about 90° C. That is, under ambient conditions with no current flowing in an ACCC cable, the composite core is able to withstand temperatures as low as about −40° C. without suffering impairment of physical characteristics. Relative amounts of each type of reinforced fiber varies depending on the desired physical characteristics of the composite cable. For example, fibers having a lower modulus of elasticity enable formation of a high strength, stiff composite core. Carbon fibers have a modulus of elasticity preferably in the range of about 22 to about 37 Msi whereas glassfibers are considered low modulus reinforced fibers having a modulus of elasticity in the range of about 6 to about 7 Msi. The two types of fibers may be combined to take advantage of the inherent physical properties of each fiber to create a high strength, high stiffness composite core with added flexibility. In one embodiment, for example, the composite core comprises an inner carbon/resin core having an area of 0.037 sq. in. and a fiber resin ratio of about 70/30 by weight and an outer glass/epoxy layer having an area of 0.074 sq. in. and a fiber/resin ratio of about 75/25 by weight. In accordance with the present invention, the physical characteristics of the composite core may be adjusted by adjusting the fiber/resin ratio of each component. Alternatively, the physical characteristics of the composite core may be adjusted by adjusting the area percentage of each component within the composite core member. For example, by reducing the total area of carbon from 0.037 sq. in. and increasing the area of glass from 0.074 sq. in., the composite core member product has reduced stiffness in the carbon core coupled with increased flexibility. In addition, due to the smaller tow diameter of glass compared to carbon, the resulting composite core is smaller in diameter enabling increased conductor for the same resulting cable size. Alternatively, a third fiber, for example basalt, may be introduced into the composite core. The additional fiber changes the physical characteristics of the end product. For example, by substituting basalt for some carbon fibers, the core has increased dielectric properties and a relative decrease in core stiffness. Composite cores of the present invention comprise reinforced fibers having relatively high tensile strength. The degree of sag in an overhead voltage power transmission cable varies as the square of the span length and inversely with the tensile strength of the cable such that an increase in the tensile strength effectively reduces sag in an ACCC cable. Carbon fibers are selected having a tensile strength preferably in the range of about 350 to about 750 Ksi. More preferably in the range between 710 Ksi to 750 Ksi. Glassfibers are selected having a tensile strength preferably in the range of about 180 to about 220 Ksi. The tensile strength of the composite is enhanced by combining glassfibers having a lower tensile strength with carbon fibers having a higher tensile strength. The properties of both types of fibers are combined to form a new cable having a more desirable set of physical characteristics. Composite cores of the present invention comprise longitudinal fibers embedded within a resin matrix having a fiber/resin volume fraction in a ratio of at least 50:50%. The volume fraction is the area of fiber divided by the total area of the cross section wherein the weight of the fiber will determine the final percentage ratio by weight. In accordance with the invention, preferably the volume fraction of fiber in the fiber/resin composite is within the range of about 50 to about 57% by value. Most preferably, the volume fraction is calculated to yield a fiber/resin ratio of 72% by weight depending on the weight of the fiber. In accordance with the present invention, the composite core is designed based on the desired physical characteristics of an ACCC reinforced cable. More preferably, the composite core is designed having an inner strengthening core member comprising an advanced composite surrounded by an outer more flexible layer. An advanced composite is a composite having continuous fibers having a greater than 50% volume fraction and mechanical properties exceeding the mechanical properties of glassfibers. Further, it is preferable to have an outer layer low modulus composite having mechanical properties in the range of glass fiber. A low modulus fiber has mechanical characteristics in the range of glass fiber. The mechanical properties of glass fibers accommodate splicing whereas the advanced composite is more brittle and does not undertake splicing well. Fibers forming an advanced composite are selected preferably having a tensile strength in the range of about 350 to about 750 Ksi; a modulus of elasticity preferably in the range of about 22 to about 37 Msi; a coefficient of thermal expansion in the range of about −0.7 to about 0 m/m/C; yield elongation percent in the range of about 1.5 to 3%; dielectric properties in the range of about 0.31 W/m·K to about 0.04 W/m·K; and density in the range of about 0.065 lb/in3 to about 0.13 lb/in3. Fibers forming the outer low modulus layer surrounding the advanced composite preferably have a tensile strength in the range within about 180 to 220 Ksi; a modulus of elasticity preferably in the range of about 6 to 7 Msi; a coefficient of thermal expansion in the range of about 5×10−6 to about 10×10−6 m/m/C; yield elongation percent in the range of about 3 to about 6%; and dielectric properties in the range of about 0.034 to about 0.04 W/m·K and density in the range of about 0.065 to about 0.13 lbs/in3. A composite core member having an inner core comprising an advanced composite in accordance with the preferred ranges of values set forth above surrounded by an outer low modulus layer in accordance with the preferred ranges of values set forth above, has increased ampacity over other conductor cables by about 0 to about 200%. In particular, the final composite core has the following preferable physical characteristics. Tensile strength in the range within about 160 to about 240 Ksi. More preferably, having tensile strength of about 185 Ksi. Modulus of elasticity preferably in the range of within about 7 to about 30 Msi. More preferably, having a modulus of elasticity of about 14 Msi. Operating temperature in the range within about 90 to about 230° C. More preferably, the composite core is able to withstand operating temperatures at least about 190° C. Thermal expansion coefficient within the range of about 0 to about 6×10−6 m/m/C. More preferably, the core thermal expansion coefficient is about 2.5×10−6 m/m/C. Preferably, particular combinations of reinforced fibers are selected based on the reinforced fiber's inherent physical properties in order to produce a composite core product having particular physical properties. In particular, to design an ACCC cable able to withstand ampacity gains, the composite core comprises both a higher modulus of elasticity and a lower coefficient of thermal expansion. The fibers preferably are not conductive but have high dielectric properties. An ACCC cable operates at higher operating temperatures without a corresponding increase in sag. Sag versus temperature calculations require input of modulus of elasticity, thermal expansion coefficient, weight of the composite strength member and conductor weight. Accordingly, these physical characteristics are taken into account in designing the composite core. While it is preferable to form a composite core having an inner advanced composite surrounded by a low modulus composite, it is feasible to make a composite core comprising interspersed high modulus of elasticity fibers and low modulus of elasticity fibers. Depending on the strain:failure ratio, this type of core may have to be segmented in order to achieve an appropriate degree of winding on transportation wheel. Moreover, the composite core is designed having the fiber of increased modulus of elasticity in the inner core surrounded by a fiber having a lower modulus of elasticity due to the decreased degree of strain on the inner core. For example, carbon is selected for high modulus of elasticity in the range of about 22 to about 37 Msi, low thermal expansion coefficient in the range of about −0.7 to about 0 m/m/C, and elongation percent in the range of about 1.5 to about 3%. Glassfibers are selected for low modulus of elasticity in the range of about 6 to about 7 Msi, low thermal expansion coefficient in the range of about 5×10−6 to about 10×10−6 m/m/C and elongation percent in the range of about 3 to about 6%. The strain capability of the composite is tied in with the inherent physical properties of the components and the volume fraction of components. After the fiber/resin composite is selected, the strain to failure ratio of each fiber/resin composite is determined. In accordance with the present invention, the resins can be customized to achieve certain properties for processing and to achieve desired physical properties in the end product. As such, the fiber/customized resin strain to failure ratio is determined. For example, carbon/epoxy has a strain to failure ratio of 2.1% whereas glassfiber/epoxy has a strain to failure ratio of 1.7%. Accordingly, the composite core is designed having the stiffness of the carbon/epoxy in the inner core and the more flexible glassfiber/epoxy in the outer core to create a composite core with the requisite flexibility and low thermal expansion coefficient. Alternatively, another advanced composite having mechanical properties in excess of glassfiber could be substituted for at least a portion of the carbon fibers and another fiber having the mechanical property range of glassfiber could be substituted for glassfiber. For example, basalt has the following properties: high tensile strength in the range of about 701.98 Ksi (compared to the range of about 180 to about 500 Ksi for glassfibers), high modulus of elasticity in the range of about 12.95 Msi, low thermal expansion coefficient in the range of about 8.0 ppm/C (compared to about 5.4 ppm/C for glassfibers), and elongation percent in the range of about 3.15% (compared the range of about 3 to about 6% for glassfibers). The basalt fibers provide increased tensile strength, a modulus of elasticity between carbon and glassfiber and an elongation % close to that of carbon fibers. A further advantage is that basalt has superior dielectric properties to carbon. Preferably, the composite core comprises an inner strength member that is non-conductive. By designing an advanced composite core having fibers of inherent physical characteristics surrounded by low modulus fiber outer core, a new property set for the composite core is obtained. Sag versus temperature is determined by considering the modulus of elasticity, the thermal expansion coefficient, the weight of the composite strength member, and the conductor weight. The higher modulus of elasticity and lower coefficient of thermal expansion in the resulting composite core enables an ACCC cable to withstand ampacity gains and operating temperatures between about 90 to about 230° C. The composite core of the present invention comprises thermosetting resins having physical properties that are adjustable to achieve the objects of the present invention. Depending on the intended cable application, suitable thermosetting resins are selected as a function of the desired cable properties to enable the composite core to have long term durability at high temperature operation. Suitable thermosetting resins may also be selected according to the process for formation of the composite core in order to minimize friction during processing, increase process speed and preferable viscosity to achieve the appropriate fiber/resin ratio in the final composite core. The composite core of the present invention comprises resins having good mechanical properties and chemical resistance at prolonged exposure for at least about 60 years of usage. More preferably, the composite core of the present invention comprises resins having good mechanical properties and chemical resistance at prolonged exposure for at least about 70 years of usage. Further, the composite core of the present invention comprises resins that operate preferably within the range of about 90 to about 230° C. More preferably, the resin operates within the range of about 170 to about 200° C. The composite core of the present invention comprises a resin that is tough enough to withstand splicing operations without allowing the composite body to crack. An essential element of the present invention is the ability to splice the composite core member in the final cable product. The composite core of the present invention comprises resin having a neat resin fracture toughness preferably within the range of about 0.87 INS-lb/in to about 1.24 INS-lb/in. The composite core of the present invention comprises a resin having a low coefficient of thermal expansion. A low coefficient of thermal expansion reduces the amount of sag in the resulting cable. A resin of the present invention preferably operates in the range of about 15×10−6 C and about 42×10−6 C. The composite core of the present invention comprises a resin having an elongation greater than about 4.5%. A composite core of the present invention comprises fibers embedded in a high temperature resin having at least a 50% volume fraction. The fiber to resin ratio affects the physical properties of the composite core member. In particular, the strength, electrical conductivity, and coefficient of thermal expansion are functions of the fiber volume of the composite core. Generally, the higher the volume fractions of fibers in the composite, the higher the tensile strength for the resulting composite. A fiber to resin volume fraction of the present invention preferably is within the range of about 50 to 57% corresponding to preferably within about 62 to about 75% by weight. More preferably, the fiber/resin ratio in the present invention is about 65 to about 72% by weight. Most preferably, the fiber volume fraction in the present invention meets or exceeds about 72% by weight. Each fiber type of the composite core may have a different fiber/resin ratio by weight relative to the other fibers. This is accomplished by selecting the appropriate number of each fiber type and the appropriate resin type to achieve the desired ratio. For example, a composite core member having a carbon/epoxy inner core surrounded by an outer glass/epoxy layer may comprise 126 spools of glass fiber and epoxy resin having a viscosity of about 2000 to about 6000 cPs at 50° C. which yields a pre-determined fiber/resin ratio of about 75/25 by weight. Preferably, the resin may be tuned to achieve the desired viscosity for the process. The composite may also have 16 spools of carbon fiber and epoxy resin having a viscosity of about 2000 to about 6000 cPs at 50° C. which yields a predetermined fiber/resin ratio of about 70/30 by weight. Changing the number of spools of fiber changes the fiber/resin by weight ratio thereby changing the physical characteristics of the composite core product. Alternatively, the resin may be adjusted thereby increasing or decreasing the resin viscosity to change the fiber/resin ratio. The composite cables made in accordance with the present invention exhibit physical properties wherein these certain physical properties may be controlled by changing parameters during the composite core forming process. More specifically, the composite core forming process is adjustable to achieve desired physical characteristics in a final ACCC cable. In accordance with the invention, a multi-phase B-stage forming process produces a composite core member from substantially continuous lengths of suitable fiber tows and heat processable resins. In a further step, the composite core member is wrapped with high conductivity aluminum. A process for making composite cores for ACCC cables according to the invention is described as follows. Referring to FIG. 1, the conductor core B-stage forming process of the present invention is shown and designated generally by reference number 10. The B-stage forming process 10 is employed to make continuous lengths of composite core members from suitable fiber tows or rovings and heat processable resins. The resulting composite core member comprises a hybridized concentric core having an inner and outer layer of uniformly distributed substantially parallel fibers. In starting the operation, the pulling and winding spool mechanism is activated to commence pulling. The unimpregnated initial fiber tows extending from the exit end of the cooling portion in zone 9 serve as leaders at the beginning of the operation to pull fiber tows 12 from spools 11 through fiber tow guide 18 and the composite core processing system. In FIG. 1, multiple spools of fiber tows 12 are contained within a rack system 14 and are provided with the ends of the individual fiber tows 12, leading from spools 11, being threaded through a fiber tow guide 18. The fibers undergo tangential pulling to prevent twisted fibers. Preferably, a puller 16 at the end of the apparatus pulls the fibers through the apparatus. Each dispensing rack 14 comprises a device allowing for the adjustment of tension for each spool 11. For example, each rack 14 may have a small brake at the dispensing rack to individually adjust the tension for each spool. Tension adjustment minimizes caternary and cross-over of the fiber when it travels and aids in the wetting process. The tows 12 are pulled through the guide 18 and into a preheating oven 20 that evacuates moisture. The preheating oven 20 uses continuous circular air flow and a heating element to keep the temperature constant. The tows 12 are pulled into a wet out tank 22. Wet out tank 22 is filled with resin to impregnate the fiber tows 12. Excess resin is removed from the fiber tows 12 during wet out tank 22 exit. The fiber tows 12 are pulled from the wet out tank 22 to a secondary system, B-stage oven 24. The B-stage oven heats the resin to a temperature changing the liquid stage of resin to a semi-cure stage. B-stage cure resin is in a tacky stage which permits the fiber tows 12 to be bent, changed, compressed and configured. The tackiness is controlled by manipulation of the type of resin, the fiber type, thread count and size of the fibers and temperature of the oven. Fiber tows 12 maintained separated by the guide 18, are pulled into a second B-stage oven 26 comprising a plurality of consecutive bushings to compress and configure the tows 12. In the second B-stage oven 26, the fiber tows 12 are directed through a plurality of passageways provided by the bushings. The consecutive passageways continually compress and configure the fiber tows 12 into the final uniform composite core member. Preferably, the composite core member is pulled from the second B-stage oven 26 to a next oven processing system 28 wherein the composite core member is cured and pulled to a next cooling system 30 for cooling. After cooling, the composite core is pulled to a next oven processing system 32 for post curing at elevated temperature. The post-curing process promotes increased cross-linking within the resin matrix resulting in improved physical characteristics of the composite member. The process generally allows an interval between the heating and cooling process and the pulling apparatus 36 to cool the product naturally or by convection such that the pulling device 34 used to grip and pull the product will not damage the product. The pulling mechanism pulls the product through the process with precision controlled speed. Referring now more particularly to FIG. 1, in a preferred embodiment, the process continuously pulls fiber from left to right of the system through a series of phases referred to herein as zones. Each zone performs a different processing function. In this particular embodiment, the process comprises 9 zones. The process originates from a series of fiber dispensing racks 14 whereby a caterpuller 34 continuously pulls the fibers 12 through each zone. One advantage to the caterpullar system is that it functions as a continuous pulling system driven by an electrical motor as opposed to the traditional reciprocation system. The caterpullar system uses a system of two belts traveling on the upper and lower portions of the product squeezing the product there between. Accordingly, the caterpuller system embodies a simplified uniform pulling system functioning at precision controlled speed using only one device instead of a multiplicity of interacting parts functioning to propel the product through the process. Alternatively, a reciprocation system may be used to pull the fibers through the process. The process starts with zone 1. Zone 1 comprises a type of fiber dispensing system. Fibers that can be used for example are: glass fibers, carbon fibers, both HM and HS (pitch based), basalt fibers, Aramid fibers, liquid crystal fibers, Kevlar fibers, boron fibers, high performance polyethylene fibers and carbon nanofiber (CNF). In one embodiment, the fiber dispensing system comprises two racks 13 each rack containing a plurality of spools 11 containing fiber tows 12. Further, the spools 11 are interchangeable to accommodate varying types of fiber tows 12 depending on the desired properties of the composite core member. For example, a preferred composite core member formed by the B-stage forming process comprises a carbon/resin inner core surrounded by a glass/resin outer core layer. Preferably, high strength and high quality carbon is used. The resin matrix also protects the fibers from surface damage, and prevents cracking through a mass of fibers improving fracture resistance. The conductor core B-stage forming process 10 creates a system for pulling the fibers to achieve the optimum degree of bonding between fibers in order to create a composite member with optimal composite properties. As previously mentioned, the components of the composite core are selected based on desired composite core characteristics. One advantage of the process is the ability to adjust composite components in order for a composite core to achieve the desired goals of a final ACCC cable, namely, a cable that can carry current without undue thermal expansion causing sag and without tensile strength reduction. It is preferable to combine types of fibers to combine the physical characteristics of each. Performance can be improved by forming a core with increased strength and stiffness, coupled with a more flexible outer layer. The process increases the optimal characteristics of the composite by preventing twisting of rovings leading to more uniform wetting and strength characteristics. For example, in a preferred embodiment of the composite core member, the composite core comprises glass and carbon. Using the B-stage forming process, the racks 13 hold 126 spools 11 of glass and 16 spools 11 of carbon. The fiber tows 12 leading from spools 11 are threaded through a fiber tow guide 18 wherein fiber tow passageways are arranged to provide a configuration for formation of a core composite member having a uniform carbon core and outer glass layer. The carbon layer is characterized by high strength and stiffness and is a weak electrical conductor whereas the outer low modulus glass layer is more flexible and non-conductive. Having an outer glass layer provides an outer insulating layer between the carbon and the high conductivity aluminum wrapping in the final composite conductor product. The fiber dispensing system dispenses fiber tangent from the fiber package pull. Tangent pull from the spool will not twist the fiber. The center pull method will twist fibers dispensed from the spool. As such, the center pull method results in an increased number of twisted fibers. Twisted fiber will occasionally lay on top of other twisted fiber and create a composite with multiple spots of dry fiber. It is preferable to use tangent pull to avoid dry spots and optimize wet out ability of the fibers. The fiber tows 12 are threaded through a guidance system 18. Preferably, the guide 18 comprises a polyethylene and steel bushings containing a plurality of passageways in a predetermined pattern guiding the fibers to prevent the fibers from crossing. Referring to FIG. 2, the guide comprises a bushing with sufficiently spaced passageways for insertion of the fibers in a predetermined pattern. The passageways are contained within an inner square portion 40. The passageways are arranged in rows of varying number wherein the larger diameter carbon fibers pass through the center two rows of passageways 42 and the smaller diameter glass fibers pass through the outer two rows 44 on either side of the carbon passageways 42. A tensioning device, preferably on each spool, adjusts the tension of the pulled fibers and assures the fibers are pulled straight through the guide 18. At least two fibers are pulled through each passageway in the guide 18. For example, a guide 18 comprising 26 passageways pulls 52 fibers through, wherein each passageway has two fibers. If a fiber of a pair breaks, a sensing system alerts the composite core B-stage forming process 10 that there is a broken fiber and stops the puller 34. Alternatively, in one embodiment, a broken fiber alerts the process and the repair can be made on the fly without stopping the process depending on where the breakage occurs. To repair, a new fiber is pulled from the rack 13 and glued to the broken end of the new fiber. After the fiber is repaired, the conductor core B-stage forming machine 10 is started again. In preferred form, the fibers are grouped in a parallel arrangement for a plurality of rows. For example, in FIG. 2, there are six parallel rows of passageways. The outer two rows comprise 32 passageways, the two inner rows comprise 31 passageways, and the two center rows comprise 4 passageways each. Fibers are pulled at least two at a time into each passageway and pulled into zone 2. Zone 2 comprises an oven processing system that preheats the dry fibers to evacuate any moisture. The fibers of the present invention are preferably heated within the range of about 150 to 250° F. to evaporate moisture. The oven processing system comprises an oven portion wherein the oven portion is designed to promote cross-circular air flow against the flow of material. FIG. 9 illustrates a typical embodiment of the oven system. An oven is generally designated 60. The fibers pass through the oven from upstream to downstream direction, the air passes in the reverse direction. The oven processing system comprises a heat drive system housing 64 that houses a blower 68 powered by electric motor 70 located upstream from a heater assembly 66 to circulate air in a downstream direction through air flow duct 62. The heat drive system housing houses a blower 68 upstream of the heater assembly 66. The blower 68 propels air across the heater assembly 66 and through the oven system. The air flows downstream to a curved elbow duct 72. The curved elbow duct 72 shifts air flow 90 degrees up into an inlet duct 78 and through the oven inlet 76. Through the inlet air flow shifts 90 degrees to flow upstream through the oven 60 against the pull direction of the fibers. At the end of the oven 60, the air flow shifts 90 degrees down through the oven outlet 80 through the outlet duct 74 through the motor 70 and back into the heat drive system housing 64. The motor 70 comprises an electrical motor outside of the heat drive system to prevent overheating. The motor 70 comprises a pulley with a timing belt that moves the bladed blower 68. Preferably, the system is computer controlled allowing continuous air circulation at a desired temperature. More preferably, the process allows for the temperature to change at any time according to the needs of the process. For example, the computer senses a temperature below the required temperature and activates the heating element or disactivate the heater when the temperature is too high. The blower blows air across the heating element downstream. The system forces the air to travel in a closed loop circle continuously circulating through the oven keeping the temperature constant. FIG. 10 is a more detailed view of a preferred embodiment of the heating element 66. In one embodiment, the heater assembly comprises nine horizontal steel electrical heaters 82. Each heater unit is separate and distinct from the other heater. Each heater unit is separated by a gap. Preferably, after sensing a temperature differential, the computer activates the number of heaters to provide sufficient heat. If the system requires the computer activates one of nine heaters. Alternatively, depending on the needs of the process, the computer activates every other heater in the heater assembly. In another embodiment the computer activates all heaters in the heater assembly. In a further alternative, the computer activates a portion of the heaters in the heater assembly or turns all the heaters off. In an alternate embodiment, electromagnetic fields penetrate through the process material to heat the fibers and drive off any moisture. In another embodiment pulsed microwaves heat the fibers and drive off any moisture. In another embodiment, electron beam processing uses electrons as ionizing radiation to drive off any excess moisture. In another embodiment, the puller pulls the fibers from zone 2 to zone 3, the fiber impregnation system. Zone 3 comprises a wet out tank 22. In a preferred embodiment, the wet out tank 22 contains a device that allows the redirection of fibers during wet out. Preferably, the device is located in the center of the tank and moves the fibers vertically up and down perpendicular to the direction of the pull whereby the deflection causes the fibers to reconfigure from a round configuration to a flat configuration. The flat configuration allows the fibers to lay side by side and allows for the fibers to be more thoroughly wetted by the resin. Various alternative techniques well known in the art can be employed to apply or impregnate the fibers with resin. Such techniques include for example, spraying, dipping, reverse coating, brushing and resin injection. In an alternate embodiment, ultrasonic activation uses vibrations to improve the wetting ability of the fibers. Generally, any of the various known heat curable thermosetting polymeric resin compositions can be used with the invention. The resin may be for example, PEAR (PolyEther Amide Resin), Bismaleimide, Polyimide, liquid-crystal polymer (LCP), and high temperature epoxy based on liquid crystal technology or similar resin materials. Resins are selected based on the process and the physical characteristics desired in the composite core. Further, the viscosity of the resin affects the rate of formation. To achieve the desired proportion of fiber/resin for formation of the composite core member, preferably the viscosity ranges within the range of about 200 to about 1500 Centipoise at 20° C. More preferably, the viscosity falls in the range of about 200 to about 600 Centipoise 20° C. The resin is selected to have good mechanical properties and excellent chemical resistance to prolonged exposure of at least 60 years and more preferably, at least 70 years of operation up to about 230° C. A particular advantage of the present invention is the ability for the process to accommodate use of low viscosity resins. In accordance with the present invention, it is preferable to achieve a fiber/resin ratio within the range of 62-75% by weight. More preferable is a fiber/resin ratio within the range of 72-75% by weight. Low viscosity resins will sufficiently wet the fibers for the composite core member. A preferred polymer provides resistance to a broad spectrum of aggressive chemicals and has very stable dielectric and insulating properties. It is further preferable that the polymer meets ASTME595 outgassing requirements and UL94 flammability tests and is capable of operating intermittently at temperatures ranging between 220 and 280° C. without thermally or mechanically damaging the strength member. To achieve the desired fiber to resin ratio, the upstream side of the wet out tank comprises a number of redirectional wiping bars. As the fibers are pulled through the wet out tank the fibers are adjusted up and down against a series of wiping bars removing excess resin. Alternatively, the redirection system comprises a wiper system to wipe excess resin carried out of the tank by the fibers. Preferably, the excess resin is collected and recycled into the wet out tank 22. Alternatively, the wet out tank uses a series of squeeze out bushings to remove excess resin. During the wet out process each bundle of fiber contains as much as three times the desired resin for the final product. To achieve the right proportion of fiber and resin in the cross section of the composite core members, the amount of pure fiber is calculated. The squeeze out bushing in designed to remove a predetermined percentage of resin. For example, where the bushing passageway is twice as big as the area of the cross section of the fiber, a resin concentration greater than 50% by value won't be pulled through the bushing, the excess resin will be removed. Alternatively, the bushing can be designed to allow passage of 100% fiber and 20% resin. Preferably, a recycle tray extends lengthwise under the wet out tank 22 to catch overflow resin. More preferably, the wet out tank has an auxiliary tank with overflow capability. Overflow resin is returned to the auxiliary tank by gravity through the piping. Alternatively, tank overflow is captured by an overflow channel and returned to the tank by gravity. In a further alternate, the process uses a drain pump system to recycle the resin back through the auxiliary tank and into the wet out tank. Preferably, a computer system controls the level of resin within the tank. Sensors detect low resin levels and activate a pump to pump resin into the tank from the auxiliary mixing tank into the processing tank. More preferably, there is a mixing tank located within the area of the wet out tank. The resin is mixed in the mixing tank and pumped into the resin wet out tank. The pullers pull the fibers from zone 3 to zone 4, the B-stage zone. Zone 4 comprises an oven processing system 24. Preferably, the oven processing system is an oven with a computer system that controls the temperature of the air and keeps the air flow constant wherein the oven is the same as the oven in zone 2. The pullers pull the fibers from zone 3 to zone 4. The oven circulates air in a circular direction downstream to upstream by a propeller heating system. The computer system controls the temperature at a temperature to heat the wet fiber to B-stage. Preferably, the process determines the temperature. B-stage temperature of the present invention ranges from within about 200 to 250° F. One advantage of the B-stage semi-cure process in the present invention is the ability to heat the resin to a semi-cure state in a short duration of time, approximately 1-1.5 minutes during the continuation of the process. The advantage is that the heating step does not affect the processing speed of the system. The B-stage process allows for the further tuning of the fiber/resin ratio by removing excess resin from the wet-out stage. Further, B-stage allows the fiber/resin matrix to be further compacted and configured during the process. Accordingly, the process differs from previous processes that use pre-preg semi-cure. Heating semi-cures the fibers to a tacky stage. More specifically, in traditional composite processing applications, the wetted fibers are heated gradually to a semi-cure stage. However, the heating process generally takes periods of one hour or longer to reach the semi-cure stage. Moreover, the composite must be immediately wrapped and frozen to keep the composite at the semi-cure stage and prevent curing to a final stage. Accordingly, the processing is fragmented because it is necessary to remove the product from the line to configure the product. In accordance with the present invention, the B-stage heating is dedicated to a high efficiency commercial application wherein semi-cure is rapid, preferably 1-1.5 minutes during a continuous process in line within the process. Preferably, the resins are designed to allow rapid B-stage semi-curing that is held constant through the process allowing for shaping and configuring and further compaction of the product. The pullers pull the fibers from B-stage zone 4 to zone 5 for the formation of the composite core member. Zone 5 comprises a next oven processing system 26 having a plurality of bushings. The bushings function to shape the cross section of the fiber tows 12. Preferably, the bushings are configured in a series comprising a parallel configuration with each other. In this embodiment, there is a set of seven bushings spaced laterally within the oven processing system 26. Preferably, the spacing of the bushings are adjusted according to the process. The bushings can be spaced equi-distance or variable distance from each other. The series of bushings in zone 5 minimize friction due to the relatively thin bushing ranging within about ½ to ⅜ inch thick. Minimizing friction aids in maximizing the process speed. Zones 4, 5 and 6 of the present invention extends within the range of about 30-45 feet. Most preferably, the zones 4, 5 and 6 extend at least 30 feet. This pulling distance and the decreased friction due to thin bushing plates aids in achieving a desired pull speed in the range of about 9 ft/min to about 50 ft/min. Most preferably about 20 ft/min. Processing speed is further increased due to the high fiber/resin ratio. Referring to FIG. 3, for example, the bushings 90 comprise a flat steel plate with a plurality of passageways through which the fiber tows 12 are pulled. The flat plate steel bushing 90 preferably ranges from ⅜ inch to ½ inch thick determined by the process. The bushings 90 have relatively thin walls to reduce friction and the amount of heat which must be added or removed by the heating and cooling process in order to achieve the temperature changes required to effect curing of the fiber resin matrix. The thickness of the bushing 90 is preferably the minimum thickness required to provide the structural strength necessary to constrain forces imposed upon the bushing 90 by the material passing therethrough. In particular, the thickness of the bushing 90 is preferably the minimum needed to limit deformation of the bushing wall to a tolerable level which will not interfere with the pulling of the material through the system. Preferably, the design and size of the bushings 90 are the same. More preferably, the passageways within each bushing 90 diminish in size and vary in location within each successive bushing 90 in the upstream direction. FIG. 3 illustrates a preferred embodiment of a bushing 90. The bushing 90 comprises two hooked portions 94 and an inner preferably square portion 92. The inner square portion 92 houses the passageways through which the pulling mechanism pulls the fibers. The outer hooked portions 94 form a support system whereby the bushing 90 is placed within the oven in zone 5. The outer hooked portion 94 connects with interlocking long steel beams within the oven that function to support the bushings 90. Zone 5 comprises a series of eight consecutive bushings. The bushings have two functions: (1) guide the fiber in the configuration for the final product; and (2) shape and compress the fibers. In one embodiment, the bushings 90 are placed apart within the oven supported on the hooked structures. The bushings 90 function to continually compress the fibers and form a composite core comprising, in this embodiment, carbon and glass while the process is under appropriate tension to achieve concentricity and uniform distribution of fiber without commingling of fibers. The bushings 90 may be designed to form bundles of a plurality of geometries. For example, FIG. 5 illustrates the variations in cross sections in composite member. Each cross section results from different bushing 90 design. The passageways in each successive bushing 90 diminish in size further compacting the fiber bundles. For example, FIG. 6 shows each bushing 90 superimposed on top of one another. Several changes are apparent with each consecutive bushing 90. First, each overlayed bushing 90 shows that the size of each passageway decreases. Second, the superimposed figure shows the appearance of the center hole for compaction of the core element. Third, the figure shows the movement of the outer corner passageways towards the center position. Referring to FIG. 4, there are two bushings illustrated. The first bushing 100 illustrated, is in a similar configuration as the guide bushing 18. The second bushing 104 is the first in the series of bushings that function to compress and configure the composite core. The first bushing 100 comprises an inner square portion 92 with a plurality of passageways 102 prearranged through which the fibers are pulled. The passageways 102 are designed to align the fibers into groups in bushing two 104 having four outer groups 106 of fibers and four inner groups 108 of fibers. The inner square portion of the bushing 100 comprises six rows of passageways 110. The arrangement of the passageways 110 may be configured into any plurality of configurations depending on the desired cross section geometry of the composite core member. The top and bottom row, 112 and 114 respectively, contain the same number of passageways. The next to top and next to bottom rows, 116 and 118 respectively, contain the same number of passageways and the two inner rows 120 and 122 contain the same number of passageways. In a preferred embodiment, the top and bottom rows contain 32 passageways each. The next level of rows contain 31 passageways each. The middle rows contain 4 passageways each. The pulling mechanism pulls two fibers through each passageway. Referring to FIG. 4 for example, the pulling mechanism pulls 126 glass fibers through rows 112, 114, 116 and 118. Further, the pulling mechanism pulls 16 carbon fibers through rows 120 and 122. Referring to FIG. 7, the next bushing 130, bushing three in the series comprises an inner square portion 131 having four outer corner passageways 132a, 132b, 132c and 132d and four inner passageways 134a, 134b, 134c and 134d. The fibers exit bushing two and are divided into equal parts and pulled through bushing three. Each passageway in bushing three comprises one quarter of the particular type of fiber pulled through bushing two. More specifically, the top two rows of the top and the bottom of bushing two are divided in half whereby the right half of the top two rows of fibers are pulled through the right outer corner of bushing three. The left half of the top two rows of fibers are pulled through the upper left corner 132a of bushing three 130. The right half of the top two rows of fibers are pulled through the upper right corner 132b of bushing three 130. The right half of the bottom two rows of fibers are pulled through the lower right corner 132c of bushing three. The left half of the bottom two rows of fibers are pulled through the lower left corner 132d of bushing three 130. The inner two rows of bushing one are divided in half whereby the top right half of the top middle row of fibers is pulled through the inner upper right corner 134b of bushing three 130. The left half of the top middle row of fibers is pulled through the inner upper left corner 134a of bushing three 130. The right half of the lower middle row of fibers is pulled through the inner lower right corner 134c of bushing three 130. The left half of the lower middle row of fibers is pulled through the inner lower left corner 134d of bushing three 130. Accordingly, bushing three 130 creates eight bundles of impregnated fibers that will be continually compressed through the series of next bushings. The puller pulls the fibers through bushing three 130 to bushing four 140. Bushing four 140 comprises the same configuration as bushing three 130. Bushing four 140 comprises a square inner portion 141 having four outer corner passageways 142a, 142b, 142c and 142d and four inner passageways 144a, 144b, 144c and 144d. Preferably, the four outer corner passageways 142a-d and the four inner passageways 144a-d are slightly smaller in size than the similarly configured passageways in bushing three 130. Bushing four 140 compresses the fibers pulled through bushing three. The puller pulls the fibers from bushing four 140 to bushing five 150. Preferably, the four outer corner passageways 152a, 152b, 152c and 152d and the four inner passageways 154a, 154b, 154c and 154d are slightly smaller in size than the similarly configured passageways in bushing four 140. Bushing five 150 compresses the fibers pulled through bushing four 140. For each of the successive bushings, each bushing creates a bundle of fibers with an increasingly smaller diameter. Preferably, each smaller bushing wipes off excess resin to approach the optimal and desired proportion of resin to fiber composition. The puller pulls the fibers from bushing five 150 to bushing six 160. Preferably, the four outer corner passageways 162a, 162b, 162c and 162d and the four inner passageways 164a, 164b, 164c and 164d are slightly smaller in size than the similarly configured passageways in bushing five 150. Bushing six 160 compresses the fibers pulled through bushing five 150. Bushing seven 170 comprises an inner square 171 having four outer corner passageways 172a, 172b, 172c and 172d and one inner passageway 174. The puller pulls the fibers from the four inner passageways 164 of bushing six 160 through the single inner passageway 174 in bushing seven 170. The process compacts the product to a final uniform concentric core. Preferably, fibers are pulled through the outer four corners 172a, 172b, 172c, 172d of bushing seven 170 simultaneous with compacting of the inner four passageways 164 from bushing six 160. The puller pulls the fibers through bushing seven 170 to bushing eight 180. The puller pulls the inner compacted core 184 and the outer four corners 182a, 182b, 182c, 182d migrate inwardly closer to the core 184. Preferably, the outer fibers diminish the distance between the inner core and the outer corners by half the distance. The puller pulls the fibers through bushing eight 180 to bushing nine 190. Bushing nine 190 is the final bushing for the formation of the composite core. The puller pulls the four outer fiber bundles and the compacted core through a passageway 192 in the center of bushing nine 190. Preferably, bushing nine 190 compacts the outer portion and the inner portion creating an inner portion of carbon and an outer portion of glass fiber. FIG. 8 for example, illustrates a cross-section of a composite cable. The example illustrates a composite core member 200 having an inner reinforced carbon fiber composite portion 202 surrounded by an outer reinforced glass fiber composite portion 204. Temperature is kept constant throughout zone 5. The temperature is determined by the process and is high enough to keep the resin in a semi-cured state. At the end of zone 5, the product comprises the final level of compaction and the final diameter. The puller pulls the fibers from zone 5 to zone 6 a curing stage preferably comprising an oven with constant heat and airflow as in zone 5, 4 and 2. The oven uses the same constant heating and cross circular air flow as in zone 5, zone 4 and zone 2. The process determines the curing heat. The curing heat remains constant throughout the curing process. In the present invention, the preferred temperature for curing ranges from about 350° F. to about 400° F. The curing process preferably spans within the range of about 8 to about 15 feet. More preferably, the curing process spans about 10 feet in length. The high temperature of zone 6 results in a final cure forming a hard resin. Zone 6 may incorporate a bushing ten to assure that the final fiber composite cor member holds its shape. In addition, another bushing prevents bluming of the core during curing. During the next stages the composite core member product is pulled through a series of heating and cooling phases. The post cure heating improves cross linking within the resin matrix improving the physical characteristics of the product. The pullers pull the fibers to zone 7, a cooling device. Preferably, the mechanical configuration of the oven is the same as in zones 2, 4, 5 and 6. More specifically, the device comprises a closed circular air system using a cooling device and a blower. Preferably, the cooling device comprises a plurality of coils. Alternatively, the coils may be horizontally structured consecutive cooling elements. In a further alternative, the cooling device comprises cooling spirals. The blower is placed upstream from the cooling device and continuously blows air in the cooling chamber in an upstream direction. The air circulates through the device in a closed circular direction keeping the air throughout at a constant temperature. Preferably, the cooling temperature ranges from within about 40 to about 180° F. The pullers pull the composite member through zone 7 to zone 8, the post-curing phase. The composite core member is heated to post-curing temperature to improve the mechanical properties of the composite core member product. The pullers pull the composite core member through zone 8 to zone 9, the post curing cooling phase. Once the composite core has been reheated, the composite core is cooled before the puller grabs the compacted composite core. Preferably, the composite core member cools for a distance ranging about 8 to about 15 feet by air convection before reaching the puller. Most preferably, the cooling distance is about 10 feet. The pullers pull the composite core member through the zone 9 cooling phase into zone 10, a winding system whereby the fiber core is wrapped around a wheel for storage. It is critical to the strength of the core member that the winding does not over stress the core by bending. In one embodiment, the core does not have any twist and can only bend a certain degree. In another embodiment, the wheel has a diameter of seven feet and handles up to 6800 feet of B-stage formed composite core member. The wheel is designed to accommodate the stiffness of the B-stage formed composite core member without forcing the core member into a configuration that is too tight. In a further embodiment, the winding system comprises a means for preventing the wheel from reversing flow from winding to unwinding. The means can be any device that prevents the wheel direction from reversing for example, a brake system. In a further embodiment, the process includes a quality control system comprising a line inspection system. The quality control process assures consistent product. The quality control system may include ultrasonic inspection of composite core members; record the number of tows in the end product; monitor the quality of the resin; monitor the temperature of the ovens and of the product during various phases; measure formation; measure speed of the pulling process. For example, each batch of composite core member has supporting data to keep the process performing optimally. Alternatively, the quality control system comprises a marking system. The marking system wherein the marking system marks the composite core members with the product information of the particular lot. Further, the composite core members may be placed in different classes in accordance with specific qualities, for example, Class A is high grade, Class B and Class C. The fibers used to process the composite core members can be interchanged to meet specifications required by the final composite core member product. For example, the process allows replacement of fibers in a composite core member having a carbon core and a glass fiber outer core with high grade carbon and E-glass. The process allows the use of more expensive better performing fibers in place of less expensive fibers due to the combination of fibers and the small core size required. In one embodiment, the combination of fibers creates a high strength inner core with minimal conductivity surrounded by a low modulus nonconductive outer insulating layer. In another embodiment, the outer insulating layer contributes to the flexibility of the composite core member and enables the core member to be wound, stored and transported. Another embodiment of the invention, allows for redesign of the composite core cross section to accommodate varying physical properties and increase the flexibility of the composite core member. Referring again to FIG. 5, the different composite shapes change the flexibility of the composite core member. Changing the core design may enable winding of the core on a smaller diameter wheel. Further, changing the composite core design may affect the stiffness and strength of the inner core. As an advantage, the core geometry may be designed to achieve optimal physical characteristics desired in a final ACCC cable. In another embodiment of the invention, the core diameter is greater than 0.375 inches. A core greater than 0.375 inches cannot bend to achieve a 7-foot wrapping diameter. The potential strength on the outside bend shape exceeds the strength of the material and the material will crack. A core diameter of ½ to ⅝ inch may require a wheel diameter of 15 feet and this is not commercially viable. To increase the flexibility of the composite core, the core may be twisted or segmented to achieve a wrapping diameter that is acceptable. One 360 degree twist of fiber orientation in the core for one revolution of core. Alternatively, the core can be a combination of twisted and straight fiber. The twist may be determined by the wheel diameter limit. If the limit is prohibited then twist by one revolution of diameter of the wheel. The tension and compression stresses in the core are balanced by one revolution. Winding stress is reduced by producing a segmented core. FIG. 5 illustrates some examples of possible cross section configurations of segmented cores. The segmented core under the process is formed by curing the section as separate pieces wherein the separate pieces are then grouped together. Segmenting the core enables a composite member product having a core greater than 0.375 inches to achieve a desirable winding diameter without additional stress on the member product. Variable geometry of the cross sections in the composite core members are preferably processed as a multiple stream. The processing system is designed to accommodate formation of each segment in parallel. Preferably, each segment is formed by exchanging the series of consecutive bushings for bushings having predetermined configurations for each of the passageways. In particular, the size of the passageways may be varied to accommodate more or less fiber, the arrangement of passageways may be varied in order to allow combining of the fibers in a different configuration in the end product and further bushings may be added within the plurality of consecutive bushings to facilitate formation of the varied geometric cross sections in the composite core member. At the end of the processing system the five sections in five streams of processing are combined at the end of the process to form the composite cable core. Alternatively, the segments may be twisted to increase flexibility and facilitate winding The final composite core is wrapped in lightweight high conductivity aluminum forming a composite cable. Preferably, the composite core cable comprises an inner carbon core having an outer insulating glass fiber composite layer and two layers of trapezoidal formed strands of aluminum. In one embodiment, the inner layer of aluminum comprises a plurality of trapezoidal shaped aluminum segments wrapped in a counter-clockwise direction around the composite core member. Each trapezoidal section is designed to optimize the amount of aluminum and increase conductivity. The geometry of the trapezoidal segments allows for each segment to fit tightly together and around the composite core member. In a further embodiment, the outer layer of aluminum comprises a plurality of trapezoidal shaped aluminum segments wrapped in a clockwise direction around the composite core member. The opposite direction of wrapping prevents twisting of the final cable. Each trapezoidal aluminum element fits tightly with the trapezoidal aluminum elements wrapped around the inner aluminum layer. The tight fit optimizes the amount of aluminum and decreases the aluminum required for high conductivity. EXAMPLE A particular embodiment of the invention is now described wherein the composite strength member comprises E-glass and carbon type 13 sizing. E-glass combines the desirable properties of good chemical and heat stability, and good electrical resistance with high strength. The cross-sectional shape or profile is illustrated in FIG. 8 wherein the composite strength member comprises a concentric carbon core encapsulated by a uniform layer of glass fiber composite. In a preferred embodiment the process produces a hybridized core member comprising two different materials. The fiber structures in this particular embodiment are 126 ends of E-glass product, yield 900, Veterotex Amer and 16 ends of carbon Torayca T7DOS yield 24K. The resin used is Aralite MY 721 from Vantico. In operation, the ends of 126 fiber tows of E-glass and 16 fiber tows of carbon are threaded through a fiber tow guide comprising two rows of 32 passageways, two rows inner of 31 passageways and two innermost rows of 4 passageways and into a preheating stage at 150° F. to evacuate any moisture. After passing through the preheating oven, the fiber tows are pulled through a wet out tank. In the wet out tank a device effectually moves the fibers up and down in a vertical direction enabling thorough wetting of the fiber tows. On the upstream side of the wet out tank is located a wiper system that removes excess resin as the fiber tows are pulled from the tank. The excess resin is collected by a resin overflow tray and added back to the resin wet out tank. The fiber tows are pulled from the wet out tank to a B-state oven that semi-cures the resin impregnated fiber tows to a tack stage. At this stage the fiber tows can be further compacted and configured to their final form in the next phase. The fiber tows are pulled to a next oven at B-stage oven temperature to maintain the tack stage. Within the oven are eight consecutive bushings that function to compact and configure the fiber tows to the final composite core member form. Two fiber tow ends are threaded through each of the 134 passageways in the first bushing which are machined to pre-calculated dimensions to achieve a fiber volume of 72 percent and a resin volume of 28 percent in the final composite core member. The ends of the fiber tows exiting from passageways in the top right quarter comprising half of the two top rows are threaded through passageways 132 of the next bushing; the ends of the fiber tows exiting from passageways in the top left quarter comprising half of the top two rows are threaded through passageway 136 of the next bushing; the ends of the fiber tows exiting from passageways in the lower right quarter comprising half of the bottom two rows are threaded through passageway 140 of the next bushing; the ends of the fiber tows exiting from passageways in the lower left quarter comprising half of the bottom two rows are threaded through passageway 138 of the next bushing; the right and left quarters of passageways in the middle upper row are threaded through passageways 142 and 144 of the next bushing and the right and left quarters of passageways in the middle bottom row are threaded through passageways 134 and 146 respectively. The fiber tows are pulled consecutively through the outer and inner passageways of each successive bushing further compacting and configuring the fiber bundles. At bushing seven, the fiber bundles pulled through the inner four passageways of bushing six are combined to form a composite core whereas the remaining outer passageways continue to keep the four bundles glass fibers separate. The four outer passageways of bushing seven are moved closer inward in bushing eight, closer to the inner carbon core. The fiber tows are combined with the inner carbon core in bushing nine forming a hybridized composite core member comprising an inner carbon core having an outer glass layer. The composite core member is pulled from the bushing nine to a final curing oven at an elevated temperature of 380° F. as required by the specific resin. From the curing oven the composite core member is pulled through a cooling oven to be cooled to 150 to 180° F. After cooling the composite core member is pulled through a post curing oven at elevated temperature, preferably to heat the member to at least B-stage temperature. After post-curing the member is cooled by air to approximately 180° F. The member is cooled prior to grabbing by the caterpillar puller to the core winding wheel having 6000 feet of storage. EXAMPLE An example of an ACCC reinforced cable in accordance with the present invention follows. An ACCC reinforced cable comprising four layers of components consisting of an inner carbon/epoxy layer, a next glassfiber/epoxy layer and two layers of tetrahedral shaped aluminum strands. The strength member consists of an advanced composite T700S carbon/epoxy having a diameter of about 0.2165 inches, surrounded by an outer layer of R099-688 glassfiber/epoxy having a layer diameter of about 0.375 inches. The glassfiber/epoxy layer is surrounded by an inner layer of nine trapezoidal shaped aluminum strands having a diameter of about 0.7415 inches and an outer layer of thirteen trapezoidal shaped aluminum strands having a diameter of about 1.1080 inches. The total area of carbon is about 0.037 in2, of glass is about 0.074 in2, of inner aluminum is about 0.315 in2 and outer aluminum is about 0.5226 in2. The fiber to resin ratio in the inner carbon strength member is 70/30 by weight and the outer glass layer fiber to resin ratio is 75/25 by weight. The specific specifications are summarized in the following table: Glass Vetrotex roving R099-686 (900 Yield) Tensile Strength, psi 298,103 Elongation at Failure, % 3.0 Tensile Modulus, × 106 psi 11.2 Glass Content, % 57.2 Carbon (graphite) Carbon: Torayca T700S (Yield 24K) Tensile strength, Ksi 711 Tensile Modulus, Msi 33.4 Strain 2.1% Density lbs/ft3 0.065 Filament Diameter, in 2.8E−04 Epoxy Matrix System Araldite MY 721 Epoxy value, equ./kg 8.6-9.1 Epoxy Equivalent, g/equ. 109- Viscosity @ 50 C., cPs 3000-6000 Density @ 25 C. lb/gal. 1.1501.18 Hardener 99-023 Viscosity @ 25 C., cPs 75-300 Density @ 25 C., lb/gal 1.19-1/22 Accelerator DY 070 Viscosity @25 C., cPs <50 Density @ 25 C., lb/gal 0.95-1.05 An ACCC reinforced cable having the above specifications is manufactured according to the following. The process used to form the composite cable in the present example is illustrated in FIG. 1. First, 126 spools of glass fiber tows 12 and 8 spools of carbon are set up in the rack system 14 and the ends of the individual fiber tows 12, leading from spools 11, are threaded through a fiber tow guide 18. The fibers undergo tangential pulling to prevent twisted fibers. A puller 16 at the end of the apparatus pulls the fibers through the apparatus. Each dispensing rack 14 has a small brake to individually adjust the tension for each spool. The tows 12 are pulled through the guide 18 and into a preheating oven 20 at 150° F. to evacuate moisture. The tows 12 are pulled into wet out tank 22. Wet out tank 22 is filled with Araldite MY 721/Hardener 99-023/Accelerator DY070 to impregnate the fiber tows 12. Excess resin is removed from the fiber tows 12 during wet out tank 22 exit. The fiber tows 12 are pulled from the wet out tank 22 to a B-stage oven 24 and are heated to 200° F. Fiber tows 12 maintained separated by the guide 18, are pulled into a second B-stage oven 26 also at 200° F. comprising a plurality of consecutive bushings to compress and configure the tows 12. In the second B-stage oven 26, the fiber tows 12 are directed through a plurality of passageways provided by the bushings. The consecutive passageways continually compress and configure the fiber tows 12 into the final uniform composite core member. The first bushing has two rows of 32 passageways, two inner rows of 31 passageways each and two inner most rows of 4 passageways each. The 126 glass fiber tows are pulled through the outer two rows of 32 and 31 passageways, respectively. The carbon fiber tows are pulled through the inner two rows of 4 passageways eaten. The next bushing splits the top two rows in half and the left portion is pulled through the left upper and outer corner passageway in the second bushing. The right portion is pulled through the right upper and outer corner passageway in the second bushing. The bottom two rows are split in half and the right portion is pulled through the lower right outer corner of the second bushing and the left portion is pulled through the lower left outer corner of the second bushing. Similarly, the two inner rows of carbon are split in half and the fibers of the two right upper passageways are pulled through the inner upper right corner of the second bushing. The fibers of the left upper passageways are pulled through the inner upper left corner of the second bushing. The fibers of the right lower passageways are pulled through the inner lower right corner of the second bushing and the fibers of the left lower passageways are pulled through the inner lower left corner of the second bushing. The fiber bundles are pulled through a series of seven bushings continually compressing and configuring the bundles into one hybridized uniform concentric core member. The composite core member is pulled from the second B-stage oven 26 to a next oven processing system 28 at 330 to 370° F. wherein the composite core member is cured and pulled to a next cooling system 30 at 30 to 100° F. for cooling. After cooling, the composite core is pulled to a next oven processing system 32 at 330 to 370° F. for post curing. The pulling mechanism pulls the product through a 10 foot air cooling area at about 180° F. Nine trapezoidal shaped aluminum strands each having an area of about 0.0350 or about 0.315 sq. in. total area on the core are wrapped around the composite core after cooling. Next, thirteen trapezoidal shaped aluminum strands each strand having an area of about 0.0402 or about 0.5226 sq. in. total area on the core are wrapped around the inner aluminum layer. It is to be understood that the invention is not limited to the exact details of the construction, operation, exact materials, or embodiments shown and described, as modifications and equivalents will be apparent to one skilled in the art without departing from the scope of the invention.
<SOH> BACKGROUND OF INVENTION <EOH>This invention relates to composite core members and aluminum conductor composite core (ACCC) reinforced cable products made therefrom. This invention further relates to a forming process for an aluminum conductor composite core reinforced cable (ACCC). In the traditional aluminum conductor steel reinforced cable (ACSR) the aluminum conductor transmits the power and the steel core is designed to carry the transfer load. In an ACCC cable, the steel core of the ACSR cable is replaced by a composite core comprising at least one reinforced fiber type in a thermosetting resin matrix. Replacing the steel core has many advantages. An ACCC cable can maintain operating temperatures in the range of about 90 to about 230° C. without corresponding sag induced in traditional ACSR cables. Moreover, to increase ampacity, an ACCC cable couples a higher modulus of elasticity with a lower coefficient of thermal expansion. This invention relates to an aluminum conductor composite core reinforced cable suitable for operation at high operating temperatures without being limited by current operating limitations inherent in other cables for providing electrical power wherein provision of electrical power includes both distribution and transmission cables. Typical ACSR cables can be operated at temperatures up to 100° C. on a continuous basis without any significant change in the conductor's physical properties related to a reduction in tensile strength. These temperature limits constrain the thermal rating of a typical 230-kV line, strung with 795 kcmil ACSR “Drake” conductor, to about 400 MVA, corresponding to a current of 1000 A. Conductor cables are constrained by the inherent physical characteristics of the components that limit ampacity. More specifically, the ampacity is a measure of the ability to send power through the cable wherein increased power causes an increase in the conductor's operating temperature. Excessive heat causes the cable to sag below permissible levels. Therefore, to increase the load carrying capacity of transmission cables, the cable itself must be designed using components having inherent properties that withstand increased ampacity without inducing excessive sag. Although ampacity gains can be obtained by increasing the conductor area that wraps the core of the transmission cable, increasing conductor weight increases the weight of the cable and contributes to sag. Moreover, the increased weight requires the cable to use increased tension in the cable support infrastructure. Such large load increases typically would require structure reinforcement or replacement, wherein such infrastructure modifications are typically not financially feasible. Thus, there is financial motivation to increase the load capacity on electrical transmission cables while using the existing transmission liens. European Patent Application No. EP116374A3 discloses a composite core comprised of a single type of reinforced glass fiber and thermoplastic resin. The object is to provide an electrical transmission cable which utilizes a reinforced plastic composite core as a load bearing element in the cable and to provide a method of carrying electrical current through an electrical transmission cable which utilizes an inner reinforced plastic core. The composite core fails in these objectives. A one fiber system comprising glass fiber does have the required stiffness to attract transfer load and keep the cable from sagging. Secondly, a composite core comprising glass fiber and thermoplastic resin does not meet the operating temperatures required for increased ampacity, namely, between 90 and 230° C. Composite cores designed using a carbon epoxy composite core also have inherent difficulties. The carbon epoxy core has very limited flexibility and is cost prohibitive. The cable product having a carbon epoxy core does not have sufficient flexibility to permit winding and transport. Moreover, the cost for carbon fibers are expensive compared to other available fibers. The cost for carbon fibers is in the range of $5 to $37 per pound compared to glass fibers in the range of $0.36 to $1.20 per pound. Accordingly, a composite core constructed of only carbon fibers is not financially feasible. Physical properties of composite cores are further limited by processing methods. Previous processing methods cannot achieve a high fiber/resin ratio by volume or weight. These processes do not allow for creation of a fiber rich core that will achieve the strength to compete with a steel core. Moreover, the processing speed of previous processing methods are limited by inherent characteristics of the process itself. For example, traditional pultrusion dies are approximately 36 inches, having a constant cross section. The result is increased friction between the composite and the die slowing processing time. The processing times in such systems for epoxy resins range within about 6 inches/minute to about 12 inches/minute, which is not economically feasible. Moreover, these processes do not allow for composite configuration and tuning during the process, wherein tuning comprises changing the fiber/resin ratio. It is therefore desirable to design economically feasible ACCC cables having at least one reinforced fiber type in a thermosetting resin matrix comprising inherent physical characteristics that facilitate increased ampacity without corresponding cable sag. It is further desirable to process composite cores using a process that allows configuration and tuning of the composite cores during processing and allows for processing at speeds in the range of about 9 ft/min 2.74(m/min) to 50 ft/min (15.24 m/min).
<SOH> SUMMARY OF THE INVENTION <EOH>Increased ampacity can be achieved by using an aluminum conductor composite core (ACCC) reinforced cable. An ACCC reinforced cable is a high-temperature, low-sag conductor, which can be operated at temperatures above 100° C. while exhibiting stable tensile strength and creep elongation properties. It is further desirable to achieve practical temperature limits of up to 230° C. Using an ACCC reinforced cable, which has the same diameter as the original, at 180° C. also increases the line rating by 50% without any significant change in structure loads. If the replacement conductor has a lower thermal elongation rate than the original, then the support structures will not have to be raised or reinforced. In particular, replacing the core of distribution and transmission conductor cables with a composite strength member comprising fiber and resin with a relatively high modulus of elasticity and a relatively low coefficient of thermal expansion facilitates an increased conductor cable ampacity. It is further desirable to design composite cores having long term durability allowing the composite strength member to operate at least sixty years, and more preferably seventy years at the temperatures associated with the increased ampacity, about 90 to 230° C., without having to increase either the diameter of the composite core, or the outside diameter of the conductor. This in turn allows for more physical space to put more aluminum and for the mechanical and physical performance to be able to meet the sag limits without increased conductor weight. Further, the invention allows for formation of a composite core having a smaller core size. A smaller core size allows the conductor cable to accommodate an increased volume of aluminum wherein an ACCC cable has the same strength and weight characteristics as a conductor cable without a composite core. To achieve the desired ampacity gains, a composite core according to the invention may also combine fibers having a low modulus of elasticity with fibers having a high modulus of elasticity for increased stiffness of the core and a lower elongation percent. By combining fibers, a new property set including different modulus of elasticity, thermal expansion, density and cost is obtained. Sag versus temperature calculations show achievable ampacity gains when an advanced composite is combined with low modulus reinforced fibers having inherent physical properties within the same range as glassfiber. Composite cores according to the invention meet certain physical characteristics dependent upon the selection of reinforced fiber types and thermosetting resins with desired inherent physical properties. Composite cores according to the invention have substantially low thermal expansion coefficients, substantially high tensile strength, ability to withstand a substantially high range of operating temperatures, ability to withstand a low range of ambient temperatures, substantially high dielectric properties and sufficient flexibility to permit winding. In particular, composite cores according to the present invention have a tensile strength within the range of about 160 to about 240 Ksi, a modulus of elasticity within the range of about 7 to about 30 Msi, an operating temperature within the range of about 90 to about 230° C. and a thermal expansion coefficient within the range of about 0 to about 6×10 −6 m/m/C. These ranges can be achieved by a single reinforced fiber type or a combination of reinforced fiber types. Theoretically, although the characteristics could be achieved by a single fiber type alone, from a practical point of view, most cores within the scope of this invention comprise two or more distinct reinforced fiber types. In addition, depending on the physical characteristics desired in the final composite core, the composite core accommodates variations in the relative amounts of fibers. Composite cores of the present invention can be formed by a B-stage forming process wherein fibers are wetted with resin and continuously pulled through a plurality of zones within the process. The B-stage forming process relates generally to the manufacture of composite core members and relates specifically to an improved apparatus and process for making resin impregnated fiber composite core members. More specifically, according to a preferred embodiment, a multi-phase B-stage process forms a composite core member from fiber and resin with superior strength, higher ampacity, lower electrical resistance and lighter weight than previous core members. The process enables formation of composite core members having a fiber to resin ratio that maximizes the strength of the composite, specifically flexural, compressive and tensile strength. In a further embodiment, the composite core member is wrapped with high conductivity aluminum resulting in an ACCC cable having high strength and high stiffness characteristics.
20041019
20080506
20051013
98146.0
2
GRAY, JILL M
ALUMINUM CONDUCTOR COMPOSITE CORE REINFORCED CABLE AND METHOD OF MANUFACTURE
UNDISCOUNTED
0
ACCEPTED
2,004
10,512,034
ACCEPTED
(Co)polymers and method for the radical (co)polymerisation of olefinically unsaturate monomers
(Co)polymers preparable by free-radical (co)polymerization of olefinically unsaturated monomers in the presence of at least one thiocarbamate-functional organic compound, processes for preparing (co)polymers by free-radical (co)polymerization of olefinically unsaturated monomers, which involves (co)polymerizing the olefinically unsaturated monomers in the presence of at least one thiocarbamate-functional organic compound, and the use of thiocarbamate-functional organic compounds as regulators in the free-radical (co)polymerization of olefinically unsaturated monomers.
1. A (co)polymer comprising a free-radical (co)polymerization product of at least one olefinically unsaturated monomers prepared in the presence of at least one thiocarbamate-functional organic compound. 2. The (co)polymer as claimed in claim 1, wherein the thiocarbamate-functional organic compound contains at least one thiocarbamate group. 3. The (co)polymer as claimed in claim 2, wherein the thiocarbamate-functional organic compound contains at least two thiocarbamate groups. 4. The (co)polymer of claim 1, wherein the thiocarbamate-functional organic compound comprises a reaction product of an organic compound containing at least one isocyanate group and at least one thiol. 5. A process for preparing the (co)polymer of claim 1 comprising (co)polymerizing the at least one olefinically unsaturated monomers in the presence of the at least one thiocarbamate-functional organic compound. 6. The process as claimed in claim 5, wherein the thiocarbamate-functional organic compound contains at least one thiocarbamate group. 7. The process as claimed in claim 6, wherein the thiocarbamate-functional organic compound contains at least two thiocarbamate groups. 8. The process of claim 5, wherein the thiocarbamate-functional compound comprises a reaction product of an organic compound containing at least one isocyanate group and at least one thiol. 9. A method comprising regulating free-radical (co)polymerization of at least one olefinically unsaturated monomers by adding a thiocarbamate-functional organic compound to the (co)polymerization.
The present invention relates to novel (co)polymers preparable by free-radical (co)polymerization of olefinically unsaturated monomers. The present invention further relates to a novel process for free-radical (co)polymerization of olefinically unsaturated monomers in the presence of thiocarbamate-functional compounds. The present invention also relates to the novel use of thiocarbamate-functional compounds as regulators in the free-radical (co)polymerization of olefinically unsaturated monomers. (Co)polymers of olefinically unsaturated monomers have been known for a long time and are used, for example, as thermoplastics or as important ingredients for coating materials, adhesives, and sealing compounds. As constituents of coating materials, adhesives, and sealing compounds, in their function as binders, they characterize the technological properties of these formulations and also the technological properties of the coatings, adhesive films, and seals produced from them. In order to realize liquid coating materials, adhesives, and sealing compounds which are easy to apply, have environmental and economic advantages, and possess high solids contents, it is necessary to use binders having a very low number-average and mass-average molecular weight. Their preparation by free-radical (co)polymerization, however, causes problems and cannot be effected without using regulators or chain transfer agents. As regulators or chain transfer agents it is customary to use thiols or mercaptans. However, these compounds give rise to a severe odor nuisance, which may be manifested unpleasantly even in the (co)polymers and in the coating materials, adhesives, and sealing compounds prepared from them. This problem weighs particularly heavy when, for example, the coating materials are prepared and used on an industrial scale, such as in the OEM finishing of automobiles. It is an object of the present invention to find new (co)polymers which no longer have the disadvantages of the prior art but which instead can be prepared readily even with low molecular weights and without the odor nuisance associated with the use of regulators or chain transfer agents. The new (co)polymers ought to be suitable in particular as binders for coating materials, adhesives, and sealing compounds which are easy to apply, are environmentally unobjectionable, are free from unpleasant odors, and possess a particularly high solids content. The new coating materials, adhesives, and sealing compounds ought to give coatings, adhesive films, and seals which are particularly advantageous both economically and technologically. A further object of the present invention was to find a new process for the free-radical (co)polymerization of olefinically unsaturated compounds which no longer has the disadvantages of the prior art but which instead, in a manner simple and easy to reproduce, provides (co)polymers, especially (co)polymers with low molecular weights, without the occurrence of an odor nuisance. Yet another object of the present invention was to find new regulators or chain transfer agents for the free-radical (co)polymerization of olefinically unsaturated monomers which no longer have the disadvantages of the prior art and which in particular no longer give rise to any odor nuisance during the preparation of the (co)polymers and their application. An object of the present invention not least was to find a new use for thiocarbamate-functional organic compounds. The invention accordingly provides the novel (co)polymers preparable by free-radical (co)polymerization of olefinically unsaturated monomers in the presence of at least one thiocarbamate-functional organic compound, which are referred to below as “(co)polymers of the invention”. The invention also provides the novel process for preparing (co)polymers by free-radical (co)polymerization of olefinically unsaturated monomers, which involves (co)polymerizing the olefinically unsaturated monomers in the presence of at least one thiocarbamate-functional organic compound, and which is referred to below as “process of the invention”. The invention provides not least for the novel use of thiocarbamate-functional organic compounds as regulators in the free-radical (co)polymerization of olefinically unsaturated monomers, this being referred to below as “use in accordance with the invention”. In the light of the prior art it was surprising and unforeseeable for the skilled worker that the object on which the present invention was based could be achieved fundamentally by means of the use in accordance with the invention. In particular it was surprising that the thiocarbamate-functional organic compounds for use in accordance with the invention have an outstanding regulatory effect in the free-radical (co)polymerization of olefinically unsaturated monomers and do not give rise to any odor nuisance. It was surprising, moreover, that on the basis of the use in accordance with the invention and of the process of the invention the (co)polymers of the invention were obtained, which were substantially or entirely free from unpleasant odors and possessed outstanding performance properties. Furthermore, it was surprising that the (co)polymers of the invention were outstandingly suitable as binders for coating materials, adhesives, and sealing compounds, especially for liquid coating materials, adhesives, and sealing compounds having particularly high solids contents of up to 100% by weight (100% systems). The coating materials, adhesives, and sealing compounds of the invention in question were surprisingly free from unpleasant odors, were easy and economic to apply, and on a wide variety of substrates gave coatings, adhesive films, and seals which were particularly advantageous both economically and technologically. The thiocarbamate-functional organic compounds for use in accordance with the invention contain at least one, preferably at least two, and in particular two, thiocarbamate groups. The thiocarbamate-functional organic compounds for use in accordance with the invention are referred to below for the sake of brevity as “thiocarbamates”. In addition, the thiocarbamates may contain at least one further functional group. This further functional group is selected such that it does not induce any unwanted secondary reactions and/or does not inhibit the free-radical (co)polymerization of the olefinically unsaturated monomers and/or the regulatory effect of the thiocarbamates. Preferably, the further functional group is selected such that it is able to undergo crosslinking reactions with the crosslinking agents that may be present in the coating materials, adhesives, and sealing compounds of the invention. With particular preference, hydroxyl groups are used as further functional groups. The thiocarbamates are preferably organic compounds of low molecular mass, i.e., compounds which are not composed of monomer units. The thiocarbamates are conventional compounds and can be prepared by means of the conventional methods and techniques of organic chemistry. They are preferably prepared by reacting an organic compound containing at least one, preferably at least two, and in particular two, isocyanate group(s) (called “isocyanate” below) with at least one, especially one, thiol. The isocyanate is preferably selected from the group of the diisocyanates. Examples of suitable diisocyanates are isophorone diisocyanate (i.e., 5-isocyanato-1-isocyanatomethyl-1,3,3-trimethylcyclohexane), 5-isocyanato-1-(2-isocyanatoeth-1-yl)-1,3,3-trimethylcyclohexane, 5-isocyanato-1-(3-isocyanatoprop-1-yl)-1,3,3-trimethylcyclo-hexane, 5-isocyanato-(4-isocyanatobut-1-yl)-1,3,3-trimethylcyclohexane, 1-isocyanato-2-(3-isocyanatoprop-1-yl)cyclohexane, 1-isocyanato-2-(3-isocyanatoeth-1-yl)cyclohexane, 1-isocyanato-2-(4-isocyanatobut-1-yl)cyclohexane, 1,2-diisocyanatocyclobutane, 1,3-diiso-cyanatocyclobutane, 1,2-diisocyanatocyclopentane, 1,3-diisocyanatocyclopentane, 1,2-diisocyanatocyclohexane, 1,3-diisocyanatocyclohexane, 1,4-diisocyanatocyclohexane, dicyclohexylmethane 2,4′-diisocyanate, trimethylene diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, ethylethylene diisocyanate, trimethylhexane diisocyanate, heptamethylene diisocyanate or diisocyanates derived from dimer fatty acids, as sold under the commercial designation DDI 1410 by Henkel and described in patents WO 97/49745 and WO 97/49747, especially 2-heptyl-3,4-bis(9-isocyanatononyl)-1-pentylcyclohexane, or 1,2-, 1,4- or 1,3-bis(iso-cyanatomethyl)cyclohexane, 1,2-, 1,4- or 1,3-bis(2-isocyanatoeth-1-yl)cyclohexane, 1,3-bis(3-isocyanatoprop-1-yl)cyclohexane, 1,2-, 1,4- or 1,3-bis(4-isocyanatobut-1-yl)cyclohexane, liquid bis(4-isocyanatocyclohexyl)methane with a trans/trans content of up to 30% by weight, preferably 25% by weight, and in particular 20% by weight, as described in patents DE 44 14 032 A1, GB 1 220 717 A1, DE-A-16 18 795 or DE 17 93 785 A1; tolylene diisocyanate, xylylene diisocyanate, tetramethylxylylidene diisocyanate (TMXDI), bisphenylene diisocyanate, naphthylene diisocyanate or diphenylmethane diisocyanate. Particular preference is given to using aliphatic isocyanates, especially the aliphatic diisocyanates. Aliphatic isocyanates are isocyanates in which the isocyanate groups are attached to aliphatic carbon atoms. The thiols are preferably monothiols, which where appropriate may also contain at least one of the further functional groups described above. Examples of suitable thiols are methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, and phenyl mercaptan and 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, and 6-hydroxyhexyl mercaptan. Particular preference is given to using 2-hydroxyethyl mercaptan (2-mercaptoethanol). The isocyanates and the thiols can be used in equimolar amounts. Preferably, however, a molar excess of thiols is employed. Unreacted thiols are then separated off after the reaction from the thiocarbamates formed. Examples of suitable separation techniques are extraction, distillation, and filtration. For the reaction the customary and known apparatus and safety measures are employed, as envisaged for the handling of isocyanates. For the process of the invention it is possible to use any conventional olefinically unsaturated monomers which can be free-radically (co)polymerized. Examples of suitable olefinically unsaturated monomers are described in detail in German patent application DE 199 30 664 A1, page 4 line 28 to page 9 line 49, or in German patent application DE 100 17 653 A1, page 7 line 64, paragraph [0086], to page 9 line 40, paragraph [0092]. The process of the invention may be conducted conventionally in bulk, solution, emulsion or dispersion. As reactors for the process the conventional stirred tanks, stirred tank cascades, tube reactors, loop reactors or Taylor reactors are suitable, as are described, for example, in patents DE 198 28 742 A1 or EP 0 498 583 A1 or in the article by K. Kataoka in Chemical Engineering Science, Volume 50, number 9, 1995, pages 1409 to 1416. The free-radical copolymerization is preferably conducted in stirred tanks or Taylor reactors, the Taylor reactors being configured such that the conditions of Taylor flow are met along the entire length of the reactor, even if the copolymerization causes the kinematic viscosity of the reaction medium to undergo a sharp change, especially an increase (cf. German patent application DE 198 28 742 A1). The process of the invention is advantageously conducted at temperatures above room temperature and below the lowest decomposition temperature of the respective monomers used, the temperature range chosen being preferably from 10 to 150° C., with very particular preference from 30 to 120° C., and in particular from 40 to 110° C. When using particularly volatile monomers the process of the invention may also be conducted under pressure, preferably under from 1.5 to 3000 bar, more preferably from 5 to 1500 bar, and in particular from 10 to 1000 bar. The molar ratio of thiocarbamates to olefinically unsaturated monomers may vary very widely and is guided by the requirements of the case in hand, in particular by the intended molecular weight of the (co)polymers of the invention. The molar ratio is preferably from 10−1 to 10−4, in particular from 10−2 to 10−3. As far as the molecular weight distribution is concerned, no restrictions whatsoever are imposed in the (co)polymers of the invention. Advantageously, however, the process of the invention is conducted so as to give a ratio Mw/Mn, measured by gel permeation chromatography using polystyrene as standard, of ≦4, preferably ≦2, and especially ≦1.6. EXAMPLES Preparation Example 1 The Preparation of a Thiocarbamate A glass reaction vessel was charged with 10 g (127.9 mmol) of 2-mercaptoethanol and this initial charge was heated to 40° C. under nitrogen. At this temperature, 1.56 g (6.34 mmol) of tetramethylxylylidene diisocyanate (TMXDI) were added with stirring. The resulting reaction mixture was stirred at 40° C. for 24 hours and then poured into 200 ml of ice-water. The white precipitate was filtered off and washed with deionized water until completely odor-neutral. The precipitate was then dried at room temperature under an oil pump vacuum. Elemental analysis gave the following composition in % by weight: Element: N C H S found: 6.92 53.62 7.06 16.05 calculated: 6.99 53.98 7.05 16.01 The structure of the thiocarbamate was confirmed by nuclear magnetic resonance spectroscopy: 13C NMR, 100 MHz, DMSO-d6, δ [ppm]: 30.8 (C-8, C-8′, C-9, C-9′, primary), 31.66 (C-11, C-11′, secondary), 57.33 (C-7, C-7′, quaternary), 61.54 (C-12, C-12′, secondary), 121.41 (C-2, tertiary), 122.7 (C-4, C-6, tertiary), 127.89 (C-5, tertiary), 147.49 (C-1, C-3, quaternary), 164.38 (C-10, C-10′, quaternary). 1H NMR, 400 MHz, DMSO-d6, δ [ppm]: 1.53 (s, 12H, C8,8′,9,9′H3), 2.76 (t, 4H, C11,11′H2), 3.39 (q, 4H, C12,12′H2), 4.84 (t, 2H, OH), 7.09-7.12 (m, 2H, C4,6H), 7.18-7.22 (m, 1H, C5H), 7.26 (m, 1H, C2H), 8.37 (s, 2H, NH) Examples 1 to 3 and C1 (C=Comparative) The Free-Radical Polymerization of Styrene in the Absence (Example C1) and in the Presence (Examples 1 to 3) of the Thiocarbamate from Preparation Example 1 General Experimental Protocol On an analytical balance, the desired amount of the thiocarbamate from preparation example 1 was weighed into a 50 ml Schlenk tube and dissolved in 15 ml of tetrahydrofuran. The styrene solution, containing initiator, was then added under nitrogen. Residual traces of oxygen were removed by evacuating and charging with nitrogen several times. The styrene solution was in each case prepared fresh directly before use. This was done by distilling the styrene under reduced pressure on a column at 30° C. under inert gas, to remove the stabilizer, and then adding azoisobutyronitrile (AIBN) to give a 0.1 molar solution. For each experimental series, four Schlenk tubes were set up in parallel, their contents differing from one another in terms of the ratio of thiocarbamate to styrene (examples 1 to 3 with thiocarbamate, example C1 without thiocarbamate). The sealed Schlenk tubes were then heated on a water bath at 55° C. for 3 hours. The proportions used were those listed in table 1. TABLE 1 The amounts of styrene and thiocarbamate used Styrene Thiocarbamate solution (S) (TCA) TCA/S Example [g] [mmol] [g] [mmol] [molar] C1 18.02 173 — — 0 1 18.06 173.4 0.2294 0.5727 3.3 * 10−3 2 18.07 173.5 0.4771 1.1911 6.9 * 10−3 3 18.06 173.4 0.9324 2.3278 1.34 * 10−2 After the end of the polymerization, the reaction mixtures were each poured into 300 ml of cold methanol. The white polymers precipitated were isolated by filtration and dried under reduced pressure. The molar masses of the polystyrenes were determined by means of gel permeation chromatography using polystyrene as standard. The results can be found in table 2. TABLE 2 Conversion (%), number-average molecular weight Mn [daltons], average degree of polymerization Pn, and molecular weight polydispersity Mw/Mn Example Conversion Mn Pn Mw/Mn C1 7.5 143 945 1 382 1.47 1 7.0 75 467 725 1.53 2 7.2 46 244 444 1.43 3 7.9 26 150 251 1.42 The results underline the fact that the thiocarbamate is highly active as a regulator or in transfer agent.
20041020
20061226
20050811
72241.0
0
TESKIN, FRED M
(CO)POLYMERS AND METHOD FOR THE RADICAL (CO)POLYMERISATION OF OLEFINICALLY UNSATURATE MONOMERS
UNDISCOUNTED
0
ACCEPTED
2,004
10,512,222
ACCEPTED
Lighting apparatus
Lighting apparatus is provided comprising a light source (10), the light source being encapsulated in a protective medium (11) to seal the light source against ingress of moisture, the lighting apparatus having a heat sink (12, 13), the heat sink having a first region (12) in communication with light source (10) to receive heat from the light source (10) and a second region (13) which projects externally of the protective medium, such that the heat sink can dissipate heat to the ambient area. The invention provides light apparatus which is particularly suitable for use with caving lamps, although other uses are possible, for example in traffic lights or the lights of a motor vehicle, where the encapsulation would provide protection against rain.
1. Lighting apparatus comprising a light source, the light source being encapsulated in a protective medium to seal the light source against ingress of moisture, the lighting apparatus including a heat sink, the heat sink having a first region in communication with the light source to receive heat from the light source, and a second region which projects externally of the protective medium, such that the heat sink can dissipate heat to the ambient area. 2. Lighting apparatus as claimed in claim 1, in which the light source comprises a light emitting diode (LED). 3. Lighting apparatus as claimed in claim 1, in which the light source has a light emitting region adjacent to, and projecting from, the protective medium. 4. Lighting apparatus as claimed in claim 1, in which the light source has a light emitting region protected by a cover, the cover being sealed to the protective medium and being such that light may pass through it. 5. Lighting apparatus as claimed in claim 4, in which the cover is made of glass. 6. Lighting apparatus as claimed in claim 4, in which the cover is made of transparent or translucent plastics material. 7. Lighting apparatus as claimed in claim 4, in which the cover comprises acollimating lens. 8. Lighting apparatus as claimed in claim 1, in which there is more than one light source arranged within the protective medium. 9. Lighting apparatus as claimed in claim 1, in which the light source is arranged to transmit light to the ambient area via a light transmitting conduit such as a light pipe or fibre optic bundle. 10. Lighting apparatus as claimed in claim 1, in which the heat sink comprises a metal plate. 11. Lighting apparatus as claimed in claim 10, in which the metal is aluminium. 12. Lighting apparatus as claimed in claim 1, in which the second region of the heat sink serves more than one purpose. 13. Lighting apparatus as claimed in claim 12, in which the second region carries manufacturer's information or advertising logo information. 14. Lighting apparatus as claimed in claim 12, in which the second region is shaped into a bracket, for example to fit into a socket on a standard miner's or caver's helmet. 15. Lighting apparatus as claimed in claim, in which the second region is shaped to form a box or other enclosure. 16. Lighting apparatus as claimed in claim 12, in which the second region has a secondary function as part of a car body such as a car wing.
The invention relates to lighting apparatus comprising a light source, and particularly though not exclusively, to lighting apparatus for use in a damp or wet environment, for example when caving. The invention provides lighting apparatus comprising a light source, the light source being encapsulated in a protective medium to seal the light source against ingress of moisture, the lighting apparatus including a heat sink, the heat sink having a first region in communication with the light source to receive heat from the light source, and a second region which projects externally of the protective medium, such that the heat sink can dissipate heat to the ambient area. The light source may comprise a light emitting diode (LED). The light source may have a light emitting region adjacent to, or projecting from, the protective medium. Alternatively the light source may have a light emitting region protected by a cover, the cover being sealed to the protective medium and being such that light may pass through it. The cover may be made of glass. Alternatively the cover may be made of transparent or translucent plastics material. The cover may comprise a collimating lens. There may be more than one light source arranged within the protective medium. The light source may be arranged to transmit light to the ambient area via a light transmitting conduit such as a light pipe or fibre optic bundle. The heat sink may comprise a metal plate. A preferred metal is aluminium and the aluminium may be anodised. However other metals would be possible, for example copper. The second region of the heat sink may serve more than one purpose. It may for example carry manufacturer's information or advertising logos. The second region of the heat sink could be shaped into a bracket, for example to fit into a socket on a standard miner's or caver's helmet. The second region of the heat sink may be shaped to form a box or other enclosure. While the light apparatus according to the invention has been particularly developed for use with caving lamps, other uses are possible, for example in traffic lights or the lights of a motor vehicle, where the encapsulation would provide protection against rain. The second region of the heat sink may have a secondary function as part of a car body part such as a car wing. By way of example specific embodiments of the invention will now be described, with reference to the accompanying drawings, in which: FIG. 1 is a side cross sectional view through a first embodiment of lighting apparatus according to the invention; and FIGS. 2 to 7 are similar views of six other embodiments of the invention. In the embodiment shown in FIG. 1, an LED 10 has polyurethane 11 moulded around it to form a solid block, encapsulating the LED. The LED 10 is mounted on a heat sink in the form of an anodised aluminium plate having a first region 12 which is sealed within the block 11. The heat sink has a second region 13 which extends outside the block to enable the heat sink to dissipate heat to the ambient area. A light emitting region 14 of the LED projects slightly from the block 11 to enable light to be transmitted by the lighting apparatus. Since however the polyurethane material completely surrounds the LED, there is no possibility of moisture reaching the electrical components of the LED. The polyurethane material is substantially incompressible and as there are no hollows or voids within the lighting apparatus, it is immensely strong and resistant to shocks. The LED may be switched on and off from outside the apparatus, for example magnetically using a reed switch or Hall effect transistor. The LED may also be provided with a dimming device which can also be operated externally of the device, for example magnetically. In the alternative embodiment shown in FIG. 2 the LED 10 is protected by a glass cover 15 which is sealed to the encapsulation material 11 by means of sealant resin 16. A further embodiment is shown in FIG. 3 in which the LED 10 is protected by a transparent plastic cover 17 embedded within the encapsulation material 11. FIG. 4 illustrates how the external part 13 of the heat sink may be given a secondary purpose. In the embodiment shown in FIG. 4, the portion 13 is bent into the shape of a bracket so that the lighting apparatus can easily be clipped onto a standard miner's or caver's helmet. In the embodiment shown in FIG. 5, the LED 10 lies well within the encapsulation material 11, but light is transmitted to the outside of the encapsulation material 11 by means of a light pipe or fibre optic bundle 18. FIG. 6 illustrates yet another embodiment in which two LEDs 10 are arranged spaced apart within the encapsulating medium 11. The light emitting portions of the LEDs are protected by a cover 19, for example made of polycarbonate, sealed to the polyurethane 11. The heat sink may be shaped as shown in FIG. 6 to form a box of other enclosure. This form of light apparatus could, for example, be used as a vandal resistant luminaire, or for traffic lights, or for lighting for a motor vehicle. The exposed portions of the heat sink could for example form a car body part, such as a car wing. FIG. 7 illustrates one more embodiment which is similar to that shown in FIG. 6 but in which the exposed, heat dissipating portion 13 of the heat sink comprises only the rear face of the heat sink, the edges 20 of the heat sink being enclosed within the polyurethane 11. Each of the embodiments shown in the drawings may be provided with either an external or an internal power supply. For example, as illustrated in FIG. 1, a power supply for the LED 14 may be an external power supply, fed to the LED 14 through the encapsulation material 11 by a power cable 21. Alternatively, as shown in FIG. 5, power cells 22 may be embedded within the encapsulation material 11. The cells may be primary cells or secondary, rechargeable cells. Although the lighting apparatus has been specifically developed for use with caving lamps, the apparatus according to the invention also makes an excellent apparatus for safe use in flammable atmospheres. Such light sources are generally referred to as being “intrinsically safe”. Light apparatus according to the invention would be intrinsically safe because the light source is so well sealed from the environment and the heat sink can be sized so that operating temperatures are well below those required by safety or legislative requirements. The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.
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Method and apparatus for specifying connections for devices on a data bus network
A method and apparatus enables users to specify analog connections for devices on a data bus network such as an IEEE 1394 network in a convenient, time-efficient manner. According to an exemplary embodiment, the method includes steps of enabling an on-screen display comprising a list of devices connected to the digital data bus network requiring analog connections to the apparatus, and enabling a user to specify the analog connections responsive to the on-screen display.
1. A method for controlling a video signal processing apparatus, comprising the steps of: coupling the apparatus to a plurality of peripheral devices, each of the plurality of peripheral devices having a digital output and an analog input, wherein the apparatus is coupled to the digital outputs of the plurality of peripheral devices via a digital data bus network connection, and the apparatus is coupled to each of the analog outputs of the plurality of peripheral device via a respective analog input of the apparatus; providing an on-screen display comprising a list of the plurality of peripheral devices connected to the apparatus and a list of the analog inputs of the apparatus; and associating a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. 2. The method according to claim 1, further comprising the step of receiving identification information from each of the plurality of peripheral devices during a set up mode of the digital data bus, wherein the providing step includes providing a list of the identification information on the on-screen display. 3. The method according to claim 2, wherein the coupling step includes coupling the apparatus to at least one set of identical peripheral devices, further comprising the step of appending predetermined designators to the identification information associated with the set of identical peripheral devices to distinguish the identical peripheral devices on the digital data network. 4. The method according to claim 3, wherein the digital data bus network comprises an IEEE 1394 bus network. 5. The method according to claim 1, wherein the displayed list of plurality of peripheral devices is arranged alphabetically by model name. 6. The method according to claim 1, wherein the displayed list of plurality of peripheral devices is arranged alphabetically by manufacturer name. 7. The method according to claim 1, wherein the displayed list of plurality of peripheral devices is arranged based on digital identification codes associated with the devices. 8. A video signal processing apparatus, comprising: input/output means comprising a digital data bus connection and a plurality of analog inputs for connecting the apparatus to a plurality peripheral devices, each of the plurality of peripheral devices having a digital output and an analog output, wherein the digital outputs of the plurality of peripheral devices is coupled to the apparatus via the digital data bus network connection, and the analog outputs of the plurality of peripheral device are coupled to the apparatus via a respective analog input of the apparatus; means for receiving user input; means for generating an on-screen display; means, coupled to the digital data bus connection and the plurality of analog inputs, for processing received video signals and providing output signals suitable for display; and means for coupling the output signals to a display device, wherein the generating means provides an on-screen display including a list of the plurality of peripheral devices coupled to the apparatus and a list of the analog inputs of the apparatus, and the processing means associates a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. 9. The apparatus according to claim 8, wherein the processing means receives identification information from each of the plurality of peripheral devices during a set up mode of the digital data bus, and the generating means provides a list of the identification information on the on-screen display. 10. The apparatus according to claim 9, wherein the processing means, upon determining that the plurality of peripheral devices includes at least one set of identical peripheral devices, automatically appends predetermined designators to the identification information associated with the set of identical peripheral devices to distinguish the identical peripheral devices on the digital data network, and the generating means provides the predetermined designators in the list of the identification information. 11. The apparatus according to claim 10, wherein the plurality of peripheral devices are connected in an IEEE 1394 bus network. 12. The apparatus according to claim 8, wherein the list of plurality of peripheral devices is arranged alphabetically by model name. 13. The apparatus according to claim 8, wherein the list of plurality of peripheral devices is arranged alphabetically by manufacturer name. 14. The apparatus according to claim 8, wherein the list of plurality of peripheral devices is arranged based on digital identification codes associated with the devices. 15. A television signal receiver, comprising: input/output means comprising a digital data bus connection and a plurality of analog inputs for connecting the apparatus to a plurality peripheral devices, each of the plurality of peripheral devices having a digital output and an analog output, wherein the digital outputs of the plurality of peripheral devices is coupled to the apparatus via the digital data bus network connection, and the analog outputs of the plurality of peripheral device are coupled to the apparatus via a respective analog input of the apparatus; means for receiving user input; means for generating an on-screen display; means, coupled to the digital data bus connection and the plurality of analog inputs, for processing received television signals and providing output signals suitable for display; and means for coupling the output signals to a display device, wherein the generating means provides an on-screen display including a list of the plurality of peripheral devices coupled to the apparatus and a list of the analog inputs of the apparatus, and the processing means associates a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. 16. The television signal receiver according to claim 15, wherein the processing means receives identification information from each of the plurality of peripheral devices during a set up mode of the digital data bus, and the generating means provides a list of the identification information on the on-screen display. 17. The television signal receiver according to claim 15, wherein the processing means, upon determining that the plurality of peripheral devices includes at least one set of identical peripheral devices, automatically appends predetermined designators to the identification information associated with the set of identical peripheral devices to distinguish the identical peripheral devices on the digital data network, and the generating means provides the predetermined designators in the list of the identification information. 18. The television signal receiver according to claim 15, wherein the plurality of peripheral devices is connected in an IEEE 1394 bus network.
This application claims priority to and all benefits accruing from two provisional applications filed in the United States Patent and Trademark Office on Apr. 24, 2002, and there assigned Ser. Nos. 60/375,136 and 60/375,207. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention generally relates to a video signal processing apparatus and a method for controlling a video signal processing apparatus, and more particularly, to an apparatus and a method for enabling a user to efficiently and easily specify secondary analog connections for a plurality of peripheral devices connected to the apparatus via a digital data bus network connection and a plurality of analog inputs. 2. Related Art A data bus can be utilized for interconnecting electronic devices, such as television signal receivers, personal computers, display devices, video cassette recorders (VCRs), digital versatile disk (DVD) players, direct broadcast satellite (DBS) receivers, home control devices (e.g., security systems, temperature control devices, etc.), and/or other devices. Communication using a data bus typically occurs in accordance with a specified bus protocol. An example of such a bus protocol includes the Institute for Electrical and Electronic Engineers 1394 High Performance Serial Bus protocol (IEEE 1394, or Firewire™), which is generally known in the art. With a network, such as an IEEE 1394 network, a plurality of devices can be interconnected and the devices can exchange data, such as audio and/or video data, over the network. Moreover, a user may control one device on the network through inputs to another device on the network. Accordingly, a network such as an IEEE 1394 network provides interoperability among devices connected to the network. An IEEE 1394 bus can also accommodate a relatively large number of interconnected devices (e.g., up to 63), which may be connected in a daisy chain fashion. Electronics Industries Association (EIA) 775 is a standard that describes how a source device sends data (e.g., on-screen display data, audio/video data, etc.) to a target device over an IEEE 1394 bus. In particular, EIA 775 acknowledges the fact that some source devices can send digital data, such as Motion Picture Expert Group (MPEG) video data, as well as analog data. For example, certain set-top boxes are capable of receiving and sending digital signals such as Advanced Television Standards Committee (ATSC) signals, as well as analog signals such as National Television Standards Committee (NTSC) signals. To accommodate such devices, EIA 775 specifies that a source device can inform a target device whether the signals it is sending to the target device are digital or analog. Accordingly, when the target device receives this information, its input source can be switched, for example, to an IEEE 1394 input connector if the signals are digital, or to one of its analog input connectors if the signals are analog. With certain conventional devices, a user may interact with a potential target device to specify that a specific source device is connected to a given analog input terminal of the target device. For example, this interaction may occur when a new source device is connected to the target device, or in response to user selection of a set-up display in the target device. Unfortunately however, with such conventional devices this type of interaction is available only on a device-by-device basis. That is, conventional devices do not provide a single screen indicating all source devices connected to a target device and all of the possible analog inputs associated with the target device. Instead, a user may be required to navigate through multiple screens (e.g., one screen per source device) to specify the connections for a target device. This can be particularly inconvenient and time consuming for the user since he/she may have to navigate through many different screens to specify device connections. Moreover, the use of multiple screens to specify device connections can be problematic since the user must mentally keep track of the different source devices and connections on the target device as he/she navigates through the multiple screens. Accordingly, there is a need for a method and apparatus which avoids the foregoing problems, and thereby enables users to specify analog connections for devices on a data bus network such as an IEEE 1394 network in a more convenient, time-efficient manner. The present invention addresses these and other issues. SUMMARY OF THE INVENTION In accordance with an aspect of the present invention, a method for controlling an apparatus connected to a digital data bus network is disclosed. According to an exemplary embodiment, the method comprises the steps of: coupling the apparatus to a plurality of peripheral devices, each of the plurality of peripheral devices having a digital output and an analog input, wherein the apparatus is coupled to the digital outputs of the plurality of peripheral devices via a digital data bus network connection, and the apparatus is coupled to each of the analog outputs of the plurality of peripheral device via a respective analog input of the apparatus; providing an on-screen display comprising a list of the plurality of peripheral devices connected to the apparatus and a list of the analog inputs of the apparatus; and associating a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. In accordance with another aspect of the present invention, an electronic apparatus operative to perform the above-stated method is disclosed. According to an exemplary embodiment, the electronic apparatus comprises: input/output means comprising a digital data bus connection and a plurality of analog inputs for connecting the apparatus to a plurality peripheral devices, each of the plurality of peripheral devices having a digital output and an analog output, wherein the digital outputs of the plurality of peripheral devices is coupled to the apparatus via the digital data bus network connection, and the analog outputs of the plurality of peripheral device are coupled to the apparatus via a respective analog input of the apparatus; means for receiving user input; means for generating an on-screen display; means, coupled to the digital data bus connection and the plurality of analog inputs, for processing received video signals and providing output signals suitable for display; and means for coupling the output signals to a display device, wherein the generating means provides an on-screen display including a list of the plurality of peripheral devices coupled to the apparatus and a list of the analog inputs of the apparatus, and the processing means associates a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. BRIEF DESCRIPTION OF THE DRAWINGS The above-mentioned and other features and advantages of this invention, and the manner of attaining them, will become more apparent and the invention will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein: FIG. 1 is an exemplary apparatus suitable for implementing the present invention; FIG. 2 is a diagram illustrating an exemplary connection of devices to the apparatus of FIG. 1; FIG. 3 is a flowchart illustrating exemplary steps according to the present invention; FIG. 4 is an exemplary on-screen display according to the present invention; and FIG. 5 is another exemplary on-screen display according to the present invention. The exemplifications set out herein illustrate preferred embodiments of the invention, and such exemplifications are not to be construed as limiting the scope of the invention in any manner. DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now to the drawings, and more particularly to FIG. 1, an exemplary apparatus 100 suitable for implementing the present invention is shown. For purposes of example and explanation, apparatus 100 represents an exemplary portion of a television signal receiver embodied as a projection screen television. However, it will be intuitive to those skilled in the art that principles of the present invention may be applied to other apparatuses designed to perform the functions described below. As shown in FIG. 1, apparatus 100 comprises an audio/video input/output (AV 10) block 101, a front audio/video (FAV) connector 102, a digital processing block 103, a front panel assembly (FPA) 104, an infrared (IR) preamp 105, an audio block 106, a power supply 107, a subwoofer amp/power supply 108, a subwoofer 109, a deflection block 110, a convergence block 111, CRTs 112 to 114, and yokes 115 to 117. The foregoing elements of FIG. 1 are operatively coupled as indicated by the data lines shown in FIG. 1. As will be intuitive to those skilled in the art, many of the elements, or combinations of elements, represented in FIG. 1 may be embodied using integrated circuits (ICs). AV IO block 101 comprises various input terminals, including, but not limited to, S-video inputs, RF inputs, component inputs, and IEEE 1394 input, and is operative to receive and process audio, video, control and/or other inputs, and to output processed signals to other elements of apparatus 100, as indicated in FIG. 1. According to an exemplary embodiment, AV IO block 101 receives audio, video, and/or control inputs from a plurality of external sources such as, but not limited to, the devices represented in FIG. 2. As indicated in FIGS. 1 and 2, AV IO block 101 receives audio, video and/or other inputs from external devices 201 to 203, which for purposes of example are represented in FIG. 2 as a DBS receiver, a VCR, and a DVD player, respectively. Accordingly, devices 201 to 203 are source devices for apparatus 100. Other external devices may be connected to AV IO block 101, and the number of such devices may for example depend on the number of input terminals provided by AV IO block 101. AV IO block 101 is operatively coupled to at least one bi-directional digital data bus network 210 (see FIG. 2), such as an IEEE 1394 bus network, or the like. As indicated in FIG. 2, data bus network 210 includes up to N interconnected devices (e.g., television signal receivers, personal computers, display devices, VCRs, DVD players, DBS receivers, and/or other devices), which are capable of communicating with one another in a known manner, such as in accordance with the IEEE 1394 bus protocol. According to an exemplary embodiment, N is equal to sixty-three (63). Apparatus 100 may exchange audio, video, control, and/or other signals with any of the devices on data bus network 210 via AV IO block 101. Data bus network 210 may be arranged in a variety of different configurations such as, but not limited to, the exemplary configuration shown in FIG. 2, and/or other configurations. AV IO block 101 also receives processed audio inputs from audio block 106. According to an exemplary embodiment, AV IO block 101 processes inputs and outputs composite video signals and all audio signals to digital processing block 103 for additional processing, while outputting component video signals (e.g., 2H, 2.14H, Y, Pr, Pb video information) to deflection block 110. FAV connector 102 is operative to provide audio and/or video inputs to AV IO block 101. Digital processing block 103 is operative to perform various digital functions of apparatus 100, such as tuning, demodulation, signal decompression, memory and other functions. Digital processing block 103 outputs processed video signals to deflection block 110 which enable a visual display. As will be explained later herein, digital processing block 103 also enables, among other things, a user to specify secondary analog connections for devices connected on data bus network 210. FPA 104 is an interface operative to receive user inputs from a user input device (UID), such as an IR hand-held remote control, keyboard, or other input device, and to output signals corresponding to the user inputs to IR preamp 105. IR preamp 105 is operative to amplify the signals provided from FPA 104 for output to digital processing block 103. Audio block 106 is operative to perform various audio processing functions, to and to output processed audio signals. According to an exemplary embodiment, audio block 106 receives a center channel input signal and processes the same to generate audio output signals. As indicated in FIG. 1, audio block 106 is operative to provide audio output signals to both external and internal speakers of apparatus 100. Additionally, audio block 106 provides audio output signals to AV IO block 101, and also provides subwoofer audio signals to subwoofer amp/power supply 108. Power supply 107 is operative to receive an input alternating current power signal (AC-IN), and to output voltage signals which power the various elements of apparatus 100, as indicated in FIG. 1. According to an exemplary embodiment, power supply 107 provides such voltage signals to AV IO block 101, digital processing block 103, audio block 106, subwoofer amp/power supply 108, and deflection block 110. Subwoofer amp/power supply 108 is operative to amplify the subwoofer audio signals provided from audio block 106, and provide the amplified subwoofer audio signals to subwoofer 109. Subwoofer amp/power supply 108 also outputs a voltage signal to subwoofer 109, which serves as its power supply. Subwoofer 109 is operative to aurally output the amplified subwoofer audio signals provided from subwoofer amp/power supply 108. Deflection block 110 is operative to control deflection functions of apparatus 100. According to an exemplary embodiment, deflection block 110 outputs deflection control signals to yokes 115 to 117, which control horizontal and vertical deflection of the high-intensity beams generated by CRTs 112 to 114, respectively. Deflection block 110 is also operative to output color control signals to CRTs 112 to 114 responsive to the processed video signals and other control signals provided from digital processing block 103. Also according to an exemplary embodiment, deflection block 110 is operative to output voltage signals to convergence block 111 and CRTs 112 to 114 for their power supplies. Convergence block 111 is operative to control convergence functions of apparatus 100. According to an exemplary embodiment, convergence block 111 outputs convergence control signals to yokes 115 to 117, as indicated in FIG. 1, which control a positive convergence adjustment for precisely focusing the high-intensity beams emitted from CRTs 112 to 114 on a screen (not shown). CRTs 112 to 114 are operative to generate high-intensity red, green and blue beams, respectively, for display on a screen responsive to the color control signals from deflection block 110. Yokes 115 to 117 are operative to control CRTs 112 to 114, respectively, responsive to the deflection control signals from deflection block 110 and the convergence control signals from convergence block 111. Other suitable display devices, including, but not limited to, LCDs, plasma displays, OLEDs, and DLP displays may be used. Turning now to FIG. 3, a flowchart 300 illustrating exemplary steps according to one aspect of the present invention is shown. For purposes of example and explanation, the steps of FIG. 3 will be described with reference to apparatus 100 of FIG. 1 and the exemplary external devices of FIG. 2. The steps of FIG. 3 are merely exemplary, and are not intended to limit the present invention in any manner. At step 301, apparatus 100 is connected to external devices including devices on data bus network 210. According to an exemplary embodiment, a user physically connects devices 201 to 203 of FIG. 2 to input terminals of AV IO block 101 in a conventional manner, and thereby enables devices 201 to 203 to operate as source devices to apparatus 100 by providing audio and/or video input signals thereto. Also at step 301, the user constructs data bus network 210 of FIG. 2 by physically connecting devices 1 to N in a desired configuration, and connecting one of the devices on data bus network 210 to an input/output terminal (e.g., IEEE 1394 terminal) of AV IO block 101. According to an exemplary embodiment, apparatus 100 may represent a target device and the devices 1 to N on data bus network 210 may represent source devices. As previously indicated herein, data bus network 210 may be arranged in a variety of different configurations such as, but not limited to, the exemplary configuration shown in FIG. 2, and/or other configurations. According to an exemplary embodiment, apparatus 100 detects each device as it is connected to data bus network 210 including its need for a secondary analog connection at step 301. The operation of the bus network in recognizing and adding new devices to, or removing devices from, the network is well known. Generally, upon connection to the network, the network undergoes a configuration process, wherein each device on the network 210 provides identification data and control data, including manufacturer name, model name, identifiers including the GUID and EUID, and the various outputs and capabilities of the device, as necessary for configuring the network. Such data is generally stored in a configuration ROM of each device. Such data also indicates whether that particular device requires a secondary analog connection to apparatus 100. Apparatus 100, or a designated device on the network, stores this data (e.g., in memory of digital processing block 103) and updates it accordingly as devices are connected to and/or disconnected from data bus network 210. In this manner, apparatus 100 keeps track of all devices connected to it on data bus network 210 at any given time, including their requirements for a secondary analog connection. At this point the user may connect the analog outputs of the peripheral devices to any of the available analog inputs of apparatus 100. After apparatus 100 is connected to the external devices at step 301, process flow advances to step 302 where a user may access a setup menu of apparatus 100 that enables the user to specify secondary analog connections for all of the devices on data bus network 210 requiring such a connection. According to an exemplary embodiment, the user may access this setup menu by providing inputs to apparatus 100 via the UID which enable him/her to select from among various on-screen menus provided by apparatus 100. Such menus may for example be stored in memory of digital processing block 103. Digital processing block 103 responds to the user inputs by enabling generation of the various on-screen menus, which are displayed via CRTs 112 to 114. At step 303, a determination is made as to whether any of the devices on data bus network 210 require a secondary analog connection to apparatus 100. According to an exemplary embodiment, digital processing block 103 makes this determination based on the data received from the devices on data bus network 210 at step 301, including any data later received responsive to the addition and/or removal of devices from data bus network 210. If the determination at step 303 is negative, process flow advances to step 304 where an on-screen display is provided to indicate that apparatus 100 does not detect any devices on data bus network 210 that require a secondary analog connection. FIG. 4 shows an exemplary on-screen display 400 suitable for use at step 304. Of course, on-screen display 400 is only an example, and other items such as context sensitive help information, and/or other items may also be provided and/or other formats used in on-screen display 400 according to the present invention. According to an exemplary embodiment, the on-screen display of step 304 may be stored in memory of digital processing block 103 and displayed via CRTs 112 to 114 under the control of digital processing block 103. Alternatively, if the determination at step 303 is positive, process flow advances to step 305 where an on-screen display is provided including a list of all devices on data bus network 210 requiring a secondary analog connection to apparatus 100. FIG. 5 shows an exemplary on-screen display 500 including such a list. On-screen display 500 is also only an example, and other items such as context sensitive help information, and/or other items may also be provided and/or other formats used in on-screen display 500 according to the present invention. According to an exemplary embodiment, the on-screen display of step 305 may be stored in memory of digital processing block 103 and displayed via CRTs 112 to 114 under the control of digital processing block 103. The on-screen display of step 305 may also be provided whenever a source device is connected to data bus network 210. According to the present invention, the list of devices displayed at step 305 may be arranged in various different ways to facilitate ease of selecting the devices and associated analog input. Moreover, different target devices may differ from one another in the way they present the list of devices. In on-screen display 500 of FIG. 5 for example, the displayed list of devices is arranged alphabetically by model name. The model names may be abbreviated to conserve screen space. Also in exemplary on-screen display 500 of FIG. 5, the displayed list of devices includes at least two identical devices, that is, device having the same manufacturer and model name (i.e., model LX600). The present invention automatically recognizes the occurrence of such identical device models and distinguishes between them by appending predetermined designators, such as a numerical suffix and/or other designation, to the model name, or designations, on display 500. In FIG. 5 for example, the identical models include numerical suffixes (i.e., LX600.1 and LX600.2). Additional devices of the same model can likewise be identified (e.g., LX600.3, LX600.4, and so on). In this manner, a user can readily distinguish among multiple devices of the same model in the display list at step 305. When a character designation, such as a numerical suffix, is used to distinguish among identical models in the display list at step 305, it may be desirable to allow users to specify how the character designations are assigned. For example, a user may be allowed to designate which device includes the “0.1,” designation, which device includes the “0.2” designation, and so on. The designations may be permanently maintained by keeping a table associating the designations including the suffix, with the unique identifier, such as the EUID, associated with the device, such that the identifier is automatically maintained when the device is added back to the network. This flexibility may be advantageous when, for example, devices are frequently added to and/or removed from data bus network 210. Alternatively, with other designs, it may not be desirable to allow users to specify how the character designations are assigned. Such character designations may also be assigned automatically by apparatus 100. All of these alternatives are within the scope of the present invention. According to another exemplary embodiment, the list of devices displayed at step 305 may be arranged alphabetically by manufacturer name, and such names may be abbreviated to conserve screen space. According to yet another exemplary embodiment, the list of devices displayed at step 305 may be arranged based on digital identification codes associated with the devices. For example, each IEEE 1394 device includes a unique sixty-four (64) bit identification code (EUID). Accordingly, the list of devices displayed at step 305 may for example be arranged based on the values represented by such identification codes (e.g., from lowest value to highest value, etc.) regardless of whether such codes are actually displayed. Arranging the list of devices based on such identification codes can be useful since it may allow consistency in the order in which devices are displayed and tuned. Additionally, arranging the list of devices based on such identification codes may be useful when one or more devices have no manufacturer or device name. According to still yet another exemplary embodiment, the list of devices displayed at step 305 may be arranged based on a combination of device characteristics such as, but not limited to, the ones previously described herein (i.e., model name, manufacturer name, digital identification code). For example, the list of devices displayed at step 305 may be arranged alphabetically by manufacturer name followed by device name. As another example, the list of devices displayed at step 305 may be arranged based on device identification codes, but the devices may be identified in the display list according to another characteristic, such as model name. Other combinations may also be used according to the present invention. Moreover, users may be provided the option of selecting their own device names. At step 306, the secondary analog connections for the network devices listed at step 305 may be specified by the user. According to an exemplary embodiment, the user specifies these connections by providing inputs to apparatus 100 via the UID responsive to the on-screen display list provided at step 305. Data corresponding to the specified connections is then stored in memory (e.g., in block 103) under the control of digital processing block 103, thereby enabling the user's specified device connections to be used in the operation of apparatus 100 when necessary. For example, in FIG. 5 the user has selected input 1 for model ACT100, input 2 for model AXT100, input 5 for model LD500, input 6 for the first model LX600, input 7 for the second model LX600, and input 10 for model XSC254. The number of connections specified by the user at step 306 is of course influenced by the number of input connections available on apparatus 100, which is a matter of design choice. As described herein, the present invention provides a method and apparatus, which enables users to specify analog connections for devices on a data bus network such as an IEEE 1394 network in a convenient, time-efficient manner. The present invention is applicable to various electronic apparatuses that perform the various signal processing functions described hereinabove. Accordingly, the phrase “television signal receiver” as used herein may refer to devices or apparatuses including, but not limited to, television sets, computers, monitors, set-top boxes, VCRs, DVD players, stereos, video game boxes, personal video recorders (PVRs), and/or other apparatuses. Further, although an exemplary embodiment has been described, it is clear to those skilled in the art that the functions described above can be implemented using various elements, or combination of elements, including microprocessors, memory elements, device control elements, and software elements as required. While this invention has been described as having a preferred design, the present invention can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention generally relates to a video signal processing apparatus and a method for controlling a video signal processing apparatus, and more particularly, to an apparatus and a method for enabling a user to efficiently and easily specify secondary analog connections for a plurality of peripheral devices connected to the apparatus via a digital data bus network connection and a plurality of analog inputs. 2. Related Art A data bus can be utilized for interconnecting electronic devices, such as television signal receivers, personal computers, display devices, video cassette recorders (VCRs), digital versatile disk (DVD) players, direct broadcast satellite (DBS) receivers, home control devices (e.g., security systems, temperature control devices, etc.), and/or other devices. Communication using a data bus typically occurs in accordance with a specified bus protocol. An example of such a bus protocol includes the Institute for Electrical and Electronic Engineers 1394 High Performance Serial Bus protocol (IEEE 1394, or Firewire™), which is generally known in the art. With a network, such as an IEEE 1394 network, a plurality of devices can be interconnected and the devices can exchange data, such as audio and/or video data, over the network. Moreover, a user may control one device on the network through inputs to another device on the network. Accordingly, a network such as an IEEE 1394 network provides interoperability among devices connected to the network. An IEEE 1394 bus can also accommodate a relatively large number of interconnected devices (e.g., up to 63), which may be connected in a daisy chain fashion. Electronics Industries Association (EIA) 775 is a standard that describes how a source device sends data (e.g., on-screen display data, audio/video data, etc.) to a target device over an IEEE 1394 bus. In particular, EIA 775 acknowledges the fact that some source devices can send digital data, such as Motion Picture Expert Group (MPEG) video data, as well as analog data. For example, certain set-top boxes are capable of receiving and sending digital signals such as Advanced Television Standards Committee (ATSC) signals, as well as analog signals such as National Television Standards Committee (NTSC) signals. To accommodate such devices, EIA 775 specifies that a source device can inform a target device whether the signals it is sending to the target device are digital or analog. Accordingly, when the target device receives this information, its input source can be switched, for example, to an IEEE 1394 input connector if the signals are digital, or to one of its analog input connectors if the signals are analog. With certain conventional devices, a user may interact with a potential target device to specify that a specific source device is connected to a given analog input terminal of the target device. For example, this interaction may occur when a new source device is connected to the target device, or in response to user selection of a set-up display in the target device. Unfortunately however, with such conventional devices this type of interaction is available only on a device-by-device basis. That is, conventional devices do not provide a single screen indicating all source devices connected to a target device and all of the possible analog inputs associated with the target device. Instead, a user may be required to navigate through multiple screens (e.g., one screen per source device) to specify the connections for a target device. This can be particularly inconvenient and time consuming for the user since he/she may have to navigate through many different screens to specify device connections. Moreover, the use of multiple screens to specify device connections can be problematic since the user must mentally keep track of the different source devices and connections on the target device as he/she navigates through the multiple screens. Accordingly, there is a need for a method and apparatus which avoids the foregoing problems, and thereby enables users to specify analog connections for devices on a data bus network such as an IEEE 1394 network in a more convenient, time-efficient manner. The present invention addresses these and other issues.
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with an aspect of the present invention, a method for controlling an apparatus connected to a digital data bus network is disclosed. According to an exemplary embodiment, the method comprises the steps of: coupling the apparatus to a plurality of peripheral devices, each of the plurality of peripheral devices having a digital output and an analog input, wherein the apparatus is coupled to the digital outputs of the plurality of peripheral devices via a digital data bus network connection, and the apparatus is coupled to each of the analog outputs of the plurality of peripheral device via a respective analog input of the apparatus; providing an on-screen display comprising a list of the plurality of peripheral devices connected to the apparatus and a list of the analog inputs of the apparatus; and associating a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display. In accordance with another aspect of the present invention, an electronic apparatus operative to perform the above-stated method is disclosed. According to an exemplary embodiment, the electronic apparatus comprises: input/output means comprising a digital data bus connection and a plurality of analog inputs for connecting the apparatus to a plurality peripheral devices, each of the plurality of peripheral devices having a digital output and an analog output, wherein the digital outputs of the plurality of peripheral devices is coupled to the apparatus via the digital data bus network connection, and the analog outputs of the plurality of peripheral device are coupled to the apparatus via a respective analog input of the apparatus; means for receiving user input; means for generating an on-screen display; means, coupled to the digital data bus connection and the plurality of analog inputs, for processing received video signals and providing output signals suitable for display; and means for coupling the output signals to a display device, wherein the generating means provides an on-screen display including a list of the plurality of peripheral devices coupled to the apparatus and a list of the analog inputs of the apparatus, and the processing means associates a selected analog input to an analog output of a selected one of the plurality of peripheral device in response to user selections on the on-screen display.
20041025
20110816
20050811
95930.0
0
TAYLOR, BROOKE JAZMOND
METHOD AND APPARATUS FOR SPECIFYING ANALOG CONNECTIONS FOR DATA BUS NETWORK DEVICES HAVING BOTH DIGITAL AND ANALOG OUTPUTS
UNDISCOUNTED
0
ACCEPTED
2,004
10,512,397
ACCEPTED
Single-piece sealing cover
The invention relates to a single-pieced sealing cover (1) made of a thermoplastic elastomer, especially used to seal an opening (22, 22′, 22″) in a support (20, 20′, 20″) comprising a base body (5) with an adjacent peripheral collar (7) which turns into at least one elastic sealing lip (10, 10′) abutting against one side of the support, whereby the collar (7) presents at least one detent ring (12) positioned opposite the sealing lip (10, 10′). It is characterized in that the collar (7) is connected with the sealing lip (10, 10′) via an intermediate area (14) extending parallel to a covering surface (F) of the support (20, 20′, 20″), that the detent ring (12) protrudes into an interior space (21) formed by the intermediate area (14) and the sealing lip (10, 10′) and that an outer area of the sealing lip (10, 10′) is cementable with the covering surface (F) of the support (20, 20′, 20″).
1. A single-piece sealing cover (1) made of a thermoplastic elastomer for sealing an opening (22, 22′, 22″) in an associated support (20, 20′, 20″), the sealing cover comprising a base body (5) with an adjacent peripheral collar (7), at least one elastic sealing lip (10) abutting against one side of the support (20, 20′, 20″), the collar (7) presenting at least one detent ring (12) located opposite the sealing lip (10), the collar (7) being connected with the sealing lip (10) via an intermediate area (14), and whereby the detent ring (12) protrudes into an interior space (21) formed by the intermediate area (14) and the sealing lip (10), the intermediate area (14) extends parallel to a covering surface (F) of the support (20, 20′, 20″), and an outer area of the sealing lip (10) is cementable with the covering surface (F) of the support (20, 20′, 20″) by means of several serrated ribs (23). 2. The sealing cover according to claim 1, wherein the detent ring (12) lies in the plane of the base body (5) and includes an impact lip (25) at one end. 3. The sealing cover according to claim 1 wherein the outer surfaces (A1, A2) of the sealing lip (10) and the detent ring (12) are inclined towards each other. 4. The sealing cover according to claim 3, wherein the detent ring (12) includes an area (U) between the outer surface (A2) and the detent lip (25), the area (U) having the same inclination as the outer surface (A1) of the sealing lip (10). 5-7. (canceled) 8. A single piece sealing cover (1) for insertion into an opening (22, 22′, 22″) formed in an associated support (20, 20′, 20″) for closing and sealing the opening (22, 22′, 22″), the sealing cover (1) comprising: a main body portion (5) and an adjacent peripheral collar (7); an intermediate area (14) formed between the peripheral collar (7) and a continuous peripheral outer elastic sealing lip (10), the collar (7) being connected on a first end to the main body (5) and connected on a second end to the intermediate area (14), and the sealing lip (10) terminating at a first end with a plurality of serrated ribs (23) and connected on a second end to the intermediate area (14), the collar (7) including at least one detent ring (12) located opposite the sealing lip (10), the detent ring (12) protruding into an interior space (21) formed by the collar (7), the intermediate area (14), and the sealing lip (10), and the intermediate area (14) and the ribs (23) extending parallel to a covering surface (F) of the support (20,20′,20″) wherein the serrated ribs (23) remain in contact with the covering surface (F) during closing and sealing and are cementable to the covering surface (F). 9. The sealing cover (1) according to claim 8, wherein the detent ring (12) is substantially coplanar with the main body (5); and, the detent ring (12) at one end includes an impact lip (25) projecting into the interior space (21). 10. The sealing cover (1) according to claim 8, wherein the sealing lip (10) includes a first outer surface (A1) and the detent ring (12) includes a second outer surface (A2), the first outer surface (A1) is inclined towards the second outer surface (A2). 11. The sealing cover (1) according to claim 10, wherein the detent ring (12) includes an area (U) extending between the second outer surface (A2) and impact lip (25), the area (U) having substantially the same inclination as the first outer surface (A1) of the sealing lip (10). 12. A single piece sealing cover (1) for insertion into an opening (22, 22′, 22″) formed in an associated support (20, 20′, 20″) for closing and sealing the opening (22, 22′, 22″), the sealing cover (1) comprising: a main body portion (5) and an adjacent peripheral collar (7); a continuous peripheral outer lip (10) spaced apart from and extending circumferentially relative to the main body (5), the outer lip (10) including a plurality of serrated ribs (23) at a first end adapted to be cemented to a covering surface (F) of the associated support (20,20′,20″) adjacent the opening (22,22′,22″); and, an intermediate area (14) connecting the second end of the collar (7) with the sealing lip (10), the intermediate area (14) permitting relative axial movement between the main body (5) and the sealing lip (10) thereby maintaining contact between the ribs (23) and the covering surface (F) while closing and sealing the opening (22,22′,22″) with the cover (1). 13. The sealing cover (1) according to claim 12, wherein the collar (7) includes at least one detent ring (12) located opposite the sealing lip (10), the detent ring (12) protruding into an interior space (21) formed by the collar (7), the intermediate area (14), and the sealing lip (10). 14. The sealing cover (1) according to claim 12, wherein the collar (7) is connected on a first end to the main body (5) and connected on a second end to the intermediate area (14). 15. The sealing cover (1) according to claim 12, wherein: the detent ring (12) is substantially coplanar with the main body (5); and, the detent ring (12) at one end includes an impact lip (25) projecting into the interior space (21). 16. The sealing cover (1) according to claim 12, wherein the sealing lip (10) includes a first outer surface (A1) and the detent ring (12) includes a second outer surface (A2), the first outer surface (A1) is inclined towards the second outer surface (A2). 17. The sealing cover (1) according to claim 16, wherein the detent ring (12) includes an area (U) extending between the second outer surface (A2) and the impact lip (25), the area (U) having the same inclination as the first outer surface (A1) of the sealing lip (10).
The invention relates to a single-pieced sealing cover made of a thermoplastic elastomer, especially used to seal an opening in a support, comprising a base body, with an adjacent peripheral collar, according to the preamble of claim 1. Sealing covers of this kind (DE 35 12 582 C3, DE 37 13 503 C1) are already known as state of the art. These sealing covers respectively present an elastic sealing lip, and—opposite to same—one or several detent rings. As a result thereof; in mounted state, perfect sealing is to be assured, in addition to excellent holding property in a support. In order to satisfy the aforementioned requirements in such known constructions, it is a drawback that it is necessary to have available different sealing covers for different designs of the support in the area of its opening. Thus, the present invention is based on the object of creating a sealing cover of the initially mentioned type which will ensure secure and effective sealing of said support opening regardless of the design of the area of the support opening. Said object is solved according to the invention in that the collar is joined with the sealing lip by means of an intermediate area extending parallel vis-a-vis a covering surface of the support, so that the detent ring protrudes into an interior space formed by the intermediate area and the sealing lip, and that an exterior area of the sealing lip can be glued to the cover surface of the support. By means of the combined effect of these individual characteristics, a sealing cover of novel design is created which facilitates significant reduction in parts and which permits, due to the specifically employed thermoplastic elastomer, gluing to the cover surface in the area of the support opening. In addition to simple installation, this results in perfect sealing of the respective support opening. In further embodiment of the invention, the sealing lip can, to a large extent, cover the detent ring. According to a specific embodiment of the invention, there exists the possibility of the sealing lip presenting frontally, as exterior area, several serrated ribs, which can be glued to the covering surface of the support. These serrated ribs, in interaction with the detent ring, ensure secure sealing of the respective support opening, regardless of its configuration. Alternatively there also exists the possibility of the sealing lip being designed in conically tapering fashion vis-a-vis the covering surface of the support and that it can be glued together with same, resulting in the identical aforementioned effects. The detent ring can lie in the plane of the base body and present an impact lip in front. Furthermore, there exists the possibility that the outer surfaces of the sealing lip and the detent ring are inclined towards each other. Adjacent to the outer surface of the detent ring there may be an area which changes over into the impact lip, said area presenting the same inclination as the outer surface of the sealing lip. The invention is described in detail below by means of exemplary embodiments represented in the drawing. The drawing shows the following: FIG. 1 a center section through the invention-specific sealing cover in a first specific embodiment, FIG. 2a,b,c various design possibilities of the support opening in center section, partially refracted, FIG. 3 a bird's eye view of the sealing cover according to FIG. 1, partially refracted, FIG. 4 a lateral view of the sealing cover according to FIGS. 1 and 3, partially refracted, FIG. 5 an enlarged view of the area X according to FIG. 1, FIG. 6 another embodiment possibility of the invention in the area of the sealing lip, in center section, partially refracted. A single-piece sealing cover 1 is depicted in FIGS. 1, 3, 4 and 5, made of a thermoplastic elastomer. Said sealing cover specifically serves for sealing an opening 22 or 22′ or 22″ of a support shown schematically in FIG. 2. Said support, according to FIG. 2a, can present an outwardly oriented collar, according to FIG. 2b it can extend flat, and according to FIG. 2c, it can have an inwardly oriented collar. With the aid of the invention-specific sealing cover, there now exists the possibility of installing same in perfect fashion, even with differently designed supports 20, 20′ or 20″, in the area of the respective opening, and to seal said opening. The sealing cover 1 presents a base body 5, with an adjacent peripheral collar 7. The peripheral collar 7 passes over into at least one elastic sealing lip 10 abutting against one side of the support, whereby the collar 7 presents at least one detent ring 12, positioned opposite the sealing lip 10. As is especially apparent from FIGS. 1 and 5, collar 7 is connected with the sealing lip 10 by means of an intermediate area 14 extending parallel to a covering surface F (FIG. 2) of the support 20, 20′, 20″. Beyond that, the detent ring 12 protrudes into an interior space 21, formed by the intermediate area 14 and the sealing lip 10, as is specifically evident from FIG. 5. According to the invention, an outer area of the sealing lip 10 can now be glued to the covering surface F of the support 20, 20′, 20″. It is apparent from FIG. 1, that the sealing lip 10 largely covers the detent ring 12. In addition, in the specific embodiments according to FIGS. 1 and 5, the sealing lip 10 presents several serrated ribs 23 in front as exterior area, which can be glued to the covering surface F of the respective support. The detent ring 12 according to FIGS. 1 and 5 lies in the plane of the base body 5 and presents, frontally, an impact lip 25. It is specifically apparent from FIG. 5 that the outer surfaces A1, A2 of the sealing lip 10 and the detent ring 12 are inclined towards each other. According to the invention there also exists the possibility in this case that adjacent to the outer surface A2 of the detent ring 12 there extends is an area U, which changes over into the impact lip 25, said area U presenting somewhat the same inclination as the outer surface A1 of the sealing lip 10. If a support 20 is present according FIG. 2a with a correspondingly shaped collar, the sealing lip 10 with serrated ribs 23 impinges upon the area F of the support, while the detent ring 12 with impact lip 25 overgrips the respective collar of the support 20. With a support 20′ according to FIG. 2b, the elastic sealing lip 10 with serrated ribs 23 impinges upon the area F of support 20′, whereas the detent ring 12 with impact lip 25 overcovers the other side of the support and both elements are glued together. If a support 20″ with an opening 22″ exists, the respective collar positions itself again into the interior space 21 of the sealing cover 1, whereby the elastic sealing lip with its serrated ribs 23 is likewise glued together with the area F of support 20″. Instead of the specific embodiment according to FIGS. 1 and 5, in which the elastic sealing lip 10 presents several serrated ribs 23, there also exists the possibility according to FIG. 6 that in this case the elastic sealing lip 10′ is designed in conically tapering fashion towards the covering surface F of support 20, 20′, 20″ and is cementable with same. By virtue of the design of the interior space 21, the particular shape of the sealing lip 10 or 10′ and of the detent ring 12 and due to the special selection of material in that the sealing cover is made of a thermoplastic material, there is assurance, by simple means, of significant reduction of parts in the design of the sealing cover.
20050531
20090825
20050922
75969.0
0
MCKINLEY, CHRISTOPHER BRIAN
SINGLE-PIECE SEALING COVER
UNDISCOUNTED
0
ACCEPTED
2,005
10,512,440
ACCEPTED
Wound dressings comprising hydrated hydrogels and enzymes
A skin dressing, particularly a wound dressing, comprises oxidoreductase enzyme and, optionally, peroxidase enzyme, wherein the enzyme(s) are present in hydrated condition, e.g. being present in one or more hydrated hydrogels. The dressing is used by being located on the skin of a human or animal e.g. over a wound. The oxidoreductase enzyme catalyses a reaction that produces hydrogen peroxide from an appropriate substrate, the substrate either being naturally present in body fluids and/or being supplied separately and/or being incorporated into the dressing. The currently preferred oxidoreductase enzyme is glucose oxidase. The catalyses reaction of β-D-glucose substrate to give hydrogen peroxide and gluconic acid. A mixture of oxidoreductase enzyme can undergo reaction (optionally catalysed by the peroxidase enzyme) to produce a variety of species including reactive oxygen intermediates that have antimicrobial properties and that can therefore assist in promoting wound healing.
1. A skin dressing comprising oxidoreductase enzyme, wherein the enzyme is present in hydrated condition. 2. A dressing according to claim 1, wherein the oxidoreductase enzyme comprises glucose oxidase. 3. A dressing according to claim 1, wherein the dressing further comprises peroxidase enzyme present in hydrated condition. 4. A dressing according to claim 3, wherein the peroxidase enzyme comprises lactoperoxidase. 5. A dressing according to claim 4, wherein the dressing includes one or more hydrated hydrogels. 6. A dressing according to claim 5, wherein the gel comprises a hydrophilic polymer material. 7. A dressing according to claim 5, wherein the enzyme or enzymes are present in one or more hydrated hydrogels. 8. A dressing according to claim 1, wherein the enzyme or enzymes are located on an inert support. 9. A dressing according to claim 8, wherein the inert support comprises a cotton or cellulose woven gauze to which the enzyme or enzymes are irreversibly attached. 10. A dressing according to claim 1, wherein the dressing is of layered constructions. 11. A dressing according to claim 10, comprising a lower layer in the form of a hydrated gel and an upper layer in the form of an inert support carrying oxidoreductase enzyme and, optionally, peroxidase enzyme. 12. A dressing according to claim 11, wherein the hydrogel contains a source of substrate for the oxidoreductase enzyme. 13. A dressing according to claim 1, including a layer of barrier material at the interface with the skin in use. 14. A dressing according to claim 1, including a source of substrate for the oxidoreductase enzyme. 15. A dressing according to claim 14, wherein the substrate is located in a hydrated hydrogel. 16. A dressing according to claim 1, further including a supply of iodide. 17. A dressing according to claim 16, wherein the supply of iodide is located in a hydrated hydrogel. 18. A dressing according to claim 1, including a covering or outer layer for adhering the dressing to the skin of a human or animal subject. 19. A dressing according to claim 18, wherein the covering includes a window in or through which can be seen indicator means that indicates when the dressing chemistry is active. 20. A dressing according to claim 18, wherein immobilised catalase enzyme is provided on the inner surface of the covering. 21. A dressing according to claim 1, in the form of a multi-part system, with different elements separately packaged. 22. A dressing according to claim 21, wherein the oxidoreductase enzyme and a source of substrate for the oxidoreductase enzyme are in separate packages.
FIELD OF THE INVENTION This invention relates to skin dressings for application to a part of a human or animal body for treatment of skin, and relates particularly (but not exclusively) wound dressings for treatment of compromised skin, particularly skin lesions, i.e. any interruption in the surface of the skin, whether caused by injury or disease, including skin ulcers, burns, cuts, punctures, lacerations, blunt traumas, acne lesions, boils etc. BACKGROUND TO THE INVENTION Wounds frequently become infected. Wound dressings may carry antiseptic substances, and the physical protection they provide prevents ingress of extra infecting microbes, although this microbial exclusion is seldom absolute. Antiseptic substances carried on the dressing pad are not usually very effective, possibly because they do not readily diffuse into the wound at a steady rate. Moreover, the most effective substances, antibiotics, are not available for routine use, because of the ever-present problems of emerging drug resistance. Hydrogen peroxide (H2O2) is a known antimicrobial substance with many advantages. It is produced naturally in the body by white blood cells as part of the immune defence activities in response to infection. There are no known microbial evasion mechanisms by which microbes can escape its effects and it has a short lifetime, very rapidly breaking down to water and oxygen in the tissues. It therefore does not accumulate to dangerous levels. When it is to be applied topically (e.g. to treat acne), its effectiveness is enhanced by the fact that it readily penetrates the skin surface to reach underlying sites of infection. As hydrogen peroxide is so beneficial, it has been used for many years as an anti-microbial substance for cleansing wounds of all kinds and as a biologically compatible general antiseptic. In particular, hydrogen peroxide-containing ointments have been used, e.g., for treatment of leg ulcers, pressure sores, minor wounds and infection. There are, however, problems associated with the use of hydrogen peroxide. Hydrogen peroxide solution is very unstable and is readily oxidised to water and oxygen; further, hydrogen peroxide at high concentration can be damaging to normal skin and to cells responsible for healing in the wound bed. It is very difficult or even impossible to use hydrogen peroxide as part of a pre-dosed wound dressing: it's instability would make for a product with an impossibly short shelf-life, and dosing at the point of application would still not provide a sustained delivery over a usefully prolonged period. When it is used in wound treatment (as described in the British Pharmacopoeia, for example) very high concentrations (typically 3%) are needed to achieve a powerful antimicrobial effect over a very short time interval. Even this type of short burst can be effective, because of the great effectiveness of hydrogen peroxide, but there is the further disadvantage that such high concentrations can be relatively damaging to host cells and can impede the healing process. For this reason, use of hydrogen peroxide tends to be restricted to initial clean-up and sterilisation of wounds. Even so, it is a natural defence substance, produced by the body's own cells (at lower concentrations) and it is increasingly recognised as an intercellular and intracellular messenger molecule, involved in cell to cell molecular signalling and regulation. Undoubtedly, hydrogen peroxide is potentially a very beneficial molecule, if it can be used at the right concentrations and in the appropriate time course. U.S. Pat. No. 4,576,817 proposes a bacteriostatic fibrous wound dressing incorporating dry enzymes such as glucose oxidase and lactoperoxidase to generate e.g. hydrogen peroxide and hypoiodite on contact with serum. WO 01/28600 discloses a wound dressing including dry glucose oxidase, dry lactoperoxidase and an iodide salt in a polymeric matrix. The glucose oxidase catalyses an oxidation reaction of glucose present in body fluids of a wound site to generate hydrogen peroxide. The action of lactoperoxidase on hydrogen peroxide and iodide generates elemental iodine, which is a powerful anti-infective agent. Efficient wound healing is promoted by several factors, including a moist environment and the removal of wound exudates by absorption. Dry super-absorbent materials have often been used to gain the benefit of exudate removal, since these substances readily take up and hold fluids that exude from wounds with great efficiency. However, a highly efficient dry absorbent material can lead to an unhelpful lack of moisture, and a wound dressing constructed from such a material would not work well with antimicrobial enzymic systems, at least not until the dressing had become thoroughly wetted by wound fluid. SUMMARY OF THE INVENTION The present invention provides a skin dressing comprising oxidoreductase enzyme and optionally peroxidase enzyme, wherein the enzyme(s) are present in hydrated condition. The enzyme(s) are in hydrated condition in the dressing prior to use of the dressing, i.e. prior to application of the dressing to skin, and so also in the dressing when sealed in packaging. By providing the enzyme(s) in hydrated condition, the enzyme is present in a wet, active state in the dressing and can begin functioning immediately when brought into contact with appropriate substrate on use of the dressing. This is to be contrasted with prior art dressings where enzymes are in dry condition and require initial hydration on use, thus delaying enzyme functioning and consequent antimicrobial effects. The hydrated state of the enzyme also allows it to be formulated into a moist hydrogel or other moist dressing material in such a way that the dressing can donate moisture to a dry wound. The dressing is used by being located on the skin of a human or animal e.g. over a wound or on a region of skin to be treated for cosmetic or therapeutic purposes, e.g. for treatment of acne or other skin conditions. The oxidoreductase enzyme catalyses a reaction of an appropriate substrate with oxygen to produce hydrogen peroxide. The substrate may either be naturally present in body fluids and/or be supplied separately and/or be incorporated into the dressing. Oxidoreductase enzymes suitable for use in the invention and the corresponding substrates (which are present in blood and tissue fluids) include the following: Enzyme Substrate Glucose oxidase β-D glucose Hexose oxidase Hexose Cholesterol oxidase Cholesterol Galactose oxidase D-galactose Pyranose oxidase Pyranose Choline oxidase Choline Pyruvate oxidase Pyruvate Glycollate oxidase Glycollate Aminoacid oxidase Aminoacid The currently preferred oxidoreductase enzyme is glucose oxidase. This catalyses reaction of β-D-glucose substrate to give hydrogen peroxide and gluconic acid. A mixture of oxidoreductase enzymes may be used. If the reaction occurs on or in the vicinity of the skin, the hydrogen peroxide so produced can have a localised antibacterial effect. Alternatively or additionally, the hydrogen peroxide generated in this way may be used in a two stage arrangement, with the hydrogen peroxide undergoing a reaction catalysed by a peroxidase enzyme to produce a variety of species including reactive oxygen intermediates that have antimicrobial properties and that can therefore assist in promoting wound healing. For such embodiments, the dressing includes a peroxidase enzyme, preferably present in hydrated condition. As a further possibility the hydrogen peroxide can react directly in a non-catalysed manner with substances such as iodide ions to generate molecular iodine. Peroxidase enzymes useful in the invention include lactoperoxidase, horseradish peroxidase, iodide peroxidase, chloride peroxidase and myeloperoxidase, with lactoperoxidase currently being favoured. A mixture of peroxidase enzymes may be used. The active species produced by the action of peroxidase are difficult to define, and will to some extend depend the particular peroxidase in question. For example, horse radish peroxidase works very differently to lactoperoxidase. The detailed chemistry is complicated by the fact that the products are so reactive that they rapidly give rise to other, associated products that are also very reactive. It is believed that hydroxyl radicals, singlet oxygen and superoxide are produced, just as in the “oxidative burst” reactions identified in neutrophil and macrophage leukocytes of the human body, and in the well known “Fenton” reaction, based on the catalytic effects of ferric ions. The dressing includes a source of water so that the enzyme or enzymes are present in hydrated condition. The dressing may be in the form, e.g. of a moist cotton dressing or may include a structured wick material with moist ingredients. Preferably, however, the dressing includes one or more water-based or aqueous gels, also referred to as hydrated hydrogels. Such gels may be formed of a variety of materials and may contain a variety of reagents, as will be discussed below. A hydrated hydrogel provides a source of water for hydrating the enzyme or enzymes, promoting rapid reaction and consequent release of antimicrobial substances. The gel can also act to absorb water and other materials exuded from a wound site, enabling the dressing to perform a valuable and useful function by removing such materials from a wound site. The hydrated hydrogel also provides a source of moisture, that can function to maintain the enzyme or enzymes in the dressing in hydrated condition, and that can act in use to maintain a wound site moist, aiding healing. The or each hydrated hydrogel conveniently comprises hydrophilic polymer material. Suitable hydrophilic polymer materials include polyacrylates and methacrylates, e.g. as supplied by First Water Ltd in the form of proprietory hydrogels, including poly 2-acrylamido-2-methylpropane sulphonic acid (polyAMPS) or salts thereof (e.g. as described in WO 01/96422), polysaccharides e.g. polysaccharide gums particularly xanthan gum (e.g. available under the Trade Mark Keltrol), various sugars, polycarboxylic acids (e.g. available under the Trade Mark Gantrez AN-169 BF from ISP Europe), poly(methyl vinyl ether co-maleic anhydride) (e.g. available under the Trade Mark Gantrez AN 139, having a molecular weight in the range 20,000 to 40,000), polyvinyl pyrrolidone (e.g. in the form of commercially available grades known as PVP K-30 and PVP K-90), polyethylene oxide (e.g. available under the Trade Mark Polyox WSR-301), polyvinyl alcohol (e.g. available under the Trade Mark Elvanol), cross-linked polyacrylic polymer (e.g. available under the Trade Mark Carbopol EZ-1), celluloses and modified celluloses including hydroxypropyl cellulose (e.g. available under the Trade Mark Klucel EEF), sodium carboxymethyl cellulose (e.g. available under the Trade Mark Cellulose Gum 7LF) and hydroxyethyl cellulose (e.g. available under the Trade Mark Natrosol 250 LR). Mixtures of hydrophilic polymer materials may be used in a gel. In a hydrated hydrogel of hydrophilic polymer material, the hydrophilic polymer material is desirably present at a concentration of at least 1%, preferably at least 2%, more preferably at least 5%, possibly at least 10%, by weight based on the total weight of the gel. By using a gel comprising a relatively high concentration (at least 2% by weight) of hydrophilic polymer material, the gel can function particularly effectively to take up water in use of the dressing, e.g. from serum exudates while in contact with a wound. Because the gel is an aqueous system, use of the dressing does not have the effect of inducing an overall dryness of the wound which would be undesirable. This is because water vapour pressure is maintained in the enclosed environment surrounding the skin in use of the dressing. The gel thus functions as an absorbent entity for the removal of moisture, e.g. wound exudate, that also provides a helpful background level of moisture. The water-uptake capacity of a hydrated hydrogel, including a high concentration gel, enables the dressing to aid wound healing by removing substantial amounts of exudates, swelling-up as it does so. By using a carefully formulated, ready-hydrated gel, the wound is prevented from reaching a state of unhelpful dryness. Ready hydration also ensures the quick formation of a liquid interface between the dressing and the wound, thus preventing adhesion, which otherwise would interfere with easy lifting of the dressing when it has to be replaced. A good liquid interface between the wound and the dressing is also important in allowing the antimicrobial products of the enzymes to enter the wound through all of the available surface. The or each gel may contain various reagents, including one or more of the following: one or more oxidoreductase enzymes; one or more peroxidase enzymes; substrate for the oxidoreductase enzyme (to be discussed below); a source of iodide ions (to be discussed below); glycerol (which acts as a humectant and moisturiser), typically in an amount up to 20% by weight of the weight of the gel. In particular, the enzyme or enzymes may be present in one or more hydrated hydrogels. For example, one of the enzymes, oxidoreductase enzyme or peroxidase enzyme, may be present in a gel, e.g. an aqueous high concentration hydrophilic polymer material gel. As a further possibility both enzymes may be present in a gel, e.g. such a high concentration gel. A further option is for each enzyme to be present in a respective gel, e.g. an aqueous high concentration hydrophilic gel. As a further possibility, the dressing may include a single hydrated hydrogel (e.g. of poly AMPS), containing no enzymes but possibly containing substrate for the oxidoreductase enzyme (e.g. a source of glucose for glucose oxidase), additionally or alternatively containing a supply of iodide ions (e.g. in the form of one or more iodide salts) and optionally also containing glycerol. The or each gel may be cross-linked. For example, the gel may comprise an alginate gel, e.g. formed from alginic acid cross-linked in known manner, e.g. by use of calcium chloride. Cross-linked gels form an entrapping biopolymer matrix that can retain the enzyme within the gel if the degree of cross-linking is sufficiently tight, thus preventing release of the enzyme into the wound bed in use of the dressing. The gel may be in the form of beadlets, beads, slabs or extruded threads etc. The hydrated hydrogel, particularly a cross-linked gel, may be cast around a mechanical reinforcing structure, such as a sheet of cotton gauze or an inert flexible mesh, e.g. to providing a structurally reinforced hydrogel layer or slab. The hydrated hydrogel may alternatively be in the form of a non-cross-linked shear-thinning gel, e.g. of suitable gums such as xanthan gum (e.g. available under the Trade Mark Keltrol), in this case preferably without a mechanical reinforcing structure. Such gums are liquid when subjected to shear stress (e.g. when being poured or squeezed through a nozzle) but set when static. Thus the gel may be in the form of a pourable component, facilitating production of gels in the dressing. Such a shear-thinning gel may also be used in combination with a preformed, mechanically reinforced gel, as discussed above. The water-absorbing gel may utilise an increased concentration of hydrophilic substance, which may be the actual gel-forming polymer material, e.g. polysaccharide, itself or an additional substance added into the mixture for the sole purpose of absorbing water. One example of this type of functional mixture is that formed by a combination of cross-linked alginate at about 2% by weight and xanthan gum at about 5-10% by weight, based on the total weight of the gel. A particularly favoured version is that of covalently linked polymeric hydrogel such as polyAMPS, which is strongly water absorbing, being able to take up very large volumes of water or aqueous solutions. The enzyme or enzymes may be present in a gel in a number of possible forms, including in solution as free molecules. To improve efficiency of retention of the enzymes in the gel, the enzymes may be chemically conjugated to each other, chemically conjugated to other molecules (e.g. polyethylene imine), or incorporated in a solid support such as beads. Gels of different types, e.g. cross-linked alginate and shear-thinning, may be used together in a single dressing. Good results have been obtained with a shear-thinning gel nearest the skin, in use, and a cross-linked structurally reinforced gel remote from the skin. The enzyme or enzymes may be immobilised so they can be prevented from being released into a wound, where they would have the potential to trigger undesirable allergic responses (being generally derived from non-human sources, e.g. with most commercially available glucose oxidase being derived from the fungus Aspergillius niger and with lactoperoxidase typically being extracted from bovine milk) and would also be susceptible to degradation by the effect of proteases present in a wound. An enzyme may be immobilised in known manner, e.g. by being irreversibly bound to a solid support such as a particle, bead or fibre, e.g. of cellulose, silica, polymer etc., using coupling methods known to those skilled in the art. Incorporating an enzyme in a cross-linked alginate gel as discussed above, e.g. in the form of beadlets, slabs or extruded threads, also has the effect of immobilising the enzymes. Known encapsulation techniques using polyamide are also appropriate. In embodiments using oxidoreductase enzyme and peroxidase enzyme, the two enzymes may be located in separated hydrated hydrogels, with the oxidoreductase enzyme located in a first hydrated gel and the peroxidase located in a second hydrated gel. The first and second hydrated gels can be located in different regions of the dressing as required. The dressing desirably has a layered, stratified construction, e.g. comprising an upper (outer) layer of one gel and a lower (inner) layer of another gel. For example, the first gel (with oxidoreductase enzyme) may be located in the vicinity of the outer parts of the dressing, i.e. remote from the skin in use, where oxygen levels are highest, with the second gel (with peroxidase enzyme) being located in the vicinity of the inner parts of the dressing, i.e. adjacent the skin in use, so that the antimicrobial species (at least some of which are very short lived due to their extreme reactivity) produced thereby are close to the skin and are not expended before they reach the desired site of action. In this case the dressing thus has a layered, stratified construction, comprising an upper (outer) layer of the first gel and a lower (inner) layer of the second gel. However, experiments suggest that the relative location of the two enzymes is not critical. Some types of dressing desirably include a layer of barrier material at the interface with the skin in use, e.g. adjacent the second gel (with peroxidase enzyme) in the arrangement above, to prevent undesirable ingress to the dressing of catalase from the skin, e.g. from wound fluid or from microbes inhabiting the area. Ingress of catalase to the dressing is undesirable as this enzyme would compete with the peroxidase for reaction with hydrogen peroxide, thus reducing efficiency. Suitable barrier material includes, e.g. a semi-permeable sheet or membrane with a relatively low molecular weight cut-off that is permeable to the antimicrobial species produced by the peroxidative peroxidase but impermeable to catalase. Suitable materials are known to those skilled in the art and include cellulose acetate film such as that used to make dialysis membranes with a molecular weight cut-off of about 15 kD. As mentioned above, the dressing desirably includes a source of substrate for the oxidoreductase enzyme, e.g. glucose for glucose oxidase. Preferably the glucose is in the form of pure, pharmaceutical grade material. Glucose can also be supplied in the form of honey which naturally provides other benefits such as healing and antimicrobial factors. The substrate is desirably physically separated from the oxidoreductase enzyme prior to use of the dressing, to prevent premature reaction, although because oxygen is required for reaction then provided the supply of oxygen is limited only little reaction can occur. This will be discussed below. The substrate may be contained within an enclosure of a semi-permeable membrane material, e.g. material such as those used as dialysis membranes e.g. cellulose acetate (which is also often known as “visking tubing”), or within a gel slab or pad, e.g. of agarose. Such a gel slab or pad is desirably cast around a mechanical reinforcing structure, such as a sheet of cotton gauze etc., as discussed above. The substrate may conveniently be in the form of a shear-thinning gel, e.g. of a suitable gum such as xanthan gum as discussed above, preferably without a mechanical reinforcing structure, for pourable production. The substrate may alternatively be present in a hydrated gel, e.g. of hydrophilic polymer material as discussed above. The substrate, e.g. glucose is typically present in an amount up to about 25% by weight of the weight of the dressing. It is helpful to balance the relative amounts of enzyme and substrate such that there is an excess of hydrogen peroxide which, although less potent that the products of lactoperoxidase action, can act at a greater distance than the more reactive species. It is also believed that hydrogen peroxide can stimulate the formation of new blood vessels in the recovering wound (angiogenesis, or neovascular growth), stimulate the proliferation of new tissue-forming cells and activate enzymes (proteases) responsible for helping to reshape the developing new tissue. The substrate, e.g. glucose, may be present in various forms including dissolved within a hydrated hydrogel structure, present as a slowly dissolving solid, or encapsulated within another structure for slow release. In the embodiment of a dressing of layered construction, as mentioned above, the source of substrate can be located (in use of the dressing) sandwiched between the upper layer of first gel containing oxidoreductase enzyme and the lower layer of second gel containing peroxidase enzyme. In this case, oxidoreductase enzyme may optionally also be included in the second gel to oxidise substrate that is liable to diffuse towards the second gel. Such oxidation is dependent on the presence of oxygen, which is in restricted supply at this location, with the oxidation reaction being proportional to the available oxygen. In another alternative arrangement the peroxidase enzyme and substrate are both present in the second hydrated gel. In this case, the first hydrated gel (with oxidoreductase enzyme) is desirably located above and/or below the second gel in a layered arrangement. Yet another option is to have a 4 layered structure, with an upper layer (remote from the skin) of first hydrated gel overlying a layer of substrate that overlies a further layer of first hydrated gel, in turn overlying a second hydrated gel layer at the bottom (adjacent the skin in use). By providing an excess of substrate, so the dressing is able to function in use to generate antimicrobial species over an extended period of time, typically at least 2 days, where substrate-containing hydrated gel or gels are formulated to retard flow of substrate to the enzymes, e.g. by extensive hydrogen bonding to impede diffusion through the or from the hydrogel in which they were originally supplied. The antimicrobial efficiency of the system can be further enhanced by the inclusion of iodide ions, which can be oxidised to elemental iodine (which is a known powerful antimicrobial agents, e.g. as discussed in WO 01/28600) by the action of hydrogen peroxide, with or without catalytic effect. Thus, the dressing desirably includes a supply of iodide ions, e.g. potassium iodide or sodium iodide. As iodine is also relatively toxic to host cells in the wound (e.g. epithelial cells, keratinocytes, white blood cells) it may not be advantageous to generate iodine continuously at a high concentration throughout the time that the formulation is in use in contact with the skin. Thus, in a preferred embodiment, the supply of iodide ions, e.g. iodide salt, is provided in a relatively quick-release form, either in the substrate gel or in an additional membrane or gauze or other suitable layer. In this way, the hydrogen peroxide produced initially, in a first phase of activity, is substantially consumed in an iodine-generating reaction, exposing the skin (e.g. wound) to a surge of iodine, the duration of which can be controlled by the amount, release-rate and position of the iodide supply. Such an iodine surge can be very useful in quickly ridding a wound of a microbial burden, and its relatively short duration allows healing by minimising damage to growing cells and their repairing activity. Once the iodide has been consumed, the system automatically reverts, in a subsequent phase of activity, to the production of hydrogen peroxide and related reactive oxygen species (ROS), which maintains sterility and kills invading bacteria near the skin, e.g. wound surface. In other embodiments, however, it may be desired for the source of iodide ions to be such as to provide, in use, a sustained flux of iodine (and/or hypoiodous acid) for release into a wound, in addition (and in proportion) to hydrogen peroxide. The supply of iodide may alternatively be located with the source of substrate for the oxidoreductase enzyme, as discussed above, e.g. in a hydrated gel. The iodide may be present in various forms, including dissolved within a hydrated gel structure, present as a slowly dissolving solid, or encapsulated within another structure for slow release. Iodide salt may be present, e.g. in an amount up to about 2% by weight. However, even in the absence of iodide, antimicrobial active intermediates are still formed, as discussed above. In embodiments in which the enzyme or enzymes are not present in one or more hydrated gels, the enzyme or enzymes are conveniently irreversibly attached to an inert carrier or support. The support suitably comprises a gauze e.g. of woven material such as cotton or some other appropriate form of cellulose etc. The support may be activated in known manner so that it is able to react with protein (enzyme) to form stable imine bonds, so the enzyme is retained on the support. The attached enzyme may optionally be coated with a preserving agent, e.g. polyvinyl alcohol (PVA) e.g. at 5%, sucrose e.g. at 10%, gelatin e.g. at 2% and/or glycerol, to help maintain enzyme activity. The dressing is designed such that enzyme or enzymes are present in the dressing in hydrated condition. Covalently cross-linked gels such as polyAMPS can easily be made to exclude enzyme molecules whilst being permeable to hydrogen peroxide and iodine. In gels of this nature the enzyme or enzymes can be incorporated by dosing them onto the top surface of a substrate-containing hydrogel as an aqueous solution, and allowing the liquid to soak into the gel. Although the water penetrates the gel, the enzyme molecules are retained at the top surface. If the enzyme solution contains PVA (e.g. 6% w/v), the enzyme/PVA mixture forms a thin hydrated membrane as the water is drawn into the gel. Further, the PVA matrix stabilises the enzyme with which it is associated. It has been found that dressings in accordance with the invention act as efficient transporters of oxygen from the ambient atmosphere to a wound site, which has benefits for wound healing. In particular, the rate of oxygen transported through a dressing in accordance with the invention is greater than that of a similar dressing without oxidoreductase enzyme. The reason for this, and resulting benefits, are described below. When a conventional dressing is applied to the surface of a wound, the supply of oxygen from the atmosphere is generally inhibited and the wound becomes relatively deprived of oxygen (hypoxic or even anoxic). Hypoxia or, worse, anoxia are frequently encountered conditions known to be very bad for wound healing, because the cells responsible for the healing (keratinocytes and epithelial cells) and the leukocytes that fight infection and control the process, all need oxygen if they are to thrive. Phagocytic leukocytes need plentiful oxygen if they are to operate their “respiratory burst” biochemistry, with which they kill bacteria. Collagen is essential for rebuilding the damaged tissues, and for creating new blood vessels (angiogenesis), which need collagen fibres on which to construct capillary walls. Collagen synthesis can only take place when hydroxylase enzymes can hydroxylate lysine and proline, to give hydroxy-lysine and hydroxy-proline, both of which are essential building blocks of collagen. Hydroxylase enzymes need a plentiful supply of oxygen for their efficient functioning. For these reasons, it is widely recognized that wounds must be well oxygenated if they are to heal efficiently, and it is frequently claimed that oxygen supply can be the rate-limiting factor in wound healing. It is believed that a failure to heal is often caused by lack of adequate oxygen. Moreover, a high oxygen tension in a wound inhibits the growth of pathogenic anaerobic bacteria, which are also responsible for malodour production. For these reasons, certain secondary dressings, such as Tegaderm from 3M Healthcare Ltd or OpSite from Smith & Nephew (Tegaderm and OpSite are Trade Marks), are made from thin polyurethane film coated on one side with an adhesive layer. These are marketed as being relatively permeable to oxygen (and water vapour), because of their particular molecular structure and thin cross section. This is a purely passive effect, and the efficiency of oxygen permeation is inversely related to the thickness of the film. Hydrogels are not very permeable to oxygen, because they are composed primarily of water, and oxygen is not very soluble in water. Their permeability to oxygen will also be inversely related to the thickness of the dressing. Until the advent of this invention, the only way to increase the level of oxygen in a wound was to administer oxygen to the patient, either by increasing the amount in the blood (e.g. by causing the patient to breathe oxygen-enriched air or placing the patient in a hyperbaric oxygen environment such as that available in a compression chamber), or by applying gaseous oxygen to the wound itself. As noted above, dressings in accordance with the invention have the ability efficiently to transport oxygen from the ambient atmosphere outside the wound, into the wound bed, especially in cases where the dressing includes a layer of oxidoreductase enzyme, e.g. glucose oxidase, on the outer surface, in contact with the ambient atmosphere. Oxygen from the ambient atmosphere is converted to hydrogen peroxide (catalysed by the oxidoreductase enzyme). Hydrogen peroxide is much more soluble in water than is molecular oxygen, so hydrogen peroxide transport through the dressing (typically through one or more hydrated hydrogels) is generally much more efficient and rapid than that of molecular oxygen. Hydrogen peroxide thus diffuses rapidly through the dressing. When the hydrogen peroxide encounters catalase (which is naturally present in a wound, or which may be included as a component of the dressing), it decomposes to oxygen and water. In this way, oxygen is transported through the dressing in the form of hydrogen peroxide far more efficiently than transport of molecular oxygen. Experiments have shown that the rate of transport of oxygen can be more than doubled in dressings in accordance with the invention as compared with similar dressings without oxidoreductase enzyme. The resulting enhanced oxygen levels potentiate the healing process, as described above. The dressing conveniently includes, or is used with, a covering or outer layer for adhering the dressing to the skin of a human or animal subject (in known manner). At least part of the covering should be of oxygen-permeable material to enable oxygen from ambient air to pass through the covering and enter into the body of the dressing in use, where it is required as a cosubstrate of the oxidoreductase catalysed reaction. The oxygen-permeable material may be in the form of a “window” set into an otherwise relatively oxygen-impermeable covering, e.g. of possibly more robust material. Optionally the covering includes a window (or further window) in or through which can be seen indicator means e.g. an indicator sheet or similar structure that indicates (e.g. by changing colour) when the dressing chemistry is active. A further indicator may optionally be provided, which indicates (e.g. by changing colour) when the dressing chemistry has expired. A further useful option is to provide immobilised catalase enzyme on the inner surface of the covering (e.g. secured to adhesive thereof). This will function rapidly to break down any excess hydrogen peroxide which may escape from a wound area. This feature will prevent potentially damaging build-up of hydrogen peroxide in areas of normal, undamaged skin. The dressing may be supplied as a multi-part system, with different elements separately packaged, for assembly and use by an end user in accordance with supplied instructions. In particular, in embodiments including a source of substrate, e.g. glucose, this may be supplied packaged separately from other components, particularly the oxidoreductase enzyme, to prevent premature oxidation reaction. Alternatively, the dressing may be foldable. A typical embodiment of this sort comprises a linear arrangement of linked slabs or panels including a slab of the first hydrated gel, a slab of the second hydrated gel and a slab of substrate, with adjacent slabs linked by a respective hinge portion. Hydrophobic barrier material, e.g. a wax, is desirably impregnated into the hinge portions to prevent lateral diffusion Good results have been obtained with an embodiment comprising, in sequence, a slab of substrate, a slab of second hydrated hydrogel (containing peroxidase enzyme) and a slab of first hydrated hydrogel (containing oxidoreductase enzyme), with adjacent slabs linked by a respective foldable hinge portion. To prepare such a dressing for use the two outer slabs are folded in, to bring the slab of substrate so as to overly the slab of second gel and to bring the slab of first gel so as to overly the slab of substrate, thus forming a layered arrangement as described above. The resulting layered arrangement is placed on skin e.g. on a wound, with the slab of second gel in contact with the skin, and may be held in place e.g. by use of an adhesive covering. One or more components of the dressing may be contained within an enclosure such as a sachet or bag of barrier material that is permeable to oxygen, water and hydrogen peroxide but that prevents undesired migration of materials. Such an enclosure has the effect, inter alia, of preventing possibly interfering substances such as catalase, iron ions etc. being taken up into the dressing from a wound site. The enclosure may also prevent undesired migration of enzyme(s) into a wound. Suitable barrier material includes e.g. a semi-permeable sheet or membrane e.g. of cellulose acetate or cellulose ester, such as one that is permeable only to molecules of molecular weight less than, say, 350 Da (possibly having a nominal molecular weight cut-off of 500 Da but with an actual limit of less than 350 Da). Suitable membranes include cellulose acetate membrane code Z368024 supplied by Sigma, Spectrum SpectraPor cellulose ester membrane code 131054 supplied by NBS Biologicals and, currently favoured particularly for an anti-acne dressing, polyurethane, e.g. Tegaderm film from 3M. (Spectrum, SpectraPor and Tegaderm are Trade Marks). The water-absorbing components of the dressing can easily be applied to the wound or site of infection, especially when formulated into a workable or flowable form. There are many possible formulations that achieve this effect, and these can readily be determined by simple experimentation. Such formulations can be applied with particular ease and convenience from compressible tubes or syringe-like tubes (with a piston) with a nozzle of about 3 mm diameter. It can be especially helpful to supply the components in a simple assembly of two or more tubes, as required by the particular formulation in use, such that the desired mixture of gels can be expelled onto a particular site in a single action. Such multiple tube arrangements are well known and frequently used in the industry for other applications. This arrangement perfectly and conveniently satisfies the need to keep the gels apart from each other until the point of use. It has also been found that one or more of the components can be applied from a pressurised container, such that the gel is applied as a foam, spray or even an aerosol. Within the guidelines given here, the formulation that gives the particular physical properties (viscosity etc.) required for this mode of delivery can easily be determined by simple experimentation. Workable plastic gels from tubes or pressurised delivery gels can be used in combination with structured slabs to give an appropriate assembly of the basic ingredients. Dressings of layered construction comprising shear-thinning gels can be readily produced, e.g. by an end user, by pouring or dropping the gels one on top of the other in appropriate order to produce a desired layered assembly of gels. Thus the different dressing component gels may be supplied in separate containers e.g. tubes or bottles or possibly a multi-compartment jar. The different gels may be colour-coded with appropriately coloured latex for ease of identification. The gels may be applied directly to the skin of a user. A covering or outer layer may not be required with such embodiments. Dressings in accordance with the invention (or components thereof) are suitably supplied in sterile, sealed, water-impervious packages, e.g. laminated aluminium foil pouches. Dressings in accordance with the invention can be manufactured in a range of different sizes and shapes for treatment of areas of skin e.g. wounds of different sizes and shapes. Appropriate amounts of enzymes, and substrates and iodide if present, for a particular dressing can be readily determined by experiment. The invention will be further described, by way of illustration in the following Examples and with reference to the accompanying drawings, in which: FIGS. 1 to 6 are schematic sectional illustrations of 6 different embodiments of wound dressings in accordance with the invention. DETAILED DESCRIPTION OF EMBODIMENTS Referring to the drawings, FIGS. 1 to 4 illustrate schematically various different embodiments of wound dressings in accordance with the invention. In all of these drawings, a cross-hatched element represents a sachet of semi-permeable membrane e.g. cellulose acetate or gel slab containing an aqueous solution of glucose and potassium iodide; an element with bold hatching lines extending from upper left to lower right represents a hydrated hydrogel slab containing glucose oxidase trapped in the gel; and an element with bold hatching lines extending from upper right to lower left represents a hydrated hydrogel slab containing lactoperoxidase trapped in the gel. Filled circles represent beadlets of alginate gel (typically about 2 mm in diameter) containing entrapped glucose oxidase. Alternatively other gels (e.g. agarose) or polymers could be used to form the beadlets. Glucose is able to diffuse into these beadlets and hydrogen peroxide is able to diffuse out. Empty circles represent beadlets of alginate gel (typically about 2 mm diameter) containing entrapped lactoperoxidase. Alternatively other gels (e.g. agarose) or polymers could be used to form the beadlets. Hydrogen peroxide is able to diffuse into these beadlets and reactive oxygen species are able to diffuse out. Shaded circles represent beadlets of alginate gel (typically about 2 mm diameter) containing entrapped glucose and potassium iodide. Alternatively, other gels (e.g. agarose) or polymers could be used to form the beadlets. Glucose is able to diffuse out of these beadlets. FIG. 1 illustrates one preferred embodiment of wound dressing in accordance with the invention. The dressing is of layered construction and comprises an outer layer or covering 10 in the form of an oxygen-permeable self-adhesive plaster, suitable for adhering to the skin 12 of a subject, so as to cover a wound 14. Covering 10 encloses an upper layer comprising a first moist pad 16 with immobilised glucose oxidase, an intermediate layer comprising a solution of glucose and potassium iodide in a semi-permeable sachet or gel slab 18 and a lower layer comprising a second moist pad 20 with immobilised lactoperoxidase. Below pad 20 is a sheet 22 of gauze, for contact with the wound 14. The pads and sachet may be generally as described below. The dressing is initially supplied as a multi-part system, with the individual components separately packaged in respective sealed, sterile packages. When required for use, the dressing components are removed from the packages and applied to a wound in appropriate manner and order to produce the final dressing as shown. FIG. 2 illustrates another preferred embodiment of wound dressing, generally similar to FIG. 1, with similar components being identified by similar reference numerals. In this embodiment the upper layer comprises a first moist pad 24 with calcium alginate beads containing entrapped glucose oxidase. The intermediate layer comprises a pad 26 with gel beads containing glucose and potassium iodide. The lower layer comprises a second moist pad 28 with calcium alginate beads containing entrapped lactoperoxidase. FIG. 3 illustrates a further generally similar embodiment, but comprising an upper layer in the form of a pad 30 with gel beads containing glucose and potassium iodide, and a lower layer comprising a moist pad (or gel slab) 32 with calcium alginate beads containing entrapped glucose oxidase and calcium alginate beads containing entrapped lactoperoxidase. FIG. 4 is a variant of FIG. 3 in which the upper layer comprises a semi-permeable sachet or gel slab 34 containing glucose and potassium iodide. EXAMPLES Construction of Glucose Oxidase and Lactoperoxidase Beadlets. The enzyme, either lactoperoxidase (LPO) (from Sigma, cat no L2005) or glucose oxidase (GOX) (from Boehringer Mannheim, Cat No. 105147) is dissolved in pure water at the rate of 1 microgram per ml LPO) or 10 micrograms per ml (GOX). A solution of alginic acid (Manucol DM (Manucol DM is a Trade Mark) from C P Kelco) (1 gram per 100 ml of water) is prepared at elevated temperature and cooled. Enzyme solution is mixed with the cooled alginic acid at the appropriate rate. The resulting alginic acid/enzyme solution is then pumped through a peristaltic pump into a tube which leads to an exit nozzle conveniently formed by a standard laboratory glass pasteur pipette, placed over a setting bath of calcium chloride solution (10% w/v). The flow of the pump and height of the exit nozzle are adjusted so that the outflowing stream of alginic acid/enzyme solution forms into discrete droplets as it enters the calcium chloride solution. Each droplet rapidly starts to solidify as the calcium begins to cross-link the alginic acid molecules and, 10 minutes after the delivery of the last droplet, the setting process is complete. All the newly formed beadlets are removed from the calcium chloride solution by pouring the whole through a sieve of suitable mesh size. Residual calcium chloride is removed by rinsing with pure water. The beadlets are stored in water or in water-tight containers, or in a physiological buffer solution such as phosphate buffered saline. Alternatively, they can be placed in glycerol or glycerol in water solutions to decrease the entrained water content. Whatever storage conditions are used, they must not be allowed to dry out or harden in the absence of water or glycerol. Construction of Glucose Beadlets. The method described above is followed, except that no enzymes are added and glucose is included at the rate of 12.5 g per 100 ml in both the pure water and the calcium chloride setting bath. The gel beadlets are washed with calcium-free glucose solution, allowing removal of excess calcium without depleting the glucose. Preparation of an Enzyme Beadlet-Containing Pad. Appropriately sized cotton lint is placed on a suitable surface through which water can flow (e.g. a flat plastic mesh). A suspension of enzyme-beadlets is poured onto the cotton lint, in such a way that the beadlets become entrapped in the raised nap of the fabric, as the suspending water flows away. A second piece of lint is then placed over the first, so as to sandwich the enzyme beadlets between the two fabric layers. Adhesive or stitching or stapling may be used to secure the top layer to the bottom layer. Excess fluid is drained away, but the pad is not allowed to dry out. The number of beadlets contained per pad should be determined on the basis that each oxidase pad should carry about 100 mg of GOX, and each peroxidase pad should carry about 10 mg of LPO. Preparation of a Pad Containing Glucose Beadlets and Iodide The method described above is used with glucose-containing beadlets to prepare a pad containing entrapped glucose, except that an extra step is included at the end of the process, in which the pad is soaked in a solution of potassium iodide (10 mM). Preparation of a Glucose/Iodide Containing Sachet. Glucose is dissolved in a 5 mM aqueous solution of potassium iodide at the rate of 12.5 g per 100 ml. This solution is then placed in a dialysis bag (previously placed in boiling water for 10 mins and thoroughly rinsed) with an accessible area of about 40×20 nm, and sealed. Demonstration of the Oxidative Activity of an Assembled Composite Dressing. A 1% aqueous solution of agarose is prepared, with potassium iodide added at a concentration of 10 mM and soluble starch at concentration of 1% w/v. The solution is melted and dispensed into a petri dish to form a continuous layer about 5 mm thick, and allowed to set. Once set a peroxidase pad as described above is laid on the surface, followed by a glucose pad or sachet as described above laid on top of that, and finally a glucose oxidase pad as described above is laid on top of them both to form a three-layered stack. The development of a blue colour within the starch agar indicates the oxidative activity of the composite dressing. Use of the Assembled Composite Dressing as a Wound Treatment. The pads or sachets for this purpose prepared as described above are sealed in appropriate pouches and subjected to gamma irradiation to ensure microbiological sterility, using techniques known and routinely used in the industry. Firstly the wound is covered by a thin sheet of sterile gauze. Next the three layers of sterile pads are added as a thin stack, with the peroxidase pad first followed by the glucose pad or sachet next and the glucose oxidase pad last. The pads are cut to a size that just covers the open wound. Finally, the composite dressing is preferably held in place by adhesive film, such as normal “sticking plaster” or “Micropore” surgical tape. Other Embodiments. The enzymes can be immobilised on various types of particle or fibre, using coupling methods known by those skilled in the art. The particles can be made of cellulose, silica or various harmless polymers. Alginate can be used in forms other than beadlets, such as slabs or extruded threads, still using calcium as a setting agent. Microcapsules, such as those made by known techniques with polyamide, can be used to encapsulate each of the components. Further dressing components were prepared as follows. Preparation of an Enzyme-Containing Pad Loose woven cotton gauze is cut into a number of pieces approximately 100 mm by 100 mm and each piece is laid into a respective suitable flat bottomed container. 1% w/v alginic acid (also termed “alginate”; e.g. Manucol DM (Manucol DM is a Trade Mark), from CP Kelco) is prepared by dissolving the gel into an appropriate, heated aqueous solution. After cooling, enzyme is added to the alginate, to give a final concentration of 5 μg/ml glucose oxidase (GOX, from Boehringer Mannheim, cat. no.: 105147) or 10 μg/ml lactoperoxidase (LPO, from Sigma, cat. no.: L2005). 10 mls of each enzyme-alginate solution is prepared, and poured evenly onto the individual cotton gauze pads. The gel is set by the addition of excess 10% w/v calcium chloride (CaCl2) and allowed to stand for 10 minutes. The pads are then washed twice for 5 minutes each, in excess distilled/deionised water to remove the CaCl2. The pads can then be stored in a humid environment to prevent drying out. Preparation of Glucose-Containing Pad Loose woven cotton gauze is cut to approximately 100 mm by 100 mm and is laid into a suitable flat bottomed container. 1% w/v agarose and 40% w/v glucose is dissolved into an appropriate aqueous solution and poured onto the gauze while still molten. The gel is allowed to set by cooling. The gel pad can then be stored in a humid environment to prevent drying out. To produce a pad containing glucose and potassium iodide, a similar procedure is followed, but after the glucose and agarose have been dissolved, potassium iodide (KI) is added to a final concentration of 10 mM. The solution can then be poured, allowed to set and stored as above. Demonstration of the Anti-Microbial Properties of an Assembled Composite Dressing Example 1 Using standard practices, a 1.5% agarose microbial growth plate is prepared, but with the glucose replaced by fructose as the sole carbon source. The plates are typically in the region of 5 mm thick. Pseudomonas aeruginosa was spread over the surface of the plate in an even “lawn”. A pad containing LPO-alginate prepared as described immediately above) of approximately 20 mm2 was placed onto the surface of the plate. Placed directly onto this pad is a 20 mm2 pad containing glucose-agar (prepared as described immediately above) (with or without KI). Finally, a 20 mm2 pad containing GOX-alginate (prepared as described immediately above) was layered onto the glucose-agar pad. A clearance zone around the pad stack can be clearly seen after 24 hours, showing the production and diffusion of active anti-microbial species, preventing the growth of the applied bacteria. Removal of any one of the 3 pads (control experiments) results in no clearance zone around the pad stack, showing that both enzymes and glucose all need to be present for the cascade to progress effectively. Example 2 Alternatively, to show the production of reactive oxidative species via the stacked enzyme system, a 1% w/v agar plate is cast, that includes 1% soluble starch (e.g. ARCOS cat. no.: 177132500) and 10 mM KI. The plate is allowed to set by cooling. The LPO-alginate pad, followed by the glucose-agar pad and finally the GOX-alginate pad can then be stacked as described above in Example 1. The production of the reactive oxidative species can be then visualised by the intense blue coloured chromogen produced by the well documented interaction of elemental iodine (the oxidative species oxidise the iodide to iodine) and starch. This coloration can be clearly seen after 5 minutes, with the intensity and spread building over time. After 30 minutes, the colour intensity has built to become a deep blue, indicating continued product formation. This shows that both reactive oxidative species and iodine are produced, both of which aid in the anti-microbial activity of the composite dressing. Example 3 A variation on Example 2 is to include a low level of GOX (0.25 μg/ml) in the LPO-alginate pad, to promote an initial production of reactive oxidative species. This utilises oxygen available in the gel, and is initiated by the glucose that is diffusing into the LPO-alginate pad. This reaction is limited, due to the availability of oxygen and will cease when the oxygen is depleted. To show the production of reactive oxidative species via the stacked enzyme system, a 1% w/v agar plate is cast, that includes 1% soluble starch (e.g. ARCOS cat. no.: 177132500) and 10 mM KI. The plate is allowed to set by cooling. The combined LPO and GOX-alginate pad, followed by the glucose-agar pad and finally the GOX-alginate pad can the be stacked as described above. The accelerated production of the reactive oxidative species can be then visualised by the intense blue coloured chromogen produced by the well documented interaction of elemental iodine (the oxidative species oxidize the iodide to iodine) and starch. This coloration can be clearly seen after as little as 1 minute, with the intensity and spread building over time. The coloration will slow down noticeably after 15 minutes if the top GOX-alginate pad is not used. If the GOX-alginate pad is used as described above, the coloration will continue strongly, as seen in Example 2 above. After 30 minutes, the colour intensity has built to become a deep blue, indicating continued product formation. This shows that both reactive oxidative species and iodine are produced, both of which aid in the anti-microbial activity of the composite dressing. Further work was carried out using relatively high concentration xanthan gum gels. Preparation of Enzyme-Containing Xanthan Gum/Alginate Gels A series of solutions of xanthan gum (Keltrol) were prepared at different concentrations (5%, 10% and 20% by weight) by dissolving appropriate amounts of Keltrol into distilled/de-ionised water at room temperature (about 20° C.). A series of solutions of alginic acid (Manucol DM (Manucol DM is a Trade Mark) from CP Kelco) at different concentrations (2% and 4% by weight) were also prepared by dissolving appropriate amounts of Manucol DM into distilled/de-ionised water at appropriate elevated temperature. The resulting alginic acid solutions were cooled. A series of xanthan gum/alginate gels including the two materials in different proportions were prepared by mixing the solutions in appropriate quantities until a homogeneous mixture was obtained. For example, gels were prepared having a weight ratio of xanthan gum to alginate of 5:1 (e.g. by mixing equal amounts of 5% and 1% solutions or 10% and 2% solutions), 5:2, 10:1 etc. as required. Enzyme-containing gels were prepared by the addition of the appropriate quantity of glucose oxidase (GOX) or lactoperoxidase (LPO) enzymes to the gel samples. Enzyme solution may be added either to a xanthan gum or alginate solution prior to mixing, or to a xanthan gum/alginate gel after mixing. Experiments were carried out using LPO from Sigma, (catalogue number L2005) dissolved in pure water at the rate of 1 microgram per millilitre and GOX from Boehringer Mannheim (catalogue number 105147) dissolved in pure water at the rate of 10 micrograms per millilitre. Construction of Cross-Linked Xanthan Gum/Alginate Gel Pads Supported by Cotton Gauze A 10% xanthan gum 2% alginic acid gel mixture was prepared by mixing equal volumes of stock 20% xanthan gum solution and 4% alginic acid solution, prepared as described above. LPO and GOX were added to separate samples of this gel mixture to produce an LPO-containing gel and a GOX-containing gel. Enzyme levels can be varied according to the required level of activity. In this case enzyme levels used were 100 μg/ml for LPO and 50 μg/ml for GOX. Approximately 5 ml of the LPO-containing gel was smoothed onto a strip of cotton gauze approximately 40 mm×50 mm. A second layer of gauze of similar size was placed on top of the LPO gel with light pressure to ensure an even distribution of the gel. Approximately 5 ml of the GOX-containing gel was then dispensed onto the upper face of the second layer of cotton gauze, with a third layer of gauze of similar size applied on top of the GOX-containing gel, again with light pressure to ensure an even distribution of the GOX-containing gel. This produced a pad or slab of sandwich construction comprising three sheets of cotton gauze separated, respectively, by a layer of LPO-containing gel and a layer of GOX-containing gel. The resulting pads were placed in a bath of calcium chloride solution (10% w/v) for 10 minutes. The pads were removed from the bath and then washed to remove residual calcium chloride by two 10 minute washes in distilled/de-ionised water. Excess water was removed by drying the pads for several minutes in absorbent tissue. Demonstration of the Activity of the Cross-Linked Xanthan Gum/Alginate Gel Pad Example 4 The starch/iodine complex reaction was used to visualise the enzymatic production of reactive oxidative species (ROS) from within the cross-linked xanthan gum/alginate gel pad, prepared as described previously. In the presence of ROS, iodide is oxidised to produce elemental iodine, which complexes with starch to produce an intense blue chromogen. Experiments were carried out using a 1% w/v agar plate that includes 1% soluble starch (ARCOS catalogue number 177132500) and 10 mM potassium iodide. A slice of the cross-linked xanthan gum/alginate pad as described above (approximately 20 mm×10 mm×4 mm) was placed on the starch/iodide plate, with the GOX layer uppermost. On top of this was placed a pad of gel comprising 40% glucose in 1% agar to initiate the reaction. After about 30 minutes the lower pad had turned yellow, clearly indicating the production of elemental iodine (iodide being present due to diffusion from the plate into the gel). After about 1 hour, blue staining was visible beneath the pad, indicating the presence of ROS within the starch/iodide plate. 24 hours after initiation, a large area of the plate had turned blue, indicating continued production of ROS. Example 5 Two similar experiments were carried out using an arrangement generally as described above in Example 4 but with the glucose pad below the cross-linked xanthan gum/alginate pad. Two experiments were carried out, with the xanthan gum/alginate gel pads in different orientations, in one case with the GOX layer uppermost and with the other with the LPO layer uppermost. With the pad positioned with the GOX layer lowermost, next to the glucose pad, after approximately 1 hour blue staining could be seen under the pad. With the other experiment, with the LPO layer lowermost, next to the glucose pad, after about 2 hours blue staining could be seen under the pad. This shows that even with an arrangement using a pad with enzymes in non-optimal sequence, ROS can still be produced in sufficient quantity to produce an oxidative effect in the indicator plate. In both experiments, yellow coloration was seen in both gels, in the LPO layers, showing the presence of iodine production. After 24 hours, in both cases much of the starch/iodide plate had turned blue, again showing the production of ROS. Demonstration of the Moisture Absorbency of a Xanthan Gum Gel A 10% by weight preparation of Keltrol in water was prepared as described above. 1.06 g of the 10% gel was added to 10.22 g of distilled/de-ionised water, maintained at 21° C. and sealed to minimise evaporation effects. The water was decanted off and measured by weight to assess the degree of absorbency. After 15 minutes, 8.34 g of water remained; after 45 minutes, 7.56 g remained; after 2 hours 6.51 g remained; after 18 hours, 2.1 g remained. This experiment shows that the 10% Keltrol gel is able to absorb at least 8 times its weight in water. Demonstration of the Moisture Absorbency of a Cross-Linked Xanthan Gum/Alginate Gel Mixture A mixture of 5% by weight Keltrol and 1% by weight alginic acid was prepared as described above. Two layers of gel were cast between two layers of cotton gauze to produce a pad that was cross-linked using a 10% calcium chloride solution and washed twice for 10 minutes in water, as described above. The pad was blotted dry using absorbent tissue paper. A piece of the pad 10 mm×10 mm×3 mm was weighed to establish the initial weight (0.28 g). 1 ml of water was added to the pad. The pad was removed and weighed after various times to assess the increase in weight (due to absorption of water). After one 1 hour the weight of the pad was 0.37 g; after 2 hours 0.44 g; after 3 hours 0.49 g and after 6 hours 0.5 g. This experiment shows that the cross-linked xanthan gum/alginate gel is still able to absorb water. Compared with the Example above using 10% Keltrol, use of a lower percentage of Keltrol and cross-linked alginate results in less water absorbency. Cross-linked xanthan gum/alginate gels prepared as described above were used in the production of a wound dressing in accordance with the invention, as shown schematically in FIG. 1. Such gels were used together with a glucose/iodide containing sachet prepared as described above. In particular, glucose was dissolved in a 5 mM aqueous solution of potassium iodide at the rate of 12.5 g per 100 ml. The solution was placed in a dialysis bag (previously placed in boiling water for 10 minutes and thoroughly rinsed) with an accessible area of about 40×20 mM, and sealed. The components were assembled to form a dressing of the construction shown in FIG. 1. The dressing is of layered construction and comprises an outer layer or covering 10 in the form of an oxygen-permeable self-adhesive plaster, suitable for adhering to the skin 12 of a subjects so as to cover a wound. Covering 10 encloses an upper layer comprising a pad of glucose oxidase-containing cross-linked xanthan gum/alginate gel, prepared as described above; an intermediate layer comprising a solution of glucose and potassium iodide in a semi-permeable sachet 18, prepared as described above; and a lower layer comprising a slab of lactoperoxidase-containing cross-linked xanthan gum/alginate gel prepared as described above. Below pad 20 is a sheet 22 of gauze, for contact with the wound 14. The dressing is initially supplied as a multi-part system, with the individual components separately packaged in respective sealed, sterile packages. When required for use the dressing components are removed from the packages and applied to a wound in appropriate manner in order to produce the final dressing as shown. FIG. 5 illustrates schematically a further embodiment of dressing in accordance with the invention. This form of dressing is currently favoured. The dressing has major dimensions of 100 mm×100 mm, in the form of a square. The illustrated dressing comprises a soft, hydrated hydrogel slab 50 composed of polyAMPS (as described in WO 01/96422 supplied by First Water Ltd). The hydrogel contains up to 23% glucose (which acts as a substrate for oxidoreductase enzyme) and iodide salts e.g. 1.6% w/v potassium iodide (which are a precursor to iodine). The hydrogel may also contain up to 20% w/v glycerol (which acts as a humectant and moisturiser). The hydrogel slab 50 forms the lower layer of the dressing. The dressing also comprises an upper layer constituted by a cellulose woven gauze 52 to which are irreversibly (covalently) bound glucose oxidase and lactoperoxidase. The gauze 52 is prepared as follows. The gauze is cut to a suitable size and shape (a square 100 mm×100 mm), and is washed in water to remove any solutes or particulates. Excess fluid is removed. The gauze is then soaked in a solution of 10 mM sodium meta-periodate for 60 minutes at 25° C. After this oxidation step, where reactive aldehyde groups are formed, the gauze is extensively washed in water to remove the periodate. After the wash step, the gauze is soaked in a solution of glucose oxidase (Biocatalysts—Code G638P), at 100 μg powder per ml 50 mM sodium hydrogen carbonate at pH 9.0. This is equivalent to 7000 U/ml. Lactoperoxidase (DMV International) is also incorporated at 100 μl powder per ml 50 mM sodium hydrogen carbonate at pH 9.0. These doses can be reduced, since they represent an excessive amount of activity. The gauze is left to react with the enzyme solution for 4 hours at about 20° C., after which the gauze is removed and washed extensively between low ionic strength solution (deionised water) and high ionic strength buffer (50 mM NaH2CO3 pH 9.0+1M NaCl) to remove loosely bound enzyme. The gauze is then coated in a preservative, for example 5% PVA, 10% sucrose or 2% gelatin and dried either at room temperature (approximately 21° C.) or, preferably, at 40° C. The lower and upper layers are assembled with each other in a nitrogen atmosphere (to prevent premature reaction), and are packaged together by being sealed in an oxygen-impermeable pouch or enclosure, e.g. made of laminated aluminium foil pouches as supplied by Sigma (code Z183407). The interaction of the glucose in the gel with the immobilised glucose oxidase is limited by the rate at which the glucose can diffuse into the immobilised-enzyme layer. This delay is sufficient to allow the two layers to be assembled together in the presence of oxygen, and then placed in an oxygen-free package, before any substantial reaction can take place. Once oxygen is excluded from the assembled product, the reaction is arrested anyway, and it can only resume when the oxygen supply is renewed (e.g. when the product is removed from the packaging for use on a wound). This oxygen deprivation within the packaging prevents the glucose from being used up in premature peroxide production. The enzymes, while initially in dry form on the gauze on assembly, become hydrated with water from the hydrogel slab 52 and are maintained in hydrated condition by water from the hydrogel slab 52 while sealed in the pouch or enclosure prior to use. In use, the dressing is removed from the pouch or enclosure and placed on the skin of a patient over a wound site, shown schematically at 54, with the lower hydrogel layer 50 in contact with the skin. An oxygen-permeable and moisture-permeable covering or overlayer 56 (which may or may not form part of the dressing) is located over the upper layer 52 and is adhered to the skin surrounding the wound site by means of suitable adhesive provided on the lower face of overlayer 56. In this way the dressing is retained in position on the skin, covering the wound site. The glucose oxidase in the upper layer (which is in hydrated condition) catalyses reaction of the glucose in the lower layer with oxygen that passes through the overlayer 56 from the surroundings, producing hydrogen peroxide as discussed above. The hydrogen peroxide itself has beneficial antimicrobial effects, as discussed above. The hydrogen peroxide also undergoes a further reaction catalysed by the lactoperoxidase to produce a variety of species with antimicrobial properties, as discussed above. In addition, the iodide salts in the lower layer react to produce elemental iodine and possibly also hypoiodous acid, further powerful antimicrobial agents, as discussed above. The dressing thus has a number of very effective mechanisms for in-situ production of antimicrobial agents that can be very effective in promoting wound healing. Further, the hydrogel of the lower layer is highly fluid absorbent, allowing the take-up of high volumes of exudate from the wound. Fluid exuded from the wound, including potentially harmful bacteria etc, can thus be absorbed into the dressing and killed by the antimicrobial species generated therein. The dressing can thus be self-sterilising. The hydrogel is also able to donate fluid, should the wound require it, thus allowing the wound site to be kept moist at all times aiding the healing process. In a modification of the FIG. 5 embodiment described above, no lactoperoxidase is present. In this case, although the hydrogen peroxide produced by the reaction catalysed by the glucose oxidase does not undergo lactoperoxidase-catalysed reaction, nevertheless useful amounts of the hydrogen peroxide spontaneously undergo non-catalysed reaction with iodide ions to generate molecular iodine and valuable antimicrobial effects are nevertheless still obtained. FIG. 6 illustrates schematically yet a further embodiment of dressing in accordance with the invention. This form of dressing is currently most favoured. The dressing has major dimensions of 100 mm×100 mm, in the form of a square. The illustrated anti-bacterial and anti-fungal wound dressing comprises a glucose-containing hydrogel slab 60 as the lower layer of the dressing. Cast onto the upper surface of slab 60 is a film 62 of PVA (polyvinyl alcohol) that incorporates glucose oxidase. The hydrogel lower layer 60 was formulated to include the following reagents by weight: 20% sodium AMPS (2-acrylamido-2-methylpropanesulfonic acid, sodium salt (Lubrizol, code 2405)), 20% glucose (Fisher, analytical grade), 10% glycerol (Fisher, analytical grade), 50% deionised water, 0.1% poly ethylene glycol 400 diacrylate (UCB Chemicals) and 0.01% photoinitiator (1-hydroxycyclohexyl phenyl ketone (Aldrich)). The mixture was dispensed into casting trays, to a depth of 2-3 mm. The hydrogel was then set, by irradiation under a UV lamp, for up to 60 seconds and a power rating of approx. 100 mW/cm2. The hydrogel was then allowed to cool to 30° C. or below. The enzyme-containing PVA film 62 was prepared by dissolving high molecular weight PVA (124,000-186,000 mw, Aldrich) in water by heating the mixture. The PVA was incorporated to a final concentration of 6% w/v. Once dissolved, the solution was allowed to cool to 30° C. or below, before enzyme (glucose oxidase (GOX, Biocatalysts G638P)) was added, to a concentration of 100 μg/μl (weight freeze dried powder per volume). 50-100 μl of the PVA/GOX mixture was then added to a 20 mm2 surface of the cooled hydrogel, and allowed to set. A thin film was formed after approximately 30 mins. To prevent enzyme activation, the addition of the PVA/GOX solution to the glucose hydrogel may be carried out in an oxygen-free atmosphere (e.g. under nitrogen). When film 62 contacts the hydrogel 60, most of the water from the film is drawn into the hydrogel, leaving the PVA as a moist membrane containing the enzyme in hydrated condition. Sufficient water remains in the film for the PVA to be hydrated and to remain flexible. The resulting dressing is packaged in an oxygen-impermeable pouch or enclosure, e.g. made of laminated aluminium foil pouches as supplied by Sigma (code Z183407). The interaction of the glucose in the gel with the immobilised glucose oxidase is limited by the rate at which the glucose can diffuse into the immobilised-enzyme layer. This delay is sufficient to allow the two layers to be assembled together in the presence of oxygen, and then placed in an oxygen-free package, before any substantial reaction can take place. Once oxygen is excluded from the assembled product, the reaction is arrested anyway, and it can only resume when the oxygen supply is renewed (e.g. when the product is removed from the packaging for use on a wound). This oxygen deprivation within the packaging prevents the glucose from being used up in premature peroxide production. The enzyme is maintained in hydrated condition while sealed in the pouch or enclosure prior to use. In use, the dressing is removed from the pouch or enclosure and placed on the skin of a patient over a wound site, shown schematically at 64, with the lower hydrogel layer 60 in contact with the skin. An oxygen-permeable and moisture-permeable covering or overlayer 66 (which may or may not form part of the dressing) is located over the film 62 and is adhered to the skin surrounding the wound site by means of suitable adhesive provided on the lower face of overlayer 66. In this way the dressing is retained in position on the skin, covering the wound site. The glucose oxidase in the film 62 (which is in hydrated condition) catalyses reaction of the glucose in the lower layer with oxygen that passes through the overlayer 66 from the surroundings, producing hydrogen peroxide as discussed above. The hydrogen peroxide has beneficial antimicrobial effects, as discussed above, and the oxygen released when it is decomposed by endogenous catalase aids the healing process by supporting cellular metabolism, potentiating amino acid hydroxylation and inhibiting the growth of anaerobic bacteria. To demonstrate the generation of oxidative species, an indicator plate consisting of 1% starch (Aldrich), 100 mM potassium iodide (Fisher) and 1% agar (Sigma) was used. The dressing comprising hydrogel 60 with PVA/GOX film 62 was placed onto the indicator plate, in air, with the GOX thus being activated through the available oxygen. Hydrogen peroxide is produced in sufficient quantity to be able to diffuse through the hydrogel and reach the indicator plate below. The oxidative power of the hydrogen peroxide then oxidises iodide to iodine, which complexes with the starch to form an intense dark blue complex. By removing the activated hydrogel dressing and placing it onto new indicator plates at 24 hour intervals, sustained hydrogen peroxide release can be demonstrated over a period of at least 5 days. In addition, to demonstrate further the stability of the GOX enzyme in the PVA film, the film was removed from a hydrogel after 4 days use, and placed onto fresh 20 mm2 glucose hydrogel and placed onto an indicator plate. After 24 hours, the intense blue starch/iodide complex was clearly visible, indicating enzyme activity was still present in the PVA film. To demonstrate the localised GOX activity in a glucose-free hydrogel, a PVA/GOX film was produced as described above. The hydrogel was placed onto a bed of PBS (phosphate buffered saline) saturated cotton gauze, and allowed to swell slowly over 24 hours. The hydrogel was then sliced into two, through the horizontal plane, and bathed in a solution of 1% starch+100 mM potassium iodide+1% w/v glucose+5 mM EDTA+50 μg/ml lactoperoxidase. Very quickly, the presence of GOX can be localised, by the detection of hydrogen peroxide. The GOX activity is clearly localised to the PVA film and the contact surface of the hydrogel where the PVA film was cast. Beneath this, there was no colour generation, thus showing that GOX is not mobile in the AMPS hydrogel, even in a swollen state. The hydrogel slab 60 is highly fluid-absorbent, and so has the properties and benefits describes above in connection with the FIG. 5 embodiment.
<SOH> BACKGROUND TO THE INVENTION <EOH>Wounds frequently become infected. Wound dressings may carry antiseptic substances, and the physical protection they provide prevents ingress of extra infecting microbes, although this microbial exclusion is seldom absolute. Antiseptic substances carried on the dressing pad are not usually very effective, possibly because they do not readily diffuse into the wound at a steady rate. Moreover, the most effective substances, antibiotics, are not available for routine use, because of the ever-present problems of emerging drug resistance. Hydrogen peroxide (H 2 O 2 ) is a known antimicrobial substance with many advantages. It is produced naturally in the body by white blood cells as part of the immune defence activities in response to infection. There are no known microbial evasion mechanisms by which microbes can escape its effects and it has a short lifetime, very rapidly breaking down to water and oxygen in the tissues. It therefore does not accumulate to dangerous levels. When it is to be applied topically (e.g. to treat acne), its effectiveness is enhanced by the fact that it readily penetrates the skin surface to reach underlying sites of infection. As hydrogen peroxide is so beneficial, it has been used for many years as an anti-microbial substance for cleansing wounds of all kinds and as a biologically compatible general antiseptic. In particular, hydrogen peroxide-containing ointments have been used, e.g., for treatment of leg ulcers, pressure sores, minor wounds and infection. There are, however, problems associated with the use of hydrogen peroxide. Hydrogen peroxide solution is very unstable and is readily oxidised to water and oxygen; further, hydrogen peroxide at high concentration can be damaging to normal skin and to cells responsible for healing in the wound bed. It is very difficult or even impossible to use hydrogen peroxide as part of a pre-dosed wound dressing: it's instability would make for a product with an impossibly short shelf-life, and dosing at the point of application would still not provide a sustained delivery over a usefully prolonged period. When it is used in wound treatment (as described in the British Pharmacopoeia, for example) very high concentrations (typically 3%) are needed to achieve a powerful antimicrobial effect over a very short time interval. Even this type of short burst can be effective, because of the great effectiveness of hydrogen peroxide, but there is the further disadvantage that such high concentrations can be relatively damaging to host cells and can impede the healing process. For this reason, use of hydrogen peroxide tends to be restricted to initial clean-up and sterilisation of wounds. Even so, it is a natural defence substance, produced by the body's own cells (at lower concentrations) and it is increasingly recognised as an intercellular and intracellular messenger molecule, involved in cell to cell molecular signalling and regulation. Undoubtedly, hydrogen peroxide is potentially a very beneficial molecule, if it can be used at the right concentrations and in the appropriate time course. U.S. Pat. No. 4,576,817 proposes a bacteriostatic fibrous wound dressing incorporating dry enzymes such as glucose oxidase and lactoperoxidase to generate e.g. hydrogen peroxide and hypoiodite on contact with serum. WO 01/28600 discloses a wound dressing including dry glucose oxidase, dry lactoperoxidase and an iodide salt in a polymeric matrix. The glucose oxidase catalyses an oxidation reaction of glucose present in body fluids of a wound site to generate hydrogen peroxide. The action of lactoperoxidase on hydrogen peroxide and iodide generates elemental iodine, which is a powerful anti-infective agent. Efficient wound healing is promoted by several factors, including a moist environment and the removal of wound exudates by absorption. Dry super-absorbent materials have often been used to gain the benefit of exudate removal, since these substances readily take up and hold fluids that exude from wounds with great efficiency. However, a highly efficient dry absorbent material can lead to an unhelpful lack of moisture, and a wound dressing constructed from such a material would not work well with antimicrobial enzymic systems, at least not until the dressing had become thoroughly wetted by wound fluid.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides a skin dressing comprising oxidoreductase enzyme and optionally peroxidase enzyme, wherein the enzyme(s) are present in hydrated condition. The enzyme(s) are in hydrated condition in the dressing prior to use of the dressing, i.e. prior to application of the dressing to skin, and so also in the dressing when sealed in packaging. By providing the enzyme(s) in hydrated condition, the enzyme is present in a wet, active state in the dressing and can begin functioning immediately when brought into contact with appropriate substrate on use of the dressing. This is to be contrasted with prior art dressings where enzymes are in dry condition and require initial hydration on use, thus delaying enzyme functioning and consequent antimicrobial effects. The hydrated state of the enzyme also allows it to be formulated into a moist hydrogel or other moist dressing material in such a way that the dressing can donate moisture to a dry wound. The dressing is used by being located on the skin of a human or animal e.g. over a wound or on a region of skin to be treated for cosmetic or therapeutic purposes, e.g. for treatment of acne or other skin conditions. The oxidoreductase enzyme catalyses a reaction of an appropriate substrate with oxygen to produce hydrogen peroxide. The substrate may either be naturally present in body fluids and/or be supplied separately and/or be incorporated into the dressing. Oxidoreductase enzymes suitable for use in the invention and the corresponding substrates (which are present in blood and tissue fluids) include the following: Enzyme Substrate Glucose oxidase β-D glucose Hexose oxidase Hexose Cholesterol oxidase Cholesterol Galactose oxidase D-galactose Pyranose oxidase Pyranose Choline oxidase Choline Pyruvate oxidase Pyruvate Glycollate oxidase Glycollate Aminoacid oxidase Aminoacid The currently preferred oxidoreductase enzyme is glucose oxidase. This catalyses reaction of β-D-glucose substrate to give hydrogen peroxide and gluconic acid. A mixture of oxidoreductase enzymes may be used. If the reaction occurs on or in the vicinity of the skin, the hydrogen peroxide so produced can have a localised antibacterial effect. Alternatively or additionally, the hydrogen peroxide generated in this way may be used in a two stage arrangement, with the hydrogen peroxide undergoing a reaction catalysed by a peroxidase enzyme to produce a variety of species including reactive oxygen intermediates that have antimicrobial properties and that can therefore assist in promoting wound healing. For such embodiments, the dressing includes a peroxidase enzyme, preferably present in hydrated condition. As a further possibility the hydrogen peroxide can react directly in a non-catalysed manner with substances such as iodide ions to generate molecular iodine. Peroxidase enzymes useful in the invention include lactoperoxidase, horseradish peroxidase, iodide peroxidase, chloride peroxidase and myeloperoxidase, with lactoperoxidase currently being favoured. A mixture of peroxidase enzymes may be used. The active species produced by the action of peroxidase are difficult to define, and will to some extend depend the particular peroxidase in question. For example, horse radish peroxidase works very differently to lactoperoxidase. The detailed chemistry is complicated by the fact that the products are so reactive that they rapidly give rise to other, associated products that are also very reactive. It is believed that hydroxyl radicals, singlet oxygen and superoxide are produced, just as in the “oxidative burst” reactions identified in neutrophil and macrophage leukocytes of the human body, and in the well known “Fenton” reaction, based on the catalytic effects of ferric ions. The dressing includes a source of water so that the enzyme or enzymes are present in hydrated condition. The dressing may be in the form, e.g. of a moist cotton dressing or may include a structured wick material with moist ingredients. Preferably, however, the dressing includes one or more water-based or aqueous gels, also referred to as hydrated hydrogels. Such gels may be formed of a variety of materials and may contain a variety of reagents, as will be discussed below. A hydrated hydrogel provides a source of water for hydrating the enzyme or enzymes, promoting rapid reaction and consequent release of antimicrobial substances. The gel can also act to absorb water and other materials exuded from a wound site, enabling the dressing to perform a valuable and useful function by removing such materials from a wound site. The hydrated hydrogel also provides a source of moisture, that can function to maintain the enzyme or enzymes in the dressing in hydrated condition, and that can act in use to maintain a wound site moist, aiding healing. The or each hydrated hydrogel conveniently comprises hydrophilic polymer material. Suitable hydrophilic polymer materials include polyacrylates and methacrylates, e.g. as supplied by First Water Ltd in the form of proprietory hydrogels, including poly 2-acrylamido-2-methylpropane sulphonic acid (polyAMPS) or salts thereof (e.g. as described in WO 01/96422), polysaccharides e.g. polysaccharide gums particularly xanthan gum (e.g. available under the Trade Mark Keltrol), various sugars, polycarboxylic acids (e.g. available under the Trade Mark Gantrez AN-169 BF from ISP Europe), poly(methyl vinyl ether co-maleic anhydride) (e.g. available under the Trade Mark Gantrez AN 139, having a molecular weight in the range 20,000 to 40,000), polyvinyl pyrrolidone (e.g. in the form of commercially available grades known as PVP K-30 and PVP K-90), polyethylene oxide (e.g. available under the Trade Mark Polyox WSR-301), polyvinyl alcohol (e.g. available under the Trade Mark Elvanol), cross-linked polyacrylic polymer (e.g. available under the Trade Mark Carbopol EZ-1), celluloses and modified celluloses including hydroxypropyl cellulose (e.g. available under the Trade Mark Klucel EEF), sodium carboxymethyl cellulose (e.g. available under the Trade Mark Cellulose Gum 7LF) and hydroxyethyl cellulose (e.g. available under the Trade Mark Natrosol 250 LR). Mixtures of hydrophilic polymer materials may be used in a gel. In a hydrated hydrogel of hydrophilic polymer material, the hydrophilic polymer material is desirably present at a concentration of at least 1%, preferably at least 2%, more preferably at least 5%, possibly at least 10%, by weight based on the total weight of the gel. By using a gel comprising a relatively high concentration (at least 2% by weight) of hydrophilic polymer material, the gel can function particularly effectively to take up water in use of the dressing, e.g. from serum exudates while in contact with a wound. Because the gel is an aqueous system, use of the dressing does not have the effect of inducing an overall dryness of the wound which would be undesirable. This is because water vapour pressure is maintained in the enclosed environment surrounding the skin in use of the dressing. The gel thus functions as an absorbent entity for the removal of moisture, e.g. wound exudate, that also provides a helpful background level of moisture. The water-uptake capacity of a hydrated hydrogel, including a high concentration gel, enables the dressing to aid wound healing by removing substantial amounts of exudates, swelling-up as it does so. By using a carefully formulated, ready-hydrated gel, the wound is prevented from reaching a state of unhelpful dryness. Ready hydration also ensures the quick formation of a liquid interface between the dressing and the wound, thus preventing adhesion, which otherwise would interfere with easy lifting of the dressing when it has to be replaced. A good liquid interface between the wound and the dressing is also important in allowing the antimicrobial products of the enzymes to enter the wound through all of the available surface. The or each gel may contain various reagents, including one or more of the following: one or more oxidoreductase enzymes; one or more peroxidase enzymes; substrate for the oxidoreductase enzyme (to be discussed below); a source of iodide ions (to be discussed below); glycerol (which acts as a humectant and moisturiser), typically in an amount up to 20% by weight of the weight of the gel. In particular, the enzyme or enzymes may be present in one or more hydrated hydrogels. For example, one of the enzymes, oxidoreductase enzyme or peroxidase enzyme, may be present in a gel, e.g. an aqueous high concentration hydrophilic polymer material gel. As a further possibility both enzymes may be present in a gel, e.g. such a high concentration gel. A further option is for each enzyme to be present in a respective gel, e.g. an aqueous high concentration hydrophilic gel. As a further possibility, the dressing may include a single hydrated hydrogel (e.g. of poly AMPS), containing no enzymes but possibly containing substrate for the oxidoreductase enzyme (e.g. a source of glucose for glucose oxidase), additionally or alternatively containing a supply of iodide ions (e.g. in the form of one or more iodide salts) and optionally also containing glycerol. The or each gel may be cross-linked. For example, the gel may comprise an alginate gel, e.g. formed from alginic acid cross-linked in known manner, e.g. by use of calcium chloride. Cross-linked gels form an entrapping biopolymer matrix that can retain the enzyme within the gel if the degree of cross-linking is sufficiently tight, thus preventing release of the enzyme into the wound bed in use of the dressing. The gel may be in the form of beadlets, beads, slabs or extruded threads etc. The hydrated hydrogel, particularly a cross-linked gel, may be cast around a mechanical reinforcing structure, such as a sheet of cotton gauze or an inert flexible mesh, e.g. to providing a structurally reinforced hydrogel layer or slab. The hydrated hydrogel may alternatively be in the form of a non-cross-linked shear-thinning gel, e.g. of suitable gums such as xanthan gum (e.g. available under the Trade Mark Keltrol), in this case preferably without a mechanical reinforcing structure. Such gums are liquid when subjected to shear stress (e.g. when being poured or squeezed through a nozzle) but set when static. Thus the gel may be in the form of a pourable component, facilitating production of gels in the dressing. Such a shear-thinning gel may also be used in combination with a preformed, mechanically reinforced gel, as discussed above. The water-absorbing gel may utilise an increased concentration of hydrophilic substance, which may be the actual gel-forming polymer material, e.g. polysaccharide, itself or an additional substance added into the mixture for the sole purpose of absorbing water. One example of this type of functional mixture is that formed by a combination of cross-linked alginate at about 2% by weight and xanthan gum at about 5-10% by weight, based on the total weight of the gel. A particularly favoured version is that of covalently linked polymeric hydrogel such as polyAMPS, which is strongly water absorbing, being able to take up very large volumes of water or aqueous solutions. The enzyme or enzymes may be present in a gel in a number of possible forms, including in solution as free molecules. To improve efficiency of retention of the enzymes in the gel, the enzymes may be chemically conjugated to each other, chemically conjugated to other molecules (e.g. polyethylene imine), or incorporated in a solid support such as beads. Gels of different types, e.g. cross-linked alginate and shear-thinning, may be used together in a single dressing. Good results have been obtained with a shear-thinning gel nearest the skin, in use, and a cross-linked structurally reinforced gel remote from the skin. The enzyme or enzymes may be immobilised so they can be prevented from being released into a wound, where they would have the potential to trigger undesirable allergic responses (being generally derived from non-human sources, e.g. with most commercially available glucose oxidase being derived from the fungus Aspergillius niger and with lactoperoxidase typically being extracted from bovine milk) and would also be susceptible to degradation by the effect of proteases present in a wound. An enzyme may be immobilised in known manner, e.g. by being irreversibly bound to a solid support such as a particle, bead or fibre, e.g. of cellulose, silica, polymer etc., using coupling methods known to those skilled in the art. Incorporating an enzyme in a cross-linked alginate gel as discussed above, e.g. in the form of beadlets, slabs or extruded threads, also has the effect of immobilising the enzymes. Known encapsulation techniques using polyamide are also appropriate. In embodiments using oxidoreductase enzyme and peroxidase enzyme, the two enzymes may be located in separated hydrated hydrogels, with the oxidoreductase enzyme located in a first hydrated gel and the peroxidase located in a second hydrated gel. The first and second hydrated gels can be located in different regions of the dressing as required. The dressing desirably has a layered, stratified construction, e.g. comprising an upper (outer) layer of one gel and a lower (inner) layer of another gel. For example, the first gel (with oxidoreductase enzyme) may be located in the vicinity of the outer parts of the dressing, i.e. remote from the skin in use, where oxygen levels are highest, with the second gel (with peroxidase enzyme) being located in the vicinity of the inner parts of the dressing, i.e. adjacent the skin in use, so that the antimicrobial species (at least some of which are very short lived due to their extreme reactivity) produced thereby are close to the skin and are not expended before they reach the desired site of action. In this case the dressing thus has a layered, stratified construction, comprising an upper (outer) layer of the first gel and a lower (inner) layer of the second gel. However, experiments suggest that the relative location of the two enzymes is not critical. Some types of dressing desirably include a layer of barrier material at the interface with the skin in use, e.g. adjacent the second gel (with peroxidase enzyme) in the arrangement above, to prevent undesirable ingress to the dressing of catalase from the skin, e.g. from wound fluid or from microbes inhabiting the area. Ingress of catalase to the dressing is undesirable as this enzyme would compete with the peroxidase for reaction with hydrogen peroxide, thus reducing efficiency. Suitable barrier material includes, e.g. a semi-permeable sheet or membrane with a relatively low molecular weight cut-off that is permeable to the antimicrobial species produced by the peroxidative peroxidase but impermeable to catalase. Suitable materials are known to those skilled in the art and include cellulose acetate film such as that used to make dialysis membranes with a molecular weight cut-off of about 15 kD. As mentioned above, the dressing desirably includes a source of substrate for the oxidoreductase enzyme, e.g. glucose for glucose oxidase. Preferably the glucose is in the form of pure, pharmaceutical grade material. Glucose can also be supplied in the form of honey which naturally provides other benefits such as healing and antimicrobial factors. The substrate is desirably physically separated from the oxidoreductase enzyme prior to use of the dressing, to prevent premature reaction, although because oxygen is required for reaction then provided the supply of oxygen is limited only little reaction can occur. This will be discussed below. The substrate may be contained within an enclosure of a semi-permeable membrane material, e.g. material such as those used as dialysis membranes e.g. cellulose acetate (which is also often known as “visking tubing”), or within a gel slab or pad, e.g. of agarose. Such a gel slab or pad is desirably cast around a mechanical reinforcing structure, such as a sheet of cotton gauze etc., as discussed above. The substrate may conveniently be in the form of a shear-thinning gel, e.g. of a suitable gum such as xanthan gum as discussed above, preferably without a mechanical reinforcing structure, for pourable production. The substrate may alternatively be present in a hydrated gel, e.g. of hydrophilic polymer material as discussed above. The substrate, e.g. glucose is typically present in an amount up to about 25% by weight of the weight of the dressing. It is helpful to balance the relative amounts of enzyme and substrate such that there is an excess of hydrogen peroxide which, although less potent that the products of lactoperoxidase action, can act at a greater distance than the more reactive species. It is also believed that hydrogen peroxide can stimulate the formation of new blood vessels in the recovering wound (angiogenesis, or neovascular growth), stimulate the proliferation of new tissue-forming cells and activate enzymes (proteases) responsible for helping to reshape the developing new tissue. The substrate, e.g. glucose, may be present in various forms including dissolved within a hydrated hydrogel structure, present as a slowly dissolving solid, or encapsulated within another structure for slow release. In the embodiment of a dressing of layered construction, as mentioned above, the source of substrate can be located (in use of the dressing) sandwiched between the upper layer of first gel containing oxidoreductase enzyme and the lower layer of second gel containing peroxidase enzyme. In this case, oxidoreductase enzyme may optionally also be included in the second gel to oxidise substrate that is liable to diffuse towards the second gel. Such oxidation is dependent on the presence of oxygen, which is in restricted supply at this location, with the oxidation reaction being proportional to the available oxygen. In another alternative arrangement the peroxidase enzyme and substrate are both present in the second hydrated gel. In this case, the first hydrated gel (with oxidoreductase enzyme) is desirably located above and/or below the second gel in a layered arrangement. Yet another option is to have a 4 layered structure, with an upper layer (remote from the skin) of first hydrated gel overlying a layer of substrate that overlies a further layer of first hydrated gel, in turn overlying a second hydrated gel layer at the bottom (adjacent the skin in use). By providing an excess of substrate, so the dressing is able to function in use to generate antimicrobial species over an extended period of time, typically at least 2 days, where substrate-containing hydrated gel or gels are formulated to retard flow of substrate to the enzymes, e.g. by extensive hydrogen bonding to impede diffusion through the or from the hydrogel in which they were originally supplied. The antimicrobial efficiency of the system can be further enhanced by the inclusion of iodide ions, which can be oxidised to elemental iodine (which is a known powerful antimicrobial agents, e.g. as discussed in WO 01/28600) by the action of hydrogen peroxide, with or without catalytic effect. Thus, the dressing desirably includes a supply of iodide ions, e.g. potassium iodide or sodium iodide. As iodine is also relatively toxic to host cells in the wound (e.g. epithelial cells, keratinocytes, white blood cells) it may not be advantageous to generate iodine continuously at a high concentration throughout the time that the formulation is in use in contact with the skin. Thus, in a preferred embodiment, the supply of iodide ions, e.g. iodide salt, is provided in a relatively quick-release form, either in the substrate gel or in an additional membrane or gauze or other suitable layer. In this way, the hydrogen peroxide produced initially, in a first phase of activity, is substantially consumed in an iodine-generating reaction, exposing the skin (e.g. wound) to a surge of iodine, the duration of which can be controlled by the amount, release-rate and position of the iodide supply. Such an iodine surge can be very useful in quickly ridding a wound of a microbial burden, and its relatively short duration allows healing by minimising damage to growing cells and their repairing activity. Once the iodide has been consumed, the system automatically reverts, in a subsequent phase of activity, to the production of hydrogen peroxide and related reactive oxygen species (ROS), which maintains sterility and kills invading bacteria near the skin, e.g. wound surface. In other embodiments, however, it may be desired for the source of iodide ions to be such as to provide, in use, a sustained flux of iodine (and/or hypoiodous acid) for release into a wound, in addition (and in proportion) to hydrogen peroxide. The supply of iodide may alternatively be located with the source of substrate for the oxidoreductase enzyme, as discussed above, e.g. in a hydrated gel. The iodide may be present in various forms, including dissolved within a hydrated gel structure, present as a slowly dissolving solid, or encapsulated within another structure for slow release. Iodide salt may be present, e.g. in an amount up to about 2% by weight. However, even in the absence of iodide, antimicrobial active intermediates are still formed, as discussed above. In embodiments in which the enzyme or enzymes are not present in one or more hydrated gels, the enzyme or enzymes are conveniently irreversibly attached to an inert carrier or support. The support suitably comprises a gauze e.g. of woven material such as cotton or some other appropriate form of cellulose etc. The support may be activated in known manner so that it is able to react with protein (enzyme) to form stable imine bonds, so the enzyme is retained on the support. The attached enzyme may optionally be coated with a preserving agent, e.g. polyvinyl alcohol (PVA) e.g. at 5%, sucrose e.g. at 10%, gelatin e.g. at 2% and/or glycerol, to help maintain enzyme activity. The dressing is designed such that enzyme or enzymes are present in the dressing in hydrated condition. Covalently cross-linked gels such as polyAMPS can easily be made to exclude enzyme molecules whilst being permeable to hydrogen peroxide and iodine. In gels of this nature the enzyme or enzymes can be incorporated by dosing them onto the top surface of a substrate-containing hydrogel as an aqueous solution, and allowing the liquid to soak into the gel. Although the water penetrates the gel, the enzyme molecules are retained at the top surface. If the enzyme solution contains PVA (e.g. 6% w/v), the enzyme/PVA mixture forms a thin hydrated membrane as the water is drawn into the gel. Further, the PVA matrix stabilises the enzyme with which it is associated. It has been found that dressings in accordance with the invention act as efficient transporters of oxygen from the ambient atmosphere to a wound site, which has benefits for wound healing. In particular, the rate of oxygen transported through a dressing in accordance with the invention is greater than that of a similar dressing without oxidoreductase enzyme. The reason for this, and resulting benefits, are described below. When a conventional dressing is applied to the surface of a wound, the supply of oxygen from the atmosphere is generally inhibited and the wound becomes relatively deprived of oxygen (hypoxic or even anoxic). Hypoxia or, worse, anoxia are frequently encountered conditions known to be very bad for wound healing, because the cells responsible for the healing (keratinocytes and epithelial cells) and the leukocytes that fight infection and control the process, all need oxygen if they are to thrive. Phagocytic leukocytes need plentiful oxygen if they are to operate their “respiratory burst” biochemistry, with which they kill bacteria. Collagen is essential for rebuilding the damaged tissues, and for creating new blood vessels (angiogenesis), which need collagen fibres on which to construct capillary walls. Collagen synthesis can only take place when hydroxylase enzymes can hydroxylate lysine and proline, to give hydroxy-lysine and hydroxy-proline, both of which are essential building blocks of collagen. Hydroxylase enzymes need a plentiful supply of oxygen for their efficient functioning. For these reasons, it is widely recognized that wounds must be well oxygenated if they are to heal efficiently, and it is frequently claimed that oxygen supply can be the rate-limiting factor in wound healing. It is believed that a failure to heal is often caused by lack of adequate oxygen. Moreover, a high oxygen tension in a wound inhibits the growth of pathogenic anaerobic bacteria, which are also responsible for malodour production. For these reasons, certain secondary dressings, such as Tegaderm from 3M Healthcare Ltd or OpSite from Smith & Nephew (Tegaderm and OpSite are Trade Marks), are made from thin polyurethane film coated on one side with an adhesive layer. These are marketed as being relatively permeable to oxygen (and water vapour), because of their particular molecular structure and thin cross section. This is a purely passive effect, and the efficiency of oxygen permeation is inversely related to the thickness of the film. Hydrogels are not very permeable to oxygen, because they are composed primarily of water, and oxygen is not very soluble in water. Their permeability to oxygen will also be inversely related to the thickness of the dressing. Until the advent of this invention, the only way to increase the level of oxygen in a wound was to administer oxygen to the patient, either by increasing the amount in the blood (e.g. by causing the patient to breathe oxygen-enriched air or placing the patient in a hyperbaric oxygen environment such as that available in a compression chamber), or by applying gaseous oxygen to the wound itself. As noted above, dressings in accordance with the invention have the ability efficiently to transport oxygen from the ambient atmosphere outside the wound, into the wound bed, especially in cases where the dressing includes a layer of oxidoreductase enzyme, e.g. glucose oxidase, on the outer surface, in contact with the ambient atmosphere. Oxygen from the ambient atmosphere is converted to hydrogen peroxide (catalysed by the oxidoreductase enzyme). Hydrogen peroxide is much more soluble in water than is molecular oxygen, so hydrogen peroxide transport through the dressing (typically through one or more hydrated hydrogels) is generally much more efficient and rapid than that of molecular oxygen. Hydrogen peroxide thus diffuses rapidly through the dressing. When the hydrogen peroxide encounters catalase (which is naturally present in a wound, or which may be included as a component of the dressing), it decomposes to oxygen and water. In this way, oxygen is transported through the dressing in the form of hydrogen peroxide far more efficiently than transport of molecular oxygen. Experiments have shown that the rate of transport of oxygen can be more than doubled in dressings in accordance with the invention as compared with similar dressings without oxidoreductase enzyme. The resulting enhanced oxygen levels potentiate the healing process, as described above. The dressing conveniently includes, or is used with, a covering or outer layer for adhering the dressing to the skin of a human or animal subject (in known manner). At least part of the covering should be of oxygen-permeable material to enable oxygen from ambient air to pass through the covering and enter into the body of the dressing in use, where it is required as a cosubstrate of the oxidoreductase catalysed reaction. The oxygen-permeable material may be in the form of a “window” set into an otherwise relatively oxygen-impermeable covering, e.g. of possibly more robust material. Optionally the covering includes a window (or further window) in or through which can be seen indicator means e.g. an indicator sheet or similar structure that indicates (e.g. by changing colour) when the dressing chemistry is active. A further indicator may optionally be provided, which indicates (e.g. by changing colour) when the dressing chemistry has expired. A further useful option is to provide immobilised catalase enzyme on the inner surface of the covering (e.g. secured to adhesive thereof). This will function rapidly to break down any excess hydrogen peroxide which may escape from a wound area. This feature will prevent potentially damaging build-up of hydrogen peroxide in areas of normal, undamaged skin. The dressing may be supplied as a multi-part system, with different elements separately packaged, for assembly and use by an end user in accordance with supplied instructions. In particular, in embodiments including a source of substrate, e.g. glucose, this may be supplied packaged separately from other components, particularly the oxidoreductase enzyme, to prevent premature oxidation reaction. Alternatively, the dressing may be foldable. A typical embodiment of this sort comprises a linear arrangement of linked slabs or panels including a slab of the first hydrated gel, a slab of the second hydrated gel and a slab of substrate, with adjacent slabs linked by a respective hinge portion. Hydrophobic barrier material, e.g. a wax, is desirably impregnated into the hinge portions to prevent lateral diffusion Good results have been obtained with an embodiment comprising, in sequence, a slab of substrate, a slab of second hydrated hydrogel (containing peroxidase enzyme) and a slab of first hydrated hydrogel (containing oxidoreductase enzyme), with adjacent slabs linked by a respective foldable hinge portion. To prepare such a dressing for use the two outer slabs are folded in, to bring the slab of substrate so as to overly the slab of second gel and to bring the slab of first gel so as to overly the slab of substrate, thus forming a layered arrangement as described above. The resulting layered arrangement is placed on skin e.g. on a wound, with the slab of second gel in contact with the skin, and may be held in place e.g. by use of an adhesive covering. One or more components of the dressing may be contained within an enclosure such as a sachet or bag of barrier material that is permeable to oxygen, water and hydrogen peroxide but that prevents undesired migration of materials. Such an enclosure has the effect, inter alia, of preventing possibly interfering substances such as catalase, iron ions etc. being taken up into the dressing from a wound site. The enclosure may also prevent undesired migration of enzyme(s) into a wound. Suitable barrier material includes e.g. a semi-permeable sheet or membrane e.g. of cellulose acetate or cellulose ester, such as one that is permeable only to molecules of molecular weight less than, say, 350 Da (possibly having a nominal molecular weight cut-off of 500 Da but with an actual limit of less than 350 Da). Suitable membranes include cellulose acetate membrane code Z368024 supplied by Sigma, Spectrum SpectraPor cellulose ester membrane code 131054 supplied by NBS Biologicals and, currently favoured particularly for an anti-acne dressing, polyurethane, e.g. Tegaderm film from 3M. (Spectrum, SpectraPor and Tegaderm are Trade Marks). The water-absorbing components of the dressing can easily be applied to the wound or site of infection, especially when formulated into a workable or flowable form. There are many possible formulations that achieve this effect, and these can readily be determined by simple experimentation. Such formulations can be applied with particular ease and convenience from compressible tubes or syringe-like tubes (with a piston) with a nozzle of about 3 mm diameter. It can be especially helpful to supply the components in a simple assembly of two or more tubes, as required by the particular formulation in use, such that the desired mixture of gels can be expelled onto a particular site in a single action. Such multiple tube arrangements are well known and frequently used in the industry for other applications. This arrangement perfectly and conveniently satisfies the need to keep the gels apart from each other until the point of use. It has also been found that one or more of the components can be applied from a pressurised container, such that the gel is applied as a foam, spray or even an aerosol. Within the guidelines given here, the formulation that gives the particular physical properties (viscosity etc.) required for this mode of delivery can easily be determined by simple experimentation. Workable plastic gels from tubes or pressurised delivery gels can be used in combination with structured slabs to give an appropriate assembly of the basic ingredients. Dressings of layered construction comprising shear-thinning gels can be readily produced, e.g. by an end user, by pouring or dropping the gels one on top of the other in appropriate order to produce a desired layered assembly of gels. Thus the different dressing component gels may be supplied in separate containers e.g. tubes or bottles or possibly a multi-compartment jar. The different gels may be colour-coded with appropriately coloured latex for ease of identification. The gels may be applied directly to the skin of a user. A covering or outer layer may not be required with such embodiments. Dressings in accordance with the invention (or components thereof) are suitably supplied in sterile, sealed, water-impervious packages, e.g. laminated aluminium foil pouches. Dressings in accordance with the invention can be manufactured in a range of different sizes and shapes for treatment of areas of skin e.g. wounds of different sizes and shapes. Appropriate amounts of enzymes, and substrates and iodide if present, for a particular dressing can be readily determined by experiment. The invention will be further described, by way of illustration in the following Examples and with reference to the accompanying drawings, in which: FIGS. 1 to 6 are schematic sectional illustrations of 6 different embodiments of wound dressings in accordance with the invention. detailed-description description="Detailed Description" end="lead"?
20041025
20100608
20060216
95925.0
A61K3844
0
FERNANDEZ, SUSAN EMILY
WOUND DRESSINGS COMPRISING HYDRATED HYDROGELS AND ENZYMES
UNDISCOUNTED
0
ACCEPTED
A61K
2,004
10,512,449
ACCEPTED
Dewpoint cooler designed as a frame or part thereof
A dewpoint cooler comprises: a first air circuit and a second air circuit coupled thereto via a heat-conducting wall, through which two circuits can flow two media, wherein the second medium contains a gas, heat-conducting wall break-up means for breaking up at least the thermal boundary layer (50), the laminar boundary layer and the relative humidity boundary layer in both media, which break-up means comprise heat-conducting protrusions; wherein the surfaces of said wall and the break-up means are covered with a hydrophilic coating, which can absorb an evaporable liquid, retain it and relinquish it again (100), such that the wetted coating, the heat-conducting surfaces and the break-up means are cooled. A wetting (150) unit for subjecting the secondary medium to wetting by the evaporable liquid such that evaporated liquid entrained by the secondary medium extracts heat from the primary medium via the wall.
1. Dewpoint cooler, comprising: a first air circuit and a second air circuit thermally coupled thereto via an at least partially heat-conducting wall, through which two circuits can flow two respective media, wherein at least the second medium contains a gas, for instance air, with a relative humidity of less than 100%; which heat-conducting wall has break-up means such as fins for breaking up at least the thermal boundary layer, the laminar boundary layer and the relative humidity boundary layer at the position of at least active zones in both media for heat transfer, which break-up means comprise heat-conducting protrusions which enlarge the effective heat-conducting surface area of said wall; wherein the heat-conducting surfaces of said wall and the break-up means are at least partially covered at least in the area of the secondary medium with-a hydrophilic, for instance hygroscopic coating, which coating is for instance porous and/or can absorb water by capillary action, retain it and relinquish it again through evaporation, such that the wetted coating, and thereby also the heat-conducting surfaces and the break-up means, are cooled; primary drive means based on pressure difference, for instance a fan or pump, for the primary medium; secondary drive means based on pressure difference, for instance a fan, for the secondary medium; and a wetting unit for subjecting the secondary medium to wetting by the water by evaporating liquid from the coating such that the evaporated liquid entrained by the secondary medium extracts heat from the primary medium via the heat-conducting wall; characterized by a housing in which the walls bounding the air circuits are accommodated, which housing is adapted as border or frame, or a part thereof, for an outside door or outside window of a building, wherein the inlet of the primary circuit and the outlet of the secondary circuit are situated on the outside and the outlet of the primary circuit and the inlet of the secondary circuit are situated on the inside. 2. Dewpoint cooler as claimed in claim 1, wherein the coating consists of a porous technical ceramic material, for instance a burnt layer, a cement such as a Portland cement, or a fibrous material, for instance a mineral wool such as rockwool. 3. Dewpoint cooler as claimed in claim 1, comprising a reversing unit for reversing a part of the primary airflow at the outlet of the first air circuit in order to form the secondary airflow, wherein the primary drive means are also the secondary drive means. 4. Dewpoint cooler as claimed in claim 3, wherein the reversing unit can be switched off such that the two airflows can be separated and the wetting means can be switched off, this such that the dewpoint cooler can operate as heat exchanger for recovering heat discharged to the outside by the secondary airflow through transfer of heat in the heat exchanger to the primary airflow. 5. Dewpoint cooler as claimed in claim 3, wherein the ratio between the primary airflow and the secondary airflow can be adjusted by means of adjusting means such that the efficiency of the dewpoint cooler is adjustable. 6. Dewpoint cooler as claimed in claim 5, wherein the adjusting means are embodied as an optionally adjustable through-feed in the primary circuit and an adjustable through-feed in the secondary circuit. 7. Dewpoint cooler as claimed in claim 1, wherein the fans are at least partly powered by a rechargeable battery which is charged by a solar panel collecting sunlight from the outside. 8. Dewpoint cooler as claimed in claim 1, wherein a dewpoint cooler can be coupled in modular manner to a similar dewpoint cooler, for instance at an angle of 90. 9. Building with at least one door and/or one window witha frame, characterized in that at least one of the borders of this frame is embodied asa dewpoint cooler as claimed in any of the claims 1-8.
The invention relates to a dewpoint cooler, comprising: a first air circuit and a second air circuit thermally coupled thereto via an at least partially heat-conducting wall, through which two circuits can flow two respective media, wherein at least the second medium contains a gas, for instance air, with a relative humidity of less than 100%; which heat-conducting wall has break-up means such as fins for breaking up at least the thermal boundary layer, the laminar boundary layer and the relative humidity boundary layer at the position of at least active zones in both media for heat transfer, which break-up means comprise heat-conducting protrusions which enlarge the effective heat-conducting surface area of said wall; wherein the heat-conducting surfaces of said wall and the break-up means are at least partially covered at least in the area of the secondary medium with a hydrophilic, for instance hygroscopic coating, which coating is for instance porous and/or can absorb water by capillary action, retain it and relinquish it again through evaporation, such that the wetted coating, and thereby also the heat-conducting surfaces and the break-up means, are cooled; primary drive means based on pressure difference, for instance a fan or pump, for the primary medium; secondary drive means based on pressure difference, for instance a fan, for the secondary medium; and a wetting unit for subjecting the secondary medium to wetting by the water by evaporating liquid from the coating such that the evaporated liquid entrained by the secondary medium extracts heat from the primary medium via the heat-conducting wall. Such a dewpoint cooler is known. The known dewpoint coolers are standalone devices generally having a form and dimensions which from an aesthetic viewpoint often leave something to be desired in an interior. In this respect it is an object of the invention to provide a dewpoint cooler which is wholly integrated into the architectural structure of a building, and which is therefore practically invisible. In this context the dewpoint cooler according to the invention is characterized by a housing in which the walls bounding the air circuits are accommodated, which housing is adapted as border or frame, or a part thereof, for an outside door or outside window of a building, wherein the inlet of the primary circuit and the outlet of the secondary circuit are situated on the outside and the outlet of the primary circuit and the inlet of the secondary circuit are situated on the inside. The dewpoint cooler according to the invention is preferably embodied such that the coating consists of a porous technical ceramic material, for instance a burnt layer, a cement such as a Portland cement, or a fibrous material, for instance a mineral wool such as rockwool. With such a coating it is possible to achieve that the liquid applied to the coating by the wetting unit spreads rapidly in the coating while the coating has a substantial buffering capacity for the water. It is important that the coating has a small thickness, for instance in the order of 50-100 Hm, such that the thermal resistance caused in the coating by the water is very small. In a preferred embodiment the dewpoint cooler according to the invention has a reversing unit for reversing a part of the primary airflow at the outlet of the first air circuit in order to form the secondary airflow, wherein the primary drive means are also the secondary drive means. The secondary airflow can for instance amount to about 30% of the introduced primary airflow, whereby the secondary airflow carried to the space for cooling then amounts to about 70% of the introduced primary airflow. In a particular embodiment the dewpoint cooler can have the special feature that the reversing unit can be switched off such that the two airflows can be separated and the wetting means can be switched off, this such that the dewpoint cooler can operate as heat exchanger for recovering heat discharged to the outside by the secondary airflow through transfer of heat in the heat exchanger to the primary airflow. In the summer for instance the dewpoint cooler can thus operate effectively as dewpoint cooler, while in the winter it operates as heat-recovering heat exchanger. In yet another embodiment the dewpoint cooler has the special feature that the ratio between the primary airflow and the secondary airflow can be adjusted by means of adjusting means such that the efficiency of the dewpoint cooler is adjustable. With such an embodiment it is possible to vary from the ratio of 30:70 stated above by way of example between the secondary cooling airflow and the cooled airflow supplied to the space. The optimization can take place with control means such that the dewpoint can be approached within a very small margin, for instance 1 C. This latter variant can be embodied such that the adjusting means are embodied as an optionally adjustable through-feed in the primary circuit and an adjustable through-feed in the secondary circuit. Alternatively, use can also be made of two separated fans for respectively the primary airflow and the secondary airflow. A specific embodiment has the special feature that the fans are at least partly powered by a rechargeable battery which is charged by a solar panel collecting sunlight from the outside. Depending on the expected sunshine, the power supply from the rechargeable battery can be further assisted by additional mains supply. The dewpoint cooler according to the invention can be further embodied such that it can be coupled in modular manner to a similar dewpoint cooler, for instance at an angle of 90. The fans can for instance be supplied as separate blocks such that, when a number of dewpoint coolers according to the invention are coupled, use need only be made of a total of two fans. The invention also relates to a building with at least one door and/or one window with a frame. This building has the feature according to the invention that at least one of the borders of this frame is embodied as a dewpoint cooler in accordance with the above stated specifications. The dewpoint cooler according to the invention is very cheap to manufacture and install, and combines the function of window frame with that of dewpoint cooler. The invention is therefore very practical when there is shortage of space. The dewpoint cooler is further always embodied as independent or standalone unit, whereby it is possible to dispense with lines, cables and the like. A simple mains cable may well be necessary for power supply to the fans. When old buildings are renovated the dewpoint cooler according to the invention can be utilized very successfully. When frames are replaced, parts thereof, or at least specific borders, can be embodied as dewpoint coolers according to the invention. In this case it is also possible to dispense with the installation of expensive air-conditioning systems. In buildings the concept of double flux and single flux is used in the case of a controlled ventilation. With a double flux there is a complete control of both the incoming and outgoing airflow. This is for instance the case in a dewpoint cooler, whether or not it be of the type according to the invention, wherein the building is hermetically sealed apart from the dewpoint cooler. In the case of a single flux there is a ventilation flow to the outside, wherein gaps, chinks and cracks provide the introduced air. Window and door frames consist of a frame with profiles in aluminium, PVC, steel, wood or combinations thereof. The dewpoint cooler according to the invention can be used in different positions. For an outside wall it can be vertical, in a pitched roof it can be arranged obliquely, in a horizontal roof it can be placed horizontally. The dewpoint cooler according to the invention can be embodied as built-in border or surface-mounted border. The housing can for instance be designed such that the dewpoint cooler fits therein by means of a snap system. The same applies for filters which may be applied for the primary and secondary airflow. The dewpoint cooler according to the invention can be applied in any desired position and on any edge of a door or window. The following four options are particularly important:—heat exchanger air/air, double flux—dewpoint cooler, single flux—dewpoint cooler, double flux—the combination of heat exchanger air/air, single or double flux. It should be appreciated that the dewpoint cooler according to the invention can be a fully standalone unit and requires no coupling to other systems. The airflow rate in both the primary and secondary circuits is preferably a minimum of 6 m3/h, but the flow rate can also be greater in accordance with the wishes of the user and the application. It is also necessary to consider whether the air-conditioning is total or partial. The dewpoint cooler according to the invention can be embodied in double flux with equal flow rates, but also with different flow rates. In this manner the possibility can readily be created of ventilating for instance sanitary spaces with single flux. Reference is made by way of example to the possibility of two rooms in a building being supplied from outside with 60 m3/h (primary circuit) while 50 m3/h is discharged. There then remains a surplus of 10 m3/h. Two rooms therefore give a surplus of 20 m3/h. By way of for instance cracks or holes in the door of a sanitary space this flow of 20 m3/h can be discharged to the outside by means of an additional sanitary space fan. The dewpoint cooler according to the invention can also function as heat recovery heat exchanger by optionally reversing the fans or making use of a built-in automatic or controlled valve. It will be apparent that the dewpoint cooler itself must be practically silent, for instance may not produce more noise than 38 dB (A) at a distance of 1 m. In addition, the dewpoint cooler may only have a negligible sound transmission. The dewpoint cooler may not, particularly in a gale, produce any noise nuisance in the form of whistling, sighing, rattling and so on. Power supply preferably takes place at a maximum voltage of 48V direct current or alternating current. Below this value there is no specific safety norm in force, and low-voltage connecting means can be used, for instance mini-socket outlets. These socket outlets can be important for, among others, the following aspects: power supply to the fans and possible electronic control means, remote control, adjustment, failure report or report of the measure of fouling, central closing in the case a stench wave occurs, central closing in the case a fire protection becomes operative, connection to buildings, management centre, burglar alarm and a frequency control system, which can optionally also be driven wirelessly. In the latter case it is possible to largely dispense with the use of lines, which will stimulate the standalone character of the dewpoint cooler according to the invention. It is important to provide the dewpoint cooler with filters. On the one hand this is to prevent fouling of the dewpoint cooler itself, which could have an adverse effect on the heat transfer, on the other hand to prevent floating dirt and dust being carried for instance from outside to the inside and, conversely, from inside to the outside. The filters can be of per se known type and can preferably be embodied in the form of insert units such that they are easily replaceable. In the case of a dewpoint cooler of the type according to the invention which is installed on a window frame, the operation of the fans has to be stopped at the moment the window is opened. A built-in magnetic contact can for instance be used for this purpose. Use can further be made of a failure reporting means, for instance relating to the operation of the fans and possible fouling of the filters and the heat-exchanging surfaces. Simple computer fans with low flow rate can be used as fans. A fan with a relatively high rotation speed can also be applied. As alternative it is possible to envisage the use of one drive motor with two fan blades, one for the primary circuit and one for the secondary circuit. A bypass valve can be used for switching between winter operation with heat exchanger and summer operation without heat exchanger. In air-conditioning applications the heat exchanger is always used. A bypass valve is also suitable for preventing icing up. The bypass valve can be controlled for hand-operated or automatic deicing. During the free cooling period, particularly at nighttime, fresh outside air can be carried inside without heat exchange. This can optionally take place at an increased airflow rate, which will possibly be accompanied by a slightly increased noise production. When two fans are used in the dewpoint cooler according to the invention, both circuits can then be used for this ventilation. An overpressure-relief valve can optionally be arranged elsewhere in the ventilated space for this purpose. In the case of gale or other dramatic overpressure conditions, use can for instance be made of a non-return valve in the form of an air valve or the like. A very quickly responding air valve can for instance be based on the use of a table-tennis ball. Use can also be made of a protective plate to prevent the inlet and outlet being directly influenced on the outside. An air valve can also be based on a rubber bellows or other type of valve. Protection against rainwater can take place with per se known protective measures, particularly covers. Covering by curtains on the inside of a window with dewpoint coolers according to the invention in the vertical borders can be prevented by directing the blown-out airflow obliquely inward instead of perpendicularly of the main plane of the window. This prevents the curtains flapping too much. The air from outside is also prevented from being blown inward ineffectively. Use can be made of one or more nozzles with adjustable angle. The flow rate of the airflow is also kept relatively low so as to prevent an undesirable increase in the k-factor of the pane in question. Radiators are often placed under a window. In such a situation it is desirable to have the air discharge take place on the upper border. There is otherwise the danger of warm air from the radiator being drawn off. When curtains are closed the air discharge must remove the air from the room. Account must therefore be taken of curtains in the placing of inlets and outlets. In the case of office buildings, where curtains are not usually applied, nozzles driven in oscillating manner can also be applied, whereby the air in question is properly spread through the space. The invention will now be elucidated with reference to the annexed drawings of a random embodiment. In the drawings: FIG. 1 shows a partly cut-away perspective view of a known dewpoint cooler; FIG. 2 shows a longitudinal section through the dewpoint cooler of FIG. 1; FIG. 3 shows a perspective view, partly drawn in exploded view, of a frame with the dewpoint cooler according to FIGS. 1 and 2; FIG. 4 shows a view corresponding with FIG. 1 of the dewpoint cooler according to the invention; FIG. 5 shows a view corresponding with FIG. 2 of the dewpoint cooler according to the invention; and FIG. 6 shows a view corresponding with FIG. 2 of an alternative dewpoint cooler according to the invention. FIG. 1 shows a dewpoint cooler 1 embodied in this embodiment as heat exchanger, i.e. without wetting means, whereby the heat exchanger could operate according to the invention as dewpoint cooler. Dewpoint cooler 1 comprises two very schematically shown sets of air through-flow channels which form respectively a primary circuit I and a secondary circuit II, through which two airflows 2 and 3 respectively can flow in heat-exchanging contact to be described hereinbelow. Between the channels drawn in this case as being single, generally the circuits I and II, is situated a heat-conducting wall 4 on which symbolically designated fins 5,6 are placed respectively in primary circuit I and secondary circuit II. These fins are manufactured for instance from copper and increase the effective heat-exchanging capacity of wall 4 considerably. A housing 26 bounds the dewpoint cooler and co-acts sealingly with wall 4 such that circuits I and II are completely separated physically. Housing 6 has four passages for the two circuits I, II, viz. inlet 7 of the primary circuit, outlet 8 of the primary circuit, inlet 9 of the secondary circuit and outlet 10 of the secondary circuit. Passages 8 and 9 are situated on the inside, thus in the space to be ventilated or conditioned, while passages 7,10 are situated on the outside, and are thus in contact with the ambient air. A fan 11 is situated in circuit I; a fan 12 is situated in circuit II. as described above, the flow rates of flows 2 and 3 can be the same as each other, but can also differ from each other in controlled manner such that a residual flow rate has to discharged or supplied elsewhere. As FIG. 3 shows, dewpoint cooler 1 is embodied as the lower border of a frame 13 which forms the framework for a window pane 14. In a particular embodiment one or more of the remaining borders 13,15 can also be embodied as a dewpoint cooler according to the invention. These dewpoint coolers 6, 13,14 etc. can be coupled to each other in modular manner and for instance have a number of passages and fans in common. It is pointed out emphatically that the construction shown in FIG. 2 is only very schematic and symbolic. A dewpoint cooler, or in the narrow sense a heat exchanger, will generally comprise a number of heat-exchanging walls with fins combined into a package. This real practical structure is omitted for the sake of clarity in the drawings. Attention is further drawn to the fact that passages 8,9 and 10,7 do not necessarily have to be placed adjacently of each other, but can also be arranged spaced apart from each other. There is a smaller risk hereby of the flows 2 and 3 influencing each other. This can also be realized by jet-streams or nozzles with an angle differing from the drawn angles, optionally adjustable. The dewpoint cooler according to FIG. 1 further comprises a solar panel 16 which can collect sunlight and convert it into electricity, which is used to charge a rechargeable battery (not shown) which is adapted to supply power to fans 11,12 via electronic means. Solar panel is accommodated in a protruding part 17 of housing 26, but can also form part thereof. The unit 16,17 is not shown in FIGS. 2 and 3. Fins 6 and the surface of wall 4 directed toward the secondary circuit II are preferably treated such that the relevant surfaces are hydrophilic. By making use of the wetting means an effective wetting hereby takes place which brings about a cooling effect when airflow 3 is guided therealong. Via the heat transfer to the other side of wall 4 and fins 5, this cooling effect is converted into a cooling of primary airflow 2. FIG. 4 shows a dewpoint cooler 41 according to the invention. The exterior differs from the heat exchanger 1 of FIG. 1 in the sense that it has only one outlet tube 8 on the inside of the building. This aspect will be further elucidated with reference to FIG. 5. The appearance is otherwise identical to that of heat exchanger 1. FIG. 5 shows very schematically the internal and functional structure of dewpoint cooler 41. Downstream of fan 11 the primary airflow 2 is split into two partial flows, viz. the outgoing cooled airflow 2′ (for instance 70% of airflow 2) and a second branched flow 2″ of cooling air (for instance 30% of airflow 2) which is guided through an opening 42. The through-feed of opening 42 relative to the through-feed of passage 8 determines said ratio between flow rates 2″ and 2. Not shown in the schematic view of FIG. 5 are the wetting means which serve to feed water for evaporation directly to a coating on secondary fins 6. This coating consists for instance of Portland cement with a thickness of 70 Am. The water supplied by feed conduits from a dispensing system makes the cement coating wet. The secondary airflow 3, which has a humidity of less than 100%, provides evaporation of the water on the relevant surface, this water in the form of water vapour in the secondary outlet airflow 3 being generated to the outside via opening 10. The heat extracted from fins 6, and thereby wall 4, due to the evaporation of the water is fed via fins 5 from the primary airflow 2, which is thereby cooled. FIG. 6 shows a hybrid embodiment of the dewpoint cooler according to the invention. Other than dewpoint cooler 41, this dewpoint cooler 51 is not provided with a fixed opening 42 downstream of fan 11, but with a valve 43 which can be displaced by an actuator 44 between the first position shown in full lines and the second position 43′ shown in broken lines. In position 43 the airflow 2 is generated directly to the inside via passage 8, while in position 43′ the valve 43 leaves opening 42 clear and closes passage 9. The same function is then thus obtained as in FIG. 5. In the first position the dewpoint cooler 51 can operate as heat exchanger for heat recovery. If desired, it could also function as cooler, although it is noted in this respect that in that case the ability to control the mutual ratio of flows 2 and 3 is less good. This is a drawback in the case the best possible efficiency is desired. It is further noted that in order to reduce noise production the fans 11,12 can be spring mounted. Use can further be made of known acoustic damping means which can effectively reduce sound exiting via the housing and passages 8,9. In order to prevent resonance phenomena at the rotation frequency of the fans, the housing 6 can be manufactured from a material which strong internal damping or be provided with a bituminous inner layer, or a large mass, and thus have a great wall thickness. Attention is finally drawn to the fact that in the case of a different placing of the passages it may be necessary to apply interlacing units and manifolds connecting the diverse passages to the sets of channels.
20050923
20070703
20060427
73380.0
E06B104
0
BOLES, DEREK
DEWPOINT COOLER DESIGNED AS A FRAME OR PART THEREOF
UNDISCOUNTED
0
ACCEPTED
E06B
2,005
10,512,524
ACCEPTED
Dehumidifying device
A dehumidifying device for absorbing water vapour from ambient air comprising a container having an opening to permit water vapour to enter the container, the container having a water-absorbing agent disposed therein for absorbing water vapour, wherein a first portion of the water-absorbing agent is adapted to provide an indication of water absorption faster than a second portion of the water-absorbing agent following exposure of the first and second portions of water-absorbing agents to water vapour, thereby providing an early indication of the operation of the device.
1. A dehumidifying device for absorbing water vapour from ambient air comprising a container having an opening to permit water vapour to enter the container, the container having a water-absorbing agent disposed therein for absorbing water vapour, wherein a first portion of the water-absorbing agent is adapted to provide an indication of water absorption faster than a second, separate, portion of the water-absorbing agent following exposure of the first and second portions of water-absorbing agents to water vapour, thereby providing an early indication of the operation of the device. 2. A dehumidifying device according to claim 1 wherein the first portion of the water-absorbing agent is a deliquescent agent. 3. A dehumidifying device according to 2 wherein the second portion of the water-absorbing agent is a deliquescent agent. 4. A dehumidifying device according to claim 2 wherein the or each deliquescent agent forms a liquid or gel on absorption of water vapour, thereby providing an indication of the operation of the device. 5. A dehumidifying device according to claim 1 wherein the first portion of water-absorbing agent is adapted to provide an indication of water absorption in greater than or equal to 12 hours following exposure to water vapour. 6. A dehumidifying device according to claim 1 wherein the mass of the first portion of water-absorbing agent is less than the mass of the second portion of water-absorbing agent. 7. A dehumidifying device according to claim 1 wherein the first portion of water-absorbing agent is partially pre-saturated. 8. A dehumidifying device according to claim 1 wherein the first and second portions of water-absorbing agent comprise calcium chloride. 9. A dehumidifying device according to claim 1 wherein the composition of the first portion of water-absorbing agent is different from the composition of the second portion of water-absorbing agent. 10. A dehumidifying device according to claim 9 wherein the first portion of water-absorbing agent comprises magnesium chloride. 11. A dehumidifying device according to claim 9 wherein the second portion of water-absorbing agent comprises calcium chloride. 12. A dehumidifying device according to claim 1 wherein the first and second portions of water-absorbing agent are disposed on a shelf positioned above the base of the container. 13. A dehumidifying device according to claim 12 wherein the shelf is perforate. 14. A dehumidifying device according to claim 12 wherein the shelf defines two separate shelf portions, a first shelf portion having the first portion of water-absorbing agent disposed thereon and a second separate shelf portion having the second portion of water-absorbing agent disposed thereon. 15. A dehumidifying device according to claim 14 wherein the container comprises two separate reservoirs, a first reservoir for receiving the first shelf portion and a second separate reservoir for receiving the second shelf portion. 16. A dehumidifying device according to claim 15 wherein the first reservoir is not in fluid communication with the second reservoir. 17. A dehumidifying device according to claim 1 wherein the opening of the container is covered with a semi-permeable membrane. 18. A method for removing water vapour from a locus, comprising locating a dehumidifying device according to claim 1 in the locus. 19. (canceled) 20. (canceled)
The present invention relates to a device for absorbing water vapour. Particularly, although not exclusively, it relates to a device for dehumidifying air in a confined or limited space; and to associated methods. Humidity, or water vapour in air, is often undesirable as it may interfere with the storage of moisture sensitive materials, such as foodstuffs, cosmetics, pharmaceuticals, household goods and clothes, or it may adversely effect the operation of moisture sensitive equipment. This problem may be particularly pronounced in those areas where humidity levels are particularly high, such as those countries having hot humid climates. It is therefore often desirable to dehumidify air. Traditional methods for dehumidifying air include the use of mechanical refrigeration equipment and water absorbent materials, such as silica gel. Typically, methods employing refrigeration equipment involve cooling air to a predetermined temperature below its dew point, so that water condenses from the air and the water may be drained away. Thereafter, the air may be reheated to a predetermined warmer temperature. Techniques including absorbent materials may include continuous operation systems so that water is absorbed by the absorbent in a first cycle and then water desorbed from the absorbent by the application of heat in a second cycle. Suitably, these techniques suffer from various disadvantages as they typically require bulky and heavy equipment, such as compressors, fans and heaters, which are interconnected by a network of pipes so that water vapour is absorbed continuously from air. Typically, such systems are ill-suited for operation in a confined or limited space. Moreover, the cost associated with such systems may prohibit their use in a domestic environment. In an attempt to overcome the disadvantages associated with using the aforementioned systems in a confined or limited space, alternative techniques have been developed that include exposing air to an absorbent material. In particular, portable smaller devices comprising a container housing an absorbent material have been employed for dehumidifying air in a limited or confined space, particularly in a domestic environment. Although absorbents such as silica gel may be employed in these devices, typically silica gel only absorbs up to 30% its weight of water and it is necessary to employ an absorbent having a higher capacity for water vapour absorption to prolong the life and improve the efficiency of the device. Suitably, hygroscopic deliquescent agents, such as calcium chloride, which may absorb 4 to 5 times its weight of water, have been employed in such devices. Upon prolonged exposure to water vapour, typically in the order of days, the degree of saturation of the deliquescent agent increases and the deliquescent agent forms a liquid of gel, and is such that liquid seeps from it. Typically, the deliquescent agent is placed on a perforate shelf in the container so that the liquid drips into a region of the base of the container, thereby providing an indication that the container is functioning satisfactorily. Although these devices have gone some way to solving the problems associated with absorbing water vapour in a confined space, particularly in a domestic environment, a major disadvantage with these devices, particularly those employing a deliquescent agent, is that they only provide the user with an indication that the device is functioning satisfactorily after it has been placed in a humid environment for prolonged periods of time. Typically, these devices do not provide the user with an early indication that the device is functioning satisfactorily shortly after being placed in a humid environment, because it typically takes a number of days before the deliquescent agent reaches a level of saturation to form a liquid or gel. The present invention seeks to solve the aforementioned problems associated with the efficient absorption of water vapour, in particular, absorption of water vapour from air in a confined space, particularly in a domestic environment. According to a first aspect the present invention provides a dehumidifying device for absorbing water vapour from ambient air comprising a container having an opening to permit water vapour to enter the container, the container having a water-absorbing agent disposed therein for absorbing water vapour, wherein a first portion of the water-absorbing agent is adapted to provide an indication of water absorption faster than a second, separate, portion of the water-absorbing agent following exposure of the first and second portions of water-absorbing agents to water vapour, thereby providing an early indication of the operation of the device. Conveniently, the dehumidifying device includes two portions of a water-absorbing agent which, when exposed to water vapour, provide an indication of water absorption at different rates thereby providing an early indication that the device is functioning satisfactorily and maintaining the environment in which it is placed at an acceptable humidity level. Preferably, the first portion of the water-absorbing agent is a deliquescent agent that forms a liquid or gel on absorption of water vapour, preferably such that liquid seeps from it, thereby providing an early indication of the operation of the device. Preferably, the second portion of the water-absorbing agent is a deliquescent agent that forms a liquid or gel on absorption of water vapour, preferably such that liquid seeps from it, thereby providing a later indication of the operation of the device. Most preferably, both the first and second portions of the water-absorbing agent are deliquescent agents. Conveniently, the first portion of deliquescent agent provides an early indication of the operation of the device and the second portion of deliquescent agent provides a later indication of the further operation of the device following placement of the device in a humid environment for a prolonged time. Preferred deliquescent agents include calcium chloride and magnesium chloride as these not only exhibit an acceptable water absorption capacity but they are relatively non-caustic which render them suitable for use in devices that may be placed in a domestic environment. This does not exclude other deliquescent salts, for example when intended for use in other environments, for example industrial environments One preferred water-absorbing agent is calcium chloride alone. Another is magnesium chloride. Especially preferred is calcium chloride providing up to 20 wt % of the total content and the balance comprising a different water-absorbing agent, preferably magnesium chloride. Suitably, the water-absorbing agent as defined herein may include other components selected from a binder or thickener, for example starch, a pest control agent, a perfume, and odour absorbing agent (for example a zeolite), an antimicrobial agent, and combinations thereof. Preferably, when the water-absorbing agent comprises a deliquescent agent then an antimicrobial agent is included to prevent microbe formation in liquid formed by dissolution of the deliquescent agent. Preferably, the first portion of the water-absorbing agent is adapted to provide an indication of water absorption in greater than or equal to 12 hours, more preferably greater than or equal to 18 hours, even more preferably greater than or equal to 24 hours, even more preferably greater than or equal to 36 hours, most preferably greater than or equal to 48 hours following exposure to water vapour. By the term “provide an indication of water absorption” we mean the time when the water-absorbing agent has absorbed sufficient water vapour so that it provides an indication of the operation of the device. For example, when the first and/or second portions of water-absorbing agent comprise a deliquescent agent, we mean the respective times when each portion of deliquescent agent has absorbed sufficient water vapour to generate a liquid or gel, preferably so that liquid seeps from it, thereby providing an indication of the operation of the device. Preferably, the second portion of water-absorbing agent is adapted to reach saturation in greater than or equal to 2 days, more preferably greater than or equal to 3 days, even more preferably greater than or equal to 5 days, most preferably greater than or equal to 7 days following exposure to water vapour. It will be appreciated that when the first and second portions of water-absorbing agents “provide an indication of water absorption” as defined herein, the first and second portions of water-absorbing agent may still continue to absorb water vapour from the environment. Preferably, the first portion of water-absorbing agent is adapted to provide an indication of water absorption at a rate of greater than or equal to 2 times, more preferably greater than or equal to 3 times, most preferably greater than or equal to 5 times the rate at which the second portion of water-absorbing agent is adapted to provide an indication of water absorption, following exposure of the first and second portions of water-absorbing agents to the same level of water vapour. Preferably, the second portion of water-absorbing agent is adapted to provide an indication of water absorption following exposure to water vapour at substantially the same time as when the first portion of water-absorbing agent is exhausted. For example, when the first and second portions of water-absorbing agent comprise deliquescent agents, the time when the second portion has absorbed sufficient water vapour to generate a liquid or gel, preferably so that liquid seeps from it, corresponds substantially to the same time when the first portion has absorbed its maximum capacity of water vapour. Conveniently, in this preferred embodiment of the present invention, the first and second portions of water-absorbing agent respectively provide an early indication and a continuous further indication of the operation of the device when placed in a humid environment. Preferably, the mass of the first portion of water-absorbing agent is less than the mass of the second portion of water absorbing agent. Conveniently, the composition of the first and second water-absorbing agents may be substantially identical. Preferably, the first portion of water-absorbing agent is partially or fully pre-saturated prior to exposure to water vapour. By the term “pre-saturated” we mean that the first portion of water-absorbing agent includes moisture so that it reaches saturation faster than the same mass of an identical anhydrous water-absorbing agent when both the pre-saturated and anhydrous water-absorbing agents are exposed to the same level of water vapour. Conveniently, when the first portion of water-absorbing agent is partially or fully pre-saturated prior to exposure to water vapour, the composition of the first and second water-absorbing agents of the container of the present invention may be substantially identical. Preferably, the first portion of water-absorbing agent is partially or fully pre-saturated prior to exposure to water vapour so that it reaches saturation at a rate of greater than or equal to 2 times, more preferably greater than or equal to 3 times, most preferably greater than or equal to 5 times the rate at which the same mass of an identical anhydrous water-absorbing agent reaches saturation following exposure of both the pre-saturated and anhydrous water-absorbing agents to the same level of water vapour. As mentioned hereinbefore, the composition of the first and second portions of water-absorbing agents may be substantially identical. Suitably, when the water-absorbing agent comprises a deliquescent agent as defined herein the first and second portions of the water-absorbing agent may comprise the same deliquescent agent, for example calcium chloride or magnesium chloride. Alternatively, the composition of the first and second portions of the water-absorbing agent may be different. Conveniently, the compositions of the first and second portions of water-absorbing agent may be chosen so that the first portion of water-absorbing agent provides an indication of water absorption faster than the second portion of water-absorbing agent. Suitably, when the water-absorbing agent comprises a deliquescent agent as defined herein, the first portion of water-absorbing agent may comprise magnesium chloride and the second portion of water-absorbing agent may comprise calcium chloride. Preferably, the first portion of water-absorbing agent is disposed on a shelf positioned above the base of the container. Preferably, the second portion of water-absorbing agent is disposed on a shelf positioned above the base of the container. More preferably, both of the first and second potions of water-absorbing agent are disposed on a shelf positioned above the base of the container. Most preferably, the shelf comprises a perforate shelf. Conveniently, the use of a perforate shelf permits liquid to seep from the first and/or second portions of water-absorbing agent (e.g. deliquescent agent) into a region of the base of the container. As mentioned above the first portion of water-absorbing agent is separate from the second portion of water-absorbing agent. By the term “separate” we mean that the first portion of water-absorbing agent is not in physical contact with the second portion of water-absorbing agent. In other words, the second portion of water-absorbing agent, for example is not coated with the first portion of water-absorbing agent, and vice versa. Suitably the first and second portions of water-absorbing agent are located at different positions in the container. Preferably, the first and second portions of water-absorbing agent are located at different positions on the shelf as defined herein. Preferably, the shelf defines a first shelf portion having the first portion of water-absorbing agent disposed thereon and a second separate shelf portion having the second portion of water-absorbing agent disposed thereon. Conveniently, the dehumidifying device may include a single shelf defining the first and second separate shelf portions. Alternatively, the dehumidifying device may include two separate shelves. Suitably, when the shelf defines a first and second shelf portion; the first shelf portion is perforate. Suitably, when the shelf defines a first and second shelf portion, the second shelf portion is perforate. Preferably, both the first and second shelf portions are perforate. Preferably, when the dehumidifying device comprises two separate shelf portions the container comprises two separate reservoirs: a first reservoir for receiving the first shelf portion; and, a second reservoir for receiving the second shelf portion. Conveniently, such an arrangement may allow the container to be dimensioned so that the early indication of the operation of the device is more visible to the user. Moreover, such an arrangement may prevent mixing of liquids formed from the first and second portions of water-absorbing agent upon absorption of water vapour. This may be desirable to prevent adverse reactions between liquids formed from the respective water-absorbing agents, particularly when the composition of the first and second portions of water-absorbing agent are different. Conveniently, when the dehumidifying device comprises two separate perforate shelf portions, a first reservoir for receiving the first perforate shelf portion and a separate second reservoir for receiving the second perforate shelf portion, such an arrangement may permit liquid to seep from the first and second portions of water-absorbing agent into separate regions of the base of the container. Preferably, the shelf extends between the side wall(s) of the container. Conveniently, where the shelf includes a first and second shelf portion, the first shelf portion extends between the side walls(s) of the first reservoir and the second shelf portion extends between the side wall(s) of the second reservoir. In a particularly preferred embodiment of the present invention the container comprises two separate reservoirs as defined above, wherein the first reservoir for receiving the first shelf portion is not in fluid communication with the second reservoir for receiving the second shelf portion. Conveniently, such an arrangement may not only prevent mixing of liquids formed from the first and second portions of water absorbing agent upon absorption of water vapour but also may prevent transfer of water vapour from the first to second portion of water-absorbing agent, and vice-versa, thereby restricting, preferably preventing, equilibration of the degree of saturation between the first and second portions of water-absorbing agent. Consequently, this arrangement may further ensure that the first portion of water-absorbing agent provides an indication of water absorption before the second portion of water-absorbing agent. Suitably, when the shelf comprises a perforate shelf, the openings in the perforate shelf, and first and second shelf portions when present, are dimensioned to allow liquid to drip from the first and second portions of water-absorbing agent. The openings may be of any shape and of any size which allows for good passage of liquid, but retention of the water-absorbing material on the shelf. Suitable shapes include circles, squares and slits. Typically, the openings as defined above have a minimum width of 0.1 mm to 2 mm. Preferably, the container opening is covered with a vapour-permeable liquid-impermeable membrane to permit water vapour to enter the container and prevent liquid from exiting the container. Suitably, when the container includes a first and second reservoir as defined herein, the opening of the first reservoir may be covered with a first vapour-permeable liquid-impermeable membrane and the opening of the second reservoir may be covered by a second separate vapour-permeable liquid-impermeable membrane. Alternatively, the openings of the first and second reservoirs may be covered with a single vapour-permeable liquid-impermeable membrane. Suitable membranes are well known to those skilled in the art, such as polytetrafluoroethylene (PTFE) membranes available from W L Gore and Associates Inc., or polyolefin films available under the trade mark TYVEK, or polyurethane films. The vapour-permeable liquid-impermeable membrane not only permits the container of the present invention to function satisfactorily but also prevents spillage of liquid from the container formed by dissolution of the water-absorbing agent, when a deliquescent agent is used. Unexpectedly, we have found that the rate of absorption of water vapour by the water-absorbing agent may be increased when the water-absorbing agent is in contact with the vapour-permeable liquid-impermeable membrane. Thus, according to a preferred embodiment of the present invention, the first portion of water-absorbing agent and/or the second portion of water-absorbing agent contacts the vapour-permeable liquid-impermeable membrane. More preferably, both the first and second portions of water-absorbing agent contact the vapour-permeable liquid-impermeable membrane. Preferably, the membrane is immovably secured across the opening of the container to prevent a user accessing the interior of the container and contacting the water-absorbing agent, thereby improving the safety rating of the container. Preferably, a membrane used in the present invention is of a type which provides moisture transmission of at least 1000 g, preferably at least 5000 g, and most preferably at least 10000 g water/m2 through the membrane/day. Suitably, the inlet of the container includes a removable fluid tight seal so that it may be stored without degradation of the water-absorbing agent. Suitably, the fluid tight seal extends across the semi-permeable membrane. Preferably, the container further includes an outlet having a resealable fluid tight seal to permit drainage of liquid from the container and/or to permit water-absorbing agent to be added to the container. Conveniently, this enables the container of the present invention to be re-used thereby decreasing the amount of expenditure required when it is necessary to replace an exhausted device with a new one. Suitably, the dehumidifying device of the present invention is dimensioned so that it may be used in a confined space, particularly a confined space in a domestic environment, such as a drawer, chest, wardrobe, cupboard, packing case, refrigerator, freezer, cool box, caravan, car, car boot or boat. Suitably, the container of the present invention is 5 to 30 cm high, 10 to 50 cm long, and 5 to 30 cm wide. Typically, the device includes 50-1000 g of water-absorbing agent, preferably 100-500 g. Suitably, the container is rigid or flexible. Most preferably, the container is rigid. Preferably, the container and the shelf are formed from a plastics material, for example a polyolefin, by techniques well known to those skilled in the art such as injection moulding, blow moulding and vacuum forming. According to a further aspect, the present invention provides a method for removing water vapour from a locus, preferably an enclosed locus, comprising locating a dehumidifying device as described herein in the locus. The present invention will now be illustrated by way of the following non-limiting examples, in which: FIG. 1 is a perspective view of a dehumidifying device of the present invention; FIG. 2 is a side view of the dehumidifying device of FIG. 1; FIG. 3 is a perspective view of the component parts of the dehumidifying device of FIG. 1; and FIG. 4 is a cross-sectional view of the dehumidifying device of FIG. 1 taken along the line A-A′. The dehumidifying device (1) of FIGS. 1 to 4 comprises a container (2) formed by injection moulding having integral first (4) and second (6) separate reservoirs. The first (4) and second (6) reservoirs have an arched-shaped base (8, 10) and separate side walls (12, 14) extending upwardly from the respective bases (8, 10) to define separate openings (16, 17) at the upper end of the first and second reservoir, respectively. The upper end of side walls (12, 14) terminate in an annular rim (18) that extends around the openings (16, 17). The first smaller reservoir (4) of the container (2) is separated from the second larger reservoir (6) by interior dividing wall (20) extending across container (2). A first vapour-permeable liquid-impermeable membrane (19) comprised of TYVEK material (Trade Mark; HDPE material from DuPont) is heat-sealed to rim (18) so that it extends across and covers opening (16). A second vapour-permeable liquid-impermeable membrane (21) comprised of TYVEK material is heat sealed to rim (18) and dividing wall (2) so that it extends across and covers opening (17). Suitably, the first (4) and second (6) reservoirs are not in fluid communication with each other. The interior of the first (4) and second reservoirs (6) of the container (2) include a first (22) and second (24) perforate shelf, respectively, formed from translucent HDPE. The first shelf includes a perforate container (23) having a lip (26) that rests on rim (18) and dividing wall (20). The second shelf includes a perforate container (25) having a lip (28) that rests on rim (18) and dividing wall (20). A plurality of circular holes (not shown) of diameter 1 mm pass through each shelf (22, 24). The first smaller shelf supports a pre-saturated magnesium chloride water-absorbing agent (29). The second larger shelf supports an anhydrous calcium chloride water-absorbing agent (30). The first (19) and second (21) vapour-permeable liquid-impermeable membranes are covered by a perforate liquid-permeable plastic net (32). The plastic net (32) is covered by a perforate lid (34) that snap-fits over rim (18) of the container (2). The operation of the container shown in FIGS. 1 to 4 is simple. After purchase the user removes an impermeable plastics cover (not shown). This is provided during manufacture in order to maintain the water-absorbing material in a substantially desiccated condition, prior to the commencement of use. The user places the container on a level surface in an air space in which reduction of humidity is desired. Water vapour is absorbed by both the magnesium chloride and calcium chloride water-absorbing agents. The magnesium chloride water-absorbing agent absorbs sufficient water vapour after approximately 24 hours and forms a gel so that liquid seeps from the magnesium chloride water-absorbing agent through the shelf (22) and into reservoir (4), thereby providing an early indication that the device (1) is functioning satisfactorily and maintaining the environment at an acceptable humidity level. After approximately 2 days the magnesium chloride water-absorbing agent is exhausted and at substantially the same time the calcium chloride water-absorbing agent has absorbed sufficient water vapour such that gel and liquid seeps from it through the shelf (24) and into reservoir (6), thereby providing a further indication that the container is still operating satisfactorily. When the calcium chloride water-absorbing agent is exhausted, the liquid dripping through shelf (26) stops thereby providing an indication that the device needs to be replaced.
20050511
20080129
20051006
60254.0
0
LAWRENCE JR, FRANK M
DEHUMIDIFYING DEVICE
UNDISCOUNTED
0
ACCEPTED
2,005
10,512,611
ACCEPTED
Method and computer program product for generation of bus functional models
In accordance with the present invention, there is provided a method for creating a Bus Functional Model of an Integrated Circuit. The method comprises the following steps: providing (102) a detailed specification of said Integrated Circuit, defining (104) an architecture for said Bus Functional Model. In the following step data contained in the detailed specification of the Integrated Circuit are mapped (106) between the specification and the predefined BFM architecture. The BFM architecture contains at least one of the following constructs: Interface Tasks (202), Internal Data Elements (204), Processes (208), Finite State Machines (210), Conditions (206), Actions (212) and Signals (214). In the following step (110) the formal description of Bus Functional Model in Formal Description Language is created.
1. A method of creating a Bus Functional Model of an Integrated Circuit wherein said method comprising the steps of: (a) providing (102) a detailed specification of said Integrated Circuit, (b) defining (104) an architecture for said Bus Functional Model, (c) mapping (106) between said Integrated Circuit specification and said defined Bus Functional Model architecture wherein said Bus Functional Model architecture contains at least one of the following constructs: Interface Tasks (202), Internal Data Elements (204), Processes (208), Finite State Machines (210), Conditions (206), Actions (212), Signals (214), (d) Creating (110) formal description of said Bus Functional Model in a Formal Description Language in a computer readable form. 2. A method according to claim 1 further comprising the steps: (e) providing (112) said formal description of said Bus Functional Model in a computer readable form to a computer; (f) providing (114) templates for generation of BFM in particular target language to said computer; (g) generating (116) BFM source code in said target language by applying said formal description on said templates. 3. A method according to claim 2 further comprising the step of debugging (118) said BFM source code. 4. A method according to claim 1 wherein said steps (a) to (d) are performed manually. 5. A method according to claim 1 wherein said Integrated Circuit specification is provided to a computer in computer readable form and steps (b) to (d) are performed automatically in said computer. 6. A computer program product stored on a computer usable medium, comprising computer readable program means for causing a computer to perform all the steps of the method according to claim 1. 7. A computer program product stored on a computer usable medium, comprising computer readable program means, said computer program being result of performing all the steps of the method according to claim 1. 8. A method according to claim 2 wherein said steps (a) to (d) are performed manually. 9. A method according to claim 2 wherein said Integrated Circuit specification is provided to a computer in computer readable form and steps (b) to (d) are performed automatically in said computer.
TECHNICAL FIELD The present invention relates to a method and a computer program product for generation of Bus Functional Models. In particular the invention is applicable to hardware/software integration, and verification of electronic hardware designs. BACKGROUND As improvements and development of integrated circuits result in miniaturization and complexity of the Integrated Circuits (IC) consideration has to be given to ensure that the ICs built in real hardware will function correctly. To avoid releasing products with errors that can lead to malfunctioning it is desirable to verify that the new device operates according to defined earlier functional specifications. A standard method to provide such verification in the conventional technology is the one based on Bus Functional Model (BFM) approach. In this approach a synthesizable model of the IC, called Full Functional Model (FFM), is verified against the BFM that is a behavioural model of the same IC. FFM is also used to produce the IC itself. There are hardware simulators, known in the art (e.g. Verilog), that support such verification. Another major application of BFM is using it to provide an early hardware/software integration and reduce the development time and debug the software even before the physical IC is ready. BFM can both generate and verify simulation vectors that are sent to and received from the simulated IC. In this approach it is verified how the software part works with other devices on the bus. The software communicates with other devices on the bus using the BFM that, in this case, is a layer between the software and the bus. As mentioned earlier in the specification the Bus Functional Model (BFM) is a behavioural model, and is developed in Hardware Description Language (HDL) (one of the existing industry standard languages such as Verilog, VHDL, SystemC, etc.) that allows stimulating bus activity or an activity on any specified interface to IC, based upon given stimulus. A bus functional model typically interacts with an IC during a simulation by sending data to and receiving data from the IC. Stimuli are transferred to and from BFM using task based Application Program Interface (API) function calls. BFM can be used together with different simulation instruments. Usually BFM includes interface to bus functions as well as some functionality of the device that uses this interface. BFM works as a bus interface unit. In the common approach it has two interfaces: bus pin interface and transaction task interface. Pin interface is used for communication with other bus devices according to the bus protocol. Transaction task interface is used for the execution of transactions that allow using special high level commands such as “READ” or “WRITE” which are translated into sequences of low-level signals in the pin interface. Such approach allows the model to generate different bus activities without execution of the whole program. In methods known in the art the BFM code is developed according to three main inputs: IC Specification, HDL language, developers' experience. HDL language is taken as an instrument for creation of BFM through the analysis of the IC Specification applying the developers, experience in the area of modelling. There are no well-defined rules established for the interaction between these inputs. Therefore, each time BFM is created, the task of BFM design, the way of usage of IC Specification, and choice of the particular way of implementation is resolved individually according to the developer's team experience. Results of such technique are several basic problems in the BFM development. First, BFM structure is not formalized, thus the task of BFM development requires a deep knowledge on modelling and experience in BFM design. Another big problem results form the fact that each time a BFM is being created, the architecture of it shall be developed again. Yet another problem is that languages currently used for model development are not aimed for development of BFM as such and are not enough high-level. On the one hand they allow generating a wide range of different models (including BFMs) but on the other hand they are not very effective to produce BFMs in particular. The above general problems lead to the following derivative problems of non-optimal code. The code that is not strictly structured and not enough high-level, which is big and complex, potentially contains much more defects, and the efforts to locate these defects and resolve them consequently increase. The maintenance and modification of such code is also rather difficult. Furthermore, not structured BFM code tends to be asynchronous. And one of the major problem of the asynchronous code is “signal racing”. The “signal racing” problem occurs in situations when at the same simulation time a certain data element is set in one process and is being read in the other process. This leads to the situation when it is not guaranteed that the reading process will get correct value of the data element (it can be set and then read and also vice versa). This problem cannot be exposed during testing. The code may work correctly on the tests but may occasionally fail sometime when these two events are rescheduled in the simulator for some reason. So the behaviour of the model becomes unpredictable. As this kind of defects cannot be revealed by tests with certainty (it may be unrepeatable or even not detected at all) the only reliable way to find and resolve this problem is the analysis of the code by means of code inspection. But these method is very expensive and effort consuming, especially if the code is big and complex. BFM HDL code is dependant on the specific of the particular source language and is very difficult to transfer to another source language. Additionally the code that is complex and not strictly structured is very difficult to be reused. In the U.S. Pat. No. 5,920,711 a method of automatic generation of models specified by frame protocols is disclosed. The method proposes to specify the model by a Frame State Machines using visual tools and then the model HDL code may be automatically generated from it. The problem of this approach is that not every protocol may be easily specified by Frame State Machine and thus this method is not applicable (or hardly applicable) for the whole range of BFMs. Hence, considering the above problems, better method of BFM development is needed. The new method should make it less effort consuming and reduce BFM code size and complexity. SUMMARY OF THE INVENTION There is a need for a method for generation of BFM and a computer program product which alleviate or overcome the disadvantages of the prior art. The method and the computer program product of the invention are preferably for use in hardware/software integration, and verification of electronic hardware designs. In accordance with the present invention, there is thus provided a method for creating a Bus Functional Model of an Integrated Circuit. The method comprises the following steps: providing a detailed specification of said Integrated Circuit, in the next step an architecture for said Bus Functional Model is defined. In the following step data contained in the detailed specification of the Integrated Circuit are mapped between the specification and the predefined BFM architecture. The BFM architecture contains at least one of the following constructs: Interface Tasks, Internal Data Elements, Processes, Finite State Machines, Conditions, Actions and Signals. In the final step the formal description of Bus Functional Model in Formal Description Language (FDL) is created. The formal description is created in a computer readable form. These steps described above can be performed both manually by the designer as well as by means of a computer. The method further comprises the step of providing the formal description of the Bus Functional Model to a computer. To generate the BFM in particular target language, templates for such generation are then entered to said computer. Finally the Bus Functional Model source code in the target language is generated by applying said formal description on said templates. In accordance with another aspect of the present invention there is thus provided a first computer program product stored on a computer usable medium, comprising computer readable program means for causing a computer to perform all the steps in accordance with the invention described herein. In accordance with yet another aspect of the present invention there is thus provided a second computer program product stored on a computer usable medium, comprising computer readable program means, said computer program being result of performing all the steps in accordance with the invention described herein. The method and the first computer program product according to the present invention allow generating of Bus functional Models, which can be used for verification of electronic hardware designs. As a result of structurization of BFM the source code in target language is also structurized. Thanks to this formalized structure the source code of the BFM is not asynchronous and the problem of “signal racing” is eliminated. There are also other advantages of the invention that are results of the formal structurization. One of the basic advantages is 3 to 8 times reduced size of the source code. And reduced size of the code means that the number of defects and time necessary to resolve them is also significantly reduced. Because of well defined structure of the BFM generated according to the present invention it is possible to reuse some parts of the generated BFM when the IC is further developed. BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be understood and appreciated more fully from the following detailed description taken in conjunction with the drawings in which: FIG. 1 is a flowchart illustrating the method of creating Bus Functional Models in accordance with an embodiment of the invention; FIG. 2 is a schematic illustration of the architecture of the Bus Functional Model of an Integrated Circuit and relations between its constructs in accordance with an embodiment of the invention; FIG. 3 is a timing diagram illustrating time dependencies of constructs' interactions in accordance with an embodiment of the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Terms used herein below will be easier understood when considered in connection with FIG. 2. The term Interface Tasks 202 herein below refers to description of the interface between user and BFM. The term Internal Data 204 herein below refers to description of the BFM system data. It has three main types of data elements: transaction table—it stores the data and status information for the separate bus transactions in the table form; queues—it is aimed at ordering the information in the transaction table. It stores the pointers to the separate lines of the table; registers—it stores the BFM global data (e.g. the BFM current state or configuration). The term Processes 208 herein below refers to description of a BFM's active element that initiate all other BFM activity. The following information can be specified for each Process 208: start condition used for the Process' 208 activation list of: Actions 212 to execute; Finite State Machines 210 to start; Finite State Machines 210 to terminate. The lists are managed consequentially within the single Process 208, but different Processes 208 are executed concurrently. The Process 208 can be in wait state and in execution state. At first, all the Processes 208 are in wait state. If the Process 208 is in wait state the Condition 206 is evaluated on each clock edge. If the Condition 206 is true, the Process 208 goes to execution state, the Actions 212 are executed and the Finite State Machines 210 are started and/or terminated. The term Finite State Machines (FSM) 210 herein below refers to description of Actions 212 sequence. The sequence is a set of states and transitions between the states. When an FSM 210 is being executed, the Condition 206 associated with the transition from the current state is evaluated on each clock edge, and if it is true the transition is executed and the associated Actions 212 are performed. The same is repeated for the next state, etc. Otherwise (if the current Condition 206 is false) the execution of the FSM 210 continues on the next clock edge. FSM 210 can have the following types of conditional transitions: wait until a certain condition becomes true; wait for the next clock edge; branching according to the certain condition's value; unconditional transition; call of another FSM 210 (thus allowing nesting of FSM 210). The term Conditions 206 herein below refers to description of expressions (used arithmetical and logical operations) with a true/false output. Condition 206 can be named to allow referring to it in other Conditions 206. The term Actions 212 contains a set of operators used to: change contents of the Internal Data 204 construct activation of the Signals' 214 primitive Several operators in the Actions 212 construct can be grouped together and named, so this named Action 212 expands valid operators set. The term Signals 214 herein below refers to description of BFM pin interface which is used to connect the BFM to an Integrated Circuit. The following information can be specified for each signal: signal's outward form (name, dimension and direction) primitives for operating with the signal (signal timing). Referring to FIG. 1 in step 102 a detailed specification of an IC is provided to create a BFM that describes the behaviour of this IC. In the step 104 an architecture of the BFM is to be defined. Then starts a process of mapping 106 between IC specification and predefined in step 104 architecture of the BFM. The predefined architecture contains at least one of the following constructs: Interface Tasks (202), Internal Data Elements (204), Processes (208), Finite State Machines (210) Conditions (206), Actions (212), Signals (214). Each of the defined constructs interacts with other constructs and the relations between them are explained with reference to FIG. 2. Interface Task construct 202 interacts with Internal Data construct 204 by setting/getting its content. Internal Data construct 204 interacts with Actions 212 and Task Interface 202 constructs by providing an interface (a set of operators) for data setting/getting and by providing data values to them. Internal Data construct 204 interacts also with Conditions construct 206 by providing data values to it. Conditions construct 206 interacts with Processes 208, FSMs 210 and Signals 214 constructs by providing conditions for evaluation. This construct also interacts with Internal Data 204 and Signals 214 constructs by getting their data values to use as operands. Actions construct 212 interacts with Internal Data construct 204 by modification of its content, with Signals construct 214 by activation of the primitives, and with Processes 208, FSMs 210 constructs by providing a set of operators for execution. Signals construct 214 interacts with Actions construct 212 by providing primitives as a valid Actions' 212 operators and with Conditions 206 construct by providing data values to it. FSMs construct 210 interacts with Conditions construct 206 by evaluating its values, with Actions construct 212 by executing its operators and with Processes construct 208 by causing FSMs to be started or interrupted. Processes construct 208 interacts with Conditions construct 206 by evaluating its values and with Actions construct 212 by executing its operators as well as with FSM construct 210 by starting/terminating them. Time dependencies of the constructs' interactions are presented with reference to FIG. 2 and 3. A Process (of the Processes construct 208) illustrated on FIG. 3 has: COND1 as a start condition (of the Conditions construct 206), ACT1 as an action (of the Actions construct 212) and FSM1 as an FSM to execute (of the FSM construct 210. Between clock edges 1 and 2 COND1 becomes true and this let the Process 208 starts on the clock edge 2, when its start Condition 206 is true. The Actions 212 are made on the clock edge 2 but the results are visible only on the clock edge 3. If there is a Condition (of the Conditions construct 206) like (ID1=1) it would be true on clock edge 3 and yet false on clock edge 2. Similarly, the FSM 210 starts working on the clock edge 2. The Condition 206 on the transition from the starting state is checked on the clock edge 2 and if true, the transition is executed on the clock edge 2. All the Actions 212 made are visible only on the clock edge 3. The next transition(s) are checked on the same clock edge 2 until some Condition 206 is false and the corresponding transition is blocked. All the modifications made while executing the transitions are queued and actually made so as to be visible only on the clock edge 3. With reference to FIG. 1, during the process of mapping 106 a data from the specification are allocated to respective construct (202-214) depending on what the data is related to. For example the data related to description of expressions (using arithmetical and logical operations) with a true/false output are allocated to Conditions 206 construct. Same way data related to description of a set of states and transitions between states are allocated to Finite State Machine 210 construct. In the step 110 a formal description of the Bus Functional Model is created in FDL, in computer readable form. The FDL is a BFM-oriented high-level language that incorporates the general BFM architecture. The FDL can be used to express whole BFM structure or separate aspects of the BFM operation. The FDL operates with the constructs that are used to specify the BFM. The interaction of these constructs is also organized in a predefined way that provides such features of the FDL as full synchronization and strict structure, and well-defined purpose of each construct. The full synchronization makes possible elimination of the problem of “signal racing”. There are also a set of special data structures incorporated in the FDL that allows to specify easily different BFM queues, transactions etc. The FDL used for description of the BFM according to the present invention was developed by the applicant. The FDL consists of a number of elements and the most important ones are presented in the Table I as an example only. TABLE I FDL element Grammar Rule Handle handle_specifier ::= <queue_name>.Get(<numeral_expression>) | <queue_name>.First | <queue_name>.Last | r: <register_name> | handle | name of tenure local variable Internal Data data_specifier ::= s:<signal_name> | p:<parameter_name>(<handle_specifier>) | <queue_name>.rq_count | <handle_specifier> | l:<local_parameter_name> Numeral Value numeral_value ::= number | <data_specifier> Numeral Expression numeral_expression ::= any numerical operations under <numeral_value> Comments comments ::= // any text comments here \n | /* any text comments here */ Macro Definition macro ::= m:<macro_name>(<parameter_1_value>, <parameter_2_value>, ...) Condition condition ::= <numeral_expression> relational operator <numeral_expression> | IsSet (<handle_specifier>) | IsAsserted (<data_name>) | IsNegated (<data_name>) | <condition> logical operator <condition> | c:<name_of_named_condition> Referring to FIG. 1 the method further comprises the step in which said formal description in computer readable form is provided 112 to the computer. Then, the templates that defines the rules of generation of BFM in particular target language are provided 114 to this computer. In the step 116 the computer generates a source code of the BFM in the target language by applying the formal description on the templates. In the last step 118 the BFM source code is debugged. The method in accordance with the present invention may be used for generating Bus Functional Models of different Integrated Circuits. In particular, the invention is usable in simulating bus activity or an activity of any specified interface to IC, based upon given stimulus. Therefore the method may be used in hardware/software integration, and verification of electronic hardware designs. It will be understood that the invention tends to provide the following advantages singly or in any combination: by generating a code that is synchronous the problem of signal racing is eliminated; source code of the BFM is significantly reduced in comparison with the one produced by means of prior art methods; by reducing the code size also the number of errors is significantly reduced; structurized form of the code make debugging easier and additionally some parts of the code can be reused when the IC is further developed.
<SOH> BACKGROUND <EOH>As improvements and development of integrated circuits result in miniaturization and complexity of the Integrated Circuits (IC) consideration has to be given to ensure that the ICs built in real hardware will function correctly. To avoid releasing products with errors that can lead to malfunctioning it is desirable to verify that the new device operates according to defined earlier functional specifications. A standard method to provide such verification in the conventional technology is the one based on Bus Functional Model (BFM) approach. In this approach a synthesizable model of the IC, called Full Functional Model (FFM), is verified against the BFM that is a behavioural model of the same IC. FFM is also used to produce the IC itself. There are hardware simulators, known in the art (e.g. Verilog), that support such verification. Another major application of BFM is using it to provide an early hardware/software integration and reduce the development time and debug the software even before the physical IC is ready. BFM can both generate and verify simulation vectors that are sent to and received from the simulated IC. In this approach it is verified how the software part works with other devices on the bus. The software communicates with other devices on the bus using the BFM that, in this case, is a layer between the software and the bus. As mentioned earlier in the specification the Bus Functional Model (BFM) is a behavioural model, and is developed in Hardware Description Language (HDL) (one of the existing industry standard languages such as Verilog, VHDL, SystemC, etc.) that allows stimulating bus activity or an activity on any specified interface to IC, based upon given stimulus. A bus functional model typically interacts with an IC during a simulation by sending data to and receiving data from the IC. Stimuli are transferred to and from BFM using task based Application Program Interface (API) function calls. BFM can be used together with different simulation instruments. Usually BFM includes interface to bus functions as well as some functionality of the device that uses this interface. BFM works as a bus interface unit. In the common approach it has two interfaces: bus pin interface and transaction task interface. Pin interface is used for communication with other bus devices according to the bus protocol. Transaction task interface is used for the execution of transactions that allow using special high level commands such as “READ” or “WRITE” which are translated into sequences of low-level signals in the pin interface. Such approach allows the model to generate different bus activities without execution of the whole program. In methods known in the art the BFM code is developed according to three main inputs: IC Specification, HDL language, developers' experience. HDL language is taken as an instrument for creation of BFM through the analysis of the IC Specification applying the developers, experience in the area of modelling. There are no well-defined rules established for the interaction between these inputs. Therefore, each time BFM is created, the task of BFM design, the way of usage of IC Specification, and choice of the particular way of implementation is resolved individually according to the developer's team experience. Results of such technique are several basic problems in the BFM development. First, BFM structure is not formalized, thus the task of BFM development requires a deep knowledge on modelling and experience in BFM design. Another big problem results form the fact that each time a BFM is being created, the architecture of it shall be developed again. Yet another problem is that languages currently used for model development are not aimed for development of BFM as such and are not enough high-level. On the one hand they allow generating a wide range of different models (including BFMs) but on the other hand they are not very effective to produce BFMs in particular. The above general problems lead to the following derivative problems of non-optimal code. The code that is not strictly structured and not enough high-level, which is big and complex, potentially contains much more defects, and the efforts to locate these defects and resolve them consequently increase. The maintenance and modification of such code is also rather difficult. Furthermore, not structured BFM code tends to be asynchronous. And one of the major problem of the asynchronous code is “signal racing”. The “signal racing” problem occurs in situations when at the same simulation time a certain data element is set in one process and is being read in the other process. This leads to the situation when it is not guaranteed that the reading process will get correct value of the data element (it can be set and then read and also vice versa). This problem cannot be exposed during testing. The code may work correctly on the tests but may occasionally fail sometime when these two events are rescheduled in the simulator for some reason. So the behaviour of the model becomes unpredictable. As this kind of defects cannot be revealed by tests with certainty (it may be unrepeatable or even not detected at all) the only reliable way to find and resolve this problem is the analysis of the code by means of code inspection. But these method is very expensive and effort consuming, especially if the code is big and complex. BFM HDL code is dependant on the specific of the particular source language and is very difficult to transfer to another source language. Additionally the code that is complex and not strictly structured is very difficult to be reused. In the U.S. Pat. No. 5,920,711 a method of automatic generation of models specified by frame protocols is disclosed. The method proposes to specify the model by a Frame State Machines using visual tools and then the model HDL code may be automatically generated from it. The problem of this approach is that not every protocol may be easily specified by Frame State Machine and thus this method is not applicable (or hardly applicable) for the whole range of BFMs. Hence, considering the above problems, better method of BFM development is needed. The new method should make it less effort consuming and reduce BFM code size and complexity.
<SOH> SUMMARY OF THE INVENTION <EOH>There is a need for a method for generation of BFM and a computer program product which alleviate or overcome the disadvantages of the prior art. The method and the computer program product of the invention are preferably for use in hardware/software integration, and verification of electronic hardware designs. In accordance with the present invention, there is thus provided a method for creating a Bus Functional Model of an Integrated Circuit. The method comprises the following steps: providing a detailed specification of said Integrated Circuit, in the next step an architecture for said Bus Functional Model is defined. In the following step data contained in the detailed specification of the Integrated Circuit are mapped between the specification and the predefined BFM architecture. The BFM architecture contains at least one of the following constructs: Interface Tasks, Internal Data Elements, Processes, Finite State Machines, Conditions, Actions and Signals. In the final step the formal description of Bus Functional Model in Formal Description Language (FDL) is created. The formal description is created in a computer readable form. These steps described above can be performed both manually by the designer as well as by means of a computer. The method further comprises the step of providing the formal description of the Bus Functional Model to a computer. To generate the BFM in particular target language, templates for such generation are then entered to said computer. Finally the Bus Functional Model source code in the target language is generated by applying said formal description on said templates. In accordance with another aspect of the present invention there is thus provided a first computer program product stored on a computer usable medium, comprising computer readable program means for causing a computer to perform all the steps in accordance with the invention described herein. In accordance with yet another aspect of the present invention there is thus provided a second computer program product stored on a computer usable medium, comprising computer readable program means, said computer program being result of performing all the steps in accordance with the invention described herein. The method and the first computer program product according to the present invention allow generating of Bus functional Models, which can be used for verification of electronic hardware designs. As a result of structurization of BFM the source code in target language is also structurized. Thanks to this formalized structure the source code of the BFM is not asynchronous and the problem of “signal racing” is eliminated. There are also other advantages of the invention that are results of the formal structurization. One of the basic advantages is 3 to 8 times reduced size of the source code. And reduced size of the code means that the number of defects and time necessary to resolve them is also significantly reduced. Because of well defined structure of the BFM generated according to the present invention it is possible to reuse some parts of the generated BFM when the IC is further developed.
20060221
20091215
20061012
57365.0
G06F1750
0
CRAIG, DWIN M
METHOD AND COMPUTER PROGRAM PRODUCT FOR GENERATION OF BUS FUNCTIONAL MODELS
UNDISCOUNTED
0
ACCEPTED
G06F
2,006
10,512,668
ACCEPTED
Stand for albums, scrapbooks and the like
The present invention provides a stand for albums, scrapbooks and the like which is simple and compact causing no trouble to a user. Means for fixing an attaching portion of a stand capable to bend through a fold line to a back cover of an album, a scrapbook or the like and connecting the back cover and the support leg with a strip to adjust a bending angle of the support leg are adapted. Means for providing one end of a strip between a core material and a cloth material at a bottom line of a support leg and providing another end of the strip between a core material and an end paper at a bottom border of a back cover are applied.
1. A stand for albums, scrapbooks and the like using a stand which is composed of a support leg capable to bend through a fold line and a attaching portion, also developed by fixing the attaching portion of the stand to a back cover of an album, a scrapbook and the like and connecting the back cover with the support leg by way of a strip to adjust a bending angle of the support leg. 2. A stand for albums, scrapbooks and the like, wherein a back cover of an album, a scrapbook and the like has a double-structure, developed with: two slits provided from a bottom border to a middle point in an outer side of the back cover, a support leg made by standing a slit portion through a fold line, and a strip for connecting the back cover and the support leg to adjust a bending angle of the support leg. 3. A stand for albums, scrapbooks and the like, wherein a back cover of an album, a scrapbook and the like has a double-structure, developed with: a support leg made by standing a half bottom of an outer side of the back cover through a fold line, and a strip for connecting the back cover and the support leg to adjust a bending angle of the support leg. 4. A stand for albums, scrapbooks and the like according to claim 1, wherein a strip is fixed at bottom lines of a back cover and a support leg. 5. A stand for albums, scrapbooks and the like according to claim 4, wherein one end of a strip is provided between a core material and a cloth material at a bottom border of a support leg and another end is provided between a core material and an end paper at a bottom border of a back cover. 6. A stand for albums, scrapbooks and the like according to claim 2, wherein a strip is fixed at bottom lines of a back cover and a support leg. 7. A stand for albums, scrapbooks and the like according to claim 3, wherein a strip is fixed at bottom lines of a back cover and a support leg. 8. A stand for albums, scrapbooks and the like according to claim 6, wherein one end of a strip is provided between a core material and a cloth material at a bottom border of a support leg and another end is provided between a core material and an end paper at a bottom border of a back cover. 9. A stand for albums, scrapbooks and the like according to claim 7, wherein one end of a strip is provided between a core material and a cloth material at a bottom border of a support leg and another end is provided between a core material and an end paper at a bottom border of a back cover.
BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a stand structure which enables an album, a scrapbook and the like to be self-sustaining and be decoration such as a photo stand by attaching a support leg to a back of the album, the scrapbook and the like. 2. Description of the Related Art There have been already articles such as an album, a photo mount and a file, to which a stand is attached for a purpose to display a photograph decoratively as an alternative to a conventional photo stand. For example, an album disclosed in Japanese Utility Model Open Gazette No. S59-14218 is composed of a mount and a cover shielding front and back surfaces of the mount around. In this album, a triangular stand is to be formed by folding suitable parts of the cover. However, the cover of the album is hard chartaceous and therefore becomes unstable when placed on an uneven ground contacting surface such as a laced mat. This problem arises from a fact that a stand contacts a ground on a plane. Accordingly, a preferred placing way is to let a stand up on a line or a point. Further, each support leg disclosed in a photo box and an account book in Japanese Open Gazette for Utility Model No. S57-34477 and Japanese Utility Model Gazette No. S 30-12111 respectively has a similar structure and naturally has the same problem. In addition, these two inventions are inconvenient to carry or store, for the support leg thereof become bulky when folded down. On the other hand, a stand for a pocket album in Japanese Patent Gazette No. H4-31879 and an album with a stand in Japanese Open Gazette for Utility Model No. S61-200264 are both not handy for a user since the stand thereof has to be put together by the user. A stand structure as explained above has not been suggested so far as to an album that is comprised of conventional front and back covers and binder inserts, or a scrapbook. SUMMARY OF THE INVENTION In light of this situation, the present invention discloses a stable stand for albums, scrapbooks and the like, a structure of which is simple and compact causing no trouble to a user. Albums, scrapbooks and the like mentioned in this specification should not be limited to those comprised of front and back covers and binder inserts but broadly include books, picture books, photo collections and booklets which are bound or bound temporarily like a file. To solve the above problem, this invention utilizes a stand composed of a support leg capable to bend through a fold line, and an attaching portion. In the claim 1, means for fixing the attaching portion of the stand to a back cover of an album, a scrapbook and the like and connecting the support leg with the back cover by way of a strip to adjust a bending angle of the support leg are adapted. A back cover of an album, a scrapbook and the like has a double-structure and an outer side of the double-structured back cover has two slits therein from a bottom border to a middle point. A portion made by the two slits is to be a support leg by standing thereof through a fold line and a bending angle of the support leg is adjusted with a strip which connects the back cover and the support leg. This invention further provides a double-structured back cover, a half bottom of which is to be a support leg by standing thereof through a fold line and a bending angle of the support leg is adjusted with a strip which connects the back cover and the support leg. The above structure enables a support leg to support an album and the like for being self-sustaining and in this case, a strip may keep the support leg stood at a certain angle. In a stand of this invention, a strip connects a back cover and a support leg at bottom borders of the back cover and the support leg. One end of strip is bonded between a core material and a cloth material at a bottom border of a support leg and another end of the strip is bonded between a core material and an end paper at a bottom border of a back cover. Adequate strength against tensile put on the strip can be gained by running the strip between the bottom borders of the back cover and the support leg, particularly by stretching the strip as if reeling the core material. As further means, a width of a strip is equalized with a width of a bottom line of a support leg. A number of strips may be allowed as plural. Adequate strength can be gained through broadening a width of a strip or providing plural number of strips, for tensile put on a strip is to be dispersed. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view showing one embodiment of a stand structure in the present invention applied to a scrapbook. FIG. 2 shows a front side, a back side and a partly omitted sectional view of a stand. FIG. 3 is side elevational view comparing fixing method of a strip. FIG. 4 shows a process of fixing a strip to a stand. FIG. 5 shows a process of fixing a strip to a back cover. FIG. 6 is a perspective view showing the second embodiment of a stand structure in the present invention. FIG. 7 is a perspective view showing the third embodiment of a stand structure in the present invention. DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereafter, preferred embodiments of a stand for albums, scrapbooks, and the like in the present invention are discussed referring to the drawings. FIG. 1 (A) and (B) are perspective view showing an example that a stand structure in the present invention is applied to a scrapbook. In this figure, 1 is a scrapbook, wherein a discretionary number of binder inserts 4 are bound between a front cover 2 and a back cover 3. A store portion 5 having a display window is provided within the front cover 2. The front cover 2 may be decorated with the store portion 5 by placing a sheet (a binder insert) with a photograph and/or a picture and so forth into the store portion 5. This type of scrapbook has been disclosed in our Japanese Patent Application No. 2000-205517 (U.S. patent application Ser. No. 09/898,120). A binder insert used in this scrapbook is made by placing a sheet, to which a photograph or a pamphlet and so forth having a sheet form may be attached or a picture and/or an illustration and so forth may be drawn, into a transparent resin pocket (a protector). While binding a plurality of binder inserts 4 between the front cover 2 and the back cover 3, a favored binder insert 4 can be displayed by placing in the store portion 5 within the front cover 2. Accordingly, when self-support of this scrapbook is realized, the scrapbook can be used as a decoration of a desk like a conventional photo stand. 6 is a stand fixed on the back cover 3 of the scrapbook 1. A shape of the stand is almost trapezoid and the stand is divided into two parts, an attaching portion 8 and a support leg 9 through a fold line 7. The support leg 9 may be bended downwards through the fold line 7 optionally. 10 is a strip connected between borders of the support leg 9 and the back cover 3 for adjusting a bending angle of the support leg 9. A pliable material is preferrable for the strip 10 such as cloth, non-textile, a paper, a thread, a resin film, for pliability and bendability of the material will absorb unevenness of a place keeping the support leg 9 at a required bending angle for the scrapbook 1 to stand still stably. In light of strength of a material or a sense of beauty, a width of the strip 10 may be suitably decided by selecting from a thread type to a wide type having the same width with a bottom border of the support leg 9. The number of strip may be also decided optionally. Hereafter, a concrete structure of the stand 6, particularly a fixing condition of a strip is discussed. FIG. 2(A) shows a front side, (B) shows a back side and (C) is an outlined perspective view of the stand. In this figure, 11 is a core material for the attaching portion 8 and 12 is a core material for the support leg 9. Both of the core materials are composed of a cardboard and so forth. 13 is a cloth material which is composed of paper or cloth and preferably the same material with the front and back cover of the scrapbook. 14 is an end paper. As obvious from the FIG. 2(C), each core material 11 and 12 is covered with the cloth material 13 leaving a space therebetween for the fold line 7. Further, the end paper 14 is pasted on to the cloth material 13 as folded back to a back side. The above core material may be seriate and a fold line portion can be bendable by creating a line with pressure by a press. In this case, it is essential that an end of the strip 10 is fixed as if reeling between the core material 12 and the cloth material 13. With the above fixing way, the strip can withstand tensile put thereon. In other words, the strip 10 has a function to keep a regular interval between contacting points of the back cover 3 and the support leg 9 when the stand is opened. Since the scrapbook 1 itself is rather heavy, a considerable tensile will be put on the strip 10. Accordingly, as shown in FIG. 3(A), if the strip is provided between the back cover 3 and the support leg 9 simply by attaching to opposite surfaces of the back cover 3 and the support leg 9, an attached portion of the strip 10 may be likely to be peeled off by this tensile. FIG. 4 shows one example of manufacturing process of the stand 6. Process 1 illustrates a process of spreading adhesive all over a back surface of the cloth material 13 and fixing an end of the strip at a bottom part. Process 2 illustrates a process of attaching each core materials 11 and 12 to suitable places. Process 3 illustrates a process of folding back each end portions of the cloth material 13 to a back side and pasting thereof. And process 4 illustrates a process of pasting the end paper 14 to the whole back side to arrange an appearance. With the above processes, a strip can be fixed firmly enough to withstand tensile. The above process can be applied to a case of fixing the strip 10 to the back cover 3. To be precise, as shown in FIG. 5, process 1 illustrates a process of attaching a core material 16 to a cloth material 15, folding back an end of the cloth material 15 and fixing an end of the strip 10 to a bottom portion. Process 2 illustrates a process of pasting an end paper 17 to cover a whole back side. Providing the strip 10 as explained above enables the strip 10 to be able to adequately withstand tensile applied when the stand opens, for the strip 10 as shown in FIG. 3(B) is run as if reeling each core materials. Further, even if a strip is provided as explained, the strip will not become an obstacle when closing the stand, for the strip is composed of a pliable thin material. FIG. 6 shows another preferable embodiment of a stand structure. In this figure, 18 is a back cover having a double-structure of a scrapbook. Two slits are provided within only an outer cover from a bottom line to a middle point and a portion made by the two slits is to be a support leg 20 by standing thereof through a fold line 19. A strip 21 is provided between bottom lines of the support leg 20 and the back cover 18 to adjust a bending angle of the support leg 20. As to the strip 21, the same material and attaching condition with the aforesaid strip are applied. According to this structure, the scrapbook can be self-sustaining and used as decoration by standing the stand 20 up. Further, if the support leg 20 is folded down, the back cover 18 becomes flat, which is convenient to store in a shelf or carry around. FIG. 7 shows another embodiment of a stand structure, wherein a back cover of a scrapbook has a double-structure and a half bottom of an outer side of the back cover is to be a support leg 23 through a fold line 22. Further, a plurality of strips 24 are provided between an inner side of the back cover and the support leg 23 to adjust a bending angle of the support leg 23. This structure also enables the scrapbook to become self-sustaining by standing the support leg 23 up and be convenient to store by folding down the support leg 23. In addition, a strength will be increased as plural strips diffuse tensile. The aforesaid embodiments take a scrapbook having a display window within a front cover as an example but should not be limited to scrapbooks. In other words, conventional albums have elaborately designed front covers and some thereof can be used as decoration by printing a photograph or a picture. Applying a stand structure in the present invention allows these albums to be a photo stand for use as decoration. The same effect will be obtained on picture books and/or photo collections since those books also have elaborately designed front covers. Accordingly, a stand structure in the present invention can be practical to a wide range of books, files and the like. As described above, a stand structure of albums, scrapbooks and the like in the present invention is an excellent invention capable of being an interior decoration with a stand attached to a back surface of the albums, scrapbooks and the like to be self-sustaining. Since a structure is markedly simple and not bulky, an album can be easily put away and meantime, quickly function as a stand if necessary. A stable stand structure is obtained owing to a particular way of fixing by which a strip reels core materials of a support leg and a back cover enabling adequately to withhold tensile put on the strip when an album is self-sustaining as a stand. Further, a strip is flexible and pliable enabling an album to be placed stably even on an uneven surface.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention relates to a stand structure which enables an album, a scrapbook and the like to be self-sustaining and be decoration such as a photo stand by attaching a support leg to a back of the album, the scrapbook and the like. 2. Description of the Related Art There have been already articles such as an album, a photo mount and a file, to which a stand is attached for a purpose to display a photograph decoratively as an alternative to a conventional photo stand. For example, an album disclosed in Japanese Utility Model Open Gazette No. S59-14218 is composed of a mount and a cover shielding front and back surfaces of the mount around. In this album, a triangular stand is to be formed by folding suitable parts of the cover. However, the cover of the album is hard chartaceous and therefore becomes unstable when placed on an uneven ground contacting surface such as a laced mat. This problem arises from a fact that a stand contacts a ground on a plane. Accordingly, a preferred placing way is to let a stand up on a line or a point. Further, each support leg disclosed in a photo box and an account book in Japanese Open Gazette for Utility Model No. S57-34477 and Japanese Utility Model Gazette No. S 30-12111 respectively has a similar structure and naturally has the same problem. In addition, these two inventions are inconvenient to carry or store, for the support leg thereof become bulky when folded down. On the other hand, a stand for a pocket album in Japanese Patent Gazette No. H4-31879 and an album with a stand in Japanese Open Gazette for Utility Model No. S61-200264 are both not handy for a user since the stand thereof has to be put together by the user. A stand structure as explained above has not been suggested so far as to an album that is comprised of conventional front and back covers and binder inserts, or a scrapbook.
<SOH> SUMMARY OF THE INVENTION <EOH>In light of this situation, the present invention discloses a stable stand for albums, scrapbooks and the like, a structure of which is simple and compact causing no trouble to a user. Albums, scrapbooks and the like mentioned in this specification should not be limited to those comprised of front and back covers and binder inserts but broadly include books, picture books, photo collections and booklets which are bound or bound temporarily like a file. To solve the above problem, this invention utilizes a stand composed of a support leg capable to bend through a fold line, and an attaching portion. In the claim 1 , means for fixing the attaching portion of the stand to a back cover of an album, a scrapbook and the like and connecting the support leg with the back cover by way of a strip to adjust a bending angle of the support leg are adapted. A back cover of an album, a scrapbook and the like has a double-structure and an outer side of the double-structured back cover has two slits therein from a bottom border to a middle point. A portion made by the two slits is to be a support leg by standing thereof through a fold line and a bending angle of the support leg is adjusted with a strip which connects the back cover and the support leg. This invention further provides a double-structured back cover, a half bottom of which is to be a support leg by standing thereof through a fold line and a bending angle of the support leg is adjusted with a strip which connects the back cover and the support leg. The above structure enables a support leg to support an album and the like for being self-sustaining and in this case, a strip may keep the support leg stood at a certain angle. In a stand of this invention, a strip connects a back cover and a support leg at bottom borders of the back cover and the support leg. One end of strip is bonded between a core material and a cloth material at a bottom border of a support leg and another end of the strip is bonded between a core material and an end paper at a bottom border of a back cover. Adequate strength against tensile put on the strip can be gained by running the strip between the bottom borders of the back cover and the support leg, particularly by stretching the strip as if reeling the core material. As further means, a width of a strip is equalized with a width of a bottom line of a support leg. A number of strips may be allowed as plural. Adequate strength can be gained through broadening a width of a strip or providing plural number of strips, for tensile put on a strip is to be dispersed.
20041026
20071023
20050804
59546.0
0
MCDUFFIE, MICHAEL D
STAND FOR ALBUMS, SCRAPBOOKS AND THE LIKE
UNDISCOUNTED
0
ACCEPTED
2,004
10,512,672
ACCEPTED
Method for stimulation of liquid flow in a well
An improved method of controlled energy delivery utilizing solid, liquid, and gaseous carbon dioxide (CO2) into a water well and the surrounding aquifer to remove deposited material which may cause loss of capacity in wells and a variety of water quality problems. After proper study and evaluation of problems associated with a well to be treated, adequate injection of the required amount of CO2 and energy is achieved by real-time monitoring during the injection and manipulating the phase changes in the CO2 that take place in the well and the aquifer.
1. A method of stimulating a flow of water into a well from water in strata surrounding the well, comprising the steps of gathering information about the history and physical characteristics of the well and surrounding aquifer; providing telemetry machinery to monitor internal conditions within the well; sealing the well in a manner such that pressurization of the well can be accomplished; introducing liquid and gaseous carbon dioxide (CO2) into the well at a downhole pressure such that the liquid CO2 solidifies within the well forming solid CO2; manipulating and regulating the phase of CO2 delivered into the sealed well according to information provided by the telemetry machinery; continuing introduction of the liquid and gaseous CO2 into the well until a desired level of filling of the well with solid CO2 is attained; allowing the sealed well containing solid CO2 to stand for a time sufficient to sublime the solid CO2 contained in the sealed well; releasing residual pressure in the sealed well; and releasing the seal from the well. 2. The method according to claim 1, wherein sealing of the well comprises placing a sealing means on a casing of the well or in the well and securing the sealing means thereto. 3. The method according to claim 1, further comprising purging the sealed well with gaseous CO2 prior to introduction of the liquid CO2. 4. The method according to claim 1, wherein the steps of the method are repeated a plurality of times in order to obtain the desired flow of water. 5. The method according to claim 1, wherein the phase of CO2 is manipulated and regulated through maintaining a downhole pressure within the range of between about 0 to 70 psi. 6. The method according to claim 5, wherein the means of manipulating and regulating the phase of CO2 comprises delivering intermittent pulses of a negative pressure to stimulate the formation of solid CO2. 7. The method according to claim 1, further comprising removing bacterial growth within the well. 8. The method according to claim 1, further comprising removing scale contained within the well. 9. The method according to claim 7, wherein sublimation of the solid CO2 within the sealed well generates pressure within the sealed well and time releases carbonic acid into strata of the well. 10. The method according to claim 1, wherein the downhole pressure is sufficient to assure freezing of the water within the formation and surrounding strata. 11. The method according to claim 1, wherein the telemetry machinery comprises a downhole temperature and pressure telemetry transducer.
CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority from Mansuy, “Aqua Freed Process,” U.S. Provisional Application No. 60/254,149, filed Dec. 8, 2000, herein incorporated by reference. BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to water wells, and more particularly to an improved method of removing deposited material from a well and the surrounding aquifer. This method generally comprises initially properly evaluating problems associated with a particular well and then utilizing the controlled and telemetry-monitored injection into the well of energy derived from phase changes in solid, gaseous, and liquid carbon dioxide (CO2) to remove such deposited material. 2. Description of the Prior Art The prior art reveals techniques for stimulating the flow of water in a dry well or one providing insufficient water. For example, in U.S. Pat. No. 5,394,942 issued to Catania, et al., the disclosures of which are herein incorporated by reference, pressure in a dry or inefficient well is regulated to a desired level through use of a sealing cap, and nontoxic gaseous and liquid carbon dioxide (CO2) is introduced into the well. The pressure and flow of gaseous and or liquid are regulated to such a level, between about 0 and 70 psi pressure, that the liquid CO2, upon entering the sealed well, rapidly solidifies within the well. This liquid CO2 can be added until the well is filled with solid CO2; the solid sealed CO2-filled well is then allowed to sit, and the solid CO2 gradually sublimes. Because of the temperature differential between the well formation and the solid CO2, the solid CO2 sublimates releasing gaseous CO2 into the formation; consequently carbonic acid (H2CO3) is produced upon contact of the CO2 with water in the formation. The presence of the H2CO3 in the well aids in the removal of bacteria from surfaces in the formation, especially iron-related bacteria, such that a bactericidal effect can be achieved. After the solid CO2 sublimation is completed, any residual pressure in the well is released, and the well is unsealed. Additionally, because of the freezing within the well and well formation, encrustation in the well from such material as drilling mud, natural clay and silt, and other physical blocking agents and/or mineral scaling in the well formation and in the well screens is removed. If desired, the process may be repeated until the flow of water into the well is sufficient. However, every well that is to be treated with such a process is slightly different than any other well to be treated. Prior to treating a dry or inefficient well, it is therefore desirable to evaluate the aquifer and the type of problem in the well. This evaluation shall aid the determination of the most effective method of delivering the requisite energies of agitation, dissolution, and detachment delivered during the phase changes of CO2 to allow the effective cleaning of deposits from the surfaces of a well and the surrounding aquifer. For example, the amount of injection of energy during the process disclosed in U.S. Pat. No. 5,394,942 can vary depending upon well design, well problems, well construction, and site considerations. Additionally, the liquid CO2 is most often introduced into a well in short pulses of liquid while still feeding gaseous CO2. These short pulses are for the purpose of determining how a water well will respond to the injection of the additional energy. It is very important to observe the various pressures during the stages of liquid CO2 injection, because the pressures of injection can range from 0 to 300 psi depending on the individual type of well. It is therefore desirable to provide a method of injection of CO2 into a well to clean out deposited material wherein real-time monitoring of the pressures and temperature inside the well takes place. This monitoring would provide the information necessary to determine the required injection rates of gaseous and liquid CO2 in order to manipulate the phases of CO2 and phase changes in the well, and therefore allow better control of the energy delivery into the well. Finally, due to the physical properties of CO2 and the conditions inside a well when CO2 is injected, not all the desired phase changes can be achieved with just the injection of gaseous and liquid CO2. In deep wells or wells that have a hydrostatic pressure greater than 75 psi, desired phase changes are not always achieved. Inside a well and under hydrostatic pressures greater than 75 psi, a well is very similar to a pressure vessel, with a phase change taking place from pressure dissipating into the surrounding aquifer and with temperature changes as calories are transferred to and from the water and surrounding formation. When the pressure in the well is greater than 75 psi and the hydrostatic pressure is greater than 75 psi, liquid CO2 would penetrate into the surrounding formation and then convert to a gas without going to a solid. This would be a more rapid phase change than is sometimes desired. Consequently, it is desirable to have a method of temperature and pressure manipulation which will allow for more efficient and useful phase changes in the CO2 in the well. OBJECTS OF THE INVENTION It is therefore a general object of the present invention to provide a method of controlled energy delivery utilizing gaseous and liquid CO2 into a water well and the surrounding aquifer to remove deposited material which may cause loss of capacity in wells and a variety of water quality problems. It is an object of the present invention to provide a method of controlled energy delivery utilizing gaseous and liquid CO2 into a water well and the surrounding aquifer to remove deposited material wherein the well is initially examined in such an adequate and detailed manner that it is then possible to predetermine the precise and accurate amount of energy needed to effectively remove deposited material that is plugging the pore volume of the well and aquifer. It is a further object of the present invention to provide a method of controlled energy delivery utilizing gaseous and liquid CO2 into a water well and the surrounding aquifer to remove deposited material wherein the well is monitored during the injection of CO2 in order to obtain information about pressures and temperature inside the well, thereby allowing better control of the energy delivery into the well. It is a still further object of the present invention to provide for manipulation of the phase changes of the injected gaseous and liquid CO2 through control of the various pressure dependent changes that may take place in the subsurface environment. SUMMARY OF THE INVENTION The problems of the prior art have been solved by the present invention, which relates to an improved method of removing deposited material from a dry or inefficient well and the surrounding aquifer through initial proper evaluation of problems associated with a particular well and through controlled and telemetry-monitored injection of energy derived from phase changes in solid, gaseous, and liquid CO2 into the capped and sealed well to remove such deposited material. Before any type of work is to be done on a dry or inefficient well, the practitioner is to gather information about the history and characteristics of the well, through examining the chemistry of the water contained therein, geophysical logs or drillers logs, groundwater microbiology, downhole video images, and any other information that may exist. Monitoring various physical and chemical reactions inside the well during injection of gaseous and liquid CO2, such as disclosed in U.S. Pat. No. 5,394,942, allows better manipulation of and control over the materials during such a process. For example, the use of telemetry to monitor pressure and temperature during the entire process on a well allows data collection for quality control and potential improvements. It is also possible to incorporate direct and continuous monitoring of such parameters as pH, total dissolved solids, conductivity, CO2, etc. This would allow the refinement of the process to make it more effective as well as more efficient, such as indicating the efficient use of less CO2, and concomitant lowering of injected CO2 levels, during the process. The most important aspect of injecting CO2 into a water well is to inject enough liquid or gaseous CO2 into the well and the surrounding formation without excessive freezing of the water in the well through the phase changes of vaporization (liquid to gas), freezing (liquid to solid), and sublimation (solid to gas) . It is the energy delivered during these phase changes that allows the surfaces of a well and the surrounding aquifer to be effectively cleaned of deposits. To prevent freezing, the first part of the process is the injection of gaseous CO2 for a long enough period of time to evacuate water from both the well and from a certain distance into the formation. This could be described as a bubble into which liquid CO2 is then injected. After some of the water is evacuated, liquid CO2 is then introduced into the sealed well, most often in short pulses, while still feeding gaseous CO2. The pulses are short for the purpose of determining how a well will respond to the injection of the additional energy. It is very important to observe the various pressures during the stages of liquid CO2 injection. Additionally, in the event that the hydrostatic pressure or the pressure inside the well during injection is greater than 75 psi, intermittent pulses of a negative pressure vacuum can stimulate the formation of solid CO2. Finally, it is important to prevent the phase change from liquid CO2 to solid CO2 inside the injection lines, as this can cause spiking of the pressure gauges and also create a potentially dangerous situation with trapping of liquid CO2. This is prevented by maintaining a pressure of greater than 75 psi in the injection lines. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagrammatic view of the apparatus utilized in the present method. DETAILED DESCRIPTION OF THE INVENTION Prior to any work to be performed to increase the output of a dry or inefficient well, it is necessary to evaluate the aquifer and the type of problem in the well. This is so because every well is slightly different from any other well in terms of physical characteristics and properties and the type of problems presented in water flow. Additionally, the amount of injection of energy during the process disclosed in U.S. Pat. No. 5,394,942 can vary depending upon well design, well problems, well construction, and site considerations. Hence, before any type of work is to be done on a dry or inefficient well, the practitioner is to gather information about the history and characteristics of the well. Such evaluative information is contained within geophysical logs or drillers logs, analysis of the chemistry of the water contained within the well, analysis of the groundwater microbiology, downhole video images, and from other information sources that may exist. By proper information-gathering and analysis, this pre-treatment workup shall aid in determining the most effective and appropriate method of increasing the output or efficiency of a well. For example, it is important to introduce gaseous CO2 for a sufficient period of time at the beginning of the process to allow evacuation of the water in the well and for some distance into the surrounding formation. This allows the liquid CO2, where most of the energy is contained, to be delivered into the surrounding formation with less associated freezing close to the well bore. The pore volume of the aquifer is significantly less close to the well bore than into the surrounding formation. If liquid CO2 is introduced too early in the injection process, then freezing of water close to the well can prevent the energy penetrating into the surrounding aquifer. Greater penetration and more effective removal of plugging deposits may therefore be achieved with flowing various combinations of gaseous and liquid CO2 at the same time. This will allow the gaseous CO2 to be used as a carrier for liquid CO2 such that the additional energy may be dispersed into the surrounding aquifer to effectively remove deposited material that is plugging the pore volume of the well and aquifer. The most important aspect of injecting CO2 into a water well is to inject enough product into the well and the surrounding formation without excessive freezing of the water in the well. This is achieved by injecting gaseous CO2 as the first part of the process. The injection of gaseous CO2 for a long enough period of time allows evacuation of water from the well and for a certain distance into the formation. This could be described as a bubble into which liquid CO2 could then be injected. After some of the water is evacuated, liquid CO2 can be then introduced into a sealed well. Liquid CO2 is most often introduced into a well in short pulses of liquid while still feeding gaseous CO2. These short pulses are for the purpose of determining how a water well will respond to the injection of the additional energy. It is very important to observe the various pressures during the stages of liquid CO2 injection. The liquid CO2 is where the majority of the energy is contained. From experience on many wells, the pressures of injection can be from 0-300 psi. Turning to FIG. 1 of the application, then, there is depicted an apparatus placed in a well to be used according to the method of the present invention. The general procedure involves placing all the injection and monitoring equipment, the packer well cap 1, the well casing 6, the downhole telemetry probe 9, and the alternating vacuum and pressure monitoring line 10, into the well screen 5 at the zone that is selected for the injection of energy based upon the evaluative workup done on the well. Once this equipment is in the well, the packer 1 is inflated to seal the well to optimize the injection of pressurized gaseous and liquid CO2, and therefore the energy contained in the CO2. The packer 1 is normally placed inside the well casing 6. The packer 1 can be inflated through an inflation line 3, and the pressure on the packer 1 can be monitored with a pressure gauge 4. After the well is sealed, gaseous CO2 is discharged from the CO2 storage vessel either from the vapor space of the vessel or from the vaporizer (all not illustrated) and placed in the well through a CO2 injection line 11 to assure that all water is displaced from the transport lines as well as the area immediately below the well seal. Liquid CO2 hoses (not illustrated) are also connected to the injection line 11. Gaseous and/or liquid CO2, or nitrogen, can then be injected into the injection zone 16 of the sealed well. The injection of gaseous and/or liquid CO2 has the energy necessary to detach the sediments from the surfaces of the well and allow them to be removed from the well, both during the development of the well and at later times. The injection of gaseous and or liquid CO2 through the injection line 11 can take place over different periods of time, from several seconds to minutes or even hours, depending upon pressures within the well determined by monitoring the casing pressure gauge 8, the vacuum and pressure monitoring gauge 13, or the injection line pressure gauge 14. There can be a plurality of injection lines 11, this plurality not shown in the figure, placed in the well at various depths, as determined by such factors as well depth, well diameter, operation, etc. Finally, the injection of gaseous and liquid CO2 through the injection line 11 can be performed in repeated cycles until the desired amount of CO2 is injected into the well. By real-time monitoring of the pressure and temperature within the well via the casing pressure gauge 8, the vacuum and pressure monitoring gauge 13, or the injection line pressure gauge 14, and a thermometer 15, or with the aid of a computer 7 connected to a downhole temperature and pressure telemetry transducer 9, the phase of the injected CO2 can be determined. The pressure can then be manipulated by varying the injection of the ratio of gaseous and liquid CO2 through the injection line 11. It can also be manipulated by creating intermittent pulses of vacuum inside the injection zone 16 of the sealed well at the desired point on injection or monitoring by a vacuum pump 2 through the alternating vacuum and pressure monitoring line 10. A rupture diaphragm (not illustrated) is provided and is set at a slightly higher pressure setting to ensure containment of the well seal in the event that the safety valve 12 in the injection line 11 is defective or rendered inoperable. The beneficial actions inside a well when gaseous and liquid CO2 are injected under pressure include the formation of carbonic acid (H2CO3). According to Henry's Law, the solubility of a gas is dependent upon pressure and temperature. The solubility of CO2 in water increases as the pressure increases and the temperature decreases; dissolving CO2 into water creates H2CO3. This is normally considered a mild acid, but with increased solubility the acid becomes stronger acid. The resultant pH will vary depending upon the depth of the well and the stage of the injection process. In deeper wells that have a higher hydrostatic pressure, the pH will be lower than that in shallow wells. This can result in a stronger acid that would have greater capability of chemical dissolution due to the availability of the H+ ions. In addition to the pressure, the temperature of the water will be lowered during the CO2 injection process. As the temperature is lowered, the solubility of CO2 increases and the pH decreases. Further on into the process, then, the acid will be stronger and have a greater capability of chemically dissolving minerals impeding the flow of water from the well. Thus, when the well is allowed to remain shut, normally overnight, H2CO3 can dissolve mineral deposits. There are three forms of phase changes which occur when CO2 is injected under pressure into a sealed well. First, there is vaporization, the phase change from liquid CO2 to gaseous CO2 with various volumes of expansion depending upon the pressure inside the well and surrounding aquifer. Depending upon the depth of the injection point, and more importantly the hydrostatic pressure at that point, the volume of gas released per pound of CO2 will vary. For example, the volume increase at atmospheric pressure is approximately 560 times, whereas at a pressure of 300 psi the volume increase is approximately 19 times. Next is freezing, the phase change from liquid CO2 to solid CO2. The pressure directly below the packer 1 is regulated to a level such that liquid CO2 will rapidly lo solidify upon entry into the sealed well. This pressure is regulated to be preferably between about 0 and 70 psi. The temperature of the liquid CO2 is now approximately −110° F. The formation of solid CO2 inside a well is desirable due to the slower release of energy as the solid CO2 sublimes to gaseous CO2. This allows ongoing energy of agitation and energy of detachment to take place. Finally, the sublimation of solid CO2 to gaseous CO2 is a beneficial phase change involved in the process disclosed in U.S. Pat. No. 5,394,942, as it allows ongoing energy of agitation, energy of dissolution, and energy of detachment to be released into the well and the surrounding aquifer. This phase change is much slower than the others and allows the release of energy into the well and the surrounding formation over a longer period of time. This longer release of energy allows ongoing scrubbing to take place, which can lead to additional detachment and removal of deposits from surfaces. This ongoing release of energy can occur when wells are shut in or closed overnight. The phase of CO2 delivered into the sealed well can be manipulated and regulated according to the method of injection. This manipulation is achieved by injecting gaseous CO2 to remove some of the water from the well. Removal of the water from the well allows the liquid and gaseous CO2 to penetrate the aquifer without freezing water too close to the well. If the water inside the well is frozen, it limits the ability to penetrate energy into the surrounding formation. Removal of water inside the well also allows reduction in the hydrostatic pressure and therefore could allow the formation of solid CO2 even though the hydrostatic pressure prior to starting injection is greater than 75 psi. In the event that the hydrostatic pressure or the pressure inside the well during injection is greater than 75 psi, intermittent pulses of a negative pressure vacuum can create the formation of solid CO2. This would allow the manipulation of phase changes inside the well and particularly the formation of the beneficial solid CO2. The bulk of the beneficial energy that CO2 contains is in its liquid form. It is therefore desirable to deliver liquid CO2 into the well and then allow the phase changes to occur in the subsurface and not inside the injection lines. Frozen CO2 in the injection lines can cause spiking of the pressure gauges and also create a potentially dangerous situation with the concomitant trapping of liquid. The prevention of phase change from liquid CO2 to solid CO2 inside the injection lines can be prevented by maintaining a pressure of greater than 75 psi in the injection lines. This is easy to achieve in deep wells but is more difficult in shallow wells due to lower hydrostatic pressure. In shallow wells regulating the ratio of gaseous and liquid CO2 feed can therefore increase the pressure in the injection lines. Additionally, there is a difference in the viscosity between gaseous and liquid CO2. The pulses of liquid CO2 that are introduced into the well with a continuous gaseous CO2 feed can be increased in frequency and length as the process continues. The feed of liquid with the gaseous CO2 allows the liquid to be carried into the well and the surrounding formation more effectively. The gaseous CO2 can therefore be looked at as a carrier for the liquid CO2. Also, gaseous CO2 is more viscous and thus does not flow as easily through injection lines as liquid CO2. By increasing the ratio of gaseous CO2 in the gas-liquid mix, the flow through the line is impeded and there will be more back pressure on the line. With more back pressure, it is possible to increase the pressure to a point where liquid CO2 does not freeze. This will then allow that phase change to take place inside the well and the surrounding formation instead of inside the injection lines. After the well is filled with solid CO2 and the solid CO2 sublimes, the remaining residual pressure within the well can be released and the packer 1 removed. The water flow in the well has now been stimulated and bacteria within the well controlled. If desired, the process can be repeated a number of times until the desired effect is achieved. Normally, one cycle is sufficient in obtaining the desired effect. In special circumstances, a number of cycles can be employed. It should be noted that the energy delivery ability of the process disclosed in U.S. Pat. No. 5,394,942 is also effective in aiding the removal of drilling mud and other physical blocking agents during the drilling and development of a well. The removal of drilling mud, natural clay and silt, and other physical blocking agents can be the most difficult part of traditional development procedures. The energy in gaseous and liquid CO2 can be effective in breaking down and dispersing these agents. The present invention comprises an improved method for stimulating the flow of water in a dry or inefficient well. The method is not limited to any type of well and, in fact, the present method can be used to stimulate water flow in any known type of well. The process disclosed in U.S. Pat. No. 5,394,942 has proven very effective in the development of horizontally or directionally drilled wells. Thus, while the present invention has been described in connection with exemplary embodiments thereof, it will be understood that many modifications in both design and use will be apparent to those of ordinary skill in the art; and this application is intended to cover any adaptations or variations thereof. It is therefore manifestly intended that this invention be limited only by the claims and the equivalents thereof.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention relates to water wells, and more particularly to an improved method of removing deposited material from a well and the surrounding aquifer. This method generally comprises initially properly evaluating problems associated with a particular well and then utilizing the controlled and telemetry-monitored injection into the well of energy derived from phase changes in solid, gaseous, and liquid carbon dioxide (CO 2 ) to remove such deposited material. 2. Description of the Prior Art The prior art reveals techniques for stimulating the flow of water in a dry well or one providing insufficient water. For example, in U.S. Pat. No. 5,394,942 issued to Catania, et al., the disclosures of which are herein incorporated by reference, pressure in a dry or inefficient well is regulated to a desired level through use of a sealing cap, and nontoxic gaseous and liquid carbon dioxide (CO 2 ) is introduced into the well. The pressure and flow of gaseous and or liquid are regulated to such a level, between about 0 and 70 psi pressure, that the liquid CO 2 , upon entering the sealed well, rapidly solidifies within the well. This liquid CO 2 can be added until the well is filled with solid CO 2 ; the solid sealed CO 2 -filled well is then allowed to sit, and the solid CO 2 gradually sublimes. Because of the temperature differential between the well formation and the solid CO 2 , the solid CO 2 sublimates releasing gaseous CO 2 into the formation; consequently carbonic acid (H 2 CO 3 ) is produced upon contact of the CO 2 with water in the formation. The presence of the H 2 CO 3 in the well aids in the removal of bacteria from surfaces in the formation, especially iron-related bacteria, such that a bactericidal effect can be achieved. After the solid CO 2 sublimation is completed, any residual pressure in the well is released, and the well is unsealed. Additionally, because of the freezing within the well and well formation, encrustation in the well from such material as drilling mud, natural clay and silt, and other physical blocking agents and/or mineral scaling in the well formation and in the well screens is removed. If desired, the process may be repeated until the flow of water into the well is sufficient. However, every well that is to be treated with such a process is slightly different than any other well to be treated. Prior to treating a dry or inefficient well, it is therefore desirable to evaluate the aquifer and the type of problem in the well. This evaluation shall aid the determination of the most effective method of delivering the requisite energies of agitation, dissolution, and detachment delivered during the phase changes of CO 2 to allow the effective cleaning of deposits from the surfaces of a well and the surrounding aquifer. For example, the amount of injection of energy during the process disclosed in U.S. Pat. No. 5,394,942 can vary depending upon well design, well problems, well construction, and site considerations. Additionally, the liquid CO 2 is most often introduced into a well in short pulses of liquid while still feeding gaseous CO 2 . These short pulses are for the purpose of determining how a water well will respond to the injection of the additional energy. It is very important to observe the various pressures during the stages of liquid CO 2 injection, because the pressures of injection can range from 0 to 300 psi depending on the individual type of well. It is therefore desirable to provide a method of injection of CO 2 into a well to clean out deposited material wherein real-time monitoring of the pressures and temperature inside the well takes place. This monitoring would provide the information necessary to determine the required injection rates of gaseous and liquid CO 2 in order to manipulate the phases of CO 2 and phase changes in the well, and therefore allow better control of the energy delivery into the well. Finally, due to the physical properties of CO 2 and the conditions inside a well when CO 2 is injected, not all the desired phase changes can be achieved with just the injection of gaseous and liquid CO 2 . In deep wells or wells that have a hydrostatic pressure greater than 75 psi, desired phase changes are not always achieved. Inside a well and under hydrostatic pressures greater than 75 psi, a well is very similar to a pressure vessel, with a phase change taking place from pressure dissipating into the surrounding aquifer and with temperature changes as calories are transferred to and from the water and surrounding formation. When the pressure in the well is greater than 75 psi and the hydrostatic pressure is greater than 75 psi, liquid CO 2 would penetrate into the surrounding formation and then convert to a gas without going to a solid. This would be a more rapid phase change than is sometimes desired. Consequently, it is desirable to have a method of temperature and pressure manipulation which will allow for more efficient and useful phase changes in the CO 2 in the well.
<SOH> SUMMARY OF THE INVENTION <EOH>The problems of the prior art have been solved by the present invention, which relates to an improved method of removing deposited material from a dry or inefficient well and the surrounding aquifer through initial proper evaluation of problems associated with a particular well and through controlled and telemetry-monitored injection of energy derived from phase changes in solid, gaseous, and liquid CO 2 into the capped and sealed well to remove such deposited material. Before any type of work is to be done on a dry or inefficient well, the practitioner is to gather information about the history and characteristics of the well, through examining the chemistry of the water contained therein, geophysical logs or drillers logs, groundwater microbiology, downhole video images, and any other information that may exist. Monitoring various physical and chemical reactions inside the well during injection of gaseous and liquid CO 2 , such as disclosed in U.S. Pat. No. 5,394,942, allows better manipulation of and control over the materials during such a process. For example, the use of telemetry to monitor pressure and temperature during the entire process on a well allows data collection for quality control and potential improvements. It is also possible to incorporate direct and continuous monitoring of such parameters as pH, total dissolved solids, conductivity, CO 2 , etc. This would allow the refinement of the process to make it more effective as well as more efficient, such as indicating the efficient use of less CO 2 , and concomitant lowering of injected CO 2 levels, during the process. The most important aspect of injecting CO 2 into a water well is to inject enough liquid or gaseous CO 2 into the well and the surrounding formation without excessive freezing of the water in the well through the phase changes of vaporization (liquid to gas), freezing (liquid to solid), and sublimation (solid to gas) . It is the energy delivered during these phase changes that allows the surfaces of a well and the surrounding aquifer to be effectively cleaned of deposits. To prevent freezing, the first part of the process is the injection of gaseous CO 2 for a long enough period of time to evacuate water from both the well and from a certain distance into the formation. This could be described as a bubble into which liquid CO 2 is then injected. After some of the water is evacuated, liquid CO 2 is then introduced into the sealed well, most often in short pulses, while still feeding gaseous CO 2 . The pulses are short for the purpose of determining how a well will respond to the injection of the additional energy. It is very important to observe the various pressures during the stages of liquid CO 2 injection. Additionally, in the event that the hydrostatic pressure or the pressure inside the well during injection is greater than 75 psi, intermittent pulses of a negative pressure vacuum can stimulate the formation of solid CO 2 . Finally, it is important to prevent the phase change from liquid CO 2 to solid CO 2 inside the injection lines, as this can cause spiking of the pressure gauges and also create a potentially dangerous situation with trapping of liquid CO 2 . This is prevented by maintaining a pressure of greater than 75 psi in the injection lines.
20050428
20070918
20051006
71879.0
1
SUCHFIELD, GEORGE A
METHOD FOR STIMULATION OF LIQUID FLOW IN A WELL
SMALL
0
ACCEPTED
2,005
10,512,818
ACCEPTED
Steering wheel for boat rudder
A steering wheel for a boat rudder, which can be mounted on a rudder actuating shaft, comprising a substantially circular body (2) with an external peripheral edge (3) for gripping by a user and a central hub (4) defining an axis of rotation (L), characterized in that the body (2) is formed by a plurality of circle portions (5) which are movable with respect to each other, so as to pass selectively from an open operative configuration, where the circle portions (5) are adjacent and contained in a main plane of extension, to a closed rest configuration, where the circle portions (5) are at least partly superimposed so as to limit the volume in the main plane of extension, and vice versa. Owing to this particular arrangement it will be possible to increase the available space on-board the boat when the rudder is not used and, in so doing, facilitate the movements of the crew.
1. A steering wheel for a boat rudder, which can be mounted on a rudder actuating shaft, comprising a substantially circular body with an external peripheral edge for gripping by a user and a central hub defining an axis of rotation, characterized in that said body is formed by a plurality of circle portions which are movable with respect to each other, so as to pass selectively from an open operative configuration, where said circle portions are adjacent and contained in a main plane of extension, to a closed rest configuration, where said circle portions are at least partly superimposed so as to limit the volume in said main plane of extension, and vice versa. 2. The steering wheel according to claim 1, wherein said hub comprises a plurality of constraining elements, one said elements being fixed with respect to the rudder actuating shaft, while the other elements are movable with respect to said fixed element coaxially relative to said axis of rotation, each of said circle portions being fastened to a respective constraining element. 3. The steering wheel according to claim 2, wherein said constraining means have guiding means able to impart to them relative rotational translatory movements with respect to said axis of rotation. 4. The steering wheel according to claim 3, wherein said guiding means comprise at least one substantially cylindrical portion of suitable axial extension formed on each of said constraining elements. 5. The steering wheel according to claim 4, characterized in that the cylindrical portion of at least one of said constraining elements comprises a groove able to interact with a radial projection associated with one or more adjacent constraining elements so as thereto a relative translational and rotary movement of predetermined axial and angular amplitude. 6. The steering wheel according to claim 5, wherein said groove comprises an axial section and a circumferential section. 7. The steering wheel according to claim 5, wherein said groove is of the helical type. 8. The steering wheel according to claim 4, wherein the cylindrical portion of at least one of said constraining elements has at least one radial shoulder directed towards the inside and/or towards the outside and able to limit the axial relative travel of one or more adjacent constraining elements so as to prevent involuntary separation thereof. 9. The steering wheel according to claim 3, wherein said hub comprises locking means for locking selectively the position of said constraining elements relative to each other, both in said open operative configuration and in said closed rest configuration. 10. The steering wheel according to claim 1, wherein said circle portions comprise at least one circle segment of predetermined angular amplitude. 11. The steering wheel according to claim 10, each of said circle portions comprise a pair of circle segments diametrically opposite and symmetrical with respect to said axis of rotation. 12. The steering wheel according to claim 11, wherein said circle segments have the same angular extension such that in the open operative configuration they cover overall a complete round angle. 13. The steering wheel according to claim 2, wherein said external peripheral edge is formed by circular rim arcs connected to respective constraining elements of said hub by means of one or more substantially radial spokes. 14. The steering wheel according to claim 13, wherein the adjacent circular rim arcs are fastened at their ends by means of suitable coupling means. 15. The steering wheel, according to claim 1, comprising a ball joint having one end connected to said hub and the other end which can be connected to the rudder actuating shaft, so as to vary the inclination between the latter and said axis of rotation. 16. A Method for reducing the volume of a circular steering wheel in which the wheel comprises a substantially circular body formed of a plurality of circle portions and a central hub defining an axis of rotation, the hub consisting of a plurality of constraining elements, one of which is fixed on the rudder actuating shaft and the other constraining elements being movable with respect to the fixed constraining element, wherein the movable constraining elements are initially subjected to a sequence of rotational and translatory movements with respect to the fixed constraining element, so as to bring the wheel into a closed rest configuration, and are then being locked with respect to the fixed constraining element in said closed rest configuration. 17. The method according to claim 16, in which the succession of rotational and translatory movements comprises a first series of axial translatory movements of the movable constraining elements with respect to the fixed constraining element, followed by a second series of rotations of the movable constraining elements with respect to the fixed constraining element. 18. The method according to clam 17, in which the axial translatory movements of the first series occur respectively in the same direction and in opposite directions relative to said fixed constraining elements. 19. The method according to claim 16, in which the succession of rotational and translatory movements comprises one or more translatory movements alternating with one or more rotations of each of said movable constraining elements. 20. The method according to claim 16, in which the succession of rotational translatory movements comprises a plurality of helical movements of the movable constraining elements with respect to the fixed constraining element.
TECHNICAL FIELD The present invention relates to the nautical field and in particular relates to a steering wheel for rudders of boats of various types and dimensions, i.e. sailing boats or motorboats. BACKGROUND ART A steering wheel for a boat rudder may have different dimensions depending on the type and dimensions of the craft and may sometimes hinder the movements of persons on-board. U.S. Pat. No. 5,048,444 describes a rudder wheel for boats which is mounted rotatably on a support column by means of a suitable pivot, having a longitudinal axis parallel to the stern-prow direction of the boat itself. This pivot is formed by two portions which are aligned and fastened together by means of a rotational coupling having a direction of rotation substantially perpendicular to the pivot itself. In this way the wheel of the rudder can be rotated from the operative position into an angular rest position, laterally with respect to the support column. A drawback of this solution consists in the fact that the overall volume of the rudder wheel is not reduced since the wheel is simply rotated. In particular, in the rotated rest position, the available space close to the support column in the transverse direction is increased, but at the same time the free space in the longitudinal direction is decreased. In field other than the nautical one, for example in the motor-car field, numerous applications aimed at reducing the volume of the driving or steering devices are known. In particular, U.S. Pat. No. 5,199,319 describes a steering device for a vehicle, comprising a wheel mounted axially on a rotatable steering shaft. The steering device comprises adjusting means for varying the inclination and the length of the rotatable steering shaft, so as to adjust the inclination and the axial position of the steering wheel and find the most comfortable configuration. A similar device could also be used in the nautical field in order to vary the length and the inclination of the column which supports the rudder steering wheel. The application of this solution to boats would make it possible to find the optimum position for use of the steering wheel, but would be unlikely to achieve a significant reduction in the overall volume. JP-58030867 describes a steering wheel for motor vehicles having a circular rim supported by three spokes converging towards the rotatable shaft of the steering system. The circular rim is divided into three segments, each of which is fastened to a respective spoke. Each spoke is connected to the rotatable shaft by means of a rotational coupling having an axis of rotation perpendicular to the shaft itself. In this way it is possible to fold a spoke and the respective rim segment towards the inside of the steering wheel and reduce the volume of the steering wheel itself, for example in order to facilitate entry into and exit from the motor vehicle. This solution could also be applied in the nautical field to a rudder steering wheel, but would be of limited usefulness since it would allow only one segment of the rim to be folded. In so doing, the volume of the steering wheel would be reduced on one side only and the non-folded portion of the wheel would continue to hinder movements on-board. SUMMARY OF THE INVENTION A primary object of the present invention is to eliminate the drawbacks mentioned above, by providing a steering wheel for a boat rudder which increases the space available on-board the boat itself and facilitates the movements of the crew when the rudder is not used. A particular object is that of providing a steering wheel which is robust and effective during steering of the boat by a helmsman. A further object of the invention is that of providing a steering wheel, the volume of which may be reduced in a simple and rapid manner so as to increase the space available for the crew. Another particular object is that of providing a steering wheel which is safe, free of play or other undesirable movements, both during use and the non-operative phases. An additional object is that of providing a steering wheel which is practical, robust and cheap. These objects along with others which will appear more clearly hereinafter, are achieved, in accordance with Claim 1, by a steering wheel for a boat rudder, which can be mounted on a rudder actuating shaft, comprising a substantially circular body with an external peripheral edge for gripping by a user and a central hub defining an axis of rotation, characterized in that the circular body is formed by a plurality of circle portions which are movable with respect to each other, so as to pass selectively from an open operative configuration, where the circle portions are adjacent and contained in a main plane of extension, to a closed rest configuration, where the circle portions are at least partly superimposed so as to limit the volume in the main plane of extension, and vice versa. Owing to this particular arrangement it will be possible to increase the space available on-board the boat when the rudder is not used, and in so doing, facilitate the movements of the crew. Preferably, the hub comprises a plurality of constraining elements, to each of which a respective circle portion is fastened. One of the constraining elements is fixed with respect to the rudder actuating shaft, while the other elements are movable with respect to the fixed element coaxially relative to the axis of rotation. Moreover, the constraining elements have guiding means able to impart to the them relative rotational translatory movements with respect to the axis of rotation. Owing to this particular embodiment it will be possible to convert the wheel from the open operative configuration into the closed rest configuration and vice versa in a simple and rapid manner. Suitably, the hub comprises means for selectively locking the position of the central constraining elements relative to each other, both in the open operative configuration and in the closed rest configuration. Moreover, the circular edge advantageously consists of circular rim arcs connected to respective constraining elements by means of one or more substantially radial spokes. The adjacent circular rim arcs may be fastened at their ends by means of suitable coupling means. Owing to these particular features, it will be possible to obtain a steering wheel which is robust, safe and free of play or other undesirable movements both during use by a user and during the non-operative phases. BRIEF DESCRIPTION OF THE DRAWINGS Further features and advantages of the invention will be more clearly understood from the detailed description of some preferred, but not exclusive embodiments of a steering wheel according to the invention, illustrated by way of a non-limiting example with the aid of the accompanying plates of drawings in which: FIG. 1 shows a front view of a first embodiment of an steering wheel according to the invention; FIG. 2 shows a front view of a second embodiment of a steering wheel according to the invention; FIG. 3 shows a front view of a third embodiment of a steering wheel according to the invention; FIG. 4 shows an exploded perspective view of the hub of the wheel according to FIG. 1; FIGS. 5 to 7 show sectioned side views of the hub according to FIG. 4, respectively in an open operative configuration, in an intermediate configuration and in a closed rest configuration; FIGS. 8 to 10 show enlarged perspective views of the hub according to FIG. 4, respectively in an open operative configuration, in an intermediate configuration and in a closed rest configuration; FIG. 11 shows an exploded perspective view of the hub of the wheel according to FIG. 2; FIGS. 12 to 14 show sectioned side views of the hub according to FIG. 11, respectively in the closed rest configuration, in an intermediate configuration and in an open operative configuration; FIGS. 15 to 17 show enlarged perspective views of the hub according to FIG. 11, respectively in a closed rest configuration, in an intermediate configuration and in an open operative configuration; FIG. 18 show an exploded perspective view of the hub of a steering wheel according to the invention; FIGS. 19 to 21 show enlarged perspective views of the hub according to FIG. 18, respectively in a closed rest configuration, in an intermediate configuration and in an open operative configuration; FIG. 22 shows a side view of a steering wheel according to the invention; FIG. 23 shows an enlarged view of a detail of FIG. 22. FIG. 24 shows a perspective view of the wheel according to FIG. 2, respectively in an open or expanded operative configuration and in a closed rest configuration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S) With particular reference to the above figures, a steering wheel according to the invention, generally identified with reference number 1, is described. The steering wheel 1 can be mounted on an actuating shaft of a rudder for boats so as to allow a user to determine easily the route of the boat itself. The boats on-board which the steering wheel 1 may be advantageously used, may be of various types and dimensions, i.e. sailing boats or exclusively propeller-driven boats. The wheel 1 comprises a body 2 which is substantially circular with an external peripheral edge 3 for gripping by a user and a central hub 4 defining an axis of rotation L. The central body 2 is formed by a plurality of circle portions 5 which are movable with respect to each other. In this way the wheel 1 is able to pass from an open operative configuration, where the circle portions 5 are adjacent and contained in a main plane of extension, to a closed rest configuration, where the circle portions 5 are at least partially superimposed so as to limit the volume in the main plane of extension. The conversion from the open operative configuration into the closed rest configuration is completely reversible and may be inverted in a simple manner. Each circle portion 5 may comprise at least one circle segment 6 with a predetermined angular amplitude, and more particularly, each circle portion 5 may consist of a pair of circle segments 6, 6′ which are diametrically opposite and symmetrical with respect to the axis of rotation L. In the closed rest configuration, each pair of circle segments 6, 6′ is placed in the superimposed condition with respect to the other pairs of segments 6, 6′. In these conditions there is the maximum reduction in the main plane of extension when all the circle segments 6, 6′ have the same angular extension. However, in the open operative configuration the circle segments 6, 6′ cover overall a complete round angle. Therefore, the angular extension of each circle segment 6, 6′ may be determined by dividing the round angle by the total number of segments 6, 6′ which are used. The hub 4 comprises a plurality of constraining elements 7, 7′, to each of which a respective circle portion 5 or a respective pair of circle segments 6, 6′ is fastened. One constraining element 7 is fixed with respect to the actuating shaft of the rudder, so as to transmit to the latter the commands imparted by the helmsman, while the other elements 7′ are movable, coaxially relative to the axis of rotation L, with respect to the fixed element 7. The relative movements of the constraining elements 7, 7′ are guided by suitable guiding means 8 associated with the said constraining elements. In this way, the guiding means 8 allow relative rotation-translation movements, with respect to the axis of rotation L, to be imparted to the constraining elements 7, 7′. The hub 4 comprises locking means 9 for selectively locking the position of the constraining elements 7, 7′ relative to each other, both in the open operative configuration and in the closed rest configuration. In this way, in the open operative configuration the circle portions 5 or the pairs of circle segments 6, 6′ cover the entire round angle and are all fixed relative to each other, allowing the helmsman to operate any one of them manually. Moreover, the relative movements of the constraining elements 7, 7′ are also locked in the closed rest configuration and, as a result, the circle portions 5 or the pairs of circle segments 6, 6′ cannot accidentally move with respect to each other, for example owing to the pitching movements of the boat when moored. Suitably, the guiding means 8 comprise at least one substantially cylindrical portion 10 of suitable axial extension, formed on each constraining element 7, 7′. The cylindrical portion 10 of each constraining element 7, 7′ is able to come into contact at least partially with the cylindrical portion 10 of an adjacent constraining element 7, 7′, making possible a relative rotation-translation movement of the pair of constraining elements 7, 7′ making contact with each other. In particular, the cylindrical portion 10 of at least one constraining element 7, 7′ comprises a groove 11 which has an axial section and a circumferential section and is able to interact with a radial projection 12 associated with one or more adjacent constraining elements 7, 7′. The engagement between the groove 11 of a constraining element 7, 7′ and the radial projection 12 associated with an adjacent constraining element 7, 7′ forms a cylindrical cam able to impart to the two constraining elements 7, 7′ involved a relative translatory and rotational movement of predetermined axial and angular amplitude. For greater ease of manufacture, the radial projection 12 associated with a constraining element 7, 7′ may consist of an end of the locking means 9 which engages with the constraining element itself. Suitably, the groove 11 may be of the helical type, so as to impart to the constraining elements 7, 7′ forming the cam coupling thus obtained, a helical relative movement with a helical pitch of predetermined amplitude. Two adjacent constraining elements 7, 7′, when they are not fastened to each other by means of a cam-type coupling between a groove 11 and a radial projection 12, could be subject to relative axial sliding as a result of the contact between their respective cylindrical portions 10, having an extension such as to produce separation between the two elements, and the consequent undesirable separation of a circle portion 5 or a pair of circle segments 6, 6′ from the circular body 2. In order to prevent such a possibility from arising, the cylindrical portion 10 of at least one constraining element 7, 7′ may have at least one radial shoulder 13 directed towards the inside and/or towards the outside and able to limit the axial relative displacement of one or more adjacent constraining elements 7, 7′. Advantageously, the external peripheral edge 3 may consist of arcs 14 of a circular rim, which are connected to respective constraining means 7, 7′ of the hub 4 by means of one or more substantially radial spokes 15. In order to increase the rigidity of the wheel 1 in its open operative configuration and to improve the sensation of robustness when it is gripped by a user, the adjacent circular rim arcs 14 may be fastened at their ends 16 by means of suitable coupling means 17. In particular, the coupling means 17 comprise a pair of joints 18, each of which has the function of fastening together a respective pair of adjacent circular rim arcs 14. Each end 16 of a circular rim arc 14 has a joint 18 able to engage selectively with a corresponding joint 18 of complementary shape and integral with an adjacent arc 14, as a result of the relative movement of the respective pairs of circle segments 6, 6′. In a preferred embodiment shown in FIG. 3, the circular rim arc 14 of each circle segment 6, 6′ forms one piece with a respective pair of spokes 15 of the same circle segment 6, 6′. Moreover, the joining angles 19 between the circular rim arc 14 of each circle segment 6, 6′ and the respective pair of spokes 15 may be rounded. Suitably, the wheel 1 comprises a ball joint (not shown in the drawings) having one end connected to the hub and the other end which can be connected to the rudder actuating shaft, in order to vary the inclination between the latter and the axis of rotation L. The conversion of the wheel 1 from the open operative configuration into the closed rest configuration is performed using a method for reducing the volume of the said wheel, comprising a sequence of successive operations. The movable constraining elements 7′ are initially subjected to a sequence of rotational and translatory movements with respect to the fixed constraining element 7 so as to bring the circle portions 5 or the pairs of circle segments 6, 6′ into the superimposed position. Then the circle portions 5 or the pairs of circle segments 6, 6′ are locked with respect to the fixed constraining element 7 by operating the locking means 9. In particular, the succession of rotational translatotory movements may comprise a first series of axial translatory movements of the movable constraining elements 7′ with respect to the fixed constraining element 7, followed by a second series of rotations of the movable constraining element 7′ with respect to the fixed constraining element 7. The axial translatory movements of the first series are all performed in the same direction, in a preferred example of embodiment of the wheel 1, shown in FIGS. 11 to 17, while they are performed in opposite directions with respect to the fixed constraining element 7, in a second example of embodiment, shown in FIGS. 18 to 21. Advantageously, the succession of rotational and translatory movements may be performed by actuating a circle portion 5 or a pair of movable circle segments 7′ at the same time. In this case, one or more translatory movements alternating with one or more rotations of each movable constraining element 7′ are performed. Suitably, the succession of rotational and translatory movements may comprise a plurality of helical movements of the movable constraining elements 7′ with respect to the fixed constraining element 7. From that described above it is obvious that the steering wheel according to the invention achieves the predefined objects and in particular the form of the hub constraining elements, to which the circle portions or the pairs of circle segments are connected, allows a reduction in the volume of the wheel in a simple and rapid manner so as to increase the space available for the crew. Moreover, the presence of the hub locking means and, suitably, the means for coupling the adjacent circular rim arcs result in a steering wheel which is robust and devoid of play or other undesirable movements. The steering wheel according to the invention may be subject to numerous modifications and variations all falling within the inventive idea expressed in the accompanying claims. All the details may be replaced by other technically equivalent elements and the materials may be different depending on the requirements, without departing from the scope of the invention. Although the steering wheel has been described with particular reference to the accompanying figures, the reference numbers used in the description and in the claims are used in order to improve the comprehensibility of the invention and do not impose any limitation on the scope of protection claimed. The instant application is based upon and claims priority of patent application No. Vl2001A000199, filed on 21 Sep. 2001 in Italy, the disclosure of which is hereby expressly incorporated here in reference thereto.
<SOH> BACKGROUND ART <EOH>A steering wheel for a boat rudder may have different dimensions depending on the type and dimensions of the craft and may sometimes hinder the movements of persons on-board. U.S. Pat. No. 5,048,444 describes a rudder wheel for boats which is mounted rotatably on a support column by means of a suitable pivot, having a longitudinal axis parallel to the stern-prow direction of the boat itself. This pivot is formed by two portions which are aligned and fastened together by means of a rotational coupling having a direction of rotation substantially perpendicular to the pivot itself. In this way the wheel of the rudder can be rotated from the operative position into an angular rest position, laterally with respect to the support column. A drawback of this solution consists in the fact that the overall volume of the rudder wheel is not reduced since the wheel is simply rotated. In particular, in the rotated rest position, the available space close to the support column in the transverse direction is increased, but at the same time the free space in the longitudinal direction is decreased. In field other than the nautical one, for example in the motor-car field, numerous applications aimed at reducing the volume of the driving or steering devices are known. In particular, U.S. Pat. No. 5,199,319 describes a steering device for a vehicle, comprising a wheel mounted axially on a rotatable steering shaft. The steering device comprises adjusting means for varying the inclination and the length of the rotatable steering shaft, so as to adjust the inclination and the axial position of the steering wheel and find the most comfortable configuration. A similar device could also be used in the nautical field in order to vary the length and the inclination of the column which supports the rudder steering wheel. The application of this solution to boats would make it possible to find the optimum position for use of the steering wheel, but would be unlikely to achieve a significant reduction in the overall volume. JP-58030867 describes a steering wheel for motor vehicles having a circular rim supported by three spokes converging towards the rotatable shaft of the steering system. The circular rim is divided into three segments, each of which is fastened to a respective spoke. Each spoke is connected to the rotatable shaft by means of a rotational coupling having an axis of rotation perpendicular to the shaft itself. In this way it is possible to fold a spoke and the respective rim segment towards the inside of the steering wheel and reduce the volume of the steering wheel itself, for example in order to facilitate entry into and exit from the motor vehicle. This solution could also be applied in the nautical field to a rudder steering wheel, but would be of limited usefulness since it would allow only one segment of the rim to be folded. In so doing, the volume of the steering wheel would be reduced on one side only and the non-folded portion of the wheel would continue to hinder movements on-board. SUMMARY OF THE INVENTION A primary object of the present invention is to eliminate the drawbacks mentioned above, by providing a steering wheel for a boat rudder which increases the space available on-board the boat itself and facilitates the movements of the crew when the rudder is not used. A particular object is that of providing a steering wheel which is robust and effective during steering of the boat by a helmsman. A further object of the invention is that of providing a steering wheel, the volume of which may be reduced in a simple and rapid manner so as to increase the space available for the crew. Another particular object is that of providing a steering wheel which is safe, free of play or other undesirable movements, both during use and the non-operative phases. An additional object is that of providing a steering wheel which is practical, robust and cheap. These objects along with others which will appear more clearly hereinafter, are achieved, in accordance with Claim 1 , by a steering wheel for a boat rudder, which can be mounted on a rudder actuating shaft, comprising a substantially circular body with an external peripheral edge for gripping by a user and a central hub defining an axis of rotation, characterized in that the circular body is formed by a plurality of circle portions which are movable with respect to each other, so as to pass selectively from an open operative configuration, where the circle portions are adjacent and contained in a main plane of extension, to a closed rest configuration, where the circle portions are at least partly superimposed so as to limit the volume in the main plane of extension, and vice versa. Owing to this particular arrangement it will be possible to increase the space available on-board the boat when the rudder is not used, and in so doing, facilitate the movements of the crew. Preferably, the hub comprises a plurality of constraining elements, to each of which a respective circle portion is fastened. One of the constraining elements is fixed with respect to the rudder actuating shaft, while the other elements are movable with respect to the fixed element coaxially relative to the axis of rotation. Moreover, the constraining elements have guiding means able to impart to the them relative rotational translatory movements with respect to the axis of rotation. Owing to this particular embodiment it will be possible to convert the wheel from the open operative configuration into the closed rest configuration and vice versa in a simple and rapid manner. Suitably, the hub comprises means for selectively locking the position of the central constraining elements relative to each other, both in the open operative configuration and in the closed rest configuration. Moreover, the circular edge advantageously consists of circular rim arcs connected to respective constraining elements by means of one or more substantially radial spokes. The adjacent circular rim arcs may be fastened at their ends by means of suitable coupling means. Owing to these particular features, it will be possible to obtain a steering wheel which is robust, safe and free of play or other undesirable movements both during use by a user and during the non-operative phases.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>Further features and advantages of the invention will be more clearly understood from the detailed description of some preferred, but not exclusive embodiments of a steering wheel according to the invention, illustrated by way of a non-limiting example with the aid of the accompanying plates of drawings in which: FIG. 1 shows a front view of a first embodiment of an steering wheel according to the invention; FIG. 2 shows a front view of a second embodiment of a steering wheel according to the invention; FIG. 3 shows a front view of a third embodiment of a steering wheel according to the invention; FIG. 4 shows an exploded perspective view of the hub of the wheel according to FIG. 1 ; FIGS. 5 to 7 show sectioned side views of the hub according to FIG. 4 , respectively in an open operative configuration, in an intermediate configuration and in a closed rest configuration; FIGS. 8 to 10 show enlarged perspective views of the hub according to FIG. 4 , respectively in an open operative configuration, in an intermediate configuration and in a closed rest configuration; FIG. 11 shows an exploded perspective view of the hub of the wheel according to FIG. 2 ; FIGS. 12 to 14 show sectioned side views of the hub according to FIG. 11 , respectively in the closed rest configuration, in an intermediate configuration and in an open operative configuration; FIGS. 15 to 17 show enlarged perspective views of the hub according to FIG. 11 , respectively in a closed rest configuration, in an intermediate configuration and in an open operative configuration; FIG. 18 show an exploded perspective view of the hub of a steering wheel according to the invention; FIGS. 19 to 21 show enlarged perspective views of the hub according to FIG. 18 , respectively in a closed rest configuration, in an intermediate configuration and in an open operative configuration; FIG. 22 shows a side view of a steering wheel according to the invention; FIG. 23 shows an enlarged view of a detail of FIG. 22 . FIG. 24 shows a perspective view of the wheel according to FIG. 2 , respectively in an open or expanded operative configuration and in a closed rest configuration. detailed-description description="Detailed Description" end="lead"?
20051014
20091013
20060504
58455.0
G05D102
0
BASINGER, SHERMAN D
STEERING WHEEL FOR BOAT RUDDER
SMALL
0
ACCEPTED
G05D
2,005
10,512,833
ACCEPTED
Horn antenna combining horizontal and vertical ridges
A horn antenna combining horizontal and vertical corrugations. It is made up of two well differentiated parts, the first part being an antenna with horizontal corrugations, i.e. parallel to the axis of propagation, and a second part with vertical corrugations, i.e. transverse to the axis of propagation. The aperture of the arrangement of the corrugations, in the two parts, can preferably follow linear or Gaussian functions.
1. A corrugated horn antenna whose fundamental mode is TE11 for circular waveguide, characterised in that the horn antenna is configured such that a first part with horizontal corrugations parallel to the axis of propagation is followed by a second part with vertical corrugation transversal to the axis of propagation to provide substantially a fundamental Gaussian beam at the end of the horn antenna. 2. The corrugated horn antenna according to claim 1; characterized in that the horizontal corrugations of the first part are arranged from the beginning to the end of this part according to a linear function, such that the ratio between the radial distance of each horizontal corrugation and its horizontal position remains constant. 3. The corrugated horn antenna according to claim 1; characterized in that the horizontal corrugations of the first part are arranged from the beginning to the end of the first part according to a non-linear function describing the propagation of the fundamental Gaussian beam through the first part. 4. The corrugated horn antenna according to claim 1; characterized in that the horizontal corrugations of the first part are arranged from the beginning to the end of this part according to the equation, r ⁡ ( z ) = r 0 ⁢ 1 + ( λ ⁢ ⁢ z 2 ⁢ ⁢ π ⁢ ⁢ α ⁢ ⁢ r 0 2 ) 2 where α is a parameter controlling the maximum slope of the converter, r0 is the input radius of the antenna, and λ is the wavelength, calculated according to the working frequency by means of the ratio λ = c f where f is the working frequency and c is the light velocity in the vacuum or inside the material filling the horn antenna. 5. The corrugated horn antenna according to claim 2; characterized in that the vertical corrugations of the second part are arranged from the beginning to the end of this part according to a linear function, such that the ratio between the radial distance of each horizontal corrugation and its horizontal position remains constant. 6. The corrugated horn antenna according to claim 2; characterized in that the vertical corrugations of the second part are arranged from the beginning to the end of this part according to a non-linear function describing the propagation of the fundamental Gaussian beam through the second part. 7. The corrugated horn antenna according to claim 2; characterized in that the vertical corrugations of the second part are arranged from the beginning to the end of this part according to the equation, r ⁡ ( z ) = r 0 ⁢ 1 + ( λ ⁢ ⁢ z 2 ⁢ ⁢ π ⁢ ⁢ α ⁢ ⁢ r 0 2 ) 2 where α is a parameter controlling the maximum slope of the converter, r0 is the input radius of this second part of the antenna, and lambda is the wavelength, calculated according to the working frequency by means of the ratio λ = c f where f is the working frequency and c is the light velocity in the vacuum or inside the material filling the horn antenna. 8. The corrugated horn antenna according to claim 1 to 7; characterised in that the depth of the horizontal and vertical corrugations varies along the axis of propagation of the horn antenna.
SECTOR OF THE ART TO WHICH INVENTION REFERS The component presented is encompassed within electromagnetic systems for guiding energy at millimeter wave and microwave frequencies, and optimally adapts any electromagnetic field structure present inside a waveguide with a Gaussian structure. PRIOR STATE OF THE ART Currently, applications are more demanding with regard to the performances the antennas included in the telecommunication systems must comply with, whether they are land links or links via satellite. Smaller and smaller levels of side lobes are required, since, in short, they imply an effective loss of power in the desired radiation direction. At the same time, and due to the large demand of services, it becomes necessary to reuse frequencies using polarization diversity to differentiate two signals. This fact generates a great interest in having very low cross polarization levels, which, in short, is the measure of isolation between these two possible signals at the same frequency using different polarization. In addition to these two electromagnetic aspects, and since in the majority of cases this type of antennas must be borne by satellites, the size these antennas can have is also an important parameter. Usually, good radiation features corresponding to electromagnetic impositions, could be achieved by means of the use of shorter corrugated antennas, whether they have Gaussian profiles (R. Gonzalo, J. Teniente and C. del Río, “Very Short and Efficient Feeder Design for Monomode Waveguide”, Proceedings IEEE AP-S International Symposium, Montreal, Canada, July 1997; C. Del Río, R. Gonzalo and M. Sorolla, “High Purity Beam Excitation by Optimal Horn Antenna”, Proceedings ISAP'96, Chiba, Japan), or another type of already known and widely used design techniques (A. D. Olver, P. J. B. Clarricoats, A. A. Kishk and L. Shafai, “Microwave Horns and Feeds”, IEE Electromagnetic waves series 39, The Institution of Electrical Engineers, 1994, and A. W. Rudge, K. Milne, A. D. Olver and P. Knight, “The Handbook of Antenna Design”, IEE Electromagnetic waves series 15 and 16. The Institution of Electrical Engineers, 1982). The main drawback of the corrugated horn antennas used until today is that abrupt changes of the internal radius imply a significant reduction of the performances of the antennas. This forces having antennas with smooth flare angles, which gives way to long profiles, whether they are linear or not. Furthermore, a corrugation depth matchmaker, in the form of an impedance match-making unit, must be incorporated in the first part of the corrugated horn antennas, the first corrugations necessarily having a depth somewhat greater than the aperture radius, matching the smooth circular guide aperture radius. The fact that the component has these deep corrugations at the beginning complicates the manufacturing process. The present invention provides a competitive solution from two points of view: the electromagnetic and geometric points of view. Furthermore, since it does not contain vertical corrugations near the aperture (where the internal radius is smaller), it allows a much simpler manufacture, which could be carried out by means of machining with a simple numerical control machine. EP 0 079 533 discloses a corrugated horn with conical cross-section having horizontal corrugations parallel to the axis of the propagation. EXPLANATION OF THE INVENTION The aperture of this type of antennas must match a transmission guide of the monomode smooth circular waveguide type, the only possible mode of which, known as fundamental, is TE11. The present invention consists in an antenna comprising horizontal corrugations at the aperture which present no mechanical complication, being able to noticeably increase in that first part the internal radius of the antenna in a very short length. Usually, in addition to increasing the internal radius of the antenna, it is necessary to advance lengthwise. However, according to the specific application, a first part with horizontal corrugations which did not advance at all in the axis of revolution is also possible, i.e. the radius increased at no expense whatsoever with regard to the length of the device. This design of the first part of the antenna achieves a distribution of fields in a greater radius than that of the aperture guide, with more or less defined radiation features, and with a certain resemblance to a distribution of the field transversal to the propagation of the Gaussian type. The antenna design object of the invention comprises a second section with vertical corrugations, preferably, but not necessarily, defined according to a Gaussian profile. It is thus possible to improve the radiation features of the first section of the antenna until generating a fundamental Gaussian beam of a purity exceeding 99%. The depth of both the horizontal and vertical corrugations can be kept constant, or it can vary along the axis of revolution of the device. The result is the practical disappearance of side lobes, together with a very low cross polarization. On the other hand, the length of the antenna thus designed is much smaller than other antennas designed with traditional techniques of similar electromagnetic performance. DESCRIPTION OF THE DRAWINGS To better understand the description, two drawings are attached which, only as an example, show one practical embodiment of the antenna combining horizontal and vertical corrugations. FIG. 1 shows a longitudinal sectional view of an antenna with horizontal and vertical corrugations. The component has symmetry of revolution according to the horizontal axis, it is therefore completely defined with this single sectional view. FIG. 2 shows the measured radiation diagrams of the antenna corresponding to FIG. 1, in the copolar sections of E, H and 45° Plane, and the maximum contrapolar component section corresponding to 45°. Just as the antenna has a symmetry of revolution, the diagrams also have this same symmetry, with the exception that, due to the representation, in this case the axis of revolution would correspond to the y-axis (the left-hand vertical axis of the graph). EMBODIMENT OF THE INVENTION To see a specific embodiment of this type of antennas, the monomode circular waveguide type, starting from the fundamental mode, TE11, is focused on. As indicated, FIG. 1 shows a cross sectional view of this type of antennas, where horizontal corrugations (corrugations parallel to the axis of propagation), in this case defined according to a line, can be seen in the first part; and a second part with vertical corrugations (corrugations transversal to the propagation) defined with, in this case, a Gaussian profile antenna section, can be seen. The frequency of this specific design is f=9.65 GHz, and total antenna length is 194 mm (6.2 wavelengths, λ=c/f=31 mm, where c=3*10ˆ8 is the speed of light in free space). The aperture radius is 11.7 mm, and the output radius is 81.2 mm. The horizontal corrugations have a 5 mm period with a 2 mm tooth width and 7 mm depth. The vertical corrugations have a 7 mm period, a 3 mm tooth width and 8.8 mm depth. The first section has the corrugations distributed according to a linear function with a slope of 25°. The second section is defined by a Gaussian function of the type: r ⁡ ( z ) = r 0 ⁢ 1 + ( λ ⁢ ⁢ z 2 ⁢ ⁢ π ⁢ ⁢ α 0 2 ) 2 ( 1 ) with α=0.725, where r0 is the radius of connection of the two parts, approximately 39 mm, and λ is the previously defined wavelength of 31 mm. The radiation features of this antenna, defined by these parameters and dimensions, are shown in FIG. 2. The reduced side lobe level, under 40 dB with regard to the maximum, as well as the cross polarization, can be seen. Applications This new type of antennas is especially applicable in the field of both space and land telecommunications since they are fairly short and light antennas with excellent radiation features. Traditional horn antennas, which would be directly exchangeable for those presented herein, are currently used in a multitude of communications applications using microwave and millimeter wave band frequencies, improving the electromagnetic performances of the antennas, at the same time decreasing the size and total weight of the overall system.
20050726
20060815
20060302
97884.0
H01Q1300
0
HO, TAN
HORN ANTENNA COMBINING HORIZONTAL AND VERTICAL RIDGES
SMALL
0
ACCEPTED
H01Q
2,005
10,512,837
ACCEPTED
Data preservation
A method ensures that a reduction in data throughput is minimized in the event of a cell change in a GPRS network. When it is determined that cell change is appropriate for a mobile station, the BSS ensures that no further data for the mobile station is transmitted form the SGSN, and then continues to transmit all buffered data to the mobile station. The throughput may be deliberately reduced for a part of this time, so that the system timers become adapted to the reduction in throughput which will occur at the cell change. When the buffer has been emptied, the cell change is effected and, thereafter, that mobile station is prioritised in the BSS, in order to allow any buffered data on the uplink or downlink to be cleared.
1. A method of controlling a cell change in a mobile communications network, in which data is transmitted from a core network node to a radio access node for transmission to a mobile station, and in which data is buffered in the radio access node before transmission to the mobile station, the method comprising: determining in a radio access node that a cell change is required; sending a message from the radio access node to the core network node, instructing the core network node not to send further data intended for the mobile station; continuing to transmit buffered data from the radio access node to the mobile station; and when the buffered data has been transmitted to the mobile station, sending a message from the radio access node to the mobile station instructing the cell change. 2. A method as claimed in claim 1, comprising transmitting at least a part of the buffered data from the radio access node to the mobile station at a reduced data rate. 3. A method as claimed in claim 1, comprising transmitting at least a part of the buffered data from the radio access node to the mobile station with a more robust coding scheme than previous transmissions. 4. A method as claimed in claim 1, comprising determining in the radio access node that a cell change is required on the basis of measurement reports sent from the mobile station. 5. A method as claimed in claim 1, comprising determining in the radio access node that a cell change is required on the basis or a cell change notification sent from the mobile station. 6. A method as claimed in claim 5, further comprising, in response to the cell change notification sent from the mobile station, sending a message from the radio access node to the mobile station delaying the cell change. 7. A method as claimed in claim 1, further comprising, after effecting the cell change, in the radio access node, prioritizing the mobile station relative to other mobile stations in respect of transmissions between the radio access node and said mobile station. 8. A method as claimed in claim 1, for use in a GPRS network, wherein the core network node is a SGSN, and the radio access node is a BSS. 9. A method as claimed in claim 5, for use in a GPRS network, wherein the core network node is a SGSN, the radio access node is a BSS, and the cell change notification is a Packet Cell Change Notification message. 10. A method as claimed in claim 6, for use in a GPRS network, wherein the core network node is a SGSN, the radio access node is a BSS, the cell change notification is a Packet Cell Change Notification message, and the message sent from the radio access node to the mobile station delaying the cell change directs the mobile station to enter Network Control mode 2. 11. A radio access node, for connection to a core network node in a mobile communications network, the radio access node comprising means for storing data packets before transmission to a mobile station, the radio access node further comprising: means for determining that a cell change is required; means for sending a message to the core network node, in response to a determination that a cell chance is required, instructing the core network node not to send further data intended for the mobile station; means for continuing to transmit buffered data from the radio access node to the mobile station; and means for sending a message from the radio access node to the mobile station instructing the cell change when the buffered data has been transmitted to the mobile station. 12. A radio access node as claimed in claim 11, adapted to transmit at least a part of the buffered data to the mobile station at a reduced data rate. 13. A radio access node as claimed in claim 11, adapted to transmit at least a part of the buffered data to the mobile station with a more robust coding scheme than previous transmissions. 14. A radio access node as claimed in claim 11, wherein the means for determining that a cell change is required makes said determination on the basis of measurement reports sent from the mobile station. 15. A radio access node as claimed in claim 11, wherein the means for determining that a cell change is required makes said determination on the basis of a cell change notification sent from the mobile station. 16. A radio access node as claimed in claim 15, further comprising means or sending a message from the radio access node to the mobile station delaying the cell change, in response to the cell change notification sent from the mobile station. 17. A radio access node as claimed in claim 11, further comprising means or, after effecting the cell change, prioritizing the mobile station relative to other mobile stations in respect of transmissions between the radio access node and said mobile station. 18. A radio access node as claimed in claim 11, for use in a GPRS network, wherein the radio access node is a BSS. 19. A radio access node as claimed in claim 15, for use in a GPRS network, wherein the radio access node is a BSS, and the cell change notification is a Packet Cell Change Notification message. 20. A radio access node as claimed in claim 16, for use in a GPRS network, wherein the radio access node is a BSS, the cell change notification is a Packet Cell Change Notification message, and the message sent from the radio access node to the mobile station delaying the cell change directs the mobile station to enter Network Control mode 2.
TECHNICAL FIELD OF THE INVENTION The invention relates to a mobile communications network, and in particular to a method for compensating for a decrease in the rate of data transfer, which usually occurs when a mobile device moves between different cells in a cellular system. BACKGROUND OF THE INVENTION In a known General Packet Radio Service (GPRS) mobile communications network, a Gateway GPRS Support Node (GGSN) acts as a gateway to and from an Internet Service Provider (ISP), and has a connection to a general data communications network. Connected to the GGSN is a Serving GPRS Support Node (SGSN), which is further connected to multiple Base Station Systems (BSS). A mobile station (MS), which is active within the network, has a connection to one BSS, and the SGSN handles the routing of data from the GGSN to the BSS. Each BSS has at least one Packet Control Unit (PCU), which handles the different GPRS users, and schedules data on the radio resources which are available for GPRS users in the cell. When downlink data is transmitted to an MS in a GPRS network, the data is buffered, in the form of Logical Link Control (LLC) Packet Data Units (PDU) both in the SGSN and in the BSS. The LLC is the protocol which provides a logical link between the MS and the SGSN. When a Mobile Station moves in the area covered by the network, procedures are provided to control the way in which its connection changes from one cell to another. The BSS specifies a Network Control (NC) mode, and broadcasts this to the Mobile Station on control channels. In Network Control mode 0 (NC0) or Network Control mode 1 (NC1), the MS may perform cell reselection autonomously, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, section 5.5.1.1. Thus, the MS measures the signal strengths of neighbouring cells and, when it determines that a cell change is appropriate, it performs the cell change. The BSS determines that the MS has changed cell only when it receives a Cell Update message from the MS in the new cell. In Network Control mode 2 (NC2), the cell reselection is initiated by the network, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, section 8.4. Thus, the MS measures the signal strengths of the serving cell and of neighbouring cells, and sends measurement reports to the BSS. When the BSS determines that a cell change is appropriate, it directs the MS accordingly. A cell change, as described above, whether performed autonomously by the MS or initiated by the BSS, typically takes 3-5 seconds, during which time data transfer is interrupted. If it is supported by the MS, the functionality Network Assisted Cell Change, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, sections 5.51.1a and 8.8, can reduce this interruption to less than 1 second. In this case, when the MS determines that a cell change is appropriate, it sends a Packet Cell Chance Notification message to the BSS. The BSS responds with the system information for the proposed cell reselection, thereby allowing the MS to make a faster access in the new cell. However, there remains an interruption, during which there is no data transfer. Further, the interruption may lead to timeouts and/or reduced data throughput in higher layer protocols. Moreover, when an SGSN detects a cell change, it sends a FLUSH-LL PDU message to the old BSS, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 08.18 V8.9.0, section 8.1. In some cases, this will allow buffered data, awaiting transmission to the MS, to be transferred to the PCU for the new cell. However, in other cases, particularly in the case of a cell change between routing areas or between Network Service Entities, the buffered data cannot be transferred, and must be retransmitted at a higher layer protocol. Again, this can lead to reduced data throughput for the MS. SUMMARY OF THE INVENTION According to a first aspect of the present invention, there is provided a method which allows data throughput to be maintained in the event of a cell change. The method comprises delaying a cell change, and continuing to transfer data from a radio access node to the mobile station until all buffered data has been transferred, while preventing further data from being sent from a core network node to the radio access node. The proposed cell change is then performed when all buffered data has been sent. This has the advantage that data transfer interruption, and/or the need for higher layer retransmissions, are minimized. More specifically, the serving radio access node determines that a cell change is required, for example on the basis of measurement reports sent from the mobile station or on the basis of a cell change notification sent from the mobile station, sends a message to the core network node instructing the core network node not to send further data intended for the mobile station, while continuing to transmit buffered data to the mobile station, and, when the buffered data has been transmitted to the mobile station, sends a message to the mobile station instructing the cell change. In particular, if the radio access node receives a cell change notification from the mobile station, it sends a message to the mobile station delaying the cell change. Preferably, the data transferred from the radio access node to the mobile station are transferred with a reduced data throughput in a period before the cell change. This allows the higher layer protocol timers to adapt to a reduced data throughput before the cell change. The reduced data rate can for example be achieved by transferring data at a reduced data rate, or by transferring data with a more robust coding scheme. Alternatively, or additionally, a portion of a higher layer protocol data can be omitted from the data transferred from the radio access node to the mobile station. In accordance with another aspect of the invention, after the cell change, the mobile station is prioritised for data transfer with the core network node. This has the advantage that, if large amounts of data have been buffered for the mobile station in the core network node (or vice versa) during the cell change, this backlog of data can be cleared more quickly. In preferred embodiments of the invention, the network is a GPRS network, the radio access node is a Base Station System (BSS), and the core network node is a SGSN. In the case of a GPRS network, cell changes in which data are deleted at a radio access node are usually inter-Routing Area or inter-Network Service Entity cell changes. A Routing Area may be defined to be equivalent to a Base Station System (BSS) or a Radio Access Network (RAN), and a Network Service Entity may be defined to be equivalent to a BSS, but this is not required. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a schematic representation of a mobile communications network in accordance with the present invention. FIG. 2 illustrates the data transmission protocols in use in a part of the network shown in FIG. 1. FIG. 3 illustrates a method in accordance with the present invention. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS FIG. 1 is a schematic representation of a part of a General Packet Radio Service (GPRS) mobile communications network, for example operating in accordance with the standards set by the 3rd Generation Partnership Project. The invention is described herein with reference to this access technology, although it will be appreciated that it is equally applicable to other access technologies. The network includes at least one Gateway GPRS Support Node (GGSN) 10, which is the gateway to a general data communications network (not shown), for example through an Internet Service Provider (ISP) 12. Each GGSN 10 is connected to one or more Serving GPRS Support Nodes (SGSN) 14, of which only one is shown in FIG. 1. Each SGSN is connected to a plurality of Base Station Systems (BSSs) 16, 18. It will be apparent to the person skilled in the art that a real network will include more SGSNs and BSSs than the small number illustrated in FIG. 1. However, description of those additional nodes is not required for an understanding of the present invention. As is known, each BSS 16, 18 is in radio communication with any Mobile Stations (MS) which are active within their respective cells. For example, FIG. 1 shows a first MS 20, having a connection over the air interface to the BSS 16. Again, it will be apparent that the network can provide service to many more such Mobile Stations. When transmitting data to an MS 20 in a GPRS network, the data is buffered in a buffer 26 in the SGSN, and in a buffer 22, 24 in the respective BSS. A Routing Area (RA) is a collection of cells, which may be equivalent to the cells served by one Base Station System, or may be a subset of the cells served by a Base Station System, or may be a collection of cells served by more than one Base Station System. A Network Service Entity (NSE) is a logical entity located in the Base Station System or in the SGSN. One Network Service Entity in the Base Station System communicates with one Network Service Entity In the SGSN (In a one-to-one relationship) One or more Network Service Entities may be defined per Base Station System. Similarly one or more Network Service Entities may be defined per SGSN. A Network Service Entity cannot comprise more than one Base Station System, or more than one SGSN. FIG. 2 illustrates the protocol stacks which are in use between the Mobile Station MS and Base Station System BSS on the air interface (or Um interface) between the BSS and the SGSN on the Gb interface, between the MS and the GGSN, and between the MS and a server in the ISP. The protocol stack is generally conventional. It will therefore not be described further herein, but is provided only to illustrate the protocols used in the present invention, in particular the Logical Link Control (LLC), which provides a logical link between the MS and SGSN; the BSS GPRS Protocol (BSSGP), which is used between the BSS and SGSN; and the higher layer protocols, such as TCP, UDP or IP, which may be in use between the MS and a server in the ISP. The type of data that is buffered in the SGSN and in the BSS is in the form of Logical Link Control (LLC) Packet Data Units (PDUs). FIG. 3 illustrates the sequence of messages sent in a method according to the present invention, between a mobile station (MS), a radio access node in the form of a GPRS BSS, and a core network node in the form of a GPRS SGSN. The sequence illustrated in FIG. 3 assumes that the MS and BSS support Network Control mode 2 (NC2), but that the MS is initially operating in Network Control mode 0 or 1 (NC0 or NC1), and that the MS and BSS also support the Network Assisted Cell Change functionality. The sequence begins in this illustrated embodiment with a Packet Cell Change Notification message 60, sent from the MS to the BSS, indicating a cell reselection. The BSS replies with a message 62, which directs the MS into Network Control mode 2. Although the sequence illustrated in FIG. 3 assumes that the MS is initially operating in Network Control mode 0 or 1, the following steps can however also be taken if the MS is initially operating in Network Control mode 2, following a determination by the BSS that a cell change is appropriate for the MS. The procedure is described herein with reference to a cell change within one BSS, and is particularly useful in the case of a cell change in which data is discarded or would otherwise need to be retransmitted. For example, this can occur in the case of a GPRS cell change between routing areas or between Network Service Entities, or in the case of a cell change from GPRS to Universal Mobile Telecommunications System (UMTS), or in the case of a cell change from GPRS to a Wireless Local Area Network (W-LAN) The BSS sends a Flow Control message 64 to the SGSN, instructing it to send no more data for this MS. This allows the BSS to empty its buffer for the MS, as further described below, but may mean that a large amount of data is buffered for the MS in the SGSN. As shown by message 66 in FIG. 3, the BSS continues to transfer data to the MS in the first cell, until the PCU buffer 22 is emptied for the MS, and all of the data has been successfully received and acknowledged. While transferring this data, the BSS takes steps to reduce the data throughput. The data being sent from the BSS to the MS at this time is advantageously transferred with a more robust coding scheme or modulation-coding scheme. This generally reduces the data throughput, but should also ensure that the cell change is completed as quickly as possible, by avoiding the need for data retransmissions as far as possible. Alternatively, or additionally, the data rate may be deliberately decreased for a period (e.g. 0.5-2 seconds) before the cell change is effected. This allows the timers on the higher layer protocol to become adapted to the reduced throughput. A similar effect can be achieved, for example if TCP or another similar protocol is the higher layer protocol in use, by deliberately removing the oldest TCP segment from the PCU buffer 22, while continuing to transmit data at the maximum rate appropriate to the radio conditions. When the sender receives an acknowledgement indicating the missing segment, which will occur only after the BSS has polled the MS for a sufficiently long time, this forces the TCP protocol into a congestion avoidance mechanism. This mechanism allows the higher layer protocol to become adapted to the reduced throughput which will be available, before the cell change is effected. This technique can be applied selectively. For example, it may be applied if TCP is the higher layer protocol in use, but not for UDP services, since UDP does not become adapted in this way to the operating conditions. When the PCU buffer 22 in the BSS has been emptied for this MS, the BSS sends a message 68 to the MS, directing it to change to the cell proposed in the Packet Cell Change Notification message, or to the most appropriate cell. This message, or another message sent from the BSS to the MS, may then also release the MS from Network Control mode 2. After the cell change has been effected, there may be a large amount of data for the MS buffered in the SGSN 14, as mentioned earlier. Moreover, there may be timers running in the higher layer protocols. Therefore, in order to allow these buffers to be emptied, and to reduce the possibility of timeouts in the higher layer protocols, the MS 20 is given a higher priority in the BSS than other MSs. Downlink data transmission from the SGSN to the BSS (in message 70), and onwards from the BSS to the MS in the new cell (in message 72) can then be resumed. Similarly, uplink data transmission from the MS to the BSS (in message 74), and onwards from the BSS to the SGSN (in message 76) can also be resumed. In addition to the advantages mentioned above, prioritizing the MS in the BSS can also speed uD any necessary retransmissions in the higher protocol layers, and can assist in higher layer protocol recovery mechanisms such as TCP Slow Start, both on the downlink and the uplink. It should also be noted that this prioritisation after a cell change is advantageous even without the other steps described above, and irrespective of whether the MS supports Network Assisted Cell Change and of the Network Control mode. The invention therefore minimizes the effect of a cell change on the data throughput, in particular in cases where the cell change would otherwise involve discarding or retransmitting data.
<SOH> BACKGROUND OF THE INVENTION <EOH>In a known General Packet Radio Service (GPRS) mobile communications network, a Gateway GPRS Support Node (GGSN) acts as a gateway to and from an Internet Service Provider (ISP), and has a connection to a general data communications network. Connected to the GGSN is a Serving GPRS Support Node (SGSN), which is further connected to multiple Base Station Systems (BSS). A mobile station (MS), which is active within the network, has a connection to one BSS, and the SGSN handles the routing of data from the GGSN to the BSS. Each BSS has at least one Packet Control Unit (PCU), which handles the different GPRS users, and schedules data on the radio resources which are available for GPRS users in the cell. When downlink data is transmitted to an MS in a GPRS network, the data is buffered, in the form of Logical Link Control (LLC) Packet Data Units (PDU) both in the SGSN and in the BSS. The LLC is the protocol which provides a logical link between the MS and the SGSN. When a Mobile Station moves in the area covered by the network, procedures are provided to control the way in which its connection changes from one cell to another. The BSS specifies a Network Control (NC) mode, and broadcasts this to the Mobile Station on control channels. In Network Control mode 0 (NC 0 ) or Network Control mode 1 (NC 1 ), the MS may perform cell reselection autonomously, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, section 5.5.1.1. Thus, the MS measures the signal strengths of neighbouring cells and, when it determines that a cell change is appropriate, it performs the cell change. The BSS determines that the MS has changed cell only when it receives a Cell Update message from the MS in the new cell. In Network Control mode 2 (NC 2 ), the cell reselection is initiated by the network, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, section 8.4. Thus, the MS measures the signal strengths of the serving cell and of neighbouring cells, and sends measurement reports to the BSS. When the BSS determines that a cell change is appropriate, it directs the MS accordingly. A cell change, as described above, whether performed autonomously by the MS or initiated by the BSS, typically takes 3-5 seconds, during which time data transfer is interrupted. If it is supported by the MS, the functionality Network Assisted Cell Change, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 44.060 V5.0.0, sections 5.51.1a and 8.8, can reduce this interruption to less than 1 second. In this case, when the MS determines that a cell change is appropriate, it sends a Packet Cell Chance Notification message to the BSS. The BSS responds with the system information for the proposed cell reselection, thereby allowing the MS to make a faster access in the new cell. However, there remains an interruption, during which there is no data transfer. Further, the interruption may lead to timeouts and/or reduced data throughput in higher layer protocols. Moreover, when an SGSN detects a cell change, it sends a FLUSH-LL PDU message to the old BSS, as described in the 3rd Generation Partnership Project Technical Specification 3GPP TS 08.18 V8.9.0, section 8.1. In some cases, this will allow buffered data, awaiting transmission to the MS, to be transferred to the PCU for the new cell. However, in other cases, particularly in the case of a cell change between routing areas or between Network Service Entities, the buffered data cannot be transferred, and must be retransmitted at a higher layer protocol. Again, this can lead to reduced data throughput for the MS.
<SOH> SUMMARY OF THE INVENTION <EOH>According to a first aspect of the present invention, there is provided a method which allows data throughput to be maintained in the event of a cell change. The method comprises delaying a cell change, and continuing to transfer data from a radio access node to the mobile station until all buffered data has been transferred, while preventing further data from being sent from a core network node to the radio access node. The proposed cell change is then performed when all buffered data has been sent. This has the advantage that data transfer interruption, and/or the need for higher layer retransmissions, are minimized. More specifically, the serving radio access node determines that a cell change is required, for example on the basis of measurement reports sent from the mobile station or on the basis of a cell change notification sent from the mobile station, sends a message to the core network node instructing the core network node not to send further data intended for the mobile station, while continuing to transmit buffered data to the mobile station, and, when the buffered data has been transmitted to the mobile station, sends a message to the mobile station instructing the cell change. In particular, if the radio access node receives a cell change notification from the mobile station, it sends a message to the mobile station delaying the cell change. Preferably, the data transferred from the radio access node to the mobile station are transferred with a reduced data throughput in a period before the cell change. This allows the higher layer protocol timers to adapt to a reduced data throughput before the cell change. The reduced data rate can for example be achieved by transferring data at a reduced data rate, or by transferring data with a more robust coding scheme. Alternatively, or additionally, a portion of a higher layer protocol data can be omitted from the data transferred from the radio access node to the mobile station. In accordance with another aspect of the invention, after the cell change, the mobile station is prioritised for data transfer with the core network node. This has the advantage that, if large amounts of data have been buffered for the mobile station in the core network node (or vice versa) during the cell change, this backlog of data can be cleared more quickly. In preferred embodiments of the invention, the network is a GPRS network, the radio access node is a Base Station System (BSS), and the core network node is a SGSN. In the case of a GPRS network, cell changes in which data are deleted at a radio access node are usually inter-Routing Area or inter-Network Service Entity cell changes. A Routing Area may be defined to be equivalent to a Base Station System (BSS) or a Radio Access Network (RAN), and a Network Service Entity may be defined to be equivalent to a BSS, but this is not required.
20050527
20110920
20051027
97582.0
0
ZEWARI, SAYED T
A METHOD OF DATA PRESERVATION AND MINIMIZING REDUCTION IN DATA THROUGHPUT IN THE EVENT OF A CELL CHANGE
UNDISCOUNTED
0
ACCEPTED
2,005
10,512,880
ACCEPTED
Method for producing unsaturated halogenic hydrocarbons and device suitable for use with said method
The invention relates to a method for producing ethylenically unsaturated aliphatic halogenic hydrocarbons by the thermal cleavage of saturated aliphatic halogenic hydrocarbons. According to said method, an educt gas stream is introduced into a reactor, which comprises at least one supply conduit that opens into said reactor. The supply conduit feeds a heated gas formed from cleavage promoters and radicals into the reactor. The method permits an increase in the yield of the cleavage reaction.
1-70. (canceled) 71. A process for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons, which comprises the steps of: a) introducing a feed gas stream comprising heated gaseous halogen-containing aliphatic hydrocarbon into a reactor into whose interior at least one feed line for a gas opens, b) introducing a heated gas containing free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line or lines opening into the reactor, with, in the case of generation of the free radicals by thermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the reaction mixture in the reactor prevailing at the point at which the feed line opens and with, in the case of generation of the free radicals by nonthermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the dew point of the reaction mixture at the point at which the feed line opens into the reactor, and c) setting such a pressure and such a temperature in the interior of the reactor that hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon are formed by thermal dissociation of the halogen-containing aliphatic hydrocarbon, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. 72. A process for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons, which comprises the steps of: a) introducing a feed gas stream comprising heated gaseous halogen-containing aliphatic hydrocarbon into a reactor into whose interior at least one feed line for a heated gas comprising dissociation promoters opens, d) generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the reactor, e) introducing the heated gas comprising dissociation promoters through the feed line into the predetermined volume, with, in the case of generation of the free radicals by thermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the reaction mixture in the reactor prevailing at the point at which the feed line opens and with, in the case of generation of the free radicals by nonthermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the dew point of the reaction mixture at the point at which the feed line opens into the reactor, and c) setting such a pressure and such a temperature in the interior of the reactor that hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon are formed by thermal dissociation of the halogen-containing aliphatic hydrocarbon. 73. The process as claimed in claim 71, characterized in that the saturated halogen-containing aliphatic hydrocarbon used is 1,2-dichloroethane from which vinyl chloride is produced by thermal dissociation. 74. The process as claimed in claim 72, characterized in that the saturated halogen-containing aliphatic hydrocarbon used is 1 ,2-dichloroethane from which vinyl chloride is produced by thermal dissociation. 75. The process as claimed in claim 71, characterized in that the heated gas is produced from dissociation promoters which are chlorine-containing compounds. 76. The process as claimed in claim 75, wherein said chlorine-containing compounds are molecular chlorine, nitrosyl chloride, trichloroacetyl chloride, chloral, hexachloroacetone, benzotrichloride, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane or hydrogen chloride. 77. The process as claimed in claim 72, characterized in that the heated gas is produced from dissociation promoters which are chlorine-containing compounds. 78. The process as claimed in claim 77, wherein said chlorine-containing compounds are molecular chlorine, nitrosyl chloride, trichloroacetyl chloride, chloral, hexachloroacetone, benzotrichloride, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane or hydrogen chloride. 79. The process as claimed in claim 71, characterized in that the heated gas has a temperature in the range from 500 to 1500° C. 80. The process as claimed in claim 72, characterized in that the heated gas has a temperature in the range from 500 to 1500° C. 81. The process as claimed in claim 71, characterized in that the total amount of the heated gas introduced into the reactor is not more than 10% by weight, based on the total mass flow in the reactor. 82. The process as claimed in claim 72, characterized in that the total amount of the heated gas introduced into the reactor is not more than 10% by weight, based on the total mass flow in the reactor. 83. The process as claimed in claim 71, characterized in that the generation of the free radicals from dissociation promoters is carried out by means of a device for generating free radicals installed at the end of the feed line for the gas comprising dissociation promoters. 84. The process as claimed in claim 71, characterized in that the free radicals are generated from dissociation promoters by means of a spark, barrier or corona discharge. 85. The process as claimed in claim 72, characterized in that the free radicals are generated from dissociation promoters by means of a spark, barrier or corona discharge. 86. The process as claimed in claim 71, characterized in that the free radicals are generated from dissociation promoters by means of a microwave discharge or high-frequency discharge. 87. The process as claimed in claim 72, characterized in that the free radicals are generated from dissociation promoters by means of a microwave discharge or high-frequency discharge. 88. The process as claimed in claim 71, characterized in that a feed line for the heated gas opens into the reactor at least in the vicinity of the entry of the feed gas stream into the reactor. 89. The process as claimed in claim 72, characterized in that a feed line for the heated gas opens into the reactor at least in the vicinity of the entry of the feed gas stream into the reactor. 90. The process as claimed in claim 86, characterized in that the feed gas stream comes into contact with a plurality of feed lines for the heated gas opening into the reactor during passage through the reactor. 91. The process as claimed in claim 88, characterized in that the number of feed lines opening into the first third of the reactor is greater than that in the second third and/or in the third third. 92. The process as claimed in claim 71 for the thermal dissociation of the product gas in an adiabatic after-reactor installed downstream of the reactor, which comprises the steps of: f) introducing the product gas stream comprising heated halogen-containing aliphatic hydrocarbon, hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon from the reactor into an adiabatic after-reactor in which the reaction is continued with the aid of the heat supplied by the product gas stream with cooling of the product gas, and in whose interior at least one feed line for a heated gas which comprises free radicals and has been formed from dissociation promoters optionally opens, and g) optionally, introducing a heated gas comprising free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line(s) opening into the adiabatic after-reactor or generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the adiabatic after-reactor, with, in the case of generation of the free radicals by thermal decomposition, the temperature of the heated gas being at least the temperature prevailing in the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor and, in the case of generation of the free radicals by nonthermal decomposition, being at least the temperature which corresponds to the dew point of the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. 93. The process as claimed in claim 72 for the thermal dissociation of the product gas in an adiabatic after-reactor installed downstream of the reactor, which comprises the steps of: f) introducing the product gas stream comprising heated halogen-containing aliphatic hydrocarbon, hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon from the reactor into an adiabatic after-reactor in which the reaction is continued with the aid of the heat supplied by the product gas stream with cooling of the product gas, and in whose interior at least one feed line for a heated gas which comprises free radicals and has been formed from dissociation promoters optionally opens, and g) optionally introducing a heated gas comprising free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line(s) opening into the adiabatic after-reactor or generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the adiabatic after-reactor, with, in the case of generation of the free radicals by thermal decomposition, the temperature of the heated gas being at least the temperature prevailing in the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor and, in the case of generation of the free radicals by nonthermal decomposition, being at least the temperature which corresponds to the dew point of the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. 94. A process for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons, which comprises the steps of: a) introducing a feed gas stream comprising heated gaseous halogen-containing aliphatic hydrocarbon into a reactor, b) setting such a pressure and such a temperature in the interior of the reactor that hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon are formed by thermal dissociation of the halogen-containing aliphatic hydrocarbon, f) introducing the product gas stream comprising heated halogen-containing aliphatic hydrocarbon, hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon from the reactor into an adiabatic after-reactor which is located downstream of the reactor and in which the reaction is continued with the aid of the heat supplied by the product gas stream with cooling of the product gas, and in whose interior at least one feed line for a heated gas opens, and g) introducing a heated gas comprising free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line(s) opening into the adiabatic after-reactor or generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the adiabatic after-reactor, with, in the case of generation of the free radicals by thermal decomposition, the temperature of the heated gas being at least the temperature prevailing in the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor and, in the case of generation of the free radicals by nonthermal decomposition, being at least the temperature which corresponds to the dew point of the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. 95. A reactor for carrying out the process as claimed in claim 71, which comprises the elements: i) a feed line for the feed gas stream comprising saturated halogen-containing aliphatic hydrocarbon opening into the reactor, ii) at least one feed line for a heated gas opening into the interior of the reactor, iii) a source of a dissociation promoter connected to the feed line, iv) a device for nonthermally generating free radicals from dissociation promoters installed in the feed line, v) optionally, a heating device for heating the gas in the feed line, vi) a heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) an outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. 96. A reactor for carrying out the process as claimed in claim 72, which comprises the elements: i) a feed line for the feed gas stream comprising saturated halogen-containing aliphatic hydrocarbon opening into the reactor, ii) at least one feed line for a heated gas opening into the interior of the reactor, iii) a source of a dissociation promoter connected to the feed line, viii) device for generating free radicals from dissociation promoters installed at the reactor end of the feed line, iv) optionally, a heating device for heating the gas in the feed line, vi) a heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) an outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. 97. A reactor for carrying out the process as claimed in claim 72, which comprises the elements: i) a feed line for the feed gas stream comprising saturated halogen-containing aliphatic hydrocarbon opening into the reactor, ix) a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor, x) at least one feed line for a heated gas comprising dissociation promoters opening into the predetermined volume in the interior of the reactor, iii) a source of a dissociation promoter connected to the feed line, v) a heating device for heating the gas in the feed line, vi) a heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) an outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. 98. The reactor as claimed in claim 95, characterized in that the reactor is a tube reactor. 99. The reactor as claimed in claim 96, characterized in that the reactor is a tube reactor. 100. The reactor as claimed in claim 97, characterized in that the reactor is a tube reactor. 101. The reactor as claimed in claim 95, characterized in that it comprises a generator for a thermal plasma which is connected to the feed line to the reactor, with the feed line being connected to a further feed line for an inert gas and to a further feed line for a dissociation promoter. 102. The reactor as claimed in claim 96, characterized in that it comprises a generator for a thermal plasma which is connected to the feed line to the reactor, with the feed line being connected to a further feed line for an inert gas and to a further feed line for a dissociation promoter. 103. The reactor as claimed in claim 97, characterized in that it comprises a generator for a thermal plasma which is connected to the feed line to the reactor, with the feed line being connected to a further feed line for an inert gas and to a further feed line for a dissociation promoter. 104. The reactor as claimed in claim 95, characterized in that it comprises a device for generating an electric discharge which is connected to the feed line to the reactor. 105. The reactor as claimed in claim 96, characterized in that it comprises a device for generating an electric discharge which is connected to the feed line to the reactor. 106. The reactor as claimed in claim 97, characterized in that it comprises a device for generating an electric discharge which is connected to the feed line to the reactor. 107. The reactor as claimed in claim 104, wherein the electric discharge is a spark, barrier or corona discharge. 108. The reactor as claimed in claim 105, wherein the electric discharge is a spark, barrier or corona discharge. 109. The reactor as claimed in claim 106, wherein the electric discharge is a spark, barrier or corona discharge. 110. The reactor as claimed in claim 95, characterized in that it comprises a device for generating a microwave discharge or a high-frequency discharge, which is connected to the feed line to the reactor. 111. The reactor as claimed in claim 96, characterized in that it comprises a device for generating a microwave discharge or a high-frequency discharge, which is connected to the feed line to the reactor. 112. The reactor as claimed in claim 97, characterized in that it comprises a device for generating a microwave discharge or a high-frequency discharge, which is connected to the feed line to the reactor. 113. The reactor as claimed claim 95, characterized in that it comprises a radiation source which is located in the feed line to the reactor or whose radiation is introduced into the feed line to the reactor. 114. The reactor as claimed claim 96, characterized in that it comprises a radiation source which is located in the feed line to the reactor or whose radiation is introduced into the feed line to the reactor. 115. The reactor as claimed claim 97, characterized in that it comprises a radiation source which is located in the feed line to the reactor or whose radiation is introduced into the feed line to the reactor. 116. The reactor as claimed claim 96, characterized in that the device viii) provided is at least one device for generating and introducing a nonthermal plasma comprising free radicals which comprises a gas inlet, a plasma generation region having at least two electrodes and a gas outlet which opens into a reaction space, with the reaction space and plasma generation region being physically separate from one another. 117. The reactor as claimed claim 97, characterized in that the device ix) provided is at least one device for generating and introducing a nonthermal plasma comprising free radicals which comprises a gas inlet, a plasma generation region having at least two electrodes and a gas outlet which opens into a reaction space, with the reaction space and plasma generation region being physically separate from one another. 118. The reactor as claimed in claim 116, characterized in that the device viii) has an essentially cylindrical housing having a rear end and a front end, and in that the housing is provided along at least part of its outside with a cone and a thread made of a conductive material which is stable under the conditions prevailing in the reactor. 119. The reactor as claimed in claim 116, characterized in that it comprises a reaction tube onto which a holder having a thread and a shoulder is welded and the device viii) is screwed into this holder. 120. The reactor as claimed in claim 117, characterized in that it comprises a reaction tube onto which a holder having a thread and a shoulder is welded and the device ix) is screwed into this holder. 121. The reactor as claimed in claim 116, characterized in that it comprises an oven and a reaction tube running in a looping fashion in the oven, with the oven having a radiation zone, a convection zone and at least two unheated compartments from or into which loops of the reaction tube are passed from or into the radiation or convection zone, with at least one device viii) being located in at least one compartment, and in which the reaction tube is installed so that the feed gas stream can be brought into contact at these points with a heated gas comprising free radicals. 122. The reactor as claimed in claim 117, characterized in that it comprises an oven and a reaction tube running in a looping fashion in the oven, with the oven having a radiation zone, a convection zone and at least two unheated compartments from or into which loops of the reaction tube are passed from or into the radiation or convection zone, with at least one device ix) being located in at least one compartment, and in which the reaction tube is installed so that the feed gas stream can be brought into contact at these points with a heated gas comprising free radicals. 123. The reactor as claimed in claim 95, characterized in that an adiabatic after-reactor which comprises at least one device viii) is located downstream of it and wherein said device viii) is a device for generating free radicals from dissociation promoters installed at the reactor end of the feed line. 124. The reactor as claimed in claim 96, characterized in that an adiabatic after-reactor which comprises at least one device ix) is located downstream of it and wherein said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 125. The reactor as claimed in claim 97, characterized in that an adiabatic after-reactor which comprises at least one device ix) is located downstream of it. 126. The reactor as claimed in claim 97, characterized in that an adiabatic after-reactor which comprises at least one device viii) is located downstream of it and wherein said device viii) is a device for generating free radicals from dissociation promoters installed at the reactor end of the feed line. 127. The reactor as claimed in claim 96, characterized in that the device viii) provided is at least one device for generating and introducing a gas comprising free radicals which comprises a compartment which is separated from the actual reaction space but is connected to this via at least one opening and has devices for introducing a gas comprising dissociation promoters, and devices for irradiating this gas, so that free radicals are generated photolytically in the compartment and travel through the opening or openings into the reaction space. 128. The reactor as claimed in claim 97, characterized in that the device ix) provided is at least one device for generating and introducing a gas comprising free radicals which comprises a compartment which is separated from the actual reaction space but is connected to this via at least one opening and has devices for introducing a gas comprising dissociation promoters, and devices for irradiating this gas, so that free radicals are generated photolytically in the compartment and travel through the opening or openings into the reaction space. 129. The reactor as claimed in claim 127, characterized in that the device viii) or device ix) wherein has an optical window and/or another light guide into the compartment and said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 130. The reactor device as claimed in claim 129, characterized in that the optical window and/or the transparent end of the other light guide is coated with an optically semitransparent layer which comprises a metal which is suitable as hydrogenation catalyst. 131. The reactor as claimed in claim 127, characterized in that the device viii) or ix) forms two conical shells which are installed so that an intermediate space which is provided with at least one gas feed line is formed between the shells and, in that a compartment separated from the reaction space and from the exterior space is formed and in that the shell located farthest from the reactor contains an optically transparent window and/or another light guide and wherein said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 132. The reactor as claimed in claim 127, characterized in that irradiation devices which make it possible for the entire compartment and the adjacent reaction space to be irradiated are provided. 133. The reactor as claimed in claim 101, characterized in that the intermediate space has a further gas inlet which extends into the compartment to near the surface of the optical window and/or the other light guide and makes it possible for the optical window and/or the other light guide and its surroundings to be flushed with inert gas or with inert gas and hydrogen. 134. The reactor as claimed in claim 127, characterized in that it comprises a reaction tube onto which a holder having a thread and a shoulder is welded and the device viii) or ix) is screwed into this holder and wherein said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 135. The reactor as claimed in claim 127, characterized in that it comprises an oven and a reaction tube running in a looping fashion in the oven, with the oven having a radiation zone, a convection zone and at least one unheated compartment from or into which loops of the reaction tube are passed from or into the radiation or convection zone, with at least one device viii) or ix) being located in at least one compartment, and in which the reaction tube is installed so that the feed gas stream can be brought into contact at these points with a heated gas comprising free radicals and wherein said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 136. The reactor as claimed in claim 95, characterized in that an adiabatic after-reactor which comprises at least one device viii) or ix) is located downstream of it and wherein said device viii) is a device for generating free radicals from dissociation promoters installed at the reactor end of the feed line and said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 137. The reactor as claimed in claim 96, characterized in that an adiabatic after-reactor which comprises at least one device viii) or ix) is located downstream of it and wherein said device ix) is a device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor. 138. The reactor as claimed in claim 97, characterized in that an adiabatic after-reactor which comprises at least one device viii) or ix) is located downstream of it and wherein said device viii) is a device for generating free radicals from dissociation promoters installed at the reactor end of the feed line.
The present invention relates to a process for preparing unsaturated halogen-containing hydrocarbons from saturated halogen-containing hydrocarbons and also a device which is particularly useful for carrying out the process. A preferred process relates to the preparation of vinyl chloride (hereinafter also referred to as “VC”) from 1,2-dichloroethane (hereinafter also referred to as “DCE”). The incomplete thermal dissociation of DCE to produce VC has been carried out industrially for many years. This is carried out using dissociation ovens in which the DCE is partly thermally dissociated into VC and in hydrogen chloride at oven inlet pressures of from 0.8 to 4 MPa and at temperatures of from 450 to 550° C. Typical dissociation conversions are about 55 mol % of the DCE used. The process requires considerable amounts of energy for the various process steps, e.g. heating of the DCE to the dissociation temperature, the reaction itself and the subsequent purification of the product mixture. A group of measures for improving the economics of the process is directed at energy recovery, as proposed, for example, in EP-B-276,775, EP-A-264,065 and DE-A-36 30 162. A further improvement in the economics of the process could also be achieved by seeking a very high conversion in the dissociation reaction. For this purpose, so-called dissociation promoters (hereinafter also referred to as “pyrolysis promoters”) have already been added to the feed gas. These dissociation promoters are compounds which disintegrate into free radicals under the conditions prevailing in the reactor and participate in the chain reaction which leads to formation of the desired products. The use of such compounds is known, for example, from U.S. Pat. No. 4,590,318 or DE-A-3,328,691. Further processes in which dissociation promoters are used in the pyrolysis of DCE are known from WO-A-96/35,653, U.S. Pat. No. 4,584,420, U.S. Pat. No. 3,860,595, DE-A-1,952,770 and DE-A-1,953,240. In all these processes, these dissociation promoters are added to the gas mixture to be dissociated and free radicals are generated therefrom by thermal decomposition. A step of free radical generation preceding the addition of the dissociation promoters is not disclosed in the prior art. The earlier WO-A-02/94,743, which is not a prior publication, describes a process and a device for carrying out free-radical gas-phase reactions. Here, a gas which comprises free radicals and is produced by thermal decomposition of dissociation promoters in a preceding step outside the reactor is introduced into the reactor. It is also known from WO-A-00/29,359 that the operating life of the catalyst can be increased by the presence of hydrogen. The hydrogen is in this case mixed into the feed gas. It has also already been proposed that a feed gas comprising DCE be mixed with a hot particle and/or gas stream or a hot gas stream and the heat transferred from the latter be used for the pyrolysis of EDC. In the process described in U.S. Pat. No. 5,488,190, the pyrolysis of the feed gas in a dissociation oven is replaced by an ultrapyrolysis in which the hot particles or gases transfer their energy very quickly to the feed gas and in which the pyrolysis has to be carried out within less than one quarter of a second. This document also proposes adding dissociation promoters to the hot particles or gases. In this case, all of the heat of reaction for dissociation of the DCE is introduced into the reaction zone by means of the hot medium injected. Furthermore, it has already been proposed that DCE be dissociated into free radicals by means of laser light and that these be used in free-radical chain reactions, e.g. for the preparation of vinyl chloride. Examples may be found in SPIE, Vol. 458 Applications of Lasers to Industrial Chemistry (1984), pp. 82-88, in Umschau 1984, number 16, pp. 482, and in DE-A-2,938,353, DE-C-3,008,848 and EP-A-27,554. However, this technology has not been employed in industrial production up to the present time. A reason for this may be that the reactors proposed hitherto are not suitable for long-operation. The present invention provides a process which allows continuous operation of a dissociation oven for a period longer than in conventional processes. According to the invention and in contrast to known processes, free initiator radicals are generated from dissociation promoters by means of nonthermal or thermal decomposition in one or more physically delineated regions within or outside the reactor but separately from the actual dissociation reaction and these are, in a subsequent step, introduced into the gas stream moving through the reactor. The provision of elevated concentrations of free initiator radicals in physically delineated regions of the reactor interior promotes the subsequent thermal dissociation of the starting material. In addition, the conditions employed in the generation of the free initiator radicals are such that the formation of carbon deposits is minimized. It is an object of the present invention to provide a pyrolysis process for halogen-containing aliphatic hydrocarbons, by means of which higher conversions than in conventional processes are possible at the same operating temperature or by means of which the operating temperature can be reduced compared to conventional processes at identical conversions. It has now been found that an increase in the product yield in the continuous pyrolysis can be produced by introduction of small amounts of gases comprising free initiator radicals into the reactor, without large amounts of these gases having to be added. In one embodiment (hereinafter referred to as “variant I”), the present invention provides a process for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons, which comprises the measures: a) introducing a feed gas stream comprising heated gaseous halogen-containing aliphatic hydrocarbon into a reactor into whose interior at least one feed line for a gas opens, b) introducing a heated gas containing free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line or lines opening into the reactor, with, in the case of generation of the free radicals by thermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the reaction mixture in the reactor prevailing at the point at which the feed line opens and with, in the case of generation of the free radicals by nonthermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the dew point of the reaction mixture at the point at which the feed line opens into the reactor, and c) setting such a pressure and such a temperature in the interior of the reactor that hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon are formed by thermal dissociation of the halogen-containing aliphatic hydrocarbon, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. In a further embodiment (hereinafter referred to as “variant II”), the invention provides a process for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons, which comprises the measures: a) introducing a feed gas stream comprising heated gaseous halogen-containing aliphatic hydrocarbon into a reactor into whose interior at least one feed line for a heated gas comprising dissociation promoters opens, d) generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the reactor, e) introducing the heated gas comprising dissociation promoters through the feed line into the predetermined volume, with, in the case of generation of the free radicals by thermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the reaction mixture in the reactor prevailing at the point at which the feed line opens and with, in the case of generation of the free radicals by nonthermal decomposition, the heated gas having at least the temperature corresponding to the temperature of the dew point of the reaction mixture at the point at which the feed line opens into the reactor, and c) setting such a pressure and such a temperature in the interior of the reactor that hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon are formed by thermal dissociation of the halogen-containing aliphatic hydrocarbon. The process of the invention will be described by way of example for the system DCE/VC. It is also suitable for preparing other halogen-containing unsaturated hydrocarbons from halogen-containing saturated hydrocarbons. In all these reactions, the dissociation is a free-radical chain reaction in which, in addition to the desired product, undesirable by-products are formed and lead to carbon deposits in the equipment in long-term operation. The preparation of vinyl chloride from 1,2-dichloroethane is preferred. As heated gas for introduction via the feed line(s) into the feed gas stream, it is possible to use any gas which comprises free radicals derived from dissociation promoters. In variant I of the process of the invention, the formation of free radicals from dissociation promoters occurs in the feed line to the reactor, preferably just before where the feed line opens into the reactor. The feed line can open at the reactor wall or preferably opens into the interior of the reactor in order to avoid reaction of the free radicals generated with the wall. In this variant, the device for generating free radicals is thus located in the feed line or preferably at its end in the reactor and the free radicals formed are fed via the feed line into the reactor. In variant II of the process of the invention, the gas comprising dissociation promoters is fed via a feed line into a predetermined volume of the interior of the reactor and the dissociation promoters are dissociated into free radicals there by the action of a device for generating free radicals. Here too, the feed line can open at the reactor wall or preferably opens into the interior of the reactor in order to prevent recombinations of the free radicals generated at the reactor wall. In this variant, feed line and device for generating free radicals are thus separate from one another and the free radicals are formed in the interior of the reactor by action of the device for generating free radicals. In both variants of the process of the invention, it can also be useful to install a further feed line through which heated inert gas can be introduced into the volume of the reactor, into which the free radicals are introduced or in which free radicals are generated from the dissociation promoters in the vicinity of the opening of the feed line for the gas comprising free radicals or dissociation promoters. This inert gas serves to dilute the reactive components and to prevent the formation of carbon deposits. Examples of dissociation promoters are known per se. These are generally halogen-containing, preferably chlorine-containing, compounds or molecular oxygen. Examples may be found in the abovementioned U.S. Pat. No. 4,590,318 and DE-A-3,328,691. Under the particular conditions of the process of the invention, DCE, for example, is also regarded as a promoter for the pyrolysis reaction since it disintegrates at, for example, the elevated temperatures set for thermal generation of free radicals into free radicals which promote the further course of the pyrolysis reaction. These free radicals can also be generated by nonthermal decomposition of the DCE, e.g. by means of electric discharges or photolytically. Preferred dissociation promoters are molecular chlorine, nitrosyl chloride, trichloroacetyl chloride, chloral, hexachloroacetone, benzotrichloride, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane or hydrogen chloride. The gas which is to be introduced and comprises dissociation promoters or free radicals generated therefrom can further comprise inert gas and/or gases which are constituents of the reaction system. Examples of inert gases are gases which are inert under the reaction conditions prevailing in the reactor, for example nitrogen, noble gases, e.g. argon, or carbon dioxide. Examples of gases which are constituents of the reaction system are hydrogen chloride and dichloroethane. Since the introduction of the gas comprising free radicals should not reduce the temperature in the reactor, it is advisable for the temperature of gases comprising nonthermally generated free radicals to be at least as high as the temperature of the gas stream at the point at which the feed line opens into the reactor, while the temperature of gases comprising thermally generated free radicals is usually considerably higher than the temperature of the gas stream at the point at which the feed line opens into the reactor. When the free radicals are generated by nonthermal decomposition, it is also possible for the heated gas which comprises free radicals or dissociation promoters and is to be introduced into the reactor to have a temperature which is below the temperature of the reaction mixture at the point at which the feed line opens into the reactor. However, it is necessary for the temperature of the heated gas which comprises free radicals or dissociation promoters and is to be introduced into the reactor to have a temperature which is at least equal to the dew point of the reaction mixture at the point at which the feed line opens into the reactor. The gas to be introduced is preferably heated only shortly before it is introduced or injected into the feed gas stream. Typical temperatures of the gas to be introduced are in the range from 250 to 1500° C., preferably from 300 to 1000° C. Typical temperatures of the feed gas stream are in the range from 250 to 500° C. The effect produced by the gas introduced is dependent not only the selected temperature but also on the nature of the gas and on its amount. It is usual to add a total of not more than 10% by weight, preferably not more than 5% by weight, particularly preferably from 0.0005 to 5% by weight, based on the total mass flow in the reactor. Typically more than 90%, preferably more than 95%, of the heat of reaction required is supplied by heating of the reactor walls, while the heat introduced via the hot gas comprising free radicals in the case of thermal generation of free radicals produces preliminary decomposition of the promoter substance. In the case of nonthermal generation of free radicals, the heat introduced via the hot gas comprising free radicals serves to keep its temperature above the dew point temperature of the reaction mixture at the point of introduction. It is assumed that the introduction of a heated gas comprising free radicals promotes the free-radical chain reaction in the feed gas, which ultimately leads to an increased concentration of free radicals and an increased conversion in the dissociation reaction. As feed lines for the heated gas comprising free radicals, it is possible to use all devices known to those skilled in the art for this purpose. Examples are pipes which open into the reactor and have a nozzle at their end which opens into the reactor. Preference is given to feed lines which have a heating device for the heated gas directly before their end which opens into the reactor. The open end of the feed lines can be at the reactor wall. The feed lines preferably open into the interior of the reactor, in particular into the middle of the gas stream in the reactor, so that the heated gas does not come into contact with the reactor walls to any significant extent. The generation of the free radicals from dissociation promoters can occur in the feed lines of the reactor. However, it is also possible for a device for generating free radicals to be installed at the end of the feed line for the gas comprising dissociation promoters or for the device for generating free radicals to be installed in the interior of the reactor and produce an increased concentration of free radicals within a predetermined volume and the feed line to the reactor to open into this predetermined volume and allow the introduction of heated gas, e.g. inert gas and/or gas comprising dissociation promoters. The generation of free radicals from dissociation promoters can be achieved by thermal or nonthermal methods. Examples of nonthermal methods are photolytic dissociation by means of electromagnetic radiation or particle radiation or the generation of nonthermal plasmas by means of electric discharges. In variant I of the process of the invention, in the case of generation of free radicals by thermal decomposition, a gas diluted with inert gas and comprising dissociation promoters is used or the gas comprising dissociation promoters is passed over a heat source whose surface is flushed with inert gas. These measures contribute significantly to reducing the tendency for carbon deposits to be formed. In a preferred embodiment, the gas which comprises the radicals, is diluted with inert gas and is to be introduced is heated electrically in the feed line directly before introduction into the reactor. In a further preferred embodiment, the gas which comprises dissociation promoters, is preferably diluted with inert gas and is to be introduced is passed through a device for generating free radicals, in particular through an electric discharge section at the end of the feed line directly before introduction into the reactor. A further preferred variant of the process of the invention comprises generation of a thermal plasma from inert gas, cooling of the thermal plasma to the desired temperature by introduction of inert gas so as to produce a gas having a temperature which is sufficiently high to generate free radicals from a dissociation promoter, mixing of this gas with a dissociation promoter and introduction of this mixture comprising free radicals into the reactor. A further preferred variant of the process of the invention relates to the use of gases which are derived from dissociation promoters and in which free radicals have been generated by means of an electric discharge, preferably a spark, barrier or corona discharge. A further preferred variant of the process of the invention relates to the use of gases which are derived from dissociation promoters and in which free radicals have been generated by means of a microwave discharge or a high-frequency discharge. Another preferred variant of the process of the invention relates to the use of gases which are derived from dissociation promoters and in which heat and free radicals have been generated simultaneously by means of a chemical reaction. Examples are the combustion or catalytic reaction of an excess of chlorine with hydrogen in or just before the point at which the feed line opens into the reactor. Thus, it is possible to use a chlorine/hydrogen flame, with chlorine being used in excess and an inert gas preferably being added. Very particular preference is given to the reaction of an excess of chlorine with hydrogen in the presence of inert gas over a catalytically active surface, e.g. over platinum. Another preferred variant of the process of the invention relates to the use of gases which are derived from dissociation promoters and in which free radicals have been generated by means of a photochemical reaction in the feed line to the reactor or in a predetermined volume in the interior of the reactor. An example is the use of a radiation source suitable for generating free radicals which has been installed in the feed line to the reactor, e.g. an excimer lamp, a mercury vapor lamp, a laser, or injection of electromagnetic radiation suitable for generating free radicals or of particle radiation, e.g. alpha or beta particles, into the feed line to the reactor or into the reactor. In a further preferred embodiment of the process of the invention, a reactor which has at least one catalytically active metal located on a gas-permeable support in the interior of the reactor is used. As catalytically active metal, it is possible to use any metal including metal alloys which is stable under the reaction conditions prevailing in the reactor, for example does not melt. It is assumed that metallic surfaces and/or metal halides formed in the dissociation reaction reduce the activation energy of one or more steps of the free-radical chain reaction and thereby accelerate the reaction further. Preference is given to using a metal or a metal alloy from transition group 8 of the Periodic Table of the Elements, in particular iron, cobalt, nickel, rhodium, ruthenium, palladium or platinum, or alloys of these metals with gold as catalytically active metal. Very particular preference is given to rhodium, ruthenium, palladium and platinum. As gas-permeable supports, it is possible to use all supports which are known -to those skilled in the art and can be applied in selective regions of the interior wall of the reactor and/or the interior of the reactor and are provided with feed lines for flushing gas. The support can be a cage which is formed, for example, by a wire mesh or a perforated metal plate and can accommodate a catalyst bed and through which flushing gas can flow, for example through a central inlet by means of a perforated tube. Furthermore, the gas-permeable support can be a gas-permeable plate which is surrounded by a flat structure, for example a wire gauze, of catalytically active metal. The gas-permeable support is preferably a porous shaped body. This can consist of the catalytically active metal. It is preferably a porous ceramic which is, in particular, coated with the catalytically active metal; or it is a porous ceramic doped with the catalytically active metal. The catalytically active metal can have been applied in any form. in or on the gas-permeable support. Such structures are known to those skilled in the art. For example, the catalytically active metal can be present in a form having a very large surface area:volume ratio. The catalytically active metal is preferably applied as a coating and/or as dopant on or in the gas-permeable support. To maintain a very long period of operation, it is necessary for the catalytic activity of the metal to be retained for as long as possible and/or to be able to be restored or regenerated during continuing operation of the reactor. It has been found that this can be achieved by flushing the catalytic surface with a gaseous reducing agent. As gaseous reducing agent, it is possible to use all reducing agents for carbonization products which are gaseous at the temperatures prevailing in the reactor. Examples are hydrogen or a mixture of hydrogen and inert gas. The gaseous reducing agent is introduced via the gas-permeable support and is applied through this to the catalytically active metal. The gaseous reducing agent can be introduced continuously or at predetermined time intervals. The gaseous reducing agent can be introduced in undiluted form or together with inert gases such as nitrogen and/or noble gases. The temperature of the gaseous reducing agent introduced via the gas-permeable support is advantageously matched to the temperature prevailing in the interior of the reactor at the position of the gas-permeable support. Continuous or intermittent injection of hot gases into the reaction mixture enables the conversion in the pyrolysis reaction to be increased and the product yield to be increased; parallel flushing with inert gas and/or reducing agent enables the formation of carbon deposits on the surface of any catalytically active metal present in the interior of the reactor to be efficiently prevented or retarded and, as a result, the period of operation of the dissociation oven to be increased and the conversion in the dissociation reaction to be raised further. Operation of the reactor is not interrupted during the flushing procedure. Instead of or together with the gaseous reducing agent, dissociation promoters can also be supplied to the catalytically active metal in the reactor via the gas-permeable support. Examples of these have been mentioned above. It is preferred that at least one feed line for hot gas comprising dissociation promoters opens in the vicinity of the entry of the feed gas stream into the reactor. In this way, a heated gas comprising free radicals which is formed from dissociation promoters can be introduced into the reactor at this point, so that a high concentration of free radicals is already present when the feed gas is introduced into the reactor, which helps the chain reaction proceed efficiently. In a preferred variant of the process of the invention, a heated gas comprising free radicals which is formed from dissociation promoters is introduced into the feed gas stream via a plurality of feed lines during passage through the reactor. The number of feed lines in the first third of the reactor is very particularly preferably greater than that in the second third and/or in the third third. The process of the invention can be carried out using the pressures and/or temperatures which are customary per se. Useful operating pressures are in the range from 0.8 to 4 MPa (oven inlet); useful operating temperatures are in the range from 450 to 550° C. (oven outlet) and in the range from 250 to 350° C. (oven inlet). The endothermic dissociation reaction requires continual introduction of energy; this is effected during passage of the gas to be dissociated through the reactor. The process of the invention makes it possible to reduce the customary operating temperatures. This makes more economical operation possible. Instead of a reduction in the operating temperatures, it is possible to obtain an increase in yield. A further embodiment of the process of the invention relates to the thermal dissociation of the product gas in an adiabatic after-reactor installed downstream of the reactor, which comprises the measures: f) introducing the product gas stream comprising heated halogen-containing aliphatic hydrocarbon, hydrogen halide and ethylenically unsaturated halogen-containing aliphatic hydrocarbon from the reactor into an adiabatic after-reactor in which the reaction is continued with the aid of the heat supplied by the product gas stream with cooling of the product gas, and in whose interior at least one feed line for a heated gas which comprises free radicals and has been formed from dissociation promoters optionally opens, and g) if appropriate, introducing a heated gas comprising free radicals generated by thermal or nonthermal decomposition of dissociation promoters through the feed line(s) opening into the adiabatic after-reactor or generating free radicals thermally or nonthermally from dissociation promoters by means of a suitable device within a predetermined volume in the interior of the adiabatic after-reactor, with, in the case of generation of the free radicals by thermal decomposition, the temperature of the heated gas being at least the temperature prevailing in the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor and, in the case of generation of the free radicals by nonthermal decomposition, being at least the temperature which corresponds to the dew point of the reaction mixture at the point at which the feed line opens into the adiabatic after-reactor, with the proviso that, in the case of generation of free radicals by thermal decomposition, this is achieved by heating a gas comprising dissociation promoters diluted with inert gas or by passing a gas comprising dissociation promoters over a heat source whose surface is flushed with inert gas. Here, the process of the invention can comprise only the measures f) and g) in the adiabatic after-reactor without using an upstream reactor into whose interior space at least one feed line for a heated gas opens. However, the process of the invention with the measures f) and g) in the adiabatic after-reactor is preferably combined with the use of an upstream reactor into whose interior space at least one feed line for a heated gas opens. The invention further provides a reactor for carrying out the above-defined process, which comprises the elements: i) feed line for the feed gas stream comprising saturated halogen-containing aliphatic hydrocarbon opening into the reactor, ii) at least one feed line for a heated gas opening into the interior of the reactor, iii) source of a dissociation promoter connected to the feed line, iv) device for generating free radicals from dissociation promoters installed in the feed line, v) if appropriate, heating device for heating the gas in the feed line, vi) heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. In a further preferred embodiment, the invention also provides a reactor for carrying out the above-defined process, which comprises the elements: i) feed line for the feed gas stream comprising saturated halogen-containing aliphatic hydrocarbon opening into the reactor, ii) at least one feed line for a heated gas opening into the interior of the reactor, iii) source of a dissociation promoter connected to the feed line, viii) device for generating free radicals from dissociation promoters installed at the end of the feed line, v) if appropriate, heating device for heating the gas in the feed line, vi) heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. In a likewise preferred embodiment, the invention provides a reactor for carrying out the above-defined process, which comprises the elements: i) feed line for the feed gas stream comprising satuarated halogen-containing aliphatic hydrocarbon opening into the reactor, ix) device which is installed in the interior of the reactor and generates free radicals from dissociation promoters within a predetermined volume in the interior of the reactor, x) at least one feed line for a heated gas comprising dissociation promoters opening into the predetermined volume in the interior of the reactor, iii) source of a dissociation promoter connected to the feed line, v) heating device for heating the gas in the feed line, vi) heating device for heating and/or maintaining the temperature of the gas stream in the reactor, and vii) outlet line for the product gas stream of the thermal dissociation comprising ethylenically unsaturated halogen-containing aliphatic hydrocarbon leading from the reactor. As reactor, it is possible to use all types which are known to those skilled in the art for such reactions. Preference is given to a tube reactor. An adiabatic after-reactor which preferably comprises the above-defined elements ii), iii) and iv) or ii), iii) and viii) or ix), x), iii) and v) can be located downstream of the reactor of the invention. In the adiabatic after-reactor, the heat of reaction required is supplied by the heat of the product gas stream fed in, which is cooled thereby. Instead of the reactor of the invention being combined with an adiabatic after-reactor comprising the elements ii), iii) and iv) or ii), iii) and viii) or ix), x), iii) and v), such an adiabatic after-reactor can also be connected to a reactor known per se which does not have the elements ii), iii) and iv) or ii), iii) and viii) or ix), x), iii) and v). The feed line for the heated gas preferably comprises metal pipes which open at the wall or preferably into the interior of the reactor and have a nozzle at their ends opening into the reactor and preferably have an electric heating device for the heated gas directly before their ends opening into the reactor. In a preferred variant, this heating device consists entirely of ceramic. A further preferred embodiment of the reactor of the invention comprises a generator for a thermal plasma, for example a high-frequency plasma generator, which is connected to the reactor, via the feed line for the gas comprising free radicals, with the high-frequency plasma generator being connected, if appropriate, to a further feed line for an inert gas and to a further feed line for a dissociation promoter. The high-frequency plasma generator is preferably installed on the outer wall of the reactor in the vicinity of the opening of the feed line into the reactor. A further preferred embodiment of the reactor of the invention comprises a device for generating an electric discharge, preferably a spark, barrier or corona discharge, which is connected to the feed line to the reactor. This is likewise preferably installed on the outer wall of the reactor in the vicinity of the opening of the feed line into the reactor. A further preferred embodiment of the reactor of the invention comprises a device for generating a microwave discharge or a high-frequency discharge which is connected to the feed line to the reactor. This is likewise preferably installed on the outer wall of the reactor in the vicinity of the opening of the feed line into the reactor. Another preferred embodiment of the reactor of the invention comprises a device in which heat and free radicals are generated simultaneously by means of a chemical reaction and which has at least two feed lines for the reactants and also a burner which opens directly into the reactor. A further preferred embodiment of the reactor of the invention comprises a radiation source which is located in the feed line to the reactor or whose radiation is introduced into the feed line to the reactor. This is likewise preferably installed on the outer wall of the reactor in the vicinity of the opening of the feed line into the reactor. In a very particularly preferred embodiment of the reactor of the invention at least one porous ceramic in the form of a stub whose surface is coated with catalytically active metal and/or which is doped with catalytically active metal is present inside the reactor, and the stub is provided with a feed line for a gaseous reducing agent and/or a dissociation promoter for supply to the catalytically active metal. Further particularly preferred embodiments of the process and reactor of the invention are described below with the aid of FIGS. 1 to 9. In the figures, FIG. 1 shows a preferred device for heating and introducing a heated gas which comprises free radicals and has been formed from dissociation promoters into a dissociation reactor shown in longitudinal section, FIG. 2 shows the device of FIG. 1 installed in a reaction tube shown in cross section, FIG. 3 shows a longitudinal section of a tube reactor with a device as shown in FIG. 1, FIG. 4 shows a preferred device for generating free radicals by means of a nonthermal plasma and for introducing the heated gas which comprises free radicals and has been formed from dissociation promoters into a dissociation reactor shown in longitudinal section, FIG. 5 shows a further preferred device for generating free radicals by means of a nonthermal plasma and for introducing the heated gas which comprises free radicals and has been formed from dissociation promoters into a dissociation reactor shown in longitudinal section, FIG. 6 shows the device of FIG. 4 or 5 installed in a reaction tube shown in longitudinal section, FIG. 7 shows a further preferred device for generating free radicals from dissociation promoters by means of radiation and for introducing the gas which comprises free radicals and has been formed from dissociation promoters into a dissociation reactor shown in longitudinal section, FIG. 8 shows a longitudinal section of a modification of the device of FIG. 7, FIG. 9 shows a longitudinal section of a further modification of the device of FIG. 7. In a particularly preferred variant of the process of the invention, the feed gas stream comes into contact with a gas comprising free radicals which has been generated in one or more heating devices of the type depicted in FIG. 1 during passage through the reactor. The heating device is an electrically operated heating cartridge (1) which is preferably provided with ceramic cladding and is preferably installed in a housing (2) having one or more concentric annular gaps (3). The housing (2) comprises ceramic and/or metal. The housing preferably has a cylindrical shape. The heating cartridge (1) is fixed in the housing (2) by means of a gastight, pressure- and heat-resistant lead-through (4). The lead-through (4) is preferably provided with a screw thread so that the heating cartridge can be screwed and fixed into it. The housing (2) has a gas inlet (5) through which a gas stream which comprises dissociation promoters and may have been diluted with inert gas can be introduced. The gas inlet (5) is preferably located at the outer wall of the housing (2). A plurality of concentric annular gaps (3) are preferably formed in the housing, and the gas comprising dissociation promoters flows through these. These annular gaps (3) have at least two openings through which the gas comprising dissociation promoters flows into and out of the annular gap. These openings are preferably located at the height of the front and rear ends of the heating device. As a result, the gas stream flows through each annular gap along the entire length of the heating device and the flow direction of the gas stream is reversed in each annular gap. In the embodiment shown, the gas stream travels from the outside of the housing (2) through the annular gap (3), its flow direction is reversed repeatedly in the annular gaps (3) and the gas stream finally flows along the heating cartridge (1) installed in the middle and then through a gas outlet (6), which is preferably configured as a nozzle, into the reaction space. However, the housing (2) can also have only one annular gap. In this case, the gas immediately flows along the heating cartridge (1) and through the gas outlet (6) into the reaction space. The embodiment having a plurality of annular gaps shown in FIG. 1 offers the advantage that the strong heating of the gas comprising dissociation promoters at the heating cartridge (1) does not result in the outer wall of the heating device being heated to a temperature significantly above the temperature prevailing in the reaction space. This prevents increased formation of carbon deposits on the outer wall. In a further embodiment, the outer wall of the heating device, in particular the part of the heating device which projects into the reaction space, can be coated with an inert material, e.g. a metal oxide, ceramic, boron nitride or silicon nitride. The interior wall of the heating device opposite the heating cartridge (1) can also be coated with such material. In a further embodiment, the device has at least two separate gas feed lines, with one feed line serving to introduce an inert gas and the other feed line serving to introduce a promoter substance. The feed line for the promoter substance is preferably arranged so that mixing with the inert gas occurs only just before entry into the reaction space. The heating device shown in FIG. 1 is provided on its exterior wall with a cone (8) on whose outside there is a thread (7). The cone (8) and that part of the heating device which forms the sealing edge for the seal to the line consist of materials which have approximately the same thermal expansion, in particular of the same material. A possible arrangement of the heating device on the reaction tube is shown in FIG. 2. A holder (10) which has a thread (11) and a shoulder (12) which forms a circumferential sealing edge is welded onto the reaction tube (9). When the heating device described in FIG. 1 is screwed into the holder (10), the shoulder (12) cuts into the cone (8) and thus forms a reliable seal. This sealing principle has been described in DE-A-44 20 368. Likewise as described in 44 20 368, an additional seal can be provided by means of a gland packing (not shown in FIG. 2). The heating device shown in FIG. 1 can be installed in a conventional tube reactor for preparing ethylenically unsaturated halogen-containing aliphatic hydrocarbons by thermal dissociation of saturated halogen-containing aliphatic hydrocarbons. Such installation is shown schematically in FIG. 3. The tube reactor comprises an oven and a reaction tube. In general, such an oven fired with a primary energy source such as oil or gas is divided into a radiation zone (16) and a convection zone (17). In the radiation zone (16), the heat required for pyrolysis is transferred to the reaction tube primarily by radiation from the oven walls which have been heated by means of burners. In the convection zone (17), the energy content of hot flue gases leaving the radiation zone is exploited, so that convective heat transfer occurs. In this way, the starting material for the pyrolysis reaction, e.g. EDC, can be preheated, vaporized or superheated. The generation of steam and/or preheating of combustion air are likewise possible. In a typical arrangement as shown, for example, in EP-A-264,065, liquid EDC is firstly preheated in the convection zone of the dissociation oven and is then vaporized in a specific vaporizer outside the dissociation oven. The gaseous EDC can again be passed into the convection zone and superheated there, with the pyrolysis reaction being able to commence at this point. After superheating is complete, the EDC enters the radiation zone where the conversion into vinyl chloride and hydrogen chloride takes place. Due to the high temperatures prevailing in the radiation zone and at the entry into the convection zone, it is advantageous for the device depicted in FIG. 1 not to be positioned directly within these zones since otherwise, for example, setting a defined temperature of the heated gas or gas mixture comprising free radicals which is introduced to promote the dissociation reaction is impossible or possible only with difficulty. Preference is therefore given to an arrangement as shown schematically in FIG. 3. Here, the dissociation furnace is extended to include at least two additional, unheated compartments (18) which may be thermally insulated. Loops of the reaction tube are then passed from the actual radiation or convection zone (16, 17) through these compartments (18). The heating device shown in FIG. 1 (19) for introducing a heated gas comprising free radicals is then installed in these loops, preferably at the bends of the loops and opening into the straight lengths of these loops, i.e. built into the reaction tube so that the feed gas stream can be brought into contact with the heated gas comprising free radicals at these points. The loops of the reaction tube passed from the radiation or convection zone (16, 17) into the unheated compartments (18) are preferably provided with thermal insulation. In a further, particularly preferred variant of the process of the invention, the feed gas stream comes into contact, during passage through the reactor, with a nonthermal plasma comprising free radicals which has been generated in one or more devices of the type depicted in FIGS. 4 and 5. FIGS. 4 and 5 show a device known per se for the upstream generation of free radicals by means of a nonthermal plasma derived from a vaporous dissociation promoter or a mixture of dissociation promoter and inert gas and for introduction of the plasma into the reactor of the invention. Here, free radicals are generated from a gaseous dissociation promoter by means of an electric discharge in a volume separate from the reaction space of the dissociation reaction. It is possible to use the undiluted dissociation promoter, or the promoter can be diluted with an inert gas such as nitrogen or noble gas. The electric discharge is preferably a barrier or corona discharge. The free radicals generated in this way are then fed into the actual reaction space of the reactor of the invention. The device shown in FIGS. 4 and 5, which is preferably used in the reactor of the invention, is known from DE-A-196 48 999. The previously known device is used for the treatment of surfaces with a high-pressure plasma. The device for generating a nonthermal plasma is advantageously combined with a sealing system as is known from DE-A-44 20 368 for the introduction of a measuring sensor into a dissociation oven for the production of vinyl chloride. As a difference from the procedure described in DE-A-196 48 999, the device for plasma generation is operated at significantly higher pressures of at least 5 bar, preferably from 12 to 26 bar, according to the invention. In contrast to the operation at atmospheric pressure known from DE-A-196 48 999, significantly higher electric potentials are necessary for generating, for example, a barrier discharge. The device for plasma generation which is preferably used according to the invention comprises a gas inlet (43), a plasma generation region (32) having at least two electrodes (33, 34) and a gas outlet (28) which opens into a reaction space (46), with the reaction space (46) and plasma generation region (32) being physically separate from one another. An example of the device used in the reactor of the invention and described in DE-A-196 48 999 is described in more detail below with reference to FIG. 4, which shows a longitudinal section. The device has an essentially cylindrical housing (20) having a rear end (21) and a front end (22). Along its outside (23), the housing (20) is provided with a cone (24) and a thread (25). The housing (20) consists of a conductive material such as metal, preferably steel or another metal, which is stable under the conditions prevailing in the reactor. In the region of its front end (22), the cylindrical housing (22) tapers and has an opening serving as gas outlet (28) in the region of its cylinder axis (26). This opening can be formed by a port. In the region of its rear end (21), the housing (20) bears a flange (29) which has channels and inlets as described further below. In the interior of the housing (20), a ceramic tube (30) which is closed at one end in the region of the gas outlet (27) is installed axially symmetrically to the axis (26). The external diameter of this ceramic tube (30) is selected so that an annular gap which will hereinafter be referred to as the plasma generation region (32) is formed between the ceramic tube (30) and the inside (31) of the housing (20). The. inside of the ceramic tube (30) is provided with a conductive coating comprising a metal, for example a conductive silver coating, and forms one electrode (33) of a plasma generation device. The other electrode (34) is formed by the electrically conductive housing (20) itself. The ceramic tube (30) and the plasma generation region (32) in the form of an annular gap are thus present between the electrode (33) configured as an interior coating and the electrode (34) formed by the housing (20). A further tube (35) is present in the interior of the ceramic tube (30) and is likewise installed axially symmetrically to the cylinder axis (26) but is open at both ends. This further tube (35) is fixed with a spacing in the region of the front end (22) of the housing (20) within the ceramic tube (30) with the aid of a spring (37) which presses against the closed end (36) of the ceramic tube (30), so that an annular gap (38) is formed between the outside of the further tube (35) and the conductively coated inside of the ceramic tube (30). The spring (37) is, for example, three- or four-bladed and in each case allows unhindered passage of gas from the interior space of the further tube (35) into the annular gap (38). The spring (37) also connects a high-voltage lead (39) located axially symmetrically within the further tube (35) with the electrically conductive coating which forms the one electrode (33), so that an alternating current can be supplied to the latter. On the other hand, the housing (20) forming the other electrode (34) is earthed, so that it can be touched without danger. The flange (29) at the rear end (21) of the cylindrical housing (20) serves essentially to supply gas and high-voltage power and to earth and conduct the gas flow through the various gaps within the housing (20). The cylindrical flange (29) is fastened to the cylindrical housing (20) by means of screws (40) which are screwed into the outer region of the cylindrical housing (20). In its middle, the flange (29) has an insulating, gastight and pressure-resistant lead-through (41) through which the high-voltage lead (39) is passed axially into the housing (20). Furthermore, the flange (29) has a gas inlet (43) which leads from an outer connecting piece via a channel (42) into the interior region of the further tube (35), and the rear end of the further tube (35) seals against a sealing web (44) of the flange (29). Furthermore, the flange (29) has on its side facing the housing (20) a circular groove (45) whose diameter is measured such that it connects the annular gap (38) between the further tube (35) and the ceramic tube (30) to the annular gap of the plasma generation region (32) between the ceramic tube (30) and the inside (31) of the housing in a gastight fashion. To operate the device, the gas inlet (43) is supplied with the chosen gas or gas mixture and a high-frequency high voltage is applied between the high-voltage lead (39) and the housing (20). The voltage and frequency to be selected depend on the type of gas, the geometry of the assembly, the type of surface treatment and further factors and can be chosen freely by a person skilled in the art. The gas goes from the gas inlet (43) into the interior of the further tube (35), flows through this further tube (35) to the spring (37), enters the region between the spring (37) and the closed end of the ceramic tube (30) and travels back down again into the annular gap (38) between the ceramic tube (30) and the further tube (35). The gas then again reaches the flange (29) in its circular groove (45) and is once again deflected, this time in an upward direction, into the annular gap between the outside of the ceramic tube (30) and the inside of the housing (20), which forms the plasma generation region (32). After flowing through this plasma generation region, the gas reaches the region of the gas outlet (28) and there leaves the device and enters the reaction space (46) where the reaction to be initiated occurs. Since the conductive coating of the ceramic tube (30) is at the same electric potential as the high-voltage lead (39), the gas remains uninfluenced electrically both within the further tube (35) and in the annular gap (38). The diversion of the gas through the further tube (35) and the annular gap (38) is carried out essentially for the purpose of internal cooling of the device. The working gas thus acts simultaneously as cooling gas, which enables further internal cooling to be dispensed with. Only in the plasma generation region (32) is the gas present between the electrodes (33), formed by the conductive coating of the ceramic tube (30), and (34), formed by the housing (20), and is partially ionized by the applied high-frequency high voltage, i.e. converted into the plasma state desired for generation of free radicals. In operation of the device, the flow velocity selected should be sufficiently high for the plasma state to be maintained even after exit of the plasma gas through the gas outlet (28). In a further embodiment, the exterior wall of the device used according to the invention, in particular the part of the device which projects into the reaction space, can be coated with an inert material, e.g. a metal oxide, ceramic, boron nitride or silicon nitride, to retard or prevent the deposition of carbon. In a further embodiment shown in FIG. 5, the device has one or more drilled holes (47) in the housing (20) in place of the gas outlet (28), so that the gas comprising free radicals can travel out through these holes (47) into the reaction space (46). The device used according to the invention is preferably provided on its exterior wall with a cone (24) and a thread (25). A preferred way of installing the devices of FIGS. 4 and 5 on the reaction tube is shown in FIG. 6. A holder (49) which has a thread (50) and a shoulder (51) which forms a circumferential sealing edge is welded onto the reaction tube (48). When the device described in FIG. 4 or FIG. 5 is screwed into the holder, the sealing edge (51) cuts into the cone (46) and a reliable metallic seal is formed. This sealing principle is known from DE-A-4,420,368. Likewise as described there, an additional seal can be provided by a gland packing (not shown in the figure). The entire device can be installed on the reactor in the same way-as shown in FIG. 3. In a further, particularly preferred variant of the process of the invention, the feed gas stream comes into contact with a gas which comprises free radicals and has been generated in one or more devices of the type depicted in FIGS. 7, 8 and 9 during passage through the reactor. In this device, free radicals are generated by photolysis of a gaseous promoter substance which can either be in pure form or be present in admixture with an inert gas and/or with a gaseous reducing agent. Photolysis takes place in a compartment which is separate from the actual reaction space and through which the respective gas (mixture) flows and is dissociated photolytically into free radicals. The gas (mixture) comprising free radicals then goes through an opening, which can be configured as a nozzle, into the actual reaction space. During flow through the compartment, but optionally also after exit from the nozzle, the promoter substance is photolyzed by interaction with light from a suitable light source. This results in formation of free radicals which then promote the reaction occurring in the actual reaction space. This procedure has the advantage that only small amounts of promoter substance are needed. The direct introduction of a promoter substance into the reaction space, as is known from the literature, leads to generation of free radials by thermal disintegration of the promoter at the temperature level of the reaction to be influenced, for example in the range 450-550° C., or by heterogeneous disintegration (wall reactions). In this case, the promoter has to be added in amounts which have an appreciable effect on the reaction system and lead not only to the. desired increase in conversion but also to increased formation of by-products, i.e. to a reduction in the selectivity, and to an increase in the rate of formation of carbon deposits. These disadvantages nullify the economic advantage gained by the increasing conversion and lead to the use of promoter substances not having been able to become established in industrial practice to the present day. The procedure described here overcomes this disadvantage by the promoter substance being decomposed into free radicals specifically and effectively in a compartment separate from the actual reaction, so that it is necessary to add only small amounts of promoter substance. Promoter substances in the preparation of halogen-containing ethylenically unsaturated hydrocarbons are usually substances which form chlorine radicals under the reaction conditions of the process. These can be chlorine itself or chlorine compounds such as CCl4 or other chlorinated hydrocarbons. In the process described here, the promoter substance can also be DCE, which is then preferably diluted with an inert gas. To carry out the process variant described, light from a light source suitable for the purpose described is introduced via a light conductor or an optically transparent window, preferably a fused silica window, into a compartment separate from the actual reaction space and passes through the compartment itself and preferably also part of the adjoining reaction space. In the compartment, the promoter gas (which can consist of the pure promoter substance or be a mixture of promoter substance with an inert gas) forms a gas buffer which largely isolates the light conductor or the optical window chemically from the reaction space. The purpose of this measure will be explained below for the example of EDC dissociation. An undesirable secondary reaction in EDC dissociation is the deposition of carbon on the reactor walls. The process of carbon deposition proceeds more slowly on nonmetallic materials, e.g. fused silica, than on metallic materials. Good use has in recent times been made of this fact to retard the formation of carbon deposits in reactor tubes by application of nonmetallic coatings to the interior wall of the tube. Despite this fact, carbon would also be deposited on the optical window if this were exposed directly to the reaction mixture, i.e., for example, were to be installed directly in the wall of the reactor. These problems have been described in DE-A-30 08 848. There, photochemical initiation of the dissociation reaction by direct radiation of light into the reaction space is proposed, both when using metal vapor lamps and when using lasers as light source. The observation that the window is rapidly covered with by-products when continuously operating light sources such as metal vapor lamps are used while it remains free when lasers are used is also described there. As a remedy, operation using a high flow velocity in the region of the optical window is proposed, so that the by-products formed are formed in an appreciable amount only downstream of the window. However, this procedure has the disadvantage that the “self-cleaning” of the window is probably restricted to the use of pulsed lasers, since in this case pressure pulses are generated by brief local heating of the gas in and around the carbon particles and these pressure pulses then detach the carbon particles or the carbon layer from the window. Although the use of pulsed lasers is not mentioned explicitly in DE-A-30 08 848, it is mentioned in DE-A-29 38 353 which is expressly incorporated by reference in DE-A-30 08 848. The experiments on which DE-A-30 08 848 and DE-A-29 38 353 are based were carried out in fused silica reactors. However, in industrial reactors made of metal, carbon deposits would be formed in the inlet region of the reactor and thus “upstream” of any optical window installed. Possible causes for this are, firstly, that precursors of carbon deposits are formed in the inlet region of the reactor by reactions at the wall and, secondly, that small amounts of precursors of carbon deposits can be introduced into the reactor together with the starting material in the industrial process even when the starting DCE is carefully purified by distillation. There is therefore a need for further processes which can readily be implemented in industrial practice and in which formation of carbon deposits can be avoided effectively. These disadvantages are overcome by means of the present invention and a process and/or a reactor is available in which light can be introduced into a reactor operated under the conditions of VC production or under similar conditions is/are proveded. For this purpose, a promoter substance is firstly photolytically dissociated in a compartment separate from the actual reaction space and then introduced into the reaction space. FIG. 7 shows a device for the photolytic generation of free radicals from dissociation promoters which is preferably used in the reactor of the invention. A holder which has a thread (52) and a circumferential sealing edge (53) in its interior is welded on at a bend of the reaction tube. A conical shell (54) whose front end can be configured as a nozzle and can have, for example, an internal hexagonal hole (55) to aid screwing on can be screwed into this holder. When the conical shell (54) is screwed into the holder (56), it forms a seal which is reliable under the conditions of the reaction with the sealing edge (53) of the holder. This tried-and-tested sealing principle has been described in DE-A-44 20 368. Using the same sealing principle, a further shell (57) having an optically transparent window (58), e.g. a fused silica window which can be coated with a semitransparent metal layer (59), can be screwed into the holder (56). The metal is preferably a hydrogenation catalyst and very particularly preferably a platinum metal. The optical window is clamped between holders (60, 61) which on their sides facing the window have circumferential recesses (62) which can each accommodate a seal (63, 64), preferably a metal seal and very particularly preferably a gold seal. The window (58) is pressed against the holder (61) by the holder (60). This can be achieved by screwing the holder (60) in by means of a bearing ring or bearing blocks (65) provided with, for example, pocket holes (66). The holders (60) and (61), the recesses (62) and the thicker of the seals have dimensions such that when the assembly is screwed together, the seals exert a defined pressure and the optical window is not damaged. The intermediate space (67) between the shells (54) and (57) is provided with one or more gas feed lines and forms a compartment separated from the reaction space (68) and the surrounding space (69). The pyrolysis of, for example, DCE to form VC takes place in the reaction space (68). The entire assembly is installed at a bend of the reaction tube which projects from the actual radiation zone of the oven and is thermally insulated from this. An inert gas, e.g. nitrogen or a noble gas, or a mixture of an inert gas with a promoter substance or a gaseous promoter substance flows through the gas inlet (70) into the compartment (67). The gas leaves the compartment and flows through the opening (71) into the reaction space. As a result of the permanent flushing of the compartment, the optical window is separated by a gas buffer from the reaction space (68). Precursors of carbon deposits, e.g. acetylene, benzene or chloroprene, can therefore not reach the window and form carbon deposits there. In a preferred embodiment, the optical window is coated with an optically semitransparent metal layer, with the metal being a hydrogenation catalyst, e.g. palladium. If a small amount of hydrogen is then mixed into the promoter gas, precursors of carbon deposits which despite the flushing reach the optical window are reduced on its surface. As a result, carbon deposits cannot form on the surface of the window. The light from the light source passes through the optical window and transfers energy to the molecules of the promoter substance which as a result disintegrates into free radicals (photolysis) which then promotes the reaction occurring in the actual reaction space (68). The generation of free radicals and their subsequent transport into the reaction space is normally difficult, since the free radicals rapidly recombine under the prevailing pressure conditions (typically 9-25 bar). However, in the arrangement according to the invention, radiation passes through the entire compartment and preferably also the reaction space. This results in the desired free radicals also being formed from the promoter substance in the opening (71) and in the zone of the reaction space adjoining this opening and thus being able to participate with certainty in the reaction. There is therefore no need for high flow velocities of the initiator or flushing gas to transport free radicals generated in the compartment quickly into the reaction space. This also means that initiation can be carried out using very small amounts of promoter gas, as a result of which the reaction system is affected to only a small extent and the formation of undesirable by-products is largely suppressed. In a further preferred embodiment shown in FIG. 8, the compartment (67) has a further gas inlet (72) which extends to close to the surface of the optical window (58). This makes it possible to flush the window and its immediate surroundings with inert gas or a mixture of inert gas and hydrogen, while the promoter substance or a mixture of promoter substance and inert gas is introduced through the gas inlet (70). Such an arrangement allows the optical window to be protected against carbon deposits even more effectively. A further preferred embodiment shown in FIG. 9 is similar to the embodiment shown in FIG. 8. However, the further gas inlet (72) is in this case directed in the direction of the opening (71) and is employed for introducing the promoter substance. The gas inlet (70) is employed purely for the introduction of inert gas or flushing gas. In this way, the free radicals are generated from the promoter substance in the vicinity of the reaction space (68) and away from the optical window (58). This provides further protection for the optical window (58) against carbon deposits. As light source, it is possible to use any light source whose light is suitable for photolyzing the promoter substance used. This can be a UV lamp (e.g. a metal vapor lamp) or a laser. When lasers are used, it is immaterial in the case of the arrangement proposed here whether a pulsed laser or a continuous laser is used. Excimer lamps can also be used as light source. The radiation used can be introduced in various ways. Thus, for example, the light can be introduced through a bundle of optical fibers (as indicated in FIG. 8). Furthermore, the light source (e.g. when a metal vapor lamp or excimer lamp is used) can be installed directly in the shell (57) behind the optical window. In this case, appropriate cooling is preferably provided. The light can also be introduced into the shell (57) through a further window and deflected by means of a mirror onto the window (58). In a particular embodiment, a device similar to that described in DE-A-198 45 512 or DE-Gbm-200 03 712 is used for the introduction of light. The previously known devices are employed for observing processes in the combustion chamber of internal combustion engines during operation and are, for example, used in the form of spark plug adaptors. In addition to their actual intended use, viz. the visual observation of combustion processes, such devices are, owing to their pressure- and heat-resistance, likewise suitable for introducing light into chemical reactors in which the pressure and temperature conditions are similar to those in running internal combustion engines. If such devices are used, the optical window shown in FIGS. 7, 8 and 9 together with the sealing system described could be omitted. The light guide would then be screwed in the form of an adaptor analogous to one or more spark plug adaptors into a dividing wall located in the shell (55). The installation of the device for the photolytic generation of free radicals from dissociation promoters on the reactor according to the invention can be effected in the same way as shown in FIG. 3.
20050111
20071218
20050609
96331.0
0
BHAT, NINA NMN
METHOD FOR PRODUCING UNSATURATED HALOGENIC HYDROCARBONS AND DEVICE SUITABLE FOR USE WITH SAID METHOD
UNDISCOUNTED
0
ACCEPTED
2,005
10,513,012
ACCEPTED
Radio system, apparatus, and method of operating the radio system
A method of determining the relative position of a secondary station (SS) in a radio system including at least one master station (MS) and a plurality of secondary stations (SS), comprises the master station establishing a master log of the time stamp of signals transmitted by active stations and their identities and active secondary stations (SS) establishing a log of the time stamp of signals transmitted by other stations and their respective measured received quality. One of the active secondary stations forwards its log to the master station and the master station correlates the time stamps in the received log with the time stamps in the master log in order to determine the identities of the transmitters and utilises the measured signal quality indications in the received log to determine the relative position of the secondary station with respect to the locations of the transmitters identified.
1. A radio system comprising at least one master station and a plurality of secondary stations, the master station having means for establishing a master log of the time stamp of signals transmitted by active stations and their identities, each of the secondary stations having means for establishing a log of the time stamp of received signals together with their measured quality and means for forwarding at least a portion of their log to the master station, the master station further comprising means for correlating the time stamps in the log forwarded to it with the time stamps in its master log in order to identify the transmitters originating the signals received and for utilising the signal quality measurements in the received log to determine the relative position of a secondary station. 2. A method of determining the relative position of a secondary station in a radio system including at least one master station and a plurality of secondary stations, the method comprising the primary station establishing a master log of the time stamp of signals transmitted by active stations and their identities, active secondary stations establishing a log of the time stamp of signals transmitted by other stations and their respective measured received quality, one of the active secondary stations forwarding its log to the master station and the master station correlating the time stamps in the received log with the time stamps in the master log in order to determine the identities of the transmitters and utilising the measured signal quality indications in the received log to determine the relative position of the secondary station with respect to the locations of the transmitters identified. 3. A method as claimed in claim 2, characterised in that the secondary stations measure the RSSI of a received signal. 4. A method as claimed in claim 2 or 3, characterised in that the master log stores the relative locations of at least some of the non-portable features in the space being monitored and in that the position of a secondary station is indicated relative to at least one of the non-portable features. 5. A method as claimed in claim 2, 3 or 4, characterised in that the position of a secondary station is indicated visually. 6. A master station for use in a radio system having a plurality of secondary stations, the master station comprising receiving means, means for establishing a master log of the time stamp of signals transmitted by active stations and their identities, means for correlating time stamps in a log forwarded to it by one of the plurality of secondary stations with the time stamps in its master log in order to identify the transmitters originating the signals received and for utilising the signal quality measurements in the received log to determine the relative position of the secondary station. 7. A secondary station for use in a radio system comprising a master station and a plurality of secondary stations, the secondary station comprising receiving means, means for establishing a log of the time stamp of received signals together with their measured quality and means for forwarding at least a portion of their log to the primary station.
The present invention relates to a radio system, apparatus for use in the system, and to a method of operating the radio system, particularly but not exclusively, for determining the position of a radio unit or station in the radio system. Radio positioning systems are well known and include triangulation where bearings are made on at least two signal sources and position is determined to be at the point of intersection of the two bearings. European Patent Specification EP 1 111 951 A2 discloses a wireless system such as DECT (Digitally Enhanced Cordless Telephone) or a wireless LAN, comprising a plurality of base stations, each of which transmits a unique base station identifier. A portable station whose position is to be determined makes signal quality measurements, such as received signal strength or bit error rate, on downlink signals from at least three base stations. The portable station reports these signal quality measurements together with the respective base station identities to a server which correlates the signal quality measurements against a layout architecture plan of the base stations within the coverage area of the communication system. A relative location of the portable device is then ascertained by the server, with the relative location information being made available to a requesting client, such as a PC. Such a system is intended for use in relatively large environments, such as offices, which require a wireless network to have strategically sited base stations in order to provide a substantially continuous radio coverage area. Also it essential for the cited system that the portable station remain energised for a sufficiently long time period that the base station identities can be recorded. Such a system is unsuited to determining position in a relatively small network such as may be found in a domestic situation where there may be only one base station and the portable units are inexpensive low power radio devices, such as may be provided with a key ring. An object of the present invention is to provide a simple, reliable, low cost radio positioning system. According to one aspect of the present invention there is provided a radio system comprising at least one master station and a plurality of secondary stations, the primary station having means for establishing a master log of the time stamp of signals transmitted by active stations and their identities, each of the secondary stations having means for establishing a log of the time stamp of received signals together with their measured quality and means for forwarding at least a portion of their log to the master station, the master station further comprising means for correlating the time stamps in the log forwarded to it with the time stamps in its master log in order to identify the transmitters originating the signals received and for utilising the signal quality measurements in the received log to determine the relative position of a secondary station. According to a second aspect of the present invention there is provided a method of determining the relative position of a secondary station in a radio system including at least one primary station and a plurality of secondary stations, the method comprising the primary station establishing a master log of the time stamp of signals transmitted by active stations and their identities, active secondary stations establishing a log of the time stamp of signals transmitted by other stations and their respective measured received quality, one of the active secondary stations forwarding its log to the primary station and the primary station correlating the time stamps in the received log with the time stamps in the master log in order to determine the identities of the transmitters and utilising the measured signal quality indications in the received log to determine the relative position of the secondary station with respect to the locations of the transmitters identified. If desired the secondary stations measure the RSSI of a received signal. This has the advantage that the secondary station only has to remain powered-up to measure the strength of the signal, which can be brief, and avoids the necessity of having to determine the identity of the station transmitting the signal. This avoids the need for the secondary station to synchronise with the received signal and to demodulate and decode it which saves battery power consumption. Other known methods of measuring the quality of radio signals include bit error rate (BER), Phase of Arrival (POA), Time of Arrival (TOA) and Frequency of Arrival (FOA). Optionally the master log may store the relative locations of some of the non-portable features, for example fixtures such as hi-fi systems, smoke alarms, security sensors, light switches, central heating controls, in the space being monitored and the position of a secondary station is indicated relative to at least one of the non-portable features. The position of a secondary station may be indicated visually for example as a message displayed on the screen of a television receiver. According to a third aspect of the present invention there is provided a master station for use in a radio system having a plurality of secondary stations, the master station comprising receiving means, means for establishing a master log of the time stamp of signals transmitted by active stations and their identities, means for correlating time stamps in a log forwarded to it by one of the plurality of secondary stations with the time stamps in its master log in order to identify the transmitters originating the signals received and for utilising the signal quality measurements in the received log to determine the relative position of the secondary station. According to a fourth aspect of the present invention there is provided a secondary station for use in a radio system comprising a master station and a plurality of secondary stations, the secondary station comprising receiving means, means for establishing a log of the time stamp of received signals together with their measured quality and means for forwarding at least a portion of their log to the primary station. The present invention will now be described, by way of example, with reference to the accompanying drawings, wherein: FIG. 1 is a block schematic diagram of a radio LAN, FIG. 2 is a block schematic diagram of a secondary station, FIG. 3 is a block schematic diagram of a master station, and FIG. 4 is a flow chart of an embodiment of the method in accordance with the present invention. In the drawings the same reference numerals have been used to indicate corresponding features. Referring to FIG. 1, the illustrated radio LAN is provided to enable a user with a remote controller 10, which may be incorporated into a cellular/cordless phone, to control and/or monitor the behaviour of appliances such as a television (TV) receiver 12, a hi-fi system 14, a video cassette recorder (VCR) 16, a table lamp 18 and a security sensor 20. Such a radio LAN may operate in accordance with a known protocol such as Bluetooth, Registered Trade Mark, ZigBee or IEEE 802.11. As details of these protocols are published they will not be discussed further as they are not relevant to the understanding of the present invention. In order to determine position, radio units are associated with articles whose position or location needs to be known to a user. In the illustrated embodiment the radio units are shown attached to not only the nominally fixed appliances 12 to 20 but also to portable devices such as the remote controller 10 and a key 22. The architecture of the radio system is configured around a master station MS, which in FIG. 1 is mounted on and connected to the TV receiver 12, and a plurality of secondary stations SS. Before describing embodiments of the secondary and master stations, the operation of the system will be briefly described. The basic principle for determining position/location relies on the master station MS determining the position/location of an appliance or article based on the quality, for example the strength, of radio signals from some known transmitters as received by the secondary stations SS and stored in a log which is forwarded by radio to the master station MS. As the secondary stations are low power consuming radio units, it is desired that their on-times are as brief as possible. With this object in mind, the method in accordance with the present invention assumes that the times of receipt of signals by the secondary stations can be correlated with the times of transmission of the signals, which may occur at regular intervals or at random, and therefore it is unnecessary for the secondary stations to remain powered-up to demodulate a received signal and decode the signal to determine the transmitter's identity. However if battery economy is not of prime significance then the quality of the received signals can be determined using techniques such as bit error rate (BER), Phase of Arrival (POA), Time of Arrival (TOA) and Frequency of Arrival (FOA) which require some processing of the received signal. Each time one of the transmitters transmits, the master station MS notes from the transmission the identification of the transmitter and the time at which the transmission occurs (time stamp) and stores this information in a master log. The secondary stations SS when active detect any in-range transmissions and note the time and signal quality, normally the received radio signal strength (RSS) which has a value dependent on the distance from a transmitter and the transmit power, and stores in its own log the time of transmission (time stamp) and the radio signal strength indicator (RSSI). Because only the RSS is measured, it is unnecessary to demodulate the signal or obtain the transmitter identifier. Therefore the radio units attached to the appliances 12 to 20 need not all operate using the same radio LAN protocol such as Bluetooth, Zigbee & IEEE 802.11 but may use different protocols, so there is no requirement for a plurality of the secondary stations SS to operate a common protocol. Furthermore, because it is unnecessary for a secondary station whose location is to be determined to demodulate signals transmitted by the other secondary stations, such a secondary station need not conform with the same protocol as these other secondary stations. Whenever appropriate or necessary, a secondary station SS forwards its log to the master station MS. A processor in the master station MS correlates the time stamp entries in the secondary station's log with those in its master log and determines the identities of the transmitters and their respective transmit powers. Using this information together with the corresponding RSSIs in the secondary station's log, the position/location of the secondary station is determined. Optionally the nominal output powers of the transmitters are also stored with their identities by the master station MS and when a radio signal is received from one of the transmitters its signal strength is noted and compared to the nominal output power thereby checking that the transmitter is operating satisfactorily and/or if it has been shifted from its previous position. If there is any doubt about the performance of the transmitter it can be ignored when computing the position of a secondary station. Referring to FIG. 2, a secondary station SS comprises a transceiver consisting of an antenna 24 coupled to the input of a receiver (Rx) stage 26 and to the output of a transmitter (Tx) stage 28. A RSS measuring stage 30 is coupled to the Rx stage 26. The RSS stage 30 produces a RSSI which is supplied to a microprocessor 32. A clock 34 is coupled to the microprocessor 32. The microprocessor 32 forwards the RSSI and time of receipt to a log 36, constituted by a RAM, which has pairs of memory locations 38A, 40A to 38n, 40n, for storing, respectively, the time and the RSSI. In an alternative, non-illustrated arrangement the receiver stage 26 and the RSS stage 30 have inputs coupled to the antenna 14 and outputs coupled to respective inputs of the microprocessor 32. The microprocessor 32 is also coupled to a modulator 42 which modulates entries read-out from the log 36 onto a carrier wave for onward transmission by the Tx 28 to the master station MS. Referring to FIG. 3, the architecture of the master station MS is slightly different from that of the secondary station SS. In the interests of brevity only the differences will be described in the following. The microprocessor 32 is coupled to a first memory (RAM) 44 which has pairs of storage locations for storing transmitter identifications and their respective locations, optionally their output powers may also be stored, to a second memory (RAM) which functions as the master log 46 which has pairs of storage locations 48A, 50A to 48n, 50n for storing, respectively, the time of transmission by one of the transmitters and its identity, and to a third memory (RAM) 52 which has pairs of storage locations for storing times and RSSIs of a secondary station's log which has been forwarded to the master station MS. The first, second and third memories may be respective areas of a large RAM which may be an integrated circuit or some other suitable memory device such as a computer hard drive. Correlation of the entries in the master log 46 and in the third memory 52 is carried out by the microprocessor 32 which subsequently generates position/location information which may displayed on the TV receiver 12, transmitted to the remote controller 10 or sent as a text message to a cellular telephone or as an e-mail to a WAP phone or personal computer. The flow chart shown in FIG. 4 illustrates the processing steps in carrying-out an embodiment of the method in accordance with the present invention. Block 60 relates to the master station MS storing the transmitter identities, locations and, optionally, their nominal or measured output powers in the first memory 44 (FIG. 3). Block 62 relates to the master station receiving transmissions and identifying the transmitters and noting their transmission times as time stamps. Block 64 denotes adding entries to the master log 46 (FIG. 3). The operations shown by the blocks 62, 64 continue as indicated by the output of the block 64 being coupled back to the input of the block 62. In the meantime block 66 denotes the secondary stations SS receiving transmissions and measuring the RSSs and times. The block 68 denotes each secondary station SS storing the RSSIs and associated time stamp in its log 36 (FIG. 2). The process denoted by the blocks 66, 68 is also a repetitive one. Block 70 denotes the master station MS instructing one of the secondary stations to forward its log. Block 72 denotes the respective secondary station forwarding the entries from its log and their storage in the third memory 52 (FIG. 3). Block 74 relates to the master station MS correlating the forwarded time stamps with the time stamps in its master log 46 and determining the identities of the transmitters. Block 76 denotes the microprocessor 32 in the master station MS computing the position/location of the secondary station SS. Finally, block 78 denotes the master station informing a user of the position/location determined. Optionally, if correlating the time stamps or computing the position of the secondary station SS results in an ambiguity, the ambiguity may be resolved by the master station MS measuring the time of flight of a signal transmitted by the secondary station SS and, from the time of flight, calculating the distance of the secondary station SS. The following example illustrates the method in accordance with the present invention in a practical way. A home automation wireless system is operational in a domestic environment. A single master station integrated into a TV receiver is used to route signals between low power secondary stations. Several secondary stations have a requirement for positional information and thus have the appropriate functionality to monitor and maintain a log of received signal strengths and the corresponding time stamps. Over the previous 30 minutes these secondary stations have been logging all signals present in the room. These might include signals from security sensors, hi-fi, light switches, remote controls, central heating controllers and the like. A user requests a positional indicator for a key or a set of keys, for example the key 22 in FIG. 1. The master station MS requests secondary station SS associated with the key 22 to upload the log of RSSIs and time stamps and cross references these against the entries in the master log of all recently active transmitters. A high correlation is calculated between the hi-fi 14 (FIG. 1) and the security sensor 20 (FIG. 1). A message is flashed on the screen of the TV receiver 12 to indicate that the keys are probably midway between the hi-fi 14 and the security sensor 20 on the ceiling. If a user has provided the master station MS with location information for more significant items of furniture, the master station may be able to produce a suggestion to the user that the keys may be on say, a shelf, above the hi-fi unit. The present invention may be embodied into wireless systems, whether in a master-slave or peer-to-peer architecture, as it provides a low power solution in which essential processing and cross-referencing of data is done in a single location. This minimises data across the network and allows devices to enter a “sleep” mode as RSSI measurements could be monitored and logged in separate circuitry. In the present specification and claims the word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements. Further, the word “comprising” does not exclude the presence of other elements or steps than those listed. From reading the present disclosure, other modifications will be apparent to persons skilled in the art. Such modifications may involve other features which are already known in the design, manufacture and use of wireless LANs and component parts therefor and which may be used instead of or in addition to features already described herein.
20041028
20060704
20050728
69140.0
0
KIM, WESLEY LEO
RADIO SYSTEM, APPARATUS, AND METHOD OF OPERATING THE RADIO SYSTEM
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,023
ACCEPTED
Fresnel lens sheet, transmission screen using this and rear transmission display unit
A Fresnel lens sheet has an entrance surface (1a) and an exit surface (1b). A plurality of prisms (2) each having a refraction surface (3) and a total-reflection surface (4) are formed on the entrance surface (1a). Light rays projected by a light source (M) disposed on the side of the sloping refraction surfaces (3) onto the entrance surface (1a) are refracted at the refraction surfaces (3), and the refracted light rays are totally reflected by a total-reflection surfaces (4) in a direction substantially perpendicular to a sheet surface (1c). Angles (α) between the refraction surfaces (3) and the total-reflection surfaces (4) corresponding to the refraction surfaces (3) of all the prisms (2) are substantially equal to each other. The angle δ between the refraction surface (3) of the prism (P2) farthest from the light source (M) and the sheet surface (1c) is approximately equal to a right angle.
1. A total-reflection Fresnel lens sheet having an entrance surface and an exit surface and capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface, said Fresnel lens sheet comprising a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted on the refraction surface; wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface of the Fresnel lens sheet. 2. The Fresnel lens sheet according to claim 1, wherein the angle between the total-reflection surface of at least the prism farthest from the light source and the sheet surface is determined such that the total-reflection surface reflects light rays in a direction tilted at an angle toward the side of the light source with respect to a perpendicular direction perpendicular to the sheet surface. 3. The Fresnel lens sheet according to claim 1, wherein a low-refraction index layer of a material having a low refractive index is formed on the entrance surface. 4. The Fresnel lens sheet according to claim 1 further comprising; at least one of a light diffusing element that diffuses light and a light absorbing element that absorbs light. 5. The Fresnel lens sheet according to claim 4, wherein the light diffusing element is formed by dispersing a diffusing material so that diffusion half angle is 10° or below. 6. The Fresnel lens sheet according to claim 4, wherein the light diffusing element is a horizontal lenticular lens sheet formed on the exit surface so that diffusion half angle is 10° or below. 7. The Fresnel lens sheet according to claim 4, wherein the light absorbing element contains a coloring material so that the light absorbing element has a light absorptance of 50% or below. 8. The Fresnel lens sheet according to claim 4, wherein the light absorbing element includes a light absorbing layer perpendicular to the sheet surface. 9. A transmission screen comprising: a total-reflection Fresnel lens sheet having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted on the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface of the Fresnel lens sheet; and a light diffusing element for diffusing light rays formed integrally with the Fresnel lens sheet. 10. A transmission screen comprising: a total-reflection Fresnel lens sheet having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted on the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface of the Fresnel lens sheet; and a light diffusing element for diffusing light rays positioned on the exit surface of the Fresnel lens sheet. 11. A rear projection display comprising: a box serving as a housing and having a front wall provided with a window; a transmission screen including a total-reflection Fresnel lens sheet placed in the window formed in the front wall of the box, having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted at the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface of the Fresnel lens sheet, and a light diffusing element for diffusing light rays formed integrally with the Fresnel lens sheet in the Fresnel lens sheet; and a projector disposed in the box and capable of projecting image light rays from behind the transmission screen at acute incidence angles on the entrance surface of the transmission screen. 12. A rear projection display comprising: a box serving as a housing and having a front wall provided with a window; a transmission screen including a total-reflection Fresnel lens sheet placed in the window formed in the front wall of the box, having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface, and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted at the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface, and a light diffusing element for diffusing light rays positioned on the exit surface of the Fresnel lens sheet; and a projector disposed in the box and capable of projecting image light rays from behind the transmission screen at acute incidence angles on the entrance surface of the transmission screen.
TECHNICAL FIELD The present invention relates to a Fresnel lens sheet to be included in a transmission screen for a projection television set (PTV) or the like, a transmission screen provided with the Fresnel lens sheet, and a rear projection display. More specifically, the present invention relates to a Fresnel lens suitable for application to a transmission screen on which light rays fall at acute angles from behind, a transmission screen provided with the same Fresnel lens sheet, and a rear projection display. Referring to FIG. 16, a known Fresnel lens sheet disclosed in JP 61-208041A (pp. 2-5, FIG. 8) has an entrance surface provided with a plurality of prisms 72 each having a refraction surface 73 and a total-reflection surface 74. FIGS. 17A and 17B are enlarged views of parts A and B in FIG. 16, respectively. As shown in FIGS. 17A and 17B, a light ray X projected by a projector M disposed behind the Fresnel lens sheet 71 and falling on the back surface of the Fresnel lens sheet 71 at a very acute angle is refracted at the refraction surface 73, the refracted light ray X travels through the prism 72, and is totally reflected by the total-reflection surface 74 in a direction perpendicular to a surface of the Fresnel lens sheet 71. Thus the light ray X emitted by the projector M falls on the Fresnel lens sheet 71 at a very acute angle. The incidence angle θA of a light ray X2 that falls on a prism P2 farther from the projector M is larger than the incidence angle θB of a light ray X1 that falls on a prism P1 nearer to the projector M. Therefore, the prisms 72 need to be formed such that the angle β between the total-reflection surface 74 of the prism 72 farther from the projector M is smaller than that between the total-reflection surface 74 of the prism 72 nearer to the projector M to make the total-reflection surfaces 74 of all the prisms 72 reflect light rays in a direction perpendicular to the exit surface of the Fresnel lens sheet 71. On the contrary, the angle δ between the refraction surface 73 of the prism 72 farther from the projector M and a sheet surface is larger than that between the refraction surface 73 of the prism 72 nearer to the projector M. When a transmission screen provided with the Fresnel lens sheet 71 of such a configuration is applied to a rear projection transmission display, the projector M is able to project light rays at large incidence angles on the transmission screen, and hence the rear projection transmission display can be formed in a small thickness. However, this known Fresnel lens sheet 71 has 1) a problem in manufacturing the same and 2) a double-image problem due to a ghost image formed by stray light rays. 1) Problem in Manufacture Generally, the Fresnel lens sheet 71 is formed by a UV/radiation curable resin molding process or a hot-pressing process. The UV/radiation curable resin molding process fills a UV/radiation curable resin in a Fresnel lens sheet forming mold, cures the UV/radiation curable resin by irradiating the same with UV rays or radiation, and removes a Fresnel lens sheet 71 thus formed from the mold. The hot-pressing process fills a heated resin in a Fresnel lens sheet forming mold, presses the heated resin, and removes a Fresnel lens sheet thus formed from the mold. The molds employed in those forming processes are formed by machining work for cutting a metal workpiece, such as a workpiece of aluminum, brass, copper or steel, with a cutting tool. As mentioned above, the prisms 72 at different positions of the Fresnel lens sheet 71 have refraction surfaces 73 and total-reflection surfaces 74 inclined at different angles, respectively, to the surface of the Fresnel lens sheet 71. Therefore, the fabrication of the mold requires very complicated machining. A Fresnel lens sheet thus molded needs to be removed from the mold. It is difficult to remove some molded Fresnel lens sheets having prisms with surfaces inclined at some angles. A Fresnel lens sheet having prisms 72 with refraction surfaces 73 inclined at angles larger than 90° to the surface of the Fresnel lens sheet is difficult to remove from the mold because the prisms 72 act like a wedge. Even if such a Fresnel lens sheet could be removed from the mold, it is possible that the Fresnel lens sheet would be damaged. 2) Double Image Due to Stray Light Rays As shown in FIGS. 17B and 18, in some cases, some light rays projected by a projector, not shown, fallen on the foregoing Fresnel lens sheet 71, and refracted at the refraction surfaces 73 fall on the exit surface instead of falling on the total-reflection surfaces 74. The light rays fallen on the exit surface are refracted further at the refraction surfaces 73 and reflected further by the total-reflection surfaces 74 so as to travel forward through the exit surface in stray light rays Y. A ghost image formed by the stray light rays Y and a desired image formed by the desired light rays overlap each other to form a double image. The effect of the prisms 72 near to the projector, on which light rays fall at small incidence angles θ, on forming a double image is particularly remarkable. DISCLOSURE OF THE INVENTION The present invention has been made in view of the foregoing circumstances and it is therefore an object of the present invention to provide a Fresnel lens sheet capable of being easily molded, of refracting and reflecting light rays so that the stray light ray ratio, i.e., the ratio of stray light rays to total light rays, may be small and of transmitting light rays at high transmission efficiency, a transmission screen employing the Fresnel lens sheet, and a rear projection display. To achieve the object, the present invention provides a total-reflection Fresnel lens sheet having an entrance surface and an exit surface and capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface, and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted on the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest from the light source is substantially at right angles to a sheet surface of the Fresnel lens sheet. Since the angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms of this Fresnel lens sheet are substantially equal to each other, a machining operation for fabricating a Fresnel lens sheet forming mold for forming the Fresnel lens sheet does not require a plurality of cutting tools, a part for each prism of the workpiece does not need to be shaped by a plurality of cutting passes, and hence the Fresnel lens sheet forming mold can be efficiently fabricated. Since the refraction surface of the prism farthest from the light source is inclined substantially at right angles to the sheet surface, the Fresnel lens sheet and the mold will not be locked together and the molded Fresnel lens sheet can be separated from the mold without being damaged. Since the refraction surfaces of the Fresnel lens sheet are inclined at the largest angle (90°) that will not impede the fabrication of the Fresnel lens sheet to the sheet surface, the stray light ray ratio can be minimized. In the Fresnel lens sheet according to the present invention, the angle between the total-reflection surface of at least the prism farthest from the light source and the sheet surface is determined such that the total-reflection surface reflects light rays in a direction tilted at an angle toward the side of the light source with respect to a perpendicular direction perpendicular to the sheet surface. When at least the prism farthest from the light source is thus formed, the stray light ray ratio can be reduced. It is desirable that the total-reflection surfaces reflect light rays in directions at small angles on the side of the light source to a perpendicular to the sheet surface. More concretely, it is desirable that the total-reflection surface of the prism farthest from the light source reflects light rays in a direction inclined at an angle on the side of the light source in the range of 3° to 15°, more desirably, in the range of 5° to 10°. If this angle is excessively large, the quantity of light reflected by the total-reflection surface of farthest prism and reaching the viewer decreases and part of an image corresponding to the farthest prism becomes faint. If this angle is excessively small, reflection of light rays in a direction at an angle to the perpendicular to the sheet surface is not sufficiently effective. The angle of the total-reflection surface of at least the prism farthest from the light source may be determined so that the total-reflection surface reflects light rays in a direction tilted at a small angle toward the light source with respect to the perpendicular direction perpendicular to the sheet surface. The angles of the total-reflection surfaces of the prisms at distances within about 600 mm from the farthest prism may be determined so that those total-reflection surfaces reflect light rays in a direction tilted at a small angle toward the light source with respect to the perpendicular direction perpendicular to the sheet surface. Although the angles of reflection of those prisms at distances within about 600 mm from the farthest prism may be the same, it is desirable that the angle of reflection of the prisms farthest from the light source is the largest, and the angles of reflection of the prisms nearer to the light source are smaller. When the angles of reflection of the prisms are thus changed gradually, the viewer will not feel there is something wrong with the image. In the Fresnel lens sheet according to the present invention, a low-refraction index layer of a material having a low refractive index is formed on the entrance surface. The low-refraction layer coating the entrance surface reduces the reflection of image light, and an image having a high contrast can be displayed. The Fresnel lens sheet according to the present invention further includes at least one of a light diffusing element that diffuses light and a light absorbing element that absorbs light. Stray light rays in the conventional Fresnel lens sheet are refracted at the refraction surfaces and reflected by the total-reflection surfaces and the exit surface, travel through the Fresnel lens sheet and partly outside the Fresnel lens sheet, and some of the stray light rays are sent out through the exit surface and form a ghost image that overlaps a normal image to form a double image. According to the present invention, stray light rays traveling through the Fresnel lens sheet are diffused by the light diffusing element and absorbed by the light absorbing element to prevent the formation of a double image or to make the ghost image indistinct. In the Fresnel lens sheet according to the present invention, the light diffusing element is formed by dispersing a diffusing material so that diffusion half angle is 10° or below. In the Fresnel lens sheet according to the present invention, the light diffusing element is a horizontal lenticular lens sheet formed on the exit surface so that diffusion half angle is 10° or below. The present invention can solve the problem caused by the double image due to the stray light rays. Since the diffusion half angle is 10° or below, the normal function of the Fresnel lens sheet is never spoiled by excessive diffusion of light rays. Preferably, the diffusion half angle is 5° or below, more preferably, on the order of 2°. In the Fresnel lens sheet according to the present invention, the light absorbing element contains a coloring material so that the light absorbing element has a light absorptance of 50% or below. The Fresnel lens sheet provided with such a light absorbing element can solve the problem caused by a double image due to stray light rays. The light absorbing element having a light absorptance of 50% or below does not absorb desired light rays excessively. In the Fresnel lens sheet according to the present invention, the light absorbing element includes a light absorbing layer perpendicular to the sheet surface. The Fresnel lens sheet provided with such light absorbing layers can solve the problem caused by a double image due to stray light rays. The light absorbing layer perpendicular to the sheet surface does not absorb desired light rays. The present invention provides a transmission screen including: a total-reflection Fresnel lens sheet having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface, and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted at the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest form the light source is inclined substantially at right angles to a sheet surface of the Fresnel lens sheet; and a light diffusing element for diffusing light rays formed integrally with the Fresnel lens sheet. The stray light ray ratio in the Fresnel lens sheet of the transmission screen is small, and the transmission screen is capable of transmitting light at a high transmission efficiency. The light diffusing element is, for example, a diffusing material dispersed in the Fresnel lens sheet or a lenticular sheet formed on the exit surface of the Fresnel lens sheet. Preferably, the light diffusing element, such as the diffusing material or the lenticular sheet, for the transmission screen has a diffusion half angle of 10° or above, more preferably, 20° or above. A transmission screen according to the present invention includes: a total-reflection Fresnel lens sheet having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface, and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted on the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest form the light source is inclined substantially at right angles to a sheet surface of the Fresnel lens sheet; and a light diffusing element for diffusing light rays positioned on the exit surface of the Fresnel lens sheet. The stray light ray ratio in the Fresnel lens sheet of the transmission screen is small, and the transmission screen is capable of transmitting light at a high transmission efficiency. A rear projection display according to the present invention includes: a box serving as a housing and having a front wall provided with a window; a transmission screen including a total-reflection Fresnel lens sheet placed in the window formed in the front wall of the box, having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted at the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest form the light source is inclined substantially at right angles to a sheet surface of the Fresnel lens sheet, and a light diffusing element for diffusing light rays formed integrally with the Fresnel lens sheet in the Fresnel lens sheet; and a projector disposed in the box and capable of projecting image light rays from behind the transmission screen at acute incidence angles on the entrance surface of the transmission screen. A rear projection display according to the present invention includes: a box serving as a housing and having a front wall provided with a window; a transmission screen including a total-reflection Fresnel lens sheet placed in the window formed in the front wall of the box, having an entrance surface and an exit surface, capable of sending out light through the exit surface, that is emitted by a light source and fallen on the entrance surface and including a plurality of prisms formed on the entrance surface and each having a refraction surface where light emitted by the light source is refracted and a total-reflection surface that totally reflects the light refracted at the refraction surface, wherein angles between the refraction surfaces and the total-reflection surfaces corresponding to the refraction surfaces of all the prisms are substantially equal to each other, and the refraction surface of the prism farthest form the light source is substantially at right angles to a sheet surface, and a light diffusing element for diffusing light rays positioned on the exit surface of the Fresnel lens sheet; and a projector disposed in the box and capable of projecting image light rays from behind the transmission screen at acute incidence angles on the entrance surface of the transmission screen. The stray-total light ray ratio in the Fresnel lens sheet of the transmission screen is small, and the rear projection display is capable of transmitting light at high transmission efficiency. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a sectional view of a Fresnel lens sheet in a first embodiment according to the present invention; FIG. 2A is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 1; FIG. 2B is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 1; FIG. 3 is a flow chart of a method of fabricating a Fresnel lens sheet according to the present invention; FIG. 4A is a typical view of assistance in explaining a machining method of making a forming mold for forming a Fresnel lens sheet according to the present invention; FIG. 4B is a typical view of assistance in explaining a machining method of making a forming mold for forming a Fresnel lens sheet according to the present invention; FIG. 5 is a perspective view of a transmission screen in the first embodiment according to the present invention; FIG. 6 is a perspective view of another transmission screen in the first embodiment according to the present invention; FIG. 7 is a perspective view of a third transmission screen in the first embodiment according to the present invention; FIG. 8 is a perspective view of a fourth transmission screen in the first embodiment according to the present invention; FIG. 9 is a perspective view of a fifth transmission screen in the first embodiment according to the present invention; FIG. 10 is a sectional view of a rear projection display in a first embodiment according to the present invention; FIG. 11A is a diagrammatic view of assistance in explaining the transmission efficiency of a Fresnel lens sheet according to the present invention; FIG. 11B is a diagrammatic view of assistance in explaining the transmission efficiency of a Fresnel lens sheet according to the present invention; FIG. 12A is a fragmentary enlarged view of a Fresnel lens sheet in a second embodiment according to the present invention; FIG. 12B is a fragmentary enlarged view of the Fresnel lens sheet in the second embodiment; FIG. 13 is a sectional view of a Fresnel lens sheet in a third embodiment according to the present invention; FIG. 14 is a sectional view of another Fresnel lens sheet in the third embodiment-according to the present invention; FIG. 15 is a sectional view of a third Fresnel lens sheet in the third embodiment according to the present invention; FIG. 16 is a sectional view of a conventional Fresnel lens sheet; FIG. 17A is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 16; FIG. 17B is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 16; and FIG. 18 is a diagrammatic view of assistance in explaining stray light rays in a Fresnel lens sheet. BEST MODE FOR CARRYING OUT THE INVENTION Fresnel lens sheets according to the present invention, transmission screens employing those Fresnel lens sheets and a rear projection display in preferred embodiments according to the present invention will be described with reference to the accompanying drawings. First Embodiment Fresnel Lens Sheet A Fresnel lens sheet in a first embodiment according to the present invention will be described. FIG. 1 is a sectional view of a Fresnel lens sheet in the first embodiment, and FIGS. 2A and 2B are fragmentary enlarged views of Parts A and B in FIG. 1. Referring to FIGS. 1, 2A and 2B, a Fresnel lens sheet 1 has an entrance surface 1a and an exit surface 1b. The Fresnel lens sheet 1 is a total-reflection type of lens sheet that receives light rays emitted by a light source M through the entrance surface 1a and sends out the light rays through the exit surface 1b. A plurality of prisms 2 are formed on the entrance surface 1b. Each of the prisms 2 has a refraction surface 3 where light rays X fallen on the Fresnel lens sheet 2 are refracted and a total-reflection surface 4 that reflects totally the light rays X refracted on the refraction surface 3 toward the viewing side. The angle between the refraction surface 3 and the total-reflection surface 4 of each of all of the prisms 2 is α, which is the same for all of the prisms. The refraction surface 3 and the total-reflection surface 4 are inclined at angles δ and β, respectively, with respect to a sheet surface (reference surface of the Fresnel lens sheet 1) 1c of the Fresnel lens sheet. The angle β is determined such that the total-reflection surface 4 reflects incident light rays in a total reflection mode in a direction perpendicular to the sheet surface 1c. Light rays projected by a projector M, namely, a light source, fall on a prism P1, the nearest to the projector M, of the Fresnel lens sheet 1 at the smallest incidence angleθ, i.e., the angle between the incident light ray and a normal 1d to the sheet surface 1c, and the light rays fall at larger incidence angles θ on the Fresnel lens sheet 1 for prisms farther from the projector M. Therefore, the angle β for the prism P1 the nearest to the projector M is the largest, and the angles β for the prisms farther from the projector M are smaller. Since the angle α is the same for all of the prisms, the angle δ for the prism P1 the nearest to the projector M is the smallest and the angles δ for the prisms farther from the projector M are larger. In this Fresnel lens sheet 1 of the present invention, the angle δ for the prism P2 the farthest to the projector M is approximately 90°. Method of Fabricating the Fresnel Lens Sheet A Fresnel lens sheet fabricating method of fabricating the Fresnel lens sheet 1 will be explained. The Fresnel lens sheet 1 is fabricated by, for example, a UV/radiation curable resin molding process. A Fresnel lens sheet fabricating method using a UV/radiation curable resin molding process will be described. FIG. 3 shows steps of a Fresnel lens sheet fabricating method. A mold for forming the Fresnel lens sheet 1 is made by a mold making step. Referring to FIG. 4, in the mold making step a Fresnel lens sheet forming mold is made by engraving a shape corresponding to that of the Fresnel lens sheet 1 in a metal workpiece 11 of aluminum, a brass, copper or a steel with a cutting tool 12. The cutting tool 12 has a tool angle substantially equal to the angle α between the refraction surface 3 and the total-reflection surface 4 of the prism 2 of the Fresnel lens sheet 1. When cutting a part for the prism farthest from the projector M with the cutting tool 12, the cutting tool 12 is held perpendicularly to the surface of the metal workpiece 11, and an inclined surface corresponding to the total-reflection surface 4 is cut with the edge of an inclined surface 12a of the cutting tool 12 and a vertical surface corresponding to the refraction surface 3 is cut with the edge of a vertical surface 12b of the cutting tool 12 as shown in FIG. 4A. When cutting a part of the metal workpiece 11 for the prism 2 next to the prism farthest from the projector M on the side of the projector M, the cutting tool 12 is tilted in the direction of the arrow shown in FIG. 4B by a tilt angle equal to the remainder of subtraction of the angle δ of the refraction surface 3 of the prism 2 from 90° as shown in FIG. 4B. The cutting tool 12 is tilted by a greater tilt angle for cutting a part of the metal workpiece 11 for a prism nearer to the projector M. Thus, the machining operation for fabricating the Fresnel lens sheet forming mold does not need to use a plurality of cutting tools, a part for each prism of the workpiece 11 does not need to be shaped by a plurality of cutting passes, and hence the Fresnel lens sheet forming mold can be efficiently fabricated. In some cases, a part for each prism is machined by a plurality of cutting passes to finish the surfaces defining a groove corresponding to the prism in a high accuracy. Even in such a case, the number of passes for finishing the surfaces in a high accuracy is smaller than that of passes necessary for finishing surfaces defining a groove corresponding to each of the prisms of the conventional Fresnel lens sheet in the same accuracy. Then, a resin application step is carried out. In the resin application step, a UV/radiation curable resin is applied to the forming surface of the Fresnel lens sheet forming mold by a roller coating method, a dispenser method, a curtain coating method or a die coating method to form a UV/radiation curable resin film. Then, a lamination step is carried out. In the lamination step, a substantially transparent substrate permeable to UV/radiation rays is laminated to the UV/radiation curable resin film formed by the resin application step, and pressure is applied to the substrate to join the UV/radiation curable resin film and the substrate close together. Then, a curing step is carried out. In the curing step, the UV/radiation curable resin film is irradiated through the substrate with UV/radiation rays to cure the UV/radiation curable resin film. Lastly, a molding removing step is carried out. In the molding removing step, a laminated structure (Fresnel lens sheet 1) of the cured UV/radiation curable resin film and the substrate is removed from the Fresnel lens sheet forming mold. Since the refraction surfaces 3 of the prisms 2 of the Fresnel lens sheet 1 are inclined at angles δ below 90° to the sheet surface 1c, the Fresnel lens sheet 1 and the mold will not be locked together and the molded Fresnel lens sheet 1 can be separated from the mold without being damaged. Although the Fresnel lens sheet fabricating method described above is a UV/radiation curable resin molding process, the Fresnel lens sheet fabricating method may be a hot-pressing process. A Fresnel lens sheet forming mold for the hot-pressing process can be made by efficient machining, and the Fresnel lens sheet can be easily and safely removed from the Fresnel lens sheet forming mold like the Fresnel lens sheet formed by the UV/radiation curable resin molding presses. Transmission Screen A transmission screen provided with the Fresnel lens sheet 1 will be described. FIG. 5 is a perspective view of a transmission screen 21 in a first embodiment according to the present invention. Referring to FIG. 5, the transmission screen 21 is formed by disposing a lenticular sheet (lenticular lens sheet) 22, namely, light diffusing element, in front of the exit surface 1b of the Fresnel lens sheet 1. The lenticular sheet 22 has vertical, semicylindrical lenses 23a and 22b formed on the entrance surface 22a and the exit surface 22b thereof, respectively. A light absorbing layer 24 is formed on the exit surface 22b so as to cover parts between the adjacent lenses 23b of the exit surface 22b. The lenses 23a and 23b of the lenticular sheet 22 horizontally diffuse light rays projected by a projector M and collimated by the Fresnel lens sheet 1 so as to travel perpendicularly to the sheet surface 1c of the Fresnel lens sheet 1 to display an image so as to be viewable from directions in a wide viewing angle. The light absorbing layer 24 absorbs external light falling on the exit surface 22b of the lenticular sheet 22 to form an image having a high contrast. The lenticular sheet 22 is formed such that horizontal diffusion half angle is 10° or larger, preferably, 20° or larger. The horizontal diffusion half angle is a horizontal angle, from a perpendicular to the front surface of the transmission screen, of a direction from which an image displayed on a transmission screen looks in a brightness (luminance) half a maximum brightness (maximum luminance). The maximum brightness of the same image is made as viewed from a direction perpendicular to the surface of the transmission screen. FIG. 6 shows a transmission screen 25 provided with a lenticular sheet (lenticular lens sheet) 26. The lenticular sheet 26 includes vertical semicylindrical lenses 27 only on its entrance surface 26a. The lenses 27 are coated with a light absorbing layer 28. The lenses 27 of the lenticular sheet 26 horizontally diffuse light rays projected by a projector M and collimated by the Fresnel lens sheet 1 so as to travel perpendicularly to the sheet surface 1c of the Fresnel lens sheet 1 to display an image so as to be viewable from directions in a wide viewing angle. The light absorbing layer 28 absorbs external light falling on the exit surface 26b of the lenticular sheet 26 to form an image having a high contrast. External light penetrated the exit surface 26b and fallen on the light absorbing layer 28 is reflected by the inner surface of the light absorbing layer 28 and travels along the light absorbing layer 28 in the light absorbing layer 28. Consequently, most part of the external light is absorbed by the light absorbing layer 28. On the other hand, light fallen on the entrance surface 26a travels across the light absorbing layer 28 in the direction of the thickness of the light absorbing layer 28. Consequently, the light is absorbed scarcely the by light absorbing layer 28 and hence an image having a high contrast can be formed. A transmission screen may be formed by putting a light diffusing element in the Fresnel lens sheet 1. The light diffusing material may be a diffusing material 29 dispersed in the Fresnel lens sheet 1 as shown in FIG. 7. Vertical, semicylindrical lenses 30 can be formed on the exit surface 1b of the Fresnel lens sheet 1 as shown in FIG. 8 or vertical lenses 31 having a trapezoidal cross section can be formed on the exit surface 1b of the Fresnel lens sheet 1 as shown in FIG. 9. The semicylindrical lenses 30 and the lenses 31 having a trapezoidal cross section may be used in combination with the diffusing material 29 as shown in FIGS. 8 and 9. Rear Projection Display FIG. 10 is a sectional view of a rear projection display 41 in a first embodiment according to the present invention. The rear projection display 41 includes, as principal components, a box 42 serving as a housing and having a front wall provided with a window 42a, a transmission screen 21 disposed in an upper part of the front wall of the box 42, and a projector 43 disposed behind the transmission screen 21 in the box 42 and capable of projecting image light rays obliquely upward on the transmission screen 21 from behind the transmission screen 21. The box 42 is formed of a resin, a metal or the like, and the window 42a is formed in an upper part of the front wall of the box 42. When necessary, the box 42 is finished by a decorative process, such as a coloring process, to improve the aesthetic design of the box 42. The transmission screen 21 is fabricated as mentioned above. Generally, the transmission screen 21 is formed in a laterally elongate rectangular shape having an aspect ratio of 3 to 4 (standard screen) or an aspect ratio of 9 to 16 (wide screen). The transmission screen 21 is placed in the window 42a of the box 42 with its front surface, namely, with the exit surface facing out. The projector 43 includes an optical imaging device, such as a CRT or an LCD, and a projection lens for enlarging an optical image formed by the optical imaging device. The projector 43 projects the optical image from behind the transmission screen 21 in an enlarged optical image on the transmission screen 21. The projector 43 is disposed such that image light rays projected by the projector 43 and fallen on the transmission screen 21 are reflected by the total-reflection surfaces 4 of the Fresnel lens sheet 1 in a direction perpendicular to the sheet surface of the Fresnel lens sheet 1. In other words, the angles β between the total-reflection surfaces 4 of the Fresnel lens sheet 1 and the screen surface of the Fresnel lens sheet 1 are determined so that the image light rays projected by the projector 33 are reflected in a direction perpendicular to the sheet surface of the Fresnel lens sheet 1. In the rear projection display 41, image light rays projected by the projector 43 fall on the transmission screen 21 at acute incidence angles. The image light rays are refracted on the refraction surfaces 3 of the Fresnel lens sheet 1, and the refracted image light rays are reflected totally by the total-reflection surfaces 4 in a direction perpendicular to the sheet surface. The image light rays emerging from the Fresnel lens sheet 1 in the direction perpendicular to the sheet surface are diffused horizontally, and the diffused image light rays are emitted toward the viewing side. Some of the image light rays projected by the projector 43 and fallen on the prisms 2 comparatively near to the projector 43 are unable to reach the total-reflection surfaces 4 and becomes stray light rays. In the Fresnel lens sheet 1 of the present invention, the angle δ between the sheet surface 1c and the refraction surface 3 of the prism P2 farthest from the projector 43 is substantially equal to 90°, which is the largest angle δ that does not impede the fabrication of the Fresnel lens sheet 1. Therefore, the angle δ between the refraction surface 3 of the prism 2 near the projector 43 and the sheet surface is large and hence the stray light ray ratio is small. Referring to FIGS. 11A and 11B, the stray light ray ratio in the prism 2 of the Fresnel lens sheet 1 of the present invention shown in FIG. 11A is smaller than that of the prism 2 of the conventional Fresnel lens sheet 1 in which the maximum angle δ between the refraction surface 3 and the sheet surface 1c is less than 90° shown in FIG. 11B. The stray light ray ratio in the Fresnel lens sheet 1 of the present invention is small because the angle δ between the refraction surface 3 of the prism P2 the most distance from the projector M and the sheet surface 1c is 90° and the angle δ between the refraction surface 3 of the prism P1 near the projector M and the sheet surface 1c is comparatively large. Thus, the Fresnel lens sheet 1 of the present invention has a high transmittance and hence the rear projection display 41 provided with the Fresnel lens sheet 1 of the present invention is able to display an image having a high contrast. Although the rear projection display 41 provided with the transmission screen shown in FIG. 5 has been described, the rear projection display 41 may be provided with any one of the transmission screens shown in FIGS. 6 to 9. Second Embodiment A second embodiment employs a Fresnel lens sheet having a prism farthest from a projector and capable of collimating light rays in a direction slightly inclined toward the side of the projector with respect to a direction perpendicular to the sheet surface of the Fresnel lens sheet. The Fresnel lens sheet in the second embodiment is similar in construction, function and effect to the Fresnel lens sheet in the first embodiment, except that former Fresnel lens sheet has the prism farthest from the projector and capable of collimating light rays in a direction slightly inclined toward the side of the projector with respect to a direction perpendicular to the sheet surface thereof. A method of fabricating the Fresnel lens sheet in the second embodiment and a method of constructing a rear projection display provided with the same Fresnel lens sheet are the same as those mentioned in connection with the first embodiment. Therefore, only the construction of the Fresnel lens sheet in the second embodiment will be described. Fresnel Lens Sheet A Fresnel lens sheet 51 in the second embodiment will be described with reference to FIGS. 12A and 12B, in which parts like or corresponding to those of the Fresnel lens sheet 1 in the first embodiment shown in FIG. 1 are denoted by the same reference characters and the description thereof will be omitted. Referring to FIGS. 12A and 12B, the Fresnel lens sheet 51 has an entrance surface 51a and an exit surface 51b. The angle β between a total-reflection surface 4 included in at least a prism P2 farthest from a projector M and a sheet surface 51c is determined such that light rays reflected by the total-reflection surface 4 travel in a direction inclined at a small angle γ toward the side of the projector M with respect to a direction perpendicular to the sheet surface 51c. When the direction in which the total-reflection surface 4 reflects light rays is declined toward the side of the projector, the angle β between the total-reflection surface 4 and the sheet surface 51c is larger than the angle β between the total-reflection surface that reflects light rays in a direction perpendicular to the sheet surface and the sheet surface and, consequently, the angle α between the total-reflection surface 4 and the refraction surface 3 of the same prism is small. The small angle α is effective in reducing the stray light ray ratio. The angle δ between the refraction surface of the prism P2 and the sheet surface 51c is 90°. Although only the prism P2 farthest from the projector M may be formed so as to reflect light rays in the direction inclined toward the projector M at the small angle with respect to the direction perpendicular to the sheet surface 51c, it is desirable to determine the angles β of prisms 2 in a range between the prism P2 farthest from the projector M and a position a predetermined distance, such as about 600 mm away from the prism P2, such that those prisms 2 can reflect light rays in directions inclined toward the side of the projector M. In this case, the refraction surfaces 3 of those prisms 2 can be easily inclined at angles δ not greater than 90° with respect to the sheet surface 51c. A prism P1 reflects light rays in a direction perpendicular to the sheet surface 51c. Third Embodiment A third embodiment employs a Fresnel lens sheet formed by coating the surface of the Fresnel lens sheet in the first embodiment with a coating layer, and dispersing a diffusing material in the Fresnel lens sheet in the first embodiment. The Fresnel lens sheet in the third embodiment is similar in construction, function and effect to the Fresnel lens sheet in the first embodiment, except that former Fresnel lens sheet is provided with the coating layer and contains the diffusing material. A method of fabricating the Fresnel lens sheet in the third embodiment and a method of constructing a rear projection display provided with the same Fresnel lens sheet are the same as those mentioned in connection with the first embodiment. Therefore, only the construction of the Fresnel lens sheet in the third embodiment will be described. Fresnel Lens Sheet A Fresnel lens sheet 61 in the third embodiment will be described with reference to FIG. 13, in which parts like or corresponding to those of the Fresnel lens sheet 1 in the first embodiment shown in FIG. 1 are denoted by the same reference characters and the description thereof will be omitted. Referring to FIG. 13, the Fresnel lens sheet 61 has an entrance surface 61a and an exit surface 61b. The entrance surface 61a is coated with a coating layer 62 formed of a substantially transparent material having a refractive index smaller than that of a material forming prisms 2. The coating layer 62 reduces the reflection of image light rays projected thereon by a projector M. The coating layer 62 is formed of, for example, a fluorocarbon resin or a silicone resin. The Fresnel lens sheet 61 has a diffusing layer 64 containing a diffusing material 63, namely, a light diffusing element, dispersed therein. The diffusing layer 64 prevents the formation of double images due to stray light rays Y refracted on the refraction surfaces 3 and not reached the total-reflection surfaces 4. In the conventional Fresnel lens sheet, for example, stray light rays Y refracted on the refraction surfaces 3 are reflected by the exit surface 61b toward the refraction surfaces 3 and the total-reflection surfaces 4. The stray light rays are refracted again on the refraction surface 3 and are refracted at or reflected by the total-reflection surfaces 4 again, and the stray light rays Y thus refracted and reflected emerge from the exit surface 61b to form a double image. According to the present invention, the diffusing material 63 dispersed in the diffusing layer 64 diffuses the stray light rays Y while the stray light rays Y travel between the refraction surfaces 3 and the total-reflection surfaces 4, and the exit surface 61b to reduce the intensity of the stray light rays Y. As a result, a ghost image formed by the stray light rays Y is reduced and the problem attributable to the double image can be made insignificant. The diffusing material 63 is, for example, an organic material, such as an acrylic resin, styrene resin or a melamine resin, or an inorganic material, such as a vitreous material, titanium oxide, coating mica, calcium carbonate or ZnO. The amount of the diffusing material 63 dispersed in the diffusing layer 64 is adjusted such that the diffusing layer 64 has a diffusion half angle of 10° or below, preferably 5° or below, more preferably, on the order of 2°. The Fresnel lens sheet 61 may include a horizontal lenticular sheet (horizontal lenticular lens sheet) 65 formed on the exit surface 61b, including horizontal semicylindrical lenses as shown in FIG. 14 as the light diffusing element instead of the diffusing layer 64. Stray light rays Y reflected by the exit surface 61b are diffused by the horizontal lenticular sheet 65. As a result, the intensity of the stray light rays Y emerging from the exit surface 61b is reduced and the problem attributable to a double image can be made insignificant. The Fresnel lens sheet 61 may be provided with light receiving plates (light absorbing layers) 66 perpendicular to the exit surface 61b as the light absorbing element as shown in FIG. 15 instead of the diffusing layer 64. In this case, desired light rays X, namely incident light rays other than stray light rays, travel in a direction perpendicular to the exit surface 61b and do not fall on the light absorbing plates 66. On the other hand, the stray light rays Y traveling obliquely to the exit surface 61b fall on the light absorbing plates 66 and are absorbed by the light absorbing plates 66. Consequently, the amount of stray light rays Y emerging from the exit surface 61b can be reduced and the problem attributable to a double image can be solved. The light absorbing plates 66 may be formed of only a light-absorptive material, such as carbon black or may be plates coated with a light-absorptive material, such as carbon black. The Fresnel lens sheet 61 may be formed of a material containing a coloring material as the light absorbing element instead of being provided with the diffusing layer 64. Since distances traveled by the stray light rays Y in the Fresnel lens sheet 61 is longer than those traveled by the desired light rays, the amount of the stray light rays Y absorbed by the coloring matter is greater than that of the desired light rays X absorbed by the coloring matter, so that the ghost image of the double image can be obscured. The coloring material may have a black pigment or the like. Since the coloring material absorbs the desired light rays also, it is desirably to adjust the coloring material content of the Fresnel lens sheet 61 so that the normal light absorptance of the Fresnel lens sheet 61 is 50% or below. EXAMPLES Examples of the present invention and comparative examples will be comparatively described. Fresnel lens sheets in Examples 1 and 2 and Fresnel lens sheets in Comparative examples 1 and 2 were fabricated, and the abilities of those Fresnel lens sheets were examined. A Fresnel lens sheet was set in a vertical manner and light was projected by a projector disposed at a position at a vertical distance of 200 mm below the lower end of a Fresnel lens sheet and at a horizontal distance of 285 mm from the entrance surface of the Fresnel lens sheet. The ability of the Fresnel lens sheet was evaluated in terms of the transmission efficiency of a prism the nearest to the projector (hereinafter referred to as “the innermost prism) of the Fresnel lens sheet. Transmission efficiency is the ratio of the quantity of light reflected by the total-reflection surface and emerged from the Fresnel lens sheet to the quantity of incident light upon the Fresnel lens sheet. Concretely, transmission efficiency was determined by the following procedure. (1) A laser beam is projected so as to fall on the Fresnel lens sheet at a predetermined incidence angle. (2) Energy A of the incident laser beam is measured by an actinometer. (3) Energy B of the outgoing laser beam traveling in a direction at a predetermined angle is measured by the actinometer. (4) Transmission efficiency B/A is calculated. Example 1 A Fresnel lens sheet in Example 1 was formed of a resin having a refracting index of 1.55 in a height of 762 mm and a width of 1016 mm (50 in. Fresnel lens sheet of an aspect ratio of 3 to 4). Angles β between the total-reflection surfaces of the prisms and the sheet surface were determined such that total-reflection surfaces reflect light rays in a direction perpendicular to the sheet surface. The prisms were arranged at a pitch (distance between the peaks of the two adjacent prisms) of 0.11 mm. The angle δ between the refraction surface of a prism farthest from the projector (hereinafter referred to as “the outermost prism”) and the sheet surface was 90°. Example 2 A Fresnel lens sheet in Example 2 was formed of a resin having a refracting index of 1.55 in a height of 762 mm and a width of 1016 mm. Angles β between the total-reflection surfaces of the prisms and the sheet surface were determined such that the total-reflection surface of the outermost prism reflected light rays in a direction at an angle of 5° downward from a direction perpendicular to the sheet surface. The angle of a direction in which the total-reflection surface of a prism nearer to the innermost prism reflected light rays, with respect to the direction perpendicular to the sheet surface was smaller. The angle of a direction in which the total-reflection surface of a prism at a distance of 588 mm toward the projector from the outermost prism reflected light rays, with respect to the direction perpendicular to the sheet surface was 0°. The prisms were arranged at a pitch (distance between the peaks of the two adjacent prisms) of 0.11 mm. The angle δ between the refraction surface of the outermost prism and the sheet surface was 90°. The angle of a direction in which the total-reflection surface of each prism between the prism at the distance of 588 mm and the innermost prism reflected light ray, with respect to the direction perpendicular to the sheet surface is 0° Comparative Example 1 A Fresnel lens sheet in Comparative example 1 was formed of a resin having a refracting index of 1.55 in a height of 762 mm and a width of 1016 mm (50 in. Fresnel lens sheet of an aspect ratio of 3 to 4). Angles β between the total-reflection surfaces of the prisms and the sheet surface were determined such that total-reflection surfaces reflected light rays in a direction perpendicular to the sheet surface. The prisms were arranged at a pitch (distance between the peaks of the two adjacent prisms) of 0.11 mm. The angle δ between the refraction surface of the outermost prism and the sheet surface was 61.6° Comparative Example 2 A Fresnel lens sheet in Comparative example 2 was formed of a resin having a refracting index of 1.55 in a height of 762 mm and a width of 1016 mm (50 in. Fresnel lens sheet of an aspect ratio of 3 to 4). Angles β between the total-reflection surfaces of the prisms and the sheet surface were determined such that total-reflection surfaces reflected light rays in a direction perpendicular to the sheet surface. The prisms were arranged at a pitch (distance between the peaks of the two adjacent prisms) of 0.086 mm. The angle δ between the refraction surface of the outermost prism and the sheet surface was 100.3°. Results of Evaluation In the Fresnel lens sheet in Example 1, the angles δ between the refraction surfaces of all the prisms and the sheet surface and the angles β between the total-reflection surfaces and the sheet surface were 90° or below. Thus the Fresnel lens sheet in Example 1 could be satisfactorily formed and could easily be removed from the mold. The innermost prism had a transmission efficiency of 64.8%, which was considerably higher than that of, for example, the Fresnel lens sheet, namely, a conventional Fresnel lens sheet which was designed by placing importance on facility in removing the same from the mold. In the Fresnel lens sheet in Example 2, the angles δ between the refraction surfaces of all the prisms and the sheet surface and the angles β between the total-reflection surfaces and the sheet surface were 90° or below. Thus the Fresnel lens sheet in Example 2 could be satisfactorily formed and could be easily removed from the mold. The innermost prism had a transmission efficiency of 69.2%, which was higher by about 4% than that of the innermost prism of the Fresnel lens sheet in Example 1. In the Fresnel lens sheet in Comparative example 1, the angles δ between the refraction surfaces of all the prisms and the sheet surface and the angles β between the total-refraction surfaces of all the prisms and the sheet surface were 90° or below. Thus the Fresnel lens sheet could be satisfactorily formed and could be easily removed from the mold. The innermost prism had a transmission efficiency of 44.9%, which was far less than 50% and Fresnel lens sheet in Comparative example 2 was unacceptable. In the Fresnel lens sheet in Comparative example 2, the angle δ between the refraction surface of the outermost prism and the sheet surface was 100.3°. Consequently, the Fresnel lens sheet was very difficult to be removed from the mold, and the removal of the Fresnel lens sheet from the mold caused damage to the Fresnel lens sheet. The innermost prism had a high transmission efficiency of 71.3%. As obvious from the results of evaluation, the Fresnel lens sheets in Examples 1 and 2 were satisfactory in both molding facility and transmission efficiency. As apparent from the foregoing description, the Fresnel lens sheet according to the present invention can be easily formed, can reduce the ratio of stray light rays to the desired light rays and transmits light rays at a high transmission efficiency. The transmission screen of the present invention employing the Fresnel lens sheet of the present invention and the rear projection display employing the transmission screen of the present invention can be easily fabricated, the transmission screen transmits light rays at a high transmission efficiency, and the rear projection display can be formed in a small thickness and is capable of displaying images having high contrast.
<SOH> TECHNICAL FIELD <EOH>The present invention relates to a Fresnel lens sheet to be included in a transmission screen for a projection television set (PTV) or the like, a transmission screen provided with the Fresnel lens sheet, and a rear projection display. More specifically, the present invention relates to a Fresnel lens suitable for application to a transmission screen on which light rays fall at acute angles from behind, a transmission screen provided with the same Fresnel lens sheet, and a rear projection display. Referring to FIG. 16 , a known Fresnel lens sheet disclosed in JP 61-208041A (pp. 2-5, FIG. 8) has an entrance surface provided with a plurality of prisms 72 each having a refraction surface 73 and a total-reflection surface 74 . FIGS. 17A and 17B are enlarged views of parts A and B in FIG. 16 , respectively. As shown in FIGS. 17A and 17B , a light ray X projected by a projector M disposed behind the Fresnel lens sheet 71 and falling on the back surface of the Fresnel lens sheet 71 at a very acute angle is refracted at the refraction surface 73 , the refracted light ray X travels through the prism 72 , and is totally reflected by the total-reflection surface 74 in a direction perpendicular to a surface of the Fresnel lens sheet 71 . Thus the light ray X emitted by the projector M falls on the Fresnel lens sheet 71 at a very acute angle. The incidence angle θA of a light ray X 2 that falls on a prism P 2 farther from the projector M is larger than the incidence angle θB of a light ray X 1 that falls on a prism P 1 nearer to the projector M. Therefore, the prisms 72 need to be formed such that the angle β between the total-reflection surface 74 of the prism 72 farther from the projector M is smaller than that between the total-reflection surface 74 of the prism 72 nearer to the projector M to make the total-reflection surfaces 74 of all the prisms 72 reflect light rays in a direction perpendicular to the exit surface of the Fresnel lens sheet 71 . On the contrary, the angle δ between the refraction surface 73 of the prism 72 farther from the projector M and a sheet surface is larger than that between the refraction surface 73 of the prism 72 nearer to the projector M. When a transmission screen provided with the Fresnel lens sheet 71 of such a configuration is applied to a rear projection transmission display, the projector M is able to project light rays at large incidence angles on the transmission screen, and hence the rear projection transmission display can be formed in a small thickness. However, this known Fresnel lens sheet 71 has 1) a problem in manufacturing the same and 2) a double-image problem due to a ghost image formed by stray light rays. 1) Problem in Manufacture Generally, the Fresnel lens sheet 71 is formed by a UV/radiation curable resin molding process or a hot-pressing process. The UV/radiation curable resin molding process fills a UV/radiation curable resin in a Fresnel lens sheet forming mold, cures the UV/radiation curable resin by irradiating the same with UV rays or radiation, and removes a Fresnel lens sheet 71 thus formed from the mold. The hot-pressing process fills a heated resin in a Fresnel lens sheet forming mold, presses the heated resin, and removes a Fresnel lens sheet thus formed from the mold. The molds employed in those forming processes are formed by machining work for cutting a metal workpiece, such as a workpiece of aluminum, brass, copper or steel, with a cutting tool. As mentioned above, the prisms 72 at different positions of the Fresnel lens sheet 71 have refraction surfaces 73 and total-reflection surfaces 74 inclined at different angles, respectively, to the surface of the Fresnel lens sheet 71 . Therefore, the fabrication of the mold requires very complicated machining. A Fresnel lens sheet thus molded needs to be removed from the mold. It is difficult to remove some molded Fresnel lens sheets having prisms with surfaces inclined at some angles. A Fresnel lens sheet having prisms 72 with refraction surfaces 73 inclined at angles larger than 90° to the surface of the Fresnel lens sheet is difficult to remove from the mold because the prisms 72 act like a wedge. Even if such a Fresnel lens sheet could be removed from the mold, it is possible that the Fresnel lens sheet would be damaged. 2) Double Image Due to Stray Light Rays As shown in FIGS. 17B and 18 , in some cases, some light rays projected by a projector, not shown, fallen on the foregoing Fresnel lens sheet 71 , and refracted at the refraction surfaces 73 fall on the exit surface instead of falling on the total-reflection surfaces 74 . The light rays fallen on the exit surface are refracted further at the refraction surfaces 73 and reflected further by the total-reflection surfaces 74 so as to travel forward through the exit surface in stray light rays Y. A ghost image formed by the stray light rays Y and a desired image formed by the desired light rays overlap each other to form a double image. The effect of the prisms 72 near to the projector, on which light rays fall at small incidence angles θ, on forming a double image is particularly remarkable.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a sectional view of a Fresnel lens sheet in a first embodiment according to the present invention; FIG. 2A is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 1 ; FIG. 2B is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 1 ; FIG. 3 is a flow chart of a method of fabricating a Fresnel lens sheet according to the present invention; FIG. 4A is a typical view of assistance in explaining a machining method of making a forming mold for forming a Fresnel lens sheet according to the present invention; FIG. 4B is a typical view of assistance in explaining a machining method of making a forming mold for forming a Fresnel lens sheet according to the present invention; FIG. 5 is a perspective view of a transmission screen in the first embodiment according to the present invention; FIG. 6 is a perspective view of another transmission screen in the first embodiment according to the present invention; FIG. 7 is a perspective view of a third transmission screen in the first embodiment according to the present invention; FIG. 8 is a perspective view of a fourth transmission screen in the first embodiment according to the present invention; FIG. 9 is a perspective view of a fifth transmission screen in the first embodiment according to the present invention; FIG. 10 is a sectional view of a rear projection display in a first embodiment according to the present invention; FIG. 11A is a diagrammatic view of assistance in explaining the transmission efficiency of a Fresnel lens sheet according to the present invention; FIG. 11B is a diagrammatic view of assistance in explaining the transmission efficiency of a Fresnel lens sheet according to the present invention; FIG. 12A is a fragmentary enlarged view of a Fresnel lens sheet in a second embodiment according to the present invention; FIG. 12B is a fragmentary enlarged view of the Fresnel lens sheet in the second embodiment; FIG. 13 is a sectional view of a Fresnel lens sheet in a third embodiment according to the present invention; FIG. 14 is a sectional view of another Fresnel lens sheet in the third embodiment-according to the present invention; FIG. 15 is a sectional view of a third Fresnel lens sheet in the third embodiment according to the present invention; FIG. 16 is a sectional view of a conventional Fresnel lens sheet; FIG. 17A is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 16 ; FIG. 17B is a fragmentary enlarged view of the Fresnel lens sheet shown in FIG. 16 ; and FIG. 18 is a diagrammatic view of assistance in explaining stray light rays in a Fresnel lens sheet. detailed-description description="Detailed Description" end="lead"?
20041101
20071002
20050818
59555.0
0
CRUZ, MAGDA
FRESNEL LENS SHEET, TRANSMISSION SCREEN PROVIDED WITH THE SAME AND REAR PROJECTION DISPLAY
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,254
ACCEPTED
Monolithic rail platform and bolt assemblies for a firearm
A firearm assembly for a firearm can include a monolithic rail platform with a handguard portion and an upper receiver portion. The barrel of the firearm can be positioned through the bandguard portion and secured with the upper receiver portion. A firearm assembly can also include a bolt assembly with a bolt carrier having minimized land area and a forward end sized for receipt in the barrel extension at the rearward end of the barrel.
1. A monolithic rail platform for a firearm, comprising: a handguard portion adapted to receive at least a portion of a barrel assembly of the firearm therein; and an upper receiver portion extending rearwardly from and integrally formed with said handguard portion, said upper receiver portion adapted to receive a bolt carrier therein. 2. The platform of claim 1, wherein said upper receiver portion includes a bore extending along a longitudinal axis thereof, said bolt carrier being movably received in said bore of said upper receiver portion along said longitudinal axis. 3. The platform of claim 1, further comprising a coupling portion at a forward end of said upper receiver portion and integral with said handguard portion, said coupling portion adapted to releasably clamp a rearward end of said barrel assembly extending through said handguard portion to said upper receiver portion. 4. The platform of claim 3, wherein said upper receiver portion includes a longitudinal axis and said coupling portion includes a slot extending in the direction of said longitudinal axis separating said coupling portion into first and second clamping portions positioned on respective sides of said slot. 5. The platform of claim 4, further comprising at least one fastener positionable through said coupling portion transversely to said longitudinal axis, said at least one fastener operable to bring said clamping portions toward one another to clamp said barrel assembly in said coupling portion. 6. The platform of claim 5, further comprising a pair of fasteners positionable through said coupling portion transversely to said longitudinal axis, one of said pair of fasteners positioned against a an enlarged portion of said barrel assembly to resist forward movement of said barrel assembly. 7. The platform of claim 1, wherein said handguard portion includes a number of rails extending therealong separated by recessed portions therebetween. 8. The platform of claim 7, wherein said number of rails includes an upper rail extending rearwardly along said upper receiver portion. 9. The platform of claim 8, wherein said upper rail includes a passage formed therealong for delivering gas from a forward end of said barrel. 10. The platform of claim 1, wherein said handguard portion extends along said barrel assembly to a position adjacent a forward end of said barrel assembly. 11. The platform of claim 1, wherein said upper receiver portion includes a first opening along a bottom side thereof adapted to receive a trigger assembly and a second opening along said bottom side thereof in communication with and forming a forward extension of said first opening, said second opening adapted to receive a magazine therein. 12. The platform of claim 1, wherein said barrel assembly is attachable to said upper receiver portion and extends through said handguard portion in a floating relationship therewith. 13. The platform of claim 1, wherein the monolithic rail platform comprises a portion of a bolt action rifle. 14. The platform of claim 1, wherein: said barrel assembly includes a barrel extension at a rearward end thereof; said upper receiver portion includes a longitudinal bore extending therethrough in communication with said barrel extension; and said bolt carrier including a protrusion at a forward end thereof, said protrusion being sized for receipt in said barrel extension thereby increasing a stroke length of said bolt carrier in said longitudinal bore of upper receiver portion. 15. A firearm assembly, comprising: a handguard portion; a barrel assembly extending through said handguard portion, said barrel assembly including a barrel extension at a rearward end thereof; an upper receiver portion extending from a rearward end of said handguard portion, said upper receiver portion including a longitudinal bore extending therethrough in communication with said barrel extension; and a bolt assembly movably positioned in said longitudinal bore, said bolt assembly including a bolt carrier having a protrusion at a forward end thereof, said protrusion being sized for receipt in said barrel extension thereby increasing a stroke length of said bolt carrier in said longitudinal bore of said upper receiver portion. 16. The platform of claim 15, wherein said handguard portion is integrally formed with said upper receiver portion. 17. The assembly of claim 15, further comprising a coupling portion at a forward end of said upper receiver portion integral with said handguard portion, said coupling portion adapted to releasably clamp a rearward end of said barrel assembly extending through said handguard portion to said upper receiver portion. 18. The assembly of claim 17, wherein said upper receiver portion includes a longitudinal axis and said coupling portion includes a slot extending in the direction of said longitudinal axis separating said coupling portion into first and second clamping portions positioned on respective sides of said slot. 19. The assembly of claim 18, further comprising at least one fastener positionable through said coupling portion transversely to said longitudinal axis, said at least one fastener operable to bring said clamping portions toward one another to clamp said barrel assembly in said coupling portion. 20. The assembly of claim 15, wherein said handguard portion includes a number of rails extending therealong separated by recessed portions therebetween. 21. The assembly of claim 20, wherein said number of rails includes an upper rail extending rearwardly along said upper receiver portion. 22. The assembly of claim 15, wherein said handguard portion extends along said barrel assembly to a position adjacent a forward end of said barrel assembly. 23. The assembly of claim 15, wherein said barrel assembly is attachable to said upper receiver portion and said handguard portion extends around and is separated from said barrel assembly. 24. The assembly of claim 15, wherein said bolt carrier includes a forward end portion and a rearward end portion, said forward end portion including a number of lands extending therealong and spaced thereabout for contacting said upper receiver portion in said bore, said number of lands occupying from about 1% to about 12% of a surface area of said forward end portion along which said number lands extend. 25. The assembly of claim 15, wherein said protrusion extends into said barrel extension for a distance of one hundred thousandths of an inch when said bolt carrier is positioned completely forwardly in said upper receiver portion. 26. A firearm assembly, comprising: a handguard portion; a barrel assembly extending through said handguard portion; an upper receiver portion extending from a rearward end of said handguard portion, said upper receiver portion including a longitudinal bore extending therethrough in communication with said barrel extension; and a bolt assembly movably positioned in said longitudinal bore, said bolt assembly including a bolt carrier including a forward end portion and a rearward end portion, said forward end portion including a number of lands extending therealong and spaced thereabout, said number of lands occupying from about 1% to about 12% of a surface area of said forward end portion along which said number of lands extend. 27. The assembly of claim 26, wherein said number of lands occupy from about 1% to about 8% of said surface area of said forward end portion. 28. The assembly of claim 26, wherein said number of lands occupy from about 1% to about 4% of said surface area of said forward end portion. 29. The assembly of claim 26, wherein said number of lands occupy about 4% of said surface area of said forward end portion. 30. The assembly of claim 26, wherein said barrel assembly includes a barrel extension at a rearward end thereof. 31. The assembly of claim 26, wherein said bolt carrier includes a protrusion at a forward end thereof, said protrusion being sized for receipt in said barrel extension thereby increasing a stroke length of said bolt carrier in said longitudinal bore of said upper receiver portion. 32. The assembly of claim 26, wherein said handguard portion and said upper receiver portion are formed as an integral unit. 33. The assembly of claim 26, further comprising a coupling portion at a forward end of said upper receiver portion and integral with said handguard portion, said coupling portion adapted to releasably clamp a rearward end of said barrel assembly extending through said handguard portion to said upper receiver portion. 34. The assembly of claim 33, wherein said upper receiver portion includes a longitudinal axis and said coupling portion includes a slot extending in the direction of said longitudinal axis separating said coupling portion into first and second clamping portions positioned on respective sides of said slot. 35. The assembly of claim 26, wherein said handguard portion extends along said barrel assembly to a position adjacent a forward end of said barrel assembly. 36. The assembly of claim 26, wherein said barrel assembly is attachable to said upper receiver portion and extends through said handguard portion in a floating relationship therewith.
BACKGROUND The use of automatic and semi-automatic rifles is commonly known to be prevalent in the military. Such weapons typically employ an upper receiver and bolt action operating system. One standard weapon for the U.S. Military is the M-16 rifle. Semi-automatic rifles such as the AR15 type are used in the civilian sector. Such rifles can be further adapted for single shot action. The structure and mechanisms of semi-automatic and automatic rifles have been the subject of much refinement and variation over the years. While there have been advances in the designs of prior art rifles, there remains room for additional improvements. The present invention is directed toward providing various improvements to semi-automatic and automatic rifles. SUMMARY The present invention is directed to monolithic rail plate platforms and bolt assemblies for rifles. According to one aspect, there is provided a monolithic rail platform that includes a handguard portion and an upper receiver portion integrally formed with one another as a single component. According to another aspect, there is provided an improved bolt carrier for a semi-automatic or automatic rifle. According to a further aspect, there is provided an improved operating system for a semi-automatic or automatic rifle. According to yet another aspect, there is provided an improved rifle assembly for attachment of peripheral components thereto. These and other aspects will also be apparent from the following description of the illustrated embodiments. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an exploded view of an upper portion of a firearm. FIG. 2 is a top view of an monolithic rail platform comprising the upper portion of FIG. 1. FIG. 3 is a side view of the monolithic rail platform of FIG. 2. FIG. 4 is a bottom view of the monolithic rail platform of FIG. 2. FIG. 5 is an inverted side view of the monolithic rail platform of FIG. 2 looking at the side opposite the side shown in FIG. 3. FIG. 6 is a right end view of the monolithic rail platform of FIG. 2. FIG. 7 is a left end view of the monolithic rail platform of FIG. 2. FIG. 8 is a top view of a bolt carrier comprising a portion of the upper portion of FIG. 1. FIG. 9 is a side view of the bolt carrier of FIG. 8. FIG. 10 is a right end view of the bolt carrier of FIG. 8. FIG. 11 is a bottom view of the bolt carrier of FIG. 8. FIG. 12 is a left end view of the bolt carrier of FIG. 8 as oriented in FIG. 11. FIG. 13 is a section view through line 13-13 of FIG. 12. DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Any such alterations and further modifications in the illustrated device, and any such further applications of the principles of the invention as illustrated herein are contemplated as would normally occur to one skilled in the art to which the invention relates. An assembly 20 for an upper portion of a firearm is shown in FIG. 1 in an exploded view. The lower receiver assembly, butt stock and magazine are not shown in FIG. 1, it being understood that the lower receiver, butt stock and magazine can be provided in any configuration suitable for an automatic M16/AR15 type rifle or other type or caliber semi-automatic or automatic rifle. Assembly 20 includes a barrel assembly 21 that includes a barrel 22 having a gas block 24 attachable to a forward end thereof. A gas tube 26 extends rearwardly from gas block 24 to the weapon operating system. A barrel extension 28 is attachable to the rearward end of barrel 22 adjacent cartridge chamber 30. Barrel extension 28 is configured to interlock with the bolt, such as bolt 102. Further details regarding one embodiment bolt 102 and barrel extension 28 are provided in U.S. Pat. No. 6,182,389, which is incorporated herein by reference in its entirety. Assembly 20 further includes an monolithic rail platform 50 that includes a handguard portion 52 integrally formed with an upper receiver portion 70. Referring now further to FIGS. 2-7, when assembly 20 is assembled, a bolt carrier 120 housing bolt 102 is positioned in and movably received along the longitudinal axis of bore 70a of upper receiver portion 70, and barrel assembly 21 is positioned in bore 52a of handguard portion 52. Barrel assembly 21 is secured to monolithic rail platform 50 with fasteners 54a, 54b and clamping nuts 55a, 55b. Fasteners 54a, 54b extend through respective ones of the holes 56a, 56b through monolithic rail platform 50. Clamping nuts 55a, 55b are coupled to the threaded ends of fasteners 54a, 54b to clamp monolithic rail platform 50 around enlarged portion 22a of barrel 22 at the forward end of upper receiver portion 70. It is further contemplated that fastener 54b can act as a locating and retaining pin by interacting with enlarged portion 28a of barrel extension 28 to ensure that barrel 22 is properly positioned and located in monolithic rail platform 50. For example, fastener 54b can be received in a recess formed in an outer surface of enlarged portion 28a of barrel extension 28 when barrel 22 is at the proper locating in bore 52a of handguard portion 52. Fastener 54b can resist any forward movement of barrel 22 and barrel extension 28 that might be created b contact of the bolt carrier therewith. Handguard portion 52 includes a number of rails 58 extending therealong separated by recesses 60 therebetween. Rails 58 include transverse grooves 59 formed therein to facilitate gripping of handguard portion 52. A number of threaded holes 63 are spaced along each rail 58 to allow attachment of peripheral devices, such as a grenade launcher, site, sling and/or scope, for example. Recesses 60 each include a number of holes 62 formed therein along handguard portion 52 to allow air flow and heat from barrel 22 to vent therethrough. Handguard portion 52 further includes a rearward extension 58a for the upper rail 58 that extends along upper receiver portion 70. The rearward extension 58a includes a passage 64 formed therethrough that communicates gas tube 26 to provide a path for delivering gas to the operating system of the rifle. The forward end 52b of handguard portion 52 includes a triangular shaped opening 52c adapted to receive the upper extension 24a of gas block 24. Gas tube 26 is coupled to upper extension 24a of gas block 24. Upper receiver portion 70 includes a forward end 70b integrally formed with handguard portion 52 and a rearward end 70c. Forward end 70b can comprise a clamping portion having clamping members 70e, 70f positioned on opposite sides of slot 70d to facilitate clamping of upper receiver portion 70 about barrel 22. A cut-out 65 is formed in forward end 70b to reduce weight. Upper receiver portion 70 further includes a forward lug 72a and a rearward lug 72b extending downwardly from a bottom side thereof. The lower receiver assembly (not shown) is attachable to lugs 72a, 72b. Upper receiver portion 70 further includes ejection port opening 74 and ejection port cover receptacles 76a, 76b on opposite sides thereof. Ejection port receptacles 76a, 76b receive pins that pivotally couple an ejection port cover (not shown) over opening 74. A deflector 78 extends outwardly from upper receiver portion 70 adjacent the rearward end of ejection portion opening 74 to deflect ejected cartridges away from the shooter. Upper receiver portion 70 further includes a forward assist port 80 that receives a forward assist mechanism (not shown) to assist in positioning the bolt carrier assembly 100 in its forward battery position in upper receiver portion 70 if needed. Opposite ejection port receptacle 74 there is a lip of material 84 to support a cam pin cut-out in the upper receiver portion 70. Upper receiver portion 70 further includes in the bottom side thereof a first opening 82a along a rearward portion thereof for receiving the trigger assembly of the lower receiver assembly. Upper receiver portion 70 also includes a second opening 82b along a forward portion thereof communicating with the magazine receptacle of the lower receiver assembly for receiving cartridges therethrough from the magazine of the rifle. Second opening 82b is wider than first opening 82a and first and second openings 82a, 82b are in communication with one another along the bottom portion of upper receiver portion 70. The rearward end 70c of upper receiver portion 70 is positionable adjacent the lower receiver extension assembly and buttstock assembly of the lower receiver assembly when the rifle is assembled. With barrel 22 secured to the coupling portion at forward end 70b of upper receiver portion 70, handguard portion 52 can extend around barrel 22, but need not be supported by, or in contact with, or coupled to barrel 22. Accordingly, barrel 22 can float in bore 52a of handguard portion 52. Monolithic rail platform 50 allows the hoop strength of handguard portion 52 to be maximized since, in one embodiment, it is provided as a single continuous ring extending along barrel 22. The integral unitary construction of upper receiver portion 70 and handguard portion 52 provide a stronger, reliable rifle assembly since there are fewer parts that require assembly. Peripheral devices, such as scope mounts, sites, slings, and grenade launchers, for example, that are mounted on handguard portion 52 do not apply load on or influence barrel 22, improving rifle accuracy. Rather, such loads and other influences created by these peripherals are transmitted from handguard portion 52 to upper receiver portion 70. Furthermore, in one embodiment, any threaded connection between barrel 22 and upper receiver portion 70 is eliminated, allowing rapid attachment and detachment of barrel 22 via fasteners 54a, 54b. The integral upper receiver and handguard portions and means of attaching the barrel allow for rapid assembly and disassembly of rifle components, which can be critical in the field. Referring now to FIGS. 8-13, further details regarding bolt carrier 120 of bolt assembly 100 will be provided. Bolt carrier 120 includes a forward end 120a and an opposite rearward end 120b. Forward end 120a is oriented toward barrel 22 when bolt carrier 120 is positioned in upper receiver portion 70. A passage 120d extends between forward end 120a and rearward end 120b along a longitudinal axis of bolt carrier 120. Passage 120d has a minimum diameter portion 120c sized to receive the reduced diameter end portion 102a of bolt 102 when positioned therein. Passage 120d further includes a bolt receiving portion 120e extending forwardly from minimum diameter portion 120c to forward end 120a to receive the remaining portion of bolt 102. Bolt 102 is mounted in bolt carrier 120 for axial sliding movement in forward portion 120e. Bolt 102 includes a cartridge extractor 104 pivotally coupled thereto, and includes lugs 106 at the forward end thereof that releasably interlock with barrel extension 28. A firing pin (not shown) extends through a central bore through bolt 102. A cam slot 124 is formed adjacent forward end 120a which receives a cam member therethrough for contacting bolt 102 to rotate it as it moves rearwardly and forwardly for engagement with barrel extension 28. Bolt carrier 120 includes a slot 134 therethrough that receives the hammer from the lower receiver assembly to strike the firing pin in bolt 102. Bolt carrier 120 further includes gas key mounting holes 136 formed in an upper mounting surface 131 of bolt carrier 120. Gas key mounting holes 136 communicate with passage 120d. A gas port 138 is further provided in mounting surface 131 and includes ports extending therefrom in communication with passage 120d. One side of bolt carrier 120 is provided with forward assist notches 144 which are engageable by a forward assist mechanism (not shown) in forward assist port 80 of upper receiver portion 70. Bolt carrier 120 further includes a door opener 122 that is recessed in the body of bolt carrier 120 to provide room for the door latch to close. Bolt carrier 120 includes a charging handle contact portion 146 adjacent forward end 120a. Rearward end portion 130 includes a groove 132 cut therein along the longitudinal axis of bolt carrier 120 to maintain alignment of bolt carrier 120 as it axially reciprocates in upper receiver portion 70. Bolt carrier 120 further includes forward lands 126a, 126b, 126c, and 126d extending along the forward half of bolt carrier 120. Lands 126a, 126b extend along the upper portion of bolt carrier 120 along mounting surface 131 and terminate at contact portion 146. Lands 126c and 126d extend along the bottom portion of bolt carrier 120 and terminate at forward end 120a. The lands 126a, 126b 126c, 126d contact the inner wall of bore 70a of upper receiver portion 70 to maintain alignment of bolt carrier 120 centrally therein and also in alignment with the centerline of barrel 22. The land area along bolt carrier 120 and also along forward end portion 148 is minimized by reducing the land area in the range from one-half to one twenty-fifth of that of prior art bolt carriers. The portion of bolt carrier 120 along which each of the lands 126a, 126b, 126c, 126d extends has a surface area, and lands 126a, 126b, 126c, 126d occupy a portion of that surface area. In one embodiment, a section of bolt carrier 120 including lands 126a, 126b, 126c, 126d occupies a surface area that ranges from 1% to 12% of the surface area of the occupied portion of the bolt carrier 120. In another embodiment, lands 126a, 126b, 126c, 126d occupy a surface area that ranges from 1% to 8% of the surface area of the occupied portion of the bolt carrier. In another embodiment, lands 126a, 126b, 126c, 126d occupy a surface area that ranges from 1% to 4% of the surface area of the occupied portion of the bolt carrier. By minimizing the land area, the contact surface area between bolt 120 and the wall of bore 70a of upper receiver portion 70. This allows greater ease of movement of bolt carrier 120 in upper receiver portion 70. The reduced contact area also provides greater clearance between bolt carrier 120 and any particles in bore 70a of upper receiver portion 70, allowing bolt carrier 120 to deposit such particles and debris in the recessed areas between the lands to provide a self-cleaning action that reduces malfunction in harsh environments and with prolonged usage. The protrusion 125 at the forward end of bolt carrier 120 is sized for receipt in the rearwardly facing opening of barrel extension 28. Protrusion 125 is positioned radially inwardly from the outer perimeter of forward end 120a, and includes a sloped or chamfered outer surface that extends from a first diameter at rearward end 125b adjacent forward end 120a to a reduced diameter forward face 125b at the forward end of protrusion 125. Bore 120d extends through protrusion 125. Protrusion 125 allows bolt carrier 120 to be positioned more forwardly in upper receiver portion 70 as compared to a bolt carrier having the same overall length without protrusion 125. By positioning bolt carrier 120 more forwardly in upper receiver portion 70, the time required to move bolt carrier 120 rearwardly to turn bolt 102 is increased. Protrusion 125 thus increases the stroke length for bolt carrier 120 in upper receiver portion 70. The additional stroke length provided by protrusion 125 increases the dwell time of bolt 102 in barrel extension 28, allowing residual gas pressure in barrel 22 more time to vent before bolt 102 unlocks with barrel extension 28. In one embodiment, protrusion 125 is sized to extend forwardly a distance of one hundred thousandths of an inch to increase the dwell time of bolt 102 by up to two times that provided in bolt carriers without protrusion 125. It is contemplated that other embodiments may provide other lengths and/or other dwell times associated with protrusion 125. The reduced gas pressure in the blowback operation reduces the load exerted on extractor 104 during the extraction cycle, improving system operation in the extraction and ejection cycles for the spent cartridge. For example, by venting additional gas pressure before extraction, expansion of the spent cartridge casing is reduced facilitating extraction and reducing the extraction loading. The load and forces exerted on bolt 102, barrel extension 28, and upper receiver portion 70 are reduced. Thus, rather than having excess energy from the gas pressure consumed in the recoil cycle, more energy is directed for use in the counter recoil cycle and feeding and chambering of cartridges. The increased stroke length thus increases overall system operability, reliability and the life of the firearm. Operating performance with attachments that affect the gas operation of the rifle are also improved. For example, silencers accumulate gas to muffle the noise. The additional dwell time allows more gas to vent to the breech, reducing load on the barrel and providing longer barrel life when silencers are employed. While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character. All changes and modifications that come within the spirit of the invention are desired to be protected.
<SOH> BACKGROUND <EOH>The use of automatic and semi-automatic rifles is commonly known to be prevalent in the military. Such weapons typically employ an upper receiver and bolt action operating system. One standard weapon for the U.S. Military is the M-16 rifle. Semi-automatic rifles such as the AR15 type are used in the civilian sector. Such rifles can be further adapted for single shot action. The structure and mechanisms of semi-automatic and automatic rifles have been the subject of much refinement and variation over the years. While there have been advances in the designs of prior art rifles, there remains room for additional improvements. The present invention is directed toward providing various improvements to semi-automatic and automatic rifles.
<SOH> SUMMARY <EOH>The present invention is directed to monolithic rail plate platforms and bolt assemblies for rifles. According to one aspect, there is provided a monolithic rail platform that includes a handguard portion and an upper receiver portion integrally formed with one another as a single component. According to another aspect, there is provided an improved bolt carrier for a semi-automatic or automatic rifle. According to a further aspect, there is provided an improved operating system for a semi-automatic or automatic rifle. According to yet another aspect, there is provided an improved rifle assembly for attachment of peripheral components thereto. These and other aspects will also be apparent from the following description of the illustrated embodiments.
20050811
20120807
20061026
60868.0
F41C2300
0
CLEMENT, MICHELLE RENEE
MONOLITHIC RAIL PLATFORM AND BOLT ASSEMBLIES FOR A FIREARM
UNDISCOUNTED
0
ACCEPTED
F41C
2,005
10,513,308
ACCEPTED
Method of producing a digital fingerprint sensor and the corresponding sensor
An embodiment of the present invention related to fingerprint sensors is described. The sensor comprises an integrated-circuit chip having a sensitive surface, a substrate provided with electrical connections and wire-bonding wires connecting the chip to the electrical connections. The sensor further includes a molded protective resin at least partly covering the substrate and the chip and completely encapsulating the wire-bonding wires. The resin forms, on at least one side of the chip and at most three sides, a bump rising to at least 500 microns above the sensitive surface, this bump encapsulating the wire-bonding wires and constituting a guide for a finger, the fingerprint of which it is desired to detect.
1. A method of manufacturing a fingerprint sensor the sensor is designed to allow fingerprint detection by the finger sliding over the active surface, the method comprising the following steps: fabricating a sensor chip, the chip being in the form of an elongate strip having two short sides; mounting the chip on a substrate; connecting the chip to the substrate by wire-bonding wires placed on one short side of the chip; placing the chip/substrate assembly in a mold; and pouring a protective resin into the mold so as to at least partly cover the substrate and the chip and to completely encapsulate the wires, the mold having a shape such that a bump of resin, projecting by at least 500 microns above a sensitive surface of the chip, is formed on at least one side of the chip, the bump protecting the wire-bonding wires and forming a positioning guide for the finger, the fingerprint of which is desired to be detected, so that the latter moves opposite a sensitive active surface of the chip when the finger slides against the bump. 2. The method as claimed in claim 1, wherein the two short sides of the chip are provided with a guiding bump, the mold being shaped so that the other two sides of the chip do not have a bump. 3. The method as claimed in claim 1, wherein the mold is shaped so that the active surface of the chip is covered with a thin, molded resin layer that protects this surface. 4. The method as claimed in claim 3, wherein, before the substrate is placed in the mold, spacers of calibrated height, against which the bottom of the mold will bear, are placed on the front face of the integrated-circuit chip, before the chip is placed in the mold, in order for the thickness of resin that will cover the sensitive surface of the sensor to be perfectly defined. 5. The method as claimed in claim 3, wherein the thickness of the spacers above the sensitive surface of the chip ranges from about 10 microns to several tens of microns. 6. The method as claimed in claim 1, wherein the bump is less than one millimeter in height. 7. A fingerprint sensor comprising: a sensor chip in the form of an elongate strip having two short sides and having a sensitive surface; a substrate provided with electrical connections and wire-bonding wires connecting a short side of the chip to the electrical connections, the long sides having no wire-bonding wires, wherein the sensor chips includes a molded protective resin at least partly covering the substrate and the chip and completely encapsulating the wire-bonding wires, and the resin forming, on at least one side of the chip and at most on two sides, a bump rising to at least 500 microns above the sensitive surface, the bump encapsulating the wire-bonding wires and constituting a guide for a finger, the fingerprint of which is desired to be detected when the finger is slid over the sensor perpendicular to the long direction of the chip. 8. The sensor as claimed in claim 7, wherein the bump is less than one millimeter above the height of the sensitive surface. 9. The method as claimed in claim 2, wherein the mold is shaped so that the active surface of the chip is covered with a thin, molded resin layer that protects this surface. 10. The method as claimed in claim 4, wherein the thickness of the spacers above the sensitive surface of the chip ranges from about 10 microns to several tens of microns. 11. The method as claimed in claim 2, wherein the bump is less than one millimeter in height. 12. The method as claimed in claim 3, wherein the bump is less than one millimeter in height. 13. The method as claimed in claim 4, wherein the bump is less than one millimeter in height. 14. The method as claimed in claim 5, wherein the bump is less than one millimeter in height.
The invention relates to fingerprint sensors, and more particularly to a method of manufacture that minimizes the production costs and makes it easier to use the sensor and to protect the sensor against external attack. A fingerprint sensor is produced from an integrated circuit, in principle based on silicon, comprising especially an array of sensitive spots for generating a representation of the fingerprint of a finger placed directly on the surface of the array. Fingerprint detection may be optical or capacitive or thermal or piezoelectric. Some sensors operate when a finger is placed statically on the surface of a sensor, the rectangular or square active detection array of which has an area corresponding to the fingerprint area to be detected; other sensors operate by the finger sliding over a sensor, the detection array of which, having a much smaller area than the fingerprint to be detected, is a thin elongate strip. In both cases, but especially in the case of finger-sliding operation, the integrated circuit must be protected by wear-resistant layers. These layers depend on the type of sensor (for example, if it is an optical sensor, it is obvious that the optional protective layers must be protected by transparent layers). It has been proposed to use protective lacquers or else mineral coatings, such as silicon oxide coatings. Moreover, the integrated-circuit chip forming the core of the sensor must be electrically connected to the outside (especially to supply sources, control circuits and circuits for processing the electrical signals representative of the fingerprint). Given that the finger has to be placed on (or has to slide over) the sensitive surface of the sensor, this surface must remain accessible. This is why, for such sensors, a conventional electrical connection solution is adopted, using bonded flexible wires that connect contact pads on the front face (active face) of the integrated-circuit chip to contact pads located on a surface on which the chip is mounted. In integrated-circuit applications other than sensors (for example, microprocessors, memories, etc.), these wires are conventionally protected by a thick protective layer, deposited or overmolded, which encapsulates the chip and its wires. It is an object of the invention to propose a method of manufacturing a fingerprint sensor in which the following steps are carried out: a sensor chip is fabricated; this chip is mounted on a substrate; the chip is connected to the substrate by wire-bonding wires; the chip/substrate assembly is placed in a mold; a protective resin is poured into the mold so as to at least partly cover the chip and the substrate and to completely encapsulate the wires, the mold having a shape such that a bump of resin, projecting by at least 500 microns above a sensitive surface of the chip, is formed on at least one side of the chip, this bump protecting the wire-bonding wires and forming a positioning guide for the finger, the fingerprint of which it is desired to detect, so that the latter comes opposite a sensitive surface of the chip when the finger comes against the bump. Preferably, at least one side of the chip will have no such guiding bump. In the case of detection by the finger sliding over a chip of elongate strip shape, perpendicular to the direction of sliding of the finger, two sides of the chip will have no such guiding bump: a bump will be provided either on one side of the chip or on two opposed sides (these facing each other in the long direction of the strip), but not on the other two sides. In the case of a capacitive fingerprint sensor, the mold will be such that the sensitive surface of the chip is not covered with resin and the bumps will rise directly above the surface of the chip, leaving the sensitive surface of the chip free. However, it is advantageous in the case of a thermal or piezoelectric sensor to cover the sensitive surface with a thin, molded resin layer that protects this surface (preferably a uniform layer approximately 20 to 60 microns in thickness); the bumps will rise a few millimeters above this thin resin layer. The integrated-circuit chip thus encapsulated therefore includes, right from its fabrication, an ergonomic element (a finger-guiding element), so that this chip can be installed directly in applications without it being necessary to design the environment for these applications using specific guiding elements. For example, to install this sensor on a computer keyboard, it is unnecessary to redesign the keyboard casing. The sensor can be installed on a flat surface of this keyboard. The substrate may be rigid or flexible and will include electrical contacts left free (not covered with molded resin) for connecting the sensor to the outside. Preferably, the encapsulation by resin molding will be carried out on several chips simultaneously, the individual sensors thus encapsulated being subsequently detached from one another. If a thin molded resin layer covers the active surface of the sensor, it is preferred to install, on the front face of the integrated-circuit chip, before the chip is placed in the mold, spacers of calibrated height, against which the bottom of the mold will bear, in order for the thickness of resin that will cover the active surface of the sensor to be perfectly defined. These spacers are preferably placed all around this active surface so as not to impede the operation of the fingerprint detection. They may consist of bumps, a few tens of microns in height, formed during the actual fabrication of the chip and consequently integrated into the chip. They may also consist of balls or cylinders of calibrated diameter, these being laid on the surface of the chip in areas precoated with adhesive. To summarize, the aim of the invention is to end up with a fingerprint sensor comprising a sensor chip having a sensitive surface, a substrate provided with electrical connections and wire-bonding wires connecting the chip to the electrical connections, characterized in that it includes a molded protective resin at least partly covering the substrate and the chip and completely encapsulating the wire-bonding wires, and in that the resin forms, on at least one side of the chip and at most on three sides, a bump rising to at least 500 microns above the sensitive surface, this bump encapsulating the wire-bonding wires and constituting a guide for a finger, the fingerprint of which it is desired to detect. For a sensor designed to detect a fingerprint when a finger is slid perpendicular to the long direction of the chip, the latter being in the form of a strip, a resin bump is provided on at most two sides of the chip, these sides being the short sides. Other features and advantages of the invention will become apparent on reading the detailed description that follows, this being given with reference to the appended drawings, in which: FIG. 1 shows the fingerprint sensor before encapsulation; FIG. 2 shows, in cross section, the principle of the sensor encapsulation; FIG. 3 shows the encapsulated sensor, in perspective; FIG. 4 shows in perspective, seen from above and from below, an alternative embodiment of the sensor; and FIG. 5 shows, in cross section, an embodiment with the active surface of the sensor coated with a thin, molded resin layer. FIG. 1 shows an example of a fingerprint sensor produced from an integrated-circuit chip 10 in the form of an elongate strip (i.e. the length is much greater than the width) over which a finger has to be slid in order to detect, in succession, finger image portions as the finger progressively slides over the surface of the chip. The finger is slid perpendicular or approximately perpendicular to the length of the strip. The chip comprises an array of several rows (for example 5 to 10 rows) of many elementary detectors (for example, from about one hundred to several hundred elementary detectors per row) and each image therefore comprises several rows of many dots. By correlation of the partial images obtained in succession as the finger is moved along, an overall image of the fingerprint that has traveled over the surface of the sensor is reconstructed. The sensor may be a thermal sensor (measuring differences in heat exchange between the finger and a detector depending on whether a ridge or a valley of a fingerprint is opposite an elementary detector). It may also be a piezoelectric sensor (measuring the difference in pressure exerted depending on whether a ridge or a valley is present) or a capacitive sensor (measuring the difference in capacitance depending on whether a ridge or a valley is present); finally, it may be an optical sensor (measuring the difference in reflected light intensity). In the example shown, the elongate chip 10 has a sensitive active region 12 that is subjected to the influence of the fingerprint relief and consists essentially of an array of several rows of elementary detectors, and a peripheral region comprising, on the one hand, circuits associated with the array (supply circuit, control circuit, circuit for receiving signals delivered by the array) and, on the other hand, conducting contact pads 14 used for connecting the chip to the outside. The chip is conventionally mounted on a substrate 20 which itself includes corresponding conducting pads 22, electrical connections 24 connected to these pads 22, and contacts or pins 26 intended for connecting the chip/substrate assembly to elements external to the actual sensor (for example in order to communicate with a computer to which it will be desired to transfer, for processing and use, the electrical signals allowing the detected fingerprint image to be displayed). The chip is mounted on this substrate 20 via its rear, inactive face; the front, sensitive face remains accessible to the finger. The most conventional method of connection, namely wire bonding, is preferably used to connect the pads 14 on the chip to the pads 22 on the substrate. The wire-bonding wires are denoted by 28 in FIG. 1. The encapsulation operation after the chip 10 has been mounted on the substrate 20 consists in mounting the integrated-circuit chip/substrate assembly in a mold into which a resin for protecting the delicate parts of the assembly is injected. These delicate parts include, of course, the wire-bonding wires 28. The resin is liquid and cures in the mold, forming a solid. Conventionally, it is a two-component resin. The shape of the mold is designed so that the solidified resin forms one or more relatively thick bumps (in practice, the thickness is greater than that strictly needed to simply protect the chip and its wire-bonding wires 28) above the sensitive surface of the chip, on at least one side of the chip. The thickness of the bumps is preferably about one millimeter, but no more, above the surface on which the finger will rest during use. This means that, if the surface of the chip remains uncovered with resin, the bumps project by about one millimeter from the upper surface of the chip, but if the surface of the active part of the chip is itself covered with a thin resin layer on which the finger will press, the bumps will project one millimeter above this layer. FIG. 2 shows, in cross section, the chip 10 and its substrate 20 both encapsulated in the resin, which has two bumps, one on each side of the elongate chip, on the short sides. In this example, all the wire-bonding wires 28 for connecting the chip to the substrate are located on just one short side of the elongate chip. A resin bump 30 covers and protects them. This bump constitutes the main element for positioning and guiding the finger in its sliding movement transverse to the long direction of the strip. An optional second bump 32 may be formed, by molding, on the other short side of the strip. The finger 40 is then placed between the two bumps. The sensitive upper surface of the chip 10 is not covered with resin in this embodiment shown in FIG. 2. In the case of a sensor over which the finger slides, at most two bumps are provided. In the case of a sensor on which the finger remains static, with a square or rectangular chip, but not one in the form of a strip, up to three bumps may be provided, allowing three sides of the active surface to be defined, the finger being able to bear on two or three of these bumps. The external connection contacts 26 are not covered with the molding resin. In the example shown in FIGS. 1 and 2, these contacts are on the upper surface of the substrate 20. The pads 22 on the substrate, the connections 24 and the contacts 26 are produced as a metal film covering the surface of the substrate, which is made of a plastic or a ceramic. The contacts 26 are located on the top side of the substrate (that on which the chip is mounted). However, it is also possible to use other types of connection and in particular connections via beam leads. This involves a rigid conducting leadframe which itself constitutes simultaneously the substrate on which the chip is mounted, the pads 22, the connections 24 and the contacts 26. In this case, it will be understood that the contacts 26 may be accessible via the rear of the substrate, rather than via the front. In yet other embodiments, the contacts 26 may be accessible via the rear of the substrate. This is the case, for example, if the substrate is a multilayer substrate that includes interconnection conductors both on its front surface and on its rear surface with conducting vias between the two. FIG. 3 shows in perspective an example of an embodiment in which the conducting contacts 26 are made in the form of a male connector. For connecting the substrate to the outside, a complementary connector may be plugged into the contacts 26 or applied against these contacts, depending on the configuration of the latter. FIG. 4 shows in perspective another example of an embodiment in which the connection contacts 26 on the substrate are located on the underside of the substrate, the latter being formed by a multilayer structure. FIG. 4 shows bumps 30 and 32 differing in shape from that of FIG. 3, but fulfilling the same function of protecting the wire-bonding wires and of guiding the finger. FIG. 5, in which connection contacts 26 have also been provided on the underside of the substrate 20, shows, in cross section, another embodiment in which the resin 36 covers, as a thin layer a few tens of microns in thickness, the active surface of the chip between the bumps 30 and 32. In order to define this small thickness, spacers 38 are preferably provided on the surface of the chip, these spacers having the desired thickness. The bottom of the mold bears against the spacers and the liquid resin can be injected into the gap that is thus left between the front surface of the chip and the bottom of the mold. This embodiment is advantageous in the case of a thermal sensor, the surface of the chip of which cannot in practice be covered with a silica passivation layer, as it would be in the case, for example, of an optical sensor. The spacers 38 may be produced in several ways. They are placed not directly in the active region of the sensor, but in a peripheral region of the front face of the chip. In one example, they consist of glass balls or cylinders of calibrated diameter, placed on spots of adhesive deposited beforehand around the periphery of the active region. The balls may be made of glass. The cylinders may be made of glass fiber fragments ranging from about ten to several tens of microns in diameter. In another example, the spacers are integrated into the surface of the chip, for example in the form of localized deposits of metal. These deposits may be formed electrolytically. The sensors are preferably manufactured by molding a batch of several sensors on a common substrate. The individual sensors, each comprising a respective chip and each provided with their bumps and their connections, are detached from one another after molding. Molding onto a continuous ribbon of substrates attached to one another is the preferred solution. Depending on the applications, several chips may be provided in one and the same sensor, these being encapsulated in just one operation. The resin used may be a transparent resin, in particular when the sensor is an optical sensor and when the active surface is covered with resin.
20041103
20080701
20050818
63034.0
0
ZARNEKE, DAVID A
METHOD OF MANUFACTURING A FINGERPRINT SENSOR AND CORRESPONDING SENSOR
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,336
ACCEPTED
Stent and stent graft
A stent (1) formed in the shape of a generally tubular body which has a spring function with which the tubular body is diameter-contractible toward the central axis (C) of the tubular body and which is expandable to the initial diameter after contraction, the stent being loaded into a sheath and being to be delivered to a diseased part to be treated, wherein the stent (1) maintains a configuration curved along the longitudinal direction of the stent when not inserted in the sheath, and (B) when the stent (1) is inserted into the sheath, the stent (1) is contracted toward the central axis (C) of the stent (1) and is elongated in the form of a generally straight line along the longitudinal direction of the stent (1), whereby the stent (1) is loaded into the sheath in the form of a substantially straight line, and the stent can remarkably improve safety and conformity during delivery in the artery, and the like.
1-13. (canceled) 14. A stent formed in a shape of a generally tubular body, said tubular body having a central axis, said stent having a spring function with which said tubular body is diameter-contractible toward the central axis of said tubular body, said tubular body being expandable to an initial diameter after contraction, the stent being loaded and housed in a sheath and being delivered to a diseased part to be treated, wherein: said stent maintaining a configuration curved along a longitudinal direction of said stent when the stent is not inserted in the sheath, said stent is contracted toward the central axis of the stent and is elongated in a form of a generally straight line along the longitudinal direction of the stent when the stent is inserted into the sheath, whereby the stent is loaded and housed in the sheath in the form of a generally straight line, and said stent, being housed in the sheath in the form of a generally straight line, is inserted into a diseased part together with the sheath, is released from the sheath, and radially expands, outwardly after release, to restore and maintain a configuration curved along the longitudinal direction of the stent. 15. The stent as recited in claim 14, wherein the stent comprises generally V-letter-shaped zigzag patterns having at least one central curved portion and generally straight line portions substantially same in length on both sides thereof, the zigzag patterns being formed by repeatedly bending a portion between two ends of a wire base material made of a metal, a plurality of said zigzag patterns are arranged to surround the central axis of the stent, at least one annular unit is formed by bonding end portions of said wire metal at least in one portion, and a plurality of the annular units are constituted, a plurality of said annular units constituted are arranged in series in the longitudinal direction of the stent, said annular units adjacent to each other are connected to each other with connection struts having substantially same lengths each at least in two portions, the struts forming connection portions, and said generally straight line portions are formed at a connection angle of 0°±30° with said connection portions. 16. The stent as recited in claim 14, wherein said strut has at least one annular unit having an odd number of the zigzag patterns and at least one annular unit having an even number of the zigzag patterns. 17. The stent as recited in of claim 14, wherein the annular units has an odd number of the zigzag patterns and the annular units having an even number of the zigzag patterns are disposed to be adjacent to each other and arranged alternately along the longitudinal direction of the stent. 18. The stent as recited in claim 14, wherein, in a state where the stent maintains a configuration curved along the longitudinal direction of the stent, at least 1 to 4 central curved portions constituting the zigzag patterns are arranged to be substantially opposed to each other between two connection portions between two annular units when viewed from a outermost curved line side of the stent, and the central curved portions of the zigzag patterns constituting one of the annular units adjacent to each other and inside spaces of the zigzag patterns of the other of the annular units are disposed so that said central curved portions and inside spaces are substantially facing each other when viewed from an innermost curved line side of said stent. 19. The stent as recited in claim 14, wherein the connection portions are each of a straight line or a curved line. 20. The stent as recited in claim 14, wherein the connection portion has a length S, the generally straight line portion have a length L, and the connection portion and the generally straight line portion having a ratio of length φ (=S/L) of 0.1 to 2.0. 21. The stent as recited in claim 14, wherein the central curved portion having a form of generally R or a ring. 22. The stent as recited in claim 14, wherein the generally tubular body under no load is contracted in diameter by 20% to 90% when said tubular body is inserted into a diseased part. 23. The stent as recited in claim 15, wherein a pipe unit having at least one of functions for reinforcement, marker protection, and sustained release of a drug is fitted to the wire base material made of a metal constituting the tent. 24. A stent graft formed by covering the stent recited in claim 14 with a tubular member made of a synthetic resin. 25. A stent in a form of a generally tubular body comprising: annular units formed by bonding end portions of a stent main line made of a metal line wire base material formed in a zigzag form and connection struts connecting said annular units in series, wherein a pipe unit is fitted to a changed portion of the stent main line and/or the connection strut in said annular unit and fixed to said stent main line, or a pipe unit is fitted to a portion of the stent main line provided with an element different from the stent main line and/or the strut in said annular unit, thereby causing the stent to exhibit at least one of functions for reinforcement, marker protection, and sustained release of a drug. 26. A stent graft comprising the stent as recited in claim 25 and a tubular member made of a synthetic resin covering said stent.
TECHNICAL FIELD The present invention relates to a stent and a stent graft for use in the treatment of duct-like organs typified by a blood vessel, particularly in the treatment of an aneurysm of the aorta formed in the main artery. The stent and stent graft of the present invention have a configuration that remarkably improves safety and conformity in or to a treatment site of a patient or during the delivery to the treatment site in an artery, etc., and the performance of stable anchoring in a diseased part for a long period of time. TECHNICAL BACKGROUND There are many duct-like organs such as a blood vessel, a biliary tract, a urinary tract, a digestive tract, and the like. These duct-like organs may be caused to have characteristic diseases such as a stricture, occlusion, dilation, or the like due to respective various causes. For example, the blood vessel may be caused to have stenosed diseases such as a stricture and occlusion or dilative diseases such as an aneurysm of the aorta and a varix. Particularly, the aneurysm of the aorta refers to the abnormal dilation of weakened arterial wall caused by hardening or inflammation of the main artery, and it is a critical disease wherein the arterial wall, if left untreated, is gradually dilated from the pressure of a blood flow, and the swelling wall can no longer resist the blood pressure to burst. It therefore requires an immediate treatment or procedure for preventing the bursting and bleeding. In recent years, a tubular device made of a metal called a stent is often used when an abnormal stenosed part or dilated part of a blood vessel is treated, since no excess invasion such as a surgical operation is required. For example, when an aneurysm of the aorta is treated, the treatment is conducted in such a manner that a stent graft, a device, obtained by covering the above mentioned stent with a tubular member made of a synthetic resin, is used as an artificial blood vessel, and the stent graft is placed within the aneurysm to allow the blood to flow inside the artificial blood vessel, so that the blood pressure is not exerted directly on the swelling wall. As a stent, conventionally, some types of stents have been provided. Of these, there is used a tubular device obtained by bending a linear material (wire) made of a metal typified by stainless steel to form zigzag patterns, forming the top portion thereof into the form of a curve or curved line, connecting both ends of the linear material to form it into an annular unit, arranging such annular units in series and connecting them with connection struts. It is also another practice to constitute a tubular device from a metal mesh. For example, when the stent is anchored or placed in a treatment site (diseased part), the stent or stent graft generally inserted in a sheath is restrained, diameter-contracted and loaded into a delivery kit such as a pipe-like cylindrically formed catheter through the inside of which a guide wire is placed. It is introduced into a blood vessel from an incision of a peripheral artery of joint of a leg along the guide wire and delivered to a treatment site such as an aneurysm of the aorta, and when it reaches the treatment site, the above delivery kit is released to remove the contraction of the stent or the like. The stent released from the contraction expands in diameter by itself, and in this state, it is placed or left in a diseased part inside the blood vessel thereby to protect the blood vessel. However, it has been found that the above conventional stent or stent graft (to be sometimes simply referred to as “stent or the like” hereinafter) has the following problems. (1) The above mentioned stent or the like is basically formed of a tubular body made of a linear metal framework before it is inserted in a sheath. The stent or the like of the above type is to some degree improved in conformity after inserted in a diseased part, by means of design change on configuration or form of the metal framework as required. However, it is composed of a linear tubular body as a basic structure, it exhibits poor conformity to a bent portion of the main artery, so that the deformation of the stent and the damage of the blood vessel are liable to be produced with the passage of time or after a long period of time. (2) Meanwhile, with a stent graft of a metal mesh type which is manufactured to gain improved flexibility, to be sure, it shows good flexibility and improved conformity. However, the problem is that when the stent is diameter-contracted, the total length thereof increases accordingly, thereby making its positioning for placing the same in the diseased part difficult, the stent-placed position moves or drifts after a long period of time following an operation, or the stent is liable to suffer a structure change with the passage of time, such as deformation, etc., caused by the expansion of the stent toward an aneurysm side. (3) Further, in case of a tubular body stent formed by connecting annular units having the same diameter and the same number of zigzag patterns, there is no problem to be in the form of a straight line so long as it is not bent. When it is bent, however, from the form of a straight line to a curved form, all of central curved portions nearly face or oppose to each other, or central curved portions and inside spaces between curved portions face or opposed to each other, on the inside of curved line R of the stent. Therefore, i) when the central curved portions of adjacent annular units of a stent face each other, and when the stent is bent, the central curved portions on the inside of the curved line R of the stent overlap and touch each other, so that the stent comes to have difficulties in keeping flexibility and durability. ii) on the other hand, when the central curved portion of an annular unit of a stent and the inside space of the curved portion of an adjacent unit of the stent face each other, and when the stent is curved, the connection portion and the generally straight line portion are not aligned in generally straight line, so that the stent is liable to be kinked when the annular units connected in the form of a curve are contracted or are restored from contraction, and the stent is liable to be deformed with the passage of time. Thus the prior stent formed by arranging annular units composed of zigzag patterns each and connected in a linear structure is, in principle, not suitable for bending to make a curved form as described above. (4) There may be employed a constitution in which the connection portion between the annular units is so arranged to have a larger length than the generally straight line portion that the zigzag patterns do not overlap and touch. However, in this constitution, undesirably, the connection portion may be kinked or suffer torture after a long period of time, or the above constitution may result in insufficient expansion force of the connection portion against a diseased part. In the light of importance of the above problems of the conventional stent, etc., particularly, for providing a stent that is remarkably improved in safety and conformity during delivery within an artery, or the like, and with the performance of stable anchoring or placing at a diseased part for a long period time, the present inventors have made diligent studies and as a result have arrived at the present invention. DISCLOSURE OF THE INVENTION The present invention has been made from the above viewpoint, and according to the present invention, the following invention is provided. [1] A stent 1 formed in the shape of a generally tubular body, said tubular body having a central axis C, said stent having a spring function with which said tubular body being diameter-contractible toward the central axis C of said tubular body, said tubular body being expandable to the initial diameter after contraction, the stent being loaded and housed in a sheath and being delivered to a diseased part to be treated, wherein (A) said stent 1 maintaining a configuration curved along the longitudinal direction of said stent when the stent is not inserted in the sheath, (B) said stent 1 is being contracted toward the central axis (C) of the stent 1 and is being elongated in the form of a generally straight line along the longitudinal direction of the stent 1 when the stent 1 is inserted into said sheath, whereby the stent 1 is being loaded and housed in the sheath in the form of a generally straight line, and (C) said stent 1, being housed in the sheath in the form of a generally straight line, is being inserted into a diseased part together with the sheath, is being released from the sheath, and radially expanding outwardly after release, to restore and maintain the configuration curved along the longitudinal direction of the stent. [2] The stent 1 as recited in [1], wherein the stent 1 comprises generally V-letter-shaped zigzag patterns 7 having at least one central curved portion 8, 8A, 8B and generally straight line portions 6, 61, 62, 63, 64 substantially same in length on both sides thereof, the zigzag patterns 7 being formed by repeatedly bending a portion between two ends of a wire base material made of a metal, a plurality of said zigzag patterns 7 are being arranged to surround the central axis C of the stent 1, an annular unit 4A, 4B is being formed by bonding end portions of said wire metal at least in one portion, and a plurality of such annular units 4A, 4B are being constituted, a plurality of said annular units 4A, 4B constituted are being arranged in series in the longitudinal direction (central axis direction) of the stent 1, said annular units 4A, 4B adjacent to each other are being connected to each other with connection struts having substantially the same lengths S each at least in two portions, the struts forming connection portions 5, 5A, 5B, and said generally straight line portions 6, 61, 62, 63, 64 are being formed at a connection angle (θ) of 0°±30° with said connection portions. [3] The stent 1 as recited in [1] or [2], wherein said strut having at least one annular unit 4A, 4B having an odd number of the zigzag patterns 7 and at least one annular unit 4A, 4B having an even number of the zigzag patterns 7. [4] The stent 1 as recited in any one of [1] to [3], wherein the annular units 4A, 4B having an odd number of the zigzag patterns 7 and the annular units 4A, 4B having an even number of the zigzag patterns 7 are being disposed to be adjacent to each other and arranged alternately along the longitudinal direction of the stent 1. [5] The stent 1 as recited in any one of [1] to [4], wherein, in a state where the stent 1 maintains a configuration curved along the longitudinal direction of the stent 1, at least 1 to 4 central curved portions 8, 8A, 8B constituting the zigzag patterns 7 and at least 1 to 4 central curved portions 8, 8A, 8B constituting the zigzag patterns 7 are arranged to be substantially opposed to each other between two connection portions 5, 5A, 5B between two annular units 4A, 4B when viewed from the outermost curved line R side of the stent 1, and the central curved portions 8, 8A, 8B of the zigzag patterns 7 constituting one of the annular units 4A, 4B adjacent to each other and inside spaces 9 of the zigzag patterns 7 of the other of the annular units 4A, 4B are being disposed so that said central curved portions 8, 8A, 8B and inside spaces 9 are substantially facing each other when viewed from the innermost curved line R′ side of said stent 1. [6] The stent 1 as recited in any one of [1] to [5], wherein the connection portions 5, 5A, 5B are of a straight line or a curved line each. [7] The stent 1 as recited in any one of [1] to [6], wherein the connection portion 5, 5A, 5B having a length s, the generally straight line portion 6, 61, 62, 63, 64 having a length L, and the connection portion 5, 5A, 5B and the generally straight line portion 6, 61, 62, 63, 64 having a ratio of length φ (=S/L) of 0.1 to 2.0. [8] The stent as recited in any one of [1] to [7], wherein the central curved portion 8, 8A, 8B having the form of generally R or a ring. [9] The stent 1 as recited in any one of [1] to [8], wherein the generally tubular body under no load is being contracted in diameter by 20% to 90% when said tubular body is inserted into a diseased part. [10] The stent 1 as recited in any one of [1] to [9], wherein a pipe unit having at least one of functions for reinforcement, marker protection and sustained release of a drug is being fitted to the wire base material made of a metal constituting the tent. [11] A stent graft formed by covering the stent 1 recited in any one of [1] to [10] with a tubular member 12 made of a synthetic resin. [12] A stent A′ in the form of a generally tubular body comprising generally annular units 2′ formed by bonding end. portions of a stent main line 1′ made of a metal line wire base material formed in a zigzag form and connection struts 4′ connecting said annular units 2′ in series, wherein a pipe unit 3′ being fitted to a changed portion of the stent main line 1′ and/or the connection strut 4′ in said annular unit 2′ and fixed to said stent main line 1′, or a pipe unit 5′, 7′ being fitted to that portion of the stent main line 1′ which is being provided with an element different from the stent main line 1′ and/or the strut 4′ in said annular unit 2′, thereby causing the stent to exhibit at least one of functions for reinforcement, marker protection and sustained release of a drug. [13] A stent graft comprising the stent A′ as recited in [12] and a tubular member 12′ made of a synthetic resin covering said stent A′. BRIEF DESCRIPTION OF DRAWINGS FIGS. 1 to 7 are drawings showing the stent and stent graft of the present invention. FIG. 1(A) is a schematic drawing (plan view) of the stent of the present invention, and FIG. 1(B) is a partial enlarged view of the zigzag patterns 7. FIG. 2 is a plan view obtained by viewing the stent in FIG. 1 from X side. FIG. 3 is a plan view obtained by viewing the stent in FIG. 1 from Y side. FIG. 4 is a partial enlarged view showing one embodiment of the connection between the connection portion 5 and each substantially straight portion 6 of the stent of the present invention. FIG. 5 is a schematic drawing showing the state wherein the stent graft of the present invention is contracted. FIG. 6 is a schematic drawing showing a state wherein the stent graft of the present invention is inserted in a sheath 10 having a curved form at the forward end. FIG. 7 is a schematic drawing showing a state wherein the stent graft of the present invention is inserted in a sheath 20 having a straight line form at the forward end. In FIGS. 1 to 7, 1 indicates a stent, 3 indicates a bonded portion, 4A, 4B, 4C, 4D and 4E indicate annular units, 5, 5A and 5B indicate connection portions or connection struts, 6, 61, 62, 63 and 64 indicate substantially straight line portions, 7 indicates zigzag patterns, 8, 8A and 8B indicate central curved portions, 9 indicate an inside space of the zigzag pattern, 10 and 20 indicate sheaths, 11 indicates a stent graft, 12 indicates a tubular member made of a synthetic resin or a graft, θ indicates a connection angle (formed between the substantially straight line portion and the connection portion), and θ1, θ2 and θ3 indicate angles between annular units. FIGS. 8 to 12 are drawings showing another embodiment of the stent and stent graft of the present invention. FIG. 8 is a drawing for explaining a stent formed by connecting two annular units with connection struts. FIG. 9 is a drawing for explaining a structure of welded portion of the stent main line. FIGS. 10(a) and 10(b) are drawings for explaining a state wherein an X ray impermeable portion 6 is protected with a pipe unit 5′. FIGS. 11(a), 11(b) and 11(c) are drawings for explaining a state wherein a pipe unit charged with a drug and sealed is attached. FIGS. 12(a) and 12(b) are drawings for explaining a state where a hook is connected to the stent main line with a pipe unit. In FIGS. 8 to 12, A′ indicates a stent, 1′ indicates the stent main line, 1a′ indicates a welded region, 1b′ and 1c′ indicate regions adjacent thereto, 1d′ indicates a top portion, 2′ indicates an annular unit, 3′ indicates a pipe unit for reinforcement, 4′ indicates a connection strut, 5′ indicates a pipe unit for protection, 6′ indicates an X ray impermeable portion, 7′ indicates a pipe unit for sustained release of a drug, or the like, 7a′ indicates a hole portion, 8′ indicates a drug or the like, 10′ indicates a guide wire, 11′ indicates a hook, 12′ indicates an annular member or graft made from a synthetic resin, 13 indicates a sheath, 14′ indicates a dilator, and 14a′ indicates a notched portion. BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be explained in detail with reference to the drawings hereinafter. FIGS. 1 to 4 show the stent of the present invention, and the present invention will be explained first with reference to these drawings. FIG. 1(A) is a schematic drawing (plan view) that conceptually shows the stent 1 of the present invention, and it shows the form of the stent of the present invention in a load-free state, that is, in a stationary state. FIG. 1(B) is a partially enlarged view of a zigzag pattern 7. FIG. 2 is a plan view of the stent viewed from X side in FIG. 1, and there is shown one embodiment viewed from the outermost curved line R side of the stent 1, in which two central curved portions 8A of an annular unit 4A constituting zigzag patterns 7 and two central curved portions 8B of an annular unit 4B constituting zigzag patterns 7 are arranged between connection portions 5A and 5B of the two annular units 4A and 4B adjacent to each other, that is, the central curved portions 8A and 8B are arranged between the connection portions 5A and 5B in a state where they are opposed to each other. FIG. 3 is a plan view of the stent 1 viewed from Y side in FIG. 1, and there is shown one embodiment viewed from the innermost curved line R′ of the stent 1, in which the central curved portions BA or 8B of the zigzag patterns 7 of the two annular units 4A and 4B and inner spaces 9 of the zigzag patterns 7 are so arranged that they are substantially opposed to each other (they face each other with a close distance between them). FIG. 4 is a partially enlarged view showing one embodiment of connection of the connection portion 5 (5A, 5B) and generally straight line portions 6 (61, 62, 63, 64). The basic idea of design of the stent 1 of the present invention is as follows. That is, the stent is a stent 1 formed in the shape of a generally tubular body, said tubular body having a central axis C, said stent 1 having a spring function with which said tubular body is diameter-contractible toward the central axis C of said tubular body, said tubular body being expandable to the initial diameter after contraction, the stent 1 is to be loaded and housed in a sheath (sheath member) and is to be delivered to a diseased part to be treated, wherein (A) said stent 1 maintains a configuration curved along the longitudinal direction of said stent 1 as shown in FIG. 1(A) when the stent 1 is not inserted in the sheath, that is, in a stationary state, and (B) when the stent 1 is inserted into said sheath, the stent 1 is contracted toward the central axis C of the stent 1 and is elongated in the form of a generally straight line along the longitudinal direction of the stent 1, whereby the stent 1 is loaded and housed in the sheath, in the form of a generally straight line, or in a curved form as required, as shown in FIGS. 5 and 6, particularly, at the forward end of the sheath, and (C) said stent 1, housed in the sheath in the form of a generally straight line, is being inserted, together with the sheath, into a diseased part, and being released from the sheath, and radially expands outwardly after release, to restore and maintain the curved configuration along the longitudinal direction of the stent, said curved configuration being the stationary state. In the annular units 4A, 4B and (4C, 4D and 5E) constituting the stent 1 of the present invention, that portion of a wire base material (stent main line) made of a metal which is located between two ends thereof is repeatedly bent to form substantially V-letter-shaped zigzag pattern(s) 7 having at least one central curved portion 8, 8A, 8B and generally straight line portions 6, 61, 62, 63, 64 having substantially the same lengths each on both sides of said central curved portion 8, 8A, 8B, a plurality of such zigzag patterns 7 are cylindrically arranged to surround the central axis C of the stent 1, and each annular unit is formed by bonding and fixing in at least one portion (e.g., portion 3 shown in FIG. 3) of said wire base material made of a metal by known means such as welding, brazing, calking, or the like. The stent 1 of the present invention has a constitution in which a plurality of the thus-formed annular units 4A, 4B are arranged or extended from one to the other in the longitudinal direction of the stent 1 (that is, in the direction of central axis C) and said adjacent annular units 4A and 4B are connected at least in two portions with connection portions (connection struts) having substantially the same lengths each. The stent 1 of the present invention can give a three-dimensionally curved or bent shape, according to the form of blood vessels, as shown in FIG. 11 by shifting positions of the above connection portions 5, 5A, 5B between the annular units 4A and 4B. In the stent 1 of the present invention, the above generally straight line portion 6 (61, 62, 63, 64) is connected to the above connection portion 5 (5A, 5B) at a connection angle θ of 0°±30° as shown in FIG. 4, for readily adjusting the curve angle as required. The above connection angle θ refers to an angle formed between an extending line from the connection portion and the generally straight line portion. In an embodiment shown in FIGS. 1 and 2, for example, the generally straight line portion 6, 61, 62, 63, 64 adjacent to the left or right side of the connection portion 5, 5A, 5B is connected in the form of a generally straight line (i.e., at a connection angle of 0°). However, when the generally straight line portions 6 are connected symmetrically with regard to the connection portion 5 at a connection angle that is not 0°](−20° to +20°, θ≠0°) as shown in FIG. 4, the curve angle can be adjusted in the connection portion 5, 5A, 5B with a higher degree of freedom, which is more effective against kinking that occurs after a long period of time. FIG. 4 shows an embodiment in which the connection portion 5 and the generally straight line portion 6 are connected to each other at a connection angle θ of 8°. While the connection portion 5, 5A, 5B in FIGS. 1 and 2 is shown as a straight line, the connection portion shall not be limited thereto, and it may be a curved line. The above curved line stands for a line having at least one curved portion and includes a substantially S-letter-shaped line. For connecting the annular unit and the connection portion, specifically, the connection portion 5, 5A, 5B and the generally straight line portion 6, 61, 62, 63, 64 are bonded to each other by known bonding means such as welding, brazing (welding), calking, or the like. When calking is employed, the connection may be made by calking with a pipe unit to be described later. In the stent 1 of the present invention, the central curved portion 8, 8A, 8B is formed in the form of a substantial R as shown in FIGS. 1 to 3 (or as shown in FIGS. 8 and 10 to be discussed later), while it may be formed in some other form such as a ring or the like. In the stent 1 of the present invention, adjacent annular units are connected to each other with at least two connection portions 5, 5A, 5B above, and these connection portions are disposed (arranged) with a space between them. That is, as shown in FIGS. 1 and 2, the annular units are arranged with a space of at least one central curved portion 8, 8A, 8B (generally a space of 1 to 4 central curved portions) constituting the above zigzag patterns 7. For example, FIG. 2 shows an embodiment in which the annular units 4A and 4B are connected with the connection portions 5A and 5B, and it can be understood that two central curved portions 8A and two central curved portions 8B are arranged or placed between the connection portions 5A and 5B. The above point will be explained further in detail. In an embodiment of the stent 1 of the present invention as shown in FIG. 1, five annular units 4A, 4B, 4C, 4D and 4E are connected with connection portions 5A, 5B. With the connection of annular units 4B and 4C, three central curved portions 8A and three central curved portions 8B are arranged between connection portions 5A and 5B (n3=3) (calculated on the basis of the configuration that two central curved portions 8A and two central curved portions 8B are arranged between 4A and 4B as described above). With the connection of the annular units 4C and 4D, two central curved portions 8A and two central curved portions 8B are arranged (n2=2) like 4A and 4C, and with the connection of annular units 4D and 4E, one central curved portion 8A and one central curved portion 8B are arranged (n1=1). As shown in FIG. 1, the stent 1 of the present invention has a configuration curved along the longitudinal direction thereof. Accordingly, angles (θi′) at which those lines of the annular units constituting the stent, drawn in the radius directions of the stent, cross each other, increases with an increase in the number (ni) of the central curved portions 8A, 8B arranged between the connection portions 5A and 5B, that is, n1<n2<n3, and thereby the relationship of θ1<θ2<θ3 holds. As described above, by adjusting the angles (θi) and the number (ni), the degree of curve angle (degree of curvature) of the above adjacent annular units 4A and 4B. (4C, 4D, 4E) in the longitudinal direction of the stent can be adjusted, wherein the angles (θi) are the angles at which those lines of the annular units constituting the stent which are drawn in the radius directions of the stent cross each other and the number (ni) is the number of the central curved portions 8A, 8B arranged between the connection portions 5A and 5B. Further, FIG. 1 shows the case wherein the connection portions 5 having the same lengths each, the degree of curve angle (degree of curvature) of the above adjacent annular units 4A and 4B (4C, 4D, 4E) in the longitudinal direction of the stent can be adjusted by changing the length of connection portions 5, 5A and 5B. While the ratio φ (=S/L) of the length S of the connection portion 5, 5A, 5B to the length L of the generally straight line portion 6, 61, 62, 63, 64 is made and shown as approximately 0.4 in FIG. 1, the above ratio is preferably made in the range of 0.1 to 2.0. When the ratio φ is less than 0.1, it is difficult to adjust the angles between the annular units 4, 4A and 4B. When the length ratio φ exceeds 2.0, undesirably, the stent may produce kinking after a long period of time or the expansion strength of the connection portions 5, 5A and 5B decreases. In the stent 1 of the present invention, the number of the zigzag patterns may be changed as required for improving the stent in flexibility. Preferably, at least one annular unit 4A, 4B having an odd number of the zigzag patterns 7 and at least one annular unit 4A, 4B having an even number of the zigzag patterns 7 are provided, and these are combined as required for constituting the stent 1. Preferably, in particular, the annular units 4A, 4B having an odd number of the zigzag patterns 7 and the annular units 4A, 4B having an even number of the zigzag patterns 7 are arranged to be adjacent to each other and alternately placed in the longitudinal direction of the stent 1. Specifically, for example, one of the above annular units 4A and 4B adjacent to each other is constituted of an odd number (e.g., 7, 9, 11 or the like) of the zigzag patterns 7, and the other is constituted of an even number (e.g., 8, 10, 12 or the like) of the zigzag patterns 7. Further, preferably, the annular units 4A, 4B having both an odd number (7, 9, 11) of the zigzag patterns 7 and the annular units 4A, 4B having both an even number (8, 10, 12) of the zigzag pattern 7 are alternately arranged along the longitudinal direction of the stent 1. In the stent 1 of the present invention, contact of the zigzag patterns of the adjacent annular units can be prevented and arranged to overlap during expansion, so that a sharp curved configuration can be secured. The reason therefor is as follows. As shown in FIGS. 1 to 3, when the stent 1 is viewed from the outermost curved line R side of the stent 1 in a state where the stent 1 has a configuration curved in the longitudinal direction of the stent 1, 1 to 4 central curved portions 8, 8A, 8B constituting the zigzag patterns 7 are arranged between the two connection portions 5, 5A, 5B between the annular units 4A and 4B adjacent to each other and are opposed to each other (see FIG. 2, when the FIG. 1 is viewed from the X side), and on the other hand, the central curved portions 8, 8A, 8B of the zigzag patterns 7 constituting one of the annular units 4A and 4B adjacent to each other and the inside spaces 9 of the zigzag patterns 7 constituting the other are arranged substantially to be opposed to each other when the stent 1 is viewed from the innermost curved line R′ side of the stent 1 (see FIG. 3, when FIG. 1 is viewed from the Y side). The stent of the present invention is thus constituted, the zigzag patterns 7 can overlap, without contacting, the adjacent zigzag patterns 7 during expansion, and the configuration of the curved line R can be adjusted to take a sharper curve. From the above viewpoint, in the stent 1 shown in FIG. 1, the annular units 4A, 4B, 4C, 4D and 4E having respectively, 9, 10, 9, 10 and 9 zigzag patterns 7 are connected. FIG. 1 to 3 show an embodiment of the stent 1 of the present invention in which annular units 4A, 4B having an odd number of the zigzag patterns 7 and annular units 4A, 4B having an even number of the zigzag patterns 7 are adjacent to each other and arranged alternately in the longitudinal direction of the stent 1 as described above for forming a structure of the stent more adaptable to the curved portion of a diseased part, that is, an arrangement pattern of odd number • even number • odd number • even number • • • is made. The other arrangement pattern may also be employed. For example, when a diseased part (blood vessel) includes a diseased part (blood vessel) having the form of a straight line or a generally straight line, there can be preferably employed an arrangement pattern of odd number • odd number • • • and/or even number • even number • • •, or the like for that part. Preferably, the stent 1 of the present invention is formed such that the ratio (contract ratio) of the contracted diameter of the generally tubular body, when inserted to a diseased part such as an aneurysm, or the like to the unloaded diameter of the generally annular body is between 20% to 90%. In a diseased part (blood vessel), the stent of the present invention is thus diameter-contracted as required thereby to exert a higher radial force against a diseased part, so that the initial leak of blood to a swelling wall, including the leak immediately after the treatment, can be reliably stopped. When the contract ratio is too large (less than 20%), or too small (over 90%), undesirably, the above desired radial force is not exerted. The metal wire base material for forming the stent 1 of the present invention is not specially limited, and the stent 1 is formed from a wire made of a metal generally used, such as stainless steel such as SUS316L or the like, a superelastic alloy such as a Ti—Ni alloy or the like, titanium, a titanium alloy, tantalum, a tantalum alloy, platinum, a platinum alloy, tungsten, a tungsten alloy, or the like. The stent made of any one of the above metals may be surface-coated with biocompatible polymer materials such as polyurethane, polyvinyl pyrrolidone, polyvinyl alcohol, or the like, with physiologically active substances such as heparin, urokinase or the like immobilized to the above coated polymer materials by chemical bonding, or with antithrombotic drugs such as argatroban, cilostazol, sarpogrelate HCl, or the like mixed to the above coated polymer materials. The stent graft constituted of the above stent, provided by the present invention, will be explained with reference to FIGS. 5 and 6 hereinafter. The stent graft 11 of the present invention comprises the stent 1 and a tubular member 12 made of a synthetic resin, wherein the stent being covered with the tubular member 12. Like the stent 1, the stent graft 11 is used for repairing a blood vessel damaged by a stenosis, an aneurysm or the like or used as a replacement for a hollow organ. FIG. 5 is a schematic drawing of the stent graft 11 of the present invention, and it shows a state wherein the stent 1 shown in FIG. 1 is contracted to a size, the size with which the stent 1 inserted in a diseased part, and the stent 1 is circumferentially covered with a tubular member 12 (also called “graft”) (indicated by a dotted line) made of a synthetic resin. FIG. 6 is a schematic drawing showing a state where the stent 1 is loaded into a sheath 10 having a curved forward end, and FIG. 7 is a schematic drawing showing a state wherein the stent 1 is loaded in a sheath 20 having a straight-line forward end. (In addition, the tubular member (graft) made of a synthetic resin is fitted to the outside of the stent 1 and is diameter-contracted in conformity with the form of the stent 1, while FIGS. 6 and 7 omit showing its diameter-contraction). Specifically, the stent graft 11 can be manufactured by covering the above stent 1 with the tubular member 12 made of Dacron (polyethylene terephthalate fiber, E.I. du Pont de Nemours and Company, trade name), a film made of a fluorine resin (PTFE: polytetrafluoroethylene), or the like. In one embodiment of the stent graft, for example, a stent having a diameter of 40 mm under no load is provided and contracted to 30 mm (75%), a tubular member made of Dacron, having a diameter of 31 mm, sutured at end portion and any portion with a suture thread is covered and fixed on/to the above stent, whereby the stent graft 11 can be manufactured. In the stent graft 11 of the present invention, the stent 1 that has a spring function and has good flexibility is covered with the tubular member 12 made of a synthetic resin in the form of a fiber or a film, so that the stent graft 11 can conform, as a stent graft, to the three-dimensional curve of a blood vessel as required. While the annular units 4A, 4B of the stent 1 shown in FIGS. 1 to 3 have the same diameter each, both ends of the stent 1 may have different diameter(s) depending upon a diseased part (blood vessel). In this case, desirably, annular units 4A, 4B having different diameters each are combined in conformity with the form of a diseased part (blood vessel), and the stent graft 11 is manufactured in conformity with the form thereof. For example, when two ends of a diseased part have different diameters, the stent graft 11 can be adapted thereto by bringing the diameters of the annular units 4A, 4B forming both ends thereof into conformity with the form of the diseased part (blood vessel). According to the stent, etc., of the present invention explained in detail hereinabove, the stent is designed initially and normally to be in a curved state easily adaptable to a curved blood vessel in a diseased part, so that there can be provided the stent 1 having excellent conformity to a curved portion of the main artery of a patent. Further, the stent, etc., of the present invention can have a curved form without increasing the length of the connection portion 5, 5A, 5B between the annular units 4A and 4B, and it does not easily undergo kinking or deformation, so that it does not move even when it is anchored or left in a diseased part for a long period of time. For the stent, etc., of the present invention, some combinations of diameters of the annular units 4, 4B and the zigzag patterns 7 are prepared or stored in advance. Consequently, then, there can be manufactured the appropriate stent 1 wherein selection with regard to positions of the annular units 4A, 4B and the connection portions 5, 5A, 5B are made as required depending upon the targeted diseased part, thereby preferable stent 1 usable for an acute or subacute case of disease can be readily provided. The basic embodiment of the stent, etc., of the present invention has been explained hereinabove. Other working embodiment of the present invention will be explained with reference to drawings hereinafter. FIGS. 8 to 11 are drawings showing a stent in which a pipe unit that exhibits the function of reinforcement, sustained release of a drug, or the like is fitted to the stent main line made of a metal line wire base material. FIG. 8 is a drawing for explaining a state wherein two annular units are connected to each other with connection struts to form a stent and the connected stent is provided with pipe units. FIG. 9 is a drawing for explaining a structure of a welded portion as a change in the stent main line. FIG. 10 is a drawing for explaining a state wherein an X ray impermeable portion is protected with a pipe. FIG. 11 is a drawing for explaining a state wherein a pipe charged with a drug and sealed is attached. FIG. 12 is a drawing for explaining a state wherein a hook is connected to the stent main line with a pipe. The other working embodiment of the present invention has a characteristic feature in that a pipe unit is fitted to the stent main line to cause the stent to exhibit the various functions of reinforcement, sustained release of a drug, and the like. The targeted stent, to which the pipe unit for imparting the above functions is most effectively applied, is naturally, and in the first principle, to the stent having a curved configuration in the longitudinal direction in a stationary or normal state as shown in FIG. 1. However, the technical feature or idea thereof is not limited thereto and can be applied to a more general stent. The following explanation therefore includes an explanation with regard to a general stent. That is, the stent with a pipe unit, provided by the present invention, is a stent A′ that is generally a tubular body comprising generally annular units 2′ formed by bonding end portions of a stent main line 1′ made of a metal line wire base material formed in a zigzag form and connection struts 4′ connecting said annular units 2′ in series, wherein a pipe unit 3′ being inserted and fitted to a changed portion of the stent main line 1′ and/or the connection strut 4′ in said annular unit 2′ and fixed to said stent main line 1′, or wherein a pipe unit 5′, 7′ being fitted to that portion of the stent main line 1′ which is provided with an element different from the stent main line 1′ and/or the strut 4′ in said annular unit 2′, thereby causing the stent to exhibit at least one of functions for reinforcement, sustained release of a drug and marker protection. The above mentioned change of the stent main line, etc., includes a change in diameter and a change in structure, and for example, it means that site of the stent main line or the strut, at which site its diameter is reduced, for connection of strut to the stent is to be arranged along the stent main line, and a portion or site that comes to have coarse-particle-structure due to heat or thermal effect caused by welding both ends of the stent main line or welding end portions of the stent main line and that of the strut. The pipe unit is arranged and fixed to the above site for reinforcement as will be described later. Further, the element different from the stent main line, etc., means solid substances such as an X ray impermeable portion (X ray imaging marker such as a plating, a foil, etc.) formed in the stent main line or the connection strut, or a solid drug. The pipe unit is arranged and fixed so as to be opposed or faced thereto as will be described later, so that it can prevent a plating or foil constituting the above X ray impermeable portion from coming off, and that it can prevent these substances from entering in blood stream even when the substances come off. The stent A′ shown in FIG. 8 is formed of annular units as described already. Specifically, the stent main line (wire base material made of a metal) 1′ is bent in a predetermined zigzag form (zigzag patterns), and both ends of the stent main line 1′ are faced and bonded to each other by welding to form an annular unit (which is, sometimes referred to as “loop”) 2. A pipe unit 3′ for reinforcement is arranged in the above welded portion to reinforce it, further, a plurality of such annular units 2′ (two annular units here) are arranged in series, at least two connection struts 4′ and 4′ are disposed between the adjacent annular units 2′, the adjacent annular units (stent main lines thereof) are fixed and connected with the above connection struts 4′ preferably by welding, and the welded portions are reinforced with pipe units 5′. There may be employed a constitution wherein the connection strut 4′ and the stent main line 1′ of the annular unit is connected to each other by calking with the pipe unit 5′. As the stent main line 1′, there is used a material such as generally provided austenitic stainless steel or a wire material of SUS316L particularly provided as a stainless steel for implants as described already. And these stainless wire material materials are subjected to cold wire drawing so that the structure thereof is extended in the form of fibers (fibrous structure), thereby causing the material to exhibit work hardening to improve its mechanical properties. The stent formed of the above material has excellent biocompatibility and has proper expandability, and, therefore, when it is released from the sheath in an intended diseased part, it easily restores the initial form. Further, the above material has strong resistance against age-deterioration, so that it is suitable for anchoring or leaving the stent in a diseased part in a human body for a long period of time. In the present invention, the annular unit is formed by bonding end portions of the stent main line (wire base material made of a metal) made of stainless steel having excellent properties to each other by welding. In this case, however, the following problem of a decrease in the strength of the welded portion can occur. That is, FIG. 9 is a drawing for explaining a change in the structure of metal in the welded portion of the stent main line when the end portions of the stent main line 1′ formed in a zigzag form are cause to face each other and resistance-welded to form the annular unit. As shown in this Figure, in a welded region 1a′ formed mainly of butt ends, the metal structure is caused to be coarse due to welding heat and comes to be granulated, and the strength thereof as a wire base material of the stent main line is greatly decreased. Further, regions 1b′ and 1b′ outside the above area are affected by the welding heat to some extent, so that the metal structure thereof is caused to granulate, and a decrease in strength also occurs in these regions. Regions 1c′ and 1c′ outside them are regions that do not substantially suffer the heat effect of welding, and the original structure in the form of extended fibers remains intact and maintains the strength inherent to the wire base material. In the present invention, therefore, a pipe unit 3′ is arranged, for reinforcement, in those portions of the welded portion of the stent main line 1′ which include the welded region 1a′ as a center and the regions 1b′, 1b′, which suffer a relatively large decrease in strength as: compared with the areas 1c′, 1c′, thereby securing the strength inherent to the annular unit 2′. Specifically, the pipe unit 3′ that has a length capable of covering at least the region 1a′ up to the regions 1c′, 1c′ on both sides thereof is inserted and fitted to the stent main line 1′ as shown in FIG. 9, and in this position, both end portions of the above pipe unit 3′ are calked to fix and integrate the pipe unit 3′ to/with the stent main line 1. The above pipe unit 3′ for reinforcement, thus applied, can reinforce that site of the metal structure which is decreased in strength by suffering from the welding heat. The size (length) of the welded region 1a′ and the regions 1b′ in the annular unit 2′ is not uniquely determined and takes a value that differs depending upon the diameter of the stent main line 1′ used. However, the above length is not so great, and in any case, it is on the unit of several millimeters at the greatest. For example, when the stent main line 1′ has a diameter of approximately 0.45 mm, generally, the total length of the region 1a′ and the regions 1b′ is approximately 0.7 mm. It is therefore sufficient that the pipe unit 3′ has a length of approximately 1 mm. Practically, however, the pipe unit 3′ may have a length of 7 mm by taking into account of a calking margin, and it is practical to use a cylindrical pipe having an outer diameter of approximately 0.65 mm and an inner diameter of approximately 0.46 mm. While the material of the pipe unit 3′ is not specially limited, it is preferred to use a pipe made of the same material as that of the stent, such as SUS316L provided as a stainless steel for implants, since it is anchored or left in a diseased part together with the stent for a long period of time. As described above, according to the present invention, for example, an austenitic stainless steel having an extended fibrous structure, or the like, is used for the stent main line 1′, and the pipe unit 3′ for reinforcement is arranged and calked in a welded site of the annular unit 2′ formed by welding end portions of the stent main line 1′, whereby reinforcement can be made with the welded site of the above annular unit. Meanwhile, when the stent is to be formed, the annular units are connected with the connection unit, and welding is also employed therefor, so that the same problem as above arises. Therefore, the connection portion (welded portion) of the annular unit and the connection member (connection strut) can be reinforced with a pipe unit 5′ as shown in FIG. 8. The pipe unit 5′ for reinforcement, which is to reinforce the connection portion (welded portion) of the stent main line 1′ constituting the annular unit 2′ and the connection strut 4′, is inserted and fitted to the stent main line 1′ after the stent main line 1′ is formed into the zigzag patterns but before the end portions are welded (before the annular unit is formed). It is therefore required to pass the pipe unit 5′ through the peak portion(s) (central curved portions) 1d, of the zigzag pattern(s). The above portion 1d′ has the form of generally or substantially R or a ring as shown in FIG. 10. Preferably, the pipe unit is designed to have such small dimensions that said pipe unit can easily pass through the above peak portion 1d′ with regard to its length, and a plurality of such pipe units 5′ (generally, about 3 pipe units) are arranged in each connection portion. Generally, the pipe unit 5′ is preferably designed to have a length that is three times as long as the diameter of the stent main line 1′ or less. According to the present inventors' finding, when the stent main line 1′ has a diameter of 0.45 mm, and if the pipe unit 5′ has a length of approximately 0.98 mm, working can be most smoothly carried out. On the other hand, it has been found that if the length is smaller than 0.5 mm, it is difficult to secure smooth workability. Then, the pipe unit is fitted to that portion of the stent main line of the stent A′ at which is to be provided with the element different from the connection strut, the different element being such as a drug or an X ray imaging marker, thereby the stent A′ can perform the above function for marker protection, sustained release of a drug, or the like. In the present invention, the stent is delivered to a diseased part (blood vessel) while monitoring the stent position, it is preferred to form an imaging marker such as an X ray impermeable portion 6′ or the like at some part of the stent main line 1′. For obtaining a clear X ray contrast image, a metal material or inorganic material, an X ray impermeable material having a specific gravity of 8 or more, is caused to adhere or fixed to part of a long line of a zigzag pattern, a foil thereof is attached thereto, or a thin film thereof is formed thereon, as a marker. Examples of the above X ray impermeable material (marker material) include gold, silver, platinum, tungsten, barium, molybdenum, tantalum, iridium, bismuth and oxides, carbides, nitrides, borides, etc., of these. The means of forming a thin film of any of these can be selected as required depending upon each metal, etc., and there can be applied any means such as plating, sputtering, reactive sputtering, vacuum vapor deposition, bonding of a thin film thereof (gold foil, etc.), pressure-bonding, or the like. In the present invention, for example, it is relatively easy to apply gold plating or a gold foil to an end portion of the relatively short and generally straight-shaped connection strut 4′, so that the X ray impermeable portion 6′ is formed in a predetermined range (such a length that can be covered with the length of pipe unit 5′) in an end portion of the connection strut 4′ by plating gold. The X ray impermeable portion 6′ may be any portion so long as the position of the stent A′ can be reliably monitored with X ray imaging, and particulars thereof shall not be limited. According to the finding of the present inventors, when the stent main line 1′ has a diameter of 0.45 mm and the connection strut 4′ has a diameter of 0.35 mm, and if a gold plate having a thickness of 2 μm is formed in a range of 3.5 mm to 4 mm, the monitoring of the position can be reliably made with X ray imaging. In this case, the pipe unit 5′ has a length of approximately 1 mm, and 5 to 6 pipe units 5′ are arranged side by side by connection and calked, thereby covering of the X ray impermeable portion 6′ and the connection of stent main line 1′ and the strut 4′ can be both provided. When the annular units 2′ are connected with the connection strut 4′, the end portion of the connection strut 4′ on which the X ray impermeable portion 6′ is formed is arranged along the stent main line 1′, and a plurality of the pipes 5′ are inserted and fitted them and calked, whereby the X ray impermeable portion 6′ can be covered and protected with the pipes 5′. Further, when the stent A′ is anchored or left in a diseased part, the X ray impermeable portion 6′ is not exposed directly to a blood flow. When the stent A′ is anchored or left in the main artery, therefore, a gold plating or a gold foil is not peeled off. Even if it should be peeled off, it does not in the least pass through the pipe unit 5′ to enter a blood vessel, thereby preventing the peeled gold plating or gold foil from causing a thrombosis. When the connection strut 4′ with the X ray impermeable portion 6′ formed thereon is connected to the stent main line 1′ constituting the annular unit 2′, preferably, the position to which the gold plating or gold foil is applied is in the vicinity of the peak portion (central curved portion) 1d′ of the annular unit 2′ so that the passageway through which the stent A′ reaches a diseased part can be reliably monitored by x ray imaging. Another embodiment in which, as an element imparted with a function different from the stent main line 1′ and the connection strut 4′, a fluid drug 8′ containing a powder or liquid is administered from the stent A′ by sustained release, will be explained below with reference to FIG. 11. Since a narrow blood vessel is liable to have a thrombosis, generally, an anti-thrombosis drug is externally administered. When the drug can be fitted to the stent A′ inserted in a blood vessel and gradually released from the stent directly into blood at an intended place, advantageously, the effect of the drug can be more effectively produced. When the stent A′ is fitted with a drug such as an anti-thrombosis drug, a relatively long pipe unit 7′ is used as shown in FIG. 11(a), a powder, preferably fluid drug 8′, is charged into the pipe unit 7′ and sealed, and the pipe unit is fitted and arranged to/on the stent main line 1′. As a drug 8′, an optimum one is selected in advance depending upon a patient to be treated and an operation method employed and charged into the pipe unit 7′. FIG. 11(b) is a cross sectional view taken along line a-a in FIG. 11(a), and FIG. 11(c) is a cross sectional view taken along line b-b in FIG. 11(a). Accordingly, there is provided a constitution in which the pipe unit 7′ has a very small hole portion 7a′ formed in a predetermined position (e.g., a position that permits a contact with blood flow, such as an end surface or a side surface), the drug comes in contact with blood, which enters and flows away through the above hole portion 7a′, and the drug can be dissolved gradually in the blood and released. The pipe unit 7′ for sealing a drug therein and gradually releasing it is formed generally to be relatively long. Therefore, even when attempts are made to fit and arrange the above pipe unit 7′ after the stent main line 1′ is formed in zigzag patterns, it is difficult to pass the pipe unit 7′ through the peak portion (central curved portion) 1d′. It is thus preferred to arrange the pipe unit 7′ in the straight line portion in the vicinity of a welded area of the stent main line 1′. Particularly, for increasing the inner volume of the pipe unit 7′, preferably, the stent main line 1′ is shaped in a form including a semicircular at cross section beforehand as shown in FIG. 11(b), and the pipe unit 7′ is arranged in the thus shaped portion. The pipe unit 7′ is fixed to the stent main line 1′ by calking both ends thereof. When the above-constituted stent A′ is anchored or left in an intended diseased part, along with the blood flow in the direction of an arrow f′, part of the blood flows into the pipe unit 7′ through the upstream hole portion 7a′ and comes in contact with the drug 8′ charged therein to gradually dissolve it. And, the blood in which the drug is dissolved flows out of the downstream hole portion 7a′ of the pipe unit 7′ and joins the main blood flow, thereby the above drug can be gradually released into the blood. That is, when the stent is fitted with the pipe unit having a fine hole portion charged with a drug, the gradual release of the drug can be made at a desired position in a blood, particularly, in the vicinity of a diseased part. According to the present invention, the stent A′ is fitted with the pipe unit charged with a drug such as a thrombolytic agent, or the like, whereby the stent A′ , when anchored or left in a diseased part, can itself exhibit an action of effective DDS (Drug Delivery System) (sustained release system) without carrying out any special external blood transfusion or administration such as an injection or the like. Finally, an embodiment in which a hook 11′ for gripping a guide wire 10′, which is arranged through the sheath when the stent A′ is anchored in a diseased part, is arranged as an element different from the stent main line 1′ and the strut 4′ will be explained with reference to FIG. 12. The hook 11′ is caught on a notched portion 14a′ formed in a dilator 14′, and when the sheath 13′ is moved backward after the dilator 14′ is fixed in a diseased part, the hook 11′ works to discharge the stent A′ housed in the above sheath 13′. The hook 11′ is formed, for example, using a wire material of an austenitic stainless steel like the connection struts 4′. As shown in FIG. 12, the stent A′ is covered with a cylindrical graft 12′, and the stent A′ is diameter-contracted in conformity with the internal diameter of the sheath 13′ and is housed in the sheath 13′. The dilator 14′ is housed in the sheath 13′, and further, the guide wire 10′ having a top portion externally exposed is housed in the dilator 14′. And, an operation portion at hand that is not shown is operated, to fix a forward end loop 2′ at an intended diseased part with the dilator 14′, and in this state, the sheath 13′ is withdrawn toward the operator side, thereby the stent A′ is discharged from the sheath 13, expanded and anchored in the diseased part. Concerning the hook 11′, for example, one wire material made of an austenitic stainless steel is curved, both ends thereof are arranged along the stent main line 1′, the pipe unit 5′ is disposed, and the hook 11′ is fitted to the annular unit 2′ integrally with the stent main line 1′ and the pipe unit 5′, by simultaneously calking them. Particularly preferably, a gold plating or gold foil is applied to those two ends of the hook 11′ which are attached to the stent main line 1′, thereby forming an imaging marker such as the X ray impermeable portion 6′. In this case, the X ray impermeable portion 6′ can be covered and protected with the pipe unit 5′ as discussed already. Further, when the hook 11′ is connected to the stent main line 1′ by welding, the welded portion can be covered with the pipe unit 5′ and can be reinforced by calking. In the stent of the present invention, the pipe unit is fitted and fixed to that portion of the stent main line and/or the connection strut which suffers a change in metal structure due to welding heat and is decreased in strength as explained already, thereby the thus-changed stent main line and/or connection strut can be reinforced. Particularly, the pipe unit is arranged and fixed to such a portion of the stent main line at which metal structure comes to have coarse particles due to heat effect caused by welding ends of the stent main line, thereby this portion can be reinforced with the above pipe unit. Further, the pipe unit is arranged and fixed to face a solid element as a function-imparting element different from the stent main line and the connection strut, for example, the X ray impermeable portion formed on the stent main line or the connection strut, thereby said fixed pipe unit can prevent the gold plating or gold foil constituting the above X ray impermeable portion from coming off, and prevent such a substance from, in the least, entering the blood flow even if it comes off. Further, the pipe unit charged with a fluid, for example, a drug such as a liquid or powder containing an anti-thrombosis drug and sealed, is fitted and fixed to the stent main line or the connection strut, the above drug sealed therein is maintained, and hole portion(s) opened to an inside thereof is (are) formed in predetermined position(s) of the above pipe unit, thereby the drug can be dissolved in the blood flow and can be gradually released. As described above, the pipe unit is selectively imparted with the function of protection, the function of protecting an X ray marker, the function of sustained release of a drug, or the like, thereby a multi-purpose stent can be provided.
<SOH> TECHNICAL BACKGROUND <EOH>There are many duct-like organs such as a blood vessel, a biliary tract, a urinary tract, a digestive tract, and the like. These duct-like organs may be caused to have characteristic diseases such as a stricture, occlusion, dilation, or the like due to respective various causes. For example, the blood vessel may be caused to have stenosed diseases such as a stricture and occlusion or dilative diseases such as an aneurysm of the aorta and a varix. Particularly, the aneurysm of the aorta refers to the abnormal dilation of weakened arterial wall caused by hardening or inflammation of the main artery, and it is a critical disease wherein the arterial wall, if left untreated, is gradually dilated from the pressure of a blood flow, and the swelling wall can no longer resist the blood pressure to burst. It therefore requires an immediate treatment or procedure for preventing the bursting and bleeding. In recent years, a tubular device made of a metal called a stent is often used when an abnormal stenosed part or dilated part of a blood vessel is treated, since no excess invasion such as a surgical operation is required. For example, when an aneurysm of the aorta is treated, the treatment is conducted in such a manner that a stent graft, a device, obtained by covering the above mentioned stent with a tubular member made of a synthetic resin, is used as an artificial blood vessel, and the stent graft is placed within the aneurysm to allow the blood to flow inside the artificial blood vessel, so that the blood pressure is not exerted directly on the swelling wall. As a stent, conventionally, some types of stents have been provided. Of these, there is used a tubular device obtained by bending a linear material (wire) made of a metal typified by stainless steel to form zigzag patterns, forming the top portion thereof into the form of a curve or curved line, connecting both ends of the linear material to form it into an annular unit, arranging such annular units in series and connecting them with connection struts. It is also another practice to constitute a tubular device from a metal mesh. For example, when the stent is anchored or placed in a treatment site (diseased part), the stent or stent graft generally inserted in a sheath is restrained, diameter-contracted and loaded into a delivery kit such as a pipe-like cylindrically formed catheter through the inside of which a guide wire is placed. It is introduced into a blood vessel from an incision of a peripheral artery of joint of a leg along the guide wire and delivered to a treatment site such as an aneurysm of the aorta, and when it reaches the treatment site, the above delivery kit is released to remove the contraction of the stent or the like. The stent released from the contraction expands in diameter by itself, and in this state, it is placed or left in a diseased part inside the blood vessel thereby to protect the blood vessel. However, it has been found that the above conventional stent or stent graft (to be sometimes simply referred to as “stent or the like” hereinafter) has the following problems. (1) The above mentioned stent or the like is basically formed of a tubular body made of a linear metal framework before it is inserted in a sheath. The stent or the like of the above type is to some degree improved in conformity after inserted in a diseased part, by means of design change on configuration or form of the metal framework as required. However, it is composed of a linear tubular body as a basic structure, it exhibits poor conformity to a bent portion of the main artery, so that the deformation of the stent and the damage of the blood vessel are liable to be produced with the passage of time or after a long period of time. (2) Meanwhile, with a stent graft of a metal mesh type which is manufactured to gain improved flexibility, to be sure, it shows good flexibility and improved conformity. However, the problem is that when the stent is diameter-contracted, the total length thereof increases accordingly, thereby making its positioning for placing the same in the diseased part difficult, the stent-placed position moves or drifts after a long period of time following an operation, or the stent is liable to suffer a structure change with the passage of time, such as deformation, etc., caused by the expansion of the stent toward an aneurysm side. (3) Further, in case of a tubular body stent formed by connecting annular units having the same diameter and the same number of zigzag patterns, there is no problem to be in the form of a straight line so long as it is not bent. When it is bent, however, from the form of a straight line to a curved form, all of central curved portions nearly face or oppose to each other, or central curved portions and inside spaces between curved portions face or opposed to each other, on the inside of curved line R of the stent. Therefore, i) when the central curved portions of adjacent annular units of a stent face each other, and when the stent is bent, the central curved portions on the inside of the curved line R of the stent overlap and touch each other, so that the stent comes to have difficulties in keeping flexibility and durability. ii) on the other hand, when the central curved portion of an annular unit of a stent and the inside space of the curved portion of an adjacent unit of the stent face each other, and when the stent is curved, the connection portion and the generally straight line portion are not aligned in generally straight line, so that the stent is liable to be kinked when the annular units connected in the form of a curve are contracted or are restored from contraction, and the stent is liable to be deformed with the passage of time. Thus the prior stent formed by arranging annular units composed of zigzag patterns each and connected in a linear structure is, in principle, not suitable for bending to make a curved form as described above. (4) There may be employed a constitution in which the connection portion between the annular units is so arranged to have a larger length than the generally straight line portion that the zigzag patterns do not overlap and touch. However, in this constitution, undesirably, the connection portion may be kinked or suffer torture after a long period of time, or the above constitution may result in insufficient expansion force of the connection portion against a diseased part. In the light of importance of the above problems of the conventional stent, etc., particularly, for providing a stent that is remarkably improved in safety and conformity during delivery within an artery, or the like, and with the performance of stable anchoring or placing at a diseased part for a long period time, the present inventors have made diligent studies and as a result have arrived at the present invention.
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIGS. 1 to 7 are drawings showing the stent and stent graft of the present invention. FIG. 1 (A) is a schematic drawing (plan view) of the stent of the present invention, and FIG. 1 (B) is a partial enlarged view of the zigzag patterns 7 . FIG. 2 is a plan view obtained by viewing the stent in FIG. 1 from X side. FIG. 3 is a plan view obtained by viewing the stent in FIG. 1 from Y side. FIG. 4 is a partial enlarged view showing one embodiment of the connection between the connection portion 5 and each substantially straight portion 6 of the stent of the present invention. FIG. 5 is a schematic drawing showing the state wherein the stent graft of the present invention is contracted. FIG. 6 is a schematic drawing showing a state wherein the stent graft of the present invention is inserted in a sheath 10 having a curved form at the forward end. FIG. 7 is a schematic drawing showing a state wherein the stent graft of the present invention is inserted in a sheath 20 having a straight line form at the forward end. In FIGS. 1 to 7 , 1 indicates a stent, 3 indicates a bonded portion, 4 A, 4 B, 4 C, 4 D and 4 E indicate annular units, 5 , 5 A and 5 B indicate connection portions or connection struts, 6 , 61 , 62 , 63 and 64 indicate substantially straight line portions, 7 indicates zigzag patterns, 8 , 8 A and 8 B indicate central curved portions, 9 indicate an inside space of the zigzag pattern, 10 and 20 indicate sheaths, 11 indicates a stent graft, 12 indicates a tubular member made of a synthetic resin or a graft, θ indicates a connection angle (formed between the substantially straight line portion and the connection portion), and θ 1 , θ 2 and θ 3 indicate angles between annular units. FIGS. 8 to 12 are drawings showing another embodiment of the stent and stent graft of the present invention. FIG. 8 is a drawing for explaining a stent formed by connecting two annular units with connection struts. FIG. 9 is a drawing for explaining a structure of welded portion of the stent main line. FIGS. 10 ( a ) and 10 ( b ) are drawings for explaining a state wherein an X ray impermeable portion 6 is protected with a pipe unit 5 ′. FIGS. 11 ( a ), 11 ( b ) and 11 ( c ) are drawings for explaining a state wherein a pipe unit charged with a drug and sealed is attached. FIGS. 12 ( a ) and 12 ( b ) are drawings for explaining a state where a hook is connected to the stent main line with a pipe unit. In FIGS. 8 to 12 , A′ indicates a stent, 1 ′ indicates the stent main line, 1 a ′ indicates a welded region, 1 b ′ and 1 c ′ indicate regions adjacent thereto, 1 d ′ indicates a top portion, 2 ′ indicates an annular unit, 3 ′ indicates a pipe unit for reinforcement, 4 ′ indicates a connection strut, 5 ′ indicates a pipe unit for protection, 6 ′ indicates an X ray impermeable portion, 7 ′ indicates a pipe unit for sustained release of a drug, or the like, 7 a ′ indicates a hole portion, 8 ′ indicates a drug or the like, 10 ′ indicates a guide wire, 11 ′ indicates a hook, 12 ′ indicates an annular member or graft made from a synthetic resin, 13 indicates a sheath, 14 ′ indicates a dilator, and 14 a ′ indicates a notched portion. detailed-description description="Detailed Description" end="lead"?
20050610
20100914
20051027
76936.0
0
HOUSTON, ELIZABETH
STENT AND STENT GRAFT
UNDISCOUNTED
0
ACCEPTED
2,005
10,513,403
ACCEPTED
Method and arrangement for producing radiation
A method of producing a radiating plasma with an increased flux stability and uniformity is disclosed. The method comprises the steps of generating a primary target by urging a liquid under pressure through a nozzle; directing an energy pre-pulse onto the primary target to generate a secondary target in the form of a gas or plasma cloud; allowing the thus formed secondary target to expand for a predetermined period of time; and directing a main energy pulse onto the secondary target when the predetermined period of time has elapsed in order to produce a plasma radiating X-ray or EUV radiation. The pre-pulse has a beam waist size that is larger, in at least one dimension, than the corresponding dimension of the primary target.
1. A method for producing X-ray or EUV radiation by emission from an energy beam produced plasma, comprising the steps of generating (210) a primary target (302, 402, 502) by urging a liquid under pressure through a nozzle; directing (220) a first energy pulse (301, 401, 501) onto said primary target to generate a secondary target (303, 403, 603); allowing the secondary target to expand (230) for a predetermined period of time; directing (240) a second energy pulse (304, 404, 604) onto said secondary target when said predetermined period of time has elapsed, the second energy pulse having an energy that is higher than the energy of the first energy pulse, in order to produce a plasma that emits the X-ray or EUV radiation; wherein the first energy pulse (301, 401, 501) has a beam waist size at the target (302, 402, 502) that is larger, in at least one dimension, than the corresponding size of said primary target, whereby influence from primary target positional fluctuations relative to the energy beam, in said at least one dimension, on the stability of the radiation emitted by the plasma is reduced. 2. A method as claimed in claim 1, wherein the second energy pulse (304, 404, 604) has a beam waist size that is smaller than the corresponding dimension of the secondary target (303, 403, 603) at the time when the second energy pulse is directed onto said secondary target. 3. A method as claimed in claim 1, wherein beam waist size and shape of the first energy pulse (301, 403, 501) is substantially equal to that of the second energy pulse (304, 404, 604). 4. A method as claimed in claim 1, wherein the predetermined period of time between the first and the second energy pulse is in the range from 20 ns to 500 ns. 5. A method as claimed in claim 1, wherein at least one of the energy pulses (301, 401, 501; 304, 404, 604) is a laser pulse. 6. A method as claimed in claim 2, wherein the primary target is a cylindrical jet or droplets having a diameter of about 20 μm, and the beam waists of both the first and second energy pulses are round and have a diameter of about 250 μm when focused onto the primary target and the secondary target, respectively. 7. A method as claimed in claim 1, wherein the first and the second energy pulses are directed onto the primary target and the secondary target, respectively, at a distance of more than 10 mm from the nozzle. 8. A method as claimed in claim 1, wherein the primary target is spatially continuous or semi-continuous jet. 9. A method as claimed in claim 1, wherein the primary target is a droplet. 10. A method as claimed in claim 8, wherein the primary target is in a frozen state at the point where the first energy pulse is directed onto said primary target. 11. A method as claimed in claim 1, wherein the target material is Xe. 12. A method as claimed in claim 1, wherein the energy in the first energy pulse is between 1% and 10% of the energy in the second energy pulse. 13. A method as claimed in claim 1, wherein the pulse length of both the first energy pulse and the second energy pulse is about 5 ns. 14. A method as claimed in claim 1, wherein the beam waist size of the first energy pulse is between 2 and 20 times larger than the smallest dimension of the primary target. 15. A method as claimed in claim 1, wherein the produced radiation is utilized in connection with EUV lithography. 16. A method as claimed in claim 15, wherein the produced radiation is utilized in a EUV lithography stepper apparatus. 17. A method as claimed in claim 15, wherein the produced radiation is utilized in a EUV metrology or inspection apparatus. 18. A method as claimed in claim 1, further comprising the step of performing X-ray microscopy with the produced radiation. 19. A method as claimed in claim 1, further comprising the step of performing X-ray fluorescence with the produced radiation. 20. A method as claimed in claim 1, further comprising the step of performing X-ray diffraction with the produced radiation. 21. A method as claimed in claim 2, wherein beam waist size and shape of the first energy pulse (301, 403, 501) is substantially equal to that of the second energy pulse (304, 404, 604). 22. A method as claimed in claim 2, wherein the predetermined period of time between the first and the second energy pulse is in the range from 20 ns to 500 ns. 23. A method as claimed in claim 3, wherein the predetermined period of time between the first and the second energy pulse is in the range from 20 ns to 500 ns. 24. A method as claimed in claim 2, wherein at least one of the energy pulses (301, 401, 501; 304, 404, 604) is a laser pulse. 25. A method as claimed in claim 3, wherein at least one of the energy pulses (301, 401, 501; 304, 404, 604) is a laser pulse. 26. A method as claimed in claim 4, wherein at least one of the energy pulses (301, 401, 501; 304, 404, 604) is a laser pulse.
TECHNICAL FIELD The present invention relates to a method for producing X-ray or extreme ultraviolet (EUV) radiation. In particular, the present invention relates to improvements in flux stability and uniformity in connection with energy beam produced plasmas. BACKGROUND OF THE INVENTION EUV and X-ray sources of high intensity are applied in many fields, for instance surface physics, materials testing, crystal analysis, atomic physics, medical diagnostics, lithography and microscopy. Conventional X-ray sources, in which an electron beam is brought to impinge on an anode, generate a relatively low X-ray intensity. Large facilities, such as synchrotron light sources, produce a high average power. However, there are many applications that require compact, small-scale systems which produce a relatively high average power. Compact and more inexpensive systems yield better accessibility to the applied user and are thus of potentially greater value to science and society. An example of an application of particular industrial importance is future narrow-line-width lithography systems. Ever since the 1960s, the size of the structures that constitute the basis of integrated electronic circuits has decreased continuously. The advantage thereof is faster and more complicated circuits needing less power. Typically, photolithography is used to industrially produce such circuits having a line width of about 0.18 μm with projected extension towards 0.065 μm. In order to further reduce the line width, other methods will probably be necessary, of which EUV projection lithography is a prime candidate and X-ray lithography may become interesting for some technological niches. In EUV projection lithography, use is made of a reducing extreme ultraviolet (EUV) objective system in the wavelength range around 10-20 nm. Proximity X-ray lithography, employing a contact copy scheme, is carried out in the wavelength range around 1 nm. Laser produced plasmas are attractive table-top X-ray and EUV sources due to their high brightness, high spatial stability and, potentially, high-repetition rate. However, with conventional bulk or tape targets, the operating time is limited, especially when high-repetition-rate lasers are used, since fresh target material cannot be supplied at a sufficient rate. Furthermore, such conventional targets produce debris which may destroy or coat sensitive components such as X-ray optics or EUV multi-layer mirrors positioned close to the plasma. Several methods have been designed to eliminate the effect of debris by preventing the already produced debris from reaching the sensitive components. As an alternative, the amount of debris actually produced can be limited by replacing conventional solid targets by for example gas targets, gas-cluster targets, liquid-droplet targets, or liquid-jet targets. Targets in the form of microscopic liquid droplets, such as disclosed in the article “Droplet target for low-debris laser-plasma soft X-ray generation” by Rymell and Hertz, published in Opt. Commun. 103, p. 105, 1993, are attractive low-debris, high-density targets potentially capable of high repetition-rate laser-plasma operation with high-brightness emission. Such droplets are generated by stimulated breakup of a liquid jet which is formed at a nozzle in a low-pressure chamber. However, the hydrodynamic properties of some fluids result in unstable drop formation. Furthermore, the operation of the laser must be carefully synchronized with the droplet formation. Another problem may arise in the use of liquid substances with rapid evaporation, namely that the jet freezes immediately upon generation so that drops cannot be formed. Such substances primarily include media that are in a gaseous state at normal pressure and temperature and that are cooled to a liquid state for generation of the droplet targets. To ensure droplet formation, it is necessary to provide a suitable gas atmosphere in the low-pressure chamber, or to raise the temperature of the jet above its freezing temperature by means of an electric heater provided around the jet, such as disclosed in the article “Apparatus for producing uniform solid spheres of hydrogen” by Foster et al., published in Rev. Sci. Instrum. 6, pp 625-631, 1977. As an alternative, as known from U.S. Pat. No. 6,002,744, which is incorporated herein by reference, the laser radiation is instead focused on a spatially continuous portion of a jet which is generated by urging a liquid substance through an outlet or nozzle. This liquid-jet approach alleviates the need for temporal synchronization of the laser with the generation of the target, while keeping the production of debris equally low as from droplet targets. Furthermore, liquid substances having unsuitable hydrodynamic properties for droplet formation can be used in this approach. Another advantage over the droplet-target approach is that the spatially continuous portion of the jet can be allowed to freeze. Such a liquid-jet laser-plasma source has been further demonstrated in the article “Cryogenic liquid-jet target for debris-free laser-plasma soft x-ray generation” by Berglund et al, published in Rev. Sci. Instrum. 69, p. 2361, 1998, and the article “Liquid-jet target laser-plasma sources for EUV and X-ray lithography” by Rymell et al, published in Microelectronic Engineering 46, p. 453, 1999, by using liquid nitrogen and xenon, respectively, as target material. In these cases, a high-density target is formed as a spatially continuous portion of the jet, wherein the spatially continuous portion can be in a liquid or a frozen state. Such laser-plasma sources have the advantage of being high-brightness, low-debris sources capable of continuous high-repetition-rate operation, and the plasma can be produced far from the outlet nozzle, thereby limiting thermal load and plasma-induced erosion of the outlet nozzle. Such erosion may be a source of damaging debris. Further, by producing the plasma far from the nozzle, self-absorption of the generated radiation can be minimized. This is due to the fact that the temperature of the jet (or train of droplets) decreases with the distance from the outlet, resulting in a correspondingly decreasing evaporation rate. Thus, the local gas atmosphere around the jet (or train of droplets) also decreases with the distance from the outlet. However, many substances, and in particular liquid substances formed by cooling normally gaseous substances, gives a jet or a train of droplets that experiences stochastic changes in its direction from the jet-generating nozzle. Typically the change in direction can be as large as about ±1° and occurs a few times per minute to a few times per second. This comparatively coarse type of directional instability can be eliminated by means of, for example, the method disclosed in Swedish patent application No. SE 0003715-0. However, for some applications, an extremely high flux stability and uniformity is required. One example of an application where a very high degree of flux stability and uniformity is required is in EUV lithography. In particular, this high degree of stability is required in so-called steppers and in metrology and inspection apparatuses. Even though the method as disclosed in the above-mentioned Swedish application is employed, there are still some micro-fluctuations left in the position of the target. This in turn results in a spatial instability at the focus of the laser beam, i.e. at the desired area of beam-target-interaction, which should be as far away from the outlet nozzle as possible for the reasons given above. The spatial instability leads to pulse-to-pulse fluctuations in the emitted X-ray and EUV radiation flux and spatial instability of the radiating plasma. SUMMARY OF THE INVENTION Therefore, it is an object of the present invention to provide an improved method for producing X-ray or EUV radiation by energy beam produced plasma emission, wherein the detrimental effects of these positional fluctuations in the target are eliminated, or at least considerably reduced. In general, it is an object of the present invention to improve pulse-to-pulse and long-term stability of position, flux and spatial distribution of the emitted radiation from a plasma produced by directing an energy pulse such as a laser pulse onto a target. To this end, a method according to claim 1 of the appended claims is provided. The invention is based upon a new way of employing “pre-pulses” for plasma production. A pre-pulse is an energy pulse that precedes the main plasma-producing pulse. Pre-pulses have previously been utilized in order to enhance the total X-ray emission from a laser produced plasma. See for example “Ultraviolet prepulse for enhanced x-ray emission and brightness from droplet-target laser plasmas”, by M. Berglund et al., Applied Physics Letters, Vol. 69, No. 12 (1996), pages 1683-1685. Berglund et al. identifies small variations in droplet position with respect to the laser-beam focus as a cause of fluctuations in the X-ray flux. However, no solution to the said problem is suggested. Although energy pulses in the form of laser pulses are preferred, other types of energy pulses are also conceivable, such as electron beam pulses. However, in the following description, energy pulses in the form of laser pulses will be taken as the preferred example. In general, it is desirable to produce the radiating plasma as far away from the nozzle as possible, in order to minimize the thermal load and erosion of the nozzle caused by the presence of the plasma. However, the further away from the nozzle the energy beam is directed onto the target, the more sensitive is the flux of the produced radiation to directional instabilities in the target relative to the energy beam. The reason for this has been identified as that the plasma-producing beam simply does not “hit” the target optimally, thus intermittently producing an unstable or weakly radiating plasma. Moreover, there are other reasons that the energy pulse might not hit the target optimally. For example, in the case when the target is a droplet or a train of droplets, there may be a variation in the time of arrival of the droplets to the area of interaction (the area where the energy pulse is directed onto the target). This leads to a positional uncertainty regarding the target position relative to the energy pulse, and hence to fluctuations in the produced radiation. Also, the target might in fact be a frozen jet that has broken up into fragments, causing a similar positional uncertainty. Regardless of the reason for the positional uncertainty of the target relative to the energy pulse, the present invention provides improvements of the pulse-to-pulse and long term stability of position, flux and spatial distribution of the emitted radiation. Simply going to larger target jets is not a good solution due to vacuum problems. When using cryogenic targets (i.e. targets that freeze by evaporation in the vacuum chamber), evaporation of target material makes it hard to maintain a good vacuum. Therefore, it is preferred to use small target jets, where a higher propagation speed can be utilized without causing a too high evaporation (and hence deterioration of the vacuum). In addition, a high propagation speed for the target jet may improve the stability of the target. According to the present invention, pre-pulses are used in order to form an expanding gas or plasma cloud (a secondary target), upon which a main energy pulse is directed in order to produce a plasma with a high degree of ionization that radiates the desired X-ray or EUV radiation. The pre-pulse is directed onto the target in a state where the target is said to be a primary target, while the main energy pulse is directed onto the gas or plasma cloud formed by the pre-pulse. In this application, the gas or plasma cloud formed by means of the pre-pulse is called a secondary target. According to the present invention, an expanded pre-pulse is used that has a beam waist size that is larger than the dimension of the target in at least one dimension, in order to form a secondary target. In other words, the pre-pulse is given a beam waist that is larger than the target in the smallest dimension thereof. The expanded pre-pulse should have a size equal to or larger than the expected variation in target position (relative to the energy beam), in order to “hit” the target on every shot. In order to provide the above-mentioned stability with regard to pulse-to-pulse or long-term fluctuations in flux, position and distribution, the energy pre-pulse should provide a secondary target that can be hit in a similar way on every shot of a main plasma-producing energy pulse. The gas or plasma cloud produced by the pre-pulse is then allowed to expand for a predetermined period of time in order to form an expanded secondary target. Then, the main energy pulse is directed onto the secondary target to form a radiating plasma having a comparatively high degree of ionization. The beam waist size and shape of the main energy pulse is preferably adapted to the size and shape of the secondary target. By using a pre-pulse having a comparatively low energy, although having a beam waist size that is larger than the smallest dimension of the target, only a small amount of energy is wasted by the pre-pulse. At the same time, the pre-pulse produces a gas or plasma cloud that expands, forming a secondary target. Since the pre-pulse is larger than the primary target in the smallest dimension of the target, the influence from possible deviations in the position of the primary target on the secondary target is reduced. Then, supported by the fact that the main energy pulse is preferably adapted in size with the expanded plasma cloud (the secondary target), the influence of fluctuations in the position of the primary target on the total flux is drastically reduced. Micro-fluctuations in the relative position of the laser focus and the primary target gives only a small relative change in the overlap between the main energy pulse and the expanded secondary target cloud. Fluctuations in x-ray or EUV flux are effectively reduced. Hence, since the absolute positional fluctuations are the same for the primary and the secondary targets, the relative positional fluctuations for the secondary target are drastically reduced, due to its increased size. The present invention provides improved stability in the radiation flux from the plasma, both in terms of pulse-to-pulse fluctuations and in long-term stability. Furthermore, the present invention provides an increased uniformity in the achieved radiation flux. Preferably, the beam waist size and shape of the pre-pulse and the main pulse are equal. This is particularly attractive since the same focusing optics may be used for both pulses. However, many different choices of both beam waist sizes and time separation between pre-pulse and main pulse are conceivable within the scope presented by the appended claims. Among the advantages of the method according to the present invention is a possibility to direct the energy pulse onto the target far away from the nozzle without causing large fluctuations in the radiation flux of the generated X-ray or EUV radiation. In general, regardless of whether the distance from the plasma to the nozzle is increased, a striking increase in the flux stability is achieved by the inventive method. Hence, in one aspect, the present invention provides a method for producing X-ray of EUV radiation by energy beam produced plasma emission, in which fluctuations in radiation flux is considerably reduced. In the preferred embodiment, the energy beam is a laser beam. In another aspect, the present invention provides a method for producing X-ray or EUV radiation, in which a plasma may be formed further away from a target-generating nozzle than what has been appropriate in the prior art, without lowering the flux stability or uniformity. Also, according to the present invention, a method for producing X-ray or EUV radiation is provided, in which a laser of comparatively poor beam quality can be used as the plasma-producing energy source. This is allowed since any focal spots used are considerably larger than what has been used in the prior art. For some commercially available lasers, the beam quality is simply not good enough to be focused to a small spot. In this application, where the size of a beam waist is mentioned, it is the full width at half maximum (FWHM) that is referred to. BRIEF DESCRIPTION OF THE DRAWINGS Further aspects and advantages of the invention will become apparent when the following detailed description of some preferred embodiments is read. In the detailed description, reference is made to the accompanying drawings, on which: FIG. 1 schematically shows the problem of positional fluctuations of the target relative to the energy beam as encountered in the prior art; FIG. 2 is a schematic chart outlining the method steps according to the present invention; FIG. 3 schematically illustrates an implementation of the invention when a cylindrical target is used; FIG. 4 schematically illustrates an implementation of the invention when a droplet target is used; FIG. 5a-e schematically shows different combinations of pre-pulse and target; and FIG. 6 schematically shows the matching of main energy pulse to secondary target. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Referring now to FIG. 1 of the accompanying drawings, the stability problem encountered in the prior art will be briefly discussed. Typically, in the field of laser produced plasma emission, the laser focus 101 has an ideally fixed position in space. However, even in good laser systems, there might be beam pointing stability issues that cause, or add to, relative positional fluctuations between the target 102 and the laser beam 101. Any perturbation of the target position or the laser beam will therefore cause the laser pulses to partially or entirely miss the target 102. As schematically shown in FIG. 1, the laser pulse 101 is ideally centered at the same position (shown in the figure by a broken line). At time t1 the position of the target may have moved such that the: laser pulse 101 only partially hits the target 102; at time t2 the position of the target 102 may actually be appropriate; and at time t3 the position of the target 102 may be such that the laser pulse 101 misses the target entirely. Such positional fluctuations of the target leads to lowered pulse-to-pulse stability of position, flux and spatial distribution of the radiation emitted from the produced plasma, as well as lowered long-term stability. To overcome this problem, the present invention provides a method in which an expanded pre-pulse of energy is utilized in order to produce a secondary target, upon which a main energy pulse is directed to produce the radiating plasma. As schematically illustrated in FIG. 2, the method according to the invention comprises the steps of 210 generating a primary target by urging a liquid under pressure through a nozzle; 220 directing a pre-pulse of energy on the target to form a secondary target in the form of a gas or plasma cloud; 230 allowing the secondary target to expand for a predetermined period of time; and 240 sending a main energy pulse on the secondary target to produce the radiating plasma. According to the invention, the pre-pulse of energy has a beam waist size that is larger, in at least one dimension, than the corresponding size of the primary target, whereby influence from the above-mentioned primary target positional fluctuations relative to the energy beam, in said at least one dimension, on the stability of the radiation emitted by the plasma is reduced. Preferably, as mentioned above, the energy pulses are laser pulses. Reference is now made to FIG. 3. In a preferred embodiment of the present invention, xenon (Xe) is used as the target material. The Xe is cooled to a liquid state and kept in a pressurized container (not shown) at about 20 bar. From the container, the Xe is urged through an outlet orifice, or nozzle, (not shown) to form a jet 302 in an evacuated chamber. The evacuated chamber has a base pressure of about 10−8 mbar. The diameter of the nozzle in the preferred embodiment is 20 μm, thus producing the jet 302 with a similar diameter. Typically, when Xe is used as the target material, the jet thus formed will freeze to a solid state due to evaporation in the evacuated chamber before any laser pulse is directed thereon. Evaporation of target material gives a xenon partial pressure in the evacuated chamber of about 10−3 mbar. However, the target may consist of other substances, and may be kept at liquid state. The target may also be separated into a train of droplets, which may be frozen or liquid. Furthermore, the container for the target material, the nozzle, and any control means may be adapted to deliver droplets on demand into the evacuated chamber. Hence, the generated Xe jet may have a diameter of about 20 μm and propagate at a speed of about 30 m/s. About 50 mm from the nozzle, the radiating plasma is to be formed. The steps towards producing a radiating plasma start by first directing a laser pre-pulse 301 at time t1 having a beam waist size of about 250 μm onto the target 302. The pre-pulse 301 cause a gas or plasma cloud to form. During a time period Δt of about 100 ns, this cloud is allowed to expand, to form the secondary target 303 for the main laser pulse 304. After said time period has elapsed, at the time t1+Δt, the main laser pulse 304 is directed onto the secondary target 303 in order to form a highly ionized, radiating plasma, which is the actual source for the X-ray or EUV radiation. The pulse-to-pulse and long-term stability of position, flux and spatial distribution of the emitted radiation is further-increased by making the main laser pulse 304 slightly smaller than the size of the expanded secondary target 303. More particularly, the main pulse 304 should have a sufficiently small cross section to fall within the extension of the secondary target 303, subject to expected variations in the position of the secondary target. By further adjusting the pulse energy and pulse length for the main pulse 304, this increased stability can be obtained with a maintained high conversion efficiency of energy into X-ray or EUV radiation. As briefly mentioned in the summary above, when using the same beam waist size for both the pre-pulse 301 and the main laser pulse 304, an optical system common to both the laser pulses can be employed. This is taken advantage of in the preferred embodiment. The same laser could in principle be used for both the pre-pulse and the main pulse. However, a delay of 100 ns, as in the preferred embodiment, corresponds to an optical path length difference of about 30 m. Therefore, for the pre-pulse and the main pulse, respectively. In the preferred embodiment, two Nd:YAG lasers emitting light at 1064 nm are used. However, other lasers are also possible, having other pulse lengths, wavelengths, pulse energies etc. The lasers are Q-switched in order to deliver energetic, 5 ns long pulses at a repetition rate of 20 Hz. The light constituting the main pulse 304 is delayed 100 ns relative to the light constituting the pre-pulse 301. The energy of the pre-pulse is about 10 mJ, while the energy in the main pulse is about 200 mJ. In the preferred embodiment, the pre-pulse and the main pulse both have the same pulse length equal to 5 ns. The expansion of the secondary target 303 produced by the laser pre-pulse 301 (the first energy pulse) is primarily driven by thermal energy. Because Xe atoms are relatively heavy, the rate of expansion is rather slow. Therefore, the time Δt between the first laser pulse 301 and the second, main laser pulse 304 must be long enough for allowing the gas or plasma cloud 303 to expand appropriately. For a target material of lower atomic mass, the time period Δt between the first and the second laser pulse should be shorter. Also, the higher the energy in the pre-pulse 301, the faster the rate of expansion of the cloud (due to a higher temperature). Therefore, the period of time between the pre-pulse and the main pulse should be set according to the target material used and the energy of the pre-pulse, with a view to achieve a secondary target cloud of appropriate size and density for the main laser pulse. The appropriate settings for each situation will be found by the skilled person after having read and understood this specification. Since the primary target 302 in the preferred implementation is a cylindrical jet, there is only a risk of not hitting the target with the pre-pulse 301 in the transverse dimension with respect to the propagation direction of the jet 302. Therefore, it might be preferred to use a line focus for the pre-pulse, having an elongated extension transverse to the jet. This is schematically shown in FIG. 5c. Hence, depending on the geometry of the primary target, it may be sufficient for the pre-pulse to be larger than the primary target in only one dimension. FIG. 4 schematically shows a similar implementation to that shown in FIG. 3. In FIG. 4, however, droplets 402 are used as the primary target, rather than a cylindrical jet of target material. In this case, there is also a potential risk of not hitting the primary target 402 in the longitudinal dimension (the propagation direction of the droplet). Therefore, in this case, a pre-pulse 401 having a circular beam waist cross section is preferably used. Any jitter in the timing of the target droplets 402 arrival at the position where the laser pulse 401 is directed onto the target will lead to primary target positional fluctuations or uncertainties. Again, by using a pre-pulse 401 that is larger than the target, any influence from such fluctuations on the radiation flux stability is reduced. Although the most preferred embodiment employs rotationally symmetric focal spots 501a (FIG. 5a), other embodiments have made use of extended focal shapes, such as line focuses 501b, 501c (FIG. 5b, 5c). FIG. 5b shows a situation where a line focus 501b coextending with the cylindrical target 502b is used, and FIG. 5c shows a situation where a line focus 501c transverse to the cylindrical target 502c is used. In all other aspects, the features of the embodiment with line focuses are similar to those of the embodiment with round focal spots described above. When using a primary target consisting of a droplet 502d or a train of droplets 502e, a circular pre-pulse 501d, 501e is preferably used (FIGS. 5d and 5e). In general, any type of focus for the energy beam (laser beam) can be used when implementing the present invention, as long as the laser beam focus is larger than the target in at least one dimension (viz. the dimension in which influence from positional fluctuations is to be reduced). In FIG. 6, the matching of the main energy pulse to the secondary target is illustrated. The expanded secondary target is shown by broken lines 603, and the beam waist of the main energy pulse at the secondary target is shown by solid lines 604. Although the relative position of the expanded secondary target 603 varies only slightly, there is still some uncertainty regarding the position of the secondary target at the time the main energy pulse 604 is directed thereon. For this reason, the main energy pulse 604 preferably has a beam waist that is slightly smaller than the expanded secondary target 603. If the position of the secondary target 603 is changed by a small amount from pulse to pulse, the entire main pulse 604 still hits target material, leading to an increased stability. The present invention has been described above with reference to some preferred embodiments. However, it is apparent to the skilled person that variations and modifications are conceivable within the scope of the invention as defined in the appended claims. For example, the diameter of the nozzle producing the primary target may have other dimensions than what has been disclosed herein. It is to be understood that the absolute magnitude of the diameter of the primary target is of minor relevance for the purposes of the present invention. In addition, the primary target may be a semi-continuous jet or a frozen jet that has broken up into fragments. Moreover, the pressure inside the container for the target material, which is set to about 20 bar in the preferred embodiment, may be from below 10 bar to far above 100 bar. Again, this is a parameter that has minor relevance for the principles of the present invention. Furthermore, the invention has been described with reference to Xe as the target material. However, the teachings of the present invention may be applied also to other target materials, such as other noble gases (cooled to a liquid state); various compounds and mixtures; liquid metals, such as tin; as well as various kinds of organic liquids, such as ethanol. In addition, it is of course possible within the scope of the invention to use a plurality of first and second energy pulses, which are simultaneously directed onto the target. Conclusion In conclusion, a method of producing a radiating plasma with an increased flux stability and uniformity has been disclosed. The method comprises the steps of generating a primary target by urging a liquid under pressure through a nozzle; directing an energy pre-pulse onto the primary target to generate a secondary target in the form of a gas or plasma cloud; allowing the thus formed gas or plasma cloud to expand for a predetermined period of time; and directing a main energy pulse onto the gas or plasma cloud when the predetermined period of time has elapsed in order to produce a plasma radiating X-ray or EUV radiation. The pre-pulse has a beam waist size that is larger, in at least one dimension, than the corresponding dimension of the primary target, whereby influence from primary target positional fluctuations, in said at least one dimension, on the radiation flux stability is reduced.
<SOH> BACKGROUND OF THE INVENTION <EOH>EUV and X-ray sources of high intensity are applied in many fields, for instance surface physics, materials testing, crystal analysis, atomic physics, medical diagnostics, lithography and microscopy. Conventional X-ray sources, in which an electron beam is brought to impinge on an anode, generate a relatively low X-ray intensity. Large facilities, such as synchrotron light sources, produce a high average power. However, there are many applications that require compact, small-scale systems which produce a relatively high average power. Compact and more inexpensive systems yield better accessibility to the applied user and are thus of potentially greater value to science and society. An example of an application of particular industrial importance is future narrow-line-width lithography systems. Ever since the 1960s, the size of the structures that constitute the basis of integrated electronic circuits has decreased continuously. The advantage thereof is faster and more complicated circuits needing less power. Typically, photolithography is used to industrially produce such circuits having a line width of about 0.18 μm with projected extension towards 0.065 μm. In order to further reduce the line width, other methods will probably be necessary, of which EUV projection lithography is a prime candidate and X-ray lithography may become interesting for some technological niches. In EUV projection lithography, use is made of a reducing extreme ultraviolet (EUV) objective system in the wavelength range around 10-20 nm. Proximity X-ray lithography, employing a contact copy scheme, is carried out in the wavelength range around 1 nm. Laser produced plasmas are attractive table-top X-ray and EUV sources due to their high brightness, high spatial stability and, potentially, high-repetition rate. However, with conventional bulk or tape targets, the operating time is limited, especially when high-repetition-rate lasers are used, since fresh target material cannot be supplied at a sufficient rate. Furthermore, such conventional targets produce debris which may destroy or coat sensitive components such as X-ray optics or EUV multi-layer mirrors positioned close to the plasma. Several methods have been designed to eliminate the effect of debris by preventing the already produced debris from reaching the sensitive components. As an alternative, the amount of debris actually produced can be limited by replacing conventional solid targets by for example gas targets, gas-cluster targets, liquid-droplet targets, or liquid-jet targets. Targets in the form of microscopic liquid droplets, such as disclosed in the article “Droplet target for low-debris laser-plasma soft X-ray generation” by Rymell and Hertz, published in Opt. Commun. 103, p. 105, 1993, are attractive low-debris, high-density targets potentially capable of high repetition-rate laser-plasma operation with high-brightness emission. Such droplets are generated by stimulated breakup of a liquid jet which is formed at a nozzle in a low-pressure chamber. However, the hydrodynamic properties of some fluids result in unstable drop formation. Furthermore, the operation of the laser must be carefully synchronized with the droplet formation. Another problem may arise in the use of liquid substances with rapid evaporation, namely that the jet freezes immediately upon generation so that drops cannot be formed. Such substances primarily include media that are in a gaseous state at normal pressure and temperature and that are cooled to a liquid state for generation of the droplet targets. To ensure droplet formation, it is necessary to provide a suitable gas atmosphere in the low-pressure chamber, or to raise the temperature of the jet above its freezing temperature by means of an electric heater provided around the jet, such as disclosed in the article “Apparatus for producing uniform solid spheres of hydrogen” by Foster et al., published in Rev. Sci. Instrum. 6, pp 625-631, 1977. As an alternative, as known from U.S. Pat. No. 6,002,744, which is incorporated herein by reference, the laser radiation is instead focused on a spatially continuous portion of a jet which is generated by urging a liquid substance through an outlet or nozzle. This liquid-jet approach alleviates the need for temporal synchronization of the laser with the generation of the target, while keeping the production of debris equally low as from droplet targets. Furthermore, liquid substances having unsuitable hydrodynamic properties for droplet formation can be used in this approach. Another advantage over the droplet-target approach is that the spatially continuous portion of the jet can be allowed to freeze. Such a liquid-jet laser-plasma source has been further demonstrated in the article “Cryogenic liquid-jet target for debris-free laser-plasma soft x-ray generation” by Berglund et al, published in Rev. Sci. Instrum. 69, p. 2361, 1998, and the article “Liquid-jet target laser-plasma sources for EUV and X-ray lithography” by Rymell et al, published in Microelectronic Engineering 46, p. 453, 1999, by using liquid nitrogen and xenon, respectively, as target material. In these cases, a high-density target is formed as a spatially continuous portion of the jet, wherein the spatially continuous portion can be in a liquid or a frozen state. Such laser-plasma sources have the advantage of being high-brightness, low-debris sources capable of continuous high-repetition-rate operation, and the plasma can be produced far from the outlet nozzle, thereby limiting thermal load and plasma-induced erosion of the outlet nozzle. Such erosion may be a source of damaging debris. Further, by producing the plasma far from the nozzle, self-absorption of the generated radiation can be minimized. This is due to the fact that the temperature of the jet (or train of droplets) decreases with the distance from the outlet, resulting in a correspondingly decreasing evaporation rate. Thus, the local gas atmosphere around the jet (or train of droplets) also decreases with the distance from the outlet. However, many substances, and in particular liquid substances formed by cooling normally gaseous substances, gives a jet or a train of droplets that experiences stochastic changes in its direction from the jet-generating nozzle. Typically the change in direction can be as large as about ±1° and occurs a few times per minute to a few times per second. This comparatively coarse type of directional instability can be eliminated by means of, for example, the method disclosed in Swedish patent application No. SE 0003715-0. However, for some applications, an extremely high flux stability and uniformity is required. One example of an application where a very high degree of flux stability and uniformity is required is in EUV lithography. In particular, this high degree of stability is required in so-called steppers and in metrology and inspection apparatuses. Even though the method as disclosed in the above-mentioned Swedish application is employed, there are still some micro-fluctuations left in the position of the target. This in turn results in a spatial instability at the focus of the laser beam, i.e. at the desired area of beam-target-interaction, which should be as far away from the outlet nozzle as possible for the reasons given above. The spatial instability leads to pulse-to-pulse fluctuations in the emitted X-ray and EUV radiation flux and spatial instability of the radiating plasma.
<SOH> SUMMARY OF THE INVENTION <EOH>Therefore, it is an object of the present invention to provide an improved method for producing X-ray or EUV radiation by energy beam produced plasma emission, wherein the detrimental effects of these positional fluctuations in the target are eliminated, or at least considerably reduced. In general, it is an object of the present invention to improve pulse-to-pulse and long-term stability of position, flux and spatial distribution of the emitted radiation from a plasma produced by directing an energy pulse such as a laser pulse onto a target. To this end, a method according to claim 1 of the appended claims is provided. The invention is based upon a new way of employing “pre-pulses” for plasma production. A pre-pulse is an energy pulse that precedes the main plasma-producing pulse. Pre-pulses have previously been utilized in order to enhance the total X-ray emission from a laser produced plasma. See for example “Ultraviolet prepulse for enhanced x-ray emission and brightness from droplet-target laser plasmas”, by M. Berglund et al., Applied Physics Letters, Vol. 69, No. 12 (1996), pages 1683-1685. Berglund et al. identifies small variations in droplet position with respect to the laser-beam focus as a cause of fluctuations in the X-ray flux. However, no solution to the said problem is suggested. Although energy pulses in the form of laser pulses are preferred, other types of energy pulses are also conceivable, such as electron beam pulses. However, in the following description, energy pulses in the form of laser pulses will be taken as the preferred example. In general, it is desirable to produce the radiating plasma as far away from the nozzle as possible, in order to minimize the thermal load and erosion of the nozzle caused by the presence of the plasma. However, the further away from the nozzle the energy beam is directed onto the target, the more sensitive is the flux of the produced radiation to directional instabilities in the target relative to the energy beam. The reason for this has been identified as that the plasma-producing beam simply does not “hit” the target optimally, thus intermittently producing an unstable or weakly radiating plasma. Moreover, there are other reasons that the energy pulse might not hit the target optimally. For example, in the case when the target is a droplet or a train of droplets, there may be a variation in the time of arrival of the droplets to the area of interaction (the area where the energy pulse is directed onto the target). This leads to a positional uncertainty regarding the target position relative to the energy pulse, and hence to fluctuations in the produced radiation. Also, the target might in fact be a frozen jet that has broken up into fragments, causing a similar positional uncertainty. Regardless of the reason for the positional uncertainty of the target relative to the energy pulse, the present invention provides improvements of the pulse-to-pulse and long term stability of position, flux and spatial distribution of the emitted radiation. Simply going to larger target jets is not a good solution due to vacuum problems. When using cryogenic targets (i.e. targets that freeze by evaporation in the vacuum chamber), evaporation of target material makes it hard to maintain a good vacuum. Therefore, it is preferred to use small target jets, where a higher propagation speed can be utilized without causing a too high evaporation (and hence deterioration of the vacuum). In addition, a high propagation speed for the target jet may improve the stability of the target. According to the present invention, pre-pulses are used in order to form an expanding gas or plasma cloud (a secondary target), upon which a main energy pulse is directed in order to produce a plasma with a high degree of ionization that radiates the desired X-ray or EUV radiation. The pre-pulse is directed onto the target in a state where the target is said to be a primary target, while the main energy pulse is directed onto the gas or plasma cloud formed by the pre-pulse. In this application, the gas or plasma cloud formed by means of the pre-pulse is called a secondary target. According to the present invention, an expanded pre-pulse is used that has a beam waist size that is larger than the dimension of the target in at least one dimension, in order to form a secondary target. In other words, the pre-pulse is given a beam waist that is larger than the target in the smallest dimension thereof. The expanded pre-pulse should have a size equal to or larger than the expected variation in target position (relative to the energy beam), in order to “hit” the target on every shot. In order to provide the above-mentioned stability with regard to pulse-to-pulse or long-term fluctuations in flux, position and distribution, the energy pre-pulse should provide a secondary target that can be hit in a similar way on every shot of a main plasma-producing energy pulse. The gas or plasma cloud produced by the pre-pulse is then allowed to expand for a predetermined period of time in order to form an expanded secondary target. Then, the main energy pulse is directed onto the secondary target to form a radiating plasma having a comparatively high degree of ionization. The beam waist size and shape of the main energy pulse is preferably adapted to the size and shape of the secondary target. By using a pre-pulse having a comparatively low energy, although having a beam waist size that is larger than the smallest dimension of the target, only a small amount of energy is wasted by the pre-pulse. At the same time, the pre-pulse produces a gas or plasma cloud that expands, forming a secondary target. Since the pre-pulse is larger than the primary target in the smallest dimension of the target, the influence from possible deviations in the position of the primary target on the secondary target is reduced. Then, supported by the fact that the main energy pulse is preferably adapted in size with the expanded plasma cloud (the secondary target), the influence of fluctuations in the position of the primary target on the total flux is drastically reduced. Micro-fluctuations in the relative position of the laser focus and the primary target gives only a small relative change in the overlap between the main energy pulse and the expanded secondary target cloud. Fluctuations in x-ray or EUV flux are effectively reduced. Hence, since the absolute positional fluctuations are the same for the primary and the secondary targets, the relative positional fluctuations for the secondary target are drastically reduced, due to its increased size. The present invention provides improved stability in the radiation flux from the plasma, both in terms of pulse-to-pulse fluctuations and in long-term stability. Furthermore, the present invention provides an increased uniformity in the achieved radiation flux. Preferably, the beam waist size and shape of the pre-pulse and the main pulse are equal. This is particularly attractive since the same focusing optics may be used for both pulses. However, many different choices of both beam waist sizes and time separation between pre-pulse and main pulse are conceivable within the scope presented by the appended claims. Among the advantages of the method according to the present invention is a possibility to direct the energy pulse onto the target far away from the nozzle without causing large fluctuations in the radiation flux of the generated X-ray or EUV radiation. In general, regardless of whether the distance from the plasma to the nozzle is increased, a striking increase in the flux stability is achieved by the inventive method. Hence, in one aspect, the present invention provides a method for producing X-ray of EUV radiation by energy beam produced plasma emission, in which fluctuations in radiation flux is considerably reduced. In the preferred embodiment, the energy beam is a laser beam. In another aspect, the present invention provides a method for producing X-ray or EUV radiation, in which a plasma may be formed further away from a target-generating nozzle than what has been appropriate in the prior art, without lowering the flux stability or uniformity. Also, according to the present invention, a method for producing X-ray or EUV radiation is provided, in which a laser of comparatively poor beam quality can be used as the plasma-producing energy source. This is allowed since any focal spots used are considerably larger than what has been used in the prior art. For some commercially available lasers, the beam quality is simply not good enough to be focused to a small spot. In this application, where the size of a beam waist is mentioned, it is the full width at half maximum (FWHM) that is referred to.
20050105
20070703
20050616
63883.0
0
KAO, CHIH CHENG G
METHOD AND ARRANGEMENT FOR PRODUCING RADIATION
UNDISCOUNTED
0
ACCEPTED
2,005
10,513,461
ACCEPTED
Electric power switch with an electronic memory unit for parameters and conversion factors
An electrical power breaker includes an electronic protective device and an electronic memory. The memory is accommodated in the power breaker such that it is physically separated from said protective device, for operational data for the power breaker. Data security when using the additional electronic memory is increased by the electronic memory being connected to the protective device via a data bus, which can be used to transmit control signals for the purpose of activating or deactivating a write protection device of the electronic memory. The data bus is preferably an I2C bus, and the write protection device is controlled by an I/O module which is likewise controlled by the I2C bus.
1. An electrical power breaker comprising: an electronic protective device; an electronic memory, accommodated in the power breaker such that it is physically separated from the protective device, and which can be read or written to by the protective device, for operational data for the power breaker, wherein the electronic memory includes, a write protection device which can be at least one of activated and deactivated via a write protection input of the electronic memory, wherein the electronic memory is connected to the protective device via a serial data bus, and an associated digital I/O module, controllable by the protective device via the serial data bus, the output of the I/O module being connected to the write protection input of the electronic memory for the purpose of at least one of activating and deactivating the write protection device. 2. The electrical power breaker as claimed in claim 1, wherein the serial data bus is in the form of an I2C bus. 3. The power breaker as claimed in claim 1, wherein the electronic memory in the form of an EEPROM and the digital I/O module are accommodated in a common housing arranged in the path of a four-core cable harness. 4. The power breaker as claimed in claim 2, wherein the electronic memory in the form of an EEPROM and the digital I/O module are accommodated in a common housing arranged in the path of a four-core cable harness.
This application is the national phase under 35 U.S.C. § 371 of PCT International Application No. PCT/DE03/01258 which has an International filing date of Apr. 10, 2003, which designated the United States of America and which claims priority on German Patent Application number DE 102 21 572.3 filed May 8, 2002, the entire contents of which are hereby incorporated herein by reference. FIELD OF THE INVENTION The invention generally relates to an electrical power breaker. Preferably, it relates to one having an electronic protective device and having an electronic memory, which is accommodated in the power breaker such that it is physically separated from the protective device and which can be read and written to by the protective device, for operational data for the power breaker. BACKGROUND OF THE INVENTION A power breaker of this type has been disclosed in, for example, DE 100 19 092 A1. The protective device, which, in a known manner, is in the form of an electronic overcurrent release, is in this case located in a front region of the power breaker behind a control panel. On the other hand, current transformers or current sensors, which detect measured values for the current in each of the poles of the power breaker and supply auxiliary power required for operating the protective device, are arranged on the rear side of the power breaker which is opposite the control panel. A cable harness connects these two regions of the power breaker. The electronic memory, which serves the purpose of storing characteristics and conversion factors which are dependent on the physical size and design of the power breaker, is arranged in the path of the cable harness. A further known application of an electronic memory which is physically separated from the protective device is a rated current plug according to U.S. Pat. No. 4,958,252. In this case, the memory serves the purpose of recording operational events. In particular, the events include the number of switching operations and the level of the respectively interrupted current in order to determine from this the time for required maintenance work to be carried out on the power breaker. Also known is an electrical switch having an electronic protective device and a memory which are connected via a parallel data bus (U.S. Pat. No. 4,996,646 A). If an electronic memory of the abovementioned type is arranged in the power breaker such that it is physically separated from the protective device, a connection line or cable harness is required for there to be communication between these units. In this case, the electronic memory can be arranged in the path of the cable harness, as is described in the mentioned DE 100 19 092 A1. All of the interacting components and units are thus subjected to the disruptive influence of the magnetic, electrical and electromagnetic fields occurring in a power breaker. Since the sensitivity of electronic components and circuits to influences of this type is known, shields have been fitted in order to prevent disturbances to the operation of the protective devices (U.S. Pat. No. 5,303,113). However, the increasing requirements placed on the switching capacity of power breakers lead to the electromagnetic influences on all of the electronic components of a power breaker also being increased correspondingly. Although there is extensive experience in controlling these influences, it appears to be desirable in the interest of safety to increase the electromagnetic compatibility (EMC) in particular of the electronic memory which is arranged separately. In this case, at the forefront is the consideration that, in the case of communication between the protective device and the memory, address information as well as write and read information can be altered by an interference field which has accidentally been greatly increased. For example, it may be possible for a write operation to take place instead of a read operation without a user being capable of recognizing this. In certain circumstances, it is possible in this way to influence the behavior of the protective device, which can lead to undesired tripping of the power breaker or to this tripping being suppressed even though it is required. It is obvious per se to eliminate these undesirable influences by using the internal write protection of the electronic memory. The memory modules (EEPROM) have for this purpose a separate input (WC=WRITE CONTROL) which cancels or establishes the write protection depending on the potential applied, as is described, for example, in U.S. Pat. No. 5,363,334. However, in a power breaker, the memory is not accessible, for example in the case of the arrangement in the path of a cable harness according to DE 100 19 092 A1. It is therefore not possible to use a jumper which is conventionally provided. Even an electrical connection of the write protection input of a memory (EEPROM) is subject to difficulties, since an additional line required for this purpose is not available and undesirable additional complexity is required to install it retrospectively. SUMMARY OF THE INVENTION Against this background, an embodiment of the invention is based on the object of using methods/devices which are as simple but as effective as possible to significantly improve data security when using an electronic memory in a power breaker. According to an embodiment of the invention, an object may be achieved by the electronic memory having a write protection device which can be activated or deactivated via a write protection input of the electronic memory, by the electronic memory being connected to the protective device via a serial data bus, and by the electronic memory having an associated digital I/O module which can likewise be controlled by the protective device via the serial data bus, the output of the I/O module being connected to the write protection input of the electronic memory for the purpose of activating or deactivating the write protection device. With such a design for the electrical power breaker, there is no additional complexity as regards the connection between the protective device and the memory, since only two conductors are required for data transmission (serial bus). In addition there are two conductors for the power supply, meaning that in total four conductors are required. This number of conductors has also been used to date, but did not allow the write protection of the electronic memory to be used. In the context of an embodiment of the invention, the data bus may be in the form of an I2C bus. The arrangement described in DE 100 19 092 A1, the entire contents of which are hereby incorporated herein by reference, may also be used in the context of an embodiment of the invention, specifically such that the electronic memory in the form of an EEPROM and the digital I/O module are accommodated in a common housing arranged in the path of a four-core cable harness. BRIEF DESCRIPTION OF THE DRAWINGS The invention will be explained in more detail below with reference to the exemplary embodiments described below and shown in the figures. The low-voltage power breaker 1 shown in FIG. 1 has, in a known manner, a housing 2, in which for each pole one switching contact arrangement 3 having an associated arcing chamber 4 and one drive apparatus 5 are accommodated for the purpose of simultaneously actuating all of the switching contact arrangements provided. Each of the switching contact arrangements 3 has an upper connection rail 6 and a lower connection rail 7 in order to connect the power breaker 1 to a circuit. Each of the lower connection rails 7 is provided with a set of transformers 8 which detects the current flowing through the associated switching contact arrangement 3 and in addition supplies auxiliary power for the purpose of operating an electronic overcurrent release 10. For this purpose, each set of transformers 8 comprises a current transformer 11 and a power transformer 12. The connection rails 6 and 7 as well as the sets of transformers 8 are located on the rear side of the housing 2, whereas the electronic overcurrent release provided as the protective device 10 is accessible from the opposite front side of the housing 2. For the purpose of connecting the sets of transformers 8 to the protective device 10, a cable harness 13 is provided which is laid in channels which are provided for this purpose in the housing 2 and which bypass the drive apparatus 5 and the switching contact arrangements 3. Proper interaction between the protective device 10 and the current transformers 11 requires the protective device 10 to process the current signals fed to it using a conversion factor which depends on the rated current for the current transformers, the physical size of the power breaker and, if necessary, further parameters. For this purpose it is known to provide electrical and/or electronic modules which are referred to as the rated current plug (rating plug), the interface module or the switch identification module and which are not arranged in the protective device 10 itself but are connected to it as a peripheral module. Some of the conventional arrangements are illustrated in FIG. 1. 14 denotes here a rated current plug, for example according to DE 100 27 934 A1 or U.S. Pat. No. 4,958,252. In addition, an information memory of the mentioned type according to EP 0 847 587 B1 (corresponds to U.S. Pat. No. 6,034,859) can be arranged on the rear side of the protective device 10, as is indicated by 15. A further possibility for the arrangement of an information memory is described in DE 100 19 092 A1, according to which the information memory is arranged at 16 in the path of a cable harness connecting the protective device 10 and the set of transformers. In the embodiment of the mentioned information memory as an electrically erasable programmable read-only memory (EEPROM), according to an embodiment of the present invention significantly improved data security is achieved using the write protection system provided in the electronic memories. Details on this write protection system will be explained in more detail below with reference to FIG. 2. FIG. 2 illustrates the circuit for the electronic memory 16 arranged in the cable harness 13. The memory is accommodated together with an I/O module 17 in a housing 18. Only that part of the cable harness 13 is shown which extends between the housing 18 and the protective device 10, since the part passed on to the current transformers 11 and 12 is not essential to the understanding of an embodiment of the invention. The electronic memory 16 is a memory of the EEPROM (electrically erasable programmable read-only memory) type, specifically with a design envisaged for use with the I2C bus. The I2C bus, as is documented, for example, at the Internet address http://www.embedded.com/97/feat9711.htm, acts as a series control device for connecting integrated circuits. Accordingly, the memory 16 has only four connections required for operation, namely two for the power supply and two further connections for data transmission. In FIG. 2, the connections envisaged for the power supply are denoted +5V and GND, whereas the connections envisaged for data transmission are denoted SDA (data) and SCL (clock). As a further connection, the memory 16 has a connection /WC (write control) which activates the write protection when it is subjected to a high level and deactivates the write protection when it is subjected to a low level, i.e. allows the memory to be written to. The four connections of the memory 16 are connected with corresponding conducting cores of the cable harness 13 to the protective device 10. Controlled by the protective device 10 or using an external operating panel, or one connected to the protective device 10, data can thus be read to and from the memory 16. In particular, this may be data which contains the conversion factor of measured values for the current transformers 11 and further parameters relating to the design of the power breaker 1. The memory 16 is normally provided with its basic data when the power breaker 1 is produced and equipped at the manufacturer's. During operation, the protective device 10 refers to the stored data, i.e. reads the stored data and processes it together with the measured values, supplied by the set of transformers 8, for the current for tripping purposes in the event of an overcurrent, a ground fault and a short circuit. Changes to the power breaker 1 as regards the current transformers fitted to it or an altered mode of operation may be cause for the stored data in the memory 16 to be altered. During operation of the power breaker 1 (FIG. 1), the memory content of the memory 16 is thus read regularly. However, this data traffic handled via the cable harness 13, like other electronic modules accommodated in the power breaker 1, is subject to the influence of disruptive magnetic, electrical and electromagnetic fields which emanate from the current-carrying switching contact arrangements and switching arcs in the arcing chambers 4. Similar, although weaker, disruptive influences can emanate from adjacent power breakers considering that power breakers are often incorporated close to one another in switchgear assemblies. Although during operation over relatively long periods of time it has been established that said interference fields do not impair data traffic between the protective device 10 and the memory 16, it cannot be ruled out that, depending on the level of the interference fields and a statistical coincidence of unfavorable conditions, faults may nevertheless occur. Such a fault may be, for example, a write operation taking place instead of a read operation. If by this means, for example, a stored value representing the conversion factor is altered, this may be cause for tripping in the event of a current which is too low, which can lead to operational faults. If, on the other hand, tripping is shifted to higher current values, this may mean that safety is seriously impaired. Operations of the described type are largely eliminated according to the invention by a write protection device being used which is provided as standard on the memory 16. This takes place without the number of conductors provided in the cable harness 13 needing to be increased for this purpose. The cable harness provided having four conductors can thus be used without any alterations. The write protection input /WC of the memory 16 is controlled by an additional I/O module 17 which has the same design as the memory 16 for operation using the I2C bus system. Accordingly, the I/O module 17 has the same connections +5V, SDA, SCL and GND. In addition, outputs are provided which the user can use as required. The write protection connection /WC of the memory 16 is connected directly to one of these outputs. Owing to a connection of the write protection connection /WC of the memory 16 to the connection +5V via a resistor R1, the write protection is normally activated, i.e. it is not possible for data to be read to the memory 16, if such an instruction were to be issued erroneously owing to interference. Only when, via the I2C bus, by means of the cable harness 13 or by way of a plug apparatus fitted to the connection of the cable harness on the housing 18, a control command is transmitted to the I/O module 17 which deactivates the write protection at the input /WC of the memory 16 can the stored data be altered or overwritten in the memory 16 or can additional data be written to said memory 16. As a result of the fact that the memory 16 and the I/O module 17 are accommodated in the immediate vicinity of one another within the housing 18, it can be assumed from this that faults owing to this circuit module being directly subjected to interference fields are improbable. Where the memory 16 arranged in the path of the cable harness 13 is described above, this is merely to be understood as an example for connection of memories arranged at another point in the power breaker 1. The memories 14 or 15, which are likewise arranged such that they are physically separated from the protective device 10, can thus be combined in the same manner with an I/O module 17 and as a result protected against faulty writing by way of the control via the I2C bus. List of Reference Numerals 1 Power breaker 2 Housing of the power breaker 3 Switching contact arrangement 4 Arcing chamber 5 Drive apparatus 6 Upper connection rail 7 Lower connection rail 8 Set of transformers 10 Protective device 11 Current transformer 12 Power transformer 13 Cable harness 14 Electronic memory (rating plug) 15 Electronic memory (information memory) 16 Electronic memory (switch identification module) 17 I/O module Exemplary embodiments being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims. DESCRIPTION Electrical power breaker having an electronic memory for characteristics and conversion factors The invention relates to an electrical power breaker having an electronic protective device and having an electronic memory, which is accommodated in the power breaker such that it is physically separated from the protective device and which can be read and written to by the protective device, for operational data for the power breaker. A power breaker of this type has been disclosed in, for example, DE 100 19 092 A1. The protective device, which, in a known manner, is in the form of an electronic overcurrent release, is in this case located in a front region of the power breaker behind a control panel. On the other hand, current transformers or current sensors, which detect measured values for the current in each of the poles of the power breaker and supply auxiliary power required for operating the protective device, are arranged on the rear side of the power breaker which is opposite the control panel. A cable harness connects these two regions of the power breaker. The electronic memory, which serves the purpose of storing characteristics and conversion factors which are dependent on the physical size and design of the power breaker, is arranged in the path of the cable harness. A further known application of an electronic memory which is physically separated from the protective device is a rated current plug according to U.S. Pat. No. 4,958,252. In this case, the memory serves the purpose of recording operational events, in particular the number of switching operations and the level of the respectively interrupted current in order to determine from this the time for required maintenance work to be carried out on the power breaker. Also known is an electrical switch having an electronic protective device and a memory which are connected via a parallel data bus (U.S. Pat. No. 4,996,646 A). If an electronic memory of the abovementioned type is arranged in the power breaker such that it is physically separated from the protective device, a connection line or cable harness is required for there to be communication between these units. In this case, the electronic memory can be arranged in the path of the cable harness, as is described in the mentioned DE 100 19 092 A1. All of the interacting components and units are thus subjected to the disruptive influence of the magnetic, electrical and electromagnetic fields occurring in a power breaker. Since the sensitivity of electronic components and circuits to influences of this type is known, shields have been fitted in order to prevent disturbances to the operation of the protective devices (U.S. Pat. No. 5,303,113). However, the increasing requirements placed on the switching capacity of power breakers lead to the electromagnetic influences on all of the electronic components of a power breaker also being increased correspondingly. Although there is extensive experience in controlling these influences, it appears to be desirable in the interest of safety to increase the electromagnetic compatibility (EMC) in particular of the electronic memory which is arranged separately. In this case, at the forefront is the consideration that, in the case of communication between the protective device and the memory, address information as well as write and read information can be altered by an interference field which has accidentally been greatly increased. For example, it may be possible for a write operation to take place instead of a read operation without a user being capable of recognizing this. In certain circumstances, it is possible in this way to influence the behavior of the protective device, which can lead to undesired tripping of the power breaker or to this tripping being suppressed even though it is required. It is obvious per se to eliminate these undesirable influences by using the internal write protection of the electronic memory. The memory modules (EEPROM) have for this purpose a separate input (WC=WRITE CONTROL) which cancels or establishes the write protection depending on the potential applied, as is described, for example, in U.S. Pat. No. 5,363,334. However, in a power breaker, the memory is not accessible, for example in the case of the arrangement in the path of a cable harness according to DE 100 19 092 A1. It is therefore not possible to use a jumper which is conventionally provided. Even an electrical connection of the write protection input of a memory (EEPROM) is subject to difficulties, since an additional line required for this purpose is not available and undesirable additional complexity is required to install it retrospectively. Against this background, the invention is based on the object of using means which are as simple but as effective as possible to significantly improve data security when using an electronic memory in a power breaker. According to the invention, this object is achieved by the electronic memory having a write protection device which can be activated or deactivated via a write protection input of the electronic memory, by the electronic memory being connected to the protective device via a serial data bus, and by the electronic memory having an associated digital I/O module which can likewise be controlled by the protective device by means of the serial data bus, the output of the I/O module being connected to the write protection input of the electronic memory for the purpose of activating or deactivating the write protection device. With such a design for the electrical power breaker there is no additional complexity as regards the connection between the protective device and the memory, since only two conductors are required for data transmission (serial bus). In addition there are two conductors for the power supply, meaning that in total four conductors are required. This number of conductors has also been used to date, but did not allow the write protection of the electronic memory to be used. In the context of the invention, the data bus may be in the form of an I2C bus. The arrangement described in DE 100 19 092 A1 may also be used in the context of the invention, specifically such that the electronic memory in the form of an EEPROM and the digital I/O module are accommodated in a common housing arranged in the path of a four-core cable harness. The invention will be explained in more detail below with reference to the exemplary embodiments shown in the figures. The low-voltage power breaker 1 shown in FIG. 1 has, in a known manner, a housing 2, in which for each pole one switching contact arrangement 3 having an associated arcing chamber 4 and one drive apparatus 5 are accommodated for the purpose of simultaneously actuating all of the switching contact arrangements provided. Each of the switching contact arrangements 3 has an upper connection rail 6 and a lower connection rail 7 in order to connect the power breaker 1 to a circuit. Each of the lower connection rails 7 is provided with a set of transformers 8 which detects the current flowing through the associated switching contact arrangement 3 and in addition supplies auxiliary power for the purpose of operating an electronic overcurrent release 10. For this purpose, each set of transformers 8 comprises a current transformer 11 and a power transformer 12. The connection rails 6 and 7 as well as the sets of transformers 8 are located on the rear side of the housing 2, whereas the electronic overcurrent release provided as the protective device 10 is accessible from the opposite front side of the housing 2. For the purpose of connecting the sets of transformers 8 to the protective device 10, a cable harness 13 is provided which is laid in channels which are provided for this purpose in the housing 2 and which bypass the drive apparatus 5 and the switching contact arrangements 3. Proper interaction between the protective device 10 and the current transformers 11 requires the protective device 10 to process the current signals fed to it using a conversion factor which depends on the rated current for the current transformers, the physical size of the power breaker and, if necessary, further parameters. For this purpose it is known to provide electrical and/or electronic modules which are referred to as the rated current plug (rating plug), the interface module or the switch identification module and which are not arranged in the protective device 10 itself but are connected to it as a peripheral module. Some of the conventional arrangements are illustrated in FIG. 1. 14 denotes here a rated current plug, for example according to DE 100 27 934 A1 or U.S. Pat. No. 4,958,252. In addition, an information memory of the mentioned type according to EP 0 847 587 B1 (corresponds to U.S. Pat. No. 6,034,859) can be arranged on the rear side of the protective device 10, as is indicated by 15. A further possibility for the arrangement of an information memory is described in DE 100 19 092 A1, according to which the information memory is arranged at 16 in the path of a cable harness connecting the protective device 10 and the set of transformers. In the embodiment of the mentioned information memory as an electrically erasable programmable read-only memory (EEPROM), according to the present invention significantly improved data security is achieved using the write protection system provided in the electronic memories. Details on this write protection system will be explained in more detail below with reference to FIG. 2. FIG. 2 illustrates the circuit for the electronic memory 16 arranged in the cable harness 13. Said memory is accommodated together with an I/O module 17 in a housing 18. Only that part of the cable harness 13 is shown which extends between the housing 18 and the protective device 10, since the part passed on to the current transformers 11 and 12 is not essential to the understanding of the invention. The electronic memory 16 is a memory of the EEPROM (electrically erasable programmable read-only memory) type, specifically with a design envisaged for use with the I2C bus. The I2C bus, as is documented, for example, at the Internet address http://www.embedded.com/97/feat9711.htm, acts as a series control means for connecting integrated circuits. Accordingly, the memory 16 has only four connections required for operation, namely two for the power supply and two further connections for data transmission. In FIG. 2, the connections envisaged for the power supply are denoted +5V and GND, whereas the connections envisaged for data transmission are denoted SDA (data) and SCL (clock). As a further connection, the memory 16 has a connection /WC (write control) which activates the write protection when it is subjected to a high level and deactivates the write protection when it is subjected to a low level, i.e. allows the memory to be written to. Said four connections of the memory 16 are connected with corresponding conducting cores of the cable harness 13 to the protective device 10. Controlled by the protective device 10 or using an external operating panel, or one connected to the protective device 10, data can thus be read to and from the memory 16. In particular, this may be data which contains the conversion factor of measured values for the current transformers 11 and further parameters relating to the design of the power breaker 1. The memory 16 is normally provided with its basic data when the power breaker 1 is produced and equipped at the manufacturer's. During operation, the protective device 10 refers to the stored data, i.e. reads the stored data and processes it together with the measured values, supplied by the set of transformers 8, for the current for tripping purposes in the event of an overcurrent, a ground fault and a short circuit. Changes to the power breaker 1 as regards the current transformers fitted to it or an altered mode of operation may be cause for the stored data in the memory 16 to be altered. During operation of the power breaker 1 (FIG. 1), the memory content of the memory 16 is thus read regularly. However, this data traffic handled via the cable harness 13, like other electronic modules accommodated in the power breaker 1, is subject to the influence of disruptive magnetic, electrical and electromagnetic fields which emanate from the current-carrying switching contact arrangements and switching arcs in the arcing chambers 4. Similar, although weaker, disruptive influences can emanate from adjacent power breakers considering that power breakers are often incorporated close to one another in switchgear assemblies. Although during operation over relatively long periods of time it has been established that said interference fields do not impair data traffic between the protective device 10 and the memory 16, it cannot be ruled out that, depending on the level of the interference fields and a statistical coincidence of unfavorable conditions, faults may nevertheless occur. Such a fault may be, for example, a write operation taking place instead of a read operation. If by this means, for example, a stored value representing the conversion factor is altered, this may be cause for tripping in the event of a current which is too low, which can lead to operational faults. If, on the other hand, tripping is shifted to higher current values, this may mean that safety is seriously impaired. Operations of the described type are largely eliminated according to the invention by a write protection device being used which is provided as standard on the memory 16. This takes place without the number of conductors provided in the cable harness 13 needing to be increased for this purpose. The cable harness provided having four conductors can thus be used without any alterations. The write protection input /WC of the memory 16 is controlled by an additional I/O module 17 which has the same design as the memory 16 for operation using the I2C bus system. Accordingly, the I/O module 17 has the same connections +5V, SDA, SCL and GND. In addition, outputs are provided which the user can use as required. The write protection connection /WC of the memory 16 is connected directly to one of these outputs. Owing to a connection of the write protection connection /WC of the memory 16 to the connection +5V via a resistor R1, the write protection is normally activated, i.e. it is not possible for data to be read to the memory 16, if such an instruction were to be issued erroneously owing to interference. Only when, via the I2C bus, by means of the cable harness 13 or by means of a plug apparatus fitted to the connection of the cable harness on the housing 18, a control command is transmitted to the I/O module 17 which deactivates the write protection at the input /WC of the memory 16 can the stored data be altered or overwritten in the memory 16 or can additional data be written to said memory 16. As a result of the fact that the memory 16 and the I/O module 17 are accommodated in the immediate vicinity of one another within the housing 18, it can be assumed from this that faults owing to this circuit module being directly subjected to interference fields are improbable. Where the memory 16 arranged in the path of the cable harness 13 is described above, this is merely to be understood as an example for connection of memories arranged at another point in the power breaker 1. The memories 14 or 15, which are likewise arranged such that they are physically separated from the protective device 10, can thus be combined in the same manner with an I/O module 17 and as a result protected against faulty writing by means of the control via the I2C bus.
<SOH> BACKGROUND OF THE INVENTION <EOH>A power breaker of this type has been disclosed in, for example, DE 100 19 092 A1. The protective device, which, in a known manner, is in the form of an electronic overcurrent release, is in this case located in a front region of the power breaker behind a control panel. On the other hand, current transformers or current sensors, which detect measured values for the current in each of the poles of the power breaker and supply auxiliary power required for operating the protective device, are arranged on the rear side of the power breaker which is opposite the control panel. A cable harness connects these two regions of the power breaker. The electronic memory, which serves the purpose of storing characteristics and conversion factors which are dependent on the physical size and design of the power breaker, is arranged in the path of the cable harness. A further known application of an electronic memory which is physically separated from the protective device is a rated current plug according to U.S. Pat. No. 4,958,252. In this case, the memory serves the purpose of recording operational events. In particular, the events include the number of switching operations and the level of the respectively interrupted current in order to determine from this the time for required maintenance work to be carried out on the power breaker. Also known is an electrical switch having an electronic protective device and a memory which are connected via a parallel data bus (U.S. Pat. No. 4,996,646 A). If an electronic memory of the abovementioned type is arranged in the power breaker such that it is physically separated from the protective device, a connection line or cable harness is required for there to be communication between these units. In this case, the electronic memory can be arranged in the path of the cable harness, as is described in the mentioned DE 100 19 092 A1. All of the interacting components and units are thus subjected to the disruptive influence of the magnetic, electrical and electromagnetic fields occurring in a power breaker. Since the sensitivity of electronic components and circuits to influences of this type is known, shields have been fitted in order to prevent disturbances to the operation of the protective devices (U.S. Pat. No. 5,303,113). However, the increasing requirements placed on the switching capacity of power breakers lead to the electromagnetic influences on all of the electronic components of a power breaker also being increased correspondingly. Although there is extensive experience in controlling these influences, it appears to be desirable in the interest of safety to increase the electromagnetic compatibility (EMC) in particular of the electronic memory which is arranged separately. In this case, at the forefront is the consideration that, in the case of communication between the protective device and the memory, address information as well as write and read information can be altered by an interference field which has accidentally been greatly increased. For example, it may be possible for a write operation to take place instead of a read operation without a user being capable of recognizing this. In certain circumstances, it is possible in this way to influence the behavior of the protective device, which can lead to undesired tripping of the power breaker or to this tripping being suppressed even though it is required. It is obvious per se to eliminate these undesirable influences by using the internal write protection of the electronic memory. The memory modules (EEPROM) have for this purpose a separate input (WC=WRITE CONTROL) which cancels or establishes the write protection depending on the potential applied, as is described, for example, in U.S. Pat. No. 5,363,334. However, in a power breaker, the memory is not accessible, for example in the case of the arrangement in the path of a cable harness according to DE 100 19 092 A1. It is therefore not possible to use a jumper which is conventionally provided. Even an electrical connection of the write protection input of a memory (EEPROM) is subject to difficulties, since an additional line required for this purpose is not available and undesirable additional complexity is required to install it retrospectively.
<SOH> SUMMARY OF THE INVENTION <EOH>Against this background, an embodiment of the invention is based on the object of using methods/devices which are as simple but as effective as possible to significantly improve data security when using an electronic memory in a power breaker. According to an embodiment of the invention, an object may be achieved by the electronic memory having a write protection device which can be activated or deactivated via a write protection input of the electronic memory, by the electronic memory being connected to the protective device via a serial data bus, and by the electronic memory having an associated digital I/O module which can likewise be controlled by the protective device via the serial data bus, the output of the I/O module being connected to the write protection input of the electronic memory for the purpose of activating or deactivating the write protection device. With such a design for the electrical power breaker, there is no additional complexity as regards the connection between the protective device and the memory, since only two conductors are required for data transmission (serial bus). In addition there are two conductors for the power supply, meaning that in total four conductors are required. This number of conductors has also been used to date, but did not allow the write protection of the electronic memory to be used. In the context of an embodiment of the invention, the data bus may be in the form of an I 2 C bus. The arrangement described in DE 100 19 092 A1, the entire contents of which are hereby incorporated herein by reference, may also be used in the context of an embodiment of the invention, specifically such that the electronic memory in the form of an EEPROM and the digital I/O module are accommodated in a common housing arranged in the path of a four-core cable harness. detailed-description description="Detailed Description" end="lead"?
20041108
20061107
20050811
96012.0
0
WILLOUGHBY, TERRENCE RONIQUE
ELECTRIC POWER SWITCH WITH AN ELECTRONIC MEMORY UNIT FOR PARAMETERS AND CONVERSION FACTORS
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,595
ACCEPTED
Method and apparatus for selecting user policies
The present invention provides a method and system which matches application sessions to user network usage or buying policies based upon a scoring system which reflects a user value to each policy for different applications. Several user policies are stored, each containing a list of matching criteria. Each criterion has a score for each element. The content of an application session description is used to compare with each user policy, and a policy score is awarded to each criterion if matched, or else, no score is awarded. The user policy which scores the highest policy score (which may be adjusted to be expressed as a percentage) is then chosen as the policy to use for the application session.
1. A method of selecting a user network usage policy for use with an application session, comprising the steps of: a) storing a plurality of user network usage policies; b) for each policy of at least a subset of the stored policies, comparing one or more characteristics of the application session with one or more policy characteristics to determine a policy score for each policy in the subset; and c) selecting a policy for use in dependence on the policy scores. 2. A method according to claim 1, wherein the comparing step further comprises comparing one or more predetermined application session characteristics with one or more predetermined policy characteristics according to one or more predetermined logical conditions contained in a user policy. 3. A method according to claim 1, wherein the comparing step further comprises comparing one or more contemporary environmental conditions with one or more predetermined policy characteristics AND/OR predetermined application session characteristics according to one or more predetermined logical conditions contained in a user policy. 4. A method according to claims 2, wherein each logical condition has a condition score allocated thereto, said policy score comprising a sum of the condition scores for each logical condition found to be true. 5. A method according to claim 4, wherein each condition score is adjustable by a user. 6. A method according to claim 1, wherein the application session characteristics are defined in accordance with any version of the Internet Engineering Task Force Session Description Protocol. 7. A method according to claim 1, wherein the selecting step comprises the further steps of expressing each policy score as a percentage of a respective predetermined policy pass-score, and selecting the policy with the greatest percentage as the policy for use. 8. A method according to claim 1, wherein the selecting step further comprises comparing the absolute policy scores, and selecting the policy with the greatest absolute score as the policy for use. 9. A method according to claim 1, wherein the selecting step further comprises calculating a difference value for each policy score, being the difference between the policy score and a respective predetermined policy pass-score, and selecting the policy with the greatest positive difference as the policy for use. 10. A computer program arranged such that when executed on a computer it causes the computer to perform a method according to claim 1. 11. A computer readable storage medium storing a computer program according to claim 10. 12. An apparatus for selecting a user network usage policy for use with an application session, comprising: a) storage means for storing data representing a plurality of user network usage policies; b) comparison means arranged, for each policy of at least a subset of the stored policies, to compare one or more characteristics of the application session with one or more policy characteristics and to determine a policy score for each policy in the subset in dependence on the comparison; and c) selection means arranged to select a policy for use in dependence on the policy scores. 13. An apparatus according to claim 12, wherein the comparing means is further arranged to compare one or more predetermined application session characteristics with one or more predetermined policy characteristics according to one or more predetermined logical conditions contained in a user policy. 14. An apparatus according to claim 12, wherein the comparing means further comprises environmental comparing means for comparing one or more contemporary environmental conditions with one or more predetermined policy characteristics and/or predetermined application session characteristics according to one or more predetermined logical conditions contained in a user policy. 15. An apparatus according to claim 13, wherein each logical condition has a condition score allocated thereto, said policy score comprising a sum of the condition scores for each logical condition found to be true. 16. An apparatus according to claim 15, further comprising user input means to allow each condition score to be adjusted by a user. 17. An apparatus according to claim 12, wherein the application session characteristics are defined in accordance with any version of the Internet Engineering Task Force Session Description Protocol. 18. An apparatus according to claim 12, wherein the selecting means further comprises percentage calculation means for expressing each policy score as a percentage of a respective predetermined policy pass-score, and percentage selecting means for selecting the policy with the greatest percentage as the policy for use. 19. An apparatus according to claim 12, wherein the selecting means further comprises score comparison means for comparing the absolute policy scores, and score selecting means for selecting the policy with the greatest absolute score as the policy for use. 20. An apparatus according to claim 12, wherein the selecting means further comprises difference calculating means for calculating a difference value for each policy score, being the difference between the policy score and a respective predetermined policy pass-score, and difference selecting means for selecting the policy with the greatest positive difference as the policy for use.
TECHNICAL FIELD The present invention relates to: a method; a computer program; a computer program product; and an apparatus; all for selecting a user network usage policy, and in particular for selecting a user policy to use with a particular application session. BACKGROUND TO THE PRESENT INVENTION AND PRIOR ART The mapping of application sessions to user policies is a very important requirement for both present and future Internet technologies such as Quality of Service (QoS) provision, usage control and QoS control. At the present time, there is no direct way for users to control their Internet traffic behaviour, behaviour such as transmission rate and aggressiveness. Instead, users rely on TCP, UDP and other closed loop transport layer control protocols to control the traffic on their behalf. Nowadays, users use the Internet for several different things at a time, for instance, downloading articles from a newsgroup and having a voice-chat with her friends in a chat room. In spite of both applications are using the same network connection, they have different network resource requirements such as bandwidth and delay. At the moment, using TCP, both applications will have to fight against each other to get the network resources they need. In a dynamic pricing scenario (such as, for example, that being considered by the M3I Consortium (see www.m3i.org)) an agent can be set up to help the user to react to dynamic pricing signals. It requires the user to specify a control policy, usually represented as the user utility. As the user may have different preferences to each application task, so a different control policy is applied to them. Clearly, if the agent doesn't have a policy input, it will not be able to react to the dynamic price. According to present research in advanced Internet technology, what is still missing in order to address the above problem is the bonding of Internet traffic flows, application sessions and user policies. Solutions which partially address this problem are starting to appear, and in particular our own earlier co-pending European Patent Application No 02251983.9 discloses a system to map data traffic flows with application sessions. This solves part of the problem in that it allows data flows generated by application sessions to be identified and mapped thereto, but what is still missing is the additional step of then mapping an application session to a user network usage policy, which contains information on, for example, how the user wishes to respond to different network prices, whether different types of data should be given a higher priority (and hence paid for at a higher charge for network transport thereof), how the system should respond to dynamic pricing signals received from the network, etc. etc. As will be apparent from the foregoing, the proper mapping of user usage policies to applications sessions is essential for dynamic internet charging scenarios. The application session to user policy mapping problem has been considered before, but problems arise with previous solutions in that they are not particularly flexible. An example is where a user's preference is hardwired to the system. In this case the system has a pre-programmed user's preference set in the system, and hence the preference may not truly represent what the user wants at all times or for each different type of network application. An example of this is where a default user policy is provided to the user by the user's Internet Service Provider for use with all network applications. In another known solution, the user has to select his/her utility before the start of a session (e.g. in most M3I scenarios). However, to keep asking a user what they want for every application session which is launched is not a practical solution, as it wastes time and furthermore tends to cater only for the needs of expert users who know the significance of the options available. For an average lay user of networks such as the Internet, the specific tuning required by this solution upon the launching of each and every network application session is not a viable option, and both expensive mistakes may be made by inexperienced users who select a high utility for data (indicating that they would be willing to pay a high price for its transport over the network) for which in reality the user has only a relatively low utility. SUMMARY OF THE INVENTION The present invention addresses the problems noted above by the provision of a method and system which provides the matching of application sessions to user network usage or buying policies based upon a scoring system which reflects a user value to each policy for different applications. Several user policies are stored, each containing a list of matching criteria. Each criterion has a score for each element. The content of an application session description is used to compare with each user policy, and a policy score is awarded to each criterion if matched, or else, no score is awarded. The user policy which scores the highest policy score (which may be adjusted to be expressed as a percentage) is then chosen as the policy to use for the application session. In view of the above, according to a first aspect of the present invention there is provided a method of selecting a user network usage or buying policy for use with an application session, comprising the steps of: a) storing a plurality of user network usage policies; b) for each policy of at least a subset of the stored policies, comparing one or more characteristics of the application session with one or more policy characteristics to determine a policy score for each policy in the subset; and c) selecting a policy for use in dependence on the policy scores. As the mapping of application sessions to user policies has always been a huge difficulty for service provider as much as for researcher the present invention provides the advantage that it significantly helps service providers to flexibly provide Quality of Service to their customers with multiple different services. The policy mapping obtained using the present invention also gives the possibility to extend control decisions of Internet traffic to the user's preference (or user utility) where previously this could not be done without sacrificing flexibility and practicality. Preferably, the comparing step further comprises comparing one or more predetermined application session characteristics with one or more predetermined policy characteristics according to one or more predetermined logical conditions contained in a user policy. The use of logical conditions allows for operations other than straightforward identity comparisons to be performed, thus further increasing the flexibility of the system. In the preferred embodiment, the comparing step further comprises comparing one or more contemporary environmental conditions with one or more predetermined policy characteristics and/or predetermined application session characteristics according to one or more predetermined logical conditions contained in a user policy. This allows the system to use fuzzy logic in dependence upon environmental conditions such as time, network congestion, occurrence of certain events, or the like so that the most appropriate policy can be chosen not only because of the match to the applications session, but also taking into account the contemporaneous system environmental conditions prevalent at the time the mapping is to be made and/or the session is to take place. Preferably each logical condition has a condition score allocated thereto, and the policy score comprises a sum of the condition scores for each logical condition found to be true. This allows some logical conditions to be rated more importantly than others, such that they contribute more to the policy score. In the preferred embodiment, each condition score is adjustable by a user. This feature allows expert tuning of the score obtained from each logical condition so that the policy can be made to match precisely a user's requirements. Moreover, preferably the application session characteristics are defined in accordance with any version of the Internet Engineering Task Force Session Description Protocol. This allows application descriptions to be compiled by different application vendors in accordance with agreed standards. Moreover, it allows policy compilation to be rendered easier, as the policy characteristics may simply match those relevant categories of the IETF Session Description Protocol. The use of IETF SDP (whichever version) ensures that policy compilers and session description compilers are essentially speaking the same language. The selecting step may further comprise the further steps of expressing each policy score as a percentage of a respective predetermined policy pass-score, and selecting the policy with the greatest percentage as the policy for use. In an alternative embodiment, the selecting step may further comprise comparing the absolute policy scores, and selecting the policy with the greatest absolute score as the policy for use. However, in a yet further embodiment the selecting step may further comprise calculating a difference value for each policy score, being the difference between the policy score and a respective predetermined policy pass-score, and selecting the policy with the greatest positive difference as the policy for use. In other embodiments logical combinations of the three alternatives described above may be used, for example, a policy may be chosen if it has the greatest absolute score and the greatest percentage score. Which method is chosen as the selecting step is preferably left to user preference. From a second aspect there is further provided an apparatus for selecting a user network usage policy for use with an application session, comprising: a) storage means for storing data representing a plurality of user network usage policies; b) comparison means arranged, for each policy of at least a subset of the stored policies, to compare one or more characteristics of the application session with one or more policy characteristics and to determine a policy score for each policy in the subset in dependence on the comparison; and c) selection means arranged to select a policy for use in dependence on the policy scores. The second aspect further provides the corresponding features and associated advantages as described previously in respect of the first aspect. In addition, from a third aspect the present invention also provides a computer program arranged such that when executed on a computer it causes the computer to perform a method according to the first aspect. Furthermore, from a fourth aspect there is also provided a computer readable storage medium storing a computer program according to the third aspect. The computer readable storage medium may be any magnetic, optical, magneto-optical, solid-state, or other storage medium capable of being read by a computer. BRIEF DESCRIPTION OF THE DRAWINGS Further features and advantages of the present invention will become apparent from the following description of an embodiment thereof, presented by way of example only, and by reference to the accompanying drawings, wherein like reference numerals refer to like parts, and wherein: FIG. 1 is a block diagram of a computer system which forms the embodiment of the present invention; FIG. 2 is a block diagram of the functional elements required by the embodiment of the present invention; FIG. 3 is a graphical illustration showing the semantic data which is contained within a user policy used in the embodiment of the present invention; FIG. 4 is a system diagram illustrating how the features of FIGS. 2 and 3 are derived and interact; and FIG. 5 is a flow diagram illustrating the operation of the policy selector program of FIG. 1. DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will now be described with reference to FIGS. 1 to 5. FIG. 1 illustrates the operating environment of the present invention. More particularly, an embodiment of the present invention provides a policy selector software program 4812, which is stored on a computer-readable storage medium such as the hard disk 48 provided in a user computer 40. By way of example, the policy selector program 4812 may be part of a software application, part of a middleware, or a stand-alone program in its own right. Also stored on the hard disk 48 is an operating system program 484, program policy data files 482, and a number of executable application programs App1 486, App2 488 and App3 4810, each of which possess functionality to access or send data over a network. The computer is further provided with a central processing unit 44 capable of executing computer program instructions, a central data bus 47 to provide internal communications between the components, a network input and output card 42 to allow interconnection of the computer to a network, and local input and output interface means 46 to allow connection of user input and output devices such as monitors, keyboard, mouse, printer, or the like. It should of course be noted and would be understood by the intended reader that the above description is for illustrative purposes in respect of the present invention only, and in reality many more systems, sub-systems and components would be required to provide a fully operational computer. Such additional elements are well known in the art, and should be taken as being implied herein. In use the operation of the above described operating environment may be as follows, by way of example. Suppose the user of the computer starts up one or more of the three applications App1, App2, or App3 to give one or more respective application sessions for each. Each session involves setting up one or more data traffic flows F1 to F6 via the network interface 42, such that, for example, App1 might create outward flows F1, and F2. App2 might create outward flow F3 and receives inward flows F5 and F6. App 3 might create a single outward flow F4. The applications App1, App2, and App3 may be any type of software applications which create data traffic flows over a network, such as, by way of non-limiting example, file-sharing utilities such as Napster or Gnutella, FTP clients and servers, Internet browsers such as Netscape® or Microsoft® Explorer®, streaming multimedia applications such as those provided by RealNetworks Inc., 2601 Elliott Avenue, Suite 1000 Seattle, Wash. 98121, voice-over-IP applications, video-conferencing applications, etc. etc. It should be noted that the data traffic flows may be almost any protocol, although within the embodiment either TCP or UDP over IP is preferred. Although we have described above specific mappings of Flow-Ids to applications, in reality the Flow-ID's chosen by applications would be randomly generated, and hence the flow mappings would not be apparent. In order to address this problem it is necessary to use a flow-mapper system such as is described in our earlier co-pending European patent application no. 02251983.9., any details of which necessary for understanding the present invention being disclosed herein by reference. The present invention is, however, concerned with mapping application user network use policies to application sessions, and hence complements, rather than relies upon, our earlier invention. When an application session is launched, the policy selector program 4812 is run to select a user network usage policy for the application session. The semantic structure of a user network usage policy is shown in FIG. 3 whence it will be seen that a policy contains service related information and matching criteria. Service related information contains important information that are related to the service provided by the service provider, information such as the user's preferred tariff (Users may not have a definite answer to what tariff they want to select, but they have a preference to what they want, for example, a cheap service or a high quality service), the user's utility for the service (a user preference of an application traffic profile) and the service reference (a unique identity of a service offered by a service provider e.g. service id 1000=premium service). The matching criteria are a list of constraints for the processing elements of the present invention to compare with a session description. It should be noted that in practice user policies may contain much additional information in addition to that mentioned above. Within each user policy there is a section that describes the matching criteria. Each criterion has a score for each element. Content of the session description and environmental constraints are used to compare with a user policy, and a condition score is awarded to each criterion if matched, or else, no score will be awarded. Here is an example of a set of matching criteria: Pass score = 590 Preferred policy name: {matching criterion} If Name = BestQoS, then Score = 100 {element, award score} If Name = MaxQoS, then Score = 100 FlowID: If Source IP address = 10.0.1.10, then Score = 100 ApplicationInfo: If Name = RealPlayer and Version = 8.0, then Score = 100 If Name = RealPlayer and Version = 7.0, then Score = 90 StreamType: If Name = RealPlayer data stream, then Score = 100 EnvironmentalConstraints {this will be address further later} If Network Status.AvailableBandwidth >= MaxRate, then Score = 100 If System.time = tariff.offPeakHour, then Score = 100 {the user prefer this policy to be used in off-peak hours} It will be seen from the above example matching criteria that characteristics of the policy are compared with characteristics of the application session according to predetermined logical conditions. Thus, for example, with respect to the Applicationinfo part of the policy, the Name and Version of the launched application (being characteristics thereof) are compared with “RealPlayer” and “7.0” or “8.0”, being characteristics of the policy according to an “equals to” logical condition. Note also that although not displayed so above for ease of understanding, preferably the user policy including the matching criteria and the associated logical conditions are written in XML. In addition to specific user policies, It is also useful to define a “one-fits-all” policy as a default policy for the user, along with a set of policies that fits to particular application task, and some specific policies that are written for a particular service used by a particular application session. This example forms a structured scheme to help user in organising the policy files. In order to allow for comparison of the session characteristics with those prescribed within the policy, each application session is provided with a session description which describes the application session and the network-related properties thereof which will result when the application session is created. An example session description is shown below. <ApplicationInfo> <Name>RealPlayer</Name> <Version>8.0</Version> </ApplicationInfo> <DataStreamInfo StreamType=“Realplayer data stream”> <Control> <URL>rstp://10.0.1.10:554/mtv.rm</URL> <1-- Rate in bit/s --> <MinRate>56000</MinRate> <InitialRate>256000</InitialRate> <MaxRate>450000</MaxRate> </Control> <FlowDescription> <Flow> <SourceIP>10.0.1.10</SourceIP> <SourcePort>*</SourcePort> {* means anything} <DestinationIP>10.0.1.2</DestinationIP> <DestinationPort>*</DestinationPort> <ProtocolID>TCP</ProtocolID> </Flow> <Flow> <SourceIP>10.0.1.10</SourceIP> <SourcePort>*</SourcePort> <DestinationIP>10.0.1.2</DestinationIP> <DestinationIPort>* </DestinationPort> <ProtocolID>UDP</ProtocolID> </Flow> </FlowDescription> </DataStreamInfo> <PreferPolicy> <Name>BestQoS</Natfle> </PreferPolicy> This session description describes a RealPlayer™ v8.0 video playback session, where video data is sent to the user machine (10.0.1.2) from the content server (10.0.1.10). The request URL (in the control tag) is rstp://10.0.1.10:554/mtv.rm with a minimum stream rate of 56 kbps and a maximum rate of 450 kbps, and an initial rate of 256 kbps. There are 2 streams of traffic (in flow description tag), one TCP stream and one UDP stream. The “PreferPolicy” field shows that a best quality Internet transport is preferred for this session to maintain a good quality video playback. Note that although not shown so above for reasons of clarity and ease of understanding, preferably within the presently described embodiment the session description and user policies are structured with a common standard, for instance, or Internet Engineering Task Force (IETF) Session Description Protocol (SDP) or Internet Engineering Task Force (IETF) Session Description Protocol next generation (SDPng). This ensures that the session and policy characteristics can be directly compared using essentially the same descriptive language as a finite namespace is defined for the session description. Hence, the evaluation engine which performs the comparison between session descriptions and matching criterion can locate and understand the keywords in the description. This produces a high coupling between the content of session descriptions and the user policies. Preferably, the session description is obtained from session negotiation or generated by the operating systems, the application itself, the middleware or collected from the session directory. Having described the structure of the user policies and the session description, a brief overview of the operation of the matching process will be described with respect to FIG. 2, followed by a detailed description of the whole policy selection process with respect to FIGS. 4 and 5. Turning to FIG. 2, it will be seen that that core of the system provided by the embodiment of the invention is a processing module referred to in the Figure as the “Evaluation Engine” 20. The evaluation engine 20 acts to receive the following data: a session description 22 of an application session for which a policy is to be selected; some environmental constraints 24; any user direct input 26; and several user policies 28 (of which one will be selected) obtained from a policy repository 482. The evaluation engine then looks for the most appropriate user policy for a particular application session. The Environmental constraints mentioned above are contemporary system or external characteristics that are present at the time the policy matching is to be made. Example constraints are, for example, user budget, system time, bandwidth price, network status, urgency of data to be transported by the network, importance of data, and recorded user behaviour. The environmental constraints are an important input to the Evaluation Engine and cover a wider area of logical decision making for the engine. By including such environmental constraints within the decision making logic, the system is not only able to compare the standard matching criteria to a session description but is also able to know when it is a better circumstance to use a certain policy in a certain scenario. For instance, there may be two “best QoS” user policies with different environmental constraints. Policy “BestQoSA” may state that this policy should be used only when the network can cope with the requirement and when the time slot is known as off-peak, whereas policy “BestQoSB” may be used when the time slot is known as on peak and the user is in an “urgent state”. Thus, environmental constraints play a very important role in the decision making process. Without environmental constraint, the system can only determine which policy may suit the application task, but not what the user needs. In order to build this interaction, a user interface, event listeners and data adapters are provided, as are generally known in the art. The user direct input considered by the evaluation engine could be for example user commands to specifically override the selection of a particular policy, of to specifically alter one or more of the logical condition scores contained within the policy so as to change the probability of a policy being selected. It is necessary to consider direct input from the user in the decision logic as the user may want to override the decision making process of the Evaluation Engine. This can be done by manually selecting a dedicated user policy or changing the score weighting of each matching criterion. The score weighting behaves like a multiplier for each criterion. For instance, a user may have a higher preference in policy which emphasis good quality, the system allows the user to put a higher weighting to the matching criteria of quality by giving them the ability to double or multiple folds. A user interface (which is preferably although not necessarily a graphical user interface) is provided by the system to facilitate the interaction. Provision of user interfaces in general which would be suitable for use with the present invention is well known in the art. In use the Evaluation Engine 20 assists the user in selecting the most suitable policy for a particular session. It goes through the user policies 28 stored in the policy repository 482 and matches them with the provided session description 22 and environmental constraints 24. The Evaluation Engine is based on a scoring system. The score reflects a user value to each policy for different applications. An example of the application of the example policy matching criterion given earlier to the example session description given earlier will make the process clearer. In order to evaluate the matching criterion against the session description, the Evaluation Engine 20 reads the content of the session description 22 and compares them with the user policy of interest 28. First the engine looks into the XML tag <Name> & <Version>. In the examples above the session description shows that this is a session for RealPlayer 8.0; the user policy states that if it is RealPlayer and the version is 8.0, a score of 100 will be awarded. Therefore, this policy will get 1 00 marks for the criterion “ApplicationInfo”. However, the session description may be created for an older version such as RealPlayer 7.0, so 90 marks will be awarded instead. Furthermore, the session description also contains a field with: <ApplicationInfo> <Name >Real Player</Name> <Version>8.0</Version> </ApplicationInfo> From the user policy there is a field with: ApplicationInfo: If Name=RealPlayer and Version=8.0, then Score=100 If Name=RealPlayer and Version=7.0, then Score=90 and hence the first of the above logical conditions will be found to be true and a score of 100 generated. This score of 100 is added to any previous score which has been generated from earlier positive logical conditions, and a cumulative score kept. This matching procedure is repeated for each matching criterion within the policy i.e. the session description is parsed to see if there is an equivalent entry. After going through each matching criterion, scores are added together from each criterion to form a final score. Then the final score is compared with a policy pass score, which is pre-determined and contained within each policy. If the final score of a policy is higher than the policy pass score, then the policy will be taken into account for the final comparison. Within the previous example the pass score for the policy is 590. However, from a consideration of the individual logical condition scores it is possible to score 600 which is a much more preferable score than the pass score. Once each policy has been processed in accordance with the above a final comparison step is then performed within the preferred embodiment, which represents an additional layer of processing to consider the scores achieved by each policy. There are several ways to perform the final comparison, for instance, we may compare the final score regardless of the pass score; we may compare it with a percentage mark; or we may compare a difference between the policy pass score and the policy final score. If we assume that three policies A, B, and C have been matched and have achieved respective policy scores with respect to respective pass-cores as follows:— Policy A scores 545/500=109% Policy B scores 440/400=110% Policy C scores 600/590=102% then by using a comparison of the respective percentages of the policy scores against the respective pass-scores (shown above), then it will be seen that policy B is the winner with 110%, and would be selected as the policy for use with the application session. In contrast, if an absolute policy-score is considered which does not take into account the respective policy pass-score, then policy C would be selected with a policy-score of 600. Finally, if the third method of final comparison is used wherein the respective differences between the policy scores and the respective pass-scores are found, policy A would be selected with the greatest positive difference of 45. The above example shows that the method used in the final comparison seriously affects the result. However, it is preferably left for the user to decide which method suits them best, as it greatly depends upon how the scores are distributed among each element. It may happen that the system is not able to identify the most appropriate user policy for an application session. For instance: there are two or more policies which have the highest score; there is no policy that passes the pass score; there is no policy defined for that particular application session. For these circumstances, the system should ask the user for a preference by displaying a user interface or revert to a default policy. Additionally, the user should be able to manually select a policy in the policy repository, change the weighting, or request the system to re-evaluate again. There are many ways that we can handle this situation, the example solutions above are only part of them. A second example of the operation of the presently described embodiment will now be described with reference to FIGS. 4 and 5, which will make clearer the operation of the matching of environmental constraints with multiple policies. Here, assume that the time of day when the matching is being performed corresponds to an “off-peak” time as defined by the present network tariff, that the maximum available bandwidth on the network is 480 kbps, and that we have four user policies from which one is to be selected, the details of the policies being as follows: Policy A Pass score=500 Preferred Policy Name: If Name=BestQoS, then Score=200 If Name=MaxQoS, then Score=200 ApplicationInfo: If Name=RealPlayer and Version=8.0, then Score=200 If Name=RealPlayer and Version=7.0, then Score=190 EnvironmentalContraints: If Network Status.AvailableBandwidth >=MaxRate, then Score=100 If System.time=tariff.on PeakHour, then Score=100, else Score=45 Policy B Pass score=350 Preferred Policy Name: If Name=BestQoS, then Score=200 If Name=MaxQoS, then Score=200 ApplicationInfo: If Name=Windows® Media Player and Version=7.0, then Score=200 If Name=Windows® Media Player and Version=6.0, then Score=190 EnvironmentalContraints: If Network Status.AvailableBandwidth >=MinRate, then Score=100 If System.time=tariff.offPeakHour, then Score=100, else Score=45 Policy C Pass score=590 Preferred Policy Name: If Name=BestQoS, then Score=100 If Name=MaxQoS, then Score=100 FlowID: If Source IP address=10.0.1.10, then Score=100 ApplicationInfo: If Name=RealPlayer and Version=8.0, then Score=100 If Name=RealPlayer and Version=7.0, then Score=90 StreamType: If Name=RealPlayer data stream, then Score=100 EnvironmentalContraints: If Network Status.AvailableBandwidth >=MaxRate, then Score=100 If System.time=tariff.offPeakHour, then Score=100 Policy D Pass score=590 Preferred Policy Name: If Name=MaxQoS, then Score=100 FlowID: If Source IP address=10.0.1.10, then Score=100 ApplicationInfo: If Name=RealPlayer and Version=8.0, then Score=100 If Name=RealPlayer and Version=7.0, then Score=90 StreamType: If Name=RealPlayer data stream, then Score=100 EnvironmentalContraints: If Network Status.AvailableBandwidth >=InitialRate, then Score=100 If System.time=tariff.offPeakHour, then Score=100 Assume that the launched application session for which one of the four policies A, B, C, or D corresponds to the RealPlayer session described in the example session description given previously. FIG. 5 is a flow diagram showing the process flow undertaken by the policy selector program 4812 in order to select a user policy for an application session. Firstly, at step 5.2 the application is launched. In this case the launched application is RealPlayer version 8, and hence a RealPlayer session is established. The launching of the application is detected by an appropriate event detector, which is arranged to activate the policy selector program 4812 upon application launch. Preferably the event detector is part of a middleware that takes care of the application session initiation, and produces a session description before the application session is begun. Once the policy selector program 4812 has been activated, at step 5.4 it operates to access the RealPlayer application session description from the application directory. The application session description is preferably written in IETF SDP, or SDPng, but for the purposes of this example corresponds to the session description given previously on page 9. Having accessed the application session description, at step 5.6 the policy selector program 4812 parses the session description, and stores the characteristics thereof in memory. Next, at step 5.8 the various contemporary environmental conditions of the system are accessed, such as, for example, the system time, and the network bandwidth availability. In this example we assume that the system time corresponds to an “off peak” time and that the maximum available bandwidth on the network at the present time is 480 kbps. The accessed environmental conditions are also stored in memory for later use in the comparison steps. Having obtained the above mentioned information, the policy selector program 4812 is now ready to compare the obtained information with the matching criteria contained in each available user policy. Therefore, at step 5.10 the program accesses the first policy, being in this case policy A, from the policy repository 482. Then, at step 5.12 the policy is parsed to determine the matching criteria contained therein, and the discovered matching criteria stored for use in the matching process. The program is then ready to perform a comparison of the matching criteria of policy A with the characteristics of the session description. Therefore, at step 5.14 the characteristics of the session description are compared with the logical conditions in the policy. With respect to policy A as given previously (please refer here to the session description on page 9, and Policy A given earlier), the first characteristic to be tested is the preferred policy name. Here, the application session description specifies that the preferred policy name should be “best QOS” and according to the logical conditions contained in the matching criterion, if the preferred policy name equals “best QOS” then a score of 200 is obtained. The next characteristic in the policy is that of the application_info, and in this respect the session description specifies the application_info as being of name real player and of version 8.0. With respect to the matching criteria in the policy, it will be seen that if the application_info name equals real player and the version equals 8.0, then a score of 200 is obtained. Thus so far a cumulative total of 400 has been obtained for policy A. Next, the environmental constraints specified in the policy are tested. Recall that the available bandwidth of the network was determined at step 5.8 to be 480 kbps, and that the session description specifies a max rate of 450 kbps. Therefore, according to the first logical condition in the environmental constraints part of the policy A, provided the available network bandwidth is greater than or equal to max rate specified in the session description, then a score of 100 is obtained. This criteria is met in the present case, and hence a cumulative total of 500 is obtained. Next, the system time is compared. The policy specifies that if the system at the time the matching is being performed corresponds to a peak hour as defined by the network tariff then a score of 100 is obtained, and in other cases a score of 45 is obtained. Recall that at step 5.8 it was determined that the system time corresponded to an off peak time, and hence the score of 45 is obtained to give a cumulative total of 545. As the pass score of policy A is specified as being 500, the cumulative total of 545 exceeds this pass score, and hence policy A will be considered as a candidate for selection in the final comparison stage. Therefore, at step 5.18 the policy cumulative score of 545 is stored in memory for later use. Next, having processed the first policy (policy A), a comparison is made by the policy selector program 4812 at step 5.20 to see if there are any further policies which require processing. In this case the answer is yes, and hence the processing flow returns to step 5.10 wherein the next policy, policy B, is accessed from the policy repository 482. The identical procedure as previously described in respect of policy A is then carried out in respect of policy B. To wit, at step 5.12 the policy is parsed to determine the matching criterion, and at step 5.14 the conditions of the matching criterion are compared with those of the session description. Following that at step 5.16 the conditions of the matching criterion are compared with the environmental conditions determined at step 5.8. The cumulative score obtained by the conditions is then stored at step 5.18. With respect to policy B (please refer here to the session description on page 9, and Policy B given earlier), the first criterion to be measured is again that of the preferred policy name. Here, as the session description specifies a preferred policy name of “best QOS” a score of 200 is obtained. Next, the application_info criteria are tested, but here, as the application_info given in the session description does not correspond to the characteristics of the policy then no score is obtained. Finally, the environmental constraints are tested. Recall that the network available bandwidth is 480 kbps but that the matching criterion in the policy specified in the bandwidth must be more than the session min rate to obtain a score of 100. Since the session description specifies min rate as 56 kbps, a score of 100 is obtained, to give a cumulative score of 300. Next, the system time criteria is measured, and here the policy specifies that if the time corresponds to an off-peak time as defined by the present tariff then a score of 100 is obtained, else a score of 45 is obtained. In this case it will be recalled that it was determined at step 5.8 that the time corresponded to an off-peak time as defined by the present tariff, and hence a score of 100 is achieved, to give an overall cumulative total policy score for policy B of 400. In view of the policy pass score of 350, it will be seen that policy B can also be considered in the final comparison step. Following the performance of step 5.18 in respect of policy B, a comparison of step 5.20 is again undertaken, an in this case processing returns to step 5.10 wherein policy C is accessed from the policy repository. Then the steps 5.12, 5.14, 5.16, and 5.18 are performed as described previously, but this time in respect of policy C. With respect to policy C, it will be seen (please refer to the session description on page 9, and Policy C given earlier) that a score of 100 is obtained due to the policy names matching and a further score of 100 due to the matching source addresses. An additional score of 100 is obtained due to the matching application info and a further 100 (to give a cumulative score of 400) for the matching stream type given in the policy with that as given in the session description. When the environmental constraints are tested, it will be seen that the network available bandwidth of 480 kbps is greater than the session max rate of 450 kbps, and hence a further 100 is a obtained, and furthermore since the time corresponds to an off peak time as defined by the presently in force tariff an additional score of another 100 is obtained. Therefore, the cumulative policy score for policy C is 600, which is greater than the policy pass score of 590. Thus the policy C will also be considered in the final comparison. After considering policy C, the evaluation at step 5.20 returns that there is one further policy still to process, and hence process flow returns to step 5.10 wherein policy D is accessed from the policy repository 482. Policy D is then processed in accordance with steps 5.12, 5.14, 5.16, and 5.18 in the same manner as previously described. With respect to the score obtained by policy D, (please refer here to the session description on page 9, and Policy D given earlier) it will be seen that the preferred policy name does not match that given in the description, and hence no score is obtained there. However the flow_ID criteria is met, as is the application_info criteria. In addition, the stream_type criteria is met and both of the environmental constraints. However, the above logical conditions which are met only give a cumulative score of 500, whereas the pass score for the policy is 590. Therefore, as the policy score achieved by policy D when compared against the session does not meet the pass score for the policy, policy D is deemed to have failed and is not put forward for further consideration by the final comparison. Once all of the policies have been considered, those candidate policies which met their pass scores are then considered in the final comparison. As will be recalled from the previous discussion, the final comparison can be determined in a number of ways. Firstly it is possible to merely compare the respective policy scores achieved by each policy, and select as the policy for use that one which achieved the absolute greatest policy score. Note that it is not necessary to perform further processing to obtain the absolute scores, as these have each already been stored in memory at step 5.18. A second method of performing the final selection is instead to calculate the percentage of the policy score for each policy with respect to its own respective pass score, and this is performed at step 5.22. A third method of performing the final comparison is to calculate a difference value for each policy representing the difference between the policy score which is achieved when compared with the session description with respect to its respective pass score. Therefore, at step 5.25 this “difference value” is calculated for each policy and stored. Following the calculation of these various values, at step 5.26 the appropriate policy is selected depending upon which of the various policy matching criteria the user has selected to be used. In the present example, if the first method of simply comparing the absolute policy scores is used then policy C will be selected from the candidate policies A, B, and C, as policy C has the highest absolute pass score of 600. In contrast, if the second method of selecting the policy with the greatest percentage of its policy score with respect to its pass score is used, then policy B will be selected with a percentage of 114%. If the third matching criteria of comparing the differences between respective pass scores and policy scores is used, then again here policy B will be selected with a difference of 50, in comparison with the differences of 45 for policy A, and 10 for policy C. Thus, the precise selecting step used by step 5.26 is dependent on user preference setting. In the preferred embodiment, the inventors have found the second method of comparing percentage values to possess an advantage, as it effectively normalises out the potential differences in absolute scores when policies which have widely different numbers of logical conditions (and hence in theory could give very high or very low absolute scores) are tested against each other. In the embodiment described above, at step 5.8 the present environmental conditions (such as time and available network bandwidth) are accessed from the system as a prelude to any of the user policies being accessed and processed in accordance with steps 5.10, 5.12, 5.14, 5.16, 5.18, and 5.20. In another embodiment, however, the step 5.8 of accessing the present environmental conditions can be performed separately for each policy, such that the step 5.8 is performed within the loop formed by steps 5.10, 5.12, 5.14, 5.16, 5.18, and 5.20. More particularly, the step 5.8 is performed after the step 5.12 where the presently processed policy is parsed, but before the step 5.16 where the environmental conditions are compared with the policy logical conditions, and therefore either immediately preceding or following step 5.14. By parsing the policy prior to the performance of step 5.8, it is possible to obtain knowledge of which environmental conditions are required for comparison by the policy, and hence only those conditions which are required as input to one or more of the policy's logical conditions as determined by the parsing step 5.12 are accessed from the system at step 5.8. With this exception of these differences, however, the alternative embodiment operates in exactly the same manner as the main embodiment described previously. With respect to the performance of the embodiments, in the worst scenario where there are many user policies stored in the policy repository it is going to take the system a longer time to evaluate all the policies. In addition, managing those policies would be tedious. If policies are grouped together in a structure and stored in a Database, this will improve the performance of the search and this will make it easier to manage and organise policies. Preferably service providers should provide a collection of default policies for the services they provide to their customers. Otherwise the system will have no idea which policy to use, or it will make it very difficult for a novice user to find out which policy suits him/her. Moreover the system should be able to respond to the Environmental Constraints stated in the user policies. For instance, if the policy contains a statement that asks for the usage cost, the system should be able to respond with a measurement system to measure usage cost. Alternatively, the user should not be able to add constraints that the system is not able to react to. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising” and the like are to be construed in an inclusive as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.
<SOH> BACKGROUND TO THE PRESENT INVENTION AND PRIOR ART <EOH>The mapping of application sessions to user policies is a very important requirement for both present and future Internet technologies such as Quality of Service (QoS) provision, usage control and QoS control. At the present time, there is no direct way for users to control their Internet traffic behaviour, behaviour such as transmission rate and aggressiveness. Instead, users rely on TCP, UDP and other closed loop transport layer control protocols to control the traffic on their behalf. Nowadays, users use the Internet for several different things at a time, for instance, downloading articles from a newsgroup and having a voice-chat with her friends in a chat room. In spite of both applications are using the same network connection, they have different network resource requirements such as bandwidth and delay. At the moment, using TCP, both applications will have to fight against each other to get the network resources they need. In a dynamic pricing scenario (such as, for example, that being considered by the M3I Consortium (see www.m3i.org)) an agent can be set up to help the user to react to dynamic pricing signals. It requires the user to specify a control policy, usually represented as the user utility. As the user may have different preferences to each application task, so a different control policy is applied to them. Clearly, if the agent doesn't have a policy input, it will not be able to react to the dynamic price. According to present research in advanced Internet technology, what is still missing in order to address the above problem is the bonding of Internet traffic flows, application sessions and user policies. Solutions which partially address this problem are starting to appear, and in particular our own earlier co-pending European Patent Application No 02251983.9 discloses a system to map data traffic flows with application sessions. This solves part of the problem in that it allows data flows generated by application sessions to be identified and mapped thereto, but what is still missing is the additional step of then mapping an application session to a user network usage policy, which contains information on, for example, how the user wishes to respond to different network prices, whether different types of data should be given a higher priority (and hence paid for at a higher charge for network transport thereof), how the system should respond to dynamic pricing signals received from the network, etc. etc. As will be apparent from the foregoing, the proper mapping of user usage policies to applications sessions is essential for dynamic internet charging scenarios. The application session to user policy mapping problem has been considered before, but problems arise with previous solutions in that they are not particularly flexible. An example is where a user's preference is hardwired to the system. In this case the system has a pre-programmed user's preference set in the system, and hence the preference may not truly represent what the user wants at all times or for each different type of network application. An example of this is where a default user policy is provided to the user by the user's Internet Service Provider for use with all network applications. In another known solution, the user has to select his/her utility before the start of a session (e.g. in most M3I scenarios). However, to keep asking a user what they want for every application session which is launched is not a practical solution, as it wastes time and furthermore tends to cater only for the needs of expert users who know the significance of the options available. For an average lay user of networks such as the Internet, the specific tuning required by this solution upon the launching of each and every network application session is not a viable option, and both expensive mistakes may be made by inexperienced users who select a high utility for data (indicating that they would be willing to pay a high price for its transport over the network) for which in reality the user has only a relatively low utility.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention addresses the problems noted above by the provision of a method and system which provides the matching of application sessions to user network usage or buying policies based upon a scoring system which reflects a user value to each policy for different applications. Several user policies are stored, each containing a list of matching criteria. Each criterion has a score for each element. The content of an application session description is used to compare with each user policy, and a policy score is awarded to each criterion if matched, or else, no score is awarded. The user policy which scores the highest policy score (which may be adjusted to be expressed as a percentage) is then chosen as the policy to use for the application session. In view of the above, according to a first aspect of the present invention there is provided a method of selecting a user network usage or buying policy for use with an application session, comprising the steps of: a) storing a plurality of user network usage policies; b) for each policy of at least a subset of the stored policies, comparing one or more characteristics of the application session with one or more policy characteristics to determine a policy score for each policy in the subset; and c) selecting a policy for use in dependence on the policy scores. As the mapping of application sessions to user policies has always been a huge difficulty for service provider as much as for researcher the present invention provides the advantage that it significantly helps service providers to flexibly provide Quality of Service to their customers with multiple different services. The policy mapping obtained using the present invention also gives the possibility to extend control decisions of Internet traffic to the user's preference (or user utility) where previously this could not be done without sacrificing flexibility and practicality. Preferably, the comparing step further comprises comparing one or more predetermined application session characteristics with one or more predetermined policy characteristics according to one or more predetermined logical conditions contained in a user policy. The use of logical conditions allows for operations other than straightforward identity comparisons to be performed, thus further increasing the flexibility of the system. In the preferred embodiment, the comparing step further comprises comparing one or more contemporary environmental conditions with one or more predetermined policy characteristics and/or predetermined application session characteristics according to one or more predetermined logical conditions contained in a user policy. This allows the system to use fuzzy logic in dependence upon environmental conditions such as time, network congestion, occurrence of certain events, or the like so that the most appropriate policy can be chosen not only because of the match to the applications session, but also taking into account the contemporaneous system environmental conditions prevalent at the time the mapping is to be made and/or the session is to take place. Preferably each logical condition has a condition score allocated thereto, and the policy score comprises a sum of the condition scores for each logical condition found to be true. This allows some logical conditions to be rated more importantly than others, such that they contribute more to the policy score. In the preferred embodiment, each condition score is adjustable by a user. This feature allows expert tuning of the score obtained from each logical condition so that the policy can be made to match precisely a user's requirements. Moreover, preferably the application session characteristics are defined in accordance with any version of the Internet Engineering Task Force Session Description Protocol. This allows application descriptions to be compiled by different application vendors in accordance with agreed standards. Moreover, it allows policy compilation to be rendered easier, as the policy characteristics may simply match those relevant categories of the IETF Session Description Protocol. The use of IETF SDP (whichever version) ensures that policy compilers and session description compilers are essentially speaking the same language. The selecting step may further comprise the further steps of expressing each policy score as a percentage of a respective predetermined policy pass-score, and selecting the policy with the greatest percentage as the policy for use. In an alternative embodiment, the selecting step may further comprise comparing the absolute policy scores, and selecting the policy with the greatest absolute score as the policy for use. However, in a yet further embodiment the selecting step may further comprise calculating a difference value for each policy score, being the difference between the policy score and a respective predetermined policy pass-score, and selecting the policy with the greatest positive difference as the policy for use. In other embodiments logical combinations of the three alternatives described above may be used, for example, a policy may be chosen if it has the greatest absolute score and the greatest percentage score. Which method is chosen as the selecting step is preferably left to user preference. From a second aspect there is further provided an apparatus for selecting a user network usage policy for use with an application session, comprising: a) storage means for storing data representing a plurality of user network usage policies; b) comparison means arranged, for each policy of at least a subset of the stored policies, to compare one or more characteristics of the application session with one or more policy characteristics and to determine a policy score for each policy in the subset in dependence on the comparison; and c) selection means arranged to select a policy for use in dependence on the policy scores. The second aspect further provides the corresponding features and associated advantages as described previously in respect of the first aspect. In addition, from a third aspect the present invention also provides a computer program arranged such that when executed on a computer it causes the computer to perform a method according to the first aspect. Furthermore, from a fourth aspect there is also provided a computer readable storage medium storing a computer program according to the third aspect. The computer readable storage medium may be any magnetic, optical, magneto-optical, solid-state, or other storage medium capable of being read by a computer.
20041105
20141216
20051027
95515.0
0
SMARTH, GERALD A
METHOD AND APPARATUS FOR SELECTING USER POLICIES
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,616
ACCEPTED
Incubator and culture device
Contamination by dust particles, bacteria and so forth in each processing step can be reduced by a simple constitution. A culture vessel is used in which a medium vessel in which a medium is sealed and a waste medium vessel capable of housing the fluid in a main culture vessel are connected to the main culture vessel by connecting lines capable of restricting the flow of fluid between them in a state in which they are sealed from the outside. A culture apparatus is composed in which the inner volume of each vessel is variable, and is provided with a case provided with indentations for housing each vessel, and a pressing means that contracts the vessels housed in the indentations by applying external pressure.
1. A culture vessel comprising: at least one medium vessel having one main culture vessel in which a medium is sealed, and at least one waste medium vessel capable of housing the fluid in the culture vessel; said medium vessel and culture vessel being sealed from the outside by connecting lines capable of restricting the flow of fluid between the vessels. 2. A culture vessel according to claim 1, wherein the connecting lines are provided with valves, and the flow of fluid within the connecting lines is allowed or restricted by said valves. 3. A culture vessel according to claim 1, wherein the connecting lines are made of a flexible material and the flow of fluid therein is restricted by clamping those connecting lines. 4. A culture vessel according to claim 1, wherein a blood collection line is connected to the main culture vessel. 5. A culture vessel according to claim 1, wherein at least one enzyme vessel in which a protease enzyme is sealed is connected to the main culture vessel by a connecting line capable of restricting the flow of fluid between them in a state in which it is sealed from the outside. 6. A culture vessel according to claim 1, wherein a body tissue supplement material is sealed in the main culture vessel. 7. A culture vessel according to claim 6, wherein at least one type of growth accelerator vessel, in which a growth accelerator containing growth factor is sealed, is connected to the main culture vessel by a connecting line capable of restricting the flow of fluid between them in a state in which it is sealed from the outside. 8. A culture vessel according to claim 1, wherein the connecting lines are made of a material that can be sealed or fused by heat. 9. A culture vessel according to claim 1, wherein the main culture vessel is provided with an occluded connecting line, the end of which is occluded, and the occluded connecting line is made of a material that can be sealed or fused by heat. 10. A culture vessel according to claim 1, wherein the main culture vessel, the medium vessel and the waste medium vessel have a variable inner volume. 11. A culture vessel according to claim 10, wherein at least one enzyme vessel having a variable inner volume and in which a protease enzyme is sealed is connected to the main culture vessel by a connecting line capable of restricting the flow of fluid between them in a state in which it is sealed from the outside. 12. A culture vessel according to claim 10 wherein, a body tissue supplement material is sealed in the main culture vessel, and at least one growth accelerator vessel having a variable inner volume, in which a growth accelerator containing growth factor is sealed, is connected to the main culture vessel by a connecting line capable of restricting the flow of fluid between them in a state in which it is sealed from the outside. 13. A culture apparatus comprising: a culture vessel according to any of claims 1 through 12, and a means for allowing a fluid within the vessels that compose the culture vessel to flow into the connecting lines provided in said vessels. 14. A culture apparatus according to claim 13, wherein each vessel that composes the culture vessel has a variable inner volume, and the culture apparatus is provided with a case provided with indentations for housing each vessel that composes the culture vessel, and a pressing means that contracts each vessel housed in the indentations by applying external pressure. 15. A culture apparatus according to claim 14, wherein the connecting lines are made of a flexible material, the flow of fluid within the connecting lines is restricted by clamping the lines, connecting line pathways are provided in the case through which the connecting lines of the culture vessel pass, and valve means are provided that restrict the flow of fluid through the connecting lines by clamping the connecting lines disposed in the connecting line pathways in the radial direction. 16. A culture apparatus according to claim 14, wherein a centrifuge is provided that rotates the case with the culture vessel inside, and the indentations that house the main culture vessels are disposed at intervals from the axis of rotation. 17. A culture apparatus according to claim 14, wherein an occluded connecting line having an occluded end is provided on the main culture vessel, the occluded connecting line is made of a material that can be sealed or fused with heat, the case is provided with a centrifuge that rotates the case with culture vessels inside, and the occluded connecting line is disposed outward in the radial direction of the main reaction vessel centered about the center of the axis of rotation in the state in which the main culture vessel is housed in indentations of the case.
TECHNICAL FIELD The present invention relates to a culture vessel and culture apparatus for culturing cells. BACKGROUND ART In order to culture cells, a plurality of steps are carried out in order, including an extraction step in which the cells to be cultured are extracted from bone marrow fluid or other liquid extracted from a patient, a medium preparation step in which a medium suitable for the cells to be cultured is prepared, a primary culturing step in which the extracted cells are placed in a medium in a suitable culture vessel and subjected to predetermined culturing conditions, and a secondary culturing step in which the primary cultured cells are mixed into a body tissue supplement material followed by additional culturing. This type of cell culturing has conventionally been considered to be carried out in a clean room for which particle levels are controlled after sealing the entire culture (see, for example, Japanese Examined Patent Application, Second Publication No. 3-57744, page 2, column 3). Namely, an air flow is formed inside a clean room by which air flows from the ceiling towards the floor, and in the case dust particles and so forth are generated in each treatment step, the dust particles are carried towards the floor by the flow of air and then collected by a dust collector disposed beneath the floor. Robot arms are installed within the clean room, and cells can be transferred between each step. However, in the case of carrying out all of the treatment steps within a clean room in this manner, since the space in which each step is carried out is continuous, dust particles generated in one step have the potential for contaminating cells allocated to the next step. Thus, in the case of simultaneously culturing a plurality of cells, problems result due to the occurrence of contamination between cells or contamination of added substances. In consideration of the aforementioned circumstances, the object of the present invention is to provide a culture vessel and culture apparatus capable of reducing contamination by dust, bacteria and so forth in each treatment step using a simple constitution. DISCLOSURE OF THE INVENTION The present invention provides a culture vessel comprising: at least one medium vessel having one main culture vessel in which a medium is sealed, and at least one waste medium vessel capable of housing the fluid in the culture vessel; said medium vessel and culture vessel being sealed from the outside by connecting lines capable of restricting the flow of fluid between the vessels. In a culture vessel having the aforementioned constitution, cells are placed in the main culture vessel, and restriction on the flow of fluid in the connecting line between the medium vessel and main culture vessel is removed to allow medium to flow from the medium vessel into the main culture vessel through the connecting line. By then again restricting the flow of fluid in the aforementioned connecting line while in this state, the inside of the main culture vessel can be sealed from other vessels. As a result, cells can be cultured in the main culture vessel while sealed from the outside. In addition, in the case it becomes necessary to replace the medium in the main culture vessel after a predetermined amount of time has elapsed, restriction on the flow of fluid through the connecting line between the main culture vessel and waste medium vessel is removed, and medium is allowed to flow from the main culture vessel towards the waste medium vessel. As a result, waste medium that is no longer required in the main culture vessel can be discharged into the waste medium vessel. Subsequently, cell culturing is continued by again allowing medium to flow from the medium vessel towards the main culture vessel and restricting the flow of fluid in the connecting line. In this manner, since cell culturing and the supply and replacement of medium required for cell culturing can be carried out in a vessel that is completely sealed, even if the culturing of numerous types of cells is carried out in extremely close proximity, intermixing of cells and contamination by bacteria and so forth can be inhibited. In addition, the present invention provides a culture vessel in which the aforementioned connecting lines are provided with valves, and the flow of fluid within the connecting lines is allowed or restricted by said valves. According to this culture vessel, the flow of fluid in the connecting lines can be controlled by controlling the valves. As a result, the connecting lines can be opened and closed easily making it possible to switch between steps such as inflow of medium from the medium vessel to the main culture vessel, discharge of medium from the main culture vessel to the waste medium vessel and culturing of cells within the main culture vessel. In addition, the present invention provides a culture vessel in which the connecting lines are made of a flexible material and the flow of fluid therein is restricted by clamping those connecting lines. According to this culture vessel, the flow of fluid is restricted as a result of the connecting lines made of a flexible material being crushed when they are pressed on from outside the culture vessel, thereby blocking the flow path inside. As a result, the constitution of the culture vessel can be simplified without providing valves in the connecting lines. The use of a simpler constitution to reduce costs is preferable in the case a disposable culture vessel is used for each batch of cells. In addition, the present invention provides a culture vessel in which a blood collection line is connected to the main culture vessel. According to this culture vessel, by inserting the blood collection line into a patient and collecting blood, bone marrow or other body fluid from the patient, cells to be cultured can be supplied to the main culture vessel. In addition, the present invention provides a culture vessel in which at least one enzyme vessel in which a protease enzyme is sealed is connected to the main culture vessel by a connecting line that restricts the flow of fluid between them in a state in which it is sealed from the outside. According to this culture vessel, in the case of, for example, culturing adhesive cells such as mesenchymal stem cells, cells grow by adhering to the inner wall of the main culture vessel after a predetermined culturing period has elapsed. Thus, in the case of collecting such cells, the cells can be detached from the inner wall of the main culture vessel by removing the restriction on flow in the connecting line between the enzyme vessel and main culture vessel and allowing protease enzyme to flow into the main culture vessel after having discharged the medium in the main culture vessel into the waste medium vessel. In addition, the present invention provides a culture vessel in which a body tissue supplement material is sealed. According to this culture vessel, when cells are placed in the main culture vessel and medium is supplied to the main culture vessel, the cells adhere to the body tissue supplement material sealed within the main culture vessel, allowing the cells to grow by using the body tissue supplement material as a scaffold. By then repeating the supply of medium from the medium vessel to the main culture vessel and the discharge of unnecessary medium from the main culture vessel to the waste medium vessel during a suitable culturing period, a body tissue supplement can be produced in which cells have adequately grown on the body tissue supplement material. In addition, the present invention provides a culture vessel in which a body tissue supplement material is sealed in the main culture vessel, and at least one type of growth accelerator vessel, in which a growth accelerator containing growth factor is sealed, is connected to the main culture vessel by a connecting line capable of restricting the flow of fluid between them in a state in which it is sealed from the outside. According to this culture vessel, the growth of cells can be accelerated during culturing by removing the restriction on the flow of fluid in the connecting line between the main culture vessel and growth accelerator vessel and allowing growth accelerator containing growth factor to flow into the main culture vessel. In addition, the present invention provides a culture vessel in which the connecting lines are made of a material that can be sealed or fused by heat. According to this culture vessel, only the main culture vessel in particular can be separated from the other vessels by sealing the connecting lines with heat. Thus, for example, by separating only the main culture vessel by sealing the connecting lines with heat at completion of the culturing period, only the cells that have grown can be transported or delivered. In addition, in the case of culturing with a body tissue supplement material, by separating only the main culture vessel, only the body tissue supplement can be transported and delivered in a sealed form. In addition, as a result of composing the connecting lines with a material that can be fused by heat, cells can be transferred from one main culture vessel to another main culture vessel by fusing the corresponding connecting lines. In this case, since cell transfer can also be carried out in a space that is sealed from the outside, contamination by bacteria and so forth can be inhibited. In addition, the present invention provides a culture vessel in which the main culture vessel is provided with an occluded connecting line, the end of which is occluded, and the occluded connecting line is made of a material that can be sealed or fused by heat. According to this culture vessel, two main culture vessels can be connected by severing and then fusing an occluded connecting line provided on one main culture vessel and an occluded connecting line provided on another main culture vessel with heat. For example, a body tissue supplement can be produced by passing cells adequately grown in one main culture vessel through an occluding connecting line and transferring them to another main culture vessel in which a body tissue supplement material is sealed. In addition, the present invention preferably composes each of the vessels that compose the culture vessel to have a variable inner volume. According to this constitution, fluid can be transferred between vessels by reducing the inner volume of the vessel. In addition, the present invention provides a culture apparatus provided with a culture vessel as claimed in the present invention, and a means for allowing a fluid within the vessels that compose the culture vessel to flow into the connecting lines provided in said vessels. In the culture apparatus of the present invention, a constitution is preferably employed in which each vessel that composes the culture vessel has a variable inner volume, and the culture apparatus is provided with a case provided with indentations for housing each vessel that composes said culture vessel, and a pressing means that contracts each vessel housed in the indentations by applying external pressure. According to this culture apparatus, by housing each vessel of a culture vessel in which a plurality of vessels are connected with connecting lines in indentations formed in the case, the culture vessel is held in the case, thereby improving ease of handling by being able to be handled as a single unit. By allowing the pressing means to act in this state, each vessel is contracted by selectively applying external force. At this time, by removing the restrictions on flow of the connecting tubes connecting the contracted vessels, the fluid sealed inside the contacted vessels can be transferred to another vessel through the connecting lines. At this time, since each vessel is held in an indentation provided in the case, the fluid inside can be made to efficiently flow out simply by pressing the pressing means. In addition, the present invention provides a culture apparatus in which the connecting lines are made of a flexible material, the flow of fluid within the connecting lines is restricted by clamping the lines, connecting line pathways are provided in the case through which the connecting lines of the culture vessel pass, and valve means are provided that restrict the flow of fluid through the connecting lines by clamping the connecting lines disposed in the connecting line pathways in the radial direction. According to this culture apparatus, as a result of housing each vessel that composes the culture vessel in indentations provided in the case, each vessel is integrally held in the case thereby improving handling ease. In this case, the connecting lines that connect each vessel are disposed so as to pass through the connecting line pathways provided in the case. Since valve means are disposed in the connecting line pathways, the connecting lines disposed in the case are crushed so as to block the flow path inside as a result of external force being applied in the radial direction by the valve means, thereby restricting the flow of fluid. In addition, the present invention provides a culture apparatus provided with a centrifuge that rotates the case with the culture vessel inside, and the indentations that house the main culture vessels are disposed at intervals from the axis of rotation. According to this culture apparatus, as a result of the operation of the centrifuge rotating the case to which culture vessels are attached with the culture vessels still attached, medium and cells arranged inside the main culture vessels can be separated by centrifugation. Since the main culture vessels are disposed at intervals from the axis of rotation of the centrifuge, separated cells accumulate at a fixed location farthest away in the radial direction from the center of the axis of rotation. In addition, the present invention provides a culture apparatus in which an occluded connecting line having an occluded end is provided on the main culture vessel, the occluded connecting line is made of a material that can be sealed or fused with heat, the case is provided with a centrifuge that rotates the case with reaction vessels inside, and the occluded connecting line is disposed outward in the radial direction of the main reaction vessel centered about the center of the axis of rotation in the state in which the main culture vessel is housed in indentations of the case. According to this culture apparatus, although separated cells accumulate at the location farthest away in the radial direction from the center of the axis of rotation, since occluded connecting lines are disposed at this location, the centrifuged cells can be efficiently removed to the outside from the occluded connecting lines when pushed out from the main culture vessel. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a front view showing a culture vessel as claimed in a first embodiment of the present invention. FIG. 2 is an explanatory drawing for explaining a culturing step that applies the present invention. FIG. 3 is a schematic drawing for explaining a step in which medium is supplied from a medium vessel to a main culture vessel using the culture vessel of FIG. 1. FIG. 4 is a schematic drawing similar to FIG. 3 for explaining a step in which medium is discharged from a main culture vessel to a waste medium vessel. FIG. 5 is a front view showing a variation of the culture vessel of FIG. 1. F is front view showing another variation of the culture vessel of FIG. 1. FIG. 7 is a front view showing another variation of the culture vessel of FIG. 1. FIGS. 8A, 8B and 8C are perspective views for explaining the order of steps for aseptically severing a tube. FIGS. 9A, 9B and 9C are perspective views for explaining the order of steps for aseptically connecting a tube. FIG. 10 is a longitudinal cross-sectional view showing the end structure of an occluded connecting tube. FIG. 11 is a front view showing culture vessels used in a culture apparatus as claimed in a second embodiment of the present invention. FIG. 12 is an overhead view showing a case in which the culture vessels of FIG. 11 are housed. FIG. 13 is a longitudinal cross-sectional view showing the culture apparatus of FIG. 11 partially severed. FIG. 14 is an overhead view showing a culture apparatus as claimed in a third embodiment of the present invention. FIG. 15 is a longitudinal cross-sectional view showing a variation of the culture apparatuses of the first, second and third embodiments. FIG. 16 is a front view showing a culture apparatus as claimed in a fourth embodiment of the present invention. FIG. 17 is a side view of the culture apparatus of FIG. 16. FIG. 18 is a front view showing culture vessels used in the culture apparatus of FIG. 16. FIG. 19 is a front view showing a step in which medium is discharged from a main culture vessel to a waste medium vessel in the culture apparatus of FIG. 16. FIG. 20 is a front view showing a step in which medium is supplied from a medium vessel to a main culture vessel in the culture apparatus of FIG. 16. FIG. 21 is a front view showing a variation of the culture vessels in the culture apparatus of FIG. 16. FIG. 22 is a perspective view of the culture vessels shown in FIG. 21. FIG. 23 is a side view showing a culture apparatus as claimed in a fifth embodiment of the present invention. FIG. 24 is a front view of the culture apparatus shown in FIG. 23. FIG. 25 is an overhead view showing a culture apparatus as claimed in a sixth embodiment of the present invention. FIG. 26 is a front view of the culture apparatus shown in FIG. 25. FIG. 27 is a front view showing a step in which medium is discharged from a main culture vessel to a waste medium vessel in the culture apparatus of FIG. 25. FIG. 28 is a front view showing a step in which medium is supplied from a medium vessel to a main culture vessel in the culture apparatus of FIG. 25. BEST MODE FOR CARRYING OUT THE INVENTION First Embodiment Culture Vessel The following provides an explanation of a culture vessel as claimed in a first embodiment of the present invention with reference to the drawings. As shown in FIG. 1, the culture vessel as claimed in the present embodiment is composed of one main culture vessel 2, one medium vessel 3, one waste medium vessel 4, a first connecting line 5 that connects main culture vessel 2 and medium vessel 3, and a second connecting line 6 that connects main culture vessel 2 and waste medium vessel 4. Main culture vessel 2, medium vessel 3 and waste medium vessel 4 are respectively composed of a flexible material such as vinyl chloride. In addition, first and second connecting lines 5 and 6 are also composed of flexible tubes such as those made from vinyl chloride. Each of these vessels 2 through 4 and connecting lines 5 and 6 are able to mutually connect their internal spaces, and are connected in a state in which their inner space is sealed from the outside. Namely, valves 7 and 8 that can be opened and closed from the outside are provided at intermediate locations of first and second connecting lines 5 and 6. In addition, a medium such as minimum essential medium (MEM), fetal bovine serum (FBS) and an antibiotic and so forth is sealed in the aforementioned medium vessel 3 adjusted to a predetermined blending ratio of, for example, 84:15:1. Human serum may be used instead of FBS. The aforementioned waste medium vessel 4 is initially empty and arranged in a sufficiently contracted state. The aforementioned main culture vessel 2 is provided with an injection port 9 that can be penetrated with an injection needle and closes due to elasticity after the injection needle has been removed. As a result, a body fluid such as bone marrow fluid can be injected into the main culture vessel by puncturing the injection port with an injection needle of a syringe used to collect bone marrow fluid, and the inside of main culture vessel 2 can be isolated from the outside by retracting the injection needle from the injection port. Prior to explaining the operation of culture vessel 1 as claimed in the present embodiment composed in this manner, a general explanation is provided of the production process of a bone supplement used as a body tissue supplement. As shown in FIG. 2, in order to produce a bone supplement, bone marrow fluid is first collected from the iliac bone and so forth of a patient. The collected bone marrow fluid is placed in a centrifuge and spun to extract the bone marrow cells having a larger specific gravity. The extracted bone marrow cells are loaded into a culture vessel together with pre-prepared medium and mixed. A portion of the medium is removed and subjected to examination for infection. Subsequently, the cells are subjected to primary culturing by culturing the mixed bone marrow fluid and medium under fixed culturing conditions for a predetermined amount of time by maintaining at culturing conditions such as a predetermined temperature (e.g., 37±0.5° C.), humidity (e.g., 100%) and CO2 concentration (e.g., 5%). The medium is discarded from the culture vessel at predetermined replacement times during the course of cell culturing. Medium is then again mixed in and culturing is continued by repeating the culturing step. A portion of the discarded medium is subjected to examination for infection. Following the completion of a predetermined culturing period, and after the medium is discarded from the culture vessel, a protease enzyme such as trypsin is added to the culture vessel and mixed. As a result, mesenchymal stem cells that have grown by adhering to the bottom of the culture vessel are detached from the bottom of the main culture vessel. The mesenchymal cells that have been detached in this manner are then extracted by spinning in a centrifuge. After adjusting the number of cells, the extracted mesenchymal stem cells are mixed in a culture vessel containing a bone supplement material and a suitable medium. In actuality, the mesenchymal stem cells are loaded into the medium by adhering to the bone supplement material. The mixed mesenchymal stem cells and medium are then cultured under fixed culturing conditions over a predetermined amount of time by maintaining at culturing conditions such as a predetermined temperature (e.g., 37±0.5° C.), humidity (e.g., 100%) and CO2 concentration (e.g., 5%) in the same manner as previously described to carry out secondary culturing. In this secondary culturing step as well, the medium is periodically replaced in the same manner as in the primary culturing step, and a portion of the added medium and a portion of the discarded medium are respectively subjected to examinations for infection. After a predetermined culturing period has elapsed, specimens for quality testing for shipping and for infection examinations are extracted, and the produced bone supplement material is sealed and provided as a finished product. The following provides an explanation of the operation of culture vessel 1 as claimed in the present embodiment. The culture vessel 1 as claimed in the present embodiment is the culture vessel 1 used in the primary culturing step among the culturing steps described above. As was previously described, bone marrow fluid is injected into main culture vessel 2 by penetrating an injection port 9 with the injection needle of a syringe used to collect bone marrow fluid. Together with opening valve 7 provided in first connecting line 5, as shown in FIG. 3, the inner volume of medium vessel 3 is contracted by applying a force from the outside such as pressing by piston 10. As a result, a predetermined amount of medium is supplied from medium vessel 3 into main culture vessel 2, and mixed with the bone marrow fluid injected into main culture vessel 2. At this time, valve 8 provided in second connecting line 6 is closed. Culturing is then carried out by then subjecting main culture vessel 2 to culturing conditions such as a temperature of 37±0.5° C. and CO2 concentration of 5% while in this state. The CO2 culturing conditions can be achieved by either dissolving CO2 in the medium or composing all or a portion of main culture vessel 2 with a CO2-permeable filter. Subsequently, when a predetermined medium replacement time has been reached, as shown in FIG. 4, valve 8 provided in second connecting line 6 is opened and main culture vessel 2 is contracted by applying an external force such as a pressing force with piston 11. As a result, medium that is no longer necessary is discharged from main culture vessel 2 into waste medium vessel 4 through valve 8. When a predetermined amount of medium has been discharged, valve provided in second connecting line 6 is again closed, valve 7 provided in first connecting line 5 is opened, and as shown in FIG. 3, medium vessel 3 is contracted. As a result, fresh medium is again supplied to main culture vessel 2. Mesenchymal stem cells are then adequately grown by continuing culturing while repeating this medium replacement step. Main culture 2 that houses the grown mesenchymal stem cells can be transported separately by sealing all connecting lines 5 and 6 that are connected to said main culture vessel 2 and then severing those lines. In this manner, according to culture vessel 1 as claimed in the present embodiment, medium and so forth required for culturing can be sealed in advance, and the contents of culture vessel 1 can be isolated from the outside in a sealed state throughout the culturing period of the primary culturing step. As a result, together with being able to prevent contamination by dust particles and bacteria from the outside, the effects of contamination and infection by other outside cells can also be eliminated. As a result, numerous types of cells can be cultured simultaneously in close proximity thereby improving culturing efficiency. Furthermore, although culture vessel 1 as claimed in the present embodiment has been explained as being applicable to a primary culturing step in which mesenchymal stem cells are grown while replacing the medium a plurality of times at predetermined times, culture vessel 1 can also be composed so as to be applicable to a secondary culturing step in which a bone supplement material such as a β-tricalcium phosphate porous body is sealed in main culture vessel 2 so as to allow addition of mesenchymal stem cells cultured in a primary culturing step. In addition, as shown in FIG. 5, a blood collection line 12 may be connected to main culture vessel 2, and bone marrow fluid collected from a patient can be added to main culture vessel 2 by said blood collection line 12. In addition, as shown in FIG. 6, a variable inner volume enzyme vessel 13 may be connected to main culture vessel 2 by means of a third connecting line 14. A protease enzyme such as trypsin, for example, is loaded into enzyme vessel 13, and a valve 15 is provided in third connecting line 14. According to a culture vessel 16 composed in this manner, following completion of a primary culturing step in which mesenchymal stem cells have grown by adhering to the inner walls of main culture vessel 2, valve 8 provided in second connecting line 6 is opened and medium that is no longer necessary is discharged from inside main culture vessel 2 to waste medium vessel 4 through valve 8. After then closing valve 8 of second connecting line 6, valve 15 in third connecting line 14 is opened and trypsin is supplied to main culture vessel 2. As a result, mesenchymal stem cells are detached from the inner walls of main culture vessel 2 and can then be collected. Furthermore, temperature-responsive treatment switching between hydrophilic and hydrophobic properties bordering on a predetermined temperature may also be carried out on the inner walls of main culture vessel 2 without using trypsin or other protease enzyme. Temperature-responsive treatment is carried out by immobilizing the temperature-responsive polymer poly(N-isopropylacrylamide) on the inner walls by covalent bonding. Although the region subjected to temperature-responsive treatment exhibits weak hydrophobic properties to the same degree as commercially available cell culture vessels at temperatures equal to or above a boundary temperature of 32° C., this region exhibits highly hydrophilic properties by cooling the temperature to equal to or below the boundary temperature. Thus, by culturing at 37° C. followed by cooling to 32° C. or below, for example, the inner walls of main culture vessel 2 are changed so as to exhibit highly hydrophilic properties, thereby enabling non-invasive detachment of mesenchymal stem cells. In addition, as shown in FIG. 7, main culture vessel 20 may also be provided with an occluded connecting line 17 having an occluded end. This occluded connecting line 17 is composed of a material such as vinyl chloride that can be sealed or fused by heat. An occluded connecting line 17 composed in this manner can be obtained by using a heating plate 18 that moves in the direction of shearing as shown in FIG. 8A, severing while melting the connecting line as shown in FIG. 8B, and occluding the severed end while maintaining the inside of the connecting tube in a sterile and sealed state as shown in FIG. 8C. This severing procedure is referred to as aseptic tube severing. In addition, after simultaneously severing two occluded connecting lines 17A and 17B arranged in parallel as shown in FIG. 9A, and shifting the lines so that one connecting tube 17A aligns with the other connecting line 17B as shown in FIG. 9B, the one connecting line 17A is connected to the other connecting line 17B by removing heating plate 18 as shown in FIG. 9C. Although the joined portion 17b is occluded during connection, the internal flow path is able to be continuous while the line walls are connected by an external force. Namely, different connecting lines 17A and 17B can be connected while maintaining the inside in a sterile state. This connection procedure is referred to as aseptic tube connection. Namely, by providing this type of occluded connecting line 17, cells can be transferred to another main culture vessel 2 by connecting a first main culture vessel 2 in which cells have been cultured to another main culture vessel 2 using aseptic tube connection. A primary culturing step and a secondary culturing step can then be linked by using the first main culture vessel 2 as the primary culture vessel and another main culture vessel 2 as a secondary culture vessel. Furthermore, in the case cells C are present in occluded connecting line 17, since there is the risk of the cells C being damaged by heating plate 18, as shown in FIG. 10, a spare space 19 for severing may be formed in the end of occluded connecting line 17. Namely, by severing along cross-sectional line A that passes through spare space 19, heating plate 18 is prevented from making direct contact with cells C in occluded connecting line 17, thereby making it possible to carry out aseptic tube connection while maintaining the viability of cells C. Second Embodiment Culture Apparatus Next, an explanation is provided of a culture apparatus as claimed in an embodiment of the present invention with reference to the drawings. As shown in FIGS. 11 through 13, culture apparatus 20 as claimed in the present embodiment is provided with a culture vessel 21, a case 22 in which it is housed, a pressing apparatus that presses on culture vessel 21, and a control apparatus 24 that controls these operations. As shown in FIG. 11, culture vessel 21 is provided with two main culture vessels 2A and 2B that are mutually connected by a first connecting line 25, a first medium vessel 3A, a fist waste medium vessel 4A and an enzyme vessel 29 connected to a first main culture vessel 2A by second through fourth connecting lines 26 through 28, and a second medium vessel 3B, a second waste medium vessel 4B and a growth accelerator vessel 33 connected to a second main culture vessel 2B by fifth through seventh connecting lines 30 through 32. Each of these vessels 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 are thin-walled vessels made of vinyl chloride in the same manner as each of vessels 2, 3 and 4 of culture vessel 1 as claimed in the first embodiment, and are composed to have a variable inner volume when pressed by an external force. A bone supplement material such as a β-tricalcium phosphate porous body is sealed within the second main culture vessel 2B. Medium, a protease enzyme such as trypsin and a growth factor such as dexamethasone similar to the first embodiment are respectively sealed in medium vessels 3A and 3B, enzyme vessel 29 and growth accelerator vessel 33. In addition, first through seventh connecting lines 25 through 28 and 30 through 32 are each composed of a flexible material such as vinyl chloride. As a result, together with each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 being able to be arranged at an arbitrary position by bending each connecting line 25 through 28 and 30 through 32, the flow of liquid therein can be restricted by clamping connecting lines 25 through 28 and 30 through 32 with a clip or pinching valve in the radial direction at an intermediate location in the lengthwise direction thereof. Furthermore, in the state prior to first through seventh connecting lines 25 through 28 and 30 through 32 being attached to case 22, said connecting lines are occluded by a film, for example, that is ruptured by external force (not shown), to restrict the flow of fluid. As shown in FIG. 12, the aforementioned case 22 is provided with a plurality of indentations 34 through 41 capable of respectively housing each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 that compose the aforementioned culture vessel 21 in an upper surface formed to have the shape of a flat plate. These indentations 34 through 41 are formed to dimensions of a degree to which each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 is held without shifting position as a result of indentations 34 through 41 housing each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33. Housing grooves 42 through 48 are formed between each indentation 34 through 41 that house each connecting line 25 through 28 and 30 through 32 connecting vessels 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33. In addition, pinching valves 49 through 55 are arranged in each housing groove 42 through 48 that are able to clamp connecting lines 25 through 28 and 30 through 32 arranged in housing grooves 42 through 48 in the direction of diameter at an intermediate position in the direction of length of said housing grooves 42 through 48. In addition, the aforementioned case 22 is divided by an insulating material (not shown) into a first area X, which contains indentations 34 and 35 that house the two main culture vessels 2A and 2B, and a second area Y, which contains indentations 36 through 41 that house the remaining vessels 3A, 3B, 4A, 4B, 29 and 33. The first area X can be maintained at a temperature of 37±0.5° C. suitable for culturing, and the periphery of main culture vessels 2A and 2B can be maintained in an atmosphere having a CO2 concentration of 5%. In addition, the second area Y can be maintained in a cooled state at about, for example, 4° C. As shown in FIG. 13, the aforementioned pressing apparatus 23 is provided with an apparatus body 56 that is placed on the upper surface of the aforementioned case 22, and pistons 57 through 62. Pistons 57 through 62 are provided at locations corresponding to each indentation 34 through 41 of case 22, and are composed so as to be able to be lowered and raised to a desired height. When pistons 57 through 62 are lowered, vessels 2A, 2B, 3A, 3B, 29 and 33 housed in indentations 34 through 36, 38, 39 and 41 arranged below are pressed and as a result, vessels 2A, 2B, 3A, 3B, 29 and 33 are contracted allowing the fluid inside to be pressed out from vessels 2A, 2B, 3A, 3B, 29 and 33. The following provides an explanation of the operation of culture apparatus 20 as claimed in the present embodiment composed in this manner. In order to culture cells C with the culture apparatus 20 as claimed in the present embodiment, control apparatus 24 is first operated to restrict the flow of fluid by clamping connecting lines 25 through 28 and 30 through 32 by closing all pinching valves 49 through 55. While in this state, patient bone marrow fluid is collected by a blood collection line or syringe not shown and loaded into first main culture vessel 2A. Next, control apparatus 24 is operated to open pinching valve 50 that had been closing second connecting line 26 and then operate pressing apparatus 26 to lower piston 59 arranged above first medium vessel 3A and supply medium in first medium vessel 3A to first main culture vessel 2A through second connecting line 26. Subsequently, first main culture vessel 2A is sealed from the outside by again closing pinching valve 50 of second connecting line 26. Since first main culture vessel 2A is arranged in first area X, it is subjected to predetermined culturing conditions. By allowing to stand for a predetermined amount of time in this state, cells C within first main culture vessel 2A grow in the medium by adhering to the bottom of main culture vessel 2A. After a predetermined culturing period has elapsed, control apparatus 24 is operated to open pinching valve 51 that had been closing third connecting line 27, and lower piston 57 arranged above first main culture vessel 2A. As a result, the medium within first main culture vessel 2A is discharged into first waste medium vessel 4A. In this case, all of the medium in first main culture vessel 2A may be discharged or only a portion may be discharged. At this time, since cells C are maintained in an adhered state to the inner walls of first main culture vessel 2A, they remain within first main culture vessel 2A without flowing out to first waste medium vessel 4A. Subsequently, pinching valve 51 of third connecting line 27 is again closed, and pinching valve 50 that had been closing second connecting line 26 is operated and opened. Simultaneous to this, piston 57 that had been pressing on first main culture vessel 2A from above is raised, and piston 59 arranged above first medium vessel 3A is lowered. As a result, medium in first medium vessel 3A is supplied to first main culture vessel 2A resulting in replacement of the medium inside first main culture vessel 2A. After periodically repeating this medium replacement step a plurality of times, all or a portion of the medium in first main culture vessel 2A is discharged to first waste medium vessel 4A, and in the state in which pinching valve 51 of third connecting line 27 is closed, pinching valve 52 that had been closing fourth connecting line 28 is opened. Accompanying this, piston 57 above first main culture vessel 2A is raised up while lowering piston 60 arranged over enzyme vessel 29. As a result, the trypsin within enzyme vessel 29 is supplied to first main culture vessel 2A, and the cells C that had been growing by adhering to the inner walls of first main culture vessel 2A are detached from the inner walls. Next, the entire culture vessel 21 is centrifuged while still in case 22 in the state in which the pinching valves of first through fourth connecting lines 25 through 28 connecting to first main culture vessel 2A are all closed. As a result, cells C in first main culture vessel 2A are separated from the medium and trypsin. When placing culture vessel 21 in the centrifuge, it is convenient to place culture vessel 21 so that first connecting line 25 that connects first main culture vessel 2A and second main culture vessel 2B is arranged outwardly in the radial direction when viewed from the centrifugal axis with respect to first main culture vessel 2A since the separated cells C collect in first connecting line 25. After having been separated in this manner, cells C are transferred to second main culture vessel 2B through first connecting line 25 by opening pinching valve 49 arranged in first connecting line 25 and lowering piston 57 arranged above first main culture vessel 2A. Medium is then supplied to second main culture vessel 2B by opening pinching valve 53 of fifth connecting line 30 connected to second main culture vessel 2B and lowering piston 61 located above second medium vessel 3B. In addition, simultaneous or subsequent to this, dexamethasone or other growth factor is supplied to second main culture vessel 2B by opening pinching valve 55 of seventh connecting line 32 and lowering piston 62 located above growth accelerator vessel 33. Since a bone supplement material is sealed within second main culture vessel 2B, cells C supplied from first main culture vessel 2A, medium supplied from second medium vessel 3B and growth factor supplied from growth accelerator vessel 33 are mixed therein. Since second main culture vessel 2B is arranged in first region X maintained at predetermined culturing conditions, secondary culturing is carried out by maintaining this state. During the secondary culturing period, medium replacement is carried out a plurality of times by periodically controlling the opening and closing of pinching valves 53 through 55 provided in fifth through seventh connecting lines 30 through 32, and the raising and lowering of pistons 58 through 62 arranged above second main culture vessel 2B, second medium vessel 3B and growth accelerator vessel 33. After a predetermined secondary culturing period has elapsed, a bone supplement is produced within second main culture vessel 2B by growing cells C using the bone supplement material as a scaffold. The medium inside second main culture vessel 2B is then discharged into second waste medium vessel 4B by opening pinching valve 54 provided in sixth connecting line 47 and pressing on second main culture vessel 2B with piston 58. In this case, only a portion of the medium may be discharged. The bone supplement is then sealed in second main culture vessel 2B by closing pinching valves 49 and 53 through 55 of all connecting lines 25 and 30 through 32 connected to second main culture vessel 2B while in this state. The bone supplement can be shipped independently as a finished product by severing all connecting lines 25 and 30 through 32 while in the occluded state using, for example, aseptic tube severing, to separate the second main culture vessel 2B in which the bone supplement is sealed from the other vessels 2A, 3A, 3B, 4A, 4B, 29 and 33. According to a culture apparatus 20 as claimed in the present embodiment composed in this manner, culturing can be carried out in a closed system that is completely isolated from the outside during the time from blood collection from a patient to completion of secondary culturing. Thus, contamination by dust particles and so forth from the outside can be prevented. Namely, cells can be maintained in a viable state by preventing contamination by dust particles from the outside in each of the transport, handling and culturing steps. In addition, since culturing is carried out by arranging culture vessel 21 in case 22 having indentations 34 through 41, culture vessel 21 can be easily placed in culture apparatus 20. Thus, cells C can be cultured easily even by an operator unfamiliar with the apparatus. Moreover, different cells can be easily cultured in succession by replacing culture vessel 21 in which is sealed all the medium and other required substances. In the aforementioned embodiment, since the media used in the primary and secondary culturing steps is stored in first and second waste medium vessels 4A and 4B, infection examinations and so forth may be carried out at each stage by using the media stored in these vessels 4A and 4B. In this case, first and second waste medium vessels 4A and 4B may be respectively and independently sent to an inspection step by severing third and sixth connecting lines 27 and 31 by aseptic tube severing. In addition, separate specimen extraction vessels not shown may be connected to first and second main culture vessels 2A and 2B. In addition, medium remaining in first connecting line 25 may also be used for examination. In this manner, each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 can be separated by carrying out aseptic tube severing on first through seventh connecting lines 25 through 28 and 30 through 32 in the present embodiment. Symbols, and particularly bar codes, which indicate that the vessels are mutually related vessels, may be affixed to each vessel 2A, 2B, 3A, 3B, 4A, 4B, 29 and 33 to prevent the relationship between the cultured cells C, the discarded medium and so forth from becoming unclear as a result of the aforementioned separation. The bar codes may be identical bar codes or mutually correlated bar codes. Furthermore, although the second main culture vessel 2B has been explained as being linked to the first main culture vessel 2A by means of first connecting line 25 from the outset in the aforementioned embodiment, second main culture vessel 2B may alternatively be connected to first main culture vessel 2A, second medium vessel 3B or second waste medium vessel 4B and so forth by aseptic tube connection. When this is done, a second main culture vessel 2B containing a bone supplement material corresponding to the amount and shape of the bone supplement desired to be produced can be suitably selected for use. In addition to porous blocks, granular, gel-like or other arbitrary forms of bone supplement materials can be made available for the bone supplement material sealed inside. In addition, an arbitrary biocompatible material can be used for the material. In addition, a portion or all of first and second main culture vessels 2A and 2B may be composed to be transparent, and observation windows (not shown) may be formed in indentations 34 and 35 of case 22 that house these main culture vessels 2A and 2B. According to this, culturing status can be observed with, for example, an inverted microscope through an observation window during the culturing period. In addition, although the finally produced bone supplement is loaded into an injection gun for injection into a patient's body, in order to carry this out in a sealed state, the injection gun (not shown) may be connected in advance by a connecting line (not shown) to second main culture vessel 2B. In addition, an injection gun may be subsequently connected to second main culture vessel 2B by aseptic tube connection. In addition, an injection gun capable may be made available that is capable of loading second main culture vessel 2B directly after separating from the other vessels 2A, 3A, 4A and 33 by aseptic tube severing, and a composition may be employed in which second main culture vessel 2B is ruptured within the injection gun allowing the bone supplement inside to be injected aseptically. In addition, a porous bone supplement material may be arranged at the inlet to sixth connecting line 31 in second main culture vessel 2B. As a result, cells C suspended in medium discharged to second waste medium vessel 4B can be captured on the porous bone supplement material when discharged together with the medium. Thus, cells C can be recovered without waste. In addition to a β-tricalcium phosphate porous body, any arbitrary biocompatible material such as an apatite sheet can be used for the porous bone supplement material. Moreover, when opening first through seventh connecting lines 25 through 28 and 30 through 32 with pinching valves 49 through 55 provided at intermediate locations in connecting lines 25 through 28 and 30 through 32, check valves (not shown), which allow the fluid therein to only flow in a desired direction of flow while prohibiting flow in the opposite direction, may be provided at intermediate locations in each of the connecting lines 25 through 28 and 30 through 32. Third Embodiment Culture Apparatus Next, an explanation is provided of a culture apparatus 70 as claimed in a third embodiment of the present invention with reference to the drawings. Furthermore, the same reference symbols are used for those locations in the present embodiment that are the same as the constitutions of each of the aforementioned embodiments, and their explanations are omitted. As shown in FIG. 14, culture apparatus 70 as claimed in the present embodiment is a culture apparatus 70 for carrying out a primary culturing step, and is provided with a culture vessel 71 composed by connecting a main culture vessel 2, a medium vessel 3 and a waste medium vessel 4 with connecting lines 5, 6 and 14, a case 84, a pressing apparatus (now shown) arranged above case 84, and a control apparatus for controlling them. Case 84 is provided with indentations 72 through 78 that house vessels 2 through 4 and 13 and connecting lines 5, 6 and 14. Case 84 is formed in the shape of a disc, and is composed so as to be able to be rotated horizontally about vertical axial center 82 that passes through its center by the operation of a rotary drive mechanism not shown. In addition, each vessel 2 through 4 and 13 is the same as the second embodiment with respect to being composed of a flexible material capable of changing volume, connecting lines 5, 6 and 14 are the same as the second embodiment with respect to being composed of a flexible material capable of closing the flow path inside as a result of being clamped in the radial direction, and pinching valves 79 through 81 that open and close connecting lines 5, 6 and 14 are the same as the second embodiment with respect to being provided in case 84. In addition, a first region X is maintained at a temperature of 37±0.5° C. and a second region Y is maintained at a temperature of 4° C. in the same manner as the second embodiment by a suitable heating means and cooling means. In culture apparatus 70 as claimed in the present embodiment, indentations 72 through 78 that house each vessel 2 through 4 and 13, and particularly indentation 72 that houses main culture vessel 2 used to culture cells C, are arranged in a location away from the axial center of rotation. As a result, when case 84 is rotated about axial center of rotation 82, centrifugal force acts towards the outside in the radial direction on fluid inside main culture vessel 2 housed in indentation 72. Furthermore, indentations 73 through 75 that house the other vessels 3, 4 and 13 are also arranged at locations away from axial center of rotation 82 by the nearly same distance as indentation 72 housing main culture vessel 2. In addition, culture vessel 71 of culture apparatus 70 as claimed in the present embodiment is provided with an occluded connecting line 17 connected to main culture vessel 2. This occluded connecting line 17 is made of vinyl chloride, and the end of which is occluded to prevent leakage of fluid inside. As shown in the drawing, this occluded connecting line 17 is arranged to the outside in the radiating direction of main culture vessel 2 as viewed from axial center of rotation 82 of case 84. In addition, the aforementioned pressing apparatus is installed, for example, at the location indicated with broken lines in FIG. 14, and is provided with a single piston 83 that is moved up and down. Piston 83 is able to press on main culture vessel 2, medium vessel 3 and waste medium vessel 4, respectively, as a result of case 84 being rotated about axial center of rotation 82. The following provides an explanation of the operation of culture apparatus 70 as claimed in the present embodiment composed in this manner. The control apparatus is operated with cells C collected from a patient loaded in main culture vessel 2 to activate the rotary drive mechanism and arrange medium vessel 3 below piston 83. Medium inside medium vessel 3 then flows into main culture vessel 2 by means of a first connecting line 5 by opening pinching valve 79, which closes first connecting line 5 between main culture vessel 2 and medium vessel 3, and lowering piston 83. The descent of piston 83 is then stopped and pinching valve 79 is closed again when a predetermined amount of medium has flown into main culture vessel 2. As a result, since cells C are mixed in the medium, primary culturing of cells C is begun by allowing to stand in this state. Next, case 84 is rotated to arrange main culture vessel 2 below piston 83 at a suitable medium replacement time after a predetermined amount of time has elapsed. The medium inside main culture vessel 2 is then discharged into waste medium vessel 4 by opening pinching valve 80, which closes second connecting line 6 between main culture vessel 2 and waste medium vessel 4, and lowering piston 83. At this time, since cells C are adhered to the bottom of main culture vessel 2, the cells remain in main culture vessel 2 without being discharged into waste medium vessel 4. Medium inside medium vessel 3 is then supplied to main culture vessel 2 by again rotating case 84 to arrange medium vessel 3 below piston 83, and controlling piston 83 and pinching valve 79. As a result, the medium is replaced. Following completion of the primary culturing step in which cells are cultured while replacing the medium a plurality of times at predetermined replacement intervals, case 84 is rotated to arrange main culture vessel 2 below piston 83. Medium is then discharged from main culture vessel 2 into waste medium vessel 4 by controlling piston 83 and pinching valve 80. Subsequently, by again rotating case 84 to arrange enzyme vessel 13 below piston 83, and controlling piston 83 and pinching valve 81, trypsin is supplied from enzyme vessel 13 to main culture vessel 2. The trypsin acts on cells C in main culture vessel 2 causing the cells C adhered to the inner walls to be detached. Case 84 is then rotated at high speed while in this state by closing all pinching valves 79 through 81 and operating the rotary drive mechanism. As a result, cells C suspended in the trypsin within main culture vessel 2 are collected to the outside in the radial direction from the trypsin by centrifugal separation. Since occluded connecting line 17 is arranged to the outside in the radial direction of main culture vessel 2, the separated cells C are collected in occluded connecting line 17. After then stopping case 84 at the location where main culture vessel 2 is arranged below piston 83, and connecting a second main culture vessel (not shown) in which a bone supplement material is sealed to occluded connecting line 17 by, for example, aseptic tube connection, cells C that have been collected in occluded connecting line 17 can be efficiently transferred to the second main culture vessel. In this manner, according to culture apparatus 70 as claimed in the present embodiment, the number of pistons 83 of the pressing means can be reduced by causing case 84 to rotate, thereby simplifying the structure. In addition, since main culture vessel 2 is arranged at a location away from axial center of rotation 82 of case 84, and occluded connecting line 17 is provided to the outside in the radial direction of main culture vessel 2 housed in indentation 72 of case 84, centrifuged cells C are collected in occluded connecting line 17, thereby allowing culturing to efficiently continue to a subsequent secondary culturing step. Furthermore, the shapes of the case and vessels are not limited to those shown in each of the aforementioned embodiments. In addition, although the explanation used the example of providing one each of the vessels, a plurality of medium vessels and waste medium vessels, for example, may be provided instead. In addition, although the explanations of each of the aforementioned embodiments described a method whereby medium and so forth is transferred by pressing each vessel with a piston on the side on which medium and so forth is discharged, as shown in FIG. 15, a method may alternatively be employed in which each vessel 2 and 4 is arranged in a housing chamber 90 and 91 that are sealed from the outside, and medium and so forth is aspirated by reducing the pressure in said housing chambers 90 and 91 in which the vessels are housed on the side on which medium and so forth is received. More specifically, as shown in FIG. 15, is order to supply medium to main culture vessel 2, in addition to opening pinching valve 50 that has closed first connecting line 26 by operating control apparatus 24, the pressure within housing chamber 90 in which main culture vessel 2 is arranged is lowered by operating a first vacuum pump 92. Since housing chamber 93 in which medium vessel 3 is housed is made to be open to the atmosphere by communicating holes 94, medium vessel 3 contacts freely resulting in medium being aspirated into main culture vessel 2. In addition, after a predetermined culturing period has elapsed, in addition to opening a second connecting line 27 by operating pinching valve 57 that had been closing second connecting line 27 by operating control apparatus 24, the pressure inside housing chamber 90 housing main culture vessel 2 is opened to the atmosphere. The pressure in housing chamber 91 in which waste medium vessel 4 is housed is then lowered by operating a second vacuum pump 95. As a result, medium inside main culture vessel 2 is aspirated towards waste medium vessel 4. Fourth Embodiment Culture Apparatus Next, an explanation is provided of a culture apparatus as claimed in a fourth embodiment of the present invention with reference to the drawings. Culture apparatus 101 as claimed in the present embodiment is used in the aforementioned culturing process, and particularly in a primary culturing step. As shown in FIGS. 16 and 17, culture apparatus 101 as claimed in the present embodiment is composed of a culture vessel 102 and a rotary drum (level difference adjustment means) 103 on which said culture vessel 102 is attached to the outer peripheral surface. As shown in FIG. 18, culture vessel 102 is composed of a single main culture vessel 104, a single medium vessel 105, a single waste medium vessel 106, a first connecting line 107 that connects main culture vessel 104 and medium vessel 105, and a second connecting line 108 that connects main culture vessel 104 and waste medium vessel 106. Main culture vessel 104, medium vessel 105 and waste medium vessel 106 are respectively composed of a material such as hard polystyrene. In addition, first and second connecting lines 107 and 108 are composed of flexible tubes like those made of vinyl chloride. As a result, together with being able to arrange each vessel 104, 105 and 106 at arbitrary locations by bending each connecting line 107 and 108, the flow of fluid inside can be restricted by clamping an intermediate site in the lengthwise direction of connecting lines 107 and 108 with a clip or pinching valve that clamps in the radial direction. Furthermore, prior to being attached to rotary drum 103, first and second connecting lines 107 and 108 are closed by removable clips (not shown), for example, to restrict the flow of fluid. In addition, medium vessel 105 on the side of main culture vessel 104 and main culture vessel 104 on the side of waste medium vessel 106 are respectively provided with inclined surfaces 105a and 104a to facilitate the flow of fluid within medium vessel 105 into main culture vessel 104 and the flow of fluid within main culture vessel 104 into waste medium vessel 106. In FIG. 18, reference symbol 109 indicates mounting holes for installing each vessel 104, 105 and 106 on rotary drum 103. In addition, a medium is sealed inside the aforementioned main culture vessel 104 and medium vessel 105 that is prepared with minimum essential medium (MEM), fetal bovine serum (FBS) and antibiotic and so forth at a predetermined blending ratio such as 84:15:1. Human serum may also be used instead of FBS. Any arbitrary antibiotic can be used for the antibiotic, examples of which include penicillin-based, cepham-based, macrolide-based, tetracycline-based, fosfomycin-based, aminoglycoside-based and new quinolone-based antibiotics. A gas such as CO2 gas at a concentration of 5% is sealed in a sterile state in the aforementioned waste medium vessel 106. The aforementioned main culture vessel 104 is provided with an injection port 110 that can be penetrated with an injection needle and closes due to elasticity after the injection needle has been removed. As a result, a body fluid such as bone marrow fluid can be injected into main culture vessel 104 by puncturing the injection port 110 with an injection needle of a syringe used to collect bone marrow fluid, and the inside of main culture vessel 104 can be isolated from the outside by retracting the injection needle from injection port 110. The aforementioned rotary drum 103 has a cylindrical surface centering around the horizontal axis of rotation, and is connected to a rotary drive source like a motor (not shown). In addition, vessel mounting brackets 111, 112 and 113 for installing each of the aforementioned vessels 104, 105 and 106 are provided on the outer surface of the cylindrical surface serving as the outer peripheral surface of rotary drum 103. Vessel mounting bracket 111 of main culture vessel 104 is arranged between vessel mounting bracket 112 of medium vessel 105 and vessel mounting bracket 113 of waste medium vessel 106, and are respectively arranged at intervals in the circumferential direction of rotary drum 103. For example, in the example shown in FIGS. 16 and 17, the mounting brackets are arranged at 90° intervals in the circumferential direction of rotary drum 103. Each vessel 104, 105 and 106 is installed on rotary drum 103 using, for example, bolts 114. Thumbscrews, belts, hooks or other arbitrary fastening means may also be used instead of bolts 114. In addition, when each vessel 104, 105 and 106 has been attached to each vessel mounting bracket 111, 112 and 113, pinching valves 115 and 116 that clamp each connecting line 107 and 108 in the radial direction at an intermediate location in the lengthwise direction are provided in the connecting line pathways in which connecting lines 107 and 108 are arranged between vessels 104, 105 and 106. Pinching valves 115 and 116 are provided with two pins 115a and 116a extending to the outside in the radial direction towards the outside of the cylindrical surface from the inside of rotary drum 103, and connecting lines 107 and 108 can be opened and closed by switching the distance of pins 115a and 116a simply by inserting connecting lines 107 and 108 between these pins 115a and 116a. Opening and closing of each pinching valve 115 and 116 is controlled by a controller not shown. The following provides an explanation of the operation of culture apparatus 101 as claimed in the present embodiment composed in this manner. In order to culture cells using culture apparatus 101 as claimed in the present embodiment, first bone marrow liquid is injected into main culture vessel 104 by puncturing injection port 110 with a syringe needle of a syringe used to collect bone marrow fluid as previously described. Rotary drum 103 is then rotated by a predetermined angle, and rotary drum 103 is locked at the position where main culture vessel 104 is positioned horizontally at the highest location. While in this state, culturing is carried out by subjecting main culture vessel 104 to predetermined culturing conditions such as a temperature of 37±0.5° C., humidity of 100% and CO2 concentration of 5%. The CO2 culturing conditions can be achieved by either dissolving CO2 in the medium or composing all or a portion of main culture vessel 104 with a CO2-permeable filter. Subsequently, when a predetermined medium replacement time has been reached, as shown in FIG. 19, rotary drum 103 is rotated by a predetermined angle to position main culture vessel 104 at a higher location than medium vessel 106. In the case of the present embodiment, since main culture vessel 104 is arranged at the highest location during culturing, rotary drum 103 does not have to be rotated. However, in order to transfer the medium in main culture vessel 104 to waste medium vessel 106 more smoothly, as shown in FIG. 19 for example, main culture vessel 104 is preferably oriented diagonally upward while waste medium vessel 106 is preferably oriented diagonally downward. While in this state, pinching valve 116 that had been closing second connecting line 108 is opened. As a result, medium that is no longer necessary is discharged by its own weight from main culture vessel 104 into waste medium vessel 106 through second connecting line 108. When a predetermined amount of medium in main culture vessel 104 has been discharged, pinching valve 116 is operated to again close second connecting line 108. Next, rotary drum 103 is rotated by a predetermined angle so that main culture vessel 104 is arranged at a lower location than medium vessel 105 as shown in FIG. 20. Namely, main culture vessel 104 is oriented diagonally downward while medium vessel 105 is oriented diagonally upward. Pinching valve 115 that had been closing first connecting line 117 is then opened. As a result, fresh medium is supplied from medium vessel 105 to main culture vessel 104 through first connecting line 117. As a result, since the medium replacement step is completed, rotary drum 103 is rotated by a predetermined angle to return main culture vessel 104 to the highest location and continue culturing. As a result of continuing culturing while repeating this medium replacement step a plurality of times, mesenchymal stem cells adequately grow on the bottom of main culture vessel 104. Main culture vessel 104 that houses the grown mesenchymal stem cells can be transported independently by sealing with heat and then severing all of the connecting lines 107 and 108 connected to said main culture vessel 104. In this manner, according to culture apparatus 101 as claimed in the present embodiment, medium and so forth required for culturing can be sealed in advance, and the inside of main culture vessel 102 can be isolated from the outside in a sealed state throughout the culturing period of the primary culturing step. As a result, contamination by dust particles and so forth from the outside can be prevented. In addition, even when replacing the medium during which medium droplets are dispersed easily, medium can be transferred between vessels 104, 105 and 106 by gravity while sealed within each vessel 104, 105 and 106 and connecting lines 107 and 108 simply by rotating rotary drum 103 and arranging each vessel 104, 105 and 106 at a predetermined position. Thus, the effects of contamination by other bacteria from the outside can be eliminated. Furthermore, although culture vessel 102 in the present embodiment has been explained as being applicable to a primary culturing step in which mesenchymal stem cells are grown while replacing the medium a plurality of times at predetermined times, culture vessel 102 may also be composed to be applicable to a secondary culturing step by sealing a bone supplement material such as a β-tricalcium phosphate porous body in main culture vessel 104 and loading mesenchymal stem cells cultured in a primary culturing step. In addition, a blood collection line (not shown) may be connected to main culture vessel 104, and bone marrow fluid collected from a patient with said blood collection line may be loaded directly into main culture vessel 104. In addition, although connecting lines 107 and 108 are opened and closed by pinching valves 115 and 116 provided in rotary drum 103, instead of these pinching valves, opening and closing valves may also be provided directly in connecting lines 107 and 108. In addition, although culture apparatus 101 as claimed in the aforementioned embodiment has been explained using the example of culture vessel 102 in which main culture vessel 104, medium vessel 105 and waste medium vessel 106 are mutually connected by connecting lines 107 and 108, as shown in FIG. 21, each culture vessel 104, 105 and 106 and connecting lines 107 and 108 may be integrally attached to a bendable, flexible sheet 117. Bolt mounting holes 118 for attaching to rotary drum 103 and through holes 119 for allowing the pins of pinching valves 115 and 116 to pass through are provided in sheet 117. As a result of being composed in this manner, when attaching culture vessel 102 to rotary drum 103, sheet 117, which integrates each vessel 104, 105 and 106 and connecting lines 107 and 108 into a single unit, is bent into a cylindrical shape as shown in FIG. 22 and attached to the outer surface of rotary drum 103. Thus, the need to position each vessel 104, 105 and 106 and connecting lines 107 and 108 can be eliminated, thereby facilitating mounting work. Fifth Embodiment Culture Apparatus Next, an explanation is provided of a culture apparatus as claimed in a fifth embodiment of the present invention with reference to FIG. 23. Furthermore, in the explanation of culture apparatus 120 as claimed in the present embodiment, the same reference symbols are used for those locations in the present embodiment that are the same as the constitution of culture apparatus 101 as claimed in the aforementioned fourth embodiment, and their explanations are omitted. As shown in FIG. 23, culture vessel 121 of culture apparatus 120 as claimed in the present embodiment differs from culture vessel 102 in the aforementioned fourth embodiment in that it is provided with an enzyme vessel 124 connected to main culture vessel 122 by means of a third connecting line 123, and in that a cell recovery line 125 is provided for main culture vessel 122. A protease enzyme such as trypsin is sealed in enzyme vessel 124, and third connecting line 123 is occluded by a removable clip. Enzyme vessel 124 is installed on a rotary drum 126 arranged in a row in the lengthwise direction, for example, at the same position in the circumferential direction as medium vessel 105. In addition to a vessel mounting bracket 127 for installing enzyme vessel 124 being provided on rotary drum 126, a pinching valve 128 is provided that occludes third connecting line 123 by clamping in the radial direction when enzyme vessel 124 has been installed. The aforementioned cell recovery line 125 is provided in the center of the surface arranged to the outside in the radial direction when main culture vessel 122 is attached to rotary drum 126. In addition, as shown in FIG. 24, the surface of main culture vessel 122 on which this cell recovery line 125 is provided is formed into the shape of a funnel that gradually narrows from the periphery towards cell recovery line in the center. Cell recovery line 125 is composed of a vinyl chloride or other flexible tube in the same manner as connecting lines 107, 108 and 123, and is in the form of an occluded tube, the end of which is occluded. The following provides an explanation of the operation of culture apparatus 120 as claimed in the present embodiment composed in this manner. The operation until cells are cultured while periodically replacing the medium is the same as culture apparatus 101 as claimed in the fourth embodiment. According to culture apparatus 120 as claimed in the present embodiment, after mesenchymal stem cells have grown in an adhered state in main culture vessel 122, by rotating rotary drum 126 by a predetermined angle, main culture vessel 122 is arranged diagonally upward while waste medium vessel 106 is arranged diagonally downward. By then operating pinching valve 116 that had been closing second connecting line 108 to open second connecting line 108, a predetermined amount of medium to be discharged in main culture vessel 122 is discharged to waste medium vessel 106 by gravity. Subsequently, enzyme vessel 124 is then positioned at a higher location that main culture vessel 122 by again rotating rotary drum 126 by a predetermined angle. By then opening third connecting line 123 by operating pinching valve 128 that has been closing third connecting line 123, trypsin stored in enzyme vessel 124 is supplied by gravity to main culture vessel 122 through third connecting line 123. Mesenchymal stem cells that had been adhered to the bottom of main culture vessel 122 are then detached by allowing to stand for a predetermined amount of time or applying vibrations to main culture vessel 122 by rocking rotary drum 126 in the state in which third connecting line 123 is again closed by operating pinching valve 128. As a result, the detached mesenchymal stem cells are mixed in fluid consisting of trypsin and medium in a state in which the adhesion between cells has been severed. Subsequently, the medium containing mesenchymal stem cells and trypsin in main culture vessel 122 is then centrifuged by continuously rotating rotary drum 126 in a single direction. Since the mesenchymal stem cells have a higher specific gravity than the trypsin and other substances, the cells are spun to the outside in the radial direction as a result of centrifugation. According to culture apparatus 120 as claimed in the present embodiment, since main culture vessel 122 is formed in the shape of a funnel, mesenchymal stem cells that have been spun to the outside in the radial direction are gathered in the center by the funnel-shaped vessel walls. Since cell recovery line 125 is provided in the center, the gathered mesenchymal stem cells are recovered in cell recovery line 125. In addition, since this cell recovery line 125 is composed of vinyl chloride that can be sealed or fused by heat, severed end 125a can be occluded together with severing cell recovery line 125 by aseptic tube severing. Namely, as shown in FIG. 8A, severed end 125a can be occluded by using a heating plate 129 that moves in the direction of shearing as shown in FIG. 8A, severing while melting as shown in FIG. 8B, and occluding the severed end while maintaining the inside of the connecting tube in a sterile and sealed state as shown in FIG. 8C. In addition, aseptic tube connection can also be carried out as shown in FIGS. 9A through 9C. Namely, cell recovery line 125 can be connected to another connecting line 130 by simultaneously severing cell recovery line 125 and another connecting line 130 arranged in parallel as shown in FIG. 9A followed by shifting the lines so that cell recovery line 125 aligns with the other connecting line 130 as shown in FIG. 9B, and then removing heating plate 129 as shown in FIG. 9C. Although the joined portion 17b is occluded during connection, the internal flow path is able to be continuous while the line walls are connected by an external force. Namely, cell recovery line 125 and another connecting line 130 can be connected while maintaining the inside in a sterile state. Namely, by connecting cell recovery line 125 in which mesenchymal stem cells have been recovered to connecting line 130, which is linked to another main culture vessel (not shown) in which a body tissue supplement material is sealed, by aseptic tube connection, culturing of the recovered mesenchymal stem cells can be continued in a secondary culturing step in a aseptic state. Furthermore, since mesenchymal stem cells are present inside cell recovery line 125, a spare space 131 for severing may be formed in the end of cell recovery line 125 as shown in FIG. 10 since there is the risk of the mesenchymal stem cells being damaged by heating plate 129. Namely, by severing along cross-sectional line A that passes through spare space 131, heating plate 129 is prevented from making direct contact with mesenchymal stem cells in cell recovery line 125, thereby making it possible to carry out aseptic tube connection while maintaining the viability of the mesenchymal stem cells. Furthermore, although enzyme vessel 124 is provided and the mesenchymal stem cells are detached by trypsin in the present embodiment, temperature-responsive treatment switching between hydrophilic and hydrophobic properties bordering on a predetermined temperature may be carried out on the inner walls of main culture vessel 122 instead of using trypsin. This temperature-responsive treatment is the same as that previously described. Sixth Embodiment Culture Apparatus Next an explanation is provided of a culture apparatus 140 as claimed in a sixth embodiment of the present invention with reference to the drawings. As shown in FIGS. 25 and 26, this culture apparatus 140 as claimed in the present embodiment is provided with a main culture vessel 141, a culture vessel 146 having a medium vessel 144 and a waste medium vessel 145 connected to said main culture vessel 141 by means of connecting lines 142 and 143, and a mounting frame (level difference adjustment means) 147 on which said culture vessel 146 is installed and which changes its inclination angle. The aforementioned main culture vessel 141 is formed in the shape of a flat, thin box that has a comparatively large bottom surface area. The aforementioned medium vessel 144 and waste medium vessel 145 are formed in the shape of boxes having a larger height than main culture vessel 141, while also having an inner volume that is several times the inner volume of main culture vessel 141. This medium vessel 144 and waste medium vessel 145 are disposed on the same side of main culture vessel 141. In addition, medium similar to that previously described is sealed in main culture vessel 141 and medium vessel 144, while the inside of waste medium vessel 145 is empty. The aforementioned mounting frame 147 is provided with a tray section 148 that immobilizes culture vessel 146, and an oscillating device 149 that rocks said tray section 148 about the horizontal axis. Pinching valves 150 and 151 similar to the fourth embodiment are provided in tray section 148, and are capable of opening and closing connecting lines 142 and 143 by clamping in the radial direction intermediate locations in the lengthwise direction of each connecting line 142 and 143. Oscillating device 149 is provided with a base 152 and a motor 153 that rocks tray section 148 relative to base 152. The following provides an explanation of the operation of culture apparatus 140 as claimed in the present embodiment composed in this manner. In order to culture cells using culture apparatus 140 as claimed in the present embodiment, bone marrow cells are first supplied to main culture vessel 141, tray section 148 is made to be level, and the cells are cultured under predetermined culturing conditions similar to those indicated in the previous embodiments while maintaining the bottom of main culture vessel 141 level. When a predetermined medium replacement time has been reached, by operating motor 153 of mounting frame 147 and rocking tray section 148 relative to base 152, main culture vessel 141 is disposed at a higher position than waste medium vessel 145 as shown in FIG. 27. While in this state, pinching valve 151 of pinching valves 150 and 151 provided in tray section 148, which had been closing connecting line 143 that connects main culture vessel 141 and waste medium vessel 145, is then opened. As a result, medium to be discarded in main culture vessel 141 is discharged by gravity into waste medium vessel 145. Since adhesive mesenchymal stem cells remain adhered to the bottom surface within main culture vessel 141, connecting line 143 is again closed by operating the aforementioned pinching valve 151. Subsequently, motor 153 of mounting frame 147 is operated to dispose medium vessel 144 at a higher position than main culture vessel 141 as shown in FIG. 28. Pinching valve 150, which had been closing connecting line 142 that connects main culture vessel 141 and medium vessel 144, is then opened. As a result, fresh medium sealed in medium vessel 144 is supplied by gravity to main culture vessel 141. As a result, since the medium within main culture vessel 141 is replaced with fresh medium, medium replacement is completed by again closing pinching valve 150. As a result of continuing culturing while repeating this medium replacement step a plurality of times, mesenchymal stem cells are grown to the required number on the bottom surface of main culture vessel 141. Following completion of culturing, main culture vessel 141 can be transported independently in a state in which mesenchymal stem cells are sealed inside by severing connecting lines 142 and 143 by aseptic tube severing. In this manner, according to culture apparatus 140 as claimed in the present embodiment, cells can be grown to a required number in an aseptic state by replacing the medium in main culture vessel 141 simply by rocking tray section 148. In addition, since cells are cultured in culture vessel 146 while sealed from the outside, contamination by other bacteria and so forth from the outside can be prevented. Moreover, costs can be reduced and operation simplified as a result of employing a simple constitution involving simply rocking tray section 148. In addition, since main culture vessel 141 is formed into the shape of a thin box to achieve the minimum required medium depth, the amount of medium used can be reduced. In addition, since each vessel 141, 144 and 145 as well as connecting lines 142 and 143 are installed in a flat tray section 148, their installation work is made easy. Furthermore, although medium vessel 144 and waste medium vessel 145 are linked to the same side of main culture vessel 141 in the present embodiment, they may also be linked on different sides or on the top and bottom instead. In this case, it is necessary to provide a mechanism that rocks tray section 148 so that a level difference is formed between main culture vessel 141 and medium vessel 144 or waste medium vessel 145 attached to it. In addition, an enzyme vessel or other vessel may also be connected to main culture vessel 141. In addition, cultured mesenchymal stem cells may be centrifuged in main culture vessel 141 by providing a rotary mechanism that rotates tray section 148 about its normal axis. Moreover, an occluded connecting line for recovering centrifuged mesenchymal stem cells or transferring them to another culture vessel may be provided on one side of main culture vessel 141. In addition, since each vessel 141, 144 and 145 can be separated by performing aseptic tube severing on connecting lines 142 and 143, symbols, and particularly bar codes, which indicate that the vessels are mutually related vessels, may be affixed to each vessel 141, 144 and 145 to prevent the relationship between the cultured mesenchymal stem cells, the discarded medium and so forth from becoming unclear as a result of the aforementioned separation. The bar codes may be identical bar codes or mutually correlated bar codes. In addition, a portion or all of main culture vessel 141 may be composed to be transparent, and an observation window (not shown) may be formed in tray section 148 in which main culture vessel 141 is mounted. According to this, culturing status can be observed with, for example, an inverted microscope through an observation window during the culturing period. Furthermore, in the aforementioned fourth through sixth embodiments, the shapes of rotary drums 103 and 126, mounting frame 147 and vessels 104, 105, 106, 122, 124, 141, 144 and 145 are not limited to those indicated in each of the aforementioned embodiments. In addition, although the previous explanations have used the example of providing one each of vessels 104, 105, 106, 122, 124, 141, 144 and 145, a plurality of, for example, medium vessels 105 and 144 or waste medium vessels 106 and 145 may be provided instead. In addition, in addition to these vessels 104, 105, 106, 122, 124, 141, 144 and 145, in the case of a secondary culturing step for example, a vessel in which is sealed a differentiation induction factor such as dexamethasone may be connected in advance, or may be connected by aseptic tube connection. Furthermore, although the cultured cells in each of the aforementioned embodiments were explained by using the example of mesenchymal stem cells, the present invention may also be applied to the case of culturing other cells instead, examples of which include ES cells, somatic stem cells, osteocytes, chondrocytes and neurocytes. In addition, in addition to bone marrow fluid, peripheral blood or placental blood may be used for the liquid supplied to the main culture vessel. In addition, only bone marrow cells, obtained by centrifuging collected bone marrow fluid, may be supplied to the main culture vessel. In addition, although the body tissue supplement material was explained by using the example of a bone supplement material composed of β-tricalcium phosphate, any arbitrary biocompatible material such as ceramics, collagen or polylactic acid may be used. INDUSTRIAL APPLICABILITY According to the culture vessel and culture apparatus as claimed in the present invention, cells can be cultured while replacing the medium a plurality of times in a culture vessel that is occluded from the outside. As a result, cells can be cultured in a viable state without the cultured cells being contaminated by dust particles and so forth from the outside. In addition, since the cells are sealed in a vessel, there is no risk of intermixing even if a plurality of types of cells are cultured simultaneously in close proximity, thereby improving culturing efficiency.
<SOH> BACKGROUND ART <EOH>In order to culture cells, a plurality of steps are carried out in order, including an extraction step in which the cells to be cultured are extracted from bone marrow fluid or other liquid extracted from a patient, a medium preparation step in which a medium suitable for the cells to be cultured is prepared, a primary culturing step in which the extracted cells are placed in a medium in a suitable culture vessel and subjected to predetermined culturing conditions, and a secondary culturing step in which the primary cultured cells are mixed into a body tissue supplement material followed by additional culturing. This type of cell culturing has conventionally been considered to be carried out in a clean room for which particle levels are controlled after sealing the entire culture (see, for example, Japanese Examined Patent Application, Second Publication No. 3-57744, page 2, column 3). Namely, an air flow is formed inside a clean room by which air flows from the ceiling towards the floor, and in the case dust particles and so forth are generated in each treatment step, the dust particles are carried towards the floor by the flow of air and then collected by a dust collector disposed beneath the floor. Robot arms are installed within the clean room, and cells can be transferred between each step. However, in the case of carrying out all of the treatment steps within a clean room in this manner, since the space in which each step is carried out is continuous, dust particles generated in one step have the potential for contaminating cells allocated to the next step. Thus, in the case of simultaneously culturing a plurality of cells, problems result due to the occurrence of contamination between cells or contamination of added substances. In consideration of the aforementioned circumstances, the object of the present invention is to provide a culture vessel and culture apparatus capable of reducing contamination by dust, bacteria and so forth in each treatment step using a simple constitution.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a front view showing a culture vessel as claimed in a first embodiment of the present invention. FIG. 2 is an explanatory drawing for explaining a culturing step that applies the present invention. FIG. 3 is a schematic drawing for explaining a step in which medium is supplied from a medium vessel to a main culture vessel using the culture vessel of FIG. 1 . FIG. 4 is a schematic drawing similar to FIG. 3 for explaining a step in which medium is discharged from a main culture vessel to a waste medium vessel. FIG. 5 is a front view showing a variation of the culture vessel of FIG. 1 . F is front view showing another variation of the culture vessel of FIG. 1 . FIG. 7 is a front view showing another variation of the culture vessel of FIG. 1 . FIGS. 8A, 8B and 8 C are perspective views for explaining the order of steps for aseptically severing a tube. FIGS. 9A, 9B and 9 C are perspective views for explaining the order of steps for aseptically connecting a tube. FIG. 10 is a longitudinal cross-sectional view showing the end structure of an occluded connecting tube. FIG. 11 is a front view showing culture vessels used in a culture apparatus as claimed in a second embodiment of the present invention. FIG. 12 is an overhead view showing a case in which the culture vessels of FIG. 11 are housed. FIG. 13 is a longitudinal cross-sectional view showing the culture apparatus of FIG. 11 partially severed. FIG. 14 is an overhead view showing a culture apparatus as claimed in a third embodiment of the present invention. FIG. 15 is a longitudinal cross-sectional view showing a variation of the culture apparatuses of the first, second and third embodiments. FIG. 16 is a front view showing a culture apparatus as claimed in a fourth embodiment of the present invention. FIG. 17 is a side view of the culture apparatus of FIG. 16 . FIG. 18 is a front view showing culture vessels used in the culture apparatus of FIG. 16 . FIG. 19 is a front view showing a step in which medium is discharged from a main culture vessel to a waste medium vessel in the culture apparatus of FIG. 16 . FIG. 20 is a front view showing a step in which medium is supplied from a medium vessel to a main culture vessel in the culture apparatus of FIG. 16 . FIG. 21 is a front view showing a variation of the culture vessels in the culture apparatus of FIG. 16 . FIG. 22 is a perspective view of the culture vessels shown in FIG. 21 . FIG. 23 is a side view showing a culture apparatus as claimed in a fifth embodiment of the present invention. FIG. 24 is a front view of the culture apparatus shown in FIG. 23 . FIG. 25 is an overhead view showing a culture apparatus as claimed in a sixth embodiment of the present invention. FIG. 26 is a front view of the culture apparatus shown in FIG. 25 . FIG. 27 is a front view showing a step in which medium is discharged from a main culture vessel to a waste medium vessel in the culture apparatus of FIG. 25 . FIG. 28 is a front view showing a step in which medium is supplied from a medium vessel to a main culture vessel in the culture apparatus of FIG. 25 . detailed-description description="Detailed Description" end="lead"?
20041104
20090217
20051027
70438.0
0
RAMDHANIE, BOBBY
INCUBATOR AND CULTURE DEVICE
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,648
ACCEPTED
Metal packaging
A packaging comprising a first and second outer part of metallic material, an inner part of non-metallic material made in one piece and comprising a first and second opposed side between which an element can be stored and a hinging part forming at least one hinge connecting said sides and allowing the sides to be rotated relative to each other within an angle so as to open the packaging and adapting the packaging and adapting the packaging for packing in an automated packing machine. At least a part of a perimeter of the first and second outer part is adapted to retain the inner part in order to attach said outer parts to said respective sides of said inner part for covering s substantial part of the outer surfaces of the sides.
1-49. (canceled) 50. A media storage disk box comprising: a first metal cover pivotally engaged to a second metal cover to be movable between i. a closed condition to provide an enclosure within which a mounting region to support a media storage disk is located ii. an open condition to provide access to said enclosure, and a hinge of a plastic material affixed to said first metal cover and to said second metal cover, said hinge including at least one flexible region defining an axis of rotation for pivotal movement of said first metal cover with said second metal cover between said open and closed condition an extension panel integrally formed with said hinge, said extension panel affixed to said first metal cover and disposed to the enclosure side thereof, said extension panel including and presented to the enclosure side thereof a means to releasably affix a media storage disk. 51. A media storage disk box as claimed in claim 50 wherein said hinge has disposed therefrom extension panels from each side to the axis of rotation, each extension panel being affixed to a respective first and second metal covers. 52. A media storage disk box as claimed in claim 50 wherein said hinge includes a spine intermediate of said first metal cover and said second metal cover, said spine providing two flexible regions each defining an axis of rotation extending parallel with the spine. 53. A media storage disk box as claimed in claim 50 wherein said hinge includes a spine intermediate of said first metal cover and said second metal cover, said spine providing two flexible regions each defining an axis of rotation extending parallel with the spine wherein said extension panel is disposed from said spine extending from one of said axis of rotation. 54. A media storage disk box as claimed in claim 50 wherein said hinge includes a spine intermediate of said first metal cover and said second metal cover, said spine providing two flexible regions each defining an axis of rotation extending parallel with the spine wherein two extension panels are disposed from said spine, each extending from a respective said axis of rotation. 55. A media storage disk box as claimed in claim 50 wherein said extension panel is affixed to said first metal cover in an interlocking relationship defined by a folded region of said first metal cover. 56. A media storage disk box as claimed in claim 54 wherein each said extension panel is affixed with a respective metal cover by an interlocking relationship defined by a folded region of said respective metal cover. 57. A media storage disk box as claimed claim 50 wherein said extension panel is substantially co-extensive with said first metal cover. 58. A media storage disk box as claimed in claim 54 wherein both said extension panels are substantially co-extensive with its respective metal cover. 59. A media storage disk box as claimed in claim 50 wherein said extension panel is substantially co-extensive with said first metal cover, wherein said means to releasably affix includes a rosette to locate at a central aperture of said media storage disk. 60. A media storage disk box as claimed in claim 55 wherein both said extension panels are substantially co-extensive with its respective metal cover and each present at their distal most from said hinge edge, means to mutually interlock to allow said box to be releasably retained in said closed condition. 61. A media storage disk box as claimed in claim 50 wherein said extension panel includes perimeter wall upstands projecting from a base to the enclosure disposed side of said base and at perimeter sides of said extension panel save for where said extension panel is connected to said hinge. 62. A media storage disk box as claimed in claim 61 wherein said first metal cover includes perimeter flanges projecting from at least part of the perimeter of said first metal cover and locating with the outward to said enclosure facing perimeter walls of said extension panel. 63. A media storage disk box as claimed in claim 55 wherein each said extension panels include perimeter wall upstands projecting from a base to the enclosure disposed side of said base and at perimeter sides of said extension panel save for where said extension panel is connected to said hinge. 64. A media storage disk box as claimed in claim 63 wherein said second metal cover includes perimeter flanges projecting from at least part of the perimeter of said second metal cover and locating with the outward to said enclosure facing perimeter walls of said second mentioned extension panel. 65. A media storage disk box as claimed in claim 52 wherein said spine has affixed to be disposed from a non enclosure disposed side thereof a metal spine panel. 66. A media storage disk box as claimed in claim 65 wherein said metal spine panel is substantially coextensive with said spine. 67. A media storage disk box as claimed in claim 65 wherein said metal panel is clipped to said spine at the longitudinally disposed ends of said spine. 68. A media storage disk box comprising: a first metal cover pivotally engaged to a second cover to be movable between a. an open condition to provide access to a media storage disk mounting region disposed from one of said first metal cover and second cover, and b. a closed condition to provide an enclosure within which said mounting region is located a hinge of a plastic material affixed to said first metal cover and to said second cover, said hinge defining an axis of rotation for pivotal movement of said first metal cover with said second cover. 69. A media storage disk box comprising: a first metal cover pivotally engaged by a hinge to a second cover to be movable between i. a closed condition to provide an enclosure within which a mounting region to support a media storage disk is located, and ii. an open condition to provide access to said enclosure, said hinge forming part of a unitary moulded plastic base structure which includes a first extension panel affixed to the enclosure side of said first metal cover, said hinge defining at least one axis of rotation for pivotal movement of said first metal cover with said second cover and wherein said extension panel is disposed to one of said at least one axis of rotation said first said extension panel being substantially coextensive with said first metal cover. 70. A media storage disk box as claimed in claim 69 wherein said second cover is part of said unitary moulded plastic base structure. 71. A media storage disk box as claimed in claim 70 wherein said second cover defines to the enclosure side thereof said mounting region including a rosette to realisably affix to the central aperture of a said disk. 72. A media storage disk box as claimed in claim 69 wherein said second cover is a second metal cover and wherein a second extension panel formed part of said unitary moulded plastic base structure, is disposed from the other side of said hinge and affixed to the enclosure side of said second-metal cover. 73. A media storage disk box as claimed in claim 72 wherein said second extension panel defines to the enclosure side thereof said mounting region including a rosette to releasably affix to the central aperture of a said disk. 74. A media storage disk box as claimed in claim 69 wherein said first metal cover and said extension panel are of a quadrilateral perimeter, said first metal cover folded to affix to at least part of the perimeter of all of the four sides of said first extension panel. 75. A media storage disk box as claimed in claim 72 wherein said second metal cover and said second extension panel are of a quadrilateral perimeter, said second metal cover folded to affix to at least part of the perimeter of all of the four sides of said second extension panel. 76. A media storage disk box as claimed in claim 69 wherein first extension panel includes a base panel having perimeter walls upstanding from the enclosure disposed side of said base panel, said perimeter walls in said closed condition locating with said second cover. 77. A media storage disk box as claimed in claim 69 wherein first extension panel includes a base panel having perimeter walls upstanding from the enclosure disposed side of said base panel and to the exterior to the enclosure side of at least part of said perimeter walls, is affixed said first metal cover. 78. A media storage disk box as claimed in claim 72 wherein second extension panel includes a base panel having perimeter walls upstanding from the enclosure disposed side of said base panel and to the exterior to the enclosure side of at least part of said perimeter walls, is affixed said second metal cover. 79. A media storage disk box as claimed in claim 72 wherein second extension panel includes a base panel having perimeter walls upstanding from the enclosure disposed side of said base panel and to the exterior to the enclosure side of at least part of said perimeter walls, is affixed said second metal cover and wherein first extension panel includes a base panel having perimeter walls upstanding from the enclosure disposed side of said base panel and to the exterior to the enclosure side of at least part of said perimeter walls, is affixed said first metal cover and wherein in said closed condition, the free edges of at least some of said perimeter wall of said first extension panel and the free edge of at least some of said perimeter wall of said second extension panel abut each other. 80. A media storage disk box comprising: formed as a unitary plastic body, a first base panel, a second base panel and a spine panel intermediate of said first base panel and said second base panel, wherein formed intermediate of said first base panel and said spine panel is a first hinge defining a first axis of rotation and between said second base panel and said spine panel is a second hinge defining a second axis of rotation parallel to said first axis of rotation, said hinges allowing movement of said first base panel relative to said second base panel between i. a closed condition to provide an enclosure within which a mounting region to support a media storage disk is located ii. an open condition to provide to allow access to said enclosure, said first base panel and second base panel are of a complementary size to, in said closed condition, provide perimeter to perimeter engagement of said first and second base panels a first sheet metal cover is affixed to and overlaying the first base panel to the non enclosure side of said first base panel. 81. A media storage disk box as claimed in claim 80 wherein a second sheet metal cover is affixed to and overlaying the second base panel to the non enclosure side of said second base panel. 82. A media storage disk box as claimed in claim 80 wherein a third sheet metal cover is affixed to and overlaying the hinge panel to the non enclosure side of said hinge panel. 83. A media storage disk box as claimed in claim 81 wherein said first base panel presents to the enclosure side thereof said mounting region. 84. A media storage disk box as claimed in claim 81 wherein said second base panel presents to the enclosure side thereof said mounting region. 85. A media storage disk box as claimed in claim 80 wherein said first base panel includes a planar base panel from which and to the enclosure side thereof is provided perimeter walls upstanding from said planar base panel to, in said closed condition engage with the second base panels and clipped about, and to the outwardly directed surfaces of at least part of said perimeter walls of, said first base panel are complementary upstanding perimeter walls. 86. A media storage disk box as claimed in claim 80 wherein a. a second sheet metal cover is affixed to and overlaying the second base panel to the non enclosure side of said second base panel and wherein b. said first base panel includes a planar base panel from which and to the enclosure side thereof is provided perimeter walls upstanding from said planar base panel and clipped about, and to the outwardly directed surfaces of at least part of said perimeter walls of, said first base panel are complementary upstanding perimeter walls and wherein c. said second base panel includes a planar base panel from which and to the enclosure side thereof is provided perimeter walls upstanding from said planar base panel to in said closed condition engage with the upstanding walls of said first base panels and clipped about, and to the outwardly directed surfaces of at least part of said perimeter walls of, said second base panel are complementary upstanding perimeter walls of said second sheet metal cover. 87. A media storage disk box as claimed in claim 85 wherein said complementary upstanding perimeter walls of said first sheet metal panel are provided to at least part of diametrically opposed perimeter regions of said first sheet metal panel. 88. A media storage disk box as claimed in claim 86 wherein said complementary upstanding perimeter walls of said first sheet metal panel are provided to at least part of diametrically opposed perimeter regions of said first sheet metal panel and wherein said complementary upstanding perimeter walls of said second sheet metal panel are provided to at least part of diametrically opposed perimeter regions of said second sheet metal panel. 89. A media storage disk box as claimed in claim 80 wherein said first base panel is quadrilateral in plan shape and said second base panel is quadrilateral in plan shape said hinge panel being provided intermediate of complementary perimeter edges of said first and second base panels, and wherein said hinge panel is of a length shorter than said complementary perimeter edges of said first and second base panels. 90. A media storage disk box comprising: formed as a unitary plastic body, a first base panel, a second base panel and a hinge formed intermediate of said first base panel and said second base panel, said hinge allowing movement of said first base panel relative to said second base panel between i. a closed condition to provide an enclosure within which a mounting region to support a media storage disk is located ii. an open condition to provide to allow access to said enclosure, said first base panel and second base panel are of a complementary size to, in said closed condition, provide perimeter to perimeter engagement of said first and second base panels a first sheet metal cover is affixed to and overlaying the first base panel to the non enclosure side of said first base panel.
FIELD OF THE INVENTION The present invention relates to metal packaging for storing elements, such as data-carrying elements like Compact Discs or DVDs, which packaging is adapted to be packed in automated packing machines for plastic packaging. BACKGROUND OF THE INVENTION The CD and DVD industries have for decades invested substantial sums of money in developing metal packaging. However, all these many efforts have not led to metal packaging, which is capable of being packed in the standard automated packing machines commonly used in these industries for plastic packaging. The total sum of investments in such automated packing machinery is huge and the total number of packaging, produced in the CD- and DVD-industries, exceeds 5 billion pieces per year. Metal as a component of packaging for CDs, DVDs and other forms of media gives a large number of advantages, including supplying the packaging with substantially additional strength and giving an exclusive look. Further advantages are that it is possible to emboss a surface relief directly onto the surface and that it is easier to print on metal surfaces. However, as stated the CD- and DVD-industries have not been able to provide a packaging that utilises these advantages, combined with the ability of being packed in the automated packing machines in the industries. The packing machines require that the packaging is openable like a book with an angle of more than 180°, preferably 240°. An example of such a packing machine is shown in FIG. 25. The common plastic CD- and DVD-packaging can be bent in that angle which is needed in the process of inserting a printed paper cover between the actual packaging and the transparent foil wrapped around it. When the plastic packaging is bent 240° the transparent foil and the packaging will separate and thus make space for the insertion of the printed paper cover. The reason for this ability is that CD- and DVD-plastic packaging has a hinge, which enables the sides of the packaging to be rotated relative to each other in order to open the packaging with an angle of, in principle, 360°. Metal packaging developed so far does not have this ability, as such packaging cannot be opened like a book with an angle of more than 180°, preferably 240°. Such as packaging is shown in FIG. 24. The challenge has thus been to achieve that metal packaging will be able to “act” like or emulate a plastic packaging in the automated packing machines, e.g. that the metal packaging may be opened like a book with an angle of more than 180°, preferably 240°. The demand in the market for such packaging is overwhelming, but the technical challenges even bigger. The reason for this is, as stated, that such packaging must be able to integrate different materials, i.e. metal and e.g. plastic. This requires that focus be put on the tolerances allowed when metal and plastic has to cooperate. Until now no one has succeeded in creating the metal packaging, which is “perceived” by the automated packing machines as plastic packaging, i.e. which allows the metal packaging to open with an angle of more than 180°, preferably 240° while still ensuring that the metal may cooperate, e.g. plastic. Packaging adapted to store data carrying elements like CDs and DVDs are known in the art. EP 0 576 256 B1 discloses a package structure for a recording medium or other items and which is composed of a plastic support frame and a laminated flexible body. EP 744 746 and EP 874 768 discloses systems comprising metal. However, these packaging systems can not be designed like a book due to the characteristics of the metal material. U.S. Pat. No. 6,431,352 discloses a holder for CD's or DVD's including a plastic molded container sized to accommodate the disc. Along a side of the container on an inner wall thereof is a living hinge. The disc is removed from or inserted into the holder by pressing against the sides of the container so that a slit widens into a gap through which gap the disc can pass. The sides of the holder cannot be separated. WO 96/35628 discloses a composite package for use in storing a laser or optically readable disc. The package includes a lightweight frame for storing the disc, and the frame is encompassed by a sheath, which is securely bonded to an exterior surface of the frame. The frame is made of plastic and the sheath is made of a suitable flexible material, such as paperboard, as it forms part of a hinge that requires high flexibility. Other documents relating to storage/packing of media are U.S. Pat. No. 6,220,431, EP 0 895 243, U.S. Pat. No. 4,714,157, U.S. Pat. No. 5,908,109, U.S. Pat. No. 6,375,003, U.S. Pat. No. 5,725,105, EP 0 671 743, WO 03/023783, EP 1 100 088, WO 00/74057, FR 2 753 297, U.S. Pat. No. 4,722,439, U.S. Pat. No. 5,477,961, EP 0 866 458, U.S. Pat. No. 5,788,068, U.S. Pat. No. 6,502,694 and U.S. Pat. No. D473,520. The common characteristics of these systems is that they can not be designed like a book with the ability to open with an angle of more than 180°, preferably 240° due to the characteristics of i.a. the metal material and thus cannot be packed in the automated packing machines. It is an object of the present invention to provide a metal packaging, which overcomes the above mentioned disadvantages. Thus, it is an object of the present invention to provide a metal packaging which is adapted for and can be packed in traditional automated packing machines in order to avoid the need for investing additional, very substantial sums of money in the development and implementation of new automated packing machines. It is a further object of the present invention to provide packaging for CD or DVD's having an improved strength and more exclusive look than known packaging. DESCRIPTION OF THE INVENTION Generally, in order to achieve the above mentioned objectives a packaging consisting of outer metal parts attached to an inner part of non-metallic material with a hinge for opening the packaging is provided. This provides the freedom of design known from non-metal material, such as plastic, and the strength and exclusivity of metal, while still allowing the packaging to be packed in automated packing machine assemblies. Thus, according to a first aspect, the present invention relates to a packaging comprising; a first and second outer part of metallic material, an inner part of non-metallic material made in one piece and comprising; a first and second opposed side between which an element can be stored, a hinging part forming at least one hinge connecting said sides and allowing the sides to be rotated relative to each other within an angle so as to open the packaging and adapting the packaging for packing in an automated packing machine, at least a part of a perimeter of the first and second outer part being adapted to retain the inner part in order to attach said outer parts to said respective sides of said inner part for covering a substantial part of the outer surfaces of the sides. Preferably, the width of the packaging is between 134 mm and 138 mm, and the length of the packaging is between 188 mm and 194 mm when packaging is in a closed condition. The width of the packaging is preferably between 280 mm and 286 mm in an open condition where the sides are rotated 180° relative to each other. The hinge preferably allows the sides to be rotated relative to each other within an angle of 180° or more, such as 190° or 200° or 210° or 220° or 230° or 240° or more than 240°. The inner part of the packaging is preferably made in one piece comprising a first side and a second side interconnected by a hinging part, which may comprise one or more hinges provided in groups or evenly distributed. The first and second side together defines a cavity in which the element can be stored. This provides the possibility of opening and closing the packaging like a book with an angle of more than 180°, preferably 240°, which is essential in order to be packed in automated packing machines, which require that the two sides of the packaging must be opened like a book within an angle of more than 180°, preferably 240°. This is possible for the packaging according to the invention, as the inner part and hinging part may be made of a flexible material, such as a flexible plastic, enabling the sides to be bend backwards in an angle of more than 180°, preferably 240°. At least a part of a perimeter of the first and second outer parts may be adapted to retain the inner part. At least a part of the perimeter of the first and second outer parts may comprise a curled edge portion and/or a flange extending transverse to a plane defined by a middle part of the parts. Accordingly, the inner part may be pressed into the first and second outer parts and in order to be removed it must pass the curled edge portion. It may be possible to provide the bend portion and the curled edge portion by means of a punching machine or a deep drawing machine. Such machines provide the possibility of making a part wherein at least a part of the perimeter of the part comprises said curled edge portion and/or a flange extending transverse—or any other area of the part. Said curl portion may be provided by step(s) of rolling the edge. The rolled curl portion may extend around the entire perimeter of the outer part(s) depending on the radius of curvature of the corners. The curling of the outer part(s) ensure(s) that there are no sharp edges contrary to known metal packaging. In a preferred embodiment, the outer parts comprise shell-like members consisting of a middle part having upwardly extending sidewall(s) so that the inner part is pressed into said shells. Preferably, the sidewall(s) terminate in a curled or slightly bend edge portion that is adapted to grip around corresponding edges of the inner part so as to retain the inner part. The packaging is preferably quadrangular, and the shell-like members comprise upwardly extending sidewalls on at least three edges so that the shell substantially surrounds the sides of the inner part on at least three sides. In an embodiment, the first and second sides comprise indentations along a perimeter for receiving corresponding protrusions provided on said outer parts so as to provide the attachment between said sides and said parts. Thus, the first and second part may be attached to the inner part by clicking them on. The first and second part may be U-shaped such that the legs of the “U” define sidewalls of the parts, said sidewalls may comprise the protrusions for attaching them to the inner part. Alternatively or additionally, the inner part may be attached to the first and second part by means of glue and/or welding and/or at least one snap-lock. The inner part may be integrated with the first and second parts by means of inject-moulding. Thus the inner part may be moulded around the first and second part. This may be done by means of insert-moulding wherein the outer parts are placed in the tool in which the moulding is taking place. Other production processes may be suitable, such as blow-moulding, extrusion or thermo-moulding, depending on the desired design. The first and second parts may be riveted or screwed to the inner part depending on e.g. the type of advertisement that is preferred. The outer parts may cover a part of or the whole outer surface of the inner part. In a preferred embodiment, the outer parts substantially cover all the outer surfaces of the inner part. In the embodiment where the outer parts is U-shaped, they only cover a central part and two sides of the inner part. It is preferred that the packaging can be closed in only one step not needing any “post squeezing” on the locking parts. Therefore, the locking part(s) are preferably arranged close to indentations, that is used to open and close the packaging like a book, in order to reduce the amount of force to close and to make sure that the packaging is closed in one step. Further, the outer part may be substantially thick and/or comprise reinforcement ribs in order to provide a more stiff cover that does not wrench when closing or opening the packaging. The edge portion of the first and second part may extend around the entire edge of each of the two sides of the inner part, inclusive said indentations used for opening. Thus, the indentations may be formed in metal in order to provide a strong and stiff handgrip. The inner part may comprise one or more locking pins provided as protrusions so as to lock the first and second part to the inner part. Said pins are preferably provided on the inner part at a location adjacent to said indentations of the first and second part (when these parts are attached to the inner part). Thus, the pins may engage an edge portion of the first and second part, respectively, in order to provide a lock there between, and thus prevent that the first and second parts detach from the inner part by accident. In particular, a metal edge portion may be provided on the outer parts and which extends along the sides of the two sides of the inner part, which constitute the back edge of each side, i.e. the edge near the hinge area. A back part of the inner part may compose the hinging part between the two sides, and the back part may be covered by a metal part/layer. The back edge is preferably displaced inwards towards to internal area of each two sides of the inner part so that the back part be on level with the outermost edge of the back side of the packaging when the packaging is closed. The metal part/layer covering the back part may be glued thereto. Alternatively or additionally, the metal part/layer may comprise slips that may be bent around an upper and lower edge of the back part in order to attach the metal part/layer. Edges of the metal part/layer may be bent or curled so as to reinforce its stiffness. The metal part/layer may be attached to the back part by insert moulding and/or click-on means. In a preferred embodiment, the hinging part comprises two hinges, one for each side of the inner part. Preferably, the hinges each defines a groove extending inwardly on the backside of the packaging, the grooves being provided for clicking first and second outer parts onto the inner part, as protrusions on each outer part may enter and engage the grooves, respectively. Also the above-mentioned metal layer/part covering the back part may be attached to the back part by click on. Preferably, the grooves extend along the entire length of the hinges so that a corresponding curled or bent edge defining the protrusions on the outer parts and metal layer/part may extend along the entire length thereof, which reinforces the parts/layer. Furthermore, the grooves provides that any sharp edges on said outer parts and metal part/layer may be hidden or surrounded by said groove, and thus no sharp edges can be seen and touched. When opening the packaging with an angle of 180°, the level of the back part between the two hinges is preferably higher than the level of the two sides of the inner part. Thus, the back part is displaced inwards in relation to the sides. This embodiment provides that the back part may be displaced more inwards towards the internal of the packaging when the packaging is closed, which then increases the strength and provides a more smooth finish where the inner part is better covered by the outer metal parts. The described embodiment is shown in FIG. 21. When attaching the metal part/layer to the back part the combining of two materials requires certain precautions such as choosing the adequate means of attachment such as an adhesive such as glue and facilitating the co-operation of the two materials. In a preferred embodiment the metal part/layer is thus not covering the whole of the back part, and thereby allowing the back part to change dimensions without the metal part/layer becoming inadequately sized, and the means of attachment such as an adhesive such as glue is choozen from a range of means, which are capable of absorbing the different reactions of the two materials under various circumstances such as climatic circumstances. Preferably, the means of attachment is a glue, which may be “double-sided” adhesive such as TESA 4965 and/or 3M 9088FL. However, any glue or other adhesive, which are capable of absorbing the different reactions of the two materials under various circumstances may be used. In another embodiment, the back part may be labelled by in-mould labelling. Preferably, the packaging comprises guiding members for providing that the step of closing is done in a controlled manner avoiding the two sides of the packaging from displacing in relation to each other. The guiding members may comprise a male member having a tapered end (such as a conical end) that engages into a female member. Said guiding members may be positioned in the corners of the inner part, so that they also provide a reinforcement of the corners of the packaging. Thus, the corners of the first and second outer part may not be dented if the packaging is dropped. In another embodiment, the guiding members are provided adjacent to the corners first meeting each other when closing the packaging. The guiding members comprise one or more protrusions provided on one of said sides and being of adapted to engage grooves provided on the opposite side. Preferably, there is a space between the inner part and the first and/or second outer part (such as 0.5 mm) so as to provide space for an inwardly extending embossing relief in the inner side(s) of the outer part(s) and/or an outwardly extending embossing relief in the outer side(s) of the inner part(s). The space may be obtained by countersinking at least a part of the inner part when moulding it. If an embossing relief must extend outwardly in the outer part, then the part containing said relief might be countersunk prior to emboss so that the packaging can be stacked on each other though embossing is provided in the surface. There may also be an embossing relief on the inner sides of the inner parts. The inner part and/or the first and/or second outer part may serve as a lock adapted to lock the book-like packaging. This lock may be operable with one hand or two hands may be used to open the book and thereby unlock the packaging. The inner part of the packaging may be provided with a locking part such that the first and second side may be locked together. Such a locking part may comprise magnets, which hold the first and second side together. In other embodiments the locking part is a snap-lock or a lock which requires a key or a lock which only can be opened once where after it can not be locked again. The locking parts may comprise a male locking member engageable with a female locking member. The first and second outer part may cover at least the central part of the outer surface of the inner part, and the outer surface of the inner part may comprise recesses having a shape and depth substantially corresponding to the shape and thickness of the outer parts, respectively. Thus, the outer parts may be attached to the inner part so that the outermost surface of the outer part is levelled with the outermost surface of the inner part. The shape of the first and second outer parts are preferably provided by bending or extruding or deep drawing. The inner part may comprise one or more protrusions extending inwardly in the packaging. Protrusions may be provided on one side of the inner part, and which pushes the element(s) towards an opposite side of the inner part, when the packaging is closed. Thus, the element is even more fixated in the packaging. Preferably, the protrusions are positioned on the inner part in the hinge area and also in the area near the edge of the inner part near the locking parts. The first and second outer parts comprise a metallic material. E.g. the outer part may be a composite comprising reinforcing metal elements and/or fibre material. In some embodiments the outer parts are all made of the same material while in other embodiments the outer parts are each made of a different material. E.g. the outer part may be made of a metal and/or alloy comprising aluminium and/or bronze and/or steel and/or stainless steel and/or iron and/or magnesium and/or titanium and/or copper and/or nickel and/or zinc and/or silver and/or gold and/or platinum and/or sheet metal and/or tinplate or a combination hereof. A layer of metallic or non-metallic material may be provided on the outer part(s) which in such embodiments may be made of foil, cardboard, paperboard, veneer, polymer, textiles or laminates of foil. One embodiment may comprise a metal layer on the outside of the packaging. As an example the layer may be a gold layer having a decorative effect. The metal layer may be polished or grinded. The inner and/or outer surface of the first and second parts could in some embodiments be covered/coated by a protective layer and/or a decorative layer e.g. comprising colours. The protective layer may be in contact with the outer parts or it may be in contact with the decorative layer. The protective layer and/or the decorative layer may cover the whole and or a part of the inner and/or outer surface. The layer may be metallic or non-metallic. The inner part comprises a non-metallic material. E.g. the inner material may be made of paper and/or cardboard and/or rubber and/or wood and/or leather and/or silicone and/or plastic (polymer), such as PP, PA, PMMA, PC, PELD, PEHD, PET or elastomers or polymers or rubber or any combination thereof. In some embodiments the inner part may comprise one part made of one plastic or other non-metallic material while another inner part—e.g. the hinging part—is made of another non-metallic material such as polypropylene. The element may be welded together with at least a part of the inner part and/or the first and/or second outer part(s). Thus in order to use the element for the first time the welded area must be raptured and this makes it possible to see that the element had been used at least once. The packaging may comprise one or more boxes. At least a part of the inner part may be shaped so as to engage at least a part of the at least one element in the packaging. E.g. a part of the inner part may have the same or substantially the same shape as the element such that the element fits into the inner part. The shape of the inner part may be the complementary shape of the element, i.e. if the element has a round shape, then a round hole may be provided a part of the packaging and the round shape then fits into the round hole. When the element is placed in the packaging it can then be fixated such that it does not move around in the packaging when said packaging is moved from one place to another or when the packaging is shaken. The inner part and/or the first and second outer parts may comprise means adapted to engage the element by means of snap-locks or other locks. Such other locks could be locks, which require a key in order to lock and/or un-lock. The lock could also be of the kind, which must be partly damaged in order to remove the element. This makes it possible to see if the element has ever been removed from the packaging. In some embodiments the element may be replaced while in others it is not possible to replace the element. In one embodiment at least a part of the inner part is shaped so as to retain at least one element in the packaging in a predetermined position. The inner element could be shaped such that only a part of the element is retained in a predetermined position. E.g. the inner part may comprise a round protruding element which is adapted to engage a round hole in the element. Such an element could be a CD and/or a DVD or any other data-carrying element having a similar hole and shape or any other data-carrying element. The inner part of the packaging may comprise an retaining member adapted to be moved between an retaining position wherein it retains the element in a predetermined position and a non-retaining position wherein the element is not retained. The retaining member may be shaped such that it engages a hole in the element. Thus the retaining member may have a shape which is complementary the shape of the sides of the hole, i.e. if the hole is circular then the retaining member may comprise two parts which are shaped as half-circles. When an object or a finger applies pressure to the two half-circles the retaining member may be moved out of engagement as it is moved into the non-retaining position. When the retaining member is in the non-retaining position, the element may be removed. The inner part may comprise more than one retaining member, such as one on each of the sides of the inner part. Thus, the packaging may store one, two, three or more elements, such as CD's or DVD's. In another embodiment, the inner part may comprise a retaining member having a plurality of retaining taps adjacently arranged on a circle and surrounding a “release tap” and adapted to engage the edge of a hole of a CD or DVD. The taps are positioned elevated in relation to the inner part, so that the taps may disengage said hole by pushing downwards on the release tap and thereby releasing the CD or DVD from the taps. Preferably, the taps are adapted to retain one, two or three CD's or DVD's stacked on each other. The packaging may comprise more than one such retaining member, such as two, e.g. one positioned on each side of the inner part. When the retaining member is in the retaining position it may be possible to insert an object underneath the retaining member between the retaining member and the inner part and/or one of the first and second outer parts. If an object is inserted it may not be possible to move the retaining member towards the non-retaining position. This results in a situation wherein it is not possible to remove the element. Accordingly the packaging may in one embodiment comprise a security member adapted to retain the retaining member in the retaining position. The security member may be shaped such that the packaging must be opened in order to access the security member. One advantage of such a packaging is that if the packaging is supplied with means for detecting whether or not the packaging has ever been opened, then one will know that if the product has not been opened then the security member will be present in the packaging. In other embodiments the security member can be inserted from the exterior of the packaging. Thus it is possible for a shop to insert the security member e.g. on arrival of the product. This makes it possible for a shop to use a security system of their own choice. Thus a shop is not forced to use the security member supplied by the supplier. The security member may be of the type described in U.S. Pat. No. D468 621. In some embodiments the security member comprises signal emitting means. Such signal emitting means could be adapted to emit electromagnetic signals and/or magnetic fields. Thus when the packaging is moved out of a specific area e.g. out between two signal detecting means, it is possible to activate an alarm. As at least a part of the packaging is made of a metal material it is essential that the packaging does not shield the magnetic field and/or the electromagnetic signals. This may be done by removing the metal from an area such that the remaining metal is so thin that it is possible for the fields/signals to pass through the metal surface. In other embodiments an antenna may be provided. The antenna may be adapted to transmit the fields/signals from the inside of the packaging to the outside. In some embodiments the first and/or second outer part serves as the antenna and thus the ability of the metal part to transmit fields/signals may be utilised. A part of the at least one of the elements can be integrated in the inner part. As an example a sleeve or cover of a book may be a part of the inner part. Such an integrated part may be separated from the rest of the inner part by a weakened line, which makes it possible to remove the integrated part by tearing it out or pushing it out of the inner part. The inner part may furthermore comprise means to retain such an element, which originally has been an integrated part of the inner part. In some embodiments a foil is provided in the inner part and the foil must be removed in order to access the element. The removed foil may comprise information about the product in the packaging and thus means for holding the foil after removal can be provided e.g. in such a way that it is viewable from the outside of the packaging. The foil may be made such that it is possible to place it in a laser printer and thus it is possible to print information on the surface e.g. about music stored on an optical storage disc kept in the packaging. At least a part of the inner part may be slidable in relation to the first and second outer part and/or other inner parts. The slidable part can be slidable between a protected position wherein it is stored in the packaging and an accessible position wherein it has been slided out of the packaging and thus is accessible. Such a slidable part could comprise a protruding part adapted to engage the stored element. The slidable part may be rotated out of the packaging. A plurality of slidable and/or rotatable parts may be provided in the packaging. In some embodiments the inner part and/or the first and second outer parts may comprise magnetic properties. The magnetic properties make it possible to retain the element by means of a magnetic force. E.g. an optical storage medium made of a metal material which is attractable by the force of a magnet may be retained in a predetermined position. As an example the slidable part may be made of a plastic material comprising magnets in certain positions and when the part is slided out of the packaging the disc may be placed on the slidable part which holds the optical element by means of the magnets. In one embodiment the stored element comprises an optical or electronical medium, such as an optical or electronical medium comprising a central hole. The diameter of the stored element may be between 119.7 and 120.3 millimetres or between 78.8 and 80.2 millimetres. In some embodiments the diameter of the element is between 10 and 500 millimetres, such as between 5 and 300 millimetres such as between 10 and 250 millimetres, such as between 20 and 200 millimetres such as between 50 and 150 millimetres, such as between 75 and 125 millimetres. The diameter of the centre hole of the optical storage medium may be between 15.25 and 15.35 millimetres or between 15.3 and 15.4 millimetres. In other embodiments the diameter of the centre hole is between 1 and 50 millimetres, such as between 5 and 25 millimetres, such as between 10 and 15 millimetres. At least one side of the inner part may comprise a fixture for a CD(s). The fixture may engage the CD(s) in the centre hole or the outer edge of the disc. A first outer dimension of the packaging may be between 135.1 and 136.8 millimetres. The first outer dimension may be the width of the packaging. A second outer dimension of the packaging may be between 190.2 and 192.0 millimetres. The second outer dimension may be the length of the packaging. A third outer dimension of the packaging may be between 14.7 and 15.3 millimetres. The third outer dimension may be the thickness of the packaging. In particular, the first and second dimension is important for the packaging in order to be packed in a traditional automated packing machine. The automated packing machine will typically be of the type called Ilsemann KVD-30, Kyoto DVD100 and GIMA DVD872. In some embodiments the first and/or the second and/or the third outer dimension is/are between 10 and 5000 millimetres, such as between 25 and 3000 millimetres, such as between 50 and 2000 millimetres, such as between 75 and 1500 millimetres, such as between 100 and 1250 millimetres such as between 150 and 1000 millimetres, such as between 175 and 750 millimetres, such as between 200 and 500 millimetres, such as between 300 and 400 millimetres. However, in an alternative embodiment, the first outer dimension may be between 124.6 and 125.0 millimetres and/or a second outer dimension may be between 142.2 and 142.6 millimetres and/or a third outer dimension could be between 6.9 and 7.1 millimetres or between 10.2 and 10.6 millimetres. Such an embodiment may also be packed in an automated packing machine. In some embodiments the first and/or second outer parts may comprise a decoration. The decoration may contain text, pictures, figures, drawing etc. and could contain information about the content of the packaging. If the content is a data-carrying medium the decoration may give details about the songs, files or movies contained on the medium. The decoration may cover all or a part of the packaging. Preferably, each side of the first and/or second outer part is decorated, so that decorations appear on both the inner and outer side of the packaging. The inner part is in this embodiment transparent in order to make the decoration on the inner side visible. This combination allows for unique possibilities of decorations and thus visual effects on the packaging. One embodiment of the present invention may comprise a surface relief on an inner or outer surface of the packaging. Such a surface relief may be a hologram, a grating, a picture or any other kind of surface relief. The surface relief may be used for security purposes as it may prove the genuineness of the product. The surface relief may serve as identification of the product or as price information. The hologram may be readable for an optical reader and thus form part of an information package comprised in the packaging. The surface relief may be embossed in the surface of the first and/or second outer part. The process of embossing may be done by means of a roller or a stamping process. The packaging may on a top or bottom edge be provided with embossed surface relief indicating the contents of the packaging, e.g. the name of the composer and the title of a data-carrying medium. Thus, the packaging can be distinguished from other packaging, if it is stacked on a shelf or in a drawer. The first and second outer part may comprise embossed surface relief and/or graphical printings on one or more surfaces both outside and/or inside the packaging. The packaging may be adapted to comprise and accommodate a memory element readable by a computer, such as a memory card. In some embodiments the surface relief is embossed with a device for processing a substrate, said device having a tool plan and a reaction plan, the tool plan comprising a multiple layer construction with: a core having a substantially inflexible outer surface, and at least one tool being attached to the surface of the core, wherein flexible force absorbing means is provided in at least a part of the tool plan and/or the reaction plan, so as to locally absorbing the forces applied by the planes. The flexible force absorbing means may be a double-sided adhesive tape, which is used to attach a tool to the tool plan. The flexible properties of the tape are used to absorb local differences in the pressure applied. The method of embossing may be the one described in PCT/DK02/00787, which is hereby incorporated by reference. The inner part i.e. one of the sides may be substantially transparent. Thus a decoration or a surface relief may be visible from both sides through the transparent material. This makes it possible to see information provided on the inside or outside surface of the first and second outer part. In order to provide further visual effects the inner part can comprise a transparent colour. In some areas the colour may be solid i.e. such that it is not possible to see through the colour while in other areas the colour may be transparent. If e.g. a surface relief is provided on the inner surface of the first and second outer part then the transparent colour may give the visual effect of colouring of some of the areas of the surface relief. Colours may further be provided on the surface relief and/or the decoration. Thus the designer will be provided with the possibility of providing colour directly over the decoration and/or surface relief. Another option is that he may provide the colours distanced from the decoration and/or surface relief by providing it on the inner part. The inner part may be provided with text, logos, marks, frosting/grinding, super transparent surfaces, or it may be decorated, provided with labels, holograms or metal layers. According to a second aspect, the present invention relates to a retaining member for retaining a data carrying medium comprising a central hole in a packaging, the member comprising a plurality of taps adjacently arranged on a circle on a base part and surrounding a release tap, the taps being adapted to engage an edge of said hole, the taps being elevated positioned in relation to said base part, such that the taps are adapted to be released from the medium upon pushing the release tap towards said base part. Preferably, the medium comprises a CD or DVD, and the retaining member may be adapted to retain one, two or three stacked CD's or DVD's. According to a third aspect, the present invention relates to a packaging adapted to store an element, the packaging comprising one or more outer parts and one inner part, the inner part comprising a first side and a second side interconnected by a hinging part, and wherein an outer part is attached to the first and/or second side, respectively. The outer parts may be attached to the sides, respectively, by means of glue and/or welding and/or a snap-lock, or they may be integrated with the inner part by means of moulding, curling, bending or likewise. The inner part may be made of plastic, such as transparent plastic or coloured plastic, and the outer parts may be made of metal. The inner part may comprise indentations along a circumference for receiving corresponding protrusions provided on the outer parts, so as to provide a click-on attachment therebetween. The outer parts are preferably U-shaped, the legs of the U-shape comprising said protrusions. Thus, the outer parts are clicked on to the inner part which may be an inner part according to the invention, or another inner part. The inner part may comprise recesses on each side having a shape and depth substantially corresponding to the shape and thickness of the outer parts, respectively. The shape of the outer parts is provided by bending or extruding. The packaging according to each of the various aspects may comprise any of the features mentioned in connection with the other aspects. BRIEF DESCRIPTION OF THE FIGURES An embodiment of the invention will now be described in details with reference to the drawing in which: FIG. 1 shows an open packaging, FIG. 2 shows two closed packaging according to the present invention, FIG. 3 shows a sectional view of the packaging, FIGS. 4-9 show different embodiments of attachment of the first and second sides and outer first and second parts, FIGS. 10-12 shows cross-sectional views of the packaging, and FIGS. 13-22E shows pictures of the packaging, FIG. 23 shows a packaging with preferred dimensions in order to be packed in a packing machine, FIG. 24 shows a prior art packaging, and FIG. 25 shows an automated packing machine for packing the packaging according to the invention. DETAILED DESCRIPTION OF THE FIGURES I FIG. 1 is shown a packaging 2 comprising an inner part with a first side 4 and a second side 6 interconnected by a hinging part 8. The packaging 2 is openable like a book and thus the sides 4 and 6 may be swung away from each other like the covers of a book. A first outer part 10 is attached to the side 4 and a second outer part 12 is attached to the side 6. The side 4 further comprises a lower inner element 14, which is attached to the outer part 10. These two are glued together. In a similar way the second side 6 comprises an upper inner element 16 glued to the outer part 12. The outer part 10 and 12 are made of a metal material and the inner parts 14 and 16 are made of a plastic material. The upper inner element 16 is adapted to store an optical element by means of engaging means 18. The engaging means 18 is circular in shape and comprises an outer ring 20 and a retaining element in the centre of said ring (not shown). The outer ring 20 comprises an indentation 22, which makes it easier to grab the storage medium. The lower inner element 14 comprises longitudinal reinforcing 24 bar and a latitudinal reinforcing bar 26. The lower inner element 14 furthermore comprises two holding members 28 which are adapted to hold an element e.g. a booklet comprising information about the optical storage medium. The lower part 4 and the upper part 6 comprises handling indentations 30 which the user may use when the packaging is to be opened like a book. When opening the storage medium 2 the male locking member 32 disengages the female locking member 34. FIG. 2 shows two packaging 2 comprising a first side 4, a second side 6 and a hinging part 8. The packaging furthermore comprise handling indentations 30. FIG. 3 shows a sectional view of the packaging 2, comprising a first side 4, a second side 6 and a hinging part 8. The figure shows the holding member 28, which is movable as shown by arrow 36. The male locking member 32 comprises a protruding part 38 which is adapted to engage the edge 40 of the female locking member 34. The handling indentations 30 are seen on the figure. FIG. 4-9 shows different embodiments of first and/or second outer parts 42 having a middle part 44. The parts are made of a metal material, which is bend so as to provide a first flange 46 extending transverse or even perpendicular to the middle part 44. In some embodiments the first flange 46 is furthermore bend so as to define a second flange 48 which an inner element 54 must pass in order to be removed from the outer part 42, see FIGS. 7-9. In other embodiments the first flange 46 or the second flange 48 defines a curled edge portion 50. Yet in other embodiments the first flange 46 defines a protrusion 52. The protrusion 52, the curled edge portion 50 and the second flange 48 may be adapted to retain an inner element 54. In some embodiments the second flange 48 is provided along the entire periphery of the flange 46 as shown in FIG. 7 (A-A′) and FIG. 8. In other embodiments the second flange 48 is provided in different locations along the first flange 48 as shown in FIG. 7 (B-B′) and FIG. 9. FIG. 10 shows a cross-sectional view of the side of the inner part 60 (such as the upper part 6 of FIG. 1) of the packaging 2 comprising an retaining member for engaging and retaining a CD or DVD. The retaining member has a plurality of retaining taps 55 adjacently arranged on a circle and surrounding a “release tap” 56. The taps 55 are adapted to engage an edge of a hole of a CD or DVD. The taps 55,56 are positioned elevated 57 in relation to the base 58 of the inner part, so that the taps may disengage said hole by pushing downwards on the release tap and thereby releasing the CD or DVD from the taps. The engaging means further comprises a plurality of half-circles 59 that encircles the CD or DVD. The edge portion 61 of the outer part 62 holds the inner part 60, and the sidewall of the inner part 60 comprises reinforcement ribs 63. FIG. 11 shows a cross-sectional view of an open packaging comprising to sides 64 and 65 and a hinge part 66. One single inner part 60 constitutes both the left, right side and hinging part of the packaging. An outer metallic part 62 is attached onto one of the two sides of the inner part, and an outer metallic part 67 is attached to the hinge part of the inner part. Each of the outer metallic parts 62 comprises an edge portion 68 that constitutes the back edge of the packaging. The hinging part 66 is displaced a distance from the level of the metallic parts 62 such that when the packaging is closed, the hinging part 66 will be in line with the corners 69 of the metallic parts. When opening the packaging 2, the male locking member 32 disengages the female locking member 34. The hinging part comprises a reinforcement rib 70. There is provided a small space between the outer parts 62 and the inner part 60 in order to provide space for embossed relief in the outer parts. FIG. 12 shows a cross-sectional view of the holding member 28, which is movable as shown by the arrow 36. FIGS. 13 shows the packaging in open condition. FIGS. 14-15 shows the packaging in a closed condition from the front and backside, respectively. The back part 71 of the inner part composes the hinge connection between the two sides, and the back part is covered by a metal part/layer 72. As shown, the back edge is displaced inwards towards to internal area of each two side of the inner part so that the back part 71 be on level with the outermost edge 73 of the back side of the packaging when the packaging is closed. The handgrips 76 for opening the packaging are provided in the outer parts 62. FIG. 16 shows the inner part 60 detached from the outer parts 62 and the metal layer 72. FIGS. 17 and 17A shows an inner part 60 detached from the outer parts 62, the outer parts comprising two U-shaped metal parts, which are clicked on to the inner part. The inner part 60 has indentations 74, which the legs 75 of the U-shaped metal parts may grip into when clicking them onto there. FIG. 18 shows an open packaging, where the outer parts 62 are clicked on to the inner part 60. A plurality of packaging stacked next to each other are also shown. FIGS. 19-20 shows an open packaging, where the outer part 62 is clicked on to the inner part 60. As shown the packaging is opened like a book with an angle (α) of more than 180°, preferably 240°. Thus, it is possible to put the packaging into a conventional packing machine for packing it. FIG. 21 shows a cross-section of an embodiment of the packaging comprising an inner part with two sides 64, 65 and a back part 71 defining the hinging part with two hinges 77, one for each side of the inner part. The hinges 77 each defines a groove 78, said grooves being provided for clicking first and second outer parts 79 onto the inner part, as protrusion 80 provided as a bent edge on each outer may enter and engage the grooves 77, respectively. Also a metal layer/part (not shown) covering the back part may be attached to the back part by click on. Thus, any sharp edges on said outer parts and metal part/layer may be hidden or surrounded by said groove, and thus no sharp edges can be seen and touched. Preferably, the grooves extend along the entire length of the hinges so that the protrusions 80 may extend along the entire length of the edge of the outer parts and/or metal layer/part which reinforces said parts. As seen in FIG. 21, when opening the packaging with an angle of 180° as shown, the level of the back part 71 between the two hinges is higher than the level of the two sides 64, 65 of the inner part. This embodiment provides that the back part may be displaced more inwards towards the internal of the packaging when the packaging is closed, which then increases the strength and provides a more smooth finish where the inner part is better covered by the outer metal parts. FIGS. 22A-E shows an embodiment of the packaging according to the invention. The inner part 60 comprises locking pins 81 provided as protrusions for locking the first and second part 62 to the inner part 60. Said pins 81 are provided on the inner part 60 at the location adjacent to the indentations 82 on the first and second part 62, which defines the handgrips for opening the packaging. The pins 81 engage an edge portion 83 of the first and second part, respectively, in order to provide a lock therebetween, and thus prevent that the first and second parts 62 detach from the inner part 60 by accident. FIG. 23 shows a packaging with preferred dimensions in order to be packed in an automated packing machine. Thus, the packaging according to the invention has been developed in order to fulfil these dimensions, said dimensions being preferably; A: from 282 mm to 284 mm, B: 191 mm±0.8 mm, C: 135.6 mm±0.9/−0.5, D: 15 mm±0.5, and E: from 68.7 mm to 70.3 mm. FIG. 24 shows a prior art packaging. The packaging is an example of the known packages, which cannot be bent more than approximately 190° (α) and not up to 240°, and thus, it cannot be packed in an usual automated packing machine, as the packaging according to the invention. FIG. 25 shows an automated packing machine (Ilsemann) for packing a packaging 2 according to the invention. The empty packaging 2 is stored in a container 84 from where the packaging 2 is loaded to the conveyor 85. The packaging 2 is opened within an angle of approximately 180° and thereafter, a CD or DVD and other material is introduced into the packaging 2 by a rotating packing module 86 in which module 86 the packaging 2 is bent backwards into an angle of more than 180°, preferably 240°. At the end of the conveyor 85, the packaging is closed and packed together with the other packaging and stacked in piles 87.
<SOH> BACKGROUND OF THE INVENTION <EOH>The CD and DVD industries have for decades invested substantial sums of money in developing metal packaging. However, all these many efforts have not led to metal packaging, which is capable of being packed in the standard automated packing machines commonly used in these industries for plastic packaging. The total sum of investments in such automated packing machinery is huge and the total number of packaging, produced in the CD- and DVD-industries, exceeds 5 billion pieces per year. Metal as a component of packaging for CDs, DVDs and other forms of media gives a large number of advantages, including supplying the packaging with substantially additional strength and giving an exclusive look. Further advantages are that it is possible to emboss a surface relief directly onto the surface and that it is easier to print on metal surfaces. However, as stated the CD- and DVD-industries have not been able to provide a packaging that utilises these advantages, combined with the ability of being packed in the automated packing machines in the industries. The packing machines require that the packaging is openable like a book with an angle of more than 180°, preferably 240°. An example of such a packing machine is shown in FIG. 25 . The common plastic CD- and DVD-packaging can be bent in that angle which is needed in the process of inserting a printed paper cover between the actual packaging and the transparent foil wrapped around it. When the plastic packaging is bent 240° the transparent foil and the packaging will separate and thus make space for the insertion of the printed paper cover. The reason for this ability is that CD- and DVD-plastic packaging has a hinge, which enables the sides of the packaging to be rotated relative to each other in order to open the packaging with an angle of, in principle, 360°. Metal packaging developed so far does not have this ability, as such packaging cannot be opened like a book with an angle of more than 180°, preferably 240°. Such as packaging is shown in FIG. 24 . The challenge has thus been to achieve that metal packaging will be able to “act” like or emulate a plastic packaging in the automated packing machines, e.g. that the metal packaging may be opened like a book with an angle of more than 180°, preferably 240°. The demand in the market for such packaging is overwhelming, but the technical challenges even bigger. The reason for this is, as stated, that such packaging must be able to integrate different materials, i.e. metal and e.g. plastic. This requires that focus be put on the tolerances allowed when metal and plastic has to cooperate. Until now no one has succeeded in creating the metal packaging, which is “perceived” by the automated packing machines as plastic packaging, i.e. which allows the metal packaging to open with an angle of more than 180°, preferably 240° while still ensuring that the metal may cooperate, e.g. plastic. Packaging adapted to store data carrying elements like CDs and DVDs are known in the art. EP 0 576 256 B1 discloses a package structure for a recording medium or other items and which is composed of a plastic support frame and a laminated flexible body. EP 744 746 and EP 874 768 discloses systems comprising metal. However, these packaging systems can not be designed like a book due to the characteristics of the metal material. U.S. Pat. No. 6,431,352 discloses a holder for CD's or DVD's including a plastic molded container sized to accommodate the disc. Along a side of the container on an inner wall thereof is a living hinge. The disc is removed from or inserted into the holder by pressing against the sides of the container so that a slit widens into a gap through which gap the disc can pass. The sides of the holder cannot be separated. WO 96/35628 discloses a composite package for use in storing a laser or optically readable disc. The package includes a lightweight frame for storing the disc, and the frame is encompassed by a sheath, which is securely bonded to an exterior surface of the frame. The frame is made of plastic and the sheath is made of a suitable flexible material, such as paperboard, as it forms part of a hinge that requires high flexibility. Other documents relating to storage/packing of media are U.S. Pat. No. 6,220,431, EP 0 895 243, U.S. Pat. No. 4,714,157, U.S. Pat. No. 5,908,109, U.S. Pat. No. 6,375,003, U.S. Pat. No. 5,725,105, EP 0 671 743, WO 03/023783, EP 1 100 088, WO 00/74057, FR 2 753 297, U.S. Pat. No. 4,722,439, U.S. Pat. No. 5,477,961, EP 0 866 458, U.S. Pat. No. 5,788,068, U.S. Pat. No. 6,502,694 and U.S. Pat. No. D473,520. The common characteristics of these systems is that they can not be designed like a book with the ability to open with an angle of more than 180°, preferably 240° due to the characteristics of i.a. the metal material and thus cannot be packed in the automated packing machines. It is an object of the present invention to provide a metal packaging, which overcomes the above mentioned disadvantages. Thus, it is an object of the present invention to provide a metal packaging which is adapted for and can be packed in traditional automated packing machines in order to avoid the need for investing additional, very substantial sums of money in the development and implementation of new automated packing machines. It is a further object of the present invention to provide packaging for CD or DVD's having an improved strength and more exclusive look than known packaging.
<SOH> BRIEF DESCRIPTION OF THE FIGURES <EOH>An embodiment of the invention will now be described in details with reference to the drawing in which: FIG. 1 shows an open packaging, FIG. 2 shows two closed packaging according to the present invention, FIG. 3 shows a sectional view of the packaging, FIGS. 4-9 show different embodiments of attachment of the first and second sides and outer first and second parts, FIGS. 10-12 shows cross-sectional views of the packaging, and FIGS. 13-22E shows pictures of the packaging, FIG. 23 shows a packaging with preferred dimensions in order to be packed in a packing machine, FIG. 24 shows a prior art packaging, and FIG. 25 shows an automated packing machine for packing the packaging according to the invention. detailed-description description="Detailed Description" end="lead"?
20041105
20060530
20050804
92271.0
1
FIDEI, DAVID
METAL PACKAGING
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,765
ACCEPTED
Compressor
The invention provides a compressor that can reduce occurrence of vibration and noise due to self-induced vibration of an suction valve at the time of a low flow rate surely with an inexpensive structure. In the compressor according to the invention, an opening regulating valve 40 provided in a refrigerant suction channel 13c to a cylinder 11a is formed by an elastically deformable spiral member 41, and intervals of spiral portions 41a of the spiral member 41 are changed according to a flow rate of a refrigerant, whereby an opening of the channel 13c is regulated. Thus, it is possible to reduce occurrence of vibration and noise due to self-induced vibration of an suction valve 14c at the time of a low flow rate surely, and it is possible to simplify a structure of the opening regulating valve 40.
1. A compressor that includes a cylinder comprising a refrigerant inlet and a refrigerant outlet at one end, a cylinder head comprising a refrigerant suction chamber communicating with a refrigerant inlet and a refrigerant discharge chamber communicating with a refrigerant outlet, a piston reciprocating in the cylinder, and an suction valve provided in the refrigerant inlet, and a discharge valve provided in the refrigerant outlet, the refrigerant inlet and the refrigerant outlet being opened and closed by deformation of the suction valve and the discharge valve characterized by comprising an opening regulating valve that is provided in a refrigerant channel communicating with the refrigerant suction chamber or the refrigerant discharge chamber, consists of an elastically deformable spiral member fixed in the channel at one end thereof, and regulates an opening of the channel by changing intervals among spiral portions of the spiral member according to a flow rate of the refrigerant. 2. The compressor according to claim 1, wherein the spiral member of the opening regulating valve is formed such that diameters of the spiral portions gradually decrease from one end side toward the other end side. 3. The compressor according to claim 1, further comprising a blocking member, which blocks a part of the spiral member, is provided in the opening regulating valve. 4. The compressor according to claim 2, further comprising a blocking member, which blocks a part of the spiral member, is provided in the opening regulating valve.
TECHNICAL FIELD The present invention relates to a compressor that is used in, for example, a refrigeration circuit of an air conditioner for vehicles. BACKGROUND ART In general, as a compressor of this type, for example, as described in Japanese Patent Publication 2001-289177, there is known a compressor that includes a cylinder having a refrigerant inlet and a refrigerant outlet at one end, a piston reciprocating in the cylinder, and a tabular suction valve and a tabular discharge valve provided in the refrigerant inlet and the refrigerant outlet, such that the refrigerant inlet and the refrigerant outlet are opened and closed by elastic deformation of the suction valve and the discharge valve, respectively. Incidentally, in the compressor, there is provided a stopper that locks the one end side (free end side) of the suction valve in a predetermined opening position such that the suction valve opens and closes within a predetermined range. However, when a flow rate is low, the suction valve may open and close in a range in which the suction valve does not come into abutment against the stopper. In such a case, there is a problem in that pulsation occurs in the suction refrigerant due to self-induced vibration of the suction valve, which causes vibration and noise in an evaporator and the like that are set in an external circuit on the refrigerant suction side. Thus, in the compressor, an opening regulating valve, which regulates an opening of a channel according to a flow rate of a refrigerant, is provided in a refrigerant suction side channel of a cylinder head to reduce the opening of the opening regulating valve when a flow rate is low, whereby pulsation of the suction refrigerant propagating to the evaporator side is attenuated to reduce the vibration and noise of the evaporator and the like. However, the opening regulating valve has a complicated structure in which a valve body is housed in an exclusive valve case and biased in a predetermined direction by a spring attached in the valve case. Thus, there is a problem in that manufacturing cost increases. The present invention has been devised in view of the problems, and it is an object of the invention to provide a compressor that can reduce occurrence of vibration and noise due to self-induced vibration of an suction valve at the time of a low flow rate surely with an inexpensive structure. DISCLOSURE OF THE INVENTION The present invention provides a compressor that includes a cylinder having a refrigerant inlet and a refrigerant outlet at one end, a cylinder head having a refrigerant suction chamber communicating with a refrigerant inlet and a refrigerant discharge chamber communicating with a refrigerant outlet, a piston reciprocating in the cylinder, and an suction valve provided in the refrigerant inlet, and a discharge valve provided in the refrigerant outlet, the refrigerant inlet and the refrigerant outlet being opened and closed by deformation of the suction valve and the discharge valve, respectively, characterized by including an opening regulating valve that is provided in a refrigerant channel communicating with the refrigerant suction chamber or the refrigerant discharge chamber, consists of an elastically deformable spiral member fixed in the channel at one end thereof, and regulates an opening of the channel by changing intervals among spiral portions of the spiral member according to a flow rate of the refrigerant. Consequently, the intervals among the spiral portions of the opening regulating valve are widened when a flow rate is high, and the opening of the refrigerant channel increases. In addition, when a flow rate is low, since the intervals among the spiral portions of the opening regulating valve are narrowed and the opening of the refrigerant channel decreases, even in the case in which pulsation occurs in the refrigerant due to self-induced vibration of the suction valve or the discharge valve at the time of a low flow rate, the pulsation of the refrigerant propagating to an external circuit on the refrigerant channel side is attenuated by the opening regulating valve. In addition, in the above-described structure, the invention forms the spiral member of the opening regulating valve such that diameters of the spiral portions gradually decrease from one side toward the other side thereof. Consequently, since the spiral member is formed such that the diameters of the spiral portions of the opening regulating valve gradually decrease from the one side toward the other side, the spiral member assumes a conical shape that is susceptible to a flow resistance of the refrigerant. Further, in the above-described structure, the invention provides a blocking member, which blocks a part of the spiral member, in the opening-regulating valve. Consequently, in addition to the actions of claims 1 and 2, since the refrigerant does not pass the part where the blocking member is provided, a flow rate of the refrigerant is regulated so much more for that. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a side sectional view of a compressor representing a first embodiment of the invention; FIGS. 2A and 2B are main part side sectional views of the compressor; FIGS. 3A and 3B are side sectional views of an opening regulating valve; FIGS. 4A and 4B are side sectional views of an opening regulating valve representing a second embodiment of the invention; and FIGS. 5A and 5B are side sectional views of an opening regulating valve representing a third embodiment of the invention. BEST MODE FOR CARRYING OUT THE INVENTION FIGS. 1 to 3 show a first embodiment of the invention. This compressor includes a compressor body 10 that sucks and discharges a refrigerant, a piston 20 that is provided inside the compressor body 10, a drive unit 30 that drives the piston 20, and an opening regulating valve 40 that regulates an opening according to a flow rate of the refrigerant. Power from the outside is inputted to the drive unit 30. The compressor body 10 is formed in a cylindrical shape and includes a first housing 11 that is formed on the position of the piston 20 side, a second housing 12 that is formed on the position of the drive unit 30 side, a cylinder head 13 that is arranged on one end side of the first housing 11, and a valve plate 14 that is arranged between the first housing 11 and the cylinder head 13. The first housing 11 has a cylinder 11a that extends in an axial direction of the compressor body 10 and one end of the cylinder 11a opens to one end face of the first housing 11. In addition, a stopper 11b, which locks an suction valve 14c to be described later in a predetermined opening position, is provided on one end side of the cylinder 11a, and the stopper 11b is formed by cutout of an edge of the cylinder 11a. The second housing 12 opens on one end side, and the inside thereof communicates with the cylinder 11a of the first housing 11. The cylinder head 13 is attached to one end of the first housing 11 via the valve plate 14, and a refrigerant discharge chamber 13a opening to the valve plate 14 side is provided in the center of the cylinder head 13. An annular refrigerant suction chamber 13b opening to the valve plate 14 side is provided around the refrigerant discharge chamber 13a, and the refrigerant suction chamber 13b communicates with a refrigerant suction channel 13c provided on a side of the cylinder head 13. In addition, the refrigerant discharge chamber 13a communicates with a refrigerant discharge channel (not shown) provided in the cylinder head 13. A refrigerant inlet 14a and a refrigerant outlet 14b communicating with the cylinder 11a are provided in the valve plate 14. The refrigerant inlet 14a communicates with the refrigerant suction chamber 13b of the cylinder head 13, and the refrigerant outlet 14b communicates with the refrigerant discharge chamber 13a. A tabular suction valve 14c and a tabular discharge valve 14d, which opens and closes the refrigerant inlet 14a and the refrigerant outlet 14b, respectively, are attached to the valve plate 14 such that the refrigerant inlet 14a and the refrigerant outlet 14b are opened and closed by elastic deformation of the suction valve 14c and the discharge valve 14d. One end side of the suction valve 14c is locked by the stopper 11b. As shown in FIG. 2A, in a discharge process of the piston 20, the one end side of the suction valve 14c comes into pressed contact with the valve plate 14 side to close the refrigerant inlet 14a. As shown in FIG. 2B, in an suction process of the piston 20, the one end side of the suction valve 14c bends to the cylinder 11a side to open the refrigerant outlet 14b. In this case, the suction valve 14c has a maximum opening in a position where one end side (free end side) of the suction valve 14c is locked by the stopper 11b. In addition, a stopper plate 14e, which locks the discharge valve 14d, is provided in the center of the valve plate 14. The discharge valve 14d is openable to a position where the discharge valve 14d is locked by the stopper plate 14e. The piston 20 is housed in the cylinder 11a so as to slide freely so as to suck and discharge a refrigerant to one end face side thereof. In addition, a semispherical shoe 21, which is coupled with the drive unit 30 side, is attached to the other side of the piston 20 so as to slide freely. The drive unit 30 includes a drive shaft 31 that is rotated by power from the outside, an inclining plate 32 that is rotated by the drive shaft 31, and an inclination regulating member 33 that regulates an inclination angle of the inclining plate 32 within a predetermined range. The drive shaft 31 is supported by the first housing 11 and the second housing 12 on one end side and the other end side so as to rotate freely via roller bearings 34, and for example, power of an engine of a vehicle is transmitted to the other end side via a not-shown pulley. The inclining plate 32 is supported by the drive shaft 31 via an annular slide member 32a so as to move freely in an axial direction and attached to the slide member 32a via a support shaft 32b. Thus, an inclination angle of the inclining plate 32 with respect to an axial direction of the drive shaft 31 changes arbitrarily around the support shaft 32b. In addition, a peripheral end of the inclining plate 32 is fitted in the shoe 21 of the piston 20 so as to slide freely such that the piston 20 reciprocates according to the inclination angle of the inclining plate 32 when the inclining plate 32 rotates. The inclination regulating member 33 is provided so as to rotate together with the drive shaft 31. A pin 33a provided at one end of the inclination regulating member 33 is inserted in a slit 32c provided in the inclining plate 32. Thus, when the inclining plate 32 slides, the pin 33a moves in the slit 32c such that an inclination angle of the inclining plate 32 is regulated within a predetermined range according to a moving range of the pin 33a in the slit 32c. The opening regulating valve 40 is provided in the refrigerant suction channel 13c of the cylinder head 13 and includes an elastically deformable spiral member 41 fixed in the channel 13c at one end thereof. The spiral member 41 is formed such that diameters of spiral portions 41a gradually decrease from one end side to the other end side. Thus, when a flow rate of a refrigerant increases, intervals among the spiral portions 41a are widened by a flow resistance of the refrigerant. In the compressor constituted as described above, when the drive shaft 31 of the drive unit 30 is rotated by drive power from the outside, the inclining plate 32 rotates and the piston 20 reciprocates in the cylinder 11a according to an inclination angle of the inclining plate 32. In addition, a refrigerant in the refrigerant suction chamber 13b is sucked into the cylinder 11a and discharged to the refrigerant discharge chamber 13a according to the reciprocation of the piston 20. In that case, the inclination angle of the inclining plate 32 is changed according to a pressure applied to the other end side (housing 12 side) of the piston 20 due to a pressure difference, which is caused between the refrigerant suction chamber 13b and the second housing 12 by not-shown pressure control means, whereby a discharge amount of the piston 20 is controlled. When a flow rate is high, as shown in FIG. 2B, the suction valve 14c opens to a position where the suction valve 14c is locked by the stopper 11b and, as shown in FIG. 3B, the intervals among the spiral portions 41a of the opening regulating valve 40 are widened and an opening of the refrigerant suction channel 13c increases. In addition, when a flow rate is low, as shown in FIG. 3A, since the intervals among the spiral portions 41a of the opening regulating valve 40 are narrowed and the opening of the refrigerant suction channel 13c decreases. Thus, even in the case in which pulsation occurs in an suction refrigerant due to self-induced vibration of the suction valve 14c at the time of a low flow rate, the pulsation of the suction refrigerant propagating to the external circuit on the refrigerant suction channel 13c side is attenuated by the opening regulating valve 40, and vibration and noise of an evaporator (not shown) and the like arranged in the external circuit are reduced. In this way, according to the compressor of this embodiment, the opening regulating valve 40, which is provided in the refrigerant suction channel 13c to the cylinder 11a, is formed by the elastically deformable spiral member 41, and the intervals among the spiral portions 41a of the spiral member 41 are changed according to a flow rate of a refrigerant, whereby an opening of the channel 13c is regulated. Thus, it is possible to reduce occurrence of vibration and noise due to self-induced vibration of the suction valve 14c at the time of a low flow rate surely, simplify the structure of the opening regulating valve 40, and realize reduction in manufacturing cost. In this case, the spiral member 41 of the opening regulating valve 40 is formed such that the diameters of the spiral portions 41a gradually decrease from one end side to the other end side. Thus, the spiral member 41 assumes a conical shape that is susceptible a flow resistance of a refrigerant, and it is possible to perform opening and closing of the channel 13c surely. Note that, in this embodiment, the opening regulating valve 40 is provided in the refrigerant suction channel 13c communicating with the refrigerant suction chamber 13b. However, it is possible to obtain the same effect even in the case in which the opening regulating valve 40 is provided in a refrigerant discharge side channel communicating with the refrigerant discharge chamber 13a. FIGS. 4A and 4B show a second embodiment of the invention, and components equivalent to those in the above-described embodiment are denoted by the identical reference numerals and signs. In short, an opening regulating valve 50 shown in the figures has a spiral member 51, which is the same as that in the above-described embodiment, and is formed such that diameters of spiral portions 51a thereof gradually decrease from one end side toward the other end side. In addition, a blocking member 52, which blocks a part of the other end side of the spiral member 51, is attached to the other end side of the opening regulating valve 50. This blocking member 52 is formed in, for example, a size for blocking intervals among the spiral portions 51a by about one round trip and is held by the topmost spiral portion 51a. In the opening regulating valve 50 of this embodiment, as in the first embodiment, intervals among the spiral portions 51a of the spiral member 51 change according to a flow rate of a refrigerant, an opening of the channel 13c is regulated, and the refrigerant does not pass a part where the blocking member 52 is attached. Thus, a flow rate of the refrigerant is regulated so much more for that. Hereby, since a flow rate in the refrigerant suction channel 13c can be made appropriate by the blocking member 52, it is possible to realize improvement of compression efficiency. In this case, it is possible to regulate an suction amount of the refrigerant arbitrarily by forming the blocking member 52 in an arbitrary size. FIGS. 5A and 5B show a third embodiment of the invention, and components equivalent to those in the above-described embodiments are denoted by the identical reference numerals and signs. In short, an opening regulating valve 60 shown in the figures has an elastically deformable spiral member 61, and diameters of spiral portions 61a thereof are formed uniformly from one end side to the other end side. In addition, a blocking member 62, which blocks the other end side of the spiral member 61, is attached to the opening regulating valve 60. This blocking member 62 consists of a tabular member, and a hole 62a allowing a refrigerant to flow is provided in the center of the blocking member 62. In the opening regulating valve 60 of this embodiment, as in the first embodiment, intervals among the spiral portions 61a of the spiral member 61 change according to a flow rate of a refrigerant, an opening of the channel 13c is regulated, and the refrigerant does not pass a part where the blocking member 62 is attached. Thus, a flow rate of the refrigerant is regulated so much more for that. In other words, as in the second embodiment, since a flow rate in the refrigerant suction channel 13c can be made appropriate by the blocking member 62, it is possible to realize improvement of compression efficiency. In this case, it is possible to regulate an suction amount of the refrigerant by forming a hole 62a of the blocking member 62 in an arbitrary size. INDUSTRIAL APPLICABILITY As explained above, according to the invention, it is possible to reduce occurrence of vibration and noise due to self-induced vibration of an suction valve at the time of a low flow rate surely, and it is possible to simplify a structure of an opening regulating valve. Thus, it is possible to realize a reduction in manufacturing cost. In addition, according to the invention, since a spiral member of an opening regulating valve assumes a conical shape that is susceptible to a flow resistance f a refrigerant, it is possible to perform opening and closing of a refrigerant suction side channel surely. Further, according to the invention, since it is possible to regulate a flow rate of a refrigerant in an opening regulating valve such that a flow rate in a refrigerant suction side channel is made appropriate, it is possible to improve compression efficiency.
<SOH> BACKGROUND ART <EOH>In general, as a compressor of this type, for example, as described in Japanese Patent Publication 2001-289177, there is known a compressor that includes a cylinder having a refrigerant inlet and a refrigerant outlet at one end, a piston reciprocating in the cylinder, and a tabular suction valve and a tabular discharge valve provided in the refrigerant inlet and the refrigerant outlet, such that the refrigerant inlet and the refrigerant outlet are opened and closed by elastic deformation of the suction valve and the discharge valve, respectively. Incidentally, in the compressor, there is provided a stopper that locks the one end side (free end side) of the suction valve in a predetermined opening position such that the suction valve opens and closes within a predetermined range. However, when a flow rate is low, the suction valve may open and close in a range in which the suction valve does not come into abutment against the stopper. In such a case, there is a problem in that pulsation occurs in the suction refrigerant due to self-induced vibration of the suction valve, which causes vibration and noise in an evaporator and the like that are set in an external circuit on the refrigerant suction side. Thus, in the compressor, an opening regulating valve, which regulates an opening of a channel according to a flow rate of a refrigerant, is provided in a refrigerant suction side channel of a cylinder head to reduce the opening of the opening regulating valve when a flow rate is low, whereby pulsation of the suction refrigerant propagating to the evaporator side is attenuated to reduce the vibration and noise of the evaporator and the like. However, the opening regulating valve has a complicated structure in which a valve body is housed in an exclusive valve case and biased in a predetermined direction by a spring attached in the valve case. Thus, there is a problem in that manufacturing cost increases. The present invention has been devised in view of the problems, and it is an object of the invention to provide a compressor that can reduce occurrence of vibration and noise due to self-induced vibration of an suction valve at the time of a low flow rate surely with an inexpensive structure.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a side sectional view of a compressor representing a first embodiment of the invention; FIGS. 2A and 2B are main part side sectional views of the compressor; FIGS. 3A and 3B are side sectional views of an opening regulating valve; FIGS. 4A and 4B are side sectional views of an opening regulating valve representing a second embodiment of the invention; and FIGS. 5A and 5B are side sectional views of an opening regulating valve representing a third embodiment of the invention. detailed-description description="Detailed Description" end="lead"?
20041109
20080715
20051013
72369.0
0
KIM, TAE JUN
COMPRESSOR
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,806
ACCEPTED
N-acylaminoacetonitrile derivatives and their use for controlling parasites
The invention relates to compounds of the general formula in which R1, R2, R3, R4, R5, R6, W, X, A1, A2, a, b and c are as defined in the specification, and to any enantiomers thereof. The active ingredients have advantageous pesticidal properties. They are particularly suitable for controlling parasites in warm-blooded animals.
1. A compound of the formula A compound of formula I in which A1 and A2are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenylmethoxyimino; unsubstituted or mono- or polysubstituted phenylhydroxymethyl; unsubstituted or mono- or polysubstituted 1-phenyl-1-hydroxyethyl; unsubstituted or mono- or polysubstituted phenylchloromethyl; unsubstituted or mono- or polysubstituted phenylcyanomethyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; unsubstituted or mono- or polysubstituted phenylacetylenyl; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl, indazolyl or quinolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, C3-C6cycloalkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; R1 is hydrogen, C1-C6alkyl, halo-C1-C6alkyl, allyl or C1-C6alkoxymethyl; R2, R3, R4, R5 and R6 are either, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C1-C6alkyl, unsubstituted or mono- or polysubstituted C2-C6alkenyl, unsubstituted or mono- or polysubstituted C2-C6alkynyl, unsubstituted or mono- or polysubstituted C1-C6alkoxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C1-C6alkoxy and halo-C1-C6alkoxy; unsubstituted or mono- or polysubstituted C3-C6cycloalkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C6alkyl; or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino and di-C1-C6alkylamino; or R2 and R3 are jointly C2-C6alkylene; W is O, S, S(O)2 or N(R7); X is O, S or N(R7); R7 is hydrogen or C1-C6alkyl; a is 1,2, 3 or 4; b is 0, 1, 2, 3 or 4; and c is 0 or 1. 2. A compound of the formula I, in each case in the free form or in the salt form, according to claim l, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl. 3. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl. 4. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl, C1-C2alkoxycarbonyl, and unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C3-C4cycloalkyloxy, C3-C4cycloalkylamino, C3-C4cycloalkylthio, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl. 5. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl or oxadiazolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl. 6. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl or pyrrolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C5alkylthio, halo-C1-C5alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl. 7. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A3 is unsubstituted or mono- or polysubstituted thienyl or furanyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl. 8. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R1 is hydrogen, C1-C4alkyl, halo-C1-C4alkyl or C1-C4alkoxymethyl. 9. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R1 is hydrogen, C1-C2alkyl or halo-C1-C2alkyl. 10. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R1 is hydrogen or C1-C2alkyl. 11. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C4alkoxy; C3-C5cycloalkyl or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy and halo-C1-C4alkoxy. 12. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C2alkoxy; or C3-C5cycloalkyl. 13. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, C1-C2alkyl or C3-C5cycloalkyl. 14. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which W is O or S. 15. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which W is O. 16. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which X is O or S. 17. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which X is O. 18. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which a is 1, 2 or 3. 19. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which a is 1 or 2. 20. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which a is 1. 21. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which c is 0. 22. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy. C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl or oxadiazolyl, which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; R1 is hydrogen, C1-C4alkyl, halo-C1-C4alkyl or C1-C4alkoxymethyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C4alkoxy; C3-C5cycloalkyl or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy and halo-C1-C4alkoxy; W is O or S; X is O or S; a is 1, 2 or 3; b is 0, 1 or 2; and c is 0. 23. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl or pyrrolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C5alkylthio, halo-C1-C5alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; R1 is hydrogen, C1-C2alkyl or halo-C1-C2alkyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C2alkoxy; or C3-C5cycloalkyl; W and X are O; a is 1 or 2; b is 0 or 1; and c is 0. 24. A compound of the formula I, in each case in the free form or in the salt form, according to claim 1, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro cyano, C1-C2alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl, C1-C2alkoxycarbonyl and unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C3-C4cycloalkyloxy, C3-C4cycloalkylamino, C3-C4cycloalkylthio, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted thienyl or furanyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; R1 is hydrogen or C1-C2alkyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, C1-C2alkyl or C3-C5cycloalkyl; W and X are O; a is 1; and b and c are 0. 25. A compound of the formula I, in the free form or in the salt form, according to claim 1 with the name N-[2-cyano-1-(4,5-difluoro-2-thien-3-ylphenoxy)-2-propyl]-4-trifluoromethoxybenzamide. 26. A process for the preparation of a compound of the formula I, in each case in the free form or in the salt form, according to claim 1, which comprises a) for the preparation of a compound of the formula I in which c is 1, the reaction of a compound of the formula II which is known or can be prepared by analogy to relevant known compounds and in which R1, R2, R3, R4, R5, R6, W, X, A2, A3, a and b are as defined in the formula I and c is 1, with a compound of the formula III which is known or can be prepared by analogy to relevant known compounds and in which A1 is as defined in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, or b) for the preparation of a compound of the formula I in which c is 0, the reaction of a compound of the formula IV which is known or can be prepared by analogy to relevant known compounds and in which R1, R2, R3, R4, R5, R6, W, A2, a and b are as defined in the formula I and Q1 is a leaving group, with a compound of the formula III, which is known or can be prepared by analogy to relevant known compounds and in which A1 is as defined in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, and the reaction of the intermediate of formula V produced in this way with a compound of the formula VI Q2-A3 VI, which is known or can be prepared by analogy to relevant known compounds and in which A3 is as defined in the formula I and Q2 is a leaving group, if desired in the presence of a metal catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt. 27. A process for the preparation of a compound of the formula II, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula VII which is known or can be prepared by analogy to relevant known compounds and in which R2, R3, R4, R5, R6, W, X, A2, A3, a, b and c are as defined in the formula I, with an inorganic or organic cyanide and a compound of the formula R1—NH2, which is known or can be prepared by analogy to relevant known compounds and in which R1 is as defined in the formula I, and in each case, if desired, the conversion of a compound of the formula II obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula II, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula II obtainable according to the process to a salt or the conversion of a salt of a compound of the formula II obtainable according to the process to the free compound of the formula II or to another salt. 28. A process for the preparation of a compound of the formula IV, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula VIII which is known or can be prepared by analogy to relevant known compounds and in which R2, R3, R4, R5, R6, W, A2, A3, a and b are as defined in the formula I and Q1 is a leaving group, with an inorganic or organic cyanide and a compound of the formula R1 —NH2, which is known or can be prepared by analogy to relevant known compounds and in which R1 is as defined in the formula I, and in each case, if desired, the conversion of a compound of the formula IV obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula IV, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula IV obtainable according to the process to a salt or the conversion of a salt of a compound of the formula IV obtainable according to the process to the free compound of the formula IV or to another salt. 29. A composition for controlling parasites, which comprises, in addition to carriers and/or dispersants, at least one compound of the formula I according to claim 1 as active ingredient. 30-33. (canceled) 34. A method for controlling parasites comprising applying to said parasites or its habitat a parasiticidal effective amount of at least one compound of formula I of claim 1. 35. The method of claim 34 wherein said parasiticidal effective amount of said at least one compound of formula I of claim 1 is administered to an animal host of said parasite. 36. The method of claim 35 whereby said at least one compound of formula I of claim 1 is administered to said animal host topically, perorally, parenterally, or subcutaneously. 37. The method of claim 34 whereby said compound is in a formulation consisting of the group of pour-on, spot-on, tablet, chewie, powder, boli, capsules, suspension, emulsion, solution, injectable, water-additive, and food-additive. 38. The method of claim 34 wherein said parasites are endo-parasites. 39. The method of claim 38 wherein said endo-parasites are helminthes. 40. A method of treating an animal for parasites comprising administering to said animal in need of treatment thereof a parasiticidal effective amount of the composition of claim 29. 41. The method of claim 40 wherein said administration to said animal is topically, perorally, parenterally, or subcutaneously. 42. The method of claim 40 wherein said composition of claim 29 is in a formulation consisting of the group of pour-on, spot-on, tablet, chewie, powder, boli, capsules, suspension, emulsion, solution, injectable, water-additive, and food-additive. 43. The method of claim 40 wherein said parasites are endo-parasites. 44. The method of claim 43 wherein said endo-parasites are helminthes.
The present invention relates to novel amidoacetonitrile compounds of the formula in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, 2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenylmethoxyimino; unsubstituted or mono- or polysubstituted phenylhydroxymethyl; unsubstituted or mono- or polysubstituted 1-phenyl-1-hydroxyethyl; unsubstituted or mono- or polysubstituted phenylchloromethyl; unsubstituted or mono- or polysubstituted phenylcyanomethyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; unsubstituted or mono- or polysubstituted phenylacetylenyl; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsufonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl, indazolyl or quinolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyloxy, halo-C1-C6alkylsulfonyloxy, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C1-C6alkylamino, C3-C6cycloalkylamino, di-C1-C6alkylamino, C1-C6alkylsulfonylamino, halo-C1-C6alkylsulfonylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; R1 is hydrogen, C1-C6alkyl, halo-C1-C6alkyl allyl or C1-C6alkoxymethyl; R2, R3, R4, R5 and R6 are either, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C1-C6alkyl, unsubstituted or mono- or polysubstituted C2-C6alkenyl, unsubstituted or mono- or polysubstituted C2-C6alkynyl, unsubstituted or mono- or polysubstituted C1-C6alkoxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C1-C6alkoxy and halo-C1-C6alkoxy, unsubstituted or mono- or polysubstituted C3-C6cycloalkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C6alkyl; or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfinyl, halo-C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, halo C1-C6alkylsulfonyl, C1-C6alkylamino and di-C1-C6alkylamino; or R2 and R3 are jointly C2-C6alkylene; W is O, S, S(O)2 or N(R7); X is O, S or N(R7); R7 is hydrogen or C1-C6alkyl; a is 1, 2, 3 or 4; b is 0, 1, 2, 3 or 4; and c is 0 or 1; if desired to diastereoisomers, E/Z isomers, mixtures of E/Z isomers and/or tautomers, in each case in the free form or in the salt form, to their preparation and use in the control of endo- and ectoparasites, especially helminths, in and on warm-blooded animals, especially productive livestock and domestic animals, as well as on plants, and also to pesticides which comprise at least one of these compounds. Substituted amidoacetonitrile compounds with pesticidal action are disclosed in EP-0 953 565 A2, for example. The active ingredients specifically revealed therein may not, however, always meet the requirements concerning strength and activity spectrum. There consequently exists a need for active ingredients with improved pesticidal properties. It has now been found that the amidoacetonitrile compounds of the formula I have outstanding pesticidal properties, in particular against endo- and ectoparasites in and on warm-blooded animals and plants. Alkyl—as group per so and as structural component of other groups and compounds, for example of haloalkyl, alkoxy, alkylthio, alkylsulfinyl and alkylsulfonyl,—is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, either straight-chain, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl. Alkenyl—as group per se and as structural component of other groups and compounds—is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. allyl, 2-butenyl, 3-pentenyl, 1-hexenyl or 1,3-hexadienyl, or branched, e.g. isopropenyl, isobutenyl, isoprenyl, tert-pentenyl or isohexenyl. Alkynyl—as group per se and as structural component of other groups and compounds—is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. propargyl, 2-butynyl, 3-pentynyl, 1-hexynyl, 1-heptynyl or 3-hexen-1-ynyl, or branched, e.g. 3-methylbut-1-ynyl, 4-ethylpent-1-ynyl or 4-methylhex-2-ynyl. Cycloalkyl—as group per se and as structural component of other groups and compounds, for example of halocycloalkyl, cycloalkoxy or cycloalkylthio,—is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Aryl is phenyl or naphthyl. Hetaryl is pyridyl, pyridyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl, indazolyl or quinolyl. Halogen—as group per se and as structural component of other groups and compounds, such as of haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl,—is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine, especially fluorine or chlorine. Halogen-substituted carbon-comprising groups and compounds, such as haloalkyl, halo-alkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, can be partially halogenated or perhalogenated, it being possible, in the case of polyhalogenation, for the halogen substituents to be identical or different. Examples of haloalkyl—as group per se and as structural component of other groups and compounds, such as of haloalkoxy or haloalkylthio,—are methyl substituted up to three times by fluorine, chlorine and (or bromine, such as CHF2 or CF3; ethyl substituted up to five times by fluorine, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CCl3, CF2CHCl2, CF2CHF2, CF2CFCl2, CF2CHBr2, CF2CHClF, CF2CHBrF or CClFCHClF; propyl or isopropyl substituted up to seven times by fluorine, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CH2CF2CF3 or CH(CF3)2; butyl or one of its isomers substituted up to nine times by fluorine, chlorine and/or bromine, such as CF(CF3)CHFCF3 or CH2(CF2)2CF3; pentyl or one of its isomers substituted up to eleven times by fluorine, chlorine and/or bromine, such as CF(CF3)(CHF)2CF3 or CH2(CF2)3CF3; and hexyl or one of its isomers substituted up to thirteen times by fluorine, chlorine and/or bromine, such as (CH2)4CHBrCH2Br, CF2(CHF)4CF3, CH2(CF2)4CF3 or C(CF3)2(CHF)2CF3. Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms. For example, alkoxy is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, and also the pentyloxy and hexyloxy isomers; preferably methoxy and ethoxy. Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms. Haloalkoxy is, e.g., fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Preferred embodiments within the context of the invention are: (1) a compound of the formula I, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkyl sulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cyclo-alkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6alkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; particularly, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C6cycloalkyl, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; very particularly, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylcarbonyl halo-C1-C2alkylcarbonyl, C1-C2alkoxycarbonyl, and unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C3-C4cycloalkyloxy, C3-C4cycloalkylamino, C3-C4cycloalkylthio, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; (2) a compound of the formula I, in which A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl or oxadiazolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsufonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; particularly unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl or pyrrolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C5alkylthio, halo-C1-C5alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; very particularly unsubstituted or mono- or polysubstituted thienyl or furanyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; (3) a compound of the formula I, in which R1 is hydrogen, C1-C4alkyl, halo-C1-C4alkyl or C1-C4alkoxymethyl; particularly hydrogen, C1-C2alkyl or halo-C1-C2alkyl; very particularly hydrogen or C1-C2alkyl; (4) a compound of the formula I, in which R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C3-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C4alkoxy; C3-C5cycloalkyl or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy and halo-C1-C4alkoxy; particularly, independently of one another, hydrogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C2alkoxy; or C3-C5cycloalkyl; very particularly, independently of one another, hydrogen, C1-C2alkyl or C3-C5cycloalkyl; (5) a compound of the formula I, in which W is O or S; particularly O; (6) a compound of the formula I, in which X is O or S; particularly O; (7) a compound of the formula I, in which a is 1, 2 or 3; particularly 1 or 2; very particularly 1: (8) a compound of the formula I, in which b is 0, 1 or 2; particularly 0 or 1; very particularly 0; (9) a compound of the formula I, in which c is 0; (10) a compound of the formula I, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C2-C6alkenyloxy, halo-C2-C6alkenyloxy. C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino; unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy; and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy, C3-C6cycloalkylamino, C3-C6cycloalkylthio, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl and C1-C6alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl or oxadiazolyl, which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, halo-C1-C6alkoxy, C3-C6cycloalkyl, C1-C6alkylthio, halo-C1-C6alkylthio, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C1-C6alkylamino, di-C1-C6alkylamino, C1-C6alkylcarbonyl, halo-C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl and di-C1-C6alkylaminocarbonyl; R1 is hydrogen, C1-C4alkyl, halo-C1-C4alkyl or C1-C4alkoxymethyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, halogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C4alkoxy; C3-C5cycloalkyl or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy and halo-C1-C4alkoxy; W is O or S; X is O or S; a is 1, 2 or 3; b is 0, 1 or 2; and c is 0; (11) a compound of the formula I, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl; unsubstituted or mono- or polysubstituted phenoxy, and unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-C5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; or unsubstituted or mono- or polysubstituted hetaryl which is bonded via a ring carbon atom, in which the substituents of A1 and A2 can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, Ct-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C3-5cycloalkyloxy, C3-C5cycloalkylamino, C3-C5cycloalkylthio, C1-C4alkylthio, halo-C1-C4alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl or pyrrolyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C4alkyl, halo-C1-C4alkyl, C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cloalkyl, C1-C5alkylthio, halo-C1-C5alkylthio, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkylcarbonyl, halo-C1-C4alkylcarbonyl and C1-C4alkoxycarbonyl; R1 is hydrogen, C1-C2alkyl or halo-C1-C2alkyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, unsubstituted or mono- or polysubstituted C1-C4alkyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen and C1-C2alkoxy; or C3-C5cycloalkyl; W and X are O; a is 1 or 2; b is 0 or 1; and c is 0; (12) a compound of the formula I, in which A1 and A2 are, independently of one another, unsubstituted or mono- or polysubstituted aryl, in which the substituents of A1 and A2, independently of one another, are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C4alkyl. C1-C4alkoxy, halo-C1-C4alkoxy, C3-C5cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl, C1-C2alkoxycarbonyl and unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C3-C4cycloalkyloxy, C3-C4cycloalkylamino, C3-C4cycloalkylthio, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; A3 is unsubstituted or mono- or polysubstituted thienyl or furanyl which is bonded via a ring carbon atom, in which the substituents in each case, independently of one another, are chosen from the group consisting of halogen, cyano, C1-C2alkyl, halo-C1-C2alkyl, C1-C2alkoxy, halo-C1-C2alkoxy, C3-C4cycloalkyl, C1-C2alkylthio, halo-C1-C2alkylthio, C1-C2alkylamino, di-C1-C2alkylamino, C1-C2alkylcarbonyl, halo-C1-C2alkylcarbonyl and C1-C2alkoxycarbonyl; R1 is hydrogen or C1-C2alkyl; R2, R3, R4, R5 and R6 are, independently of one another, hydrogen, C1-C2alkyl or C3-C5cycloalkyl; W and X are O; a is 1; and b and c are 0. The compounds of the formula I listed in Table 1 are particularly preferred within the context of the invention and the compounds of the formula I mentioned in the synthetic examples are very particularly preferred. A further subject-matter of the invention is the process for the preparation of the compounds of the formula I, in each case in the free form or in the salt form, e.g. which comprises a) for the preparation of a compound of the formula I in which c is 1, the reaction of a compound of the formula which is known or can be prepared by analogy to relevant known compounds and in which R1, R2, R3, R4, R5, R6, W, X, A2, A3, a and b are as defined in the formula I and c is 1, with a compound of the formula which is known or can be prepared by analogy to relevant known compounds and in which A1 is as defined in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, or b) for the preparation of a compound of the formula I in which c is 0, the reaction of a compound of the formula which is known or can be prepared by analogy to relevant known compounds and in which R1, R2, R3, R4, R5, R6, W, A2, a and b are as defined in the formula I and Q1 is a leaving group, with a compound of the formula III, which is known or can be prepared by analogy to relevant known compounds and in which A1 is as defined in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, and the reaction of the intermediate produced in this way with a compound of the formula Q2-A3 VI which is known or can be prepared by analogy to relevant known compounds and in which A3 is as defined in the formula I and O2 is a leaving group, if desired in the presence of a metal catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt. That which has been said above for salts of compounds I applies analogously to starting materials mentioned hereinabove and hereinafter with regard to the salts thereof. The reactants can be reacted with one another as such, i.e. without addition of a solvent or diluent, e.g. in the molten form. For the most part, however, it is advantageous to add an inert solvent or diluent or a mixture thereof. Mention may be made, as examples of such solvents or diluents, of: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachloroethene; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydrofuran or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; amides, such as N,N-dimethylformamide, N,N-diethylformamide, N,N-methylacetamide, N-methylpyrrolidone or hexamethylphosphoramide; nitriles, such as acetonitrile or propionitrile; and sulfoxides, such as dimethyl sulfoxide. Preferred leaving groups Q are halogens, tosylates, mesylates and triflates, particularly preferably halogens, especially chlorine. Preferred leaving groups Q1 are halogens, especially bromine. Preferred leaving groups Q2 are boric adds. Suitable bases for facilitating the reaction are, e.g., alkali metal or alkaline earth metal hydroxides, hydrides, amides, alkoxides, acetates, carbonates, dialkylamides or alkylsilylamides, alkylamines, alkylenediamines, if desired N-alkylated and saturated or unsaturated, cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Mention may be made, by way of examples, of sodium hydroxide, sodium hydride, sodamide, sodium methoxide, sodium acetate, sodium carbonate, potassium t-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1,5-diazabicyclo[5.4.0]undec 5-ene (DBU). Diisopropylethylamine and 4-(N,N-dimethylamino)pyridine are preferred. Preferred metal catalysts are palladium complexes, particularly preferably tetrakis(triphenylphosphine)palladium. The reaction is advantageously carried out at a temperature from approximately 0° C., to approximately +100° C., preferably from approximately 10° C. to approximately +40° C. A further subject-matter of the invention is the process for the preparation of the compounds of the formulae II and IV, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula which are known or can be prepared by analogy to relevant known compounds and in which R2, R3, R4, R5, R6, W, X, A2, A3, a, b and c are as defined in the formula I and Q1 is a leaving group, with an inorganic or organic cyanide and a compound of the formula R1—NH2, which is known or can be prepared by analogy to relevant known compounds and in which R1 is as defined in the formula I, and in each case, if desired, the conversion of a compound of the formula II, respectively IV, obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula II, respectively IV, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula II, respectively IV, obtainable according to the process to a salt or the conversion of a salt of a compound of the formula II, respectively IV, obtainable according to the process to the free compound of the formula II, respectively IV, or to another salt. Suitable cyanides are sodium cyanide, potassium cyanide, trimethylsilyl cyanide and acetone cyanohydrin. The general method for the reaction of carbonyl compounds, for example of the formula IV, with cyanides and amines, for example of the formula R6—NH2, is known as a Strecker reaction, for example in Organic Synthesis Coll. Vol. 3, 88 (1973). Salts of compounds I can be prepared in a way known per se. Thus, for example, acid addition salts of compound I are obtained by treatment with a suitable acid or a suitable ion-exchange reagent and salts with bases are obtained by treatment with a suitable base or a suitable ion-exchange reagent. Salts of compounds I can be converted in the usual way to the free compounds I, acid addition salts, e.g. by treatment with a suitable basic agent or a suitable ion exchange reagent, and salts with bases, e.g. by treatment with a suitable acid or a suitable ion-exchange reagent. Salts of compounds I can be converted in a way known per se to other salts of compounds I, acid addition salts for example to other acid addition salts, e.g. by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, e.g. with silver acetate, in a suitable solvent, in which an inorganic salt, e.g. silver chloride, being formed is insoluble and for this reason precipitates from the reaction mixture. According to the method or reaction conditions, the compounds I with salt-forming properties can be obtained in the free form or in the form of salts. The compounds I can also be obtained in the form of their hydrates and/or can incorporate other solvents, which might, for example, be used in the crystallization of compounds existing in the solid form. The compounds I can exist if desired as optical and/or geometrical isomers or mixtures thereof. The invention relates both to the pure isomers and to all possible mixtures of isomers and is to be correspondingly understood in each case heretofore and hereinafter, even if stereochemical details are not specifically referred to in every case. Mixtures of diastereoisomers of compounds I obtainable according to the process or otherwise obtainable can be separated in a known way into the pure diastereoisomers on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography. Correspondingly obtainable mixtures of enantiomers can be resolved into the pure isomers by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, e.g. high performance liquid chromatography (HPLC) on acetylcellulose, with the help of suitable microorganisms, by cleavage with specific immobilized enzymes, via the formation of inclusion complexes, e.g. by using chiral crown ethers, in which only one enantiomer is complexed. In addition to through separation of the corresponding mixtures of isomers, pure diastereoisomers or enantiomers according to the invention can also be obtained through generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the invention with educts with correspondingly suitable stereochemistry. Advantageously, the biologically most effective isomer, e.g. enantiomer, is isolated or synthesized each time, provided that the individual components have different biological activity. In the process of the present invention, use is preferably made of such starting materials and intermediates which result in the compounds I described at the beginning as particularly valuable. The invention relates in particular to the preparation process described in the examples. Starting materials and intermediates used according to the invention for the preparation of the compounds I which are novel, their use and processes for their preparation likewise form a subject-matter of the invention. The compounds I according to the invention are characterized by a particularly broad activity spectrum and are valuable active ingredients in the field of pest control which are well tolerated by warm-blooded species, fish and plants, including for the control of endo- and ectoparasites, especially helminths, in and on warm-blooded animals, especially productive livestock and domestic animals, as well as on plants. In the context of the present invention, the term “ectoparasites” is understood to mean, in particular, insects, mites and ticks. This includes insects of the orders: Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, reference may in particular be made to ectoparasites which are a nuisance to man or animals and which transmit pathogens, for example flies, such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga camaria, Lucilia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia irritans, and mosquitoes (Nematocera), such as Culicidae, Simuliidae, Psychodidae, but also bloodsucking parasites, for example fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsyila cheopis, Pulex irritans, Dermatophilus penetrans, lice, such as Damalina ovis, Pediculus humanis, stable flies and horseflies (Tabanidae), Haematopota spp., such as Haematopota pluvialis, Tabanidea spp., such as Tabanus nigrovittatus, Chrysopsinae spp., such as Chrysops caecutiens, tsetse flies, such as Glossinia species, biting insects, in particular cockroaches, such as Blatella germanica, Blatta orientalls, Periplaneta americana, mites, such as Dermanyssus gallinae, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp., and last but not least ticks. The latter belong to the order Acarina. Known representatives of ticks are, e.g., Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Omithodoros and the like, which preferably infest warm-blooded animals, including farm animals, such as cows, pigs, sheep and goats, poultry, such as chickens, turkeys and geese, fur-bearing animals, such as mink, foxes, chinchillas, rabbits and the like, and pets, such as cats and dogs, but also man. The compounds I according to the invention are also effective against all or individual development stages of normally sensitive but also of resistant animal pests, such as insects and representatives of the order Acarina. The insecticidal, ovicidal and/or acaricidal action of the active ingredients according to the invention may in the process be displayed directly, i.e. in killing the pests, immediately or only after some time, for example during moulting, or their eggs, or indirectly, e.g. in reduced egg laying and/or in a reduced hatching rate, in which the good action corresponds to a kill rate (mortality) of at least 50 to 60%. The compounds I can also be used against hygiene pests, in particular of the order Diptera with the families Sarcophagidae, Anophilidae and Cullidae; of the orders Orthoptera, Dictyoptera (e.g. the family Blattidae) and Hymenoptera(e.g. the family Formicidae). The compounds I also have lasting activity in the case of phytoparasitic mites and insects. In the case of spider mites of the order Acarina, they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.). They are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera, Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders Lepidoptera, Coleoptera, Diptera and Orthoptera. They are also suitable as soil insecticides against pests in the soil. The compounds of the formula I are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others. The compounds of the formula I are also active against plant nematodes of the genera Meloldogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus, Rizoglyphus and others. The compounds are particularly active against helminths, among which the endoparasitic nematodes and trematodes can be the cause of serious diseases in mammals and poultry. e.g. in sheep, pigs, goats, cattle, horses, donkeys, dogs, cats, guinea pigs and ornament birds. Typical nematodes of this indication are: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capiliaria, Heterakis, Toxocara, Ascaridla, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Mention may specifically be made, among the trematodes, of the family of the Fasciolideae, in particular Fasciola hepatica. It could also be shown, surprisingly and unexpectedly, that the compounds of the formula I have extraordinarily high activity against nematodes, which are resistant to many active substances. This can be demonstrated in vitro through the LDA test and in vivo, for example, in Mongolian gerbils and sheep. It could be shown that amounts of active substance which kill sensitive strains of Haemonchus contortus or Trichostrongylus colubriformis are also sufficiently active to control corresponding strains which are resistant to benzimidazoles, levamisole and macrocyclic lactones (such as, for example, ivermectin). Certain species of the genera Nematodirus, Cooperia and Oesophagostonum attack the intestinal tract of the host animal, while others of the genera Haemonchus and Ostertagia parasitize in the stomach and others of the genus Dictyocaulus parasitize in lung tissue. Parasites of the families Filariidae and Setariidae are found in internal cell tissue and in organs, e.g. the heart, blood vessels, lymph vessels and subcutaneous tissue. Mention may particularly be made here of the dog heartworm, Dirofilaria immitis. The compounds of the formula I are highly effective against these parasites. The pests which can be controlled with the compounds of the formula I also include, from the class Cestoda (tapeworms), the families Mesocestoidae, in particular the genus Mesocestoides, especially M. lineatus; Dilepididae, in particular Dipylidium caninum, Joyeuxiella spp., especially Joyeuxiella pasquali, and Diplopylidium spp.; and Taeniidae, in particular Taenia pisiformis, Taenia cervi, Taenia ovis, Taenia hydatigena, Taenia multiceps, Taenia taeniaeformis, Taenia serialis and Echinococcus spp., particularly preferably Taenia hydatigena, Taenia ovis, Taenia multiceps, Taenia serialis; Echinococcus granulosus and Echinococcus granulosus and Echinococcus multilocularis, and Multiceps multiceps. In a very particularly preferred way, Taenia hydatigena, T. pisformis, T. ovis, T. taeniae-formis, Multiceps multiceps, Joyeuxiella pasquali, Dipylidium caninum, Mesocestoides spp., Echinococcus granulosus and E. multilocularis are controlled simultaneously with Dirofilaria immitis, Ancylostoma spp., Toxocara spp. and/or Trichuris vulpis on or in dogs and cats. Also in a preferred way, Ctenocephalides fells and/or C. canis are controlled simultaneously with the abovementioned nematodes and cestodes. The compounds of the formula I are also suitable for controlling parasites which are pathogenic to man, among which may be mentioned, as typical representatives occurring in the digestive tract, those of the genera Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius. The compounds of the present invention are also active against parasites of the genera Wuchereria, Brugia, Onchocerca and Loa from the family of the Filariidae, which occur in the blood, in tissue and in various organs, and also against Dracunculus and parasites of the genera Strongyloides and Trichinella, which specifically infect the gastrointestinal tract. In addition, the compounds of the formula I are also active against harmful fungi which cause disease in plants and in man and animals. The good pesticidal action of the compounds of the formula I according to the invention corresponds to a kill rate (mortality) of at least 50-60% of the pests mentioned. In particular, the compounds of the formula I are characterized by an extraordinarily long duration of action. The compounds of the formula I are used as such or preferably together with the auxiliaries conventional in formulation technology and can accordingly be processed in a known way, for example to emulsifiable concentrates, directly dilutable solutions, dilute emulsions, soluble powders, granules and also encapsulations in polymer substances. The application methods as well as the compositions are chosen in accordance with the intended aims and the prevailing circumstances. The formulation, i.e. the compositions, preparations or combinations comprising the active ingredient of the formula I, or combinations of these active ingredients with other active ingredients, and, if desired, a solid or liquid additive, is prepared in a known way, for example by intimately mixing and/or grinding the active ingredients with extenders, for example with solvents, solid carriers and, if desired, surface-active compounds (surfactants). The following are possible as solvents: alcohols, such as ethanol, propanol or butanol, and glycols, and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, isophorone or diacetone alcohol, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide or water, vegetable oils, such as rapeseed oil, castor oil, coconut oil or soybean oil; and, if desired, silicone oils. Preferred application forms for use in warm-blooded animals for controlling helminths include solutions, emulsions, suspensions (drenches), feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and pour-on formulations, care having to be taken over the physiological compatibility of the formulation auxiliaries. Suitable binders for tablets and boluses are chemically modified polymeric natural products which are soluble in water or alcohol, such as starch, cellulose or protein derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxyethylcellulose, proteins, such as zein, gelatin, and the like), and synthetic polymers, for example polyvinyl alcohol, polyvinylpyrrolidone, and the like. Tablets also comprise fillers (e.g., starch, microcrystalline cellulose, sugar, lactose, and the like), lubricants and disintegrating agents. If the anthelmintic compositions are present in the form of feed concentrates, then high-performance feed, feed cereals or protein concentrates, for example, are used as carriers. Such feed concentrates or compositions can, in addition to the active ingredients, also comprise additives, vitamins, antibiotics, chemotherapeutics, or other pesticides, mainly bacteriostats, fungistats, coccidiostats, or also hormone preparations, anabolics or substances which promote growth, influence the quality of meat from animals for slaughter or are useful to the organism in another way. If the compositions or the active ingredients of the formula I present therein are added directly to the feed or to the drinking water for the animals, the finished feed or the finished drinking water comprises the active ingredients preferably in a concentration from approximately 0.0005 to 0.02% by weight (5-200 ppm). The compounds of the formula I according to the invention can be used alone or in combination with other biocides. They can, e.g., be combined with pesticides possessing the same direction of action, in order to enhance the action, or can be combined with substances possessing another direction of action, in order to broaden the activity spectrum. It may also make sense to add substances which repel, known as repellents. If it is desired to expand the activity spectrum with regard to endoparasites, for example worms, the compounds of the formula I are appropriately combined with substances having endoparasiticidal properties. They can also, naturally, be used in combination with antibacterial compositions. Since the compounds of the formula I represent adulticides, i.e. since they are effective in particular against the adult stages of the target parasites, the addition of pesticides which are more likely to attack the Juvenile stages of parasites can be highly advantageous. In this way, most of those parasites causing great economic damage are namely included. In addition, a substantial contribution is also made as well to avoiding the formation of resistance. Some combinations can also lead to synergistic effects, i.e. that the total amount of active substance consumed can be reduced, which is desirable from an ecological viewpoint Preferred groups of combination participants and particularly preferred combination participants are mentioned subsequently, which combinations can, in addition to a compound of the formula I, comprise one or more of these participants. Suitable participants in the mixture include biocides, for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellents or detachers. Nonlimiting examples of suitable insecticides and acaricides are: 1. Abamectin 2. AC 303 630 3. Acephate 4. Acrinathrin 5. Alanycarb 6. Aldicarb 7. α-Cypermethrin 8. Alphamethrin 9. Amitraz 10. Avermectin B1 11. AZ 60541 12. Azinphos E 13. Azinphos M 14. Azocyclotin 15. Bacillus subtil. toxin 16. Bendiocarb 17. Benfuracarb 18. Bensultap 19. β-Cyfluthrin 20. Bifenthrin 21. BPMC 22. Brofenprox 23. Bromophos E 24. Bufencarb 25. Buprofezin 26. Butocarboxim 27. Butylpyridaben 28. Cadusafos 29. Carbaryl 30. Carbofuran 31. Carbophenothion 32. Cartap 33. Cloethocarb 34. Chlorethoxyfos 35. Chlorfenapyr 36. Chlorfluazuron 37. Chlormephos 38. Chlorpyrifos 39. Cis-Resmethrin 40. Clocythrin 41. Clofentezine 42. Cyanophos 43. Cycloprothrin 44. Cyfluthrin 45. Cyhexatin 46. D 2341 47. Deltamethrin 48. Demeton M 49. Demeton S 50. Demeton-S-methyl 51. Dichlofenthion 52. Dicliphos 53. Diethion 54. Diflubenzuron 55. Dimethoate 56. Dimethylvinphos 57. Dioxathion 58. DPX-MP062 59. Edifenphos 60. Emamectin 61. Endosulfan 62. Esfenvalerate 63. Ethiofencarb 64. Ethion 65. Ethofenprox 66. Ethoprophos 67. Etrimfos 68. Fenamiphos 69. Fenazaquin 70. Fenbutatin oxide 71. Fenitrothion 72. Fenobucarb 73. Fenothiocarb 74. Fenoxycarb 75. Fenpropathrin 76. Fenpyrad 77. Fenpyroximate 78. Fenthion 79. Fenvalerate 80. Fipronil 81. Fluazinam 82. Fluazuron 83. Flucycloxuron 84. Flucythrinate 85. Flufenoxuron 86. Flufenprox 87. Fonofos 88. Formothion 89. Fosthiazate 90. Fubfenprox 91. HCH 92. Heptenophos 93. Hexaflumuron 94. Hexythiazox 95. Hydroprene 96. Imidacloprid 97. Insect-active fungi 98. Insect-active nematodes 99. Insect-active viruses 100. Iprobenfos 101. Isofenphos 102. Isoprocarb 103. Isoxathion 104. Ivermectin 105. λ-Cyhalothrin 106. Lufenuron 107. Malathion 108. Mecarbam 109. Mesulfenfos 110. Metaldehyde 111. Methamidophos 112. Methiocarb 113. Methomyl 114. Methoprene 115. Metolcarb 116. Mevinphos 117. Milbemectin 118. Moxidectin 119. Naled 120. NC 184 121. NI-25, Acetamiprid 122. Nitenpyram 123. Omethoate 124. Oxamyl 125. Oxydemeton M 126. Oxydeprofos 127. Parathion 128. Parathion-methyl 129. Permethrin 130. Phenthoate 131. Phorate 132. Phosalone 133. Phosmet 134. Phoxim 135. Pirimicarb 136. Pirimiphos E 137. Pirimiphos M 138. Promecarb 139. Propaphos 140. Propoxur 141. Prothiofos 142. Prothoate 143. Pyrachlofos 144. Pyradaphenthion 145. Pyresmethrin 146. Pyrethrum 147. Pyridaben 148. Pyrimidifen 149. Pyriproxyfen 150. RH-5992 151. RH-2485 152. Salithion 153. Sebufos 154. Silafluofen 155. Spinosad 156. Sulfotep 157. Sulprofos 158. Tebufenozide 159. Tebufenpyrad 160. Tebupirimfos 161. Teflubenzuron 162. Tefluthrin 163. Temephos 164. Terbam 165. Terbufos 166. Tetrachlorvinphos 167. Thiafenox 168. Thiodicarb 169. Thiofanox 170. Thionazin 171. Thuringiensin 172. Tralomethrin 173. Triarathene 174. Triazamate 175. Triazophos 176. Triazuron 177. Trichlorfon 178. Triflumuron 179. Trimethacarb 180. Vamidothion 181. XMC (3,5-xylyl methylcarbamate) 182. Xylylcarb 183. Yl 5301/5302 184. ζ-Cypermethrin 185. Zetamethrin Nonlimiting examples of suitable anthelmintics are mentioned subsequently, in which some representatives, in addition to the anthelmintic activity, also have an insecticidal and acaricidal activity and are already included in the above list: (A1) Praziquantel=2-Cyclohexylcarbonyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-α]isoquinoline (A2) Closantel=3,5-Diiodo-N-[5-chloro-2-methyl-4-(α-cyano-4-chlorobenzyl)phenyl]-salicylamide (A3) Triclabendazole=5-Chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole (A4) Levamisole=L-(−)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole (A5) Mebendazole=Methyl 5-benzoyl-1H benzimidazol-2-ylcarbamate (A6) Omphalotin=a macrocyclic fermentation product from the fungus Omphalotus olearius disclosed in WO 97/20857 (A7) Abamectin=Avermectin B1 (A8) Ivermectin=22,23-Dihydroavermectin B1 (A9) Moxidectin=5-O-Demethyl-28-deoxy 25-(1,3-dimethyl-1-butenyl)-6,28-epoxy-23 (methoxyimino)milbemycin B (A10) Doramectin=25-Cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)avermectin Ala (A11) Milbemectin=Mixture of Milbemycin A3 and Milbemycin A4 (A12) Milbemycin oxime=5-Oxime of Mibemectin Nonlimiting examples of suitable repelling substances (repellents or detachers) are: (R1) DEET (N,N-Diethyl-m-toluamide) (R2) KBR 3023 N-Butyl-2-oxycarbonyl-2-(2-hydroxyethyl)piperidine (R3) Cymiazole=N-2,3-Dihydro-3-methyl-1,3-thiazol-2-ylidene-2,4-xylidine The participants in the mixture which are mentioned are very well known to a person skilled in the art Most are described in the various editions of The Pesticide Manual, The British Crop Protection Council, London, others in the various editions of The Merck Index, Merck & Co. Inc., Rahway, N.J., USA, or in the patent literature. The following listing is accordingly restricted to a few references by way of examples. (I) 2-Methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime (Aldicarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 26; (II) S-(3,4-Dihydro-4-oxobenzo[d][1,2,3]triazin-3-ylmethyl) O,O-dimethyl phosphorodithioate (Azinphos-methyl), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 67; (III) Ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]N-isopropyl-β-alaninate (Benfuracarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 96; (IV) 2-Methylbiphenyl-3-ylmethyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate (Bifenthrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 118; (V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-4-one (Buprofezin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 157; (VI) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (Carbofuran), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 186; (VII) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl(dibutylamlnothio)methylcarbamate (Carbosulfan), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 188; (VIII) S,S-(2-Dimethylaminotrimethylene)bis(thiocarbamate) (Cartap), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 193; (IX) 1-[3,5-Dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-difluorobenzoyl)urea (Chlorfluazuron), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 213; (X) O,O-Diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate (Chlorpyrifos), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 235; (XI) (RS)-α-Cyano-4-fluoro-3-phenoxybenzyl(1RS,3RS;1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Cyfluthrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 293; (XII) Mixture of (S)-α-cyano-3-phenoxybenzyl (Z)-(1R,3R)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate and (R)-α-cyano-3-phenoxybenzyl (Z)-(1S,3S)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (Lambda-Cyhalothrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 300; (XIII) Racemate consisting of (S)-α-cyano-3-phenoxybenzyl(1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and (R)-α-cyano-3-phenoxybenzyl(1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Alpha-cypermethrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 308; (XIV) A mixture of the stereoisomers of (S)-α-cyano-3-phenoxybenzyl(1RS,3RS,1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-Cypermethrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 314; (XV) (S)-α-Cyano-3-phenoxybenzyl(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (Deltamethrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 344; (XVI) 1-(4-Chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 395; (XVII) (1,4,5,6,7,7-Hexachloro-8,9,10-trinorborn-5-en-2,3-ylenebismethylene)sulfite (Endosulfan), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 459; (XVIII) α-Ethylthio-o-tolyl methylcarbamate (Ethiofencarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 479; (XIX) O,O-Dimethyl O-4-nitro-m-tolyl phosphorothioate (Fenitrothion), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 514; (XX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 516; (XXI) (RS)-α-Cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalerate), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 539; (XXII) S-[Formyl(methyl)carbamoylmethyl]O,O dimethyl phosphorodithioate (Formothion), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 625; (XXIII) 4-Methylthio-3,5-xylyl methylcarbamate (Methiocarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 813; (XXIV) 7-Chlorobicyclo[3.2.0]hepta-2,6-yl dimethyl phosphate (Heptenophos), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 670; (XXV) 1-(6-Chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine (Imidacloprid), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 706; (XXVI) 2-Isopropylphenyl methylcarbamate (Isoprocarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 729; (XXVII) O,S-Dimethyl phosphoramidothioate (Methamidophos), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 808; (XXVIII) S-Methyl N-(methylcarbamoyloxy)thioacetimidate (Methomyl), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 815; (XXIX) Methyl 3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 844; (XXX) O,O-Diethyl O-4-nitrophenyl phosphorothioate (Parathion), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 926; (XXXI) O,O-Dimethyl O-4-nitrophenyl phosphorothioate (Parathion-methyl), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 928; (XXXII) S-6-Chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl O,O-diethyl phosphorodithloate (Phosalone), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 963; (XXXIII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl dimethylcarbamate (Pirimicarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 985; (XXXIV) 2-Isopropoxyphenyl methylcarbamate (Propoxur), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1036; (XXXV) 1-(3,5-Dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea (Teflubenzuron), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1158; (XXXVI) S-tert-Butylthlomethyl O,O-diethyl phosphorodithloate (Terbufos), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1165; (XXXVII) Ethyl(3-tert-butyl-1-dimethylcarbamoyl-1H-1,2,4-triazol-5-ylthio)acetate (Triazamate), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1224; (XXXVIII) Abamectin, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 3; (XXXIX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 516; (XL) N-tert-Butyl-N-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (Tebufenozide), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1147; (XLI) (±)-5-Amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole-3-carbonitrile (Fipronil), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 545; (XLII) (RS)-α-Cyano-4-fluoro-3-phenoxybenzyl(1RS,3RS;1RS,3SR-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (beta-Cyfluthrin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 295; (XLIII) (4-Ethoxyphenyl)[(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (Silafluofen), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1105; (XLIV) tert-Butyl (E)-α-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate (Fenpyroximate), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 530; (XLV) 2-tert-Butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one (Pyridaben), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1161; (XLVI) 4-[[4-(1,1-Dimethylethyl)phenyl]ethoxy]quinazoline (Fenazaquin), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 507; (XLVII) 4-Phenoxyphenyl (RS)-2-(2-pyridyloxy)propyl ether (Pyriproxyfen), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1073; (XLVIII) 5-Chloro-N-(2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl)-6-ethylpyrimidin-4-amine (Pyrimidifen), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1070; (XLIX) (E)-N-(6-Chloro-3-pyridylmethyl)-Methyl-N-methyl-2-nitrovinylidenediamine (Nitenpyram), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 880; (L) (E)-N1-[(6-Chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine (NI-25, Acetamiprid), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 9; (LI) Avermectin B1, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 3; (LII) An insect-active extract from a plant, in particular (2R,6aS,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furo[2,3-h]chromen-6-one (Rotenone), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1097; and an extract from Azadirachta indica, in particular azadirachtin, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 59; (LIII) A preparation comprising insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 671; Steinernema feltiae, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1115, and Steinernema scapterisci, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1116; (LIV) A preparation obtainable from Bacillus subtilis, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 72; or from a Bacillus thuringiensis strain except for compounds isolated from GC91 or from NCTC11821; The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 73; (LV) A preparation comprising insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 83; (LVI) A preparation comprising insect-active viruses, preferably Neodipridon Sertifer NPV, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonelia granulosis virus, from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 291; (CLXXXI) Methyl 7-chloro-2,3,4a,5-tetrahydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)carbamoyl]indol[1,2-e]oxazoline 4a-carboxylate (DPX-MP 062, indoxacarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 453; (CLXXXII) N′-tert-Butyl-N′-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH-2485, Methoxyfenozide), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 1094; (CLXXXIII) Isopropyl N′-[4-methoxybiphenyl-3-yl]hydrazinecarboxylate (D 2341), from Brighton Crop Protection Conference, 1996, 487493; and (R2) Book of Abstracts, 212th ACS National Meeting, Orlando, Fla., Aug. 25-29 (1996), AGRO-020. Publisher American Chemical Society, Washington, D.C. CONEN: 63BFAF. According to what has been said above, a further essential aspect of the present invention relates to combination preparations for the control of parasites in warm-blooded animals, which comprise, in addition to a compound of the formula I, at least one further active ingredient with an identical or different direction of action and at least one physiologically compatible carrier. The present invention is not restricted to combinations of two. The anthelmintic compositions according to the invention generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of active ingredient of the formula I or mixtures thereof, and 99.9 to 1% by weight, in particular 99.8 to 5% by weight, of a solid or liquid additive, including 0 to 25% by weight, in particular 0.1 to 25% by weight, of a surfactant. The compositions according to the invention can be applied topically, perorally, parenterally or subcutaneously to the animals to be treated, the compositions being present in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses, capsules and as pour-on formulations. The pour-on or spot-on method consists in applying the compound of the formula I to a locally restricted part of the skin or fur, advantageously on the neck or back of the animal. This is carried out, e.g., by applying a spot or dash of the pourn-on or spot-on formulation to a relatively small area of the fur, from where the active substance spreads out virtually unaided over wide regions of the fur because of the spreading components of the formulation and supported by the movements of the animal. It is advantageous for pour-on or spot-on formulations to comprise carriers which promote speedy distribution on the surface of the skin or in the fur of the host animal and which are generally described as spreading oils. Suitable carriers are, e.g., oily solutions; alcoholic and isopropanolic solutions, for example solutions of 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxal ester, oleyl oleate, decyl oleate, hexyl laurate, capric acid esters of saturated fatty alcohols with a chain length of C12-C18; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate or di(n-butyl) adipate, or also solutions of esters of aliphatic acids, e.g. glycols. It can be advantageous if a dispersant known from the pharmaceutical or cosmetics industry is additionally present. Examples are 2-pyrrolidone, 2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and ethers and esters thereof, propylene glycol or synthetic triglycerides. The oily solutions include, e.g., vegetable oils, such as olive oil, groundnut oil, sesame oil, pine oil, linseed oil or castor oil. The vegetable oils can also be present in epoxidized form. Paraffin oils and silicone oils can also be used. In general, a pour-on or spot-on formulation comprises 1 to 20% by weight of a compound of the formula I, 0.1 to 50% by weight of dispersant and 45 to 98.9% by weight of solvent. The pour-on or spot-on method can be used particularly advantageously with gregarious animals, such as cattle, horses, sheep or pigs, where it is difficult or time-consuming to treat all the animals orally or via injection. Because of its simplicity, this method can naturally also be used with all other animals, including individual domestic animals or pets, and is very popular with animal owners because it can often be implemented without the expert assistance of a veterinary surgeon. While concentrated compositions are more preferred as commercially available products, the end user generally uses dilute compositions. Such compositions can comprise yet further additives, such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects. Such anthelmintic compositions used by the end user likewise form part of the present invention. In each of the methods according to the invention for controlling pests or of the pesticides according to the invention, the active ingredients of the formula I can be used in all their steric configurations or mixtures thereof. The invention also includes a method for the prophylactic protection of warm-blooded animals, in particular of productive livestock, domestic animals and pets, against parasitic helminths, which comprises applying the active ingredients of the formula I or the active ingredient formulations prepared therefrom as a feed additive or drinking water additive or also in the solid or liquid form, orally, by injection or parenterally, to the animals. The invention also includes the compounds of the formula I according to the invention for use in one of the methods mentioned. The following examples serve merely to illustrate the invention, without limiting it, the term “active ingredient” representing a substance listed in Table 1. Preferred formulations are in particular composed in the following way: (%=percent by weight) FORMULATION EXAMPLES 1. Granules a) b) Active ingredient 5% 10% Kaolin 94% — Highly dispersed silica 1% — Attapulgite — 90% The active ingredient is dissolved in methylene chloride and sprayed onto the carrier, and the solvent is subsequently evaporated under reduced pressure. Such granules can be added to the animal feed. 2. Granules Active Ingredient 3% Polyethylene glycol (MW 200) 3% Kaolin 94% (MW = molecular weight) The finely milled active ingredient is applied evenly in a mixer to the kaolin, which has been moistened with polyethylene glycol. In this way, dust-free coated granules are obtained. 3. Tablets or Boluses I Active ingredient 33.00% Methylcellulose 0.80% Highly dispersed silica 0.80% Maize starch 8.40% II Cryst. lactose 22.50% Maize starch 17.00% Microcryst. cellulose 16.50% Magnesium stearate 1.00% I Methylcellulose is stirred into water. After the material has swollen, silica is stirred in and the mixture is homogeneously suspended. Active ingredient and maize starch are mixed. The aqueous suspension is incorporated in this mixture and kneaded to a dough. The substance thus obtained is granulated through a 12 M sieve and dried. II All 4 auxiliaries are intimately mixed. III The premixes obtained according to I and II are mixed and pressed to give tablets or boluses. 4. Injectables A. Oily vehicle (slow release) 1. Active ingredient 0.1-1.0 g Groundnut oil ad 100 ml 2. Active ingredient 0.1-1.0 g Sesame oil ad 100 ml Preparation: The active ingredient is dissolved in a portion of the oil with stirring and, if desired, gentle heating, made up to the required volume after cooling and sterilely filtered through a suitable membrane filter with a size of 0.22 μm. B. Water-miscible solvent (medium release rate) 1. Active ingredient 0.1-1.0 g 4-Hydroxymethyl-1,3-dioxolane (glycerol formal) 40 g 1,2-Propanediol ad 100 ml 2. Active ingredient 0.1-1.0 g Glycerol dimethyl acetal 40 g 1,2-Propanediol ad 100 ml Preparation: The active ingredient is dissolved in a portion of the solvent with stirring, made up to the required volume and sterilely filtered through a suitable membrane filter with a size of 0.22 μm. C. Aqueous solubilisate (rapid release) 1. Active ingredient 0.1-1.0 g Polyethoxylated castor oil (40 ethylene oxide units) 10 g 1,2-Propanediol 20 g Benzyl alcohol 1 g Water for injections ad 100 ml 2. Active ingredient 0.1-1.0 g Polyethoxylated sorbitan monooleate 8 g (20 ethylene oxide units) 4-Hydroxymethyl-1,3-dioxolane (glycerol formal) 20 g Benzyl alcohol 1 g Water for injections ad 100 ml Preparation: The active ingredient is dissolved in the solvents and the surfactant and made up to the required volume with water. Sterile filtration is carried out through a suitable membrane filter with a pore diameter of 0.22 μm. 5. Pour-on A. Active ingredient 5 g Isopropyl myristate 10 g Isopropanol ad 100 ml B. Active Ingredient 2 g Hexyl laurate 5 g Triglycerides of medium chain length 15 g Ethanol ad 100 ml C. Active ingredient 2 g Oleyl oleate 5 g N-Methylpyrrolidone 40 g Isopropanol ad 100 ml The aqueous systems can preferably also be used for oral and/or intraruminal administration. The compositions can also comprise further additives, such as stabilizers, e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil), antifoaming agents, e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects. Further biologically active substances or additives which are neutral towards the compounds of the formula I and have no adverse effect on the host animal to be treated, and mineral salts or vitamins, can also be added to the compositions described. The following examples serve to clarify the invention. They do not limit the invention. The symbol ‘h’ denotes hour. PREPARATION EXAMPLES Example 1 N-[2-Cyano-1-(4,5-difluoro-2-(thien-3-yl)phenoxy)-2-propyl]-4-trifluoromethoxybenzamide a) 2.5 g of chloroacetone, 3 g of potassium carbonate and 0.3 g of potassium iodide are added to 4 g of 2-bromo-4,5-difluorophenol in 40 ml of acetone and stirred at ambient temperature for 3 h. After filtration, the solution is evaporated, producing 1-(2-bromo-4,5-difluorophenoxy)propan-2-one as crude product, which is processed further without further purification. b) 5.1 g of 1-(2-bromo-4,5-difluorophenoxy)propan-2-one, 1.1 g of sodium cyanide and 1.5 g of ammonium chloride are added to 19 ml of a 25% aqueous ammonia solution and stirred overnight at ambient temperature. The reaction mixture is then extracted with ethyl acetate and the organic phase is washed with water and saturated sodium chloride solution and dried with magnesium sulfate. After filtering and evaporating under vacuum, 2-amino-3-(2-bromo-4,5-difluorophenoxy)-2-methylpropionitrile is obtained as crude product, which is processed further without further purification. c) A mixture of 300 mg of 2-amino-3-(2-bromo-4,5-difluorophenoxy)-2-methylpropionitrile, 129 mg of ethyldiisopropylamine, 270 mg of 4-trifluoromethoxybenzoyl chloride and 12 mg of 4-dimethylaminopyridine is stirred in 10 ml of dichloromethane at ambient temperature for 12 h. The reaction mixture is subsequently diluted by addition of ethyl acetate and washed, each time twice, with a saturated sodium bicarbonate solution, a 1N aqueous hydrochloric acid solution and finally with saturated sodium chloride solution, the organic phase, after filtration, is evaporated and the residue is purified by means of flash chromatography, through which N-[2-cyano-1-(2-bromo-4,5-difluorophenoxy)-2-propyl]-4-trifluoromethoxybenzamide is obtained. d) 120 mg of N-[2-cyano-1-(2-bromo-4,5-difluorophenoxy)-2-propyl]-4-trifluoromethoxybenzamide, 160 mg of thiophene-3-boronic acid and 3 ml of saturated aqueous sodium bicarbonate solution are dissolved in 4 ml of toluene and degassed for 15 minutes using a stream of nitrogen. Subsequently, 9 mg of tetrakis(triphenylphosphine)palladium are added and the mixture is stirred at reflux for 20 h. The mixture is subsequently diluted with ethyl acetate and washed with water and saturated sodium chloride solution. The organic phase is dried with magnesium sulfate, filtered and evaporated. After purifying by means of HPLC, the title compound is obtained with a melting point of 128-30° C. The substances mentioned in the following table can also be prepared analogously to the procedure described above. The melting point values are given in ° C. TABLE 1 No. (R8)m R9 (R10)n Physical data 1.1 4-F 2-(2-Thienyl) 4-F 1.2 4-F 2-(2-Thienyl) 4-CF3 1.3 4-F 2-(2-Thienyl) 4-OCF3 1.4 4-F 2-(3-Thienyl) 4-F 1.5 4-F 2-(3-Thienyl) 4-CF3 1.6 4-F 2-(3-Thienyl) 4-OCF3 1.7 4-F 2-(3-Methyl-2-thienyl) 4-F 1.8 4-F 2-(3-Methyl-2-thienyl) 4-CF3 1.9 4-F 2-(3-Methyl-2-thienyl) 4-OCF3 1.10 4-F 2-(4-Methyl-2-thienyl) 4-F 1.11 4-F 2-(4-Methyl-2-thienyl) 4-CF3 1.12 4-F 2-(4-Methyl-2-thienyl) 4-OCF3 1.13 4-F 2-(5-Methyl-2-thienyl) 4-F 1.14 4-F 2-(5-Methyl-2-thienyl) 4-CF3 1.15 4-F 2-(5-Methyl-2-thienyl) 4-OCF3 1.16 4-F 2-(3-Cl-2-thienyl) 4-F 1.17 4-F 2-(3-Cl-2-thienyl) 4-CF3 1.18 4-F 2-(3-Cl-2-thienyl) 4-OCF3 1.19 4-F 2-(5-Cl-2-thienyl) 4-F 1.20 4-F 2-(5-Cl-2-thienyl) 4-CF3 1.21 4-F 2-(5-Cl-2-thienyl) 4-OCF3 1.22 4-F 2-(2-Furyl) 4-F 1.23 4-F 2-(2-Furyl) 4-CF3 1.24 4-F 2-(2-Furyl) 4-OCF3 1.25 4-F 2-(3-Furyl) 4-F 1.26 4-F 2-(3-Furyl) 4-CF3 1.27 4-F 2-(3-Furyl) 4-OCF3 1.28 4-F 2-(2-Thienoxy) 4-F 1.29 4-F 2-(2-Thienoxy) 4-CF3 1.30 4-F 2-(2-Thienoxy) 4-OCF3 1.31 4-F 2-(3-Thienoxy) 4-F 1.32 4-F 2-(3-Thienoxy) 4-CF3 1.33 4-F 2-(3-Thienoxy) 4-OCF3 1.34 4-F 2-(2-Furyloxy) 4-F 1.35 4-F 2-(2-Furyloxy) 4-CF3 1.36 4-F 2-(2-Furyloxy) 4-OCF3 1.37 4-F 2-(3-Furyloxy) 4-F 1.38 4-F 2-(3-Furyloxy) 4-CF3 1.39 4-F 2-(3-Furyloxy) 4-OCF3 1.40 4-F 2-(3-Benzothienyl) 4-F 1.41 4-F 2-(3-Benzothienyl) 4-CF3 1.42 4-F 2-(3-Benzothienyl) 4-OCF3 1.43 5-Cl 2-(2-Thienyl) 4-F 1.44 5-Cl 2-(2-Thienyl) 4-CF3 1.45 5-Cl 2-(2-Thienyl) 4-OCF3 1.46 5-Cl 2-(3-Thienyl) 4-F 1.47 5-Cl 2-(3-Thienyl) 4-CF3 1.48 5-Cl 2-(3-Thienyl) 4-OCF3 1.49 5-Cl 2-(3-Methyl-2-thienyl) 4-F 1.50 5-Cl 2-(3-Methyl-2-thienyl) 4-CF3 1.51 5-Cl 2-(3-Methyl-2-thienyl) 4-OCF3 1.52 5-Cl 2-(4-Methyl-2-thienyl) 4-F 1.53 5-Cl 2-(4-Methyl-2-thienyl) 4-CF3 1.54 5-Cl 2-(4-Methyl-2-thienyl) 4-OCF3 1.55 5-Cl 2-(5-Methyl-2-thienyl) 4-F 1.56 5-Cl 2-(5-Methyl-2-thienyl) 4-CF3 1.57 5-Cl 2-(5-Methyl-2-thienyl) 4-OCF3 1.58 5-Cl 2-(3-Cl-2-thienyl) 4-F 1.59 5-Cl 2-(3-Cl-2-thienyl) 4-CF3 1.60 5-Cl 2-(3-Cl-2-thienyl) 4-OCF3 1.61 5-Cl 2-(5-Cl-2-thienyl) 4-F 1.62 5-Cl 2-(5-Cl-2-thienyl) 4-CF3 1.63 5-Cl 2-(5-Cl-2-thienyl) 4-OCF3 1.64 5-Cl 2-(2-Furyl) 4-F 1.65 5-Cl 2-(2-Furyl) 4-CF3 1.66 5-Cl 2-(2-Furyl) 4-OCF3 1.67 5-Cl 2-(3-Furyl) 4-F 1.68 5-Cl 2-(3-Furyl) 4-CF3 1.69 5-Cl 2-(3-Furyl) 4-OCF3 1.70 5-Cl 2-(2-Thienoxy) 4-F 1.71 5-Cl 2-(2-Thienoxy) 4-CF3 1.72 5-Cl 2-(2-Thienoxy) 4-OCF3 1.73 5-Cl 2-(3-Thienoxy) 4-F 1.74 5-Cl 2-(3-Thienoxy) 4-CF3 1.75 5-Cl 2-(3-Thienoxy) 4-OCF3 1.76 5-Cl 2-(2-Furyloxy) 4-F 1.77 5-Cl 2-(2-Furyloxy) 4-CF3 1.78 5-Cl 2-(2-Furyloxy) 4-OCF3 1.79 5-Cl 2-(3-Furyloxy) 4-F 1.80 5-Cl 2-(3-Furyloxy) 4-CF3 1.81 5-Cl 2-(3-Furyloxy) 4-OCF3 1.82 5-Cl 2-(3-Benzothienyl) 4-F 1.83 5-Cl 2-(3-Benzothienyl) 4-CF3 1.84 5-Cl 2-(3-Benzothienyl) 4-OCF3 1.85 4,5-F2 2-(2-Thienyl) 4-F 1.86 4,5-F2 2-(2-Thienyl) 4-CF3 1.87 4,5-F2 2-(2-Thienyl) 4-OCF3 131-2° 1.88 4,5-F2 2-(3-Thienyl) 4-F 1.89 4,5-F2 2-(3-Thienyl) 4-CF3 1.90 4,5-F2 2-(3-Thienyl) 4-OCF3 128-30° 1.91 4,5-F2 2-(3-Methyl-2-thienyl) 4-F 1.92 4,5-F2 2-(3-Methyl-2-thienyl) 4-CF3 1.93 4,5-F2 2-(3-Methyl-2-thienyl) 4-OCF3 1.94 4,5-F2 2-(4-Methyl-2-thienyl) 4-F 1.95 4,5-F2 2-(4-Methyl-2-thienyl) 4-CF3 1.96 4,5-F2 2-(4-Methyl-2-thienyl) 4-OCF3 136-8° 1.97 4,5-F2 2-(5-Methyl-2-thienyl) 4-F 1.98 4,5-F2 2-(5-Methyl-2-thienyl) 4-CF3 1.99 4,5-F2 2-(5-Methyl-2-thienyl) 4-OCF3 1.100 4,5-F2 2-(3-Cl-2-thienyl) 4-F 1.101 4,5-F2 2-(3-Cl-2-thienyl) 4-CF3 1.102 4,5-F2 2-(3-Cl-2-thienyl) 4-OCF3 1.103 4,5-F2 2-(5-Cl-2-thienyl) 4-F 1.104 4,5-F2 2-(5-Cl-2-thienyl) 4-CF3 1.105 4,5-F2 2-(5-Cl-2-thienyl) 4-OCF3 1.106 4,5-F2 2-(2-Furyl) 4-F 1.107 4,5-F2 2-(2-Furyl) 4-CF3 1.108 4,5-F2 2-(2-Furyl) 4-OCF3 134-5° 1.109 4,5-F2 2-(3-Furyl) 4-F 1.110 4,5-F2 2-(3-Furyl) 4-CF3 1.111 4,5-F2 2-(3-Furyl) 4-OCF3 60-3° 1.112 4,5-F2 2-(2-Thienoxy) 4-F 1.113 4,5-F2 2-(2-Thienoxy) 4-CF3 1.114 4,5-F2 2-(2-Thienoxy) 4-OCF3 1.115 4,5-F2 2-(3-Thienoxy) 4-F 1.116 4,5-F2 2-(3-Thienoxy) 4-CF3 1.117 4,5-F2 2-(3-Thienoxy) 4-OCF3 1.118 4,5-F2 2-(2-Furyloxy) 4-F 1.119 4,5-F2 2-(2-Furyloxy) 4-CF3 1.120 4,5-F2 2-(2-Furyloxy) 4-OCF3 1.121 4,5-F2 2-(3-Furyloxy) 4-F 1.122 4,5-F2 2-(3-Furyloxy) 4-CF3 1.123 4,5-F2 2-(3-Furyloxy) 4-OCF3 1.124 4,5-F2 2-(3-Benzothienyl) 4-F 1.125 4,5-F2 2-(3-Benzothienyl) 4-CF3 1.126 4,5-F2 2-(3-Benzothienyl) 4-OCF3 m.p. 121-2° BIOLOGICAL EXAMPLES 1. In Vivo Test Against Trichostrongylus colubriformis and Haemonchus contortus in Mongolian gerbils (Meriones unquiculatus) by Peroral Administration Six- to eight-week-old Mongolian gerbils are infected, using manufactured feed, with in each case approximately 2000 larvae of the 3rd stage of T. colubriformis and H. contortus. Six days after infecting, the gerbils are lightly anaesthetized with N2O and are treated by peroral administration with the test compounds, dissolved in a mixture of 2 parts of DMSO and 1 part of polyethylene glycol (PEG 300), with amounts of 100, 32 and 10-0.1 mg/kg. On day 9 (3 days after treating), when most of the H. contortus larvae still existing are in the late 4th stage and most of the T. colubriformis are immature adults, the gerbils are sacrificed in order to count the worms. The activity is calculated in % reduction in the number of worms in each gerbil by comparison with the geometric mean of the number of worms from 8 infected and untreated gerbils. In this test, a large decrease in the nematode infestation is obtained with compounds of the formula I. The following test methods can be employed in investigating the insecticidal and/or acaricidal action of the compounds of the formula I on animals and plants. 2. Action Against L1 Larvae of Lucilia sericata 1 ml of an aqueous suspension of the active substance to be tested is thus mixed at approximately 50° C. with 3 ml of a special medium for raising larvae, so that a homogenate with an active ingredient content of either 250 or 125 ppm is formed. Approximately 30 Lucilia larvae (L1) are introduced into each test tube sample. After 4 days, the mortality rate is determined. 3. Acaricidal Action Against Boophilus Microplus (Biarra Strain) An adhesive tape is attached horizontally to a PVC plate such that 10 female Boophilus microplus ticks (Biarra strain) which have sucked themselves full of blood can be adhesively attached to the tape via their backs in a row, next to one another. Each tick is injected, using an injection needle, with 1 μl of a liquid which is a 1:1 mixture of polyethylene glycol and acetone and in which a certain amount of active ingredient of alternatively 1, 0.1 or 0.01 μg per tick is dissolved. Control animals receive an injection not comprising an active ingredient. After the treatment, the animals are kept in an insectarium under standard conditions at approximately 28° C. and 80% relative humidity until egg laying has occurred and the larvae have hatched from the eggs of the control animals. The activity of a test substance is determined using the IR90, i.e. that dose of active ingredient is ascertained at which, after 30 days, 9 out of 10 female ticks (=90%) lay eggs which are not able to hatch. 4. In Vitro Activity Against Fed Boophilus microplus Females (Biarra): 4×10 fed female ticks of the OP-resistant Biarra strain are attached to an adhesive tape and are covered for 1 h with a wad of cotton which has been impregnated with an emulsion or suspension of the test compound in concentrations in each case of 500, 125, 31 and 8 ppm. The mortality, egg laying and larval hatching are evaluated 28 days later. An indication of the activity of the test compounds is the number of the females which quickly die, before laying eggs, survive for some time, without laying eggs, lay eggs in which no embryos develop, lay eggs in which embryos develop but from which no larvae hatch, and lay eggs in which embryos develop and from which larvae hatch normally in 26 to 27 days. 5. In Vitro Activity Against Nymphs of Amblyomma hebraeum About 5 hungry nymphs are placed in a polystyrene test tube comprising 2 ml of the test compound in solution, suspension or emulsion. After immersing for 10 minutes and shaking for 2×10 seconds on a vortex mixer, the test tubes are plugged with a thick wad of cotton wool and are inverted. As soon as all the liquid has been soaked up by the wad of cotton, the wad is pushed halfway into the still inverted test tube, so that most of the liquid is squeezed out of the wad of cotton and flows into a petri dish placed underneath. The test tubes are now, until evaluation, stored at ambient temperature in a room lit by daylight. After 14 days, the test tubes are immersed in a beaker of boiling water. If, in reaction to the heat, the ticks begin to move, the test substance is inactive at the test concentration; otherwise, the ticks are considered to be dead and the test substance is considered to be active at the test concentration. All substances are tested in a concentration range from 0.1 to 100 ppm. 6. Action Against Dermanyssus gallinae 2 to 3 ml of a solution comprising 10 ppm of active ingredient and approximately 200 mites (Dermanyssus gallinae) at various development stages are placed in a glass vessel open at the top. The vessel is subsequently plugged with a wad of cotton, shaken for 10 minutes, until the mites have been completely wetted, and then briefly inverted, so that the remaining test solution can be absorbed by the cotton wool. After 3 days, the mortality of the mites is ascertained by counting the dead individuals and is given in percent. 7. Action Against Musca domestica A sugar cube is treated with a solution of the test substance such that the concentration of test substance in the sugar, after drying overnight, is 250 ppm. This treated cube is placed with a wet wad of cotton and 10 adult Musca domestica of an OP-resistant strain on an aluminium dish, is covered with a beaker and is incubated at 25° C. The mortality rate is determined after 24 hours.
20041108
20081104
20050818
75363.0
0
SACKEY, EBENEZER O
N-ACYLAMINOACETONITRILE DERIVATIVES AND THEIR USE FOR CONTROLLING PARASITES
UNDISCOUNTED
0
ACCEPTED
2,004
10,513,807
ACCEPTED
Solid dosage form comprising a fibrate
The invention provides stable, solid dosage forms and pharmaceutical compositions in particulate form comprising a fibrate, for example fenofibrate, dissolved in an non-aqueous vehicle in order to ensure improved bioavailability of the active ingredient upon oral administration relative to known fibrate formulations.
1. A solid oral dosage form comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible. 2. The solid dosage form according to claim 1 in the form of tablets, beads, capsules, grains, pills, granulates, granules, powder, pellets, sachets or troches. 3. The solid dosage form according to claim 1, which is a tablet. 4. The solid dosage form according to claim 1, wherein the fibrate is selected from the group consisting of gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate and active metabolites and analogues thereof. 5. The solid dosage form according to claim 1, wherein the fibrate is fenofibrate or an analogue thereof. 6. The solid dosage form according to claim 1, wherein the vehicle has a melting point of at the most about 250° C. 7. The solid dosage form according to claim 1, wherein the vehicle is hydrophobic and is selected from the group consisting of straight chain saturated hydrocarbons, paraffins; fats and oils; higher fatty acid; hydrogenated tallow, substituted and/or unsubstituted triglycerides, yellow beeswax, white beeswax, carnauba wax, castor wax, Japan wax, and mixtures thereof. 8. The solid dosage form according to claim 7, wherein the vehicle is a water-miscible polar lipid; higher alcohols such as cetanol, stearyl alcohol; glyceryl monooleate, substituted and/or unsubstituted monoglycerides, substituted and/or unsubstituted diglycerides, and mixtures thereof. 9. The solid dosage form according to claim 1, wherein the vehicle is hydrophilic or water-miscible. 10. The solid dosage form according to claim 9, wherein the hydrophilic or water-miscible vehicle is selected from the group consisting of polyethylene glycols, polyoxyethylene oxides, poloxamers, polyoxyethylene stearates, poly-epsilon caprolactone and mixtures thereof. 11. The solid dosage form according to claim 9, wherein the hydrophilic or water-miscible vehicle is a polyglycolized glyceride. 12. The solid dosage form according to claim 9, wherein the hydrophilic or water-miscible vehicle is selected from the group consisting of polyvinylpyrrolidones, polyvinyl-polyvinylacetate copolymers-(PVP-PVA), polyvinyl alcohol (PVA), PVP polymers, acrylic polymers, polymethacrylic polymers, myristyl alcohol, cellulose derivatives including hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, pectins, cyclodextrins, galactomannans, alginates, carragenates, xanthan gums and mixtures thereof. 13. The solid dosage form according to claim 10, wherein the vehicle is a polyethylene glycol (PEG). 14. The solid dosage form according to claim 13, wherein the polyethylene glycol has an average molecular weight of at least 3000. 15. The solid dosage form according to claim 9 comprising a mixture of two or more hydrophilic or water-miscible vehicles. 16. The solid dosage form according to claim 15, wherein the mixture comprises a polyethylene glycol and a poloxamer in a weight proportion of between 1:3 and 10:1, preferably between 1:1 and 5:1, more preferably between and 3:2 4:1, especially between 2:1 and 3:1, in particular about 7:3. 17. The solid dosage form according to claim 16, wherein the poloxamer is poloxamer 188. 18. The solid dosage form according to claim 16, wherein the polyethylene glycol has an average molecular weight of about 6000. 19. The solid dosage form according to claim 1, wherein the vehicle is non-aqueous. 20. The solid dosage form according to claim 1, wherein the concentration of fibrate in the vehicle is at least 10% w/w, based on the total weight of the fibrate and the vehicle. 21. The solid dosage form according to claim 1, wherein the concentration of fibrate in the vehicle is at least 15% w/w, or at least 16% w/w, or at least 17% w/w, or at least 20% w/w, preferably at least 25% w/w, more preferably at least 30% w/w, especially at least 35% w/w, based on the total weight of the fibrate and the vehicle. 22. The solid dosage form according to claim 1, wherein the concentration of fibrate in the vehicle is at the most 90% w/w, based on the total weight of the fibrate and the vehicle. 23. The solid dosage form according to claim 1, wherein the concentration of fibrate in the vehicle is at the most 80% w/w, or at the most 75% w/w, or at the most 70% w/w, or at the most 60% w/w, preferably at the most 50% w/w, more preferably at the most 40% w/w, especially at the most 35% w/w, based on the total weight of the fibrate and the vehicle. 24. The solid dosage form according to claim 1, wherein at least 90% w/w of the fenofibrate is dissolved in the vehicle. 25. The solid dosage form according to claim 1, wherein at least 93% w/w, or at least 95% w/w, or at least 97% w/w, or at least 98% w/w, or at least 99% w/w, or at least 99.5% w/w, or at least 99.9% w/w, of the fenofibrate is dissolved in the vehicle. 26. The solid dosage form according to claim 1, wherein at least 75% of the fibrate is released within about 45 min when tested in an in vitro dissolution test according to Ph. Eur. dissolution test (paddle) employing water with 0.75% sodium lauryl sulfate as dissolution medium, 50 rpm and a temperature of about 37° C. 27. The solid dosage form according to claim 26, wherein the dissolution test is carried out after 3 months of storage at a temperature of about 40° C. and a relative humidity of about 75%. 28. The solid dosage form according to claim 1 which further comprises one or more pharmaceutically acceptable excipients. 29. The solid dosage form according to claim 28, wherein the pharmaceutically acceptable excipients are selected from the group consisting of fillers, diluents, disintegrants, binders, glidants and lubricants. 30. The solid dosage form according to claim 28, wherein at least one pharmaceutically acceptable excipient is a silica acid or a derivative or salt thereof. 31. The solid dosage form according to claim 28, wherein at least one pharmaceutically acceptable excipient is a silica acid or a derivative or salt thereof selected from the group consisting of silicates, silicon dioxide and polymers thereof, magnesium aluminosilicase, magnesium aluminometasilicate, bentonite, kaolin, magnesium trisilicate, montmorillonite and/or saponite. 32. The solid dosage form according to claim 28, wherein at least one pharmaceutically acceptable excipient is silicon dioxide or a polymer thereof. 33. The solid dosage form according to claim 28, wherein the silicon dioxide product has properties corresponding to Aeroperl® 300. 34. The solid dosage form according to claim 1, which further comprises a pharmaceutically acceptable additive selected from the group consisting of flavoring agents, coloring agents, taste-masking agents, pH-adjusting agents, buffering agents, preservatives, stabilizing agents, anti-oxidants, wetting agents, humidity-adjusting agents, surface-active agents, suspending agents and absorption enhancing agents. 35. The solid dosage form according to claim 1, which further comprises at a pharmaceutically acceptable oil-sorption material. 36. The solid dosage form according to claim 1, which is a unit dosage form. 37. The solid dosage form according to claim 1, wherein the individual units of the solid dosage form are coated with a coating selected from the group consisting of film coatings, modified release coatings, enteric coatings, protective coatings and anti-adhesive coatings. 38. The solid dosage form according to claim 1, wherein the fibrate is embedded in a matrix that releases the fibrate by diffusion. 39. The solid dosage form according to claim 38, wherein the matrix remains substantially intact during the period of drug release. 40. The solid dosage form according to claim 1, wherein the fibrate is embedded in a matrix that releases the fibrate by eroding. 41. The solid dosage form according to claim 1, wherein the fibrate is released from the dosage form by diffusion through a substantially water-insoluble coating. 42. The solid dosage form according to claim 1, which results in an increased bioavailability of fibrate relative to existing commercial fibrate dosage forms when administered to a mammal in need thereof. 43. The solid dosage form according to claim 42, which provides an AUC value relative to that of commercially available Tricor® tablets of at least about 1.1, or at least about 1.2, or at least about 1.3, or at least about 1.4, or at least about 1.5, or at least about 1.75 or more, or at least about 2.0, or at least about 2.5, or at least about 3.0, the AUC values being determined under similar conditions. 44. The solid dosage form according to claim 42, which provides a cmax value relative to that of commercially available Tricor® tablets of at least about 1.1, or at least about 1.2, or at least about 1.3, or at least about 1.4, or at least about 1.5, or at least about 1.6 or more, or at least about 2.0, or at least about 2.5, or at least about 3.0, the cmax values being determined under similar conditions. 45. The solid dosage form according to claim 1, wherein the fibrate is stable. 46. The solid dosage form according to claim 45, wherein the fibrate is present in an amount of at least 90%, or at least 95%, or at least 100%, relative to the amount prior to storage, when assayed after 3 months of storage at a temperature of about 40° C. and a relative humidity of about 75%. 47. A composition comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible. 48. The composition according to claim 47, wherein the vehicle has a melting point of at the most about 250° C. 49. The composition according to claim 47, wherein the vehicle is selected from the group consisting of straight chain saturated hydrocarbons, sorbitan esters, paraffins; fats and oils such as cacao butter, beef tallow, lard, polyether glycol esters; higher fatty acid such as stearic acid, myristic acid, palmitic acid, higher alcohols such as cetanol, stearyl alcohol; low melting point waxes such as glyceryl monostearate, glyceryl monooleate, hydrogenated tallow, myristyl alcohol, stearyl alcohol, substituted and/or unsubstituted monoglycerides, substituted and/or unsubstituted diglycerides, substituted and/or unsubstituted triglycerides, yellow beeswax, white beeswax, carnauba wax, castor wax, japan wax, acetylate monoglycerides; PVP polymers, acrylic polymers; polyethylene glycols, polyoxyethylene oxides, poloxamers, polyoxyethylene stearates, poly-epsilon caprolactone, polyglycolized glycerides such as Gelucire®, polyvinylpyrrolidones, polyvinyl-polyvinylacetate copolymers (PVP-PVA), polyvinyl alcohol (PVA), polymethacrylic polymers (Eudragit RS; Eudragit RL, Eudragit NE, Eudragit E), cellulose derivatives including hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, pectins, cyclodextrins, galactomannans, alginates, carragenates, xanthan gums; and mixtures thereof. 50. The composition according to claim 47, wherein the mixture comprises a polyethylene glycol and a poloxamer in a weight proportion of between 1:3 and 10:1, preferably between 1:1 and 5:1, more preferably between and 3:2 4:1, especially between 2:1 and 3:1, in particular about 7:3. 51. The composition according to claim 47, wherein the concentration of fibrate in the vehicle is at least 10% w/w, or at least 15% w/w, or at least 16% w/w, or at least 17% w/w, or at least 20% w/w, preferably at least 25% w/w, more preferably at least 30% w/w, especially at least 35% w/w, based on the total weight of the fibrate and the vehicle. 52. The composition according to claim 47, wherein at least 90% w/w, or at least 93% w/w, or at least 95% w/w, or at least 97% w/w, or at least 98% w/w, or at least 99% w/w, of the fenofibrate is dissolved in the vehicle. 53. The composition according to claim 47, which further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of fillers, diluents, disintegrants, binders, glidants and lubricants. 54. The composition according to claim 47, which further comprises at a pharmaceutically acceptable oil-sorption material. 55. The composition according to claim 47, which provides an AUC value relative to that of commercially available Tricor® tablets of at least about 1.1, or at least about 1.2, or at least about 1.3, or at least about 1.4, or at least about 1.5, or at least about 1.75 or more, or at least about 2.0, or at least about 2.5, or at least about 3.0, the AUC values being determined under similar conditions. 56. The composition according to claim 47, which provides a cmax value relative to that of commercially available Tricor® tablets of at least about 1.1, or at least about 1.2, or at least about 1.3, or at least about 1.4, or at least about 1.5, or at least about 1.6 or more, or at least about 2.0, or at least about 2.5, or at least about 3.0, the cmax values being determined under similar conditions. 57. The composition according to claim 47 in the form of particles, i.e. in particulate form. 58. The composition according to claim 47, which exhibits a suitable flowability when determined according to the method described in Ph.Eur., measuring the flow rate of the composition out of a funnel with a nozzle diameter of 10.0 mm. 59. A solid composition in particulate form comprising a fibrate, a hydrophobic or a hydrophilic or water-miscible vehicle and an oil-sorption material, which composition exhibits an oil threshold value of at least 10%, and which composition further fulfills one or both of i) and ii): i) the composition releases at least 30% of the hydrophobic or a hydrophilic or water-miscible vehicle; ii) the composition, in the form of a tablet, contains at least about 90% w/w of the oil-sorption material, and exhibits a disintegration time of at the most 60 minutes. 60. A method of manufacturing the solid oral dosage form of claim 1 comprising the steps of: i) Bringing the vehicle in liquid form, if applicable, ii) Maintaining the liquid vehicle at a temperature below the melting point of the fibrate, iii) Dissolving the desired amount of fibrate in the vehicle, iv) Spraying the resulting solution onto a solid carrier having a temperature below the melting point of the vehicle, v) Mechanically working the resulting composition to obtain particles, i.e. a particulate material, and vi) Optionally subjecting the particulate material to conventional methods for preparing solid dosage forms. 61-62. (canceled)
The present invention relates to novel solid dosage forms and pharmaceutical compositions comprising a fibrate, notably fenofibrate. Particularly, the invention discloses solid dosage forms having increased bioavailability. The solid dosage forms of the invention comprise fibrate dissolved in a suitable vehicle or mixture of vehicles. The dosage forms are especially intended for oral use and exhibit excellent storage stability, i.e. are stable. The invention also relates to methods for preparation of the solid dosage forms and pharmaceutical compositions and the use thereof. BACKGROUND OF THE INVENTION Fibrates are lipid regulating agents. Examples of fibrates include gemifibrozil, fenofibrate, bezafibrate, clofibrate and ciprofibrate. The compounds are regarded as prodrugs and are metabolised in vivo to their active metabolites. For illustrative purposes only, the following is based on a specific example of a fibrate, namely fenofibrate. Fenofibrate is chemically named 2-[4-(4-chlorobenzoyl]-2-methyl-propanoic acid, 1-methylethyl ester and has the following structural formula: Fenofibrate is a white solid. The compound is insoluble in water. The melting point is 79-82° C. Fenofibrate is metabolised to the active substance fenofibric acid. Fenofibric acid has an elimination half-life of about 20 hours. Measurement of the detected amount of fenofibric acid in the blood of a patient can reflect the efficacy of fenofibrate uptake. Fenofibric acid produces reductions in total cholesterol (total-C), LDL-C, apo-lipoprotein B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apo-lipoprotein apoAl and apo All. Fenofibrate acts as a potent lipid regulating agent offering unique and clinical advantages over existing products in the fibrate family of drug substances. Fenofibrate produces substantial reduction in plasma triglyceride levels in hypertriglyceridemic patients and in plasma cholesterol and LDL-C in hypercholesterolemic and mixed dyslipidemic patients. Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal subjects by increasing the urinary excretion of uric acid. Clinical studies have demonstrated that elevated levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), and apo-lipoprotein B (apo B) are associated with human atherosclerosis. Decreased levels of high density lipoprotein cholesterol (HDL-C) and its transport complex, apolipoprotein A (apo Al and apo All) are associated with the development of atherosclerosis. Fenofibrate is also effective in the treatment of Diabetes Type II and metabolic syndrome. Fenofibrate is also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types IV and V hyperlipedemia). Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually reduce fasting triglycerides and eliminate chylomicronemia and thereby obviating the need for pharmacologic intervention. Fibrates are drug substances known to be are poorly and variably absorbed after oral administration. Normally they are prescribed to be taken with food in order to increase the bioavailability. There have been a number of improvements in dosage form of the currently most used fibrate, fenofibrate, in an effort to increase the bioavailability of the drug and hence it's efficacy. However, there is still a need for improved dosage forms relative to the currently available compositions and dosage forms, which provide crystalline fenofibrate in micronized form. In particular, there remains a need for a composition and a dosage form exhibiting a suitable bioavailability, which substantially can reduce or overcome the differential between the bioavailability of the drug in patients who are fasted versus the bioavailability of the drug in patients who are fed, and/or which substantially can reduce or overcome the intra- and/or inter-individual variations observed with the current treatment with the available commercial products. Furthermore, there is also a need for novel dosage forms and/or compositions that enable reduction in observed side-effects. Especially, there is an unmet need for developing a solid composition in particulate form in which the fibrate is in a dissolved state and that appears as a composition that is in the form of a powder, granules, granulates, particles, beads, pellets or other forms for particulate material and not in the form of a soft dosage form containing a liquid medium. SUMMARY OF THE INVENTION The inventors have now found that the bioavailabilty of fenofibrate can be significantly enhanced by dissolving a fibrate, for example fenofibrate, in a suitable vehicle and using the resulting composition for preparing a solid dosage form, i.e. a dosage form excluding material in liquid form. Fibrate, especially fenofibrate, is known to be insoluble in water, but the present invention provides pharmaceutical compositions and formulations exhibiting immediate release profiles which are comtemplated having significantly increased in vivo bioavailability in patients in need thereof. Especially, the inventors have succeeded in preparing a solid dosage form, such as a tablet, comprising the fibrate in dissolved form. The advantages of a solid and stable dosage form useful for oral administration are well-known. Accordingly, in a first aspect the present invention relates to a solid oral dosage form comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible. Useful solid dosage forms are in the form of tablets, beads, capsules, grains, pills, granulates, granules, powder, pellets, sachets or troches, and useful fibrates are, fenofibrate, bezafibrate, clofibrate, ciprofibrate and active metabolites and analogues thereof including any relevant fibric acid such as fenofibric acid. In a second aspect, the invention relates to a pharmaceutical composition comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible; and in a further aspect, the invention relates to a solid pharmaceutical composition in particulate form comprising a fibrate, a hydrophobic or a hydrophilic or water-miscible vehicle and an oil-sorption material, which composition exhibits an oil threshold value of at least 10%. In yet another aspect, the invention relates to a method of manufacturing the solid oral dosage form or the pharmaceutical composition of the invention. Further aspects of the invention are evident from the following description. Comparison in vivo tests in dogs have shown, cf. the examples herein, that solid dosage forms and compositions of the invention exhibit significantly enhanced bioavailability of fenofibrate compared to commercially available solid dosage forms containing the same active ingredient, i.e. to Tricor® tablet and Lipanthyl® capsules. Further, it is strongly believed that the present invention provides solid dosage forms and/or compositions of fibrate capable of significantly reducing the intra- and/or inter-individual variation normally observed after oral administration. Furthermore, compositions and/or dosage forms according to the invention provide for a significant reduced food effect, i.e. the absorption is relatively independent on whether the patient takes the composition or dosage form together with or without any meal. It is contemplated that a modified release of the fibrate may reduce the number of gastro-intestinal related side effects. Furthermore, it is contemplated that a significantly larger amount of the fibrate is absorbed and, accordingly, an equally less amount is excreted unchanged via feces. DETAILED DESCRIPTION Definitions As used herein, the term “active ingredient” or “active pharmaceutical ingredient” means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and are present in the drug product in a modified form intended to furnish the specified activity or effect. In the present context, the term “hydrophilic” describes that something ‘likes water’, i.e. a hydrophilic molecule or portion of a molecule is one that typically is electrically polarized and capable of forming hydrogen bonds with water molecules, enabling it dissolve more readily in water than in oil or other “non-polar” solvents. In the present context, the term “amphiphilic” describes a molecule (as a surfactant) having a polar water-soluble group attached to a water-insoluble hydrocarbon chain. Thus, one end of the molecule is hydrophilic (polar) and the other is hydrophobic (non-polar). In the present context, the term “hydrophobic” denotes a compound tending to be electrically neutral and non-polar, and thus preferring other neutral and nonpolar solvents or molecular environments. As used herein, the term “water-miscible” denotes a compound being fully or partly miscible with water. For example, certain polar lipids are partly water-miscible. As used herein, the term “vehicle” means any solvent or carrier in a pharmaceutical product that has no pharmacological role. For example, water is the vehicle for xilocaine and propylene glycol is the vehicle for many antibiotics. In the present context, the term “solid dispersion” denotes a drug or active ingredient or substance dispersed on a particulate level in an inert vehicle, carrier, diluent or matrix in the solid state, i.e. usually a fine particulate dispersion. In the present context, the term “solid solution” denotes a drug or active ingredient or substance dissolved on a molecular level in an inert vehicle, carrier, diluent or matrix in the solid state. As used herein, the term “analogue” means a chemical compound that is structurally similar to another. The term “drug” means a compound intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals. In this context, the term “dosage form” a means the form in which the drug is delivered to the patient. This could be parenteral, topical, tablet, oral (liquid or dissolved powder), suppository, inhalation, transdermal, etc. As used herein, the term “bioavailability” denotes the degree means to which a drug or other substance becomes available to the target tissue after administration. As used herein, the term “bioequivalency” denotes a scientific basis on which generic and brand name drugs are compared with one another. For example, drugs are bioequivalent if they enter circulation at the same rate when given in similar doses under similar conditions. Parameters often used in bioequivalence studies are tmax, Cmax, AUC0-infinity, AUCo-t. Other relevant parameters may be W50, W75 and/or MRT. Accordingly, at least one of these parameters may be applied when determining whether bioequivalence is present. Furthermore, in the present context, two compositions are regarded as bioequivalent if the value of the parameter used is within 80-125% of that of Prograf® or a similar commercially available tacrolimus-containing product used in the test. In the present context “tmax” denotes the time to reach the maximal plasma concentration (cmax) after administration; AUC0-infinity or AUC denotes the area under the plasma concentration versus time curve from time 0 to infinity; AUC0-t denotes the area under the plasma concentration versus time curve from time 0 to time t; W50 denotes the time where the plasma concentration is 50% or more of Cmax; W75 denotes the time where the plasma concentration is 75% or more of Cmax; and MRT denotes mean residence time for a fibrate such as fenofibrate (and/or an analogue thereof. In this context, the term “medicine” means a compound used to treat disease, injury or pain. Medicine is justly distributed into “prophylactic,” i.e. the art of preserving health, and “therapeutic”, i.e. the art of restoring health. In the present context, the terms “controlled release” and “modified release” are intended to be equivalent terms covering any type of release of tacrolimus from a composition of the invention that is appropriate to obtain a specific therapeutic or prophylactic response after administration to a subject. A person skilled in the art knows how controlled release/modified release differs from the release of plain tablets or capsules. The terms “release in a controlled manner” or “release in a modified manner” have the same meaning as stated above. The terms include slow release (that results in a lower Cmax and later tmax, but t1/2 is unchanged), extended release (that results in a lower Cmax, later tmax, but apparent t1/2 is longer); delayed release (that result in an unchanged Cmax, but lag time and, accordingly, tmax is delayed, and t1/2 is unchanged) as well as pulsatile release, burst release, sustained release, prolonged release, chrono-optimized release, fast release (to obtain an enhanced onset of action) etc. Included in the terms is also e.g. utilization of specific conditions within the body e.g. different enzymes or pH changes in order to control the release of the drug substance. In this context, the term “erosion” or “eroding” means a gradual breakdown of the surface of a material or structure, for example of a tablet or the coating of a tablet. The Active Drug Substance The drug or active substance of the dosage forms and pharmaceutical compositions of this invention is a fibrate. Examples of useful fibrates are bezafibrate, ciprofibrate, clinofibrate, clofibrate, etofylline, clofibrate, fenofibrate, gemfibrozil, pirifibrate, simfibrate and tocofibrate; particularly useful are gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate and active metabolites and analogues thereof including any relevant fibric acid such as fenofibric acid. In a preferred embodiment, the fibrate is fenofibrate or an analogue thereof. However, the dosage forms and compositions of the invention may also comprise a mixture of two, three or even four different fibrates and/or fibric acids. The concentration of fibrate in the vehicle is at least 10% w/w, based on the total weight of the fibrate and the vehicle; preferably at least 15% w/w, or at least 16% w/w, or at least 17% w/w, or at least 20% w/w, or at least 25% w/w, or at least 30% w/w, especially at least 35% w/w, based on the total weight of the fibrate and the vehicle; and the concentration of fibrate in the vehicle is at the most 90% w/w, based on the total weight of the fibrate and the vehicle, or at the most 80% w/w, or at the most 75% w/w, or at the most 70% w/w, or at the most 60% w/w, or at the most 50% w/w, or at the most 40% w/w, or not above 35% w/w, based on the total weight of the fibrate and the vehicle. Preferably, the fibrate is fully dissolved in the non-aqueous vehicle. However, a minor occurrence of crystalline or microcrystalline active drug may not influence on the enhanced bioavailability of the solid dosage forms and pharmaceutical compositions of the invention. Accordingly, at least 90% w/w of the fenofibrate is dissolved in the vehicle, preferably is at least 93% w/w, or at least 95% w/w, or at least 97% w/w, or at least 98% w/w, or at least 99% w/w, or at least 99.5% w/w, or at least 99.9% w/w, of the fenofibrate present in the dosage form or the pharmaceutical compostion fully dissolved in the vehicle or the vehicle system. In addition to the content of fibrate, the dosage forms and pharmaceutical compositions of the invention may comprise further active drug substances, preferably one additional drug substances. Preferably, such an additional drug substance is of a type normally employed for the same indications as fibrate. A specific example is ezetimibe. However, combination products with three or even four drug substances used for the same indication are contemplated as well as combination products comprising two, three or four active ingredients for different indications or therapies. Examples of additional drug substances are other antilipidemic agents like statins; lipid regulators like: acipimox, binifibrate, etofibrate, niceritrol, nicofibrate, pirozadil, ronifibrate, tocoferil nicotinate; combination with cardiovascular drugs like ace inhibitors: alacepril, benazepril, captopril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, moexipril, perindopril, quinapril, ramipril, spirapril, temocapril, teprotide, trandolapril, zofenopril; calcium channel blockers like: amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, bepridil, cilnidipine, diltiazem, efonidipine, felodipine, gallopamil, isradipine, lacidipine, lercanidipine, manidipine, mibefradil, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, verapamil; alpha-blockers like: alfuzosin, bunazosin, doxazosin, indoramin, naftopidil, phenoxybenzamine, phentolamine, prazosin, tamsulosin, terazosin, thymoxamine, tolazoline, urapidil; beta-blockers like: acebutolol, alprenolol, amosulalol, arotinolol, atenolol, befunolol, betaxolol, bevantolol, bisoprolol, bopindolol, bucindolol, bunitrolol, bupranolol, carazolol, carteolol, carvedilol, celiprolol, esmolol, indenolol, labetalol, landiolol, levobetaxolol, levobunolol, mepindolol, metipranolol, metoprolol, nadolol, nebivolol, nipradilol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, talinolol, tertatolol, timolol; angiotensin ii blockers like: candesartan, eprosartan, irbesartan, losartan, olmesartan, tasosartan, ref. telmisartan, valsartan; vasodilators like: cadralazine, diazoxide, dihydralazine, endralazine, hydralazine, minoxidil, todralazine, tolazoline, carbocromen, cinepazet, ref. cloridarol, dilazep, etafenone, fendiline, hexobendine, oxyfedrine, trapidil, trimetazidine, azapetine, bamethan, bencyclane, buflomedil, butalamine, calcitonin gene-related peptide, cetiedil, cinepazide, cyclandelate, di-isopropylammonium ichloroacetate, fasudil, ifenprodil, inositol nicotinate, naftidrofuryl, nicotinyl alcohol, oxpentifylline [pentoxifylline], pentifylline, pipratecol, propentofylline, raubasine, xantinol icotinat; centrally acting hypertensives: apraclonidine, brimonidine, clonidine, guanabenz, guanfacine, methyldopa, moxonidine, rilmenidine, tiamenidine; anti arrhythmic drugs like: ajmaline, cibenzoline, disopyramide, hydroquinidine, pirmenol, procainamide, quinidine, aprindine, mexiletine, tocainide, diprafenone, encainide, flecainide, lorcainide, pilsicainide, propafenone, bretylium, acecainide, amiodarone, azimilide, bretylium, cibenzoline, dofetilide, ibutilide, nifekalant, sotalol, cibenzoline, verapamil; anti platelets like: abciximab, aspirin, cilostazol, clopidogrel, cloricromen, dipyridamole, ditazole, eptifibatide, indobufen, lamffiban, orbofiban, picotamide, sarpogrelate, sibrafiban, ticlopidine, tirofiban, trapidil, triflusal, xemilofiban; diuretics like: acetazolamide, brinzolamide, diclofenamide, dorzolamide, methazolamide, azosemide, bumetanide, etacrynic acid, etozolin, frusemide, piretanide, torasemide, isosorbide, mannitol, amiloride, canrenone, potassium canrenoate, spironolactone, triamterene, altizide, bemetizide, bendrofluazide, benzthiazide, butizide, chlorothiazide, chlortalidone, clopamide, cyclopenthiazide, cycloithiazide, epitizide, hydrochlorothiazide, hydroflumethiazide, indapamide, mebutizide, mefruside, methyclothiazide, meticrane, metolazone, polythiazide, quinethazone, teclothiazide, trichlormethiazide, tripamide, xipamide; antidiabetic drugs like: acarbose acetohexamide biguanide antidiabetcs buformin carbutamide chlorpropamide epalrestat glibenclamide glibomuride gliclazide glimepiride glipizide gliquidone glisentide glisolamide glisoxepide glybuzole glyclopyramide glycyclamide glymidine sodium mefformin hydrochloride midaglizole miglitol nateglinide phenformin hydrochloride pimagedine pioglitazone hydrochloride pramlintide repaglinide rosiglitazone sorbinil tolazamide tolbutamide troglitazone voglibose substances like: q10, vitamins (nicotinamid, pyridoxine hcl, b12, tocopheroles, ascorbic acids, and others), and antioxidants in general are also included in the useful combinations. The additional drug substance or substances may also be included in or used in combination with drugs that may lead to an undesired level of triglycerides and/or cholesterol. Thus, a composition according to the invention may be included in or used in combination with drugs like e.g. isotretinoin or a retroviral protease inhibitor like HIV protease inhibitors, with an antipsychotic like olanzapine and others. As mentioned, combination products with fibrates are not limited to combinations of two active substances, triple or quadruple therapies could also be of particular interest. The Vehicle Vehicles useful in the present context are vehicles, which are water-miscible, hydrophilic or hydrophobic. Useful vehicles are non-aqueous substances. Examples of hydrophobic vehicles useful in the present invention are straight chain saturated hydrocarbons, paraffins; fats and oils such as cacao butter, beef tallow, lard; higher fatty acid such as stearic acid, myristic acid, palmitic acid; hydrogenated tallow, substituted and/or unsubstituted triglycerides, yellow beeswax, white beeswax, carnauba wax, castor wax, japan wax, and mixtures thereof. Examples of water-miscible vehicles useful in the present invention are water-miscible polar lipids such as sorbitan esters, polyether glycol esters; higher alcohols such as cetanol, stearyl alcohol; glyceryl monooleate, substituted and/or unsubstituted monoglycerides, substituted and/or unsubstituted diglycerides, and mixtures thereof. In a more preferred embodiment, the vehicle is hydrophilic or water-miscible. Preferably, the vehicle is selected from the group consisting of polyethylene glycols, polyoxyethylene oxides, poloxamers, polyoxyethylene stearates, poly-epsilon caprolactone and mixtures thereof. However, the vehicle may advantageously also be a polyglycolized glyceride such as one of the numerous products sold under the registered trade mark Gelucire®, for example Gelucire 44/14. Examples of useful hydrophilic or water-miscible vehicles are polyvinylpyrrolidones, polyvinylpolyvinylacetate copolymers (PVP-PVA), polyvinyl alcohol (PVA), PVP polymers, acrylic polymers, polymethacrylic polymers (Eudragit RS; Eudragit RL, Eudragit NE, Eudragit E), myristyl alcohol, cellulose derivatives including hydroxypropyl methyl-cellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, pectins, cyclodextrins, galactomannans, alginates, carragenates, xanthan gums and mixtures thereof. The vehicle is preferably a mixture of two or more substances. The vehicle may also be an oily material as defined and described below. Preferably, the melting point of the vehicle is preferably in the range of 10° C. to 250° C., preferably in the range of 30° C. to 100° C., more preferably in the range of 40° C. to 75° C., especially in the range of 40° C. to 70° C. In a preferred embodiment of the invention, the vehicle is polyethylene glycol (PEG), preferably having an average molecular weight of at least 3000, more preferably at least 4000, optionally in admixture with a poloxamer such as e.g. poloxamer 188, in a preferred weight ratio of between 1:3 and 10:1, preferably between 1:1 and 5:1, more preferably between and 3:2 4:1, especially between 2:1 and 3:1, in particular about 7:3. Bioavailability In general, it is known that the absorption and bioavailability of a therapeuticcally active substance can be affected by a variety of factors when administered orally. Such factors include the presence of food in the gastrointestinal tract and, in general, the gastric residence time of a drug substance is significantly longer in the presence of food than in the fasted state. If the bioavailability of a drug substance is affected beyond a certain point due to the presence of food in the gastrointestinal tract, the drug substance is said to exhibit a food effect. Food effects are important because there is a risk associated with administering the drug substance to a patient who has eaten recently. The risk derives from the potential that absorption into the bloodstream may be adversely affected to the point that the patient risks insufficient absorption to remedy the condition for which the drug was administered. In the case of e.g. fenofibrate the situation is different in that food increases the uptake. Thus, lack of intake of food simultaneously with the drug substances may lead to insufficient absorption. The extent of absorption of a commercially available product Tricor® containing fenofibrate (from Abbott) is increased by approximately 35% under fed as compared to fasting conditions. As described above, there remains a need for new pharmaceutical compositions comprising one or more fibrates exhibiting, suitable bioavailability of the active compound and/or reduced or eliminated food effect. In the present context, the term “suitable bioavailability” is intended to mean that administration of a composition according to the invention will result in a bioavailability that is improved compared to the bioavailability obtained after administration of the active substance(s) in a plain tablet; or the bioavailability is at least the same or improved compared to the bioavailability obtained after administration of a commercially available product containing the same active substance(s) in the same amounts. In particular it is desired to obtain more complete uptake of the active compound, and thereby provide for a possible reduction of the administered dosages. Further, pharmaceutical compositions and dosage forms comprising a fibrate may also reduce or negate the need for food to be takes simultaneously with the dosage form thereby allowing patients more freedom on when the drug is taken. Also, improved or enhanced bioavailability will lead to an improved treatment because it will be possible to obtain the same therapeutic response with a decreased dose and/or a less frequent administration and less variability in plasma levels and no food restrictions. Another way of obtaining an improved treatment of conditions where e.g. fenofibrate is indicated is by balancing the release of fenofibrate to the gastro-intestinal tract in such a manner that an enhanced plasma concentration of fenofibrate is obtained initially or delayed with respect to the time of administration, i.e. by applying modified or delayed release compositions containing one or more fibrates. In one embodiment, the invention relates to a pharmaceutical composition in particulate form or solid dosage form comprising one or more fibrates, wherein the composition upon oral administration to a mammal in need thereof exhibits an AUC/AUCcControl value of at least about 1.0, the AUCControl being determined using a commercially available product containing the same fibrate, and the AUC values being determined under similar conditions. No absolute bioavailability data based on an injectable composition are available e.g. for fenofibrate (most likely due to solubility problems in aqueous media). The commercially available compositions containing fenofibrate include surface-active agents and/or e.g. a lipophilic medium. The surface-active agents may impart improved bioavailability and therefore, the bioavailability of such a composition may be sufficient already. However, there is still a need for developing a flexible formulation technique that enables preparation of a variety of dosage forms. Accordingly, the requirement to such improved and/or more flexible compositions may be to obtain the same or better bioavailability than already seen from the commercially available products. Accordingly, in further embodiments of the invention, the AUC/AUCControl value obtained by administering the solid dosage form or pharmaceutical composition of the invention is at least about 1.1 such as, e.g., at least about 1.2, at least about 1.3, at least about 1.4, at least about 1.5, about 1.75 or more, about 1.8 or more, about 1.9 or more, about 2.0 or more, about 2.5 or more, about 2.75 or more, about 3.0 or more, about 3.25 or more, about 3.5 or more, about 3.75 or more, about 4.0 or more, about 4.25 or more, about 4.5 or more, about 4.75 or more or about 5.0 or more, the AUC values being determined under similar conditions. Likewise, the cmax value obtained by administering the solid dosage form or pharmaceutical composition of the invention relative to the cmax value of commercially available Tricor® tablets is at least about 1.1, or at least about 1.2, or at least about 1.3, or at least about 1.4, or at least about 1.5, or at least about 1.6 or more, or at least about 2.0, or at least about 2.5, or at least about 3.0, the cmax values being determined under similar conditions. Another object of the invention is to reduce or eliminate the food effect. Thus, in another aspect, the invention relates to a pharmaceutical composition in particulate form or solid dosage form comprising one or more fibrates, wherein the composition or solid dosage form upon oral administration to a mammal in need thereof does not exhibit a significant adverse food effect as evidenced by a value of (AUCfed/AUCfasted) of at least about 0.85 with a lower 90% confidence limit of at least 0.75. In a specific embodiment, the pharmaceutical composition or solid dosage form of the invention has a value of (AUCfed/AUCfasted) that is about 0.9 or more such as, e.g., about 0.95 or more, about 0.97 or more or about 1 or more. In other words, the difference between a bioequivalence parameter measured after oral administration to a mammal with and without food, respectively, is less than 25% such as, e.g., less than 20%, less than 15%, less than 10% or less than 5%. In another aspect, the invention relates to a pharmaceutical composition in particulate form or solid dosage form comprising a fibrate, wherein the composition upon oral administration to a mammal in need thereof is essentially bioequivalent with a commercially available product containing the same fibrate when administered in the same or lower dose as the commercially available product containing the same fibrate. In specific embodiments thereof, the dose is at the most about 98% w/w such as, e.g., at the most about 95% w/w, at the most about 90% w/w, at the most about 85% w/w, at the most about 80% w/w, at the most about 75% w/w, at the most about 70% w/w, at the most about 65% w/w, at the most about 60% w/w, at the most about 55% w/w or at the most about 50% w/w of the dose of the fibrate administered in the form of a commercially available product containing the same fibrate. Normally, the bioequivalence is determined by means of at least one of the following parameters: tmax (time to reach maximal plasma concentration), cmax (maximal plasma concentration), AUC0-t (area under the curve from time 0 to time t), AUC0-infinity (area under the curve from time 0 to time infinity), W50 (time period where the plasma concentration is 50% or more of Cmax), W75 ((time period where the plasma concentration is 75% or more of cmax) and/or MRT (mean residence time). A major problem with treatment with a fibrate is the large intra- or inter-individual variation. Thus, in a further aspect the invention relates to a pharmaceutical composition in particulate form comprising one or more fibrates, wherein the composition upon oral administration to a mammal in need thereof reduces inter- and/or intra-individual variations compared to those of a commercially available product containing the same fibrate under the same conditions and in a dose that provides an equivalent therapeutic effect. In the comparison tests mentioned above, the commercially available product is Tricor® in the form of tablets or, alternatively, Tricor® in the form of capsules, when the fibrate is fenofibrate. When the fibrate is gemfibrozil then a suitable commercially available product is Lopid®; when the fibrate is bezafibrate a suitable commercially available product is Bezalip®; when the fibrate is clofibrate then a suitable commercially available product is Atromid®; and when the fibrate is ciprofibrate then a suitable commercially available product is Lipanon®. A convenient method for determining whether a suitable amount of a fibrate has been absorbed may be to determine the content of unchanged fibrate excreted via the feces. Thus, in one embodiment the invention relates to a solid pharmaceutical composition or solid dosage form, wherein at most about 25% w/w such as, e.g., at the most about 20% w/w, at the most about 15% w/w, at the most about 10% w/w, at the most about 5% w/w of the fibrate contained in the composition is excreted in the feces after oral administration. Method of Manufacture The particulate composition of the invention may be prepared by any method which is suitable for incorporation of poorly water-soluble active substances. The pharmaceutical compositions may be prepared by any convenient method such as, e.g. granulation, mixing, spray drying etc. A particularly useful method is the method disclosed in the international application published as WO 03/004001, which describes a process for preparation of particulate material by a controlled agglomeration method, i.e. a method, which enables a controlled growth in particle size. The method involves spraying a first composition comprising the active substance and a vehicle in liquid form onto a solid carrier. Normally, the vehicle has a melting point of at least 5° C., but the melting point must indeed be below the melting point of the active substance. In the present invention, the melting point of the vehicle and should not exceed 250° C. It is within the skills of the average practioner to select a suitable vehicle being pharmaceutical acceptable, capable of dispersing or fully or at least partly dissolving the active substance and having a melting point in the desired range using general knowledge and routine experimentation. Suitable candidate for carriers are described in WO 03/004001, which is herein incorporated by reference. In the present context, suitable vehicles are e.g. those mentioned as vehicles or as oily materials as well as those disclosed in WO 03/004001. An advantage of using the controlled agglomeration method described in WO 03/004001 is that it is possible to apply a relatively large amount of a liquid system to a particulate material without having an undesirable growth in particle size. Accordingly, in one embodiment of the invention, the particulate material of a pharmaceutical composition has a geometric weight mean diameter dgw of ≧10 μm such as, e.g. ≧20 μm, from about 20 to about 2000, from about 30 to about 2000, from about 50 to about 2000, from about 60 to about 2000, from about 75 to about 2000 such as, e.g. from about 100 to about 1500 μm, from about 100 to about 1000 μm or from about 100 to about 700 μm, or at the most about 400 μm or at the most 300 μm such as, e.g., from about 50 to about 400 μm such as, e.g., from about 50 to about 350 μm, from about 50 to about 300 μm, from about 50 to about 250 μm or from about 100 to about 300 μm. The compositions and dosage forms of the invention are preferably formed by spray drying techniques, controlled agglomeration, freeze-drying or coating on carrier particles or any other solvent removal process. The dried product contains the active substance present preferably in dissolved form either fully dissolved as a solid solution or partly dissolved as a solid dispersion including a molecular dispersion and a solid solution. However, the composition and dosage forms of the invention are preferably manufactured by a method comprising the steps of: i) bringing the vehicle in liquid form, i.e. melting the vehicle if solid at room temperature, ii) maintaining the liquid vehicle at a temperature below the melting point of the fibrate, iii) dissolving the desired amount of fibrate in the vehicle, iv) spraying the resulting solution onto a solid carrier having a temperature below the melting point of the vehicle, v) mechanically working the resulting composition to obtain particles, i.e. a particulate material, and vi) optionally subjecting the particulate material to conventional methods for preparing solid dosage forms. The pharmaceutical compositions comprising the active substance at least partly in form of a solid dispersion or solution may in principle be prepared using any suitable procedure for preparing pharmaceutical compositions known within the art. A solid dispersion may be obtained in different ways e.g. by employing organic solvents or by dispersing or dissolving the active substance in another suitable medium (e.g. an oily material that is in liquid form at room temperature or at elevated temperatures). Solid dispersions (solvent method) are prepared by dissolving a physical mixture of the active substance (e.g. a drug substance) and the carrier in a common organic solvent, followed by evaporation of the solvent. The carrier is often a hydrophilic polymer. Suitable organic solvents include pharmaceutical acceptable solvent in which the active substance is soluble such as methanol, ethanol, methylene chloride, chloroform, ethylacetate, acetone or mixtures thereof. Suitable water-soluble carriers include polymers such as polyethylene glycol, poloxamers, polyoxyethylene stearates, poly-epsilon-caprolactone, polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-polyvinylacetate copolymer PVP-PVA (Kollidon VA64), polymethacrylic polymers (Eudragit RS, Eudragit RL, Eudragit NE, Eudragit E) and polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), methyl cellulose, and poly(ethylene oxide) (PEO). Polymers containing acidic functional groups may be suitable for solid dispersions, which release the active substance in a preferred pH range providing acceptable absorption in the intestines. Such polymers may be one ore more selected from the group comprising hydroxypropyl methylcellulose phtalate (HMPCP), polyvinyl acetate phtalate (PVAP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), alginate, carbomer, carboxymethylcellulose, methacrylic acid copolymer (Eudragit L, Eudragit S), shellac, cellulose acetate phthalate (CAP), starch glycolate, polacrylin, methyl cellulose acetate phtalate, hydroxypropyulcellulose acetate phthalate, cellulose acetate terephtahalate, cellulose acetate isophthalate and cellulose acetate trimellitate. The weight ratio of active substance to polymer may be in a range of from about 3:1 to about 1:20. However, narrower ranges of from about 3:1 to about 1:5, such as, e.g., from about 1:1 to about 1:3 or about may also be used. Apart from using the organic solvent based method, solid dispersion or solid solutions of one or more fibrates may be also obtained by dispersing and/or dissolving the active compound in the carrier composition used in the controlled agglomeration method. Stabilizing agents etc. may be added in order to ensure the stability of the solid dispersion/solution. Pharmaceutical Excipients and Additives In the present context the terms “pharmaceutically acceptable excipient” are intended to denote any material, which is inert in the sense that it substantially does not have any therapeutic and/or prophylactic effect per se. Such excipient(s) may be added with the purpose of making it possible to obtain a pharmaceutical, cosmetic and/or foodstuff composition, which have acceptable technical properties. Examples of suitable excipients for use in a composition or solid dosage form according to the invention include fillers, diluents, glidants, disintegrants, binders, lubricants etc. or mixture thereof. As the composition or solid dosage form according to the invention may be used for different purposes, the choice of excipients is normally made taken such different uses into considerations. Other pharmaceutically acceptable excipients for suitable use are e.g. acidifying agents, alkalizing agents, preservatives, antioxidants, buffering agents, chelating agents, coloring agents, complexing agents, emulsifying and/or solubilizing agents, flavors and perfumes, humectants, sweetening agents, wetting agents etc. Examples of suitable fillers, diluents and/or binders include lactose (e.g. spray-dried lactose, α-lactose, β-lactose, Tabletose®, various grades of Pharmatose®, Microtose® or Fast-Floc®), microcrystalline cellulose (various grades of Avicel®, Elcema®, Vivacel®, Ming Tai® or Solka-Floc®), hydroxypropylcellulose, L-hydroxypropylcellulose (low substituted), hydroxypropyl methylcellulose (HPMC) (e.g. Methocel E, F and K, Metolose SH of Shin-Etsu, Ltd, such as, e.g. the 4,000 cps grades of Methocel E and Metolose 60 SH, the 4,000 cps grades of Methocel F and Metolose 65 SH, the 4,000, 15,000 and 100,000 cps grades of Methocel K; and the 4,000, 15,000, 39,000 and 100,000 grades of Metolose 90 SH), methylcellulose polymers (such as, e.g., Methocel A, Methocel A4C, Methocel A15C, Methocel A4M), hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylene, carboxymethylhydroxyethylcellulose and other cellulose derivatives, sucrose, agarose, sorbitol, mannitol, dextrins, maltodextrins, starches or modified starches (including potato starch, maize starch and rice starch), calcium phosphate (e.g. basic calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate hydrate), calcium sulfate, calcium carbonate, sodium alginate, collagen etc. Specific examples of diluents are e.g. calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, powdered cellulose, dextrans, dextrin, dextrose, fructose, kaolin, lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose, sugar etc. Specific examples of disintegrants are e.g. alginic acid or alginates, microcrystalline cellulose, hydroxypropyl cellulose and other cellulose derivatives, croscarmellose sodium, crospovidone, polacrillin potassium, sodium starch glycolate, starch, pregelatinized starch, carboxymethyl starch (e.g. Primogel® and Explotabo®) etc. Specific examples of binders are e.g. acacia, alginic acid, agar, calcium carrageenan, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropyl methylcellulose, methylcellulose, pectin, PEG, povidone, pregelatinized starch etc. Glidants and lubricants may also be included in the second composition. Examples include stearic acid, magnesium stearate, calcium stearate or other metallic stearate, talc, waxes and glycerides, light mineral oil, PEG, glyceryl behenate, colloidal silica, hydrogenated vegetable oils, corn starch, sodium stearyl fumarate, polyethylene glycols, alkyl sulfates, sodium benzoate, sodium acetate etc. Other excipients which may be included in a composition or solid dosage form of the invention are e.g. flavoring agents, coloring agents, taste-masking agents, pH-adjusting agents, buffering agents, preservatives, stabilizing agents, anti-oxidants, wetting agents, humidity-adjusting agents, surface-active agents, suspending agents, absorption enhancing agents, agents for modified release etc. Other additives in a composition or a solid dosage form according to the invention may be antioxidants like e.g. ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, potassium metabisulfite, propyl gallate, sodium formaldehylde sulfoxylate, sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol, tocopherol acetate, tocopherol hemisuccinate, TPGS or other tocopherol derivatives, etc. The carrier composition may also contain e.g. stabilising agents. The concentration of an antioxidant and/or a stabilizing agent in the carrier composition is normally from about 0.1% w/w to about 5% w/w. A composition or solid dosage form according to the invention may also include one or more surfactants or substances having surface-active properties. It is contemplated that such substances are involved in the wetting of the slightly soluble active substance and thus, contributes to improved solubility characteristics of the active substance. Suitable surfactans for use in a composition or a solid dosage form according to the invention are surfactants such as, e.g., hydrophobic and/or hydrophilic surfactants such as those disclosed in WO 00/50007 in the name of Lipocine, Inc. Specific examples of suitable surfactants are polyethoxylated fatty acids such as, e.g. fatty acid mono- or diesters of polyethylene glycol or mixtures thereof such as, e.g. mono—or diesters of polyethylene glycol with lauric acid, oleic acid, stearic acid, myristic acid, ricinoleic acid, and the polyethylene glycol may be selected from PEG 4, PEG 5, PEG 6, PEG 7, PEG 8, PEG 9, PEG 10, PEG 12, PEG 15, PEG 20, PEG 25, PEG 30, PEG 32, PEG 40, PEG 45, PEG 50, PEG 55, PEG 100, PEG 200, PEG 400, PEG 600, PEG 800, PEG 1000, PEG 2000, PEG 3000, PEG 4000, PEG 5000, PEG 6000, PEG 7000, PEG 8000, PEG 9000, PEG 1000, PEG 10,000, PEG 15,000, PEG 20,000, PEG 35,000, polyethylene glycol glycerol fatty acid esters, i.e. esters like the above-mentioned but in the form of glyceryl esters of the individual fatty acids; glycerol, propylene glycol, ethylene glycol, PEG or sorbitol esters with e.g. vegetable oils like e.g. hydrogenated castor oil, almond oil, palm kernel oil, castor oil, apricot kernel oil, olive oil, peanut oil, hydrogenated palm kernel oil and the like, polyglycerized fatty acids like e.g. polyglycerol stearate, polyglycerol oleate, polyglycerol ricinoleate, polyglycerol linoleate, propylene glycol fatty acid esters such as, e.g. propylene glycol monolaurate, propylene glycol ricinoleate and the like, mono- and diglycerides like e.g. glyceryl monooleate, glyceryl dioleae, glyceryl mono- and/or dioleate, glyceryl caprylate, glyceryl caprate etc.; sterol and sterol derivatives; polyethylene glycol sorbitan fatty acid esters (PEG-sorbitan fatty acid esters) such as esters of PEG with the various molecular weights indicated above, and the various Tween® series; polyethylene glycol alkyl ethers such as, e.g. PEG oleyl ether and PEG lauryl ether; sugar esters like e.g. sucrose monopalmitate and sucrose monolaurate; polyethylene glycol alkyl phenols like e.g. the Triton® X or N series; polyoxyethylene-polyoxypropylene block copolymers such as, e.g., the Pluronic® series, the Synperonic® series, Emkalyx®, Lutrol®, Supronic® etc. The generic term for these polymers is “poloxamers” and relevant examples in the present context are Poloxamer 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403 and 407; sorbitan fatty acid esters like the Span® series or Ariacel® series such as, e.g. sorbinan monolaurate, sorbitan monopalmitate, sorbitan monooleate, sorbitan monostearate etc.; lower alcohol fatty acid esters like e.g. oleate, isopropyl myristate, isopropyl palmitate etc.; ionic surfactants including cationic, anionic and zwitterionic surfactants such as, e.g. fatty acid salts, bile salts, phospholipids, phosphoric acid esters, carboxylates, sulfates and sulfonates etc. When a surfactant or a mixture of surfactants is present in a composition or a solid dosage form of the invention, the concentration of the surfactant(s) is normally in a range of from about 0.1-80% w/w such as, e.g., from about 0.1 to about 20% w/w, from about 0.1 to about 15% w/w, from about 0.5 to about 10% w/w, or alternatively, from about 0.10 to about 80% w/w such as, e.g. from about 10 to about 70% w/w, from about 20 to about 60% w/w or from about 30 to about 50% w/w. In a specific aspect of the invention, the at least one of the one or more pharmaceutically acceptable excipients is selected from the group consisting of silica acid or a derivative or salt thereof including silicates, silicon dioxide and polymers thereof; magnesium aluminosilicate and/or magnesium aluminometasilicate, bentonite, kaolin, magnesium trisilicate, montmorillonite and/or saponite, Nuesellin™. Sorption Materials Materials such as those mentioned immediately above are especially useful as a sorption material for oily materials in pharmaceuticals, cosmetics and/or foodstuff. In a specific embodiment, the material is used as a sorption material for oily materials in pharmaceuticals. The material that has the ability to function as a sorption material for oily materials is also denoted “oil sorption material”. Furthermore, in the present context the term “sorption” is used to denote “absorption” as well as “adsorption”. It should be understood that whenever one of the terms is used it is intended to cover the phenomenon absorption as well as adsorption. The terms “sorption material” and “oil sorption material” is intended to have the same meaning. A sorption material suitable for use according to the present invention is a solid pharmaceutically acceptable material, which—when tested as described herein— i) has an oil threshold value of 10% or more, when tested according to the Threshold Test disclosed herein, and which material is used in a composition of the invention further fulfilling one or both of i) and ii): i) the compositon releases at least 30% of the hydrophobic or a hydrophilic or water-miscible vehicle, when tested according to the Release Test; ii) the composition, in the form of a tablet, contains at least about 90% w/w of the oil-sorption material, and exhibits a disintegration time of at the most 60 minutes when tested according to the Ph. Eur. Disintegration Test. The material is especially useful as a sorption material for oily materials in pharmaceuticals, cosmetics and/or foodstuff, especially in pharmaceuticals. It is important that the oil sorption material fulfills at least two tests. One of the tests is mandatory, i.e. the Threshold Test must be met. This test gives a measure for how much oily material the oil sorption material is able to absorb while retaining suitable flowability properties. It is important that an oil sorption material for use according to the invention (with or without oil absorbed) has a suitable flowability so that it easily can be admixed with other excipients and/or further processed into compositions without significant problems relating to e.g. adherence to the apparatus involved. The test is described below in Materials and Methods and guidance is given for how the test is carried out. The Threshold Test involves the determination of the flowability of the solid material loaded with different amounts of oil. From above it is seen that the oil threshold value normally must exceed 10% and often the oil sorption material has an oil threshold value of at least about 15%, such as, e.g., at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, or at least about 45%. An especially suitable material for use according to the invention, Aeropearl 300, has a very high oil threshold value of about 60%. Accordingly, materials that have an oil threshold value of at least about 50%, such as, e.g., at least about 55% or at least about 60% are used in specific embodiments of the present invention. Furthermore, an oil sorption material for use according to the invention must fulfill at least one further test, namely a release test and/or a disintegration test. The release test gives a measure of the ability of an oil sorption material to release the oil that is absorbed to the material when contacted with water. This ability is very important especially in those situations where an active substance is contained in the oily material. If the oil sorption material is not capable of releasing the oil from the material then there is a major risk that the active substance will only to a minor degree be released from the material. Accordingly, it is envisaged that bioavailability problems relating to e.g. poor absorption etc. will occur in such situations. The requirements for the release test are that the solid pharmaceutical acceptable material, when tested as described herein, releases at least about 30% such as, e.g., at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55% or at least about 60% of an oil. As it appears from the examples herein a suitable oil sorption material like Aeroperl 300 has a much higher release. Therefore, in a specific embodiment of the invention, the solid pharmaceutical acceptable material, when tested as described herein, releases at least about 65% such as, e.g., at least about 70%, at least about 75% or at least about 80% of an oil. The disintegration test is not performed on the solid material in particulate form but on a tablet made of the solid material. A requirement with respect to disintegration is important in order to ensure that the solid material, when included in solid dosage forms, does not impart unwanted properties to the dosage form e.g. leading to unwanted properties with respect to dissolution and bioavailability of the active substance contained in the dosage form. For some of the materials suitable for use according to the invention it is possible to press tablets containing 100% w/w of the solid material itself. If this is the case, the test is carried out on such tablets. However, it is envisaged that there may be situations where it is rather difficult to prepare tablets from the solid material alone. In such cases it is possible to add pharmaceutically acceptable excipients normally used in the preparation of compressed tablets up to a concentration of 10% wtw or less. Examples of suitable pharmaceutically acceptable excipients include fillers, diluents, binders and lubricants. However, excipients, normally classified as disintegrants, should be avoided. Accordingly, the solid pharmaceutical acceptable material for use according to invention, when tested as described herein, in the form of a tablet should have a disintegration time of at the most 1 hour, when tested according to Ph. Eur. Disintegration test, the tablet containing about 90% w/w or more, such as, e.g., about 92.5% w/w or more, about 95% w/w or more, about 97.5% w/w or more or about 100% of the pharmaceutically acceptable material. In a further embodiment, the solid pharmaceutical acceptable material, when tested as described herein, in the form of a tablet has a disintegration time of at the most about 50 min, such as, e.g., at the most about 40 min, at the most about 30 min, at the most about 20 min, at the most about 10 min or at the most about 5 min, when tested according to Ph. Eur. Disintegration test, the tablet containing about 90% w/w or more, such as, e.g., about 92.5% w/w or more, about 95% w/w or more, about 97.5% w/w or more or about 100% of the pharmaceutically acceptable material. In a specific embodiment, the solid material used as a sorption material fulfils all three tests. Thus, the solid pharmaceutical acceptable material, when tested as described herein, i) has an oil threshold value of at least about 10%, such as, e.g., at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55% or at least about 60%, ii) releases at least about 30% such as, e.g., at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75% or at least about 80% of an oil, and iii) in the form of a tablet has a disintegration time of at the most 1 hour such as at the most about 50 min, at the most about 40 min, at the most about 30 min, at the most about 20 min, at the most about 10 min or at the most about 5 min, when tested according to Ph. Eur. Disintegration test, the tablet containing about 90% w/w or more, such as, e.g., about 92.5% w/w or more, about 95% w/w or more, about 97.5% w/w or more or about 100% of the pharmaceutically acceptable material. Other specific embodiments of the invention are those, wherein the solid pharmaceutical material used as a sorption material in a composition according of the invention, when tested as described herein, i) has an oil threshold value of at least about 55%; the solid pharmaceutical material, when tested as described herein, ii) releases at least about 75% of an oil; and/or the solid pharmaceutical material, when tested as described herein, iii) in the form of a tablet has disintegration time of at the most about 10 min, when tested according to Ph. Eur. Disintegration test, the tablet containing about 97.5% w/w of the pharmaceutically acceptable material. The solid pharmaceutically acceptable material used as a sorption material in a composition according to the invention is normally a particulate material in the form of e.g. powders, particles, granules, granulates etc. Such particulate material suitable for use as an oil sorption material has normally a bulk density of about 0.15 g/cm3 or more such as, e.g., at least about 0.20 g/cm3 or at least about 0.25 g/cm3. Furthermore, the oil sorption material normally has an oil absorption value of at least about 100 g oil/100 g such as, e.g., at least about 150 g oil/100 g, at least about 200 g oil/100 g, at least about 250 g oil/100 g, at least about 300 g oil/100 g or at least about 400 g oil/100 g pharmaceutically acceptable material. The oil absorption value is determined as described in the experimental section herein. The present inventors have found that a common feature of some of the materials suitable for use as oil sorption material is that they have a relatively large surface area. Accordingly, pharmaceutically acceptable material for use as an oil sorption material according to the invention may have a BET surface area of at least 5 m2/g such as, e.g., at least about 25 m2/g, at least about 50 m2/g, at least about 100 m2/g, at least about 150 m2/g, at least about 200 m2/g, at least about 250 m2/g or at least about 275 m2/g. As mentioned above one of the characteristic features of a pharmaceutically acceptable material for use as an oil sorption material according to the invention is that it retains a good flowability even if it has been loaded with oily material. Thus, the flowability of the pharmaceutically acceptable material loaded with 25% w/w or more such as, e.g. 30% w/w or more, 40% wow or more, 45% w/w or more, 50% w/w or more, 55% w/w or more, 60% w/w or more, 65% w/w or more or about 70% w/w viscoleo will normally meet the Ph. Eur. requirements. Notably, the oil sorption material may comprise a silica acid or a derivative or salt thereof such as, e.g., silicon dioxide or a polymer thereof as a pharmaceutically acceptable excipient. However, dependent on the quality employed a silicon dioxide may be a lubricant or it may be an oil sorption material. Qualities fulfilling the latter function seem to be most important. In a specific embodiment, a composition or solid dosage form according to invention comprises a pharmaceutically acceptable excipient that is a silicon dioxide product that has properties corresponding to Aeroperl® 300 Use of an oil sorption material in compositions or dosage forms according to the invention is very advantageous for the preparation of pharmaceutical, cosmetic, nutritional and/or food compositions, wherein the composition comprises oily material. One of the advantages is that is it possible to incorporate a relatively large amount of and oily material and still have a material that is solid. Thus, it is possible to prepare solid compositions with a relatively high load of oily materials by use of an oil sorption material according to the invention. Within the pharmaceutical field it is an advantage to be able to incorporate a relatively large amount of an oily material in a solid composition especially in those situation where the active substance does not have suitable properties with respect to water solubility (e.g. poor water solubility), stability in aqueous medium (i.e. degradation occurs in aqueous medium), oral bioavailability (e.g. low bioavailability) etc., or in those situations where it is desired to modify the release of an active substance from a composition in order to obtain a controlled, delayed, sustained and/or pulsed delivery of the active substance. Thus, in a specific embodiment it is used in the preparation of pharmaceutical compositions. The oil sorption material for use in the processing into solid compositions normally absorbs about 5% w/w or more, such as, e.g., about 10% w/w or more, about 15% w/w or more, about 20% w/w or more, about 25% w/w or more, about 30% w/w or more, about 35% w/w or more, about 40% w/w or more, about 45% w/w or more, about 50 w/w or more, about 55% w/w or more, about 60% w/w or more, about 65% w/w or more, about 70% w/w or more, about 75% w/w or more, about 80% w/w or more, about 85% w/w or more, about 90% w/w or more or about 95% wow or more of an oil or an oily material and is still a solid material. Oily Materials An important aspect of the invention is compositions or solid dosage forms comprising an oily material. In the present context the term “oily materials” is used in a very broad sense including oils, waxes, semi-solid materials and materials that normally are used as solvents (such as organic solvents) or cosolvents within the pharmaceutical industry, and the term also includes therapeutically and/or prophylactically active substances that are in liquid form at ambient temperature; furthermore the term includes emulsions like e.g. microemulsions and nanoemulsions and suspensions. The oils and oily-like materials that can be absorbed will normally be liquid at ambient or elevated temperature (for practical reasons the max. temperature is about 250° C.). They may be hydrophilic, lipophilic, hydrophobic and/or amphiphilic materials. The oily materials that are suitable for use in the present context are substances or materials, which have a melting point of at least about 10° C. and at the most about 250° C. In specific embodiments of the invention, the oily material has a melting point of about 5° C. or more such as, e.g., about 10° C. or more, about 15° C. or more, about 20° C. or more or about 25° C. or more. In further embodiments of the invention, the oily material has a melting point of at least about 25° C. such as, e.g., at least about 30° C. at least about 35° C. or at least about 40° C. For practical reasons, the melting point may normally not be too high, thus, the oily material normally has a melting point of at the most about 300° C. such as, e.g., at the most about 250° C., at the most about 200° C., at the most about 150° C. or at the most about 100° C. If the melting point is higher a relatively high temperature may promote e.g. oxidation or other kind of degradation of an active substance in those cases where e.g. a therapeutically and/or prophylactically active substance is included. In the present context, melting points are determined by DSC (Differential Scanning Calorimetry). The melting point is determined as the temperature at which the linear increase of the DSC curve intersects the temperature axis (see FIG. 1 for further details). Interesting oily materials are in general substances, which are used in the manufacture of pharmaceuticals as so-called melt binders or solid solvents (in the form of solid dosage form), or as co-solvents or ingredients in pharmaceuticals for topical use. It may be hydrophilic, hydrophobic and/or have surface-active properties. In general hydrophilic and/or hydrophobic oily materials are suitable for use in the manufacture of a pharmaceutical composition comprising a therapeutically and/or prophylactically active substance that has a relatively low aqueous solubility and/or when the release of the active substance from the pharmaceutical composition is designed to be immediate or non-modified. Hydrophobic oily materials, on the other hand, are normally used in the manufacture of a modified release pharmaceutical composition. The above-given considerations are simplified to illustrate general principles, but there are many cases where other combinations of oily materials and other purposes are relevant and, therefore, the examples above should not in any way limit the invention. Typically, a suitable hydrophilic oily material is selected from the group consisting of: polyether glycols such as, e.g., polyethylene glycols, polypropylene glycols; polyoxyethylenes; polyoxypropylenes; poloxamers and mixtures thereof, or it may be selected from the group consisting of: xylitol, sorbitol, potassium sodium tartrate, sucrose tribehenate, glucose, rhamnose, lactitol, behenic acid, hydroquinon monomethyl ether, sodium acetate, ethyl fumarate, myristic acid, citric acid, Gelucire 50/13, other Gelucire types such as, e.g., Gelucire 44/14 etc., Gelucire 50/10, Gelucire 62/05, Sucro-ester 7, Sucro-ester 11, Sucro-ester 15; maltose, mannitol and mixtures thereof. A suitable hydrophobic oily material may be selected from the group consisting of: straight chain saturated hydrocarbons, sorbitan esters, paraffins; fats and oils such as e.g., cacao butter, beef tallow, lard, polyether glycol esters; higher fatty acid such as, e.g. stearic acid, myristic acid, palmitic acid, higher alcohols such as, e.g., cetanol, stearyl alcohol, low melting point waxes such as, e.g., glyceryl monostearate, glyceryl monooleate, hydrogenated tallow, myristyl alcohol, stearyl alcohol, substituted and/or unsubstituted monoglycerides, substituted and/or unsubstituted diglycerides, substituted and/or unsubstituted triglycerides, yellow beeswax, white beeswax, carnauba wax, castor wax, japan wax, acetylate monoglycerides; NVP polymers, PVP polymers, acrylic polymers, or a mixture thereof. In an interesting embodiment, the oily material is a polyethylene glycol having an average molecular weight in a range of from about 400 to about 35,000 such as, e.g., from about 800 to about 35,000, from about 1,000 to about 35,000 such as, e.g., polyethylene glycol 1,000, polyethylene glycol 2,000, polyethylene glycol 3,000, polyethylene glycol 4,000, polyethylene glycol 5,000, polyethylene glycol 6000, polyethylene glycol 7,000, polyethylene glycol 8,000, polyethylene glycol 9,000 polyethylene glycol 10,000, polyethylene glycol 15,000, polyethylene glycol 20,000, or polyethylene glycol 35,000. In certain situations polyethylene glycol may be employed with a molecular weight from about 35,000 to about 100,000. In another interesting embodiment, the oily material is polyethylene oxide having a molecular weight of from about 2,000 to about 7,000,000 such as, e.g. from about 2,000 to about 100,000, from about 5,000 to about 75,000, from about 10,000 to about 60,000, from about 15,000 to about 50,000, from about 20,000 to about 40,000, from about 100,000 to about 7,000,000 such as, e.g., from about 100,000 to about 1,000,000, from about 100,000 to about 600,000, from about 100,000 to about 400,000 or from about 100,000 to about 300,000. In another embodiment, the oily material is a poloxamer such as, e.g. Poloxamer 188, Poloxamer 237, Poloxamer 338 or Poloxamer 407 or other block copolymers of ethylene oxide and propylene oxide such as the Pluronic® and/or Tetronic® series. Suitable block copolymers of the Pluronic® series include polymers having a molecular weight of about 3,000 or more such as, e.g. from about 4,000 to about 20,000 and/or a viscosity (Brookfield) from about 200 to about 4,000 cps such as, e.g., from about 250 to about 3,000 cps. Suitable examples include Pluronic® F38, P65, P68LF, P75, F77, P84, P85, F87, F88, F98, P103, P104, P105, F108, P123, F123, F127, 10R8, 17R8, 25R5, 25R8 etc. Suitable block copolymers of the Tetronic® series include polymers having a molecular weight of about 8,000 or more such as, e.g., from about 9,000 to about 35,000 and/or a viscosity (Brookfield) of from about 500 to about 45,000 cps such as, e.g., from about 600 to about 40,000. The viscosities given above are determined at 60° C. for substances that are pastes at room temperature and at 77° C. for substances that are solids at room temperature. The oily material may also be a sorbitan ester such as, e.g., sorbitan diisostearate, sorbitan dioleate, sorbitan monolaurate, sorbitan monoisostearate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesqui-isostearate, sorbitan sesquioleate, sorbitan sesquistearate, sorbitan tri-isostearate, sorbitan trioleate, sorbitan tristearate or mixtures thereof. The oily material may of course comprise a mixture of different oily materials such as, e.g., a mixture of hydrophilic and/or hydrophobic materials. Other suitable oily materials may be solvents or semi-solid excipients like, e.g. propylene glycol, polyglycolised glycerides including Gelucire 44/14, complex fatty materials of plant origin including theobroma oil, carnauba wax, vegetable oils like e.g. almond oil, coconut oil, corn oil, cottonseed oil, sesame oil, soya oil, olive oil, castor oil, palm kernels oil, peanut oil, rape oil, grape seed oil etc., hydrogenated vegetable oils such as, e.g. hydrogenated peanut oil, hydrogenated palm kernels oil, hydrogenated cottonseed oil, hydrogenated soya oil, hydrogenated castor oil, hydrogenated coconut oil; natural fatty materials of animal origin including beeswax, lanolin, fatty alcohols including cetyl, stearyl, lauric, myristic, palmitic, stearic fatty alcohols; esters including glycerol stearate, glycol stearate, ethyl oleate, isopropyl myristate; liquid interesterified semi-synthetic glycerides including Miglycol 810/812; amide or fatty acid alcolamides including stearamide ethanol, diethanolamide of fatty coconut acids, acetic acid esters of mono and diglycerides, citric acid esters of mono and diglycerides, lactic acid esters of mono and diglycerides, mono and di-glycerides, poly-glycerol esters of fatty acids, poly-glycerol poly-ricinoleate, propylene glycol esters of fatty acids, sorbitan monostearates, sorbitan tristearates, sodium stearoyl lactylates, calcium stearoyl lactylates, diacetyl tartaric acid esters of mono and diglycerides etc. The pharmaceutical composition or a solid dosage form according to the invention may have a concentration of the oily material in the composition or the dosage form of about 5% w/w or more such as, e.g., about 10% w/w or more, about 15% w/w or more, about 20% w/w or more, about 25% w/w or more, about 30% w/w or more, about 35% w/w or more, about 40% w/w or more, about 45% w/w or more, about 50 w/w or more, about 55% w/w or more, about 60% w/w or more, about 65% w/w or more, about 70% w/w or more, about 75% w/w or more, about 80% w/w or more, about 85% w/w or more, about 90% w/w or more or about 95% w/w or more. In specific embodiments the concentration of the oily material in a composition or solid dosage form of the invention is in a range from about 20% to about 80% w/w such as, e.g., from about 25% to about 75% w/w. One of the advantages is that is it possible to incorporate a relatively large amount of oily material and still have a solid material. Thus, it is possible to prepare solid compositions with a relatively high load of oily materials by use of an oil sorption material according to the invention. Within the pharmaceutical field it is an advantage to be able to incorporate a relatively large amount of an oily material in a solid composition especially in those situation where the active substance does not have suitable properties with respect to water solubility (e.g. poor water solubility), stability in aqueous medium (i.e. degradation occurs in aqueous medium), oral bioavailability (e.g. low bioavailability) etc., or in those situations where it is desired to modify the release of an active substance from a composition in order to obtain a controlled, delayed, sustained and/or pulsed delivery of the active substance. A further advantage is that the particulate material obtained is a free-flowing powder and therefore readily processable into e.g. solid dosage forms such as tablets, capsules or sachets. Normally, the particulate material has properties that are suitable in order to manufacture tablets by direct compression without addition of large amounts of further additives. A suitable test for test the flowability of the particulate material is the method described in Ph.Eur. and measuring the flow rate of the material out of a funnel with a nozzle (orifice) diameter of 10.0 mm. In an embodiment of the invention, at least a part of the fibrate may be present in the composition in the form of a solid dispersion including a molecular dispersion and a solid solution. Normally, 10% or more such as, e.g., 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more such as, e.g., 95% or more or about 100% w/w of the active substance thereof is present in the composition in dissolved form. Solid Dosage Forms The pharmaceutical composition according to the invention is in particulate form and may be employed as such. However, in many cases it is more convenient to present the composition in the form of granules, pellets, microspheres, nanoparticles and the like or in the form of solid dosage forms including tablets, tablets, beads, capsules, grains, pills, granulates, granules, powder, pellets, sachets, lozenges, troches and the like. A solid dosage form according to the invention may be a single unit dosage form or it may in the form of a polydepot dosage form contain a multiplicity of individual units such as, e.g., pellets, beads and/or granules. Usually, a pharmaceutical composition or a solid dosage form of the invention is intended for administration via the oral, buccal or sublingual administration route. The invention also relates to the above-mentioned presentation form. Within the scope of the invention are compositions/solid dosage forms that are intended to release the active substance in a fast release, a delayed release or modified release manner. A solid dosage form according to the present invention comprises a pharmaceutical composition in particulate form as described above. The details and particulars disclosed under this main aspect of the invention apply mutatis mutandis to the other aspects of the invention. Accordingly, the properties with respect to increase in bioavailability, changes in bioavailability parameters, reduction in adverse food effect as well as release of one or more fibrates etc. described and/or claimed herein for pharmaceutical compositions in particulate form are analogues for a solid dosage form according to the present invention. Usually, the concentration of the pharmaceutical composition in particulate form is in a range of from about 5 to 100% w/w such as, e.g., from about 10% to about 90% w/w, from about 15% to about 85% w/w, from about 20% to about 80% w/w, from about 25% to about 80% w/w, from about 30% to about 80% w/w, from about 35% to about 80% w/w, from about 40% to about 75% w/w, from about 45% to about 75% w/w or from about 50% to about 70% w/w of the dosage form. In an embodiment of the invention, the concentration of the pharmaceutical composition in particulate form is 50% w/w or more of the dosage form. The solid dosage forms of the invention are very stable. For example, the fibrate is present in an amount of at least 90%, or at least 95%, or at least 100%, relative to the amount prior to storage, when assayed after 3 months of storage at a temperature of about 40° C. and a relative humidity of about 75%. Also, the physical stability is very high as can be seen from the Examples below. The solid dosage form according to the invention is obtained by processing the particulate material according to the invention by means of techniques well-known to a person skilled in the art. Usually, this involves further addition of one or more of the pharmaceutically acceptable excipients mentioned herein. The composition or solid dosage form according to the invention may be designed to release one or more fibrates in any suitable manner provided that the increase in bioavailability is maintained. Thus, the active substance may be released relatively fast in order to obtain an enhanced on-set of action, it may be released so as to follow zero or first order kinetics or it may be released in a controlled or modified manner in order to obtain a predetermined pattern of release. Plain formulations are also within the scope of the present invention. The composition or solid dosage form according to the invention may also be coated with a film coating, an enteric coating, a modified release coating, a protective coating, an anti-adhesive coating etc. A solid dosage form according to the invention may also be coated in order to obtain suitable properties e.g. with respect to release of the active substance. The coating may be applied on single unit dosage forms (e.g. tablets, capsules) or it may be applied on a polydepot dosage form or on its individual units. Suitable coating materials are e.g. methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, acrylic polymers, ethylcellulose, cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinylalcohol, sodium carboxymethylcellulose, cellulose acetate, cellulose acetate phthalate, gelatin, methacrylic acid copolymer, polyethylene glycol, shellac, sucrose, titanium dioxide, carnauba wax, microcrystalline wax, zein. Plasticizers and other ingredients may be added in the coating material. The same or different active substance may also be added in the coating material. The pharmaceutical composition or a solid dosage form according to the invention is designed to release the fibrate in a suitable manner. Specific release patterns are disclosed in the appended claims to which reference is made. Herein is also given specific relevant absorption patterns. Other Embodiments of the Invention In yet another aspect, the invention relates to a solid pharmaceutical composition in particulate form comprising one or more fibrates and one or more oily materials, the composition having a suitable flowability as determined according to the method described in Ph.Eur. measuring the flow rate of the composition out of a funnel with a nozzle diameter of 10.0 mm. In order to avoid any adherence to the manufacturing and/or filling equipment it is important that the particulate material is freely flowing. This characteristic is also important in those cases where it is desired to process the particulate material further into other kinds of formulations such as, e.g., solid dosage forms. Yet another aspect of the invention relates to a solid pharmaceutical composition in particulate form comprising one or more fibrates, one or more oily materials and one or more oil-sorption materials, which i) has an oil threshold value of 10% or more, when tested according to the Threshold Test herein, and fulfills at least one of ii) releases at least 30% of an oil, when tested according to the Release Test herein, and iii) in the form of a tablet has a disintegration time of at the most 1 hour, when tested according to Ph. Eur. Disintegration test, the tablet containing about 90% w/w or more of the oil-sorption material. In certain situations, it has been found that it is an advantage to incorporate a sorption material in the composition in order e.g. to enable a high concentration of an oily material. In those cases where the oily material has a melting point of at the most about 250° C., it may be especially suitable to incorporate a sorption material. Suitable examples of oily materials as well as sorption materials are given herein. In a further specific embodiment, the fibrate is present at least partly in the form of a solid dispersion including a solid solution. In a further embodiment, the present invention relates to a solid pharmaceutical composition in particulate form or a solid dosage form comprising one or more fibrates dissolved in one or more oily materials. In this aspect, the fibrate is present in the form of a solid solution in the particulate composition and the presence of a solid solution can be tested by the DSC test mentioned herein. In this aspect, the particulate composition is prepared by dissolving the fibrate in an oily material optionally at elevated temperature and (optionally after addition of further active substances and/or one or more pharmaceutically acceptable excipients) the mixture is sprayed on a carrier as described herein. Preferably, the concentration of the oily material is at least about 10% w/w. Materials and Methods Materials Fenofibrate (supplied by Sigma) Lactose monohydrate 200 mesh (from DMV) Granulated silicium oxide, Aeroperl® 300, (Degussa) Polyethylene glycol 6000, Pluracol® E6000 (from BASF) Poloxamer 188, Pluronic® F-68 (from BASF) Glyceryl monostearate, Rylo® MD50, (from Danisco Cultor), Ph.Eur. Avicel PH200 (microcrystalline cellulose) (from FMC) Magnesium stearate Tablets, capsules or granules might be enteric coated with different types of polymers such as hydroxypropylmethylcellulose acetate succinate (Aqoat), cellulose acetate phthalate CAP, hydroxypropylmethylcellulose phtalate HPMCP or methacrylic acid copolymers such as Eudragit L30D, Eudragit 100/S, Eudragit 100/L. Tricor Tablet Formulation TRICOR® tablets are fenofibrate-containing tablets available for oral administration, either containing 54 mg or 160 mg of micronized fenofibrate per tablet. The tablets contain the following inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, lecithin, microcrystalline cellulose, polyvinyl alcohol, povidone, sodium lauryl sulfate, sodium stearyl fumarate, talc, titanium dioxide, xanthan gum, colorant. Tricor® is indicated as a lipid regulating agent. The recommended dosage of Tricor® is 54-160 mg/day taken with food. Tricor® tablets are provided in strengths of 54 and 160 mg, whereas Tricor® capsules are provided in strengths of 67 and 200 mg. The tablets have a higher bioavailability than the capsules. Other trade names are Lipanthyl®, Lipantil® or Catalip®. Lipanthyl Formulation Lipanthyl®67M results from a process in which fenofibrate is co-micronized with a solid surface-active component to give an intimate and finely divided mixture of the two ingredients. Equipment Laboratory scale fluid bed equipment: Strea-1. The melt feed unit is a prototype composed of separate units for heating of air supplies for the atomizer, pressure tank and feeding tube. Granulate was sieved manually and mixed with extragranular excipients in a Turbula mixer. Tablet compression was performed on a single punch press, Diaf TM20. Methods According to the method of the invention, the fenofibrate drug was dissolved into the melted vehicle(s) and applied on the particulate carrier(s) as follows: The vehicle(s) was melted in a beaker placed in a microwave oven. The beaker was transferred to a temperature controlled heating plate supplied with magnetic stirring. Fenofibrate was dissolved slowly in the melt at a temperature of 75° C. under magnetic stirring. The hot solution was transferred to the pressure tank for melt spray application onto the carrier in the fluid bed. The granulate product was discharged from the fluid bed and sieved through sieve 0.7 mm or 1.0 mm manually. The sieved product was blended with magnesium stearate for 0.5 min in a Turbula mixer. If an extragranular phase has to be incorporated, the extragranular phase was premixed with the granulate in 3 minutes in a Turbula mixer. The tablet compression was performed on a single punch machine Diaf TM20. Threshold Test The test involves determination of flowability according to the method described in Ph.Eur. by measuring the flow rate of the material out of a funnel with a nozzle diameter of 10.0 mm. Viscoleo (medium chain triglycerides MCT; Miglyol 812 N from Condea) was added to 100 g of the solid pharmaceutically acceptable material to be tested for use according to the invention and mixed manually. The mixture obtained was sieved through sieve 0.3 mm to assure a homogenous mixture. The oil was added successively until a flow of 100 g of the mixture could not flow through the nozzle. If the material to be tested has a high bulk volume (e.g. like that of Aeroperl 300) only 50 g of the mixture is used when testing these blends. The maximal concentration of oil where flow of material could be obtained is called the Threshold Value (given as % w/w). Release Test A fat-soluble colorant Sudan II (BDH Gur®) obtained from BDH VWR International 14.3 mg was dissolved in 50.0 g viscoleo (fractionated medium chain triglycerides). 10 g of the oil was added to 10.0 g of the solid pharmaceutically acceptable material to be tested for use according to the present invention and mixed until the oil was fully absorbed in the solid material. The mixture was subsequently sieved through sieve 0.3 mm to achieve a homogeneous mixture. 1.00 g of the mixture was transferred to a centrifugal tube and 3.00 ml of water was added. The suspension was mixed in a blood sample turner for 1 hour and subsequently centrifuged for 10 minutes at 5000 rpm. The upper phase of oil and water was transferred carefully to a beaker and the water was evaporated in an oven at 80° C. until constant weight. The amount of oil released from the solid material was calculated on basis of the weight of the remaining after evaporation of the water phase. Disintegration Test The disintegration time was determined according to the method described in to Ph. Eur. Dissolution Test The test was performed in accordance with Ph. Eur 2.9.3 using the paddle apparatus. The quantification was performed using HPLC with UV-detection. Medium: 900 ml water with 0.75% sodium lauryl sulfate (SLS) Rotation speed: 50 rpm Temperature: 37° C. Sampling time: 10, 20, 30, 45 and 60 minutes Acceptance criteria: >75% at 45 minutes Determination of Bulk Density The bulk density was measured by pouring 100 g of the powder in question in a 250 ml graduated cylinder. The bulk density is given as the tapped bulk density in g/ml. The determination was performed according to Ph. Eur. (apparent volume). Determination of Oil Absorption Value The oil absorption value is determined by adding well-defined amounts (a 10 g) of viscoleo to a well-defined amount of the pharmaceutically acceptable material (100 g) to be tested. The oil absorption value (expressed as g viscoleo/100 g material) is reached when a further addition of 10 g oil results in a material that does not have suitable properties with respect to flowability, i.e. the material does not meet the meet the requirements when tested according to Ph.Eur. (flowability test; see above under Threshold Test herein). Determination of BET Surface Area The apparatus applied was a Micromertics Gemini 2375. The method applied was according to USP volumetric methods based on multiple point determination. Determination of Flowability The flowability was determined according to the method described in Ph.Eur. measuring the flow rate of the material out of a funnel with a nozzle diameter of 10.0 mm. Determination of Weight Variation The tablets prepared in the Examples herein were subject to a test for weight variation performed in accordance with Ph. Eur. Determination of Average Tablet Hardness The tablets prepared in the Examples herein were subject to at test for tablet hardness employing Schleuniger Model 6D apparatus and performed in accordance with the general instructions for the apparatus. Determination of Solid Solution According to the present invention, the fibrate is dissolved in a vehicle. In order to substantiate this, a test involving differential scanning calometry is performed. The test is performed on the particulate composition, solid dosage form or mixture of vehicle and fibrate (after the solid solution is supposed to form). Standard DSC equipment connected to a PC is used. Sample size: 10 mg in alu pans Heating rate: 5° C./min from 27° C. to 110° C. Evaluation: The fibrate is considered to be in dissolved state or non- crystalline if no fibrate endoterm peak is observed and if the melting interval does not significantly shift compared with the vehicle alone. Determination of Geometric Weight Mean Diameter dgw The geometric weight mean diameter was determined by employment of a method of laser diffraction dispersing the particulate material obtained (or the starting material) in air. The measurements were performed at 1 bar dispersive pressure in Sympatec Helos equipment, which records the distribution of the equivalent spherical diameter. This distribution is fitted to a log normal volume-size distribution. When used herein, “geometric weight mean diameter” means the mean diameter of the log normal volume-size distribution. In Vivo Studies in Beagle Dogs In vivo studies with the purpose of determining the bioavailability of the compositions of the present invention relative to the bioavailability of the commercially available fenofibrate tablet formulation, i.e. Tricor®, was performed using Beagle dogs. The experimental work was performed in Denmark using four male Beagle dogs each having a body weight of 12-18 kg (starting weight). The studies were conducted as open, non-randomised, cross-over studies. Each animal was its own control. Oral doses of fenofibrate was administered according to the data below. The dogs were fasted overnight prior to dosing (water ad libitum) and were fed 5 hours after dosing (water ad libitum). Each dog was dosed with the specified dose of fenofibrate without taking the weight of the dog into consideration. Blood samples were collected at vena jugularis extema at the following points of time: Pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing. 4 ml of blood were collected, mixed with EDTA, and the samples were frozen (−80° C.). The blood samples were analyzed using on-line extraction LC/MS and results were given in mg/mL. The determined full blood concentration profiles of fenofibrate were treated using the Pharmacokinetic softwear WinNonlin®, (Pharsight, California; USA) to calculate the pharmacokinetic parameters. All data are dose adjusted, when necessary. The following examples serve the purpose of illustration of the invention and are not intended to limiting the scope of the present invention. Pharmaceutical compositions and dosage forms of the invention are exemplified in examples 1-7. Results of in vitro dissolution tests of dosage forms of the invention are found in example 8. Results of stability tests of dosage forms of the invention are found in example 9. Results of in vivo comparison studies in Beagle dogs (blood plasma concentration) are found in example 10-12. EXAMPLE 1 Immediate Release Tablet with Improved Bioavailability Fenofibrate was dissolved at a concentration of 17% in polyethylene glycol 6000 and Poloxamer 188 (70:30 w/w ratio) at 75° C. 244 g of the melted solution was sprayed on 200 g lactose in a fluid bed Strea-1 at 75° C. The granular product was sieved through sieve 0.7 mm and blended with magnesium stearate for 0.5 min in a Turbula mixer. The mixture was compressed into 10 mm tablets with a strength of 50 mg (540 mg tablet with compound cup shaped). Substance % mg Fenofibrate 9.30 50.00 Lactose 44.78 240.64 PEG 6000 31.80 170.88 Poloxamer 188 13.63 73.24 Magnesium stearate 0.50 2.69 Total 100.00 537.45 Mean disintegration time: 26 min, Hardness: 45 N EXAMPLE 2 Immediate Release Tablet with Improved Bioavailability 10 mm tablets of 50 mg strength (540 mg tablet with compound cup shaped) and having the following composition were prepared as described in Example 1: Substance % mg Fenofibrate 9.30 50.00 Lactose 44.78 240.64 PEG 6000 45.43 244.12 Magnesium stearate 0.50 2.69 Total 100.00 537.45 Mean disintegration time: 21 min, Hardness: 55 N EXAMPLE 3 Immediate Release Tablet with Improved Bioavailability 10 mm tablets of 50 mg strength (540 mg tablet with compound cup shaped) and having the following composition were prepared as described in Example 1: Substance % mg Fenofibrate 9.30 50.00 Lactose 44.78 240.64 PEG 4000 31.80 170.88 Poloxamer 188 13.63 73.24 Magnesium stearate 0.50 2.69 Total 100.00 537.45 Mean disintegration time: 22 min, Hardness: 48 N EXAMPLE 4 Immediate Release Tablet with Improved Bioavailability Fenofibrate was dissolved in polyethylene glycol 4000 in a concentration of 17% at 75° C. 244 g of the melted solution was sprayed on 200 g lactose in a fluid bed Strea-1 at 75° C. The granular product was sieved through sieve 0.7 mm and blended with magnesium stearate for 0.5 min in a Turbula mixer. The mixture was compressed into 10 mm tablets of 50 mg strength (540 mg tablet with compound cup shaped). Substance % mg Fenofibrate 9.30 50.00 Lactose 44.78 240.64 PEG 4000 45.43 244.12 Magnesium stearate 0.50 2.69 Total 100.00 537.45 Mean disintegration time: 21 min, Hardness: 55 N EXAMPLE 5 Immediate Release Tablet with Improved Bioavailability Fenofibrate was dissolved in polyethylene glycol 4000 in a concentration of 17% at 75° C. 244 g of the melted solution was sprayed on 190 g lactose in mixture with 10 g sodium lauryl sulfate (SDS) in a fluid bed Strea-1 at 75° C. The granular product was sieved through sieve 0.7 mm and blended with magnesium stearate for 0.5 min in a Turbula mixer. The mixture was compressed into 10 mm tablets of 50 mg strength (540 mg tablet with compound cup shaped). Substance % mg Fenofibrate 9.30 50.00 Lactose 42.54 228.61 SDS 2.23 12.03 PEG 4000 45.43 244.12 Magnesium stearate 0.50 2.69 Total 100.00 537.45 Mean disintegration time: 18 min, Hardness: 65 N EXAMPLE 6 Immediate Release Tablet with Improved Bioavailability Fenofibrate was dissolved in a concentration of 30% in polyethylene glycol 4000 and Poloxamer 188 (70:30 w/w ratio) at 75° C. 466 g of the melted solution was sprayed on 200 g Aeroperl 300 in a fluid bed Strea-1 at 75° C. The granular product was sieved through sieve 0.7 mm and blended with magnesium stearate for 0.5 min in a Turbula mixer. The mixture was compressed into 13.5 mm tablets of 150 mg strength (720 mg tablet with compound cup shaped). Substance % mg Fenofibrate 20.90 150.00 Aeroperl 300 29.85 214.29 PEG 6000 34.13 245.00 Poloxamer 188 14.63 105.00 Mg-stearat 0.50 3.59 Total 100.00 717.88 Mean disintegration time: 35 min, Hardness: 35 N EXAMPLE 7 Formulations of the Invention Tablets of 50 mg and 160 mg strength, respectively and having the following compositions were prepared as described in Examples 1, 4 and 6: A B C D E Substance Ingredient mg mg mg mg mg Drug Fenofibrate 160.09 50.05 50.08 50.09 159.99 Vehicle 1 PEG6000 208.12 171.09 124.29 — — PEG4000 — — — 244.57 — GMS (Rylo) — — — — 86.15 Vehicle 2 Poloxamer188 89.19 73.33 53.27 — — Carrier Lactose 356.51 231.87 — 232.02 163.01 Aeropearl 300 — — 63.89 — — Excipients Mg stearate 4.09 2.65 1.47 5.32 8.35 Avicel — — — — 417.50 Total 818.00 529.00 293.00 532.00 835.00 Hardness N 60 44 44 47 102 Disintegration Minutes 25 14 30 48 >55 time Diameter Mm Oblong 12 12 10 Oblong EXAMPLE 8 Dissolution Tests The inventive tablet formulation A of example 7 was subjected to a dissolution test as described in Methods with the following results: Time (min) % dissolved 0 0 10 28 20 56 30 74 45 88 60 97 EXAMPLE 9 Stability Tests Samples of the inventive tablet formulation A of example 7 was stored under the following conditions, respectively, and subjected to a dissolution (stability) test as described in Methods after 1 month and 3 months of storage; % dissolved is the percentage of fenofibrate dissolved after 45 minutes: % dissolved Months 25° C. and 60% RH 30° C. and 65% RH 40° C. and 75% RH 0 88 — — 1 99 88 90 3 90 97 90 Samples of the inventive tablet formulation A of example 7 was stored under the following conditions, respectively, and subjected to a fibrate assay with the following results: mg fenofibrate Months 25° C. and 60% RH 30° C. and 65% RH 40° C. and 75% RH 0 163.8 — — 1 161.9 160.1 160.8 3 162.6 164.9 164.4 Samples of the inventive tablet formulation A of example 7 was stored under the following conditions, respectively, and subjected to a degradation product test according to Ph. Eur. (Degradation products A, B, G and Unknown accumulated into Total Degradation Product; HPLC method) with the following results: Total Degradation Product, % w/w, impurity Months 25° C. and 60% RH 30° C. and 65% RH 40° C. and 75% RH 0 0.05 — — 1 0.05 0.05 0.05 3 0.05 0.05 0.05 EXAMPLE 10 In Vivo Study in Dogs An in vivo study of formulation A of example 7,160 mg in Beagle dogs, performed as described above under Methods, relative to Tricor®, 160 mg (Batch no.: 098212E21), gave the following results: Blood concentrations (mg/mL) (average of 4 dogs) after administration of formulation: Formulation Time Invention, A (hr) Tricor ® (160 mg) (160 mg) 0 n.a. n.a. 0.5 367.5 995.8 1.0 612.5 2209.3 1.5 722.0 2627.8 2.0 725.8 2097.3 3.0 443.8 1219.5 4.0 295.3 930.5 6.0 160.5 642.0 8.0 250.3 869.5 12.0 211.8 615.3 24.0 133.3 394.0 48.0 n.a. 164.5 Relative bioavailability based on AUC (invention, A/Tricor®): 306%. Relative cmax(invention, A/Tricor®): 356%. EXAMPLE 11 In Vivo Study in Dogs A second in vivo study of formulation A of example 7, 160 mg in Beagle dogs, performed as described above under Methods, relative to Tricor®, 160 mg (Batch no.: 09821 2E21), gave the following results: Blood concentrations (mg/mL) (average of 4 dogs) after administration of formulation: Formulation Time Invention, A (hr) Tricor ® (160 mg) (160 mg) 0 0 0 0.5 339.3 3616.0 1.0 1318.8 3724.8 1.5 1313.3 2982.0 2.0 1390.0 2355.8 3.0 1361.3 1359.5 4.0 1019.3 1309.5 6.0 969.3 973.8 8.0 667.0 1113.0 12.0 390.3 768.5 24.0 183.3 295.0 48.0 85.0 302.0 Relative bioavailability based on AUC (invention, A/Tricor®): 198%. Relative cmax(invention, A/Tricor®): 238%. EXAMPLE 12 In Vivo Study in Dogs An in vivo study of the formulations B, C and D of example 7, 2×50 mg in Beagle dogs, performed as described above under Methods, relative to Lipanthyl®67M, 2×67 mg (Batch no.: 75641), gave the following results: Blood concentrations (mg/mL) (average of 4 dogs) after administration of formulation: Formulation Time Lipanthyl ® 67M Invention, B Invention, C Invention, D (hr) (2 × 67 mg) (2 × 50 mg) (2 × 50 mg) (2 × 50 mg) 0 0 0 0 0 0.5 187.3 2769.5 227.3 546.0 1.0 669.5 3526.8 521.5 1381.5 1.5 960.3 3106.3 858.3 1615.5 2.0 895.3 2938.0 989.3 1566.8 3.0 433.0 2465.5 902.5 1503.3 4.0 240.0 1492.3 783.8 1719.0 6.0 77.8 809.5 655.8 1034.5 8.0 79.3 1202.8 409.0 1056.0 12.0 291.3 848.0 269.8 597.3 24.0 82.5 378.0 163.8 282.8 48.0 19.3 18.8 51.5 36.5 72.0 0 0 0 0 Relative bioavailability based on AUC (invention, B/Lipanthyl®67M): 532%. Relative cmax(invention, BA/Lipanthyl®67M): 548%. Relative bioavailability based on AUC (invention, C/Lipanthyl®67M): 228%. Relative cmax(invention, C/Lipanthyl®67M): 161%. Relative bioavailability based on AUC (invention, D/Lipanthyl®67M): 424%. Relative cmax(invention, D/Lipanthyl®67M): 329%.
<SOH> BACKGROUND OF THE INVENTION <EOH>Fibrates are lipid regulating agents. Examples of fibrates include gemifibrozil, fenofibrate, bezafibrate, clofibrate and ciprofibrate. The compounds are regarded as prodrugs and are metabolised in vivo to their active metabolites. For illustrative purposes only, the following is based on a specific example of a fibrate, namely fenofibrate. Fenofibrate is chemically named 2-[4-(4-chlorobenzoyl]-2-methyl-propanoic acid, 1-methylethyl ester and has the following structural formula: Fenofibrate is a white solid. The compound is insoluble in water. The melting point is 79-82° C. Fenofibrate is metabolised to the active substance fenofibric acid. Fenofibric acid has an elimination half-life of about 20 hours. Measurement of the detected amount of fenofibric acid in the blood of a patient can reflect the efficacy of fenofibrate uptake. Fenofibric acid produces reductions in total cholesterol (total-C), LDL-C, apo-lipoprotein B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apo-lipoprotein apoAl and apo All. Fenofibrate acts as a potent lipid regulating agent offering unique and clinical advantages over existing products in the fibrate family of drug substances. Fenofibrate produces substantial reduction in plasma triglyceride levels in hypertriglyceridemic patients and in plasma cholesterol and LDL-C in hypercholesterolemic and mixed dyslipidemic patients. Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal subjects by increasing the urinary excretion of uric acid. Clinical studies have demonstrated that elevated levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), and apo-lipoprotein B (apo B) are associated with human atherosclerosis. Decreased levels of high density lipoprotein cholesterol (HDL-C) and its transport complex, apolipoprotein A (apo Al and apo All) are associated with the development of atherosclerosis. Fenofibrate is also effective in the treatment of Diabetes Type II and metabolic syndrome. Fenofibrate is also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types IV and V hyperlipedemia). Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually reduce fasting triglycerides and eliminate chylomicronemia and thereby obviating the need for pharmacologic intervention. Fibrates are drug substances known to be are poorly and variably absorbed after oral administration. Normally they are prescribed to be taken with food in order to increase the bioavailability. There have been a number of improvements in dosage form of the currently most used fibrate, fenofibrate, in an effort to increase the bioavailability of the drug and hence it's efficacy. However, there is still a need for improved dosage forms relative to the currently available compositions and dosage forms, which provide crystalline fenofibrate in micronized form. In particular, there remains a need for a composition and a dosage form exhibiting a suitable bioavailability, which substantially can reduce or overcome the differential between the bioavailability of the drug in patients who are fasted versus the bioavailability of the drug in patients who are fed, and/or which substantially can reduce or overcome the intra- and/or inter-individual variations observed with the current treatment with the available commercial products. Furthermore, there is also a need for novel dosage forms and/or compositions that enable reduction in observed side-effects. Especially, there is an unmet need for developing a solid composition in particulate form in which the fibrate is in a dissolved state and that appears as a composition that is in the form of a powder, granules, granulates, particles, beads, pellets or other forms for particulate material and not in the form of a soft dosage form containing a liquid medium.
<SOH> SUMMARY OF THE INVENTION <EOH>The inventors have now found that the bioavailabilty of fenofibrate can be significantly enhanced by dissolving a fibrate, for example fenofibrate, in a suitable vehicle and using the resulting composition for preparing a solid dosage form, i.e. a dosage form excluding material in liquid form. Fibrate, especially fenofibrate, is known to be insoluble in water, but the present invention provides pharmaceutical compositions and formulations exhibiting immediate release profiles which are comtemplated having significantly increased in vivo bioavailability in patients in need thereof. Especially, the inventors have succeeded in preparing a solid dosage form, such as a tablet, comprising the fibrate in dissolved form. The advantages of a solid and stable dosage form useful for oral administration are well-known. Accordingly, in a first aspect the present invention relates to a solid oral dosage form comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible. Useful solid dosage forms are in the form of tablets, beads, capsules, grains, pills, granulates, granules, powder, pellets, sachets or troches, and useful fibrates are, fenofibrate, bezafibrate, clofibrate, ciprofibrate and active metabolites and analogues thereof including any relevant fibric acid such as fenofibric acid. In a second aspect, the invention relates to a pharmaceutical composition comprising a fibrate dissolved in a vehicle, which is hydrophobic, hydrophilic or water-miscible; and in a further aspect, the invention relates to a solid pharmaceutical composition in particulate form comprising a fibrate, a hydrophobic or a hydrophilic or water-miscible vehicle and an oil-sorption material, which composition exhibits an oil threshold value of at least 10%. In yet another aspect, the invention relates to a method of manufacturing the solid oral dosage form or the pharmaceutical composition of the invention. Further aspects of the invention are evident from the following description. Comparison in vivo tests in dogs have shown, cf. the examples herein, that solid dosage forms and compositions of the invention exhibit significantly enhanced bioavailability of fenofibrate compared to commercially available solid dosage forms containing the same active ingredient, i.e. to Tricor® tablet and Lipanthyl® capsules. Further, it is strongly believed that the present invention provides solid dosage forms and/or compositions of fibrate capable of significantly reducing the intra- and/or inter-individual variation normally observed after oral administration. Furthermore, compositions and/or dosage forms according to the invention provide for a significant reduced food effect, i.e. the absorption is relatively independent on whether the patient takes the composition or dosage form together with or without any meal. It is contemplated that a modified release of the fibrate may reduce the number of gastro-intestinal related side effects. Furthermore, it is contemplated that a significantly larger amount of the fibrate is absorbed and, accordingly, an equally less amount is excreted unchanged via feces. detailed-description description="Detailed Description" end="lead"?
20041108
20100209
20060525
91976.0
A61K920
3
MERCIER, MELISSA S
SOLID DOSAGE FORM COMPRISING A FIBRATE
UNDISCOUNTED
0
ACCEPTED
A61K
2,004
10,513,821
ACCEPTED
Grin-lens arrangement
A lens arrangement for transforming a divergent, generally astigmatic laser beam from a diode laser into a beam having a high degree of rotational symmetry is disclosed. The arrangement comprises, in series, a first cylindrical gradient index lens arranged with its principal axes parallel to the principal axes of the astigmatic laser beam; a second cylindrical gradient index lens arranged with its principal axes parallel to the principal axes of the astigmatic laser beam; and a third cylindrical gradient index lens arranged with its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic laser beam. The first and the second gradient index lenses have such refractive powers that both the fast and the slow axis of the astigmatic laser beam are converged to a focus inside the third gradient index lens.
1. A lens arrangement (100) for transforming a divergent, generally astigmatic laser beam from a diode laser (110) into a beam having a high degree of rotational symmetry, comprising in series: a first cylindrical gradient index lens (101) arranged with its principal axes parallel to the principal axes of the astigmatic laser beam for converging the fast axis of the astigmatic laser beam; a second cylindrical gradient index lens (102) arranged with its principal axes parallel to the principal axes of the astigmatic laser beam for converging the slow axis of the astigmatic laser beam; and a third cylindrical gradient index lens (103) arranged with its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic laser beam for twisting the converged astigmatic laser beam into a beam having a high degree of rotational symmetry, wherein the first and the second gradient index lenses have such refractive powers that both the fast and the slow axis of the astigmatic laser beam are converged to a focus inside the third gradient index lens. 2. A lens arrangement as claimed in claim 1, wherein the refractive powers of the first and the second cylindrical gradient index lenses are matched such that the fast and the slow axes have substantially the same Rayleigh lengths for the focus inside the third gradient index lens. 3. A lens arrangement as claimed in claim 1, wherein the refractive powers of the first and the second lenses are such that the fast and the slow axis of the astigmatic laser beam are converged to a focus is the center of the third gradient index lens. 4. A lens arrangement as claimed in claim 1, wherein the first and the second lens, and the second and the third lens, are separated by means of a respective spacer (104, 105). 5. A lens arrangement as claimed in claim 4, wherein the spacers (104, 105) are made of glass having a refractive index similar to the central refractive index of the lenses (101, 102, 103). 6. A lens arrangement as claimed in claim 4, wherein the lenses and the spacers are bonded together to form a monolithic lens arrangement (100). 7. A method of manufacturing an arrangement (100) of gradient index lenses for transforming a divergent, generally astigmatic laser beam into a beam having a high degree of rotational symmetry, comprising the steps of: arranging a first cylindrical gradient index lens (101) that is adapted to converge the fast axis of the divergent astigmatic beam; arranging a second cylindrical gradient index lens (102) that is adapted to converge the slow axis of the divergent astigmatic beam; and arranging a third cylindrical gradient index lens (103) with its principal axes at 45 degrees with respect to the principal axes of the astigmatic beam, said third cylindrical gradient index lens being adapted to twist the astigmatic beam into a rotationally symmetric beam, wherein the first and the second lenses are adapted to focus the fast and slow axes, respectively, of the astigmatic beam to a focus inside the third lens. 8. A method as claimed in claim 7, wherein the focusing powers of the first and second lenses are matched by polishing the first and/or the second cylindrical gradient index lens to an appropriate length, such that the focusing powers of the first and the second lenses are matched to provide similar Rayleigh lengths for the fast and the slow axes at the focus inside the third lens. 9. A method as claimed in claim 7, further comprising the step of adjusting the length of the third gradient index lens to an appropriate length, in order to transform the focused astigmatic beam into a beam of high rotational symmetry after passage of the third lens. 10. A method as claimed in claim 9, wherein the length of the third gradient index lens is adjusted by polishing and/or grinding the lens to an appropriate length. 11. A method as claimed in claim 7, comprising the further steps of: arranging a first spacer between the first and the second lens; arranging a second spacer between the second and the third lens; and bonding the spacers to the lenses to form a monolithic lens arrangement. 12. A method as claimed in claim 11, wherein the refractive index of each of the spacers is equal to the central refractive index of the lenses. 13. A lens arrangement as claimed in claim 2, wherein the refractive powers of the first and the second lenses are such that the fast and the slow axis of the astigmatic laser beam are converged to a focus is the center of the third gradient index lens. 14. A lens arrangement as claimed claim 2, wherein the first and the second lens, and the second and the third lens, are separated by means of a respective spacer (104, 105). 15. A lens arrangement as claimed claim 3, wherein the first and the second lens, and the second and the third lens, are separated by means of a respective spacer (104, 105). 16. A lens arrangement as claimed claim 13, wherein the first and the second lens, and the second and the third lens, are separated by means of a respective spacer (104, 105). 17. A lens arrangement as claimed in claim 5, wherein the lenses and the spacers are bonded together to form a monolithic lens arrangement (100). 18. A method as claimed in claim 8, further comprising the step of adjusting the length of the third gradient index lens to an appropriate length, in order to transform the focused astigmatic beam into a beam of high rotational symmetry after passage of the third lens. 19. A method as claimed in claim 8, comprising the further steps of: arranging a first spacer between the first and the second lens; arranging a second spacer between the second and the third lens; and bonding the spacers to the lenses to form a monolithic lens arrangement. 20. A method as claimed in claim 9, comprising the further steps of: arranging a first spacer between the first and the second lens; arranging a second spacer between the second and the third lens; and bonding the spacers to the lenses to form a monolithic lens arrangement. 21. A method as claimed in claim 9, comprising the further steps of: arranging a first spacer between the first and the second lens; arranging a second spacer between the second and the third lens; and bonding the spacers to the lenses to form a monolithic lens arrangement.
FIELD OF THE INVENTION The present invention generally relates to beam transformation of astigmatic optical radiation. More particularly, the present invention relates to a lens arrangement for symmetrization of divergent, generally astigmatic optical radiation and to a method of constructing such an arrangement of lenses. BACKGROUND OF THE INVENTION Solid state lasers that are optically pumped by diode lasers have gained an increased attention during the last years. Solid state lasers are often favored in comparison to diode lasers, because a much better beam quality is obtained from solid state lasers. In order for the optical pumping of a solid state laser to be efficient, it is important to match the beam size and beam shape of the pump beam to the size and shape of the transverse area of the lasing mode in the solid state laser. If the pump beam is larger than the lasing mode, there is a loss of energy because not all energy supplied by the optical pumping can be extracted into the lasing mode. For three-level or quasi three-level lasers, there is also a problem if the pump beam is smaller than the lasing mode. In this latter case, no gain is provided to the lasing mode outside the volume occupied by the pump beam, but instead absorption losses occur due to reabsorption of energy from the lasing mode. For the above reasons, the size and shape of the pump beam in a diode pumped solid state laser have generally been adjusted in order to match the lasing mode of the solid state laser to the largest possible extent. To this end, various types of focusing arrangements have been employed. One example of a beam shaper for shaping a beam from a diode laser for the purpose of pumping a solid state laser consists of a thick cylindrical lens that is arranged with its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic diode beam. An arrangement of this type is sometimes called a “beam twister”, and makes an initially.astigmatic beam rotationally symmetric by beam twisting. A theoretical background to beam twisting by means of a thick cylindrical lens is given by Laabs et al. in the article “Twisting of three-dimensional Hermite-Gaussian beams”, Journal of Modern Optics, 1999, vol. 46, no. 4, pp 709-719. Diode lasers in general have very astigmatic emissions, with a highly elliptical beam (large difference in M2-values). The dimension having the highest degree of divergence in the emission from a diode laser is referred to as the fast axis, and the dimension having the lowest degree of divergence is referred to as the slow axis. In order for the beam twister to function properly according to the above-mentioned theory for standard thick lenses, the fast and the slow axis must somehow be made to have similar Rayleigh lengths inside the beam twister. This is generally obtained by means of two intermediate cylindrical lenses arranged between the diode laser and the beam twister. The first of the two intermediate lenses converges the emission in the fast axis, and the second converges the emission in the slow axis. In this way, both the fast and the slow axis can be focused simultaneously inside the beam twister such that a rotationally symmetrical beam is ideally obtained behind the twister. The above-mentioned arrangement for beam twisting has proven to be adequately effective in order to provide a beam for pumping of solid state lasers. However, the cylindrical lenses used makes the arrangement very bulky. Moreover, cumbersome alignment of each individual lens is usually required. Therefore, there is a need for improved arrangements for shaping the output beam from a diode laser. In particular, there is a need for more compact arrangements for beam twisting an astigmatic beam into an ideally rotationally symmetric beam. More compact arrangements are particularly attractive for compact laser sources, where lower cost, automation of manufacturing, and simpler alignment of optical elements are some of the advantages. Furthermore, diode-pumped solid-state lasers are often incorporated as sub-assemblies in other instruments, further increasing the requirements on compactness. In addition, the beam of high rotational symmetry obtained by the present invention may be used directly for various purposes. SUMMARY OF THE INVENTION It is an object of the present invention to meet the need mentioned above, by providing a compact arrangement for symmetrization of an astigmatic laser beam. More particularly, it is an object of the present invention to provide a compact lens arrangement for beam twisting of a divergent, generally astigmatic laser beam into an ideally rotationally symmetric beam (a beam having a high degree of rotational symmetry), which lens arrangement is based on gradient index lenses (GRIN-lenses). Also, it is an object of the present invention to provide an arrangement for equalizing M2-values of emission from a diode laser. By way of introduction, some characteristics of a typical diode laser will be briefly discussed. A diode laser often emits light from an elongated bar or strip. The dimensions of the emitting bar may be about, for example, 1 μm×100 μm. Due to diffraction, the divergence of the emitted light is much greater parallel to the smaller dimension than it is parallel to the larger dimension. Hence, the output from a diode laser is typically a very divergent, astigmatic beam. The transverse axis of the emitted light parallel to the smaller dimension of the emitting bar is called the fast axis, because the divergence is larger in this direction (the light cone spreads faster). The transverse axis of the emitted light parallel to the larger dimension of the emitting bar is called the slow axis, because the divergence is smaller in this direction (the light cone spreads slower than in the former transverse direction). As presented in the article by Laabs et al., mentioned in the background above, a Hermite-Gaussian beam (an astigmatic beam) can be transformed into a Laguerre-Gaussian beam (a rotationally symmetric beam) by a thick cylindrical lens (or two or more thin cylindrical lenses) having its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic Hermite-Gaussian beam. In total, three or four lenses must be aligned simultaneously in the prior art arrangement. A requisite for the transformation to be successful is that the Rayleigh lengths of both transverse directions of the input beam are equal in the transforming cylindrical lens. If this condition is not met, the result is not a rotationally symmetric Laguerre-Gaussian beam, but rather some kind of astigmatic Hermite-Gaussian beam. According to the same article, this kind of transformation is also applicable to astigmatic beams with partial coherence and hence to the astigmatic output from a diode laser. The present invention provides an improvement to the arrangement theoretically described by Laabs et al. by introducing gradient index lenses in a beam transformation arrangement of this kind. Notably, previous set-ups have employed standard curved lenses. Gradient lenses, both spherical and cylindrical, are per se well known in the art. Going from standard lenses to gradient index lenses is not an easy task. One fundamental difference between standard lenses and gradient index lenses is that light is refracted at the surface interface in a standard lens, while refracted throughout the lens in a gradient index lens. Therefore, when constructing a system of gradient index lenses, the length and position of each lens is dependent upon the length and position of the other lenses, in a more complicated way than for standard lenses. There is no existing theory for beam twisting by means of gradient index lenses. Nevertheless, the inventors have found that it is possible to achieve beam twisting in a system of gradient index lenses. However, the potential advantages of gradient index lens arrangements are very attractive. One very attractive feature is that the lenses may be arranged in close contact with each other, to form a substantially monolithic entity, thus allowing a much more compact lens system than is possible to obtain by standard lenses. Moreover, the outer, physical dimensions of gradient index lenses may be the same, even though the refractive powers of different lenses are different. In particular, a cylindrical gradient index lens having a refractive power in a first direction may be physically identical in its outer dimensions to a cylindrical gradient index lens having a refractive power in a second direction. This lack of curved lens surfaces may also facilitate mass-production of compact beam transforming arrangements. Moreover, the use of gradient index lenses provides for easier alignment of individual lenses in a lens arrangement. According to the present invention, a new arrangement of lenses is provided for transforming a divergent, generally astigmatic laser beam into a rotationally symmetric beam. By the present invention, a high degree of rotational symmetry and substantially equal M2-values for an initially astigmatic laser beam can be obtained. In addition, a method of constructing an arrangement of gradient index lenses for transforming a divergent, generally astigmatic laser beam into a rotationally symmetric beam is provided. According to the invention, the arrangement of gradient index lenses comprises a first and a second converging cylindrical gradient index lens for converging the fast and slow axes, respectively, of a divergent laser beam to a focus, and a third cylindrical gradient index lens arranged with its principal axes at 45 degrees with respect to the first and the second lenses (and with respect to the principal axes of the astigmatic laser beam). Preferably, the first and the second lenses converge the divergent laser beam to a focus inside the third cylindrical gradient index lens. In order to achieve the best possible transformation of the astigmatic beam into a rotationally symmetrical beam, it is assumed that, similar to the prior art arrangement, the Rayleigh lengths for the two principal axes of the astigmatic beam should be substantially equal for the focus inside the third lens. As known in the art, the Rayleigh length is the distance from the beam waist (the focus) where the beam diameter has increased by a factor of sqrt(2). Furthermore, the third lens should have a refractive power that is appropriate for transformation into an ideally rotationally symmetrical beam. However, as will be clarified below, the transformed beam is not perfectly rotationally symmetric. Nevertheless, the beam is given a very high degree of rotational symmetry by means of the inventive arrangement. It is to be noted that the refractive power of a gradient index lens is a function of both the refractive index profile therein, and the length thereof. Typically, the refractive effect of a gradient index lens is adjusted by polishing or grinding the lens to an appropriate length. BRIEF DESCRIPTION OF THE DRAWINGS In the following detailed description of preferred embodiments, reference is made to the accompanying drawings, in which: FIG. 1 is a schematic side view of an arrangement according to the invention; FIG. 2 is a schematic top view of the arrangement shown in FIG. 1; FIG. 3 is a schematic drawing of a monolithic lens arrangement according to the invention; FIG. 4 illustrates the fast and slow axes in the arrangement, as well as the dimensions height (h), width (w) and length (l); and FIG. 5 shows a typical focal spot of a beam from a diode laser (a) without beam twisting, and (b) with beam twisting according to the invention. On the drawings, like parts are designated like reference numerals. DESCRIPTION OF PREFERRED EMBODIMENTS An arrangement 100 according to the present invention generally comprises a first 101, a second 102 and a third 103 cylindrical gradient index lens. The lens arrangement 100 has an input side where a divergent, astigmatic-laser beam (e.g. from a diode laser 110) is to be received, and an output side where a transformed beam with a high degree of rotational symmetry is to be delivered. The first lens 101 is on the input side, and the third lens 103 is on the output side. In the following, the action of each of the three lenses will be described with reference to FIGS. 1 and 2, FIG. 1 showing a side view of the arrangement 100 and FIG. 2 showing a top view. In FIGS. 1 and 2, there is also shown a schematic diode laser 110 on the input side. As indicated in FIG. 1, the first cylindrical GRIN-lens 101 has the task of converging the astigmatic laser beam in the fast axis (the most divergent axis). Since it is a cylindrical lens, there is no converging power along the slow axis, as can be seen from FIG. 2. The first lens converges the fast axis light to a focus inside the third cylindrical GRIN-lens 103, virtually without affecting the slow transverse direction. The second cylindrical lens 102, on the other hand, has the task of converging the astigmatic laser beam in the slow axis (the least divergent axis). Again, it being a cylindrical lens, there is no converging power in the fast axis, as illustrated in FIG. 1. Hence, the second lens 102 converges the slow axis light to a focus inside the third cylindrical GRIN-lens 103, virtually without affecting the fast transverse direction. The first cylindrical GRIN-lens 101 is arranged with its principal axes parallel to the principal axes of the astigmatic beam and with its converging power in the fast direction. The second cylindrical lens 102 is also arranged with its principal axes parallel to the principal axes of the astigmatic beam, but with its converging power in the slow direction. Consequently, the first and the second lenses 101 and 102 are arranged at mutually orthogonal orientations. The converging power of each of the first and the second lens is selected such that the fast axis and the slow axis have substantially equal Rayleigh lengths for the focus inside the third lens. This can be accomplished since the focusing lens for the fast axis (viz. the first lens 101) is closer to the diode laser than is the focusing lens for the slow axis (the second lens 102). This situation is illustrated in FIGS. 1 and 2. The third lens 103 is also a cylindrical GRIN-lens. However, the third lens is arranged with its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic beam, in line with the previously discussed beam twisting theory. When the astigmatic beam enters the third lens at 45 degrees, it undergoes a focusing that is different for different portions of the beam. Consequently, the beam cross-section exhibits a twisting effect in the third lens. The length of the third GRIN-lens 103 is adjusted such that the beam is optimally just rotationally symmetric when it exits said lens. If the third lens is too long or too short, the output beam after the lens will not be optimally rotationally symmetric (have a lower degree of rotational symmetry). Turning now to FIG. 3 of the accompanying drawings, a preferred embodiment of the invention will be described in more detail. The beam shaping arrangement 100 comprises a first, a second, and a third lens 101, 102, 103. The lenses are separated by spacers 104, 105, and all of the lenses as well as the spacers are bonded together to form a monolithic lens arrangement. On the input side of the arrangement, a laser diode package 110 is located. It is to be understood that the first lens of the lens arrangement need not be in physical contact with the laser diode package, but may be separated there from. The purpose of the lens arrangement is thus to transform the emission from the laser diode into an output beam on the output side that has a high degree of rotational symmetry (in contrast to the direct output from the laser diode). In this example, the laser diode is a 4W diode commercially available from Sony, having an emitting area of 1 μm×200 μm. Reference is now made both to FIG. 3, showing the physical arrangement; and to FIG. 4, showing the geometry discussed below. The first lens 101 is the lens for converging the fast axis of the light from the laser diode. The dimensions of the first lens are (l, h, w) 1.1×1.3×0.5 mm3. Hence, the distance d1=1.1 mm. The second lens 102 is the lens for converging the slow axis of the light from the laser diode. The dimensions of the second lens are 1.0×1.3×1.3 mm3. Hence., the distance d3=1.0 mm. The first lens and the second lens are separated by a first spacer 104 having the dimensions 5.2×1.3×1.3 mm3 (distance d2=5.2 mm). As mentioned earlier, the first and the second lenses are arranged such that their respective refracting powers are orthogonal. The third lens 103 is the actual beam twisting lens. This lens is arranged with its principal axes at 45 degrees with respect to the first and the second lens. The dimensions of the third lens (the beam twister) are 4.4×1.3×1.3 mm3 (distance d5=4.4 mm). The third lens is separated from the second lens by means of a second spacer 105 having the dimensions 4.1×1.3×1.3 mm3 (distance d4=4.1 mm). Hence, the total length of the lens arrangement is 15.8 mm—a compact arrangement indeed. As for the optical properties of the lenses 101, 102, 103 and the spacers 104, 105, they are as follows. The first lens has a nominal focal length of 0.48 mm (pitch=0.24). The refractive index at the center of the first lens is 1.62, and the lens has a constant refractive index gradient of 1.30 mm−1. The second lens has a nominal focal length of 2.55 mm (pitch=0.08). The refractive index at the center is 1.62, and the refractive index gradient is constant at 0.51 mm−1. The third lens (the beam twister) has a nominal focal length of 1.55 mm (pitch=0.36), a center refractive index of 1.62 and a constant index gradient of 0.51 mm−1. The spacers, of course, have no refractive powers, and a refractive index of 1.62. The lenses and spacers are bonded together by means of an optical glue, such that the monolithic arrangement is achieved. For comparison, FIG. 5 shows the resulting focal spot in absence of the beam twister (FIG. 5a) and with the beam twister (FIG. 5b). For the situation shown in FIG. 5a (only focusing optics, no beam twister), the divergence in the fast axis is about 1/500 mrad and in the slow axis about 50/260 mrad. The focal spot achieved without any twister (third lens) is actually just an image of the emitting surface of the laser diode. As can be seen from FIG. 5a, this focal spot has a very low degree of rotational symmetry. Addition of the beam twister, as illustrated in FIG. 5b, gives equal divergences at 15/15 mrad in both lateral directions. The focal spot size in the case shown in FIG. 5b is about 100×100 μm, which is a reduction of spot size in the slow axis of about 40%. Commercial laser diodes are sometimes provided with a collimating fiber lens on the emitting surface thereof. If such a laser diode is used, the first cylindrical lens of the arrangement according to the present invention can be left out, and the second lens can be replaced by a spherical lens arranged to converge both the fast and the slow axis of the emitted beam. Hence, in this case, the lens arrangement comprises a first fiber lens provided on the emitting surface of the laser diode for collimating/converging the fast axis of the emitted light, a second spherical gradient index lens for converging both the fast and the slow axis towards a focus in the third lens. As previously, the third lens is a cylindrical gradient index lens that is arranged with its principal axes at 45 degrees with respect to the fast and the slow axes of the emitted light. Furthermore, it is in some cases possible to use a cylindrical gradient index lens for the second lens also in this case. In conclusion, it has been shown in the present description how the thick cylindrical lens beam twister described by Laabs et al. can be replaced by a single cylindrical gradient index lens. Moreover, it has been shown how the collecting (converging) lens system prior to the beam twister can be implemented by means of cylindrical gradient index lenses. One particularly attractive advantage of the present invention is that all the cylindrical lenses may be cemented together to form a substantially monolithic entity, wherein the individual lenses are separated from each other by means of glass spacers.
<SOH> BACKGROUND OF THE INVENTION <EOH>Solid state lasers that are optically pumped by diode lasers have gained an increased attention during the last years. Solid state lasers are often favored in comparison to diode lasers, because a much better beam quality is obtained from solid state lasers. In order for the optical pumping of a solid state laser to be efficient, it is important to match the beam size and beam shape of the pump beam to the size and shape of the transverse area of the lasing mode in the solid state laser. If the pump beam is larger than the lasing mode, there is a loss of energy because not all energy supplied by the optical pumping can be extracted into the lasing mode. For three-level or quasi three-level lasers, there is also a problem if the pump beam is smaller than the lasing mode. In this latter case, no gain is provided to the lasing mode outside the volume occupied by the pump beam, but instead absorption losses occur due to reabsorption of energy from the lasing mode. For the above reasons, the size and shape of the pump beam in a diode pumped solid state laser have generally been adjusted in order to match the lasing mode of the solid state laser to the largest possible extent. To this end, various types of focusing arrangements have been employed. One example of a beam shaper for shaping a beam from a diode laser for the purpose of pumping a solid state laser consists of a thick cylindrical lens that is arranged with its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic diode beam. An arrangement of this type is sometimes called a “beam twister”, and makes an initially.astigmatic beam rotationally symmetric by beam twisting. A theoretical background to beam twisting by means of a thick cylindrical lens is given by Laabs et al. in the article “Twisting of three-dimensional Hermite-Gaussian beams”, Journal of Modern Optics, 1999, vol. 46, no. 4, pp 709-719. Diode lasers in general have very astigmatic emissions, with a highly elliptical beam (large difference in M 2 -values). The dimension having the highest degree of divergence in the emission from a diode laser is referred to as the fast axis, and the dimension having the lowest degree of divergence is referred to as the slow axis. In order for the beam twister to function properly according to the above-mentioned theory for standard thick lenses, the fast and the slow axis must somehow be made to have similar Rayleigh lengths inside the beam twister. This is generally obtained by means of two intermediate cylindrical lenses arranged between the diode laser and the beam twister. The first of the two intermediate lenses converges the emission in the fast axis, and the second converges the emission in the slow axis. In this way, both the fast and the slow axis can be focused simultaneously inside the beam twister such that a rotationally symmetrical beam is ideally obtained behind the twister. The above-mentioned arrangement for beam twisting has proven to be adequately effective in order to provide a beam for pumping of solid state lasers. However, the cylindrical lenses used makes the arrangement very bulky. Moreover, cumbersome alignment of each individual lens is usually required. Therefore, there is a need for improved arrangements for shaping the output beam from a diode laser. In particular, there is a need for more compact arrangements for beam twisting an astigmatic beam into an ideally rotationally symmetric beam. More compact arrangements are particularly attractive for compact laser sources, where lower cost, automation of manufacturing, and simpler alignment of optical elements are some of the advantages. Furthermore, diode-pumped solid-state lasers are often incorporated as sub-assemblies in other instruments, further increasing the requirements on compactness. In addition, the beam of high rotational symmetry obtained by the present invention may be used directly for various purposes.
<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the present invention to meet the need mentioned above, by providing a compact arrangement for symmetrization of an astigmatic laser beam. More particularly, it is an object of the present invention to provide a compact lens arrangement for beam twisting of a divergent, generally astigmatic laser beam into an ideally rotationally symmetric beam (a beam having a high degree of rotational symmetry), which lens arrangement is based on gradient index lenses (GRIN-lenses). Also, it is an object of the present invention to provide an arrangement for equalizing M 2 -values of emission from a diode laser. By way of introduction, some characteristics of a typical diode laser will be briefly discussed. A diode laser often emits light from an elongated bar or strip. The dimensions of the emitting bar may be about, for example, 1 μm×100 μm. Due to diffraction, the divergence of the emitted light is much greater parallel to the smaller dimension than it is parallel to the larger dimension. Hence, the output from a diode laser is typically a very divergent, astigmatic beam. The transverse axis of the emitted light parallel to the smaller dimension of the emitting bar is called the fast axis, because the divergence is larger in this direction (the light cone spreads faster). The transverse axis of the emitted light parallel to the larger dimension of the emitting bar is called the slow axis, because the divergence is smaller in this direction (the light cone spreads slower than in the former transverse direction). As presented in the article by Laabs et al., mentioned in the background above, a Hermite-Gaussian beam (an astigmatic beam) can be transformed into a Laguerre-Gaussian beam (a rotationally symmetric beam) by a thick cylindrical lens (or two or more thin cylindrical lenses) having its principal axes rotated 45 degrees with respect to the principal axes of the astigmatic Hermite-Gaussian beam. In total, three or four lenses must be aligned simultaneously in the prior art arrangement. A requisite for the transformation to be successful is that the Rayleigh lengths of both transverse directions of the input beam are equal in the transforming cylindrical lens. If this condition is not met, the result is not a rotationally symmetric Laguerre-Gaussian beam, but rather some kind of astigmatic Hermite-Gaussian beam. According to the same article, this kind of transformation is also applicable to astigmatic beams with partial coherence and hence to the astigmatic output from a diode laser. The present invention provides an improvement to the arrangement theoretically described by Laabs et al. by introducing gradient index lenses in a beam transformation arrangement of this kind. Notably, previous set-ups have employed standard curved lenses. Gradient lenses, both spherical and cylindrical, are per se well known in the art. Going from standard lenses to gradient index lenses is not an easy task. One fundamental difference between standard lenses and gradient index lenses is that light is refracted at the surface interface in a standard lens, while refracted throughout the lens in a gradient index lens. Therefore, when constructing a system of gradient index lenses, the length and position of each lens is dependent upon the length and position of the other lenses, in a more complicated way than for standard lenses. There is no existing theory for beam twisting by means of gradient index lenses. Nevertheless, the inventors have found that it is possible to achieve beam twisting in a system of gradient index lenses. However, the potential advantages of gradient index lens arrangements are very attractive. One very attractive feature is that the lenses may be arranged in close contact with each other, to form a substantially monolithic entity, thus allowing a much more compact lens system than is possible to obtain by standard lenses. Moreover, the outer, physical dimensions of gradient index lenses may be the same, even though the refractive powers of different lenses are different. In particular, a cylindrical gradient index lens having a refractive power in a first direction may be physically identical in its outer dimensions to a cylindrical gradient index lens having a refractive power in a second direction. This lack of curved lens surfaces may also facilitate mass-production of compact beam transforming arrangements. Moreover, the use of gradient index lenses provides for easier alignment of individual lenses in a lens arrangement. According to the present invention, a new arrangement of lenses is provided for transforming a divergent, generally astigmatic laser beam into a rotationally symmetric beam. By the present invention, a high degree of rotational symmetry and substantially equal M 2 -values for an initially astigmatic laser beam can be obtained. In addition, a method of constructing an arrangement of gradient index lenses for transforming a divergent, generally astigmatic laser beam into a rotationally symmetric beam is provided. According to the invention, the arrangement of gradient index lenses comprises a first and a second converging cylindrical gradient index lens for converging the fast and slow axes, respectively, of a divergent laser beam to a focus, and a third cylindrical gradient index lens arranged with its principal axes at 45 degrees with respect to the first and the second lenses (and with respect to the principal axes of the astigmatic laser beam). Preferably, the first and the second lenses converge the divergent laser beam to a focus inside the third cylindrical gradient index lens. In order to achieve the best possible transformation of the astigmatic beam into a rotationally symmetrical beam, it is assumed that, similar to the prior art arrangement, the Rayleigh lengths for the two principal axes of the astigmatic beam should be substantially equal for the focus inside the third lens. As known in the art, the Rayleigh length is the distance from the beam waist (the focus) where the beam diameter has increased by a factor of sqrt(2). Furthermore, the third lens should have a refractive power that is appropriate for transformation into an ideally rotationally symmetrical beam. However, as will be clarified below, the transformed beam is not perfectly rotationally symmetric. Nevertheless, the beam is given a very high degree of rotational symmetry by means of the inventive arrangement. It is to be noted that the refractive power of a gradient index lens is a function of both the refractive index profile therein, and the length thereof. Typically, the refractive effect of a gradient index lens is adjusted by polishing or grinding the lens to an appropriate length.
20050104
20060627
20050804
59616.0
0
SCHWARTZ, JORDAN MARC
GRIN-LENS ARRANGEMENT
UNDISCOUNTED
0
ACCEPTED
2,005
10,513,835
ACCEPTED
Image display device
An image display comprises: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements; an image guide (20) coupled to the image output surface of the display device and comprising a plurality of light transmission guides (80) each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or for a cluster comprising at least a subset of the light transmission guides (80): at the outer periphery of the cluster, the input ends of the light transmission guides are constrained against expansion by a frame formed of a material having thermal expansion properties which are substantially similar to the thermal expansion properties of the image output surface.
1. An image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements; an image guide coupled to the image output surface of the display device and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements; in which, for a cluster comprising at least a subset of the light transmission guides: at the outer periphery of the cluster, the input ends of the light transmission guides are constrained against expansion by a frame formed of a material having thermal expansion properties which are substantially similar to the thermal expansion properties of the image output surface. 2. A display according to claim 1, in which the input ends of light transmission guides within the cluster are coupled to one another by a compressible coupling. 3. A display according to claim 2, in which the compressible coupling is a compressible adhesive. 4. A display according to claim 1, in which the frame is formed of a glass material. 5. A display according to claim 1, in which the frame is formed of a metal material. 6. A display according to claim 1, in which the cluster comprises substantially all of the light transmission guides. 7. A display according to claim 1, in which the frame is coupled to the light transmission guides in a manner which is optically similar to the manner in which light transmission guides are coupled to each other. 8. A display according to claim 7, in which the frame comprises an inner frame having optical properties substantially similar to the optical properties of the light transmission guides, and an outer frame having thermal expansion properties substantially similar to the thermal expansion properties of the image output surface. 9. A display according to claim 8, wherein the inner frame comprises a continuous boundary of material surrounding the cluster of light transmission guides. 10. A display according to claim 8, wherein the inner frame comprises a boundary of truncated light transmission guides surrounding the cluster of light transmission guides, the truncated light transmission guides having input ends adjacent to the image output surface and truncated output ends. 11. A display according to claim 9, further comprising an absorbing material arranged with respect to a light propagation path(s) defined by the continuous boundary of material to inhibit light transmission along the light propagation path. 12. A display according to claim 10, further comprising an absorbing material arranged with respect to a light propagation path(s) defined by the truncated light transmission guides to inhibit light transmission along the light propagation path. 13. An image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements; an image guide coupled to the image output surface of the display device and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that each light transmission guide receives light from respective groups of one or more pixel elements; in which: the input ends of the light transmission guides are individually coupled to respective areas on the image output surface; and the input ends of the light transmission guides are not coupled to one another along a predetermined distance measured from the input ends. 14. A display according to claim 13, wherein the predetermined distance is less than the length of the light transmission guides. 15. An image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over an active pixel region of the image output surface; an image guide coupled to the active pixel region of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements; in which: the image output surface has further pixel elements disposed around the periphery of the active pixel region; and the image guide can expand thermally so that the input of the image guide encompasses the further pixels. 16. A display according to claim 15, in which the image output surface has further pixel elements disposed around the periphery of the active pixel region over a guard band region narrower than the input end of a light transmission guide. 17. A display according to claim 15, in which each light transmission guide is arranged to receive light from two or more pixel elements. 18. A display according to claim 15, in which the further pixels are arranged to display substantially the same picture information as nearby pixels within the active pixel region. 19. A tiled image display comprising: a tiled array of displays according to claim 15, arranged so that viewing surfaces formed by the output ends of the image guides abut to form a larger composite viewing surface; in which the further pixels are arranged to display substantially the same picture information as pixels within the active pixel region of an adjacent display in the tiled array which are adjacent to the further pixels in the composite viewing surface. 20. A tiled image display comprising: a tiled array of displays according to claim 15, arranged so that viewing surfaces formed by the output ends of the image guides abut to form a larger composite viewing surface; in which the further pixels are selectably operable to display either substantially the same picture information as pixels within the active pixel region of an adjacent display in the tiled array which are adjacent to the further pixels in the composite viewing surface or substantially the same picture information as nearby pixels within the active pixel region of the same display. 21. A tiled image display according to claim 20, wherein the picture information displayed by the further pixels is user selectable. 22. A tiled image display according to claim 20, wherein the picture information displayed by the further pixels is automatically selected on the basis of predetermined criteria. 23. A tiled display according to claim 22, further comprising a detector for detecting the type of information being displayed by the nearby pixels and selecting the picture information displayed by the further pixels on the basis of the detection result. 24. A tiled display according to claim 23, wherein if the detector detects information having at least a threshold rate of change of contrast and/or hue, the picture information displayed by the further pixels will be selected to be substantially the same picture information as nearby pixels within the active pixel region of the same display. 25. A tiled display according to claim 23, wherein if the detector detects information having less than the threshold rate of change of contrast and/or hue, the picture information displayed by the further pixels will be selected to be substantially the same picture information as pixels within the active pixel region of an adjacent display in the tiled array which are adjacent to the further pixels in the composite viewing surface. 26. An image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over a plurality of separated active pixel regions of the image output surface; an image guide coupled to the active pixel regions of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements and the output ends of the light transmission guides forming a contiguous output surface; in which: the input ends of the light transmission guides are arranged into a plurality of sections, each section being associated with a different one of the active pixel regions of the image output surface, the light transmission guides in each section being coupled to the active pixel region associated with that section. 27. A display according to claim 26, further comprising a registration aid disposed adjacent to the active areas of the image output surface, each section of input ends of the light transmission guides being butted against the registration aid. 28. A display according to claim 27, wherein the registration aid has thermal expansion properties substantially similar to the thermal expansion properties of the image output surface. 29. A display according to claim 27 or 28, wherein the registration aid comprises a cruciform frame attached to non-active areas of the image output surface. 30. An image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over an active pixel region of the image output surface; an image guide coupled to the active pixel region of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements, the light transmission guides being coupled together along at least a portion of their length; in which: the image guide is coupled to the image output surface over less than the whole active pixel region of the image output surface, the image guide being coupled to the image output surface such that the image guide can expand with respect to the area coupled. 31. A display according to claim 30, wherein the image guide is coupled to 30% or less of the active pixel region of the image output surface. 32. A display according to claim 30, wherein the image guide is coupled to 10% or less of the active pixel region of the image output surface. 33. A display according to claim 30, wherein the image guide is coupled to the image output surface using an adhesive. 34. A display according to claim 33, wherein the uncoupled area between the active pixel region of the image output surface and the image guide is substantially filled with a non-adhesive material having substantially similar optical properties to the adhesive, and having a lower modulus of elasticity than the adhesive. 35. A display according to claim 33, wherein the uncoupled area between the active pixel region of the image output surface and the image guide is substantially filled with a non-adhesive liquid or gel material having substantially similar optical properties to the adhesive. 36. A display according to claim 35, wherein the liquid or gel material is sufficiently viscous to prevent it spontaneously flowing out of the uncoupled area. 37. A display according to claim 30, wherein the image is displayed as a spaced array of pixel elements over a plurality of separated active pixel regions of the image output surface, and the input ends of the light transmission guides are arranged as a plurality of groups, each group being coupled to a different one of the active pixel regions of the image output surface. 38. A display according to claim 30, further comprising one or more reference points coupled to the image output surface at the perimeter of the image guide and arranged to impede rotation of the image guide with respect to the image output surface. 39. A display according to claim 1, in which the input ends of the light transmission guides are coupled to a substrate having thermal expansion properties substantially similar to the thermal expansion properties of the image output surface, the substrate being removably coupled to the image output surface. 40. A display according to claim 1, in which the display device is a panel display device. 41. A display according to claim 40, in which the panel display device is a liquid crystal panel display device. 42. A display according to claim 1, in which the image output surface is formed of a glass material. 43. A display according to claim 42, wherein a polymeric layer is adhered to the image output surface, the expansion of the image output surface resulting in equivalent expansion of the further layer. 44. A display according to claim 1, in which the light transmission guides are formed of a polymer or plastics material. 45. An array of image displays according to claim 1, arranged so that viewing surfaces formed by the output ends of the image guides abut to form a larger composite viewing surface. 46. A method of manufacture of a display according to claim 15, comprising the steps of: assembling an array of light transmission guides; inserting interdigital guide members through the array in two lateral directions so as to guide each light transmission guide to a required position for coupling to the image output surface of a display device; coupling the light transmission guides to the image output surface of the display device; and withdrawing the guide members. 47. A method according to claim 46, in which the coupling step comprises gluing the light transmission guides to the image output surface.
This invention relates to displays. The technology behind flat-panel displays, such as liquid crystal or plasma displays, has advanced to the stage where a single display can be economically manufactured to about the screen size of a modest domestic television set. To increase the display size of a single-unit display beyond this level introduces greater costs, lower manufacturing yields and other significant technical problems. To provide larger displays, therefore, a hybrid technology has been developed whereby multiple smaller rectangular displays are tessellated to form the required overall size. For example, a 2×2 tessellated array of 15 inch diagonal displays, with appropriate addressing electronics to route pixel information to the appropriate sub-display, would provide a 30 inch diagonal display. A drawback of this type of arrangement is that the active area of an individual display, that is to say, the area of the front face of the display on which pixel information is displayed, does not extend to the very edge of the physical area of the display. The technologies used, whether plasma, liquid crystal or other, require a small border around the edge of the active display area to provide interconnections to the individual pixel elements and to seal the rear to the front substrate. This border can be as small as a few millimetres, but still causes unsightly dark bands across a tessellated display. Various solutions have been proposed to this problem, most of which rely on bulk optic or fibre optic image guides to translate or expand the image generated at the active area of the individual sub-displays. For example, U.S. Pat. No. 4,139,261 (Hilsum) uses a wedge structure image guide formed of a bundle of optical fibres to expand the image generated by a panel display so that by abutting the expanded images, the gap between two adjacent panels, formed of the two panels' border regions, is not visible. The input end of each fibre is the same size or less than a pixel element. The optical fibres are aligned, at their input ends, with individual pixel elements of the panel display, so that the pixel structure of the display is carried over to the output plane of the image expander. Other image guides formed in this way may translate the image to provide a border-less abutment between a pair of adjacent panels. Various types of light transmission guide may be used, such as rigid or semi-rigid light transmission guides. It has been proposed that the image guides should be fabricated from polymer materials, for ease of manufacture. In order to allow the input of an image guide to be aligned correctly with a large array of pixel elements on a panel display, it is necessary that the input ends of the light transmission guides are maintained in the correct relative positions, often as a rectangular array of pixel positions. Whatever means is used for registering the input ends of the light transmission guides in their correct relative positions, a problem can arise when the temperature of the display arrangement changes. Most commonly, panel displays are fabricated of glass or a closely related material. The surface of the panel display may have a thin layer or film of another material coupled (e.g. adhered) to it (for instance polarising filters for a Liquid Crystal (LC) display). This layer may have different thermal expansion properties to those of the underlying surface. Of course the skilled person will understand that where this is the case, the layer will expand (e.g. stretch or compress) with the underlying surface when the underlying surface expands in response to temperature variations. Image guides proposed so far tend to use polymer materials for the light transmission guides and/or for an arrangement (if one is used) for registering the input ends of the light transmission guides in the correct relative positions. A problem therefore arises because the thermal expansion properties of glass and polymer materials are different. Consider an example display where the different thermal expansions of the input end of the image guide and of the display substrate mean that the image guide has expanded across its width by one pixel-width more than the panel substrate. This could have two major effects on the image displayed at the output of the image guide. The first is a change to the spatial resolution of the display. At positions within the display area, some light transmission guides could be receiving substantially equal amounts of light from two adjacent pixel elements. This has a low-pass spatial filtering effect on the displayed image, and this effect will vary across the display area. The second is that the outermost light transmission guides will be receiving no light at all, as they will have expanded beyond the display area of the panel. This will cause an unsightly dark line at the output of the image guides. Viewed from a first aspect this invention provides an image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements; an image guide coupled to the image output surface of the display device and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements; in which, for a cluster comprising at least a subset of the light transmission guides: at the outer periphery of the cluster, the input ends of the light transmission guides are constrained against expansion by a frame formed of a material having thermal expansion properties which are substantially similar to the thermal expansion properties of the image output surface. In this aspect, the invention provides a physical constraint against the expansion of the input end of the image guide (or a part of it) beyond the extent defined by a frame which should have expansion properties which are generally similar to those of the image output surface. So, as the image output surface expands, so the frame should expand. If the input end of the image guide has a tendency to expand more than this, the extra expansion is taken up by the compressible coupling between the light transmission guides. Although they could be loose from one another, for example only being attached to the image output surface, it is preferred that the input ends of light transmission guides within the cluster are coupled to one another by a compressible coupling such as a compressible adhesive. In order to approximate the expansion properties of a typical glass display, it is preferred that the frame is formed of a glass or metal material. Preferably the cluster comprises substantially all (e.g. all) of the light transmission guides. Viewed from a second aspect this invention also provides an image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements; an image guide coupled to the image output surface of the display device and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that each light transmission guide receives light from respective groups of one or more pixel elements; in which: the input ends of the light transmission guides are individually coupled to respective areas on the image output surface; and the input ends of the light transmission guides are not coupled to one another along a predetermined distance measured from the input ends. The invention addresses the problems described above by allowing some freedom of movement (or rather, bending) of the input ends of the light transmission guides. This is achieved by not joining the input ends together of a portion of their length, but joining them individually to the image output surface of the display. So, if there is a slight differential expansion causing relative movement between the image output surface and the input ends of the light transmission guides, this is accommodated by a slight distortion of the uncoupled lengths of the light transmission guides. Viewed from a third aspect this invention also provides an image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over an active pixel region of the image output surface; an image guide coupled to the active pixel region of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements; in which: the image output surface has further pixel elements disposed around the periphery of the active pixel region; and the image guide can expand thermally so that the input of the image guide encompasses the further pixels. In this aspect, the invention addresses the problems described above by providing, in effect, extra pixels at the outer periphery of the active pixel region. So, if there is a differential expansion causing the input of the image guide to expand beyond the extent of the active pixel region, there is still some light launched into the outermost light transmission guides of the image guide. This avoids the unsightly black line referred to above. To allow for a typical level of differential expansion, it is preferred that the image output surface has further pixel elements disposed around the periphery of the active pixel region over a guard band region narrower than the input end of a light transmission guide. Preferably each light transmission guide is arranged to receive light from two or more pixel elements. To further reduce the visibility of an expansion of the image guide beyond the active pixel region, it is preferred that the further pixels are arranged to display substantially the same picture information as nearby (e.g. adjacent) pixels within the active pixel region or, alternatively (in a tiled or similar system), to display duplicate information to that of the peripheral pixels within the active pixel region of an adjacent display. Preferably the light transmission guides are coupled to the image output surface using an adhesive, although they could alternatively be held in place by a mechanical arrangement such as a clip. Although the invention is suitable for use with display devices such as cathode ray tube devices, it is preferred that the display device is a panel display device such as a liquid crystal panel display device. The invention is particularly suitable for use when the image output surface is formed of a glass material and/or the light transmission guides are formed of a polymer or plastics material. The invention also provides an array of image displays as defined above, arranged so that viewing surfaces formed by the output ends of the image guides abut to form a larger composite viewing surface. Viewed from a fourth aspect this invention also provides an image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over a plurality of separated active pixel regions of the image output surface; an image guide coupled to the active pixel regions of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements and the output ends of the light transmission guides forming a contiguous output surface; in which: the input ends of the light transmission guides are arranged into a plurality of sections, each section being associated with a different one of the active pixel regions of the image output surface, the light transmission guides in each section being coupled to the active pixel region associated with that section. In this aspect, the invention provides gaps between active regions on the image output surface. In a preferred embodiment, the image guide is able to expand into this gap, reducing the degree of misregistration occurring under conditions of thermal expansion of the image guide. In an alternative preferred embodiment, there is provided a registration aid having thermal expansion properties substantially similar to those of the structure determining the expansion of the image output surface, to which the image guide is abutted. The registration aid is provided between the active areas of the image output surface and acts to minimise misregistration. Viewed from a fifth aspect this invention also provides an image display comprising: a display device having an image output surface at which an image is displayed as a spaced array of pixel elements over an active pixel region of the image output surface; an image guide coupled to the active pixel region of the image output surface and comprising a plurality of light transmission guides each having an input end and an output end, the input ends of the light transmission guides being arranged relative to one another so that groups of one or more light transmission guides receive light from respective groups of one or more pixel elements, the light transmission guides being coupled together along at least a portion of their length; in which: the image guide is coupled to the image output surface over less than the whole active pixel region of the image output surface, the image guide being coupled to the image output surface such that the image guide can expand with respect to the area coupled. In this aspect the invention aims to reduce mechanical distortion in, for instance, an adhesive layer coupling the image output surface and the image guide together. The reduction in mechanical distortion during variations in temperature reduces the presence of adverse effects in image quality and the probability of failure of the adhesive bond. In one preferred embodiment, reference points are provided to prevent rotational displacement of the image guide with respect to the image output surface. In an alternative preferred embodiment, a plurality of separate active regions are provided on the image output surface, with each of a number of groups of light transmission guides being attached to an active regions. With this arrangement, rotational displacement is controlled because the image guide as a whole is attached to the image output surface at a plurality of locations. Various other respective aspects and features of the invention are defined in the appended claims. Features from the dependent claims may be combined with features of the independent claims as appropriate and not merely as explicitly set out in the claims. Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings in which: FIG. 1 is a schematic isometric rear view of a tiled array of display panels; FIG. 2 is a schematic isometric front view of the array of FIG. 1; FIG. 3 is a schematic side view of a display comprising a light source, a collimator/homogeniser, a display panel and an image guide; FIG. 4 is a schematic side elevation of an array of light transmission guides coupled to an image output surface, in accordance with a first embodiment of the present invention; FIG. 5 is a schematic side elevation of an array of light transmission guides coupled to an image output surface, in accordance with a second embodiment of the present invention; FIG. 6 is a schematic plan view at a level A-A during the assembly of an array as shown in FIG. 5; FIG. 7 schematically illustrates the image output surface of a display panel having an active pixel region and a guard band; FIG. 8 is a schematic side elevation of an array of light transmission guides coupled to the image output surface of FIG. 7, in accordance with a third embodiment of the present invention; FIG. 9 is a schematic plan view of the arrangement of FIG. 8; FIG. 10 is a schematic plan view of an array of light transmission guides coupled to an image output surface, in accordance with a fourth embodiment of the present invention; FIG. 11 is a schematic side elevation of the arrangement of FIG. 10; FIGS. 12a and 12b schematically illustrate a side elevation of a light guide and a plan view of an image output surface in accordance with the first to fourth embodiments of the present invention; FIGS. 12c to 12e are a schematic side elevation of a light guide and schematic plan views of an image output surface in accordance with a fifth embodiment of the present invention; FIGS. 13a to 13d are schematic plan views of a selection of registration aids applicable to the arrangement of FIG. 12e; FIG. 14 is a schematic plan view of an image output surface and the input ends of a light guide in accordance with a sixth embodiment of the invention; FIG. 15 is a schematic plan view of an image output surface and the input ends of a light guide (split into a plurality of groups) in accordance with a seventh embodiment of the invention; FIG. 16a is a schematic plan view of an image output surface and registration aid in accordance with an eighth embodiment of the invention; FIG. 16b is a schematic plan view of an image output surface and registration aid in accordance with a ninth embodiment of the invention; FIGS. 17a and 17b schematically illustrate two alternative modes of operation of a guard band in accordance with embodiments of the invention; and FIG. 18 schematically illustrates tiled display control circuitry in accordance with an embodiment of the invention. FIG. 1 is a schematic isometric rear view of a tiled array of display panels. The array comprises four display panels in a horizontal direction and three display panels in a vertical direction. Each display panel comprises a light emitting surface 10 and an image guide 20. The light emitting surfaces 10 are each arranged as a plurality of pixels or picture elements. In practice, they would include, for example, a back light arrangement, focusing, concentrating and/or collimating and/or homogenising optics and a liquid crystal panel or the like, but much of this has been omitted for clarity of the diagram. The panels each display portions of an overall image to be displayed. The portions represent adjacent tiles in a tessellated arrangement. However, because of the need to run electrical connections and physical support around the edge of the light emitting surfaces 10, they cannot be directly abutted without leaving a dark band or “black matrix” in between. So, the light guides 20 are used to increase the size of the image from each light emitting surface 10 so that the output surfaces of the light guides 20 can be abutted to form a continuous viewing plane. This arrangement is shown in FIG. 2 which is a schematic isometric front view of the array of FIG. 1. Here, the output surfaces of the light guides 20 abut so as to form a substantially continuous viewing surface 30. FIG. 3 is a schematic side view of a display comprising a light source 40, a collimator/homogeniser 50, a liquid crystal panel 60 and a light guide 70. The light source 40 and the homogeniser 50 are shown in highly schematic form but in general terms are arranged to provide the back light required by the liquid crystal panel 60. The liquid crystal panel 60 may be of a type which uses a white or other visible colour back light and provides liquid crystal picture elements to modulate that back light for that display. Alternatively, the liquid crystal panel 60 may be a photo luminescent panel which employs an ultra-violet back light and modulates the ultra-violet light onto an array of phosphors to generate visible light for display. Of course, many other types of light emitting surface 10 may be used such as an organic light emitting diode array or even a cathode ray tube display. A typical example of the surface material of the display might be Corning LCD Glass. The image guide 70 comprises an array of light transmission guides 80, each of which carries light from a particular area on the liquid crystal panel 60 to a corresponding particular area on an output surface 90. In doing so, the light transmission guides are arranged to diverge so that the area covered on the output surface 90 is physically larger than the image display area on the liquid crystal panel 60. This, as described above, allows an array of displays as shown in FIG. 3 to be abutted without an unsightly black matrix at the viewing plane. Some examples of materials used to fabricate the light transmission guides are Bayer Makrolon Polycarbonate and Dow Caliber Polycarbonate. FIG. 4 is a schematic side elevation of an array of light transmission guides 80′ forming part of the image guide 20. The light transmission guides 80′ are coupled, for example glued by a transparent adhesive, to pixel elements 100 of a display panel 60′. In the example shown in FIG. 4, each light transmission guide 80′ is coupled to a respective individual pixel element 100. However, in this and other embodiments to be described, each light transmission guide could be coupled to several pixels (for example, a group of one or more each of red, green and blue pixels) or each pixel could be coupled to several light transmission guides. It will be appreciated throughout this description that the term “coupled to a pixel element” is to be understood in the context of a panel or other display. In the strictest sense, in for example a liquid crystal display, the “pixel element” could be considered to be actually within the sandwich structure of the various layers constituting the display. However, using the term in an engineering sense, the skilled person will of course understand that the light transmission guides are in fact coupled to positions on the outer surface of the display which receive light from the pixel element. Examples of suitable transparent adhesives for this purpose are as follows: Epoxy Technology Epotech OG134 Hughes Associates Epoxy 330 Norland NOA61 Over a portion 110 of the length of the light transmission guides 80′, the light transmission guides are separate from one another. The gaps 120 between the light transmission guides may be filled by air, near-vacuum, an inert gas, or even a low density flexible filler such as a silicone elastomer. This arrangement allows the input ends of the light transmission guides 80′ to track any differential expansion between the image guide 20 and the image output surface of the display 60′ by a very slight distortion such as a bending or buckling at the input end. So, even if the image output surface 60′ and the image guide expand laterally by different amounts, each light transmission guide remains registered and in contact with the correct one of the pixel elements 100. The length of the unjoined region 110 depends on the dimensions of the light transmission guides, their flexibility, and the strength of the bond between the light transmission guides 80′ and the pixel elements 100 on the image output surface 60′. The range of temperatures over which the performance of the display is specified is also relevant. The skilled person may establish an appropriate length of the region 110 by routine experiment once these parameters are established. FIG. 5 is a schematic side elevation of an array of light transmission guides 80″ coupled to an image output surface 60″ in accordance with a second embodiment of the present invention. As before, each light transmission guide 80″ is coupled to a respective individual pixel element 100″ but other arrangements are of course possible. The light transmission guides 80″ are substantially independent over much of their length, being (for example) discrete optical fibres. However, a support 130 is provided along the length of the light transmission guides 80″, partly to help support the weight of the light transmission guides and also to assist in aligning each light transmission guide to the appropriate place on the image output surface 60″ during assembly of the display arrangement. The position of the support 130 defines a distance 110″ over which the light transmission guides are not coupled to one another. Again, this distance allows for differential thermal expansion between the image output surface 60″ and the image guide. If substantially flexible light transmission guides 80″ are used, then in the case of a display having a large number of pixel elements 100″, it is useful to provide a technique for assembling the input ends of the light transmission guides 80″ to the correct place for gluing on to the image output surface 60″. FIG. 6 schematically illustrates such a technique and is a schematic plan view taken along a section A-A of FIG. 5. Referring to FIG. 6, each light transmission guide 80″ is held in place laterally by crossed sets of wires or blades 140. The crossed sets of wires or blades define (in this example) square apertures in which each light transmission guide 80″ sits during the process of gluing the light transmission guide on to the appropriate pixel position on the image output surface 60″. The wires or blades 140 are supported at one end on a support member 150. This holds them at the correct spacing for the pixel elements of the display panel in use. If fine blades are used, these may be self-supporting along their length and so no support is needed at the distal end of each blade. If some distal support is needed, then the blades may be held by a clamp or an electromagnetic support to allow for an easy release. So, the two sets of blades 140 are inserted in orthogonal directions through the array of light transmission guides 80″ close to the surface of the panel display. If necessary, the blades are held at their distal ends to maintain the correct spacing and to give structural rigidity during the gluing process. An adhesive is applied to the surface of the panel display and the image output surface 60″ is offered up to the array of light transmission guides 80″. An image may be displayed on the image output surface 60″ during this process to assist in obtaining the correct lateral positioning. Once the image output surface 60″ is in the correct position with respect to the array of light transmission guides 80″, the adhesive is cured, for example by exposure to ultra-violet light, by heat or simply by time elapsing. Then, if any support was used at the distal ends of the blades 140, the support is released and the blades are carefully withdrawn along their length. If flexible wires are used instead of rigid or semi-rigid blades, some tension is required between the support member 150 and an arrangement used to grip the wires at their distal ends, in order to maintain the correct spacing along the length of the wires. In this case, the distal end of each wire may be passed into a respective spaced groove in a further support member (not shown), clamped in place and then pulled to place the wire under tension. The process would then continue as described above, but at the end of the assembly the tension would be released and the wires allowed to leave the respective grooves. A third embodiment of the invention will now be described. FIG. 7 schematically illustrates the image output surface 60′″ of a display panel having an active pixel region 170 which contains all of the pixels needed for an appropriate connection to an image guide, and a so-called “guard band” 180 formed of extra pixels disposed around the peripheral edge of the active pixel region 170. The guard band provides additional pixels to give some light input into the very outer light transmission guides of the image guide, in the case that the image guide expands laterally beyond the active pixel region 170. If this does happen, then the precise registration between each light transmission guide and the respective one or more pixel elements on the image output surface will be lost, and this could lead to some undesirable spatial low-passed filtering across the image. However, by providing the guard band 180 having additional pixel elements, at least an unsightly dark line around the edge of the image guide is avoided. In this embodiment, pixels in the guard band 180 display the same colour and luminance as the nearest adjacent pixels in the active pixel region 170. So, some pixel information is duplicated around the edge of the display, but again this is less undesirable than an unsightly dark band around the output of the image guide. In other embodiments, the pixels in the guard band 180 display the same colour and luminance as the nearest adjacent pixels in the next adjacent display in a tiled array of displays as shown in FIG. 1. Two alternative modes of operation of the guard bands of a display will now be described with reference to FIGS. 17a and 17b. FIG. 17a is a schematic illustration of a first mode of operation of the guard bands of a tiled display comprising four tiles. Each tile comprises an active area 170a, b, c and d and a guard band area 180a, b, c and d. In this mode of operation, pixels 520a, b, c and d in a given guard band 180a, b, c or d will display the same information as the nearest neighbouring pixels in the active areas 170a, b, c or d of a neighbouring tile. For instance, the guard pixel 520a which lays on the edge of the active area 170d will display the same information as the pixel 510a in the active area 170c. Similarly, the guard pixel 520c and the guard pixel 520d (laying on the edge of active areas 170b and 170d respectively) will display the same information as the pixels 510c and 510d respectively (these pixels being part of the active areas 170d and 170b respectively). In the case of the guard pixel 520b, which lays on the corner of the active area 170a, the guard pixel 520b will display the same information as the corner pixel 510b of the diagonally adjacent active area 170c. This is in contrast to the previous cases where the information is taken from an active area either horizontally or vertically adjacent to the guard area. FIG. 17b is a schematic illustration of a second mode of operation of a guard band. This mode of operation may apply to either a single display, or to a tiled display. Here, the information to be displayed by the pixels 540a, b, c, d and e in a guard band 180e matches the information to be displayed by the closest pixels 530a, b or c in an active area 170e around which the guard band 180e is formed. For instance, the information used to drive the pixel 530a, located on one edge of the active area 170e will also be used to drive the neighbouring pixel 540a. Similarly, the information used to drive the pixel 530b, located on another edge of the active area 170e will also be used to drive the neighbouring pixel 540b. In the case of the pixel 530c, located on a corner of the active area 170e, the information driving this pixel will also be used to drive the guard band pixels 540c, d and e. Experimentation has shown that where pixels in the guard band 180 display the same colour and luminance as the nearest adjacent pixels in the active pixel region 170, this provides preferable visual image properties for text/graphics-based image data (here, the term “text/graphics” is used to signify hand-drawn or computer-generated material (graphs, letters etc) which have the characteristic of rapid contrast and/or hue changes (in the spatial domain), whereas other images (photographs, paintings etc) have (generally) more gradual spatial changes of contrast and/or hue. On the other hand, where the pixels in the guard band 180 display the same colour and luminance as the nearest adjacent pixels in the next adjacent display, this provides preferable visual image properties for non-text/graphics image data. A single image frame to be displayed over an array of tiled displays may include regions comprising text/graphics and regions without text/graphics. In this case, it is desirable that guard band pixels falling within regions comprising text/graphics should be written to duplicate the colour and luminance of the nearest adjacent pixels in the active region 170 and that guard band pixels falling within regions without text/graphics (or with only small amounts of text/graphics) should be written to duplicate the colour and luminance of the nearest adjacent pixels in the next adjacent display. Both the guard bands, and the regions of the active areas used to drive them, are not necessarily limited to a single width of pixels, but may include a plurality of rows and columns. Preferably, the basis on which the colour and luminance of the guard band pixels is determined (i.e. the mode of operation) is selectable. In particular, the mode of operation may be either auto-selectable by control circuitry in the display device, or manually selectable by a user. The display may include an electronic detector operable to detect the type of information being displayed (e.g. text/graphic or image only) and to write the guard band pixels appropriately. More specifically, the type of information displayed at each inter-tile boundary can be analysed, and the guard band of each tile can be written accordingly. The electronic detector may be included in the control circuitry driving the display. An example display controller operable to detect and isolate text/graphic regions from other image regions is the Phillips SAA6713 display controller. FIG. 18 schematically illustrates example control circuitry which may be used to drive a tiled array of displays. The control circuitry receives image data 600 representing the image to be displayed on the tiled array of displays. The image data 600 is passed to a demultiplexer 610 and a tile edge region detector 620. The demultiplexer 610 is arranged to separate the incoming image data 600 into image data representative of the image to be displayed at individual tiles of the tiled display. The separated image data is passed to the appropriate respective individual tiles 650a, b and c. The tile edge region detector 620 is arranged to detect parts of the incoming image data 600 which are close to an inter-tile boundary. The edge regions do not necessarily need to correspond to the areas of further pixels, but can extend beyond this, potentially to include the entire tile. The image data categorised by the tile edge region detector 620 as being at a tile edge is passed to an image type detector 630. The image type detector 630 detects whether the image data relates to (for instance) text/graphics only data or data comprising image, the result of this detection being used to generate a control signal 640 to be passed to the demultiplexer. The demultiplexer 610 includes information regarding the guard pixels in the image data to be sent to the tiles 650a, b and c, in response to the control signal 640. FIG. 8 is a schematic side elevation of an array of light transmission guides 80′″ coupled to pixel elements 100′″ on an image output surface 60′″. The coupling is such that lateral movement between the light transmission guides 80′″ and the image output surface 60′″ is not completely inhibited. In this example arrangement, each light transmission guide 80′″ receives light from a rectangular array of 4×4 pixel elements 100′″. The arrangement shown in FIG. 7 illustrates the light transmission guides exactly covering the active pixel region 170 of the image output surface 60′″. However, if any expansion occurs in which the image guide expands to a greater extent than the panel display, the image guide will tend to move outwards in a direction 190. This will bring the outer most light transmission guide over pixels in the guard band 180. FIG. 9 is a schematic plan view of the arrangement of FIG. 8, showing one corner of the image output surface 60′″ including the guard band 180 which is a row of pixels two pixels wide running around the active pixel area 170. FIG. 10 is a schematic plan view of an array of light transmission guides 80′″ coupled to an image output surface 60′″ in accordance with a fourth embodiment of the present invention. FIG. 11 is a schematic side elevation of the arrangement of FIG. 10, in which the spacing between the light transmission guides 80′″ has been exaggerated for clarity. Each light transmission guide 80′″ overlies a respective pixel element, although other arrangements as described above are of course possible. The light transmission guides 80′″ are separated by gaps 200 which are filled with a compressible material such as an open cell foam adhesive. Surrounding the whole array of light transmission guides 80′″ at their input end, is a rigid frame 210 formed of a material having substantially identical thermal expansion properties to that of the image output surface 60′″. Generally, this will be a glass material, but it has been found that metals may also be used as they have thermal expansion properties which are much closer to those of glass than to those of plastics or polymers. For some display types, such as LC displays, the image output surface 60′″ may include a layer formed of a material having different thermal expansion properties to the frame 210. For instance, with LC displays, the image output surface 60′″ may have a polymeric film acting as a polariser adhered to it. In this case, where a polymeric polarising film is adhered to an underlying structure (which may for instance be formed of glass), the expansion properties of the polarising film will remain substantially those of the underlying structure, with the polarising film being “stretched” as the underlying structure expands (and compressed as the underlying structure contracts). Although the frame 210 may be coupled to the polarising film, because the expansion of the film will be determined by the thermal expansion properties of the underlying structure, the thermal expansion properties of the frame 210 should be substantially the same as those of the underlying structure. If some differential expansion occurs, the whole array of light transmission guides 80′″ cannot expand at their input end (in a lateral direction) beyond the rigid frame 210. The frame in turn expands at substantially the same rate as the image output surface 60′″. So, expansion at the input end of the light transmission guides is taken up by the compressible material in the gaps 200. Assuming that the gaps are relatively uniformly filled, this provides a uniform compression of the compressible material across the array of light transmission guides 80′″. This in turn means that the alignment or registration between the light transmission guides at their input end and pixel elements on this image output surface 60′″ is not compromised. Preferably, the means by which the frame 210 is attached to the array of light transmission guides 80′″ will conserve the optical characteristics that exist between non-peripheral fibres in the array. Embodiments of the invention which address this are illustrated in FIGS. 16a and 16b. There may be an inner frame 212 of a material having the substantially similar optical characteristics to the light transmission guides 80′″ and being coupled to the peripheral light transmission guides (i.e. those adjacent to the frame) in a manner that is optically substantially identical to the manner in which the light transmission guides 80′″ are attached to each other. The inner frame 212 would be sandwiched between the outer row of light transmission guides 80′″ and the outer frame 211 (which would lend rigidity to the structure). The inner frame 212 could for instance take the form of a continuous boundary of material surrounding all sides of the array or could comprise an additional boundary of light transmission guides 213 around the array. In the latter case, the additional light transmission guides 213 would be truncated so as not to reach the plane of the output ends of the light transmission guides 80′″. The outer frame 211 may have the same or similar optical characteristics to the light transmission guides 80′″, but different thermal expansion characteristics. Preferably, light entering into the inner frame 212 will be prevented or at least inhibited from exiting the inner frame 212 in a manner that would degrade the visual properties of the display. For instance, where the inner frame 212 comprises truncated light transmission guides 213, these could have their truncated ends covered (e.g. coated) with a light absorbing layer. Alternatively, where the inner frame 212 comprises a continuous boundary of material, the part of its surface not in contact with the peripheral light transmission guides 80 could be covered (e.g. coated) with a light absorbing layer. FIG. 12a schematically illustrates a side elevation view of a typical arrangement as described above and FIG. 12b schematically illustrates a plan view of the image output surface 60 of the same arrangement. In FIG. 12a, a single light guide 20 is coupled to an active region 170 of an image output surface 60. FIG. 12b shows that the input ends of light transmission guides 80 making up the light guide 20 are arranged to receive light from an active area 170 of the image output surface 60. With this arrangement, each light guide 20 may be formed of an array of individual light transmission guides 80 (channels) that are close-packed as a regular array (typically square packed) at input and output with thin layers of glue between the light transmission guides. This packing configuration means that the array behaves more as a single large area (i.e. a continuous sheet) than as a group of individual light transmission guides (in terms of expansion) and the expansion in the plane parallel to the input apertures of the light transmission guides 80 and the image output surface 60 is cumulative. For instance, if each input aperture expands by 1% of its linear dimension then the linear expansion of the inputs of a close packed line of ten light transmission guides 80 will be approximately 10% of the linear dimension of a single light transmission guide 80. For a large number of light transmission guides 80, the cumulative expansion of the input face of the light guide 20 relative to the lower expansion of the image output surface 60 (such as the modulator plane of a LC panel) may cause serious loss of registration if a large image output surface 60 (e.g. large area modulator of LC display) is used. In an effort to contain the effect of the relative motion of the input ends of light transmission guides 80 relative to the pixel elements of the image output surface 60, the accumulation of the error should be limited. One method of addressing this problem is to limit the linear dimension of the input surface of the light guide 20. However, reducing the dimensions of the input surface of the light guide 20 necessitates using a larger number of reduced dimension output image surfaces (e.g. small modulating arrays) rather than a smaller number of regular image output surfaces (e.g. standard or large modulating arrays). It is desirable to use fewer image output surfaces 60 to reduce cost, improve efficiency and aid manufacturing. FIGS. 12c and 12d schematically illustrate an alternative embodiment of the invention in which the input face of a light guide 20a is split into a plurality of groups 25a, b, c, d of light transmission guides 80 while a continuous array is maintained at the output face of the light guide 20a. FIG. 12d shows how the image output surface 60b comprises a plurality of active regions 170a, b, c and d, separated from each other by non-active regions 185, in this case a cruciform shape of “dead” or boundary pixels. Each group 25a, b, c, d of light transmission guides 80 is coupled to a different one of the active regions 170a, b, c or d and receives light from pixel elements in that active region. Fabricating a light guide 20a in this way, to have a plurality of (e.g. four) segments enables expansion to take place inwards (into the non-active regions 185 between the segments) as well as outwards, therefore reducing the degree of pixel-light transmission guide misregistration at the edges of the light guide 20a. For an input end which is divided into four sections, the linear dimensions of each section will be half the linear dimension of a continuous input end, minus half the desired dimension of the non-active area 185. For an N group by N group division, the degree of misaligmnent resulting from thermal expansion can be reduced to 1/N of that expected for a continuous input end. Additionally, it may be advantageous in helping to fill and index match the near planar area between the light guide input and the image output display surface (e.g. LC panel) to have four smaller areas rather than one large area, due to the difficulties involved in evenly applying index matching gel between two large-area planes. It is possible to provide this arrangement with very little difference (or no difference at all) in the moulding (assuming for instance, that for a four group light guide, one quarter of a single row would usually be moulded as a single unit in the single group light guide embodiment). In one embodiment, the displacement towards the centre (to cover the unused pixels of the image output surface 60a) is moulded into the quarter row (or whatever fraction of a row is moulded at one time) such that when the complete rows are assembled the output of the light guide 20a is continuous and the input of the light guide 20a has a cruciform gap that matches the active regions/modulation areas 170. The width of the gaps between the active areas of the image output surface 60a can be either small (e.g. 2 pixels=0.615 mm for 0.3075 mm pixels) or for wider (e.g. 20 pixels=6.15 mm for 0.3075 mm pixels). The former (small width of unused pixels) is advantageous in one respect, because large areas of unused pixels on an image output surface 60a are wasteful and inefficient. A further advantage of having a gap at the centre of the image output surface 60a is that the expansion of the light guide 20a can take place inwards as well as outwards thereby reducing the loss of registration by a factor of approximately 2. Where there is a very small gap (i.e. small number of unused pixels) between the active areas 170 on the image output surface 60a, it is not strictly necessary to mould the inward bend into the quarter (or other relevant fraction) row. Instead, because the displacement is small and the resulting stresses would therefore also be small, the output apertures of the four quarters could be pushed together and glued during the assembly process, resulting in a more straightforward manufacturing process. The latter (wider width of unused pixels) has a different advantage in that it allows the possible addition of a registration aid between the respective groups of input ends of the light guide 20a. The registration aid may be attached to the image output surface 60a of the display device. FIG. 12e schematically illustrates a display arrangement comprising a registration aid 300. The registration aid 300 could take the form of a cruciform frame attached to the image output surface 60a (e.g. a metal or glass frame fixed to the output glass of an LC panel) such that the input channels can be butted against it as a means of registering it or even of securing it. Further possible forms include unconnected bars (illustrated schematically in FIG. 13a), connected or interlocking bars, and ‘L’ shaped objects to locate corners of the input end of the light guide 20a (illustrated schematically in FIGS. 13b and 13c). Expansion would be outwards from the points of contact between the light guide 20a and the registration aid 300. Preferably, the registration aid 300 would be made of glass having the same or similar thermal expansion properties to the image output surface 60a. Registration aids can also be provided in non-active areas external to the regions between the active areas. A further embodiment of the invention, illustrated schematically in FIG. 13d provides a frame 210a which constrains the periphery of the input face of the light guide 20a The input face would be “shoehorned” into the frame 210a on assembly of the unit. The lack of adhesive between the sections allows expansion to occur inwards from the frame 210a. In the case of, for instance, an LC display, the image output surface 60 may have a different (e.g. lower) coefficient of thermal expansion (CTE) than a light guide 20 coupled to it. If the image output surface 60 and the light guide 20 are attached together by means of a rigid, or semi-rigid adhesive, the adhesive layer will become stressed in conditions where the temperature varies from the temperature at which the attachment was made. Consequently, mechanical distortion of the light guide 20 and/or the image output surface 60 (or the LC display itself) may arise. This mechanical distortion may adversely affect the performance of the display, and may ultimately lead to failure of the adhesive bond and thus to the decoupling of the image output surface 60 and the light guide 20. On the other hand, if the adhesive layer used is elastically compliant, then misregistration between the pixels of the active area 170 of the display 60 and the light transmission guides 80 of the light guide 20 may occur. An alternative method of attaching a light guide to an image output surface is schematically illustrated in FIG. 14. In this arrangement, instead of using a continuous layer of adhesive, an adhesive 400 is confined to a small area, the dimensions of which should be sufficient to support its share of the display mass attached to a light guide 20b. The adhesive 400 is disposed centrally in the integral area of the light guide 20b. The remainder of the area between the light guide 20b and an image output surface 60c that is required to be optically coupled is filled with a gel having an extremely high viscosity or an elastomeric resin having an extremely low modulus of elasticity such that expansion differences produce no significant stress within the layer, and having substantially the same refractive index as the adhesive 400. A suitable combination of adhesive 400 and low modulus elastomer would be Dymax X413-25-A (refractive index, n=1.42) as the adhesive 400 and Dow Corning 787T (refractive index, n=1.428) as the elastomer. Other suitable adhesives include Norland NOA81 (refractive index, n=1.56), Dymax OP4-20655 (refractive index, n=1.48) and Dymax OP4-20641 (refractive index, n=1.505). These could be used with gels such as LS-3238 Curing Encapsulation Gel (refractive index, n=1.38), LS-3246 (refractive index, n=1.46), LS-3249 (refractive index, n=1.49), LS-3252 (refractive index, n=1.52) and LS-3357 (refractive Index, n=1.57). These adhesives may be advantageous over the lower refractive index combination above, having refractive indices between those of a polarising layer present on the image output surface, and of the light transmission guides 80, where the light transmission guides 80 are formed of polycarbonate. In the embodiment of FIG. 14, the adhesive 400 alone may not provide sufficient torsional rigidity to prevent misregistration through rotation of the light guide 20b and the image output surface 60c with respect to each other. To overcome this, two (or more) reference points 410 are glued rigidly to the image output surface 60c. The reference points 410 comprise low modulus glue that will yield to expansion forces resulting from variations in temperature. With this arrangement, strain is allowed to occur at minimum stress by using adhesive over only a small area of the interface between the image output surface 60c and the light guide 20b. This advantageously provides that the area of rigid or semi-rigid adhesive sufficiently small to reduce stresses within the adhesive layer and that any expansion will take place symmetrically from the centre of the display, halving the misalignment compared to a method that fixes alignment from one corner of the display. FIG. 15 schematically illustrates another embodiment which uses a small area of adhesive 400 to fix a light guide 20c to an image output surface 60d. In FIG. 15, the light guide 20c is split into a plurality of groups of light transmission guides 80 (in this case, four groups) as described above with reference to FIG. 12, in an arrangement otherwise similar to that described with reference to FIG. 14. Here, where multiple input segments of the light guide 20c are used, registration points 410 on the image output surface are not required, since sufficient torsional rigidity can be provided by the multiple adhesive areas 400. Although the above embodiments of the invention are described such that the light transmission guides 80 of the light guide 20 are attached directly to the image output surface 60 of the display device, the ends of the light transmission guides 80 could also be attached to a substrate having substantially the same expansion properties as the display device. The substrate could be removably coupled to the image output surface 60 of the display device. This arrangement might be more desirable than attaching the light transmission guides 80 directly to the display device (for yield, cost and maintenance reasons). The ends of the light transmission guides 80 could be glued directly to a substrate by applying glue to the ends of the light transmission guides 80 or to the substrate, placing the light transmission guides 80 row by row accurately in position using a linear stage or stages and holding the light transmission guides 80 in position whilst the glue is cured. This would avoid the need for the blades 140 described in relation to FIG. 6.
20050606
20100622
20051006
65305.0
0
RUDE, TIMOTHY L
IMAGE DISPLAY DEVICE
UNDISCOUNTED
0
ACCEPTED
2,005
10,513,900
ACCEPTED
System and method of facilitating and evaluating user thinking about an arbitrary problem
Preferred embodiments of the invention provide systems and methods of facilitating and evaluating user thinking about an arbitrary problem. The system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion, related to the problem specification, to populate a conclusion statement structure. It also includes third logic to facilitate user creation and specification of knowledge, related to at least one of the problem specification and the conclusion specification, to populate a knowledge structure. Certain embodiments include control logic to persuade user interaction with the first through third logic to a sequence of interactions within a predefined set of interaction sequences, wherein the predefined set of interactions define an archetype process for user thinking about the problem. Other embodiments the first through third logic to construct a user model structure of user development and population of the user model structure, conclusion statement structure, and knowledge structure, and structure analysis logic to analyze the user model structure relative to an archetype model structure. Some embodiments include model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, and knowledge structure; and visual feedback logic to depict an archetype problem-solution structure and to depict the user model structure. And other embodiments include tracking logic to monitor user interactions with the first through third logic and to build a corresponding model of such interactions so that the model, and the corresponding user thinking process, may be evaluated. The system may monitor the user's process of problem solving and the structure of the user's problem solving approach and make suggestions to the user.
1. A system for facilitating user thinking about an arbitrary problem, comprising: first logic to facilitate user specification of the problem to populate a problem statement structure; second logic to facilitate user specification of a conclusion, related to the problem specification, to populate a conclusion statement structure; third logic to facilitate user creation and specification of knowledge, related to at least one of the problem specification and the conclusion specification, to populate a knowledge structure; control logic to persuade user interaction with the first through third logic to a sequence of interactions within a predefined set of interaction sequences, wherein the predefined set of interactions define an archetype process for user thinking about the problem. 2. The system of claim 1 wherein the user specification of knowledge includes the user specification of data and wherein the knowledge structure is a data structure to hold data. 3. The system of claim 1 wherein the user specification of knowledge includes the user specification of information and wherein the knowledge structure is an information stricture to hold information. 4. The system of claim 1 wherein the user specification of knowledge includes the user specification of analysis and wherein the knowledge structure is an analysis structure to hold analysis. 5. The system of claim 1 further including fourth logic to facilitate user specification of at least one subtopic statement, related to the problem, to populate a corresponding at least one subtopic statement structure to disaggregate the problem into related subtopics, and wherein the control logic persuades user interactions with the first through fourth logic to a sequence of interactions within a predefined set of interaction sequences. 6. The system of claim 5 further including fifth logic to facilitate user specification of at least one meaning statement, related to a corresponding at least one problem or subtopic statement, to populate a corresponding at least one meaning statement structure, and wherein the control logic persuades user interactions with the first through fifth logic to a sequence of interactions within a predefined set of interaction sequences. 7. The system of claim 2 wherein the specification of knowledge includes text specification. 8. The system of claim 2 wherein the specification of knowledge includes at least one of graphic, image, or drawing specification. 9. The system of claim 3 wherein the specification of information includes text specification. 10. The system of claim 3 wherein the specification of information includes at least one of graphic, image, or drawing specification. 11. The system of claim 4 wherein the specification of analysis includes text specification. 12. The system of claim 4 wherein the specification of analysis includes at least one of graphic, image, or drawing specification. 13. The system of claim 5 wherein the specification of at least one subtopic includes text specification. 14. The system of claim 5 wherein the specification of at least one subtopic includes at least one of graphic, image, or drawing specification. 15. The system of claim 6 wherein the specification of at least one meaning statement includes text specification. 16. The system of claim 6 wherein the specification of at least one meaning statement includes at least one of graphic, image, or drawing specification. 17. The system of claim 1 wherein the control logic includes logic to cause a presentation to the user, including depiction of suggested next steps for the user. 18. The system of claim 1 wherein the control logic includes logic to cause a view presentation to the user, wherein the view presentation includes a subset of the problem specification, conclusion specification, and knowledge specification, and includes a depiction of relationships therebetween. 19. The system of claim 6 wherein the control logic includes logic to cause a view presentation to the user, wherein the view presentation includes a subset of the problem specification, conclusion specification, knowledge specification, at least one subtopic statement specification, and meaning statement specification, and includes a depiction of relationships therebetween. 20. The system of claim 1 further including logic to present to the user at least a subset of content of the problem statement structure, the conclusion statement structure, and the knowledge structure. 21. The system of claim 20 wherein the logic to present includes logic to depict relationships among content of the problem statement structure, the conclusion statement structure, and the knowledge structure. 22. The system of claim 21 wherein the logic to depict relationships includes logic to depict hierarchical relationships. 23. The system of claim 22 wherein the logic to present depicts all relationships among the problem statement structure, the conclusion statement structure, and the knowledge structure. 24. The system of claim 23 wherein the logic to present includes logic to present user controls to create at least one new problem statement structure, conclusion statement structure, or knowledge structure. 25. The system of claim 23 wherein the logic to present includes logic to present user controls to modify at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 26. The system of claim 20 wherein the logic to present includes logic to present structures all of similar type. 27. The system of claim 26 wherein the logic to present includes logic to present user controls to modify or create at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 28. The system of claim 20 wherein the logic to present includes logic to present an individual structure only. 29. The system of claim 28 wherein the logic to present includes logic to present user controls to modify or create at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 30. The system of claim 1 wherein the control logic includes logic to provide suggestion feedback to the user of next steps for a user to take, wherein the logic to provide is responsive to prior user interactions. 31. The system of claim 30 wherein the logic to provide suggestion feedback includes logic to perform gap analysis on the at least a subset of the problem statement structure, the conclusion statement structure, the knowledge structure, and the relations therebetween to suggest next steps for the user to create or populate structures identified from the gap analysis. 32. The system of claim 31 wherein the logic to perform gap analysis includes logic to analyze linkages among the at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure to detect gaps. 33. The system of claim 31 wherein the logic to provide suggestion feedback includes filtering logic to determine whether to provide suggestion feedback based on the state of development of the user interactions. 34. The system of claim 30 wherein the logic to provide suggestions includes content analysis logic to analyze content entered by the user to determine relevant suggestions for next steps to the user. 35. The system of claim 34 wherein the content analysis logic parses user entry to determine if the entry corresponds to a predefined set of phrases. 36. The system of claim 30 wherein the logic to provide suggestions includes relationship analysis logic to identify suggestions of next steps according to predefined relationship criteria. 37. The system of claim 30 wherein the logic to provide suggestions includes logic to present suggestions for next steps to the user in a visually distinctive manner. 38. The system of claim 37 wherein the logic to present suggestions for next steps to the user presents user controls in emphasis. 39. The system of claim 37 wherein the logic to present suggestions for next steps to the user presents workspace controls to activate a workspace corresponding to suggested next steps in proximity to a current workspace. 40. The system of claim 30 wherein the logic to provide suggestion feedback includes logic to provide content analysis of at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 41. The system of claim 1 wherein the archetype model structure is specified in a set of rules specifying relationships among the problem structure, conclusion statement structure, and knowledge structure. 42. (canceled) 43. (canceled) 44. (canceled) 45. (canceled) 46. (canceled) 47. (canceled) 48. (canceled) 49. (canceled) 50. (canceled) 51. (canceled) 52. (canceled) 53. (canceled) 54. (canceled) 55. (canceled) 56. (canceled) 57. (canceled) 58. (canceled) 59. (canceled) 60. (canceled) 61. (canceled) 62. (canceled) 63. (canceled) 64. 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A system for facilitating user thinking about an arbitrary problem, comprising: first logic to facilitate user specification of the problem to populate a problem statement structure; second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure; third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure; model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the user model structure, conclusion statement structure, and knowledge structure; and structure analysis logic to analyze the user model structure relative to an archetype model structure. 96. The system of claim 95 wherein the archetype model structure is a dynamic structure that changes in response to the user model structure. 97. The system of claim 95 wherein the archetype model structure is specified in a set of rules specifying relationships among the problem structure, conclusion statement structure, and knowledge structure. 98. The system of claim 95 wherein the user specification of knowledge includes the user specification of data and wherein the knowledge structure is a data structure to hold data. 99. The system of claim 95 wherein the user specification of knowledge includes the user specification of information and wherein the knowledge structure is an information structure to hold information. 100. The system of claim 95 wherein the user specification of knowledge includes the user specification of analysis and wherein the knowledge structure is an analysis structure to hold analysis. 101. The system of claim 95 further including fourth logic to facilitate user specification of at least one subtopic statement, related to the problem, to populate a corresponding at least one subtopic statement structure to disaggregate the problem into related subtopics, and wherein the model logic tracks user interaction with the first through fourth logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, knowledge structure, and the at least one subtopic statement structure. 102. The system of claim 101 further including fifth logic to facilitate user specification of at least one meaning statement, related to a corresponding at least one problem or subtopic statement, to populate a corresponding at least one meaning statement structure, and wherein the model logic tracks user interaction with the first through fifth logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, knowledge structure, the at least one subtopic statement structure, and the at least one meaning statement structure. 103. The system of claim 95 further including logic to cause a presentation to the user, including depiction of suggested next steps for the user. 104. The system of claim 95 further including logic to present to the user at least a subset of content of the problem statement structure, the conclusion statement structure, and the knowledge structure. 105. The system of claim 104 wherein the logic to present includes logic to depict relationships among content of the problem statement structure, the conclusion statement structure, and the knowledge structure. 106. The system of claim 105 wherein the logic to depict relationships includes logic to depict hierarchical relationships. 107. The system of claim 106 wherein the logic to present depicts all relationships among the problem statement structure, the conclusion statement structure, and the knowledge structure. 108. The system of claim 107 wherein the logic to present includes logic to present user controls to create at least one new problem statement structure, conclusion statement structure, or knowledge structure. 109. The system of claim 107 wherein the logic to present includes logic to present user controls to modify at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 110. The system of claim 104 wherein the logic to present includes logic to present structures all of similar type. 111. The system of claim 110 wherein the logic to present includes logic to present user controls to modify or create at least one of the problem statement structure, the conclusion state ment structure, and the knowledge structure. 112. The system of claim 104 wherein the logic to present includes logic to present an individual structure only. 113. The system of claim 112 wherein the logic to present includes logic to present user controls to modify or create at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 114. The system of claim 95 wherein the control logic includes logic to provide suggestion feedback to the user of next steps for a user to take, wherein the logic to provide suggestion feedback is responsive to prior user interactions. 115. The system of claim 114 wherein the logic to provide suggestion feedback includes logic to perform gap analysis on the at least a subset of the problem statement structure, the conclusion statement structure, the knowledge structure, and the relations therebetween to suggest next steps for the user to create or populate structures identified from the gap analysis. 116. The system of claim 115 wherein the logic to perform gap analysis includes logic to analyze linkages among the at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure to detect gaps. 117. The system of claim 115 wherein the logic to provide suggestion feedback includes filtering logic to determine whether to provide suggestion feedback based on the state of development of the user interactions. 118. The system of claim 114 wherein the logic to provide suggestions includes content analysis logic to analyze content entered by the user to determine relevant suggestions for next steps to the user. 119. The system of claim 118 wherein the content analysis logic parses user entry to determine if the entry corresponds to a predefined set of phrases. 120. The system of claim 114 wherein the logic to provide suggestions includes relationship analysis logic to identify suggestions of next steps according to predefined relationship criteria. 121. The system of claim 114 wherein the logic to provide suggestions includes logic to present suggestions for next steps to the user in a visually distinctive manner. 122. The system of claim 121 wherein the logic to present suggestions for next steps to the user presents user controls in emphasis. 123. The system of claim 121 wherein the logic to present suggestions for next steps to the user presents workspace controls to activate a workspace corresponding to suggested next steps in proximity to a current workspace. 124. The system of claim 114 wherein the logic to provide suggestion feedback includes logic to provide content analysis of at least one of the problem statement structure, the conclusion statement structure, and the knowledge structure. 125. A system for facilitating user thinking about an arbitrary problem, comprising: first logic to facilitate user specification of the problem to populate a problem statement structure; second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure; third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure; model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, and knowledge structure; and visual feedback logic to depict an archetype problem-solution structure and to depict the user model structure. 126. The system of claim 125 wherein the model logic builds a three-dimensional graphic to represent the user model structure and the archetype problem-solution structure and wherein the three dimensional graphic includes a distinct graphical feature for each of the problem structure, conclusion statement structure, and knowledge structure. 127. The system of claim 126 wherein the three-dimensional graphic is an object with faces defining the surface of the object and wherein each distinct graphical feature for each of the problem structure conclusion statement structure, and knowledge structure is a facet of the object. 128. The system of claim 127 wherein the appearance of the three-dimensional graphic is representative of the development of the user thinking of the arbitrary problem. 129. The system of claim 127 wherein the distinct graphical feature is displayed to suggest the relative development of the corresponding problem structure, conclusion statement structure, or knowledge structure. 130. The system of claim 129 wherein the distinct graphical feature is displayed to suggest whether a corresponding problem structure, conclusion statement structure, or knowledge structure is lacking in user-provided content. 131. The system of claim 126 wherein the archetype problem-solution structure is a dynamic structure that changes in response to the user model structure. 132. The system of claim 130 wherein the archetype problem-solution structure is a dynamic structure that changes in response to the user model structure and wherein the three-dimensional graphic depiction of the archetype problem-solution structure includes a depiction to suggest a corresponding problem structure, conclusion statement structure, or knowledge structure is lacking in user-provided content and said depiction is a suggestion of a next step for the user in thinking about the arbitrary problem. 133. The system of claim 126 wherein user-activation of a graphical feature launches a corresponding workspace for the user to develop the corresponding problem structure, conclusion statement structure, and knowledge structure. 134. The system of claim 133 wherein a workspace presents content populating the problem structure, conclusion statement structure, and knowledge structure and includes user controls to develop content and relationships of the problem structure, conclusion statement structure, and knowledge structure. 135. The system of claim 134 wherein the workspace further includes user controls to suggest next steps for the user. 136. The system of claim 135 wherein the model logic arranges facets on the surface in an older to suggest next steps to the user. 137. The system of claim 136 wherein a first facet and second facet are arranged adjacent to suggest activation of the second facet as a next step to the user. 138. The system of claim 136 wherein the order is based on relative amount of development for corresponding problem structure, conclusion statement structure, and knowledge structure. 139. The system of claim 136 wherein the order is based on relationships among corresponding problem structure, conclusion statement structure, and knowledge structure. 140. The system of claim 135 wherein the user derivation and specification of knowledge includes the user specification of data and wherein the knowledge structure is a data structure to hold data. 141. The system of claim 135 wherein the user derivation and specification of knowledge includes the user derivation and specification of information and wherein the knowledge structure is an information structure to hold information. 142. The system of claim 135 wherein the user derivation and specification of knowledge includes the user derivation and specification of analysis and wherein the knowledge structure is an analysis structure to hold analysis. 143. The system of claim 135 further including fourth logic to facilitate user specification of at least one subtopic statement, related to the problem, to populate a corresponding at least one subtopic statement structure to disaggregate the problem into related subtopics, and further including fifth logic to facilitate user specification of at least one meaning statement, related to a corresponding at least one problem or subtopic statement, to populate a corresponding at least one meaning statement structure, and wherein the model logic tracks user interaction with the first through fifth logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, knowledge structure, at least one subtopic statement and the at least one meaning statement. 144. A system for evaluating user thinking about an arbitrary problem, comprising: first logic to facilitate user specification of the problem to populate a problem statement structure; second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure; third logic to facilitate user derivation and specification of knowledge, related to the problem statement and the conclusion statement, to populate a knowledge structure; tracking logic to monitor user interactions with the first through third logic and to build a corresponding model of such interactions so that the model, and the corresponding user thinking process, may be evaluated. 145. The system of claim 144 further including fourth logic to facilitate user specification of at least one subtopic statement, related to the problem, to populate a corresponding at least one subtopic statement structure to disaggregate the problem into related subtopics, and further including fifth logic to facilitate user specification of at least one meaning statement, related to a corresponding at least one problem or subtopic statement, to populate a corresponding at least one meaning statement structure, and wherein the tracking logic further monitors user interactions with the fourth and fifth logic to build the model. 146. The system of claim 145 wherein the model depicts a problem-solution structure utilized by the user during the thinking process, and wherein the model may be analyzed to evaluate the problem-solution structure of the user. 147. The system of claim 146 wherein the model may be compared to an archetype problem-solution structure.
COPYRIGHT NOTICE A portion of the disclosure of this patent document contains or may contain material, which is subject to copyright protection. The copyright owner has no objection to the photocopy reproduction by anyone of the patent document or the patent disclosure in exactly the form it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. FIELD OF THE INVENTION The invention relates to systems and methods of facilitating and evaluating user thinking about an arbitrary problem. BACKGROUND It is widely recognized that good problem solving and thinking skills need to be learned and supported. The availability of computers and electronic information bring an opportunity to support this need. There is today no approach that teaches and supports creative problem solving and thinking as a whole, integrated discipline, including the evolution of the person's understanding of the problem, exercising of logic and judgment, development of knowledge and ideas, and the mastery of a comprehensive answer. Today's problems are often complex, many are highly qualitative and difficult to specify, many often lack absolute answers. At the same time, information availability is almost limitless. In addition, more alternative points of view lead to and require more complicated arguments and solutions. In school, problems like understanding the causes of WWII and its impact on the peoples and governments of Europe, in business problems like deciding whether a widely held directional view is accurate or desirable—both are examples that demand understanding multiple inputs, multiple possible solutions and many thinking interrelationships. Educational experts including the U.S. Department of Education recognize thinking and problem solving as a significant and important challenge for educators and workers in the 21st century. In a 2003 report, skills critical to teach children for the future include: “thinking and problem-solving skills that use information and communications technologies to manage complexity, solve problems and think critically, creatively and systematically.” Today, the teaching of problem solving and thinking and related topics occurs as a result of many disparate activities. Beginning in about the fourth grade and continuing through high school, college and into adulthood, students are exposed to some of the components of problem solving in manners designed to increase their understanding, experience, and comfort. In the fourth grade, they often have their first exposure to independent research. Most are exposed to the scientific process and its defined steps and to some form of steps for researching and writing papers; some have experiences in developing multi-media presentations. But these exercises are mostly taught separately and independently, and unpredictable in their results. Whether a student becomes an “end to end” problem solver—capable of defining a problem, finding and researching information, developing their own understanding, defining alternatives and eventually an answer supported by their work—is uncertain. Computer and information technology support of problem solving and thinking is fractured and focuses primarily on the information handling activities. Separate and independent software programs support search and retrieval, information manipulation and management, information presentation and communication, and others. While this may be comfortable for many adults, little computer support exists for “thinking” and analysis logic particularly for the more qualitative topics that predominate. There are no software enabled processes that help guide good thinking and address the complexity of today's problems. It is also well documented that different people learn differently (Howard Gardner, in Frames of Mind, The Theory of Multiple Intelligences, for example). Similarly, adults solve problems by applying their own styles. These alternative learning and problem solving styles may be equally good as long as they lead to an equally good “answer” and the thinking that has occurred has developed a robust, internally valid set of understanding and choices, sound logic and consistent support of conclusion and arguments. The learning of many skills is enhanced by observing models; students and adults often learn by observing and emulating model behavior. Expert problem solvers know how to approach the problem, how to organize their thinking, how to manage the information and knowledge activities they need to do, how to evaluate where they are along the way and adjust their emphases to achieve a good result. Teachers and expert adults can try to serve as models in teaching problem solving, but consistent, comprehensive problem solving and thinking models are hard to find and even harder to see and understand. There is a need for a software tool that enables and supports a comprehensive problem solving and thinking process, especially in information intensive situations. SUMMARY The invention provides systems and methods of facilitating and evaluating user thinking about an arbitrary problem. According to one aspect of the invention a system and method facilitate user thinking about an arbitrary problem. The system includes (and the method performs) first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion, related to the problem specification, to populate a conclusion statement structure. It also includes third logic to facilitate user creation and specification of knowledge, related to at least one of the problem specification and the conclusion specification, to populate a knowledge structure. Lastly it includes control logic to persuade user interaction with the first through third logic to a sequence of interactions within a predefined set of interaction sequences, wherein the predefined set of interactions define an archetype process for user thinking about the problem. According to another aspect of the invention, a system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure. It also includes third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure. It also includes model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the user model structure, conclusion statement structure, and knowledge structure, and structure analysis logic to analyze the user model structure relative to an archetype model structure. With the above, the system and method can facilitate and evaluate user thinking by monitoring the user's process to address the arbitrary problem and by monitoring the users structure of problem-solving. According to another aspect of the invention, the system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure, and third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure. It also includes model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, and knowledge structure; and visual feedback logic to depict an archetype problem-solution structure and to depict the user model structure. In this fashion, the visual feedback logic may help coach the user in his or her problem solving approach. According to another aspect of the invention, the system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure, and third logic to facilitate user derivation and specification of knowledge, related to the problem statement and the conclusion statement, to populate a knowledge structure. It also includes tracking logic to monitor user interactions with the first through third logic and to build a corresponding model of such interactions so that the model, and the corresponding user thinking process, may be evaluated. According to another aspect of the invention, the knowledge structure may contain data, information, or analysis specifications. According to another aspect of the invention, the system may include logic to specify meaning statements or subtopic statements. According to another aspect of the invention, various views may be created to display relevant structures and to provide workspaces to create, derive or specify knowledge, conclusions, problem specifications and the like. According to another aspect of the invention, the system includes logic to provide suggestion feedback to the user of next steps for a user to take, in which the logic to provide is responsive to prior user interactions. The suggestion feedback may include logic to perform gap analysis on the at least a subset of the problem statement structure, the conclusion statement structure, the knowledge structure, and the relations therebetween to suggest next steps for the user to create or populate structures identified from the gap analysis. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 is a conceptual depiction of the preferred embodiment. FIG. 1A is a schematic diagram of an overview of one embodiment of groups of components of the archetype structure. FIG. 1B is a schematic diagram of an example development path for an integrated thinking and knowledge construct. FIG. 1C is a schematic diagram of an example alternative development path for an integrated thinking and knowledge construct. FIG. 1D is a schematic diagram of another example alternative development path for an integrated thinking and knowledge construct. FIG. 1E is a schematic diagram of example alternative viewpoints that may be provided to the user by representations. FIG. 2 is a schematic diagram of one example computing implementation environment for one embodiment. FIG. 3 is a schematic diagram of an example architecture for one embodiment. FIG. 3A is a flowchart showing the general interaction of the architecture modules of one embodiment. FIG. 3B is a flowchart further related to the transactions and functions associated with one embodiment of process manager suggestor. FIG. 3B-10 is an additional flowchart further related to the transactions and functions associated with one embodiment of process manager suggestor. FIG. 3C is a flowchart of transactions related to the general functions of the example software module view and representation manager. FIG. 3C-10 is a flowchart providing further detail regarding one embodiment of the example view and representation manager module. FIG. 3C-20 is a flowchart providing further detail regarding optimization by one embodiment of the view and representation manager. FIG. 4A is an example structure for a topic set as a thinking structure of an integrated construct of one embodiment. FIG. 4A-10 is an example of one embodiment of a topic set, specifically a topic set created for a history assignment in an educational setting. FIG. 4B is an example of the addition of information constructs to an integrated construct of one embodiment, in the case in which a topic set has been previously defined. FIG. 4C is an example of the addition of an analysis construct to an integrated construct of one embodiment, in the case in which a topic set and certain information constructs have been previously defined. FIG. 4D is an example of the addition of a meaning statement to an integrated construct of one embodiment, in the case in which a topic set, certain information constructs, and an analysis construct have been previously defined. FIG. 4E is an example of linkages between components of an integrated construct of one embodiment. FIG. 5 is a flow diagram of one embodiment of the method and process provided through the archetype process. FIG. 5A is a flow chart showing additional detail regarding defining the project initiation, goal and problem definition. FIG. 5B is a flow chart showing additional detail regarding one embodiment of the question and topic assistance tool. FIG. 5B-10 is an example embodiment of the categories of model topics or questions of one embodiment of the topic assistance tool. FIG. 5B-20 is an example embodiment of the subcategories of model topics or questions of one embodiment of the topic assistance tool. FIG. 5B-30 is an example embodiment of model subtopics topics of one embodiment. FIG. 5B-40 is an example embodiment of model secondary subtopics of one embodiment of the present invention. FIG. 5C is a flowchart of transactions related to one embodiment of creating a new information construct. FIG. 5D is a flowchart of transactions related to one embodiment of formatting or modifying an information construct. FIG. 5D-10 is an example of an unformatted entry approach for the information construct of one embodiment. FIG. 5D-20 is an example of formatted entry approach for the information construct of one embodiment. FIG. 5E is a flow chart of transactions related to one embodiment of acquiring information through an Internet browser or other electronic source. FIG. 5F is a flowchart of transactions related to one embodiment of creating a new analysis construct. FIG. 5G is a flowchart of transactions related to one embodiment of formatting an analysis construct. FIG. 5H is a flowchart of transactions related to one embodiment of adding elements to an analysis construct. FIG. 5H-10 is an example of relationships between an analysis construct and information constructs of one embodiment. FIG. 5H-20 is an example of a partially completed analysis construct work space of one embodiment. FIG. 5H-30 is another example of a completed analysis construct. FIG. 6 is a schematic diagram of an example of one embodiment of regions that may be used in representing an integrated thinking and knowledge construct and the associated method and process. FIG. 6A is a schematic view of example types of views or representations that may be provided by one embodiment of the present invention, being shown as regions and slices as well as the overall and individual component views. FIG. 6B is a schematic depiction of one example embodiment of regions as representational areas in one 3-D embodiment. FIG. 6C is another schematic depiction of one example embodiment of regions as representational areas in one 3-D embodiment. FIG. 6D is schematic depiction of one example embodiment of “slices” as a means of providing representations in one 3-D embodiment. FIG. 6E shows a schematic depiction of the use of next visible views and implied next visible views in a 3-D embodiment. FIGS. 6I to 6V are alternative example shapes which may be used to represent the integrated construct of the present invention as a three dimensional object. FIG. 7 is a flow chart of the views provided by one embodiment of the present invention and example navigational paths between these views. FIG. 7A is an example of one embodiment of a representation focused on a subtopic in one 3 dimensional representation form. FIG. 7B is a schematic illustrating an example of a 2 dimensional embodiment of regions and subset or slice views. FIG. 7C is an example of one representation in a 2 dimensional embodiment, focused on an individual subtopic view. FIG. 7D is an example of one representation of an embodiment of a linkage view, specifically focused on a person information construct. FIG. 7E is an example of a navigator device used in one embodiment. DETAILED DESCRIPTION The system provides a software tool to evaluate, facilitate and convey user thinking about an arbitrary problem. In preferred embodiments, the tool begins with a base-line structure in which to address an arbitrary problem. At its simplest, this structure includes the idea of specifying and inter-relating the problem or topic to be addressed, specifying a proposed conclusion to the problem, and specifying knowledge. The tool provides various user mechanisms for the user to develop their thinking. The tool provides the ability to populate various structures with various specifications of topics, conclusions, and knowledge, and their interrelationships. More significantly, the tool provides intelligence to the process and the structure of the user's work. The tool monitors and tracks the interactions of the user to determine whether the user's approach or process toward addressing the problem might benefit with certain specific suggestions to aid the user's development or thinking. In addition, the tool monitors the structure of the user's thinking to determine whether the user's problem definition, knowledge, and proposed conclusion and underlying thinking is well-founded in a structural and in some cases, logical sense. To do the former, the tool tracks the specific interactions of the user to monitor things like interactions spent specifying details and collecting data vs. developing conclusions. To do the latter, the tool analyzes the structure of the user's presently proposed conclusion, for example, analyzing whether it is supported by knowledge. In preferred embodiments, the former and latter are implemented with rules-based inference engines to make suggested actions for the user, in a variety of ways. The tool provides an ability to encapsulate or contain the state of thinking and development in an entity called an ITKC. This entity integrates the topic, conclusion and knowledge, and the tool conveys this integrated state preferably using a visual, physical metaphor such as a three-dimensional object, although two dimensional embodiments may also be used. The tool inherently contains an exemplary ITKC, and in some sense this is a core, exemplary or archetype structure for an arbitrary problem. The tool uses the archetype problem solution structure and the archetype or preferred process as the basis for providing guidance to the user in their development of their thinking, and in response their actions. Initially, the user is provided with a starting point for their project that in a preferred embodiment is undeveloped other than to model that an exemplary structure includes at least a topic, conclusion, and knowledge area. A more specific starting point for user development may be provided, for example, a super-user, teacher or other source may provide more specific structure to the problem and perhaps some initial content or the like to provide a more specific ITKC starting point. The user then may further develop this provided initial ITKC in the process of their thinking evolution. As they add structures, content and relationships to their thinking, their personal ITKC will correspondingly modify. The tools to track user interactions and make suggestions combine with the interrelated visual feedback views to in effect guide the user in an archetype process for developing their thinking about an arbitrary problem. By this it is meant, a model or exemplary process or way to approach the problem procedurally. Since the user will develop their ITKC, the applicable archetype problem solution structure and applicable portions of the exemplary process will change in relation to the present ITKC (i.e., model or exemplary structure will depend on the user's current ITKC to which it is compared). Thus, the applicable archetype structure and exemplary process are in some sense dynamic. In addition, the archetype process is state dependent, meaning the process suggestions made and monitored will depend on the state of the user's actual processing and interactions. The tool thus facilitates an exemplary process for accomplishing sound thinking and knowledge development about arbitrary problems and provides the user with the ability to develop their own thinking and knowledge about the problem through the development an ITKC or integrated thinking and knowledge construct. The archetype process and structure facilitate the user from conception of the problem (or question, issue, subject, topic, or area of interest) through the creation and viewing of a summary understanding, answer or other result. For purposes of this application, the terms ITKC, “integrated thinking and knowledge construct,” “thinking and knowledge construct,” “integrated knowledge and thinking construct,” “knowledge and thinking construct” and “integrated construct” are used interchangeably. Referring now to the Figures, in FIG. 1, in a preferred embodiment, the tool provides (i) an archetype structure (block 1500) which provides components and options for creating, structuring, developing, and relating the set of components a user may employ in developing their thinking and knowledge about an arbitrary problem; (ii) the user developed model or ITKC, indicated in block 1000, which is comprised of user selected and developed thinking and knowledge structures and encapsulates the relationships and process history conducted by the user; (iii) an archetype process, as indicated in block 2000, for thinking about and solving arbitrary problems, which enables and helps guide the user in their work; (iv) tracking, evaluating, and inference modules which monitor and evaluate the user's actions against archetype or exemplary structure and process rules, and make suggestions to the user accordingly; and (v) an ongoing representation of the user's developed model or ITKC, as indicated in block 100, against various views that convey archetype structure and process, as well as potential natural next thinking and working steps, and therefore provide ongoing coaching to the user through visual feedback. The user developed model is referred to herein as an ITKC or Integrated Thinking and Knowledge Construct. It should be understood that the use of the word construct is employed to convey both (i) a component that is constructed and evident to the user; and (ii) the underlying data storage and retrieval requirements for achieving the described component or components and parts (see additional description below regarding options which may be employed in the data structure and implementation approach). In a preferred embodiment, the user developed model can subsequently be tracked and evaluated against archetype structural expectations by the tool, including but not limited to items such as the types of components selected, the prevalence of components selected, the completeness of components used at various stages in the development of the ITKC (in terms of content, structure, and linkages) and others. The user process can similarly be tracked and evaluated against the archetype process rules, including but not limited to items such as what portions of process the user elects to try or use, the user's response history to suggestions made by the system, and the user's selection and use of various views which constitute thinking subsets. As described elsewhere herein, in a preferred embodiment, such tracking is used for direct feedback to the user, the generation of suggestions, and various reporting and tracking activities for the primary user and potentially for users like teachers. In one preferred embodiment, as shown in FIG. 1A, the archetype structure for an arbitrary problem 10 may include a thinking construct 20 and a knowledge construct 40 which may each include a plurality of components. The groups of components of the thinking construct 20 preferably include a number of thinking structures which in a preferred embodiment may include: (i) a topic set 22 for defining and maintaining the definition of the subject, topic, questions, problem, issue, area of interest or other suitable descriptions of the project, and preferably including both a main topic or problem and one or more subtopics; (ii) a meaning statement set 24 for developing and maintaining the user's perspectives regarding the data and/or analysis including one or more but not limited to: conclusions, observations, hypotheses, theories, summary statements, perspectives, ideas, or any similar items; and (iii) an answer or summary set 26 for developing and maintaining the highest level answer or summary viewpoint of the results attained relating to the project. In a preferred embodiment, the components of the knowledge construct 40 may generally include: (i) information constructs 42 for creating, organizing, and maintaining data and information elements regarding the project, including structured and unstructured formats; (ii) analysis constructs 44 for developing or associating a plurality of analyses regarding the project, which may be based on data, information elements and/or information constructs created with via this invention or gathered from other electronic sources and associated with the integrated construct, and for maintaining the analytical components in structured and/or unstructured formats; and (iii) portions of data 46 which are not structured according to information constructs or analysis constructs, but which are associated with the integrated construct. The integrated construct further includes the linkages or relationships 60 that may exist or be created among and between any of these individual components and groups of components. In certain cases, the preferred embodiment provides one or more links automatically in response to user actions as the user proceeds through the various stages of development of the integrated construct. As discussed below, these links help the user understand and document the relationship between various construct knowledge or thinking components. For simplicity purposes, this application primarily refers to the building, creation, use and sharing of a single ITKC or integrated construct, although it should be appreciated that the preferred embodiment is preferably operable to enable one or more users to create one or more integrated constructs, which may be standalone or related to one another. It should also be appreciated that a user may include one person or a group of people. The integrated construct or ITKC which is built by the user can be associated with or contain as little information as the title or label the user assigns to the integrated construct. The integrated construct can be associated with or contain one, some or none of the component types enabled to the user by the preferred embodiment. The integrated construct can also contain or be associated with a one, none or a plurality of empty, partially completed, or completed components, as described below. The output of the preferred embodiment may be electronic or paper based. The method and system also enables users to include electronic information from other standard computerized tools and information formats such as images and documents that may be copied and pasted into or otherwise associated with portions of the integrated construct. The archetype structure and method and process of the preferred embodiment are preferably modular in their embodiment to enable the use of individual or subset combinations of components in the progressive building of the integrated construct, and the corresponding associated portions of method and process. The method and components provided by the preferred embodiment are based on the understanding of experts in completing information intensive development, thinking and knowledge development about arbitrary problems. The method and system preferably includes guidance for the user as the user proceeds in the creation of the integrated construct, through the options and tools that are provided to the user, through tracking user actions and providing suggestions to the user, and through the design of the visual feedback representations, work spaces and navigation provided to the user. The method and process can be used or implemented in a linear fashion, but are preferably modular to enable creation of the components or the use of the archetype process in a non-linear fashion thereby supporting different individual thinking and problem solving styles, and different kinds and complexities of problems or topics, as discussed further below. The representations and user interfaces provided by the preferred embodiment offer several distinct advantages, including but not limited to the following: (i) the design of the one or more two-dimensional or preferably three dimensional representations depict the development of an ITKC and help guide and provide access for the user to the associated archetype process and archetype structure; (ii) in the three-dimensional form, the display and manipulation of the integrated construct behaves as though it were a physical three dimensional object, in that the integrated construct can be rotated, flipped, turned, zoomed in on and zoomed out on; (iii) each two or three dimensional representation of the total integrated construct represents the whole thinking for a user about a problem or project, with parts that have meaning in relation to that whole, and the relationships are made readily apparent; (iv) the representations provided by the preferred embodiment are in and of themselves a form of guidance, as they differentiate types of thinking work, provide meaningful workspaces for working on their problem from different vantage points, and suggest by their visual and place relationships and specific design where the user is in relation to the archetype process and structure, and next steps the user might want to consider (as discussed below). Order of Work and Thinking in the Construction of the Integrated Construct The preferred embodiment facilitates the development of an integrated construct through a plurality of different paths, according to the user's preferred thinking and problem solving approaches, the nature and complexity of the problem being addressed, and other determinants. Referring now to FIGS. 1B, 1C and 1D, the order in which problems or inquiry based projects may be completed and the integrated constructs and their various components are built and used can vary widely. The starting point, for instance, as shown schematically in FIG. 1B, may be defining the topic set 22 by inputting or defining an issue, question or problem and its descriptors, with subsequent focus on developing data 46 and information constructs 42 and analysis constructs 44 and finally in developing views on an answer or summary view 26 (as would be the case in conducting most independent student projects or research papers). Alternatively, as schematically shown in FIG. 1C, the starting point may be an answer or summary set 26 by inputting a single or set of alternative answers, hypotheses, or summary views 26, for example, with subsequent activities focusing on collecting and analyzing information in data 46, information constructs 42 and/or analysis constructs 44, the clarification of topics or questions 22 relevant to the alternative answers or views, and so on (as would often be the case with adults who are deliberating between alternative answers to a problem or have a hypothesis that is to be tested and proved; this is also the general process for the scientific method). Similarly, as schematically shown in FIG. 1D, the starting point may be a set of information constructs 42 which includes a set of information that has been previously gathered, that are to be interpreted, with subsequent focus on the meaning statements 24 and analysis constructs 44 that may be developed based on such information (as might be the case in educational settings and activities around a set of content, for example). It should be appreciated that a plurality of paths and a plurality of orders of use of the components as well as choice of the component types that may comprise an integrated construct are all in accordance with the preferred embodiment. The modularity and flexibility of the method and process that facilitates the flexibility in paths for integrated construct development provides a significant advantage. It should thus be appreciated that the preferred embodiment preferably provides certain visual and general method of stability or familiarity to the user from the very outset of the definition of an arbitrary problem through the completion of an integrated construct. The preferred embodiment thus provides guidance while also providing flexibility in the approach to problems and inquiry based projects, enabling the user to address an inquiry based project in a natural, progressive way. Applications of the Integrated Construct The archetype structure and process that provides for the ability to develop integrated constructs and the associated process, method and system of the preferred embodiment can be employed in a wide variety of different circumstances. As discussed above, one of the most prevalent uses is likely to be in supporting a user faced with a problem or similar project that may generally involve one, some or all of the following: (i) some degree of defining one or more problems, issues, questions or other area of interest; (ii) gathering, organizing and depicting information and/or preparing understanding or analysis about that problem, issue, question or area of interest; (iii) determining and developing the user's own understanding, perspectives and/or opinion about that problem, issue, topic, question, or area of interest and the knowledge they have developed; (iv) constructing meaning about the problem, issue, topic or area of interest, and/or adding the user's own thinking, which may include the user's creative thoughts, theories, conclusions, and/or perspectives or other similar items; (v) determining some kind of culminating answer or summary view for their project or problem; (vi) evaluating progress and adjusting their approach along the way, evaluating that the results are sound and follow principles of good thinking and problem solving; (vii) portraying or otherwise communicating the user's results in completed form and/or while in process. Although the preferred embodiment supports the totality of activities involved in such arbitrary problems or inquiry based projects, the preferred embodiment can be used effectively to support and enable any one, some or all of these activities in absence of a complete process for an arbitrary problem or inquiry based project or for any subset of combination of these activities. The preferred embodiment may be used in learning environments (such as primary or secondary schools, colleges and universities) as well as in commercial environments (such as corporations, partnerships and other businesses) and non-commercial environments (such as in home or personal projects). In a preferred embodiment, the archetype process and structure can be used in almost any understanding and/or problem solving or opinion situation, in place of a text paper, an electronic presentation, or a web site. Certain Advantages of Preferred Embodiments of the Invention The preferred embodiment can be employed in many different circumstances and by many different types of users. This enables better transfer of learning of thinking skills across problems or projects for a single user, and sharing such learning across users. Another advantage of the preferred embodiment is that the archetype process and structure provide a modular approach that enable the user to navigate flexibly across the components of the integrated construct and the steps of the process and method, including a plurality of different entry points. Different thinking and problem solving styles can be supported, and yet still benefit from the guidance and tracking abilities of the tool. While the preferred embodiment provides for support of a wide range of types and complexities of problems, issues and topics from definition of a topic of interest through creation and depiction of the summary understanding, solution or result, the steps and components of the preferred embodiment can be used individually or in subset combinations thereof. The preferred embodiment enables the visualization and feedback of developing and completed thinking and knowledge about a problem not only for the immediate user, but the ITKC can be shared with other users. Other advantages of the preferred embodiment include, but are not limited to the following: (i) the scope of the archetype structure and process may include and integrate not only data and information or knowledge related to a problem, but importantly, how the user chooses to define the problem, question or topic they are trying to solve and the meaning, viewpoint or answer the user chooses to create from the information and analyses the user collects and/or creates; (ii) the ITKC that the user develops is an ongoing detailed and high level, highly related construction that encapsulates their thinking and knowledge work and can therefore be tracked and used as the basis for guidance; (iii) the preferred embodiment provides the ability to create, manage, view, and maintain components and simple and complex linkages between the components as the integrated construct is developed, both vertically (such as in levels of detail) and horizontally (such as in informational relationships); (iv) the archetype structure and representations may differentiate classes of types of thinking and knowledge related work into a set of identifiable regions which focus on the particular thinking or knowledge activity; (v); (vi) the representations may provide a way of abstracting away from the detailed content and linkages during appropriate thinking and knowledge activities, while still providing access to detail as desired; (vii) the representations may provide optimal combinations of components for different work activities with their associated method and process, and may use visual representations and other methods to provide the user with suggestions on next steps or views, and others as evident elsewhere herein. Implementation Approach One embodiment within a computer environment is depicted in FIG. 2, with elements of this embodiment generally including: (i) a set of computer software programs 90 resident on or operating through a computer processor 91a and 91b; (ii) a suitable form of data storage and management 93 capable of facilitating the storage and retrieval of multiple components of the integrated construct, any associated linkages, as well as process history, user profiles, and specific ITKC component content and characteristics; (iii) a graphical user interface 96 or other suitable representation mechanism or form 97, whether directly connected to a CPU 91 or working through a network 95c to access a remote CPU 91 or other display mechanism of some kind; and (iv) likely access to other electronic information sources such as the Internet 95a and other electronic sources, whether resident on the same CPU as indicated in block 94d, as the programs or accessible via a local or other network 95b. The preferred embodiment may also co-reside with other standard tools, such as a word processor 94a, a spreadsheet processor 94c, and Internet browser 94b and other such tools. As stated below, the preferred embodiment may be resident on a local CPU 91 or accessible remotely over local networks 95b or the Internet block 95a. As also described more fully below, the embodiments are not limited by type of operating system, 92. FIG. 3 depicts one example architecture for one embodiment is operable to provide the logic, method and process, capabilities and components, and representations for one or more users. In this embodiment, the architecture software modules represented in FIG. 3 interact to provide the functionality described herein, and which in one embodiment generally include: (i) a representation or graphical user interface 100; (ii) a view manager 200 or like module(s) which facilitates the representations or graphical user interface, the status of their evolving ITKC and portions of associated process and content being presented to the user; (iii) a process manager suggestor 300 which utilizes the archetype structure and process to provide help and guides to the user; (iv) a process manager 400 or like module which facilitates the user in constructing their ITKC based on and guided by the archetype structure; iv) a linkage manager 600 or like module which updates linkages among and between the components of the integrated construct and groups of components, in some cases automatically and in other cases in response to user actions; (vi) an update manager 700 or like module which updates the content and structure of the integrated construct in response to user actions; and (vii) the content of the integrated construct and its associated structure or formats, stored in a suitable form of data storage and retrieval mechanisms 800. These general software architectural modules are described in greater detail following the description of the method and process of the invention provided below. It should be appreciated that the specific embodiment may be operative in a plurality of electronic and computerized environments, as described more fully below. It should further be appreciated that the precise boundaries of computer programs or other implementation mechanisms can differ from those represented in the general software architecture depicted in FIG. 3 and still be in accordance with the preferred embodiment. It should further be appreciated that although the embodiments rendered in FIG. 2 and in FIG. 3 show a division between process and data, a preferred embodiment of the present invention is be object oriented or at the least highly based on object oriented design principles. The modularity of the method and process and its correspondence in structure to the components of the integrated construct lend themselves readily to object oriented implementation. The storage and management of the data/information and structural relationships that comprise the integrated construct can be created and accomplished through the use of a plurality of alternative, readily available mechanisms and approaches. It should be appreciated that a plurality of different data storage formats and associated creation mechanisms may be used to facilitate the process and integrated construct in accordance with the present invention. Given the general purpose and nature of the invention, the optimal implementation mechanisms for data storage and creation will differ according to the amount and complexity of the information, as well as the size and complexity of knowledge and thinking constructs being included in or associated with the integrated construct. These options will be readily apparent to those skilled in the art. One of the advantages of the integrated construct's architecture is that the process and construct can be implemented over a broad range of project complexities and broad range of amounts of data/information while still utilizing the same general user components, process, tools, regions, methods, and to a great extent, interface or representations. The interface representation, process, method, and underlying logic and information architecture for the integrated construct do not employ assumptions about the underlying operating system. In one computerized embodiment, the present invention may be implemented using one or more computer programs, each of which executes under the control of an operating system, such as Windows, OS2, DOS, AIX, UNIX, MAC OS and others, and causes the computer to perform the desired functions as described herein. Using the present specifications, the invention may be implemented as a machine, process, or article of manufacture by using standard programming and/or engineering techniques to produce software, firmware, hardware and any combination thereof. Generally, in the computerized embodiment, the computer programs and/or operating system are tangibly embodied in a computer readable device or media, such as memory, data storage devices, and/or data communication devices, thereby making a computer program product or article of manufacture according to the present invention, which may encompass a computer program accessible from any suitable computer or electronic readable device or media. The present invention can similarly be implemented with a plurality of configurations and devices. Moreover, in the computerized embodiment, the computer programs and operating system are generally comprised of instructions which, when read and executed by computers, cause the computers to perform the steps necessary to implement and/or use the present invention. Under control of the operating system, the computer programs may be loaded from memory, data storage devices, and/or data communication devices into the memories of the computers for use during actual operations. The present invention can thus be implemented in a local or remote processing environment, including use of a single computer, servers, the Internet or other forms of networked processing and communication. It should be appreciated that many modifications can be made to this implementation configuration in accordance with the present invention. Media Types The present invention facilitates the incorporation of a plurality of media types in each of its components and activities, including but not limited to alphanumeric characters, images, graphics, video, quantitative sets, three dimensional renderings, etc. It is common in the art of manually or paper based inquiry based projects to incorporate and use any or all of these information or media types, and it is similarly common in the art of computer programming, data delivered via the Internet and other electronic based information to incorporate a plurality of different information or media types. It should therefore be appreciated that the present invention is not intended to exclude any media type from the description, but rather to incorporate the plurality of media types common in the forms described above and likely to be incorporated into such forms over time. User Interaction In one embodiment of the present invention, user interaction with the system is accomplished through the manipulation of one or more user interaction, interface or input devices, such as a computer mouse, trackball, keyboard, touch pad, touch screen or stylus. Actions by a user with one or more of these interaction devices may cause a plurality of results, including but not limited to: (i) movement of a visual marker (e.g., pointer or cursor) across or on a representation provided by the system such as on a suitable display device; (ii) changes in the representations provided by the invention; or (iii) indication by the user that a component available to the user is to be selected for further action in some manner. Throughout the description of the detailed method, process, and system of the present invention, reference is made to user interactions such as these. “Selection” as used herein is intended to convey any suitable electronic means by which a user can indicate that the user wishes to initiate the relevant action associated with that selection. Similarly, movements by the user within and across the representations provided by the system are described as a way to change position and therefore access the relevant aspects of the method and system, or to change views of the integrated construct, its components or the regions or cognitive regions of the integrated construct as described herein. Such event handling approaches are well known to those skilled in the art. It should be appreciated that the use of other user interaction devices that result in similar inputs or cues to the system of the present invention may be used in accordance with the present invention. For example, user interaction can be accomplished through voice activation mechanisms, or through prompting from electronic transactions from other sources that result in an electronic signal to the system that is the functional equivalent of either entry through user interaction devices such as a keyboard or a mouse. Display Devices In the preferred embodiment of the present invention, the system displays a plurality of representations that may be provided on one or more of a plurality of devices. The present invention contemplates the display on one or more of a variety of suitable of display devices or displays. The present invention can be embodied through any suitable device that generally provides the functional equivalent of the computer screen or projected screen, hologram, or other electronic projection, as well as via paper or other media type. An alternative embodiment of the present invention provides for printing or otherwise displays portions of or the totality of the integrated construct and representations of the in-process or completed region views onto paper or other non-electronic media. Another embodiment of the present invention provides for the construction of a physical construct, with the ability to place, arrange or associate the information associated with each of the components of the integrated construct on or to a physical structure (as might be done, for example, on a physical exhibit). Potential Components of the Integrated Construct in One Embodiment A key enabler to the preferred embodiment is the archetype structure for the content created and associated with accomplishing an inquiry based project, preferably made up of both thinking and knowledge constructs. The component classes or types that make up the archetype structure are provided for the user to create, select, edit and link in the building of their ITKC. Linkages and relationships between components may be created directly by the user or automatically by the system, as described more fully below. In a preferred embodiment, the creation of components by the user creates subsequent thinking subset structures and workspaces customized to facilitate focus and thinking on meaningful subsets of the project and at a plurality of levels of detail. The following describes in greater detail examples of components of the archetype structure that may be used to comprise a user's thinking and knowledge construct, or ITKC as originally depicted generally in FIG. 1A. The manner in which the archetype structure is subsequently used to evaluate and further guide the user is described in a later section herein. In a preferred embodiment, types of components are synonymous with classes, as the archetype structure lends itself easily to object oriented implementation, although such implementation is not required. Thinking Constructs in one preferred embodiment are made up of a Topic Set, (including a Main Topic or Problem and subtopics), a Meaning Statement Set, and an Answer or Summary View. Topic Set Referring again to FIG. 1, one of the thinking structures that may be used as a part of a thinking construct includes the topic set 22, which may be used to define the scope of the problem, question, issue, subject or topic or area of interest intended for pursuit by the user. Components of the topic set may include items such as one or more topics, subjects, questions, problems, issues, areas of interest or any suitable other way of defining an area of interest. Components of the topic set may exist in a plurality of information media forms, including but not limited to text statements, drawings, images, or other commonly used or suitable information media forms or formats. FIG. 4A generally illustrates an example structure of a topic set 22. In this preferred embodiment, the topic set of an integrated construct includes at least one statement of main topic 1220, generally representing the highest level or summary topic, subject, question, problem or issue intended to be included in the integrated construct (for example, in an educational context, the main topic might be “What caused the development of the Constitution?”). The topic set may also include one or more subtopics 1222, 1224 and 1226 that are labeled Subtopics 1, 2 and 3 in FIG. 4A. Subtopics may be defined in order to partition or otherwise further elaborate the topic, subject, question, problem or issue of interest into smaller, more targeted or defined topics, subjects, questions, or issues of interest (for example, continuing in an education context, subtopics might include “Who created the Constitution?”, and “What events led up to the Constitution?”). The subtopics associated with a main topic may also take on a plurality of information forms. Referring again to FIG. 4A, in a preferred embodiment, subtopics may be further associated with one or more secondary subtopics such as secondary sub-topics 1222a, 1222b, 1222c, 1224a, 1224b, and 1226a respectively. These subtopics may provide a lower level of partitioning or other further elaboration of the subtopic, sub-question, sub-problem, sub-issue or sub-area of interest. For example, the subtopic “Who created the Constitution?” might be further partitioned or elaborated through two additional secondary subtopics, such as “Who were the Convention delegates?” and “What were their beliefs?” The secondary subtopics associated with any subtopic may again be comprised of information in any form: textual, drawing, video, image, graphic, etc. A secondary subtopic may be linked to more than one subtopic. Although the most often utilized linking is likely to be that of subdividing into greater detail or parts, the preferred embodiment also allows for the identification of other kinds of linkages across and among subtopics. It should be appreciated that the number of levels provided for the topic set may be varied and will generally be limited only by the processing robustness of the technology and data storage platforms on which the present invention is implemented. FIG. 4A-10 illustrates an example of a topic set, in this case created for a history project for an educational assignment. The present invention generally provides several representation choices, described more fully below. One preferred embodiment of the present invention also provides assistance in the form of a topic or question help tool, described in greater detail as a part of the method and process description below. The topic set 22 is preferably available throughout the process and method of the present invention for viewing, editing, adding to or deleting topics, subtopics, and/or secondary subtopics. This enables the user to for instance add additional relevant questions after the user is further along in the user's thinking process and investigation on the project. Linkages among and between components within the topic set are managed and can be changed, via the link or linkage manager 600 generally illustrated in FIG. 3 and described below. For example, secondary subtopics that are associated with a subtopic can subsequently be changed or moved to be linked to a different subtopic. Similarly, secondary subtopics can be changed or moved to become higher level subtopics, associated then with the main topic, if the user desires to do so. It should also be appreciated that other components of the integrated construct may be linked to components of the topic set and then available for viewing and editing accordingly, as will be described more fully in the detailed description of the method and process set forth below. In a preferred embodiment, topics, questions, issues or other areas of interest defined in the Topic Set also provide the basis for one form of subsetting the project into meaningful subsets for work and consideration by the user (as described more fully below). In one embodiment, the archetype structure provides for more than one topic set for the same problem, as in providing alternative means of subsetting or elaborating the problem of concern. Information Constructs Referring back to FIG. 1, in a preferred embodiment, information constructs 42 provide a way for the user to create, organize, group, format, and reference the collection of information or data that the user chooses to enter, create, or associate with their project and the integrated construct. In the educational project “What caused the Constitution?” for example, the user may wish to create information constructs for some of the key framers (James Madison, George Washington), the Constitution, the key parts of the Federal government (the Legislative, Executive, and Judicial branches perhaps) and state government. Information constructs in the invention may be formatted with specific elements, partially formatted, of highly unstructured (as in including or being associated with just a block of text for example). In a preferred embodiment, an information construct 42 may be made up of a large amount of information and/or high number of information elements, or may include as little information as the title, label or number assigned to it by the user. Reference points from other integrated construct components to information constructs 42 may be provided to the information construct in at least two ways including but not limited to: (a) to the information construct as a whole; and/or (b) to the information elements or groups of information elements associated with the information construct. FIG. 4B generally illustrates an example of the addition of an information construct such as 1422, 1424 or 1426 to an integrated construct 10, specifically in the case where a topic set 22 has been defined. An information construct may be defined uniquely in the integrated construct with a label, number or title. The title, number or label for the information construct may serve as a reference point to the collection of information or data elements that are to be associated with the unique label or title. In a preferred embodiment, information constructs 42 generally may be unformatted, fully formatted or partially formatted in their form. Unformatted information constructs provide the ability to add text, drawings, and/or other portions of information to be stored and associated with the title or label given uniquely to the information construct, and therefore available to the user and for linkage or use with other information construct or integrated construct components. An example of one embodiment of the entry of an unformatted information construct 1422a is shown in FIG. 4D-10. As specified elsewhere herein, the information or data may include a plurality of media forms when included in or associated with information constructs. The preferred embodiment may facilitates the assignment or association of information constructs with one or a number of subclasses or types. In one embodiment of the present invention, information constructs may be classified as “People,” “Places,” “Things,” “Media,” “Ideas,” “Events,” “Issues” and “Other.” The present invention also generally facilitates the creation of user specified, customized classes or types of information constructs. In the preferred embodiment, the assignment of information constructs to class types is not required. Information constructs can be seen and manipulated at a plurality of levels of detail, including but not limited to the detailed level, the summary level and at an overall title or symbolic or icon level via the present invention. The method and system also provides the ability to link and reference information constructs from the appropriate internal fields of other information constructs, and to define the nature of those relationships (for example, the person information construct “James Madison” having a birthplace element that is associated with the place information construct “Virginia”). The present invention facilitates the user associating and labeling information constructs as belonging to a similar category or group; information constructs may be associated with more than one group at the same time or in the same project. For example, information constructs of the type “People” might be grouped according to categories such as “Political Leaders,” “Explorers” and “Artists.” In a preferred embodiment, the present invention provides for the creation of groups of information constructs, the labeling or naming or titling of such groups, and the inclusion of descriptive or explanatory information to describe or otherwise explain the nature or definition of the group. Once created in the preferred embodiment, groups also behave and may be treated by the user similarly to information constructs in their own right. For example, the user can add information to the group—in formatted, unformatted or a combination form; groups can be linked or otherwise associated with topics, meaning statements, and other Integrated Construct components; groups can be associated with or otherwise linked with Analysis Constructs. The present invention in a preferred embodiment facilitates the visual distinction of different types or classes of information constructs in the display or representations of the integrated construct, such as through the use of different colors, icon designs, and/or shapes. In one embodiment, different colors and intensities of representation are used to depict the user's rating of the importance of the different information constructs. It should also be appreciated that different visual solutions may be used to differentiate the type or class of information construct in accordance with the present invention. In one preferred embodiment, the method and system of the present invention provides a number of available formats to assist the user in structuring information elements of a particular subclass or type. An example of such a structured format 42b is illustrated in FIG. 5D-20. Structured formats provided for information elements are generally associated with unique labels and a defined field or data type. For example, the information construct type “People” may include optional use of structured fields or data elements such as birth date. If selected to be associated with a particular information construct, the structured element format may become an empty data field associated with the information construct's label, and ready for receiving or otherwise being associated with information either via direct input by the user, or through other data entry mechanisms as described in the detailed method and process section below. Information Constructs may be linked or associated with one another in a variety of ways, including but not limited to: 1.) the association of one information construct as a whole with another information construct as a whole (for example, that the Information Construct James Madison, of type Person, helped create the Information Construct The Constitution, of type Thing or Media Thing); 2.) the association of a field that has been associated with or made a part of an Information Construct with another Information Construct (for example, that the Information Construct James Madison's, of type Person, birthplace—a field—was the Information Construct Virginia, of type Place). Additional links can be created between Information Constructs by the user to represent other relationships, either using labels for relationship types that are provided by the invention, or by entering their own custom labels (see later descriptions included in this document regarding links). For example, the Information Construct James Madison might be linked or related to the Information Construct Benjamin Franklin and labeled with the indication that they are “alike” in some way. Such links may also include internal data available to the user, such as in the user describing how the Information Constructs described above are “alike.” The resulting linkages or associations made with an Information Construct (and potentially made at different points of use and from different views as the user uses the invention) may then be represented to the user for review, editing, adding, in a representation such as shown in FIG. 7D, which shows an example of one embodiment of a linkage view for the information construct James Madison, 42. In a preferred embodiment, the present invention allows a user to change such formatting of an Information Construct over time. For example, a user may initially create a Person Information Construct, labeled James Madison, but have no additional information they wish to add to that Information Construct at the time they create the construct. Once created, the Information Construct (even in its “empty” form) may be associated or otherwise linked to other Integrated Construct Components (such as topics, meaning statements, analysis constructs, and others). Subsequently, the user may find some research information—perhaps over the Internet (as described more fully elsewhere herein) that he/she wants to associate with the James Madison Information Construct. Using the methods described later in this document, the user can select some such information and associate with the “empty” James Madison Information Construct, either as a section of text without further formatting, or by creating an element or field associated with the Information Construct and then associating the information with that element or field (such as Accomplishments, for example). Similarly, subsequently the user may decide that they wish to format the information additionally, instead of just having the text associated with a field or element label such as Accomplishments. The user may subsequently decide they wish to create fields or elements separately for Career and Publications, for example, and may do so with the present invention at any time during the life of the Information Construct. Elements, fields or sub areas of information associated with an Information Construct may be created by selecting from the predefined set provided by the present invention, or by creating custom elements, fields, or sub areas. The user may also subsequently format a field that was text, for example, as a date. In one preferred embodiment of the invention, information constructs may all have one or more common fields, such a separate field, element or information sub area for the inclusion of the user's opinion of the importance of the information construct, in light of the project, and for a summary story about the information Construct. In another embodiment of the invention, the user is provided with options to add required or standard fields, elements or sub areas to the different Information Constructs they will be creating in their project. The robustness and flexibility of Information Constructs provided by the present invention make them a valuable set of components, not only as part of an integrated construct, but also in conjunction with subsets of the total integrated construct, Analysis Constructs Referring back to FIG. 1, analysis constructs 44 are one component type provided by the archetype structure that generally enable useful views of information and constructed understanding which may provide a basis for the user to discern meaning. For example, in the educational project “What caused the development of the Constitution?”, analysis constructs might be created which included a sequence of events, a comparison of the beliefs of the different framers of the Constitution, or a visual depiction of the members who were Federalists vs. Antifederalists. Analysis constructs 44 may be developed based on previously created information constructs 42 and data 46, and may also be created based on new user's actions and not directly connected to previously created information constructs 42 or data 46. Analysis constructs may also be created and linked or otherwise referenced to other standard electronic analysis forms, such as spreadsheets. Like information constructs, the present invention provides that analysis constructs may be defined by a unique label or title, which may be in a variety of different information media forms, including but not limited to textual characters, images, graphics or any other suitable media type. Once created, an analysis construct preferably provides a workspace for the user, which may contain text, drawings, images or a plurality of information media forms. It should be appreciated that analysis constructs as described herein include both the provisioning of an interactive workspace for the user and the storage of the information components and relationships that must be stored to enable the user to retrieve and subsequently view or edit the analysis construct. Analysis constructs 44 may generally work as components within the larger integrated construct 10 structure. As such, analysis constructs may be labeled, referenced, and linked to the other components of the integrated construct, such as elements of the topic set 22, meaning statement set 24, and answer or summary set 26. Analysis constructs can also provide value to the user as standalone information subsets, or as constructs associated with information constructs (whether formatted or unformatted). Like information constructs, analysis constructs may also be unformatted, fully formatted or partially formatted. FIG. 4C depicts an example of the addition of an analysis construct 1442 to an integrated construct, specifically in the case in which a topic set 22 and certain information constructs 1422, 1424 and 1426 have been defined previously for the integrated construct. Referring again to FIG. 1, analysis constructs 44 may reference the information constructs and/or information elements. Analysis constructs 44 may show relationships between and among the information constructs 42, whether formatted, partially formatted, or unformatted, as previously described. These relationships may be based upon and built out of several different approaches by the user including, for example: (a) based on the contents of one or more information elements associated with a particular information construct 42; (b) relationships between information constructs 42 either perceived by the user or automatically defined within the integrated construct 10; and/or (c) the judgment of the user regarding the information elements within the information constructs 42, or any combination thereof. Analysis Constructs may also be created without any reference to prior created information constructs. As described more fully in the method and process later in this document, the user may create an Analysis Construct without reference to Information Constructs, either through the use of Unstructured Notes, or through the direct creation of an Analysis Construct using the drawing, text, image, and video import capabilities associated with the Analysis Construct. For example, a user may choose to draw the relationships he or she has been seeing in the information collected, or sketch a diagram of a hypothetical causation relationship freehand, as opposed to using the preformatted Analysis Constructs or specific references to the Information Constructs themselves. FIG. 5H-10 generally depicts examples of relationships that may be defined in one embodiment of the present invention between analysis constructs 44a and information constructs 1422, 1424, 1426, and 1428 in an integrated construct. In a preferred embodiment, analysis constructs 44 may be used in conjunction with information constructs 42 and unstructured data 46 to comprise the knowledge construct 40 portion of the integrated construct 10. Capabilities of analysis constructs in a preferred embodiment may generally include for example, but not limited to, the following abilities: (a) analysis constructs may reference, link and display information construct labels and/or icons or summary depictions in order to enable views and create understanding across individual information constructs, while still maintaining links to the detail within those information constructs for access by the user when desired; (b) analysis constructs may reference, link to and display information elements from within information constructs with similar access to related detail information; (c) analysis constructs may generate analysis construct views or portions of analysis construct views based on the contents of the information elements associated with specific Information constructs (as in the construction of a timeline from date elements within information constructs); (d) analysis constructs may enable the user to create a depiction of their understanding freeform, through text, drawings, graphics, images or other media forms (as in drawing the causal relationships between concepts or issues they have identified in their project); and, as described previously, (e) analysis constructs may provide visual representations and/or reference links to analyses created with other software or electronic capabilities, including but not limited to spreadsheets, graphs, images, and others. FIG. 5H-20 illustrates an example of a partially completed workspace 44b for an analysis construct. In this particular embodiment, the analysis construct 44b provides a view of understanding of information across different information constructs, as depicted in the “event” icons and labels shown on FIG. 5H-20. The present invention enables the user to create a particular analysis view across multiple information constructs. At the same time, any detail information elements associated with each of the information constructs may be available to the user by selecting the individual information construct and having the view manager (see FIG. 3) display the detailed information elements for the selected information construct. In one preferred embodiment, analysis constructs may also include fields such as a field associated with each unique analysis construct for the creation and entry by the user of an observational or summary statement about the analysis construct. This observational or summary statement field is generally preferably textual, but may also be comprised of a plurality of information media forms. An example of such an observational field is show in FIG. 5H-20, which is an example of a partially completed analysis construct. In one preferred embodiment, observations that are entered associated with an analysis construct are then later made available to the user in a combined view as basis for creating higher-level meaning (see later descriptions of method and process and representations). In one embodiment, the present invention provides for the ability to save formats created for analysis constructs for future use. For example, the format illustrated in FIG. 5H-30 may be saved as “history timeline.” In this way, a user can create new analysis constructs with new content and less work than the original analysis construct. In one preferred embodiment, the method, process and system provide a set of preformatted analysis constructs as models to choose from for the user. For example, in one embodiment, the present invention provides preformatted analysis constructs for sequence, timeline, qualitative comparison and contrast, quantitative comparison, categorization analysis, family tree, and causation analysis. It should be readily apparent that additional preformatted analysis constructs are obvious extensions and well within the scope and intent of the present invention, especially if they share the same general fields and capabilities and relationships with respect to information constructs as described herein. For preformatted analysis constructs (whether provided as standard with the method and process of the invention, or created as custom and saved by the user), the preferred embodiment provides the additional ability to automatically generate analysis constructs based on the data contained in or associated with information constructs and/or their fields or elements. For example, if information constructs have been created with fields or elements of type “date” associated with them, then the user is able to select those dates and automatically generate a timeline for their review. Similarly, if information constructs have been created with commonly defined fields or elements, then the user is able to select those commonly defined fields or elements and automatically generate a compare and contrast analysis construct. Once generated, the user is able to decide about the generated analysis construct whether to “keep as is,” “modify” or “delete” the analysis construct. In a preferred embodiment, analysis constructs as a type of component or class generally include 1.) a title, number, label or other identifier and 2.) an observational or other summary field or fields; 3.) a backdrop visual and/or overall structure for the analysis construct; and then may include any or all of the following: 4.) a structure for the inclusion of information constructs and/or information elements, 5) visual and/or data references to whole information constructs, summary views of the selected information constructs, and/or the elements or fields associated with Information Constructs; 6.) the inclusion of tools provided specifically by the present invention, as described further elsewhere herein, 7.) unstructured information notes; 8.) the creation of drawing, links with or without labels or other visual depictions by the user, and/or 9.) drawings, text, images or videos included with the analysis construct as provided by the user, and others. In the preferred embodiment, the archetype structure provides for the ability to create analysis constructs that include references to other software tools. Meaning Statement Set Referring back to FIG. 1, the preferred embodiment facilitates the creation of a meaning statement set 24, preferably as a portion of the thinking construct 20 of a completed inquiry project and integrated construct 10. The meaning statement set 24 generally includes the collection of statements or other informational depictions and their relationships to one another and to other project components, as created by the user to represent understanding, meaning and judgment about the knowledge construct components, whether in the form of a hypothesis, idea or a fully formed set of conclusions or understanding. Continuing the example for the project “What caused the development of the Constitution?”, meaning statements might include items like “Framers had some very different beliefs” and “Big states and little states wanted different approaches.” Meaning statements can be developed at different levels of specificity and abstraction, and the present invention assists in building higher levels of meaning from lower level, or more specific statements of meaning (as described further in the method and process and representations for the system). In one embodiment, individual meaning statements as a type or class of component available to the ITKC are generally uniquely identified by their contents. In one embodiment of the present invention, meaning statements may be assigned a unique number identifier and/or a reference as well. Although one embodiment of the present invention includes meaning statements made up of textual characters, the method and system of the present invention also facilitates the use of drawings, images, and a plurality of other media forms as meaning statements. In a preferred embodiment, the method and system provide that meaning statements may exist independently as a part of an integrated construct (i.e., not linked to any other components or group of components of the integrated construct), or may be linked to any one or more or all of the components of the integrated construct. Links among meaning statements and between meaning statements and other components of the integrated construct may be added, changed, or deleted using the method and system of the preferred embodiment. In one embodiment, meaning statements may be assigned a relationship to one another, including but not limited to supporting, contradicting and others. Meaning statements may also be assigned a lateral relationship to one another. FIG. 4D illustrates an example of one embodiment of the relationships inherent in the addition of a meaning statement 1242 to an integrated construct, specifically in the case in which a topic set 22, some information constructs 1422, 1424, and 1426, and an analysis construct 1442 have been defined for the integrated construct previously. In one embodiment, the relationships between a meaning statement and another type of component of an integrated construct may similarly be constructed and labeled as to its type. For example, a meaning statement may be linked to an analysis construct (or to a portion of an analysis construct) with a link indicating that the meaning statement is “supported by” the analysis construct. Similarly, a meaning statement may be linked to an information construct or a portion of an information construct with a link indicating that the meaning statement is “not supported by” or “is contradicted by” the information construct or portion of the information construct. In one embodiment, the present invention provides the user with a number of predefined link types for their selection and use, included but not limited to link types such as “supports”, “contradicts”, “is related to”, and others. In one preferred embodiment, the present invention also provides the user the capability to define their own label for the link. Meaning statements may be linked to one another in hierarchical, lateral or other relationships and also labeled. One preferred embodiment facilitates the linking of multiple meaning statements to one another at least partially through hierarchical relationships, to allow the building up of lower level, more specific meaning statements to higher level, more comprehensive meaning statements, eventually in support of the chosen answer for the project. As discussed below, in one preferred embodiment, in the case of the use of multiple or alternative answers, one integrated construct may have multiple sets of meaning statements. These multiple sets of meaning statements may be related to the respective alternative answers, regardless of the stage of completion of the answer. The present invention also provides the user with the ability to create multiple meaning statement sets as a means of creating alternative “views of meaning” across the same or similar sets of knowledge components. Alternative or multiple sets of meaning statements associated with the same integrated construct may have all, some, or none of the same meaning statements and linkages associated with them. Similarly, alternative or multiple sets of meaning statements associated with the same integrated construct may have all, some or none of the same information constructs, analysis constructs, and topics associated with them. In one preferred embodiment, the creation of meaning statements provides one means for the system to subset the project as a whole into meaningful subsets, for work and consideration by the user. Such a subset or individual meaning statement “view” is more fully described later in the representation discussion. In a preferred embodiment, the present invention also provides for a view of all meaning statements with their associated supporting observations, importance statements, or other supporting links to knowledge constructs such as information constructs and/or analysis constructs. Answer or Summary Set Referring back to FIG. 1, the preferred embodiment facilitates the development of the answer or summary component or answer or summary set 26 of the integrated construct 10, that is preferably a portion of the thinking construct 20 of an integrated construct. The answer or summary set 26 may be made up of textual characters, and/or a drawing, image, graphic, diagram, or a plurality of other information media forms. The answer or summary set 26 is preferably linked to the main topic of the integrated construct, especially in a completed construct. The answer or summary set 26 preferably may be linked via the link manager to meaning statements 24. In one embodiment of the present invention, links between the answer or summary set and meaning statements set can be labeled and categorized, including but not limited to such relationships as supportive or consistent with the answer or summary, or refuting or being inconsistent with the answer or summary set. The answer or summary set may similarly be linked via the link manager to information constructs 42, analysis constructs 44, unstructured data 46 or any other component that may be associated with the integrated construct 10. One embodiment of the present invention provides for the creation of the answer or summary set 26 which may include one or more answers or summaries, such as with alternative answers or summaries under consideration by the user, which may be associated at the same time to the same integrated construct 10. Similarly, in this embodiment of the present invention, the linkages 60 between the multiple answers or summary and meaning statements or other components can differ, according to the specific answer or summary being linked. For example, answer “A” may have links to meaning statements “A,” “B” and “C,” while answer “B” may have links to meaning statement “B,” “D” and “E.” The answer or summary set is preferably available to the user throughout the course of the use of the present invention in developing and editing an integrated construct, and may therefore be changed or added to in the course of the project. This enables users to develop initial answers and refine those answers as the user's work on the project proceeds. Such actions may be included as the present invention documents and tracks the user's thinking processes, and subsequently makes such tracking available. In one preferred embodiment, the answer or summary set may also be associated with a definition by the user of the goals, requirements, or characteristics regarding what is important that the answer or summary Set achieve. These goals, requirements, characteristics or other description of what the answer or summary set should be like are similarly available to the user throughout the course of the project for adding, editing, or deleting. One Embodiment of Software Architecture In one embodiment, the general modules of the software architecture as depicted in FIG. 3 of one preferred embodiment interact with one another in a manner as depicted generally in FIG. 3A. Referring to FIG. 3A, the archetype process and system of the present invention facilitate the process and present options to users in the form of views and available portions of method or functions. In a preferred embodiment, such representation may take the form of a graphical user interface, as indicated in block 100. Users may generally select among available options as presented in the views, and signal an action to the present invention through a plurality of interaction devices and approaches as described above and indicated in block 110. In the preferred embodiment, the process manager evaluates the user event, as shown in block 302, and may respond in a number of ways, based on an evaluation of the action taken by the user, the history of user actions, archetype process and structure inference and completion rules, as indicated in block 3000, status of the integrated construct at the time, as evaluated in block 320, the specific portion of process being conducted by the user as indicated by their placement in the system at the time, and other relevant factors. Options for response to a user event block 110 following evaluation block 302 may include, but are not limited to the following: (i) change and re-optimize the view as indicated in block 205 and facilitated then by the view manager 200 or similar module; (ii) suggest one or more actions or alternative actions to the user based on the evaluation of the event (block 302) and ITKC status (block 320) as indicated in block 390 and then represented to the user through the View Manager, block 200; (iii) create a new component in content and/or structure as indicated in block 420 and facilitated by the process manager 400 or similar module; (iv) modify or delete an existing component both with regard to content and/or structure as indicated by block 420 and facilitated by the process manager 400 or similar module and update manager 700 or similar module; (v) create new or modify existing (automated or user created) linkages between or among components as indicated by block 605 and facilitated by the linkage manager 600 or similar module; and (vi) access and associate external data or informational sources as indicated by block 905 and facilitated by external electronic sources and the update manager or similar module 700, which may then be followed by additional user events such as creating new component, or modifying components as indicated in block 420. In this application, the aforementioned software architecture is provided as one embodiment of the general modules that may be used to implement and provide the present invention. It should be readily appreciated, however, that many alternatives in the definition, boundaries and structure of the software modules used to accomplish the capabilities and functionality of the present invention could be utilized in accordance with the present invention. Returning again to the overall software architecture of one embodiment of the present invention as depicted in FIG. 3, the general modules of the architecture of one embodiment are described in greater detail below. The description of the Process Manager and the method and process of the present invention is below, followed by further description of the other software architecture modules of one embodiment, and later a description of a set of representations that provide the method and process to the user in one embodiment. Process Manager: Method and Process Returning again to FIG. 3, the process manager 300 or similar modules facilitate the archetype process. Referring to FIG. 3A, the process manager (blocks 300, 400 and further detailed in additional charts using the 500's series) evaluates the user event (block 302) and accordingly provides a response to the user that facilitates the method and process of the present invention, whether to change the view through the view manager (block 205), provide a suggestion to the user through the process manager suggestor (block 390), provide and allow the user to select among process portions being provided in the present view (block 405), whether the user chooses to access process portions such as assistance tools or others, (block 410), or to create or modify an ITKC component (block 420), create or modify a link through the linkage manager (block 600) or access external electronic information sources (block 800). The process manager further evaluates the user event (block 302) and the status of the ITKC components and structure (block 320), and determines if suggestions are warranted (block 370) based on a number of evaluation and inference approaches, including the archetype process and structure (block 3000) described in further detail below. In conjunction with the guiding nature of the design of the representations and views provided by the present invention, the process manager thus facilitates a guided process for the user which emulates the thinking and working methods used by expert problem solvers with regard to arbitrary problems and inquiry based projects and responds to user's actions throughout the course of the project. In one preferred embodiment, the user has the choice of (i) ignoring the suggestion(s) made by the process manager, (ii) acting on the specific suggestion, or (iii) saving the suggestion for future consideration. The portions of the archetype process can be used individually, as a total set, or in any subset combination, depending upon the user's needs for a particular project. Portions of the integrated construct method and process include the following major components that are shown in FIG. 5. In one embodiment, the method and process provided by the archetype process generally include the following thinking and working functions: (i) project initiation as indicated by block 510; (ii) definition of project goals and problem as indicated by block 520; (iii) definition of and revision of project structures, being structures for thinking and working as indicated by block 540; (iv) determining and revising a project plan and to do list as indicated by block 535 (v) evaluating progress and deciding what thinking and knowledge work to do next, as indicated in block 550; (vi) selecting the appropriate subset for thinking and working, as indicated in block 555; (vii) conducting research and gathering information, as indicated in block 560; (viii) organizing information, especially through constructing, formatting and/or acquiring information for information constructs to be included in the integrated construct for the project as indicated by block 562: (ix) developing and associating analyses to the project, and defining and constructing analysis constructs to be included in the integrated construct for the project as indicated by block 564; (x) developing conclusions and meaning, especially through defining and constructing the set of meaning statements to be included in the integrated construct as indicated by block 570; (xi) developing and constructing the overall answer or summary set or portion of the integrated construct for the project as indicated by block 580; (xii) evaluating whether the answer or summary set is complete, and has met the goals and answered or solved the original problem as indicated by block 585; and (xiii) creating and formatting the presentational version of the project results, as indicated by block 590. Throughout process portions (i) to (xiii), the linkage manager defines and manages linkages among and between the components of the integrated construct, as described more fully in the discussion of the linkage manager (as indicated by block 600 on FIG. 3A) below. FIG. 5 depicts example navigation paths that generally may be provided between the major method and process work portions of the archetype process. Referring to FIG. 5, the process in one embodiment is preferably modular and generally enables multiple starting or entry points, and flexible iteration or mobility between the intermediate process portions within general guiding approaches facilitated by the archetype process. In a preferred embodiment, the archetype provides guidance to the user according to approaches preferred by expert problem solvers, but also generally enable navigation between many of the process portions. In a preferred embodiment, the ability to navigate to portions of process which are deemed less immediately related to the current process portion for the user are made available in less easily visible or accessible ways, such as through the use of a drop down menu, or visually depicted in a more removed location, as described more fully in the view description, as one means to help guide the user along the preferred navigational paths. The system generally also provides the ability to move between levels of detail within and between the process steps, as described herein. It should be appreciated that the method and process functions may be performed at additional points in the overall process in accordance with the present invention. In a preferred embodiment, portions of the archetype process and methods may be provided and differentiated to the user in several ways, including but not limited to: (i) through the view which is presented and which may focus the user on a portion of the process or a specific type of thinking and knowledge work they have selected or has been suggested by the process manager, based on the archetype process or archetype structure, that needs to be done; (ii) through the set of interrelated views which are presented and which provide to the user access to portions of process and/or methods in useful combinations with portions of the content and structure of the integrated construct, as described more fully below (iii) through the overall visual map or overview of the project that is provided by the system and which helps indicate to the user the degree of completeness and which types of thinking or problem solving approaches have been used or accessed vs. those which have not been used or accessed, (iv) direct suggestions to the user, as described more fully below, and others. In one embodiment, some portions of process and methods may be encapsulated and presented to the user as a software “tool,” or subset of method and functionality, as in a tool to construct new information constructs, a tool to construct new analysis constructs, a tool to provide help and suggestions regarding the selection and construction of the topic set. It should be readily appreciated that providing the same functionality in different encapsulations or boundaries for such logic is in accordance with the present invention. Process Manager Guidance of User Interaction and ITKC Development The preferred embodiment provides an approach to guiding the thinking and knowledge activities for a user to develop their thinking about an arbitrary problem through evaluating the user's actions and progress, and determining suggestions based on the archetype structure and archetype process. The present invention's visual depiction of the archetype project structure (representing content, structure, relationships, and thinking and working process) and the more detailed thinking modes or views provided by the present invention provide ongoing guidance and feedback to the user regarding the portions of thinking process they have done and should consider doing, as described more fully below. In addition, as shown in FIG. 3B, the process manager evaluates the user event (block 302), tracks the user event (block 304) to update the user history (block 330) and determines the process step and work underway by the user by evaluating the event, block 306. The process manager suggestor then determines if there are identifiable process gaps or lapses that have occurred (and especially changed with the last user event) by applying the archetype process rules in block 3100, to the current user event and situation. Specifically, the process manager may evaluate the specific working views being used by the user, the assistance tools being accessed, and the amount of interaction and time being spent in various regions or subsets of their ITKC. Such evaluation might determine, for example, that the user has not been focusing on the problem according to a subtopic specific view yet, or is using the question help tool but without results. Referring further to block 310 in FIG. 3B, the archetype process inference rules are also used as the basis for determining suggestions that might be made to assist the user, in areas that are not strictly gaps or lapses, but rather point out possible next steps. Continuing with FIG. 3B, the process manager in a preferred embodiment also evaluates the ITKC under construction by the user (block 320 and described in further detail below), based on the archetype structure inference engine, and any suggestions so determined are combined with those defined based on the archetype process evaluation and inferences, as shown in step 370. In a preferred embodiment, the system also checks for secondary or combination impacts based on the two sources of evaluation and both archetype process and archetype structure. For example, if the archetype structure evaluation determines that the user has primarily been building meaning statements but they are not well supported by information or analysis, then the archetype process may need to also determine whether they have in fact been searching electronic sources yet. In a preferred embodiment, after suggestions are appropriately combined as indicated in block 370 in FIG. 3B, then the process manager suggestor may optimize the suggestions, as indicated in block 385 through ordering and prioritizing algorithms that may be related to the user event that has occurred, the status of the ITKC and other factors. In block 390, the process manager suggestor provides the suggestions to the view manager and the suggestions are provided to the user appropriately. The inferences and rules used by the archetype process and the archetype structure to identify suggestions for users are different based upon the system's assessment of the current stage or phase of the ITKC. Referring to FIG. 3B-10, the process by which the user's ITKC is evaluated against the archetype structure is now described. As a consequence of a user event, the process manager suggestor in block 322 FIG. 3B-10, evaluates the status of the ITKC components and linkages, with regard to the components that have been selected and included by the user, the level of structure of those components, the amount of information in the components, and their relationship with one another. In FIG. 3B-10, block 324, the process manager suggestor then applies the archetype structure inference and completion rules, in block 3200, in order to identify gaps or lapses in the ITKC the user has built so far, as indicated in block 324. For example, the process manager suggestor may determine that certain subtopics are as yet without information, or that some meaning statements are better supported by knowledge constructs than others. Following the identification of lapses, the process manager suggestor similarly applies the archetype structure inferences and completion rules in order to identify suggestions that may be made to assist the user, as indicated in block 326. Such suggestions may be based not only on the inferences associated with the core or macro archetype structure, but significantly on applying rules based on the actions and selections that have been taken by the user thus far. For example, if a user has identified that they are working on a sequence in a project, and many of their information constructs contain dates, then the archetype structure inferences may identify the suggestion that the user try a timeline. In both the application of the archetype process and the archetype structure, the preferred embodiment incorporates a dynamic application of rules and inferences in response to decisions and choices made by the user (or choices made by another user such as a teacher, as defined elsewhere herein). These customized or dynamically applied inferences are therefore in addition to inferences and rules that may apply throughout the course of the project. Continuing with FIG. 3B-10, the process manager suggestor lastly in a preferred embodiment will search and evaluate relevant fields of the ITKC, preferably beginning with those that have most recently changed and the fields that are most closely related to those changed fields, as indicated in block 330. In one embodiment, the process manager suggestor searches for content specific matches to a set of archetype structure inferences that are content based. For example, the process suggestor manager may search topic fields for phrases that the archetype structure identifies as having relationships to other archetype components. Specific examples are described below. As with the other archetype evaluations, as shown in block 332, in this embodiment, if the process manager suggestor identifies matches to encoded relationships, then the archetype structure inferences in block 3200 will identify a potential suggestion to be made to the user. For example, if the topic the user has entered is “What caused the development of the Constitution?”, the process manager suggestor might suggest the user consider a timeline. As with the other archetype suggestions, the process manager then combines suggestions or lapses determined through content evaluation with those determined about structure through the archetype structure evaluation, as indicated in block 334. In one embodiment, suggestions determined by the process manager may include but not be limited to suggestions regarding: 1.) specific types of components or advances in components the user may want to consider adding next; 2) other views and therefore other thinking or work foci that the user may want to select next; 3.) one or more information constructs, analysis constructs, topics/questions, meaning statements, or answer(s) which the user may want to revisit and review, 3.) linkages or relationships which the user may want to add, revisit and review; 4.) specific activities that the user may want to consider next, such as additional research, revisiting and revising their questions/topics, reviewing data they have collected so far, and others. In one embodiment of the present invention, the user is also able to add their own general rules or principles regarding the process they believe works best for them, in one example as thinking prompters, as described below. In a preferred embodiment, the Process Manager may utilize a number of approaches to accomplish these evaluations and determine if one or more suggestions should be made to the user. It should be readily appreciated that an approach for determining guidance that may be useful in one type of ITKC component or thinking and knowledge activity may be employed in other types of components or activities as well. Further examples of types of inferences that may be made by the process manager suggestor in one embodiment may include the following: 1.) The process manager may determine suggestions based on comparing the existence, number, and linkages of components of the ITKC constructed by the user to those expected or desired for the archetype or exemplary structure. For example, an exemplary project may be expected to have meaning statements that are supported by one or more knowledge constructs (whether analysis constructs, information constructs, or unformatted information). In this embodiment, a meaning statement that has no knowledge construct support linked to it at the time may be evaluated by the process manager as an indication of work yet to be done by the user. Additional examples of such gaps between an exemplary project and a project as completed by the user may include items such as: topics that have little or no information or knowledge linked to them, and others. In this embodiment, the present invention's definition of the exemplary or archetype taxonomy of a inquiry based project provides a basis for gap analysis to the ITKC being developed by the user that would not be possible without such an archetype. 2.) The process manager suggestor may evaluate the user event history. For example, if most user events have been occurring in the research and data gathering regions of the system, or if the user has focused primarily on a topic by topic view and has not yet looked at the meaning that has been developing, the present invention may suggest the user “go to” the complementary or so far little used views or regions next. In one embodiment of the invention, the process manager provides a user such as a teacher with the ability to set parameters for how much emphasis the student should place on different thinking and knowledge activities and views, or how much time is to be spent accordingly, as discussed elsewhere herein. 3.) In one embodiment, the process manager may determine suggestions based on evaluating information entered by the user into the ITKC, and use of project component and relationship rules. For example, in one embodiment, the present invention may evaluate the text entered by the user into the main topic structure (for example, “What caused the development of the Constitution?” and may suggest a subtopic “What events led up to the Constitution?” 4.) In one embodiment, the process manager may determine suggestions based on identifying patterns within similar types of constructs. In one embodiment, the process manager may for example, examine and use the occurrence of patterns such as the same phrase multiple times in unstructured data notes as the basis to suggest to the user to create an information construct or grouping of the unstructured information for that phrase. 5.) Referring to block 350, in one embodiment, the process manager may determine suggestions for transitive relationships between information constructs, meaning statements, and any ITKC component which may be so logically related. For example, if information construct A has been designated through a labeled link as “like” another information construct B, and information construct B has been similarly designated by the user as “like” a third information construct C, then the process manager may prompt the user whether information construct A is also “like” information construct C. Such labeled links may also be used by the process manager to suggest other components to the user. 6.) Providing of thinking and working prompts or suggestions that are related to the specific portion of work being conducted by the user. For example, in one embodiment, the present invention preferably includes a set of thinking prompts for each analysis construct provided by the invention, to assist the user in making meaning from the analysis construct. For example, the timeline might include the availability of thinking prompters like “What things were going on at the same time?” In one embodiment of the present invention, a user is able to add their own thinking prompts to components or views for future use. It should be appreciated that the fact that the present invention provides a common taxonomy for components and structure of an ITKC, together with a modular but guided thinking and working process, in conjunction with the use of semantic and other methods readily understood by those skilled in the art, may be used to provide a rich set of suggesting abilities in the present invention. It should also be appreciated that such evaluating and guiding approaches may be used in combination with one another, and that the addition of similar types of inference and suggesting abilities does not depart from the scope and intent of the present invention. Returning to FIG. 3B, block 304, in one embodiment, the process manager tracks and evaluates actions taken by the user, and updates the history of user events as indicated in block 330. In one embodiment, the user event history may include some, all or any of the following: the user actions taken (which may be measured both in terms of interactions and in terms of time spent), the view and/or component the user had active in their display at the time those actions were taken, the recent history of any suggestions that may have been offered by the process manager, the user response to such suggestions, the status of the integrated construct content and linkages at the time, and other relevant tracking data. As the integrated construct is likely to be constructed during multiple use sessions, the user event history may also differentiate such user history for specific use sessions, including the tracking of date and time spent by the user. In one embodiment, the user event history tracks time duration between specific actions, as well as time spent on each view and/or component. In one embodiment, changes in the content of the integrated construct are also tracked as part of the user history. It should be appreciated that any action and change made with regard to user actions and/or the content, linkages or structure of the integrated construct may be tracked, evaluated, applied against project completion rules, and subsequently made available for reporting and review in accordance with the present invention. In one embodiment of the present invention, the process manager stores “snapshots” of the integrated construct as part of the project user history. For example, a “snapshot” of the integrated construct—including its content, structure, and linkages—may be taken and stored at the end of each use session. In an alternative embodiment, the project assigner (such as a teacher) or the user may select how often and under what circumstances they wish to “snapshot” their integrated construct. For example, a teacher may want the integrated construct “snapshot” view taken every half hour or every hour during the student's project. The ability to compile and store a “snapshot” of the integrated construct is made meaningful at least in part because the component types of the integrated construct differentiate thinking and knowledge content and activity types. In one embodiment, the series of “snapshots” of the integrated construct provide another mechanism by which the thinking and work processes used in the completion of a project may be tracked, mapped, and made available for further consideration of how the user works or should work best. In this manner, the Process Manager acts as an expert system component of the present invention, orchestrating a dialogue and providing suggestions to the user about the generalized inquiry project and problem solving process. The following generally describes a course activity through the method and process of the present invention, as facilitated by the archetype process. This method and process description provides a delineation of functionality generally provided by the present invention, in conjunction with the views and representations which are the primary mechanisms for delivering the functionality, which are described in further detail later. The following description of the steps or portions of the method and process components of the present invention is provided in a logically linear fashion. However, it should be appreciated that one advantage of the present invention is that the user can navigate across and between the portions of the method and process flexibly, and through a plurality of paths, as indicated above with respect to FIGS. 1A, 1B, and 1C, within the guided approaches provided by the representations and process manager suggestions and other approaches, as described elsewhere herein. In the following description, the terms “project” and “integrated construct” may be used interchangeably. Method and Process: Project Initiation and Defining Integrated Construct Title or Label Referring to FIG. 5, specifically block 510, in order to use the method and process of the present invention and initiate an integrated construct, the present invention may prompt the user for the user name or identifier. If the user has previously defined a user name or identifier in the system, the user may type in the name or identifier, and is subsequently asked for their password in order to access the system and any previously created or saved files. If the user has never set up a user name or identifier before, or wishes to define a separate user account for any reason, then the system may provide a function to enter a new user name or identifier and password for a new account. The methods and technical approaches for implementing such a “sign on” can be conventional. Similarly, any suitable approach which provides for the identification and recognition of users and their associated integrated constructs in a manner which provides protection (when desired) and access to the integrated constructs previously created by any user, and which subsequently facilitates the use of the method and system of the present invention may be employed in accordance with the present invention. In one embodiment, once a user has successfully entered the system, the present invention may prompt the user with a number of optional functions such as: (i) creating a new project/integrated construct; (ii) reviewing and/or subsequently editing an existing project/integrated construct; or (iii) reviewing integrated constructs saved for access by the user but originally created by other users, and others. In one embodiment of the present invention, suitable presentational indications may be made for the integrated constructs or projects that are currently under construction as well as those that are completed. In another embodiment, projects already completed may be grouped or categorized and subsequently labeled. In one embodiment, an integrated construct is generally initiated upon the assignment of a title, label or other unique identifier for the project. If the user enters a title label that has been entered previously, the present invention may identify the previously entered integrated construct and prompt the user whether to overwrite the previously existing project, or provide a different title label to create a new project. Similarly, if the main topic statement that is entered is identical to a main topic previously created, the present invention may identify the previously created main topic and prompts the user with a number of options such as the option to: (i) overwrite the previously created integrated construct and main topic; (ii) create a new integrated construct with the same main topic; and (iii) create a new integrated construct and a new main topic. Selection of these options, prompted by the process manager and displayed by the view manager, is accomplished more specifically through the user interaction mechanisms described in greater detail in other sections herein. Upon entering a title or label for the new integrated construct, a unique reference for a new integrated construct is preferably created, and can subsequently be displayed or depicted according to the representational approaches described more fully herein. Access attributed to this unique identifier includes the underlying content and structure of the new integrated construct in its respective stage of completion, including any linkages among or between the components of the integrated construct, and the appropriate representation thereof. In a preferred embodiment, representation of a newly created integrated construct may include delineation of regions or components of the integrated construct which have been created or which are inferred as needed by the present invention based on the archetype structure and/or archetype process but are in the project's earliest stages void of content, but may still be visible and accessible to the user (as described elsewhere herein). In one embodiment, as for a teacher's user, the present invention may also allow a user to define guidelines or parameters for the project, which may include but not be limited to items such as the number of specific components (such as topics, information constructs, analysis constructs, etc.), the types of specific components (such as types of information constructs, for example), the characteristics of specific components (such as formatted vs. unformatted, or including certain fields, or having at least a certain number of levels, for example), and other characteristics. In addition to such parameters, a preferred embodiment allows another user, such as a teacher, to provide content specific starting points for the ITKC, and the setting of rules for the archetype process or structure. In one embodiment of the present invention, a user has the ability to make only portions of the method and process and integrated construct available for a project, as might be done by a teacher in order to teach certain thinking or knowledge related skills to students, or as might be done for simple projects. For example, a teacher or other project assigner may wish to have students or other users focus only on portions of the total method and process and capabilities of the present invention. In a preferred embodiment, the project assigner can set up parameters that are later available to the project participant or user, such as project goals, project start date, project end date, and the like. Also in a preferred embodiment, the project assigner may also “turn on” or “turn off” various parts of the archetype for the duration of the project assignment. For example, a teacher may want students to create only a timeline in a particular project as their analysis construct. One preferred embodiment of the present invention includes an electronic, searchable list of all state educational standards for use by teachers in assigning projects. It should be appreciated that a number of different approaches may be used to structure and assign the project without departing from the scope of the present invention. FIG. 5A indicates the input that a teacher or other source may have on the parameters and initial content for an ITKC in block 5000. Method and Process: Definition of Project Goals and Project Problem Referring to FIG. 5, specifically block 520, the archetype process in a preferred embodiment facilitates the user in defining and revising the project goals and problem or topic definition for the project, as detailed more fully in FIG. 5A. Referring to FIG. 5A, block 521, in a preferred embodiment, the process manager facilitates the user preferably in further defining the project by entering a main problem or topic (for example, in an educational setting, the main topic or problem might be “What caused the development of the Constitution?”), which can be in the form of a topic statement, a problem statement, a question, a subject, an issue, or any suitable definition of an area of interest for the user as noted in the definition of the integrated construct components discussed above. The main topic may be in any suitable media form. Referring to block 524 in FIG. 5A, subsequent to the creation of a title or label and main topic for the integrated construct, the process manager, together with the view manager, provides for choice by the user, as indicated. If the user is ready to proceed with defining subtopics, (or sub-problem statements, sub-questions, sub-subjects, sub-issues or any other subdivision categorization of the area of interest) in the integrated construct, the user may choose to proceed with the process outlined below. For example, for the main topic “What caused the Constitution?”, the user might define subtopics like “Who created the Constitution?”, “What is the Constitution?”, “What events led up to the development of the Constitution?” or others, in one embodiment according to the process set forth below. If not, the definition of the problem ends. In addition, in a preferred embodiment, the process manager may provide at the same time for the user to document or enter notes, drawings or graphics or other media as their initial thoughts on knowledge and information. In one embodiment, these unstructured workspaces are labeled to be attributed to starting views on current knowledge of the user, and starting views on needs for additional knowledge or analysis. Referring to block 542 in FIG. 5A, the process manager in one embodiment also provides for the rapid ability for the user to indicate that other project structures are to be included in the project (for example, if the user in defining subtopics or the main topic determines that a timeline is appropriate to use in their project, they can select one in block 542, and it is created according to block 540 as an “empty” knowledge construct for future work). As defined elsewhere in this document, in one embodiment, the process manager may also make such suggestions to the user both with regard to specific subtopics, other project structures that should be included, and others. Subsequent to the creation of a title or label and main topic for the integrated construct, the process manager of the present invention may preferably provide four additional options to the user, which include but may not be limited to (as described in further detail below): (a) to enter initial comments or a drawing into the main answer or summary view component of the integrated construct; (b (d) to navigate to and proceed with functions associated with the project plan and to do's list. However, the method and process provide for the navigation to and choice of other components of the method, process, and associated integrated construct components if desired by the user, although the archetype process and navigational paths encourage the user in the more closely related activities as described here. Referring to FIG. 5A, if the user selects the option to enter subdivisions or other elaboration of the main topic, the process manager in block 525 may provide options including the following: (i) creating fields for and entering information into a plurality of subdivisions of the main topic, and subdividing and linking them appropriately in a customized fashion directly; and/or (ii) use of the topic/question help assistance portion or tool as indicated in block 526 (and which is a subset of the total process manager suggestion capability as defined more fully elsewhere herein) which is available to assist users in defining and revising the topic set, in order to define subdivisions or further elaboration of the main topic and subsequent subtopics. In a preferred embodiment, subtopics may be entered as text statements, and may also take the form of a drawing, image or any other standard or suitable information form, with or without the inclusion of additional text annotation. Using the link manager, links and associations between and across levels and individual subtopics may be created, including but not limited to the level and relationship of the subtopics to the main topic and to each other. In a preferred embodiment, multiple levels of subtopics can be entered and appropriately linked. FIG. 5B illustrates a flow chart for transactions associated with one embodiment of an additional topic/question assistance method and process portion or tool provided by as one portion of suggestions by the process manager suggestor in one preferred embodiment. As illustrated in FIG. 5B, in one embodiment, the present invention may display through the view manager the highest level of optional topic/question approach choices to the user available for such topic set assistance in block 5262 (such as by problem type, by academic subject, and others). In one embodiment, choosing a category or choice will generally lead to the ability to review samples of topics and topic structures and potential selection of the components of the sample topic structures for the user to associate with or input into the integrated construct, as described more fully below. The following discussion refers to FIG. 5B unless otherwise noted. As shown in block 5264, he user may be presented with categories or classes of model topics, questions or problem statements for selection (for example, classes of subjects). An example of these topic/question approach choices or categories is shown generally in FIG. 5B-10, depicted in outline form. Upon the selection of the desired category by the user, shown in block 5265, the process and system in one embodiment may also present subcategories that are available to the user related to the category that has been chosen. An example of the use of such subcategories is shown in FIG. 5B-20. It should be appreciated that a plurality of levels of categories could be so used and be in accordance with the invention. In a preferred embodiment, as described elsewhere, herein, the process manager may also “jump” to a suggested question or topic, either through navigating the user directly to a lower level choice, or by presenting the subtopic suggestion to the user directly, or others. Continuing with FIG. 5B, block 5266, following the selection by the user of a subcategory, in one embodiment, the topic/question assistance portion or tool may provide a set of model topics or questions to the user. An example of one embodiment of such model topics is shown in FIG. 5B-30, and an additional example embodiment of such model topics is shown in FIG. 5B-32. Following selection by the user of a model topic, in block 5268, the topic/question assistance portion or tool may provide a set of model subtopics for the user. One embodiment for the presentation of model subtopics for the user are shown in FIG. 5B-40. It should be appreciated, however, that modifications to the exact format or appearance of model topics and model questions can be made in accordance with the present invention. It should further be appreciated that the function of providing topic/question/problem assistance in this manner can be implemented in a variety of different forms with regard to the information provided at each node of the model structures, in text, or in text supplemented with images, drawings, charts, or audio support. It should also be appreciated that although the example provided herein deals with a category, a subcategory, and then specific model topics, questions, or problem statements associated with that subcategory, additional levels of subcategories may be provided and selected and navigated in a manner similar to the manner illustrated herein in accordance with the present invention and the role of the categories, sub-categories and model topics, questions or problem statements within the larger system as a whole. Options provided to the user by the process manager from such a display of model subtopics include, but are not limited to the following: (a) selecting the model topics, questions or problem statements individually (or as sets) “as is” for inclusion within the topic structure of their integrated construct (as indicated in block 5269 in FIG. 5B); (b) selecting the model, topics, questions, or problem statements and subsequently editing those statements as they see fit, according to standard editing techniques, for inclusion within the topic structure of their integrated construct; or (c) proceeding with entering subtopics directly, without referencing or using the model subtopics, questions, or problem statements offered by the system. If the user desires to include a model topic (question, problem, subject or issue statement) offered by the topic/question help tool, the user generally indicates their “selection” of the model topic. The selected model topic is placed into or associated with the topic set of the integrated construct currently under construction, indicated by block 5269 and the update manager block 500. The user is free to either leave the model topic “as is” or edit the model topic as they see fit. The method, process and system of the present invention enable the user to review and subsequently edit their topic structure throughout the course of their project as they wish. It should be appreciated that the Process Manager of the present invention may track and respond to actions by the user with regard to the topic set, such as prompting the user if the user indicates the desire to delete a topic or question that has knowledge constructs associated with it, as to whether the user wishes to delete the associated knowledge constructs as well, or leave them as part of the integrated construct, or associate them with a new or alternative topic or question, and other actions. FIG. 4A-10 is an example of topic set for an example project, “What caused the Constitution?” Referring to FIG. 5 block 535, in one embodiment, the process manager's facilitation of a user's or users' definition of a problem or main topic in block 520 results in the creation of a project structure, namely the creation of atopic set. In a preferred embodiment, the topic set may therefore be the first project structure of the archetype structure to be created, and serves as a means to subset the project into meaningful portions for thinking and knowledge work. Referring to FIG. 5, block 535, the process manager in one embodiment provides for the creation of a project plan for the project being initiated. As used herein, the project plan may be facilitated by the present invention in a number of different forms, from very unstructured notes and/or drawings, to a more formalized plan for activities that the user believes needs to be done. In one preferred embodiment, the creation of any project structures is then indicated in and added automatically to the project planning view for the user. In one preferred embodiment of the present invention, the project plan is available to the user throughout the course of the project development. As described further below, in a preferred embodiment, various views prompt the user for additional notes regarding items to consider doing next or in future, or items or additional notes on other questions they have defined. In a preferred embodiment of the present invention, the process manager collects such notes together and provides them to the user as input to development of a project plan. In one embodiment, the present invention may provide a number of model projects or templates from which the user can select in order to structure their project initially. Selecting such model projects or templates allows for the creation of a skeleton project in a quick start fashion, and may include a plurality of components, such as starting topics, starting information constructs, starting analysis constructs, skeleton or starting meaning statements or alternative answers, as well as starting or suggestions for activities. In one embodiment of this capability, the present invention may provide suggestions and options for project components and activities in response to the selection of characteristics or goals for the project by the user. In another embodiment, the present invention provides for model ITKC's for projects depending upon their problem or project type. It should be appreciated that the design of the archetype structure and archetype process lend themselves ready to additional methods of creating starting points for projects, and that these are within the scope of the present invention. Referring again to FIG. 5 block 550, the process manager together with the view manager provides ongoing mechanisms and in some cases suggestions to the user or users regarding evaluating the ITKC's progress and the user's actions and deciding what to do next (as described in greater detail elsewhere herein). Such evaluation, together with the ability to easily subset the thinking and knowledge work according to approaches and combinations used by expert problem solvers, provide an ongoing ability to develop the thinking and knowledge associated with the problem not possible otherwise. Referring again to FIG. 5, in block 555, the process manager facilitates and guides the user in selecting the appropriate subset for thinking and working on the project at various times through the course of the project's development. Method and Process: Editing the Integrated Construct Referring to FIG. 3A, in a preferred embodiment, the process manager provides the user with the ability to generally review and modify all components that are in existence at that time part of an integrated construct. In one embodiment, as described more fully elsewhere herein, the process manager through the view manager may facilitate such modification by being selected in a suitable view provided to the user in which they appear. In one embodiment of the present invention, the selection of the integrated construct component occurs through placing the computer mouse in a position to cause the pointer to appear over the icon or high level representation of the component on the representation. In one embodiment, the user then double clicks the icon or high level representation for the integrated construct component, and is presented with access to the detail of the contents, structure, linkages and label for that component. In one embodiment, one interaction with regard to a icon or highest level representation of a component (such as a double click of a mouse) may present a summary set of information about that component, while a second interaction may provide a lower, more detailed level of information about that component. In another embodiment, a left click on a mouse might present a summary view of a component while a right click might present a linkage view of that component. Views and representations are described more fully in the last section of this document. In this embodiment, elements associated with the selected component are then generally editable, through a commonly accepted mechanism for interacting with computer software, as long as such elements or the information constructs have not previously been designated as “protected In some instances, as described elsewhere herein, and indicated by block 370 of FIG. 3A, the process manager may make specific suggestions to the user related to modifying components. Referring again to FIG. 5, the process manager in a preferred embodiment facilitates the user in conducting research and gathering information to be associated with their project and integrated construct (block 560), as well as organizing the data and information (chiefly through the creation of information constructs) as indicated in block 562, and/or developing or associating analyses with the project and integrated constructs (chiefly through the creation and association of analysis constructs) as indicated by block 564. The functions to conduct research, organize information and create, information constructs and develop analyses and analysis constructs into or to be associated with the integrated construct, are in a preferred embodiment encouraged and made available from a plurality of different method and process and subset view points within the process and system, as indicated by block 555. In a preferred embodiment, the process manager may facilitate the user in conducting research and developing knowledge constructs from a number of different thinking foci, including but not limited to, for example: while focusing on an individual topic or subtopic, while focusing on the development of the set or a particular analysis construct, while focusing on a specific meaning statement, and others. As an example, the process and system facilitates the user to gather information through research, and add, edit, or delete knowledge constructs (i.e., information constructs and information elements and/or or analysis constructs) to be associated with the integrated construct from the workspace shown on the example representation layout depicted in FIG. 7A, example embodiment of a 3-D individual subtopic view. A specific example of one embodiment of this individual subtopic representation view is provided in FIG. 7A-10. In one such embodiment, for example, with the topic, problem or question of interest visibly apparent as shown for example in FIG. 7A, the process manager focuses the user on a particular subtopic, and encourages the user to conduct knowledge development activities accordingly, including but not limited to: (i) the user can access electronic information sources, as described below, while focusing on the particular subtopic; (ii) the user can peruse and edit the knowledge constructs which are already associated with that topic, problem, or question, according to any of a number of commonly accepted editing techniques and described more fully below; (iii) the can also choose to enter data and information items into a new or an existing knowledge construct, directly and/or from other available electronic information sources or data provided via networks, including but not limited to the Internet or an Intranet; (iii) the user can choose to create a new knowledge construct to be associated with the particular subtopic selected; and (iv) the user is encouraged by the process manager to develop meaning statements focused on the subtopic selected at that point in time, and others. These individual knowledge building functions are described more fully below. Similarly, as a further example of block 555 in FIG. 5, the process manager may suggest or the user may choose to work on their integrated construct content and to add or edit knowledge constructs from the reference point shown on the example representation illustrated in FIG. 7C, an example embodiment of a 3-D individual meaning statement representation or view. The process and system also enable the user to add or edit knowledge constructs from the reference point of working on an individual information construct or analysis construct and its associated content—or an the set of information constructs or analysis constructs—as also described in a later section. Method and Process: Direct Entry of Information Referring back to FIG. 5, as a part of block 560, in one embodiment, the present invention facilitates the user directly entering or associating data or information items with a component of the integrated construct using an input device. In one embodiment of the present invention, the input device is a computer keyboard. However, it should be appreciated that the entry of alphanumerical characters, numbers, symbols, drawings, etc. can be similarly achieved through other specific data entry mechanisms in accordance with the present invention (as described herein regarding user interaction approaches). In one embodiment, as depicted in FIG. 3A block 302, the system monitors the user's position relative to the representation being provided. When the user selects a displayed portion or component of the integrated construct, the process manager generally provides the detailed view of the selected component or portion, via the view manager. The representation then generally enables the user to enter information into the fields or entry space as provided for the selected components and/or adjust the format of the information. The information being entered may be generally in the form of alphanumeric characters, a drawing, or graphic depiction (in addition to the many forms of information that may be associated with or entered into the integrated construct as described above). Information previously entered and generally associated with the selected integrated construct component generally is subsequently made available for editing, additions, or deletion, as described above. In one preferred embodiment, he process and system of the present invention also allows for the entry by the user of information into a data storage area which may not be associated with any specific component of the integrated construct, but rather is to be associated with the integrated construct as a whole, primarily in the form of an unstructured information construct. Any information so entered or edited may be subsequently associated with previously or newly created labels or titles of components or information elements. Method and Process: Entry of Information From Other Electronic Sources Referring again to FIG. 5E, block 905, the process manager in one preferred embodiment facilitates access to and copying of or referencing to information from any source which allows such copying or associating to be accomplished, and in any suitable media form of electronic information. Referring to FIG. 5E, which illustrates the general process for transactions associated with acquiring information from other electronic sources, in one embodiment of the present invention, the process manager detects the event of the user selection of the function to conduct electronic research as indicated in block 905. Alternatively, the user may leave the present invention and independently launch a browser or open another electronic information source, and the process manager will facilitate the adding or associating of electronic content in a manner which is the same in FIG. 5E for steps 910 through 920. Upon detection of the event in block FIG. 5E 905, the process manager may generally suspend or otherwise hold the functions of the process and system of the present invention underway at that time, and provide the user with the ability to or otherwise allows the user to either launch the Internet browser or open the other external electronic information source. In one embodiment, the selection of the browser or other electronic source is determined by user options associated with project initiation and setup (as for example, in the setting of the default or preferred browser, or the preselection of specific electronic sources, as might be done by a teacher in assigning a project), as indicated in FIG. 5E block 515. In one embodiment, the present invention provides a button or other suitable device to the user specifically to initiate the use of other electronic information sources, as indicated in FIG. 5E, block 907. For purposes of illustration, the following description focuses on the acquisition of information via an Internet browser. However, it should be appreciated that the process for including information from other electronic sources that allow such access and use are accomplished in generally a similar manner. Continuing with FIG. 5E, in block 908, the process manager may prompt the user with whether the user wishes to automatically enter a particular subtopic or main topic into the target information source's search field (and this may be specified in advance as part of user options block 515, as described above). If such automatic entry is desired, the process manager sends the subtopic or topic content to the electronic search field, as indicated by FIG. 5E block 808. If not, in one embodiment, uupon launch of an Internet browser (or similar launch or opening of an available electronic information source), the Internet browser may be made visible and actionable to the user, along with the representation selected at that time of regions and components of the integrated construct. Access to several functions associated with the method and process of the present invention are preferably available generally at the same time that perusal of the electronic information as noted above occurs. Referring to FIG. 5E, in one embodiment, the process manager or similar module monitors inputs from the user concerning placement on the computer screen or other display device. In one embodiment, the process manager may provide to the user the ability to send a transaction or message from the present invention to launch an Internet browser or otherwise open or launch another source of electronic information. In another embodiment, the process manager tracks the location of the mouse pointer or cursor on or in the representation or display, and notifies the process manager whether the user is positioned and activated within the representation of the present invention, or is currently positioned outside of the representation of the present invention. In one embodiment, if the cursor or other display mechanism has left the representation of the present invention and is positioned and activated generally on or over the Internet browser or other electronic information source shown concurrently as described above, the process manager generally may complete any transactions currently underway in the integrated construct system, and may suspend or otherwise holds activity within the integrated construct system, and waits until the cursor or other display and interaction mechanism is once again activated over or in the representation area being taken for display of the present invention before initiating further action. The methods for evaluating the position of a cursor, mouse pointer or other similar marker mechanism relative to a screen or other display device, and monitoring the interaction of the user with regard to becoming active on or in different areas shown in the representation are well known to those skilled in the art, and can be accomplished by a plurality of approaches in accordance with the present invention. In addition, many approaches could accomplish the accessibility of the ITKC to the Internet or similar sources and still be in accordance with the present invention. Once launched or opened, as indicated in FIG. 5E block 910, in one embodiment, the Internet browser programs or electronic source programs may generally respond to and control the user's interaction with the browser or electronic source program. In one embodiment, as the user views and interacts with the Internet browser or other similarly provided electronic information set, the Internet browser or other electronic information programs control and enable the user in searching for, finding, and reviewing information of interest. In this embodiment, the ability to copy electronic information in the form of text, images, graphs, videos, or other standard forms is similar to that possible through other widely available and well understood approaches. One embodiment of adding electronic information to the integrated construct with the present invention includes the following: referring to FIG. 5E block 911, using the functions provided by the Internet browser of choice, the user uses the mouse pointer, cursor or other interaction mechanism to select and highlight a section of text, image, or any other standard form of electronic information within the Internet browser or other electronic information source. The user may then use the functionality readily available in the Internet browser (or many electronic information sources today) to copy the selected information from the Internet browser or other electronic information source as indicated in FIG. 5E block 912. The user may then move the cursor or other interaction mechanism from the space that has been allocated for the representation of the Internet browser (or other electronic information source) to the representation space of the present invention, as indicated in Figure block 913. In one embodiment of the present invention, the user may then provide a reactivation input to the view and/or process manager, as indicated by FIG. 5E block 913, which may be a click of the computer mouse to signal the user has selected a position within the integrated construct representation space. Continuing with this illustration, in FIG. 5E block 915 the process manager in one embodiment facilitates the user in selecting an available component of the integrated construct as it exists and is displayed at that time or the user may select the function to create a new component of the integrated construct through mechanisms described elsewhere herein. As indicated in FIG. 5E block 916, in one embodiment, the user may then paste the previously copied information or information element into or to be otherwise associated with the selected component of the integrated construct. Alternatively, in one embodiment, the user may create a new component of the integrated construct, as described elsewhere in this document, and then paste the previously copied information into or to be associated with the newly created component of the integrated construct. It should be appreciated that the precise mechanism for accomplishing this copying and pasting can be achieved through a plurality of approaches, and that any such suitable mechanisms can be used in accordance with the present invention. In one embodiment, upon pasting the previously copied electronic information into or to be associated with the desired component of the integrated construct, the process manager is notified by the transaction that completes the paste that such an entry has occurred. Referring to FIG. 5E block 917, the process manager may in one embodiment generally monitor that an “entry” has occurred, and prompts the user to enter information regarding the source of the electronic information that has just been copied. In one embodiment of the present invention, the process manager or other similar module may provide the web address that was active at the time the information was copied as the starting point. In another embodiment, the process manager may also provide the user through the view manager with the ability to enter additional information regarding the source of the copied information. In one preferred embodiment, such source information is thereafter associated with the information that has been so acquired for the integrated construct. In one embodiment, the process manager may provide a field to accommodate the entry of additional information regarding the title and bibliographic information regarding the information item that has been entered. In a preferred embodiment, the process manager may also provide a field in which the user can enter additional notes about the source. In another embodiment, the process manager may also provide the user with an ability to evaluate the source used for the information. In one embodiment of the present invention, the user may also be provided with a number of criteria and the ability to enter a ranking associated with each of these criteria. In another embodiment of the present invention, the user may also be provided with a field or fields in which to enter comments about their evaluation of the source for the copied information. It should be appreciated that a number of data formats may be provided to the user with regard to adding information regarding the source for the copied information in accordance with the present invention. When the user has completed the user's desired amount of entering of information or comments regarding the source used for the copied information, the user generally enters an input to the process manager that the user has completed entering the additional information about the source for this entry and evaluation session. Referring to FIG. 5E block 919, in a preferred embodiment, the user may then continue with further information searching and retrieval, or resume other process portions of the present invention. In one preferred embodiment, the process manager also evaluates the amount of information being copied from an open source and provides a warning to the user when the amount exceeds copyright limits. Referring to FIG. 5E, as shown in block 110 and block 205, in one preferred embodiment, throughout the course of searching, locating, and retrieving or copying any desired electronic information, the process manager provides the ability to the user to change the view which is currently displayed by the present invention, as described more fully in a later section of the document. Method and Process: Creating a New Unformatted Information Construct Referring to FIG. 5, the process manager and archetype process facilitates the organizing of information through the definition, population, and revision of information constructs as indicated in block 562. Referring to FIG. 5C, which illustrates one embodiment of the creation of a new information construct. Referring to FIG. 5C, when the user selects the option to create a new information construct block 5621, the process manager or similar module may prompt the user for a name or title to assign to that new information construct as indicated in block 5622, and provide a field into which the user can enter an alphanumeric character string, drawing, or picture to represent the label or title to be associated with the information item within the integrated construct. The entry of information and interaction by the user may occur using any suitable entry mechanism. In a preferred embodiment, if the user event is in response to a suggestion that has been made by the process manager, as indicated in block 5623, then the process manager creates the new information construct as specified by the process manager suggestions, as indicated in block 5628. In one embodiment, the user is provided the opportunity to accept or decline this new suggested information construct in an additional verification event. Continuing with FIG. 5C, if the user event is not the result of response to a process manager suggestion, in one embodiment, the process manager generally evaluates that a new label or title has been entered for an information construct, and checks to see whether an identical label for an information construct has been created previously, as indicated in block 5625. If there is a match between a previously created label and a new label for the same class of information construct, the process manager generally informs the user that an identical match has been found, and prompts for whether the user wants to edit the existing information construct, overwrite the existing information construct, or change the label to be assigned to the new information construct, as indicated in block 5627. In this embodiment, if there is no duplicate information construct determined by the process manager, the process manager creates a new information construct, in block 5628 and updates the data bases accordingly through the update manager, block 700. Referring now to FIG. 5D block 5635, in one embodiment of the present invention, the process manager may prompt the user, through the representation provided by the view manager, for the structure and content for the information construct the user desires to create. For a new, unstructured information construct, the process manager facilitates essentially the same capabilities to the user as described for modifying an information construct as described below. Method and Process: Formatting an Information Construct Referring to FIG. 5D, In one preferred embodiment, the process manager provides a plurality of types of information constructs available to the user, including but not limited to the following: People, Places, Things, Media, Ideas, Events, and Issues, available for choice by the user as indicated in block 5637. In a preferred embodiment, the process manager also provides the ability for the user to create custom types as indicated by block 5638, allowing the user to create a new category or type, assign user's own label and provide a description of the type). In a preferred embodiment, the process manager also provides the user with the ability to relate information elements to their custom information construct type. In a preferred embodiment, the process manager does not require the assignment of type, but provides for information constructs that are untyped (providing an unstructured note like information storage capability). In a preferred embodiment, any information construct custom type created by the user is subsequently available for use as a type. Upon selection of one of the types of information constructs provided, the user may then be presented with several options, including the option to utilize preformatted elements as part of the information construct as indicated in block 5641, create new custom formatted elements as indicated in block 5642 or the option to structure the information construct as unformatted, freeform data. If the user chooses to structure the information construct as unformatted data, the workspace and associated storage provided to the user and to be associated with the unique information construct label facilitates the inclusion of textual characters, drawings, and also for the insertion or copying and pasting of images, graphs, video, textual characters, or drawings as noted in the description of data entry and data types described elsewhere herein. Referring again to FIG. 5D, the process manager also provides the user the ability to enter or change information associated with the information construct, as indicated in block 5644 and described in further detail herein. An example of one embodiment of the entry of an unformatted information construct is shown in FIG. 5D-10. The amount of information allowed to be included and associated with any information component label will generally vary with the precise implementation of the present invention, including the complexity and scope of the project and integrated construct chosen to be developed by the user, as well as with regard to the processing power of the device on which the present invention operates, and the robustness of the data storage and retrieval mechanisms employed. As stated above, one of the benefits of the present invention is that it provides thinking and knowledge component structures and formats which are and can be generally common or similar across very different levels of complexity of the integrated construct and information, and in the associated technology employed in any specific implementation circumstance. As also generally indicated by block 5639 of FIG. 5D, in the course of the user working on their project, the present invention in one embodiment may also subsequently provide the ability to add or delete additional formats to the information elements associated with an information construct throughout the use of the method and system. As many or as few of the formatted information elements as the user chooses can generally be associated with a particular information construct. In a preferred embodiment, as indicated in block 5642, the present invention provides for the ability of the user to create custom information elements, with a label and an assigned type, and other characteristics. In a preferred embodiment, custom created information elements are made available to the user for reuse. It should be appreciated that any specific implementation of the present invention may make some limiting choices regarding amount of information to be associated with an information construct, depending upon the processing capabilities of the technology and data storage and retrieval mechanisms to be used, and the target user audience. For example, in one educational embodiment, the amount of information allowed for any one information construct may be limited or otherwise evaluated and flagged to the user as questionable. The following is a detailed illustration of one embodiment of this aspect of the present invention. Upon creating a new information construct (or selecting an existing information construct), in a preferred embodiment, the assignment of a type by the user to the information construct may be monitored. Based on the type selected, the user may be provided with the ability to select among preformatted information elements to associate with the information construct being created or edited, as indicated in block 5641. For example, if the information construct “James Madison” is identified by the user as being of the type “Person,” then the preformatted information elements associated with the class of information constructs known as “People” may be provided. An example of one embodiment is shown in FIG. 5D-20, and for a “Person” information construct preformatted information elements may include for example: birth date, death date, birth place, importance, fun facts, quotes, beliefs, accomplishments, education, family, characteristics, etc. The system may provide the user with the ability to select from among these preformatted information elements. Selection of formats for information elements by the user may be tracked, and the selected information elements may then be associated with the respective information construct label, and made available as data entry fields to the user. Some of the formatted information elements may be highly structured, such as birth date and death date. Other formatted information elements may be subsets of information storage and work space which will allow the same variety of information forms as the unformatted information component, but may be designated under a sub-label associated with the label for the information component: for example, “beliefs” may provide a space for information entry but allows significant freedom by the user in the structure or format of what information they choose to add or enter. The present invention therefore may include the provisioning of formats for information elements associated with a plurality of categories or classes of information constructs which may then be provided in representations of the present invention as subsequent data entry and storage fields. The user may also be provided with the ability to create their own classes of information constructs and associated labeled, formatted elements for their later use. Further referring to FIG. 5D block 5639, the process manager may enable the user to edit a previously unformatted information construct and add generally any or all of the structured formats to the information elements that may be associated with an information construct. The options and choices available to the user are generally the same or similar as those described above. In one embodiment, if the user selects the option to add formatted elements to an existing information construct, as indicated in block 5639 FIG. 5D the present invention may provide the ability for the user to “cut and paste” or “copy and paste” information from the general, unformatted workspace associated with the information construct, or from a different formatted element, and place the information into a formatted information element, whether newly or previously associated with the information construct. In another embodiment, the present invention may enable the user to highlight or otherwise mark a section of information. A highlighted portion may also be associated with an information element format. The newly created formatted information element is generally then subsequently associated with the information construct and unique information construct's label, as described above. As an illustration, if an unformatted information construct labeled “George Washington” has been created, and the user subsequently enters or acquires information to be associated with the “George Washington” information construct, the present invention may allow the user to later add a structured information element such as “birth date” to the “George Washington” construct, and associate a portion of the previously entered information with the structured element “birth date.” The information may be associated with the structured element “birth date” via a number of mechanisms which may include but not be limited to methods such as: (i) cutting and pasting information from unstructured data previously associated with the “George Washington” construct through direct entry as described above; (ii) copying and pasting information from other electronic sources, as described earlier herein; (iii) highlighting or otherwise marking a section of information and associating it with a format for an information element; and (iv) copying and pasting or cutting and pasting information from formatted or unformatted information elements associated with other integrated construct components created previously by the user. As a result, in a preferred embodiment, an information construct associated with a unique label can then be associated with formatted, structured information elements and unformatted information, or a combination of structured and unstructured information. In a preferred embodiment, an information construct can also be associated with either a great deal of information, and a high number of labeled information elements, or may exist as being associated with very little information as little as the label that uniquely identifies it. Method and Process: Creating a New Analysis Construct Referring back to FIG. 5, as generally indicated in block 564, the method and system of the present invention preferably provides for the creation and editing of analysis constructs as one component type of the overall integrated construct, specifically as one type of knowledge construct. For example, for the educational project “What caused the development of the Constitution?”, analysis constructs created by the user might include a timeline of events leading up to the Constitution's ratification, a comparison of the beliefs of different framers, and others. (See also description of analysis construct included as part of the description of the integrated construct, included herein). As detailed in the definition of an analysis construct included above, in a preferred embodiment, an analysis construct as implemented by the system can include any information media form. In a preferred embodiment, analysis constructs may contain or be associated with at least one field that may be a common part of all analysis constructs such as a field for entering observations or comments about the analysis construct as a whole. In a preferred embodiment, this observational or comment field which may be associated with analysis constructs may be alphanumeric, or contain an image, drawing, graphic or other media form as herein described. In a plurality of representation views of the integrated construct and at a plurality of points in the method and process of the present invention, the process manager may provide the user with the ability to create new analysis constructs, to view existing analysis constructs, and edit those constructs, as described elsewhere herein. Referring to FIG. 5F, which illustrates one embodiment of the process for creating a new analysis construct, the user may select the option to create a new analysis construct. If not already provided in the representation in use at the time, the process manager may provide a list or other like representation of the analysis constructs and/or analysis construct types that have been created previously for the integrated construct or are otherwise made available to the user for inclusion by the present invention. In another embodiment of the present invention, the process manager may allow for the presentation of a list of analysis constructs and/or preformatted analysis construct types that have been created previously for other integrated constructs as well. As indicated in block 5642 of FIG. 5F, in one embodiment the process manager may provide the user with a field in which to enter a label or title for the new analysis construct. As with the label or title for information constructs, in one embodiment, the label or title for an analysis construct may be a set of alphanumeric characters, a drawing or any other information media form. In one embodiment of the present invention, the process manager and update manager may also assign a unique numeric identifier to the new analysis construct. Referring again to FIG. 5F, n one embodiment of the present invention, upon the user entering a title or label for the new analysis construct (block 5644), the contents of the title or label for the new analysis construct may be checked for a match against the title of labels associated with previously defined analysis constructs (block 5645). In one embodiment, if the contents of the new analysis construct label or title matches with the contents of the label or title for a previously created analysis construct, the user may be prompted with the a number of options, including but not limited to the following: (i) edit or change the existing analysis construct referred to by the label or title that has been entered (block 5649); (ii) overwrite or replace the existing analysis construct with the new analysis construct (block 5648); or (iii) change the label or title that has been entered for a new analysis construct to a different label or title (block 5644). As indicated by block 5648, in one preferred embodiment, once the user has entered a new unique label or title for a new analysis construct, the system generally creates a reference for the new analysis construct. Thereafter, in that embodiment, the label or title of the new analysis construct may generally be available to be used as a reference point for several functions such as for the user: (i) o access the content associated with the new analysis construct and/or its associated observational comment field; (ii) to add to, edit or delete the content associated with the new analysis construct and/or its observational comment field; (iii) to add, delete or edit the relationships between the analysis construct and information constructs, information elements or unstructured information, and/or (iv) to link the analysis construct to other integrated construct components such as meaning statements and subtopics, or other such functions. Method and Process: Adding Structure and Content to a New or Existing Analysis Construct As further generally illustrated in FIG. 5G, once the process manager has facilitated the user in creating an analysis construct, the method and system of the present invention provide several ways for the user to structure or build the analysis construct and add or associate content to the analysis construct. As indicated in block 5681, if the user event is in response to a suggestion that has been made by the process manager, then the process manager in a preferred embodiment may create the analysis construct structure, as well as add any suggested information constructs or other content, and modify any suggested linkages accordingly. In one embodiment, the process manager presents each of the suggested substeps to the user for confirmation before proceeding. Referring again to FIG. 5G, in one preferred embodiment, the process manager provides the user with several options for formatting the structure of the analysis construct. As indicated in block 5663, the process manager may provide the user with a set of preformatted analysis types, indicated in block 5664. In this embodiment, if the user selects one of the preformatted analysis construct types, the process manager assigns the selected type to the analysis construct, as indicated in block 5665 and the resulting analysis construct structure in block 5674. The present invention may provide a plurality of analysis construct types to the user, which may include but not be limited to a sequence builder analysis construct, a timeline analysis construct, a qualitative comparison and contrast analysis construct, a cycle analysis construct, a freeform drawing and diagramming analysis construct and others. In one embodiment, the present invention may provide multiple versions or forms of any given analysis construct type. Referring again to FIG. 5G, in one embodiment of the present invention, the process manager also provides the user with the ability to create custom analysis constructs, as indicated in block 5667. In one embodiment, the process manager provides the ability to define a backdrop or visual context for the analysis construct, as indicated in block 5668, a structure for the inclusion and relationships of information constructs and information elements (block 5669), the inclusion of one, any or all of a set of tools provided by the process manager (block 5670) as described more fully below, and the assignment of a label or title to the analysis construct, and if desired, a description of the analysis construct's characteristics and use. Based on these selections and actions, in one embodiment, the process manager then creates a custom analysis construct (block 5672) and may ask the user whether the user wants to save the format for future use. In one embodiment, any such saved custom analysis construct is available for future use. Referring again to block 5670, the process manager provides in one embodiment for the user to choose to include any or all of a number of tools as part of their custom analysis construct, including but not limited to: (i) a timeline bar tool, which can be placed as part of an analysis construct and provide the ability to set timeframes and intervals and serve as the basis for visual mapping of information constructs or data at the appropriate time position for the time data element included; (ii) a linking tool, which can be placed as part of a custom analysis construct and provides for the user to define and label links between information constructs, information elements, or other visual or diagramming components; (iii) a drawing and diagramming tool; (iv) a calculating tool, and others. Continuing with FIG. 5G, block 5673, the process manager therefore creates the structured analysis construct object as defined by the user or based on a process manager suggestion above. Referring then to FIG. 5H, block 5675, in one embodiment of the present invention, the process manager provides for several options for the user to add information, information constructs, and information elements to an analysis construct. In one embodiment, these options may include but are not limited to the following: (i), adding or associating links to information constructs in block 5676 and/or information elements in block 5677, to be referenced in or associated with the analysis constructs, alone or in combination with the other options below; (ii) adding or associating analysis content previously created in other analysis software programs which allow the copying and pasting, or referencing or access to other analysis software programs; and (iii) adding information directly to be associated with the analysis construct or creating new information constructs, in block 5678, and/or (iv) entering or associating information gathered electronically with the analysis construct, as indicated in block 5679 and described more fully elsewhere herein. In one embodiment of the present invention, when a user selects an analysis construct to add or edit the content associated with that analysis construct, the user is presented with a workspace associated with the analysis construct. In one embodiment, the analysis construct workspace generally provides the ability to the user to add alphanumeric characters, drawing figures and/or graphic representations, as well as include or associate images, video or other information forms with the analysis constructs. The representation of the analysis construct workspace preferably includes access to the observational comment field associated with the analysis construct, an optional but common field across all analysis constructs. An example of a partially completed analysis construct of an integrated construct workspace is shown in FIG. 5H-20. In one embodiment, as shown in FIG. 5H-10, the process manager may provide the user the ability to add to or associate with the analysis construct references to the information constructs that have been created. The result may be a visible representation within the analysis construct workspace that such a reference and link has been made. The user can generally place these references to information constructs in any position on the analysis construct workspace while still providing for access to such items as the title of the analysis construct and any additional comment fields. In one embodiment of the present invention, there are at least two types of links or associations provided for the user to associate information constructs to analysis constructs, as illustrated in FIG. 5D-10 included herein and facilitated by the linkage manager. The first type may include creating a link to/from an analysis construct to/from the label or title or representative icon of an information construct as a whole. In this manner, the reference from the analysis construct is construed as reference to the entire information construct as a whole, via the reference to the label or title of the information construct. In one embodiment of the present invention, references between an analysis construct and an information construct may be depicted in representations of the present invention by several visual mechanisms, such as by the display of a title, label or icon associated with the information construct. A second type of reference between an analysis construct and an information construct may include creating a link to an analysis construct to/from an information element within an information construct. In a preferred embodiment, the linkage manager maintains and provides the data regarding the contents of the information element and the title or label or other reference to the information construct with which the information element is associated, with both available for inclusion visibly in the analysis construct. It should be appreciated that these two links forms are representative of links between information constructs and analysis constructs, and that additional forms of links may be provided in accordance with the present invention. In one preferred embodiment, any information element so referenced, linked or included in or associated with the analysis construct is based on the content associated with the information construct at the time the analysis construct is viewed. In this manner, any updating or changes to information constructs and their respective elements are automatically also reflected in their representation and reference with regard to analysis constructs. Method and Process: Creating a Meaning Statement Set Referring back to FIG. 5, as generally indicated by block 570, the process manager in a preferred embodiment facilitates the user's development and revision of a set of thinking structures which comprise the thinking construct of the integrated construct, and which provide meaningful thinking and working subsets to the user. As described earlier, in a preferred embodiment, these may include, for example, a set of meaning statements for inclusion with the integrated construct. The set of meaning statements may be void in an integrated construct, may be one or may include a plurality of meaning statements and/or sub-meaning statements. As discussed earlier, in one embodiment, meaning statements are most likely to be text, but may also be created in the form of a drawing, image, diagram, or other suitable information form. Characteristics of meaning statements are generally discussed in an earlier section. In the preferred embodiment, meaning statements may be linked to the answer or summary set, in order to indicate the logical support of the answer or summary set by some portion of the meaning statements. In another preferred embodiment, meaning statements that are linked via the link manager to the answer or summary set may also include additional designations, such as “supports,” “contradicts” or others. As shown in FIG. 5, the work process step represented by block 570 includes defining, populating or revising a meaning statement set that can occur in a plurality of points within the overall process. FIG. 5E-10 depicts an example meaning statement set. In one embodiment, the process manager encourages the user to create new meaning statements at key points in the overall process, in a number of different portions of method and process. For example, the process manager provides the user with a placeholder for the creation of meaning statements that acts as a reminder and encourager to do so, in a number of different portions of the overall archetype process, including but not limited to: while working on an individual subtopic or topic and constructing relevant knowledge constructs, while working on the set of analysis and/or information constructs, while working on a particular analysis construct, and others. In one preferred embodiment, the present invention facilitates the user in the creation of meaning statements and meaning statement relationships in several ways, including but not limited to: (i) through the encouragement and prompting to develop meaning statements while the user is thinking and/or working in any individual component or particular subset view; (ii) through encouragement and prompting to consider and develop meaning statements and meaning statements relationships as a set across all or a substantial subset of the rest of the integrated construct components, and through thinking prompts provided by the process suggestor. It is an advantage of the present invention that the user is also provided a portion of method and process in which the collection of the observations and meaning statements (associated with analysis constructs, subtopics, and other meaning statements) are made available to the user as a set, hiding the underlying data and analysis details from which the meaning statements were derived, while still making the details accessible to the user (through mechanisms described elsewhere herein). It is a further advantage of the present invention that the user is provided with the ability to quickly and easily access the supporting (or conflicting) knowledge constructs and the associated subtopics, if any, from such a combined meaning statement view. As discussed elsewhere with respect to the process manager suggestion process, in one embodiment, the process manager may access the contents and/or the labeled and structural relationships across meaning statements, and provide suggestions to the user. In one embodiment, the process manager may evaluate the contents and relationships of meaning statements and make suggestions regarding reclustering or regrouping meaning statements, suggestions regarding additional analysis constructs that may be considered, and/or identify meaning statements that are not well supported by the knowledge constructs at the time. Method and Process: Creating an Answer or Summary Set Referring back to FIG. 5, as generally indicated by block 580, in one embodiment, the present invention provides the user with the ability to enter or depict an overall answer or summary set for the integrated construct and its project. The overall answer or summary set may be created in a plurality of information media forms, including but not limited to text, drawings, diagrams, images, graphics, charts, etc., preferably including at least some text explanation as well. In one embodiment, the process manager may allow the user to include an analysis construct as part of the overall answer or summary, preferably along with explanatory text. In one embodiment, the process manager facilitates the user thinking about and capturing their initial, developing and eventually final thoughts regarding what the answer or highest level summary understanding, opinion, or recommendation is for the project. The method and process step of creating an answer or summary set for the integrated construct may be accessed and accomplished by the user at generally any time after the initiation of the project. In one preferred embodiment, the answer or summary for the integrated construct is linked to the main topic, issue, question (or other designation by the user of a subject area of interest). In another embodiment, the link between main topic and answer or summary set is created automatically by the present invention when the user enters any information into the answer or summary set construct. In another preferred embodiment, the process manager facilitates and encourages the user to link the answer or summary to meaning statements. In a preferred embodiment, the meaning statements may also be designated regarding the nature of their relationship to the answer or summary set, including relationships such as “supports,” “contradicts” and others. The answer or summary for the integrated construct may be edited and changed throughout the development, editing, and viewing of the overall integrated construct. From certain representations of the integrated construct (as described in the representation description below), the user may select the visual area associated with the answer or summary set for the integrated construct. Alternatively, the process manager may suggest that the user access the answer or summary set for the integrated construct at various points throughout the overall method and process. For example, if the user has created a high number of information constructs and/or analysis constructs and/or observational comments associated with analysis constructs, but has not yet created an answer or summary set, the process manager may suggest that the user try taking a guess at the overall answer or summary set. If the user has previously entered or created a portion of content (such as text, drawing, image, and/or other information media forms) to be associated with the answer or summary set of the integrated construct, that portion of content is displayed, and is available to the user for editing, additions, or deleting, according to the user interaction mechanisms defined previously in this document. The main topic as previously entered or created by the user may also be represented. If the user has not previously entered or created a portion of content to be associated with the answer or summary of the integrated construct, then the view manager may represent an empty answer or summary component to the user when this component of the integrated construct is represented. In one embodiment of the present invention, the process manager provides the user with the option to create more than one answer or summary for the integrated construct, intended as potential alternative answers or summaries. In this embodiment, with the current representation of the answer or summary being represented to the user, the user can choose to add an additional or alternative answer or summary to be associated with the integrated construct. If an additional or alternative answer or summary is so chosen by the user, a second or additional answer or summary workspace may be provided to be associated subsequently with the integrated construct. The process manager may also prompt the user to label, name, title or number the alternative answers or summary sets. Using the linkage manager, the user may then be provided with the ability to develop a second set of links between the alternative answer or summary set and the other components of the integrated construct, such as topics, information constructs, analysis constructs, and/or meaning statements. The linkage manager generally also allows the user to change links from the topic set, the meaning statement set and any linked information constructs or analysis constructs to/from the alternative answers or summary sets being developed. In one embodiment of the present invention, the user is provided with the option to create and enter their opinion into evaluative fields with the answer or summary for the integrated construct. These evaluative fields may include a number of annotations for the evaluation of alternative answer or alternative summary sets, including for example such annotation as “pros” and “cons” for each alternative answer or summary, and/or a numeric or qualitative rating according to a plurality of dimensions to indicate the user's degree of satisfaction with any one alternative answer at a point in time. In a preferred embodiment, such evaluation is accomplished with access also to any goal statements or requirements or similar descriptions that the user entered as art of the problem definition during the course of the project. In one embodiment, the process manager may provide suggestions regarding thinking prompts to be considered in the development of an answer or summary statement, based on various inferences, as indicated elsewhere herein. In another embodiment, the process manager may provide a subset of interactive suggestions for thinking prompts. Link Manager Referring to FIG. 3A, block 605, a preferred embodiment of the tool provides for a Linkage Manager or similar module, for creating, changing, maintaining, and representing multiple links that may be developed among and between selected or generally all of the components of the integrated construct. Such links may be simple or complex. Such links may be created or changed by a number of mechanisms, including but not limited to: (i) a specific user request or action (either in response to a suggestion from the process manager or initiated by the user alone), and and (ii) created or suggested automatically by the present invention. The links generally represent relationships between different components of the integrated construct that are user or method and system created. The present invention also generally facilitates the selective or continual changing or updating of those links, and the addition of new links. FIGS. 4A through 4E show an example of links that may evolve between and among components of an integrated construct as generally provided by the present invention. FIG. 7A is a representation of an example of a linkage view, showing an example of content specific links supported and enabled by the archetype process and structure, as described above. As shown in FIG. 3, the link or linkage manager or similar module generally creates, monitors changes to, maintains and in some cases suggests or automatically creates links between and among the components or elements of the components of the integrated construct. In one embodiment, the link manager generally also creates, tracks, and manages links between components of any integrated construct, and other integrated constructs or electronic content. For example, the link manager provides for the inclusion of a link to a publicly available web site on the Internet, associated with a component of an integrated construct. In another embodiment, the present invention may also provide for links between multiple integrated constructs or components of multiple integrated constructs, components of multiple integrated constructs, or elements of components of multiple integrated constructs, or any combination thereof. In one embodiment, such integrated constructs and components and elements of integrated constructs may reside locally and/or remotely, on the same processor, on different processors, or on geographically dispersed processors. Links may be created and edited between and among integrated construct components in at least two ways including but not limited to: (i) links which are specified through user actions generally according to the interaction methods and approaches described above; and (ii) links which may be suggested to the user or provided automatically by the method and system of the present invention, and which may be available to the user to change or delete if desired, as described below. It should be appreciated that numerous alternative methods or technology approaches can be used to accomplish the creation, tracking, maintenance and representation of links among and between components of the integrated construct in accordance with the present invention. In addition, as stated in other portions of this application, it is likely that the optimal choice for technology and data storage approach, for example, will be dependent upon the complexity of the integrated construct itself, and the volume of the information to be included in the components of the integrated construct. In the integrated construct of the present invention, links between or among components may be used to indicate an association or relationship between those components. A plurality of suitable links may be provided in accordance with the present invention. Examples of the types of links that may be provided include but are not limited to: (i) hierarchical links; (ii) lateral links; and (iii) unspecified links. Each of these is discussed further below. One link type which may be provided by the present invention includes hierarchical relationships, including but not limited to relationships such as (a) higher level and more detailed, or a whole and parts (examples of which include topics, subtopics, and secondary subtopics, or meaning statements and secondary meaning statements); and (b) supportive of or contradicting with (examples of which include answer or summary and meaning statements, or meaning statements and secondary meaning statements). Another link type which may be provided by the present invention includes lateral relationships, including but not limited to relationships such as: (a) associative relationships (examples of which may include topics and information constructs, topics and analysis constructs, topics and meaning statements, information constructs and sources); (b) content relationships (examples of which include information elements within an information construct and a particular analysis construct, meaning statements to meaning statements, information constructs to information constructs, analysis constructs to analysis constructs); and (c) logic relationships (examples of which may include information constructs to information constructs, meaning statements to meaning statements, topics to subtopics, subtopics to subtopics, information constructs to analysis constructs). A further link type that may be provided by the present invention may include one or more unspecified linking relationships. Similarly, the present invention may include the ability to specify that a link is likely to exist between any two components or the contents of any components without specifying the type of link at that time. In one embodiment of the present invention, this type of link is labeled as “undetermined,” “unknown,” is related to” or provided any other suitable or user defined label. In view of the nature of the components of the integrated construct, it should be appreciated that any suitable further or additional linkage relationships which can be defined among or between groups of components or individual components (i.e., group to group, individual to individual, individual to group, and group to individual) of the integrated construct can be employed in accordance with the present invention. In conjunction with specifying that a link exists between or among different components of an integrated construct, the present invention may provide the user with the ability to designate a label or type to the link. In one embodiment, the specification of the type to be associated with a link is provided as a field into which a user can input a text, graphic, or drawing designation as a label for the link. This enables the user to explain why the user believes a relationship exists and to define the nature of the relationship between two or more components and thus the purpose of the link. This is one of the functions that also allows the present invention to track and document the user's thinking. The user can subsequently change or add to the links or the reasons associated with the links and therefore this linking assists in enabling the present invention to track and document the user's thinking process. The present invention may in one embodiment save subsequently changed links to track and allow the user and others to see how the user's thinking process progressed, as it does with other integrated construct components. This may allow another person such as (i) a teacher to see the links created by the user and why the user created such links, or (ii) a person or team to share their reasoning and thinking in a project with another person or team. Such sharing can help the user in refining and developing the user's thinking processes. Such tracking may also provide the user with an ability to review their own patterns of thinking and linking in the course of completing their project. In another embodiment, the user can specify the nature of any link by the designation of an arrow-like direction (either direction or a two-way relationship). In yet another embodiment of the present invention, the specification of the type to be associated with a link may be accomplished by the present invention providing a menu of link types from which to choose. It should be appreciated that there are a plurality of approaches to accomplishing the user's ability to indicate a type or nature of the relationship to be associated with a link between or among components of the integrated construct that could be used in accordance with the present invention. The present invention provides for some linkages between and among components of the integrated construct that may be provided automatically. For example, in one embodiment, the present invention may provide for the automatic creation of links between components based upon the characteristics of the representation or view the user is using at the time a new component is created. For example, if a user is using a representation of a specific topic view at the time the user creates a new information construct, then the present invention may automatically specify a link between the information construct and the specific topic that was the focus of the view at the time of the information construct's creation. Similarly, for example, if a user is using a representation of a specific analysis construct at the time that an information construct is created, the present invention may automatically link the information construct to the analysis construct and suggest to the user that they specify how the information construct is related to the analysis construct, or delete such a recommended link. Such automatic linking makes the process of creating and managing relationships across project components—which can become very complex—significantly easier and more productive for the user. In yet another example of automatic linkages that may be provided by the present invention, the present invention may provide secondary associations to the user, based on primary associations. For example, in one embodiment of the present invention, if a component of the integrated construct “A” has a relationship with another component “B” and component “B” has a relationship with component “C,” then the present invention may provide the link “A has a relationship with C” as a suggestion or automatically. The archetype process may also show this secondary relationship to the user and ask whether the user wants this secondary relationship to be retained or not. In the preferred embodiment, such automatically generated or suggested linkages do not detract from the ability of the user to then link the newly created components to other components (or in other views). By providing these and other automatic linkages or linkage suggestions, however, the present invention reduces the users effort at creating and managing such linkages and increases the probability that meaningful linkages will be created and maintained. The system may also allow the user to override any such linkages suggested or created automatically by the present invention. View and Representation Manager Referring now to FIG. 3, one embodiment of the view and representation manager of block 200 is described and depicted in further detail in flowcharts in FIGS. 3C, 3D-10 and 3C-20. In a preferred embodiment, the present invention includes a view and representation manager which is operable to provide to the user different representations which provide the portions of archetype process, and the associated portions or totality of the integrated construct, its content, structure, linkages as it develops. In the description that follows, a distinction is intended between “views” provided by the present invention (being combinations of portions of method and process and the content, structure, and linkages of the integrated construct so as to provide meaningful thinking and working sets) and “representations” provided (being the visual and interactive provisioning of the views to the user or users, in a plurality of visual and interactive forms). In the following description, the software module(s) that accomplish these capabilities is termed “view and representation manager” but may be referred to as “view manager” as shorthand in the description that follows. Views and representations may be changed in response to user inputs and actions, as described in greater detail below. In one embodiment, different views or representations may also be suggested by the process manager to the user, as a means of guiding the user's thinking and work, based upon the evaluation of the user's current view, activities and content progress in the integrated construct, project completion rules, and other items as described herein. The views and representations provided by the present invention through the view and representation manager generally provide the user with several advantages, including but not limited to the following: (i) the representations accomplish guidance and feedback to the user by providing a meaningful subset of their content associated with their integrated construct and also the portions of method and process that the user is likely to want to use or may want to consider using, according to exemplary project approaches, with those portions of content; (ii) the views represent the user's ITKC and activities in various ways against the expectations of the archetype process and structure, to various degrees, as a means of providing coaching and feedback; (iii) the views and representations enable a user to work on an integrated construct from a plurality of viewpoints with easy navigation between these viewpoints, in a way which allows the user to follow their own instincts and thoughts regarding what type of thinking or knowledge work they should pursue next (such as working on an integrated construct from the perspective of “what questions was I trying to answer?” and then switching to “what do I think the answer might be?”) without having to do additional work to reconstitute the project's information; (iv) the present invention provides useful views and representation of focused thinking and/or knowledge activity type—(for example, focusing on the definition of the problem through a set of topics, focusing on analysis, or others), and useful “slices” or other subsets of combinations of the components of the integrated construct (such as the “slice” view of a particular subtopic and its associated components and method and process) which generally correspond to a natural thinking or knowledge related work process, and in so doing provide a way of guiding working on a potentially complex integrated construct and the archetype process, by subsetting the integrated construct and the appropriate portions of method and process into meaningful thinking and working views; (v) in one preferred embodiment, the views and representations may provide visualization of what next thinking and work steps are likely to be useful for the user to pursue, through a number of different approaches, such as by placing the visual depiction of the “visible next views” associated with the related work activity in proximity or otherwise visible or easily accessible from the current working view for the user, and by depicting gaps to the user; (vi) the views and representations provide a context for work by the user that in a preferred embodiment may allow the present invention to determine links that should be made automatically between components of the integrated construct, as described more fully in the discussion of the linkage manager, and others. A later section describes examples of the views and representation types which may be provided by the present invention in one or several embodiments. In the description provided herein, reference is primarily made to replacing a current in-use view with a different view, primarily in response to user actions and requests and evaluation and optimization by the view manager and suggestions by the process manager or similar module. However, it should be readily appreciated that allowing a user to have multiple views or representations as provided by the invention visible and/or accessible at generally the same time is in accordance with the present invention. Referring to FIG. 6A, a schematic of some categories of view types provided by a preferred embodiment, representations or views provided by the present invention in one embodiment may for example provide views of at least these general types, including both global representation and navigation approaches, and local or focused representation and navigation approaches. For example, referring to FIG. 6A, in one embodiment, global views may include but not be limited to: (i) views of the total integrated construct, conveyed against archetype expectations to varying degrees and levels of detail, as indicated by block 80; (ii) views which subset the total ITKC into visually distinctive regions and/or which may show the level of activity or work conducted and/or components constructed in those regions and/or slices. Examples of local navigation view types provided by one embodiment may include: (i) views of a region, being a similar type of archetype thinking or knowledge work process portion and the associated thinking or knowledge components as depicted in blocks 70, 72, 74, 76, and 78 in FIG. 6A (such as a topic set); (ii) views of a slice or subset of the integrated construct and its associated method and process, as indicated by block 82 in FIG. 6A, being a useful, generally filtered or subsetted combination of some of the components of the integrated construct and their associated portions of method and process of the present invention (for example, a meaning statement and its associated knowledge constructs), (iii) views of individual ITKC components, such as an individual information construct, as indicated by block 85 in FIG. 6A, (vi) views of sets of ITKC components, such as a set or sets of information constructs, analysis constructs, and others. Views and representations of one preferred embodiment are later described more specifically. t. It should be appreciated that different audiences may desire or respond better to somewhat different depictions or forms of these views, such as due to age or specific application differences. For example, the specific rendition of the interface for a ten-year-old user in an educational setting is likely to differ from the rendition of the interface for an adult problem solver, although the basic functionality may be very similar, and the general work steps and associated views may be generally similar. Given the general purpose nature of the integrated construct and its associated method and system, it is further expected that new or adjusted forms of representation of the integrated construct contents and their associated method and process may similarly be defined in accordance with the present invention. As described elsewhere herein, the views and representations provided by the present invention are not dependent upon operating system, hardware, data storage and management mechanisms, nor are they dependent upon the specific programming techniques employed for their implementation or specific transactions used to accomplish the representations and their associated functionality. The views provided by the present invention largely provide the function, value and advantage inherent in the present invention largely regardless of the technical approach taken for their implementation. It is most likely that the processing capabilities of the technology used for implementation may affect the precise form and approach used to represent the view to the user (for example, using 3D images in environments with low computer processing power, as opposed to complex, fully functioning 3D rendering of the structure for the representation), as opposed to the nature of the view elements, content, and method and process to be used. The representations may also be provided in a plurality of forms, including but not limited to electronic display and printed paper or other outputs. Referring to FIG. 3C, the view and representation manager monitors user events and determines whether the user event indicates a desired change in view, as indicated by block 205. In one embodiment of the present invention, the primary user interaction device is a computer mouse, which may move a cursor or other marker on a computer screen to indicate the location of the user's activity, and a keyboard. Alternatively, in this embodiment, the view and representation manager may also monitor the placement and level of activity associated with a computer cursor placed in a position on or within the representation or view using directional or other keys on a computer keyboard. In addition, as described above, a plurality of user interaction devices may be used, including but not limited to touch screens, voice activation, stylus pen, or other interaction mechanisms. Also, as described previously, the display device may be a plurality of display devices and mechanisms. In one embodiment, indicators to the view manager that a changed view is desired may include the selection by the user of: a component visible in the current view, subset of a current view, visible next view, selection of different level of detail, a different view from the ITKC overview, a different view from a drop down menu, and others as described elsewhere herein. If no change in view is indicated as shown in block 205 FIG. 3C, no further action is taken. Referring again to FIG. 3C, the view and representation manager in one embodiment determines in block 210 whether the user's selection of a new view is in response to a suggestion that has been provided by the process manager. If so, the view manager receives input regarding the recommended view parameters in block 215 from the process manager, which set the parameters for the view manager in block 270 as the basis for later filtering the contents, structure, linkages and method and process to be provided (block 272), composition of the appropriate view elements (block 275) and view optimization and rendering (block 290). Referring again to FIG. 3C block 210, in one embodiment, if the view manager determines that the changed view is not in response to a suggestion by the process manager, then the view manager evaluates the user position and action in block 220 and determines the appropriate new view parameters in block 265 which then set the parameters for the view in block 270. The view manager or similar module therefore determines and subsequently provides the appropriate view parameters to create the appropriate representation of the desired view, including the integrated construct content, structure, linkages, and appropriate associated portion of the method and process to the display or display device. In one preferred embodiment of the present invention, the process manager or similar module may evaluate the user movements and provide suggestions to the user for next views to try, based on an evaluation of current user actions together with items such as the status of the content and structure of the integrated construct and project completion rules, as described elsewhere herein. Referring to FIG. 3C-10, further detail of the logic of the view and representation manager for one embodiment is shown, in order to evaluate the user position and action (block 220) and determine new view parameters, block 260. The view manager in block 222 determines the current view parameters, based upon the set of specific view definitions provided by the present invention in block 224. In one embodiment, specific view definitions may include but not be limited to some or all of the following: (i) the component types included from the ITKC (such as topics, information constructs, etc.), (ii) the basis or central component on which the ITKC components are to be filtered for inclusion in the specific view, (iii) portions of method and process to be made available to the user in the specific view, (iv) subset or level of detail to be provided for included components in the specified view, (v) linkages that are to be made visible or available to the user in the specific view, and (vi) other views which are to be made most closely available or appear to be related to the user in the specified view, and others, Referring again to FIG. 3C-10, in one embodiment, the view and representation manager monitors whether the user has selected a next visible view (block 225) or used another means to select a different view, such as a drop down menu (block 226), or changed position within a view (block 227) which warrants a change in the filtering of components, linkages and portions of method and process (block 230) to be included in the specific view chosen by the user. Continuing with FIG. 3C-10, in one embodiment the view manager further evaluates whether the user has indicated a desired change of detail (block 234), which sets the filter parameters in block 240 for level of detail. Continuing with FIG. 3C-10, the view manager evaluates whether the user has indicated a change in representation type (for example, 3 dimensional, 2 dimensional, outline and matrix representational types) in block 244 or in representational type form (block 246) as the basis for determining display parameters to be used for the new view in block 250, from the display options provided by the present invention in block 242. Referring still to FIG. 3C-10 block 242, in a preferred embodiment, the present invention may provide for the selection of representation types by the user. Representation types as used herein refer to different types of representation or means of visually depicting a view to a user or group of users, which provide for sets of views which are generally functionally the same, but whose appearance is different in the manner in which they are represented. The present invention, through the view manager, may in one embodiment provide the user with a number of different representation types as options for representing and displaying the integrated construct and the associated method and process portions which are provided by the present invention. In one embodiment of the present invention, the user may be provided with the following options for representation types: (i) three-dimensional representation(s); (ii) an outline or tree-type representation; (iii) two-dimensional representation(s), and (iv) a matrix representation. In addition to personal preferences for representation by different users, it is also likely that the optimal representation type for the specific integrated construct may differ by the nature, size, and complexity of the integrated construct itself. Referring again to FIG. 3C-10, the view and representation manager in one embodiment monitors selection by the user of representation form or shape in block 244. For each representation type provided by the present invention, there may be a plurality of specific forms or shapes provided for choice by the user. In one preferred embodiment, for example, the view manager may provide for the selection of the representation form associated with a three-dimensional representation, for example, the user may be provided with a plurality of specific three dimensional shapes from which to choose the manner in which their particular integrated construct and the associated method and process will be represented (examples of which are illustrated in FIGS. 6I-6V). It should be appreciated that a plurality of three-dimensional shapes and a plurality of degrees of visual detail in the depiction can be employed in accordance with the present invention. A more detailed explanation of the characteristics of shapes that may be optimal for use in a three-dimensional representation of the integrated construct is included in the description of the specific views set forth in the representation section below. Continuing with FIG. 3C-10, the view and representation manager or similar module may monitor the specific view and representation being displayed at a particular point in time, as indicated in block 222. In one embodiment, the present invention generally provides the user with the ability to change the specific view and representation being displayed through a number of different interaction mechanisms, which may include but not be limited to the following: (i) user movement of an interaction device to send an input to the view manager or process manager indicating the selection of a different view which is visible for access in the representation of the current view which may be placed as an adjacent view (referred to hereafter as visible next view); (ii) user selection of a component of the integrated construct which is visible in the current view in order to obtain a more detailed view of the content, structure and/or linkages associated with the selected component; (iii) user selection of a link which is visible in the current representation view; (iv) user selection of an area or subset of the overall integrated construct representation, which is associated with a specific view; (v) user selection of a view provided through a conventional menu list, and others. With regard to choice (i), in one embodiment, the availability of related views may be depicted as a part of the representation in current use, or indicated or implied by the placement orientation or the integrated construct, or indicated as available at the boundaries of the screen or other display device (in the case of more detailed views in which the outer boundaries of the integrated construct are not visible). These related views are termed “visible next views” for the purposes of clarification herein. Referring to FIG. 6D, an example of a visible next view available from a specific current view block 82a is shown in FIG. 6D block 82b. More specifically, the view manager may present to the user both “visible next views” those for which a portion of the view is actually available, as shown in FIG. 6F block 82a, and also views which while not immediately visible, are implied as available through their implied position, such as the implied related next views indicated by block 82c in FIG. 6F. Referring to FIG. 6E, examples of visible next views and implied next views are indicated for one embodiment of a 2 dimensional version of the representation structure. Returning to the discussion of the 3 dimensional representation, specifically, user selection of such a visible next view may be accomplished as follows. In one embodiment, while a particular representation is being displayed, the present invention may generally monitor user actions and inputs. In this embodiment, if the user interaction device is moved in a way to place the user interaction marker within or upon an area of the representation view which represents a different, visible next view (or up to a screen boundary that implies a visible next view), the view manager generally replaces the current view with the new view so indicated. In one embodiment of the present invention, the movement may also be accompanied by an additional user interaction message, such as a click of the computer mouse or other device, in order to verify that the user does indeed wish to move and replace the existing representation view with a different view. With regard to choice (ii) above, in one embodiment, within any specific representation, the present invention may generally monitor whether a user selects a specific component that is at that time available in the view. Specifically, in one embodiment, the component of the integrated construct may be being displayed as part of a view as an icon, name, title, summary field, or other suitable high level representation. In one embodiment, the user may select the specific integrated construct component through the use of a computer mouse and a standard double click interaction (for example, the user might select the icon for the person information construct “James Madison” while working in the individual subtopic view with which James Madison is associated, such as the subtopic “Who created the Constitution?”. It should be appreciated that many approaches can be used to provide a message from the user to the view manager and process manager that the user has selected a component within a view in accordance with the present invention. In one embodiment, the view manager responds to the user event of selection of a component of the integrated construct to indicate a request for a more detailed view of that component as referenced above in (ii), and the present invention may display one, a plurality of or all of the contents, structure, and linkages associated with the selected component. In one embodiment of the present invention, this more detailed representation is provided in a pop-up like additional representation space or window on the computer screen, in the approximate position as the high level component that was selected. In one embodiment of the present invention, the detailed representation space for the selected component can also be moved and repositioned on the display area while it is open at any time. In one embodiment, more than one integrated construct component may be so visible and available to the user at the same time. Upon selection and displaying a more detailed representation of any integrated construct component, the contents and format of the selected component may be added to, changed, deleted, or reformatted as desired by the user, as described further in the method and process description of the present invention included herein. With regard to choice (iii) above, in one embodiment, the user may also indicate the selection of a link represented as associated to a component of the integrated construct. In this embodiment, the present invention may display the component associated with the chosen link, which may not be visible in the current view, and provide the user with the ability to navigate by selecting the link to a view of the referenced or linked component, thus changing the component that is central to the view. With regard to choice (iv) above, in one embodiment, the user may indicate the selection of an area or region of a representation, such as the topic set region as a whole from the viewpoint of working on one topic or question. In this embodiment, when the user selects such a region or other visually distinguishable area, the present invention may replace the current view with the view so selected. With regard to choice (v) above, in one embodiment of the present invention, the options available for representation types and specific views are also made available to the user in one or a number of more conventional manners, such as through the use of a drop down menu, through the assignment of specific key combinations on the keyboard (a common convention which is typically targeted at allowing more expert users to interact with a software program more quickly and directly than pull down menus with multiple levels of options typically provide) and others. The present invention uses a number of approaches to provide visual and process feedback to the user as they take actions. Again referring to FIG. 3A, in a preferred embodiment, when the user chooses to add or modify a component to their integrated construct (such as a new information construct) as shown in blocks 420 and 400, the process manager and update manager may add the components to the integrated construct through the update manager block 700, and the view manager may generally add the appropriate rendition of that new component to the representation view directly following the user action that initiated the action, by initiating a changed view, block 205. Continuing with FIG. 3C-20, in one embodiment, logic modules to optimize and render the appropriate representation are shown. In FIG. 3C-20, block 283, the view and representation manager evaluates the intended view elements, including the number of various component types and/or the completeness of the components, that have been determined to be included in the intended new view. In one embodiment, each representation type has a set of “default” view designs or approaches that are preferred in most cases. Continuing with FIG. 3C-20, the view manager in one embodiment may, as shown in block 284, evaluate the appropriateness of the representation type chosen by the user for the complexity, structure, number of components and other factors as evaluated by the present invention in block 283. For example, a high number and complex set of topics and subtopics may be better shown in an outline form for working than in a web like depiction as part of the 3 dimensional representation, described in greater detail below. If the view and representation manager identifies a more optimal representation type, then the suggestion is provided to the view manager, in block 290, and may result in a different user event. Continuing with FIG. 3C-20, if the user does not wish to change their representation type, or if the representation type has not been identified by the present invention as suboptimal, then the view and representation manager in block 286 composes and optimizes the representation according to the requirements of the different representation types, such as 3 dimensional, outline, 2 dimensional matrix and more conventional approaches (described more fully elsewhere herein). Based on the representational type and the specific representation composition, in block 287, in one embodiment, the view manager determines both context graphics and content and functional elements for the new view and representation. For example, in one three dimensional embodiment which may be suitable for lower processing environments, the view manager may utilize images, such as JPEG or GIF files, which depict a three dimensional like structure in various views, as a graphic backdrop against which other actionable elements are added, in order to achieve the appearance and functionality of a three dimensional representation approach without the processing overhead associated with a full 3 dimensional rendering, which is an alternative 3 dimensional representational approach. Continuing with FIG. 3C-20, in one embodiment, as shown in block 288, the view manager then determines the optimal placement and size of elements and functions to be displayed in the representation. For example, in one embodiment of the 3 dimensional representation, a visual area is defined for the addition of information constructs to a specific subtopic view. In one embodiment, if less than 12 information constructs are associated with the specified subtopic, then the information constructs are shown as icons with labels, spread out evenly in the space. In another embodiment, the placement of the information constructs associated with the specific subtopic may be arranged according to their completeness and complexity of content elements and data, or according to a rating of importance as indicated by the user. In this same embodiment, if more than 12 information constructs, for example, are associated with a specific subtopic view, then the present invention in block 288 may instead display the information constructs as a scrollable list and potentially as a ranked list, with labels and reduced or non existence icons. The present invention in one embodiment may use several different visual techniques to provide visual feedback to the user and thereby encourage appropriate thinking and knowledge behavior. For example, in one embodiment, if the new component is created and no additional information has been added to the component, the view manager may represent that new component in the appropriate view as present but empty (for example, through the depiction of an empty outline for an icon for an empty person information construct, with a title only), or otherwise lighter or less evident visually than a component with significant content. In a similar embodiment, if information is subsequently associated with the new component by the user, then the view manager may display the new component with a visual indication of no longer being empty. In one embodiment of the present invention, the distinction between empty (created but not yet used) components and those with which additional information has been associated is accomplished through the use of graphic elements which are empty or transparent and those which are later no longer transparent, or depicted in a darker and more opaque hue. It should be appreciated that a plurality of graphic and visual distinctions may be used to depict the relative completeness of a component or its links that have been added to the integrated construct in accordance with the present invention. Continuing with FIG. 3C-20, in block 283, in one embodiment, the view manager may count the number of subtopics, secondary subtopics, meaning statements, secondary meaning statements, information constructs and analysis constructs associated with the integrated construct, and calculate the number of sides, facets, or areas and size and angles required to render and include an appropriately sided polygon in the representation. In FIG. 3C-20, block 287, on one embodiment, the view manager may then utilize these counts to provide representations in which visual depictions of the integrated construct correspond to the specific numbers of components in the specific integrated construct being represented. In this manner and in these embodiments, the geometry of the representation of any integrated construct in this embodiment will generally embody the number and levels of components that have been constructed by the user to date. More specifically, in one embodiment of the three dimensional representation of the present invention, the number of visually evident sides, facets, surfaces, or areas provided visually for each region (such as the topic set region) defined by the view manager may correspond to the number of subtopics or secondary subtopics which the user has defined at that point in time. In another embodiment, the number of sides or visual areas shown for one type of the components may vary according to the number of higher level components (such as according to the number of topics as opposed to subtopics), and depict the subportions of the component as areas divided into or onto, for example, the side views, facets, surfaces or areas. In one embodiment, the view and representation manager may similarly provide visual differentiation regarding the use of different thinking and work process portions, and the underlying structure and specifically the number of components of an integrated construct if represented in the outline, two-dimensional or matrix form. Returning to FIG. 3C-20, in one embodiment, following determination of the appropriate contextual graphics and capabilities in block 287, and the placement of elements and functions appropriately for the desired view in block 288, the view and representation manager renders the representation view accordingly. Further details regarding specific views and additional details on representation approaches provided by the present invention are described below. It should also be appreciated that many representation forms can be used to create the functional advantages provided by this present invention, and therefore additional representation forms do not depart from the scope or intention of the present invention as described herein. Views and Representations The present invention provides a set of related views and a plurality of representation approaches which display portions or the totality of or the integrated construct (including content, structure and linkages) throughout its lifecycle and enable the associated method and process of the present invention to be accessed, viewed and worked upon by the user in appropriate combinations in association with the portions or the totality of the integrated construct. The present invention's definition of elements and functions that together comprise the capabilities of the views and representations, the visual combinations provided, the feedback provided by these combinations to the user, and their navigational relationships to one another, are one manner in which the present invention facilitates and guides the user according to exemplary thinking and knowledge approaches for an inquiry based project. Additional specification of the manner in which views and representations are provided in accordance with the present invention is included elsewhere in this document above, such as in the descriptions of the view and representation manager and of user interaction. In one embodiment of the invention, the view manager provides for the user to have more than one view of displayed at the same time. The contents of the integrated construct may be varied, containing a plurality of components and of linkages between components, as shown in FIG. 4E. It should be appreciated that such linkages can become complex and numerous. The representations provided by the present invention provide meaningful overall and subset views of the plurality of components and relationships between components together with portions of method and process to be used by the user in the specific view which may exist at any point in the completion of a project and creation and development of an integrated thinking and knowledge construct. As illustrated generally in FIG. 1D??, in one embodiment, the combination of views and representations provided by the present invention may enable a user to choose to work on the same integrated construct from a number of different angles or vantage points, generally without having to do additional work to edit, reconstitute, or reorganize the underlying information in order to do so. In one embodiment, the views and representations provided by the view manager may be changed and depicted in order to provide visual representation according to changes in the integrated construct components, content, and linkages, as well as the user's or users' activity and actions in different thinking and knowledge process portions, thereby providing the user with an ongoing depiction of and guidance for the progress in developing the integrated construct for a project. The views provided by the present invention generally provide a basis for stability and familiarity across projects and integrated constructs, as different integrated constructs will in one embodiment have similar view capabilities, which may include such common items as: method and process capabilities by general thinking and knowledge type of activity, common generally available method and process and tools, common general types of ITKC components that may be included in or associated with an integrated construct, and others. In addition, in one embodiment, the general characteristics of the views, regions and subset sections or slices provided by the present invention may be generally the same across integrated constructs, providing a familiar context for thinking and knowledge activities, even though the content provided in those views differ according to the content and structure of different integrated constructs and of an integrated construct at the point in which it is being represented. Although general options for method and process, components and views available are in many embodiments of the present invention generally common across different occurrences of integrated constructs, representations of specific projects and integrated constructs are likely to differ in several key respects, as described in greater detail in other sections herein. For example, the views provided by the present invention of different projects and integrated constructs are likely to differ from one another in the number and complexity of the topic set being addressed, in the selection of the components for inclusion with the particular integrated construct or associated with any portion or specific component of the ITKC, in the number and completeness of components included in the integrated construct (such as information constructs and analysis constructs), in the number of thinking and work spaces created for various components, in the specific linkages, and others. In a preferred embodiment, the present invention may employ a number of different visual and design approaches in views and representations in order to depict and feedback to the user their progress so far against the exemplary and/or potential thinking and knowledge activities that may be or are intended to be done, as described elsewhere herein. For example, in one preferred embodiment, the view and representation manager may create a representation of the ITKC and its associated thinking and working areas as a visual skeleton in the earliest steps of the user's development of their integrated construct. As the user then adds components and content to the integrated construct (as described above), the view and representation manager changes the representation accordingly. In one embodiment, for example, early portrayals of the integrated construct include representations of empty integrated construct regions or areas where no user activity has yet occurred, or where activity has occurred but no components of that region's or area's type have been created, or where the user has created “empty” components, and others. In this manner, the representations provided by the present invention are a visualization of the user's integrated construct as it develops as well as its potential for being the basis for the user to identify additional development that has not yet occurred. For example, in one embodiment, a topic or question which has been created but which has associated with it as yet no information or analysis constructs may be shown with empty working areas for the association of information constructs and analysis constructs and other related components. At a high level, such a subtopic in one embodiment would be depicted as existing but empty. In another example, the topic or question area which then had a small amount of information associated with its associated Information constructs or analysis constructs might be shown as translucent or pale in color, while the same topic or question with a significant amount of information associated with it may be shown as more opaque and brighter. The intent is to visually distinguish progress in the components and regions or areas of the integrated construct. It should be appreciated that such distinctions can be accomplished through a variety of mechanisms and not depart from the scope and intent of the present invention. In one embodiment of the present invention, as indicated in FIG. 3C-10 block 244, the view manager may provide user with the ability to represent the integrated construct and its associated method and process in a plurality of forms, based on the display options provided in block 242, such as the following: (i) three-dimensional representation(s); (ii) outline or tree form for representation(s); (iii) two dimensional representation(s), and (iv) matrix representation(s). In other embodiments, the present invention may provide one, some, or all of these different representational forms as choices for the user or users. In one embodiment, the user can choose to work on and view the integrated construct through any of these representations, and the view elements and associated method and process available to the user behave in generally the same way across the different representation types. Changes in representation type may be triggered to the view manager by the user through a plurality of selection mechanisms, including but not limited to use of a conventional drop down menu and others. Referring again to FIG. 3C-10, as shown in block 246, the present invention in one embodiment may also provide the user the ability to choose specific representation forms or shapes for a specific representation type. For example, in one 3-D embodiment of the representation provided by the present invention, the view manager also provides a choice of the specific shape in which their integrated construct will be represented, examples of which are shown for the three-dimensional representation in FIGS. 6I-6V. In one embodiment, categories of views provided by the present invention include but are not limited to the following types, depicted schematically in FIG. 6A, each of which may provide feedback to the user on their progress relative to the scope of the view, guidance on related thinking and knowledge activities, and navigation access to the user: (i) overall or global views of the integrated construct, allowing the entirety of the integrated construct and/or the entirety of the method and process of the present invention to be represented (block 80; (ii) views which correspond to regions, thereby showing the set of like integrated construct components and method and process, associated with a common type of thinking or knowledge work (as in problem definition and topic sets, analysis and analysis constructs, etc) (blocks 70, 72, 74, 76, 78); (iii) slice or subset views, which provide a view of a collection of related components of an integrated construct and their associated method and process, and enable the user to work in meaningful subsets across the integrated construct (examples which include the individual topic view, the individual meaning statement view, and others) (block 82); and (iv) individual component views (block 85), and others. Specific examples of these view types for one embodiment of the present invention are described in the following section. Referring to FIG. 3C in block 272, in one embodiment, the view and representation manager filters the total ITKC and its associated method and process based on parameters set for a new view, as indicated in block 270. The view manager may therefore create a plurality of views and subsets from such filtering. In one embodiment of the present invention, some of the views provided by the present invention may generally divide the integrated construct into distinctive regions, representative of different kinds of thinking and knowledge work, as shown schematically in FIG. 6A. As shown in FIG. 6, in one embodiment, these regions as represented to users of the present invention generally combine or relate different aspects of the present invention, such as these three different items: (i) the portion of the integrated construct content and its structure which is associated with a particular region, as representing a particular kind of thinking or knowledge activity (e.g., the region associated with the topics the user has defined); (ii) the portions of method and process of the present invention, which may be embedded in tools and guidance to assist the user in working on that portion of the integrated construct, and otherwise provided in the steps or portions of the method and process which that region is intended to enable; and (iii) the linkages between and among relevant components of the integrated construct content. The present invention may use a number of different approaches to distinguish the different regions or types of thinking and knowledge work within the total representation to the user. For example, in one embodiment of the present invention, such as in one of the three-dimensional representations of the integrated construct, regions (types of thinking and knowledge work and their associated content) are distinguished by the visual distinction of different bounded areas within the integrated construct representation. Examples of general regions being distinguished in a 3-D representation of the present invention are shown in FIGS. 6B and 6C. The regions may be further distinguished by color and background depiction or other graphical distinctions. In another embodiment of the present invention, the outline or tree representation form of the integrated construct, the regions may be distinguished by the use of common color and graphic characteristics across the components within the region and through the proximity of like components to one another. Referring again to FIG. 3C, filtering of the ITKC contents and structure in block 272 based on parameters for the new view, may also provide a view of subset or “slice” of related components of the integrated construct and associated methods and process required or desired to work on that slice. FIG. 6D shows schematically the general relationships between slice views and regions provided by the present invention. Specifically, referring to FIG. 3C, in one embodiment, the view manager uses the parameters for the new view (block 270) to filter the overall ITKC contents, structure, and linkages and available method and process portions, as indicated in block 272. For subset or slice views, in one embodiment, the view manager may utilize a specific subtopic as the basis for filtering (for example, he subtopic “Who created the Constitution?”). In this embodiment, the view manager may then filter the ITKC components, linkages, and structure to select only those that are associated or have been linked to the subtopic “Who created the Constitution?” (for example, the information constructs James Madison and George Washington, the analysis construct regarding a comparison of the beliefs of the framers, and any associated meaning statements). The view manager may create such combination subset or slice views for all other components related to the component which is the basis of the filtering (the subtopic above), and may create subset or slice views for partial subsets (such as a partial subset or slice view which includes the subtopic, information constructs, and analysis constructs but which does not make the associated meaning statements visible in the particular view). FIG. 7B show one embodiment of the use of regions and subset or slice views in a 2 dimensional embodiment. Referring to FIG. 7B, for example, in one embodiment, regions may be implemented as areas—accessible by some structured or otherwise visible map, such as the tab like look shown in FIG. 7B, with regions indicated by blocks 70, 71, 72, 73, 74, 76, and 78, and a mechanism for accessing subsets or slice views shown through the use of a navigatable menu or other visible or accessible device, as shown in block 82. FIG. 7C shows a 2 dimensional approach with one embodiment of an individual subtopic view. Similarly, a 2 dimensional visual map of progress, associating components to regions and other indicators for preferred structure and/or process may not be as compelling as 3 dimensional visual feedback, but again could implement the same or nearly same functionality. It should be appreciated that although the 2 dimensional embodiment may not have the same advantages as the preferred 3 dimensional embodiment, it may well prove the preferred embodiment for some classes of users and/or projects. The present invention therefore provides guidance generally enables the user to move freely between the representational views while utilizing the corresponding portions of the method and process of the present invention. FIG. 7 depicts one embodiment of links and navigational paths between views or representations provided by the invention. In addition, the present invention generally provides abilities to short cut navigational paths through physical manipulation of the representation, and instead navigate directly and quickly to the desired component or view. This short cut navigation may be accomplished through a plurality of mechanisms such as the use of conventional pull down menus or assigned keys or others in accordance with the present invention. As illustrated in FIG. 7, in one embodiment, specific views provided by the present invention may include but are not limited to the following: (i) topic set overview 702 and if needed topic set drilldown view; (ii) individual topic view and detail views 706; (iii) individual information construct view 710; (iv) individual analysis construct view 720; (vi) information construct set view 715; (vi) analysis construct set view 725; (vii) linkage view 780; (viii) topic—meaning statement overlay view 770; (ix) meaning statement overview 750; (x) answer or summary view; (xi) integrated construct overall overview 700, and others. In one embodiment of the present invention, the precise layout and appearance of views or representations can differ and still accomplish the desired workspace creation and relationships to other workspaces to embody the method and process of the present invention effectively for the user. Preferably in all view types, the view manager provides the ability for the user to be shown high level and more detailed depictions of the integrated construct content, structure, linkages, and associated portions of method and process. This may be accomplished through a plurality of user interaction mechanisms, including but not limited to such mechanisms as clicking “down” into a specific component, in order to see the details within that components, as well as the ability to zoom in and zoom out on components of the integrated construct and the integrated construct as a whole. When a three-dimensional representation is being used, the integrated construct representation may also be manipulated such as rotated, turned, flipped, and otherwise maneuvered in a manner that has been seen to be used in the manipulation of three-dimensional renderings of physical objects. This facilitates further visualization of the user's work on the project and also enables the user to look at the user's work on the project from different angles that may facilitate different thought processes of the user. In one embodiment, representations or views provided by the present invention may employ a combination of visual characteristics including a plurality of elements to provide visual distinction of the specific characteristics of an integrated construct and the associated thinking and knowledge processes, including but not limited to elements such as shape, structures, and color. Distinctions provided about the integrated construct may include but not be limited to the following: (i) distinction of types of thinking and/or knowledge work activities and their associated content portions; (ii) distinction between regions and sub-regions or portions of method and process that have been used in the integrated construct versus those that have not yet been used, at the point in which the integrated construct is being represented; (iii) distinction of integrated construct components which have been created or initiated in the particular integrated construct; (iv) distinction of integrated construct components which are available for use but have not yet been included or initiated in the particular integrated construct; (v) distinction between regions and integrated construct components which have information associated with them versus those which do not yet have any content or information associated with them (i.e., those which are empty); (vi) distinction of integrated construct components which have greater or lesser amounts of content associated with them at the point in which the integrated construct is being represented; (vii) distinction between components of the integrated construct which are linked to other components versus those which are associated with the integrated construct but are not linked to other components in the integrated construct; and (viii) distinction of components of an integrated construct which may be linked to components or the totality of other integrated constructs; and (ix) distinction of key aspects of components as being in existence or not, or being lightly completed versus comprehensive. It should be appreciated that many specific forms or shapes of two and three-dimensional structures may be used to implement views of the integrated construct, and they are within the scope of the present invention. Examples of shapes which may be used for 3 dimensional representations in one embodiment are provided in FIGS. 6I through 6V. In one embodiment, hapes that can accommodate the following characteristics are generally likely to be among those with an optimal shape for representation of a 3-D shape for the conveyance of the integrated construct. For example, in one embodiment, shapes which generally have the following properties may be used most readily to implement a representation of the integrated construct in the manner described herein: (i) a manner of distinguishing levels or spaces which allow for the distinction of different types of thinking and/or knowledge activities; (ii) a way of subdividing or otherwise showing the existence of different entities within or associated with these levels or spaces in order to reflect the types and/or numbers of the various integrated construct components the user is creating or viewing; (iii) proximity or the ability to achieve proximity or visible linkage between components which are closely related or need to be visually related in order to accomplish work steps (and to facilitate a way to show and work with the plurality of components and links between components of the integrated construct, and to move between different combination views that are important to work steps in a meaningful way); (iv) proximity or the ability to otherwise achieve relationships between related views; and (v) a way of providing views and access into the individual components that comprise the content and content relationships of the thinking and knowledge activities. In one preferred embodiment, referring to FIG. 3C-20 block 286, the view manager utilizes a visual depiction of a three dimensional, physical-like structure as a key representational mechanism, which may show both navigational and therefore thinking and working relationships between the views, providing navigational access, as well as providing feedback to the user regarding progress, as defined elsewhere herein. In a preferred embodiment, t the 3 dimensional visual structure assists in conveying the potential and already used thinking and knowledge portions of the method and process, as ell as the components that have been built and their relationships. In one referred embodiment, the three-dimensional representation generally uses areas, levels and facets of a three-dimensional representation structure to display the integrated construct and its associated method and process portions. For example, in one embodiment, the view manager may use the different levels of a physical-like structure to differentiate, show progress in, and provide navigation to thinking and knowledge activities and resulting components of a similar type (for example, problem definition through topics, analysis constructs, meaning statements, etc.). Similarly, in one embodiment, the view manager may use the sides, facets, or subareas of a physical like 3 dimensional representation to depict and convey the existence of different subset or slice views. In one preferred embodiment, the view manager may use the levels and sides of a 3 dimensional structure to define more specifically the basis for filtering a subset or slice view. In one embodiment, the invention may utilize at least two different approaches to the 3 dimensional representation of the integrated construct: 1) a 3D representation that is essentially views mapped onto or associated with the facets, surface areas, or spaces of a 3 dimensional looking shape (as shown in FIG. 6F, and 2.) a 3D representation that employs a three dimensional linked structure made up of the ITKC components and its linkages, either alone or in combination with the use of the facets, surface areas, or spaces of a 3 dimensional looking shape. This latter embodiment may take on the look of a three dimensional molecule, with the various linked components of the ITKC arranged with visible links, and an emphasis on navigation through nodes and links as opposed to facets. Both of these as well as combination or additional three dimensional approaches to representing the ITKC are to be understood to be within the scope of this application. The use of 3 dimensional representations may assist the user in working on a project in an intuitive manner, and makes the totality of their project and the status of the user's use of method and process portions, as well as the relationships between components easily evident. It should be readily appreciated by those skilled in the art that additional forms of 3 dimensional representation of an integrated construct are included within the scope of this invention. User navigation of 2 dimensional, outline or tree, and matrix representations provided by the present invention may be accomplished in a variety of mechanisms that are well understood by those skilled in the art, including but not limited to user selection of visible elements to initiate action or see further detail, use of drop down menus, drag and drop approaches, and others. In one embodiment, user navigation and use of the 3D representational views can occur in several ways. Two of these ways are described more fully herein. In one embodiment, the user may use an interaction device to select an area, facet, surface, or component that is visible to the user in the 3D representations. In one embodiment, the 3D representations may include both the current visible central work view, and “next views” which are made visible or accessible in an adjacent or otherwise visible area on the representation. The proximity of “next views” to the current visible central work view is one way in which the present invention provides guidance to the user in thinking, as the “next views” represent natural next work steps the user may wish to chose next. Referring to FIG. 6F, one mechanism provided by the present invention to enable guided but flexible movement between the different thinking and work steps in an inquiry based project is the provisioning of current visible views (such as the slice view depicted by block 82a on FIG. 6D) and views which are also visible and therefore appear closely related (as depicted by block 82b on FIG. 6F), which may be referred to as “next visible views,” And views which are implied to be available because of the edges or other logically available surfaces, areas, or structures that comprise the 3D structure that is being used, as in those noted as “implied related views” depicted by block 82c in FIG. 6F. The design and structure of the views, and their visible adjacency or placement in relation to one another, is one way in which the present invention provides guidance to the user in portions of method to consider next, while allowing significant freedom in addressing the problem. In this embodiment, the view manager may provide additional direct navigation to less related views through the use of mechanisms such as drop down menus and others. Other views (and corresponding work areas) may also be available to the user, and provided in a drop down menu or other fashion. This is in keeping with the design of the present invention that it provides some guidance to the user but also allows the user to move fairly freely throughout the method and process. The user therefore can choose to move from the current visible central work area to a “next view”being shown to them in the representation, by selecting the next view area (or other visible indicator for a next view) with an interactive device. Upon the user selecting such a “next view” (as shown in FIG. 3A, block 110), the user action is evaluated (FIG. 3A, block 302), and if a change in view is warranted, the View Manager (FIG. 3A block 200) changes the view being displayed to the chosen next visible view, including the current content and structure of the integrated construct (FIG. 3A). The View Manager (FIG. 3A, block 200) provides the appropriate representation to the user, in keeping with the specifics of the 3D format that is being used or has been chosen, in keeping with the above. The definition of Next Visible Views as used herein includes views that are logically apparent to the user but which may not be fully visible or indeed visible from the current view. Referring to FIG. 6E, for example, the areas noted as 82b-1 and 82b-2 are indeed areas that represent access to views for additional subtopics, and are Next Visible Views. Continuing with FIG. 6E, areas notes as 82b-4 are also Next Visible Views, although only the edge of the facet belonging to that view and the label for the subtopic may be visible from the current view. Also in FIG. 6E, area 82b-5 is also a View which is available to the user, by moving an interactive device to the edge of the construct that is the boundary of the “bottom” facet or view, by using the interactive device to select just below the visible Current View, or by other interactive mechanisms including but not limited to a pull down menu. Accordingly, user manipulation of the 3 dimensional representation is provided by the present invention is provided in a number of ways: 1.) the user may rotate, flip, zoom in and out or otherwise manipulate the 3 dimensional representation of the integrated construct through the use of a number of different mechanisms and thereby “move” to a different, selected view; 2.) the user may select an area, facet, or other component of the 3 dimensional representation by using an interactive device (such as a mouse and double clicking on the portion of the representation that indicates the presence of the next view), thereby causing the representation to be replaced by the selected next view; and/or 3.) the user may use a navigator icon or similar interface device to indicate directional movement. One embodiment of the use of a navigator icon or similar interface device is described further below. In one embodiment, user navigation from one “view” to another of the integrated construct—as associated with the different regions, facets, or other areas of a 3 dimensional looking structure—may be accomplished through the use of a directional navigator device (see FIG. 7E for one example of such an interface device). In this embodiment, a visual device with sections or other elements that indicate direction may be provided to the user on views. In this embodiment, if the user selects the component indicating the direction of “left” for example, the View Manager changes the current view to provide the representation that is associated with the next left most facet or area of the integrated construct. Specifically, for example, if the user is viewing a Question “side” View of the Construct, and selects or otherwise activates the “left” directional indicator in the navigator device, then the View Manager changes the view to correspond with the next left most view—in this case, the Question “side” View to the left of the previous view. Similarly, in one embodiment, if while viewing a Question “side” View of the Construct, the user selects or otherwise indicates the “up” directional indicator in the navigator device, the View Manager changes the view to correspond with the view which is “above” or “up” from the current view—in this example, the Topic Set or Topic Subset View. The use of significantly greater numbers or different forms of directional indicators for use in navigating a 3D or 2D representational view of an Integrated Construct are readily within the scope of this invention. In one embodiment of such a navigator device, the central region shows a depiction of the overall shape of the integrated construct, selection of which central region of the navigator device results in the View Manager presenting the user with the Integrated Construct Overall View, as described in greater detail later in this document. It should be readily apparent that the use of other interaction approaches devices (such as the physical directional movement of a mouse, use of a gaming interactive device, use of a pen, touch screen or other interaction mechanism) to accomplish navigation and use of a 3 dimensional representation of an integrated construct does not depart from the scope of this invention. In another embodiment of a navigator device, the view manager may provide the user with a miniaturized representation of the Integrated Construct as a navigational device. In this embodiment, while on any given representational view, the user may then use this miniaturized view or map of the overall Integrated Construct to select a specific view, portion or component of the Integrated Construct with some form of interactive device. Upon such selection, again, the View Manager then changes the representation of the Integrated Construct to the newly selected view or component. It should be readily appreciated that the use of any such visual or textual map of an overall inquiry based process and integrated construct as a navigational device would be readily within the scope of this invention. The value and advantage of the views and representations of the integrated construct are not dependent upon the precise coloration, shape, or screen placement of the components being provided in each slice, region, component-specific, component set or overall integrated construct representation. It should be appreciated that the same functionality and same or similar advantage can be provided by somewhat different implementations of these representations. For example, changing the icons, coloration, sizing, or screen placement of the components, or in some cases even the selection of the specific components being provided on the view would not materially change the function provided by the invention. In one embodiment of the present invention, the user is provided with the ability to define the preferred placement of items to appear in the various views. The integrated construct may also be implemented in a physical manner, as in a physical model to be used in a classroom or other learning situation to discuss and define the thinking and knowledge components of an archetype project and process. An additional physical embodiment of the integrated thinking and knowledge construct is in the use of the construct for a physical exhibit, as in a museum setting. Referring again to FIG. 7, examples of representations that may be provided by the present invention are described below. Topic Set Overview View Referring to FIG. 7, block 702, he topic set overview representation 702 provides the user with the totality of their topic set (being the definition of the problem, issues, questions or other means of defining the focus of the inquiry based project), as it exists at the time the view is performed. In one embodiment of the present invention, the topic set is represented in the form of a web as illustrated in the partial example of FIG. 5A-42. An alternative embodiment may provide the topic set in the form of an outline as illustrated in FIG. 4A-10. In one embodiment of the present invention, the following are included in the topic set overview: (i) main topic; (ii) sub-topics; (iii) secondary subtopics; (iv) any additional levels of subtopics; (v) linkages between all elements in the topic set; and (vi) method and process associated with the topic set, including the ability to create, change, edit, link, and rearrange topics, as well as problem definition or topic definition help or assistance. In one embodiment of the present invention, the top of the three-dimensional overview representation is designated for the topic set overview view In a preferred embodiment, as with all views of the integrated construct, the components that appear in this view are all generally actionable by the user (unless the components have been otherwise designated as unchangeable as discussed elsewhere herein). This means that the user may select any one of them to review, change, or add to any of the content or structure of the selected component, with the same range of functionality generally as when the user first created that component. Topic Set Drill Down View Similar to the topic set overview, the present invention may provide a view of the integrated construct which enables the user to review portions of the total topic set and its linkages and relationships in additional detail, indicated on FIG. 7 by block 704, for example to view a subset of a large or complex topic set This view may be most applicable in more complex integrated constructs. Capabilities for the subset of topics provided is similar to that provided for the Topic Set View. Individual Topic View Referring again to FIG. 7, block 706, in one embodiment, the view manager provides an individual topic (or subtopic or secondary subtopic as described elsewhere herein) view that generally enables the user to review and work on the subset of the total integrated construct which is associated with an individual topic (or subtopic), question, issue, problem or other means of defining the focus of an inquiry based project. In one embodiment of the present invention, the number of Individual topic views available corresponds to the number of subtopics the user has defined within the integrated construct. In another embodiment of the present invention, the number of individual topic views available corresponds to the number of secondary subtopics, which can be accessed from either the topic set overview view, or a topic set drilldown view as appropriate, and others. Similar subseting views may be provided to accommodate the nature and complexity of the specific integrated construct. The individual topic (or subtopic or secondary or other subtopic) view 706 generally represents the totality of the integrated construct which is associated at any given point in the development of an inquiry based project with the individual topic, question, problem or issue of interest (or first type of thinking structure). In this manner, the present invention may then provide a meaningful subset of the potentially complex total integrated construct structure, and enable focus by the user on working on one meaningful slice. An example of one 3-D embodiment for the components and depiction of an individual topic (subtopic or secondary subtopic) view is shown in FIG. 7A and may generally include: (i) subtopic or secondary, or other subtopic which is the subject of the view; (ii) any associated data, information, information elements and/or information constructs which have thus far been linked to or associated with the subtopic or secondary subtopic; (iii) any associated analysis constructs which have thus far been linked to or associated with the subtopic or secondary or other subtopic; (iv) any meaning statements which have been linked to or associated with the subtopic or secondary subtopic; (v) any notes regarding what is to be done next, what additional information is needed or, relevant project plan items which have been linked to or associated with the subtopic or secondary subtopic; (vi) access to project plans, especially any planned research; (v) access to electronic information sources (as described elsewhere herein) and (vi) access to related portions of the method and process of the present invention for the assistance or guidance in each of the above associated component types, as well as the method and process associated with creating, editing, or otherwise modifying the associated component types above, and others. FIG. 7A depicts a three dimensional ITKC with a individual subtopic view which thus far has 2 information constructs associated with it (George Washington and James Madison) but has not yet developed meaning or analysis for this subtopic. The present invention further provides for more detailed views of components associated with individual subtopics or secondary subtopics. It is to be appreciated that such additional detailed views follow from and are in accordance with the present invention on any or all of the additional views or representations provided. Individual Meaning Statement View Referring again to FIG. 7, the individual meaning statement view block 730 enables the user to view and work on the subset of the entire integrated construct that has been or is to be associated with an individual meaning statement. In one embodiment of the present invention, the number of individual highest level meaning statements views available correspond to the number of meaning statements created at the highest level as defined by the user within the integrated construct. In another embodiment of the present invention, the number of individual meaning statement views available correspond to the number of secondary meaning statements. The individual meaning statement view generally represents the totality of the integrated construct, which is associated thus far with an individual meaning statement (or second type of thinking structure). In this manner, the present invention may provide a meaningful subset of the potentially complex total integrated construct structure, and enable focus by the user on working on one meaningful slice. The meaning statement view may generally provide a focus on working on what the information and analysis components mean to the user, building toward an answer or summary view. The meaning statement view is likely to be significantly different than the views that are provided based on the individual topics, as described above. An example of one embodiment of the individual meaning statement view generally may include any or all of the following: (i) a meaning statement or secondary meaning statement which is the focus of the view; (ii) any associated information, information elements or Information constructs which have thus far been linked to or associated with the meaning statement or secondary meaning statement; (iii) any associated analysis constructs which have been linked to or associated with the meaning statement or secondary meaning statement; (iv) any notes regarding what to do next, relevant project plan which have thus far been linked to or associated with the specific meaning statement or secondary meaning statement; and (v) access to any method or process associated with all of the above. As with all representations provided by the present invention, the components represented on the meaning statement view are all generally actionable by the user. This means that the components can be: (i) selected to reveal their detailed contents; (ii) edited or changed; (iii) deleted; or (iv) replaced or enhanced with new or additional components. Individual Information Construct View Referring to FIG. 7, block 710, information constructs that have been created are indicated and made available in several representational views as icons, labels, or thumbnails of their contents. If the user selects a previously created Information construct, generally according to interactive mechanisms described herein or generally used in the art, the contents associated with the selected information construct are displayed via the individual information construct view. As with all representations provided by the present invention, the components displayed in the individual information construct view are generally actionable, unless they have been protected from change by a previous author. This means they can generally be edited, changed, deleted, or added to readily from the individual information construct view. In one embodiment, the individual information construct view may generally include the following: (i) information construct label or title; (ii) information construct type (as chosen, or undefined); (iii) information construct unformatted information elements; (iv) information construct formatted information elements; (v) links to other information constructs; (vi) links to analysis constructs; (vii) links to available topics, subtopics, secondary topics; (viii) links to available meaning statements; and (ix) access to method and process associated with the creation and editing of the information construct and its linkages. Individual Analysis Construct View Referring to FIG. 7, block 720, analysis constructs that have been created are similarly available in many representational views as icons, labels, or thumbnails of their contents. If the user selects a previously created analysis construct, according to interactive mechanisms described herein or those generally used in the art, the contents associated with the selected analysis construct are displayed via the individual analysis construct view. As with the other representations provided by the present invention, the components displayed in the individual analysis construct view are generally actionable, unless they have been specifically protected from change by a previous author. This means they generally can be edited, changed, deleted, or added to readily from the individual analysis construct view. In addition, links that appear in the representational view are generally available as navigation means to access the detail associated with the linked component. The individual analysis construct view 720 of FIG. 7 generally may include the following: (i) analysis construct label or title; (ii) analysis construct field for observational comment regarding the analysis construct; (iii) related information constructs; (iv) related information elements of information constructs; (v) related analysis constructs; (vi) related available subtopics, and secondary subtopics; (vii) related available meaning statements; (viii) other available information constructs in existence at the time of viewing; (ix) information construct formatted information elements; and (x) access to method and process associated with the analysis construct or related functions. Collection of Information Constructs View Referring again to FIG. 7, the collection of information constructs view block 715 generally may provide a representation of the totality of information constructs created for or associated with the integrated construct at the time the view is so created. Icons, thumbnails, lists, and/or labels of such items or other forms thereof may be used to depict this inventory of information constructs to date. Information constructs so displayed in such a representation are actionable (unless protected from change earlier) as in any other view: for viewing at a detailed level, for editing, for viewing or changing links, etc. In one embodiment, the representation of the collection of information constructs created may include a grouping of the information constructs according to type, and a visual distinction of how much data or information is contained in or otherwise associated with the particular Information construct. In anther embodiment, the representation of the collection of information constructs allows for grouping by category, theme, or other meaningful group, as discussed earlier herein. Collection of Analysis Constructs View Referring again to FIG. 7, the collection of analysis constructs view 725 may generally provide a representation of the totality of analysis constructs created for or associated with the integrated construct at the time the view is so created. Icons, thumbnails, lists, and/or labels of such items or other similar forms thereof may be used to depict this inventory of analysis—constructs to date. Analysis constructs so displayed in such a representation are generally actionable as in any other view (except where otherwise protected): for viewing at a detailed level, for editing, for viewing or changing links, etc. In one embodiment, the representation of the collection of analysis constructs created may include a grouping of the analysis constructs according to type, and a visual distinction of how much data or information is contained in or otherwise associated with the particular analysis construct. In another embodiment, the collection of analysis constructs may be represented in groups or categories according to their linkage to subtopics or meaning statements, or other categories or groups. Answer or Summary Set Referring to FIG. 7, block 760, the preferred embodiment further provides for a view, which focuses on the answer or summary set, and a related view, block 750 that allows for the representation of both the answer or summary set and the meaning statements as a set. Topic Meaning Statement Overlay View Referring again to FIG. 7 block 770, the present invention may provide a view which represents the topic set and the meaning statement set of the respective integrated construct, and which depicts the relationships between these two thinking structures of the integrated construct. Linkage View Referring to FIG. 7, the linkage view 780 representation may be generally available at any time for any component associated with the integrated construct. In one embodiment, the linkage view is provided when the user selects any component, and the user activates the right click on the computer mouse. In another embodiment, the linkage view is provided when the user selects any component and a subsequent choice is made from a menu provided. There are any number of specific user actions that may be used to trigger the display of the linkage view representation, without departing from the scope or the intent of the present invention. When the user invokes the linkage view, a representation is provided which shows all linkages from the chosen component to other components within the integrated construct at the time the representation is accessed. In one embodiment, the linkage view of a knowledge construct shows only links between knowledge constructs (being information constructs and analysis constructs), as opposed to links to all thinking constructs (topics, meaning statements, answers). In one embodiment, the integrated construct component, which is the focus of the linkage view, is shown as the component in the center of the representation The integrated construct component, which is the focus of the linkage view, can be selected by the user in order to show the contents of the component, as described for example, in the individual information construct view or individual analysis construct view described above. FIG. 7D is an example of a linkage view of one embodiment. Overall Integrated Construct Overview Referring to FIG. 7, when the overall integrated construct overview 700 is invoked by the user, a representation is provided which shows a depiction of the overall integrated construct, as it exists at the time the representation is invoked. Regions and other views are generally available to the user to select from this overall integrated construct overview, by selecting the portion of the integrated construct visible which the user wishes to see in greater detail. Selection of a portion of the depiction of the overall integrated construct invokes the appropriate next representation, with its associated content and method and process then available to the user. In one embodiment of the overall integrated construct overview, color and shapes may be used to distinguish and depict the boundaries of the various regions, slice or other views. In addition, the placement and shape of the facets and areas of the integrated construct as depicted in the overall integrated construct overview may be used to distinguish the views of combinations of components which are available to the user, and which thereby provide the user with the content, linkages of the integrated construct and the method and process portions relevant to creating, editing, and viewing the components of the integrated construct. As has been described elsewhere above, the overall integrated construct depiction is specifically designed to provide an overall view of the progress the structure and process of the user's ITKC is making, and uses a number of visual distinction mechanisms, as defined elsewhere herein, to depict this progress and imply the user where they might want to focus their energies next. Whether provided as a 3-D physical-like representation, an outline, a matrix or other visualization, the depiction of the integrated construct provides a visualization and map of the total project, its components, linkages and the steps that have been taken in its construction. As used herein the term arbitrary problem includes qualitative expressions of problems, quantitative problems, and combinations thereof. In addition, the description often uses the term “construct” in connection with the description of preferred implementations. By this term it is meant and organized collection of the relevant data. The term is not meant to be limited to any particular form of data structure or organization, though certain preferred implementations organize data according to object oriented design principles. When referring to the term “archetype” as in archetype process or archetype structure, the intent is to cover exemplary, though not necessarily optimal, processes or structures. When referring to the term “integrated” the intent is to cover things operating harmoniously, or uniting components that were previously regarded as separate. In the foregoing detailed description of the present invention, and its preferred and example embodiments discussed herein, reference is made in part to the accompanying drawings that form a part thereof. The drawings in conjunction with the following description and explanation show by way of illustration specific embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural and functional changes may be made without departing from the scope of the present invention. It will be appreciated that the scope of the present invention is not limited to the above described embodiments but rather is defined by the appended claims, and that these claims will encompass modifications of and improvements to what has been described.
<SOH> BACKGROUND <EOH>It is widely recognized that good problem solving and thinking skills need to be learned and supported. The availability of computers and electronic information bring an opportunity to support this need. There is today no approach that teaches and supports creative problem solving and thinking as a whole, integrated discipline, including the evolution of the person's understanding of the problem, exercising of logic and judgment, development of knowledge and ideas, and the mastery of a comprehensive answer. Today's problems are often complex, many are highly qualitative and difficult to specify, many often lack absolute answers. At the same time, information availability is almost limitless. In addition, more alternative points of view lead to and require more complicated arguments and solutions. In school, problems like understanding the causes of WWII and its impact on the peoples and governments of Europe, in business problems like deciding whether a widely held directional view is accurate or desirable—both are examples that demand understanding multiple inputs, multiple possible solutions and many thinking interrelationships. Educational experts including the U.S. Department of Education recognize thinking and problem solving as a significant and important challenge for educators and workers in the 21 st century. In a 2003 report, skills critical to teach children for the future include: “thinking and problem-solving skills that use information and communications technologies to manage complexity, solve problems and think critically, creatively and systematically.” Today, the teaching of problem solving and thinking and related topics occurs as a result of many disparate activities. Beginning in about the fourth grade and continuing through high school, college and into adulthood, students are exposed to some of the components of problem solving in manners designed to increase their understanding, experience, and comfort. In the fourth grade, they often have their first exposure to independent research. Most are exposed to the scientific process and its defined steps and to some form of steps for researching and writing papers; some have experiences in developing multi-media presentations. But these exercises are mostly taught separately and independently, and unpredictable in their results. Whether a student becomes an “end to end” problem solver—capable of defining a problem, finding and researching information, developing their own understanding, defining alternatives and eventually an answer supported by their work—is uncertain. Computer and information technology support of problem solving and thinking is fractured and focuses primarily on the information handling activities. Separate and independent software programs support search and retrieval, information manipulation and management, information presentation and communication, and others. While this may be comfortable for many adults, little computer support exists for “thinking” and analysis logic particularly for the more qualitative topics that predominate. There are no software enabled processes that help guide good thinking and address the complexity of today's problems. It is also well documented that different people learn differently (Howard Gardner, in Frames of Mind, The Theory of Multiple Intelligences , for example). Similarly, adults solve problems by applying their own styles. These alternative learning and problem solving styles may be equally good as long as they lead to an equally good “answer” and the thinking that has occurred has developed a robust, internally valid set of understanding and choices, sound logic and consistent support of conclusion and arguments. The learning of many skills is enhanced by observing models; students and adults often learn by observing and emulating model behavior. Expert problem solvers know how to approach the problem, how to organize their thinking, how to manage the information and knowledge activities they need to do, how to evaluate where they are along the way and adjust their emphases to achieve a good result. Teachers and expert adults can try to serve as models in teaching problem solving, but consistent, comprehensive problem solving and thinking models are hard to find and even harder to see and understand. There is a need for a software tool that enables and supports a comprehensive problem solving and thinking process, especially in information intensive situations.
<SOH> SUMMARY <EOH>The invention provides systems and methods of facilitating and evaluating user thinking about an arbitrary problem. According to one aspect of the invention a system and method facilitate user thinking about an arbitrary problem. The system includes (and the method performs) first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion, related to the problem specification, to populate a conclusion statement structure. It also includes third logic to facilitate user creation and specification of knowledge, related to at least one of the problem specification and the conclusion specification, to populate a knowledge structure. Lastly it includes control logic to persuade user interaction with the first through third logic to a sequence of interactions within a predefined set of interaction sequences, wherein the predefined set of interactions define an archetype process for user thinking about the problem. According to another aspect of the invention, a system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure. It also includes third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure. It also includes model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the user model structure, conclusion statement structure, and knowledge structure, and structure analysis logic to analyze the user model structure relative to an archetype model structure. With the above, the system and method can facilitate and evaluate user thinking by monitoring the user's process to address the arbitrary problem and by monitoring the users structure of problem-solving. According to another aspect of the invention, the system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure, and third logic to facilitate user creation and specification of knowledge, related to at least one of the problem statement and the conclusion statement, to populate a knowledge structure. It also includes model logic to track user interaction with the first through third logic to construct a user model structure of user development and population of the problem structure, conclusion statement structure, and knowledge structure; and visual feedback logic to depict an archetype problem-solution structure and to depict the user model structure. In this fashion, the visual feedback logic may help coach the user in his or her problem solving approach. According to another aspect of the invention, the system includes first logic to facilitate user specification of the problem to populate a problem statement structure. It also includes second logic to facilitate user specification of a conclusion statement, related to the problem statement, to populate a conclusion statement structure, and third logic to facilitate user derivation and specification of knowledge, related to the problem statement and the conclusion statement, to populate a knowledge structure. It also includes tracking logic to monitor user interactions with the first through third logic and to build a corresponding model of such interactions so that the model, and the corresponding user thinking process, may be evaluated. According to another aspect of the invention, the knowledge structure may contain data, information, or analysis specifications. According to another aspect of the invention, the system may include logic to specify meaning statements or subtopic statements. According to another aspect of the invention, various views may be created to display relevant structures and to provide workspaces to create, derive or specify knowledge, conclusions, problem specifications and the like. According to another aspect of the invention, the system includes logic to provide suggestion feedback to the user of next steps for a user to take, in which the logic to provide is responsive to prior user interactions. The suggestion feedback may include logic to perform gap analysis on the at least a subset of the problem statement structure, the conclusion statement structure, the knowledge structure, and the relations therebetween to suggest next steps for the user to create or populate structures identified from the gap analysis.
20041109
20061128
20050714
89562.0
0
HOLMES, MICHAEL B
SYSTEM AND METHOD OF FACILITATING AND EVALUATING USER THINKING ABOUT AN ARBITRARY PROBLEM
SMALL
0
ACCEPTED
2,004
10,513,972
ACCEPTED
Recording medium, recording device, reproduction device, recording method and reproduction method
In order to enhance the usability of a write-once recording medium, the recording medium is provided with an ordinary recording/reproduction area, an alternate area, a first alternate-address management information area and a second alternate-address management information area. In addition, written/unwritten state indication information is recorded in a predetermined area. The second alternate-address management information area is an area allowing alternate-address management information recorded therein to be renewed by adding alternate-address management information to the area. Alternate-address management information recorded in the second alternate-address management information area includes information recorded in a first information format and information recorded in a second information format. The first information format shows an alternate source address and an alternate destination address for each data unit. On the other hand, the second information format shows an alternate source address and an alternate destination address for a group of a plurality of physically continuous data units. The second information format is used as a format for effectively carrying out an alternate-address process on such a group of data units. All alternate-address management information is recorded in the first alternate-address management information area in the first information format.
1. A recording medium provided with a write-once recording area allowing data to be written therein only once and comprising: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in said ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing said alternate-address process using said alternate area; and a second alternate-address management information area for recording said alternate-address management information as data that can be updated, wherein said alternate-address management information recorded in said second alternate-address management information area includes information of a first information format, which shows an alternate source address and an alternate destination address for every data unit, and information of a second information format, which shows an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units. 2. The recording medium according to claim 1 wherein, said first alternate-address management information area is used for storing most recent alternate-address management information, which has been recorded in said second alternate-address management information area, all in said first information format. 3. The recording medium according to claim 1 wherein, said second information format is an information format showing an alternate source address of the first data unit in a plurality of physically continuous data units and an alternate destination address of the first data unit in a plurality of other physically continuous data units as well as an alternate source address and alternate destination address of the last ones in said data units. 4. The recording medium according to claim 1 wherein: for each data unit of said write-once recording area, written/unwritten state indication information indicating whether or not data has been written into said data unit is recorded in a predetermined area; and for a plurality of data units in an alternate source shown in said second information format and for a plurality of data units in an alternate destination shown in said same information format, said existence/non-existence indication information indicates that data has been written into each of said data units. 5. A recording apparatus provided for a recording medium provided with a write-once recording area allowing data to be written therein only once and comprising: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in said ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing said alternate-address process using said alternate area; and a second alternate-address management information area for recording said alternate-address management information as data that can be updated, said recording apparatus comprising: write means for writing data into said recording medium; and control means for controlling said write means to write alternate-address management information of: a first information format showing an alternate source address and alternate destination address for a data unit not physically continuous to other data units in an operation to update alternate-address management information stored in said second alternate-address management information area in accordance with said alternate-address process for said data unit; and a second information format showing an alternate source address and alternate destination address for a collection of a plurality of physically continuous data units in an operation to update alternate-address management information stored in said second alternate-address management information area in accordance with said alternate-address process for said data units. 6. The recording apparatus according to claim 5 wherein, when said control means controls said write means to record alternate-address management information in said first alternate-address management information area, said write means stores most recent alternate-address management information, which has been recorded in said second alternate-address management information area, all in said first information format. 7. The recording apparatus according to claim 5 wherein, said second information format is an information format showing an alternate source address of the first data unit in a plurality of physically continuous data units and an alternate destination address of the first data unit in a plurality of other physically continuous data units as well as an alternate source address and alternate destination address of the last ones in said data units. 8. The recording apparatus according to claim 5 wherein: for each data unit of said write-once recording area, said control means controls said write means to record written/unwritten state indication information in a predetermined area as information indicating whether or not data has been written into said data unit; and for a plurality of data units in an alternate source shown in said second information format and for a plurality of data units in an alternate destination shown in said same information format, said control means controls said write means to record said existence/non-existence indication information indicating that data has been written into each of said data units. 9. A reproduction apparatus provided for a recording medium provided with a write-once recording area allowing data to be written therein only once and comprising: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in said ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing said alternate-address process using said alternate area; and a second alternate-address management information area for recording said alternate-address management information as data that can be updated, wherein said alternate-address management information recorded in said second alternate-address management information area includes information of a first information format, which shows an alternate source address and an alternate destination address for every data unit, and information of a second information format, which shows an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units, said reproduction apparatus comprising: read means for reading out data from said recording medium; confirmation means for determining whether or not an address specified in a read request to read out data from said main data area is an address completing an alternate-address process on the basis of said alternate-address management information recorded in said second alternate-address management information area in said first or second information format; and control means for controlling said read means to read out data from said address specified in said read request if said confirmation means determines that said address specified in said read request is not an address completing an alternate-address process but controlling said read means to read out data requested by said read request from said alternate area on the basis of said alternate-address management information if said confirmation means determines that said address specified in said read request is an address completing an alternate-address process. 10. A recording method provided for a recording medium provided with a write-once recording area allowing data to be written therein only once and comprising: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in said ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing said alternate-address process using said alternate area; and a second alternate-address management information area for recording said alternate-address management information as data that can be updated, said recording method comprising: a first write step of writing alternate-address management information of a first information format showing an alternate source address and an alternate destination address for a data unit not physically continuous to other data units in an operation to update alternate-address management information stored in said second alternate-address management information area in accordance with said alternate-address process for said data unit; and a second write step of writing alternate-address management information of a second information format showing an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units in an operation to update alternate-address management information stored in said second alternate-address management information area in accordance with said alternate-address process for said data units. 11. The recording method according to claim 10, said recording method further provided with a third write step of recording most recent alternate-address management information recorded in said second alternate-address management information area all in said first information format in an operation to record alternate-address management information in said first alternate-address management information area. 12. The recording method according to claim 10 wherein, said second information format is an information format showing an alternate source address of the first data unit in a plurality of physically continuous data units and an alternate destination address of the first data unit in a plurality of other physically continuous data units as well as an alternate source address and alternate destination address of the last ones in said data units. 13. The recording method according to claim 10 wherein, said recording method further provided with a fourth write step of recording written/unwritten state indication information in a predetermined area as information indicating whether or not data has been written into each data unit of said write-once recording area whereby, at said fourth write step, for a plurality of data units in an alternate source shown in said second information format and for a plurality of data units in an alternate destination shown in said same information format, said existence/non-existence indication information is recorded as information indicating that data has been written into each of said data units. 14. A reproduction method provided for a recording medium provided with a write-once recording area allowing data to be written therein only once and comprising: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in said ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing said alternate-address process using said alternate area; and a second alternate-address management information area for recording said alternate-address management information as data that can be updated, wherein said alternate-address management information recorded in said second alternate-address management information area includes information of a first information format, which shows an alternate source address and an alternate destination address for every data unit, and information of a second information format, which shows an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units, said reproduction method comprising: a confirmation step of determining whether or not an address specified in a read request to read out data from a main data area is an address completing an alternate-address process on the basis of alternate-address management information recorded in said second alternate-address management information area in said first or second information format; and a first read step of reading out data from said address specified in said read request if said address specified in said read request is determined at said confirmation step to be not an address completing an alternate-address process; and a second read step of reading out data requested by said read request from said alternate area on the basis of said alternate-address management information if said address specified in said read request is determined at said confirmation step to be an address completing an alternate-address process.
TECHNICAL FIELD The present invention relates to a recording medium such as an optical recording medium used particularly as write-once recording media as well as relates to a recording apparatus, a recording method, a reproduction apparatus and a reproduction method, which are provided for the recording medium. BACKGROUND ART As a technology for recording and reproducing digital data, there is known a data-recording technology for using optical disks including magneto-optical disks as recording media. Examples of the optical disks are a CD (Compact Disk), an MD (Mini-Disk) and a DVD (Digital Versatile Disk) . The optical disk is the generic name of recording media, which is a metallic thin plate protected by plastic. When a laser beam is radiated to the optical disk, the optical disk emits a reflected signal, from which changes can be read out as changes representing information recorded on the disk. The optical disks can be classified into a read-only category including a CD, a CD-ROM and a DVD-ROM, which the user is already familiar with, and a writable category allowing data to be written therein as is generally known. The writable category includes an MD, a CD-R, a CD-RW, a DVD-R, a DVD−RW, a DVD+RW and a DVD-RAM. By adopting a magneto-optical recording method, a phase-change recording-method or a pigmented-coat change recording-method for the writable category, data can be recorded onto a disk of this category. The pigmented-coat change recording-method is also referred to as a write-once recording-method. Since this pigmented-coat change recording-method allows data recording once and inhibits renewal of data onto the disk, the disk is good for data-saving applications or the like. On the other hand, the magneto-optical recording method and the phase-change recording-method are adopted in a variety of applications allowing renewal of data. The applications allowing renewal of data include mainly an application of recording various kinds of content data including musical data, movies, games and application programs. In addition, in recent years, a high-density optical disk called a blue-ray disc has been developed in an effort to produce the product on a very large scale. Typically, data is recorded onto a high-density optical disk and read out from the disk under a condition requiring a combination of a laser with a wavelength of 405 nm and an objective lens with an NA of 0.85 to be reproduced. The laser required in this condition is the so-called blue laser. With the optical disk having a track pitch of 0.32 μm, a line density of 0.12 μm/bit, a formatting efficiency of about 82% and a diameter of 12 cm, data of the amount of up to 23.3 GB (gigabytes) can be recorded onto and reproduced from the disk in recording/reproduction units, which are each a data block of 64 KB (kilobytes). There are also two types of optical disk having such a high density, i.e., optical disks of a write-once type and optical disks of a writable type. In an operation to record data onto an optical disk allowing data to be recorded therein by adoption of the magneto-optical recording method, the pigmented-coat change recording-method or the phase-change recording-method, guide means for tracking data tracks is required. Thus, a groove is created in advance to serve as a pregroove. The groove or a land is used as a data track. A land is a member having a shape resembling a section plateau between two adjacent grooves. In addition, it is also necessary to record addresses so that data can be recorded at a predetermined location indicated by an address as a location on a data track. Such addresses are recorded on grooves by wobbling the grooves in some cases. That is to say, a track for recording data is created in advance as typically a pregroove. In this case, addresses are recorded by wobbling the side walls of the pregroove. By recording addresses in this way, an address can be fetched from wobbling information conveyed by a reflected light beam. Thus, data can be recorded at a predetermined location and reproduced from a predetermined location without creating for example pit data showing an address or the like in advance on the track. By adding addresses as a wobbling groove, it is not necessary to discretely provide an address area or the like on tracks as an area for recording typically pit data representing addresses. Since such an address area is not required, the capacity for storing actual data is increased by a quantity proportional to the eliminated address area. It is to be noted that absolute-time (address) information implemented by a groove wobbled as described above is called an ATIP (Absolute Time In Pregroove) or an ADIP (Address in Pregroove). In addition, in the case of recording media usable as media for recording these kinds of data or not as reproduction-only media, there is known a technology for changing a data-recording location on the disk by providing an alternate area. That is to say, this technology is a defect management technology whereby an alternate recording-area is provided so that, if a location improper for recording data exits on the disk due to a defect such as an injury on the disk, the alternate recording-area can be used as an area serving as a substitute for the defective location to allow proper recording and reproduction operations to be carried out properly. The defect management technology is disclosed in documents including Japanese Unexamined Patent Publication No. 2002-521786, and Japanese Patent Laid-open Nos. Sho 60-74020 and Hei 11-39801. In the case of a recordable optical recording medium, data cannot of course be recorded into an area in which data has already been recorded. Specifications of most file systems to be recorded on an optical recording medium are defined by assuming the use of the optical recording medium as a ROM-type disk or a RAM-type disk. The ROM-type disk is a reproduction-only medium and the RAM-type disk is a writable optical disk. Specifications of a file system for a write-once recording medium allowing data to be stored therein only once limit functions of the ordinary file system and include special functions. The specifications of a file system for a write-once recording medium are a reason why the file system does not become widely popular. On the other hand, a FAT file system capable of keeping up with a variety of OSes of an information-processing apparatus and other file systems cannot be applied to write-once media as they are. Write-once media is widely used typically in applications of preserving data. If the write-once media can also be used for the FAT file system by keeping the general specifications of the file system as they are, the usability of the write-once media can be further enhanced. In order to allow a widely used file system such as the FAT file system and a file system for RAMs or hard disks to be applied to write-once media as it is, however, a function to write data into the same address as that of existing data is required. That is to say, a capability of renewing data is required. Of course, one of characteristics of the write-once media is that data cannot be written onto the media for the second time. Thus, it is impossible to use a file system for such a writable recording medium as it is in the first place. In addition, when the optical disk is mounted on a disk drive or dismounted from it, the recording face of the disk may be injured in dependence on the state in which the disk is kept in the drive and the way in which the disk is used. For this reason, the aforementioned technique of managing defects has been proposed. Of course, even the write-once media must be capable of coping with a defect caused by an injury. In addition, in the case of the conventional write-once optical disk, data is recorded in a state of being compacted sequentially in areas starting from the inner side. To put it in detail, there is no space left between an area already including recorded data and an area in which data is to be recorded next. This is because the conventional disk is developed with a ROM-type disk used as a base so that, if an unrecorded area exists, a reproduction operation cannot be carried out. Such a situation limits the freedom of a random-access operation carried out on the write-once media. In addition, for a disk drive or a recording/reproduction apparatus, an operation requested by a host computer to write data at an address specified in the operation as an address in a write-once optical disk or an operation to read out data from such an address is a process of a heavy load. From what is described above, contemporary write-once media or, in particular, write-once media implemented by a high-density optical disk having a recording capacity of at least 20 GB like the aforementioned blue-ray disk, is required to meet the following requirements. The write-once media shall be capable of renewing data and managing defects by execution of proper management, improving the random accessibility, reducing the processing load borne by the recording/reproduction apparatus, keeping up with a general-purpose file system by the capability of renewing data and maintaining compatibility with writable optical disks as well as reproduction-only disks. DISCLOSURE OF INVENTION It is thus an object of the present invention addressing such a situation to improve usability of a write-once recording medium by allowing data stored on the write-once recording medium to be renewed and by executing proper management of defects while maintaining compatibility. The recording area of a write-once recording medium provided by the present invention as a recording medium allowing data to be written therein only once is divided into: an ordinary recording/reproduction area which data is recorded into and reproduced from; an alternate area used for storing data in an alternate-address process for a defect existing in the ordinary recording/reproduction area and a data renewal; a first alternate-address management information area for recording alternate-address management information for managing the alternate-address process using the alternate area; and a second alternate-address management information area for recording the alternate-address management information in an updating process (prior to finalization) as data that can be updated. The alternate-address management information recorded in the second alternate-address management information area includes information of a first information format, which shows an alternate source address and an alternate destination address for every data unit, and information of a second information format, which shows an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units. The first alternate-address management information area is used for storing most recent alternate-address management information, which has been recorded in the second alternate-address management information area, all in the first information format. The second information format is an information format showing the alternate source address of the first data unit in a plurality of physically continuous data units and the alternate destination address of the first data unit in a plurality of other physically continuous data units as well as the alternate source address and alternate destination address of the last ones in the data units. For each data unit of the write-once recording area, written/unwritten state indication information indicating whether or not data has been written into the data unit is recorded in a predetermined area. In addition, for a plurality of data units in an alternate source shown in the second information format and for a plurality of data units in an alternate destination shown in the same information format, the existence/non-existence indication information indicates that data has been written into each of the data units. Designed for the recording medium described above, a recording apparatus provided by the present invention includes write means for writing data into the recording medium and control means. The control means controls the write means to write the alternate-address management information of the first information format showing an alternate source address and alternate destination address for a data unit not physically continuous to other data units in an operation to update the alternate-address management information stored in the second alternate-address management information area in accordance with the alternate-address process for the data unit. On the other hand, the control means controls the write means to write the alternate-address management information of the second information format showing an alternate source address and alternate destination address for a collection of a plurality of physically continuous data units in an operation to update the alternate-address management information stored in the second alternate-address management information area in accordance with the alternate-address process for the data units. When the control means controls the write means to record alternate-address management information in the first alternate-address management information area, the write means stores most recent alternate-address management information, which has been recorded in the second alternate-address management information area, all in the first information format. As described above, the second information format is an information format showing the alternate source address of the first data unit in a plurality of physically continuous data units and the alternate destination address of the first data unit in a plurality of other physically continuous data units as well as the alternate source address and alternate destination address of the last ones in the data units. In addition, for each data unit of the write-once recording area, the control means controls the write means to record written/unwritten state indication information in a predetermined area as information indicating whether or not data has been written into the data unit. In addition, for a plurality of data units in an alternate source shown in the second information format and for a plurality of data units in an alternate destination shown in the same information format, the control means controls the write means to record the existence/non-existence indication information as information indicating that data has been written into each of the data units. Designed for the recording medium described above, a reproduction apparatus provided by the present invention includes: read means for reading out data from the recording medium; confirmation means for determining whether or not an address specified in a read request to read out data from a main data area is an address completing an alternate-address process on the basis of the alternate-address management information recorded in the second alternate-address management information area in the first or second information format; and control means for controlling the read means to read out data from the address specified in the read request if the confirmation means determines that the address specified in the read request is not an address completing an alternate-address process but controlling the read means to read out data requested by the read request from the alternate area on the basis of the alternate-address management information if the confirmation means determines that the address specified in the read request is an address completing an alternate-address process. Designed for the recording medium described above, a recording method provided by the present invention includes: a first write step of writing the alternate-address management information of the first information format showing an alternate source address and an alternate destination address for a data unit not physically continuous to other data units in an operation to update the alternate-address management information stored in the second alternate-address management information area in accordance with the alternate-address process for the data unit; and a second write step of writing the alternate-address management information of the second information format showing an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units in an operation to update the alternate-address management information stored in the second alternate-address management information area in accordance with the alternate-address process for the data unit. The recording method is further provided with a third write step of recording most recent alternate-address management information recorded in the second alternate-address management information area all in the first information format in an operation to record alternate-address management information in the first alternate-address management information area. As described above, the second information format is an information format showing the alternate source address of the first data unit in a plurality of physically continuous data units and the alternate destination address of the first data unit in a plurality of other physically continuous data units as well as the alternate source address and alternate destination address of the last ones in the data units. In addition, the recording method is also provided with a fourth write step of recording written/unwritten state indication information in a predetermined area as information indicating whether or not data has been written into each data unit of the write-once recording area. In addition, at this fourth write step, for a plurality of data units in an alternate source shown in the second information format and for a plurality of data units in an alternate destination shown in the same information format, the existence/non-existence indication information is recorded as information indicating that data has been written into each of the data units. Designed for the recording medium described above, a reproduction method provided by the present invention includes: a confirmation step of determining whether or not an address specified in a read request to read out data from a main data area is an address completing an alternate-address process on the basis of alternate-address management information recorded in the second alternate-address management information area in the first or second information format; and a first read step of reading out data from the address specified in the read request if the address specified in the read request is determined at the confirmation step to be not an address completing an alternate-address process; and a second read step of reading out data requested by the read request from the alternate area on the basis of the alternate-address management information if the address specified in the read request is determined at the confirmation step to be an address completing an alternate-address process. That is to say, in a write-once recording medium of the present invention, the recording area includes an ordinary recording/reproduction area, an alternate area, a first alternate-address management information area and a second alternate-address management information area. The second alternate-address management information area is an area for implementing renewal of alternate-address management information involved in an alternate-address process by allowing the alternate-address management information to be added thereto. In addition, by recording the written/unwritten state indication information, it is possible to easily grasp the recording state of each data unit on the recording medium. On top of that, the alternate-address management information includes information of a first information format, which shows an alternate source address and an alternate destination address for every data unit, and information of a second information format, which shows an alternate source address and an alternate destination address for a collection of a plurality of data units. Thus, the second information format allows an alternate-address process to be carried out on a plurality of data units with a high degree of efficiency. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an explanatory diagram showing the area structure of a disk provided by an embodiment of the present invention; FIG. 2 is an explanatory diagram showing the structure of a one-layer disk provided by the embodiment; FIG. 3 is an explanatory diagram showing the structure of a two-layer disk provided by the embodiment; FIG. 4 is an explanatory diagram showing a DMA of a disk provided by the embodiment; FIG. 5 is a diagram showing the contents of a DDS of a disk provided by the embodiment; FIG. 6 is a diagram showing the contents of a DFL of a disk provided by the embodiment; FIG. 7 is a diagram showing defect list management information of a DFL and TDFL of a disk provided by the embodiment; FIG. 8 is a diagram showing alternate-address information of a DFL and TDFL of a disk provided by the embodiment; FIG. 9 is an explanatory diagram showing a TDMA of a disk provided by the embodiment; FIG. 10 is an explanatory diagram showing a space bitmap of a disk provided by the embodiment; FIG. 11 is an explanatory diagram showing a TDFL of a disk provided by the embodiment; FIG. 12 is an explanatory diagram showing a TDDS of a disk provided by the embodiment; FIG. 13 is an explanatory diagram showing an ISA and OSA of a disk provided by the embodiment; FIG. 14 is an explanatory diagram showing a data-recording order in a TDMA of a disk provided by the embodiment; FIG. 15 is an explanatory diagram showing a utilization stage of a TDMA of the two-layer disk provided by the embodiment; FIG. 16 is a block diagram of a disk drive provided by the embodiment; FIG. 17 shows a flowchart representing a data-writing process provided by the embodiment; FIG. 18 shows a flowchart representing a user-data-writing process provided by the embodiment; FIG. 19 shows a flowchart representing an overwrite function process provided by the embodiment; FIG. 20 shows a flowchart representing a process of generating alternate-address information in accordance with by the embodiment; FIG. 21 shows a flowchart representing a data-fetching process provided by the embodiment; FIG. 22 shows a flowchart representing a TDFL/space-bitmap update process provided by the embodiment; FIG. 23 shows a flowchart representing a process of restructuring alternate-address information in accordance with the embodiment; FIG. 24 is an explanatory diagram showing the process of restructuring alternate-address information in accordance with the embodiment; FIG. 25 shows a flowchart representing a process of converting a disk provided by the embodiment into a compatible disk in accordance with the embodiment; FIG. 26 is an explanatory diagram showing a TDMA of a disk provided by another embodiment; FIG. 27 is an explanatory diagram showing a TDDS of a disk provided by the other embodiment; FIG. 28 is an explanatory diagram showing an ISA and OSA of a disk provided by the other embodiment; FIGS. 29A and 29B are each an explanatory diagram showing spare area full flags provided by the other embodiment; FIG. 30 shows a flowchart representing a data-writing process provided by the other embodiment; FIG. 31 shows a flowchart representing a process of setting a renewal function in accordance with the other embodiment; FIG. 32 shows a flowchart representing a data-fetching process provided by the other embodiment; and FIG. 33 shows a flowchart representing a TDFL/space-bitmap update process provided by the other embodiment. BEST MODE FOR CARRYING OUT THE INVENTION The following description explains an embodiment provided by the present invention as an embodiment implementing an optical disk and a disk drive employed in a recording apparatus and/or a reproduction apparatus as a disk drive designed for the optical disk. The description comprises chapters arranged in the following order: 1: Disk Structure 2: DMAs 3: First TDMA Method 3-1: TDMAs 3-2: ISAs and OSAs 3-3: TDMA-Using Method 4: Disk Drive 5: Operations for the First TDMA Method 5-1: Data Writing 5-2: Data Fetching 5-3: Updating of the TDFL/Space Bitmap 5-4: Conversion into Compatible Disks 6: Effects of the First TDMA Method 7: Second TDMA Method 7-1: TDMAs 7-2: ISAs and OSAs 8: Operations for the Second TDMA Method 8-1: Data Writing 8-2: Data Fetching 8-3: Updating of the TDFL/Space Bitmap and Conversion into Compatible Disks 9: Effects for the Second TDMA Method 1: Disk Structure First of all, an optical disk provided by the embodiment is explained. The optical disk can be implemented by a write-once optical disk referred to as the so-called blue-ray disk. The blue-ray disk pertains to the category of high-density optical disks. Typical physical parameters of the high-density optical disk provided by the embodiment are explained as follows. The disk size of the optical disk provided by the embodiment is expressed in terms of a diameter of 120 mm and a disk thickness of 1.2 mm. That is to say, from the external-appearance point of view, the optical disk provided by the embodiment is similar to a disk of a CD (Compact Disk) system and a disk of a DVD (Digital Versatile Disk) system. As a recording/reproduction laser, the so-called blue laser is used. By using an optical system having a high NA of typically 0.85, setting the track pitch at a small value of typically 0.32 microns and setting the line density at a high value of typically 0.12 microns per bit, it is possible to implement a user-data storage capacity of about 23 Gbyte to 25 Gbyte for an optical disk with a diameter of 12 cm. In addition, a two-layer disk is also developed. A two-layer disk is an optical disk having two recording layers. In the case of a two-layer disk, a user-data capacity of about 50 G can be achieved. FIG. 1 is an explanatory diagram showing the layout (or the area structure) of the entire disk. The recording area of the disk includes a lead-in zone on the innermost circumference, a data zone on a middle circumference and a lead-out zone on the outermost circumference. The lead-in zone, the data zone and the lead-out zone serve as recording and reproduction areas as follows. A prerecorded information area PIC on the innermost side of the lead-in zone is a reproduction-only area. An area starting with a management/control information area of the lead-in zone and ending with the lead-out zone is used as a write-once area allowing data to be written therein only once. In the reproduction-only area and the write-once area, a spiral recording track is created as a wobbling groove. The wobbling groove serves as a tracking guide in a tracing operation using a laser spot. The wobbling groove is thus a recording track, which data is recorded onto or read out from. It is to be noted that, this embodiment assumes an optical disk allowing data to be recorded on the groove. However, the scope of the present invention is not limited to the optical disk with such a recording track. For example, the present invention can also be applied to an optical disk adopting a land recording-technique whereby data is recorded on a land between two adjacent grooves. In addition, the present invention can also be applied to an optical disk adopting a land/groove recording-technique whereby data is recorded on a land and a groove. In addition, the groove used as a recording track in an optical disk has a shape wobbled by a wobbling signal. Thus, a disk drive for such an optical disk detects both edge positions of the groove from a reflected light beam of a laser spot radiated to the groove. Then, by extracting components fluctuating in the radial direction of the disk as fluctuations of both the edge positions in an operation to move the laser spot along the recording track, the wobble signal can be reproduced. This wobble signal is modulated by information on addresses of recording locations on the recording track. The information on addresses includes physical addresses and other additional information. Thus, by demodulating the wobble signal to produce the information on addresses, the disk drive is capable of controlling addresses, at which data are to be recorded or reproduced. The lead-in zone shown in FIG. 1 is an area on the inner side a circumference having a typical radius of 24 mm. An area between a circumference with a radius of 22.2 mm and a circumference with a radius of 23.1 mm in the lead-in zone is the prerecorded information area PIC. The prerecorded information area PIC is used for storing reproduction-only information as the wobbling state of the groove. The reproduction-only information includes disk information such as recording/reproduction power conditions, information on areas on the disk and information used for copy protection. It is to be noted that these pieces of information can also be recorded on the disk as emboss pits or the like. A BCA (Burst Cutting Area) not shown in the figure may be provided on a circumference on the inner side of the prerecorded information area PIC in some cases. The BCA is used for storing a unique ID peculiar to the disk recording medium in such a state that the ID cannot be renewed. The unique ID is recorded marks created in a concentric-circle shape to form recorded data in a bar-code format. An area between a circumference with a radius of 23.1 mm and a circumference with a radius of 24.0 mm in the lead-in zone is a management/control information area. The management/control information area has a predetermined area format to include a control data area, a DMA (Defect Management Area), a TDMA (Temporary Defect Management Area), a test write area (OPC) and a buffer area. The control data area included in the management/control information area is used for recording management/control information such as a disk type, a disk size, a disk version, a layer structure, a channel-bit length, BCA information, a transfer rate, data-zone position information, a recording line speed and recording/reproduction laser power information. The test write area (OPC) included in the management/control information area is used for a trial writing process carried out in setting data recording/reproduction conditions such as a laser power to be used in recording/reproduction operations. That is, the test write area is a region for adjusting the recording/reproduction conditions. In the case of an ordinary optical disk, the DMA included in the management/control information area is used for recording alternate-address management information for managing defects. In the case of a write-once optical disk provided by the embodiment, however, the DMA is used for recording not only the alternate-address management information of defects but also management/control information for implementing data renewals in the optical disk. In this case, particularly, the DMA is used for recording ISA management information and OSA management information, which will be described later. In order to make renewal of data possible by making use of an alternate-address process, the contents of the DMA must also be updated when data is renewed. For updating the contents of the DMA, the TDMA is provided. Alternate-address management information is added and/or recorded in the TDMA and updated from time to time. Last (most recent) alternate-address management information recorded in the TDMA is eventually transferred to the DMA. The DMA and the TDMA will be described later in detail. The area on the circumferences with radii in the range 24.0 to 58.0 mm external to the lead-in zone is used as a data zone. The data zone is an area, which user data is actually recorded into and reproduced from. The start address ADdts and end address ADdte of the data zone are included in the data zone position information recorded in the control data area described earlier. An ISA (Inner Spare Area) is provided on the innermost circumference of the data zone. On the other hand, an OSA (Outer Spare Area) is provided on the outermost circumference of the data zone. As will be described later, the ISA and the OSA are each used as an alternate area provided for defects and for implementing data renewals (overwriting). The ISA begins from the start position of the data zone and includes a predetermined number of clusters each having a size of 65,536 bytes. On the other hand, the OSA includes a predetermined number of clusters, which terminate at the end position of the data zone. The sizes of the ISA and the OSA are described in the DMA. A user-data area in the data zone is an area sandwiched by the ISA and the OSA. This user-data area is an ordinary recording/reproduction area, which user data is generally recorded into and reproduced from. The start address ADus and end address ADue of the user-data area define the location of the user-data area and are recorded in the DMA. The area on the circumferences with radii in the range 58.0 to 58.5 mm external to the data zone is the lead-out zone. The lead-out zone is a management/control information area having a predetermined format to include a control data area, a DMA and a buffer area. Much like the control data area included in the lead-in zone, the control data area of the lead-out zone is used for storing various kinds of management/control information. By the same token, much like the DMA included in the lead-in zone, the DMA of the lead-out zone is used as an area for recording management information of the ISA and management information of the OSA. FIG. 2 is a diagram showing a typical structure of the management/control information area on a one-layer disk having only one recording layer. As shown in the figure, in addition to undefined segments (reserved segments), the lead-in zone includes a variety of areas such as DMA 2, an OPC (a test write area), a TDMA and DMA 1. On the other hand, in addition to undefined segments (reserved segments), the lead-out zone includes a variety of areas such as DMA 3 and DMA 4. It is to be noted that the control data area described above is not shown in the figure. This is because, in actuality, a portion of the control data area is used as a DMA for example. Since the structure of a DMA is an essential of the present invention, the control data area is not shown in the figure. As described above, the lead-in and lead-out zones include four DMAs, i.e., DMA 1 to DMA 4. DMA 1 to DMA 4 are each used as an area for recording the same alternate-address management information. However, a TDMA is provided as an area used for temporarily recording alternate-address management information and, every time an alternate-address process is carried out due to renewal of data or a defect, new alternate-address management information is additionally recorded in the TDMA to update the information already recorded therein. Thus, till the disk is finalized, for example, the DMAs are not used. Instead, the alternate-address management is carried out and new alternate-address management information is added to the TDMA and/or recorded in the TDMA. As the disk is finalized, alternate-address management information recorded on the TDMA most recently is transferred to the DMAs so that the alternate-address process based on the DMA can be carried out. FIG. 3 is a diagram showing a two-layer disk having two recording layers. The first recording layer is referred to as layer 0 and the second recording layer is called layer 1. Data is recorded onto and reproduced from layer 0 in a direction from the inner side of the disk to the outer side thereof, as same as in the case of one-layer disk. On the other hand, data is recorded onto and reproduced from layer 1 in a direction from the outer side of the disk to the inner side thereof. The value of the physical address increases in the directions. That is to say, the value of the physical address on layer 0 increases in the direction from the inner side of the disk to the outer side thereof, and the value of the physical address on layer 1 increases in the direction from the outer side of the disk to the inner side thereof. Much like the one-layer disk, the lead-in zone on layer 0 includes a variety of areas such as DMA 2, an OPC (a test write area), TDMA 0 and DMA 1. Since the outermost circumference on layer 0 is not a lead-out zone, it is referred to simply as outer zone 0, which includes DMA 3 and DMA 4. The outermost circumference on layer 1 is referred to simply as outer zone 1, which includes DMA 3 and DMA 4. The innermost circumference of layer 1 is a lead-out zone, which includes a variety of areas such as DMA 2, an OPC (a test write area), TDMA 1 and DMA 1. As described above, the lead-in zone, outer zones 0 and 1 and the lead-out zone include eight DMAs. In addition, each of the recording layers includes a TDMA. The size of the lead-in zone on layer 0 and the size of the lead-out zone on layer 1 are equal to the size of the lead-in zone on the one-layer disk. On the other hand, the sizes of outer zones 0 and 1 are equal to the size of the lead-out zone on the one-layer disk. 2: DMAs The data structure of each DMA recorded in the lead-in zone and the lead-out zone is explained below. In the case of a two-layer disk, the DMAs also include the DMAs in outer zones 0 and 1. FIG. 4 is a diagram showing the structure of the DMA. The size of the DMA shown in the figure is 32 clusters (=32×65,536 bytes). It is to be noted that a cluster is the smallest data-recording unit. Of course, the size of a DMA is not limited to 32 clusters. In FIG. 4, the 32 clusters are identified by cluster numbers 1 to 32, which each indicate a data position of each content of the DMA. The size of each content is expressed as a cluster count. In the DMA, cluster numbers 1 to 4 identify four clusters forming a segment for recording a DDS (disc definition structure), which describes the disc in detail. The contents of the DDS will be described later by referring to FIG. 5. In actually, since the size of the DDS is one cluster, four identical DDSes are recorded in the segment. Cluster numbers 5 to 8 identify four clusters forming a segment for recording DFL #1, which is the first recording area of a DFL (defect list). The data structure of the defect list will be described later by referring to FIG. 6. The size of data stored in the defect list is four clusters forming a list of information on alternate addresses. Cluster numbers 9 to 12 identify four clusters forming a segment for recording DFL #2, which is the second recording area of the defect list. The second recording area is followed by the third and subsequent recording areas DFL #3 to DFL #6, which each have a size of four clusters. The four-cluster segment DFL #7 used as the seventh recording area of the defect list is identified by cluster numbers 29 to 32. As is obvious from the above description, the DMA having a size of 32 clusters includes seven recording areas of the defect list, i.e., DFL #1 to DFL #7. In a write-once optical disk allowing data to be recorded therein once as is the case with the disk provided by the embodiment, in order to record contents of a DMA, it is necessary to carry out a process referred to as ‘finalize’. In this case, the same contents are recorded in seven recording areas DFL #1 to DFL #7. FIG. 5 is a diagram showing the data structure of the contents of the DDS recorded at the beginning of the DMA shown in FIG. 4. As described above, the DDS has a size of one cluster (=65,536 bytes). In the figure, byte 0 is the position of the beginning of the DDS having a size of 65,536 bytes. A byte-count column shows the number of bytes included in each data content. Two bytes indicated by byte positions 0 to 1 are used as bytes for recording “DS”, which is a DDS identifier indicating that this cluster is the DDS. One byte indicated by byte position 2 is used as a byte for recording a DDS format number of the version of the DDS format. Four bytes indicated by byte positions 4 to 7 are used as bytes for recording the number of times the DDS has been updated. It is to be noted that, in this embodiment, in the finalize process, alternate-address management information is additionally written into the DMA itself instead of being used for updating the DMA. The alternate-address management information is stored in the TDMA before being written into the DMA in the finalize process. Thus, when the finalize process is eventually carried out, a TDDS (temporary DDS) of the TDMA contains the number of times the TDDS has been updated. The aforementioned number of times the DDS has been updated is the number of times the TDDS has been updated. Four bytes indicated by byte positions 16 to 19 are used as bytes for recording AD_DRV, which is the start physical sector address of a drive area in the DMA. Four bytes indicated by byte positions 24 to 27 are used as bytes for recording AD_DFL, which is the start physical sector address of a defect list DFL in the DMA. Four bytes indicated by byte positions 32 to 35 are used as bytes for recording a PSN (physical sector number or a physical sector address) of the start position of the user-data area in the data zone. That is to say, the four bytes are used as bytes for recording a PSN indicating the position of an LSN (logical sector number) of 0. Four bytes indicated by byte positions 36 to 39 are used as bytes for recording an LSN (logical sector number) of the end position of the user-data area in the data zone. Four bytes indicated by byte positions 40 to 43 are used as bytes for recording the size of the ISA in the data zone. The ISA is the ISA of a one-layer disk or the ISA on layer 0 of a two-layer disk. Four bytes indicated by byte positions 44 to 47 are used as bytes for recording the size of each OSA in the data zone. Four bytes indicated by byte positions 48 to 51 are used as bytes for recording the size of the ISA in the data zone. The ISA is the ISA on layer 1 of a two-layer disk. One byte indicated by byte position 52 is used as a byte for recording spare area full flags showing whether or not data can be renewed by using an ISA or an OSA. That is to say, the spare area full flag are used to indicate that the ISA and the OSA are being used entirely. Byte positions other than the byte positions described above are reserved (or undefined) and all filled with codes of 00h. As described above, the DDS is used as an area for storing the addresses of the user-data area, the sizes of each ISA and each OSA and spare area full flags. That is to say, the DDS is used for storing information for managing and controlling areas of each ISA and each OSA in the data zone. Next, the data structure of the defect list DFL is explained by referring to FIG. 6. As explained earlier by referring to FIG. 4, the defect list DFL is recorded in an area having a size of four clusters. In the defect list DFL shown in FIG. 6, a byte-position column shows data positions of each data content of the defect list having a size of four clusters. It is to be noted that one cluster is 32 sectors occupying 65,536 bytes. Thus, one sector has a size of 2,048 bytes. A byte-count column shows the number of bytes composing each data content. The first 64 bytes of the defect list DFL are used as bytes for recording management information of the defect list DFL. The management information of the defect list DFL includes information indicating that this cluster is the defect list DFL, a version, the number of times the defect list DFL has been updated and the number of entries forming the defect list DFL. The bytes following the 64th byte are used as bytes for recording contents of each entry of the defect list DFL. Each entry is alternate-address information ati having a length of eight bytes. A terminator having a length of eight bytes serves as an alternate-address end immediately following ati #N, which is the last one of pieces of effective alternate-address information. In this DFL, an area following the alternate-address end is filled up with 00h codes till the end of the clusters. The defect-list management information having a length of 64 bytes is shown in FIG. 7. Two bytes starting with a byte at byte position 0 are used as bytes for recording a character string DF representing the identifier of the defect list DFL. One byte at byte position 2 is used as a byte for recording the format number of the defect list DFL. Four bytes starting with a byte at byte position 4 are used as bytes for recording the number of times the defect list DFL has been updated. It is to be noted that this value is actually the number of times the TDFL (temporary defect list) to be described later has been updated and, thus, a value transferred from the TDFL. Four bytes starting with a byte at byte position 12 are used as bytes for recording the number of entries in the defect list DFL, that is, the number of pieces of alternate-address information ati. Four bytes starting with a byte at byte position 24 are used as bytes for recording cluster counts indicating the sizes of free areas available in the alternate areas ISA 0, ISA 1, OSA 0 and OSA 1. Byte positions other than the byte positions described above are reserved and all filled with codes of 00h. FIG. 8 is a diagram showing the data structure of an alternate-address information ati. The data structure includes information showing the contents of an entry completing an alternate-address process. In the case of a one-layer disk, the total number of pieces of alternate-address information ati can be up to a maximum of 32,759. Each piece of alternate-address information ati comprises eight bytes (or 64 bits, i.e., bits b63 to b0). Bits b63 to b60 are used as bits for recording status 1, which is the status of the entry. In the defect list DFL, the status is set at a value of ‘0000’ indicating an ordinary alternate-address process entry. Other values of the status will be explained later in a description of the alternate address in the TDFL of the TDMA. Bits b59 to b32 are used as bits for recording the PSN (physical sector address) of the first sector in an alternate source cluster. That is to say, in this data structure, a cluster subjected to an alternate-address process due to a defect or renewal of data is expressed by the physical sector address PSN of the first sector of the cluster. Bits b31 to b28 are reserved. It is to be noted that these bits can also be used as bits for recording status 2, which is other status in this entry. Bits b27 to b0 are used as bits for recording the physical sector address PSN of the first sector in an alternate destination cluster. That is to say, in this data structure, a destination cluster required in an alternate-address process due to a defect or renewal of data is expressed by the physical sector address PSN of the first sector of the cluster. As described above, the alternate-address information ati is treated as an entry showing an alternate source cluster and an alternate destination cluster. Then, such an entry is cataloged in the defect list DFL having a structure shown in FIG. 6. In the DMA, information on an alternate-address management information is recorded in a data structure like the one described above. As explained above, however, these kinds of information are recorded in a process to finalize the disk. In this process, most recent information on an alternate-address management information is transferred from the TDMA to the DMA. Information on defect processing and information on an alternate-address management carried out due to renewal of data are recorded in the TDMA described below and updated from time to time. 3: First TDMA Method 3-1: TDMAs The following description explains the TDMA (temporary DMA) provided in the management/control information area as shown in FIGS. 2 and 3. Much like the DMA, the TDMA is used as an area for recording information on alternate-address processes. Every time an alternate-address process is carried out to follow renewal of data or follow detection of a defect, information on the alternate-address process is added to the TDMA or recorded in the TDMA as an update. FIG. 9 is a diagram showing the data structure of the TDMA. The size of the TDMA is typically 2,048 clusters. As shown in the figure, the first cluster indicated by a cluster number of 1 is used as a cluster for recording a space bitmap for layer 0. A space bitmap comprises bits each representing a cluster of a main data area including the data zone as well as a management/control area including the lead-in zone and the lead-out zone (and the outer zones in the case of a two-layer disk). The value of each bit is write existence/non-existence information indicating whether or not data has been written into a cluster represented by the bit. All clusters ranging from the lead-in zone to the lead-out zone (including the outer zones in the case of a two-layer disk) are each represented by a bit of the space bitmap as described above, and the size of the space bitmap itself is one cluster. A cluster indicated by a cluster number of 2 is used as a cluster for recording a space bitmap for layer 1 (or the second layer). It is to be noted that, in the case of a one-layer disk, a space bitmap for layer 1 is of course unnecessary. If an alternate-address process is carried out in, for example, an operation to change data contents, a TDFL (temporary defect list) is additionally recorded to a cluster at the beginning of an unrecorded area in the TDMA. Thus, in the case of a two-layer disk, the first TDFL is recorded in an area starting from the position indicated by a cluster number of 3 as shown in the figure. In the case of a one-layer disk, a space bitmap for layer 1 is not necessary as described above. Thus, the first TDFL is recorded in an area starting from the position indicated by a cluster number of 2. Then, every time an alternate-address process is carried out thereafter, a TDFL is additionally recorded at a subsequent cluster position without providing a gap between the subsequent cluster position and the preceding cluster position. The size of a TDFL is in the range 1 to up to 4 clusters. Since a space bitmap shows recording states of clusters, the bitmap is updated every time data is written into any of the clusters to update the cluster. When the space bitmap is updated, much like a TDFL, a new space bitmap is additionally recorded in a TDMA area starting from the beginning of a free area in the TDMA. That is to say, a space bitmap and/or a TDFL is additionally recorded in the TDMA from time to time. It is to be noted that the configurations of a space bitmap and a TDFL will be described later. Anyway, a TDDS (temporary disc definition structure) is recorded in the last 2,048-byte sector of a cluster used for recording a space bitmap and the last 2,048-byte sector of 1 to 4 clusters used for recording a TDFL. The TDDS is detailed information on the optical disk. FIG. 10 is a diagram showing the data structure of a space bitmap. As described above, each bit of a space bitmap represents the recording state of one cluster on the disk, that is, each bit indicates whether or not data has been recorded in the cluster represented thereby. For example, if data has not been recorded in a cluster, a bit representing the cluster is set at 1. It is to be noted that, in the case of a two-layer disk, a space bitmap is provided for each layer and information recorded in one of the space bitmaps is independent of information recorded in the other space bitmap. For one sector=2,048 bytes, clusters on a layer having a storage capacity of 25 GB can be represented by a space bitmap with a size of 25 sectors. Since one cluster comprises 32 sectors, the space bitmap itself can be formed from one cluster. In the data structure of a space bitmap shown in FIG. 10, a cluster allocated as the bitmap comprises 32 sectors, i.e., sectors 0 to 31. A byte-position column shows byte positions of each of the sectors. Sector 0 at the beginning of the space bitmap is used as a sector for recording management information of the bitmap. Two bytes at byte positions 0 and 1 in sector 0 are used as bytes for recording an UB, which is an unallocated space bitmap ID (identifier). One byte at byte position 2 is used as a byte for recording a format version such as a version of 00h. Four bytes starting from byte position 4 are used as bytes for recording a layer number indicating whether this space bitmap corresponds to layer 0 or layer 1. 48 bytes starting from byte position 16 are used as bytes for recording bitmap information. The bitmap information comprises pieces of zone information for three zones, i.e., the inner zone, the data zone and the outer zone. The pieces of zone information are zone information for the inner zone, zone information for the data zone and zone information for the outer zone. The size of each of the pieces of zone information is 16 bytes. Each of the pieces of zone information comprises a start cluster first PSN, a start byte position of bitmap data, a validate bit length in bitmap data and a reserved area, which each have a size of four bytes. The start cluster first PSN is a PSN (physical sector address) indicating a start position of the zone on the disk. That is to say, the PSN is a start address, which is used when the zone is mapped onto the space bitmap. The start byte position of bitmap data is a byte count indicating the start position of bitmap data for the zone as a position relative to the unallocated space bit map identifier located at the beginning of the space bit map. The validate bit length in bitmap data is also a byte count representing the amount of bitmap data of the zone. Actual bitmap data is recorded on sector 1 in an area starting from byte position 0 of the sector. Sector 1 is the second sector of the space bitmap. In this area, one sector of the space bitmap represents 1 GB data. The actual bitmap data is followed by reserved areas ending with an area immediately preceding sector 31, which is the last sector of the space bitmap. The reserved areas are filled with codes of 00h. Sector 31, which is the last sector of the space bitmap, is used as a sector for recording a TDDS. The pieces of bitmap information described above are managed as follows. First of all, the description explains a space bitmap with the layer number at byte position 4 indicating layer 0. That is to say, the description explains a space bitmap for a one-layer disk or a space bitmap for layer 0 of a two-layer disk. In this case, the zone information for the inner zone is information for the inner zone of layer 0, that is, information for a lead-in zone. The start cluster first PSN of the zone is a PSN of the start position of the lead-in zone as shown by a solid-line arrow. The start byte position of bitmap data is used for recording information indicating the position of bitmap data corresponding to the lead-in zone in the space bitmap as shown by a dashed-line arrow, that is, information indicating byte position 0 of sector 1. The value of the validate bit length in bitmap data is the size of the bitmap data for the lead-in zone. The zone information for the data zone is information on the data zone of layer 0. The start cluster first PSN of the zone is a PSN of the start position of the data zone as shown by a solid-line arrow. The start byte position of bit map data is used for recording information indicating the position of bitmap data corresponding to the data zone in the space bitmap as shown by a dashed-line arrow, that is, information indicating byte position 0 of sector 2. The value of the validate bit length in bitmap data is the size of the bitmap data for the data zone. The zone information for the outer zone is information for the outer zone of layer 0, that is, information for a lead-out zone on a one-layer disk or outer zone 0 of a two-layer disk. The start cluster first PSN of the zone is a PSN of the start position of the lead-out zone or outer zone 0 as shown by a solid-line arrow. The start byte position of bitmap data is used for recording information indicating the position of bitmap data corresponding to the lead-out zone (or outer zone 0) in the space bitmap as shown by a dashed-line arrow, that is, information indicating byte position 0 of sector N. The value of the validate bit length in bitmap data is the size of the bitmap data for the lead-out zone or outer zone 0. Next, the description explains a space bitmap with the layer number at byte position 4 indicating layer 1. That is to say, the description explains a space bitmap for layer 1 of a two-layer disk. In this case, the zone information for the inner zone is information for the inner zone of layer 1, that is, information for a lead-out zone. The start cluster first PSN of the zone is a PSN of the start position of the lead-out zone as shown by a dotted-line arrow. Since the address direction on layer 1 is a direction from an outer side to an inner side, a position indicated by the dotted-line arrow is a start position. The start byte position of bit map data is used for recording information indicating the position of bitmap data corresponding to the lead-out zone in the space bitmap as shown by a dashed-line arrow, that is, information indicating byte position 0 of sector 1. The value of the validate bit length in bitmap data is the size of the bitmap data for the lead-out zone. The zone information for the data zone is information on the data zone of layer 1. The start cluster first PSN of the zone is a PSN of the start position of the data zone as shown by a dotted-line arrow. The start byte position of bitmap data is used for recording information indicating the position of bitmap data corresponding to the data zone in the space bitmap as shown by a dashed-line arrow, that is, information indicating byte position 0 of sector 2. The value of the validate bit length in bitmap data is the size of the bitmap data for the data zone. The zone information for the outer zone is information for the outer zone 1 of layer 1. The start cluster first PSN of the zone is a PSN of the start position of the outer zone 1 as shown by a dotted-line arrow. The start byte position of bitmap data is used for recording information indicating the position of bitmap data corresponding to outer zone 1 in the space bitmap as shown by a dashed-line arrow. The information is information indicating byte position 0 of sector N. The value of the validate bit length in bitmap data is the size of the bitmap data for outer zone 1. Next, the data structure of a TDFL is explained. As described above, a TDFL is recorded in a free area following a space bitmap in a TDMA. Every time an updating operation is carried out, a TDFL is recorded at the beginning of the remaining free area. FIG. 11 is a diagram showing the data structure of a TDFL. The TDFL comprises 1 to 4 clusters. By comparing with the DFL shown in FIG. 6, it is obvious that the contents of the TDFL are similar to those of the DFL in that the first 64 bytes of the defect list are used as bytes for recording management information of the defect list, the bytes following the 64th byte are used as bytes for recording contents of pieces of alternate-address information ati each having a length of 8 bytes, and a terminator having a length of 8 bytes serves as an alternate-address end immediately following ati #N, which is the last one of pieces of effective alternate-address information. However, the TDFL composed of 1 to 4 clusters is different from the DFL in that a DDS (or a TDDS) is recorded in 2,048 bytes composing the last sector of the TDFL. It is to be noted that, in the case of the TDFL, an area preceding the last sector of a cluster to which the alternate-address information terminator pertains is filled up with codes of 00h. As described above, the last sector is used as a sector for recording a TDDS. If the alternate-address information terminator pertains to the last sector of a specific cluster, an area between the specific cluster and the last sector of a cluster immediately preceding the specific cluster is filled up with codes of 0 and the last sector of the immediately preceding cluster is used as a sector for recording a TDDS. The defect-list management information having a size of 64 bytes is identical with the defect-list management information explained earlier by referring to FIG. 7 as information included in of the defect list DFL. However, as the number of times the defect list has been updated, the four bytes starting with a byte at byte position 4 are used as bytes for recording the sequence number of the defect list. That is to say, a sequence number included in defect-list management information in a most recent TDFL is the number of times the defect list has been updated. Besides, the four bytes starting with a byte at byte position 12 are used as bytes for recording the number of entries, that is, the number of pieces of alternate-address information ati. In addition, the four bytes starting with a byte at byte position 24 are used as bytes for recording values of cluster counts at the time the TDFL is updated. This cluster counts represent the sizes of free areas available in the alternate areas ISA 0, ISA 1, OSA 0 and OSA 1. The data structure of the alternate-address information ati in the TDFL is similar to the data structure shown in FIG. 8 as the structure of the alternate-address information ati in the DFL. The alternate-address information ati is included in the TDFL as an entry showing an alternate source cluster and an alternate destination cluster, which are involved in an alternate-address process. Such an entry is cataloged in the temporary defect list TDFL having a data structure shown in FIG. 11. In the case of the TDFL, however, the value of status 1 included in the alternate-address information ati in the TDFL may have a value of 0101 or 1010 in addition to 0000. Status 1 having a value of 0101 or 1010 indicates that an alternate-address process carried out on a plurality of physically continuous clusters is a burst transfer process, which handles the clusters collectively. To be more specific, status 1 having a value of 0101 indicates that the start sector physical address of an alternate source cluster and the start sector physical address of an alternate destination cluster, which are included in the alternate-address information ati, are respectively the physical address of the first sector in the first cluster of the physically continuous clusters serving as the alternate source and the physical address of the first sector in the first cluster of the physically continuous clusters serving as the alternate destination. On the other hand, status 1 having a value of 1010 indicates that the start sector physical address of an alternate source cluster and the start sector physical address of an alternate destination cluster, which are included in the alternate-address information ati are respectively the physical address of the first sector in the last cluster of the physically continuous clusters serving as the alternate source and the physical address of the first sector in the last cluster of the physically continuous clusters serving as the alternate destination. Thus, in an alternate-address process collectively treating a plurality of physically continuous clusters, it is not necessary to catalog an entry describing the alternate-address information ati for each of all the clusters. Instead, it is necessary to specify only one entry of alternate-address information ati including two physical addresses of first sectors in first clusters and another entry of alternate-address information ati including two physical addresses of first sectors in last clusters as described above. As described above, basically, the TDFL has a data structure identical with that of a DFL. However, the TDFL is characterized in that the size of the TDFL can be extended to up to four clusters, the last sector is used as a sector for recording a TDDS, and management of burst transfers can be executed by using alternate-address information ati. As shown in FIG. 9, the TDMA is used as an area for recording space bitmaps and TDFLs. As described earlier, however, the 2,048-byte last sector of each of the space bitmaps and each of the TDFLs is used as a sector for recoding a TDDS (temporary disc definition structure). FIG. 12 is a diagram showing the structure of the TDDS. The TDDS occupies one sector having a size of 2,048 bytes. The TDDS has the same contents as the DDS in a DMA. It is to be noted that, even though the DDS has a size of one cluster consisting of 65,536 bytes, only a portion not beyond byte position 52 is virtually defined as contents of the DDS as explained earlier by referring to FIG. 5. That is to say, actual contents are recorded in the first sector of the cluster. Thus, in spite of the fact that the TDDS has a size of only one sector, the TDDS covers all the contents of the DDS. As is obvious from comparison of FIG. 12 with FIG. 5, contents of the TDDS at byte positions 0 to 53 are identical with those of the DDS. It is to be noted, however, that bytes starting from byte position 4 are used as bytes for recording the sequence number of the TDDS, bytes starting from byte position 16 are used as bytes for recording the physical address of the first sector in a drive area in the TDMA and bytes starting from byte position 24 are used as bytes for recording the physical address AD_DFL of the first sector of the TDFL in the TDMA. Bytes at byte position 1,024 and subsequent byte positions in the TDDS are used as bytes for recording information, which does not exist in the DDS. Four bytes starting from byte position 1,024 are used as bytes for recording the physical address LRA of a sector on an outermost circumference included in the user-data area as a circumference on which user data has been recorded. Four bytes starting from byte position 1,028 are used as bytes for recording the physical address AD_BP0 of the first sector in a most recent space bitmap for layer 0 in the TDMA. Four bytes starting from byte position 1,032 are used as bytes for recording the physical address AD_BP1 of the first sector in a most recent space bitmap for layer 1 in the TDMA. One byte at byte position 1,036 is used as a byte for recording a flag for controlling the use of an overwrite function. Bytes at byte positions other than the byte positions described above are reserved and filled with codes of 00h. As described above, the TDDS includes addresses in the user-data area, ISA and OSA sizes and spare area full flags. That is to say, the TDDS includes management/control information for managing ISAs and OSAs in the data zone. At this point, the TDDS is similar to the DDS. Also as described above, the TDDS also includes pieces of information such as the physical address AD_BP0 of the first sector in the effective most recent space bitmap for layer 0, the physical address AD_BP1 of the first sector in the effective most recent space bitmap for layer 1 and the physical address AD_DFL of the first sector in the effective most recent TDFL (temporary DFL). Since a TDDS is recorded in the last sector of the space bitmap and the last sector of the TDFL every time a space bitmap or a TDFL is added, the recorded TDDS is a new TDDS. Thus, in the TDMA shown in FIG. 9, a TDDS included in a space bitmap added last or a TDDS included in a TDFL added last is the most recent TDDS. In the most recent TDDS, the most recent space bitmap and the most recent TDFL are shown. 1-2: ISAs and OSAs FIG. 13 is a diagram showing positions of each ISA and each OSA. An ISA (inner space area) and an OSA (outer space area) are each an area allocated in the data zone as an alternate area used in an alternate-address process carried out on a defective cluster. In addition, an ISA or an OSA is also used in an operation to write new data into a desired address as an alternate area for actually recording the new data supposed to be written into the desired address, at which other data has been recorded previously. The operation to write the new data into the desired address is thus an operation to renew the other data with the new data. FIG. 13A is a diagram showing the positions of an ISA and an OSA on a one-layer disk. As shown in the diagram, the ISA is located on the innermost-circumference side of the data zone whereas the OSA is located on the outermost-circumference side of the data zone. On the other hand, FIG. 13B is a diagram showing the positions of each ISA and each OSA on a two-layer disk. As shown in the diagram, ISA 0 is located on the innermost-circumference side of the data zone on layer 0 whereas the OSA 0 is located on the outermost-circumference side of the data zone on layer 0. On the other hand, ISA 1 is located on the innermost-circumference side of the data zone on layer 1 whereas the OSA 1 is located on the outermost-circumference side of the data zone on layer 1. On the two-layer disk, the size of ISA 0 may be different from that of ISA 1. However, the size of OSA 0 is equal to that of OSA 1. The sizes of the ISA (or ISA 0 and ISA 1) and the sizes of the OSA (or OSA 0 and OSA 1) are defined in the DDS and the TDDS, which have been described earlier. The size of the ISA is determined at an initialization time and remains fixed thereafter. However, the size of the OSA may be changed even after data has been recorded therein. That is to say, the OSA size recorded in the TDDS can be changed in an operation to update the TDDS to increase the size of the OSA. An alternate-address process using the ISA or the OSA is carried out as follows. An operation to renew data is taken as an example. For example, new data is written into the user-data zone. To be more specific, the data is written into a cluster, in which existing data has already been written previously. That is to say, a request is made as a request to renew the existing data. In this case, since the disk is recognized as a write-once optical disk, the new data cannot be written into the cluster. Thus, the new data is written into a cluster in the ISA or the OSA. This operation is referred to as an alternate-address process. This alternate-address process is managed as the alternate-address information ati described above. The alternate-address information ati is treated as a TDFL entry including the address of a cluster, in which the existing data has been recorded from the very start, as an alternate source address. The TDFL entry of the alternate-address information ati also includes the address of an ISA or OSA cluster, in which the new data has been written as alternate-address data, as an alternate destination address. That is to say, in the case of renewal of existing data, alternate-address data is recorded in the ISA or the OSA and the alternate-address process carried out on the data locations for the renewal of the existing data is controlled as alternate-address information ati cataloged on the TDFL in the TDMA. Thus, while the disk is a write-once optical disk, virtually, renewal of data is implemented. In other words, as seen from the OS of a host system, a file system or other systems, renewal of data is implemented. The alternate-address process can also be applied to management of defects in the same way. To put it in detail, if a cluster is determined to be a defective area, by carrying out the alternate-address process, data supposed to be written in the cluster is written in a cluster of the ISA or the OSA. Then, for the management of this alternate-address process, one alternate-address information ati is cataloged as an entry on the TDFL. 3-3: TDMA-Using Method As described above, every time data is renewed or an alternate-address process is carried out, a space bitmap and a TDFL in a TDMA are updated. FIG. 14 is a diagram showing the state of updating contents of a TDMA. FIG. 14A shows a state in which a space bitmap for layer 0, a space bitmap for layer 1 and a TDFL have been recorded in the TDMA. As described above, the last sector of each of the space bitmaps and the last sector of the TDFL are each used for recording a TDDS (temporary DDS). They are referred to as TDDS 1, TDDS 2 and TDDS 3. In the case of the state shown in FIG. 14A, the TDFL is related to most recently written data. Thus, TDDS 3 recorded in the last sector of the TDFL is the most recent TDDS. As explained earlier by referring to FIG. 12, this TDDS includes AD BP0, AD BP1 and AD DFL. AD BP0 and AD BP1 are information showing the locations of effective most recent space bitmaps. On the other hand, AD DFL is information showing the location of an effective most recent TDFL. In the case of TDDS 3, AD BP0, AD BP1 and AD DFL are pieces of effective information pointing to the locations of the space bitmaps and the TDFL as shown by a solid-line arrow, a dashed-line arrow and a dotted-line arrow respectively. That is to say, AD DFL in TDDS 3 is used as an address for specifying a TDFL including TDDS 3 itself as an effective TDFL. On the other hand, AD BP0 and AD BP1 in TDDS 3 are used as addresses for specifying space bitmaps for layers 0 and 1 respectively as effective space bitmaps. Later on, data is written and, since the space bitmap for layer 0 is updated, a new space bitmap for layer 0 is added to the TDMA. As shown in FIG. 14B, the new space bitmap is recorded at the beginning of a free area. In this case, TDDS 4 recorded in the last sector of the new space bitmap becomes the most recent TDDS. AD BP0, AD BP1 and AD DFL in TDDS 4 are used as addresses for specifying pieces of effective information. To be more specific, AD BP0 in TDDS 4 is used as an address for specifying a space bitmap for layer 0 as a space bitmap, which includes TDDS 4 itself and serves as effective information. Much like the state shown in FIG. 14A, AD BP1 in TDDS 4 is used as an address for specifying a space bitmap for layer 1 as effective information, and AD DFL in TDDS 4 is used as an address for specifying a TDFL as an effective TDFL. Later on, data is written again and, since the space bitmap for layer 0 is updated, a new space bitmap for layer 0 is added to the TDMA. As shown in FIG. 14C, the new space bitmap is recorded at the beginning of the free area. In this case, TDDS 5 recorded in the last sector of the new space bitmap becomes the most recent TDDS. AD BP0, AD BP1 and AD DFL in TDDS 5 are used as addresses for specifying pieces of effective information. To be more specific, AD BP0 in TDDS 4 is used as an address for specifying a space bitmap for layer 0 as a space bitmap, which includes TDDS 4 itself and serves as effective information. Much like the state shown in FIGS. 14(a) and 14(b), AD BP1 is used as an address for specifying a space bitmap for layer 1 as effective information, and AD DFL is used as an address for specifying a TDFL as an effective TDFL. As described above, when a TDFL and/or a space bitmap are updated, a TDDS recorded in the last sector of the most recent information includes addresses indicating effective information such as space bitmaps and a TDFL, which are included in the TDMA. The effective information is defined as the most recent space bitmaps and the most recent TDFL, which are cataloged in the TDMA before a finalize process. Thus, the disk drive is capable of grasping an effective TDFL and effective space bitmaps by referring to a TDDS included in a last recorded TDFL or a last recorded space bitmap recorded in the TDMA. By the way, FIG. 14 is a diagram showing the state of updating contents of a TDMA for a two-layer disk. That is to say, the TDMA includes a space bitmap for layer 0 and a space bitmap for layer 1. The two space bitmaps and the TDFL are initially cataloged in the TDMA for layer 0. That is to say, only the TDMA for layer 0 is used and, every time a TDFL and/or a space bitmap are updated, the new TDFL and/or the new space bitmap are added to the TDMA as shown in FIG. 14. The TDMA for layer 1 as the second layer is used after the TDMA for layer 0 has been all used up. Then, the TDMA for layer 1 is also used for cataloging TDFLs and/or space bitmaps one after another by starting from the beginning of the TDMA. FIG. 15 is a diagram showing a state in which the TDMA for layer 0 is all used up after recording a TDFL or a space bitmap N times. Then, a TDFL or a space bitmap is cataloged continuously in the TDMA provided for layer 1 to serve as a continuation of the TDMA provided for layer 0 as shown in FIG. 14C. In the state shown in FIG. 15, after the TDMA for layer 0 has been used up, two space bitmaps for layer 1 are further cataloged in the TDMA for layer 1. In this state, TDDS N+2 recorded in the last sector of the most recent space bitmap for layer 1 is the most recent TDDS. Much like the state shown in FIG. 14, in the most recent TDDS, AD BP0, AD BP1 and AD DFL point to pieces of effective information as shown by a solid-line arrow, a dashed-line arrow and a dotted-line arrow respectively. That is to say, AD BP1 in TDDS N+2 is used as an address for specifying a space bitmap for layer 1 as a space bitmap, which includes TDDS N+2 itself and serves as effective information. On the other hand, AD BP0 in TDDS N+2 is used as an address for specifying a space bitmap for layer 0, that is, the same space bitmap as that shown in FIG. 14C, and AD DFL in TDDS N+2 is used as an address for specifying a TDFL as effective information or most recently updated information. It is needless to say that, if the TDFL, the space bitmap for layer 0 or the space bitmap for layer 1 is updated thereafter, the updated TDFL or space bitmap is cataloged at the beginning of a free area in the TDMA for layer 1. As described above, the TDMAs for recording layers 0 and 1 are used one after another for cataloging updated TDFLs and space bitmaps. Thus, the TDMAs for the recording layers can be used jointly as a large single TDMA. As a result, a plurality of DMAs can be utilized with a high degree of efficiency. In addition, by searching only a TDDS recorded last without regard to whether the TDMA is provided for layer 0 or 1, an effective TDFL and/or space bitmap can be grasped. In this embodiment, a one-layer disk and a two-layer disk are assumed as described above. It is to be noted, however, that a disk having three or more recording layers is also conceivable. Also in the case of a disk having three or more recording layers, the TDMAs for the layers can be used one after another in the same way. 4: Disk Drive The following description explains a recording/reproduction apparatus serving as a disk drive for the write-once optical disks described above. The disk drive provided by the embodiment is capable of forming a layout of a write-once optical disk in a state explained earlier by referring to FIG. 1 by formatting the disk in a state wherein, typically, only the prerecorded information area PIC shown in FIG. 1 has been created but no write-once area has been formed. In addition, the disk drive records data into the user-data area of the disk formatted in this way and reproduces data from the user-data. If necessary, the disk drives also updates a TDMA by recording information therein and records data into an ISA or an OSA. FIG. 16 is a diagram showing the configuration of the disk drive. A disk 1 is the write-once optical disk described above. The disk 1 is mounted on a turntable not shown in the figure. In a recording/reproduction operation, the turntable is driven into rotation at a CLV (constant linear velocity) by a spindle motor 52. An optical pickup (optical head) 51 reads out ADIP addresses embedded on the disk 1 as a wobbling shape of a groove track and management/control information as information prerecorded on the disk 1. At an initialization/formatting time or in an operation to record user data onto the disk 1, the optical pickup 51 records management/control information and user data onto a track in a write-once area. In a reproduction operation, on the other hand, the optical pickup 51 reads out data recorded on the disk 1. The optical pickup 51 includes a laser diode, a photo detector, an objective lens and an optical system, which are not shown in the figure. The laser diode is a device serving as a source for generating a laser beam. The photo detector is a component for detecting a beam reflected by the disk 1. The objective lens is a component serving as an output terminal of the laser beam. The optical system is a component for radiating the laser beam to a recording face of the disk 1 by way of the objective lens and leading the reflected beam to the photo detector. In the optical pickup 51, the objective lens is held by a biaxial mechanism in such a way that the mechanism is capable of moving the objective lens in tracking and focus directions. In addition, the entire optical pickup 51 can be moved in the radial direction of the disk 1 by a thread mechanism 53. The laser diode included in the optical pickup 51 is driven to emit a laser beam by a drive current generated by a laser driver 63 as a drive signal. The photo detector employed in the optical pickup 51 detects information conveyed by a beam reflected by the disk 1, converts the detected information into an electrical signal proportional to the light intensity of the reflected beam and supplies the electrical signal to a matrix circuit 54. The matrix circuit 54 has a current/voltage conversion circuit, which is used for converting a current output by the photo detector comprising a plurality of light-sensitive devices into a voltage, and a matrix processing/amplification circuit for carrying out matrix processing to generate necessary signals. The necessary signals include a high-frequency signal (or a reproduced-data signal) representing reproduced data as well as a focus error signal and a tracking error signal, which are used for servo control. In addition, a push-pull signal is also generated as a signal related to wobbling of the groove. The signal related to wobbling of the groove is a signal for detecting the wobbling of the groove. It is to be noted that the matrix circuit 54 may be physically integrated inside the optical pickup 51. The reproduced-data signal output by the matrix circuit 54 is supplied to a reader/writer circuit 55. The focus error signal and the tracking error signal, which are also generated by the matrix circuit 54, are supplied to a servo circuit 61. The push-pull signal generated by the matrix circuit 54 is supplied to a wobble circuit 58. The reader/writer circuit 55 is a circuit for carrying out processing such as a binary conversion process on the reproduced-data signal and a process to generate a reproduction clock signal by adopting a PLL technique to generate data read out by the optical pickup 51. The generated data is then supplied to a demodulation circuit 56. The demodulation circuit 56 comprises a functional member serving as a decoder in a reproduction process and a functional member serving as an encoder in a recording process. In a reproduction process, the demodulation circuit 56 implements demodulation process for run-length limited code as decoding process on the basis of the reproduction clock signal. An ECC encoder/decoder 57 is a component for carrying out an ECC encoding process to add error correction codes to data to be recorded onto the disk 1 and an ECC decoding process for correcting errors included in data reproduced from the disk 1. At a reproduction time, data demodulated by the demodulation circuit 56 is stored in an internal memory to be subjected to error detection/correction processing and processing such as a de-interleave process to generate the eventual reproduced data. The reproduced data obtained as a result of a decoding process carried out by the ECC encoder/decoder 57 is read out from the internal memory and transferred to an apparatus connected to the disk drive in accordance with a command given by a system controller 60. An example of the apparatus connected to the disk drive is an AV (Audio-Visual) system 120 As described above, the push-pull signal output by the matrix circuit 54 as a signal related to the wobbling state of the groove is processed in the wobble circuit 58. The push-pull signal conveying ADIP information is demodulated in the wobble circuit 58 into a data stream composing ADIP addresses. The wobble circuit 58 then supplies the data stream to an address decoder 59. The address decoder 59 decodes the data received thereby to generate addresses and then supplies the addresses to the system controller 60. The address decoder 59 also generates a clock signal by carrying out a PLL process using the wobble signal supplied by the wobble circuit 58 and supplies the clock signal to other components for example as a recording-time encode clock signal. The push-pull signal output by the matrix circuit 54 as a signal related to the wobbling state of the groove is a signal originated from the prerecorded information PIC. In the wobble circuit 58, the push-pull signal is subjected to a band-pass filter process before being supplied to the reader/writer circuit 55, which carries out a binary conversion process to generate a data bit stream. The data bit stream is then supplied to the ECC encoder/decoder 57 for carrying out ECC-decode and de-interleave processes to extract data representing the prerecorded information. The extracted prerecorded information is then supplied to the system controller 60. On the basis of the fetched prerecorded information, the system controller 60 is capable of carrying out processes such as processing to set a variety of operations and copy protect processing. At a recording time, data to be recorded is received from the AV system 120. The data to be recorded is buffered in a memory employed in the ECC encoder/decoder 57. In this case, the ECC encoder/decoder 57 carries out processes on the buffered data to be recorded. The processes include processing to add error correction codes, interleave processing and processing to add sub-codes. The data completing the ECC encoding process is subjected to a demodulation process such as demodulation adopting an RLL (1-7) PP method in the demodulation circuit 56 before being supplied to the reader/writer circuit 55. In these encoding processes carried out at a recording time, the clock signal generated from the wobble signal as described above is used as the encoding clock signal, which serves as a reference signal. After completing these encoding processes, the data to be recorded is supplied to the reader/writer circuit 55 to be subjected to recording compensation processing such as fine adjustment of a recording power to produce a power value optimum for factors including characteristics of the recording layer, the spot shape of the laser beam and the recording linear speed as well as adjustment of the shape of the laser drive pulse. After completing the recording compensation processing, the data to be recorded is supplied to the laser driver 63 as laser drive pulses. The laser driver 63 passes on the laser drive pulses to the laser diode employed in the optical pickup 51 to drive the generation of a laser beam from the diode. In this way, pits suitable for the recorded data are created on the disk 1. It is to be noted that the laser driver 63 includes the so-called APC (Auto Power Control) circuit for controlling the laser output to a fixed value independent of ambient conditions such as the ambient temperature by monitoring the laser output power. A detector is provided in the optical pickup 51 to serve as a monitor for monitoring the laser output power. The system controller 60 gives a target value of the laser output power for each of recording and reproduction processes. The level of the laser output is controlled to the target value for the recording or reproduction process. The servo circuit 61 generates a variety of servo drive signals from the focus error signal and the tracking error signal, which are received from the matrix circuit 54, to carry out servo operations. The servo drive signals include focus, tracking and thread servo drive signals. To put it concretely, the focus and tracking drive signals are generated in accordance with the focus error signal and the tracking error signal respectively to drive respectively focus and tracking coils of the biaxial mechanism employed in the optical pickup 51. Thus, tracking and focus servo loops are created as loops comprising the optical pickup 51, the matrix circuit 54, the servo circuit 61 and the biaxial mechanism. In addition, in accordance with a track jump command received from the system controller 60, the servo circuit 61 turns off the tracking servo loop and carries out a track jump operation by outputting a jump drive signal. On top of that, the servo circuit 61 generates a thread drive signal on the basis of a thread error signal and an access execution control signal, which is received from the system controller 60, to drive the thread mechanism 53. The thread error signal is obtained as a low-frequency component of the tracking error signal. The thread mechanism 53 has a mechanism comprising a transmission gear, a thread motor and a main shaft for holding the optical pickup 51. The thread mechanism 53 drives the thread motor in accordance with the thread drive signal to slide the optical pickup 51 by a required distance. It is to be noted that the mechanism itself is not shown in the figure. A spindle servo circuit 62 controls the spindle motor 52 to rotate at a CLV. The spindle servo circuit 62 obtains a clock signal generated in a PLL process for the wobble signal as information on the present rotational speed of the spindle motor 52 and compares the present rotational speed with a predetermined CLV reference speed to generate a spindle error signal. In addition, a reproduction clock signal generated at a data reproduction time by a PLL circuit employed in the reader/writer circuit 55 is used as the reference clock signal of a decoding process as well as the information on the present rotational speed of the spindle motor 52. Thus, by comparing this reproduction clock signal with the predetermined CLV reference speed, a spindle error signal can be generated. Then, the spindle servo circuit 62 outputs the spindle drive signal, which is generated in accordance with the spindle error signal, to carry out the CLV rotation of the spindle motor 52. In addition, the spindle servo circuit 62 also generates a spindle drive signal in accordance with a spindle kick/brake control signal received from the system controller 60 to carry out operations to start, stop, accelerate and decelerate the spindle motor 52. A variety of operations carried out by the servo system and the recording/reproduction system as described above is controlled by the system controller 60 based on a microcomputer. The system controller 60 carries out various kinds of processing in accordance with commands received from the AV system 120. When a write instruction (or a command to write data) is received from the AV system 120, for example, the system controller 60 first of all moves the optical pickup 51 to an address into which the data is to be written. Then, the ECC encoder/decoder 57 and the demodulation circuit 56 carry out the encoding processes described above on the data received from the AV system 120. Examples of the data are video and audio data generated in accordance with a variety of methods such as MPEG2. Subsequently, as described above, the reader/writer circuit 55 supplies laser drive pulses representing the data to the laser driver 63 in order to actually record the data on the disk 1. On the other hand, when a read command to read out data such as MPEG2 video data from the disk 1 is received from the AV system 120, for example, the system controller 60 first of all carries out a seek operation to move the optical pickup 51 to a target address at which the data is to be read out from the disk 1. That is to say, the system controller 60 outputs a seek command to the servo circuit 61 to drive the optical pickup 51 to make an access to a target address specified in the seek command. Thereafter, necessary control of operations is executed to transfer data of a specified segment to the AV system 120. That is to say, the data is read out from the disk 1, processing such as the decoding and buffering processes is carried out in the reader/writer circuit 55, the demodulation circuit 56 and the ECC encoder/decoder 57, and the requested data is transferred to the AV system 120. It is to be noted that, in the operations to record data into the disk 1 and reproduce data from the disk 1, the system controller 60 is capable of controlling accesses to the disk 1 and the recording/reproduction operations by using ADIP addresses detected by the wobble circuit 58 and the address decoder 59. In addition, at predetermined points of time such as the time the disk 1 is mounted on the disk drive, the system controller 60 reads out a unique ID from the BCA on the disk 1 in case the BCA exists on the disk 1 and prerecorded information (PIC) recorded on the disk 1 as a wobbling groove from the reproduction-only area. In this case, control of seek operations is executed with the BCA and the prerecorded data zone PR set as targets of the seek operations. That is to say, commands are issued to the servo circuit 61 to make accesses by using the optical pickup 51 to the innermost-circumference side of the disk 1. Later on, the optical pickup 51 is driven to carry out reproduction tracing to obtain a push-pull signal as information conveyed by a reflected beam. Then, decoding processes are carried out in the wobble circuit 58, reader/writer circuit 55 and ECC encoder/decoder 57 to generate BCA information and prerecorded information as reproduced data. On the basis of the BCA information and the prerecorded information, which are read out from the disk 1 as described above, the system controller 60 carries out processing such as a process to set laser powers and a copy protect process. In the configuration shown in FIG. 16, a cache memory 60a is employed in the system controller 60. The cache memory 60a is used for holding typically a TDFL and/or a space bitmap, which are read out from the TDMA recorded on the disk 1, so that the TDFL and/or the space bitmap can be updated without making an access to the disk 1. When the disk 1 is mounted on the disk drive, for example, the system controller 60 controls components of the disk drive to read out a TDFL and/or a space bitmap from the TDMA recorded on the disk 1 and store them in the cache memory 60a. Later on, when an alternate-address process is carried out to renew data or due to a defect, the TDFL or the space bitmap stored in the cache memory 60a is updated. Every time an alternate-address process is carried out to write or renew data in the disk 1 and the TDFL or the space bitmap is updated, for example, the updated TDFL or space bitmap can be additionally cataloged in the TDMA recorded on the disk 1. By doing so, however, the TDMA recorded on the disk 1 will be used up at an early time. In order to solve this problem, only the TDFL or the space bitmap stored in the cache memory 60a is updated till the disk 1 is ejected from the disk drive. As the disk 1 is ejected from the disk drive, for example, the last (most recent) TDFL or space bitmap stored in the cache memory 60a is transferred to the TDMA recorded on the disk 1. In this way, the TDMA recorded on the disk 1 is updated only after the TDFL and/or the space bitmap, which are stored in the cache memory 60a, has been updated a large number of times so that the amount of the TDMA consumption can be reduced. The explanation given thereafter is based on a method to reduce the amount of consumption of the TDMA recorded on the disk 1 by using the cache memory 60a in processing such as a recording process to be described later. It is needless to say, nevertheless, that the present invention can be implemented without the cache memory 60a. Without the cache memory 60a, however, every time a TDFL or a space bitmap is updated, the updated TDFL or the updated space bitmap must be cataloged in the TDMA recorded on the disk 1. By the way, the typical configuration of the disk drive shown in FIG. 16 is the configuration of a disk drive connected to the AV system 120. However, the disk drive provided by the present invention can be connected to an apparatus such as a personal computer. In addition, the disk drive may be designed into a configuration that cannot be connected to an apparatus. In this case, unlike the configuration shown in FIG. 16, the disk drive includes an operation unit and a display unit or an interface member for inputting and outputting data. That is to say, data is recorded onto a disk and reproduced from the disk in accordance with an operation carried out by the user, and a terminal is required as a terminal for inputting and outputting the data. Of course, other typical configurations are conceivable. For example, the disk drive can be designed as a recording-only apparatus or a reproduction-only apparatus. 5: Operations for the First TDMA Method 5-1: Data Writing By referring to flowcharts shown in FIGS. 17 to 20, the following description explains processing carried out by the system controller 60 in a process to record data onto the disk 1 mounted on the disk drive. It is to be noted that, at the time the data-writing process explained below is carried out, the disk 1 has already been mounted on the disk drive, and a TDFL as well as a space bitmap have been transferred from a TDMA on the disk 1 mounted on the disk drive to the cache memory 60a. In addition, when a request for a write operation or a read operation is received from a host apparatus such as the AV system 120, the target address is specified in the request as a logical sector address. The disk drive carries out logical/physical address conversion processing to convert the logical sector address into a physical sector address but the description of the conversion process for each request from time to time is omitted. It is to be noted that, in order to convert a logical sector address specified by a host into a physical sector address, it is necessary to add ‘the physical address of the first sector in a user-data area’ recorded in the TDDS to the logical sector address. Assume that a request to write data into address N has been received from a host apparatus such as the AV system 120 by the system controller 60. In this case, the system controller 60 starts processing represented by the flowchart shown in FIG. 17. First of all, at a step F101, a space bitmap stored in the cache memory 60a is referred to in order to determine whether or not data has been recorded in a cluster at the specified address. The space bitmap stored in the cache memory 60a is a space bitmap updated most recently. If no data has been recorded at the specified address, the flow of the processing goes on to a step F102 to carry out a process to write user data into the address as represented by the flowchart shown in FIG. 18. If data has already been recorded at the specified address so that the process to write the data of this time can not be implemented, on the other hand, the flow of the processing goes on to a step F103 to carry out an overwrite process represented by the flowchart shown in FIG. 19. The process to write user data into the address as represented by the flowchart shown in FIG. 18 is a process requested by a command to write the data into the address at which no data has been recorded. Thus, the process to write user data into the address as represented by the flowchart shown in FIG. 18 is an ordinary write process. If an error is generated in the course of the write process due to a defect such as an injury on the disk 1, however, an alternate-address process may be carried out in some cases. First of all, at a step F111, the system controller 60 executes control to write the data into the specified address. That is to say, the optical pickup 51 is driven to make an access to the specified address and record the data of the write request into the address. If the operation to write the data into the address is completed normally, the flow of the processing goes on from the step F112 to the step F113 at which the space bitmap stored in the cache memory 60a is updated. To put it in detail, the space bitmap is searched for a bit corresponding to a cluster in which the data has been written this time, and the bit is set to a value indicating that data has been written into the cluster. Then, the execution of the processing for the write request is ended. If the operation carried out at the step F111 to write the data into the address is not completed normally and an alternate-address process function is in an on state, on the other hand, the flow of the processing goes on from the step F112 to the step F114. It is to be noted that the step F112 is executed also to determine whether or not the alternate-address process function is in an on state by checking whether or not an ISA and/or an OSA have been defined. If at least either an ISA or an OSA has been defined, an alternate-address process can be carried out. In this case, the alternate-address process function is determined to be in an on state. An ISA or an OSA is determined to have been defined if the size of the ISA or the OSA in the TDDS of the TDMA has been set at a value other than a zero. That is to say, at a formatting time of the disk 1, at least either an ISA or an OSA is defined as an actually existing alternate area by specifying its size at a value other than a zero in a TDDS and recording the TDDS in the first TDMA. As an alternative, for example, an OSA can be redefined by setting its size at a value other than a zero in an operation to update a TDDS in a TDMA. After all, if at least either an ISA or an OSA exists, the alternate-address process function is determined to be in an on state. In this case, the flow of the processing goes on to the step S114. If the determination result obtained at the step F112 indicates that neither an ISA nor an OSA exists, indicating that the alternate-address process function has been made ineffective, on the other hand, the flow of the processing goes on to the step S113. It is to be noted that, at this step, the space bitmap stored in the cache memory 60a is searched for a bit corresponding to a cluster at the specified address and the bit is set at a value indicating that data has been recorded in the cluster. Then, the execution of the processing is ended. In this case, however, the write request is ended in an error. In spite of the fact that a write error has been generated, at the bit in the space bitmap, a flag indicating that data has been recorded in the cluster corresponding to the bit is set in the same way as a normal termination of the processing. The setting of the flag means that the defective area is managed by using the space bitmap as a cluster in which data has been recorded. Thus, even if a request is received as a request to write data into the defective area, in which the error has been generated, by referring to the space bitmap, the processing of the request can be carried out with a high degree of efficiency. As described above, if the alternate-address process function is determined at the step F112 to be in an on state, the flow of the processing goes on to the step F114, first of all, to determine whether or not the alternate-address process can be actually carried out. In order to carry out the alternate-address process, the spare area, that is, either the ISA or the OSA, must have a free area for at least recording the data requested in the write operation. In addition, the TDMA must have a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, that is, allowing the TDFL to be updated. It is possible to determine whether or not the ISA or the OSA has such a free area by checking the number of unused ISA/OSA clusters included in the defect-list management information shown in FIG. 7. As described earlier, the defect-list management information is included in a TDFL as shown in FIG. 11. If at least either the ISA or the OSA has a free area and the TDMA has a margin for update, the flow of the processing carried out by the system controller 60 goes on from the step F114 to a step F115 at which the optical pickup 51 is driven to make an access to the ISA or the OSA and record the data requested in the write operation into the free area in the ISA or the OSA respectively. Then, at the next step F116, after the write operation requiring the alternate-address process, the TDFL and the space bitmap, which have been stored in the cache memory 60a, are updated. To put it in detail, the contents of the TDFL are updated by newly adding an entry of the alternate-address information ati representing the present alternate-address process as shown in FIG. 8 to the TDFL. In addition, in accordance with the addition of such an entry, the number of cataloged DFL entries in the defect-list management information shown in FIG. 7 is increased while the number of unused ISA/OSA clusters in the defect-list management information shown in FIG. 7 is decreased. If the alternate-address process is carried out on one cluster, the number of cataloged DFL entries is incremented by one while the number of unused ISA/OSA clusters is decremented by one. It is to be noted that a process to generate the alternate-address information ati will be described later. In addition, a bit included in the space bitmap as a bit corresponding to a cluster at the address, at which an error of the requested write operation has been generated, is set at a value indicating that data has been recorded in the cluster. By the same token, a bit included in the space bitmap as a bit corresponding to an ISA or OSA cluster, in which the data has been actually recorded, is set at a value indicating that data has been recorded in the cluster. Then, the execution of the processing of the write request is ended. In this case, however, a write error has been generated at the address specified in the write request, by carrying out the alternate-address process, the write operation can be completed. From the standpoint of the host apparatus, the processing of the write is ended normally. If the determination result obtained at the step F114 indicates that neither the ISA nor the OSA has a free area or the TDMA does not have a margin for TDFL to be updated, the flow of the processing carried out by the system controller 60 goes on to a step F117 at which an error report is returned to the host apparatus and the execution of the processing is ended. If the determination result obtained at the step F101 of the flowchart shown in FIG. 17 indicates that data has already been recorded at the address specified in the write request made by the host apparatus as evidenced by the fact that a bit included in the space bitmap as a bit corresponding to a cluster at the address has been set at a value indicating that data has been recorded in the cluster, the flow of the processing goes on to the step F103 as described earlier. At this step, the overwrite function process represented by the flowchart shown in FIG. 19 is carried out. The flowchart begins with a step F121 at which the system controller 60 determines whether or not the overwrite function or the data renewal function is effective. The system controller 60 is capable of determining whether or not the overwrite function is effective by referring to a flag included in the TDDS shown in FIG. 12 as a flag indicating whether or not the overwrite function is usable. If the flag indicating whether or not the overwrite function is usable is not set at 1 indicating that the function is not effective, the flow of the processing goes on to a step F122 at which an error report indicating incorrect specification of the address is returned to the host apparatus and the execution of the processing is ended. If the flag indicating whether or not the overwrite function is usable is set at 1 indicating that the data renewal function is effective, on the other hand, the processing of the data renewal function is started. In this case, the flow of the processing goes on to a step F123 first of all to determine whether or not the alternate-address process can be carried out. As described above, in order to carry out the alternate-address process, the spare area, that is, either the ISA or the OSA, must have a free area for at least recording the data requested in the write operation and, in addition, the TDMA must have a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, that is, allowing the TDFL to be updated. If at least either the ISA or the OSA has a free area and the TDMA has a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, the flow of the processing carried out by the system controller 60 goes on from the step F123 to a step F124 at which the optical pickup 51 is driven to make an access to the ISA or the OSA and record the data requested in the write operation into the free area in the ISA or the OSA respectively. Then, at the next step F125, after the write operation requiring execution of the alternate-address process, the TDFL and the space bitmap, which have been stored in the cache memory 60a, are updated. To put it in detail, the contents of the TDFL are updated by newly adding an entry of the alternate-address information ati representing the present alternate-address process as shown in FIG. 8 to the TDFL. However, data at the same address may have been renewed before and an entry of the alternate-address information ati representing the alternate-address process for the renewal has thus been cataloged on the TDFL. In such a case, first of all, all pieces of alternate-address information ati cataloged in the TDFL are searched for an entry including the address as an alternate source address. If alternate-address information ati has been cataloged in the TDFL as an entry including the address as an alternate source address, the alternate destination address included in the alternate-address information ati is changed to the address in the ISA or the OSA. Since the TDFL containing such alternate-address information ati as an entry has been stored in the cache memory 60a at the present point of time, the change of the alternate destination address of the alternate-address information ati can made with ease. It is to be noted that, without the cache memory 60a, every time the TDFL recorded on the disk 1 is updated, the already cataloged entry must be deleted from the TDFL before adding a new entry to the TDFL. If a new entry of the alternate-address information ati is added to the TDFL, the number of cataloged DFL entries in the defect-list management information shown in FIG. 7 is increased while the number of unused ISA/OSA clusters in the defect-list management information shown in FIG. 7 is decreased. In addition, a bit included in the space bitmap as a bit corresponding to an ISA or OSA cluster, in which the data has been actually recorded, is set at a value indicating that data has been recorded in the cluster. Then, the execution of the processing of the write request is ended. By carrying out the processing to use the ISA or the OSA as described above, the system controller 60 is capable of coping with a data renewal request, which is a request to write data into an address at which data has been recorded. If the determination result obtained at the step F123 indicates that neither the ISA nor the OSA has a free area or the TDMA does not have a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, on the other hand, the flow of the processing carried out by the system controller 60 goes on to a step F126 at which an error report indicating no free write area is returned to the host apparatus and the execution of the processing is ended. By the way, at the step F116 of the flowchart shown in FIG. 18 and the step F125 of the flowchart shown in FIG. 19, alternate-address information ati is newly generated for the alternate-address process by the system controller 60 in processing represented by the flowchart shown in FIG. 20. The flowchart shown in FIG. 20 begins with a step F151 to determine whether or not the alternate-address process is a process carried out on a plurality of physically continuous clusters. If the alternate-address process is a process carried out on a cluster or a plurality of physically discontinuous clusters, the flow of the processing goes on to a step F154 at which alternate-address information ati is generated for the cluster or each of the physically discontinuous clusters. In this case, status 1 of the data structure shown in FIG. 8 is set at 0000 for each alternate-address information ati as is the case with the normal alternate-address process. Then, at the next step F155, each alternate-address information ati generated in this way is added to the TDFL. If the alternate-address process is a process carried out on a plurality of physically continuous alternate source and alternate destination clusters, on the other hand, the flow of the processing goes on to a step F152 at which, first of all, alternate-address information ati is generated for clusters at the beginnings of the alternate source and alternate destination clusters, and status 1 of the alternate-address information ati is set at 0101. Then, at the next step F153, alternate-address information ati is generated for clusters at the ends of the alternate source and alternate destination clusters, and status 1 of the alternate-address information ati is set at 1010. Then, at the next step F155, the two pieces of alternate-address information ati generated in this way are added to the TDFL. By carrying out the processing described above, even an alternate-address process for three or more physically continuous clusters can be managed by using only two pieces of alternate-address information ati. 5-2: Data Fetching By referring to a flowchart shown in FIG. 21, the following description explains processing carried out by the system controller 60 to reproduce data from the disk 1 mounted on the disk drive. Assume that the system controller 60 receives a request to read out data recorded at an address specified in the request from a host apparatus such as the AV system 120. In this case, the flowchart representing the processing begins with a step F201 at which the system controller 60 refers to a space bitmap to determine whether or not data has been stored in the address specified in the request. If no data has been stored in the address specified in the request, the flow of the processing goes on to a step F202 at which an error report indicating that the specified address is an incorrect address is returned to the host apparatus. If data has been stored in the address specified in the request, on the other hand, the flow of the processing goes on to a step F203 at which the TDFL is searched for alternate-address information ati including the specified address as an alternate source address in order to determine whether or not an entry including the specified address has been cataloged on the TDFL. If alternate-address information ati including the specified address as an alternate source address is not found in the search, the flow of the processing goes on from the step F203 to a step F204 at which data is reproduced from an area starting at the specified address before ending the execution of the processing, which is a normal process to reproduce data from the user-data area. If the determination result obtained at the step F203 indicates that alternate-address information ati including the specified address as an alternate source address has been found in the search, on the other hand, the flow of the processing goes on from the step F203 to a step F205 at which an alternate destination address is acquired from the alternate-address information ati. This alternate destination address is an address in an ISA or an OSA. Then, at the next step F206, the system controller 60 reads out data from the ISA or OSA address, which has been cataloged in the alternate-address information ati as an alternate destination address, and transfers the reproduced data to the host apparatus such as the AV system 120 before ending the execution of the processing. By carrying out the processing described above, even if a request to reproduce data is received after the data has been renewed, the most recent data can be reproduced appropriately and transferred to the host. 5-3: Updating of the TDFL/Space Bitmap In the processing described above, the TDFL stored in the cache memory 60a is updated in case the process to write data into a cluster is accompanied by an alternate-address process and the space bitmap also stored in the cache memory 60a is updated to reflect the data write process. At a certain point of time, the updated TDFL and space bitmap need to be transferred to the TDMA recorded on the disk 1. That is to say, it is necessary to update the state of management based on alternate-address processes and the recording state, which are states recorded on the disk 1. It is most desirable to update the TDMA recorded on the disk 1 at a point of time the disk 1 is about to be ejected from the disk drive even though the timing to update the TDMA is not limited to the timing to eject the disk 1. Besides the timing to eject the disk 1, the TDMA can also be updated when the power supply of the disk drive is turned off or updated periodically. FIG. 22 shows a flowchart representing process to update the TDMA recorded on the disk 1. At an ejection time or the like, the system controller 60 determines whether or not it is necessary to update the contents of the TDMA, that is, whether or not it is necessary to catalog the updated TDFL or space bitmap in the TDMA. If necessary, a process to update information in the TDMA is carried out. At an ejection time or the like, the system controller 60 carries out processing to update the TDFL and/or the space bitmap. This processing starts at a step F301 of the flowchart shown in FIG. 22. The flowchart actually begins with a step F302 to determine whether or not the TDFL stored in the cache memory 60a has been updated. If the TDFL has been updated, the flow of the processing goes on to a step F303 at which a TDDS shown in FIG. 12 is added to the updated TDFL, being recorded in the last sector of the TDFL. Then, at the next step F304, the optical pickup 51 is driven to record the TDFL at the beginning of a free area in the TDMA recorded on the disk 1. It is to be noted that, at that time, since data is newly recorded in the TDMA, the space bitmap stored in the cache memory 60a is also updated. Then, after the TDFL is recorded in the TDMA, the flow of the processing goes on to a step F305. The flow of the processing also goes on to the step F305 from the step F302 because the TDFL was not updated. In either case, the space bitmap stored in the cache memory 60a is checked to determine whether or not the bitmap has been updated. If the TDFL has been updated as described above, at least, the space bitmap has also been updated at that time. This is because an alternate-address process has been carried out so that the space bitmap has also been updated as well in accordance with the alternate-address process. In addition, the space bitmap is also updated in accordance with an operation to record data in a cluster even if no alternate-address process has been carried out. If the space bitmap stored in the cache memory 60a has been updated in one of the situations described above, the flow of the processing goes on to a step F306, at which the TDDS shown in FIG. 12 is added to the updated space bitmap stored in the cache memory 60a, being recorded in the last sector of the space bitmap. Then, at the next step F307, the optical pickup 51 is driven to record the space bitmap at the beginning of a free area in the TDMA recorded on the disk 1. Finally, the execution of the processing to record the updated TDFL and/or the updated space bitmap in the TDMA at an ejection time or the like is ended. It is to be noted that, if no data has been written into the disk 1 at all since the disk 1 was mounted on the disk drive, the flow of the processing represented by the flowchart shown in FIG. 22 goes from the step F302 to the end by way of the step F305 without recording an updated TDFL and/or an updated space bitmap in the TDMA. At the steps F304 and F307, the TDFL and the space bitmap are recorded sequentially at the beginning of a free area in the TDMA recorded on the disk 1 as explained earlier by referring to FIGS. 14 and 15. In the case of a two-layer disk, the TDMA on layer 0 is used first as an area for recording the TDFL and the space bitmap and, after no more free area is left in the TDMA on layer 0, the TDMA on layer 1 is used. In addition, in the case of both the one-layer disk and the two-layer disk, a TDDS added to the last TDFL or space bitmap in the TDMA, being recorded in the last sector of the last TDFL or the last sector of the last space bitmap is the effective TDDS, which points to the effective TDFL and the effective space bitmap. By the way, when a TDFL is additionally recorded in the TDMA at the step F303, F304, a technique may also be adopted as a conceivable technique for restructuring pieces of alternate-address information ati stored in the cache memory 60a. FIG. 23 shows a flowchart representing a typical alternate-address information restructure process. This process can be carried out typically before the step F303 of the flowchart shown in FIG. 22. At a step F351, pieces of alternate-address information ati cataloged on the TDFL stored in the cache memory 60a are searched to verify whether or not the following condition exists. The source and destination clusters represented by specific pieces of alternate-address information ati are respectively physical continuation of the source and destination clusters represented by the other specific pieces of alternate-address information ati. If such specific pieces of alternate-address information ati were not been found in the search, the flow of the processing goes from the step F352 back to the step F303 of the flowchart shown in FIG. 11 without carrying out any process. If such two specific pieces of alternate-address information ati were found in the search, on the other hand, the flow of the processing goes on to a step F353 at which the specific pieces of alternate-address information ati are synthesized for the purpose of restructuring them. The steps F352 and F353 are executed repeatedly to synthesize any pair of such specific pieces of alternate-address information ati. After all such specific pieces of alternate-address information ati are processed, the flow of the processing goes from the step F352 back to the step F303. FIG. 24 is an explanatory diagram showing the alternate-address information restructure process. Assume for example that, as shown in FIG. 24A, requests to write data into clusters CL1, C12, C13 and C14 are received separately, and data is written into clusters CL11, C112, C113 and C114 respectively in an OSA through an alternate-address process. In this case, since the four requests to write data into the clusters are received separately, four pieces of alternate-address information ati are each cataloged as an entry having status 1 of 0000 as shown in FIG. 24B. However, two pieces of alternate-address information ati having status 1 of 0101 and status 1 of 1010 respectively can be applied to four alternate-address continuous destination clusters CL1, C12, C13 and C14 and four alternate-address continuous source clusters CL11, C112, C113 and C114 used in this example. Thus, as shown in FIG. 24C, the four entries can be restructured into a start entry with status 1 of 0101 indicating start source cluster C11 as well as start destination cluster C111 and an end entry with status 1 of 1010 indicating end source cluster C14 as well as end destination cluster C114. As a result, the number of pieces of alternate-address information ati recorded on the disk 1 can be reduced. It is to be noted that such restructuring of alternate-address information can of course be applied to any pair of entries with status 1 of 0101 and 1010 indicating a plurality of continuous source and a plurality of destination clusters as described above. For example, a first pair of entries represents a plurality of first continuous source clusters and a plurality of first continuous destination clusters. By the same token, a second pair of entries is a pair provided for a plurality of second continuous source clusters and a plurality of second continuous destination clusters. If the second continuous source clusters are a continuation of the first continuous source clusters and the second continuous destination clusters are a continuation of the first continuous destination clusters, the first pair of entries and the second pair of entries can be restructured into a new pair of entries. In addition, if a plurality of continuous source and destination clusters represented by a pair of entries with status 1 of 0101 and status 1 of 1010 as described above are respectively continuations of source and destination clusters represented another entry with status 1 of 0000, the pair of entries can be restructured into a new pair including the other entry. 5-4: Conversion into Compatible Disks By the way, in a writable optical disk, management of alternate addresses is executed by using alternate-address management information stored in the DMA recorded on the disk. That is to say, unlike the disk 1 provided by the embodiment, a TDMA is not provided so that the alternate-address management information stored in the DMA itself is renewed to keep up with an executed alternate-address process. The data structure of the DMA recorded on a writable optical disk is the same as the DMA recorded on the disk 1 provided by the embodiment. In the write-once optical disk provided by the embodiment, on the other hand, data can be written into an area including the TDMA only once so that the embodiment must adopt a technique to update the TDMA by adding alternate-address management information to the TDMA. Thus, in order make a disk drive for a writable optical disk capable of reproducing data from the disk 1 provided by the embodiment, it is necessary to reflect most recent alternate-address management information recorded in the TDMA in the DMA. In addition, in the case of a writable optical disk or the like, alternate-address information ati is recorded in the DMA for each cluster even if an alternate-address process is carried out on clusters located in a contiguous area. In the case of a write-once optical disk like the one provided by the present invention, that is, in the case of a disk with a recording capacity decreasing due to data written therein, however, it is specially important to effectively utilize the limited area of the TDMA. It is thus desirable to adopt a method of not increasing the size of the TDFL even in an alternate-address process carried out on clusters of a contiguous area. Thus, instead of including all cluster addresses completing an alternate-address process as alternate-address information ati in the temporary defect management information TDFL recorded in the TDMA, a burst-transmission format represented by a pair of entries with status 1 of 0101 and status 1 of 1010 as described above is adopted so as to reduce the number of pieces of recorded alternate-address information ati. That is to say, if addresses of three or more continuous clusters are subjected to an alternate-address process, a contiguous area is allocated as alternate-address destinations for the addresses so that only two entries of the alternate-address information ati need to be cataloged on the TDFL. In the case of a write-once optical disk provided by the embodiment, alternate-address information ati is cataloged on the TDFL every time an alternate-address process is carried out. Thus, the size of information cataloged on the TDFL changes. That is to say, as the number of clusters subjected to the alternate-address process increases, the size of information cataloged on the TDFL also rises. By collecting a plurality of continuous clusters subjected to an alternate-address process into a group of clusters dealt with by carrying out the alternate-address process only once as described above, however, the increase in TDFL used area can be reduced. If compatibility of the write-once optical disk implemented by the embodiment with the writable optical disk is taken into consideration, it is desirable to provide the write-once optical disk with the format of a DFL in the DMA identical with the corresponding format in the writable optical disk. The DFL in the DMA is obtained as a result of conversion of a TDFL recorded in the TDMA. To put it concretely, it is desirable to record all pieces of alternate-address information ati in a format with status 1 set at 0000. By using such a format, it is not necessary for the disk drive to switch processing related to information stored in the DMA from one compatible with the write-once optical disk to one compatible with the writable optical disk or vice versa so that a processing load borne by the disk driver can be reduced. For the reason described above, when information recorded in the TDMA is transferred to the DMA recorded on the disk 1, processing represented by a flowchart shown in FIG. 25 is carried out. It is to be noted that the information transferred to the DMA is final alternate-address management information so that data can no longer be renewed by using the TDMA. Thus, the processing to transfer information recorded in the TDMA to the DMA recorded on the disk 1 is carried out typically as a finalize-time process. In addition, the processing to transfer information recorded in the TDMA to the DMA recorded on the disk 1 means a process to convert the disk 1 into a disk having compatibility with a writable optical disk. When the processing to transfer information recorded in the TDMA to the DMA to convert the disk 1 into a disk having compatibility with a writable optical disk is carried out, first of all, at a step F401 of the flowchart shown in FIG. 25, the system controller 60 carries out a process to transfer a TDFL and/or a space bit map from the cache memory 60a to the TDMA. Since this process is similar to the process represented by the flowchart shown in FIG. 22 as processing carried out at an injection time or the like, its detailed description is not repeated. Then, at the next step F402, the most recent TDDS recorded in the last sector of the TDMA is read out to create information of the DDS shown in FIG. 5. Subsequently, the flow of the processing goes on to the next step F403 to determine whether or not the TDFL includes one or more pieces of alternate-address information ati. Thus, first of all, the most recent TDFL is read out from the TDMA. As explained earlier by referring to FIG. 14, information on the recording location of the effective TDFL can be obtained from the TDDS. The number of cataloged pieces of alternate-address information ati can be obtained from the defect-list management information of the TDFL as the number of cataloged DFL entries. The number of cataloged pieces of alternate-address information ati set at 0 indicates that no alternate-address information ati is cataloged. In this case, the flow of the processing goes on to a step F404 at which the TDDS is deleted from the TDFL to leave data for creating a DFL like the one shown in FIG. 6. This is because, as shown in FIG. 11, the TDFL includes the TDDS. Then, at the next step F408, the created DDS and DFL are recorded in DMA 1, DMA2, DMA 3 and DMA 4, which have been allocated on the disk 1, before the execution of the processing is ended. If the determination result obtained at the step F403 indicates that the number of cataloged pieces of alternate-address information ati is 1 or greater, on the other hand, the flow of the processing goes on to a step F405 to determine whether or not an alternate-address process has been carried out on continuous alternate-address source and destination areas. At the step F405, first of all, status 1 of alternate-address information ati cataloged on the TDFL as an entry is fetched. Alternate-address information ati with status 1 of 0101 indicates that an alternate-address process has been carried out on continuous alternate-address source and destination areas represented by the alternate-address information ati. On the other hand, all the entries cataloged on the TDFL having status 1 of 0000 indicate that no alternate-address process has been carried out on continuous alternate-address source and destination areas. In this case, the flow of the processing goes on to a step F406 at which the TDDS is deleted from the TDFL to leave data for creating a DFL. If an alternate-address process has been carried out on continuous alternate-address source and destination areas, first of all, at a step F409, entries with status 1 of 0000 are copied to the DFL. These entries each represent alternate-address information ati for an alternate-address process carried out on a normal one-to-one pair consisting of a source cluster and a destination cluster. Then, at the next step F410, alternate-address information ati with status 1 of 0101 is acquired and the alternate source address in the alternate-address information ati is saved as a start address SA. Then, alternate-address information ati following the alternate-address information ati with status 1 of 0101 is acquired and the alternate source address in the following alternate-address information ati is saved as an end address EA. Then, at the next step F411, alternate-address information ati with status 1 of 0000 is cataloged on the DFL as alternate-address information ati including the start address SA as the alternate source address. Subsequently, the start address SA is incremented by 1 (SA=SA+1). Then, alternate-address information ati with status 1 of 0000 is cataloged on the DFL as alternate-address information ati including the incremented start address (SA+1) as the alternate source address. These processes are carried out repeatedly till the incremented start address SA reaches the end address EA. By carrying out these processes repeatedly as described above, alternate-address information ati representing continuous alternate-address source and destination areas is cataloged on the DFL as a plurality of entries each describing alternate-address information ati representing a normal one-to-one pair consisting of a source cluster and a destination cluster. Then, at the next step F412, the TDFL is searched for other alternate-address information entry with status 1 of ‘0101’. If such an entry is found in the search, the flow of the processing goes back to the step F410 to repeat the processes described above. That is to say, the processes of the steps F410 and F411 are carried out on all pieces of alternate-address information ati with status 1 of 0101 on the TDFL. Then, the flow of the processing goes on from the step F406 or the step F412 to a step F407 at which the pieces of alternate-address information ati cataloged on the created DFL are rearranged in an order of increasing alternate source addresses. Then, at the next step F408, the created DDS and DFL are recorded in DMA 1, DMA 2, DMA 3 and DMA 4, which have been allocated on the disk 1, before the execution of the processing is ended. By carrying out the processing described above, alternate-address information recorded in the TDMA is recorded in the DMA by converting the information into entries each having status 1 of 0000. The disk drive designed for a writable optical disk reads out information from the DMA to verify the state of the alternate-address process. Since the disk 1 provided by the embodiment is converted into a disk having a DMA created as described above; it is possible to verify the state of the alternate-address process and carry out processing in accordance with the state in the same way as the ordinary writable optical disk. 6: Effects of the First TDMA Method The disk 1 and the disk drive, which are implemented by the embodiment, have the following effects. In accordance with the embodiment, a write request can be made more than once to write data at the same address in a write-once optical disk. Thus, it is possible to apply a file system, which used to be unusable, to the conventional write-once optical disk. For example, a file system for a variety of operating systems (OS) can be applied as it is. An example of such a file system is a FAT file system. In addition, data can be exchanged without being conscious of differences in OS. On top of that, the write-once optical disk makes it possible to renew not only user data but, of course, directory information of the FAT or the like recorded in the user-data area. Thus, the write-once optical disk provides convenience that data such as directory information of the FAT or the like can be updated from time to time. Assuming that the AV system 120 is used, video and musical data can be utilized as updateable media as long as a free area of an ISA or an OSA remains. In addition, an operation to record data into an address specified by a host computer or the like as an address in the write-once optical disk or read out data from such an address is a heavy processing load for the disk drive. If a write instruction specifying an address is received and the address is known as an address at which data has already been recorded before, an error report can be returned without actually making an access to the write-once optical disk. In order to implement such a configuration, it is necessary to manage the recording states of the write-once optical disk and, in this embodiment, a space bitmap is used as means for implementing the management of the recording states. By preparing a space bitmap, random recording on a write-once optical disk having a large storage capacity can be implemented without imposing a processing load on the disk drive. In addition, since recording states of alternate areas can be managed, an alternate destination address used in an alternate-address process of a defect or a logical overwriting process can be acquired without actually making an access to the write-once optical disk. On top of that, by using the space bitmap for managing management/control information areas allocated on the disk as the lead-in and the lead-out zones, recording states of the management/control information can also be managed. In particular, the management of the test area OPC serving as an area for adjusting the power of the laser beam is effective. With the conventional technique, an access must be actually made to the disk in order to search the disk for the address included in the OPC as an address at which data should be written. It is thus quite within the bounds of possibility that an area in which data has been recorded by using a small laser power is interpreted as an unrecorded area. By using the space bitmap for also managing the OPC area, however, it is possible to avoid such misinterpretation. By combining the overwrite function described before with the space bitmap, the processing load borne by the disk drive can be reduced. That is to say, as is obvious from the pieces of processing represented by the flowcharts shown in FIGS. 17 to 21, without actually making an access to the disk, it is possible to determine whether or not the overwrite function is to be activated. In addition, by putting a defective area detected at a write time and surroundings of the area in recorded status in the space bitmap, it is possible to eliminate a time-consuming process to record data at a defective address caused by an injury. In addition, by combining this feature of the space bitmap and the overwrite function, it is possible to carry out a write process, which appears to the host as a process having no write error. On top of that, an updated TDML serving as alternate address management information and an updated space bitmap are additionally recorded in the TDMA and, at the same time, information indicating the effective TDFL and/or the effective space bitmap is also recorded as well. Thus, the effective TDFL and/or the effective space bitmap can be identified at each point of time. That is to say, the disk drive is capable of correctly grasping the updating state of the alternate-address management information. In addition, the fact that the space bitmap is recorded in the TDMA means that the data zone serving as a main area for recording the space bit map is not used. For example, the ISA or the like is not used. Thus, it is possible to carry out an alternate-address process effectively utilizing a data zone and any one of an ISA and an OSA, which each serve as an alternate-address area. For example, either an ISA or an OSA is selected as an alternate-address area to be used in an alternate-address process typically on the basis of preference of an area closer to the alternate source address. By selecting either an ISA or an OSA in this way, an operation to make an access to data completing the alternate-address process can be made efficient. On top of that, in an operation to write data onto the disk 1, data may not be written into a specified area due to a defect detected in the area and, if data is received continuously thereafter, by carrying out an alternate-address process, the write operation can be continued without returning an error report. For clarity, refer to the flowcharts shown in FIGS. 17 and 18. In addition, if an operation to write data into a specified area cannot be carried out due to a defect detected in the area, in many cases, areas surrounding the defective area are most likely also areas into which data cannot be recorded. In this case, a write process can be carried out as a process assuming that predetermined areas following the defective area are also defective areas to which no access is actually made. If data for these areas has already been received by the disk drive, an alternate-address process can be carried out on the areas. In this case, even if three or more continuous clusters are subjected to an alternate-address process, alternate-address information ati can be cataloged on the TDFL only as two entries so that the size of the used write area can be reduced. On top of that, by carrying out a process on the space bitmap to treat a processed area as an area, in which data has been written in this way, an illegal access can be avoided. If no data for areas following an area, in which data cannot be written, has been received by the disk drive, on the other hand, predetermined ones of the following areas are cataloged on the TDFL as defective clusters each having an allocated alternate destination and treated on the space bitmap as areas, in which data has already been written. If an instruction to write data into such an area is received from the host thereafter, the disk drive refers to the space bitmap to find out that the area is an area, in which data has already been written. In this case, the overwrite function can be executed to record the data without generating an error. In addition, since the DMA has the same data structure as the writable disk, data can be reproduced by a reproduction system from the disk provided by the embodiment even if the reproduction system designed for a writable disk is used. 7: Second TDMA Method 7-1: TDMAs Next, a second TDMA method is explained. It is to be noted that, basically, the second TDMA method has a number of similarities to the first one described so far. Thus, only differences between the two methods are mainly explained. The structure of the disks are the same as those shown in FIGS. 1 to 3. In addition, the data structures of the DMA are also the same as those shown in FIGS. 4 to However, the second TDMA method is different from the first one in that, in the case of the second TDMA method, a space bitmap is not recorded in the TDMA. Instead, a space bitmap is recorded in the ISA. The data structure of the TDMA is shown in FIG. 26. The size of the TDMA is 2,048 clusters. One to four clusters identified by cluster numbers 1 to 4 are used as clusters for recording a TDFL (temporary defect list). A cluster identified by cluster number n is used as a cluster for recording a TDDS (temporary disk definition structure), which is detailed information on the optical recording medium. In the TDMA, the TDFL and the TDDS are recorded as a set. If an updated set is additionally recorded in the TDMA, the set is written at the beginning of a free area in the TDMA. That is to say, the updated set is recorded in an area immediately following a recorded TDDS. Not shown in a figure, the data structure of the TDFL having a size in the range one to four bytes is all but the same as that shown in FIG. 11. In the case of the second TDMA method, however, unlike the first method, a TDDS is not recorded in the last sector of the TDFL. That is to say, the area following the alternate-address information ati terminator as shown in FIG. 11 is all filled up with codes of 00h. Thus, the TDDS is recorded in a cluster different from the clusters used for recording the TDFL as shown in FIG. 26. The data structure of the defect-list management information included in the TDFL is exactly the same as that shown in FIG. 7. In addition, the data structure of the alternate-address information ati is entirely identical with that shown in FIG. 8. A pair of pieces of alternate-address information ati with values of status 1 set at 0101 and 1010 is interpreted as a pair of entries representing a plurality of continuous clusters serving as an alternate source and a plurality of continuous clusters serving as an alternate destination. FIG. 27 is a diagram showing the data structure of the TDDS, which is recorded in a cluster other than clusters for recording the TDFL. In this case, the size of the TDDS is one cluster, which is the same as the DDS shown in FIG. 5. The contents of the TDDS are all but the same as those explained before by referring to FIG. 5. As is obvious from comparison of the data structures shown in FIGS. 5 and 27, however, bytes starting with a byte at byte position 4 are bytes used for recording the sequence number of the TDDS, bytes starting with a byte at byte position 16 are bytes used for recording the physical address of the first sector in a drive area inside the TDMA and bytes starting with a byte at byte position 24 are bytes used for recording the physical address AD_DFL of the first sector in the TDFL inside the TDMA. It is to be noted that, in the case of a two-layer disk, a TDMA is provided for each of layers 0 and 1. Much like the first TDMA method described above, it is possible to adopt a TDMA-utilizing technique whereby, first, the TDMA provided for layer 0 is used as a TDMA for updating the TDFL and the TDDS and, as the TDMA provided for layer 0 is used up entirely, the TDMA provided for layer 1 is used. 7-2: ISAs and OSAs FIG. 28 is a diagram showing an ISA and an OSA. In the case of this embodiment, only the OSA is used as an alternate area. The ISA is used as an area for recording space bitmaps. The sizes of the ISA and the OSA are defined in the DDS and the TDDS. The size of the ISA is determined at an initialization time and remains constant thereafter. However, the size of the OSA can be changed even after data is recorded in the OSA. When recording data into the OSA in an alternate-address process, the data is written in an area starting with the last cluster of the OSA in a direction toward the cluster at the beginning of the OSA without skipping any clusters located between the last and the beginning clusters. The ISA is used one cluster after another starting with the cluster at the beginning of the ISA as an area for recording space bitmaps SBM#1 to SBM#5 as shown in the figure. To put it in detail, much like the first TDMA method described earlier, the size of a space bitmap is one cluster and the first space bitmap is recorded in the first cluster. When the space bitmap is updated thereafter, the updated space bitmap is recorded as a new bitmap at the beginning of the free area of the ISA, that is, in the area immediately succeeding the last recorded space bitmap, without creating a free space between the last recorded space bitmap and the new space bitmap. Thus, the last space bitmap among bitmaps recorded in the ISA becomes the effective information. In the case of the ISA shown in FIG. 28, space bitmap SBM#5 is the effective information. The data structure of the space bitmap is all but the same as that shown in FIG. 10 except that, in the case of the space bitmap for the second TDMA method, unlike the data structure shown in FIG. 10, the last sector is not used as a sector for recording a TDDS. It is to be noted that, in the case of a two-layer disk, a space bitmap provided for layer 0 is recorded in the ISA for layer 0 while a space bitmap provided for layer 1 is recorded in the ISA for layer 1. However, the ISA for layer 0 and the ISA for layer 1 can be regarded as a single area with a large size without regard to whether the space bitmap is a bitmap provided for layer 0 or 1. In this case, the ISA of layer 0 is first used as an area for storing space bitmaps provided for both layers and, as the ISA of layer 0 is used up entirely, the ISA of layer 1 is used. By the way, when a disk 1 provided by this embodiment as a disk with an ISA thereof used for recording space bitmaps is mounted on another disk drive, it is necessary to prevent the ISA from being used inadvertently as an alternate area. In order to prevent such an ISA from being used inadvertently as an alternate area, spare area full flags of the TDDS shown in FIG. 27 are used. In the case of a one-layer disk, the spare area full flags having a size of 1 byte has a format shown in FIG. 29A. In the case of a two-layer disk, on the other hand, the spare area full flags having a size of 1 byte has a format shown in FIG. 29B. First of all, in the case of a one-layer disk shown in FIG. 29A, bits b7 to b2 are reserved. A bit b1 is an outer spare area full flag. A value of 1 is set in this outer spare area full flag to indicate that the whole OSA has been filled up with data recorded therein. A bit b0 is an inner spare area full flag. A value of 1 is set in this inner spare area full flag to indicate that the whole ISA has been filled up with data recorded therein. In the case of a two-layer disk shown in FIG. 29B, on the other hand, in addition to bits b1 and b0 of a one-layer disk, bits b2 and b3 are respectively an OSA full flag and ISA full flag of the second layer. In this case, bits b0 and b1 are respectively an OSA full flag and ISA full flag of the first layer. Thus, if a space bitmap is recorded in an ISA as is the case with this embodiment, the inner spare area full flag provided for the ISA is set at 1. By doing so, since the disk 1 appears to another disk drive as a disk with no free area left in the ISA, the other disk drive can be prevented from using the ISA for an alternate-address process. 8: Operations for the Second TDMA Method 8-1: Data Writing In the case of the second TDMA method, the system controller 60 carries out data-writing processing represented by a flowchart shown in FIG. 30. Also in the case of the second TDMA method, it is assumed that, at a point of time the data-writing processing described below is about to be carried out, the disk 1 has been mounted on the disk drive and a TDFL, a TDDS and a space bitmap have been transferred from the TDMA recorded on the mounted disk 1 to the cache memory 60a. In addition, explanation of a process to convert a logical address into a physical address from time to time is also omitted from the following description. Let the system controller 60 receive a request to write data at a certain address from a host apparatus such as the AV system 120. In this case, the system controller 60 starts the processing represented by the flowchart shown in FIG. 30. The flowchart begins with a step F501 at which the system controller 60 refers to the space bitmap stored in the cache memory 60a (or the recent bitmap updated in the cache memory 60a) to determine whether or not data has been recorded at the address specified in the write request. If no data has been recorded at the specified address, the flow of the processing goes on from the step F502 to a step F503, at which a normal write process is carried out to execute a command to write data at the address. That is to say, at the F503, the system controller 60 executes control to write data at the specified address. In other words, the optical pickup 51 is driven to make an access to the specified address and record the data to be written as requested at the specified address. As the data-writing process is normally ended, the flow of the processing goes on to a step F504 at which a space bitmap stored in the cache memory 60a is updated. That is to say, a bit allocated in the space bitmap to a cluster in which the data has been written is set at a value indicating that data has been written in the cluster. Then, the execution of the processing carried out in response to the write request is ended. If an error is generated in the course of the write processing due to, among other causes, an injury on the disk 1, an alternate-address process may be carried out in some cases. In this case, an alternate-address process like the one explained earlier by referring to the flowchart shown in FIG. 18 is carried out. It is to be noted that a step to carry out this alternate-address process is not included in the description of the flowchart shown in FIG. 30. If the determination result obtained at the step F502 reveals a space bitmap indicating that data has been recorded at the address specified in the write request received from the host apparatus, on the other hand, the flow of the processing goes on to a step F505. At this step, the system controller 60 determines whether or not the function to renew data is effective. It is to be noted that a function to enable the function to renew data will be explained later by referring to a flowchart shown in FIG. 31 If the function to renew data is not effective, the flow of the processing goes on to a step F506 at which an error report is returned to the host apparatus before the execution of the processing is ended. If the function to renew data is effective, on the other hand, the flow of the processing goes on to a step F507 to determine first of all whether or not an alternate-address process for renewing data can be actually carried out. In order to carry out the alternate-address process, the spare area OSA must have a free area for at least recording the data requested in the write operation. In addition, the TDMA must have a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, that is, allowing the TDFL to be updated. If the OSA has a free area and the TDMA has a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, the flow of the processing carried out by the system controller 60 goes on from the step F507 to a step F508 at which the optical pickup 51 is driven to make an access to the OSA and record the data to be written as requested this time in the OSA. Then, at the next step F509, the space bitmap stored in the cache memory 60a is updated. That is to say, a bit allocated in the space bitmap to an OSA cluster including an address at which the data has been written in an alternate-address process carried out to renew data is set at a value indicating that data has been written in the cluster. Subsequently, at the next step F510, the TDFL stored in the cache memory 60a is updated. That is to say, alternate-address information ati representing the alternate-address process carried out this time is newly added as an entry to the TDFL. As an alternative, if alternate-address information ati including the same alternate source address as the address specified in the write request already exists as an entry in the TDFL, this entry is renewed. In addition, an entry count included in the defect-list management information as a count representing the number of cataloged DFL entries is incremented in case alternate-address information ati is newly added to the TDFL, and the number of unused OSA clusters is decremented. Then, the execution of the processing carried out in response to the write request is ended. By carrying out the processing to use the OSA as described above, the system controller 60 is capable of coping with a request to write data into an address, at which data has already been recorded before, that is, coping with a request to renew data. If the determination result obtained at the step F507 indicates that the OSA does not have a free area for at least recording the data requested in the write operation or the TDMA does not have a margin allowing an entry of the alternate-address information ati for managing this alternate-address process to be added, on the other hand, an alternate-address process cannot be carried out. In this case, the flow of the processing goes on to a step F511 at which an error report indicating that there is no area for writing the data is returned to the host apparatus before the execution of the processing is ended. It is to be noted that alternate-address information ati can be newly generated at the step F510 to reflect the executed alternate-address process by carrying out the processing represented by the flowchart shown in FIG. 20. It is also worth noting that, if the ISA used as an area for recording a space bitmap does not include a free area, a recording operation for updating the space bitmap cannot be carried out. In this case, the following typical countermeasures can be taken to allow a process of recording user data to be carried out: When a disk with the ISA thereof including recorded space bitmaps but having no left free area is mounted on the disk drive, the disk drive checks an RF signal serving as a reproduced-data signal for a free area available on the disk on the basis of the most recent space bitmap and reconstructs the space bitmaps. For a disk with the ISA thereof including recorded space bitmaps but having no left free area, the disk drive allows only limited write operations (or sequential write operations) to be carried out to record data in an area following the last address of recorded user data. By the way, in the case of the present embodiment, the ISA is used as a spare area for recording space bitmaps. Thus, it is necessary to make the data renewal function effective or ineffective in dependence on whether or not the disk 1 mounted on the disk drive is a disk allowing the ISA to be used as a spare area for recording space bitmaps. At the step F505, the system controller 60 determines whether or not the function to renew data has been put in effective status, which is set by the processing represented by the flowchart shown in FIG. 31. The processing to set the data renewal function as represented by the flowchart shown in FIG. 31 is carried out typically when the disk 1 is mounted on the disk drive. When the disk 1 is mounted on the disk drive, the system controller 60 checks the TDDS of the disk 1 to examine bit b0 of the spare area full flags provided at byte position 52 at a step F601. As described earlier by referring to FIGS. 29A and 29B, in the disk 1 provided by the present embodiment as a disk including the ISA used as an area for recording space bitmaps, bit b0 is set at 1. Even in the case of a disk including the ISA used as an alternate area, bit b0 is set at 1 as the entire ISA is used up. That is to say, at least, if the disk is a disk provided by the present embodiment, bit b0 is set at 1 and, if the disk is not a disk provided by the present embodiment, bit b0 is set at 0 or 1. Thus, at least, if bit b0 is set at 0, the disk is not a disk provided by the present embodiment. Thus, if bit b0 is set at 0, the flow of the processing goes on to a step F604 at which the function to renew data is turned off. In this case, the disk drive is not capable of carrying out an alternate-address process and a process to record a space bitmap on this disk. That is to say, the steps F507 to F511 of the flowchart shown in FIG. 30 are not executed. In addition, the step F504 of the flowchart shown in FIG. 30 to update a space bitmap for the case of an ordinary write operation is also not executed. However, details of operations for a disk not provided by the present embodiment are not explicitly included in the flowchart shown in FIG. 30. Thus, the data renewal operation of the present embodiment is not carried out even though the state of the ISA and the reproduction compatibility are maintained. If the examination result obtained at the step F601 indicates that bit b0 is 1, on the other hand, the flow of the processing goes on to a step F602 at which the last cluster of the ISA is examined. This is because it is quite within the bounds of possibility that the disk mounted on the disk drive is the disk provided by the present embodiment. If the last cluster of the ISA is a cluster for recording a space bitmap, the flow of the processing goes on from the step F603 to a step F605 to read out the space bitmap and store the bitmap in the cache memory 60a. Then, at the next step F606, the function for renewing data is made effective. If the examination result obtained at the step F603 reveals that the last cluster of the ISA is determined to be not a cluster for recording a space bitmap, on the other hand, the flow of the processing goes on to the step F604 at which the function to renew data is made ineffective. By carrying out the processing to set the status of the data renewal function described above, the function to renew data is made effective for a disk provided by the present invention as a disk including an ISA as an area for recording a space bitmap. In the case of a disk using the ISA as an alternate area, on the other hand, the ISA is not used as an area for recording a space bitmap and the data renewal function provided by the present embodiment is not made effective either. An example of the disk using the ISA as an alternate area is a disk containing data recorded by another disk drive. 8-2: Data Fetching By referring to a flowchart shown in FIG. 32, the following description explains processing carried out by the system controller 60 employed in the disk drive to reproduce data from the disk 1 at a reproduction time. Assume that the system controller 60 receives a request specifying an address in the disk 1 to read out data recorded at the address from a host apparatus such as the AV system 120. In this case, the system controller 60 carries out the processing starting at a flowchart step F701 at which the space bitmap is referred to in order to determine whether or not data has been recorded in the address specified in the request. If no data has been recorded in the address specified in the request, the flow of the processing goes on to a step F702 at which an error report indicating that the specified address is an incorrect address is returned to the host apparatus, and the execution of the processing is ended. If data has been recorded in the address specified in the request, on the other hand, the flow of the processing goes on to a step F703 at which the TDFL is searched for alternate-address information ati including an alternate source address matching the address specified in the request. If no alternate-address information ati including an alternate source address matching the address specified in the request was found in the search, the flow of the processing goes on from the step F703 to a step F704 at which the data is reproduced from the specified address before the execution of the processing is ended. This completed processing is a normal reproduction process to reproduce data from the user-data area. If the search result obtained at the step F703 indicates that there is alternate-address information ati including an alternate source address matching the address specified in the request, on the other hand, the flow of the processing goes on from the step F703 to a step F705 at which an alternate source address is extracted from the alternate-address information ati. That is to say, an address in the OSA is acquired. Then, at the next step F706, the system controller 60 executes control to read out the data from the acquired address in the OSA or the alternate source address extracted from the alternate-address information ati, and transfer the reproduced data to the host apparatus such as the AV system 120 before ending the execution of the processing. By carrying out the processing described above, most recent data can be correctly reproduced and transferred to the host apparatus in response to even a data reproduction request made by the host after renewal of the data. 8-3: Updating of the TDFL/Space Bitmap and Conversion into Compatible Disks Much like the first TDMA method described before, an updated TDFL and space bitmap are transferred from the cache memory 60a to the disk 1 at a predetermined point of time such as the time the disk 1 is ejected from the disk drive. In the case of the second TDMA method, alternate-address management information (including the TDFL and the TDDS) as well as a space bitmap are transferred from the cache memory 60a to the disk 1 in processing represented by a flowchart shown in FIG. 33. The flowchart begins with a step F801 at which the system controller 60 determines whether or not the TDFL stored in the cache memory 60a has been updated. If the TDFL stored in the cache memory 60a has been updated, the flow of the processing goes on to a step F802 at which the TDFL is recorded at the beginning of a free area in the TDMA recorded on the disk 1. Then, at the next step F803, the TDDS is recorded at the beginning of a free area in the TDMA recorded on the disk 1. It is to be noted that, when the TDFL and the TDDS are recorded in the TDMA, the space bitmap stored in the cache memory 60a may need to be updated to reflect the recording. At a step F804, the space bitmap stored in the cache memory 60a is examined to determine whether or not the bitmap has been updated. If the space bitmap stored in the cache memory 60a has been updated, the flow of the processing goes on to a step F805 at which the space bitmap is transferred from the cache memory 60a to the beginning of a free area in the ISA recorded on the disk 1. As described above, the TDFL and the TDDS are recorded in the TDMA whereas the space bitmap is recorded in the ISA so that alternate-address information and information indicating whether or not data has been recorded in each cluster are reflected in the disk 1. In addition, the TDFL and the TDDS are updated in the TDMA but, in order to maintain reproduction compatibility with writable disks, information recorded in the TDMA is transferred to the DMA at a finalize time. At that time, the most recent TDFL and the most recent TDDS are recorded in the DMA. However, it is necessary to convert all pieces of alternate-address information ati with status 1 other than 0000 into pieces of alternate-address information ati with status 1 of 0000 by carrying out the processes of the steps F405 to F407 of the flowchart shown in FIG. 25. 9: Effects for the Second TDMA Method Even by adopting the second TDMA method described above, basically, the same effects as the first TDMA method can be obtained. In the case of the present embodiment, space bitmaps are stored in the ISA. Since the disk layout is not changed, however, the present embodiment is good from the standpoint of compatibility with existing disks. In addition, for the ISA used as an area for recording space bitmaps, the spare area full flag is set at 1 so as to prevent another disk drive from using the ISA as an alternate area. Since no space bitmaps are recorded in the TDMA, the TDMA can be used effectively as an area for updating the TDFL and the TDDS. That is to say, the alternate-address management information can be updated more times to keep up with a larger number of data renewals. Disks provided by preferred embodiments and disk drives designed for the disks have been described so far. However, the scope of the present invention is not limited to the preferred embodiments. That is to say, a variety of modifications within the range of essentials of the present invention are conceivable. For example, as a recording medium of the present invention, a recording medium other than the optical-disk medium can be used. Examples of the recording medium other than the optical-disk medium are a magneto-optical disk, a magnetic disk and media based on a semiconductor memory. As is obvious from the above descriptions, the present invention has the following effects. In accordance with the present invention, a write-once recording medium can be used virtually as a recording medium allowing data already recorded thereon to be renewed. Thus, a file system such as a FAT file system for a writable recording medium can be used for a write-once recording medium. As a result, the present invention provides an effect that the usefulness of a write-once recording medium can be enhanced considerably. For example, the FAT file system, which is a standard file system for information-processing apparatus such as a personal computer, allows a variety of operating systems (OS) to reproduce data from a writable recording medium and record data onto only a writable recording medium. By virtue of the present invention, however, the FAT file system can also be applied to a write-once recording medium as it is and allows data to be exchanged without being conscious of differences between operating systems. These features are also good from compatibility-maintenance point of view. In addition, in accordance with the present invention, a write-once recording medium can be used as a writable recording medium as long as an alternate area and an area for updating alternate-address management information remain in the write-once recording medium. Thus, the write-once recording medium can be used effectively. As a result, the present invention provides an effect that resource wasting can be reduced. On top of that, a space bitmap can be referred to as information indicating whether or not data has been recorded in any cluster, which is used as a data unit on each recording layer of the recording medium. In general, a host computer or the like makes a request to record data at an address specified in the request as an address in a recording medium mounted on a recording apparatus or a request to reproduce data from an address specified in the request as an address in a recording medium mounted on a reproduction apparatus, and such requests are a heavy processing load that must be borne by the recording and reproduction apparatus. By referring to such a space bitmap, however, it is possible to determine whether or not data has already been recorded at an address specified for example in a write request. If data has already been recorded at the specified address, an error report can be returned to the host computer without actually making an access to the recording medium. As an alternative, the data can be renewed by carrying out an alternate-address process. In particular, it is also possible to determine whether or not the function to renew data is effective (enabled) without actually making an access to the recording medium. In addition, by referring to such a space bitmap, it is possible to determine whether or not data has already been recorded at an address specified for example in a read request. If no data has already been recorded at the specified address, an error report can be returned to the host computer without actually making an access to the recording medium. That is to say, it is possible to reduce a processing load borne by the recording and reproduction apparatus in respectively recording and reproducing data onto and from the recording medium by making random accesses to the recording medium. In addition, by using the information indicating whether or not data has been recorded in any cluster, recording states of alternate areas can be managed. Thus, it is possible to acquire an alternate destination address, which is to be used in an alternate-address process carried out due to the existence of a defect or carried out to renew data, without actually making an access to the recording medium. On top of that, management/control areas such as the lead-in and lead-out areas can also be managed by using the information indicating whether or not data has been recorded in any cluster. Thus, the information indicating whether or not data has been recorded in any cluster is suitable for typically a process to grasp the used range of the OPC for adjusting a laser power or the like. That is to say, when the OPC is searched for a trial-write area for adjusting a laser power, it is not necessary to actually make an access to the recording medium and it is also possible to avoid incorrect detection as to whether or not data has been recorded in a cluster. In addition, if the information indicating whether or not data has been recorded in any cluster reveals that an area used as a target of a write operation is defective due to an injury and data has been recorded in areas surrounding the target area, it is possible to eliminate a process for recording data at an address in the defective target area as a process that would otherwise take long time to carry out. On top of that, by combining this function with a function to renew data, it is possible to carry out a write process, which appears to the host as a process involving no write error. In addition, as alternate-address management information recorded in a second alternate-address management information area, there are two information formats, i.e., first and second information formats. In the first information format, the alternate-address management information includes an alternate source address for each data unit and an alternate destination address also for each data unit. In the second information format, the alternate-address management information includes information which shows an alternate source address and an alternate destination address for a collection of a plurality of physically continuous data units. Since each of the sequences of continuous data units is treated collectively as such a pair, the number of entries (alternate-address management information ati) cataloged in the second alternate-address management information area can be reduced so that the second alternate-address management information area can be reduced, or more such entries can be cataloged in the second alternate-address management information area. In addition, a bit is included in a space bitmap as a bit corresponding to any data unit included in the data-unit sequence as a data unit involved in an alternate-address process managed by using alternate-address management information cataloged in the second information format. As described earlier, the space bitmap is used as information indicating whether or not data has been recorded in each data unit represented by a bit in the bitmap. Since the bit included in a space bitmap as a bit corresponding to any data unit included in the data-unit sequence is also set at a value indicating that data has been recorded in the data unit, proper processing can be carried out on the basis of the information indicating whether or not data has been recorded in each data unit. Thus, it is possible to avoid an access made as an incorrect or erroneous operation. In addition, a first alternate-address management information area is used as an area for recording the same alternate-address management information recorded in the second alternate-address management information area after the second information format of all the alternate-address management information has been converted into the first information format. By converting the second information format into the first information format, a recording/reproduction apparatus for making an access to a recording medium by using the alternate-address management information recorded only in the first alternate-address management information area is capable of properly recording data and reproducing data onto and from a recording medium provided by the present invention as a recording medium including the first alternate-address management information area. Thus, the present invention has an effect to maintain compatibility with such a recording/reproduction apparatus.
<SOH> BACKGROUND ART <EOH>As a technology for recording and reproducing digital data, there is known a data-recording technology for using optical disks including magneto-optical disks as recording media. Examples of the optical disks are a CD (Compact Disk), an MD (Mini-Disk) and a DVD (Digital Versatile Disk) . The optical disk is the generic name of recording media, which is a metallic thin plate protected by plastic. When a laser beam is radiated to the optical disk, the optical disk emits a reflected signal, from which changes can be read out as changes representing information recorded on the disk. The optical disks can be classified into a read-only category including a CD, a CD-ROM and a DVD-ROM, which the user is already familiar with, and a writable category allowing data to be written therein as is generally known. The writable category includes an MD, a CD-R, a CD-RW, a DVD-R, a DVD−RW, a DVD+RW and a DVD-RAM. By adopting a magneto-optical recording method, a phase-change recording-method or a pigmented-coat change recording-method for the writable category, data can be recorded onto a disk of this category. The pigmented-coat change recording-method is also referred to as a write-once recording-method. Since this pigmented-coat change recording-method allows data recording once and inhibits renewal of data onto the disk, the disk is good for data-saving applications or the like. On the other hand, the magneto-optical recording method and the phase-change recording-method are adopted in a variety of applications allowing renewal of data. The applications allowing renewal of data include mainly an application of recording various kinds of content data including musical data, movies, games and application programs. In addition, in recent years, a high-density optical disk called a blue-ray disc has been developed in an effort to produce the product on a very large scale. Typically, data is recorded onto a high-density optical disk and read out from the disk under a condition requiring a combination of a laser with a wavelength of 405 nm and an objective lens with an NA of 0.85 to be reproduced. The laser required in this condition is the so-called blue laser. With the optical disk having a track pitch of 0.32 μm, a line density of 0.12 μm/bit, a formatting efficiency of about 82% and a diameter of 12 cm, data of the amount of up to 23.3 GB (gigabytes) can be recorded onto and reproduced from the disk in recording/reproduction units, which are each a data block of 64 KB (kilobytes). There are also two types of optical disk having such a high density, i.e., optical disks of a write-once type and optical disks of a writable type. In an operation to record data onto an optical disk allowing data to be recorded therein by adoption of the magneto-optical recording method, the pigmented-coat change recording-method or the phase-change recording-method, guide means for tracking data tracks is required. Thus, a groove is created in advance to serve as a pregroove. The groove or a land is used as a data track. A land is a member having a shape resembling a section plateau between two adjacent grooves. In addition, it is also necessary to record addresses so that data can be recorded at a predetermined location indicated by an address as a location on a data track. Such addresses are recorded on grooves by wobbling the grooves in some cases. That is to say, a track for recording data is created in advance as typically a pregroove. In this case, addresses are recorded by wobbling the side walls of the pregroove. By recording addresses in this way, an address can be fetched from wobbling information conveyed by a reflected light beam. Thus, data can be recorded at a predetermined location and reproduced from a predetermined location without creating for example pit data showing an address or the like in advance on the track. By adding addresses as a wobbling groove, it is not necessary to discretely provide an address area or the like on tracks as an area for recording typically pit data representing addresses. Since such an address area is not required, the capacity for storing actual data is increased by a quantity proportional to the eliminated address area. It is to be noted that absolute-time (address) information implemented by a groove wobbled as described above is called an ATIP (Absolute Time In Pregroove) or an ADIP (Address in Pregroove). In addition, in the case of recording media usable as media for recording these kinds of data or not as reproduction-only media, there is known a technology for changing a data-recording location on the disk by providing an alternate area. That is to say, this technology is a defect management technology whereby an alternate recording-area is provided so that, if a location improper for recording data exits on the disk due to a defect such as an injury on the disk, the alternate recording-area can be used as an area serving as a substitute for the defective location to allow proper recording and reproduction operations to be carried out properly. The defect management technology is disclosed in documents including Japanese Unexamined Patent Publication No. 2002-521786, and Japanese Patent Laid-open Nos. Sho 60-74020 and Hei 11-39801. In the case of a recordable optical recording medium, data cannot of course be recorded into an area in which data has already been recorded. Specifications of most file systems to be recorded on an optical recording medium are defined by assuming the use of the optical recording medium as a ROM-type disk or a RAM-type disk. The ROM-type disk is a reproduction-only medium and the RAM-type disk is a writable optical disk. Specifications of a file system for a write-once recording medium allowing data to be stored therein only once limit functions of the ordinary file system and include special functions. The specifications of a file system for a write-once recording medium are a reason why the file system does not become widely popular. On the other hand, a FAT file system capable of keeping up with a variety of OSes of an information-processing apparatus and other file systems cannot be applied to write-once media as they are. Write-once media is widely used typically in applications of preserving data. If the write-once media can also be used for the FAT file system by keeping the general specifications of the file system as they are, the usability of the write-once media can be further enhanced. In order to allow a widely used file system such as the FAT file system and a file system for RAMs or hard disks to be applied to write-once media as it is, however, a function to write data into the same address as that of existing data is required. That is to say, a capability of renewing data is required. Of course, one of characteristics of the write-once media is that data cannot be written onto the media for the second time. Thus, it is impossible to use a file system for such a writable recording medium as it is in the first place. In addition, when the optical disk is mounted on a disk drive or dismounted from it, the recording face of the disk may be injured in dependence on the state in which the disk is kept in the drive and the way in which the disk is used. For this reason, the aforementioned technique of managing defects has been proposed. Of course, even the write-once media must be capable of coping with a defect caused by an injury. In addition, in the case of the conventional write-once optical disk, data is recorded in a state of being compacted sequentially in areas starting from the inner side. To put it in detail, there is no space left between an area already including recorded data and an area in which data is to be recorded next. This is because the conventional disk is developed with a ROM-type disk used as a base so that, if an unrecorded area exists, a reproduction operation cannot be carried out. Such a situation limits the freedom of a random-access operation carried out on the write-once media. In addition, for a disk drive or a recording/reproduction apparatus, an operation requested by a host computer to write data at an address specified in the operation as an address in a write-once optical disk or an operation to read out data from such an address is a process of a heavy load. From what is described above, contemporary write-once media or, in particular, write-once media implemented by a high-density optical disk having a recording capacity of at least 20 GB like the aforementioned blue-ray disk, is required to meet the following requirements. The write-once media shall be capable of renewing data and managing defects by execution of proper management, improving the random accessibility, reducing the processing load borne by the recording/reproduction apparatus, keeping up with a general-purpose file system by the capability of renewing data and maintaining compatibility with writable optical disks as well as reproduction-only disks.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is an explanatory diagram showing the area structure of a disk provided by an embodiment of the present invention; FIG. 2 is an explanatory diagram showing the structure of a one-layer disk provided by the embodiment; FIG. 3 is an explanatory diagram showing the structure of a two-layer disk provided by the embodiment; FIG. 4 is an explanatory diagram showing a DMA of a disk provided by the embodiment; FIG. 5 is a diagram showing the contents of a DDS of a disk provided by the embodiment; FIG. 6 is a diagram showing the contents of a DFL of a disk provided by the embodiment; FIG. 7 is a diagram showing defect list management information of a DFL and TDFL of a disk provided by the embodiment; FIG. 8 is a diagram showing alternate-address information of a DFL and TDFL of a disk provided by the embodiment; FIG. 9 is an explanatory diagram showing a TDMA of a disk provided by the embodiment; FIG. 10 is an explanatory diagram showing a space bitmap of a disk provided by the embodiment; FIG. 11 is an explanatory diagram showing a TDFL of a disk provided by the embodiment; FIG. 12 is an explanatory diagram showing a TDDS of a disk provided by the embodiment; FIG. 13 is an explanatory diagram showing an ISA and OSA of a disk provided by the embodiment; FIG. 14 is an explanatory diagram showing a data-recording order in a TDMA of a disk provided by the embodiment; FIG. 15 is an explanatory diagram showing a utilization stage of a TDMA of the two-layer disk provided by the embodiment; FIG. 16 is a block diagram of a disk drive provided by the embodiment; FIG. 17 shows a flowchart representing a data-writing process provided by the embodiment; FIG. 18 shows a flowchart representing a user-data-writing process provided by the embodiment; FIG. 19 shows a flowchart representing an overwrite function process provided by the embodiment; FIG. 20 shows a flowchart representing a process of generating alternate-address information in accordance with by the embodiment; FIG. 21 shows a flowchart representing a data-fetching process provided by the embodiment; FIG. 22 shows a flowchart representing a TDFL/space-bitmap update process provided by the embodiment; FIG. 23 shows a flowchart representing a process of restructuring alternate-address information in accordance with the embodiment; FIG. 24 is an explanatory diagram showing the process of restructuring alternate-address information in accordance with the embodiment; FIG. 25 shows a flowchart representing a process of converting a disk provided by the embodiment into a compatible disk in accordance with the embodiment; FIG. 26 is an explanatory diagram showing a TDMA of a disk provided by another embodiment; FIG. 27 is an explanatory diagram showing a TDDS of a disk provided by the other embodiment; FIG. 28 is an explanatory diagram showing an ISA and OSA of a disk provided by the other embodiment; FIGS. 29A and 29B are each an explanatory diagram showing spare area full flags provided by the other embodiment; FIG. 30 shows a flowchart representing a data-writing process provided by the other embodiment; FIG. 31 shows a flowchart representing a process of setting a renewal function in accordance with the other embodiment; FIG. 32 shows a flowchart representing a data-fetching process provided by the other embodiment; and FIG. 33 shows a flowchart representing a TDFL/space-bitmap update process provided by the other embodiment. detailed-description description="Detailed Description" end="lead"?
20041109
20071002
20050922
68606.0
1
HALEY, JOSEPH R
RECORDING MEDIUM, RECORDING DEVICE, REPRODUCTION DEVICE, RECORDING METHOD AND REPRODUCTION METHOD
UNDISCOUNTED
0
ACCEPTED
2,004
10,514,027
ACCEPTED
Agents for preventing or ameliorating insulin resistance and /or obesity
The present invention provides a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity based on inhibition of GIP functions, which comprises, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, halogen, a nitro group or a cyano group, R2 and R3 each represent hydrogen or halogen, hydrogen or a methoxy group, or both R2 and R3 may form an optionally substituted benzene or pyrrole ring, and A represents nitrogen or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R1 or —SO2—R or may, together with R3, form an optionally substituted benzene or pyrrole ring, R7, R8 and R9 each represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group or the like, and R1 represents an optionally substituted morpholyl group or the like) or a pharmaceutically acceptable salt thereof.
1. A GIP function inhibitor comprising, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, R2 represents hydrogen or a halogen atom or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R3 represents hydrogen or a methoxy group or may, together with R2, form an optionally substituted benzene ring or an optionally substituted pyrrole ring or may, together with R4, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, and A represents a nitrogen atom or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R7, R8 and R9 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, and R11 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group) or a pharmaceutically acceptable salt thereof. 2. The GIP function inhibitor according to claim 1, comprising, as an active ingredient, a compound represented by the following general formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group and B represents —CO—, —CO—CH2—, —CH2CH2O— or —CH(R12)— whereupon R2 represents hydrogen or a C1 to C6 alkyl group, and E represents an optionally substituted phenyl group, an optionally substituted 1,3-dioxaindanyl group, an optionally substituted naphthyl group, an optionally substituted pyridyl group, an optionally substituted pyrrolyl group, an optionally substituted thienyl group, an optionally substituted oxadiazolyl group, an optionally substituted thiazolyl group, an optionally substituted 2-phenyl[1,3]dioxolanyl group, an optionally substituted C3 to C6 cycloalkyl group, an optionally substituted quinoxalyl group or an optionally substituted benzothienyl group) or a pharmaceutically acceptable salt thereof. 3. The GIP function inhibitor according to claim 1, comprising, as an active ingredient, a compound represented by the following general formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, K represents hydrogen, a C1 to C6 alkyl group substituted with a hydroxyl group, —NHCO—R13, —OR14, —CH2O—CONHR15, —CH2NH—R16, —CH2CO—NR17R18 or —SO2—R19, L represents hydrogen or -M-R20 whereupon M represents —CH2—, —CH2OCH2—, —CH2—SO—CH2—, or —CH2—SO2—CH2—, R13 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, R14 represents hydrogen or an optionally substituted C1 to C6 alkyl group, R15 represents an optionally substituted C1 to C6 alkyl group, a cyclohexyl group or an optionally substituted phenyl group, R16 represents an optionally substituted carbamoylmethyl group, R17 and R18 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, or R17 may, together with R18, form a piperidinyl group, R19 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group, and R20 represents an optionally substituted phenyl group, an optionally substituted benzylamino group, an optionally substituted benzylpiperazyl group, an optionally substituted piperidinyl group, an optionally substituted morpholyl group, an optionally substituted pyrrolidinyl group or a diethylaminocarbonylmethoxy group) or a pharmaceutically acceptable salt thereof. 4. The GIP function inhibitor according to claim 1, comprising, as an active ingredient, a compound represented by the following general formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, and Q represents an optionally substituted phenyl group, an optionally substituted oxadiazolyl group, an optionally substituted thiazolyl group, an optionally substituted pyridyl group, an optionally substituted furyl group or an optionally substituted thienyl group) or a pharmaceutically acceptable salt thereof. 5. The GIP function inhibitor according to any one of claims 1 to 4, which is used as an agent for preventing/ameliorating obesity. 6. Use of a compound represented by the following general formula (I): (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, R2 represents hydrogen or a halogen atom or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R3 represents hydrogen or a methoxy group or may, together with R2, form an optionally substituted benzene ring or an optionally substituted pyrrole ring or may, together with R4, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, and A represents a nitrogen atom or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R7, R8 and R9 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, and R11 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group) or a pharmaceutically acceptable salt thereof for producing a GIP function inhibitor. 7. Use of a compound represented by the following general formula (I): (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, R2 represents hydrogen or a halogen atom or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R3 represents hydrogen or a methoxy group or may, together with R2, form an optionally substituted benzene ring or an optionally substituted pyrrole ring or may, together with R4, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, and A represents a nitrogen atom or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R7, R8 and R9 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, and R11 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group) or a pharmaceutically acceptable salt thereof for producing an agent for preventing/ameliorating obesity.
TECHNICAL FIELD The present invention relates to a GIP function inhibitor comprising a previously known methylidene hydrazide compound as an active ingredient and, further, to an agent for preventing/ameliorating obesity. BACKGROUND ART Glucose dependent-insulinotropic polypeptide, also known as, gastric inhibitory polypeptide (hereinafter, abbreviated to GIP) is one of the gastrointestinal hormones belonging to a glucagon/secretin family. GIP, together with glucagon-like peptide 1 (GLP-1), is referred to as incretin and secreted from K cells present in the small intestine upon ingestion, and promotes the secretion of insulin by glucose in pancreatic β cells, thereby controlling the movement of nutrients in the living body upon ingestion. In addition, GIP is estimated to inhibit stomach motility and to stimulate intestinal secretion. However, its initially found inhibitory action on secretion of gastric acid is questionable at present. A GIP receptor gene is expressed widely not only in pancreatic β cells and adipocytes but also in other cells, and it is thus estimated that GIP also act in other tissues, which is however not fully elucidated. Obesity is a lifestyle-related disease increasing due to westernization of the dietary habits of the Japanese at present, and is a risk factor of lifestyle-related diseases such as fatty liver, diabetes, gout, hypertension and arteriosclerosis. Medically, obesity is recognized as a morbid state of abnormal accumulation of fat resulting from relatively excessive ingestion of calories caused by hereditary and environmental factors, and is regarded as a subject of medical treatment. Treatment of obesity is carried out by combination of dietary cure and exercise cure, and an appetite inhibitor is rarely used. In Japan, a clinically used remedy for preventing or ameliorating obesity is only madindol (sanolex), while studies on other remedies such as β3 adrenaline receptor agonists, central nervous agonists, inhibitors of digestion and absorption, inhibitors of lipid synthesis, and leptin are advancing. Madindol, which is commercially available as an adjunctive agent in dietary/exercise cures for severe obesity, is an appetite suppressant that act on the central nervous system, but its clinical effect is insufficient, and owing to the action on the central nervous system, the problem of dependence is pointed out. Other appetite suppressants working in the central nervous system, which act by different mechanisms, have been developed, but side effects in the central nervous system, such as increase in blood pressure, anxiety and headache, are worried about. A lipase inhibitor (orlistat), working mainly for inhibiting absorption of lipid and the like, is not reported to have severe side effects, but side effects such as fatty stools and flatus are reported. Leptin was expected as a promising candidate for a therapeutic agent for obesity because of its inhibitory effect on increase in body weight by decreasing food intake and accelerating energy consumption, but clinical tests revealed that the therapeutic effect is limited. β3-Receptor agonists are also expected as anti-obesity medicines, but their high receptor selectivity is essential, and side effects on the heart and the like are worried about if the selectivity is insufficient. As described above, anti-obesity medicines based on various working mechanisms are commercially available or under development, but there are no medicines having both sufficient inhibitory effect on body weight gain and safety. There are few studies on the relationship between GIP and obesity, but in recent years, the relationship is being elucidated. That is, a high-fat diet loading test on GIP receptor gene-deficient mice, conducted in a process for investigating the functions of GIP, revealed that obesity, occurring in wild-type mice, was inhibited in the GIP receptor gene-deficient mice (K. Miyawaki et al., “Inhibition of GIP Signaling Prevents Obesity”, abstract #335-PP, the 61st Scientific Sessions of American Diabetes Association (2001)). When these GIP receptor gene-deficient mice were given conventional diet, the mice showed no difference from the wild-type mice in body weight change, thus suggesting that inhibiting the functions of GIP causes no adverse influence. It is also revealed that even in ob/ob mice, which are animals with hereditary obesity, obesity can be inhibited by making the mice deficient in the GIP receptor gene (see WO 01/87341). From the foregoing, GIP was suggested to cause obesity with a new mechanism not proposed up to now, and compounds inhibiting the functions of GIP, for example antagonists of GIP receptors and inhibitors of GIP production, are promising as safe medicines having an anti-obesity effect. Examples of the compounds inhibiting the functions of GIP may include GIP receptor antagonists such as GIP(6-30) —NH2 (Regulatory Peptide, Vol. 69, pp. 151-154, 1997) and GIP(7-30) —NH2 (Am. J. Physiol., 1999, Vol. 276, pp. E1049-54). However, these compounds are long-chain peptides and problematic in oral absorptivity and stability in blood, and are not suitable as anti-obesity agents. Besides these peptides, 3-bromo-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-ol disclosed in WO 01/87341 is mentioned as a low-molecular compound inhibiting the functions of GIP, but its inhibitory activity is weak because its IC50 is about 40 μM. As described above, a low-molecular compound strongly inhibiting the functions of GIP is still not known. GIP, together with glucagon and GLP-1, is known as gastrointestinal hormone belonging to the glucagon/secretin family, and their primary amino acid sequences are highly homologous. The primary sequences of their receptor proteins are also highly homologous. However, whether or not a low-molecular inhibitor of functions of glucagon, for example, acts as an inhibitor of functions of GIP and/or GLP-1 is not evident. For example, L-168,049 known as a very potent antagonist of glucagon is considerably poor in an ability to bind to receptor for GLP-1, having the highest homology to glucagon (Margaret A. Cascieri et al., J. Biol. Chem., Vol. 274(13), 8694-8697 (1999)). The ability of L-168,049 to bind to GIP receptor is not described therein. Compounds disclosed in WO 02/00612 have a strong antagonistic activity on receptors of only glucagon, as compared with GIP and GLP-1. Further, compounds exhibiting a glucagon antagonistic activity, disclosed in WO 00/39088, are not known to have an antagonistic activity on GIP receptor. It is thus not possible to predict whether the antagonists for glucagon, belonging to the same family, act as GIP antagonists. It is an object of the present invention to provide a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity in a new mechanism based on inhibition of GIP functions. DISCLOSURE OF THE INVENTION The present inventors made extensive studies for developing a medicine inhibiting a phenomenon caused by the action of GIP on cells expressing its receptor and, as a result, they found that methylidene hydrazide compounds known as a potent antagonist of glucagon has a new activity of inhibiting the functions of GIP. As a result of further studies on the basis of this finding, the present invention was completed. That is, the present invention is directed to a GIP function inhibitor or an agent for preventing/ameliorating obesity, which comprises, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, R2 represents hydrogen or a halogen atom or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R3 represents hydrogen or a methoxy group or may, together with R2, form an optionally substituted benzene ring or an optionally substituted pyrrole ring or may, together with R4, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, and A represents a nitrogen atom or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R7, R8 and R9 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, and R11 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group) or a pharmaceutically acceptable salt thereof. The present invention provides a low-molecular compound inhibiting the functions of GIP. The present invention also provides an agent for preventing/ameliorating obesity based on a new mechanism of inhibiting the functions of GIP, which has never been achieved. BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a graph showing the ratio of the amount of cAMP formed upon addition of each compound in Pharmacological Test Example 1 in this specification to the amount of cAMP formed in the absence of the compound. BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, description will be given of a methylidene hydrazide compound used in the present invention in detail. The methylidene hydrazide compound inhibiting the functions of GIP used in the present invention is a compound represented by the following general formula (I): (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, R2 represents hydrogen or a halogen atom or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R3 represents hydrogen or a methoxy group or may, together with R2, form an optionally substituted benzene ring or an optionally substituted pyrrole ring or may, together with R4, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, and A represents a nitrogen atom or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene ring or an optionally substituted pyrrole ring, R7, R8 and R9 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, and R11 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group) or a pharmaceutically acceptable salt thereof. Herein, R1 is preferably not hydrogen, and the halogen atom represented by R1 is preferably a bromine atom, a chlorine atom or a fluorine atom. The halogen atom represented by R2 is also preferably a bromine atom, a chlorine atom or a fluorine atom. These also apply to the compounds in the following three groups. In the present invention, the methylidene hydrazide compounds inhibiting the functions of GIP can be classified into the following important compound groups. The first group is a group of compounds represented by the following formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group and B represents —CO—, —CO—CH2—, —CH2CH2O— or —CH(R12)— whereupon R12 represents hydrogen or a C1 to C6 alkyl group, and E represents an optionally substituted phenyl group, an optionally substituted 1,3-dioxaindanyl group, an optionally substituted naphthyl group, an optionally substituted pyridyl group, an optionally substituted pyrrolyl group, an optionally substituted thienyl group, an optionally substituted oxadiazolyl group, an optionally substituted thiazolyl group, an optionally substituted 2-phenyl[1,3]dioxolanyl group, an optionally substituted C3 to C6 cycloalkyl group, an optionally substituted quinoxalyl group or an optionally substituted benzothienyl group) or pharmaceutically acceptable salts thereof. The second group is a group of compounds represented by the following formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, K represents hydrogen, a C1 to C7 alkyl group substituted with a hydroxyl group, —NHCO—R13—, —OR14, —CH2O—CONHR15, —CH2NH—R16, —CH2CO—NR17R18 or —SO2—R19, L represents hydrogen or -M-R20 whereupon M represents —CH2—, —CH2OCH2—, —CH2—SO—CH2—, or —CH2—SO2—CH2—, R13 represents a C1 to C6 alkyl group, a C3 to C6 cycloalkyl group, an optionally substituted furyl group, an optionally substituted thienyl group, an optionally substituted benzyl group, an optionally substituted benzyloxymethyl group, an optionally substituted phenylvinyl group or an optionally substituted phenoxymethyl group, R14 represents hydrogen or an optionally substituted C1 to C6 alkyl group, R15 represents an optionally substituted C1 to C6 alkyl group, a cyclohexyl group or an optionally substituted phenyl group, R16 represents an optionally substituted carbamoylmethyl group, R17 and R18 independently represent hydrogen or an optionally substituted C1 to C6 alkyl group, or R17 may, together with R18, form a piperidinyl group, R19 represents an optionally substituted morpholyl group, an optionally substituted cyclopentylamino group, an optionally substituted piperidinyl group or a diethylamino group, and R20 represents an optionally substituted phenyl group, an optionally substituted benzylamino group, an optionally substituted benzylpiperazyl group, an optionally substituted piperidinyl group, an optionally substituted morpholyl group, an optionally substituted pyrrolidinyl group or a diethylaminocarbonylmethoxy group) or pharmaceutically acceptable salts thereof. The third group is a group of compounds represented by the following formula: (wherein R1 represents hydrogen, a halogen atom, a nitro group or a cyano group, and Q represents an optionally substituted phenyl group, an optionally substituted oxadiazolyl group, an optionally substituted thiazolyl group, an optionally substituted pyridyl group, an optionally substituted furyl group or an optionally substituted thienyl group) or pharmaceutically acceptable salts thereof. Hereinafter, description will be given of the substituent groups and the like in more detail. In this specification, the terms “optionally substituted” such as in the optionally substituted benzene ring are used plural times, and the terms “optionally substituted” mean that arbitrary (“arbitrary” also mean the case of plural, and the same after this) hydrogen(s) may be replaced by, for example, a C1 to C6 alkyl group, a trifluoromethyl group, a difluoromethyl group, a trifluoromethoxy group, a halogen atom, a carboxamide group, a hydroxymethyl group, a phenyl group, a dimethylamino group, a C1 to C6 alkyloxy group, or a nitro group. Specific examples of the C1 to C6 alkyl group used throughout this specification may include a linear or branched alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. Among these, the C1 to C3 alkyl group is preferable from the viewpoint of practical use. Similarly, specific examples of the C1 to C6 alkyloxy group may include linear or branched alkyloxy groups such as methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, tert-butyloxy, pentyloxy, and hexyloxy. Among these, the C1 to C3 alkyloxy group is preferable from the viewpoint of practical use. Specific examples of the C3 to C6 cycloalkyl group may include cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The pharmaceutically acceptable salts include, for example, the compounds which have formed acid addition salts with inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, and organic acids such as oxalic acid, fumaric acid, maleic acid, tartaric acid and citric acid. The methylidene hydrazide compound contained in the GIP function inhibitor according to the present invention is a well-known compound and can be produced by a method described in WO 00/39088 or a method described in J. Med. Chem., Vol. 44, 3141-3149 (2001). Alternatively, it can be purchased from library suppliers such as ChemBridge Corporation. The present invention relates to a GIP function inhibitor comprising the above-described methylidene hydrazide compound as the active ingredient and, also, to use of the compound for producing the GIP function inhibitor. It would be possible, but is not evident from test results, that the GIP function inhibitor is an antagonist of GIP receptor. The GIP function inhibitor according to the present invention is not only useful as a low-molecular compound elucidating the role of GIP in the living body, but also usable as an agent for preventing/ameliorating obesity. Usability of the GIP function inhibitor as an agent for preventing/ameliorating obesity is shown in K. Miyawaki et al., “Inhibition of GIP Signaling Prevents Obesity”, abstract #335-PP, the 61st Scientific Sessions of American Diabetes Association (2001) and WO 01/87341 supra. The administration form of the methylidene hydrazide compound according to the present invention can be selected, depending on the object, from various kinds of administration forms described in the general rules of pharmaceuticals in “the Japanese Pharmacopoeia”. For example, orally ingestible ingredients usually used in this field may be used in forming tablets. Examples of such ingredients may include excipients such as lactose, crystalline cellulose, white sugar, and potassium phosphate. If necessary, various additives used conventionally in pharmaceutical manufacturing, such as binders, disintegrators, lubricants and suspending agents, may be incorporated. The amount of the active ingredient represented by the general formula (I) to be contained in the pharmaceutical preparation of the present invention is not particularly limited, and is suitably selected from a broad range. The amount of the active ingredient is suitably selected depending on usage, the age, sex and other conditions of the patient and the severity of disease, but usually the compound according to the present invention is given in an amount of about 0.01 to 500 mg per kg of body weight a day. The pharmaceutical preparation can be administered in one to four divided portions a day. However, the dose and administration frequency shall be determined in view of related situations including the degree of conditions to be treated, selection of the compound to be administered, and selected administration route; thus, the scope of the present invention is not limited by the range of the dose and the administration frequency described above. EXAMPLES Hereinafter, description will be given of the present invention in more detail by way of examples and reference examples; however, the present invention is not limited thereto. Methylidene hydrazide compounds to be subjected to pharmacological tests are compounds described in J. Med. Chem., Vol. 44, 3141-3149 (2001) or compounds described in WO 00/39088. As typical compounds, the following compounds were subjected to the pharmacological tests. Compound 1: 4-Hydroxybenzoic Acid 2-bromobenzylidene)hydrazide Compound 1 shown below was purchased from ChemBridge Corporation. (Chemical Formula Representing Compound 1) Compound 2: 3-Cyano-4-hydroxybenzoic Acid [1-(2,3,5,6-tetramethylbenzyl)indol-4-yl]methylidene Hydrazide Compound 2 shown below was synthesized by the method described in WO 00/39088. (Chemical Formula Representing Compound 2) Compound 3: 3-Chloro-4-hydroxybenzoic Acid (4-methoxynaphthalen-1-yl)methylidene Hydrazide Compound 3 shown below was synthesized by the method described in J. Med. Chem., Vol. 44, 3141-3149 (2001). (Chemical Formula Representing Compound 3) Compound 4: 3-Chloro-4-hydroxybenzoic Acid [1-(5-chlorothiophen-2-ylmethyl)-1H-indol-5-yl]methylidene Hydrazide Compound 4 shown below was synthesized by the method described in WO 00/39088. (Chemical Formula Representing Compound 4) Next, description will be given of test examples using Compounds 1 to 4. Pharmacological Test Example 1 The system for evaluation of GIP function inhibitors (GIP receptor antagonists and the like) made use of the following method wherein their inhibitory activity on production of cAMP as GIP intracellular transmitter was used as an indicator. According to a method of Kubota et al. (Diabetes 45: 1701-1705, 1996), human GIP receptor-expressing cells prepared by introducing GIP cDNA into CHO cells were used. First, cAMP was produced by stimulation with 100 pM GIP in the presence/absence of the test chemical at 37° C. for 30 minutes in phosphate-buffered saline, pH 7.4, containing 1 mM isobutylmethylxanthine, 5.6 mM glucose and 0.5% bovine serum albumin. Then, using a cAMP assay system (PE Biosystems), the cells were lyzed with an attached lysis buffer, the amount of cAMP accumulated in the cells was measured, and the inhibitory activity of the test sample on the functions of GIP was determined. To verify the action of the test sample completely irrelevant to the action on GIP receptor, the inhibitory effect of the test sample on formation of cAMP upon stimulating, with 5 M forskolin, CHO cells into which the GIP receptor gene had not been introduced (cells not expressing the GIP receptor) was also confirmed. The inhibitory activity was expressed in terms of IC50 (concentration of the compound at which the production of cAMP by GIP is inhibited by 50%). A compound not showing any inhibitory activity on formation of cAMP in the cells not expressing the GIP receptor, but inhibiting the formation of cAMP by stimulation with GIP, in the cells expressing the GIP receptor, was regarded as an active compound. A dose/inhibition curve in this measurement is shown in FIG. 1, and the calculation results of IC50 are shown in Table 1. TABLE 1 Test Compound IC50 (μM) Compound 1 19 Compound 2 0.0063 Compound 3 0.56 Compound 4 0.44 Compounds 1 to 4 did not exhibit any inhibitory activity on cAMP formation upon stimulation with forskolin in the cells not expressing GIP receptor, but inhibited cAMP formation upon stimulation with GIP in the cells expressing the GIP receptor. That is, Compounds 1 to 4 were revealed to inhibit the functions of GIP. From detailed analysis, it can be estimated that because Compound 1 inhibited the functions of GIP though at low levels, the essential structure showing the inhibitory activity is 4-hydroxybenzoic acid benzylidene hydrazide. It can also be estimated that the activity is improved by introducing a chloride atom, a fluorine atom, a nitro group or a cyano group at the ortho-position with respect to the hydroxyl group or by changing the benzylidene group into an indole-4-methylidene group or a naphthalene-1-methylidene group. It follows that for example, Compound 2 can be estimated to be an active compound because it is an indol-4-ylmethylidene hydrazide derivative, that is, a compound having the essential structure wherein a cyano group is introduced at the ortho-position with respect to the hydroxyl group and the benzylidene group is changed into an indole-4-methylidene group. Pharmacological Test Example 2 For confirming the receptor selectivity of the test sample, the inhibitory activity of the test sample on formation of cAMP upon stimulation with GLP-1 (60 pM) in CHO cells expressing a receptor of GLP-1, which, like GIP, belongs to the glucagon/secretin family, was confirmed at the concentration of IC50 on the GIP receptor. As a comparative control, 500 nM GIP(7-30) —NH2 (tGIP) was used. Similar to tGIP, Compounds 1 to 4 did not exhibit any inhibitory activity on formation of cAMP upon stimulation with GLP-1, in the cells expressing the GLP-1 receptor.
<SOH> BACKGROUND ART <EOH>Glucose dependent-insulinotropic polypeptide, also known as, gastric inhibitory polypeptide (hereinafter, abbreviated to GIP) is one of the gastrointestinal hormones belonging to a glucagon/secretin family. GIP, together with glucagon-like peptide 1 (GLP-1), is referred to as incretin and secreted from K cells present in the small intestine upon ingestion, and promotes the secretion of insulin by glucose in pancreatic β cells, thereby controlling the movement of nutrients in the living body upon ingestion. In addition, GIP is estimated to inhibit stomach motility and to stimulate intestinal secretion. However, its initially found inhibitory action on secretion of gastric acid is questionable at present. A GIP receptor gene is expressed widely not only in pancreatic β cells and adipocytes but also in other cells, and it is thus estimated that GIP also act in other tissues, which is however not fully elucidated. Obesity is a lifestyle-related disease increasing due to westernization of the dietary habits of the Japanese at present, and is a risk factor of lifestyle-related diseases such as fatty liver, diabetes, gout, hypertension and arteriosclerosis. Medically, obesity is recognized as a morbid state of abnormal accumulation of fat resulting from relatively excessive ingestion of calories caused by hereditary and environmental factors, and is regarded as a subject of medical treatment. Treatment of obesity is carried out by combination of dietary cure and exercise cure, and an appetite inhibitor is rarely used. In Japan, a clinically used remedy for preventing or ameliorating obesity is only madindol (sanolex), while studies on other remedies such as β3 adrenaline receptor agonists, central nervous agonists, inhibitors of digestion and absorption, inhibitors of lipid synthesis, and leptin are advancing. Madindol, which is commercially available as an adjunctive agent in dietary/exercise cures for severe obesity, is an appetite suppressant that act on the central nervous system, but its clinical effect is insufficient, and owing to the action on the central nervous system, the problem of dependence is pointed out. Other appetite suppressants working in the central nervous system, which act by different mechanisms, have been developed, but side effects in the central nervous system, such as increase in blood pressure, anxiety and headache, are worried about. A lipase inhibitor (orlistat), working mainly for inhibiting absorption of lipid and the like, is not reported to have severe side effects, but side effects such as fatty stools and flatus are reported. Leptin was expected as a promising candidate for a therapeutic agent for obesity because of its inhibitory effect on increase in body weight by decreasing food intake and accelerating energy consumption, but clinical tests revealed that the therapeutic effect is limited. β3-Receptor agonists are also expected as anti-obesity medicines, but their high receptor selectivity is essential, and side effects on the heart and the like are worried about if the selectivity is insufficient. As described above, anti-obesity medicines based on various working mechanisms are commercially available or under development, but there are no medicines having both sufficient inhibitory effect on body weight gain and safety. There are few studies on the relationship between GIP and obesity, but in recent years, the relationship is being elucidated. That is, a high-fat diet loading test on GIP receptor gene-deficient mice, conducted in a process for investigating the functions of GIP, revealed that obesity, occurring in wild-type mice, was inhibited in the GIP receptor gene-deficient mice (K. Miyawaki et al., “Inhibition of GIP Signaling Prevents Obesity”, abstract #335-PP, the 61st Scientific Sessions of American Diabetes Association (2001)). When these GIP receptor gene-deficient mice were given conventional diet, the mice showed no difference from the wild-type mice in body weight change, thus suggesting that inhibiting the functions of GIP causes no adverse influence. It is also revealed that even in ob/ob mice, which are animals with hereditary obesity, obesity can be inhibited by making the mice deficient in the GIP receptor gene (see WO 01/87341). From the foregoing, GIP was suggested to cause obesity with a new mechanism not proposed up to now, and compounds inhibiting the functions of GIP, for example antagonists of GIP receptors and inhibitors of GIP production, are promising as safe medicines having an anti-obesity effect. Examples of the compounds inhibiting the functions of GIP may include GIP receptor antagonists such as GIP(6-30) —NH 2 (Regulatory Peptide, Vol. 69, pp. 151-154, 1997) and GIP(7-30) —NH 2 (Am. J. Physiol., 1999, Vol. 276, pp. E1049-54). However, these compounds are long-chain peptides and problematic in oral absorptivity and stability in blood, and are not suitable as anti-obesity agents. Besides these peptides, 3-bromo-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-ol disclosed in WO 01/87341 is mentioned as a low-molecular compound inhibiting the functions of GIP, but its inhibitory activity is weak because its IC 50 is about 40 μM. As described above, a low-molecular compound strongly inhibiting the functions of GIP is still not known. GIP, together with glucagon and GLP-1, is known as gastrointestinal hormone belonging to the glucagon/secretin family, and their primary amino acid sequences are highly homologous. The primary sequences of their receptor proteins are also highly homologous. However, whether or not a low-molecular inhibitor of functions of glucagon, for example, acts as an inhibitor of functions of GIP and/or GLP-1 is not evident. For example, L-168,049 known as a very potent antagonist of glucagon is considerably poor in an ability to bind to receptor for GLP-1, having the highest homology to glucagon (Margaret A. Cascieri et al., J. Biol. Chem., Vol. 274(13), 8694-8697 (1999)). The ability of L-168,049 to bind to GIP receptor is not described therein. Compounds disclosed in WO 02/00612 have a strong antagonistic activity on receptors of only glucagon, as compared with GIP and GLP-1. Further, compounds exhibiting a glucagon antagonistic activity, disclosed in WO 00/39088, are not known to have an antagonistic activity on GIP receptor. It is thus not possible to predict whether the antagonists for glucagon, belonging to the same family, act as GIP antagonists. It is an object of the present invention to provide a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity in a new mechanism based on inhibition of GIP functions.
<SOH> BRIEF DESCRIPTION OF THE DRAWING <EOH>FIG. 1 is a graph showing the ratio of the amount of cAMP formed upon addition of each compound in Pharmacological Test Example 1 in this specification to the amount of cAMP formed in the absence of the compound. detailed-description description="Detailed Description" end="lead"?
20050105
20060725
20050721
99230.0
0
POWERS, FIONA
AGENT FOR PREVENTING /AMELIORATING OBESITY COMPRISING METHYLIDENE HYDRIZIDE COMPOUND AS ACTIVE INGREDIENT
UNDISCOUNTED
0
ACCEPTED
2,005
10,514,303
ACCEPTED
Ph sensitive prodrugs of 2,6-diisopropylphenol
The present invention is directed to water-soluble derivatives of 2,6-diisopropylphenol (Propofol). The compounds act as prodrugs of 2,6-diisopropylphenol and metabolize rapidly to Propofol thereby providing an alternative to the water-insoluble 2,6-diisopropylphenol. Pharmaceutical compositions comprising these compounds, methods of induction and maintenance of anesthesia or sedation as well as methods of treating neurodegenerative diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
1. A compound of formula A: wherein: R1 is hydrogen, alkyl, or aryl; Each X is independently C1-10 alkyl; Y is heteroaryl, saturated heterocyclic, or NR2R3, R2 and R3 are independently hydrogen, alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, combine to form a saturated heterocyclic or heteroaryl ring; or pharmaceutically acceptable salts of any of the foregoing. 2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmacologically effective amount of a compound according to claim 1. 3. A pharmaceutical composition of claim 2, wherein the pharmaceutically acceptable carrier is selected from an aqueous solution, an injectable solution, an aeorsolizer, an inhaler or a transdermal delivery vehicle. 4. A pharmaceutical composition of claim 2 contained in a unit dosage form. 5. The pharmaceutical composition of claim 2 wherein the pharmaceutically acceptable carrier comprises a transdermal delivery vehicle, wherein the pharmaceutically acceptable carrier contains a detergent, an emulsifier or liposomes. 6. The pharmaceutical composition of claim 2 in the form of an injectable solution wherein the concentration of the compound in the injectable solution is between about 0.5 milligram per milliliter to about 200 milligram per milliliter. 7. The pharmaceutical composition of claim 2 contained in a unit dosage form wherein the unit dosage form contains about 0.5 milligram to about 1.2 gram of the compound. 8. A method for inhibiting oxidation of biological material comprising contacting the material with an effective amount of a compound of claim 1. 9. A method for the treatment of a condition having an inflammatory component, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 10. The method of claim 9, wherein the condition is selected from arthritis, a pathologic condition of the nervous system, a neurodegenerative disease, trauma to the central nervous system, Friedrich's disease, Parkinson's disease, Alzheimer's disease, Huntington's disease, Pick disease, amyotrophic lateral sclerosis, multiple sclerosis, or a spinal cord injury. 11. A method for the treatment of a respiratory condition, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 12. The method of claim 11, wherein the respiratory condition is selected from acid aspiration, adult/infant respiratory distress syndrome, airway obstructive disease, asthma, bronchiolitis, bronchopulmonary dysplasia, cancer, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, HIV-associated lung disease, idiopathic pulmonary fibrosis, immune-complex-mediated lung injury, exposure to an oxidizing agent, ischemia-reperfusion injury, mineral dust pneumoconiosis, drug-induced lung disease, silo-filler's disease, exposure to dust, exposure to ozone, exposure to hyperoxia, exposure to air pollution, exposure to diesel exhaust, exposure to nitric oxide, exposure to nitrogen dioxide, exposure to sulfur dioxide, exposure to tobacco smoke, or exposure to other combustion byproducts. 13. The method of claim 11 wherein the compound is administered by inhalation as an aerosol, mist or powder. 14. A method for inducing anesthesia, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1, wherein the compound according to claim 1 is administered in the form of an intravenous injection of an aqueous composition comprising the compound. 15. The method of claim 11 wherein the compound is administered by inhalation. 16. A method for inhibiting nausea and vomiting, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 17. A method for the treatment of epileptic or convulsive disorders, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 18. A method for the treatment of pruritus, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 19. A method for the treatment of a cancer, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1. 20. A method for treating cancer, the method comprising administering to a subject in need thereof an effective amount of at least one compound according to claim 1 in combination with at least one other chemotherapeutic agents selected from Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Cytosine arabinoside, Etoposide, 5-Fluorouracil, Gemzar, Melphalan, Methotrexate, Mitoxantrone, Taxol, Interferon, Fareston, Arzoxifene, Evista, or Tamoxifen. 21. The method of claim 20 wherein the cancer is selected from mammary cancer, prostate cancer, kidney cancer, Karposi's sarcoma, colon cancer, cervical cancer, lung cancer, cutaneous T-cell lymphoma, cancer of the head and neck, cancers of the aerodigestive pathway, skin cancer, bladder cancer, sarcomas, leukoplakias, or acute promyelocytic leukemia. 22. The method of claim 21 wherein the cancer is selected from mammary cancer, prostate cancer, kidney cancer, Karposi's sarcoma, colon cancer, cervical cancer, lung cancer, cutaneous T-cell lymphoma, cancer of the head and neck, cancers of the aerodigestive pathway, skin cancer, bladder cancer, sarcomas, leukoplakias, or acute promyelocytic leukemia. 23. A compound selected from: and pharmaceutically acceptable salts of any of the foregoing.
FIELD OF THE INVENTION The invention relates generally to prodrugs and more specifically to water-soluble derivatives of 2,6-diisopropylphenol (Propofol). BACKGROUND OF THE INVENTION 2,6-diisopropylphenol is highly lipophilic and is practically insoluble in water. For intravenous applications, it is formulated in water using a variety of solubilizing agents and/or emulsifiers. Examples of such formulations include Cremophor™, Intralipid™, Diprivan™, Disoprofol™, Disoprivan™, and Rapinovet™. The aforementioned formulations have many limitations. They cause allergic side effects and pain upon injection. Their preparation is difficult and costly and most importantly they cannot be sterilized and hence anti-microbial agents must be added to the formulations. Propofol or 2,6-diisopropylphenol is a short acting anesthetic that is administered intravenously (i.v.) to mammalian subjects. The low water solubility of this compound presents a significant formulation challenge. The currently approved mode of administration for Propofol is an emulsion that has many disadvantages including costly preparation and sterilization procedures. Oxidation of Propofol to unwanted side-products in the presence of oxygen and light drastically shortens the shelf life of such formulations. In addition, the oil-in-water emulsions cause a number of clinical side effects including pain on injection and pulmonary embolism. Thus, there exists a clear need for a water-soluble, stable, non-toxic pharmaceutical composition of 2,6-diisopropylphenol. SUMMARY OF THE INVENTION The present invention describes non-toxic and water-soluble derivatives of 2,6-diisopropylphenol or Propofol, a low molecular weight alcohol that is administered intravenously and serves as a sedative-hypnotic agent in humans and animals. 2,6-diisopropylphenol has a broad range of applications. It is an antioxidant and inhibits lipid peroxidation. It can also act as an anti-inflammatory agent and can useful in the treatment of acid aspiration, respiratory distress syndrome, airway obstructive disease, asthma, bronchiolitis, bronchopulmonary dysplasia, cancer, chronic obstructive pulmonary disease (“COPD”), cystic fibrosis, emphysema, HIV-associated lung disease, idiopathic pulmonary fibrosis, immune-complex-mediated lung injury, exposure to an oxidizing agent, ischemia-reperfusion injury, mineral dust pneumoconiosis, drug-induced lung disease, silo-filler's disease, and various neurodegenerative diseases such as Friedrich's disease, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS); multiple sclerosis (MS), Pick disease, spinal cord injury, acute neural injury and aging. The present invention is directed to water-soluble derivatives of 2,6-diisopropylphenol. The compounds of the invention act as pH sensitive prodrugs of 2,6-diisopropylphenol that degrade and metabolize rapidly to Propofol upon intravenous injection. The compounds of this invention are crystalline solids that are stable at or below ambient temperature and can be stored as aqueous solutions if the pH of the solution is kept in the range of 0 to 6. Such characteristics represent clear economic and clinical improvements over the state of the art. In one aspect, this invention describes 2,6-diisopropylphenol derivatives according to formula A: wherein: R1 is hydrogen, alkyl, or aryl; Each X is independently C1-10 alkyl; Y is heteroaryl, saturated heterocyclic, or NR2R3, R2 and R3 are independently hydrogen, alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, combine to form a saturated heterocyclic or heteroaryl ring; or a pharmaceutically acceptable salt of any of the foregoing. Specifically, the compounds of the present invention convert to 2,6-diisopropylphenol in vivo and can be used as hypnotic agents, anti-convulsives, anti-pruritics, and anti-emetics. Other uses include treatment of oxidative tissue damage, inflammation and cancer. The prodrug compounds of the present invention have many advantages over 2,6-diisopropylphenol by virtue of increased aqueous solubility and increased stability towards oxidation over the parent compound thus making them particularly suitable for intravenous (i.v.) formulations. Therefore when used in a mammalian subject, the compounds of this invention replicate every therapeutic application that has been described for 2,6-diisopropylphenol. Other advantages of the compounds of the present invention include low toxicity and high therapeutic-to-toxicity index. In another aspect, this invention is directed to a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inhibiting oxidation of biological material comprising contacting the material with an effective amount of a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic condition having an inflammatory component in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic condition of the nervous system having an inflammatory component in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic respiratory condition in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inducing anesthesia in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inhibiting nausea and vomiting in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of epileptic or convulsive disorders in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of pruritis in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides pharmaceutical compositions comprising at least one of the compounds of the invention, in a pharmaceutically acceptable vehicle, for the treatment of carcinomas. Examples of carcinomas include mammary cancer, prostate cancer, kidney cancer, Karposi's sarcoma, colon cancer, cervical cancer, lung cancer, cutaneous T-cell lymphoma, cancer of the head and neck, cancers of the aerodigestive pathway, skin cancer, bladder cancer, sarcomas, leukoplakias, acute promyelocytic leukemia, and the like. In another aspect, this invention provides pharmaceutical compositions comprising at least one the compounds of the invention in combination with other chemotherapeutic agents, in a pharmaceutically acceptable vehicle, for the treatment of carcinomas. Examples of chemotherapeutic agents contemplated for use in the practice of this particular invention include Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Cytosine arabinoside, Etoposide, 5-Fluorouracil, Melphalan, Methotrexate, Mitoxantrone, Taxol, Interferon, Fareston, Arzoxifene, Evista, Tamoxifen, and the like. In another aspect, this invention provides a method for the treatment of a subject undergoing treatment with a chemotherapeutic agent having activity as an oxidizing agent comprising the step of administering a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the use of compounds of Formula A in the manufacture of a medicament for the treatment of a pathological condition having an inflammatory component. The non-limiting examples shown in schemes 1-3, illustrate the inventors' preferred methods for carrying out the preparative process of the invention. DETAILED DESCRIPTION OF THE INVENTION In one aspect of the invention, there are provided compounds comprising the structural formula A: wherein: R1 is hydrogen, alkyl, or aryl; Each X is independently C1-10 alkyl; Y is heteroaryl, saturated heterocyclic, or NR2R3, R2 and R3 are independently hydrogen, alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, combine to form a saturated heterocyclic or heteroaryl ring; or a pharmaceutically acceptable salt of any of the foregoing. The compounds according to this invention may contain one or more asymmetric carbon atoms and can thus occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures or individual diastereomers. The term “stereoisomer” refers to a chemical compound having the same molecular weight, chemical composition, and constitution as another, but with the atoms grouped differently. That is, certain identical chemical moieties are at different orientations in space and, therefore, when pure, have the ability to rotate the plane of polarized light. However, some pure stereoisomers may have an optical rotation that is so slight that it is undetectable with present instrumentation. The compounds described herein may have one or more asymmetrical carbon atoms and therefore include various stereoisomers. All such isomeric forms of these compounds are expressly included in the present invention. Each stereogenic carbon may be of R or S configuration. Although the specific compounds exemplified in this application may be depicted in a particular configuration, compounds having either the opposite stereochemistry at any given chiral center or mixtures thereof are also envisioned. When chiral centers are found in the derivatives of this invention, it is to be understood that this invention encompasses all possible stereoisomers. The terms “optically pure compound” or “optically pure isomer” refers to a single stereoisomer of a chiral compound regardless of the configuration of the said compound. For purpose of this application, all sugars are referenced using conventional three-letter nomenclature. All sugars are assumed to be in the D-form unless otherwise noted, except for fucose, which is in the L-form. Further, all sugars are in the pyranose form. The compounds according to this invention may occur as a mixture of tautomers. The term “tautomer” or “tautomerism” refer to one of two or more structural isomers that exist in equilibrium and are readily converted from one isomeric form to another. Examples of include keto-enol tautomers, such as acetone/propen-2-ol and the like, ring-chain tautomers, such as glucose/2,3,4,5,6-pentahydroxy-hexanal and the like. The compounds described herein may have one or more tautomers and therefore include various isomers. All such isomeric forms of these compounds are expressly included in the present invention. The following example of tautomerism is provided for reference: The following example of nomenclature and numbering system is provided for reference. N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropyl-phenyl ester The term “substantially homogeneous” refers to collections of molecules wherein at least 80%, preferably at least about 90% and more preferably at least about 95% of the molecules are a single compound or a single stereoisomer thereof. As used herein, the term “attached” signifies a stable covalent bond, certain preferred points of attachment being apparent to those skilled in the art. The terms “optional” or “optionally” refer to occurrence or non-occurrence of the subsequently described event or circumstance, and that the description includes instances where said event or circumstance occurs and instances where it does not. In such context, the sentence “optionally substituted alkyl group” means that the alkyl group may or may not be substituted and the description includes both a substituted and an unsubstituted alkyl group. The term “effective amount” of a compound refers a non-toxic but sufficient amount of the compound that provides a desired effect. This amount may vary from subject to subject, depending on the species, age, and physical condition of the subject, the severity of the disease that is being treated, the particular compound used, its mode of administration, and the like. Therefore, it is difficult to generalize an exact “effective amount”, yet, a suitable effective amount may be determined by one of ordinary skill in the art. The term “pharmaceutically acceptable” refers to a compound, additive or composition that is not biologically or otherwise undesirable. For example, the additive or composition may be administered to a subject along with a compound of the invention without causing any undesirable biological effects or interacting in an undesirable manner with any of the other components of the pharmaceutical composition in which it is contained. The term “pharmaceutically acceptable salts” includes hydrochloric salt, hydrobromic salt, hydroiodic salt, hydrofluoric salt, sulfuric salt, citric salt, maleic salt, acetic salt, lactic salt, nicotinic salt, succinic salt, oxalic salt, phosphoric salt, malonic salt, salicylic salt, phenylacetic salt, stearic salt, pyridine salt, ammonium salt, piperazine salt, diethylamine salt, nicotinamide salt, formic salt, urea salt, sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt, lithium salt, cinnamic salt, methylamino salt, methanesulfonic salt, picric salt, tartaric salt, triethylamino salt, dimethylamino salt, tris (hydroxymethyl)aminomethane salt and the like. Additional pharmaceutically acceptable salts are known to those of skill in the art. When used in conjunction with a compound of this invention, the terms “elicite”, “eliciting,” modulator”, “modulate”, “modulating”, “regulator”, “regulate” or “regulating” selective gene expression refer to a compound that can act as an activator, an agonist, a pan-agonist or an antagonist of gene expression by a particular receptor, such as for example a Retinoid X Receptor and the like. The terms “therapeutic agent” and “chemotherapeutic agent”, refer to a compound or compounds and pharmaceutically acceptable compositions thereof that are administered to mammalian subjects as prophylactic or remedy in the treatment of a disease or medical condition. Such compounds may be administered to the subject via oral formulation, transdermal formulation or by injection. The term “Lewis acid” refers to a molecule that can accept an unshared pair of electrons and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “Lewis acid” includes but is not limited to: boron trifluoride, boron trifluoride etherate, boron trifluoride tetrahydrofuran complex, boron trifluoride tert-butyl-methyl ether complex, boron trifluoride dibutyl ether complex, boron trifluoride dihydrate, boron trifluoride di-acetic acid complex, boron trifluoride dimethyl sulfide complex, boron trichloride, boron trichloride dimethyl sulfide complex, boron tribromide, boron tribromide dimethyl sulfide complex, boron triiodide, triimethoxyborane, triethoxyborane, trimethylaluminum, triethylaluminum, aluminum trichloride, aluminum trichloride tetrahydrofuran complex, aluminum tribromide, titanium tetrachloride, titanium tetrabromide, titanium iodide, titanium tetraethoxide, titanium tetraisopropoxide, scandium (III) trifluoromethanesulfonate, yttrium (III) trifluoromethanesulfonate, ytterbium (III) trifluoromethanesulfonate, lanthanum (III) trifluoromethanesulfonate, zinc (II) chloride, zinc (II) bromide, zinc (II) iodide, zinc (II) trifluoromethanesulfonate, zinc (II) sulfate, magnesium sulfate, lithium perchlorate, copper (II) trifluoromethanesulfonate, copper (II) tetrafluoroborate and the like. Certain Lewis acids may have optically pure ligands attached to the electron acceptor atom, as set forth in Corey, E. J. Angewandte Chemie, International Edition (2002), 41 (10), 1650-1667; Aspinall, H. C. Chemical Reviews (Washington, D.C., United States) (2002), 102 (6), 1807-1850; Groger, H. Chemistry—A European Journal (2001), 7 (24), 5246-5251; Davies, H. M. L. Chemtracts (2001), 14 (11), 642-645; Wan, Y. Chemtracts (2001), 14 (11), 610-615; Kim, Y. H. Accounts of Chemical Research (2001), 34 (12), 955-962; Seebach, D. Angewandte Chemie, International Edition (2001), 40 (1), 92-138; Blaser, H. U. Applied Catalysis, A: General (2001), 221 (1-2), 119-143; Yet, L. Angewandte Chemie, International Edition (2001), 40 (5), 875-877; Jorgensen, K. A. Angewandte Chemie, International Edition (2000), 39 (20), 3558-3588; Dias, L. C. Current Organic Chemistry (2000), 4 (3), 305-342; Spindler, F. Enantiomer (1999), 4 (6), 557-568; Fodor, K. Enantiomer (1999), 4 (6), 497-511; Shimizu, K. D.; Comprehensive Asymmetric Catalysis I-III (1999), 3,1389-1399; Kagan, H. B. Comprehensive Asymmetric Catalysis I-III (1999), 1, 9-30; Mikami, K. Lewis Acid Reagents (1999), 93-136 and all references cited therein. Such Lewis acids maybe used by one of ordinary skill and knowledge in the art to produce optically pure compounds from achiral starting materials. The term “acylating agent” refers to a molecule that can transfer an alkylcarbonyl, substituted alkylcarbonyl or aryl carbonyl group to another molecule. The definition of “acylating agent” includes but is not limited to ethyl acetate, vinyl acetate, vinyl propionate, vinyl butyrate, isopropenyl acetate, 1-ethoxyvinyl acetate, trichloroethyl butyrate, trifluoroethyl butyrate, trifluoroethyl laureate, S-ethyl thiooctanoate, biacetyl monooxime acetate, acetic anhydride, acetyl chloride, succinic anhydride, diketene, diallyl carbonate, carbonic acid but-3-enyl ester cyanomethyl ester, amino acid and the like. The term “nucleophile” or “nucleophilic reagent” refers to a negatively charged or neutral molecule that has an unshared pair of electrons and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “nucleophile” includes but is not limited to: water, alkylhydroxy, alkoxy anion, arylhydroxy, aryloxy anion, alkylthiol, alkylthio anion, arylthiol, arylthio anion, ammonia, alkylamine, arylamine, alkylamine anion, arylamine anion, hydrazine, alkyl hydrazine, arylhydrazine, alkylcarbonyl hydrazine, arylcarbonyl hydrazine, hydrazine anion, alkyl hydrazine anion, arylhydrazine anion, alkylcarbonyl hydrazine anion, arylcarbonyl hydrazine anion, cyanide, azide, hydride, alkyl anion, aryl anion and the like. The term “electrophile” or “electrophilic reagent” refers to a positively charged or neutral molecule that has an open valence shell and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “electrophile” includes but is not limited to: hydronium, acylium, lewis acids, such as for example, boron trifluoride and the like, halogens, such as for example Br2 and the like, carbocations, such as for example tert-butyl cation and the like, diazomethane, trimethylsilyldiazomethane, alkyl halides, such as for example methyl iodide, benzyl bromide and the like, alkyl triflates, such as for example methyl triflate and the like, alkyl sulfonates, such as for example ethyl toluenesulfonate, butyl methanesulfonate and the like, acyl halides, such as for example acetyl chloride, benzoyl bromide and the like, acid anhydrides, such as for example acetic anhydride, succinic anhydride, maleic anhydride and the like, isocyanates, such as for example methyl isocyanate, phenylisocyanate and the like, chloroformates, such as for example methyl chloroformate, ethyl chloroformate, benzyl chloroformate and the like, sulfonyl halides, such as for example methanesulfonyl chloride, p-tolunesulfonyl chloride and the like, silyl halides, such as for example trimethylsilyl chloride, tertbutyldimethyl silyll chloride and the like, phosphoryl halide such as for example dimethyl chlorophosphate and the like, alpha-beta-unsaturated carbonyl compounds such as for example acrolein, methyl vinyl ketone, cinnamaldehyde and the like. The term “leaving group” refers to any atom (or group of atoms) that is stable in its anion or neutral form after it has been displaced by a nucleophile and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “leaving group” includes but is not limited to: water, methanol, ethanol, chloride, bromide, iodide, methanesulfonate, tolylsulfonate, trifluoromethanesulfonate, acetate, trichloroacetate, benzoate and the like. The term “oxidant” refers to any reagent that will increase the oxidation state of a carbon atom in the starting material by either adding an oxygen atom to this carbon or removing an electron from this carbon and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “oxidant” includes but is not limited to: osmium tetroxide, ruthenium tetroxide, ruthenium trichloride, potassium permanganate, meta-chloroperbenzoic acid, hydrogen peroxide, dimethyl dioxirane and the like. The term “metal ligand” refers to a molecule that has an unshared pair of electrons and can coordinate to a metal atom and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “metal ligand” includes but is not limited to: water, alkoxy anion, alkylthio anion, ammonia, trialkylamine, triarylamine, trialkylphosphine, triarylphosphine, cyanide, azide and the like. The term “reducing reagent” refers to any reagent that will decrease the oxidation state of a carbon atom in the starting material by either adding a hydrogen atom to this carbon or adding an electron to this carbon and as such would be obvious to one of ordinary skill and knowledge in the art. The definition of “reducing reagent” includes but is not limited to: borane-dimethyl sulfide complex, 9-borabicyclo[3.3.1.]nonane (9-BBN), catechol borane, lithium borohydride, sodium borohydride, sodium borohydride-methanol complex, potassium borohydride, sodium hydroxyborohydride, lithium triethylborohydride, lithium n-butylborohydride, sodium cyanoborohydride, calcium (II) borohydride, lithium aluminum hydride, diisobutylaluminum hydride, n-butyl-diisobutylaluminum hydride, sodium bis-methoxyethoxyaluminum hydride, triethoxysilane, diethoxymethylsilane, lithium hydride, lithium, sodium, hydrogen Ni/B, and the like. Certain acidic and Lewis acidic reagents enhance the activity of reducing reagents. Examples of such acidic reagents include: acetic acid, methanesulfonic acid, hydrochloric acid, and the like. Examples of such Lewis acidic reagents include: trimethoxyborane, triethoxyborane, aluminum trichloride, lithium chloride, vanadium trichloride, dicyclopentadienyl titanium dichloride, cesium fluoride, potassium fluoride, zinc (II) chloride, zinc (II) bromide, zinc (II) iodide, and the like. The term “coupling reagent” refers to any reagent that will activate the carbonyl of a carboxylic acid and facilitate the formation of an ester or amide bond. The definition of “coupling reagent” includes but is not limited to: acetyl chloride, ethyl chloroformate, dicyclohexylcarbodiimide (DCC), diisopropyl carbodiiimide (DIC), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCl), N-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-nitrophenol, pentafluorophenol, 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), O-benzotriazole-N,N,N′N′-tetramethyluronium hexafluorophosphate (HBTU), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate, bromo-trispyrrolidino-phosphonium hexafluorophosphate, 2-(5-norbornene-2,3-dicarboximido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), tetramethylfluoroformamidinium hexafluorophosphate and the like. The term “removable protecting group” or “protecting group” refers to any group which when bound to a functionality, such as the oxygen atom of a hydroxyl or carboxyl group or the nitrogen atom of an amino group, prevents reactions from occurring at these functional groups and which protecting group can be removed by conventional chemical or enzymatic steps to reestablish the functional group. The particular removable protecting group employed is not critical. The definition of “hydroxyl protecting group” includes but is not limited to: a) Methyl, tert-butyl, allyl, propargyl, p-chlorophenyl, p-methoxyphenyl, p-nitrophenyl, 2,4-dinitrophenyl, 2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl, methoxymethyl, methylthiomethyl, (phenyldimethylsilyl)methoxymethyl, benzyloxymethyl, p-methoxy-benzyloxymethyl, p-nitrobenzyloxymethyl, o-nitrobenzyloxymethyl, (4-methoxyphenoxy)methyl, guaiacolmethyl, tert-butoxymethyl, 4-pentenyloxymethyl, tert-butyldimethylsiloxymethyl, thexyldimethylsiloxymethyl, tert-butyldiphenylsiloxymethyl, 2-methoxyethoxymethyl, 2,2,2-trichloroethoxymethyl, bis (2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl, menthoxymethyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-[2-(trimethylsilyl)ethoxy]ethyl, 1-methyl-1-ethoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 1-methyl-1-phenoxyethyl, 2,2,2-trichloroethyl, 1-dianisyl-2,2,2-trichloroethyl, 1,1,1,3,3,3-hexafluoro-2-phenylisopropyl, 2-trimethylsilylethyl, 2-(benzylthio)ethyl, 2-(phenylselenyl)ethyl, tetrahydropyranyl, 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl, 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydropyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]4-methoxypiperidin-4-yl, 1-(2-fluorophenyl)4-methoxypiperidin-4-yl, 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl and the like; b) Benzyl, 2-nitrobenzyl, 2-trifluoromethylbenzyl, 4-methoxybenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-phenylbenzyl, 4acylaminobenzyl, 4-azidobenzyl, 4-(methylsulfinyl)benzyl, 2,4-dimethoxybenzyl, 4-azido-3-chlorobenzyl, 3,4-dimethoxybenzyl, 2,6-dichlorobenzyl, 2,6-difluorobenzyl, 1-pyrenylmethyl, diphenylmethyl, 4,4′-dinitrobenzhydryl, 5-benzosuberyl, triphenylmethyl(Trityl), α-naphthyldiphenylmethyl, (4-Methoxyphenyl)-diphenyl-methyl, di-(p-methoxyphenyl)-phenylmethyl, tri-(p-methoxyphenyl)methyl, 4-(4′-bromophenacyloxy)-phenyldiphenylmethyl, 4,4′,4″-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′-dimethoxy-3″-[N-(imidazolylmethyl)]trityl, 4,4′-dimethoxy-3″-[N-(imidazolylethyl)carbamoyl]trityl, 1,1-bis (4-methoxyphenyl)-1′-pyrenylmethyl, 4-(17-tetrabenzo[a,c,g,l]fluorenylmethyl)-4,4′-dimethoxytrityl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl and the like; c) Trimethylsilyl, triethylsilyl, triisopropylsilyl, dimethylisopropylsilyl, diethylisopropylsilyl, dimethylhexylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl, di-tert-butylmethylsilyl, tris (trimethylsilyl)silyl, (2-hydroxystyryl)dimethylsilyl, (2-hydroxystyryl)diisopropylsilyl, tert-butylmethoxyphenylsilyl, tert-butoxydiphenylsilyl and the like; d) —C(O)R20, where R20 is selected from alkyl, substituted alkyl, aryl and more specifically R20=hydrogen, methyl, ethyl, tert-butyl, adamantyl, crotyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, methoxymethyl, triphenylmethoxymethyl, phenoxymethyl, 4-chlorophenoxymethyl, phenylmethyl, diphenylmethyl, 4-methoxycrotyl, 3-phenylpropyl, 4-pentenyl, 4-oxopentyl, 4,4-(ethylenedithio)pentyl, 5-[3-bis (4-methoxyphenyl)hydroxymethylphenoxy]-4-oxopentyl, phenyl, 4-methylphenyl, 4-nitrophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-phenylphenyl, 2,4,6-trimethylphenyl, α-naphthyl, benzoyl and the like; e) —C(O)OR20, where R20 is selected from alkyl, substituted alkyl, aryl and more specifically R20=methyl, methoxymethyl, 9-fluorenylmethyl, ethyl, 2,2,2-trichloromethyl, 1,1-dimethyl-2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, 2-(phenylsulfonyl)ethyl, isobutyl, tert-Butyl, vinyl, allyl, 4-nitrophenyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl, 3,4-dimethoxybenzyl, 2-(methylthiomethoxy)ethyl, 2-dansenylethyl, 2-(4-nitrophenyl)ethyl, 2-(2,4-dinitrophenyl)ethyl, 2-cyano-1-phenylethyl, thiobenzyl, 4-ethoxy-1-naphthyl and the like. The definition of “amino protecting group” includes but is not limited to: a) 2-methylthioethyl, 2-methylsulfonylethyl, 2-(p-toluenesulfonyl)ethyl, [2-(1,3-dithianyl)]methyl, 4-methylthiophenyl, 2,4-dimethylthiophenyl, 2-phosphonioethyl, 1-methyl-1-(triphenylphosphonio)ethyl, 1,1-dimethyl-2-cyanoethyl, 2-dansylethyl, 2-(4-nitrophenyl)ethyl, 4-phenylacetoxybenzyl, 4-azidobenzyl, 4-azidomethoxybenzyl, m-chloro-p-acyloxybenzyl, p-(dihydroxyboryl)benzyl, 5-benzisoxazolylmethyl, 2-(trifluoromethyl)-6-chromonylmethyl, m-nitrophenyl, 3.5-dimethoxybenzyl, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl, o-nitrobenzyl, α-methylnitropiperonyl, 3,4-dimethoxy-6-nitrobenzyl, N-benzenesulfenyl, N-o-nitrobenzenesulfenyl, N-2,4-dinitrobenzenesulfenyl, N-pentachlorobenzenesulfenyl. N-2-nitro-4-methoxybenzenesulfenyl, N-triphenylmethylsulfenyl, N-1-(2,2,2-trifluoro-1,1-diphenyl)ethylsulfenyl, N-3-nitro-2-pyridinesulfenyl, N-p-toluenesulfonyl, N-benzenesulfonyl, N-2,3,6-trimethyl-4-methoxybenzenesulfonyl, N-2,4,6-trimethoxybenzene-sulfonyl, N-2,6-dimethyl-4-methoxybenzenesulfonyl, N-pentamethylbenzenesulfonyl, N-2,3,5,6-tetramethyl-4-methoxybenzenesulfonyl and the like; b) —C(O)OR20, where R20 is selected from alkyl, substituted alkyl, aryl and more specifically R20=methyl, ethyl, 9-fluorenylmethyl, 9-(2-sulfo)fluorenylmethyl. 9-(2,7-dibromo)fluorenylmethyl, 17-tetrabenzo[a,c,g,i]fluorenylmethyl. 2-chloro-3-indenylmethyl, benz[f]inden-3-ylmethyl, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothloxanthyl)]methyl, 1,1-dioxobenzo[b]thiophene-2-ylmethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-phenylethyl, 1-(1-adamantyl)-1-methylethyl, 2-chloroethyl, 1,1-dimethyl-2-haloethyl, 1,1-dimethyl-2,2-dibromoethyl, 1,1-dimethyl-2,2,2-trichloroethyl, 1-methyl-1-(4-biphenylyl)ethyl, 1-(3,5-di-tert-butylphenyl)-1-methylethyl, 2-(2′-pyridyl)ethyl, 2-(4′-pyridyl)ethyl, 2,2-bis (4′-nitrophenyl)ethyl, N-(2-pivaloylamino)-1,1-dimethylethyl, 2-[(2-nitrophenyl)dithio]-1-phenylethyl, tert-butyl, 1-adamantyl, 2-adamantyl, Vinyl, allyl, 1-Isopropylallyl, cinnamyl. 4-nitrocinnamyl, 3-(3′-pyridyl)prop-2-enyl, 8-quinolyl, N-Hydroxypiperidinyl, alkyldithio, benzyl, p-methoxybenzyl, p-nitrobenzyl, p-bromobenzyl. p-chlorobenzyl, 2,4-dichlorobenzyl, 4-methylsulfinylbenzyl, 9-anthrylmethyl, diphenylmethyl, tert-amyl, S-benzyl thiocarbamate, butynyl, p-cyanobenzyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclopropylmethyl, p-decyloxybenzyl, diisopropylmethyl, 2,2-dimethoxycarbonylvinyl, o-(N,N′-dimethylcarboxamido)benzyl, 1,1-dimethyl-3-(N,N′-dimethylcarboxamido)propyl, 1,1-dimethylpropynyl, di(2-pyridyl)methyl, 2-furanylmethyl, 2-Iodoethyl, isobornyl, isobutyl, isonicotinyl, p-(p′-methoxyphenylazo)benzyl, 1-methylcyclobutyl, 1-methylcyclohexyl, 1-methyl-1-cyclopropylmethyl, 1-methyl-1-(p-phenylazophenyl)ethyl, 1-methyl-1-phenylethyl, 1-methyl-1-4′-pyridylethyl, phenyl, p-(phenylazo)benzyl, 2,4,6-tri-methylphenyl, 4-(trimethylammonium)benzyl, 2,4,6-trimethylbenzyl and the like. The definition of “carboxyl protecting group” includes but is not limited to: 2-N-(morpholino)ethyl, choline, methyl, methoxyethyl, 9-Fluorenylmethyl, methoxymethyl, methylthiomethyl, tetrahydropyranyl, tetrahydrofuranyl, methoxyethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, benzyloxymethyl, pivaloyloxymethyl, phenylacetoxymethyl, triisopropylsilylmethyl, cyanomethyl, acetol, p-bromophenacyl. α-methylphenacyl, p-methoxyphenacyl, desyl, carboxamidomethyl, p-azobenzenecarboxamido-methyl, N-phthalimidomethyl, (methoxyethoxy)ethyl, 2,2,2-trichloroethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 4-chlorobutyl, 5-chloropentyl, 2-(trimethylsilyl)ethyl, 2-methylthioethyl, 1,3-dithianyl-2-methyl, 2-(p-nitrophenylsulfenyl)ethyl, 2-(p-toluenesulfonyl)ethyl, 2-(2-pyridyl)ethyl, 2-(p-methoxyphenyl)ethyl, 2-(diphenylphosphino)ethyl, 1-methyl-1-phenylethyl, 2-(4-acetyl-2-nitrophenyl)ethyl, 2-cyanoethyl, heptyl, tert-butyl, 3-methyl-3-pentyl, dicyclopropylmethyl, 2,4-dimethyl-3-pentyl, cyclopentyl, cyclohexyl, allyl, methallyl, 2-methylbut-3-en-2-yl, 3-methylbut-2-(prenyl), 3-buten-1-yl, 4-(trimethylsilyl)-2-buten-1-yl, cinnamyl, α-methylcinnamyl, propargyl, phenyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl, 2,6-di-tert-butyl-4-methylphenyl, 2,6-di-tert-butyl-4-methoxyphenyl, p-(methylthio)phenyl, pentafluorophenyl, benzyl, triphenylmethyl, diphenylmethyl, bis (o-nitrophenyl)methyl, 9-anthrylmethyl, 2-(9,10-dioxo)anthrylmethyl. 5-dibenzosuberyl, 1-pyrenylmethyl, 2-(trifluoromethyl)-6-chromonylmethyl, 2,4,6-trimethylbenzyl, p-bromobenzyl, o-nitrobenzyl, p-nitrobenzyl, p-methoxybenzyl, 2.6-dimethoxybenzyl, 4-(methylsulfinyl)benzyl, 4-Sulfobenzyl, 4-azidomethoxybenzyl, 4-{a/-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl, piperonyl, 4-picolyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, isopropyldimethylsilyl, phenyldimethylsilyl, di-tert-butylmethylsilyl, triisopropylsilyl and the like. The term “Amino acid” refers to any of the naturally occurring amino acids, as well as synthetic analogs and derivatives thereof. Alpha-Amino acids comprise a carbon atom to which is bonded an amino group, a carboxy group, a hydrogen atom, and a distinctive group referred to as a “side chain”. The side chains of naturally occurring amino acids are well known in the art and include, for example, hydrogen (e.g., as in glycine), alkyl (e.g., as in alanine, valine, leucine, isoleucine, proline), substituted alkyl (e.g., as in threonine, serine, methionine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, arginine, and lysine), arylalkyl (e.g., as in phenylalanine), substituted arylalkyl (e.g., as in tyrosine), heteroarylalkyl (e.g., as in tryptophan, histidine) and the like. One of skill in the art will appreciate that the term “amino acid” can also include beta-, gamma-, delta-, omega-amino acids, and the like. Unnatural amino acids are also known in the art, as set forth in, Natchus, M. gram. Organic Synthesis: Theory and Applications (2001), 5, 89-196; Ager, D. J. Current Opinion in Drug Discovery & Development (2001), 4 (6), 800; Reginato, gram. Recent Research Developments in Organic Chemistry (2000), 4 (Pt. 1), 351-359; Dougherty, D. A. Current Opinion in Chemical Biology (2000), 4 (6), 645-652; Lesley, S. A. Drugs and the Pharmaceutical Sciences (2000), 101 (Peptide and Protein Drug Analysis), 191-205; Pojitkov, A. E. Journal of Molecular Catalysis B: Enzymatic (2000), 10 (1-3), 47-55; Ager, D. J. Speciality Chemicals (1999), 19 (1), 10-12, and all references cited therein. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids, unnatural amino acids such as alpha, alpha-disubstituted amino acids and other unconventional amino acids may also be suitable components for compounds of the present invention. Examples of unconventional amino acids include: 4-hydroxyproline, 3-methylhistidine, 5-hydroxylysine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). The term “N-protected amino acid” refers to any amino acid which has a protecting group bound to the nitrogen of the amino functionality. This protecting group prevents reactions from occurring at the amino functional group and can be removed by conventional chemical or enzymatic steps to reestablish the amino functional group. The particular protecting group employed is not critical. The term “O-protected amino acid” refers to any amino acid which has a protecting group bound to the oxygen of the carboxyl functionality. This protecting group prevents reactions from occurring at the carboxyl functional group and can be removed by conventional chemical or enzymatic steps to reestablish the carboxyl functional group. The particular protecting group employed is not critical. The term “Prodrug” refers to an agent that is converted into the parent drug in vivo. Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. A prodrug may be converted into the parent drug by various mechanisms, including enzymatic processes and metabolic hydrolysis. See Harper, “Drug Latentiation” in Jucker, ed. Progress in Drug Research 4:221-294 (1962); Morozowich et al., “Application of Physical Organic Principles to Prodrug Design” in E. B. Roche ed. Design of Biopharmaceutical Properties through Prodrugs and Analogs, APHA Acad. Pharm. Sci. (1977); Bioreversible Carriers in Drug in Drug Design, Theory and Application, E. B. Roche, ed., APHA Acad. Pharm. Sci. (1987); Design of Prodrugs, H. Bundgaard, Elsevier (1985); Wang et al. “Prodrug approaches to the improved delivery of peptide drug” in Curr. Pharm. Design. 5 (4):265-287 (1999); Pauletti et al. (1997) Improvement in peptide bioavailability: Peptidomimetics and Prodrug Strategies, Adv. Drug. Delivery Rev. 27:235-256; Mizen et al. (1998) “The Use of Esters as Prodrugs for Oral Delivery of beta.-Lactam antibiotics,” Pharm. Biotech. 11:345-365; Gaignault et al. (1996) “Designing Prodrugs and Bioprecursors I. Carrier Prodrugs,” Pract. Med. Chem. 671-696; Asgharnejad, “Improving Oral Drug Transport”, in Transport Processes in Pharmaceutical Systems, gram. L. Amidon, P. I. Lee and E. M. Topp, Eds., Marcell Dekker, p. 185-218 (2000); Balant et al., “Prodrugs for the improvement of drug absorption via different routes of administration”, Eur. J. Drug Metab. Pharmacokinet., 15 (2): 143-53 (1990); Balimane and Sinko, “Involvement of multiple transporters in the oral absorption of nucleoside analogues”, Adv. Drug Delivery Rev., 39 (1-3): 183-209 (1999); Browne, “Fosphenyloin (Cerebyx)”, Clin. Neuropharmacol. 20 (1): 1-12 (1997); Bundgaard, “Bioreversible derivatization of drugs—principle and applicability to improve the therapeutic effects of drugs”, Arch. Pharm. Chemi 86 (1): 1-39 (1979); Bundgaard H. “Improved drug delivery by the prodrug approach”, Controlled Drug Delivery 17: 179-96 (1987); Bundgaard H. “Prodrugs as a means to improve the delivery of peptide drugs”, Adv. Drug Delivery Rev. 8 (1): 1-38 (1992); Fleisher et al. “Improved oral drug delivery: solubility limitations overcome by the use of prodrugs”, Adv. Drug Delivery Rev. 19 (2): 115-130 (1996); Fleisher et al. “Design of prodrugs for improved gastrointestinal absorption by intestinal enzyme targeting”, Methods Enzymol. 112 (Drug Enzyme Targeting, Pt. A): 360-81, (1985); Farquhar D, et al., “Biologically Reversible Phosphate-Protective Groups”, J. Pharm. Sci., 72 (3): 324-325 (1983); Freeman S, et al., “Bioreversible Protection for the Phospho Group: Chemical Stability and Bioactivation of Di(4-acetoxy-benzyl) Methylphosphonate with Carboxyesterase,” J. Chem. Soc., Chem. Commun., 875-877 (1991); Friis and Bundgaard, “Prodrugs of phosphates and phosphonates: Novel lipophilic alpha-acyloxyalkyl ester derivatives of phosphate- or phosphonate containing drugs masking the negative charges of these groups”, Eur. J. Pharm. Sci. 4: 49-59 (1996); Gangwar et al., “Prodrug, molecular structure and percutaneous delivery”, Des. Biopharm. Prop. Prodrugs Analogs, [Symp.] Meeting Date 1976, 409-21. (1977); Nathwani and Wood, “Penicillins: a current review of their clinical pharmacology and therapeutic use”, Drugs 45 (6): 866-94 (1993); Sinhababu and Thakker, “Prodrugs of anticancer agents”, Adv. Drug Delivery Rev. 19 (2): 241-273 (1996); Stella et al., “Prodrugs. Do they have advantages in clinical practice?”, Drugs 29 (5): 455-73 (1985); Tan et al. “Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships and pharmacokinetics”, Adv. Drug Delivery Rev. 39 (1-3): 117-151 (1999); Taylor, “Improved passive oral drug delivery via prodrugs”, Adv. Drug Delivery Rev., 19 (2): 131-148 (1996); Valentino and Borchardt, “Prodrug strategies to enhance the intestinal absorption of peptides”, Drug Discovery Today 2 (4): 148-155 (1997); Wiebe and Knaus, “Concepts for the design of anti-HIV nucleoside prodrugs for treating cephalic HIV infection”, Adv. Drug Delivery Rev.: 39 (1-3):63-80 (1999); Waller et al., “Prodrugs”, Br. J. Clin. Pharmac. 28: 497-507 (1989). The terms “halogen”, “halide” or “halo” include fluorine, chlorine, bromine, and iodine. The terms “alkyl” and “substituted alkyl” are interchangeable and include substituted and unsubstituted C1-C10 straight chain saturated aliphatic hydrocarbon groups, substituted and unsubstituted C2-C10 straight chain unsaturated aliphatic hydrocarbon groups, substituted and unsubstituted C4-C10 branched saturated aliphatic hydrocarbon groups, substituted and unsubstituted C4-C10 branched unsaturated aliphatic hydrocarbon groups, substituted and unsubstituted C3-C8 cyclic saturated aliphatic hydrocarbon groups, substituted and unsubstituted C5-C8 cyclic unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, the definition of “alkyl” shall include but is not limited to: methyl (Me), ethyl (Et), propyl (Pr), butyl (Bu), pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, ethenyl, propenyl, butenyl, penentyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, isopropyl (i-Pr), isobutyl (i-Bu), tert-butyl (t-Bu), sec-butyl (s-Bu), isopentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, methylcyclopropyl, ethylcyclohexenyl, butenylcyclopentyl, adamantyl, norbornyl and the like. Alkyl substituents are independently selected from the group comprising halogen, —OH, —SH, —NH2, —CN, —NO2, ═O, ═CH2, trihalomethyl, carbamoyl, arylC0-10alkyl, heteroarylC0-10alkyl, C1-10alkyloxy, arylC0-10alkyloxy, C1-10alkylthio, arylC0-10alkylthio, C1-10alkylamino, arylC0-10 alkylamino, N-aryl-N-C0-10alkylamino, C1-10alkylcarbonyl, arylC0-10alkylcarbonyl, C1-10alkylcarboxy, arylC0-10alkylcarboxy, C1-10alkylcarbonylamino, arylC0-10alkylcarbonylamino, tetrahydrofuryl, morpholinyl, piperazinyl, hydroxypyronyl, —C0-10alkylCOOR21 and —C0-10alkylCONR22R23 wherein R21, R22 and R23 are independently selected from hydrogen, alkyl, aryl, or R22 and R23 are taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 8 carbon atoms with at least one substituent as defined herein. The term “alkyloxy” (e.g. methoxy, ethoxy, propyloxy, allyloxy, cyclohexyloxy) represents a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms attached through an oxygen bridge. The term “alkyloxyalkyl” represents an alkyloxy group attached through an alkyl or substituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylthio” (e.g. methylthio, ethylthio, propylthio, cyclohexenylthio and the like) represents a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms attached through a sulfur bridge. The term “alkylthioalkyl” represents an alkylthio group attached through an alkyl or substituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylamino” (e.g. methylamino, diethylamino, butylamino, N-propyl-N-hexylamino, (2-cyclopentyl)propylamino, hexenylamino, and the like) represents one or two substituted or unsubstituted alkyl groups as defined above having the indicated number of carbon atoms attached through an amine bridge. The substituted or unsubstituted alkyl groups maybe taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 10 carbon atoms with at least one substituent as defined above. The term “alkylaminoalkyl” represents an alkylamino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylhydrazino” (e.g. methylhydrazino, diethylhydrazino, butylhydrazino, (2-cyclopentyl)propylhydrazino, cyclohexanehydrazino, and the like) represents one or two substituted or unsubstituted alkyl groups as defined above having the indicated number of carbon atoms attached through a nitrogen atom of a hydrazine bridge. The substituted or unsubstituted alkyl groups maybe taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 10 carbon atoms with at least one substituent as defined above. The term “alkylhydrazinoalkyl” represents an alkylhydrazino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylcarbonyl” (e.g. cyclooctylcarbonyl, pentylcarbonyl, 3-hexenylcarbonyl and the like) represents a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms attached through a carbonyl group. The term “alkylcarbonylalkyl” represents an alkylcarbonyl group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylcarboxy” (e.g. heptylcarboxy, cyclopropylcarboxy, 3-pentenylcarboxy and the like) represents an alkylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen. The term “alkylcarboxyalkyl” represents an alkylcarboxy group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term “alkylcarbonylamino” (e.g. hexylcarbonylamino, cyclopentylcarbonyl-aminomethyl, methylcarbonylaminophenyl and the like) represents an alkylcarbonyl group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group. The nitrogen group may itself be substituted with a substituted or unsubstituted alkyl or aryl group. The term “alkylcarbonylaminoalkyl” represents an alkylcarbonylamino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “alkylcarbonylhydrazino” (e.g. ethylcarbonylhydrazino, tert-butylcarbonylhydrazino and the like) represents an alkylcarbonyl group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of a hydrazino group. The term “aryl” represents an unsubstituted, mono-, di- or trisubstituted monocyclic, polycyclic, biaryl aromatic groups covalently attached at any ring position capable of forming a stable covalent bond, certain preferred points of attachment being apparent to those skilled in the art (e.g., 3-phenyl, 4-naphtyl and the like). The aryl substituents are independently selected from the group comprising halogen, —OH, —SH, —CN, —NO2, trihalomethyl, hydroxypyronyl, C1-10alkyl, arylC0-10alkyl, C0-10alkyloxyC0-10alkyl, arylC0-10alkyloxyC0-10alkyl, C0-10alkylthioC0-10alkyl, arylC0-10alkylthioC0-10alkyl, C0-10alkylaminoC0-10alkyl, arylC0-10alkylaminoCO0-10alkyl, N-aryl-N-C0-10alkylaminoC0-10alkyl, C1-10alkylcarbonylC0-10alkyl, arylC0-10alkylcarbonylC0-10alkyl, C1-10alkylcarboxyC0-10alkyl, arylC0-10alkylcarboxyC0-10alkyl, C0-10alkylcarbonylaminoC0-10alkyl, arylC0-10alkylcarbonylaminoC0-10alkyl, —C0-10alkylCOOR21, and —C0-10alkylCONR22R23 wherein R21, R22 and R23 are independently selected from hydrogen, alkyl, aryl or R22 and R23 are taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 8 carbon atoms with at least one substituent as defined above. The definition of “aryl” includes but is not limited to phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl and the like. The term “arylalkyl” (e.g. (4-hydroxyphenyl)ethyl, (2-aminonaphthyl)hexenyl and the like) represents an aryl group as defined above attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylcarbonyl” (e.g. 2-thiophenylcarbonyl, 3-methoxyanthrylcarbonyl and the like) represents an aryl group as defined above attached through a carbonyl group. The term “arylalkylcarbonyl” (e.g. (2,3-dimethoxyphenyl)propylcarbonyl, (2-chloronaphthyl)pentenyl-carbonyl and the like) represents an arylalkyl group as defined above wherein the alkyl group is in turn attached through a carbonyl. The term “aryloxy” (e.g. phenoxy, naphthoxy, 3-methylphenoxy, and the like) represents an aryl or substituted aryl group as defined above having the indicated number of carbon atoms attached through an oxygen bridge. The term “aryloxyalkyl” represents an aryloxy group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylthio” (e.g. phenylthio, naphthylthio, 3-bromophenylthio, and the like) represents an aryl or substituted aryl group as defined above having the indicated number of carbon atoms attached through a sulfur bridge. The term “arylthioalkyl” represents an arylthio group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylamino” (e.g. phenylamino, diphenylamino, naphthylamino, N-phenyl-N-naphthylamino, o-methylphenylamino, p-methoxyphenylamino, and the like) represents one or two aryl groups as defined above having the indicated number of carbon atoms attached through an amine bridge. The term “arylaminoalkyl” represents an arylamino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylalkylamino” represents an aryl group attached through an alkylamino group as defined above having the indicated number of carbon atoms. The term “N-aryl-N-alkylamino” (e.g. N-phenyl-N-methylamino, N-naphthyl-N-butylamino, and the like) represents one aryl and one a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms independently attached through an amine bridge. The term “arylhydrazino” (e.g. phenylhydrazino, naphthylhydrazino, 4-methoxyphenylhydrazino, and the like) represents one or two aryl groups as defined above having the indicated number of carbon atoms attached through a hydrazine bridge. The term “arylhydrazinoalkyl” represents an arylhydrazino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylalkylhydrazino” represents an aryl group attached through an alkylhydrazino group as defined above having the indicated number of carbon atoms. The term “N-aryl-N-alkylhydrazino” (e.g. N-phenyl-N-methylhydrazino, N-naphthyl-N-butylhydrazino, and the like) represents one aryl and one a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms independently attached through an amine atom of a hydrazine bridge. The term “arylcarboxy” (e.g. phenylcarboxy, naphthylcarboxy, 3-fluorophenylcarboxy and the like) represents an arylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge. The term “arylcarboxyalkyl” represents an arylcarboxy group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The term “arylcarbonylamino” (e.g. phenylcarbonylamino, naphthylcarbonylamino, 2-methylphenylcarbonylamino and the like) represents an arylcarbonyl group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group. The nitrogen group may itself be substituted with an a substituted or unsubstituted alkyl or aryl group. The term “arylcarbonylaminoalkyl” represents an arylcarbonylamino group attached through a substituted or unsubstituted alkyl group as defined above having the indicated number of carbon atoms. The nitrogen group may itself be substituted with a substituted or unsubstituted alkyl or aryl group. The term “arylcarbonylhydrazino” (e.g. phenylcarbonylhydrazino, naphthylcarbonylhydrazino, and the like) represents an arylcarbonyl group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of a hydrazino group. The terms “heteroaryl”, “heterocycle” or “heterocyclic” refers to a monovalent unsaturated group having a single ring or multiple condensed rings, from 1 to 8 carbon atoms and from 1 to 4 hetero atoms selected from nitrogen, sulfur or oxygen within the ring. The heteroaryl groups in this invention can be optionally substituted with 1 to 3 substituents selected from the group comprising: halogen, —OH, —SH, —CN, —NO2, trihalomethyl, hydroxypyronyl, C1-10alkyl, arylC0-10alkyl, C0-10alkyloxyC0-10alkyl, arylC0-10alkyloxyC0-10alkyl, C0-10alkylthioC0-10alkyl, arylC0-10alkylthioC0-10alkyl, C0-10alkylaminoC0-10alkyl, arylC0-10alkylaminoC0-10alkyl, N-aryl-N-C0-10alkylaminoC0-10alkyl, C1-10alkylcarbonylC0-10alkyl, arylC0-10alkylcarbonylC0-10alkyl, C1-10alkylcarboxyC0-10alkyl, arylC0-10alkylcarboxyC0-10alkyl, C1-10alkylcarbonylaminoC-0-10alkyl, arylC0-10alkylcarbonylaminoC0-10alkyl, —C0-10alkylCOOR21, and —CO10alkylCONR22R23 wherein R21, R22 and R23 are independently selected from hydrogen, alkyl, aryl, or R22 and R23 are taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 8 carbon atoms with at least one substituent as defined above. The definition of “heteroaryl” includes but is not limited to thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, pyrrolyl-2,5-dione, 3-pyrrolinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, indolizinyl, indazolyl, phthalimidyl (or isoindoly-1,3-dione), imidazolyl, 2H-imidazolinyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolidinyl-2,5-dione, imidazolidinyl-2,4-dione, 2-thioxo-imidazolidinyl-4-one, imidazolidinyl-2,4-dithione, thiazolidinyl-2,4-dione, 4-thioxo-thiazolidinyl-2-one, piperazinyl-2,5-dione, tetrahydro-pyridazinyl-3,6-dione, 1,2-dihydro-[1,2,4,5]tetrazinyl-3,6-dione, [1,2,4,5]tetrazinanyl-3,6-dione, dihydro-pyrimidinyl-2,4-dione, pyrimidinyl-2,4,6-trione and the like. For the purposes of this application, the terms “heteroaryl”, “heterocycle” or “heterocyclic” do not include carbohydrate rings (i.e. mono- or oligosaccharides). The term “saturated heterocyclic” represents an unsubstituted, mono-, di- or trisubstituted monocyclic, polycyclic saturated heterocyclic group covalently attached at any ring position capable of forming a stable covalent bond, certain preferred points of attachment being apparent to those skilled in the art (e.g., 1-piperidinyl, 4-piperazinyl and the like). The saturated heterocyclic substituents are independently selected from the group comprising halo, —OH, —SH, —CN, —NO2, trihalomethyl, hydroxypyronyl, C1-10alkyl, arylC0-10alkyl, C0-10alkyloxyC0-10alkyl, arylC0-10alkyloxyC0-10alkyl, C0-10alkylthioC0-10alkyl, arylC0-10alkylthioC0-10alkyl, C0-10alkylaminoC0-10alkyl, arylC0-10alkylaminoC0-10alkyl, N-aryl-N-C0-10alkylaminoC0-10alkyl, C1-10alkylcarbonylC0-10alkyl, arylC0-10alkylcarbonylC0-10alkyl, C1-10alkylcarboxyC0-10alkyl, arylC0-10alkylcarboxyC0-10alkyl, C1-10alkylcarbonylaminoC0-10alkyl, arylC0-10alkylcarbonylaminoC0-10alkyl, —C0-10alkylCOOR21, and —C0-10alkylCONR22R23 wherein R21, R22 and R23 are independently selected from hydrogen, alkyl, aryl, or R22 and R23 are taken together with the nitrogen to which they are attached forming a saturated cyclic or unsaturated cyclic system containing 3 to 8 carbon atoms with at least one substituent as defined above. The definition of saturated heterocyclic includes but is not limited to pyrrolidinyl, pyrazolidinyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithienyl, thiomorpholinyl, piperazinyl, quinuclidinyl, and the like. The term “alpha-beta-unsaturated carbonyl” refers to a molecule that has a carbonyl group directly attached to a double or triple bonded cabon and which would be obvious to one of ordinary skill and knowledge in the art. The definition of alpha-beta-unsaturated carbonyl includes but is not limited to acrolein, methyl vinyl ketone, and the like. The term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by, practitioners of the chemical, pharmaceutical, biological, biochemical and medical arts. As used herein, the term “modulation” or “modulating” refers to the alteration of the catalytic activity of an enzyme or receptor in vitro and/or in vivo. “In vitro” refers to procedures performed in an artificial environment such as, such as for example, without limitation, in a test tube or culture medium. The skilled artisan will understand that, for example, an isolated enzyme and/or receptor may be contacted with a modulator in an in vitro environment. Alternatively, an isolated cell may be contacted with a modulator in an in vitro environment. As used herein, “in vivo” refers to procedures performed within a living organism such as, without limitation, a mouse, rat, rabbit, ungulate, bovine, equine, porcine, canine, feline, primate, or human. The term “organism” refers to any living entity comprised of at least one cell. A living organism can be as simple as, for example, a single eukaryotic cell or as complex as a mammal, including a human being. The term “therapeutically effective amount” as used herein refers to that amount of the compound being administered which will relieve to some extent one or more of the symptoms of the disorder being treated. For example, in reference to the treatment of cancer, a therapeutically effective amount refers to that amount which has the effect of (1) reducing the size of the tumor, (2) inhibiting (that is, slowing to some extent, preferably stopping) tumor metastasis, (3) inhibiting to some extent (that is, slowing to some extent, preferably stopping) tumor growth, and/or, (4) relieving to some extent (or, preferably, eliminating) one or more symptoms associated with the cancer. “Pharmaceutically acceptable salt” refers to those salts which retain the biological effectiveness and properties of the free bases and which are obtained by reaction with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, malic acid, maleic acid, succinic acid, tartaric acid, citric acid, and the like. A “pharmaceutical composition” refers to a mixture of one or more of the compounds described herein, or a pharmaceutically acceptable salts thereof, with other chemical components, such as physiologically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism. As used herein, a “pharmaceutically acceptable carrier” refers to a carrier or diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. An “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate administration of a compound. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. “Treating” or “treatment” of a disease includes preventing the disease from occurring in an animal that may be predisposed to the disease but does not yet experience or exhibit symptoms of the disease (prophylactic treatment), inhibiting the disease (slowing or arresting its development), providing relief from the symptoms or side-effects of the disease (including palliative treatment), and relieving the disease (causing regression of the disease). A “subject” of treatment is an animal, such as a mammal, including a human. Animals subject to treatment include, for example, fish, birds, and mammals such as cows, sheep, pigs, horses, dogs, cats and the like. A “therapeutic treatment” is a treatment administered to a subject who exhibits signs of pathology for the purpose of diminishing or eliminating those signs. Preferred compounds of the present invention also include pharmaceutically acceptable salts of the compounds of the above formulae. A “pharmaceutically acceptable salt” is a salt that can be formulated into a compound for pharmaceutical use including, such as for example, metal salts (sodium, potassium, magnesium, calcium, etc.) and salts of ammonia or organic amines. In one aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for enteral, parenteral, topical or ocular administration. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for the prophylactic and therapeutic treatment of subjects as described herein. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for inhibiting oxidation in biological materials. The methods involve contacting the biological material with an effective amount of the compound. In the therapeutic methods of this invention, a pharmacologically effective amount of the compound is administered to a subject suffering from a pathological condition responsive to inhibition of oxidation. In the prophylactic methods of this invention a pharmaceutically effective amount of the compound is administered to a subject at risk of developing a disease as a result of exposure to oxidative stress. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for the treatment or prevention of conditions having an inflammatory component. A pharmacologically effective amount of the compound is administered to a subject suffering from, or at risk of suffering from, a pathological condition that can be improved by inhibiting inflammation. In general, an effective dose is about 100 milligram to about 1 gram taken orally per day. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for treating arthritis, both rheumatoid arthritis and osteoarthritis. The compounds preferably are delivered orally or transdermally for this purpose. A pharmacologically effective amount of the agent taken orally is about 50 milligram to about 2 gram daily. In yet another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for the prophylactic or therapeutic treatment of respiratory disorders that involve an inflammatory component. Examples of respiratory diseases that can be treated with these compounds include acid aspiration, adult/infant respiratory distress syndrome, airway obstructive disease, asthma, bronchiolitis, bronchopulmonary dysplasia, cancer, chronic obstructive pulmonary disease (“COPD”), cystic fibrosis, emphysema, HIV-associated lung disease, idiopathic pulmonary fibrosis, immune-complex-mediated lung injury, exposure to an oxidizing agent, ischemia-reperfusion injury, mineral dust pneumoconiosis, drug-induced lung disease, silo-filler's disease and the like. In the treatment of respiratory conditions, the compound is preferably delivered by inhalation. The compound can be delivered as an aerosol, mist or powder. An effective amount for delivery by inhalation is about 0.1 milligram to 10 milligram per inhalation, several times daily. The compound also can be delivered orally in amounts of about 50 milligram to about 2 gram daily. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for the treatment of nervous system disorders. Examples of such neurodegenerative conditions of the nervous system include Friedrich's disease, Parkinson's disease, Alzheimer's disease, Huntington's disease, Pick disease, amyotrophic lateral sclerosis, multiple sclerosis and the like. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for treating trauma to the central nervous system. Examples of such trauma include skull fracture and its resulting edema, concussion, contusion, brain hemorrhages, shearing lesions, subdural hematoma, epidural hematoma, spinal cord injury and the like. In the treatment of traumatic conditions of the central nervous system, the compound preferably is administered parenterally, such as by intravenous injection or injection directly into the central nervous system (i.e., intrathecally (IT) or into the brain). A pharmacologically effective amount of the compound is about 25 milligram to about 500 milligram i.v. or i.m. and about 5 milligram to about 100 milligram IT. The treatment of chronic neurodegenerative disease is best effected via oral administration of an effective amount of the compound, preferably 50 milligram to 2 gram daily. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for preventing/treating cardiovascular disease, including but not limited to ischemia-reperfusion dysfunction, atherosclerosis and restenosis following angioplasty. Oral, enteral or intravenous administration is useful for this purpose. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for the treatment of cancer or as adjuvants in the treatment of cancer. Co-administered with chemotherapeutic agents, they enhance cytotoxicity, thereby inhibiting the growth of tumors. In addition, they also inhibit oxidative damage that generally accompanies use of anticancer agents. Methods of treating cancer involve administering a pharmacologically effective amount of the compound to a subject prior to, during or after chemotherapy. The compounds are useful in the treatment of any cancer. However, they are particularly effective in the treatment of colorectal cancer and lung cancer. The compounds also are effective with chemotherapeutic agents that act by all known modes of action. In such treatments, the compounds preferably are delivered as a pharmaceutical composition in the form of an intravenous or intramuscular solution. However, other modes of delivery, such as enteral administration, also are useful. An effective amount of the agent is about 50 milligram to about 2 gram delivered daily over the course of the chemotherapy regimen. In yet another aspect, the invention relates to pharmaceutical compositions containing the novel compounds of the invention in combination with other therapeutic agents and to methods of treating diseases and/or conditions using the same. Example of diseases and/or conditions include cancer, mammary cancer, prostate cancer, kidney cancer, Karposi's sarcoma, colon cancer, cervical cancer, lung cancer, cutaneous T-cell lymphoma, cancer of the head and neck, cancers of the aerodigestive pathway, skin cancer, bladder cancer, sarcomas, leukoplakias, acute promyelocytic leukemia and the like. Examples of other therapeutic agents include Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Cytosine arabinoside, Etoposide, 5-Fluorouracil, Melphalan, Methotrexate, Mitoxantrone, Taxol, Interferon, Fareston, Arzoxifene, Evista, Tamoxifen, and the like. In another aspect, the invention relates to the use of pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, as hypnotic agents for the same indications as 2,6-diisopropylphenol. Examples of such indications include inducing and/or maintaining general anaesthesia, use as a sedative and the like. The compound is administered in an amount effective to induce hypnosis. For use as a general anaesthetic, the compounds are preferably administered as an intravenous aqueous solution. However, they also can be administered by inhalation. For use as a sedative (such as for example, for the treatment of anxiety conditions), the compounds are preferably and effectively administered orally in amounts of about 10 milligram to 2 gram daily. However, they can also be administered by inhalation, intravenously or intramuscularly. The novel compounds of this invention can be administered in similar amounts and in the same schedule as injectable emulsions of DIPRIVAN™. Dosage level of 2,6-diisopropylphenol for producing general anesthesia, both induction (for example about 2.0 to about 2.5 milligram/kg for an adult) and maintenance (for example, about 4 to about 12 milligram/kg/hr) and for producing a sedative effect (for example, about 0.3 to about 4.5 milligram/kg/hr) may be derived from the very substantial literature on 2,6-diisopropylphenol. The actual dosages of the 2,6-diisopropylphenol prodrugs, on a weight basis, may in some cases be higher than for 2,6-diisopropylphenol itself because (a) the molecular weights of the prodrugs are higher and (b) release of 2,6-diisopropylphenol from the prodrugs occurs at a finite rate. Furthermore, the anesthetist and/or physician would modify the dose to achieve the desired effect in any particular patient, in accordance with normal skill in the art. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for use as anti-emetics. Their administration is indicated in subjects at risk of vomiting or who feel nauseous. As an example, the compounds are usefully co-administered to subjects who are receiving treatments that induce nausea, such as various chemotherapy agents and surgical procedures. Accordingly, this invention provides methods for inhibiting nausea and vomiting by administering the compound to a subject in an amount effective to inhibit nausea and vomiting. In the prophylactic or therapeutic treatment of nausea or vomiting, the compounds preferably are delivered orally in a pharmaceutical composition. Accordingly, solid or liquid carriers are appropriate delivery vehicles. However, parenteral routes of administration, such as inhalation or injection, also are useful as well as topical and transdermal administration. For use as an anti-emetic, the compounds are effectively administered in amounts of about 50 milligram to about 2 gram. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for use as anti-convulsives to prevent or relieve seizures including, such as for example, epileptic seizures. This invention provides methods for inhibiting convulsions comprising administering to a subject an amount of the compound effective to inhibit convulsions. In the prophylactic or therapeutic treatment of seizures the compounds preferably are delivered orally or parenterally. For use as an anti-convulsive, the compounds are effectively administered in amounts of about 50 milligram to about 2 gram daily. In another aspect, the invention relates to pharmaceutical compositions comprising at least one of the compounds of the invention, as well as pharmaceutically acceptable prodrugs and salts of such compounds, in a pharmaceutically acceptable vehicle, for use as anti-pruritics to prevent or relieve itching. This invention provides methods of inhibiting itching comprising administering the compound to a subject in an amount effective to inhibit itching. The compounds can treat both external and internal itching. The source of itching can be any disease or exposure to a pruritic agent, such as poison ivy. In the prophylactic or therapeutic treatment of itching, the compounds preferably are delivered topically in a pharmaceutical composition. Various creams and ointments are appropriate delivery vehicles. For use as an anti-pruritic, the compounds are effectively administered in amounts of about 50 milligram to about 2 gram daily or rubbed into the skin at about 0.01 to about 5 milligram per cm2. Sub-sedative dose for pruritus may be achieved at between about one-quarter and about one-tenth the anesthetic dose. Invention compounds having structure A include but are not limited to: Before the present compounds, compositions and methods are disclosed and described, it is to be understood that this invention is not limited to specific synthetic methods, specific pharmaceutical carriers, or to particular pharmaceutical formulations or administration regimens, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a bicyclic aromatic compound” includes mixtures of bicyclic aromatic compounds, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like. Certain pharmaceutically acceptable salts of the invention are prepared by treating the novel compounds of the invention with an appropriate amount of pharmaceutically acceptable base. Representative pharmaceutically acceptable bases are ammonium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, ferrous hydroxide, zinc hydroxide, copper hydroxide, aluminum hydroxide, ferric hydroxide, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, lysine, arginine, histidine, and the like. The reaction is conducted in water, alone or in combination with an inert, water-miscible organic solvent, at a temperature of from about 0° C. to about 100° C., preferably at room temperature. The molar ratio of compounds of structural formula A to base used is chosen to provide the ratio desired for any particular salts. For preparing, for example, the ammonium salts of the starting material, compounds of formula A can be treated with approximately one equivalent of the pharmaceutically acceptable base to yield a neutral salt. When calcium salts are prepared, approximately one-half a molar equivalent of base is used to yield a neutral salt, while for aluminum salts, approximately one-third a molar equivalent of base will be used. 2,6-diisopropylphenol and the prodrugs of this invention preferably are delivered as pharmaceutical compositions. “Pharmaceutical composition” refers to a composition suitable for pharmaceutical use in a subject. The pharmaceutical compositions of this invention comprise a pharmacologically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. “Pharmacologically effective amount” refers to that amount of the compound effective to produce the intended pharmacological result, such as for example, inhibit oxidation, induce anesthesia, inhibit vomiting, inhibit convulsions, inhibit itching, or inhibit inflammation. “Pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers, buffers, and excipients, such as a phosphate buffered saline solution, aqueous solutions of dextrose, and emulsions, such as an oil/water or water/oil emulsion, and various types of wetting agents and/or adjuvants. Suitable pharmaceutical carriers and formulations are described in Remington's Pharmaceutical Sciences, 19th Ed. (Mack Publishing Co., Easton, 1995). Preferred pharmaceutical carriers depend upon the intended mode of administration of the active agent. The compounds of the invention can be formulated for administration in a variety of ways. Typical routes of administration include both enteral and parenteral. These include, without limitation, subcutaneous, intramuscular, intravenous, intraperitoneal, intramedullary, intrapericardiac, intrabursal, oral, sublingual, ocular, nasal, topical, transdermal, transmucosal, or anal. The mode of administration can be, such as for example, via swallowing, inhalation, injection or topical application to a surface (such as for example, eyes, mucus membrane, skin). Particular formulations typically are appropriate for specific modes of administration. Various contemplated formulations include, for example, aqueous solutions, solid formulations, aerosol formulations and transdermal formulations. Examples of aqueous solutions include, for example, water, saline, phosphate buffered saline, Hank's solution, Ringer's solution, dextrose/saline, glucose solutions and the like. The compositions can contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions or to improve stability, appearance or ease of administration, such as buffering agents, tonicity adjusting agents, wetting agents, detergents and the like. Additives can also include additional active ingredients such as bactericidal agents, or stabilizers. For example, the solution can contain sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate or triethanolamine oleate. These compositions can be sterilized by conventional, well-known sterilization techniques, or can be sterile filtered. The resulting aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous solution prior to administration. Aqueous solutions are appropriate for injection and, in particular, for intravenous injection. Intravenous injection is a particularly appropriate means of delivery for using the compound as a hypnotic agent. The intravenous solution can include detergents and emulsifiers such as lipids. Aqueous solutions also are useful for enteral administration as tonics and administration to mucous or other membranes as, such as for example, nose or eye drops. The composition can contain the compound in an amount of about 1 milligram per milliliter to 100 milligram per milliliter, more preferably about 10 milligram per milliliter. Solid compositions are appropriate for enteral administration. They can be formulated in the form of, such as for example, pills, tablets, powders or capsules. For solid compositions, conventional nontoxic solid carriers can be used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. For oral administration, a pharmaceutically acceptable nontoxic composition is formed by incorporating any of the normally employed excipients, such as those carriers previously listed, and generally 10%-95% of active ingredient. The carrier can be selected from various oils including those of petroleum, animal, vegetable or synthetic origin, for example, peanut oil, soybean oil, mineral oil, sesame oil, and the like. Suitable pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, sucrose, gelatin, maltose, rice, flour, chalk, silica gel, magnesium stearate, sodium stearate, glycerol monostearate, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like. A unit dosage form, such as a tablet, can have about 10 milligram to about 2 gram of the compound. Solid compositions are particularly useful for using the compound as an anti-emetic. Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, bile salts and fusidic acid derivatives. In addition, detergents can be used to facilitate permeation. Transmucosal administration can be through nasal sprays, for example, or using suppositories. For topical administration, the agents are formulated into ointments, creams, salves, powders and gels. In one aspect, the transdermal delivery agent can be DMSO. Transdermal delivery systems can include, such as for example, patches. Topical administration is particularly useful for use of the compound as an anti-pruritic or in the treatment of wounds with an inflammatory component such as burns, rashes and sunburns. However, sustained administration can deliver the compound for use as an anti-oxidant and anti-inflammatory agent internally. For inhalation, the compound is preferably administered in the form of an aerosol, liquid or solid. For aerosol administration, the compound preferably is supplied in finely divided form along with a surfactant and propellant. A surfactant may be required if the agent is immiscible in the propellant. The surfactant preferably is soluble in the propellant. Representative of such agents are the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride such as, for example, ethylene glycol, glycerol, erythritol, arabitol, mannitol, sorbitol, the hexitol anhydrides derived from sorbitol, and the polyoxyethylene and polyoxypropylene derivatives of these esters. Mixed esters, such as mixed or natural glycerides, can be employed. The surfactant can constitute 0.1%-20% by weight of the composition, preferably 0.25%-5%. The balance of the composition is ordinarily propellant. Liquefied propellants are typically gases at ambient conditions, and are condensed under pressure. Among suitable liquefied propellants are the lower alkanes containing up to 5 carbons, such as butane and propane; and preferably fluorinated or fluorochlorinated alkanes. Mixtures of the above can also be employed. In producing the aerosol, a container equipped with a suitable valve is filled with the appropriate propellant, containing the agent as a solution or as finely divided particles and surfactant. The ingredients are thus maintained at an elevated pressure until released by action of the valve. A nebulizer or aerosolizer device for administering compounds typically delivers a dose of about concentration of between about 1 and 50 milligram per inhalation. Delivery by inhalation is particularly effective for delivery to respiratory tissues for the treatment of respiratory conditions including an inflammatory component. Delivery of large doses by respiration also can induce sedation or anaesthesia. Anesthesia may be achieved by means of continuous inhalation such as occurs with 2,6-diisopropylphenol, ether, or other conventional anesthetics. Induction may occur at doses between about 200 milligram and about 400 milligram inhaled over a period of a few minutes (such as for example, about 5 to about 15 minutes). Sedation may be maintained thereafter at a dose of about 200 milligram to about 400 milligram per hour for as long as is needed. In preparing pharmaceutical compositions of the present invention, it can be desirable to modify the complexes of the present invention to alter their pharmacokinetics and biodistribution. For a general discussion of pharmacokinetics, See, Remington's Phamaceutical Sciences, supra, Chapters 37-39. A number of methods for altering pharmacokinetics and biodistribution are known to one of ordinary skill in the art. Examples of such methods include protection of the complexes in vesicles composed of substances such as proteins, lipids (for example, liposomes), carbohydrates, or synthetic polymers. Single or multiple administrations of the compositions can be carried out with dose levels and pattern being selected by the treating physician. In any event, the pharmaceutical formulations should provide a quantity of a compound sufficient to treat the patient effectively. The total effective amount of a compound of the present invention can be administered to a subject as a single dose, either as a bolus or by infusion over a relatively short period of time, or can be administered using a fractionated treatment protocol, in which the multiple doses are administered over a more prolonged period of time. One skilled in the art would know that the concentration of a compound of the present invention required to obtain an effective dose in a subject depends on many factors including the age and general health of the subject, the route of administration, the number of treatments to be administered and the judgrament of the prescribing physician. In view of these factors, the skilled artisan would adjust the dose so as to provide an effective dose for a particular use. EXAMPLES Used herein, the following abbreviations have the following meanings: Me refers to methyl (CH3—), Et refers to ethyl (CH3CH2—), i-Pr refers to isopropyl (CH3)2CH2—), t-Bu or tert-butyl refers to tertiary butyl ((CH3)3CH—), Ph refers to phenyl, Bn refers to benzyl (PhCH2—), Bz refers to benzoyl (PhCO—), MOM refers to methoxymethyl, Ac refers to acetyl, TMS refers to trimethylsilyl, TBS refers to ter-butyldimethylsilyl, Ms refers to methanesulfonyl (CH3SO2—), Ts refers to p-toluenesulfonyl (p-CH3PhSO2—), Tf refers to trifluoromethanesulfonyl (CF3SO2—), TfO refers to trifluoromethanesulfonate (CF3SO3—), DMF refers to N,N-dimethylformamide, DCM refers to dichloromethane (CH2Cl2), THF refers to tetrahydrofuran, EtOAc refers to ethyl acetate, Et2O refers to diethyl ether, MeCN refers to acetonitrile (CH3CN), NMP refers to 1-N-methyl-2-pyrrolidinone, DMA refers to N,N-dimethylacetamide, DMSO refers to dimethylsulfoxide, DCC refers to 1,3-dicyclohexyldicarbodiimide, EDCl refers to 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, Boc refers to tert-butylcarbonyl, Fmoc refers to 9-fluorenylmethoxycarbonyl, TBAF refers to tetrabutylammonium fluoride, TBAI refers to tetrabutylammonium iodide, TMEDA refers to N,N,N,N-tetramethylethylene diamine, Dess-Martin periodinane or Dess Martin reagent refers to 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3 (1H)-one, DMAP refers to 4-N,N-dimethylaminopyridine, (i-Pr)2NEt or DIEA or Hunig's base refers to N,N-diethylisopropylamine, DBU refers to 1,8-Diazabicyclo[5.4.0]undec-7-ene, (DHQ)2AQN refers to dihydroquinine anthraquinone-1,4-diyl diether, (DHQ)2PHAL refers to dihydroquinine phthalazine-1,4-diyl diether, (DHQ)2PYR refers to dihydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether, (DHQD)2AQN refers to dihydroquinidine anthraquinone-1,4-diyl diether, (DHQD)2PHAL refers to dihydroquinidine phthalazine-1,4-diyl diether, (DHQD)2PYR refers to dihydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether, LDA refers to lithium diisopropylamide, LiTMP refers to lithium 2,2,6,6-tetramethylpiperdinamide, n-BuLi refers to n-butyllithium, t-BuLi refers to tert-butyl lithium, IBA refers to 1-hydroxy-1,2-benziodoxol-3 (1H)-one 1-oxide, OsO4 refers to osmium tetroxide, m-CPBA refers to meta-chloroperbenzoic acid, DMD refers to dimethyl dioxirane, PDC refers to pyridinium dichromate, NMO refers to N-methyl morpholine-N-oxide, NaHMDS refers to sodium hexamethyldisilazide, LiHMDS refers to lithium hexamethyldisilazide, HMPA refers to hexamethylphosphoramide, TMSCl refers to trimethylsilyl chloride, TMSCN refers to trimethylsilyl cyanide, TBSCl refers to tert-butyldimethylsilyl chloride, TFA refers to trifluoroacetic acid, TFAA refers to trifluoroacetic anhydride, AcOH refers to acetic acid, Ac2O refers to acetic anhydride, AcCl refers to acetyl chloride, TsOH refers to p-toluenesulfonic acid, TsCI refers to p-toluenesulfonyl chloride, MBHA refers to 4-methylbenzhydrylamine, BHA refers to benzhydrylamine, ZnCl2 refers to zinc (II) dichloride, BF3 refers to boron trifluoride, Y (OTf)2 refers to yttrium (III) trifluoromethanesulfonate, Cu (BF4)2 refers to copper (II) tetrafluoroborate, LAH refers to lithium aluminum hydride (LiAlH4), NaHCO3 refers to sodium bicarbonate, K2CO3 refers to potassium carbonate, NaOH refers to sodium hydroxide, KOH refers to potassium hydroxide, LiOH refers to lithium hydroxide, HCl refers to hydrochloric acid, H2SO4 refers to sulfuric acid, MgSO4 refers to magnesium sulfate, and Na2SO4 refers to sodium sulfate. 1H NMR refers to proton nuclear magnetic resonance, 13C NMR refers to carbon 13 nuclear magnetic resonance, NOE refers to nuclear overhauser effect, NOESY refers to nuclear overhauser and exchange spectroscopy, COSY refers to homonuclear correlation spectroscopy, HMQC refers to proton detected heteronuclear multiplet-quantum coherence, HMBC refers to heteronuclear multiple-bond connectivity, s refers to singlet, br s refers to broad singlet, d refers to doublet, br d refers to broad doublet, t refers to triplet, q refers to quartet, dd refers to double doublet, m refers to multiplet, ppm refers to parts per million, IR refers to infrared spectrometry, MS refers to mass spectrometry, HRMS refers to high resolution mass spectrometry, EI refers to electron impact, FAB refers to fast atom bombardment, CI refers to chemical ionization, HPLC refers to high pressure liquid chromatography, TLC refer to thin layer chromatography, Rf refers to, Rt refers to retention time, GC refers to gas chromatography, min is minutes, h is hours, rt or RT is room temperature, gram is grams, mg is milligrams, L is liters, mL is milliliters, mol is moles and mmol is millimoles. For all of the following examples, standard work-up and purification methods can be utilized and will be obvious to those skilled in the art. Synthetic methodologies that make up the invention are shown in Schemes 1-3. These Schemes are intended to describe the applicable chemistry through the use of specific examples and are not indicative of the scope of the invention. Example 1 Propofol Hemisuccinate To a solution of 2,6-diisopropylphenol (4.0 g, 22.4 mmol) in 15 mL of Et3N was added succinic anhydride (2.8 g, 28 mmol) and a catalytic amount of DMAP (10 mg) under N2 atmosphere. The reaction mixture was stirred at ambient temperature overnight. The solvent was removed under vacuum and the residue was dissolved in water (30 mL) and added to a cold solution of 1 N HCl (150 mL). The precipitate was filtered and dried. Recrystallization from ethanol-water (2:1) mixture gave 2,6-diisopropylphenyl hemisuccinate as a white crystalline solid. Yield: 5.8 gram (94%). 1H-NMR (CDCl3) δ ppm: 1.2 (d, 12H), 2.82-2.84 (m, 2H), 2.85-3.0 (m, 4H), 7.1-7.21 (m, 3H). Example 2 N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester To a solution of propofol hemisuccinate (2.0 g, 7.2 mmol) in THF—CH2Cl2 (1:1, 60 mL) was added EDCl (1.72 g, 9 mmol) followed by HOBt (1.37 g, 9 mmol). The reaction mixture was stirred at ambient temperature for 15 min and 1-(2-aminoethyl)pyrrolidine (0.912 g, 8 mmol) was added and stirring was maintained overnight. 10% aqueous citric acid (50 ml) was added and the mixture was extracted with CH2Cl2 (100 ml×2). The organic layer was washed with brine and dried over anhydrous MgSO4. The solvent was removed and the product was purified by silica gel column chromatography using acetone with 1% Et3N. Removal of the solvent gave the product as an oil. Yield: 2.47 gram (92%) 1H-NMR (CDCl3) δ ppm: 1.2 (d, 12H), 1.8 (m, 4H), 2.2 (d, 1H), 2.6 (m, 8H), 2.95 (m, 4H), 3.36 (m, 2H), 7.2 (m, 3H). Example 3 N-(2-Piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester Prepared according to example 2. Yield: 86% 1H-NMR (CDCl3) δ ppm: 1.2 (d, 12H), 1.44 (m, 2H), 1.6 (m, 4H), 2.42 (t, 5H), 2.6 (t, 2H), 2.90 (m, 4H), 3.32 (m, 4H), 7.18 (m, 3H). Example 4 N-(2-Dimethylaminoethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Prepared according to example 2. Yield: 64%—Rf: 0.55 (in 50% MeOH—CH2Cl2) 1H NMR (300 MHz, CD3OD) δ ppm: 1.2 (d, 12H), 2.3 (s, 6H), 2.45 (t, 2H), 2.6 (t, 2H), 3.0 (m, 3H), 3.36 (m, 3H), 7.2 (m, 3H) Example 5 N-(2-Diethylaminoethyl)-succinamic acid 2,6-diisopropylphenyl ester Prepared according to example 2. Yield: 50%; Rf: 0.6 (in 20% MeOH—CH2Cl2) 1H NMR (300 MHz, CDCl3) δ ppm: 1 (t, 6H), 1.2 (d, 12H), 2.57 (m, 6H), 2.62 (t, 2H), 2.9 (m, 2H), 3.2 (t, 2H), 3.3 (m, 2H), 6.2 (br s, 1H), 7.2 (s, 3H) Example 6 N-(2-Diisopropylaminoethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Prepared according to example 2. Yield: 99%; Rf: 0.5 (in 20% MeOH—CH2Cl2+1% Et3N) 1H NMR (300 MHz, CDCl3) δ ppm: 1.0 (d, 12H), 1.2 (d, 12H), 2.6 (m, 4H), 2.9 (m, 2H), 3.1 (m, 4H), 3.35 (m br, 2H) 7.2 (s, 3H) Example 7 N-(2-Morpholin-4-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester Prepared according to example 2. Yield: 68%; Rf: 0.8 (20% MeOH—CH2Cl2+1% Et3N) 1H NMR (300 MHz, CDCl3) δ ppm: 1.2 (d, 12H), 2.45 (m, 6H), 2.6 (t, 2H), 2.9 (m, 2H), 3.12 (t, 2H), 3.35 (m, 2H), 3.7 (m, 4H), 6.15 (t br, 1H), 7.2 (m, 3H) Example 8 N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride A solution of N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester (700 mg) in 100 ml of ether was cooled to 0° C. and dry HCl gas was bubbled in for 10 min. The precipitate was filtered, washed with ether and dried under high vacuum to yield N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride as a white crystalline solid. Yield: 590 mg (77%). 1H-NMR (D2O) δ ppm: 1.05 (d, 12H), 1.85 (m, 2H), 2.05 (m, 2H), 2.6 (m, 2H), 2.8 (m, 2H), 2.95 (m, 4H), 3.2 (m, 2H), 3.45 (m, 2H), 3.55 (m, 2H), 7.2 (m, 3H). Example 9 N-(2-Piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride Yield: 584 mg (86%). 1H-NMR (D2O) δ ppm: 1.05 (d, 12H), 1.3 (m, 1H), 1.6 (m, 3H), 1.8 (m, 2H), 2.6 (m, 2H), 2.8 (m, 4H), 2.95 (m, 2H), 3.1 (m, 2H), 3.4 (m, 2H), 3.5 (m, 2H), 7.2 (m, 3H). Example 10 N-(2-Dimethylamino-ethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Hydrochloride Prepared according to example 8. Yield: 49% 1H-NMR (D2O) δ ppm: 0.98 (d, 12H), 2.57 (t, 2H), 2.75 (m, 8H), 2.9 (t, 2H), 3.1 (t, 2H), 3.45 (t, 2H), 7.15 (m, 3H) Example 11 N-(2-Diethylamino-ethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Hydrochloride Prepared according to example 8. Yield: 49% 1H-NMR (D2O) δ ppm: 0.98 (d, 12H), 1.11 (t, 6H), 2.57 (t, 2H), 2.75 (m, 2H), 2.9 (t, 2H), 3.1 (m, 6H), 3.45 (t, 2H), 7.15 (m, 3H), 7.45 (s, 1H). Example 12 N-(2-Diisopropylamino-ethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Hydrochloride Prepared according to example 8. Yield: 99% 1H-NMR (D2O) δ ppm: 0.98 (d, 12H), 1.17 (d, 12H), 2.59 (t, 2H), 2.75 (m, 2H), 2.9 (t, 2H), 3.1 (t, 2H), 3.38 (t, 2H), 3.6 (m, 2H), 7.15 (m, 3H), 7.45 (s, 1H). Example 13 N-(2-Morpholin-4-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester Hydrochloride Prepared according to example 8. Yield: 69% 1H-NMR (D2O) 8 ppm: 0.98 (d, 12H), 2.59 (t, 2H), 2.75 (m, 2H), 2.9 (t, 2H), 3.04 (m br, 2H), 3.17 (t, 2H), 3.38 (m br, 2H), 3.48 (t, 2H), 3.61 (m br, 2H), 3.89 (m br, 2H), 7.15 (m, 3H). Example 14 N-(2-Dibutylaminoethyl)-succinamic acid 2,6-diisopropyl-phenyl ester Prepared according to example 2. Yield: 94%; Rf: 0.55 (in 5% MeOH-DCM) 1H NMR (300 MHz, CDCl3) δ ppm: 0.95 (t, 6H), 1.2 (d, 12H), 1.22-1.42 (m, 8H), 2.4 (t, 4H), 2.45-2.6 (m, 4H), 2.9 (m, 2H), 3.02 (t, 2H), 3.3 (m, 2H), 7.1 (m, 3H) Example 15 N-(2-Dibutylaminoethyl)-succinamic acid 2,6-diisopropyl-phenyl ester hydrochloride Prepared according to example 8. Yield: 92%. 1H NMR (300 MHz, D2O) δ ppm: 0.77 (t, 6H), 0.99 (d, 12H), 1.18 (m, 4H), 1.48 (m, 4H) 2.58 (m, 2H), 2.75 (m, 2H), 2.9 (m, 2H), 3.0 (m, 4H), 3.12 (m, 2H), 3.42 (m, 2H), 7.1 (m, 3H) Example 16 In-vitro hydrolysis of N-(2-piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride A solution was prepared by dissolving 5 mg of N-(2-Piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride in 12 mL of pH=7.4 phosphate buffer. The solution was incubated at 37° C. and aliquots were drawn at 5, 15, 30 and 45 minutes and analyzed by reverse phase HPLC. A plot of UV absorption versus time clearly demonstrates the hydrolysis of the prodrug at pH=7.4. Example 17 pH Stability of N-(2-piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride A solution was prepared by dissolving 100 mg of N-(2-Piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride in 10 mL of pH=4.1 sodium acetate buffer. The buffer was prepared by adding NaOH to a 20% aqueous acetic acid solution until the desired pH was reached. The solution was incubated at ambient temperature and analyzed by LC-MS after 48 hours. No trace of decomposition was observed. Example 18 In-Vivo Induction of Anesthesia Prodrugs were formulated as aqueous isotonic solutions at pH 7.4 in sterile water before administration to animals. Female mice were obtained from Charles River Laboratories (Wilmington, Mass.). The volume of injection was set at 10 mg/kg/animal and animals were dosed IP at 100 mg/kg, 125 mg/kg, 150 mg/kg and 200 mg/kg. The monitoring of distinguishable levels of sedation started immediately after an injection and was continued for a 2-h period post-injection. The sedation level was graded according to the behavioral and reflex activity of animals injected with progressively increasing doses of each compound. Animals were graded as alert and normal when there was no observable change in their behavior; alert with decreased motor activity when ataxia with some ability to walk was observed; and awake and recumbent when loss of righting reflex occurred. Animals reaching somnolence but retaining response to painful stimuli (toe or tail pinch) were graded as sedated with normal reflexes, whereas animals that lost response to painful stimuli were graded as sedated with decreased reflexes (anesthetic level of sedation). Death resulting from the overdose was also recorded as a last level. N-(2-Pyrrolidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride 150 mg/kg: Onset of sedation—2 minutes post injection; Full anesthesia—4 minutes post injection; Duration of anesthesia—10 minutes (14 minutes post injection). 200 mg/kg: Onset of sedation—2 minutes post injection; Full anesthesia—4 minutes post injection; Duration of anesthesia—21 minutes (25 minutes post injection). N-(2-Piperidin-1-yl-ethyl)-succinamic acid 2,6-diisopropylphenyl ester hydrochloride 100 mg/kg: Onset of sedation—2 minutes post injection; Full anesthesia—not reached; Duration of anesthesia—11 minutes (13 minutes post injection). 125 mg/kg: Onset of sedation—2 minutes post injection; Full anesthesia—not reached; Duration of sedation—13 minutes (15 minutes post injection). 200 mg/kg: Onset of sedation—2 minutes post injection; Full anesthesia—5 minutes post injection; Duration of anesthesia—12 minutes (16 minutes post injection). The present invention provides pH sensitive, water soluble derivatives of 2,6-diisopropylphenol and methods of using these compounds. While specific examples have been provided, the above description is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon review of this specification. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents.
<SOH> BACKGROUND OF THE INVENTION <EOH>2,6-diisopropylphenol is highly lipophilic and is practically insoluble in water. For intravenous applications, it is formulated in water using a variety of solubilizing agents and/or emulsifiers. Examples of such formulations include Cremophor™, Intralipid™, Diprivan™, Disoprofol™, Disoprivan™, and Rapinovet™. The aforementioned formulations have many limitations. They cause allergic side effects and pain upon injection. Their preparation is difficult and costly and most importantly they cannot be sterilized and hence anti-microbial agents must be added to the formulations. Propofol or 2,6-diisopropylphenol is a short acting anesthetic that is administered intravenously (i.v.) to mammalian subjects. The low water solubility of this compound presents a significant formulation challenge. The currently approved mode of administration for Propofol is an emulsion that has many disadvantages including costly preparation and sterilization procedures. Oxidation of Propofol to unwanted side-products in the presence of oxygen and light drastically shortens the shelf life of such formulations. In addition, the oil-in-water emulsions cause a number of clinical side effects including pain on injection and pulmonary embolism. Thus, there exists a clear need for a water-soluble, stable, non-toxic pharmaceutical composition of 2,6-diisopropylphenol.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention describes non-toxic and water-soluble derivatives of 2,6-diisopropylphenol or Propofol, a low molecular weight alcohol that is administered intravenously and serves as a sedative-hypnotic agent in humans and animals. 2,6-diisopropylphenol has a broad range of applications. It is an antioxidant and inhibits lipid peroxidation. It can also act as an anti-inflammatory agent and can useful in the treatment of acid aspiration, respiratory distress syndrome, airway obstructive disease, asthma, bronchiolitis, bronchopulmonary dysplasia, cancer, chronic obstructive pulmonary disease (“COPD”), cystic fibrosis, emphysema, HIV-associated lung disease, idiopathic pulmonary fibrosis, immune-complex-mediated lung injury, exposure to an oxidizing agent, ischemia-reperfusion injury, mineral dust pneumoconiosis, drug-induced lung disease, silo-filler's disease, and various neurodegenerative diseases such as Friedrich's disease, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS); multiple sclerosis (MS), Pick disease, spinal cord injury, acute neural injury and aging. The present invention is directed to water-soluble derivatives of 2,6-diisopropylphenol. The compounds of the invention act as pH sensitive prodrugs of 2,6-diisopropylphenol that degrade and metabolize rapidly to Propofol upon intravenous injection. The compounds of this invention are crystalline solids that are stable at or below ambient temperature and can be stored as aqueous solutions if the pH of the solution is kept in the range of 0 to 6. Such characteristics represent clear economic and clinical improvements over the state of the art. In one aspect, this invention describes 2,6-diisopropylphenol derivatives according to formula A: wherein: R 1 is hydrogen, alkyl, or aryl; Each X is independently C 1-10 alkyl; Y is heteroaryl, saturated heterocyclic, or NR 2 R 3 , R 2 and R 3 are independently hydrogen, alkyl, or R 2 and R 3 , together with the nitrogen atom to which they are attached, combine to form a saturated heterocyclic or heteroaryl ring; or a pharmaceutically acceptable salt of any of the foregoing. Specifically, the compounds of the present invention convert to 2,6-diisopropylphenol in vivo and can be used as hypnotic agents, anti-convulsives, anti-pruritics, and anti-emetics. Other uses include treatment of oxidative tissue damage, inflammation and cancer. The prodrug compounds of the present invention have many advantages over 2,6-diisopropylphenol by virtue of increased aqueous solubility and increased stability towards oxidation over the parent compound thus making them particularly suitable for intravenous (i.v.) formulations. Therefore when used in a mammalian subject, the compounds of this invention replicate every therapeutic application that has been described for 2,6-diisopropylphenol. Other advantages of the compounds of the present invention include low toxicity and high therapeutic-to-toxicity index. In another aspect, this invention is directed to a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inhibiting oxidation of biological material comprising contacting the material with an effective amount of a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic condition having an inflammatory component in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic condition of the nervous system having an inflammatory component in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of a pathologic respiratory condition in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inducing anesthesia in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for inhibiting nausea and vomiting in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of epileptic or convulsive disorders in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the treatment of pruritis in a subject comprising administering to the subject a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides pharmaceutical compositions comprising at least one of the compounds of the invention, in a pharmaceutically acceptable vehicle, for the treatment of carcinomas. Examples of carcinomas include mammary cancer, prostate cancer, kidney cancer, Karposi's sarcoma, colon cancer, cervical cancer, lung cancer, cutaneous T-cell lymphoma, cancer of the head and neck, cancers of the aerodigestive pathway, skin cancer, bladder cancer, sarcomas, leukoplakias, acute promyelocytic leukemia, and the like. In another aspect, this invention provides pharmaceutical compositions comprising at least one the compounds of the invention in combination with other chemotherapeutic agents, in a pharmaceutically acceptable vehicle, for the treatment of carcinomas. Examples of chemotherapeutic agents contemplated for use in the practice of this particular invention include Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Cytosine arabinoside, Etoposide, 5-Fluorouracil, Melphalan, Methotrexate, Mitoxantrone, Taxol, Interferon, Fareston, Arzoxifene, Evista, Tamoxifen, and the like. In another aspect, this invention provides a method for the treatment of a subject undergoing treatment with a chemotherapeutic agent having activity as an oxidizing agent comprising the step of administering a pharmaceutical composition comprising one or more compound (s) of Formula A, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method for the use of compounds of Formula A in the manufacture of a medicament for the treatment of a pathological condition having an inflammatory component. The non-limiting examples shown in schemes 1-3, illustrate the inventors' preferred methods for carrying out the preparative process of the invention.
20050617
20070731
20051020
97224.0
0
BARKER, MICHAEL P
PH SENSITIVE PRODRUGS OF 2,6-DIISOPROPYLPHENOL
UNDISCOUNTED
0
ACCEPTED
2,005
10,514,352
ACCEPTED
Pseudopolymorphic forms of a hiv protease inhibitor
New pseudopolymorphic forms of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate and processes for producing them are disclosed.
1. A pseudopolymorph of (3R,3aS,6aR)-hexahydrofuro [2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate. 2. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is a hydrate solvate, alcohol solvate, alkane solvate, ketone solvate, ether solvate, cycloether solvate, ester solvate, sulfonic solvate. 3. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is a hydrate solvate, C1-C4 alcohol solvate, C1-C4 chloroalkane solvate, C1-C5 ketone solvate, C1-C4 ether solvate, cycloether solvate, C1-C5 ester solvate, C1-C4 sulfonic solvate. 4. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is a hydrate solvate, alcohol solvate, alkane solvate, ketone solvate, ether solvate, cycloether solvate, ester solvate. 5. A pseudopolymorph according to claim 1, which is pharmaceutically acceptable. 6. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is chosen from Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-ethoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate), Form K (mesylate). 7. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is chosen from Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-ethoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate). 8. A pseudopolymorph according to claim 1, wherein the pseudopolymorph is Form A (ethanolate), Form B (hydrate). 9. A pseudopolymorph according to claim 1, in which the ratio of compound to solvent ranges between (5:1) and (1:5). 10. A pseudopolymorph according to claim 9, in which the ratio of compound to solvent is about 1:1. 11. A pseudopolymorph according to claim 1, additionally comprising water molecules. 12. A process for preparing a pseudopolymorph according to claim 1, comprising the steps of combining (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate with an organic solvent, water, or mixtures of water and water miscible organic solvents, and inducing crystallization. 13. A pharmaceutical composition comprising a pseudopolymorph according to claim 1 and a pharmaceutically acceptable carrier and/or diluent. 14. (canceled)
TECHNICAL FIELD This invention relates to novel pseudopolymorphic forms of (3R,3aS,6aR)-hexahydro-furo[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate, a method for their preparation as well as their use as a medicament. BACKGROUND OF THE INVENTION Virus-encoded proteases, which are essential for viral replication, are required for the processing of viral protein precursors. Interference with the processing of protein precursors inhibits the formation of infectious virions. Accordingly, inhibitors of viral proteases may be used to prevent or treat chronic and acute viral infections. (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate has HIV protease inhibitory activity and is particularly well suited for inhibiting HIV-1 and HIV-2 viruses. The structure of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-phenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate, is shown below: Compound of formula (X) and processes for its preparation are disclosed in EP 715618, WO 99/67417, U.S. Pat. No. 6,248,775, and in Bioorganic and Chemistry Letters, Vol. 8, pp. 687-690, 1998, “Potent HIV protease inhibitors incorporating high-affinity P2-igands and (R)-(hydroxyethylamino)sulfonamide isostere”, all of which are incorporated herein by reference. Drugs utilized in the preparation of pharmaceutical formulations for commercial use must meet certain standards, including GMP (Good Manufacturing Practices) and ICH (International Conference on Harmonization) guidelines. Such standards include technical requirements that encompass a heterogeneous and wide range of physical, chemical and pharmaceutical parameters. It is this variety of parameters to consider, which make pharmaceutical formulations a complex technical discipline. For instance, and as example, a drug utilized for the preparation of pharmaceutical formulations should meet an acceptable purity. There are established guidelines that define the limits and qualification of impurities in new drug substances produced by chemical synthesis, i.e. actual and potential impurities most likely to arise during the synthesis, purification, and storage of the new drug substance. Guidelines are instituted for the amount of allowed degradation products of the drug substance, or reaction products of the drug substance with an excipient and/or immediate container/closure system. Stability is also a parameter considered in creating pharmaceutical formulations. A good stability will ensure that the desired chemical integrity of drug substances is maintained during the shelf-life of the pharmaceutical formulation, which is the time frame over which a product can be relied upon to retain its quality characteristics when stored under expected or directed storage conditions. During this period the drug may be administered with little or no risk, as the presence of potentially dangerous degradation products does not pose prejudicial consequences to the health of the receiver, nor the lower content of the active ingredient could cause under-medication. Different factors, such as light radiation, temperature, oxygen, humidity, pH sensitivity in solutions, may influence stability and may determine shelf-life and storage conditions. Bioavailability is also a parameter to consider in drug delivery design of pharmaceutically acceptable formulations. Bioavailability is concerned with the quantity and rate at which the intact form of a particular drug appears in the systemic circulation following administration of the drug. The bioavailability exhibited by a drug is thus of relevance in determining whether a therapeutically effective concentration is achieved at the site(s) of action of the drug. Physico-chemical factors and the pharmaco-technical formulation can have repercussions in the bioavailability of the drug. As such, several properties of the drug such as dissociation constant, dissolution rate, solubility, polymorphic form, particle size, are to be considered when improving the bioavailability. It is also relevant to establish that the selected pharmaceutical formulation is capable of manufacture, more suitably, of large-scale manufacture. In view of the various and many technical requirements, and its influencing parameters, it is not obvious to foresee which pharmaceutical formulations will be acceptable. As such, it was unexpectedly found that certain modifications of the solid state of compound of formula (X) positively influenced its applicability in pharmaceutical formulations. SUMMARY OF THE INVENTION Present invention concerns pseudopolymorphic forms of compound of formula (X) for the preparation of pharmaceutical formulations. Such pseudopolymorphic forms contribute to pharmaceutical formulations in improved stability and bioavailability. They can be manufactured in sufficient high purity to be acceptable for pharmaceutical use, more particularly in the manufacture of a medicament for inhibiting HIV protease activity in mammals. In a first aspect, the present invention provides pseudopolymorphs of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate. Pseudopolymorphs provided include alcohol solvates, more in particular, C1-C4 alcohol solvates; hydrate solvates; alkane solvates, more in particular, C1-C4 chloroalkane solvates; ketone solvates, more in particular, C1-C5 ketone solvates; ether solvates, more in particular, C1-C4 ether solvates; cycloether solvates; ester solvates, more in particular, C1-C5 ester solvates; and sulfonic solvates, more in particular, C1-4 sulfonic solvates, of the compound of formula (X). Preferred pseudopolymorphs are pharmaceutically acceptable solvates, such as hydrate and ethanolate. Particular pseudopolymorphs are Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-methoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate) of compound of formula (X). Another particular pseudopolymorph is Form K (mesylate) of compound of formula (X). In a second aspect, present invention relates to processes for preparing pseudopolymorphs. Pseudopolymorphs of compound of formula (X) are prepared by combining compound of formula (X) with an organic solvent, water, or mixtures of water and water miscible organic solvents, and applying any suitable technique to induce crystallization, to obtain the desired pseudopolymorphs. In a third aspect, the invention relates to the use of the present pseudopolymorphs, in the manufacture of pharmaceutical formulations for inhibiting HIV protease activity in mammals. In relation to the therapeutic field, a preferred embodiment of this invention relates to the use of pharmaceutically acceptable pseudopolymorphic forms of compound of formula (X) for the treatment of an HIV viral disease in a mammal in need thereof, which method comprises administering to said mammal an effective amount of a pharmaceutically acceptable pseudopolymorphic form of compound of formula (X). The following drawings provide additional information on the characteristics of the pseudopolymorphs according to present invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1, FIG. 2 and FIG. 3 are the powder X-ray diffraction patterns of the Form A (1:1). FIG. 4 depicts Form A (1:1) in three dimensions with the atoms identified. FIG. 5 is a comparison of the Raman spectra of Forms A, B, D, E, F, H, (1:1) and the amorphous form at the carbonyl stretching region of 1800-100 cm−1 and the region 3300-2000 cm−1. FIG. 6 is a comparison of the expanded Raman spectra of Forms A, B, D, E, F, H, (1:1) and the amorphous form at the carbonyl stretching region of 600-0 cm−1. FIG. 7 is a comparison of the expanded Raman spectra of Forms A, B, D, E, F, H, (1:1) and the amorphous form at the carbonyl stretching region of 1400-800 cm−1. In FIGS. 5, 6, and 7, P1 corresponds to Form A, P18 corresponds to Form B, P19 corresponds to amorphous form, P25 corresponds to Form E, P27 corresponds to Form F, P50 corresponds to Form D, P68 corresponds to Form H, P69 corresponds to Form C, P72 corresponds to Form I, and P81 corresponds to Form G. FIG. 8 is the Differential Scanning Calorimetric (DSC) thermograph of Form A (1:1). FIG. 9 is the Infrared (IR) spectrum that reflects the vibrational modes of the molecular structure of Form A as a crystalline product FIG. 10 is the IR spectrum that reflects the vibrational modes of the molecular structure of Form B as a crystalline product FIG. 11: IR spectrum of forms A, B, and amorphous form, at spectral range 4000 to 400 cm−1. FIG. 12: IR spectrum of forms A, B, and amorphous form, at spectral range 3750 to 2650 cm−1. FIG. 13: IR spectrum of forms A, B, and amorphous form, at spectral range 1760 to 1580 cm−. FIG. 14: IR spectrum of forms A, B, and amorphous form, at spectral range 980 to 720 cm−1. In FIGS. 11, 12, 13 and 14, curve A corresponds to Form A, curve B corresponds to Form B, and curve C corresponds to the amorphous form. FIG. 15: DSC Thermograph curves of Form A (curve D), Form A after Adsorption/Desorption (ADS/DES) (curve E), and Form A after ADS/DES hydratation tests (curve F) FIG. 16: Thermogravimetric (TG) curves of Form A (curve D), Form A after ADS/DES (curve E), and Form A after ADS/DES hydratation tests (curve F) FIG. 17: TG curve of Form A at 25° C. under dry nitrogen atmosphere in function of time FIG. 18: ADS/DES curves of Form A. FIG. 19: ADS/DES curves of the hydratation test of Form A FIG. 20: ADS/DES curves of Form B FIG. 21: IR spectrum of Form K FIG. 22: Raman spectrum of Form K FIG. 23: DSC curve of Form K FIG. 24: TG curve of Form K FIG. 25: ADS/DES isotherm of Form K, batch 1 FIG. 26: ADS/DES isotherm of Form K, batch 2 DETAILED DESCRIPTION The term “polymorphism” refers to the capacity of a chemical structure to occur in different forms and is known to occur in many organic compounds including drugs. As such, “polymorphic forms” or “polymorphs” include drug substances that appear in amorphous form, in crystalline form, in anhydrous form, at various degrees of hydration or solvation, with entrapped solvent molecules, as well as substances varying in crystal hardness, shape and size. The different polymorphs vary in physical properties such as solubility, dissolution, solid-state stability as well as processing behaviour in terms of powder flow and compaction during tabletting. The term “amorphous form” is defined as a form in which a three-dimensional long-range order does not exist. In the amorphous form the position of the molecules relative to one another are essentially random, i.e. without regular arrangement of the molecules on a lattice structure. The term “crystalline” is defined as a form in which the position of the molecules relative to one another is organised according to a three-dimensional lattice structure. The term “anhydrous form” refers to a particular form essentially free of water. “Hydration” refers to the process of adding water molecules to a substance that occurs in a particular form and “hydrates” are substances that are formed by adding water molecules. “Solvating” refers to the process of incorporating molecules of a solvent into a substance occurring in a crystalline form. Therefore, the term “solvate” is defined as a crystal form that contains either stoichiometric or non-stoichiometric amounts of solvent. Since water is a solvent, solvates also include hydrates. The term. “pseudopolymorph” is applied to polymorphic crystalline forms that have solvent molecules incorporated in their lattice structures. The term pseudopolymorphism is used frequently to designate solvates (Byrn, Pfeiffer, Stowell, (1999) Solid-state Chemistry of Drugs, 2nd Ed., published by SSCI, Inc). The present invention provides pseudopolymorphs of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate. In one embodiment pseudopolymorphs are alcohol solvates, more in particular, C1-C4 alcohol solvates; hydrate solvates; alkane solvates, more in particular, C1-C4 chloroalkane solvates; ketone solvates, more in particular, C1-C5 ketone solvates; ether solvates, more in particular C1-C4 ether solvates; cycloether solvates; ester solvates, more in particular C1-C5 ester solvates; or sulfonic solvates, more in particular, C1-C4 sulfonic solvates, of the compound of formula (X). The term “C1-C4 alcohol” defines straight and/or branched chained saturated and unsaturated hydrocarbons having from 1 to 4 carbon atoms substituted with at least a hydroxyl group, and optionally substituted with an alkyloxy group, such as, for example, methanol, ethanol, isopropanol, butanol, 1-methoxy-2-propanol and the like. The term “C1-C4 chloroalkane” defines straight and/or branched chained saturated and unsaturated hydrocarbons having from 1 to 4 carbon atoms substituted with at least one chloro atom, such as, for example, dichloromethane. The term “C1-C5 ketone” defines solvents of the general formula R′—C(═O)—R wherein R and R′ can be the same or different and are methyl or ethyl, such as, acetone and the like. The term “C1-C4 ether” defines solvents of the general formula R′—O—R wherein R and R′ can be the same or different and are a phenyl group, methyl or ethyl, such as, anisole and the like. The term “cycloether” defines a 4- to 6-membered monocyclic hydrocarbons containing one or two oxygen ring atoms, such as tetrahydrofuran and the like. The term “C1-C5 ester” defines solvents of the general formula R′—O—C(═O)—R wherein R and R′ can be the same or different and are methyl or ethyl, such as ethylacetate and the like. The term “C1-C4 sulfonic solvent” defines solvents of the general formula R—SO3H wherein R can be a straight or branched chained saturated hydrocarbon having from 1 to 4 carbon atoms, such as mesylate, ethanesulfonate, butanesulfonate, 2-methyl-1-propanesulfonate, and the like. Pseudopolymorphs of the present invention, which are pharmaceutically acceptable, for instance hydrates, alcohol solvates, such as, ethanolate, are preferred forms. Several pseudopolymorphs are exemplified in this application and include Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-methoxy-2-propanolate), Form H (anisolate), Form I (tetrahydiofuranate), Form J (isopropanolate), or Form K (mesylate) of compound of formula (X). Solvates can occur in different ratios of solvation. Solvent content of the crystal may vary in different ratios depending on the conditions applied. Solvate crystal forms of compound of formula (X) may comprise up to 5 molecules of solvent per molecule of compound of formula (X), appearing in different solvated states including, amongst others, hemisolvate, monosolvate, disolvate, trisolvate crystals, intermediate solvates crystals, and mixtures thereof. Conveniently, the ratio of compound of formula (X) to the solvent may range between (5:1) and (1:5). In particular, the ratio may range from about 0.2 to about 3 molecules of solvent per 1 molecule of compound of formula (X), more in particular, the ratio may range from about 1 to about 2 molecules of solvent per 1 molecule of compound of formula (X), preferably the ratio is 1 molecule of solvent per 1 molecule of compound of formula (X). Solvates may also occur at different levels of hydration. As such, solvate crystal forms of compound of formula (X) may in addition comprise under certain circumstances, water molecules partially or fully in the crystal structures. Consequently, the term “Form A” will be used herein to refer to the ethanolate forms of compound of formula (X) comprising up to 5 molecules of solvent per 1 molecule of compound of formula (X), intermediate solvates crystals, and the mixtures thereof; and optionally comprising additional water molecules, partially or fully in the crystal structures. The same applies for Form B through Form K. In case a particular “Form A” needs to be denoted, the ratio of solvation will follow the “Form A”, for instance, one molecule of ethanol per one molecule of compound (X) is denoted as Form A (1:1). The X-ray powder diffraction is a technique to characterise polymorphic forms including pseudopolymorphs of compound of formula (X) and to differentiate solvate crystal forms from other crystal and non-crystal forms of compound of formula (X). As such, X-ray powder diffraction spectra were collected on a Phillips PW 1050/80 powder diffractometer, model Bragg-Brentano. Powders of Form A (1:1), around 200 mg each sample, were packed in 0.5 mm glass capillary tubes and were analysed according to a standard method in the art. The X-ray generator was operated at 45 Kv and 32 mA, using the copper Ka line as the radiation source. There was no rotation of the sample along the chi axis and data was collected between 4 and 60° 2-theta step size. Form A (1:1) has the characteristic two-theta angle positions of peaks as shown in FIG. 1, 2 and 3 at: 7.04°±0.50, 9.24°±0.5°, 9.96°±0.5°, 10.66°±0.5°, 11.30°±0.5°, 12.82°±0.5°, 13.80°±0.5°, 14.56°±0.5°, 16.66°±0.5°, 17.30°═0.5°, 18.28°±0.5°, 19.10°±0.5°, 20.00°+0.5°, 20.50°±0.5°, 21.22°±0.5°, 22.68°±0.5°, 23.08°±0.5°, 23.66°±0.5°, 25.08°±0.5°, 25.58°±0.5°, 26.28°±0.5°, 27.18°±0.5°, 28.22°±0.5°, 30.20°±0.5°, 31.34°±0.5°, 32.68°±0.5°, 33.82°±0.5°, 39.18°±0.5°, 41.20°±0.5°, 42.06°±0.5°, and 48.74°±0.5°. In another set of analytical experiments, X-ray single diffraction was applied to Form A (1:1), which resulted in the following crystal configuration, listed in the table below. TABLE 1 Crystal Data Crystal shape Prism Crystal dimensions 0.56 × 0.38 × 0.24 mm Crystal color Colorless Space Group P 21 21 21 orthorhombic Temperature 293 K Cell constants a = 9.9882(6) Å b = 16.1697(8) Å c = 19.0284(9) Å alpha (α) = 90° beta (β) = 90° gamma (γ) = 90° Volume 3158.7(3) Å3 Molecules/unit cell (Z) 4 Density, in Mg/m3 1.248 μ (linear absorption coefficient) 1.340 mm−1 F(000) 1272 Intensity Measurements Diffractometer Siemens P4 Radiation Cu Kα (λ = 1.54184 {acute over (Å)}) Temperature ambient 2θmax 138.14° Correction Empirical via Ψ-scans Number of Reflections Measured Total: 3912 Structure Solution and Refinement Number of Observations 3467 [F2 > 2 σ(F2)] Residual (R) 0.0446 The resulting three-dimensional structure of Form A (1:1) is depicted in FIG. 4. Table 2 shows the atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2×103) for Form A (1:1). Atoms are numbered as exhibited in FIG. 4. The x, y and z fractional coordinates indicate the position of atoms relative to the origin of the unit cell. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x y z U(eq) O1 7778(3) 2944(2) 9946(1) 70(1) C2 7171(4) 3513(2) 9487(2) 64(1) C3 6831(3) 3046(2) 8823(2) 52(1) C3A 7953(3) 2411(2) 8793(2) 55(1) C4 7527(4) 1533(2) 8708(2) 65(1) C5 7425(5) 1241(2) 9457(2) 70(1) O6 8501(3) 1642(2) 9809(1) 76(1) C6A 8582(4) 2416(2) 9534(2) 62(1) O7 5533(2) 2702(1) 8945(1) 51(1) O8 5168(2) 2636(1) 7768(1) 53(1) C9 4791(3) 2534(1) 8368(1) 42(1) N10 3590(2) 2256(1) 8562(1) 43(1) C11 2638(3) 1916(2) 8068(2) 44(1) C12 2223(3) 1071(2) 8310(2) 58(1) C13 3381(3) 501(2) 8387(2) 56(1) C14 3937(4) 340(2) 9038(2) 67(1) C15 4989(5) −200(2) 9111(3) 80(1) C16 5494(5) −581(3) 8530(3) 96(2) C17 4975(6) −413(3) 7881(3) 98(2) C18 3926(5) 126(2) 7810(2) 78(1) C19 1423(3) 2464(2) 7976(2) 45(1) O20 494(2) 2112(1) 7502(1) 61(1) C21 1829(3) 3307(2) 7740(2) 48(1) N22 699(3) 3880(1) 7721(1) 49(1) C23 521(4) 4312(2) 7048(2) 58(1) C24 −61(4) 3785(2) 6473(2) 67(1) C25 −1453(5) 3497(3) 6654(2) 86(2) C26 −47(7) 4247(3) 5779(2) 102(2) S27 510(1) 4414(1) 8440(1) 50(1) O28 572(3) 3860(1) 9015(1) 61(1) O29 −693(2) 4873(1) 8345(1) 65(1) C30 1854(3) 5080(2) 8509(2) 50(1) C31 1803(3) 5825(2) 8159(2) 54(1) C32 2871(4) 6341(2) 8195(2) 56(1) C33 4033(4) 6133(2) 8564(2) 55(1) C34 4063(4) 5385(2) 8909(2) 59(1) C35 2998(4) 4869(2) 8883(2) 56(1) N36 5076(3) 6667(2) 8596(2) 72(1) C37 1920(10) 2231(7) 5258(4) 232(6) C38 1310(10) 1590(6) 5564(4) 191(5) O39 1768(4) 1393(2) 6249(2) 94(1) Table 3 shows the anisotropic displacement parameters (Å2×103) for Form A (1:1). The anisotropic displacement factor exponent takes the formula: −2π2[h2a*2U11+ . . . +2hka*b*U12] U11 U22 U33 U23 U13 U12 O1 65(2) 89(2) 55(1) −4(1) −12(1) −3(1) C2 53(2) 68(2) 71(2) −7(2) −8(2) −11(2) C3 38(2) 63(2) 55(2) 4(1) −2(1) −12(1) C3A 37(2) 78(2) 49(1) 9(1) 1(1) −3(2) C4 61(2) 74(2) 61(2) −4(2) −6(2) 10(2) C5 72(3) 67(2) 71(2) 8(2) −11(2) −7(2) O6 78(2) 80(2) 70(1) 16(1) −21(1) −8(2) C6A 47(2) 80(2) 59(2) 5(2) −6(2) −7(2) O7 34(1) 69(1) 50(1) 0(1) −1(1) −9(1) O8 42(1) 68(1) 50(1) 3(1) 2(1) −12(1) C9 35(2) 41(1) 49(1) 1(1) −3(1) 3(1) N10 31(1) 50(1) 49(1) −1(1) 1(1) −2(1) C11 32(2) 41(1) 57(1) −4(1) 0(1) −2(1) C12 44(2) 42(1) 87(2) 2(1) 2(2) −4(1) C13 50(2) 39(1) 78(2) 0(1) 8(2) 0(1) C14 64(2) 56(2) 80(2) 0(2) 5(2) 9(2) C15 68(3) 72(2) 100(3) 18(2) 7(2) 12(2) C16 77(3) 68(2) 143(4) 26(3) 34(3) 28(2) C17 114(4) 72(2) 109(3) −6(2) 32(3) 38(3) C18 89(3) 60(2) 85(2) −4(2) 10(2) 10(2) C19 30(2) 44(1) 61(1) −3(1) −5(1) −5(1) O20 44(1) 56(1) 83(1) −6(1) −18(1) −6(1) C21 36(2) 42(1) 64(2) 2(1) −4(1) −1(1) N22 42(1) 47(1) 57(1) 1(1) 0(1) 3(1) C23 59(2) 50(1) 64(2) 7(1) −8(2) 1(2) C24 79(3) 59(2) 62(2) 1(1) −11(2) 6(2) C25 75(3) 83(2) 101(3) 6(2) −30(3) −5(2) C26 143(5) 99(3) 65(2) 14(2) −15(3) −6(3) S27 44(1) 47(1) 61(1) 2(1) 2(1) 1(1) O28 64(2) 58(1) 61(1) 9(1) 3(1) −7(1) O29 46(1) 58(1) 92(2) −4(1) 6(1) 10(1) C30 50(2) 46(1) 54(1) 2(1) 1(1) 1(1) C31 50(2) 48(1) 64(2) 6(1) −4(2) 6(1) C32 59(2) 45(1) 65(2) 4(1) 2(2) 1(1) C33 57(2) 55(2) 52(1) −4(1) 1(1) −3(1) C34 56(2) 63(2) 59(2) 6(1) −13(2) −3(2) C35 63(2) 52(1) 53(1) 5(1) −8(2) −2(2) N36 67(2) 70(2) 80(2) 4(2) −5(2) −19(2) C37 290(10) 260(10) 145(7) 68(7) 67(8) 120(10) C38 280(10) 187(7) 104(4) 1(5) −53(6) −80(10) O39 99(2) 91(2) 93(2) 1(2) −13(2) −28(2) Raman spectroscopy has been widely used to elucidate molecular structures, crystallinity and polymorphism. The low-frequency Raman modes are particularly useful in distinguishing different molecular packings in crystal. As such, Raman spectra were recorded on a Bruker FT-Raman RFS 100 spectrometer equipped with a photomultiplier tube and optical multichannel detectors. Samples placed in quartz capillary tubes were excited by an argon ion laser. The laser power at the samples was adjusted to about 100 mW and the spectral resolution was about 2 cm−1. It was found that Forms A, B, D, E, F, and H, (1:1) and the amorphous form have the Raman spectra which appear in FIGS. 5, 6, and 7. In addition, Forms A and B were characterized using a μTATR (Micro-Attenuated Total Reflectance) accessory (Harrick Split-Pea with Si crystal). The infrared spectra were obtained with a Nicolet Magna 560 FTIR spectrophotometer, a Ge on KBr beamsplitter, and a DTGS with KBr windows detector. Spectra were measured at 1 cm−1 resolution and 32 scans each, in a wavelength range of from 4000 to 400 cm−1, and application of baseline correction. The wavenumbers for Form A obtained are exhibited in the following Table 4. TABLE 4 Wavenumbers (cm−1) and relative intensities of absorption bands (1) 3454w, 3429w, 3354w, 3301w, 3255w, 3089w, 3060w, 3041w, 3028w 2964w, 2905w, 2875w, 2856w, 2722vw, 2684vw, 2644vw, 2603vw, 2234vw 1704s, 1646w, 1595s, 1550m, 1503m, 1466w, 1453w, 1444w, 1413w 1373w, 1367w, 1340w, 1324m, 1314m, 1306m, 1290w, 1266m, 1244m, 1229m 1187w, 1146s, 1124m, 1104m, 1090m, 1076m, 1052m, 1042s, 1038m, 1024s 987s, 971m, 944m, 909w, 890w, 876w, 841m, 792w, 768s, 742s, 732w, 697m, 674s, 645w, 630m 598w, 593w, 574m, 564s, 553vs, 538m, 533m, 531m, 526m, 508m, 501m, 491m, 471m, 458w, 445w, 442w, 436w, 428w, 418w vs = very strong, s = strong, m = medium, w = weak, vw = very weak, br = broad The IR spectrum in FIG. 9 reflects the vibrational modes of the molecular structure as a crystalline product. The wavenumbers obtained for Form B are exhibited in the following Table 5. TABLE 5 Wavenumbers (cm−1) and relative intensities of absorption bands (1) 3614w, 3361m, 3291m, 3088w, 3061w, 3043w, 3028w 2967w, 2905w, 2872w, 2222vw Wavenumbers (cm−1) and relative intensities of absorption bands (1) 1703s, 1631w, 1595s, 1553m, 1502w, 1467w, 1453w, 1444w, 1436w 1388vw, 1374vw, 1366w, 1355vw, 1340w, 1308m, 1291w, 1267m, 1245m 1187w, 1148s, 1125m, 1105m, 1091m, 1077m, 1052m, 1044m, 1025s 990m, 972w, 944m, 912w, 891w, 876vw, 862w, 843w, 836w, 792w, 769m, 757w, 743m, 717w, 699m, 672m 598w, 591w, 585w, 576m, 566m, 553vs, 536m, 509w, 502m, 484w, 471w, 432vw, 425w, 418w (1) vs = very strong, s = strong, m = medium, w = weak, vw = very weak, br = broad The IR spectrum in FIG. 10 reflects the vibrational modes of the molecular structure of Form B as a crystalline product. Following the same analytical IR method, Form B and the amorphous form were also characterised and compared with Form A, as shown in FIGS. 11 to 14. IR spectra of the different physical forms showed distinct spectral differences, most relevant are those in Table 6: TABLE 6 Wavenumbers (cm−1) and relative intensities of absorption bands (1) Form A Form B Amorphous form 3454m, 3429m, 3353m, 3615m, 3356m, 3291m, 3462m, 3362m, 3249m, 3255m, 3089w, 3060m, 3089m, 3061m, 3043w, 3062m, 3026m 3041w, 3028w 3027w 2963m, 2905m, 2869m, 2966m, 2905m, 2873m 2959m, 2871m 2856m 1704s, 1646m, 1596s, 1703s, 1630m, 1595s, 1704s, 1628s, 1596s, 1525s, 1549s, 1503s 1552s, 1502m 1502s 1306s, 1266s, 1244s 1308s, 1267s, 1245s 1312s, 1259s 1146s, 1104s, 1090s, 1076s, 1148s, 1105s, 1090s, 1077s, 1143s, 1090s, 1014s 1052s, 1042s, 1038s, 1023s 1052s, 1044s, 1024s 987s, 971s, 954s, 945s, 989s, 972s, 944s, 925m, 960s, 953s, 950s, 944s, 937s, 912m, 909m, 891s, 876s, 915m, 912s, 891s, 862s, 922s, 832s 841s, 827s 843s 792m, 768s, 742s, 697s, 792s, 769s, 744s, 699s, 672s 750br, 702s, 672s 674s (1) s = strong, m = medium, w = weak, vw = very weak, br = broad The physical Forms A, B, and amorphous form are identified through spectral interpretation, focused on absorption bands specific for each form. Unique and specific spectral differences between forms are noticed in 3 spectral ranges: from 3750 to 2650 cm−1 (range 1), from 1760 to 1580 cm−1 (range 2) and from 980 to 720 cm−1 (range 3). Range 1 (from 3750 to 2650 cm−1) FIG. 11: Form A shows a double band with absorption maxima at 3454 cm−1 and 3429 cm−1. Form B shows a single absorption band at 3615 cm−1 and amorphous form shows a single absorption band at 3362 cm−1. Range 2 (from 1760 to 1580 cm−1) FIG. 12: Form A shows a single absorption band at 1646 cm−1, Form B shows a single absorption band at 1630 cm−1 and amorphous form shows a single absorption band at 1628 cm−1 with a clearly higher intensity compared to the Form B band. Additionally, amorphous form shows a less intense, broad band at 1704 cm−1 compared to both forms A and B bands at about 1704 cm−1. Range 3 (from 980 to 720 cm−1) FIG. 13: Form A shows a distinct set of 5 absorption bands at 911, 890, 876, 862 and 841 cm−1. Form B shows a similar set but the 876 cm−1 band is missing. Amorphous form shows a single broad band at about 750 cm−1, both forms A and B show two maxima at about 768 cm−1 and 743 cm−1. Thermomicroscopy is another useful technique in the study of solid-state kinetics. The kinetics of nucleation processes from solutions or melts, including the analysis of the nucleation speed, can be quantified. The simplest and most widely used method is the melting point determination. As such, a Mettler model FP 82 controller with heating stage was used on a Leitz microscope. A few particles of Form A were placed on a glass slide and observed while heating at 10° C. per minute. The melting range for Form A (1:1) was found to be between 90°and 110° C. On another means of characterization, the solubility of Form A (1:1) was also a matter subject to study. Its solubility in different solvents at approximate 23° C. was determined to be as follows: TABLE 7 Approximate solubility for Form A (1:1), in mg/ml Approximate solubility Solvent Form A (mg/ml) Acetone 106-211 Dichloromethane 105-209 1-Methoxy-2-propanol 160-213 Ethylmethylketone 102-204 Ethylacetate 71-107 Ethanol absolute <3.4 Heptane <3.4 Water <3.5 Isopropylether <3.4 Methacyanate >200 Methanol <3.4 2-Propanol <3.4 Tetrahydrofurane 102-203 Toluene <3.5 Further solubility investigations were performed in function of pH. As such, the aqueous solubilities of Form A (1:1) were measured in solvents with different pH. An excess of the solute was equilibrated with the solvent at 20° C. for at least 24 hours. After removing the undissolved compound, the concentration in solution was determined using UV spectrometry. TABLE 8 Solubility for Form A (1:1) in function of pH Solubility Solvent (mg/100 ml solution) Water 16 (pH 5.9) Buffer pH 2 (citrate/HCl) 18 (pH 2.0) Buffer pH 3 (citrate/HCl) 10 (pH 3.0) Buffer pH 4 (citrate/HCl) 9 (pH 4.0) 0.01 N HCl 18 (pH 2.1) 0.1 N HCl 83 (pH 1.1) 1.0 N HCl 620 (pH 0.2) Solubility of Form A (1:1) in function of HPβCD (hydroxypropyl-β-cyclodextrin) was measured. An excess of product was equilibrated with the solvent during 2 days at 20° C. After removing the undissolved compound, the concentration in solution was determined using UV spectrometry. TABLE 9 Solubility for Form A (1:1) in function of HPβCD Solubility in solvent mg/ml solution Water 0.16 (pH = 5.9) 5% HPβCD in water 2.4 (pH = 5.8) 10% HPβCD in water 6.5 (pH = 6.0) 20% HPβCD in water 17 (pH = 6.0) 40% HPβCD in water 40 (pH = 5.9) In a second aspect, the present invention relates to processes for preparing pseudopolymorphs. Pseudopolymorphs of compound of formula (X) are prepared by combining compound of formula (X) with an organic solvent, or water, or mixtures of water and water miscible organic solvents, applying any suitable technique to induce crystallization, and isolating the desired pseudopolymorphs. By techniques for inducing crystallization are to be understood those processes for the production of crystals, which include amongst others, dissolving or dispersing compound of formula (X) in a solvent medium, bringing the solution or dispersion of compound of formula (X) and the solvent(s) to a desired concentration, bringing the said solution or dispersion to a desired temperature, effecting any suitable pressure, removing and/or separating any undesired material or impurities, drying the formed crystals to obtain the pseudopolymorphs in a solid state, if such state is desired. Bringing the solution or dispersion of compound of formula (X) and solvents to a desired concentration does not necessarily imply an increase in the concentration of compound of formula (X). In certain cases, a decrease or no change in concentration could be preferable. By bringing the said solution or dispersion to a desired temperature, one will understand the acts of heating, cooling or leaving at ambient temperature. The techniques used for obtaining a desired concentration are those common in the art, for instance, evaporation by atmospheric distillation, vacuum distillation, fractioned distillation, azeotropic distillation, film evaporation, other techniques well known in the art and combinations thereof. An optional process for obtaining a desired concentration could as well involve the saturation of the solution of compound of formula (X) and solvent, for example, by adding a sufficient volume of a non-solvent to the solution to reach the saturation point. Other suitable techniques for saturating the solution include, by way of example, the introduction of additional compound of formula (X) to the solution and/or evaporation of a portion of the solvent from the solution. As referred to herein, saturated solution encompasses solutions at their saturation points or exceeding their saturation points, i.e. supersaturated. Removing and/or separating any undesired material or impurities may be performed by purification, filtering, washing, precipitation or similar techniques. Separation, for example, can be conducted by known solid-liquid separation techniques. Filtering procedures known to those skilled in the art can as well be used in the present process. The filtrations can be performed, amongst other methods, by centrifugation, or using Buchner style filter, Rosenmund filter or plates, or frame press. Preferably, in-line filtration or safety filtration may be advantageously intercalated in the processes disclosed above, in order to increase the purity of the resulting pseudopolymorphic form. Additionally, filtering agents such as silica gel, Arbocel®, dicalite diatomite, or the like, may also be employed to separate impurities from the crystals of interest. Crystals obtained may be also dried, and such drying process may optionally be used in the different crystallization passages, if more than one crystallization passage is applied. Drying procedures include all techniques known to those skilled in the art, such as heating, applying vacuum, circulating air or gas, adding a desiccant, freeze-drying, spray-drying, evaporating, or the like, or any combination thereof. Processes for crystallization of pseudopolymorphs of compound of formula (X) embrace multiple combinations of techniques and variations thereof. As such, and by way of example, crystallization of pseudopolymorphs of compound of formula (X) may be executed by dissolving or dispersing compound of formula (X) at a suitable temperature in the solvent whereby portion of the said solvent evaporates increasing the concentration of the compound of formula (X) in the said solution or dispersion, cooling the said mixture, and optionally washing and/or filtering and drying resulting solvate crystals of compound of formula (X). Optionally, pseudopolymorphs of compound of formula (X) may be prepared by dissolving or dispersing compound of formula (X) in a solvent medium, cooling said solution or dispersion and subsequently filtering and drying the obtained pseudopolymorph. Another example of preparation of solvates of compound of formula (X) could be by saturating compound of formula (X) in the solvent medium, and optionally filtering, washing and drying obtained crystals. Crystal formation may as well involve more than one crystallization process. In certain cases, one, two or more extra crystallization steps may be advantageously performed for different reasons, such as, to increase the quality of the resulting solvate. For instance, pseudopolymorphs of the present invention could also be prepared by adding a solvent to an initial starting base material of compound of formula (X), stirring the solution at a fixed temperature until the substances would be fully solved, concentrating the solution by vacuum distillation, and cooling. A first crystallization would take place and the formed crystals would be newly washed with a solvent, and followed by dissolution of compound of formula (X) with the solvent to form the desired pseudopolymorph. Recrystallization of the reaction mixture would occur, followed by a cooling step from reflux. The formed pseudopolymorph would optionally be filtered and allowed to dry. By dissolving or dispersing compound of formula (X) in the organic solvent, water or a mixture of water and water miscible organic solvents, one may obtain different degrees of dispersion, such as suspensions, emulsions, slurries or mixtures; or preferably obtain homogeneous one-phase solutions. Optionally, the solvent medium may contain additives, for example one or more dispersing agents, surfactants or other additives, or mixtures thereof of the type normally used in the preparation of crystalline suspensions and which are well documented in the literature. The additives may be advantageously used in modifying the shape of crystal by increasing the leniency and decreasing the surface area. The solvent medium containing the solution may optionally be stirred for a certain period of time, or vigorously agitated using, for example, a high shear mixer or homogeniser or a combination of these, to generate the desired droplet size for the organic compound. Examples of organic solvents useful for the present invention include C1-C4 alcohols such as methanol, ethanol, isopropanol, butanol, 1-methoxy-2-propanol, and the like; C1-C4 chloroalkanes such as dichloromethane; C1-C4 ketones such as acetone; C1-C4 ethers such as anisole, and the like; cycloethers such as tetrahydrofuran; C1-C4 esters such as ethylacetate; C1-C4 sulfonates such as mesylate, ethanesulfonate, butanesulfonate, 2-methyl-1-propanesulfonate; and the like. Examples of mixtures of water and water miscible organic solvents include, mixtures of water with all organic solvents listed above provided they are miscible in water, e.g. ethanol/water, for instance in a 50/50 ratio. Preferred solvents are those pharmaceutically acceptable solvents. However, pharmaceutically non-acceptable solvents may also find their use in the preparation of pharmaceutically acceptable pseudopolymorphs. In a preferred method, the solvent is a pharmaceutically acceptable solvent since it results in a pharmaceutically acceptable pseudopolymorph. In a more preferred method, the solvent is ethanol. In a particular embodiment, pharmaceutically acceptable pseudopolymorphs of compound of formula (X) can be prepared starting from pseudopolymorphic forms of compound of formula (X), which may not be necessarily pharmaceutically acceptable. For instance, Form A may be prepared starting from Form J. Pseudopolymorphs may also be prepared starting from the amorphous form. In the mixtures of water and water miscible organic solvents, the amount of water can vary from about 5% by volume to about 95% by volume, preferably from about 25% to about 75% by volume, more preferably from about 40% to about 60% by volume. It should also be noted that the quality of selected organic solvent (absolute, denaturated, or other) also influences the resulting quality of the pseudopolymorph. Control of precipitation temperature and seeding may be additionally used to improve the reproducibility of the crystallization process, the particle size distribution and form of the product. As such, the crystallization can be effected without seeding with crystals of the compound of the formula (X) or preferably in the presence of crystals of the compound of the formula (X), which are introduced into the solution by seeding. Seeding can also be effected several times at various temperatures. The amount of the seed material depends on the amount of the solution and can readily be determined by a person skilled in the art. The time for crystallization in each crystallization step will depend on the conditions applied, the techniques employed and/or solvents used. Breaking up the large particles or aggregates of particles after crystal conversion may additionally be performed in order to obtain a desired and homogeneous particle size. Accordingly, the solvate crystal forms of compound of formula (X) are optionally milled after undergoing conversion. Milling or grinding refers to physically breaking up the large particles or aggregates of particles using methods and apparatus well known in the art for particle size reduction of powders. Resulting particle sizes may range from millimeters to nanometers, yielding i.e. nanocrystals, microcrystals. The yield of the preparation process of the pseudopolymorphs of compound of formula (X) may be 10% or more, a more preferred yield would vary from 40% to 100%. Interestingly, the yield varies between 70% and 100%. Suitably, pseudopolymorphs of the present invention have a purity greater than 90 percent. More suitably, the present pseudopolymorphs have a purity greater than 95 percent. Even more suitably, the present pseudopolymorphs have a purity greater than 99 percent. In a third aspect, the present invention relates to a pharmaceutical formulation comprising a therapeutically effective amount of a pseudopolymorph of compound of formula (X), and a pharmaceutically acceptable carrier or diluent thereof. In one embodiment, present invention relates to the use of pharmaceutically acceptable pseudopolymorphic forms of compound of formula (X), preferably Form A, in the manufacture of a medicament for treating diseases caused by retroviruses, such as HIV infections, for example, Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC). In another embodiment, present invention provides a method for the treatment of a retroviral infection, for example an HIV infection, in a mammal such as a human, which comprises administering to the mammal in need thereof an effective antiretroviral amount of a pharmaceutically acceptable pseudopolymorphic form of compound of formula (X), preferably Form A. Present invention also relates to a method in which the treatment of a HIV viral infection comprises the reduction of HIV load. Present invention also relates to a method in which the treatment of said HIV viral infection comprises the increase of CD4+ cell count. Present invention relates as well to a method in which the treatment of said HIV viral infection comprises inhibiting HIV protease activity in a mammal. Pharmaceutically acceptable pseudopolymorphic forms of compound of formula (X), preferably Form A, also referred to herein as the active pharmaceutical ingredients, may be administered by any route appropriate to the condition to be treated, preferably orally. It will be appreciated however, that the preferred route may vary with, for example, the condition of the recipient. For each of the above-indicated utilities and indications the amount required of the active ingredient will depend upon a number of factors including the severity of the condition to be treated and the identity of the recipient and will ultimately be at the discretion of the attendant physician or veterinarian. The desired dose preferably may be presented as one, two, three or four or more subdoses administered at appropriate intervals throughout the day. For an oral administration form, pseudopolymorphs of the present invention are mixed with suitable additives, such as excipients, stabilizers or inert diluents, and brought by means of the customary methods into the suitable administration forms, such as tablets, coated tablets, hard capsules, aqueous, alcoholic, or oily solutions. Examples of suitable inert carriers are gum arabic, magnesia, magnesium carbonate, potassium phosphate, lactose, glucose, or starch, in particular, corn starch. In this case the preparation can be carried out both as dry and as moist granules. Suitable oily excipients or solvents are vegetable or animal oils, such as sunflower oil or cod liver oil. Suitable solvents for aqueous or alcoholic solutions are water, ethanol, sugar solutions, or mixtures thereof. Polyethylene glycols and polypropylene glycols are also useful as further auxiliaries for other administration forms. For subcutaneous or intravenous administration, the pseudopolymorphs of compound of formula (X), if desired with the substances customary therefor such as solubilizers, emulsifiers or further auxiliaries, are brought into solution, suspension, or emulsion. The pseudopolymorphs of compound of formula (X) can also be lyophilized and the lyophilizates obtained used, for example, for the production of injection or infusion preparations. Suitable solvents are, for example, water, physiological saline solution or alcohols, e.g. ethanol, propanol, glycerol, in addition also sugar solutions such as glucose or mannitol solutions, or alternatively mixtures of the various solvents mentioned. Suitable pharmaceutical formulations for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the pseudopolymorphs of compound of formula (X) in a pharmaceutically acceptable solvent, such as ethanol or water, or a mixture of such solvents. If required, the formulation can also additionally contain other pharmaceutical auxiliaries such as surfactants, emulsifiers and stabilizers as well as a propellant. Such a preparation customarily contains the active compound in a concentration from approximately 0.1 to 50%, in particular from approximately 0.3 to 3% by weight. Pseudopolymorphs of the present invention may also be presented in a formulation comprising micrometer-, nanometer- or picometer-size particles of the pseudopolymorph of compound of formula (X), which formulation may contain other pharmaceutical agents and may optionally be converted to solid form. It may be convenient to formulate the present pseudopolymorphs in the form of nanoparticles which have a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than 1000 nm. Useful surface modifiers are believed to include those that physically adhere to the surface of the antiretroviral agent but do not chemically bind to the antiretroviral agent. It may be further convenient to store the pseudopolymorphs of compound of formula (X) in packaging materials which are protective to mechanical, environmental, biological or chemical hazards, or degradation. Conditioning drug substances can be achieved by employing packaging materials impermeable to moisture, such as sealed vapour lock bags. Conditioning drug products, such as tablets, capsules, can be achieved by employing for instance, aluminium blisters. It should be understood that in addition to the ingredients particularly mentioned above, formulations of this invention includes other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents or taste masking agents. The following examples are intended for illustration only and are not intended to limit the scope of the invention in any way. EXAMPLE 1 The industrial scale synthesis of Form A (1:1) was performed using the following steps. First a solution was prepared with isopropanol and (3R,3aS,6aR)-hexahydrofuro [2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate. The solution was concentrated by vacuum distillation at 70° C. and 200-500 mbar pressure and cooled from a T>35° to a T between 15°and 20° C. for about 10 hours. The crystals formed were newly washed with 13 liters isopropanol and filtered. A subsequent recrystallization from ethanol/water (90 liters/90 liters) was performed. This was followed by a new dissolution step, but with 60 liters ethanol instead. Recrystallization of the reaction mixture from ethanol occurred, followed by a cooling step from reflux to −15° C. approximately and during 10 hours. The ethanolate formed was filtered and let to dry at about 50° C. and about 7 mbar. The yield of this process was at least 75%. EXAMPLE 2 In another example a mixture of Form D and Form B were prepared. Acetone was used as a solvent during the crystallisation process to form Form D. The crystallisation process then comprised the step of stirring the initial starting compound (10 g) in 70 ml acetone. The solution was subsequently refluxed until the compound was completely solved. 40 ml of water were added and the solution was subsequently cooled slowly until room temperature and stirred overnight. Formed crystals were filtered and dried in the vacuum oven at 50° C. 7.6 g of product resulted from the crystallization, being the yield of this process of about 75%. EXAMPLE 3 In another example Form J crystals were prepared. Isopropanol was used as a solvent during the crystallisation process to form Form J. The crystallisation process then comprised the step of solving the initial starting material in the hot solvent. The solution was subsequently cooled until room temperature. Formed crystals were filtered and dried in the vacuum oven at 50° C. The crystals contained about 50 mol % isopropanol. EXAMPLE 4 In this example, the mass losses for different pseudopolymorphs in thermogravimetric (TG) experiments were calculated. Thermogravimetry is a technique that measures the change in mass of a sample as it is heated, cooled or held at constant temperature. Approximately 2 to 5 mg of sample were placed on a pan and inserted into the TG furnace, model Netzsch Thermo-Microbalance TG 209 coupled to a Bruker FTIR Spectrometer vector 22. The samples were heated in a nitrogen atmosphere at a rate of 10° C./min, up to a final temperature of 250° C. The detection limit of residual solvents was in the order of 0.1 % for distinct stepwise solvent loss over a narrow temperature range (few degrees Celsius). The following TG data were obtained: Form A: a weight loss of 4.2% was observed in the temperature range of 25-138° C. (ethanol+little water) and of 6.9% (ethanol+CO2) in the temperature range of 25-200° C. Ethanol loss rate was maximal at 120° C. CO2 loss was due to chemical degradation and was visible at around 190° C. Form B: a weight loss of 3.4% was observed in the temperature range 25-78° C. (water) and of 5.1% in the temperature range 25-110° C. (ethanol+water for T>78° C.). From 110-200° C. further 1.1% weight was lost (ethanol). Form C: a weight loss of 2.1% was observed in the temperature range 25-83° C. (water+methanol) and of 4.2% in the temperature range 25-105° C. (methanol for T>83° C., distinct step). From 105-200° C. further 2.1% weight was lost (methanol). No ethanol was observed in the gas phase. Form D: a weight loss of 0.1% was observed in the temperature range 25-50° C., of 4.2% in the temperature range 25-108° C. (acetone+ethanol for T>50° C.), of 8.2% in the temperature range 25-157° C. (acetone+ethanol for T>108° C.) and of 10.5% in the temperature range 25-240° C. (acetone+ethanol for T>157° C.). Form E: a weight loss of 0.2% was observed in the temperature range 25-75° C. (water), of 1.8% in the temperature range 25-108° C. (dichloromethane +ethanol for T>75° C.), of 6.8% in the temperature range 25-157° C. (dichloromethane +ethanol for T>108° C.) and of 8.8% in the temperature range 25-240° C. (dichloromethane +ethanol for T>157° C.). Form F: a weight loss of 0.1% was observed in the temperature range 25-50° C. (probably water), of 1.7% in the temperature range 25-108° C. (ethylacetate+ethanol for T>50° C.), of 6.6% in the temperature range 25-157° C. (ethylacetate+ethanol for T>108° C.) and of 9% in the temperature range 25-240° C. (ethylacetate+ethanol for T>157° C.). Form G: a weight loss of 0.0% was observed in the temperature range 25-50° C., of 3.7% in the temperature range 25-108° C. (1-methoxy-2-propanol+ethanol for T>50° C., distinct step), of 8% in the temperature range 25-157° C. (1-methoxy-2-propanol+ethanol for T>108° C.) and of 12.5% in the temperature range 25-240° C. (1-methoxy-2-propanol+ethanol for T>157° C.). Form H: a weight loss of 0.8% was observed in the temperature range 25-100° C. (anisole+little ethanol) and of 8.8% in the temperature range 25-200° C. (anisole+ethanol for T>100° C.). Form I: a weight loss of 0.3% was observed in the temperature range 25-89° C. (water) and of 11.0% in the temperature range 25-200° C. (tetrahydrofurane for T>89° C.). No ethanol was observed in the gas phase. Table 10 shows approximate expected mass losses for different Forms in thermogravimetric (TG) experiments. Mass loss in % (M+x.LM=100%) Hemisol- Monosol- Disol- Trisol- Pseudopolymorph BP[° C.] vate vate vate vate Form D 56 5.0 9.6 17.5 24.1 Form H 152 9.0 16.5 28.3 37.2 Form E 40 7.2 13.4 23.7 31.8 Form G 119 7.6 14.1 24.8 33.1 Form F 76 7.4 13.9 24.3 32.6 Form A 78 4.0 7.8 14.4 20.2 Form B 100 1.6 3.2 6.2 9.0 Form C 65 2.8 5.5 10.5 14.9 Form I 66 6.2 11.6 20.8 28.3 In another set of thermogravimetric methods, Form A, Form A after Adsorption/Desorption, and Form A after Adsorption/Desorption hydratation tests, were all transferred into an aluminum sample pan. The TG curve was recorded on a TA Instrument Hi-Res TGA 2950 thermogravimeter at the following conditions: initial temperature: room temperature heating rate: 20° C./min resolution factor: 4 final condition: 300° C. or <80[(w/w)%] The TG curves of the samples are collected in FIG. 16. Table 11 shows mass losses for the forms tested: TABLE 11 TG (% weight change) Form A Up to 80° C. >80° C. Form A 0.3 7.1 Form A after ADS/DES 2.9 4.0 Form A after A/D hydratation test 5.4 0.5 The loss of weight at temperatures up to 80° C. is mainly due to the evaporation of solvent (water) present in the sample. The loss of weight at temperatures above 80° C. is mainly due to the evaporation of solvent (ethanolate) present in the sample. A TG curve of form A at 25° C. under dry nitrogen atmosphere in function of time is collected in FIG. 17. The loss of weight at 25° C. after 10 hours was around 0.6%. This was due to the evaporation of solvent. EXAMPLE 5 In another example, measurements of differential scanning calorimetry (DSC) were also performed. For such purpose, a Perkin Elmer DSC 204 thermal analysis system was used. From 2 to 5 mg sample of Form A were accurately weighed into a DSC pan. The experiments were performed in an open pan. The sample was equilibrated to approximately 30° C. and then heated at a rate of 10° C. per minute, up to a final temperature of 200° C. The DSC data was obtained following a standard method in the art. The Form A was characterized by differential scanning calorimetry (DSC) in which it showed a sharp endotherm in the range 80-119° C., showing a peak at about 105.6° C., with a delta H=−98.33 J/g onset. Accordingly, the ethanol solvate crystal Form A of compound of formula (X) (1:1) showed the thermograph pattern, which appears in FIG. 8. In another set of DSC measurements, Form A, Form A after Adsorption/Desorption, and Form A after Adsorption/Desorption hydratation tests were examined. About 3 mg of the samples were transferred into a 30 μl perforated aluminum Perkin Elmer sample pan. The sample pan was closed with the appropriate cover and the DSC curve recorded on a Perkin Elmer Pyris DSC, at the following conditions: initial temperature: 25° C. heating rate: 10° C./min final temperature: 150° C. nitrogen flow: 30 ml/min Form A showed an endothermic signal at about 104.6° C. and a heat of fusion of 95.8 J/g caused by the evaporation of the ethanolate and the melting of the product. Form A after ADS/DES showed a broad endothermic signal due to a mixture of ethanolate Form A and hydrated Form B. Form A after ADS/DES hydratation test showed an endothermic signal at about 73.5° C. and a heat of fusion of 126 J/g caused by the evaporation of water and the melting of the product. Thermograph curves are depicted in FIG. 15. EXAMPLE 6 In another example stability studies of the Form A in three different conditions were tested out. They included conditions of 25° C. and 60% RH, 40° C. and 75% RH, and 50° C. These studies revealed that at 25° C. and 60% RH long-term stability, the amount of ethanol and water is stable. Table 12 shows the Stability study for Form A. Long term stability at 25° C./60% RH (Relative Humidity), with brown glass bottles as sample container. Test Release data 0 month 1 month 3 month Residual solvent: 7.5 7.6 7.6 7.1 % (w/w) ethanol % (w/w) Water 0.10 0.27 0.26 0.55 EXAMPLE 7 Adsorption-Desorption Tests About 23 mg of Form A were transferred into a VTI vapor sorption analyzer model SGA100 and the weight change with respect to the atmospheric humidity was recorded at the following conditions: drying temperature: 40° C. equilibrium: <0.05% in 5 min. or 60 min. data interval: 0.05% or 2 min. temperature: 25° C. first cycle RH (%) adsorption: 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 RH (%) desorption: 95, 90, 80, 70, 60, 50, 40, 30, 20, 10, 5 second cycle RH (%) adsorption: 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 RH (%) desorption: 95, 90, 80, 70, 60, 50, 40, 30, 20, 10, 5 At the drying step about 0.6% weight loss was registered. The obtained dried product was not hygroscopic, it adsorbed up to 0.7% water at high relative humidity. During the desorption cycle a loss of weight of 1.4% was registered, this indicated that the product was losing ethanolate. The obtained product after ADS/DES was a mixture of ethanolate form and hydrated form. The ADS/DES curve is collected in FIG. 18. Adsorption-Desorption Hydratation Tests About 23 mg of Form A were transferred into a VTI vapor sorption analyzer model SGA100 and the weight change with respect to the atmospheric humidity was recorded at the following conditions: equilibrium: ≦0.0005% in 5 min. or 90 min. data interval: 0.05% or 2 min temperature: 25° C. cycle RH (%) adsorption/desorption: 5.95 repeat the cycle 11 times At the end of this test a loss of weight of 5.2% was registered. This was comparable with the TG result (TG 5.4% up to 80° C.). The ethanolate form was transferred into a hydrated form. The ADS/DES hydratation test curves are collected in FIG. 19. EXAMPLE 8 The stability of Form A was studied after storage of the compound in a sample container with an inner cover made of single LD-PE (string sealed), and and outer cover made of PETP/Alu/PE (Moplast) heat sealed. A long term stability study at 25° C./60% RH, and an accelerated stability study at 40° C./75% RH, were performed for a period of 6 months, and the samples analysed at different time points as shown in following tables. TABLE 13 Long term stability at 25° C./60% RH Release tests Remark Specification data 0 month 1 month 3 month 6 month Polymorphism ° C. (onset) For information only 97.3 97.3 95.5 97.9 97.5 DSC ° C. max For information only 104 104.2 103.5 104.2 104 Residual % (w/w) ethanol <=10.0% 6.71 6.31 6.33 6.40 6.33 solvents % (w/w) 2-propanol <=0.5% 0.04 0.04 0.05 0.05 0.05 % (w/w) THF <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) acetone <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) CH2Cl2 <=0.06% <0.01 <0.01 <0.01 <0.01 <0.01 Water (KF) % (w/w) <=7.0% 0.63 0.23 0.34 0.32 0.46 X-Ray For information only C C — — — powder diffraction C: chrystal TABLE 14 Accelerated stability at 40° C./75% RH Release 0 1 3 6 Tests Remark Specification data month month month month Polymorphism ° C. (onset) For information only 97.3 97.3 97.5 98.0 97.8 DSC ° C. max For information only 104 104.2 103.4 1039 104.3 Residual % (w/w) ethanol <=10.0% 6.71 6.31 6.73 6.32 6.50 solvents % (w/w) 2-propanol <=0.5% 0.04 0.04 0.05 0.05 0.05 % (w/w) THF <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) acetone <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) CH2Cl2 <=0.06% <0.01 <0.01 <0.01 <0.01 <0.01 Water (KF) % (w/w) <=7.0% 0.63 0.23 0.37 0.34 0.42 X-Ray For information only C C — — — powder diffraction Form A exhibited chemical and crystallographic stability at the conditions mentioned in tables 13 and 14. EXAMPLE 9 The stability of Form A was studied after storage of the compound in a sample container with an inner cover made of single LD-PE (string sealed), and and outer cover made of vapor loc bag (LPS) heat sealed. A long term stability study at 25° C./60% RH, and an accelerated stability study at 40° C./75% RH, were performed for a period of 6 months, and the samples analysed at different time points as shown in following tables. TABLE 15 Long term stability at 25° C./60% RH Release Tests Remark Specification data 0 month 1 month 3 month 6 month Polymorphism ° C. (onset) For information only 97.3 97.3 96.3 96.2 98.5 DSC ° C. max For information only 104 104.2 103.1 103.8 103.9 Residual % (w/w) ethanol <=10.0% 6.71 6.31 6.42 6.35 6.52 solvents % (w/w) 2-propanol <=0.5% 0.04 0.04 0.06 0.05 0.05 % (w/w) THF <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) acetone <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) CH2Cl2 <=0.06% <0.01 <0.01 <0.01 <0.01 <0.01 Water (KF) % (w/w) <=7.0% 0.63 0.23 0.32 0.38 0.49 X-Ray For information only C C — — — powder diffraction TABLE 16 Accelerated stability at 40° C./75% RH Release 0 1 3 6 Tests Remark Specification data month month month month Polymorphism ° C. (onset) For information only 97.3 97.3 97.8 97.5 97.9 DSC ° C. max For information only 104 104.2 103.4 103.7 104.0 Residual % (w/w) ethanol <=10.0% 6.71 6.31 6.35 6.31 6.30 solvents % (w/w) 2-propanol <=0.5% 0.04 0.04 0.06 0.05 0.05 % (w/w) THF <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) acetone <=0.5% <0.01 <0.01 <0.01 <0.01 <0.01 % (w/w) CH2Cl2 <=0.06% <0.01 <0.01 <0.01 <0.01 <0.01 Water (KF) % (w/w) <=7.0% 0.63 0.23 0.31 0.36 0.51 X-Ray For information only C C — — — powder diffraction Form A exhibited chemical and crystallographic stability at the conditions mentioned in tables 15 and 16. EXAMPLE 10 For the purpose of chemical stability testing, Form A was stored for a period of 1, 4 and 8 weeks under different conditions. These conditions were 40° C./75% RH, 50° C., RT/<5% RH, RT/56% RH, RT/75% RH and 0.3da ICH light. The compound was analysed after storage by HPLC and by visual inspection. The HPLC method used in this study was HPLC method 909. The results of the tests are reported in the following table. TABLE 17 HPLC Sum of impurities Appearance Conditions 1 week 4 week 8 week 1 week 4 weeks 8 weeks Reference 1.07 — — slightly-yellow — — 0.3 da ICH light 1.01 — — slightly-yellow — — 40° C./75% RH 1.03 0.98 0.99 slightly-yellow slightly-yellow slightly-yellow 50° C. 1.05 1.08 1.06 slightly-yellow slightly-yellow slightly-yellow RT/<5% RH — 1.02 1.04 — slightly-yellow slightly-yellow RT/56% RH — 1.02 0.99 — slightly-yellow slightly-yellow RT/75% RH — 1.00 1.01 — slightly-yellow slightly-yellow It was concluded that Form A is chemically stable after storage in all investigated conditions. EXAMPLE 11 Different fractions of Form B were characterized with thermogravimetry (TG), differential scanning calorimetry (DSC) and infrared spectroscopy (IR). The results of the tests are reported in the following table. TABLE 18 TG % DSC weight change Max Extra Fractions <100° C. IR (° C.) (° C.) Form B fraction 1 5.65 Hydrate, Ref 69.1 — after ADS/DES 4.30 ±Hydrate, Ref, — — +amorphous Form B fraction 2 5.91 ˜Hydrate, Ref 75.6 — after 5 d 40° C./75% RH 3.56 ˜Hydrate, Ref 74.1 — Form B fraction 3 3.13 ±Hydrate, Ref, 77.0 67.8 +amorphous after 5 d 40° C./75% RH 2.33 ±Hydrate, Ref, 77.4 62.8 +amorphous ˜hydrate, Ref: identical with reference EXAMPLE 12 The adsorption and desorption of water at 25° C. at different conditions of relative humidity was investigated on 38 mg of Form B. The weight change as a function of relative humidity was registered. The results are displayed in FIG. 20. At the drying step about 5.6% weight loss was registered for Form B. The obtained dried product was hygroscopic, it adsorbed up to 6.8% water at high relative humidity. After the desorption cycle about 1.2% water remained on the sample. The obtained product after ADS/DES was a mixture of hydrate and amorphous product. EXAMPLE 13 Aqueous solubilities of Form B were measured in solvents with different pH. An excess of the solute was equilibrated with the solvent at 20° C. for at least 24 hours. After removing the undissolved compound, the concentration in solution was determined using UV spectrometry. TABLE 19 Solubility Solvent (mg/100 ml solution) Water 10 (pH 5.1) Buffer pH 2 (citrate/HCl) 23 (pH 2.0) Buffer pH 3 (citrate/HCl) 13 (pH 3.0) Buffer pH 4 (citrate/HCl) 12 (pH 4.0) 0.01N HCl 18 (pH 2.1) 0.1N HCl 150 (pH 1.1) 1.0N HCl 510 (pH 0.14) EXAMPLE 14 The stability of the crystal structure of Form B was studied after storage of the compound for a period of two weeks at room temperature (RT) under <5%, 56% and 75% relative humidity (RH), 50° C. and 40° C./75% RH. The samples were analyzed with thermogravimetry (TG), differential scanning calorimetry (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). The results of the tests are reported in the following table. TABLE 20 TG DSC condition <100° C. <225° C. IR XRD Max (° C.) Appearance 0 days 5.65 0.16 Ref Ref 69.1 slightly yellow-orange after ADS/DES 4.30 0.18 ≠Ref — — slightly yellow-orange RT/<5% RH 0.32 0.07 ≠Ref ≠Ref 71.2 slightly yellow-orange RT/56% RH 5.71 0.25 ˜Ref ˜Ref 71.0 slightly yellow-orange RT/75% RH 6.20 0.10 ˜Ref ˜Ref 71.5 slightly yellow-orange 50° C. 0.23 0.06 ≠Ref ≠Ref 76.4 slightly yellow-orange 40° C. 75% RH 5.77 0.07 ˜Ref ±Ref 70.4 slightly yellow-orange ˜Ref: identical with reference ±Ref: similar with reference ≠Ref: different with reference EXAMPLE 15 In the chemical stability test program Form B was stored for a period of 1, 4 and 9 weeks under different conditions. These conditions were 40° C./75% RH, 50° C., RT/<5% RH, RT/56% RH, RT/75% RH and 0.3da ICH light. The compound was analysed after storage by HPLC and by visual inspection. The HPLC method used in this study was HPLC method 909. The results of the tests are reported in the following table, from which it was concluded that Form B is chemically stable. TABLE 21 HPLC Sum of impurities Appearance Condition 1 week 4 week 9 week 1 week 4 weeks 9 weeks Reference 1.35 — — lightly yellow- — — orange 0.3 da ICH 1.30 — — light-orange — — light 40° C./75% RH 1.43 1.38 1.41 lightly yellow- Orange light-orange orange 50° C. 1.46 1.50 1.46 lightly yellow- light-orange light-orange orange RT/<50% RH — 1.48 1.37 — light-orange light-orange RT/56% RH — 1.11 1.35 — lightly yellow- light-orange orange RT/75% RH — 1.34 1.29 — light-orange light-orange EXAMPLE 16 Form K was prepared by adding neat methanesulfonic acid to a solution of Form A in THF at r.t. Form K was subsequently mixed with alkali halide and pressed to a pellet (Ph. Eur.) and analyzed by Infrared spectrometry (IR) at the following conditions: apparatus: Nicolet Magna 560 FTIR spectrophotometer number of scans: 32 resolution: 1 cm−1 wavelength range: 4000 to 400 cm−1 baseline correction: yes detector: DTGS with KBr windows beamsplitter: Ge on KBr alkali halide: KBr (potassium bromide) The IR spectrum of Form K, as shown in FIG. 21, reflects the vibrational modes of the molecular structure of the mesylate solvate as a crystalline product. TABLE 22 Wavenumbers (cm−1) and relative intensities of absorption bands (1) 3362m, 3064w 2985m, 2964m, 2906m, 2873m, 2632w, 2585w 1687s, 1627w, 1601w 1554m, 1495m, 1480w, 1470w, 1452w, 1443w, 1421w 1383w, 1373w, 1369w, 1345m, 1324m, 1314m, 1299w, 1268m, 1245m, 1221m, 1202s 1190s, 1166vs, 1122m, 1091m, 1077m, 1051s, 1043s, 1023m, 1002m 992m, 969w, 943w, 912w, 888w, 867vw, 836w, 813vw 773m, 754w, 743m, 711w, 700m, 658m, 634w 581w, 556m, 505w, 472vw, 452vw, 435vw, 417vw (1) vs = very strong, s = strong, m = medium, w = weak, vw = very weak, br = broad EXAMPLE 17 Form K was transferred to a glass capillary cell and analyzed by Raman spectrometry at the following conditions: Raman mode: Nondispersive Raman apparatus: Nicolet FF-Raman module number of scans: 64 resolution: 4 cm−1 wavelength range: 3700 to 100 cm−1 laser: Nd:YVO4 laser frequency: 1064 cm−1 detector: InGaAs beamsplitter: CaF2 sample geometry: 180° reflective polarization: no The Raman spectrum of Form K, as shown in FIG. 22, reflects the vibrational modes of the molecular structure of the mesylate as a crystalline product. TABLE 23 Wavenumbers (cm1) and relative intensities of absorption bands (1) 3080m, 3068m, 3059m, 3043w, 3022w, 3006m 2989s, 2978s, 2962s, 2933vs, 2906m, 2871m 1685vw, 1628w, 1603s, 1585w, 1495w, 1479w, 1466w, 1450m, 1423w 1381w, 1346w, 1336w, 1313w, 1290w, 1271w, 1244w, 1230w, 1209m 1190w, 1182m, 1163vs, 1122w, 1105w, 1090m, 1049vs, 1032w, 1003s 968w, 955w, 941w, 914w, 897w, 877w, 866w, 845w, 823m, 814m 783m, 771m, 742w, 658w, 634m, 621w 577w, 561m, 534w, 524w, 497w, 451w, 436w 337w, 308w, 287m, 247w, 206w, 162m, 129m (1) vs = very strong, s = strong, m = medium, w = weak, vw = very weak EXAMPLE 18 About 3 mg of Form K were transferred into a standard aluminium TA-Instrument sample pan. The sample pan was closed with the appropriate cover and the DSC curve recorded on a TA-Instruments Q1000 MTDSC equipped with a RCS cooling unit, at the following conditions: initial temperature: 25° C. heating rate: 10° C./min final temperature: 200° C. nitrogen flow: 50 ml/min The DSC curve as depicted in FIG. 23, shows the melting with decomposition of a crystalline product. The melting of Form K occurs at 158.4° C. Due to the decomposition, the heat of fusion calculation can only be used to indicate the crystalline property of the product. EXAMPLE 19 Form K was transferred into an aluminum sample pan. The TG curve was recorded on a TA Instruments Hi-Res TGA 2950 thermogravimeter at the following conditions: initial temperature: room temperature heating rate: 20° C./min resolution factor: 4 final condition: 300° C. or <80[(w/w) %] The TG curve is exhibited in FIG. 24. The loss of weight of around 0.2% up to .60° C. was due to the evaporation of solvent. The loss of weight at temperatures above 140° C. was due to the evaporation and decomposition of the product. EXAMPLE 20 Adsorption-Desorption About 21 mg of Form K were transferred into a VTI vapor sorption analyzer model SGA100 and the weight change with respect to the atmospheric humidity was recorded at the following conditions: drying temperature: 40° C. equilibrium: <0.05% in 5 min. or 60 min. data interval: 0.05% or 2.0 min. temperature: 25° C. first cycle RH (%) adsorption: 5,10,20,30,40,50,60,70,80,90,95 RH (%) desorption: 95,90,80,70,60,50,40,30,20,10,5 second cycle RH (%) adsorption: 5,10,20,30,40,50,60,70,80,90,95 RH (%) desorption: 95,90,80,70,60,50,40,30,20,10,5 The Adsorption-Desorption isotherm is shown in FIG. 25. Form K is hygroscopic. At the initial drying step a loss of weight of 0.3% was registered, comparable to the TG result. Form K adsorbed up to 1.5% water at high relative humidity. The product dried completely during the desorption cycle. A different study of the adsorption and desorption of water by Form K at 25° C. at different conditions of relative humidity was investigated on an amount of about 18 mg of the mesylate solvate. The weight change as a function of relative humidity was registered. The result is displayed in FIG. 26. At the drying step about 0.6% weight loss is registered for Form K. The obtained dried product is slightly hygroscopic, it adsorbed up to 1.7% water at high relative humidity. The product dried completely during the desorption cycle. EXAMPLE 21 Aqueous solubilities of Form K were measured in solvents with different pH. An excess of the solute was equilibrated with the solvent at 20° C. for at least 48 hours. After removing the undissolved compound, the concentration in solution was determined using UV spectrometry. TABLE 24 Solubility Solvent (mg/100 ml solution) Water 19 (pH 3.3) Buffer pH 2 (citrate/HCl) 21 (pH 2.0) Buffer pH 3 (citrate/HCl) 12 (pH 3.0) Buffer pH 4 (citrate/HCl) 11 (pH 4.0) 0.01N HCl 24 (pH 2.0) 20% HPβCD in water 2100 (pH 1.6) EXAMPLE 22 The stability of the crystal structure of Form K batch 1 was studied after storage of the compound for a period of four weeks at room temperature (RT) under 75% relative humidity (RH), 50° C. and 40° C./75% RH. The stability of the crystal structure of Form K batch 2 was studied after storage of the compound for a period of four weeks at room temperature (RT) under <5%, 56% and 75% relative humidity (RH), 50° C. and 40° C./75% RH. The samples were analyzed with thermogravimetry (TG), differential scanning calorimetry (DSC) and infrared spectroscopy (IR). The results of the tests are reported in the following table. TABLE 25 TG DSC compound conditions <80° C. <125° C. IR Max (° C.) Extra (° C.) Appearance Form K 0 days 0.47 0.15 Ref 143.7 — slightly orange Batch 1 RT/75% RH 2.87 0.19 ≠Ref 146.6 64.3 slightly orange 50° C. 0.32 0.14 ˜Ref 140.6 45.6 orange 40° C./75% RH 1.48 3.71 — — — brown oil Form K 0 days 0.16 0.11 Ref 155.8 — slightly orange Batch 2 RT/<5% RH 0.00 0.03 ˜Ref 156.9 — slightly orange RT/56% RH 0.27 0.03 ±Ref 154.6 — slightly orange RT/75% RH 1.82 0.07 ≠Ref 149.2 67.0 slightly orange 50° C. 0.12 0.12 ˜Ref 156.8 — slightly orange 40° C./75% RH 3.26 3.08 — — — brown oil ˜Ref: identical with reference ±Ref: similar with reference ≠Ref: different with reference EXAMPLE 23 In the chemical stability test program Form K batch 1 was stored for a period of 1 and 4 weeks under different conditions. These conditions were 40° C./75% RH, 50° C., RT/75% RH and 0.3da ICH light. Form K batch 2 was also stored for a period of 1 and 4 weeks under different conditions. These conditions were 40° C./75% RH, 50° C., RT/<5% RH, RT/56% RH, RT/75% RH and 0.3da ICH light. The compound was analysed after storage by HPLC and by visual inspection. The HPLC method used in this study was HPLC method 909. The results of the tests are reported in the following table. TABLE 26 HPLC Sum of impurities appearance compound conditions 1 week 4 weeks 1 week 4 weeks Form K batch 1 Reference 3.57 — slightly-orange — 0.3 da ICH light 2.93 — slightly-orange — 40° C./75% RH 5.36 >90* slightly-orange brown oil 50° C. 3.99 27.53 slightly-orange orange RT/75% RH — 3.61 — slightly-orange Form K Batch 2 Reference 1.50 — slightly-orange — 0.3 da ICH light 1.17 — slightly-orange — 40° C./75% RH 1.75 >85* slightly-orange brown oil 50° C. 1.46 1.25 slightly-orange slightly-orange RT/<5% RH — 1.58 — slightly-orange RT/56% RH — 1.45 — slightly-orange RT/75% RH — 1.46 — slightly-orange EXAMPLE 24 A randomized, placebo-controlled, double-blind, multiple dose escalation trial was performed to examine the safety, tolerability and pharmacokinetics of Form A after oral administration twice or three times daily, in healthy subjects. Four dosages of Form A (400 mg b.i.d., 800 mg b.i.d., 800 mg t.i.d., and 1200 mg t.i.d.) were tested in 4 panels of 9 healthy subjects. Within each panel, 6 subjects were treated with Form A and 3 subjects with placebo for 13 days with a single intake in the morning of day 14. (b.i.d.=twice daily, t.i.d.=three times daily). Form A was readily absorbed and concentration-time profiles of Form A after repeated dosing were dependent on the dose administered. Steady-state plasma concentrations were reached generally within 3 days, although C0h (conc. at administration time) and AUC24h (area under de curve or bioavailability) slightly decreased over time at all dose levels. AUC24h and Css,av (conc. at average steady-state) were dose-proportional (daily dose) at 400 mg b.i.d., 800 mg t.i.d. and 1200 mg t.i.d., but was more than dose-proportional at 800 mg b.i.d. Cmax (maximum conc.) was dose-proportional with respect to dose per intake. Less than 2% of unchanged Form A was excreted in the urine at all dose levels.
<SOH> BACKGROUND OF THE INVENTION <EOH>Virus-encoded proteases, which are essential for viral replication, are required for the processing of viral protein precursors. Interference with the processing of protein precursors inhibits the formation of infectious virions. Accordingly, inhibitors of viral proteases may be used to prevent or treat chronic and acute viral infections. (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate has HIV protease inhibitory activity and is particularly well suited for inhibiting HIV-1 and HIV-2 viruses. The structure of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-phenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate, is shown below: Compound of formula (X) and processes for its preparation are disclosed in EP 715618, WO 99/67417, U.S. Pat. No. 6,248,775, and in Bioorganic and Chemistry Letters, Vol. 8, pp. 687-690, 1998, “Potent HIV protease inhibitors incorporating high-affinity P 2 -igands and (R)-(hydroxyethylamino)sulfonamide isostere”, all of which are incorporated herein by reference. Drugs utilized in the preparation of pharmaceutical formulations for commercial use must meet certain standards, including GMP (Good Manufacturing Practices) and ICH (International Conference on Harmonization) guidelines. Such standards include technical requirements that encompass a heterogeneous and wide range of physical, chemical and pharmaceutical parameters. It is this variety of parameters to consider, which make pharmaceutical formulations a complex technical discipline. For instance, and as example, a drug utilized for the preparation of pharmaceutical formulations should meet an acceptable purity. There are established guidelines that define the limits and qualification of impurities in new drug substances produced by chemical synthesis, i.e. actual and potential impurities most likely to arise during the synthesis, purification, and storage of the new drug substance. Guidelines are instituted for the amount of allowed degradation products of the drug substance, or reaction products of the drug substance with an excipient and/or immediate container/closure system. Stability is also a parameter considered in creating pharmaceutical formulations. A good stability will ensure that the desired chemical integrity of drug substances is maintained during the shelf-life of the pharmaceutical formulation, which is the time frame over which a product can be relied upon to retain its quality characteristics when stored under expected or directed storage conditions. During this period the drug may be administered with little or no risk, as the presence of potentially dangerous degradation products does not pose prejudicial consequences to the health of the receiver, nor the lower content of the active ingredient could cause under-medication. Different factors, such as light radiation, temperature, oxygen, humidity, pH sensitivity in solutions, may influence stability and may determine shelf-life and storage conditions. Bioavailability is also a parameter to consider in drug delivery design of pharmaceutically acceptable formulations. Bioavailability is concerned with the quantity and rate at which the intact form of a particular drug appears in the systemic circulation following administration of the drug. The bioavailability exhibited by a drug is thus of relevance in determining whether a therapeutically effective concentration is achieved at the site(s) of action of the drug. Physico-chemical factors and the pharmaco-technical formulation can have repercussions in the bioavailability of the drug. As such, several properties of the drug such as dissociation constant, dissolution rate, solubility, polymorphic form, particle size, are to be considered when improving the bioavailability. It is also relevant to establish that the selected pharmaceutical formulation is capable of manufacture, more suitably, of large-scale manufacture. In view of the various and many technical requirements, and its influencing parameters, it is not obvious to foresee which pharmaceutical formulations will be acceptable. As such, it was unexpectedly found that certain modifications of the solid state of compound of formula (X) positively influenced its applicability in pharmaceutical formulations.
<SOH> SUMMARY OF THE INVENTION <EOH>Present invention concerns pseudopolymorphic forms of compound of formula (X) for the preparation of pharmaceutical formulations. Such pseudopolymorphic forms contribute to pharmaceutical formulations in improved stability and bioavailability. They can be manufactured in sufficient high purity to be acceptable for pharmaceutical use, more particularly in the manufacture of a medicament for inhibiting HIV protease activity in mammals. In a first aspect, the present invention provides pseudopolymorphs of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate. Pseudopolymorphs provided include alcohol solvates, more in particular, C1-C4 alcohol solvates; hydrate solvates; alkane solvates, more in particular, C1-C4 chloroalkane solvates; ketone solvates, more in particular, C1-C5 ketone solvates; ether solvates, more in particular, C1-C4 ether solvates; cycloether solvates; ester solvates, more in particular, C1-C5 ester solvates; and sulfonic solvates, more in particular, C1-4 sulfonic solvates, of the compound of formula (X). Preferred pseudopolymorphs are pharmaceutically acceptable solvates, such as hydrate and ethanolate. Particular pseudopolymorphs are Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-methoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate) of compound of formula (X). Another particular pseudopolymorph is Form K (mesylate) of compound of formula (X). In a second aspect, present invention relates to processes for preparing pseudopolymorphs. Pseudopolymorphs of compound of formula (X) are prepared by combining compound of formula (X) with an organic solvent, water, or mixtures of water and water miscible organic solvents, and applying any suitable technique to induce crystallization, to obtain the desired pseudopolymorphs. In a third aspect, the invention relates to the use of the present pseudopolymorphs, in the manufacture of pharmaceutical formulations for inhibiting HIV protease activity in mammals. In relation to the therapeutic field, a preferred embodiment of this invention relates to the use of pharmaceutically acceptable pseudopolymorphic forms of compound of formula (X) for the treatment of an HIV viral disease in a mammal in need thereof, which method comprises administering to said mammal an effective amount of a pharmaceutically acceptable pseudopolymorphic form of compound of formula (X). The following drawings provide additional information on the characteristics of the pseudopolymorphs according to present invention.
20041112
20100420
20051110
99703.0
12
CHANG, CELIA C
PSEUDOPOLYMORPHIC FORMS OF A HIV PROTEASE INHIBITOR
UNDISCOUNTED
0
ACCEPTED
2,004
10,514,601
ACCEPTED
Grinder
A grinder is disclosed which has a housing (12) in which a rotatable disc (60) is mounted. The disc (60) is rotated by a motor (40)and the disc (60) has a periphery which is adjacent an inner stationary wall (102) of the housing (12 ). An air inlet (108) is arranged below the disc and the disc carries vanes (100) so that when the disc rotates, an annular air stream is created at the periphery of the disc in which a grinding zone is established between the periphery of the disc and the stationary wall (102) for grinding material into small particles. The grinding zone includes an annular flow of heavy gas R1. A material inlet (20) is provided for allowing material to enter the housing (12). Large material is grounded by energy intensification after it hits the disc (60) and collides with the inner wall (40) of the housing so as to break down the material into smaller particle size, which can then move to the grinding zone at the periphery of the disc (60) to be further ground into small particles. The small particles are collected through an outlet (16) and may be supplied to separators for separating the small particles from exhaust air from the housing (12).
1. An impact particle grinder, including; a housing having an inner wall; a grinding disc mounted in the housing for rotation within the housing; means for rotating the grinding disc; an inlet for depositing material onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and outlet means for discharge of the small particles from the grinder. 2. The grinder of claim 1 wherein the inner wall of the housing is of inverted conical shape so that deflection of material from the inner wall tends to direct the material to the second location which is a small distance from the first location, thereby producing a significant number of impacts of the material with the disc as the material bounces between the disc and the inner wall. 3. The grinder of claim 1 wherein the grinder includes hot air inlet means for introducing hot air into the housing adjacent the disc for drying the material as the material is ground. 4. The grinder of claim 1 wherein the grinder also includes inert gas introduction means for introducing inert gas to mix with the ground particles. 5. The grinder of claim 1 wherein the outlet means is arranged above the disc. 6. The grinder of claim 1 wherein the outlet means comprises a plurality of outlets which are arranged at different heights above the disc so that particles of different sizes are collected in each of the outlets, the outlets being provided in a housing wall portion which is of conical shape. 7. The grinder of claim 1 wherein the outlet means may include a recirculator for recirculating small particles from the outlet means back to the housing for reprocessing in the housing. 8. The grinder of claim 1 wherein the outlet means is connected to a cyclone particle collector. 9. The grinder of claim 8 wherein the cyclone particle collector comprises means for creating a circular flow of air in the cyclone, inlet means connected to the outlet means for receiving particles from the housing and for conveying the particles into the cyclone for circulation in the circular air flow in the cyclone, an air outlet tube in the cyclone and a particle outlet in the cyclone, and wherein particles trapped in the circular flow of air are conveyed about the cyclone with the circular flow of air and separated from air flow so that the particles can be collected in the particle outlet and air exit the cyclone through the air outlet. 10. The grinder of claim 9 wherein the air inlet means for creating the circular flow of air comprises a hot air inlet and a heater for heating air for supply to the hot air inlet. 11. The grinder of claim 1 wherein the disc has an outer periphery which is in close proximity to the inner wall of the housing so that when the disc is rotated by the rotating means, an annular rotating stream of air is formed between the periphery of the disc and the inner wall, so a heavy gas region is created between the periphery of the disc and the inner wall so that when particles enter the space between the disc and the inner wall, they contact the heavy gas in the region to further comminute the particles to smaller particle sizes. 12. The grinder of claim 11 wherein an air inlet means is provided below the disc in the housing for allowing air to enter the housing from below the disc to cause the air annulus to spill up the inner wall of the housing so that ground particles trapped in the rotating stream of air are carried by the spill of air to the outlet means. 13. The grinder of claim 1 wherein the disc includes a plurality of vanes for imparting momentum to the air when the disc rotates to create the annular rotating stream of air between the periphery of the disc and the wall, said vanes having an arcuate shape for directing air in the same direction as intended rotation of the disc for accelerating gas particles from an inner peripheral portion of the vanes to the periphery of the disc to create sufficient acceleration to enable the gas to exit the vanes in the direction of rotation of the disc without producing any substantial turbulence. 14. The grinder of claim 13 wherein the vanes are angled upwardly relative to the horizontal so that the rotating stream of air is directed upwardly above the disc to facilitate the spill of air up the inner wall. 15. The grinder of claim 1 wherein the inner wall of the housing includes a separate cylindrical wall which includes a contoured wall portion for trapping material so the material remains in the annular airflow for a long period to break down the material to smaller particle sizes, before the smaller particles travel in the spill of air up the inner wall to the outlet. 16. A method of impact grinding a material, comprising; supplying the material to a grinder which has a housing having an inner wall and a rotating disc mounted in the housing; wherein the material supplied is deposited onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and collecting the small particles from the grinder. 17. A grinder for producing small particles from material, comprising: a housing having a substantially inner wall; a disc mounted in the housing and having a periphery adjacent the inner wall; a motor for driving the disc so the disc rotates about a substantially vertical axis; a plurality of vanes on the disc for creating an annular flow of gas between the periphery of the disc and the inner wall to create a grinding zone between the inner wall and the periphery of the disc; an inlet in the housing for receiving the particulate material, so the particulate material is able to migrate to the grinding zone between the periphery of the disc and the inner wall and be broken down to small particles; and a small particles outlet for allowing outlet of the small particles from the housing. 18. The grinder of claim 17 wherein the inlet comprises an inlet tube extending within the housing from an upper portion of the housing to a position adjacent the periphery of the disc. 19. The grinder of claim 17 wherein the housing has a gas inlet below the disc and the vanes are located on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed, said vanes having an arcuate shape for directing air in the same direction as intended rotation of the disc for accelerating gas particles from an inner peripheral portion of the vanes to the periphery of the disc to create sufficient acceleration to enable the gas to exit the vanes in the direction of rotation of the disc without producing any substantial turbulence. 20. The grinder of claim 17 wherein the grinding zone comprises a first region between the wall of the housing and an intermediate location between the wall and the periphery of the disc for establishing a heavy gas, and a second region between the periphery of the disc and the intermediate location for receiving particles from the disc so those particles can move into the heavy gas and be ground into small particles. 21. The grinder of claim 20 wherein a sheer zone is created at the intermediate location between the first and second regions. 22. The grinder of claim 17 wherein the vanes are located on the lower surface of the disc and are directed upwardly so that the vanes direct the gas to the periphery of the disc and upwardly relative to the disc so that the annular flow of gas created by each of the vanes between the disc and the inner wall, and within the confines of the disc for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing. 23. The grinder of claim 17 wherein the housing has an exhaust gas outlet arranged substantially centrally of the disc. 24. The grinder of claim 18 wherein a standing wave is created between the exhaust gas outlet and the periphery of the disc so that particles which are broken down into smaller particles in the grinding zone are able to move upwardly with the airflow adjacent the inner wall of the housing to the outlet, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc and move along the upper surface of the disc back to the grinding zone for further grinding, or travel with the exhaust gas to the exhaust outlet. 25. The grinder of claim 17 wherein the outlet is connected to a first cyclone for separating gas from the small particles so the small particles can be collected at an outlet of the first cyclone. 26. The grinder of claim 23 wherein the exhaust gas outlet is connected to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. 27. The grinder of claim 25 wherein the first cyclone has a gas exhaust outlet which is connected to the second cyclone so that any small particles which remain in the gas exhausted from the first cyclone are fed to the second cyclone for separation from the gas in the second cyclone. 28. The grinder of claim 27 wherein the outlet from the first cyclone includes a gas lock for preventing high pressure gas from exiting the outlet and blowing small particles into the atmosphere. 29. The grinder of claim 27 wherein the outlet from the second cyclone also includes a gas lock for preventing high pressure gas from exiting the second cyclone through the outlet. 30. A method of producing small particles from material, comprising: supplying the material to a housing having a substantially inner wall and a rotating disc mounted in the housing and having a periphery adjacent the inner wall so that the disc creates an annular flow of gas between the periphery of the disc and the inner wall to create a grinding zone between the inner wall and the periphery of the disc; allowing the material to migrate to the grinding zone between the periphery of the disc and the inner wall and be broken down to small particles; and collecting the small particles from the housing. 31. The method of claim 30 wherein the method includes allowing the gas to enter the housing from below the disc and providing vanes on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed, and wherein the grinding zone is created by the establishment of: (a) a heavy gas formed from a mixture of the gas and minute particles in a first region between the inner wall and an intermediate position between the disc and the inner wall; (b) a second region for receiving larger particles to be ground into the smaller particles, between the intermediate position and the periphery of the disc; (c) a sheer zone between the first and second regions; and wherein particles in the first region pass through the sheer zone, and some are comminuted into heavy gas particles and others which are not sufficiently small to behave as gas particles are either ejected back to the first region for further grinding as those particles re-enter the heavy gas through the sheer zone, or move out of the grinding zone for collection from the housing. 32. The method of claim 31 wherein the annular flow of gas created by each of the vanes between the disc and the inner wall is maintained within the confines of the disc and at the grinding zone for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing for collection from the housing. 33. The method of claim 31 wherein the method also comprises extracting gas from an exhaust outlet arranged substantially centrally of the disc. 34. The method of claim 33 wherein the method further comprises creating a standing wave in the gas above the disc between the exhaust outlet and the periphery of the disc so that particles which are broken down into smaller particles in the grinding zone move upwardly with the airflow adjacent the inner wall of the housing for collection from the housing, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc and then move along the upper surface of the disc back to the grinding zone for further grinding, or travel with the exhaust gas to the exhaust outlet. 35. The method of claim 30 wherein the method further comprises supplying the collected small particles to a first cyclone for separating gas from the particles so the particles can be collected at an outlet of the first cyclone. 36. The method of claim 33 wherein small particles collected at the exhaust outlet are supplied to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. 37. A grinder for producing small particles from material, comprising: a housing having an inner wall; a rotatable mechanical member in the housing having a periphery adjacent the inner wall; a drive for driving the rotatable member for causing the rotatable member to create an annular flow of air between the periphery of the member and the inner wall, and for establishing a grinding zone between the inner periphery and the wall which comprises: (a) a first region in which a heavy gas is established, the first region being between the inner wall and an intermediate position between the periphery of the member and the inner wall; (b) a second region for receiving relatively large particles compared to the particles which make up the heavy gas, the second region being between the intermediate position and the periphery of the mechanical member; and (c) a sheer zone between the first and second regions at the intermediate location; and wherein the relatively large particles received in the first region come into contact with the heavy gas particles across the sheer zone where the relatively heavy particles are comminuted into smaller particles, some of which add to the heavy gas within the first region and the other of which form small particles of a size which do not behave as a heavy gas, and wherein the small particles, together with some of the particles which make up the heavy gas and other larger particles from the first region move out of the grinding zone with an annular flow of air from the grinding zone and travel to a first collection outlet for collection or fall back to the mechanical member and again travel to the first region for further grinding in the grinding zone. 38. The grinder of claim 37 wherein the rotatable member comprises a disc having vanes for creating the annular flow of air between the periphery of the disc and the inner wall, said vanes having an arcuate shape for directing air in the same direction as intended rotation of the disc for accelerating gas particles from an inner peripheral portion of the vanes to the periphery of the disc to create sufficient acceleration to enable the gas to exit the vanes in the direction of rotation of the disc without producing any substantial turbulence. 39. The grinder of claim 38 wherein the housing has an exhaust gas outlet for exhausting air from the housing in which some fines are entrained. 40. The grinder of claim 38 having a separator connected to the first outlet for separating small particles and air collected from the first outlet. 41. The grinder according to claim 39 wherein the exhaust outlet is connected to a second separator for separating small particles collected at the exhaust outlet from exhaust air exhausted through the exhaust outlet. 42. A method of grinding material, comprising: creating a grinding zone having a first annular region in which an annular flow of heavy gas is established and a second region spaced from the first region by a shear zone; directing the material into the grinding zone so the material passes from the second region to the first region across the shear zone into the annular flow of heavy gas and is comminuted into smaller particles by contact between heavy gas particles in the heavy gas and the material; and collecting the comminuted particles. 43. The method according to claim 42 wherein the grinding zone comprises a second annular region arranged radially inwardly with respect to the first region in which the material can locate for movement into the heavy gas in the first region for comminution whilst in the heavy gas so that the comminution creates further heavy gas particles to maintain the annular flow of heavy gas within the first region, as well as the small particles which move out of the grinding region for collection. 44. The method according to claim 43 wherein some of the small particles which move out of the first region, together with some particles of material from the first region circulate within the housing and move back into the grinding zone for further grinding before those ground particles are collected from the housing. 45. The method according to claim 42 wherein the heavy gas is established by the initial supply of material to the housing and the breakdown of that material within the housing to minute particles which form the heavy gas in the first region. 46. The method according to claim 42 wherein the heavy gas is established by supply of minute particles separate to the material to be ground. 47. The method according to claim 44 wherein the grinding zone is established by a rotatable disc arranged within the housing which has a periphery spaced from an inner wall of the housing and wherein the grinding zone is formed from the first region containing the heavy gas at a location between the wall of the housing and an intermediate location between the wall and the periphery of the disc, the second region is established between the intermediate position and the periphery of the disc, and the sheer zone is established at the intermediate position between the first and second regions. 48. The method according to claim 47 wherein the grinding zone includes a third region between the inner wall of the disc and the first region, and a sheer zone at the boundary between the first region and the third region. 49. A grinder for producing small particles comprising: a first region for establishing a heavy gas, a second region spaced from the first region and a shear zone between the first and second regions when the grinder is in use; a material inlet for delivery material so the material passes to the first region for grinding; and an outlet for collecting the small particles. 50. The grinder of claim 49 wherein the region is an annular region, and an air flow producer is provided for producing an annular flow of air in the region for. establishing and maintaining a coherent and stable annular heavy gas region. 51. A grinding installation for producing small particles from material, comprising a grinder having: (a) a housing having a stationary inner wall; (b) a disc mounted in the housing and having a periphery adjacent the inner wall; (c) a motor for driving the disc so the disc rotates about a substantially vertical axis, and whereby small particles are produced by breakdown of material impacting with the disc and the inner wall and/or in a grinding zone between the periphery of the disc and the inner wall; (d) an air inlet in the housing; (e) an air exhaust outlet from the housing; and (f) a particle outlet from the housing; a first separator connected to the particle outlet for separating air from the small particles and for delivering the small particles to a small particles outlet; and a second separator connected to the exhaust air outlet for separating small particles in the exhaust air from the exhaust air and delivering the small particles to a second small particles outlet. 52. The installation of claim 51 wherein the first separator has a first exhaust air outlet and the first exhaust air outlet is connected to the second separator. 53. The installation of claim 51 wherein the first separator comprises a cyclone separator. 54. The installation of claim 51 wherein the second separator comprises a second cyclone separator.
FIELD OF THE INVENTION This invention relates to a grinder for reducing material to small particles which can then be used, for example, as a fuel, fertiliser, or an additive to other constituents, broken down small size particles for convenient waste disposal, providing particles for use in industry, and also for separating material. In many cases, it is necessary for the small particles to be reduced down to small particles which have a size in the range of 5 to 50 microns and in some cases, less than 5 microns. BACKGROUND ART Many devices exist that can reduce material to small particle sizes, but most are large, slow, heavy, and consume large amounts of energy. However, very few machines exist which can economically reduce particles down to very small fine particle sizes. Grinding of materials to very small particles is carried out by a variety of machines. These machines employ two main processes. The first and most common, is by crushing the material between hard moving elements made from such materials as steel or silicates until the particles are of the required size. Repeated recycling may be employed to aid the process. Such machines are rolling, ball or hammer mills. The second method is by employing high-energy impact. Machines using this principle cause high speed, hard moving elements, to collide with the particles to be ground. The particles to be ground are usually transported into and out of the impact area by gravity and by a gas, usually air. In some cases, material to be ground is carried only by gravity into the impact zone in the same way. As well as collisions with the grinding element, there are particle to particle collisions. However, these impacts make only a very small contribution because the particles are of much the same kinetic level and are moving in much the same direction. To achieve significant particle size reduction, recycling of the process must also be employed. A beater hammer mill is typical of such machines. The crushing process is slow and usually limited in the mining and primary metallurgy industry. Impact grinding has the potential for fast throughput and great size reduction for other industrial and commercial particle grinding. The problem with present impact machines is that particle to particle impacts make only a small contribution, and hence the necessary energy level from the momentum transfer from the impacting elements must be at the highest energy necessary to break up the particles, that is the energy levels of the particles remain only as high as the initial impact. A need therefore exists for a small, even portable machine that can achieve these results fast and economically. SUMMARY OF THE INVENTION An object of a first invention is to provide an impact particle grinder which can reduce gross particles down to a much smaller particle size. A first invention may be said to reside in an impact particle grinder, comprising; a housing having an inner wall; a grinding disc mounted in the housing for rotation within the housing; means for rotating the grinding disc; an inlet for depositing material onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and outlet means for discharge of the small particles from the grinder. Thus, the impact grinder works using two principles. The first is by repeatedly injecting energy at higher and higher levels into the particles as they are reduced in size. This is a continuous energy intensifying process. The grinder therefore processes material step by step to higher energy levels as it impacts further out towards the periphery of the disc. This results in very great size reduction. Recycling therefore is only employed by the machine to act upon particles, which have not reached the requisite energy level by the time they impact with a radially most outward part of the disc. Depending on the size of the particle required, the particles can simply be discharged from the machine. However, if very fine particles are required, the particles can undergo further processing to reduce the particles to fines. In the preferred embodiment of the invention, the additional grinding to produce the small particles is performed in the grinder by establishing a further grinding zone between the periphery of the spinning disc and a stationary wall of the grinder. This embodiment requires the invention to operate in a gas rather than a vacuum, with the gas usually simply being air. While operating in a transport medium such as air, each particle will, as it moves to the periphery and into the grinding zone. The grounding zone is formed by a sheer zone which causes comminution of the particles to form the small particles. In the preferred embodiment of the invention, the inner wall of the housing is of inverted conical shape so that deflection of material from the inner wall tends to direct the material to the second location which is a small distance from the first location, thereby producing a significant number of impacts of the material with the disc as the material bounces between the disc and the inner wall. The result of this increased number of collisions produces a greater number of impacts which impart increased kinetic energy to the material, and therefore greater breakdown of the material due to those impacts and particle to particle collisions. In one embodiment of the invention the grinder includes hot air inlet means for introducing hot air into the housing adjacent the disc for drying the material as the material is ground. In one embodiment the grinder also includes inert gas introduction means for introducing inert gas to mix with the ground particles. In one embodiment of the invention the outlet means is arranged above the disc. In one embodiment, the outlet means comprises a plurality of outlets which are arranged at different heights above the disc so that particles of different sizes are collected in each of the outlets, the outlets being provided in a housing wall portion which is of conical shape. The outlet means may include a recirculator for recirculating small particles from the outlet means back to the housing for reprocessing in the housing. In one embodiment, the outlet means is connected to a cyclone particle collector. Preferably the cyclone particle collector comprises means for creating a circular flow of air in the cyclone, inlet means connected to the outlet means for receiving particles from the housing and for conveying the particles into the cyclone for circulation in the circular air flow in the cyclone, an air outlet tube in the cyclone and a particle outlet in the cyclone, and wherein particles trapped in the circular flow of air are conveyed about the cyclone with the circular flow of air and separated from air flow so that the particles can be collected in the particle outlet and air exit the cyclone through the air outlet. Preferably the air inlet means for creating the circular flow of air comprises a hot air inlet and a heater for heating air for supply to the hot air inlet. In one embodiment of the invention, the disc has an outer periphery which is in close proximity to the inner wall of the housing so that when the disc is rotated by the rotating means, an annular rotating stream of air is formed between the periphery of the disc and the inner wall, so a sheer zone is created between the periphery of the disc and the inner wall so that when particles enter the space between the disc and the inner wall, they are subject to the shear zone to further reduce the particles to small particles. An air inlet means is preferably provided below the disc in the housing for allowing air to enter the housing from below the disc to cause the air annulus to spill up the inner wall of the housing so that finely ground particles trapped in the rotating stream of air are carried by the spill of air to the outlet means. In another embodiment of the invention, the outlet means is arranged below the disc. This embodiment would be used in environments in which the grinder is operating in a vacuum or extremely low air pressure environments, and in which the air stream at the periphery of the disc is therefore not created. Thus, in this embodiment, small particles have no option but to fall under the influence of gravity in the space between the periphery of the disc and the inner wall of the container to the outlet means below the disc. In one embodiment the disc includes a plurality of vanes for imparting momentum to the air when the disc rotates to create the annular rotating stream of air between the periphery of the disc and the wall to create the sheer zone. Preferably the vanes are angled upwardly relative to the horizontal so that the rotating stream of air is directed upwardly above the disc to facilitate the spill of air up the inner wall. Preferably the inner wall of the housing includes a separate cylindrical wall which includes a contoured wall portion for trapping material so the material remains in the annular airflow for a long period to break down the material to small particles, before the small particles travel in the spill of air up the inner wall to the outlet. This invention also provides a method of impact grinding a material, comprising; supplying the material to a grinder which has a housing having an inner wall and a rotating disc mounted in the housing; wherein the material supplied is deposited onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and collecting the small particles from the grinder. A second invention is concerned with the breakdown of material into smaller particles. This invention provides a grinder for producing small particles from material, comprising: a housing having a substantially inner wall; a disc mounted in the housing and having a periphery adjacent the inner wall; a motor for driving the disc so the disc rotates about a substantially vertical axis; a plurality of vanes on the disc for creating an annular flow of gas between the periphery of the disc and the inner wall to create a sheer zone between the inner wall and the periphery of the disc; an inlet in the housing for receiving the particulate material, so the particulate material is able to migrate to the sheer zone between the periphery of the disc and the inner wall and be broken down to small particles; and a small particle outlet for allowing outlet of the small particles from the housing. In this invention the particulate material may be delivered to the housing from an inlet direct to a location near the periphery of the disc for substantially direct feeding into the sheer zone. Thus, in this embodiment the inlet may comprise an inlet tube extending within the housing from an upper portion of the housing to a position adjacent the periphery of the disc. However, in another embodiment, the particulate material may be gross material which is first broken down by impact with the disc and the housing into small particle size which small particles then move to the sheer zone for further breakdown into small particles. In this latter embodiment the inlet generally comprises a tube which delivers the gross particulate material to a location inwardly of the periphery of the disc. Preferably the housing has a gas inlet below the disc and the vanes are located on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed. Preferably the grinding zone comprises a first region between the wall of the housing and an intermediate location between the wall and the periphery of the disc for establishing a heavy gas, and a second region between the periphery of the disc and the intermediate location for receiving particles from the disc so those particles can move into the heavy gas and be ground into small particles. Preferably a sheer zone is created at the intermediate location between the first and second regions. Preferably the vanes are located on the lower surface of the disc and are directed upwardly so that the vanes direct the gas to the periphery of the disc and upwardly relative to the disc so that the annular flow of gas created by each of the vanes between the disc and the inner wall, and within the confines of the disc for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing. Preferably the housing has an exhaust gas outlet arranged substantially centrally of the disc. Preferably a standing wave is created between the exhaust gas outlet and the periphery of the disc so that particles which are broken down into small particles in the sheer zone are able to move upwardly with the airflow adjacent the inner wall of the housing to the outlet, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc and move along the upper surface of the disc back to the sheer zone for further grinding, or travel with the exhaust gas to the exhaust outlet. Preferably the outlet is connected to a first cyclone for separating gas from the small particles so the small particles can be collected at an outlet of the first cyclone. Preferably the exhaust gas outlet is connected to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. Preferably the first cyclone has a gas exhaust outlet which is connected to the second cyclone so that any small particles which remain in the gas exhausted from the first cyclone are fed to the second cyclone for separation from the gas in the second cyclone. Preferably the outlet from the first cyclone includes a gas lock for preventing high pressure gas from exiting the outlet and blowing small particles into the atmosphere. Preferably the outlet from the second cyclone also includes a gas lock for preventing high pressure gas from exiting the second cyclone through the outlet. This invention also provides a method of producing small particles from material, comprising: supplying the material to a housing having a substantially inner wall and a rotating disc mounted in the housing and having a periphery adjacent the inner wall so that the disc creates an annular flow of gas between the periphery of the disc and the inner wall to create a sheer zone between the inner wall and the periphery of the disc; allowing the material to migrate to the sheer zone between the periphery of the disc and the inner wall and be broken down to small particles; and collecting the small particles from the housing. Preferably the method includes allowing the gas to enter the housing from below the disc and providing vanes on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed, and wherein the grinding zone is created by the establishment of: (a) a heavy gas formed from a mixture of the gas and minute particles in a first region between the inner wall and an intermediate position between the disc and the inner wall; (b) a second region for receiving larger particles to be ground into the smaller particles, between the intermediate position and the periphery of the disc; (c) a sheer zone between the first and second regions; and wherein particles in the first region pass through the sheer zone, and some are comminuted into heavy gas particles and others which are not sufficiently small to behave as gas particles are either ejected back to the first region for further grinding as those particles re-enter the heavy gas through the sheer zone, or move out of the grinding zone for collection from the housing. Preferably the annular flow of gas created by each of the vanes between the disc and the inner wall is maintained within the confines of the disc and at the sheer zone for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing. Preferably the method comprises extracting gas from an exhaust outlet arranged substantially centrally of the disc. Preferably the method further comprises creating a standing wave between the exhaust outlet and the periphery of the disc so that particles which are broken down into small particles in the sheer zone move upwardly with the airflow adjacent the inner wall of the housing to the outlet, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc, and move along the upper surface of the disc back to the sheer zone for further grinding, or travel with the exhaust gas to the exhaust outlet. Preferably the method further comprises supplying the collected small particles to a first cyclone for separating gas from the small particles so the small particles can be collected at an outlet of the first cyclone. Preferably small particles collected at the exhaust outlet are supplied to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. The invention also provides a grinder for producing small particles from material, comprising: a housing having an inner wall; a rotatable mechanical member in the housing having a periphery adjacent the inner wall; a drive for driving the rotatable member for causing the rotatable member to create an annular flow of air between the periphery of the member and the inner wall, and for establishing a grinding zone between the inner periphery and the wall which comprises: (a) a first region in which a heavy gas is established, the first region being between the inner wall and an intermediate position between the periphery of the member and the inner wall; (b) a second region for receiving relatively large particles compared to the particles which make up the heavy gas, the second region being between the intermediate position and the periphery of the mechanical member; and (c) a sheer zone between the first and second regions at the intermediate location; and wherein the relatively large particles received in the first region come into contact with the heavy gas particles across the sheer zone where the relatively heavy particles are comminuted into smaller particles, some of which add to the heavy gas within the first region and the other of which form small particles of a size which do not behave as a heavy gas, and wherein the small particles, together with some of the particles which make up the heavy gas and other larger particles from the first region move out of the grinding zone with an annular flow of air from the grinding zone and travel to a first collection outlet for collection or fall back to the mechanical member and again travel to the first region for further grinding in the grinding zone. The invention still further provides a method of grinding material, comprising: creating a grinding zone having a first annular region in which an annular flow of heavy gas is established and a second region spaced from the first region by a shear zone; directing the material into the grinding zone so the material passes from the second region to the first region across the shear zone into the annular flow of heavy gas and is comminuted into smaller particles by contact between heavy gas particles in the heavy gas and the material; and collecting the comminuted particles. A third invention relates to a grinding installation for grinding material into small particles. This invention provides a grinding installation for producing small particles from material, comprising a grinder having: (a) a housing having a stationary inner wall; (b) a disc mounted in the housing and having a periphery adjacent the inner wall; (c) a motor for driving the disc so the disc rotates about a substantially vertical axis, and whereby small particles are produced by breakdown of material impacting with the disc and the inner wall and/or in a grinding zone between the periphery of the disc and the inner wall; (d) an air inlet in the housing; (e) an air exhaust outlet from the housing; and (f) a particle outlet from the housing; a first separator connected to the particle outlet for separating air from the small particles and for delivering the small particles to a small particles outlet; and a second separator connected to the exhaust air outlet for separating small particles in the exhaust air from the exhaust air and delivering the small particles to a second small particles outlet. Preferably the first separator has a first exhaust air outlet and the first exhaust air outlet is connected to the second separator. Preferably the first separator comprises a cyclone separator. Preferably the second separator comprises a second cyclone separator. A fourth invention provides a grinder for producing small particles comprising: a first region for establishing a heavy gas, a second region spaced from the first region and a shear one between the first and second regions when the grinder is in use; a material inlet for delivery material so the material passes to the first region for grinding; and an outlet for collecting the small particles. BRIEF DESCRIPTION OF THE DRAWINGS Preferred embodiments of the invention will be described, by way of example, with reference to the accompanying drawings in which: FIG. 1 is a view of a particle grinder according to one embodiment of the invention; FIG. 2 is a cross-sectional view through the grinder housing of FIG. 1; FIG. 3 is a detailed view of part of the grinder housing of FIG. 2; FIG. 4 is a perspective view of a particle grinder according to another embodiment; and FIG. 5 is a cross-sectional view through the embodiment of FIG. 4. FIG. 6 is a schematic view showing particle breakdown and illustrates energy intensification during particle breakdown; FIG. 7 is a cross-sectional view through a cyclone collector shown in FIG. 1; and FIG. 8 is a view of a second embodiment of the invention; FIG. 9 is a detailed cross-sectional view of a grinding housing according to the embodiment of FIG. 8; FIG. 9A is an underneath view of a disc used in the preferred embodiments showing the configuration of vanes on the disc; FIG. 10 is a cross-sectional view through a first cyclone used in the embodiment of FIG. 8; FIG. 11 is a view of a second cyclone used in the embodiment of FIG. 8; FIGS. 12 and 13 show a gas lock used in the embodiment of FIG. 8; FIG. 14 is a schematic diagram showing pressure variation used to explain the manner in which the embodiments of FIGS. 1 to 7 and 8 to 13 operate; FIG. 15 is a diagram similar to FIG. 14 but showing speed differential; FIG. 16 is a schematic diagram illustrating the primary grinding zone of the preferred embodiments; FIG. 17 is a side view partly cut away to show operation of the preferred embodiment of the invention; FIG. 18 is a schematic diagram showing air stream tubes which are created during operation of the preferred embodiments of the invention; FIG. 19 is a graph showing experimental actual measured particle size distribution; FIG. 20 is a graph showing full particle distribution; FIG. 21 is a graph showing particle sizes of small particles collected from a small particles outlet from the grinder of the preferred embodiment; and FIG. 22 is a graph showing particle sizes of small particles collected in a second separator in the preferred embodiment of the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS With reference to FIG. 1, a grinder installation 10 is shown which has a grinder 11 having grinder housing 12, and a cyclone particle separator 14. The housing 12 communicates with the cyclone 14 by a small particles outlet tube 16 from the housing 12 and an air exhaust tube 18 extending from the housing 12 to the cyclone 14. An inlet tube 20 for supply of material also communicates with the housing 12. The cyclone 14 has a small particles outlet tube 22 and an air exhaust outlet tube 24. An air heater 26 is provided for heating air and for supplying hot air through delivery tube 28 to valve 30. A first inlet 32 is coupled between the valve 30 and the housing 12 for selectively supplying hot air to the housing 12, and a second inlet tube 34 extends between the valve 30 and the cyclone 14 for providing hot air into the cyclone 14 for creating a circular cyclonic flow of air within the cyclone 14. The housing 12 is supported on a cylindrical casing 36 and flange 38 which connects to an electric motor 39. As is best shown in FIG. 2, the housing 12 is formed from a conical upper casing 40 which tapers inwardly from flange 42 at the bottom of the casing 40 to upper flange 44 at the top of the casing 40. The flange 42 is connected to a lower dish casing 46 via flange 48. The casing 40 is connected to a cap casing 50 by flange 44 on the casing 40 and flange 52 on the casing 50. The particle outlet conduit 16 communicates with the cap casing 50. A disc 60 is mounted in the casing 46 and is supported on a shaft 62 which is arranged in bearings 66 and bushes 68 within the cylindrical casing 36. Thrust bearings 70 may also be provided if desired. The cylindrical casing 36 is secured to the base 47 of the dish casing 46 by flange 68a on the cylindrical casing 38. The flanges 44 and 52, the flanges 42 and 48 and the flange 70 and base 47 can be connected together by bolts 71, which are shown joining the flanges 44 and 52, as well as the flanges 42 and 48. If the grinder is to be used for the breakdown of soft or very light material, such as feathers or the like, a separate removable cylinder 74 may be located in the housing 12 as shown in FIGS. 1-3. The cylinder 74 has a recessed contoured wall portion 102 which forms a step 103 with inner wall portion 103a. The purpose of this configuration will be described in more detail hereinafter. The material inlet tube 20 is also used in situations where very soft or light material is to be ground. This tube 20 is also used if liquid or sludge type material is to be broken down by the grinder. In the case of light or soft material, the material can be directed through the tube 20 with an airflow injected into the tube 20 for carrying that material along the tube 20 to outlet end 80. As is shown in FIG. 2, the outlet end 80 terminates at a distance radially outward from the centre of the disc 50. The location of the end 80 is selected so that at that position of the disc, the kinetic energy which will be imparted to the material exiting the end 80 is such that the material will be bounced off the disc and will not merely stick to or sit on the disc. In the case of sludge or other liquid material, if the sludge or liquid material is deposited on a central portion of the disc, it is possible that the speed of rotation at that point will not be sufficient enough to impart sufficient kinetic energy to the disc to cause the material to be flung from the disc towards the wall 40. The material may well just stick to the disc or sit on the disc, and therefore not undergo breakdown. By directing the material to a radially outer part of the disc, the material will initially have sufficient kinetic energy imparted to it by the rotating disc to cause the material to bounce from the disc towards the wall 40 so that the collisions will occur which will break down the material. As is best shown in FIG. 3, the disc 60 comprises an upper plate 85 which is supported on flange 86 of the shaft 62. A lower plate 88 is arranged below the plate 85 and connected to the plate 85 by bolts or other suitable fasteners 90. The plate 85 has a bevelled lower surface 90 and the plate 88 has an outer peripheral part 92 which is angled with respect to the remainder of the plate 88 so as to be substantially parallel to the lower bevelled surface 90. A plurality of vanes 100 are provided between the surface 90 and the inclined part 92 of the lower plate 88. The inner wall 74 has a contoured wall portion 102 adjacent the periphery of the disc 60. When the disc 60 is rotated, the disc 60 creates an annular or a circular air flow adjacent the periphery of the disc 60 between the disc 60 and the wall 74. By angling the vanes 100 upwardly, as is shown in FIG. 3, the circular air flow is directed upwardly along inner wall of the casing 40 (or cylinder 74 if in place) to facilitate spill of the annular air flow up along the inner wall 40 towards the outlet, which in the embodiment of FIGS. 1 and 2 is formed by the pipe 16 in cap casing 50. The base 47 of the casing part 46 has a plurality of air inlet openings 108 which also facilitate spillage of air up along the inner wall 40. Air can enter the inlets 108 and is drawn by the low pressure environment at the periphery of the disc (as will be described in more detail hereinafter) so as to tend to push the annular air stream at the periphery of the disc upwardly along the wall 40. FIGS. 5 and 6 show a second embodiment of the invention in which like reference numerals indicate like paths to those previously described. Thus, the disc 60, casing 40, casing 46 and shaft 62 are exactly the same as previously described. The disc 60 also creates the annular air flow in the same manner as previously described. In this embodiment, the cap 50 is replaced by an upper conical casing 120 which carries a material inlet 122, which is arranged substantially centrally with respect to the disc 60. This embodiment is intended to be used to break down relatively large or heavy material (gross material) which is unlikely to stick or sit on the rotating disc 60 and therefore can be, and most desirable is, deposited generally centrally on the disc 60 rather than some distance radially outwardly of the disc 60 as in the case of the embodiment of FIGS. 1-3. The casing 120 has a plurality of outlet openings 124 and 126 which are formed in the conical wall of the casing 120. The outlet openings provide for separation of particles of different sizes carried by the air flow which spills up the inner surface of the casing 40 and then up the inner surface of the casing 120. This separation process will be described in more detail hereinafter. Also, in the embodiment of FIG. 5, the grinder may be used to separate conglomerate material such that stones or pebbles of a particular size which are fed into the grinder through the inlet 122 initially deflect off the disc 60 and are collected at outlet 130. Material of a different size remains in the grinder and is broken down in the manner which will be described hereinafter. In this embodiment, a shelf 132 could be provided below the opening 130 to facilitate removal of the material from the opening 130. This simply enables conglomerate material to be loaded into the grinder and for a particular particle size to be initially collected without any substantial breakdown because that particle size will initially deflect from the mid portion of the disc to the region of the opening 130 for collection. Smaller and larger particles will tend to travel upon different trajectories towards the wall 40 and therefore collide with the wall 40 for breakdown into smaller particle size, as will be described hereinafter. FIG. 6 shows breakdown of gross material, such as that in a size range of 100 mm to 300 mm. The gross material is deposited into the grinder from above the disc 60 through inlet 122 (FIG. 6). A lump of material dropped into the inlet 122 will fall (arrow A) on the disc at a first location near the centre of the disc and will absorb momentum and be thrown by centrifugal force (arrow B) against the internal surface 41 of the inverted conical casing 40. The material will begin initial breakdown on first impact with the disc 60 and then on impact with the internal surface 41. The material will then fall, depending on its size, back towards the disc 60 (arrow C), and contact the disc 60 at a second. position on the disc 60 radially outwardly of the first position. That impact will again cause breakdown and throw the material towards the inner surface 41 (arrow D) where further breakdown will occur and the material will again fall (arrow E) towards the disc 60 for a still further impact, still further radially outwardly, of the disc 60. This process continues as the material is bounced back and forward between the disc 60 and the internal surface 41 as shown by arrow F, G, H, I, J and K. These impacts will therefore break up the material into smaller particle size. The shape of the casing 40 which is an inverted cone will deflect the material impinging on the inner surface 41 back towards the disc 60 so that it impinges on the disc 60 radially outwardly from the previous impact position a distance not too far radially outwardly from the initial impact. Thus, several impacts with the disc 60 and the inner wall 41 will occur as the material breaks down and gradually moves towards the outer periphery of the disc 60. As is apparent from FIG. 6, the initial impact of the material falling in the direction of arrow A is close to the centre of the disc and therefore impacts on a part of the disc which is rotating at slower speed than points of the disc radially outwardly towards the periphery of the disc. That is, whilst all points of the disc on a radial line are travelling with the same angular velocity, the actual speed of each point increases radially outwardly because of the increased distance traversed by that point during each revolution of that disc. Since the initial impact below arrow A is inwardly of the disc, the amount of energy imparted to the material is relatively small. As the material bounces back and forward between the disc and the wall 40, and falls on radially more outward parts of the disc 60, the speed of the disc is greater at those positions of impact, thereby imparting increased kinetic energy to the material. Thus, the bouncing back and forward of the material between the disc 60 and the wall 40 intensifies the kinetic energy of the material, thereby increasing the energy of the material for particle to particle collisions and also collisions with the wall 40 and the disc 60. These collisions break down the material into ever smaller sizes, with the smaller size particles gradually finding their way towards the periphery of the disc 60. It should also be noted in FIG. 6 that the direction a piece of material travels after deflection from the wall 40 and the direction a piece of material travels towards the wall 40 are almost linear, or in other words head-on, thereby causing maximum impact in particle to particle collisions as the material bounces back and forward between the disc 60 and wall 40. It should of course be understood that the movement of the material between the disc 60 and the wall 40 is somewhat chaotic because of the breakdown of the material and therefore the change in size of the material, as well as the angle of collisions, which will deflect the material in various different directions. However, the general travel of material as the material breaks down will be in accordance with the arrows shown in FIG. 6, whereby relatively large material commences impact at a radially inner location of the disc with gradually smaller particles during the breakdown process finding their way towards the edge of the disc, and in general, a significant number of collisions between the disc 60 and the wall 40 may well take place before the material has broken down to a small size where it forms relatively small particles towards the periphery of the disc 60. Whilst it is preferred that the wall 40 have an inverted conical shape, as is shown in FIGS. 1-6, a wall shape of other configurations, such as generally cylindrical, are also possible. However, a cylindrical has a disadvantage that material deflected from the wall is likely to initially land a greater distance towards the periphery of the disc as it rebounds from the wall, thereby decreasing the number of impacts which occur between the rotating disc and the wall 40. The reason for this is that the point of impact on the cylindrical wall will always be outwardly of the disc, and therefore the trajectory of the material back onto the disc is likely to take the material to a radially more outer location on the disc. Because the conical wall effectively extends inwardly and over the disc 60, impacts of material travelling in the direction of arrow B occur above a midpoint of the distance between the centre of the disc 60 and the periphery of the disc 60 and the trajectory back onto the disc 60 is likely to take the material much closer to its initial impact position than if a cylindrical wall is used. The breakdown mechanism described with reference to FIG. 6, which relates to generally larger and heavy particles which are deposited from inlet 122 on a central portion of disc 60, can also apply to smaller particles. The smaller particles will bounce back and forward between the disc in a somewhat similar fashion to that shown in FIG. 6, except the initial impact with the disc is radially outwardly of the centre, so its efficient kinetic energy is imparted to the material to cause the material to bounce up towards the wall 40. When material is ground in the manner in which we described hereinafter, at least some of that ground material moves up the housing 12 to outlet tube 16. As previously explained, the outlet tube 16 supplies the ground particles to the cyclone 14. The cyclone 14 can be used to collect the fine ground particles and also to provide some separation of particle sizes. FIG. 5 shows another technique for separating particles of different sizes as the particles travel up the inner surface of wall 40. In this embodiment, outlets 124 and 126 are formed at different heights above the disc 60 in the conical top casing 120. The formation of the outlets in the conical wall 120 is important, because it has been found that if an outlet is formed in the inverted conical wall 40, or if more than one outlet is formed in the inverted conical wall 40, all of the material tends to exit that outlet and does not separate through the additional outlets depending on size. Some of the fine material, as previously mentioned, may pass the outlet and require extraction by the cyclone or simply circulate in the grinder. However, if the plurality of outlets, such as the outlets 124 and 126, are formed in the conical wall 120, separation of particle sizes does take place because the relatively larger particles, as they flow up the inclined wall formed by the conical housing 120, can tend to drop into the outlet 126 with the smaller particles remaining in the air stream, and then drop into the higher opening 124 as their energy, or speed of motion in the air stream reduces. The reason why the separation appears to occur in the conical section 120 rather than in the section 40 is due to the respective angles of the wall and the fact that the inverted cone 40 tends to allow all of the very small particles to exit the first opening the material comes across because of the angle that opening makes with respect to the direction of air travel up the incline wall 40, whereas the angle of the wall 120 allows the even smaller particles to travel past lower openings in the airflow towards the opening above that lower opening for collection in the higher opening. As is shown by FIG. 7, fine particles could be collected by the outlet 16 and conveyed to cyclone separator 14 if desired. Whilst the cyclone is suitable for collecting very fine particles, the cyclone could also be used for collecting larger particles and the openings 119, 126 or 124, previously described, could be connected to the cyclone 16 so that the particles collected from that outlet are separated from the airflow in the cyclone 14. The air and particulate material which exits the outlet 16 is supplied to the cyclone 14. The air supply through the outlet 16 to the cyclone 14 is directed tangentially into the cylindrical cyclone 14 as shown in FIG. 1, so as to create a generally circular or cyclonic flow of air in the cyclone 14. The circular or cyclonic air flow in the cyclone 14 is also supported by entry of hot air into the hot air inlet tube 34, which is also arranged tangentially with respect to the cyclone 14. As is shown in FIG. 7, the particles which enter the cyclone 14 from the tube 16 are entrained in the air flow which creates the circular or cyclonic air flow within the cyclone 14, or which merges in with the cyclonic air flow caused by the hot air introduced through the inlet 34. The cyclonic air flow within the housing 14 separates the particles from the air flow so that the particles are able to drop under the influence of gravity into particle outlet 22 whilst the air is able to exit the cyclone 40 through air outlet tube 24. The outlet tube 24 will generally be at higher pressure than the reduced pressure region in the centre of the housing 12 and the air inlet 18 can therefore be connected to the outlet tube 24 for the supply of air back into the housing 12 through the inlet 18. Any very small particles which are still trapped in the air flow in the outlet 24 therefore have the opportunity to pass back into the housing 12 for reprocessing. In other embodiments (not shown), as well as or instead of the cyclone 14, electrostatic or magnetic precipitators, or gas scrubbers, could also be used for removing fine particles. The electrostatic or magnetic precipitators or gas scrubbers could be used in the inlet 18 shown in FIG. 1 to remove the small particles so they do not just continuously circulate. Furthermore, such devices may also be used on the outlet 24 from the cyclone. As previously mentioned, if desired, hot air can be supplied to the housing 12 through hot air inlet 32 (not shown in FIGS. 2 and 3). The supply of hot air is useful if it is desired to dry the material which is being broken down by the grinder and, in particular, if the material is in a semi-gas or wet condition. In other applications where the supply of hot air is undesirable (such as the breakdown of coal or the like, which may ignite or explode during breakdown), the valve 30 can be shut off to ensure that no hot air is supplied to the housing 12. In other embodiments, the inlet 32 could be connected to an inert gas supply for supplying inert gas in the event of breakdown of volatile materials such as coal or the like, to eliminate the possibility of ignition or explosion of the material during breakdown in the grinder 12. FIG. 8 shows a second embodiment which is similar to the embodiment of FIG. 1. Like reference numerals indicate like parts to those previously described. The grinder installation 11 is supported in a support frame 199 which could be mounted on wheels or casters 201 to enable the support frame and grinder to be moved from place to place. Alternatively, the support frame 199 may simply be fixed to the ground or floor. Support frame 199 merely supports all of the components of the grinder installation 11. In this embodiment, inlet tube 20 is vertical and is connected to a hopper 203. The hopper 203 may be connected to the inlet tube 20 by a feed regulating valve 205 so that, if desired, material in the hopper 203 can be feed in a controlled manner to the housing 12. The outlet tube 16 may also have a regulating valve 206 to control flow of ground small particles through the outlet 16 to the cyclone 14. A first blower 207 is provided for blowing air through air tube 208 to the housing 12. The air tube 208 may communicate with at least one of the holes 108 (see FIG. 9 in the housing 12). Alternatively, the tube 200 may connect to a manifold (not shown) which in turn communicates with the interior of the housing 12 to supply air into the housing 12. Air is supplied into the blower 207 through inlet 209 and valve 210. A second blower (not shown) is located behind the blower 207 and air is supplied into the second blower via inlet 212 and valve 213. The second blower 213 has an outlet tube 214 which supplies air into the cyclone 14 for increasing the speed of the vortex or cyclonic airflow within the cyclone 14. Air exhaust 18 from the housing 12 connects to air exhaust outlet pipe 215 from the cyclone 14 and the outlet pipe 215 is connected to a second cyclone 216. The cyclone 14 has a small particle outlet 217 which is provided with a gas lock 218 (see FIG. 10), and the cyclone 216 is provided with a small particles outlet 219 which is also provided with a gas lock 218 (see FIG. 11). The gas locks 218 allow the small particles to pass through the gas locks but not the high pressure air in the cyclones. The cyclone 216 also has an air exhaust 220. Thus, ground particle which exit the housing 12 through the outlet tube 16 are provided to the cyclone 14 where the particles are separated from the airflow and which can be collected in a container (not shown) arranged below the particles outlet 217. Air exits the cyclone 14 through outlet tube 215 and any very small particles which are still entrained in that airflow are supplied to the second cyclone 216. Those particles are separated in the cyclone 216 and are collected in a container (not shown) below the particles outlet 219. The air supplied to the cyclone 216 from the outlet tube 215 exhausts from the cyclone 216 through exhaust outlet tube 220. The outlet tube 220 may be connected to a final filter or scrubber for collecting the very fine particles which may remain entrained in the airflow exhausted from the second cyclone 216. The gas locks 218 are shown in FIGS. 12 and 13 and comprise an inlet tube 221 which connects to the outlet 219 (or the outlet 217 as the case may be), the inlet 221 is in communication with a cylindrical chamber 222. The cylindrical chamber 222 has an outlet tube 223. A rotor 224 is mounted for rotation within the cylindrical chamber 222 and has three vanes 224a, 224b, and 224c. The rotor 224 is mounted on an axle 225. As is shown in FIG. 13, the axle 225 is driven by an electrical motor 226 so that the rotor 222 rotates about the axis of the axle 225. Thus, small particle material which enters the inlet 221 collects in the space 227 between the vanes 224a and 224b. The particles which are collected in the space between the vanes 224b and 224c is allowed to drop through the outlet 223 and the space between the vanes 224a and 224c is empty. Thus, the outlet 223 is always sealed from the inlet 221 by the rotor 222 so that relatively high pressure air in the cyclone 216 (or 214 as the case may be) is not able to communicate with the outlet 223. This allows the fine ground material to simply drop under gravity out of the space between the adjacent pair of rotors as that space comes into communication with the outlet tube 223 and therefore will not be blown out in a cloud of fine dust, which may otherwise happen if the gas lock 218 was not provided. Thus, the spaces between adjacent vanes 224a, 224b or 224c are sequentially filled with fine ground material and are emptied as those spaces move into communication with the outlet tube 223 so that the small particles simply drop under the influence of gravity into the container (not shown) located below the outlet 223. FIG. 9 is a detailed view of disc 60 within the housing 12. This arrangement is basically the same as that shown in FIG. 3 and, once again, like reference numerals indicate like parts to those described with reference to FIG. 3. However, in this embodiment the inlet 20 is extended by an inlet pipe 20′ which has an outlet adjacent the periphery of the disc 60. This embodiment is particularly suitable for grinding smaller particles such as sand or the like which have a size less than 10 mm. In this embodiment the material is deposited directly at the periphery adjacent main grinding zone Z which will actually produce the very small particles for collection. The grinding zone Z is generally between the periphery of the disc 60 and the inner stationary wall 102, and within the confines of the disc 60 (ie. between the top surface and bottom surface of the disc 60). However, the grinding zone Z may extend to a position above the top surface of the disc 60, but still generally between the periphery of the disc 60 and the inner stationary wall 102. The sand may be deposited at the periphery because it is already in a relatively small state, as compared to the gross material previously described which is of much larger size and which needs to be broken down to a smaller size before it is ground in the main grinding zone Z to very small particles which will eventually be collected at the outlets 217, 219 or 220. The periphery of the disc is spaced from the inner wall 102 by a distance of 10 to 30 mm. However, a larger space could be used depending on the nature of the material to be ground. The disc is about 400 mm in diameter and is rotated at a speed of about 4500 rpm. The disc has a weight of about 5 to 10 kg. However, obviously larger or smaller machines could be produced by scaling these dimensions. FIG. 9A shows an underneath view of the disc 60 and, in particular, the configuration of the vanes 100. The vanes 100 are configured so they will drive the air out of the turbine formed by the vanes 100 in the same direction K as the rotation of the disc. Furthermore, the vanes 100 are shaped so that gas particles accelerating, as shown by arrows L, from an inner peripheral portion of the vanes to the periphery of the disc create sufficient acceleration to enable the air to exit in the direction of rotation without producing turbulence (as shown by arrows M). As can be seen in FIG. 9A, the vanes 100 are generally arcuate, with the radius of curvature generally increasing towards the outer periphery of the disc so that the exiting air is as near as possible tangential to the disc 60. When the disc 60 is rotated, the vanes 100 produce a flow of air from the air which enters the holes 108. The blower 207 may be used to provide an initial speed to the air as the air enters the housing 12 so that that air is collected by the vanes 100 as the disc 60 rotates to produce the high speed airflow at the periphery of the disc 60 generally in the vicinity of the contoured wall 102 which, together with the periphery of the disc 60, generally defines the main grinding zone Z. It should be understood that the blower 217 need not be used and air could simply enter the housing 12 through the openings 108 for collection by the vanes 100. Thus, the vanes 100 and the rotating disc 60 produce a generally lamina airflow at the periphery of the disc which is very fast immediately adjacent the periphery of the disc, and most preferably at least as fast as, if not faster that the speed of the periphery of the disc. The rotating disc, together with the vanes 100, therefore provides energy intensification of the air within the housing 12 at the periphery of the disc in the grinding zone Z. Thus, the stationary air below the disc 60 and within the housing 12 is therefore accelerated up to high speed at the periphery of the disc. If the air is introduced with some speed by the blower 207, then the speed of the air is further accelerated by the disc 60 and vanes 100. As is shown in FIG. 14, the pressure differential of air below the disc 60, where it can be seen that the pressure increases from a relatively low pressure region 230 inwardly of the disc to a high pressure region 232 at the periphery of the disc. The closer or more dense cross hatching in FIG. 14 shows increasing pressure regions extending towards the periphery of the disc. FIG. 15 is a diagram similar to FIG. 14, except that the diagram shows the speed differential where the speed of the airflow increases from the position 230 inwardly of the periphery to the region 232 at the periphery of the disc. Again, the more dense cross hatching shows increasing speed. The pressure and speed of the airflow at the periphery of the disc may be in the order of 150,000 Pa and 300 metres per second. If relatively large particulate material is deposited into the housing 12, such as broken glass which may have a size of about 10 mm or larger material, initial breakdown occurs due to impact with the disc 60 and the side wall of the housing 40 as previously described. Small particles will find their way into the grinding zone Z and further breakdown will occur due to particle to particle collisions in that zone and also possibly some collisions with the wall 102, although these latter collisions are likely to be much fewer than the particle to particle collisions. As the particles begin to break down into small particle sizes, the grinding zone Z starts to establish itself. The manner in which the material is ground in the grinding zone Z will be described with reference to FIGS. 14 to 17. This form of grinding is applicable to both the embodiments of FIGS. 1 to 7 and 8 to 13. Small particles in the housing 12 will eventually find their way to the periphery of the disc 60. This can happen by breakdown of large gross material in the manner described with reference to FIG. 6, or by depositing smaller material through the tube 20′ at the periphery of the disc 60. In both cases, the material in relatively large particle size, but much smaller than the gross particle size which is broken in the manner described with reference to FIG. 6, therefore tends to enter in the direction of arrow D either directly from the tube 20′ or after being broken up by impacts with the disc 60, the wall 40 and particle to particle impact above the disc 60. The kinetic energy of the relatively large particles is therefore intensified as the particles near the disc periphery, and the particles are therefore driven by centrifugal force into the zone R1 shown in FIG. 16. As the particles begin to break down into smaller particle sizes, a range of particle sizes will be created. Some of those particle sizes will be very small and probably in the order of about 200 to 800 nanometres. These particles are entrained in the annular gas flow created in the grinding zone Z between periphery 60a of the disc 60 and the wall 102. This air flow is made up of molecules of the gases making up the air and the small particles held in an aerosol suspension within the air. If the suspended particles are small enough, this air particle mixture will act generally as a gas within a certain range of temperatures and pressures, that is, it will obey gas laws relating to temperature and pressure and increase in kinetic energy of all of the particles when heated. This gas mixture is referred to herein as a heavy gas. This heavy gas generally forms in a region R1 which is radially outwardly of the periphery 60a of the disc 60. The reason for this is that the heavy gas is generally pushed out to this region by the gas flow created by the vanes 100. The very small particles which mix with the air molecules to form the heavy gas generally remain in the region R1 outwardly of the periphery of the disc 60 because they are adjacent to a stationary wall, and therefore move more slowly than the newly entering air from the vanes 100. The heavy gas region R1 is therefore moving at a slower speed than the gas in region R2 and which will form a boundary layer which will become the sheer zone S2 between the regions R1 and R2 when the larger particles migrated into the grinding zone Z from the disc 60. Thus, if heat is added to the heavy gas, kinetic energy is increased, thereby increasing the grinding effect with little, if any, added mechanical energy. The heavy gas therefore generally acts like a normal gas such as air, but is formed by molecular particles carrying a suspension of larger, but very small particles. The suspended particles usually cannot be filtered or settled in devices like cyclones, and are generally analogous to a liquid colloid suspension. As the heavy gas region R1 builds up, the sheer zone S2 is therefore created between the region R1 and the second region R2 between the sheer zone S2 and the periphery 60a of the disc 60. The region R1 of the heavy gas particles generally forms radially outwardly of the disc 60a because of the relatively small size of those particles. A low friction air cushion exists in a region R3 between the wall 102 and the region R1 which moves slower than the heavy gas flow in region R1 and a sheer zone S1 is created between the regions R3 and R1. In the region R3, the air is moving very slowly because of contact with the wall S1 and therefore the particles in the region R1 tend not to move into that region, but remain within the region R1 between the sheer zone S1 and the sheer zone S2. The larger particles which are initially provided in the region R2 will at random come into contact with the sheer zone S2 or pass through the sheer zone S2 into the region R1. At the sheer zone S2, or if they move into the region R1, they are bombarded by the heavy gas and, in particular, the small particles to cause breakdown of those larger particles into smaller particle sizes. This will in turn form particles of varying sizes and again, some of those particles will be of the very small size which simply add to the heavy gas in the region R1 and others will be slightly larger particles. The region R1 therefore fills with particles, both of a relatively small size to form the heavy gas, and also slightly larger sizes. Thus, some of the particles which pass through the sheer zone S2 or which simply arrive at the sheer zone S2 are comminuted into heavy gas particles by collision with existing heavy gas particles in the region R1 and at the sheer zone S2. Some of the particles which are communicated are not sufficiently small to behave as heavy gas particles, and some of those particles will be quickly ejected back to the region R2. This is because the differential air speeds of the heavy gas and the newly introduced gas from the vanes 100 will have a pressure difference. However, as the number of particles in the region R1 and R2 tends to build up, in the annular flow of air between the periphery of the disc 60a and the sheer zone S1, some of the particles will tend to spill upwardly out of the sheer zone Z along the wall 102. Movement of the particles in this direction is facilitated by the upwardly directed flow of air which is created by the vanes 100. The particles which move out of the grinding zone Z will be largely particles which have entered the heavy gas region R1 and which are broken down into smaller particle sizes, but not sufficiently small to act as a heavy gas, together with some of the heavy gas particles, and also some of the particles from the region R2 which are still relatively large. Of those particles which leave the region Z, most of the heavy particles will tend-to move into a complex field created above the disc 60, and which will be described in more detail hereinafter, and will be recirculated back down onto the disc 60 to migrate back to the grinding zone Z for further grinding. However, some of those larger particles, together with small particles, and also some heavy gas particles and small particles which are created in the grinding zone Z will either move with the upwardly moving air stream to the outlet 16, or be entrained in the exhaust gas exhausted from the housing 12 through the exhaust outlet 18. Because the disc 60 has a plurality of vanes 100 and is rotating relatively fast, a very stable and coherent annular generally laminar flow of air is created at the grinding zone Z which is directed slightly upwardly relative to the disc 60 and therefore, a stable and coherent annular grinding zone Z is created in the annular region around the disc 60 between the periphery 60a and the wall 102, to therefore form a grinding zone Z which has a substantial size. The continued pumping of air into the grinding zone from the plurality of vanes 100 ensures that the airflow within the grinding zone Z is stable and coherent so that the heavy gas region R1 of heavy gas particles is established and maintained. Thus, a stable and coherent grinding zone Z is built up and is maintained between the periphery of the disc 60a and the wall 102, which is comprised of the sheer zone S2 between the larger particles in region R2 and the heavy gas within the region R1. Because the disc 60 is spaced a relatively small distance from the wall 102 and effectively defines a uniform annular space between the periphery 60a and the wall 102, and air is continually fed into that space by the vanes 100 attached to the rotating disc 60 a uniform and coherent heavy gas annulus is maintained in the region R1. Thus, as larger particles move into the region R2, those particles come into contact with the heavy gas in the region R1 at the sheer zone S2 and are further comminuted by particle to particle contact at the sheer zone S2 so that those larger particles in the region R2 contribute more fine particles to the heavy gas in the region R1. As the region R1 overfills with fine heavy gas particles and small particles which are larger than the heavy gas particles, those particles begin to spill upwardly along the wall 102. The high energy environment of the heavy gas annulus in the region R1 will produce other changes in the particles within the region R1. Some of these changes will involve surface molecular dissociation and sublimation and will result in the production of continuously finer particles. The particles remain in the region R1 for a relatively short time period, and probably significantly less than one revolution of the disc 60 (although very small particles may stay in the region R1for longer), as will be described in more detail with reference to FIG. 18. The particles therefore leave the grinding zone Z quite quickly and pass through the complex vector field above the disc 60. This complex field is shown in FIG. 17. As can be seen from FIG. 17, the particles move out of the region R1 upwardly adjacent the wall 102 to the wall 103a. The step 103 is provided to maintain the particles within the region R1 for a reasonable amount of time to ensure that they do not exit the region R1 too quickly which could prevent the heavy gas in the region R1 from being established and maintained. However, it should be understood that the cylinder 74 which is provided with the wall portion 102 and the step 103 need not necessarily be provided and the housing 12 could simply have a conical or vertical wall which may be provided by the wall 40 of the housing 12 adjacent the periphery of the disc 60. As the number of heavy gas particles and small broken down particles build up in the region R1, the particles generally move upwardly with the airflow created by the vanes 100 which, as previously described, direct the airflow upwardly relative to the disc 60. The movement of the airflow may also entrain some of the particles from the region R2. The fine particles created in the region R1 with perhaps a few of the larger particles from the region R2 will move up the wall 103a and the wall 40 of the housing 12 in bands of rising air 260. Those particles are entrained in a rotating, generally lamina flow of stream tubes 280 (which will be described in more detail with reference to FIG. 18), and exit through outlet tube 16 to be conveyed to the first cyclone 14. The particles which enter the exhaust outlet tube 18 are conveyed to the second cyclone 216 via the outlet tube 215 from the first cyclone 14 as previously described. The particles which enter the complex vector field above the disc in the region 250 meet a generally standing wave 270 formed in the air above the disc 100. Large particles in those particles which meet the standing wave 270 tend to be moved back to the periphery of the disc 60 and back into the grinding zone Z for further grinding. The very light fines tend to do a loop as shown by arrow A in FIG. 17, and are extracted through exhaust tube 18 with the exhaust air from the housing 12. The larger particle which meets the standing wave 270 and which are directed back down to the disc 60, moves back to the grinding zone Z as previously described, for more grinding until those particles are broken down into a particle size which will either travel up the wall 40 in the manner previously described, or which will be entrained in the airflow exiting the exhaust outlet 18. FIG. 18 shows the lamina airflow stream tubes 280 which are created and which move up in bands adjacent the wall 40. These stream tubes 280 carry the fine particles to the outlet 16. As can be seen in FIG. 18, the stream tubes remain in the grinding zone Z for only a very small time period and which may be only 15 to 30° of the rotation of the disc 60 (for example, from point C to point D in FIG. 17). These stream tubes are created by the vanes 100 which, as can be seen in FIGS. 3 and 9, are angled upwardly to tend to push the airflow into the grinding zone Z and then upwardly away from the disc. FIG. 19 shows an actual measure distribution of small particles and other particles collected from the grinder. FIG. 20 extends this to the full distribution of small particles and particle sizes. Particles below a size of about 1.6 microns may not be collected because of their very small size and simply pass through all final filtering, and hence do not appear in the experimental actual measured distribution in FIG. 19. However, it is apparent that the distribution is generally in the form of a bell curve distribution, and when extended below the one micron size, as shown in FIG. 20, obviously much smaller particles than the smallest size actually measured are present. As can be seen from FIG. 20, the heavy gas in the region R1 is made up from the heavy gas components shown in FIG. 20 and labelled G which are minute particles or fines having a size of less than about 800 nanometres. The heavy gas particles which travel up the wall 102 to the outlet 16 probably will not be collected because of their very small size and will simply pass through the filtering stations and exit with the exhaust air. However, these could be collected by electrostatic or magnetic devices or water entrapment. In the preferred embodiments, the vanes 100 are directly upwardly as previously described. However, the vanes could be arranged substantially horizontally, and the angle of the wall 102 inclined more than that shown in the drawings so as to send the gas stream produced by the vanes 100 upwardly into the grinding zone Z. If desired, pins or other like elements may extend upwardly from the base of the housing into the grinding zone Z at about the vicinity of the sheer zone S2 to create some turbulence at the sheer zone which tends to assist the mixing of particles from the region R1 at the sheer zone with the heavy gas in the region R2 to comminute the heavy particles into smaller particles at the sheer zone S2 in the region R1. The preferred embodiment of the apparatus may also be used in a vacuum. If the apparatus is used in a vacuum, the initial grinding process described with reference to FIG. 6 will still occur. However, to obtain the additional grinding in the grinding zone Z, it will be necessary to establish the heavy gas in the region R1 by the introduction of particles which could form a functional heavy gas in the region R1. This may be achieved by directing suitable fine particles through the inlet 108 and then through the vanes 100 to the periphery of the disc so that the particles establish the heavy gas and continue to act as the transport system in the manner described above. This embodiment would only be used in environments where it would not be desirable to have any other gas involved in the process. The heavy gas may be formed by an inert gas (for example, argon) and added particles of heavier material, or alternatively, if no gas at all is desired and a true vacuum required, the heavy gas could be formed by minute particles of a suitable material such as silicates or iron or the like. If it is desired to grind very light particles such as feathers or wheat flour, and very fine particles required, it is necessary to establish the heavy gas other than from the material which is to be ground in the same manner as described above. In such embodiments, the heavy gas may be formed by adding water or some other particle such as the silicates or the like. As is shown in FIG. 21, the particle size collected by the cyclone 14 and which appear at the outlet 217 are generally in the range of 0 to 30 microns (with those over 30 microns being ignored because they are rare), with the majority of the particles being in the range of 5 to 20 microns. As shown in FIG. 22, the particle size of the particles collected at the particles outlet 219 of the second cyclone are generally in the range of 0 to 10 microns, with a majority being less than 5 microns in size. Since modifications within the spirit and scope of the invention may readily be effected by persons skilled within the art, it is to be understood that this invention is not limited to the particular embodiment described by way of example hereinabove.
<SOH> BACKGROUND ART <EOH>Many devices exist that can reduce material to small particle sizes, but most are large, slow, heavy, and consume large amounts of energy. However, very few machines exist which can economically reduce particles down to very small fine particle sizes. Grinding of materials to very small particles is carried out by a variety of machines. These machines employ two main processes. The first and most common, is by crushing the material between hard moving elements made from such materials as steel or silicates until the particles are of the required size. Repeated recycling may be employed to aid the process. Such machines are rolling, ball or hammer mills. The second method is by employing high-energy impact. Machines using this principle cause high speed, hard moving elements, to collide with the particles to be ground. The particles to be ground are usually transported into and out of the impact area by gravity and by a gas, usually air. In some cases, material to be ground is carried only by gravity into the impact zone in the same way. As well as collisions with the grinding element, there are particle to particle collisions. However, these impacts make only a very small contribution because the particles are of much the same kinetic level and are moving in much the same direction. To achieve significant particle size reduction, recycling of the process must also be employed. A beater hammer mill is typical of such machines. The crushing process is slow and usually limited in the mining and primary metallurgy industry. Impact grinding has the potential for fast throughput and great size reduction for other industrial and commercial particle grinding. The problem with present impact machines is that particle to particle impacts make only a small contribution, and hence the necessary energy level from the momentum transfer from the impacting elements must be at the highest energy necessary to break up the particles, that is the energy levels of the particles remain only as high as the initial impact. A need therefore exists for a small, even portable machine that can achieve these results fast and economically.
<SOH> SUMMARY OF THE INVENTION <EOH>An object of a first invention is to provide an impact particle grinder which can reduce gross particles down to a much smaller particle size. A first invention may be said to reside in an impact particle grinder, comprising; a housing having an inner wall; a grinding disc mounted in the housing for rotation within the housing; means for rotating the grinding disc; an inlet for depositing material onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and outlet means for discharge of the small particles from the grinder. Thus, the impact grinder works using two principles. The first is by repeatedly injecting energy at higher and higher levels into the particles as they are reduced in size. This is a continuous energy intensifying process. The grinder therefore processes material step by step to higher energy levels as it impacts further out towards the periphery of the disc. This results in very great size reduction. Recycling therefore is only employed by the machine to act upon particles, which have not reached the requisite energy level by the time they impact with a radially most outward part of the disc. Depending on the size of the particle required, the particles can simply be discharged from the machine. However, if very fine particles are required, the particles can undergo further processing to reduce the particles to fines. In the preferred embodiment of the invention, the additional grinding to produce the small particles is performed in the grinder by establishing a further grinding zone between the periphery of the spinning disc and a stationary wall of the grinder. This embodiment requires the invention to operate in a gas rather than a vacuum, with the gas usually simply being air. While operating in a transport medium such as air, each particle will, as it moves to the periphery and into the grinding zone. The grounding zone is formed by a sheer zone which causes comminution of the particles to form the small particles. In the preferred embodiment of the invention, the inner wall of the housing is of inverted conical shape so that deflection of material from the inner wall tends to direct the material to the second location which is a small distance from the first location, thereby producing a significant number of impacts of the material with the disc as the material bounces between the disc and the inner wall. The result of this increased number of collisions produces a greater number of impacts which impart increased kinetic energy to the material, and therefore greater breakdown of the material due to those impacts and particle to particle collisions. In one embodiment of the invention the grinder includes hot air inlet means for introducing hot air into the housing adjacent the disc for drying the material as the material is ground. In one embodiment the grinder also includes inert gas introduction means for introducing inert gas to mix with the ground particles. In one embodiment of the invention the outlet means is arranged above the disc. In one embodiment, the outlet means comprises a plurality of outlets which are arranged at different heights above the disc so that particles of different sizes are collected in each of the outlets, the outlets being provided in a housing wall portion which is of conical shape. The outlet means may include a recirculator for recirculating small particles from the outlet means back to the housing for reprocessing in the housing. In one embodiment, the outlet means is connected to a cyclone particle collector. Preferably the cyclone particle collector comprises means for creating a circular flow of air in the cyclone, inlet means connected to the outlet means for receiving particles from the housing and for conveying the particles into the cyclone for circulation in the circular air flow in the cyclone, an air outlet tube in the cyclone and a particle outlet in the cyclone, and wherein particles trapped in the circular flow of air are conveyed about the cyclone with the circular flow of air and separated from air flow so that the particles can be collected in the particle outlet and air exit the cyclone through the air outlet. Preferably the air inlet means for creating the circular flow of air comprises a hot air inlet and a heater for heating air for supply to the hot air inlet. In one embodiment of the invention, the disc has an outer periphery which is in close proximity to the inner wall of the housing so that when the disc is rotated by the rotating means, an annular rotating stream of air is formed between the periphery of the disc and the inner wall, so a sheer zone is created between the periphery of the disc and the inner wall so that when particles enter the space between the disc and the inner wall, they are subject to the shear zone to further reduce the particles to small particles. An air inlet means is preferably provided below the disc in the housing for allowing air to enter the housing from below the disc to cause the air annulus to spill up the inner wall of the housing so that finely ground particles trapped in the rotating stream of air are carried by the spill of air to the outlet means. In another embodiment of the invention, the outlet means is arranged below the disc. This embodiment would be used in environments in which the grinder is operating in a vacuum or extremely low air pressure environments, and in which the air stream at the periphery of the disc is therefore not created. Thus, in this embodiment, small particles have no option but to fall under the influence of gravity in the space between the periphery of the disc and the inner wall of the container to the outlet means below the disc. In one embodiment the disc includes a plurality of vanes for imparting momentum to the air when the disc rotates to create the annular rotating stream of air between the periphery of the disc and the wall to create the sheer zone. Preferably the vanes are angled upwardly relative to the horizontal so that the rotating stream of air is directed upwardly above the disc to facilitate the spill of air up the inner wall. Preferably the inner wall of the housing includes a separate cylindrical wall which includes a contoured wall portion for trapping material so the material remains in the annular airflow for a long period to break down the material to small particles, before the small particles travel in the spill of air up the inner wall to the outlet. This invention also provides a method of impact grinding a material, comprising; supplying the material to a grinder which has a housing having an inner wall and a rotating disc mounted in the housing; wherein the material supplied is deposited onto a first location on the rotating disc, so kinetic energy is supplied to the material from the disc to fling the material against the inner wall of the housing, and material deflected from the housing falls back onto the disc at a second location radially outwardly of the first location so that further kinetic energy is imparted to that material to provide an energy intensifying process as material continues to impact against the inner wall of the housing and fall back on a radially more outward part of the rotating disc, and wherein particle to particle collisions within the housing and collisions with the rotating disc and inner wall break down the material to produce small particles; and collecting the small particles from the grinder. A second invention is concerned with the breakdown of material into smaller particles. This invention provides a grinder for producing small particles from material, comprising: a housing having a substantially inner wall; a disc mounted in the housing and having a periphery adjacent the inner wall; a motor for driving the disc so the disc rotates about a substantially vertical axis; a plurality of vanes on the disc for creating an annular flow of gas between the periphery of the disc and the inner wall to create a sheer zone between the inner wall and the periphery of the disc; an inlet in the housing for receiving the particulate material, so the particulate material is able to migrate to the sheer zone between the periphery of the disc and the inner wall and be broken down to small particles; and a small particle outlet for allowing outlet of the small particles from the housing. In this invention the particulate material may be delivered to the housing from an inlet direct to a location near the periphery of the disc for substantially direct feeding into the sheer zone. Thus, in this embodiment the inlet may comprise an inlet tube extending within the housing from an upper portion of the housing to a position adjacent the periphery of the disc. However, in another embodiment, the particulate material may be gross material which is first broken down by impact with the disc and the housing into small particle size which small particles then move to the sheer zone for further breakdown into small particles. In this latter embodiment the inlet generally comprises a tube which delivers the gross particulate material to a location inwardly of the periphery of the disc. Preferably the housing has a gas inlet below the disc and the vanes are located on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed. Preferably the grinding zone comprises a first region between the wall of the housing and an intermediate location between the wall and the periphery of the disc for establishing a heavy gas, and a second region between the periphery of the disc and the intermediate location for receiving particles from the disc so those particles can move into the heavy gas and be ground into small particles. Preferably a sheer zone is created at the intermediate location between the first and second regions. Preferably the vanes are located on the lower surface of the disc and are directed upwardly so that the vanes direct the gas to the periphery of the disc and upwardly relative to the disc so that the annular flow of gas created by each of the vanes between the disc and the inner wall, and within the confines of the disc for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing. Preferably the housing has an exhaust gas outlet arranged substantially centrally of the disc. Preferably a standing wave is created between the exhaust gas outlet and the periphery of the disc so that particles which are broken down into small particles in the sheer zone are able to move upwardly with the airflow adjacent the inner wall of the housing to the outlet, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc and move along the upper surface of the disc back to the sheer zone for further grinding, or travel with the exhaust gas to the exhaust outlet. Preferably the outlet is connected to a first cyclone for separating gas from the small particles so the small particles can be collected at an outlet of the first cyclone. Preferably the exhaust gas outlet is connected to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. Preferably the first cyclone has a gas exhaust outlet which is connected to the second cyclone so that any small particles which remain in the gas exhausted from the first cyclone are fed to the second cyclone for separation from the gas in the second cyclone. Preferably the outlet from the first cyclone includes a gas lock for preventing high pressure gas from exiting the outlet and blowing small particles into the atmosphere. Preferably the outlet from the second cyclone also includes a gas lock for preventing high pressure gas from exiting the second cyclone through the outlet. This invention also provides a method of producing small particles from material, comprising: supplying the material to a housing having a substantially inner wall and a rotating disc mounted in the housing and having a periphery adjacent the inner wall so that the disc creates an annular flow of gas between the periphery of the disc and the inner wall to create a sheer zone between the inner wall and the periphery of the disc; allowing the material to migrate to the sheer zone between the periphery of the disc and the inner wall and be broken down to small particles; and collecting the small particles from the housing. Preferably the method includes allowing the gas to enter the housing from below the disc and providing vanes on a lower surface of the disc for collecting the gas and directing the gas to the periphery of the disc to provide energy intensification to the gas so that the gas at the periphery of the disc moves with high speed, and the gas adjacent the stationary inner wall is at relatively low speed, and wherein the grinding zone is created by the establishment of: (a) a heavy gas formed from a mixture of the gas and minute particles in a first region between the inner wall and an intermediate position between the disc and the inner wall; (b) a second region for receiving larger particles to be ground into the smaller particles, between the intermediate position and the periphery of the disc; (c) a sheer zone between the first and second regions; and wherein particles in the first region pass through the sheer zone, and some are comminuted into heavy gas particles and others which are not sufficiently small to behave as gas particles are either ejected back to the first region for further grinding as those particles re-enter the heavy gas through the sheer zone, or move out of the grinding zone for collection from the housing. Preferably the annular flow of gas created by each of the vanes between the disc and the inner wall is maintained within the confines of the disc and at the sheer zone for a short time period and then moves upwardly relative to the disc in annular fashion adjacent the inner wall of the housing. Preferably the method comprises extracting gas from an exhaust outlet arranged substantially centrally of the disc. Preferably the method further comprises creating a standing wave between the exhaust outlet and the periphery of the disc so that particles which are broken down into small particles in the sheer zone move upwardly with the airflow adjacent the inner wall of the housing to the outlet, or move inwardly of the disc where they meet the standing wave and are directed down back to the upper surface of the disc, and move along the upper surface of the disc back to the sheer zone for further grinding, or travel with the exhaust gas to the exhaust outlet. Preferably the method further comprises supplying the collected small particles to a first cyclone for separating gas from the small particles so the small particles can be collected at an outlet of the first cyclone. Preferably small particles collected at the exhaust outlet are supplied to a second cyclone so the gas and small particles can be separated in the second cyclone to enable the small particles to be collected at an outlet of the second cyclone. The invention also provides a grinder for producing small particles from material, comprising: a housing having an inner wall; a rotatable mechanical member in the housing having a periphery adjacent the inner wall; a drive for driving the rotatable member for causing the rotatable member to create an annular flow of air between the periphery of the member and the inner wall, and for establishing a grinding zone between the inner periphery and the wall which comprises: (a) a first region in which a heavy gas is established, the first region being between the inner wall and an intermediate position between the periphery of the member and the inner wall; (b) a second region for receiving relatively large particles compared to the particles which make up the heavy gas, the second region being between the intermediate position and the periphery of the mechanical member; and (c) a sheer zone between the first and second regions at the intermediate location; and wherein the relatively large particles received in the first region come into contact with the heavy gas particles across the sheer zone where the relatively heavy particles are comminuted into smaller particles, some of which add to the heavy gas within the first region and the other of which form small particles of a size which do not behave as a heavy gas, and wherein the small particles, together with some of the particles which make up the heavy gas and other larger particles from the first region move out of the grinding zone with an annular flow of air from the grinding zone and travel to a first collection outlet for collection or fall back to the mechanical member and again travel to the first region for further grinding in the grinding zone. The invention still further provides a method of grinding material, comprising: creating a grinding zone having a first annular region in which an annular flow of heavy gas is established and a second region spaced from the first region by a shear zone; directing the material into the grinding zone so the material passes from the second region to the first region across the shear zone into the annular flow of heavy gas and is comminuted into smaller particles by contact between heavy gas particles in the heavy gas and the material; and collecting the comminuted particles. A third invention relates to a grinding installation for grinding material into small particles. This invention provides a grinding installation for producing small particles from material, comprising a grinder having: (a) a housing having a stationary inner wall; (b) a disc mounted in the housing and having a periphery adjacent the inner wall; (c) a motor for driving the disc so the disc rotates about a substantially vertical axis, and whereby small particles are produced by breakdown of material impacting with the disc and the inner wall and/or in a grinding zone between the periphery of the disc and the inner wall; (d) an air inlet in the housing; (e) an air exhaust outlet from the housing; and (f) a particle outlet from the housing; a first separator connected to the particle outlet for separating air from the small particles and for delivering the small particles to a small particles outlet; and a second separator connected to the exhaust air outlet for separating small particles in the exhaust air from the exhaust air and delivering the small particles to a second small particles outlet. Preferably the first separator has a first exhaust air outlet and the first exhaust air outlet is connected to the second separator. Preferably the first separator comprises a cyclone separator. Preferably the second separator comprises a second cyclone separator. A fourth invention provides a grinder for producing small particles comprising: a first region for establishing a heavy gas, a second region spaced from the first region and a shear one between the first and second regions when the grinder is in use; a material inlet for delivery material so the material passes to the first region for grinding; and an outlet for collecting the small particles.
20041116
20070424
20051013
75483.0
0
ROSENBAUM, MARK
GRINDER
SMALL
0
ACCEPTED
2,004
10,514,627
ACCEPTED
Angle-multiplexing hologram recording device, method, hologram reproduction device, and method
A hologram recording apparatus (100) includes a record angle change device (19) capable of relatively changing the record angle of a hologram recording medium (200) relative to signal light (L3) and reference light (L2); and a control device (18). The control device sets a record angle for recording a specific angle record plane as a standard record angle among a plurality of angle record planes on the hologram recording medium. Furthermore, the control device controls the record angle change device so as to change and fix the record angle after then by a predetermined angle from the set standard record angle.
1. An angle-multiplex type hologram recording apparatus comprising: a light source for performing an irradiation with source light including signal light and reference light; a spatial light modulator disposed in an optical path of the signal light, for modulating the signal light; an optical system for introducing the signal light passed through the spatial light modulator and the reference light onto a hologram recording medium; a record angle change device for relatively changing a record angle of the hologram recording medium relative to the signal light and the reference light; and a control device for controlling the record angle change device to set the record angle when a specific angle record plane is recorded from among a plurality of angle record planes on the hologram recording medium as a standard record angle, and to change and fix the record angle after then by a predetermined angle from the set standard record angle. 2. The angle-multiplex type hologram recording apparatus according to claim 1, wherein the spatial light modulator records angle standard identification information indicating a standard angle record plane corresponding to the standard record angle onto the specific angle record plane, if the hologram recording medium is not recorded. 3. The angle-multiplex type hologram recording apparatus according to claim 2, wherein the control device calibrates the record angle change device on the basis of the angle standard identification information, if record information has been recorded at least on the specific angle record plane of the hologram recording medium. 4. The angle-multiplex type hologram recording apparatus according to claim 1, wherein angle standard identification information indicating standard angle record plane corresponding to the standard record angle is recorded onto at least one of a plurality of angle record planes of the hologram recording medium, and the control device calibrates the record angle change device on the basis of the angle standard identification information. 5. The angle-multiplex type hologram recording apparatus according to claim 1, further comprising a move device for moving the hologram recording medium relative to a focus position of the reference light and the signal light introduced by the optical system. 6. The angle-multiplex type hologram recording apparatus according to claim 5, wherein the spatial light modulator performs recording to all angle record planes of the hologram recording medium every time of moving by the move device. 7. The angle-multiplex type hologram recording apparatus according to claim 1, wherein the specific angle record plane is an angle record plane to be firstly recorded from among the plurality of angle record planes. 8. An angle-multiplex type hologram reproduction apparatus for reproducing recorded information from an angle-multiplex type hologram recording medium in which angle standard identification information indicating a standard angle record plane is recorded onto one of a plurality of angle record planes, said reproduction apparatus comprising: a light source for irradiating the hologram recording medium with reproduction illumination light; a photoreceptor for receiving reproduction light based on the reproduction illumination light from the hologram recording medium; a read device for reading respectively the plurality of recorded information overlappingly recorded onto the hologram recording medium, on the basis of the received reproduction light; a reproduction angle change device for changing a reproduction angle of the hologram recording medium relative to the reproduction illumination light; and a control device for controlling the reproduction angle change device so as to change and fix the reproduction angle by a predetermined angle on the basis of standard reproduction angle corresponding to the standard angle record plane, wherein the control device calibrates the reproduction angle change device on the basis of the angle standard identification information. 9. The angle-multiplex type hologram reproduction apparatus according to claim 8, further comprising: a move device for moving the hologram recording medium relative to a focus position of the reproduction illumination light. 10. The angle-multiplex type hologram reproduction apparatus according to claim 9, wherein the read device performs reproduction to all angle record planes of the hologram recording medium, every time of moving by the move device. 11. An angle-multiplex type hologram recording method in an angle-multiplex type hologram recording apparatus comprising: a light source for performing an irradiation with source light including signal light and reference light; a spatial light modulator disposed in an optical path of the signal light, for modulating the signal light; an optical system for introducing the signal light passed through the spatial light modulator and the reference light onto the hologram recording medium; and a record angle change device for relatively changing a record angle of the hologram recording medium relative to the signal light and the reference light, said method comprising: a set process of setting the record angle when a specific angle record plane from among a plurality of angle record planes of the hologram recording medium is recorded, as a standard record angle; and a control process of controlling the record angle change device so as to change and fix the record angle after then by a predetermined angle from the set standard record angle. 12. The angle-multiplex type hologram recording method according to claim 11, wherein the specific angle record plane is an angle record plane to be firstly recorded from among the plurality of angle record planes. 13. An angle-multiplex type hologram reproduction method in an angle-multiplex type hologram reproduction apparatus for reproducing the recorded information from the angle-multiplex type hologram recording medium in which angle standard identification information indicating a standard angle record plane is recorded onto one of a plurality of angle record planes, said reproduction apparatus comprising: a light source for irradiating the hologram recording medium with reproduction illumination light; a photoreceptor for receiving reproduction light based on the reproduction illumination light from the hologram recording medium; a read device for reading respectively the plurality of recorded information overlappingly recorded onto the hologram recording medium, on the basis of the received reproduction light; and a reproduction angle change device for changing a reproduction angle of the hologram recording medium relative to the reproduction illumination light, said method comprising: a calibration process of calibrating the reproduction angle change device on the basis of the angle standard identification information; and a control process of controlling the reproduction angle change device so as to change and fix the reproduction angle by a predetermined angle on the basis of standard reproduction angle corresponding to the standard angle record plane.
TECHNICAL FIELD The present invention relates to a hologram recording apparatus for and method of irradiating a hologram recording medium with signal light via a spatial light modulator to recording information and a hologram reproduction apparatus for and method of reproducing the information from the hologram recorded medium. Particularly, it relates to an angle-multiplex type hologram recording apparatus for and method of, as well as a hologram reproduction apparatus for and method of, recording different record informations overlappingly in the same area by relatively changing angles of the signal light and reference light relative to a surface of the hologram recording medium, and then reproducing the multiplex-recorded information. BACKGROUND ART Heretofore, a hologram recording apparatus, which may be provided with a liquid crystal device and the like, irradiates a spatial light modulator for modulating light depending on record information to be recorded, with laser light as signal light. Particularly, in the spatial light modulator, cells are arranged planarly in a matrix so that the signal light is modulated by changing transmittance of each cell depending on the record information. Furthermore, the modulated signal light is outputted with different output angles, as a plurality of diffraction light, such as 0th-order light, or 1st-order light and so on, due to diffraction phenomenon in the cell having a fine pitch. In this case, the output angle is defined by the cell pitch, which indicates an modulation unit. Then, the signal light modulated with the spatial light modulator constructed as above and reference light not passed through the spatial light modulator are interfered on the hologram recording medium. Thereby, the recording information is recorded as a wavefront on the hologram recording medium. An angle-multiplex type hologram recording apparatus is proposed for multiplex recording different information in the same area, by changing little by little a surface angle of the hologram recording medium relative to the reference light and the signal light, particularly during recording. In the present application, the angle of the signal light relative to the hologram recording medium surface in such an angle-multiplex type recording is referred to as a “record angle” as appropriate. Furthermore, an angle as a standard of the record angle, such as the record angle when it corresponds to a normal line of the hologram recording medium surface, is referred to as a “standard record angle”. Still further, in the present application, each record plane corresponding to each record angle is referred to as an “angle record plane”, and a record plane corresponding to the standard record angle is referred to as a “standard angle record plane”. On the other hand, a hologram reproduction apparatus consisting a pair with the hologram recording apparatus is designed to reproduce the recorded multiplex information in the same area, by changing little by little the surface angle of the hologram recording medium relative to the reproduction illumination light. In the present application, the angle of the reproduction light relative to the hologram recording medium surface in such an angle-multiplex type reproduction is referred to as a “reproduction angle” as appropriate. Furthermore, an angle as a standard of the reproduction angle, such as the reproduction angle when it corresponds to a normal line of the hologram recording medium, is referred to as a “standard reproduction angle”. In the angle-multiplex type hologram recording apparatus, recording to each angle record plane in the same record area are successively performed for each record angle, by changing the record angle in the maximum range with increment or decrement 0.01 degree from the standard record angle (e.g. by changing little by little in the range of 88-92 degree). Incidentally, in the present application, an area on the hologram recording medium surface onto which the signal light and the reference light are irradiated together is referred to as a “record area”. In the angle-multiplex type recording, a plurality of angle record planes such as 50 planes is recorded in the same record area. On the other hand, in the angle-multiplex type hologram reproduction apparatus, the recorded multiplex information in the same area is reproduced for each reproduction angle, by changing little by little the reproduction angle from the standard reproduction angle in response to the record angle. Thus, in the angle-multiplex type hologram recording apparatus and hologram reproduction apparatus, the record information can be recorded respectively on a plurality of angle record planes recorded for each record angle in the same record area, and the recorded information can be reproduced respectively. Therefore, recording density and recording capacity are expected to be remarkably increased. DISCLOSURE OF INVENTION However, generally in the hologram recording, angle selectivity is very high. For this, in the case that the recording (additional recording, tsui-ki) or reproduction is performed to the same hologram recording medium (e.g. a removable recording medium) by means of different pieces of the hologram recording apparatus, hologram record/reproduction apparatus or hologram reproduction apparatus in the same type, the set condition or mechanical state of the optical system, the mechanism for fixing the hologram recording medium according to the aforementioned standard record angle or standard reproduction angle, or the like, is not always the same in each apparatus, because of variations among pieces. For example, depending on variations among pieces, the standard angle record plane recorded as correspondent to the standard record angle in one apparatus does not actually correspond to the set condition or mechanical state of the optical system, the mechanism and the like expected to correspond to the standard record angle and standard reproduction angle in another apparatus. That is, under such a mechanical state or set condition, another angle record plane different from the standard angle record plane may be adversely recognized as the standard angle record plane. Alternatively, because of mis-recognizing the standard angle, the recording may be adversely performed to the angle record plane different from the to-be-recorded (additionally recorded) angle record plane, the angle record plane different from the to-be-reproduced angle record plane may be adversely reproduced, otherwise the reproduction becomes impossible due to the non-correspondence between the record angle and the reproduction angle. The present invention has been accomplished in view of above problems. It is therefore an object of the present invention to provide a hologram recording apparatus and method, as well as a hologram reproduction apparatus and method, capable of improving the record density and the record capacity, and capable of performing the recording operation or reproduction operation accurately and quickly. In order to solve the above problems, an angle-multiplex type hologram recording apparatus of the present invention is provided with a light source for performing an irradiation with source light including signal light and reference light; a spatial light modulator disposed in an optical path of the signal light, for modulating the signal light; an optical system for introducing the signal light passed through the spatial light modulator and the reference light onto a hologram recording medium; a record angle change device for relatively changing a record angle of the hologram recording medium relative to the signal light and the reference light; and a control device for controlling the record angle change device to set the record angle when a specific angle record plane is recorded from among a plurality of angle record plane s on the hologram recording medium as a standard record angle, and to change and fix the record angle after then by a predetermined angle from the set standard record angle. According to the hologram recording apparatus of the present invention, during the operation, the record light source such as the semiconductor laser device performs the irradiation with the source light such as laser light. The source light includes the signal light and the reference light. Here, the spatial light modulator, consisting of a liquid crystal device or the like for example, disposed in the optical path of the signal light, modulates the signal light. Then, the optical system introduces the modulated signal light and the reference light onto the hologram recording medium. As the result, the record information is recorded as a wavefront onto the hologram recording medium, due to the interference between the signal light and the reference light. Incidentally, the signal light and the reference light included in the source light may be split from each other by the optical system such as a beam splitter and then the signal light may be introduced to enter the spatial light modulator and the reference light may be introduced not to enter the spatial light modulator. Alternatively, the signal light and the reference light included in the source light may be introduced to enter the spatial light modulator without split from each other. In the latter case, Fourier 0th-order component of the signal light outputted from the spatial light modulator may be functioned as the reference light, for example by employing a so-called “self-coupling scheme”. In this case, the reference light may not have the phase information. Particularly in this case, the control device sets, as the standard record angle, the record angle when a specific angle record plane such as the first angle record plane is recorded. Then, the record angle change device changes and fixes the record angle, after the specific angle record plane is recorded, by a predetermined angle on the basis of the set standard record angle, under control of the control device. Therefore, it is possible to coincide the standard record angle defined by the set condition or mechanical state of the optical system, the record angle change device and the like at the hologram recording apparatus side, with the standard record angle at the hologram recording medium side, at a specific time point in the recording such as the first time of the recording or the like. That is, even in the case that they are used for different hologram recording apparatuses of the same type, it is possible to coincide them with each other at a specific time point in the recording for each hologram recording apparatus independent of variations among pieces. Furthermore, after then, the recording can be performed accurately to the angle record plane for any record angle, on the basis of the standard record angle set at the specific time point for each hologram recording apparatus. Here, for a comparison, it is assumed a case that the actual recording (additional recording) or reproduction is performed after confirming that the recording (additional recording) or reproduction is to be performed to any angle record plane every time when the angle is changed, by recording in advance the angle information indicating the record angle for each angle record plane and by referring to the angle information when the recording (additional recording) or reproduction is performed. In this case, since the task for confirming which angle record plane is caused every time when the record angle is changed, a quick record operation is difficult. The record capacity for the desired record information, such as contents information, to be actually recorded is reduced, because the angle information and the like are recorded. On the contrary, the hologram recording apparatus of the present invention allows the subsequent quick angle change and the record operation, on the basis of the standard record angle set at the specific record time. Thus, according to the present invention, the angle-multiplex system remarkably improves the record density and the record capacity and further allows performing the angle-multiplex type recording accurately independent of variations among pieces, as well as performing record operation quickly. Incidentally, in the present invention, the spatial light modulator may perform binary modulation depending on binary data indicated by the record information. Thereby, the record information indicating the binary data can be recorded at high density onto the hologram recording medium. Alternatively, multi-level modulation may be performed depending on gray scale data indicated by the record information. Thereby, the record information indicating the gray scale data can be recorded at high density onto the hologram recording medium. Furthermore, in the present invention, the modulated signal light outputted from the spatial light modulator comprising at least one of the diffraction 0th-order light and the diffraction L-order light (L is natural number not less than 1). For example, the hologram recording at high density can be performed by using only the 0th-order light from among the diffraction light, or using the 0th-order light and one or more higher-order lights such as the 1st-order light. Additionally, at least one of reference light phase-code-multiplex system for performing multiplex-recordings with various phases of the reference light, reference light amplitude-multiplex system for performing multiplex-recordings with various amplitudes of the reference light, reference light polarization-multiplex system for performing multiplex-recordings with various polarizations of the reference light, and focal-depth-multiplex system for performing multiplex-recordings with various focal depths of the signal light entering the hologram recording medium may be combined to the aforementioned angle-multiplex type hologram recording apparatus of the present invention. Thereby, a hologram recording at still higher density is performable. In an aspect of the angle-multiplex type hologram recording apparatuses according to the present invention, the spatial light modulator records angle standard identification information indicating a standard angle record plane corresponding to the standard record angle onto the specific angle record plane, if the hologram recording medium is not recorded. According to this aspect, if the hologram recording medium is not recorded, the spatial light modulator records the angle standard identification information to the specific angle record plane. Therefore, then, on the basis of the angle standard identification information, it can be easily recognized that the standard record angle is already set to the hologram recording medium and it can be identified which angle record plane is the standard angle record plane regardless of the difference among the hologram recording apparatuses. In another aspect of the angle-multiplex type hologram recording apparatus according to the present invention, the control device calibrates the record angle change device on the basis of the angle standard identification information, if record information has been recorded at least on the specific angle record plane of the hologram recording medium. According to this aspect, in the case that the record information is recorded to another angle record plane after the recording is performed to the specific angle record plane, the control device firstly calibrates the record angle change device on the basis of the angle standard identification information. More specifically, for example, the record angle change device detects the angle difference between the angle record plane corresponding to the set condition of the optical system, mechanical state or the like of the record angle change device at the present recording expected to correspond to the standard record angle, and the standard angle record plane indicated by the angle standard identification information, and then offsets by the detected angle difference to change the record angle. Thereby, the record information can be recorded (additionally recorded) accurately for any angle record plane, because the changes, such as the time-lapse change of the set condition of the optical system, the mechanical state or the like, the change in the setting angle or the loading of the hologram recording medium, are calibrated by the offset, even if the changes are significantly big relative to the angle selectivity of the hologram recording medium. Alternatively, in another aspect of the angle-multiplex type hologram recording apparatus according to the present invention, angle standard identification information indicating standard angle record plane corresponding to the standard record angle is recorded onto at least one of a plurality of angle record plane 8 of the hologram recording medium, and the control device calibrates the record angle change device on the basis of the angle standard identification information. According to this aspect, in the case that the recording is performed to the hologram recording medium having the angle record plane for which the recording is already performed and the angle standard identification information is recorded, the control device calibrates the record angle change device on the basis of the angle standard identification information. More specifically, for example, the record angle change device detects the angle difference between the standard angle record plane indicated by the angle standard identification information and the angle record plane corresponding to the set condition of the optical system, the mechanical state or the like expected to correspond to the standard record angle of the record angle change device at the present recording, and then offsets by the detected angle difference, to change and fix the record angle. Thereby, the record information can be recorded (additionally recorded) accurately by means of the hologram recording apparatus for the present recording, because the changes are offset even if the set condition of the optical system, mechanical state or the like of the record angle change device is not the same between the hologram recording apparatus for the present recording and another hologram recording apparatus for the first recording to the standard angle plane. In another aspect of the angle-multiplex type hologram recording apparatus according to the present invention, the apparatus further comprises a move device for moving the hologram recording medium relative to a focus position of the reference light and the signal light introduced by the optical system. According to this aspect, the move device relatively moves the hologram recording medium, when the recording to one or more angle record planes by angle-multiplex system in one record area onto which the signal light and the reference light are focused is completed. Thereby, the signal light and the reference light are focused onto another record area, and the recording is similarly performed to a plurality of angle record planes for another record area. In this aspect, it may be arranged that the spatial light modulator performs recording to all angle record planes of the hologram recording medium every time of moving by the move device. In this arrangement, the number of times or displacement for the moving by the move device can be restricted to the small extent. Furthermore, the changes in the set condition of the mechanical state of the optical system, the record angle change device and the like, which may be caused by the displacement by the move device, can be restricted to the minimum extent. Incidentally, the move device may perform the moving, before the recording to all the angle record planes in one record area is completed. Alternatively, the move device may perform the moving, every time when the recording to one angle record plane in one record area is completed. In another aspect of the angle-multiplex type hologram recording apparatus according to the present invention, the specific angle record plane is a first angle record plane to be firstly recorded from among the plurality of angle record planes. According to this aspect, the record angle when the first angle record plane of the hologram recording medium is recorded is set as the standard record angle. Therefore, the recording can be performed accurately to the angle record plane for any record angle, on the basis of the standard record angle set at the first recording. In order to solve the above problems, a hologram reproduction apparatus of the present invention is the apparatus for reproducing recorded information from an angle-multiplex type hologram recording medium in which angle standard identification information indicating a standard angle record plane is recorded onto one of a plurality of angle record planes, is provided with: a light source for irradiating the hologram recording medium with reproduction illumination light; a photoreceptor for receiving reproduction light based on the reproduction illumination light from the hologram recording medium; a read device for reading respectively the plurality of record information overlappingly recorded onto the hologram recording medium, on the basis of the received reproduction light; a reproduction angle change device for changing a reproduction angle of the hologram recording medium relative to the reproduction illumination light; and a control device for controlling the reproduction angle change device so as to change and fix the reproduction angle by a predetermined angle on the basis of standard reproduction angle corresponding to the standard angle record plane, wherein the control device calibrates the reproduction angle change device on the basis of the angle standard identification information. According to the angle-multiplex type hologram reproduction apparatus of the invention, during the operation, the light source such as the semiconductor laser irradiates the reproduction illumination light such as laser beam. Then, the photoreceptor, including a photodiode array, a CCD (Charge Coupled Device) and the like, receives the reproduction light based on the reproduction illumination light from the hologram recording medium. The “reproduction light” herein means the 0th-order light or the higher-order light such as the 1st-order light, caused when the reproduction illumination light corresponding to the reference light for the recording is irradiated onto the hologram recording medium. Then, on the basis of the reproduction light received by the photoreceptor, the read device reads, for each angle record plane, a plurality of record information recorded onto each record plane. Particularly in this case, the control device calibrates the reproduction angle change device on the basis of the angle standard identification information read from the hologram recording medium. Then, the reproduction angle change device changes and fixes each reproduction angle by a predetermined angle on the basis of the standard reproduction angle, under control of the control device. More specifically, for example, the reproduction angle change device detects the angle difference between the angle record plane corresponding to the set condition of the optical system, the mechanical state or the like expected to correspond to the standard reproduction angle of the reproduction angle change device at the present reproduction, and the standard angle record plane indicated by the angle standard identification information. Then, the reproduction angle change device offsets by the detected angle difference to change and fix the reproduction angle. Thereby, the recorded information can be reproduced accurately by means of the hologram reproduction apparatus for the present reproduction, because the change is calibrated by the offset even if the set condition of the optical system, the mechanical state or the like of the reproduction angle change device and the record angle change device is not the same among the hologram reproduction apparatus for the present record and another apparatus used for the first recording onto the standard angle record plane. For a purpose of comparison, it is assumed a case that the angle information indicating the record angle is recorded in advance onto the hologram recording medium for each angle record plane, and it is confirmed which angle record plane is to be performed every time when the angle is changed, with reference to firstly the angle information when the reproduction is performed for each angle record plane, and then the reproduction is actually performed. In this case, sine the operation for confirming which angle record plane is caused every time when the reproduction angle is changed, it is difficult to perform the reproduction operation quickly. On the contrary, the hologram reproduction apparatus of the present invention performs the calibration on the basis of the angle standard identification information and allows the subsequent prompt angle change and the prompt reproduction operation. Thus, according to the present invention, the record density and the record capacity can be remarkably improved due to the angle-multiplex system, and the angle-multiplex type reproduction is performable accurately regardless of variations among apparatuses, and the quick reproduction operation is also allowed. Additionally, at least one of reference light phase-code-multiplex system for performing multiplex-recordings with various phases of the reference light, reference light amplitude-multiplex system for performing multiplex-recordings with various amplitudes of the reference light, reference light polarization-multiplex system for performing multiplex-recordings with various polarizations of the reference light and focal-depth-multiplex system for performing multiplex-recordings with various focal depths of the signal light entering the hologram recording medium may be incorporated into the aforementioned angle-multiplex type hologram reproduction apparatus of the present invention. Thereby, the hologram reproduction can be performed at still higher density. In another aspect of the hologram reproduction apparatus according to the present invention, the apparatus further comprises: a move device for moving the hologram recording medium relative to a focus position of the reproduction illumination light. According to this aspect, when the reproduction to one or more angle record planes is completed by the angle-multiplex system, for one record area onto which the reproduction illumination light is focused, the move device relatively moves the hologram recording medium. Thereby, the reproduction illumination light is focused onto another record area, and the reproduction is similarly performed to a plurality of angle record planes for said another record area. In this aspect, it may be arranged that the read device performs reproduction to all angle record planes of the hologram recording medium, every time of moving by the move device. In this arrangement, the number of times or displacement for the moving by the move device can be restricted to the small extent. Furthermore, the changes in the set condition of the mechanical state of the optical system, the reproduction angle change device and the like, which may be caused by the displacement by the move device, can be restricted to the minimum extent. Incidentally, the move device may perform the moving, before the reproduction is completed for all the angle record planes in one record area. Alternatively, the move device may perform the moving, every time when the reproduction is completed to one angle record plane in one record area. In order to solve the above problems, a hologram recording method of the present invention is the method of recording information on a hologram recording medium in an angle-multiplex type hologram recording apparatus comprising: a light source for performing an irradiation with source light including signal light and reference light; a spatial light modulator disposed in an optical path of the signal light, for modulating the signal light; an optical system for introducing the signal light passed through the spatial light modulator and the reference light onto the hologram recording medium; and a record angle change device for relatively changing a record angle of the hologram recording medium relative to the signal light and the reference light. The method is provided with: a set process of setting the record angle when a specific angle record plane from among a plurality of angle record planes of the hologram recording medium is recorded, as a standard record angle; and a control process of controlling the record angle change device so as to change and fix the record angle after then by a predetermined angle from the set standard record angle. According to the angle-multiplex type hologram recording method, similarly to the aforementioned hologram recording apparatus of the present invention, the record density and the record capacity can be remarkably improved by the angle-multiplex system, and the angle-multiplex type recording can be performed accurately regardless of variations among apparatuses, and the quick record operation is also allowed. In an aspect of the angle-multiplex type hologram recording method according to the present invention, the specific angle record plane is a first angle record plane to be firstly recorded from among the plurality of angle record planes. According to this aspect, the record angle when the first angle record plane of the hologram recording medium is recorded is set as the standard record angle. Therefore, the recording can be performed accurately to the angle record plane for any record angle, on the basis of the standard record angle sot at the first recording. In order to solve the above problems, an angle-multiplex type hologram reproduction method of the present invention is the method of reproducing recorded information from an angle-multiplex type hologram recording medium in an angle-multiplex type hologram reproduction apparatus for reproducing the recorded information from the angle-multiplex type hologram recording medium in which angle standard identification information indicating a standard angle record plane is recorded onto one of a plurality of angle record planes, said reproduction apparatus comprising: a light source for irradiating the hologram recording medium with reproduction illumination light; a photoreceptor for receiving reproduction light based on the reproduction illumination light from the hologram recording medium; a read device for reading respectively the plurality of record information overlappingly recorded onto the hologram recording medium, on the basis of the received reproduction light; and a reproduction angle change device for changing a reproduction angle of the hologram recording medium relative to the reproduction illumination light. The method is provided with: a calibration process of calibrating the reproduction angle change device on the basis of the angle standard identification information; and a control process of controlling the reproduction angle change device so as to change and fix the reproduction angle by a predetermined angle on the basis of standard reproduction angle corresponding to the standard angle record plane. According to the angle-multiplex type hologram reproduction method of the present invention, similarly to the aforementioned hologram reproduction apparatus, the record density and the record capacity can be remarkably improved by the angle-multiplex system, and the angle-multiplex type reproduction can be performed accurately regardless of variations among apparatuses, and the quick reproduction operation is also allowed The above effects and other advantages of the present invention will be more apparent from the following explanation. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a block diagram illustrating an entire configuration of the first embodiment of the hologram recording apparatus of the present invention. FIG. 2 is a perspective view schematically illustrating the spatial light modulator employed in the first embodiment. FIG. 3 is a flow chart illustrating the angle-multiplex type record operation in the first embodiment. FIG. 4 is a flow chart illustrating the angle-multiplex type record operation in the second embodiment of the hologram recording apparatus of the present invention. FIG. 5 is a block diagram illustrating an entire configuration of an embodiment of the hologram reproduction apparatus of the present invention. FIG. 6 is a flow chart illustrating the angle-multiplex type reproduction operation in an embodiment of hologram reproduction apparatus of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION Now, embodiments of the present invention will be explained, with reference to drawings. FIRST EMBODIMENT OF HOLOGRAM RECORDING APPARATUS The first embodiment of the hologram recording apparatus of the present invention will be discussed, with reference to FIG. 1 to FIG. 3. Firstly, with reference to FIG. 1 and FIG. 2, the entire configuration of the hologram recording apparatus of the present invention will be discussed. FIG. 1 illustrates the entire configuration of the hologram recording apparatus of the present invention. FIG. 2 illustrates schematically and perspectively the spatial light modulator employed in the embodiment. As shown in FIG. 1, the hologram recording apparatus 100 in this embodiment is provided with: a laser device 11 as one example of the light source for emitting the source light L0 made of laser beam; a beam splitter 12 as one example of the optical system for splitting the source light L0 into the signal light L1 and the reference light L2; a lens 13 as one example of the enlarge optical system disposed in an optical path of the signal light L1, for enlarging a diameter of the signal light L1; a lens 14 such as a collimator lens for converting the signal light L1 outputted from the lens 13 into an approximately parallel light; a spatial light modulator 15 for modulating the signal light L1 outputted from the lens 14 in response to the recording signal to be recorded and for outputting the modulated light as the modulated signal light L3; and a lens 16 as one example of the demagnifying optical system for reducing a diameter of the signal light L3 and outputting narrowed signal light onto the hologram recording medium 200. The hologram recording apparatus 100 is further provided with: a mirror 17 as one example of the optical system for introducing the reference light L2 split by the beam splitter 12 onto the hologram recording medium 200, at the focus position where the signal light L3 corresponding to the reference light L2 is focused. Incidentally, in FIG. 1, a surface part C1 of the hologram recording medium 200 onto which the signal light L3 including the 0th-order light and four 1st-order lights diffracted by the spatial light modulator 15 is focused is enlarged. As shown in FIG. 2, the spatial light modulator 15 is made of, for example, a liquid crystal device, and divided into a plurality of cells 152. The cell 152 is the unit of the modulation. The spatial light modulator 15 can perform the modulation in each cell 152. For example, if the spatial light modulator 15 is an active matrix drive type liquid crystal device, the plurality of cells 152 is defined in response to a plurality of pixel electrodes two-dimensionally arrayed in a matrix. If the signal light L1 is introduced, the spatial light modulator 15 outputs the signal light L3 made of the modulated diffraction light including the 0th-order diffraction light L3-0 and the higher order diffraction light such as the 1st-order diffraction light L3-1, the 2nd-order diffraction light L3-2, . . . , due to the diffraction depending on a size of the cell 152. In FIG. 1 again, the hologram recording apparatus 100 is further provided with: a record angle change device 19 for changing little by little and fixing the angles of the signal light L3 and the reference light L2 relative to the surface of the hologram recording medium 200; and a control device 18 for controlling the record angle change device 19 so that the signal light L3 has the record angle corresponding to the angle record plane where the recording is performed on the hologram recording medium 200. Incidentally, in this embodiment, an angle formed by an optical axis of the signal light L3 and the surface of the hologram recording medium 200 is defined as a “record angle”. The record angle change device 19 has the function of changing relatively the record angle of the signal light L3 relative to the surface of the hologram recording medium 200. The function can be achieved, for example, by changing the angles or positions of the constitutional elements in the optical system, such as the laser device 11; the beam splitter 12; the lenses 13, 14 and 16; and the spatial light modulator 15, relative to each optical axis. Alternatively, the function can be also achieved by adding a special optical element for changing the angle of the signal light L3 or the reference light L2 to the optical system. Alternatively, the function can be achieved by mechanically changing a hold angle of the hologram recording medium 200. The angle change operation of the record angle change device 19 is controlled by the control device 18 so as to be part of a series of recording operation as discussed later. The control device 18 may include a controller comprising a microprocessor and the like, and is adapted to generate and output the control signal S1 in response to the record information and the like to be recorded onto the hologram recording medium 200, control the record angle by controlling the record angle change device 19, supply the record signal Sd corresponding to the record information to the spatial light modulator 15, and control the modulation of the spatial light modulator 15, The hologram recording apparatus 100 is further provided with: a lens 24a for focusing the reproduction light L12 which is based on the reproduction illumination light and which is obtained from the hologram recording medium 200; a photoreceptor 25a for receiving the reproduction light L12 via the lens 24a; and a read device 26a for reading a plurality of record information overlappingly recorded on the hologram recording medium 200, on the basis of the received reproduction light L12, i.e. on the basis of the receive signal Sr outputted from the photoreceptor 25a. In this embodiment, the reference light L2 can be directly used as the reproduction illumination light by cutting the signal light L1 or LS before the signal light L1 or LS reaches the hologram recording medium 200. For example, the signal light L1 or L3 can be shut out by using the spatial light modulator 15 as a shutter for shutting out the signal light L1 under control of the control device 18. Alternatively, it is possible to employ an arrangement for additionally disposing a special optical element in an optical path of the signal light L1 or L3 to shut out the signal light L1 or L3, or an arrangement for selectively inserting a light shield member in an optical path of the signal light L1 or L3. The photoreceptor 25a for receiving via the lens 24a the reproduction light L12 generated as such may include a photodiode array, a CCD (Charge Coupled Device) and the like. The read device 26a reads each recorded information by identifying the recorded information corresponding to a light-dark pattern of the received reproduction light L12. Particularly in this embodiment, an angle standard signal Sa is written in the standard angle record plane. The angle standard signal Sa is one example of the identification information for indicating the standard angle record plane corresponding to the standard record angle from among the plurality of the angle record planes on the hologram recording medium 200. The read device 26a can read the angle standard signal Sa from the standard angle record plane. The read device 26a is adapted to read the angle standard signal Sa and then output the read signal Sa to the control device 18. Particularly in this embodiment, the control device 18 sets, as the standard record angle, a record angle when the first angle record plane is recorded. The first angle record plane is one example of a specific angle record plane of the hologram recording medium 200. After the first angle record plane is recorded, the record angle change device 19 changes and then fixes the record angle by a predetermined angle on the basis of the predetermined standard record angle, under control of the control device 18. Furthermore, in the case that the hologram recording medium 200 is judged to be unrecorded by existence or inexistence of the angle standard signal Sa from the read device 26a, the control device 18 controls the spatial light modulator 15 so that the first angle record plane is set as the standard angle record plane, and further the angle standard signal Sa for indicating the standard angle record plane corresponding to the standard record angle is recorded to the first angle record plane. Then, on the basis of the angle standard signal Sa, it can be readily recognized that the standard record angle is already set to the hologram recording medium 200. Furthermore, by using the read device 26a, it is readily identified which angle record plane is the standard angle record plane, regardless whether the hologram recording medium 200 to be used for the recording is the same or different, or whether the hologram recording apparatus 100 to be used for the recording is the same or different. Furthermore, with regard to the hologram recording medium 200 after the record information is recorded onto the first angle record plane, the control device 18 calibrates the record angle change device 19 on the basis of the standard record angle indicated by the angle standard signal Sa. That is, when the first angle record plane is recorded, the first angle record plane is set as the standard angle record plane and the record angle change device 19 is not calibrated. Then, when any other angle record plane is recorded, the record angle change device 19 is calibrated, in response to the standard record angle corresponding to the standard angle record plane indicated by the angle standard signal Sa. More specifically, for example, a difference between the standard record angle corresponding to the standard angle record plane indicated by the angle standard signal Sa and the record angle under a setting condition of the optical system or mechanical state expected to correspond to the standard record angle in the record angle change device 19 at the time point of presently recording is detected. Furthermore, the record angle change device 19 is adapted to change the record angle by offsetting the detected difference of angle. Furthermore, also in the case that the angle standard signal Sa is recorded onto the hologram recording medium 200 by another hologram recording apparatus from the first, the control device 18 is adapted to calibrate the record angle change device 19 on the basis of the standard record angle indicated by the angle standard signal Sa. Additionally, the hologram recording apparatus 100 is further provided with a move device 20 for moving the focus position where the signal light L3 and the reference light L2 are focused relative to the surface of the hologram recording medium 200, in a direction along the surface. The move device 20 may move the focus position by changing the angle or position of the optical system such as the lens 16. Alternatively, it may move the focus position by changing the angle or position of another optical system such as the laser device 11, or by additionally disposing a special optical system (e.g. a mirror having variable dispose angles) in optical paths of the signal light L1 or L3 and the reference light L2. Furthermore, it may include a hologram recording medium holding mechanism to move the hologram recording medium 200 itself mechanically in a direction along its surface. The moving by the move device 20 is also controlled by the control signal S2 generated at and outputted from the control device 18, so that the moving is a part of a series of recording as mentioned later. Next, with reference to FIG. 1, the fundamental recording of the hologram recording apparatus 100 in this embodiment configured as mentioned above is explained. During its operation, the laser device 11 emits the source light L0, the beam splitter 12 splits the source light L0 into the signal light L1 and the reference light L2. Then, the signal light L1 is regulated into a diameter matched with a size of the spatial light modulator 15 via the lenses 13 and 14, and introduced into the spatial light modulator 15. Then, the spatial light modulator 15, under control of the control device 18, modulates the signal light L1 by a modulation unit of each cell 152, in response to each of a plurality of record information to be recorded. Then, the modulated signal light L3 is focused by the lens 16. Then, the record area of the hologram recording medium 200 is irradiated with the modulated and focused signal light L3 and the reference light L2 reflected at the mirror 17. Then, these lights interfere with each other, so that the record information to be recorded is holographically recorded as a wavefront. Due to the fundamental recording as mentioned above, the record information is recorded to one angle record plane for one record angle in one record area which is irradiated with the signal light L3 and the reference light L2 at the same time. Next, the detail of angle-multiplex type record operation of the hologram recording apparatus 100 in this embodiment for performing this recording for a plurality of angle record planes and further for a plurality of record areas will be explained with reference to FIG. 3. FIG. 3 is a flow chart illustrating the record operation. In FIG. 3, firstly the signal light L3 is shut out and the reference light L2 is used as the reproduction illumination light, and then the reproduction light L12 is received at the photoreceptor 25a. In response to this, the angle standard signal Sa outputted from the read device 26a is checked by the control device 18 (step S11). Then, depending on the existence or inexistence of the angle standard signal Sa, whether or not it is the first recording relative to the hologram recording medium 200 is judged by the control device 18 (step S12). At this stage, if it is the first recording (step S12: Yes), the signal light L3 and the reference light L2 are used, and the modulation is performed by the spatial light modulator 15 on the basis of the record signal Sd indicating the angle standard signal Sa so that the angle standard signal Sa is recorded. Since the angle record plane is the standard record plane at this time, the recording is performed to the standard record plane of the hologram recording medium 200 (step S13). On the other hand, as the result of the judgment at step S12, if it is not the first recording (step S12: No), the current record angle fixed by the record angle change device 19 is checked, and it is recorded into for example a built-in memory of the control device 18 (step S14). Furthermore, the record angle change device 19 is calibrated on the basis of difference between the standard record angle corresponding to the standard angle record plane indicated by the angle standard signal Sa and the current record angle under the fixed state (step S15). This calibration is performed, for example, by offsetting the aforementioned difference of angle in the control signal S1 that is inputted into the record angle change device 19. Next to processes at steps S13 and S15, the control device 18 judges whether or not the data recording of the record information is to be performed to the current angle record plane fixed by the record angle change device 19 in the current record area (i.e. an area irradiated with the signal light L3 and the reference light L2 at this time) of the hologram recording medium 200 fixed by the move device 20 (step S16). If the data recording is not to be performed (step S16: No), the process flow ends. That is, in this case, it can be said that checking the angle standard signal Sa (step S11), recording the angle standard signal Sa (step S13) and so on are effectively performed. On the other hand, as the result of the judgment at step S16, if the data recording is to be performed (step S16: Yes), the irradiation with the signal light LS and the reference light L2 is performed and the signal light L3 is modulated by the spatial light modulator 15 in response to the record signal Sd, so that the data recording is actually performed (step S17). Next, the control device 18 judges whether or not the data recording of the record information is to be performed to the next angle record plane changeable by the record angle change device 19 in the current record area of the hologram recording medium 200 fixed by the move device 20 (step S18). If the data recording is to be performed to the next angle record plane (step S18: Yes), the record angle change device 19 changes the record angle by a predetermined fine angle (e.g. 0.01 degree) under control of the control signal S1 (step S19). In this case, as mentioned above, since the record angle change device 19 is calibrated on the basis of the standard record angle, it is possible to change accurately the record angle. Then, the process flow goes back to step S16 and then repeats the processes after step S16. On the other hand, as the result of the judgment at step S18, if the data recording is not to be performed to the next angle record plane (step S18: No), the control device 18 judges whether or not the data recording of the record information is to be performed to another record area changeable by the move device 20 (step S20). If the data recording is to be performed to another record area (step S20: Yes), the record angle change device 19 resets the record angle to be changed and fixed, under control of the control signal S1. That is, the record angle change device 19 changes and fixes the record angle so that the record angle is adapted to the first angle record plane of the next record area (step S21). In this case, as mentioned above, since the record angle change device 19 is calibrated on the basis of the standard record angle, the record angle can be reset accurately, and the record angle can be changed accurately after the reset. Next, under control of the control signal S2, the move device 20 moves an area, which is irradiated with the signal light L3 and the reference light L2, by a predetermined distance to be another record area (step S22). Then, the process goes back to step S16 to repeat the following processes. On the other hand, as the result of the judgment at step S20, if the data recording is not to be performed to another record area (step S20; No), a series of recording operations ends. Thus, the multiplex recordings of the record information to a plurality of angle record planes in a plurality of record areas complete. As explained above, in this embodiment, the control device 18 sets, as the standard record angle, the record angle for recording the first angle record plane of the hologram recording medium 200. After the first angle record plane is recorded, the record angle change device 19 changes and fixes the record angle by a predetermined fine angle, from the set standard record angle, under control of the control device 18. Therefore, the record angle expected to correspond to the standard record angle defined at the hologram recording apparatus 100 side, i.e. by the set condition or mechanical state of the optical system and the like including the record angle change device 19, the laser device 11, the beam splitter 12, lenses 13, 14 and 16 can be coincided with the standard record angle at the hologram recording medium 200 side, at the first recording. That is, these angles can be coincided with each other, regardless of variations in apparatuses, even in the case that any of the same types and different hologram recording apparatuses 100 is used. Furthermore, after then, on the basis of the standard record angle, any record angle can be recorded onto the angle record plane quickly and accurately. As explained above, the hologram recording apparatus 100 in this embodiment can perform the angle-multiplex type hologram record. In this embodiment, however, any recorded multiplex information onto the hologram recording medium 200 in the angle-multiplex system can be reproduced using the lens 24a, the photoreceptor 25a and the read device 26a, by shutting out the signal light L1 or L3 and by using the reference light L2 as the reproduction illumination light. That is, in the configuration of the first embodiment shown in FIG. 1, if, on recording and on reproduction, the signal L1 or L3 is shut out, and the reproduction operation the same as the hologram reproduction apparatus mentioned later is performed by the lens 24a, the photoreceptor 25a, the read device 26a and the control device 18, the hologram recording apparatus 100 in this embodiment can be configured as the hologram record and reproduction apparatus capable of performing the recording and reproduction. In the embodiment mentioned above, the spatial light modulator 15 may binarily modulate the signal light L3 in response to binary data indicated by the record information, or may multilevel-modulate the signal light L3 in response to gray scale data indicated by the record information. Incidentally, a material for the hologram recording medium may be a known inorganic material or organic material (polymer material). Furthermore, the hologram recording medium may be in a form of card-like medium, or a disc-like medium. SECOND EMBODIMENT OF HOLOGRAM RECORDING APPARATUS The second embodiment of the hologram recording apparatus according to the present invention will be discussed, with reference to FIG. 4. FIG. 4 is a flow chart illustrating the record operation of the hologram recording apparatus in the second embodiment. In the second embodiment, the timing in changing the angle record plane and changing the record area is different from that of the first embodiment, and other constructions and operations are the same as those of the first embodiment. Therefore, in the flow chart of FIG. 4, the same steps as those of FIG. 3 carry the same numerals, and the explanation about them are omitted as appropriate. Firstly in FIG. 4, the processings from step S11 to step S17 are performed similarly to the first embodiment shown in FIG. 3. After completing the step S17, the control device 18 judges whether or not the data recording for the record information is to be performed to another record area accessible by the move device 20 (step S31). If the data recording is to be performed to another record area (step S31: Yes), under control of the control signal S2, the move device 20 moves an area, which is irradiated with the signal light L3 and the reference light L2, by a predetermined distance to be another record area (step S33). Then, the process goes back to step S16 to repeat the following processes. On the other hand, as the judgement at step S31, if the data recording is not to be performed relative to another record area (step S20: No), the control device 18 judges whether or not the data recording for the record information is to be performed to the next angle record plane changeable by the record angle change device 19 in the record area at the present time point of the hologram recording medium 200 fixed by the move device 20 (step S34). If the data recording is to be performed to the next angle record plane (step S34: Yes), under control of the control signal S1, the record angle change device 19 changes the record angle by a predetermined fine angle (e.g. 0.01 degree) (step S35). In this case, as mentioned above, since the record angle change device 19 is calibrated on the basis of the standard record angle, the record angle can be changed accurately. Then, the process goes back to step S16 to repeat the following processes. On the other hand, as the result at the judgement at step S34, if the data recording is not to be performed to the next angle record plane (step S34′ No), a series of record processes ends. Thus, the multiplex-recordings of the record information to a plurality of angle record planes in a plurality of record areas are completed. As explained above, in this embodiment, the control device 18 sets, as the standard record angle, the record angle when the first angle record plane is recorded for the hologram recording medium 200. After the first angle record plane is recorded, the record angle change device 19 changes and fixes the record angle, by a predetermined fine angle, from the set standard record angle, under control of the control device 18. Therefore, similarly to the case of the first embodiment, the record angle expected to correspond to the standard record angle defined by the set condition or the mechanical state at the hologram recording apparatus 100 side can be coincided with the standard record angle at the hologram recording medium 200 side. (Modification in Hologram Recording Apparatus) Incidentally, in each embodiment mentioned above, it is possible to integrate a reference light phase-code-multiplex type system for performing multiplex-recordings with various phases of the reference light L2, with the angle-multiplex system in the above-mentioned embodiments. In this case, for example, an optical element for changing the phase may be disposed in the optical path of the reference light L2 to change the phase of the reference light L2, so that the hologram recording is performed overlappingly to the same record area for each phase, similarly to the above case. Furthermore, instead of or in addition to such a reference light phase-code-multiplex type recording, it is possible to integrate a reference light amplitude-multiplex system for performing multiplex-recordings with various amplitudes of the reference light L2. In this case, for example, an optical element for changing the amplitude may be disposed in the optical path of the reference light L2 to change the amplitude of the reference light L2, so that the hologram recording is performed overlappingly to the same record area for each amplitude. Furthermore, instead of or in addition to these reference light phase-code-multiplex type recording or reference light amplitude-multiplex type recording, it is possible to integrate a reference light polarization-multiplex system for performing multiplex-recordings with various polarizations of the reference light L2, with the angle-multiplex system in the above-mentioned embodiments. In this case, for example, an optical element for changing the polarization may be disposed in the optical path of the reference light L2 to change the polarization of the reference light L2, so that the hologram recording is performed overlappingly to the same record area for each polarization, similarly to the above cases. Furthermore, instead of or in addition to these reference light phase-code-multiplex system, reference light amplitude-multiplex system or reference light polarization-multiplex system, it is possible to integrate a focal-depth-multiplex system for performing a multiplex-recording with various focal depths of the signal light L3, with the angle-multiplex system in the above-mentioned embodiments. In this case, for example, an optical element for changing the focal depth may be added, or positions of optical elements such as lenses 13, 14, 16 or the laser device 11 may be changed, or a mechanical element for changing the position of the hologram recording medium 200 may be added, to change the focal depth, so that the hologram recording is performed overlappingly to the same record area for each focal depth, similarly to the above cases. According to these modifications, comparing to the aforementioned embodiments, the hologram recording can be performed with higher density. EMBODIMENTS OF HOLOGRAM REPRODUCTION APPARATUS Embodiments of the hologram reproduction apparatus according to the present invention will be discussed, with reference to FIG. 5 and FIG. 6. Firstly, with reference to FIG. 5, an entire construction of the hologram reproduction apparatus in this embodiment will be discussed. FIG. 5 illustrates the entire construction of the hologram reproduction apparatus in this embodiment. The hologram reproduction apparatus 300 in this embodiment is for reading the recorded information from the hologram recording medium 200 recorded by the hologram recording apparatus 100 in the aforementioned embodiments. As shown in FIG. 5, the hologram reproduction apparatus 300 is provided with: a laser device 21 as an example of the light source such as a semiconductor laser for irradiating reproduction illumination light L10 onto the hologram recording medium 200; mirrors 22 and 23 for introducing the reproduction illumination light L10 to the hologram recording medium 200; a lens 24 for focusing reproduction light L11 based on the reproduction illumination light; a photoreceptor 25 for receiving the reproduction light L11 via the lens 24; a read device 26 for reading the recorded information recorded onto the hologram recording medium 200 on the basis of the received signal Sr outputted from the photoreceptor 25 in response to the received reproduction light L11. The hologram reproduction apparatus 300 is further provided with: a reproduction angle change device 29 for changing little by little and fixing the angles of the reproduction illumination light L10 relative to the surface of the hologram recording medium 200; and a control device 28 for controlling the reproduction angle change device 29 so that the reproduction illumination light L10 has the reproduction angle corresponding to the angle record plane where the reproduction is performed on the hologram recording medium 200. Incidentally, in this embodiment, an angle formed by an optical axis of the reproduction illumination light L10 and the surface of the hologram recording medium 200 is defined as a “reproduction angle”. The reproduction angle change device 29 has the function of changing relatively the reproduction angle of the reproduction illumination light L10 relative to the surface of the hologram recording medium 200. The function can be achieved, for example, by changing the angles or positions of the constitutional elements in the optical system, such as the laser device 21; the mirrors 22 and 23, relative to each optical axis. Alternatively, the function can be achieved by adding a special optical element for changing the angle of the reproduction illumination light L10 relative to this optical system. Alternatively, the function can be achieved by mechanically changing a hold angle of the hologram recording medium 200. The angle change operation of the reproduction angle change device 29 is controlled by the control device 28, so that it becomes a part of a series of reproduction as discussed later. The control device 28 may include a controller comprising a microprocessor and the like, and is adapted to generate and output the control signal S1′ in response to the recorded information and the like to be reproduced from the hologram recording medium 200, and control the reproduction angle with the reproduction angle change device 29. The photoreceptor 25 for receiving the reproduction light L11 generated as such via the lens 24 may include the photodiode array, the CCD and so on. The read device 26 preferably stores into the memory a table of relationship between the light-dark pattern received at the photoreceptor 25 and a plurality of recorded information values modulated by a cell unit by the spatial light modulator 15 (see FIG. 1) when recording the hologram recording medium 200. Then, each recorded information is read by identifying the light-dark pattern of the received reproduction light L11 and by identifying the recorded information corresponding to the identified light-dark pattern with reference to this table. Therefore, a plurality of record information recorded on one angle record plane in one record area can be read at the same time. Particularly in this embodiment, the read device 26 can read the angle standard signal Sa from the standard angle record plane where the angle standard signal Sa is written from among a plurality of angle record planes on the hologram recording medium 200. Then, after reading the angle standard signal Sa, the read device 26 outputs it to the control device 28. The control device 28 can readily identify which angle record plane is the standard record plane on the basis of the angle standard signal Sa, regardless of whether the hologram recording medium 200 to be used for the reproduction is the same or different, or whether the hologram reproduction apparatus 300 to be used for the reproduction is the same or different. Furthermore, the control device 28 calibrates the reproduction angle change device 29 on the basis of the standard record angle indicated by the angle standard signal Sa. That is, on reproduction any angle record plane, the reproduction angle change device 29 is firstly calibrated in response to the standard reproduction angle corresponding to the standard angle record plane indicated by the angle standard signal Sa. More specifically, for example, a difference between the standard reproduction angle corresponding to the standard angle record plane indicated by the angle standard signal Sa and the reproduction angle under a setting condition of the optical system or mechanical state expected to correspond to the standard reproduction angle in the reproduction angle change device 29 at the time point of presently reproduction is detected. Furthermore, the reproduction angle change device 29 is adapted to change the reproduction angle by offsetting the detected difference of angle. Additionally, the hologram reproduction apparatus 800 is further provided with; a move apparatus 30 for moving the focus position where the reproduction illumination light L10 is focused relative to the surface of the hologram recording medium 200 in a direction along its surface. The move device 30 may move the focus position of the reproduction illumination light L10 by changing the angle or position of the optical system such as the mirrors 22 and 23, for example. Alternatively, the focus position may be moved by changing the angle or position of another optical system such as the laser device 21, or by additionally disposing a special optical system (e.g. a mirror having a variable set angle) in an optical path of the reproduction illumination light L10. Furthermore, a hold mechanism for holding the hologram recording medium 200 may be employed to move the hologram recording medium 200 itself mechanically in a direction along its surface. Also the moving by the move device 30 is controlled by the control signal S2′ generated at and outputted from the control device 28, so that it becomes a part of a series of reproduction operations mentioned later. Next, with reference to FIG. 6, the fundamental reproduction operation of the hologram reproduction apparatus 300 in this embodiment constructed as such will be explained. During its operation, the laser device 21 irradiates the hologram recording medium 200 with the reproduction illumination light L10 via the mirrors 22 and 23. Then, the photoreceptor 25 receives the reproduction light L11 based on the reproduction illumination light L10 for the hologram recording medium 200. The reproduction light L11 may be the 0th-order light or the higher order light such as the 1st-order light generated when the hologram recording medium 200 is irradiated with the reproduction illumination light L10 corresponding to the reference light of recording. Due to the property of the hologram recording, the reproduction light L11 has the light-dark pattern the same as that of the modulated signal light L3 shown in FIG. 1. Next, on the basis of the reproduction light L11 received at the photoreceptor 25, each record information recorded onto the hologram recording medium 200 subjected to the high density recording as mentioned above is reproduced by the read device 26. Owing to the fundamental reproduction, the recorded information to one angle record plane for one reproduction angle in one record area irradiated with the reproduction illumination light L10 at one time is reproduced. Next, the angle-multiplex type reproduction operations of the hologram reproduction apparatus 300 in this embodiment for performing such a reproduction for a plurality of angle record planes and further for a plurality of record areas will be explained with reference to FIG. 6. FIG. 6 illustrates the record operation in a flow chart. In FIG. 6, the reproduction light L11 based on the reproduction illumination light L10 is firstly received at the photoreceptor 25. In response to this, the angle standard signal Sa outputted from the read device 26 is checked by the control device 28 (step S41). Then, the reproduction angle change device 29 is calibrated on the basis of the difference between the current reproduction angle fixed by the reproduction angle change device 29 and the standard reproduction angle corresponding to the standard angle record plane indicated by the angle standard signal Sa (step S42). This calibration is performed by offsetting the aforementioned difference of angle in the control signal S1′ that may be inputted into the reproduction angle change device 29. Next, the control device 28 judges whether or not the data reproduction is to be performed to the current angle record plane fixed by the reproduction angle change apparatus 29 in the current record area of the hologram recording medium 200 fixed by the move device 30 (step S43). If the data reproduction is not to be performed (step S43: No), the process flow ends. That is, in this case, it can be said that checking the angle standard signal Sa (step S41) and so on is effectively performed. On the other hand, as the result of the judgment at step S43, if the data reproduction is to be performed (step S43: yes), the irradiation with the reproduction illumination light L10 is performed, and the photoreceptor 25, the read device 26 and the like perform actually the data reproduction (step S44). Next, the control device 28 judges whether or not the data reproduction of the recorded information is to be performed to the next angle record plane changeable by the reproduction angle change apparatus 29 in the current record area of the hologram recording medium 200 fixed by the move device 30 (step S45). If the data reproduction is to be performed to the next angle record plane (step S45: Yes), the reproduction angle change device 29 changes the reproduction angle by a predetermined fine angle (e.g. 0.01 degree) under control of the control signal S1′ (step S46). In this case, as mentioned above, since the reproduction angle change device 29 is calibrated on the basis of the standard reproduction angle, it is possible to change accurately the reproduction angle. Then, the process flow goes back to step S43 to repeat the following processings. On the other hand, as the result of the judgment at step S45, if the data reproduction is not to be performed to the next angle record plane (step S45: No), the control device 28 judges whether or not the data reproduction of the recorded information is to be performed to another record area changeable by the move device 30 (step S47). If the data reproduction is to be performed to another record area (step S47: Yes), under control of the control signal S1′, the reproduction angle to be changed and fixed by the reproduction angle change device 29 is reset. That is, the reproduction angle change device 29 changes and fixes the reproduction angle to make it correspond to the first angle record plane in the next record area (step S48). In this case, as mentioned above, since the reproduction angle change device 29 is calibrated on the basis of the standard reproduction angle, the reproduction angle can be reset accurately. Furthermore, the reproduction angle after reset can be changed accurately. Next, under control of the control signal S2′, the move device 30 moves, the area onto which the reproduction illumination light L10 is irradiated, by a predetermined distance to be another record area (step S49). Then, the process goes back to step S16 to repeat the following processes. On the other hand, as the result of the judgment at step S47, if the data reproduction is not to be performed to another record area (step S47: No), a series of reproduction processings ends. Thus, the reproductions of the recorded information to a plurality of angle record planes in a plurality of record areas complete. As explained above, in this embodiment, under control of the control device 28, the reproduction angle change device 29 changes and fixes the reproduction angle by a predetermined fine angle on the basis of the standard reproduction angle corresponding to the standard angle record plane indicated by the angle standard signal Sa. Therefore, it is possible to coincide the reproduction angle expected to correspond to the standard reproduction angle defined at the hologram reproduction apparatus 300 side, i.e. defined by the set condition or the mechanical state of the optical system or the like including mirrors 22 and 23, the laser device 21 and the reproduction angle change device 29, with the standard reproduction angle at the hologram recording medium 200 side. That is, even in the case that any different hologram reproduction apparatus 300 of the same type is used, these angles can be coincided with each other regardless of variations among apparatuses. Furthermore, after then, on the basis of the standard reproduction angle, the reproduction can be performed for any reproduction angle quickly and accurately from the angle record plane. As discussed above, according to the hologram recording apparatus and method, as well as the hologram reproduction apparatus and method, of the present invention, it is possible to improve the record density and the record capacity, and further to perform the recording or the reproduction accurately and quickly. The present invention is not limited to the aforementioned embodiments, and may be modified within a range not departing from the essence or spirit of the invention read from the whole specification and the claims. Such a modified hologram recording apparatus and method, as well as such a modified hologram reproduction apparatus and method, are all encompassed within a technical scope of the present invention. INDUSTRIAL APPLICABILITY The hologram recording apparatus and method, as well as the hologram reproduction apparatus and method, according to the present invention are applicable to various recording apparatus and method for recording, with high density, various contents information such as video information and audio information, various data information for computers, a large volume of information such as control information, by irradiating a downsizable hologram recording medium with signal light, or also applicable to various reproduction apparatus and method for reproducing the large volume of information recorded with high density from a downsizable hologram recording medium, by irradiating the downsizable hologram recording medium with the reproduction light.
<SOH> BACKGROUND ART <EOH>Heretofore, a hologram recording apparatus, which may be provided with a liquid crystal device and the like, irradiates a spatial light modulator for modulating light depending on record information to be recorded, with laser light as signal light. Particularly, in the spatial light modulator, cells are arranged planarly in a matrix so that the signal light is modulated by changing transmittance of each cell depending on the record information. Furthermore, the modulated signal light is outputted with different output angles, as a plurality of diffraction light, such as 0th-order light, or 1st-order light and so on, due to diffraction phenomenon in the cell having a fine pitch. In this case, the output angle is defined by the cell pitch, which indicates an modulation unit. Then, the signal light modulated with the spatial light modulator constructed as above and reference light not passed through the spatial light modulator are interfered on the hologram recording medium. Thereby, the recording information is recorded as a wavefront on the hologram recording medium. An angle-multiplex type hologram recording apparatus is proposed for multiplex recording different information in the same area, by changing little by little a surface angle of the hologram recording medium relative to the reference light and the signal light, particularly during recording. In the present application, the angle of the signal light relative to the hologram recording medium surface in such an angle-multiplex type recording is referred to as a “record angle” as appropriate. Furthermore, an angle as a standard of the record angle, such as the record angle when it corresponds to a normal line of the hologram recording medium surface, is referred to as a “standard record angle”. Still further, in the present application, each record plane corresponding to each record angle is referred to as an “angle record plane”, and a record plane corresponding to the standard record angle is referred to as a “standard angle record plane”. On the other hand, a hologram reproduction apparatus consisting a pair with the hologram recording apparatus is designed to reproduce the recorded multiplex information in the same area, by changing little by little the surface angle of the hologram recording medium relative to the reproduction illumination light. In the present application, the angle of the reproduction light relative to the hologram recording medium surface in such an angle-multiplex type reproduction is referred to as a “reproduction angle” as appropriate. Furthermore, an angle as a standard of the reproduction angle, such as the reproduction angle when it corresponds to a normal line of the hologram recording medium, is referred to as a “standard reproduction angle”. In the angle-multiplex type hologram recording apparatus, recording to each angle record plane in the same record area are successively performed for each record angle, by changing the record angle in the maximum range with increment or decrement 0.01 degree from the standard record angle (e.g. by changing little by little in the range of 88-92 degree). Incidentally, in the present application, an area on the hologram recording medium surface onto which the signal light and the reference light are irradiated together is referred to as a “record area”. In the angle-multiplex type recording, a plurality of angle record planes such as 50 planes is recorded in the same record area. On the other hand, in the angle-multiplex type hologram reproduction apparatus, the recorded multiplex information in the same area is reproduced for each reproduction angle, by changing little by little the reproduction angle from the standard reproduction angle in response to the record angle. Thus, in the angle-multiplex type hologram recording apparatus and hologram reproduction apparatus, the record information can be recorded respectively on a plurality of angle record planes recorded for each record angle in the same record area, and the recorded information can be reproduced respectively. Therefore, recording density and recording capacity are expected to be remarkably increased.
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is a block diagram illustrating an entire configuration of the first embodiment of the hologram recording apparatus of the present invention. FIG. 2 is a perspective view schematically illustrating the spatial light modulator employed in the first embodiment. FIG. 3 is a flow chart illustrating the angle-multiplex type record operation in the first embodiment. FIG. 4 is a flow chart illustrating the angle-multiplex type record operation in the second embodiment of the hologram recording apparatus of the present invention. FIG. 5 is a block diagram illustrating an entire configuration of an embodiment of the hologram reproduction apparatus of the present invention. FIG. 6 is a flow chart illustrating the angle-multiplex type reproduction operation in an embodiment of hologram reproduction apparatus of the present invention. detailed-description description="Detailed Description" end="lead"?
20060120
20080304
20060525
70153.0
G03H126
0
ASSAF, FAYEZ G
ANGLE-MULTIPLEXING HOLOGRAM RECORDING DEVICE, METHOD, HOLOGRAM REPRODUCTION DEVICE, AND METHOD
UNDISCOUNTED
0
ACCEPTED
G03H
2,006
10,514,727
ACCEPTED
Solid catalyst component for olefin polymerization and catalyst
A solid catalyst component for polymerization of olefins prepared by contacting (a) a dialkoxy magnesium compound, (b) a tetra-valent titanium halide, and (c) an electron donor compound of the formula R1R2C(COOR3)2 suspended in (d) an aromatic hydrocarbon having a boiling point in the range of 50-150° C. The catalyst containing the catalyst component is excellent in the olefin polymerization catalyst activity to hydrogen and can produce a polymer with a high stereoregularity in a high yield.
1. A solid catalyst component (A1) for polymerization of olefins prepared by contacting (a1) a dialkoxy magnesium compound, (b) a tetravalent titanium halide, and (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, in (d) an aromatic hydrocarbon having a boiling point in the range of 50-150° C. 2. The solid catalyst component (A1) according to claim 1, prepared by further causing (e) an electron donor compound of the following formula (2), (R4)1C6H4(COOR5)(COOR6) (2) wherein R4 is a linear or branched alkyl group having 1-8 carbon atoms or a halogen atom, R5 and R6 individually represent a linear or branched alkyl group having 1-12 carbon atoms, and 1 indicates the number of substituent R4 and is 0, 1, or 2, wherein the groups R4 may be either the same or different when 1 is 2, to come into contact in the aromatic hydrocarbon (d) having a boiling point in the range of 50-150° C. 3. The solid catalyst component (A1) according to claim 1, prepared by further causing (f) an electron donor compound of the following formula (3), wherein R7 and R8 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-8 carbon atoms, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R9 and R10 individually represent a linear or branched alkyl group having 2-8 carbon atoms, to come into contact in the aromatic hydrocarbon (d) having a boiling point in the range of 50-150° C. 4. The solid catalyst component (A1) according to claim 1, prepared by further causing (g) a siloxane to come into contact in the aromatic hydrocarbon (d) having a boiling point in the range of 50-150° C. 5. The solid catalyst component (A1) according to claim 1, wherein R1 and/or R2 in the formula (1) is an isobutyl group. 6. The solid catalyst component (A1) according to claim 1, wherein R3 in the formula (1) is an ethyl group. 7. The solid catalyst component (A1) according to claim 1, wherein the electron donor compound (c) is diethyl diisobutylmalonate. 8. The solid catalyst component (A1) according to claim 3, wherein the electron donor compound (f) of the formula (3) is diethyl maleate or di-n-butyl maleate. 9. A solid catalyst component (A2) for polymerization of olefins prepared by contacting (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (e) an electron donor compound of the following formula (2), (R4)1C6H4(COOR5)(COOR6) (2) wherein R4 is a linear or branched alkyl group having 1-8 carbon atoms or a halogen atom, R5 and R6 individually represent a linear or branched alkyl group having 1-12 carbon atoms, and 1 indicates the number of substituent R4 and is 0, 1, or 2, wherein the groups R4 may be either the same or different when 1 is 2. 10. The solid catalyst component (A2) according to claim 9, prepared by further causing (g) a siloxane to come into contact. 11. A solid catalyst component (A3) for polymerization of olefins prepared by contacting (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (f) an electron donor compound of the following formula (3), wherein R7 and R8 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-8 carbon atoms, or linear or branched alkyl group having 1-8 carbon atoms substituted with one or two halogen atoms, and R9 and R10 individually represent a linear or branched alkyl group having 2-8 carbon atoms. 12. A solid catalyst component (A4) for polymerization of olefins prepared by contacting (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (g) a siloxane. 13. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 1, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 14. The catalyst according to claim 13, wherein the electron donor compound (C) is an organosilicon compound of the following formula (5), R12qSi(OR13)4-q (5) wherein the group R12 individually represents a linear or branched alkyl group having 1-12 carbon atoms, a cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, R13 individually represents a linear or branched alkyl group having 1-4 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and q is an integer satisfying an inequality of 0≦q≦3. 15. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 2, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 16. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 3, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 17. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 4, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 18. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 5, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 19. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 6, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. 20. A catalyst for polymerization of olefins, comprising (A) the solid catalyst component according to claim 7, (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound.
TECHNICAL FIELD The present invention relates to a solid catalyst component and a catalyst for polymerization of olefins, which exhibit high activity and excellent catalytic activity to hydrogen and can produce highly stereoregular polymers in a high yield. BACKGROUND ART A solid catalyst component containing magnesium, titanium, an electron donor compound, and a halogen as essential components used for the polymerization of olefins such as propylene has been known in the art. A large number of methods for polymerizing or copolymerizing olefins in the presence of a catalyst for olefin polymerization comprising the above solid catalyst component, an organoaluminum compound, and an organosilicon compound have been proposed. For example, Japanese Unexamined Patent Publication No. (hereinafter referred to as JP-A) 63310/1982 and JP-A No. 63311/1982 propose a method for polymerizing olefins, particularly olefins with three or more carbon atoms, in which a catalyst comprising a solid catalyst component containing a magnesium compound, a titanium compound, and an electron donor, an organoaluminum compound, and an organosilicon compound having an Si—O—C linkage in combination is used. However, because these methods are not necessarily satisfactory for producing highly stereoregular polymers in a high yield, improvement of these methods has been desired. JP-A No. 3010/1988 proposes a catalyst and method for polymerizing propylene. The catalyst comprises a solid catalyst component, obtained by processing a powder produced from dialkoxy magnesium, aromatic dicarboxylic acid diester, aromatic hydrocarbon, and titanium halide with heat, an organoaluminum compound, and an organosilicon compound. JP-A No. 315406/1989 proposes another propylene polymerization catalyst and a method for polymerizing propylene in the presence of this catalyst. The catalyst comprises a solid catalyst component obtained by preparing a suspension from diethoxy magnesium and alkyl benzene, causing this suspension to come into contact with titanium tetrachloride, and reacting the resulting product with phthalic acid dichloride, an organoaluminum compound, and an organosilicon compound. All of the above-described conventional technologies have attained certain results in improving catalytic activity to the extent of permitting dispensing with an ash-removal step for removing catalyst residues such as chlorine and titanium from formed polymers, improving the yield of stereoregular polymers, and improving durability of catalytic activity during polymerization. The polymers produced using these catalysts are used in a variety of applications including formed products such as vehicles and household electric appliances, containers, and films. These products are manufactured by melting polymer powders produced by polymerization and forming the melted polymers using various molds. In manufacturing formed products, particularly, large products by injection molding or the like, melted polymers are sometimes required to have a high fluidity (a melt flow rate). Accordingly, a large number of studies have been undertaken to increase the melt flow rate of polymers. The melt flow rate greatly depends on the molecular weight of the polymers. In the industry, hydrogen is generally added as a molecular weight regulator for polymers during polymerization of propylene. In this instance, a large quantity of hydrogen is usually added to produce low molecular weight polymers having a high melt flow rate. However, the quantity of hydrogen which can be added is limited because pressure resistance of the reactor is limited because of safety. In order to add a larger amount of hydrogen, the partial pressure of monomers to be polymerized has to be decreased. The decrease in the partial pressure, however, is accompanied by a decrease in productivity. Additionally, use of a large amount of hydrogen may bring about a problem of cost. Development of a catalyst capable of producing polymers with a high melt flow rate by using a smaller amount of hydrogen, in other words, a catalyst which has high activity to hydrogen and can produce a highly stereoregular polymer in a high yield has therefore been desired. However, the above-mentioned conventional technologies were insufficient to solve these problems. In addition, taking these environmental problems, development of a compound without a benzene ring instead of the compounds containing a benzene ring mainly used as electron donors for preparing the solid catalyst component in above-mentioned conventional technologies is desired. Accordingly, an object of the present invention is to solve such problems remaining in the prior art and to provide a solid catalyst component and a catalyst for polymerization of olefins, free from aromatic esters in the catalyst component, having excellent catalytic activity to hydrogen and high activity, and capable of producing polymers with high stereoregularity in a high yield. DISCLOSURE OF THE INVENTION In view of this situation, the inventor of the present invention has undertaken extensive studies to solve the problems in the conventional technologies remaining still to be solved. As a result, the inventor has found that a solid catalyst component prepared using a magnesium compound such as dialkoxy magnesium and using a malonic acid diester or a substituted malonic acid diester as an internal donor exhibits an extremely high effect and can solve the above problems. This finding has led to the completion of the present invention. To achieve the above object, a solid catalyst component (A1) for polymerization of olefins of the present invention is prepared by contacting (a1) a dialkoxy magnesium compound, (b) a tetravalent titanium halide, and (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, in (d) an aromatic hydrocarbon having a boiling point in the range of 50-150° C. In addition, another solid catalyst component (A2) for polymerization of olefins of the present invention is prepared by contacting (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (e) an electron donor compound of the following formula (2), (R4)1C6H4(COOR5)(COOR6) (2) wherein R4 is a linear or branched alkyl group having 1-8 carbon atoms or a halogen atom, R5 and R6 individually represent a linear or branched alkyl group having 1-12 carbon atoms, and 1 indicates the number of substituent R4 and is 0, 1, or 2, wherein the groups R4 may be either the same or different when 1 is 2. Still another solid catalyst component (A3) for polymerization of olefins of the present invention is prepared by contacting (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (f) an electron donor compound of the following formula (3), wherein R7 and R8 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-8 carbon atoms, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R9 and R10 individually represent a linear or branched alkyl group having 2-8 carbon atoms. Still another solid catalyst component (A4) for polymerization of olefins of the present invention is prepared by contacting one another (a2) a magnesium compound, (b) a tetravalent titanium halide, (c) an electron donor compound of the following formula (1), R1R2C(COOR3)2 (1) wherein R1 and R2 individually represent a hydrogen atom, halogen atom, linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, aralkyl group, or linear or branched alkyl group having 1-10 carbon atoms substituted with one or two halogen atoms, and R3 individually represents a linear or branched alkyl group having 1-20 carbon atoms, cycloalkyl group, phenyl group, vinyl group, allyl group, or aralkyl group, and (g) a siloxane. The catalyst for polymerization of olefins of the present invention comprises the above solid catalyst component (A1), (A2), (A3), or (A4), (B) an organoaluminum compound of the following formula (4), R11pAlQ3-p (4) wherein R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3, and (C) an electron donor compound. The catalyst for polymerization of olefins of the present invention exhibits a high catalyst activity to hydrogen and can produce olefin polymers in a high yield while maintaining high stereoregularity of the olefin polymers. The catalyst is therefore expected not only to produce polyolefins for common use at a low cost, but also to be useful in the manufacture of olefin copolymers having high functions. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a flow chart showing a process for preparing the polymerization catalyst of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION As the dialkoxy magnesium (a1) (hereinafter may be referred to as “component (a1)”) used for preparing the solid catalyst component (A1) (hereinafter may be referred to as “component (A1)”) for olefin polymerization of the present invention, a compound represented by the formula Mg (OR14) (OR15), wherein R14 and R15 individually represent an alkyl group having 1-10 carbon atoms, is preferable. Specific examples include dimethoxymagnesium, diethoxymagnesium, dipropoxymagnesium, dibutoxymagnesium, ethoxymethoxymagnesium, ethoxypropoxymagnesium, and butoxyethoxymagnesium. These dialkoxy magnesium compounds may be prepared by reacting metallic magnesium with an alcohol in the presence of a halogen or a halogen-containing metal compound. The above dialkoxy magnesium compounds may be used either individually or in combination of two or more. The dialkoxy magnesium compound used for preparing the solid catalyst component (A1) in the present invention may be in the form of either granules or powder and may be either amorphous or spherical in the configuration. For example, when spherical dialkoxy magnesium is used, the resulting polymer is in the form of a powder having a more excellent granular form and a narrower particle distribution. This improves handle ability of the polymer powder produced during polymerization operation and eliminates problems such as clogging caused by fine particles contained in the polymer powder. The spherical dialkoxy magnesium need not necessarily be completely spherical, but may be oval or potato-shaped. Specifically, the particles may have a ratio (l/w) of the major axis diameter (l) to the minor axis diameter (w) usually of 3 or less, preferably of 1 to 2, and more preferably of 1 to 1.5. Dialkoxy magnesium with an average particle size from 1 to 200 μm can be used. A more preferable average particle size is 5 to 150 μm. In the case of spherical dialkoxy magnesium, the average particle size is usually from 1 to 100 μm, preferably from 5 to 50 μm, and more preferably from 10 to 40 μm. A powder having a narrow particle size distribution with a small fine and coarse powder content is preferably used. Specifically, the content of particles with a diameter of 5 μm or less should be 20% or less, and preferably 10% or less. On the other hand, the content of particles with a diameter of 100 μm or more should be 10% or less, and preferably 5% or less. Moreover, the particle size distribution represented by ln (D90/D10), wherein D90 is a particle size of 90% of the integrated particle size and D10 is a particle size of 10% of the integrated particle size, is 3 or less, and preferably 2 or less. Methods of producing such spherical dialkoxy magnesium are described in, for example, JP-A No. 41832/1983, JP-A No. 51633/1987, JP-A No. 74341/1991, JP-A No. 368391/1992, and JP-A No. 73388/1996. The tetravalent titanium halide compound (b) used for preparing the component (A1) in the present invention is one or more compounds selected from titanium halides and alkoxy titanium halides of the formula Ti(OR16)nX4-n, wherein R16 indicates an alkyl group having 1-4 carbon atoms, X is a halogen atom such as a chlorine atom, bromine atom, or iodine atom, and n is an integer of 0-4. Specific examples include, as titanium halides, titanium tetrahalides such as titanium tetrachloride, titanium tetrabromide, and titanium tetraiodide and, as alkoxytitanium halides, methoxytitanium trichloride, ethoxytitanium trichloride, propoxytitanium trichloride, n-butoxytitanium trichloride, dimethoxytitanium dichloride, diethoxytitanium dichloride, dipropoxytitanium dichloride, di-n-butoxytitanium dichloride, trimethoxytitanium chloride, triethoxytitanium chloride, tripropoxytitanium chloride, and tri-n-butoxy titanium chloride. Of these, titanium tetrahalides are preferable, with titanium tetrachloride being particularly preferable. These titanium compounds may be used either individually or in combination of two or more. The electron donor compound (c) used for preparing the solid catalyst component (A1) in the present invention is a malonic acid diester, halogen substituted malonic acid diester, alkyl substituted malonic acid diester, or haloalkyl substituted malonic acid diester represented by the above-described formula (1). When R1 or R2 in the formula (1) is a halogen atom, a chlorine atom, bromine atom, and iodine atom can be given as the halogen atom. Of these, a chlorine atom and bromine atom are preferable. In the above formula, R1 and R2 are preferably a branched alkyl group having 3-10 carbon atoms including one or more secondary, tertiary, or quaternary carbon atoms, particularly preferably an isobutyl group, t-butyl group, isopentyl group, or neopentyl group. As R3which is a carbonyl ester residue of the above formula (1), alkyl groups, particularly linear or branched alkyl groups having 1-8 carbon atoms such as an ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, isopentyl group, and neopentyl group, are preferable. As specific examples of the malonic acid diester, diethyl malonate, dipropyl malonate, dibutyl malonate, diisobutyl malonate, dipentyl malonate, and dineopentyl malonate can be given. As specific examples of the halogen-substituted malonic acid diester, diethyl chloromalonate, diethyl dichloromalonate, diethyl bromomalonate, diethyl dibromomalonate, dipropyl chloromalonate, dipropyl dichloromalonate, dipropyl bromomalonate, dipropyl dibromomalonate, dibutyl chloromalonate, dibutyl dichloromalonate, dibutyl bromomalonate, dibutyl dibromomalonate, diisobutyl chloromalonate, diisobutyl dichloromalonate, diisobutyl bromomalonate, diisobutyl dibromomalonate, dipentyl chloromalonate, dipentyl dichloromalonate, dipentyl bromomalonate, dipentyl dibromomalonate, dineopentyl chloromalonate, dineopentyl dichloromalonate, dineopentyl bromomalonate, dineopentyl dibromomalonate, diisooctyl chloromalonate, diisooctyl dichloromalonate, diisooctyl bromomalonate, and diisooctyl dibromomalonate can be given. As specific examples of the alkyl- and halogen-substituted malonic acid diester, dibutyl ethylchloromalonate, dibutyl ethylbromomalonate, dibutyl isopropylchloromalonate, dibutyl isopropylbromomalonate, diisobutyl isopropylchloromalonate, diisobutyl isopropylbromomalonate, dineopentyl isopropylchloromalonate, dineopentyl isopropylbromomalonate, diethyl butylchloromalonate, diethyl butylbromomalonate, diethyl isobutylchloromalonate, and diethyl isobutylbromomalonate can be given. As specific examples of the alkyl-substituted malonic acid diester, diethyl diisopropylmalonate, dipropyl diisopropylmalonate, diisopropyl diisopropylmalonate, dibutyl diisopropylmalonate, diisobutyl diisopropylmalonate, dineopentyl diisopropylmalonate, diethyl diisobutylmalonate, dipropyl diisobutylmalonate, diisopropyl diisobutylmalonate, dibutyl diisobutylmalonate, diisobutyl diisobutylmalonate, dineopentyl diisobutylmalonate, diethyl diisopentylmalonate, dipropyl diisopentylmalonate, diisopropyl diisopentylmalonate, dibutyl diisopentylmalonate, diisobutyl diisopentylmalonate, dineopentyl diisopentylmalonate, diethyl isopropylisobutylmalonate, dipropyl isopropylisobutylmalonate, diisopropyl isopropylisobutylmalonate, dibutyl isopropylisobutylmalonate, diisobutyl isopropylisobutylmalonate, dineopentyl isopropylisobutylmalonate, dimethyl isopropylisopentylmalonate, diethyl isopropylisopentylmalonate, dipropyl isopropylisopentylmalonate, diisopropyl isopropylisopentylmalonate, dipropyl isopropylisopentylmalonate, diisobutyl isopropylisopentylmalonate, and dineopentyl isopropylisopentylmalonate can be given. As specific examples of the haloalkyl-substituted malonic acid diester, diethyl bis(chloromethyl)malonate, diethyl bis(bromomethyl)malonate, diethyl bis(chloroethyl)malonate, diethyl bis(bromoethyl)malonate, diethyl bis(3-chloro-n-propyl)malonate, and diethyl bis(3-bromo-n-propyl)malonate can be given. Among these electron donor compounds, diethyl isopropylbromomalonate, diethyl butylbromomalonate, diethyl isobutylbromomalonate, diethyl diisopropylmalonate, diethyl dibutylmalonate, diethyl diisobutylmalonate, diethyl diisopentylmalonate, diethyl isopropylisobutylmalonate, dimethyl isopropylisopentylmalonate, diethyl (3-chloro-n-propyl)malonate, and diethyl bis(3-bromo-n-propyl)malonate are preferable. The above compounds may be used either individually or in combination of two or more as the component (c). In the solid catalyst component (A1) of the present invention, if the above-mentioned malonic acid diesters or the substituted malonic acid diesters are used as the electron donor compound for preparing the solid catalyst component, high activity and excellent catalyst activity to hydrogen can be ensured and a polymer with high stereoregularity can be produced in a high yield without using an aromatic ester compound. In addition, environmental problems related to safety, health, and the like can be overcome. Moreover, if an electron donor compound (e) of the above-described general formula (2) is used in combination with the electron donor compound (c) in the solid catalyst component (A1), catalyst activity to hydrogen can be improved even more and a highly streoregular polymer containing only a slight amount of fine powders and having a uniform particle size distribution can be produced in a high yield. The electron donor compound (e) represented by the above-described formula (2) is a phthalic acid diester, halogen-substituted phthalic acid diester, alkyl-substituted phthalic acid diester, haloalkyl substituted phthalic acid diester, or the like. Specific examples of the phthalic acid diester include the following compounds: dimethyl phthalate, diethyl phthalate, di-n-propyl phthalate, diisopropyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, ethylmethyl phthalate, methyl(isopropyl) phthalate, ethyl(n-propyl) phthalate, ethyl(n-butyl) phthalate, ethyl(isobutyl) phthalate, di-n-pentyl phthalate, diisopentyl phthalate, dineopentyl phthalate, dihexyl phthalate, di-n-heptyl phthalate, di-n-octyl phthalate, bis(2,2-dimethylhexyl) phthalate, bis(2-ethylhexyl) phthalate, di-n-nonylphthalate, diisodecyl phthalate, bis(2,2-dimethylheptyl) phthalate, n-butyl(isohexyl) phthalate, n-butyl(2-ethylhexyl) phthalate, n-pentylhexyl phthalate, n-pentyl(isohexyl) phthalate, isopentyl(heptyl) phthalate, n-pentyl(2-ethylhexyl) phthalate, n-pentyl(isononyl) phthalate, isopentyl(n-decyl) phthalate, n-pentylundecyl phthalate, isopentyl(isohexyl) phthalate, n-hexyl(2,2-dimethylhexyl) phthalate, n-hexyl(2-ethylhexyl) phthalate, n-hexyl(isononyl) phthalate, n-hexyl(n-decyl) phthalate, n-heptyl(2-ethylhexyl) phthalate, n-heptyl(isononyl) phthalate, n-heptyl(neodecyl) phthalate, and 2-ethylhexyl(isononyl) phthalate. One or more of these compounds can be used. In the formula (2) for the phthalic acid diester, given as specific examples of the alkyl group having 1-8 carbon atoms represented by R4 are a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, 2,2-dimethylpentyl group, isooctyl group, and 2,2-dimethylhexyl group. As the halogen atom represented by R4, a fluorine atom, chlorine atom, bromine atom, and iodine atom can be given. Of these, a methyl group, a bromine atom, and a fluorine atom are preferable for R4, with a methyl group and a bromine atom being particularly preferable. The groups represented by R5 or R6 in the formula (2) include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, 2,2-dimethylpentyl group, isooctyl group, 2,2-dimethylhexyl group, n-nonyl group, isononyl group, n-decyl group, isodecyl group, and n-dodecyl group. Of these, anethylgroup, n-butylgroup, isobutylgroup, t-butyl group, neopentyl group, isohexyl group, and isooctyl group are preferable, with an ethyl group, n-butyl group, and neopentyl group, being particularly preferable. l, which indicates the number of the substituent R4, is 1 or 2, provided that when l is 2, the two R4 groups may be either the same or different. When l=1, R4 replaces the hydrogen atom at the 3, 4, or 5 position of the phthalic acid diester derivative of the formula (2), and when l=2, R4 replaces the hydrogen atoms at the 4 and 5 positions. As examples of the substituted phthalic acid diester of the formula (2), diethyl 4-methylphthalate, di-n-butyl 4-methylphthalate, diisobutyl 4-methylphthalate, dineopentyl 4-bromophthalate, diethyl 4-bromophthalate, di-n-butyl 4-bromophthalate, diisobutyl 4-bromophthalate, dineopentyl 4-methylphthalate, dineopentyl 4,5-dimethylphthalate, dineopentyl 4-methylphthalate, dineopentyl 4-ethylphthalate, t-butylneopentyl 4-methylphthalate, t-butylneopentyl 4-ethylphthalate, dineopentyl 4,5-dimethylphthalate, dineopentyl 4,5-diethylphthalate, t-butylneopentyl 4,5-dimethylphthalate, t-butylneopentyl 4,5-diethylphthalate, dineopentyl 3-fluorophthalate, dineopentyl 3-chlorophthalate, dineopentyl 4-chlorophthalate, and dineopentyl 4-bromophthalate can be given. The above ester compounds are preferably used in combination of two or more. In this instance, the esters are preferably combined so that the total carbon atom number in the alkyl group possessed by one ester may differ four or more from that possessed by another ester. In the solid catalyst component (A1) of the present invention, if the phthalic acid diester or substituted phthalic acid diester is used together with the above-mentioned malonic acid diester or substituted malonic acid diester as electron donor compounds, higher catalytic activity to hydrogen can be ensured and a polymer with higher stereoregularity containing only a slight amount of fine powders and having uniform particle distribution can be produced in a high yield as compared with the case in which either of the electron donor compounds is used alone. Moreover, if an electron donor compound (f) of the above formula (3) is used in combination with the electron donor compound (c) in the solid catalyst component (A1) of the present invention, catalytic activity to hydrogen can be improved even more while maintaining the high stereoregularity and the high yield of the polymer. The electron donor compound (f) represented by the above-described formula (3) is preferably a maleic acid diester, halogen-substituted maleic acid diester, alkyl-substituted maleic acid diester, or haloalkyl-substituted maleic acid diester. In the maleic acid diester and substituted maleic acid diester represented by the formula (3), the groups represented by R9 or R10 in the formula (3) include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, 2,2-dimethylpentyl group, isooctyl group, 2,2-dimethylhexyl group, n-nonyl group, isononyl group, n-decyl group, isodecyl group, and n-dodecyl group. Of these, an ethyl group, n-butyl group, isobutyl group, t-butyl group, neopentyl group, isohexyl group, and isooctyl group are preferable, with an ethyl group, and n-butyl group, neopentyl group, being particularly preferable. In the substituted maleic acid diester represented by the formula (3), given as specific examples of the alkyl group having 1-8 carbon atoms represented by R7 or R8 are a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 2,2-dimethylbutyl group, 2,2-dimethylpentyl group, isooctyl group, and 2,2-dimethylhexyl group. As halogen atoms for R7 or R8, a fluorine atom, chlorine atom, bromine atom, and iodine atom can be given. Of these, a methyl group, an ethyl group, a bromine atom, and a fluorine atom are preferable for R7 and R8, with a methyl group and an ethyl group being particularly preferable. Specific examples of the maleic acid diester, which is the compound of the formula (3) with both R7 and R8 hydrogen atoms, include dimethyl maleate, diethyl maleate, di-n-propyl maleate, diisopropyl maleate, di-n-butyl maleate, diisobutyl maleate, ethylmethyl maleate, methyl(isopropyl) maleate, ethyl(n-propyl) maleate, ethyl(n-butyl) maleate, ethyl(isobutyl) maleate, di-n-pentyl maleate, diisopentyl maleate, dineopentyl maleate, dihexyl maleate, di-n-heptyl maleate, di-n-octyl maleate, bis(2,2-dimethylhexyl) maleate, bis(2-ethylhexyl) maleate, di-n-nonyl maleate, diisodecyl maleate, bis(2,2-dimethylheptyl) maleate, n-butyl(isohexyl) maleate, n-butyl(2-ethylhexyl) maleate, n-pentylhexyl maleate, n-pentyl(isohexyl) maleate, isopentyl(heptyl) maleate, n-pentyl(2-ethylhexyl) maleate, n-pentyl(isononyl) maleate, isopentyl(n-decyl) maleate, n-pentylundecyl maleate, isopentyl(isohexyl) maleate, n-hexyl(2,2-dimethylhexyl) maleate, n-hexyl(2-ethylhexyl) maleate, n-hexyl(isononyl) maleate, n-hexyl(n-decyl) maleate, n-heptyl(2-ethylhexyl) maleate, n-heptyl(isononyl) maleate, n-heptyl(neodecyl) maleate, and 2-ethylhexyl(isononyl) maleate. Of these, diethyl maleate and di-n-butyl maleate are preferable. One or more of these compounds can be used. As examples of the halogen-substituted maleic acid diester represented by the formula (3), specifically the compound of the formula (3) in which both R7 and R8 are halogen atoms or either R7 or R8 is a halogen atom and the other is a hydrogen atom, diethyl 1-chloromaleate, di-n-butyl 1-chloromaleate, diethyl 1-bromodichloromaleate, di-n-butyl 1-bromomaleate, diethyl 1,2-dichloromaleate, di-n-butyl 1,2-dichloromaleate, diethyl 1,2-dibromochloromaleate, and di-n-butyl 1,2-dibromomaleate can be given. As examples of the alkyl-substituted maleic acid diester represented by the formula (3), specifically the compound of the formula (3) wherein both the R7 and R8 groups are alkyl groups, diethyl 1,2-dimethylmaleate, di-n-butyl 1,2-dimethylmaleate, diethyl 1,2-diethylmaleate, and di-n-butyl 1,2-diethylmaleate can be given. As examples of the haloalkyl substituted maleic acid diester represented by the formula (3), specifically the compound of the formula (3) with both R7 and R8 being haloalkyl groups, diethyl 1,2-bis(chloromethyl)maleate, di-n-butyl 1,2-bis(chloromethyl)methylmaleate, diethyl 1,2-bis(chloromethyl)ethylmaleate, and di-n-butyl 1,2-bis(chloromethyl)ethylmaleate can be given. These electron donor compounds (f) represented by the formula (3) can be used either individually or in combination of two or more. In the solid catalyst component (A1) of the present invention, if the electron donor compound (f) is used in combination with the electron donor compound (c) as the electron donor compound for preparing the solid catalyst component, higher catalytic activity to hydrogen can be ensured while maintaining high stereoregularity and high yield of the polymer as compared with the case in which each of these electron donor compounds are used independently. In addition, environmental problems related to safety, health and the like can be overcome due to capability of these electron donors of improving the catalyst activity to hydrogen without using an aromatic ester compound. In addition to the above components, a siloxane (g) is preferably used for preparing the solid catalyst component (A1) to improve stereoregularity of the polymer while maintaining high catalytic activity to hydrogen. The siloxane (g) is a compound having a siloxane bond (—Si—O-bond) in the main chain. Examples include disiloxanes such as an alkyl disiloxane, halogen-substituted alkyl disiloxane, 1,3-dihaloalkyl disiloxane, and 1,3-dihalophenyl disiloxane, and polysiloxanes. Polysiloxanes are polymers generally referred to as silicone oil. The polysiloxanes used in the present invention are chain-structured, partially hydrogenated, cyclic, or denatured polysiloxanes which are liquid or viscous at normal temperatures with a viscosity at 25° C. in the range of 0.02-100 cm2/s (2-10,000 cSt), and preferably in the range of 0.03-5 cm2/s (3-500 cSt). As specific examples of the disiloxanes, hexamethyldisiloxane, hexaethyldisiloxane, hexapropyldisiloxane, hexaphenyldisiloxane, 1,3-divinyltetramethyldisiloxane, 1,3-dichlorotetramethyldisiloxane, 1,3-dibromotetramethyldisiloxane, chloromethylpentamethyldisiloxane, and 1,3-bis(chloromethyl)tetramethyldisiloxane can be given. As specific examples of the trisiloxanes, tetrasiloxanes, or pentasiloxanes, 1,5-dichlorohexamethyltrisiloxane, 1,7-dichlorooctamethyltetrasiloxane, 1,5-dibromohexamethyltrisiloxane, 1,7-dibromooctamethyltetrasiloxane, 3-chloromethylheptamethyltrisiloxane, 3,5-bis(chloromethyl)octamethyltetrasiloxane, 3,5,7-tris(chloromethyl)nonamethylpentasiloxane, 3-bromomethylheptamethyltrisiloxane, 3,5-bis(bromomethyl)octamethyltetrasiloxane, and 3,5,7-tris(bromomethyl)nonamethylpentasiloxane can be given. Of these, 1,7-dichlorooctamethyltetrasiloxane is particularly preferable. As examples of the chain-structured polysiloxanes, dimethylpolysiloxane, methylphenylpolysiloxane, dichloropolysiloxane, and dibromopolysiloxanecan be given; as examples of the partially hydrogenated polysiloxanes, methyl hydrogen polysiloxanes with a hydrogenation degree of 10 to 80% can be given; as examples of the cyclic polysiloxanes, hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, 2,4,6-trimethylcyclotrisiloxane, 2,4,6,8-tetramethylcyclotetrasiloxane can be given; as examples of the modified polysiloxane, higher fatty acid group-substituted dimethylsiloxane, epoxy group-substituted dimethylsiloxane, and polyoxyalkylene group-substituted dimethylsiloxane can be given. Of these, decamethylcyclopentasiloxane and dimethylpolysiloxane are preferable, with decamethylcyclopentasiloxane being particularly preferable. These electron donor compounds (g) can be used either individually or in combination of two or more. In the present invention, the solid catalyst component (A1) is prepared by suspension contact of the raw materials in an aromatic hydrocarbon compound (d) with a boiling point of 50-150° C. As the aromatic hydrocarbon with a boiling point of 50-150° C., toluene, xylene, and ethylbenzene are preferably used. These aromatic hydrocarbons can be used either individually or in combination of two or more. Use of a saturated hydrocarbon compound or the like other than the aromatic hydrocarbons with a boiling point of 50-150° C. lowers solubility of impurities during reaction or washing, giving rise to a decrease in catalytic activity of the resulting solid catalyst component and stereoregularity of the resulting polymer. The magnesium compounds (hereinafter referred to from time to time simply as “component (a2)”) used for preparing the solid catalyst component (A2) (hereinafter referred to from time to time simply as “component (A2)”) for polymerization of olefins in the present invention include magnesium dihalide, dialkyl magnesium, alkylmagnesium halide, dialkoxy magnesium, diaryloxy magnesium, alkoxy magnesium halide, and fatty acid magnesium. Among these magnesium compounds, a dialkoxy magnesium compound is preferred. Specific examples include those described in connection with the preparation of the solid catalyst component (A1). The same compounds as used for preparing the solid catalyst component (A1), including (b) thetetravalenttitanium halide, (c) the electron donor compound of the formula (1), and (e) the electron donor compound of the formula (2), can be used for preparing the solid catalyst component (A2). The same magnesium compound (a2) used for preparing the solid catalyst component (A2) can be used for preparing the solid catalyst component (A3) of the present invention. As to (b) the tetravalent titanium halide, (c) the electron donor compound of the formula (1), and (f) the electron donor compound of the formula (2), the same compounds as used for preparing the solid catalyst component (A1) can be used for preparing the solid catalyst component (A3). In addition to the above components, a siloxane (g) is preferably used for preparing the solid catalyst components (A2) and (A3) to improve stereoregularity of the polymer while maintaining high catalyst activity to hydrogen. The same magnesium compound (a2) used for preparing the solid catalyst component (A2) can be used for preparing the solid catalyst component (A4) of the present invention. As to (b) the tetravalent titanium halide, (c) the electron donor compound of the formula (1), and (g) the siloxane of the formula (2), the same compounds as used for preparing the solid catalyst component (A1) can be used for preparing the solid catalyst component (A4). The solid catalyst components (A2) and (A3) are preferably prepared using a suspension of the components in an aromatic hydrocarbon compound (d) used for preparing the solid catalyst component (A1). Use of the aromatic hydrocarbon compound (d) can improve catalyst activity and stereoregularity of the polymer. In preparing the solid catalyst components (A1), (A2), and (A3), these components are caused to contact each other in a vessel equipped with a stirrer in an inert gas atmosphere from which water and the like have been removed while stirring. When the components contact one another by stirring for preparing the mixture or are dispersed or suspended for a denaturing treatment, the components may be stirred at a comparatively low temperature of around room temperature. When a reaction product is to be obtained by reacting the components after the contact, the mixture is preferably stirred in the temperature range of 40-130° C. The reaction does not sufficiently proceed at a reaction temperature below 40° C., resulting in a solid component with inadequate properties. On the other hand, control of the reaction becomes difficult at a temperature above 130° C. due to vaporization of the solvent and the like. The reaction time is one minute or more, preferably ten minutes or more, and still more preferably 30 minutes or more. The following examples are given as the order of contacting the components one another in preparing the solid catalyst component (A1) of the present invention. (1) (a1)→(d)→(b)→(c)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A1) (2) (a1)→(d)→(c)→(b)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A1) (3) (a1)→(d)→(b)→(c)→<<intermediate washing→(d)→(b)→(c)>>→final washing solid catalyst component (A1) (4) (a1)→(d)→(b)→(c)→<<intermediate washing→(d)→(c)→(b)>>→final washing→solid catalyst component (A1) (5) (a1)→(d)→(c)→(b)→<<intermediate washing→(d)→(b)→(c)>>→final washing solid catalyst component (A1) (6) (a1)→(d)→(c)→(b)→<<intermediate washing→(d)→(c)→(b)>>→final washing solid catalyst component (A1) The following examples are given as the order of contacting the components one another in preparing the solid catalyst component (A2) of the present invention. (7) (a2)→(d)→(b)→(c)+(e)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A2) (8) (a2)→(d)→(c)+(e)→(b)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A2) (9) (a2)→(d)→(b)→(c)+(e)→<<intermediate washing→(d)→(b)→(c)+(e)>>→final washing solid catalyst component (A2) (10) (a2)→(d)→(b)→(c)+(e)<<→intermediate washing→(d)→(c)→(e)→(b)>>→final washing→solid catalyst component (A2) (11) (a2)→(d)→(c)+(e)→(b)→<<intermediate washing→(d)→(b)→(c)+(e)>>→final washing solid catalyst component (A2) (12) (a2)→(d)→(c)+(e)→(b)→<<intermediate washing→(d)→(c)+(e)→(b)>>→final washing→solid catalyst component (A2) (13) (a2)→(d)→(e)→(b)→(c)→<<intermediate washing→(d)→(b)>>→final washing solid catalyst component (A2) (14) (a2)→(d)→(e)→(b)→(c)→<<intermediate washing→(d)→(b)+(c)>>→final washing→solid catalyst component (A2) (15) (a2)→(d)→(e)→(b)→(c)→<<intermediate washing→(d)→(b)+(e)>>→final washing→solid catalyst component (A2) (16) (a2)→(d)→(e)→(b)→(c)→<<intermediate washing→(d)→(b)+(c)+(e)>>→final washing→solid catalyst component (A2) The following examples are given more specifically as the preferable order of contacting the components one another for preparing the solid catalyst component (A3) of the present invention. (17) (a2)→(d)→(b)→(c)+(f)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A3) (18) (a2)→(d)→(c)+(f)→(b)→<<intermediate washing→(d)→(b)>>→final washing solid catalyst component (A3) (19) (a2)→(d)→(b)→(c)→(f)→<<intermediate washing→(d)→(b)→(c)→(f)>>→final washing→solid catalyst component (A3) (20) (a2)→(d)→(b)→(c)+(f)→<<intermediate washing→(d)→(c)+(f)→(b)>>→final washing→solid catalyst component (A3) (21) (a2)→(d)→(c)+(f)→(b)→<<intermediate washing→(e)→(b)→(c)+(f)>>→final washing→solid catalyst component (A3) (22) (a2)→(d)→(c)+(f)→(b)→<<intermediate washing→(d)→(c)+(f)→(b)>>→final washing solid catalyst component (A3) (23) (a2)→(d)→(f)→(b)→(c)<<→intermediate washing→(d)→(b)>>→final washing solid catalyst component (A3) (24) (a2)→(d)→(f)→(b)→(c)→<<intermediate washing→(d)→(b)+(c)>>→final washing→solid catalyst component (A3) (25) (a2)→(d)→(f)→(b)→(c)→<<intermediate washing→(e)→(b)+(d)>>→final washing→solid catalyst component (A3) (26) (a2)→(e)→(d)→(b)→(c)→<<intermediate washing→(d)→(b)+(c)+(f)>>→final washing solid catalyst component (A3) (27) (a2)→(c)+(f)+(d)→(b)→<<intermediate washing→(b)+(d)>>→final washing→solid catalyst component (A3) (28) (a2)→(c)+(f)+(d)→(b)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A3) (29) (a2)→(c)+(f)+(d)→(b)→<<intermediate washing→(b)+(d)→(c)+(f)>>→final washing solid catalyst component (A3) (30) (a2)→(c)+(f)+(d)→(b)→<<intermediate washing→(d)→(b)→(c)+(f)>>→final washing→solid catalyst component (A3) The following examples are given more specifically as the preferable order of contacting the components one another for preparing the solid catalyst component (A4) of the present invention. (31) (a2)→(d)→(b)→(c)→(g)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A4) (32) (a2)→(d)→(c)→(b)→(g)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A4) (33) (a2)→(d)→(b)→(c)→(g)→<<intermediate washing→(d)→(b)→(c)>>→final washing→solid catalyst component (A4) (34) (a2)→(d)→(b)→(c)→(g)→<<intermediate washing→(d)→(c)→(b)>>→final washing→solid catalyst component (A4) (35) (a2)→(d)→(c)→(b)→(g)→<<intermediate washing→(d)→(b)→(c)>>→final washing→solid catalyst component (A4) (36) (a2)→(d)→(c)→(b)→(g)→<<intermediate washing→(d)→(c)→(b)>>→final washing→solid catalyst component (A4) (37) (a2)→(c)+(d)→(b)→(g)→<<intermediate washing→(d)→(b)>>→final washing→solid catalyst component (A4) (38) (a2)→(c)+(d)→(b)→(g)→<<intermediate washing→(b)+(d)>>→final washing→solid catalyst component (A4) (39) (a2)→(c)+(d)→(b)→(g)→<<intermediate washing→(b)+(d)→(c)+(e)>>→final washing→solid catalyst component (A4) (40) (a2)→(c)+(d)→(b)→(g)→<<intermediate washing→(d)→(b)→(c)+(e)>>→final washing→solid catalyst component (A4) In the above methods of contacting the components one another for the solid catalyst components (A1) to (A4), catalytic activity can be further improved if the steps in the double parentheses in the above processes of contact are repeated several times, if required. The components (b) and (d) used in the steps in the double parentheses may be either newly added components or residues from the previous steps. In addition to the washing steps indicated in the above processes, the intermediate products in any of the above contact steps may be washed with a hydrocarbon compound which is liquid at normal temperatures. Based on the above description, a particularly preferable process for preparing the solid catalyst components (A1) to (A4) comprises suspending the dialkoxy magnesium compound (a1) or magnesium compound (a2) in the aromatic hydrocarbon (d) having a boiling point in the range of 50-150° C., causing the tetravalent titanium halide (b) to come into contact with the suspension, and reacting the mixture. In the above process, one or more electron donor compounds (c) and/or an electron donor compound (e), an electron donor compound (f), or a siloxane (g) are caused to come in contact with the suspension at a temperature from −20° C. to 130° C., either before or after the tetravalent titanium halide (b) is caused to contact the suspension, to obtain a solid reaction product (1) In this instance, it is desirable to carry out an aging reaction at a low temperature either before or after the electron donor compounds are caused to contact the suspension. After washing the solid reaction product (1) with a hydrocarbon compound which is liquid at normal temperatures (intermediate washing), the tetravalent titanium halide (b) is again caused to contact the solid reaction product (1) in the presence of an aromatic hydrocarbon compound at a temperature of −20° C. to 100° C., to obtain a solid reaction product (2). As required, the intermediate washing and the reaction may be further repeated several times. Next, the solid reaction product (2) is washed with a hydrocarbon compound which is liquid at normal temperatures (final washing) to obtain the solid catalyst component. Preferable conditions of the above reactions and washing operations are as follows. Low temperature aging reaction: −20° C. to 70° C., preferably −10° C. to 60° C., and more preferably 0° C. to 30° C., for 1 minute to 6 hours, preferably 5 minutes to 4 hours, and particularly preferably 10 minutes to 3 hours. Reaction: 0° C. to 130° C., preferably 40° C. to 120° C., and particularly preferably 50° C. to 115° C., for 0.5 to 6 hours, preferably 0.5 to 5 hours, and particularly preferably 1 to 4 hours. Washing: at 0° C. to 110° C., preferably 30° C. to 100° C., and particularly preferably 30° C. to 90° C., from 1 to 20 times, preferably 1 to 15 times, and particularly preferably 1 to 10 times. Hydrocarbons used for washing are preferably aromatic hydrocarbons or saturated hydrocarbons which are liquid at normal temperatures. Specific examples include aromatic hydrocarbons such as toluene, xylene, and ethylbenzene, and saturated hydrocarbons such as hexane, heptane, and cyclohexane. The aromatic hydrocarbons are preferably used for the intermediate washing, whereas the saturated hydrocarbons are preferably used for the final washing. The ratio of the compounds used for preparing the solid catalyst components (A1) to (A4) cannot be generically defined, because such a ratio varies according to the process employed. For example, the tetravalent titanium halide (b) is used in an amount of 0.5 to 100 mols, preferably 0.5 to 50 mols, still more preferably 1 to 10 mols; the electron donor compound (c) is used in an amount of 0.01 to 10 mols, preferably 0.01 to 1 mol, and still more preferably 0.02 to 0.6 mol; the aromatic hydrocarbon (d) are used in an amount of 0.001 to 500 mols, preferably 0.001 to 100 mols, and still more preferably 0.005 to 10 mols; the electron donor compound (e) is used in an amount of 0.01 to 10 mols, preferably 0.01 to 1 mol, and still more preferably 0.02 to 0.6 mol; the electron donor compound (f) is used in an amount of 0.01 to 10 mols, preferably 0.01 to 1 mol, and still more preferably 0.02 to 0.6 mol; the siloxane compound (g) is used in an amount of 0.01 to 100 g, preferably 0.05 to 80 g, and still more preferably 1 to 50 g for one mol of the dialkoxy magnesium (a1) or magnesium compound (a2). There are no specific limitations to the amount of titanium, magnesium, halogen atoms, and electron donor compounds in the solid catalyst component (A1) of the present invention. The content of titanium is 1.8 to 8.0 wt %, preferably 2.0 to 8.0 wt %, and still more preferably 3.0 to 8.0 wt %; the content of magnesium is 10 to 70 wt %, preferably 10 to 50 wt %, more preferably 15 to 40 wt %, and particularly preferably 15 to 25 wt %; the content of halogen atoms is 20 to 90 wt %, preferably 30 to 85 wt %, more preferably 40 to 80 wt %, and particularly preferably 45 to 75 wt %; and the total amount of the electron donor compounds is 0.5 to 30 wt %, preferably 1 to 25 wt %, and particularly preferably 2 to 20 wt %. To ensure well-balanced comprehensive performance of the solid catalyst component (A1) comprising the electron donor compounds and other components of the present invention, it is preferable that the contents of titanium, magnesium, halogen atoms, and electron donor compounds be respectively 3-8 wt %, 15-25 wt %, 45-75 wt %, and 2-20 wt %. Compounds represented by the formula R11pAlQ3-p can be used as the organoaluminum compound (B) for preparing the catalyst for polymerization of olefins of the present invention. In the formula, R11 represents a linear or branched alkyl group having 1-4 carbon atoms, Q represents a hydrogen atom or a halogen atom, and p represents a real number satisfying the formula 0<p≦3. As specific examples of such organoaluminum compounds (B), triethylaluminum, diethylaluminum chloride, triisobutylaluminum, diethylaluminum bromide, and diethylaluminum hydride can be given. These compounds may be used either individually or in combination of two or more. Triethylaluminum and triisobutylaluminum are preferably used. The same electron donor compounds used for preparing the solid catalyst components can be used as the extend electron donor compound (C) (hereinafter referred to as “component (C)”) for preparing the catalyst for polymerizing olefins of the present invention. Particularly preferable compounds for this purpose are ethers such as 9,9-bis(methoxymethyl)fluorine and 2-isopropyl-2-isopentyl-1,3-dimethoxypropane; esters such as methyl benzoate and ethyl benzoate; and organosilicon compounds. As the organosilicon compounds, compounds of the above formula (5) can be used. As examples of such organosilicon compounds, phenylalkoxysilane, alkylalkoxysilane, phenylalkylalkoxysilane, cycloalkylalkoxysilane, and cycloalkylalkylalkoxysilane can be given. The following compounds can be given as specific examples of such organosilicon compounds: trimethylmethoxysilane, trimethylethoxysilane, tri-n-propylmethoxysilane, tri-n-propylethoxysilane, tri-n-butylmethoxysilane, triisobutyl methoxysilane, tri-t-butylmethoxysilane, tri-n-butylethoxysilane, tricyclohexylmethoxysilane, tricyclohexylethoxysilane, cyclohexyldimethylmethoxysilane, cyclohexyldiethylmethoxysilane, cyclohexyldiethylethoxy silane, dimethyldimethoxysilane, dimethyldiethoxysilane, di-n-propyldimethoxysilane, diisopropyldimethoxysilane, di-n-propyldiethoxysilane, diisopropyldiethoxysilane, di-n-butyldimethoxysilane, diisobutyldimethoxysilane, di-t-butyldimethoxysilane, di-n-butyldiethoxysilane, n-butylmethyldimethoxysilane, bis(2-ethylhexyl)dimethoxysilane, bis(2-ethylhexyl)diethoxysilane, dicyclopentyldimethoxysilane, dicyclopentyldiethoxysilane, dicyclohexyldimethoxysilane, dicyclohexyldiethoxysilane, bis(3-methylcyclohexyl)dimethoxysilane, bis(4-methylcyclohexyl)dimethoxysilane, bis(3,5-dimethylcyclohexyl)dimethoxysilane, cyclohexylcyclopentyl dimethoxysilane, cyclohexylcyclopentyldiethoxysilane, cyclohexylcyclopentyldipropoxysilane, 3-methylcyclohexylcyclopentyldimethoxysilane, 4-methylcyclohexylcyclopentyldimethoxysilane, 3,5-dimethylcyclohexylcyclopentyldimethoxysilane, 3-methylcyclohexylcyclohexyldimethoxysilane, 4-methylcyclohexylcyclohexyldimethoxysilane, 3,5-dimethylcyclohexylcyclohexyldimethoxysilane, cyclopentylmethyldimethoxysilane, cyclopentylmethyldiethoxysilane, cyclopentylethyldiethoxysilane, cyclopentyl(isopropyl)dimethoxysilane, cyclopentyl(isobutyl)dimethoxysilane, cyclohexylmethyldimethoxysilane, cyclohexylmethyldiethoxysilane, cyclohexylethyldimethoxysilane, cyclohexylethyldiethoxysilane, cyclohexyl(n-propyl)dimethoxysilane, cyclohexyl(iso-propyl)dimethoxysilane, cyclohexyl(n-propyl)diethoxysilane, cyclohexyl(isobutyl)dimethoxysilane, cyclohexyl(n-butyl)diethoxysilane, cyclohexyl(n-pentyl)dimethoxysilane, cyclohexyl(n-pentyl)diethoxysilane, diphenyldimethoxysilane, diphenyldiethoxysilane, phenylmethyldimethoxysilane, phenylmethyldiethoxysilane, phenylethyldimethoxysilane, phenylethyldiethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, ethyltrimethoxysilane, ethyltriethoxysilane, n-propyltrimethoxysilane, isopropyltrimethoxysilane, n-propyltriethoxysilane, isopropyl triethoxysilane, n-butyltrimethoxysilane, isobutyltrimethoxysilane, t-butyltrimethoxysilane, n-butyltriethoxysilane, 2-ethylhexyltrimethoxysilane, 2-ethylhexyltriethoxysilane, cyclopentyltrimethoxysilane, cyclopentyltriethoxysilane, cyclohexyltrimethoxysilane, cyclohexyltriethoxysilane, vinyltrimethoxysilane, vinyltriethoxysilane, phenyltrimethoxysilane, phenyltriethoxysilane, tetramethoxysilane, tetraethoxysilane, tetrapropoxysilane, and tetrabutoxysilane. In addition to the organosilicon compound represented by the above formula (5), aminosilane compounds such as bis(perhydroquinolino)dimethoxysilane and bis(perhydroisoquinolino)dimethoxysilane can be used. Of these, preferable compounds are di-n-propyl dimethoxysilane, diisopropyldimethoxysilane, di-n-butyl dimethoxysilane, diisobutyldimethoxysilane, di-t-butyldimethoxysilane, di-n-butyldiethoxysilane, t-butyltrimethoxysilane, dicyclohexyldimethoxysilane, dicyclohexyldiethoxysilane, cyclohexylmethyldimethoxysilane, cyclohexylmethyldiethoxysilane, cyclohexylethyldimethoxysilane, cyclohexylethyldiethoxysilane, dicyclopentyldimethoxysilane, dicyclopentyldiethoxysilane, cyclopentylmethyldimethoxysilane, cyclopentylmethyldiethoxysilane, cyclopentylethyldiethoxysilane, cyclohexylcyclopentyldimethoxysilane, cyclohexylcyclopentyldiethoxysilane, 3-methylcyclohexylcyclopentyldimethoxysilane, 4-methylcyclohexylcyclopentyldimethoxysilane, and 3,5-dimethylcyclohexylcyclopentyl dimethoxysilane. Either one type of these organosilicon compounds (C) or a combination of two or more types of these compounds can be used in the present invention. The olefin polymerization catalyst of the present invention comprises the above-described component (A), component (B), and component (C) for the solid catalyst component for polymerizing olefins. Polymerization or copolymerization of olefins is carried out in the presence of this catalyst. The olefins, such as ethylene, propylene, 1-butene, 1-pentene, 4-methyl-1-pentene, and vinyl cyclohexane can be used either individually or in combination of two or more. Of these, ethylene, propylene, and 1-butene can be suitably used. A particularly preferable olefin is propylene. Propylene may be copolymerized with other olefins. As the olefins to be copolymerized, ethylene, 1-butene, 1-pentene, 4-methyl-1-pentene, vinyl cyclohexane, and the like can be used either individually or in combination of two or more. Of these, ethylene and 1-butene can be suitably used. The ratio of the components used is not specifically limited inasmuch as such a ratio does not influence the effect of the present invention. Usually, the organoaluminum compound (B) is used in an amount of 1-2,000 mols, and preferably 50-1,000 mols, per mol of titanium atoms in the solid catalyst component (A). The organoaluminum compound (C) is used in an amount of 0.002-10 mols, preferably 0.01-2 mols, and particularly preferably 0.01-0.5 mol per mol of the component (B). Although the order of contact of these compositions is not limited, it is desirable to first add the organoaluminum compound (B) to the polymerization system, then cause the organosilicon compound (C) to come into contact with the organoaluminum compound (B), and causing the solid catalyst component (A) to come into contact with the resulting mixture. In the present invention, polymerization can be carried out either in the presence or in the absence of an organic solvent. Olefin monomers such as propylene may be used either in a gaseous state or in a liquid state. The polymerization reaction is preferably carried out at a temperature of 200° C. or less, and preferably at 100° C. or less, under a pressure of 10 MPa or less, and preferably 5 MPa or less. Either a continuous polymerization system or a batch polymerization system may be used for the polymerization reaction. In addition, the polymerization can be completed either in one step or in two or more steps. In polymerizing olefins using the olefin polymerization catalyst component (A), component (B), and component (C), it is desirable to preliminary polymerize the olefins prior to the main polymerization reaction to improve catalytic activity, stereoregularity, properties of the resulting polymer particles, and the like. In addition to the olefins used in the main polymerization, monomers such as styrene can be used in the preliminary polymerization. Although the order of contact of the components and monomers in carrying out the preliminary polymerization is not limited, it is desirable to first add the organoaluminum compound (B) to the preliminary polymerization system in an inert gas or olefin gas atmosphere, cause the composition (A) for olefin polymerization to come into contact with the component (B), and then cause one or more olefins such as propylene to come contact with the mixture. When the preliminary polymerization is carried out, it is desirable to first add the component (B) to the preliminary polymerization system in an inert gas or olefin gas atmosphere, cause the olefin polymerization catalyst component (A) for to come into contact with the component (B), and then cause one or more olefins such as propylene to come into contact with the mixture. Polymerization of olefins in the presence of the olefin polymerization catalyst prepared by the process of the present invention can produce highly stereoregular polymers in a high yield, while exhibiting high activity and excellent catalytic activity to hydrogen as compared with the case of polymerization using a conventional catalyst. EXAMPLES The present invention will be described in more detail by way of examples, which are explained in comparison with comparative examples. Example 1 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 10 g of diethoxymagnesium and 80 ml toluene to prepare a suspension. After the addition of 20 ml of titanium tetrachloride, the suspension was heated, and when the temperature increased to as high as 80° C., 3.12 ml of diethyl dibutylmalonate was added and the mixture was heated to 110° C. Then, the mixture was reacted for one hour while stirring at 110° C. After the reaction, the resulting reaction mixture was washed three times with 100 ml of toluene at 90° C. After the addition of 20 ml of titanium tetrachloride and 80 ml of toluene, the reaction mixture was heated to 110° C. and reacted for one hour while stirring. After the reaction, the resulting reaction mixture was washed seven times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The liquid in the solid catalyst component was separated from the solid components. The content of titanium in the solid components was determined to confirm that the content was 4.1 wt %. (Preparation of Polymerization Catalyst and Polymerization) A 2.0 l autoclave equipped with a stirrer, in which the internal atmosphere had been entirely replaced by nitrogen gas, was charged with 1.32 mmol of triethylaluminum, 0.13 mmol of cyclohexylmethyldimethoxysilane, and the above solid catalyst component (A) in an amount, in terms of the titanium atoms contained therein, of 0.0026 mmol, thereby forming a polymerization catalyst. Then, with the addition of 2.0 l of hydrogen gas and 1.4 l of liquified propylene, preliminary polymerization was carried out for 5 minutes at 20° C., following which the preliminary polymerization product was heated and main polymerization was carried out for one hour at 70° C. The polymerization activity per gram of the solid catalyst component, the n-heptane insoluble matters (HI) in boiling n-heptane in the produced polymer, and the melt flow rate (MFR) of the produced polymer (a) are shown in Table 1. The polymerization activity per gram of the solid catalyst component used here was calculated by the following formula: Polymerization activity=Produced polymer(g)/Solid catalyst component(g) The proportion of boiling n-heptane insoluble matters (HI) in the produced polymer was determined by extracting the polymer for 6 hours in boiling n-heptane and determining the proportion (wt %) of the boiling n-heptane insoluble matters. The melt flow rate (MFR) of the produced polymer was determined according to the test method conforming to ASTM D1238 or JIS K7210. Example 2 A solid catalyst component was prepared in the same manner as in Example 1, except for using 3.07 ml of diethyl diisobutylmalonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 4.1 wt %. The polymerization results are shown in Table 1. Example 3 A solid catalyst component was prepared in the same manner as in Example 1, except for using 2.78 ml of diethyl isopropylmalonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 3.8 wt %. The polymerization results are shown in Table 1. Example 4 A solid catalyst component was prepared in the same manner as in Example 1, except for using 3.39 ml of diethyl bis(3-chloro-n-propyl) malonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 3.7 wt %. The polymerization results are shown in Table 1. Example 5 A solid catalyst component was prepared in the same manner as in Example 1, except for using 4.35 ml of diethyl bis(3-chloro-n-propyl) malonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 3.5 wt %. The polymerization results are shown in Table 1. Example 6 A solid catalyst component was prepared in the same manner as in Example 1, except for using 2.55 ml of diethyl butylbromomalonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 3.0 wt %. The polymerization results are shown in Table 1. Example 7 A solid catalyst component was prepared in the same manner as in Example 1, except for using 2.98 ml of diethyl butylbromomalonate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 2.9 wt %. The polymerization results are shown in Table 1. Comparative Example 1 A solid catalyst component was prepared in the same manner as in Example 1, except for using 1.80 ml of diethyl phthalate instead of 3.12 ml of diethyl dibutylmalonate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst component was 3.41 wt %. The polymerization results are shown in Table 1. Comparative Example 2 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had sufficiently been replaced with nitrogen gas, was charged with a mixture of 53 ml of decane and 51 ml of 2-ethylhexyl alcohol. 10 g of anhydrous magnesium chloride (manufactured by Toho Titanium Co., Ltd.) was added and the mixture was heated to 130° C. and kept at this temperature while stirring to dissolve the anhydrous magnesium chloride, thereby obtaining a homogeneous solution. 2.2 g of phthalic anhydride was added to the solution and the mixture was reacted for one hour while stirring at 130° C. Separately, a 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 85 ml of titanium tetrachloride. After cooling to −20° C., the above homogeneous solution was added dropwise. The mixture was heated to 110° C. and 2.78 ml of diethyl diisobutylmalonate was added. The mixture was heated for 2 hours at 110° C. After removing the supernatant solution, 85 ml of titanium tetrachloride was added and the mixture was reacted at 110° C. for 2 hours while stirring. After the reaction, the resulting reaction mixture was washed seven times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The liquid in the solid catalyst component was separated from the solid components. The content of titanium in the solid components was determined to confirm that the content was 2.5 wt %. (Preparation of Polymerization Catalyst and Polymerization) A polymerization catalyst was prepared and a polymer was produced in the same manner as in Example 1. The results are shown in Table 1. Comparative Example 3 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 10 g of diethoxymagnesium, 2.78 ml of diethyl diisobutylmalonate, and 50 ml of methylene chloride to prepare a suspension. The mixture was heated and reacted for 1 hour while stirring under reflux. Separately, a 1,000 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 400 ml of titanium tetrachloride at room temperature. The above suspension was added dropwise. The mixture was heated to 110° C. and reacted for two hours while stirring. After removing the supernatant solution, the residue was washed three times with 400 ml of decane. 400 ml of titanium tetrachloride was added and the mixture was reacted at 120° C. for 2 hours while stirring. After the reaction, the resulting reaction mixture was washed seven times with 400 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The liquid in the solid catalyst composition was separated from the solid components. The content of titanium in the solid components was determined to confirm that the content was 3.3 wt %. (Preparation of Polymerization Catalyst and Polymerization) A polymerization catalyst was prepared and a polymer was produced in the same manner as in Example 1. The results are shown in Table 1. TABLE 1 Polymerization activity HI MFR (g-PP/g-cat.) (wt %) (g/10 min) Example 1 56,900 96.5 16 Example 2 51,400 97.2 29 Example 3 53,000 98.2 25 Example 4 38,900 96.4 21 Example 5 30,600 97.6 19 Example 6 39,000 98.0 15 Example 7 34,600 97.2 12 Comparative 39,200 98.1 6.6 Example 1 Comparative 27,500 97.5 8.5 Example 2 Comparative 29,500 97.7 7.6 Example 3 As can be seen from the results shown in Table 1, olefin polymers with high stereoregularity can be obtained in a high yield by polymerizing propylene using the solid catalyst component and the catalyst of the present invention exhibiting high catalytic activity to hydrogen and high activity. Example 8 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 30 ml of titanium tetrachloride and 80 ml toluene to prepare a solution. Next, a suspension prepared from 10 g of spherical diethoxy magnesium (sphericity, l/w: 1.10), 50 ml of toluene, and 2.0 ml of di-n-butyl phthalate was added to the above solution maintained at 10° C. The mixed solution was heated to 60° C. and 4.0 ml of diethyl diisobutylmalonate was added. The mixture was further heated to 90° C. and reacted for two hours while stirring. After the reaction, the resulting solid product was washed four times with 100 ml of toluene at 90° C. After the addition of 30 ml of titanium tetrachloride and 70 ml of toluene, the reaction mixture was heated to 112° C. and reacted for two hours while stirring. After the reaction, the resulting reaction mixture was washed ten times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The content of titanium in the solid catalyst component was analyzed and found to be 2.65 wt %. (Preparation of Polymerization Catalyst and Polymerization) A polymerization catalyst was prepared and a polymer was produced in the same manner as in Example 1. The polymerization activity per gram of the solid catalyst composition, the n-heptane insoluble matters (HI) in boiling n-heptane in the resulting polymer (a), the melt flow rate (MFR) of the polymer, the amount of fine powders (212 μm or less) in the polymer, and particle size distribution [(D90-D10)/D50] of the polymer are shown in Table 2. Example 9 A solid catalyst component was prepared in the same manner as in Example 8, except for changing the amount of di-n-butyl phthalate from 2.0 ml to 2.4 ml and the amount of diethyl diisobutylmalonate from 4.0 ml to 4.4 ml. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 3.0 wt %. The polymerization results are shown in Table 2. Comparative Example 4 A solid catalyst component was prepared in the same manner as in Example 8, except that diethyl diisobutylmalonate was not added and di-n-butyl phthalate was added in an amount of 2.4 ml instead of 2.0 ml. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 3.3 wt %. The polymerization results are shown in Table 2. TABLE 2 Comparative Example 8 Example 9 Example 4 Polymerization activity 50,700 49,300 58,000 (g-PP/g-cat.) HI (wt %) 98.6 98.8 98.4 MFR (g/10 min) 8.4 11 4.5 Fine polymer powders 0 0.4 3.4 (212 μm or less) (wt %) Particle size 0.55 0.69 0.94 distribution of polymer As can be seen from the results shown in Table 2, olefin polymers with high stereoregularity can be obtained in a high yield by polymerizing propylene using the solid catalyst component and the catalyst of the present invention exhibiting high catalyst activity to hydrogen. In addition, the polymer produced using the solid catalyst component and the catalyst of the present invention has only a very small content of fine powders and has uniform particle distribution. Example 10 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 30 ml of titanium tetrachloride and 20 ml toluene to prepare a solution. Next, a suspension prepared from 10 g of spherical diethoxymagnesium (sphericity, l/w: 1.10), 3.1 ml of diethyl diisobutyl malonate, 0.6 ml of diethyl maleate, and 50 ml of toluene was added to the above solution. The mixture was heated to 90° C. and reacted for two hours while stirring. After the reaction, the resulting solid product was washed four times with 100 ml of toluene at 90° C. After the addition of 30 ml of titanium tetrachloride and 70 ml of toluene, the reaction mixture was heated to 110° C. and reacted for two hours while stirring. After the reaction, the resulting reaction mixture was washed ten times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The content of titanium in the solid catalyst component was analyzed and found to be 3.7 wt %. (Preparation of Polymerization Catalyst and Polymerization) A polymerization catalyst was prepared and a polymer was produced in the same manner as in Example 1. The results are shown in Table 3. Example 11 A solid catalyst component was prepared in the same manner as in Example 10, except that diethyl dibutylmalonate was used instead of diethyl diisobutylmalonate and di-n-butyl maleate was used instead of diethyl maleate. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 3.5 wt %. The polymerization results are shown in Table 3. Comparative Example 5 A solid catalyst component was prepared in the same manner as in Example 10, except that diethyl diisobutylmalonate was not added and diethyl malonate was added in an amount of 1.5 ml instead of 0.6 ml. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 3.7 wt %. The polymerization results are shown in Table 3. TABLE 3 Polymerization activity HI MFR (g-PP/g-cat.) (wt %) (g/10 min) Example 10 57,500 98.2 27 Example 11 56,200 98.0 25 Comparative Example 5 58,000 98.0 11 As can be seen from the results shown in Table 3, polymerization of propylene using the solid catalyst component and the catalyst of the present invention can produce highly stereoregular olefin polymers in a high yield with a higher melt flow rate (specifically at a higher catalyst activity to hydrogen) as compared with conventional catalysts. Example 12 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 30 ml of titanium tetrachloride and 80 ml toluene to prepare a solution. Next, a suspension prepared from 10 g of spherical diethoxy magnesium (sphericity, l/w: 1.10), 3.1 ml of diethyl diisobutylmalonate, and 50 ml of toluene was added to the above solution. 4 ml of decamethylcyclopentasiloxane was added at 100° C. The mixture was further heated to 110° C. Then, the mixture was reacted for one hour while stirring at 110° C. After the reaction, the resulting solid product was washed four times with 100 ml of toluene at 90° C. After the addition of 30 ml of titanium tetrachloride and 70 ml of toluene, the reaction mixture was heated to 110° C. and reacted for two hours while stirring. After the reaction, the resulting reaction mixture was washed ten times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The content of titanium in the solid catalyst component was analyzed and found to be 3.0 wt %. (Preparation of Polymerization Catalyst and Polymerization) A polymerization catalyst was prepared and a polymer was produced in the same manner as in Example 1. The results are shown in Table 4. Example 13 Preparation of Solid Catalyst Component (A) A 500 ml round bottom flask equipped with a stirrer, in which the internal atmosphere had been sufficiently replaced by nitrogen gas, was charged with 10 g of diethoxy magnesium, 2.4 ml of di-n-butyl phthalate, and 50 ml of toluene to prepare a suspension. After the addition of 20 ml of titanium tetrachloride to the suspension, the mixture was heated. 2 ml of decamethylcyclopentasiloxane was added to the mixture at temperatures of 80° C. and 100° C. Then, the mixture was further heated to 110° C. Then, the mixture was reacted for one hour while stirring at 110° C. After the reaction, the resulting reaction mixture was washed three times with 100 ml of toluene at 90° C. After the addition of 20 ml of titanium tetrachloride and 80 ml of toluene, the reaction mixture was heated to 110° C. and reacted for one hour while stirring. After the reaction, the resulting reaction mixture was washed seven times with 100 ml of n-heptane at 40° C., thereby obtaining a solid catalyst component. The liquid in the solid catalyst composition was separated from the solid components. The content of titanium in the solid components was determined to confirm that the content was 2.8 wt %. (Preparation of Polymerization Catalyst and Polymerization) Polymerization was carried out in the same manner as in Example 1, except for using the solid catalyst composition prepared above. The results are shown in Table 4. Example 14 A solid catalyst component was prepared in the same manner as in Example 12, except for using 4 ml of 1,3-dichlorotetramethyldisiloxane instead of 4 ml of decamethylcyclopentasiloxane. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 2.3 wt %. The polymerization results are shown in Table 4. Comparative Example 6 A solid catalyst component was prepared in the same manner as in Example 13, except that diethyl isobutyl malonate was not added. A polymerization catalyst was prepared from the solid catalyst component and polymerization was carried out using the catalyst. The content of titanium in the resulting solid catalyst composition was 2.6 wt %. The polymerization results are shown in Table 4. TABLE 4 Polymerization activity HI MFR (g-PP/g-cat.) (wt %) (g/10 min) Example 12 55,500 98.6 13 Example 13 59,800 98.5 8.5 Example 14 59,000 98.9 10 Comparative Example 6 59,200 98.9 3.6 As can be seen from the results shown in Table 4, olefin polymers with high stereoregularity can be obtained in a high yield by polymerizing propylene using the solid catalyst component and the catalyst of the present invention exhibiting high catalyst activity to hydrogen. INDUSTRIAL APPLICABILITY The catalyst for polymerization of olefins of the present invention exhibits a high catalyst activity to hydrogen and can produce olefin polymers in a high yield while maintaining high stereoregularity of the olefin polymers. The catalyst is therefore expected not only to produce polyolefins for common use at a low cost, but also to be useful in the manufacture of olefin copolymers having high functions.
<SOH> BACKGROUND ART <EOH>A solid catalyst component containing magnesium, titanium, an electron donor compound, and a halogen as essential components used for the polymerization of olefins such as propylene has been known in the art. A large number of methods for polymerizing or copolymerizing olefins in the presence of a catalyst for olefin polymerization comprising the above solid catalyst component, an organoaluminum compound, and an organosilicon compound have been proposed. For example, Japanese Unexamined Patent Publication No. (hereinafter referred to as JP-A) 63310/1982 and JP-A No. 63311/1982 propose a method for polymerizing olefins, particularly olefins with three or more carbon atoms, in which a catalyst comprising a solid catalyst component containing a magnesium compound, a titanium compound, and an electron donor, an organoaluminum compound, and an organosilicon compound having an Si—O—C linkage in combination is used. However, because these methods are not necessarily satisfactory for producing highly stereoregular polymers in a high yield, improvement of these methods has been desired. JP-A No. 3010/1988 proposes a catalyst and method for polymerizing propylene. The catalyst comprises a solid catalyst component, obtained by processing a powder produced from dialkoxy magnesium, aromatic dicarboxylic acid diester, aromatic hydrocarbon, and titanium halide with heat, an organoaluminum compound, and an organosilicon compound. JP-A No. 315406/1989 proposes another propylene polymerization catalyst and a method for polymerizing propylene in the presence of this catalyst. The catalyst comprises a solid catalyst component obtained by preparing a suspension from diethoxy magnesium and alkyl benzene, causing this suspension to come into contact with titanium tetrachloride, and reacting the resulting product with phthalic acid dichloride, an organoaluminum compound, and an organosilicon compound. All of the above-described conventional technologies have attained certain results in improving catalytic activity to the extent of permitting dispensing with an ash-removal step for removing catalyst residues such as chlorine and titanium from formed polymers, improving the yield of stereoregular polymers, and improving durability of catalytic activity during polymerization. The polymers produced using these catalysts are used in a variety of applications including formed products such as vehicles and household electric appliances, containers, and films. These products are manufactured by melting polymer powders produced by polymerization and forming the melted polymers using various molds. In manufacturing formed products, particularly, large products by injection molding or the like, melted polymers are sometimes required to have a high fluidity (a melt flow rate). Accordingly, a large number of studies have been undertaken to increase the melt flow rate of polymers. The melt flow rate greatly depends on the molecular weight of the polymers. In the industry, hydrogen is generally added as a molecular weight regulator for polymers during polymerization of propylene. In this instance, a large quantity of hydrogen is usually added to produce low molecular weight polymers having a high melt flow rate. However, the quantity of hydrogen which can be added is limited because pressure resistance of the reactor is limited because of safety. In order to add a larger amount of hydrogen, the partial pressure of monomers to be polymerized has to be decreased. The decrease in the partial pressure, however, is accompanied by a decrease in productivity. Additionally, use of a large amount of hydrogen may bring about a problem of cost. Development of a catalyst capable of producing polymers with a high melt flow rate by using a smaller amount of hydrogen, in other words, a catalyst which has high activity to hydrogen and can produce a highly stereoregular polymer in a high yield has therefore been desired. However, the above-mentioned conventional technologies were insufficient to solve these problems. In addition, taking these environmental problems, development of a compound without a benzene ring instead of the compounds containing a benzene ring mainly used as electron donors for preparing the solid catalyst component in above-mentioned conventional technologies is desired. Accordingly, an object of the present invention is to solve such problems remaining in the prior art and to provide a solid catalyst component and a catalyst for polymerization of olefins, free from aromatic esters in the catalyst component, having excellent catalytic activity to hydrogen and high activity, and capable of producing polymers with high stereoregularity in a high yield.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a flow chart showing a process for preparing the polymerization catalyst of the present invention. detailed-description description="Detailed Description" end="lead"?
20041124
20070424
20051013
94929.0
0
MARCANTONI, PAUL D
SOLID CATALYST COMPONENT FOR OLEFIN POLYMERIZATION AND CATALYST
UNDISCOUNTED
0
ACCEPTED
2,004
10,514,814
ACCEPTED
Dielectric barrier discharge lamp with a base
An elongated dielectric barrier discharge lamp with outer and inner electrodes has a tube that is arranged on the lamp stand end of the discharge vessel and that surrounds the lamp stand. The tube serves to receive a seal in order to install the lamp in a process chamber in a gastight manner. Power supply of the outer electrodes is separated from the power supply for the inner electrodes coming out of the lamp stand by means of the abovementioned tube. This makes it possible to prevent effectively parasitic discharges between the power supplies which are applied at different potentials during operation also in process chambers under negative pressure.
1. A dielectric barrier discharge lamp (1) having a base, the discharge lamp (1) having the following: an elongate discharge vessel (2), which is sealed at both ends, and whose wall surrounds an ionizable filling, electrodes (8a-8f, 23), at least one of the electrodes being an inner electrode (23), i.e. being arranged within the discharge vessel (2), and at least one of the electrodes being an outer electrode (8a-8f), i.e. being arranged on the outside of the wall of the discharge vessel (2), a power supply line (24) for the at least one inner electrode (23) and a lamp foot (21), through which the at least one inner electrode (23) is connected in a gas-tight manner to the power supply line (24), characterized in that the base comprises a tube (4) which is fitted to the lamp foot-side end of the discharge vessel (2) in a gas tight manner in a gas tight manner and surrounds the lamp foot (21). 2. The dielectric barrier discharge lamp having a base as claimed in claim 1, the tube (4) also having a sealing means (12). 3. The dielectric barrier discharge lamp having a base as claimed in claim 2, the sealing means (12) comprising a vacuum flange (13). 4. The dielectric barrier discharge lamp having a base as claimed in claim 3, the vacuum flange (13) being plugged onto the tube. 5. The dielectric barrier discharge lamp having a base as claimed in claim 2, a power supply line (11) for the at least one outer electrode (8a-8f) being arranged on the outside of the tube and being passed through the sealing means (12). 6. The dielectric barrier discharge lamp having a base as claimed in claim 1 having a connection plug (7) on that end of the tube (4) which faces away from the lamp, at least the power supply line (24) for the inner electrode (23) being connected to said connection plug (7). 7. The dielectric barrier discharge lamp having a base as claimed in claim 6, the connection plug (7) being of the type BNC-HT. 8. The dielectric barrier discharge lamp having a base as claimed in claim 1, the outer electrode(s) (8a-8f) and the power supply line (11) for the outer electrode(s) having conductor track-like structures. 9. The dielectric barrier discharge lamp having a base as claimed in claim 8, the conductor track-like structures comprising two or more strips (8a-8f, 11) which are fitted in the axial direction and with a mutual spacing on the outside of the discharge vessel (2). 10. The dielectric barrier discharge lamp having a base as claimed in claim 3, the vacuum flange (13) being made of the same material as the tube and being fused to the free end of the tube. 11. The dielectric barrier discharge lamp having a base as claimed in claim 3, the vacuum flange (13) being made of metal and being fused to the free end of the tube by means of glass transition elements. 12. The dielectric barrier discharge lamp having a base as claimed in claim 1, the inner electrode (23) being helical and being oriented axially with respect to the discharge vessel (2). 13. The dielectric barrier discharge lamp having a base as claimed in claim 1, the tube (4) having a cylindrical (6) and a conical section (5), and the conical section (5) connecting the discharge vessel (2) to the cylindrical section (6). 14. The dielectric barrier discharge lamp having a base as claimed in claim 3, a power supply line (11) for the at least one outer electrode (8a-8f) being arranged on the outside of the tube and being passed through the sealing means (12). 15. The dielectric barrier discharge lamp having a base as claimed in claim 4, a power supply line (11) for the at least one outer electrode (8a-8f) being arranged on the outside of the tube and being passed through the sealing means (12). 16. The dielectric barrier discharge lamp having a base as claimed in claim 2 having a connection plug (7) on that end of the tube (4) which faces away from the lamp, at least the power supply line (24) for the inner electrode (23) being connected to said connection plug (7). 17. The dielectric barrier discharge lamp having a base as claimed in claim 3 having a connection plug (7) on that end of the tube (4) which faces away from the lamp, at least the power supply line (24) for the inner electrode (23) being connected to said connection plug (7). 18. The dielectric barrier discharge lamp having a base as claimed in claim 4 having a connection plug (7) on that end of the tube (4) which faces away from the lamp, at least the power supply line (24) for the inner electrode (23) being connected to said connection plug (7). 19. The dielectric barrier discharge lamp having a base as claimed in claim 5 having a connection plug (7) on that end of the tube (4) which faces away from the lamp, at least the power supply line (24) for the inner electrode (23) being connected to said connection plug (7). 20. The dielectric barrier discharge lamp having a base as claimed in claim 2, the outer electrode(s) (8a-8f) and the power supply line (11) for the outer electrode(s) having conductor track-like structures.
TECHNICAL FIELD The invention is based on a dielectric barrier discharge lamp. The term “dielectric barrier discharge lamp” in this case encompasses sources of electromagnetic radiation based on dielectrically impeded gas discharges. The spectrum of radiation may in this case include both the visible range and the UV (ultraviolet)/VUV (vacuum ultraviolet) range as well as the IR (infrared) range. In addition, a fluorescent layer may also be provided for the purpose of converting VUV radiation into radiation having longer wavelengths, for example UVA or visible radiation (light). A precondition for a dielectric barrier discharge lamp is, by definition, at least one so-called dielectrically impeded electrode. A dielectrically impeded electrode is separated from the interior of the discharge vessel or the discharge gas by means of a dielectric. This dielectric (the dielectric barrier) may be in the form of, for example, a dielectric layer covering the electrode, or it may be formed by the discharge vessel of the lamp itself, namely when the electrode is arranged on the outside of the wall of the discharge vessel. The latter case is referred to below for short as “outer electrode”. The present invention relates to a dielectric barrier discharge lamp which has at least one outer electrode of the abovementioned type which is essentially in the form of a strip. In addition, the lamp comprises an elongate or tubular discharge vessel which is closed at both ends and surrounds an ionizable filling. The ionizable filling generally consists of a noble gas, for example xenon or a gas mixture. During the gas discharge, which is preferably operated using a pulsed operating method as described in U.S. Pat. No. 5,604,410, so-called excimers are formed. Excimers are excited molecules, for example Xe2*, which emit electromagnetic radiation when they return to their original, generally unbound state. In the case of Xe2*, the maximum molecular band radiation is approximately 172 nm. As a result, such lamps are suitable as UV/VUV radiators in process technology, for example surface cleaning, photolytics, ozone generation, metallization and UV curing. For this purpose, it is generally necessary to operate the lamp directly in a low-pressure process gas atmosphere or vacuum. In this case, suitable precautions should be taken to install such radiators in a gas-tight manner in an appropriate process chamber. PRIOR ART The specification U.S. Pat. No. 6,060,828, in particular FIGS. 5a to 5c, has already disclosed such a lamp having an Edison screw base for general lighting. This lamp has a helical electrode within the discharge vessel. In addition, four electrodes in the form of strips are arranged on the outer wall of the discharge vessel. EP-A 1 088 335 discloses a dielectric barrier discharge lamp, which is suitable for UV irradiation, having a base. Although the base has a flange which is connected to the pinched foot of the lamp by means of a potting compound and is suitable for low-pressure applications, this design is less suitable for high-vacuum applications. An additional disadvantage is the fact that a relatively large amount of potting compound is required if it is intended to fill all of the space between the pinched foot and the circular-cylindrical inner wall of the base shell. However, if gaps are left exposed, a low pressure prevails, in the case of low-pressure applications, in the region between the pinched foot end and the subsequent seal, too. There is then the risk of parasitic gas discharges between the power supply lines. SUMMARY OF THE INVENTION The object of the present invention is to provide an improved dielectric barrier discharge lamp. A further aspect is for it to be possible to use the dielectric barrier discharge lamp in a low-pressure environment. This object is achieved by a dielectric barrier discharge lamp having a base, the discharge lamp having the following: an elongate discharge vessel, which is sealed at both ends, and whose wall surrounds an ionizable filling, electrodes, at least one of the electrodes being an inner electrode, i.e. being arranged within the discharge vessel, and at least one of the electrodes being an outer electrode, i.e. being arranged on the outside of the wall of the discharge vessel, a power supply line for the at least one inner electrode and a lamp foot, through which the at least one inner electrode is connected in a gas-tight manner to the power supply line, characterized in that the base comprises a tube which is fitted to the lamp foot-side end of the discharge vessel and surrounds the lamp foot. Particularly advantageous refinements are described in the dependent claims. The basic idea of the invention is to fit a tube, which surrounds the lamp foot, to the lamp foot-side end of the discharge vessel of the dielectric barrier discharge lamp. This makes it possible to separate, in a gas-tight manner, the two power supply lines for the outer and inner electrodes. This makes it possible to prevent the parasitic gas discharges mentioned initially between the power supply lines at a low pressure. In order also to make possible different diameters for the discharge vessel and the tube fitted thereon, it may be expedient to provide a suitable transition region. In this case, the tube has a cylindrical and a conical section, the conical section connecting the discharge vessel to the cylindrical section. For the purpose of installing the lamp according to the invention in a gas-tight manner in a process chamber, the tube expediently also has sealing means. In one preferred embodiment, this sealing means is realized by a small flange seal which is plugged over the tube. Suitable for this purpose are, in principle, conventional small vacuum flange seals, which may have been modified in a suitable manner, for glass tubes. The power supply line for the outer electrodes has a conductor track-like structure, as do the outer electrodes themselves. The thickness of these structures is typically only a few micrometers. This makes it possible for the power supply line, which is arranged on the outside of the tube, of the outer electrodes to be passed through, in a gas-tight manner, the O ring which is generally used as the seal in the case of small vacuum flanges. In addition, a connection plug, for example of the type BNC-HT, is expediently provided on that end of the tube which faces away from the lamp, said connection plug being connected to the two power supply lines. Further details in this regard are given in the exemplary embodiment. Alternatively, either a metallic vacuum flange may be connected to the free end of the tube by means of glass transition elements or a glass flange may be connected to the free end of the tube by being fused on directly. In addition, the power supply line for the outer electrode need not necessarily be arranged in the manner of a conductor track on the outside of the tube. Since the outer electrodes are preferably connected to ground potential, it may also be advantageous for the outer electrodes to be connected directly, for example by means of a suitable contact spring, to the metallic process chamber. If in any case, as is explained above, the lamp according to the invention is installed in a process chamber in a gas-tight manner with the aid of the sealing base, the attached tube separates the power supply line, which is surrounded by air pressure, of the inner electrode from that part of the power supply line, connected to the outer electrodes, which is subjected to the process gas atmosphere or vacuum. This effectively prevents the initially mentioned parasitic discharges between the power supply lines lying at different potentials during operation. BRIEF DESCRIPTION OF THE DRAWING The invention will be explained in more detail below with reference to an exemplary embodiment. The FIGURE shows: a plan view of a dielectric barrier discharge lamp according to the invention having a base, including a base adapter (sectional illustration). PREFERRED EMBODIMENT OF THE INVENTION The FIGURE shows a schematic illustration of a dielectric barrier discharge lamp 1 according to the invention having a base. In this case it is a UV/VUV radiator, for example for surface cleaning, photolytics, ozone generation, metallization or UV curing. This radiator is designed for an electrical power consumption of approximately 20 W. The discharge lamp 1 has a circular-cylindrical discharge vessel 2 made of 0.7 mm to 1.5 mm thick quartz glass. The discharge vessel 2 has an outer diameter of approximately 40 mm and a length of approximately 120 mm. The interior of the discharge vessel 2 is filled with xenon at a pressure of 20 kPa. The discharge vessel 2 is sealed at a first end in the form of a dome and has an exhaust tip 3 in the center of the dome. In the region of the lamp foot opposite the exhaust tip 3, a quartz tube 4 is fused to the discharge vessel 2. Alternatively, this quartz tube may also be attached by means of glass solder. The quartz tube 4 has a conical section 5 and a circular-cylindrical section 6. The conical section 5 connects the tubular discharge vessel 2 to the circular-cylindrical section 6, whose outer diameter is approximately 25 mm. Arranged on that end of the quartz tube 4 which faces away from the lamp is a connection plug 7 of the type BNC-HT. Six outer electrodes 8a-8f (the outer electrodes 8d-8f cannot be seen in FIG. 1) in the form of 12 cm long, approximately 1 to 1.5 mm wide, thin platinum strips are fitted to the outside of the discharge vessel 2 equidistantly and parallel to the lamp longitudinal axis. The ends of the electrode strips 8a-8f are each connected to one another by means of a peripheral platinum strip 9, 10. One platinum strip 9, which is attached in the immediate vicinity of the connection between the discharge vessel 2 and the quartz tube 4, is connected to a further platinum strip 11. This further platinum strip 11 extends to the outside of the quartz tube 4 and ends at the connection plug 7, and it is connected to the first pole of said connection plug 7. In this manner, this platinum strip 11 acts as a power supply line for the outer electrodes 8a-8f. Arranged on the circular-cylindrical section 6 of the quartz tube 4 is a modified base adapter 12 of the type ISO KF 40 (sectional illustration). It comprises a small vacuum flange 13 and an inner sleeve 14 which is screwed thereto. The inner sleeve 14 presses an O ring 16 against a bevel 17 of the small flange 13 by means of a metal ring 15. This O ring 16 thus acts as a seal against the outside of the quartz tube 4. A further O ring 18 is inserted in an inner groove 19 on the thread-free end of the inner sleeve 14. This results in a stress-free, gas-tight mounting of the lamp 1 in the base adapter 12. An annular groove 20 on the sealing side of the small flange 13 serves the purpose of accommodating a centering ring, known per se, having an O ring (not illustrated) for installation in a process chamber (not illustrated). At the end opposite the exhaust tip 3, the discharge vessel 2 is tapered and forms a pinch seal 21. The pinch seal 21 ensures, with the aid of a molybdenum sealing film 22, a gas-tight connection between the inner electrode 23 and an outer power supply line 24. This power supply line 24 is connected to the second pole of the connection plug 7 (not shown). The inner electrode 23 is a helical metal wire arranged centrically within the discharge vessel 2. That end of the coil electrode 23 which is opposite the pinch seal 21 is fixed in the exhaust tip 3. The respective diameters of the metal wire and the coil are 1 mm and 8 mm. The pitch, i.e. the path within which the coil performs a complete rotation, is 12 mm. Details of the way in which the electrodes function during lamp operation are described in the above-cited U.S. Pat. No. 6,060,828, in particular in the description relating to FIGS. 5a to 5c.
<SOH> TECHNICAL FIELD <EOH>The invention is based on a dielectric barrier discharge lamp. The term “dielectric barrier discharge lamp” in this case encompasses sources of electromagnetic radiation based on dielectrically impeded gas discharges. The spectrum of radiation may in this case include both the visible range and the UV (ultraviolet)/VUV (vacuum ultraviolet) range as well as the IR (infrared) range. In addition, a fluorescent layer may also be provided for the purpose of converting VUV radiation into radiation having longer wavelengths, for example UVA or visible radiation (light). A precondition for a dielectric barrier discharge lamp is, by definition, at least one so-called dielectrically impeded electrode. A dielectrically impeded electrode is separated from the interior of the discharge vessel or the discharge gas by means of a dielectric. This dielectric (the dielectric barrier) may be in the form of, for example, a dielectric layer covering the electrode, or it may be formed by the discharge vessel of the lamp itself, namely when the electrode is arranged on the outside of the wall of the discharge vessel. The latter case is referred to below for short as “outer electrode”. The present invention relates to a dielectric barrier discharge lamp which has at least one outer electrode of the abovementioned type which is essentially in the form of a strip. In addition, the lamp comprises an elongate or tubular discharge vessel which is closed at both ends and surrounds an ionizable filling. The ionizable filling generally consists of a noble gas, for example xenon or a gas mixture. During the gas discharge, which is preferably operated using a pulsed operating method as described in U.S. Pat. No. 5,604,410, so-called excimers are formed. Excimers are excited molecules, for example Xe 2 *, which emit electromagnetic radiation when they return to their original, generally unbound state. In the case of Xe 2 *, the maximum molecular band radiation is approximately 172 nm. As a result, such lamps are suitable as UV/VUV radiators in process technology, for example surface cleaning, photolytics, ozone generation, metallization and UV curing. For this purpose, it is generally necessary to operate the lamp directly in a low-pressure process gas atmosphere or vacuum. In this case, suitable precautions should be taken to install such radiators in a gas-tight manner in an appropriate process chamber.
<SOH> SUMMARY OF THE INVENTION <EOH>The object of the present invention is to provide an improved dielectric barrier discharge lamp. A further aspect is for it to be possible to use the dielectric barrier discharge lamp in a low-pressure environment. This object is achieved by a dielectric barrier discharge lamp having a base, the discharge lamp having the following: an elongate discharge vessel, which is sealed at both ends, and whose wall surrounds an ionizable filling, electrodes, at least one of the electrodes being an inner electrode, i.e. being arranged within the discharge vessel, and at least one of the electrodes being an outer electrode, i.e. being arranged on the outside of the wall of the discharge vessel, a power supply line for the at least one inner electrode and a lamp foot, through which the at least one inner electrode is connected in a gas-tight manner to the power supply line, characterized in that the base comprises a tube which is fitted to the lamp foot-side end of the discharge vessel and surrounds the lamp foot. Particularly advantageous refinements are described in the dependent claims. The basic idea of the invention is to fit a tube, which surrounds the lamp foot, to the lamp foot-side end of the discharge vessel of the dielectric barrier discharge lamp. This makes it possible to separate, in a gas-tight manner, the two power supply lines for the outer and inner electrodes. This makes it possible to prevent the parasitic gas discharges mentioned initially between the power supply lines at a low pressure. In order also to make possible different diameters for the discharge vessel and the tube fitted thereon, it may be expedient to provide a suitable transition region. In this case, the tube has a cylindrical and a conical section, the conical section connecting the discharge vessel to the cylindrical section. For the purpose of installing the lamp according to the invention in a gas-tight manner in a process chamber, the tube expediently also has sealing means. In one preferred embodiment, this sealing means is realized by a small flange seal which is plugged over the tube. Suitable for this purpose are, in principle, conventional small vacuum flange seals, which may have been modified in a suitable manner, for glass tubes. The power supply line for the outer electrodes has a conductor track-like structure, as do the outer electrodes themselves. The thickness of these structures is typically only a few micrometers. This makes it possible for the power supply line, which is arranged on the outside of the tube, of the outer electrodes to be passed through, in a gas-tight manner, the O ring which is generally used as the seal in the case of small vacuum flanges. In addition, a connection plug, for example of the type BNC-HT, is expediently provided on that end of the tube which faces away from the lamp, said connection plug being connected to the two power supply lines. Further details in this regard are given in the exemplary embodiment. Alternatively, either a metallic vacuum flange may be connected to the free end of the tube by means of glass transition elements or a glass flange may be connected to the free end of the tube by being fused on directly. In addition, the power supply line for the outer electrode need not necessarily be arranged in the manner of a conductor track on the outside of the tube. Since the outer electrodes are preferably connected to ground potential, it may also be advantageous for the outer electrodes to be connected directly, for example by means of a suitable contact spring, to the metallic process chamber. If in any case, as is explained above, the lamp according to the invention is installed in a process chamber in a gas-tight manner with the aid of the sealing base, the attached tube separates the power supply line, which is surrounded by air pressure, of the inner electrode from that part of the power supply line, connected to the outer electrodes, which is subjected to the process gas atmosphere or vacuum. This effectively prevents the initially mentioned parasitic discharges between the power supply lines lying at different potentials during operation.
20041117
20070529
20051006
92907.0
0
SANTIAGO, MARICELI
DIELECTRIC BARRIER DISCHARGE LAMP WITH A BASE
UNDISCOUNTED
0
ACCEPTED
2,004
10,514,901
ACCEPTED
Digital rights management method and system
A method of controlling access to a content item in a domain comprising a set of mutually authenticated devices, the method comprising deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain aces to the content item. Also system comprising a set of mutually authenticated devices, said set making up a domain, the system comprising a central rights manager arranged for executing said method.
1. A method of controlling access to a content item in a domain comprising a set of mutually authenticated devices, the method comprising deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. 2. The method of claim 1, in which the right associated with the content item is imported into the domain only if it originated from a compliant source. 3. The method of claim 1, in which the one or more domain-specific rights are revoked if the right associated with the content item is revoked or removed from the domain. 4. The method of claim 1, in which the content item is stored on a removable storage medium together with the right associated with the content item, and the one or more domain-specific rights are derived only if the removable storage medium indicates that making a one-generation copy is permitted. 5. The method of claim 1, in which the content item is stored on a removable storage medium together with the right associated with the content item, and the one or more domain-specific rights are derived only if the removable storage medium indicates that making a single copy of the content item is permitted. 6. The method of claim 1, in which the content item is stored on a removable storage medium together with the right associated with the content item, and the one or more domain-specific rights are derived even though the removable storage medium indicates that making a copy of the content item is not permitted. 7. The method of claim 1, in which the content item is stored on a removable storage medium together with the right associated with the content item, and the one or more domain-specific rights are derived even though the removable storage medium indicates that making a copy of the content item is no longer permitted. 8. The method of claim 1, in which the right associated with the content item is a right that can be exercised a predetermined number of times, and in which the number of domain-specific rights derived from the right associated with the content item corresponds to the predetermined number. 9. The method of claim 1 or 8, in which the one or more domain-specific rights derived from the right associated with the content item are rights that can be exercised a predetermined number of times. 10. The method of claim 9, in which the predetermined number of times the one or more domain-specific rights can be exercised is one. 11. The method of claim 9, in which the predetermined number of times the one or more domain-specific rights can be exercised is determined by the right associated with the content item. 12. The method of claim 9, in which the predetermined number of times the one or more domain-specific rights can be exercised is a characteristic of the domain. 13. The method of claim 9, in which the predetermined number of times the one or more domain-specific rights can be exercised is a characteristic of the device through which the content item is imported into the domain. 14. The method of claim 1, in which the content item is permitted to be copied freely and a single specimen of the right associated with the content item is permitted to exist in the domain. 15. The method of claim 1, in which every device in the domain has one or more domain identifiers and only communicates with other devices having at least one identical domain identifier. 16. The method of claim 15, in which a new device that successfully authenticates itself to a device in the domain receives one or more of the one or more domain identifiers. 17. The method of claim 16, every device in the domain having a device identifier, the one or more domain identifiers comprising a list of device identifiers for devices that are members of the domain. 18. The method of claim 16, in which the new device receives the one or more of the one or more domain identifiers from a central controller device. 19. The method of claim 18, in which the new device receives the one or more of the one or more domain identifiers from a central controller device conditional upon approval by a majority of the devices in the domain. 20. The method of claim 18, in which the one or more domain identifiers comprise the device identifier of the central controller device. 21. The method of claim 15, comprising deleting the one or more domain identifiers stored in a particular device when the particular device leaves or is removed from the domain. 22. The method of claim 1, in which the number of domain-specific rights is limited to a predetermined amount. 23. The method of claim 1, in which the number of domain-specific rights relating to playback of the content item is limited to a predetermined amount. 24. The method of claim 22 or 23, in which the predetermined amount is determined by the right associated with the content item. 25. A system comprising a set of mutually authenticated devices, said set making up a domain, the system comprising a central rights manager arranged for deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. 26. The system of claim 25, in which every device in the domain has one or more domain identifiers and is arranged to only communicate with other devices having at least one identical domain identifier. 27. The system of claim 26, in which a device in the domain is arranged to authenticate a new device and upon successful authentication to supply the one or more domain identifiers to the new device. 28. The system of claim 27, in which the device arranged to authenticate the new device is a central controller device and the one or more domain identifiers comprise the device identifier of the central controller device.
The invention relates to a method of controlling access to a content item in a domain comprising a set of mutually authenticated devices. The invention further relates to a system comprising a set of mutually authenticated devices, said set making up a domain. INTRODUCTION TO THE INVENTION In recent years, the amount of content protection systems is growing in a rapid pace. Some of these systems only protect the content against illegal copying, while others are also prohibiting the user to get access to the content. The first category is called Copy Protection (CP) systems. CP systems have traditionally been the main focus for consumer electronics (CE) devices, as this type of content protection is thought to be cheaply implemented and does not need bi-directional interaction with the content provider. Some examples are the Content Scrambling System (CSS), the protection system of DVD ROM discs and DTCP, the protection system for IEEE 1394 connections. The second category is known under several names. In the broadcast world, systems of this category are generally known as conditional access (CA) systems, while in the Internet world they are generally known as Digital Rights Management (DRM) systems. Some type of CP systems can also provide services to interfacing CA or DRM systems. Examples are the systems currently under development by the DVB-CPT subgroup and the TV-Anytime RMP group. The goal is a system in which a set of devices can authenticate each other through a bi-directional connection. Based on this authentication, the devices will trust each other and this will enable/allow them to exchange protected content. The accompanying licenses describe which rights the user has and what operations he is allowed to perform on the content. The license is protected by means of some general network secret, which is only exchanged between the devices within a certain household. This network of devices is called an Authorized Domain (AD). The concept of authorized domains tries to find a solution to both serve the interests of the content owners (that want protection of their copyrights) and the content consumers (that want unrestricted use of the content). The basic principle is to have a controlled network environment in which content can be used relatively freely as long as it does not cross the border of the authorized domain. Typically, authorized domains are centered around the home environment, also referred to as home networks. Of course, other scenarios are also possible. A user could for example take a portable television with him on a trip, and use it in his hotel room to access content stored on his Personal Video Recorder at home. Even though the portable television is outside the home network, it is a part of the user's authorized domain. A home network can be defined as a set of devices that are interconnected using some kind of network technology (e.g. Ethernet, IEEE 1394, BlueTooth, 802.11b, . . . ). Although network technology allows the different devices to communicate, this is not enough to allow devices to interoperate. To be able to do this, devices need to be able to discover and address the functions present in the other devices in the network. Such interoperability is provided by home networking middleware (HN-MW). Examples of home networking middleware are Jini, HAVi, UPnP, AVC. The use of network technology and HN-MW allows one to view a set of individual devices as one large virtual device. From a HN-MW point of view, a network can be seen as a set of functions that can be used and connected. Such a system provides a user with capabilities to address any content or service from anywhere in the home network. HN-MW can be defined as a system that provides two services. It allows an application in the network to locate devices and functions in the network. Furthermore, some kind of mechanism, such as remote procedure calls (RPC), defines how to use these functions. From a HN-MW point of view, systems related to handling secure content appear in several ways. Certain functions in the network require access to protected content. Other functions in the network provide functionality that can be used by the elements in the network handling content security. Furthermore, security frameworks like OPIMA can use the HN-MW to locate each other and communicate in an interoperable way. Of course authorized domains can also be implemented in other ways. For a more extensive introduction to the use of DRM in home networks, see F. L. A. J. Kamperman, S. A. F. A. van den Heuvel M. H. Verberkt, Digital Rights Management in Home Networks, Philips Research, The Netherlands, IBC 2001 conference publication vol. I, pages 70-77. Various systems already exist that implement the concept of authorized domains to some extent. Examples of such systems are SmartRight (Thomson Multimedia), xCP (4C, mainly IBM), and NetDRM (Matshushita). The SmartRight system has, amongst others, the following properties: Smart cards can be inserted in all devices. The system uses authentication of those smart cards. The system uses a common network secret. New smart cards added to the domain will receive the network secret. All smart cards can open the licenses (=rights) in the domain. The xCP system has, amongst others, the following properties: Uses common network secret (key space). Key spaces based on MKB structure. When devices are added, the key spaces are merged. Also a new common secret (Media_key) is then generated. All licenses are re-encrypted with the new secret. A central domain manager decides if merger is allowed. The NetDRM system has, amongst others, the following properties: A central server to register device to domain. This server can be at home or in the outside network. Uses network (domain) secret. Secret is distributed from central server, which could also be in the home. Licenses are typically stored in the outside network, but may also be stored locally. Virtual Private Networks (VPNs) could to some extent be considered similar, but their purpose and therefore their implementation is different. Roughly it can be said that the purpose of VPNs is to keep internally generated content in the network (typically accessible in the whole network), while authorized domains try to keep externally generated content (such as purchased copyrighted content) in the domain (typically accessible in the whole domain). SUMMARY OF THE INVENTION It is an object of the invention to provide a method of controlling access to a content item in a domain comprising a set of mutually authenticated devices, which is flexible with respect to handling content and rights associated with content. This object is achieved according to the invention in a method comprising deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. Preferably the devices in the domain receive the domain-specific rights from a central rights manager device in the domain, although decentralized rights distribution or other solutions are also possible. The number of domain-specific rights may be limited to a predetermined amount This may apply to all domain-specific rights or just to those of the ‘playback’ type. This allows unlimited copying but limits simultaneous playback. In an embodiment the one or more domain-specific rights are revoked if the right associated with the content item is revoked or removed from the domain. This way it is not possible to exercise the domain-specific rights if there exists no valid corresponding right associated with the content item. The content item may be stored on a removable storage medium together with the right associated with the content item. In that case, the one or more domain-specific rights might be derived only if the removable storage medium indicates that making a one-generation copy is permitted. Alternatively, they are derived only if the removable storage medium indicates that making a single copy of the content item is permitted. This way of deriving domain-specific rights is in line with the permissions (rights) indicated on the removable storage medium. Another option is to derive the one or more domain-specific rights even though the removable storage medium indicates that making a copy of the content item is not permitted, or is no longer permitted (referred to as “copy no more” content). These options make it possible to use content on a removable storage medium such as a Compact Disc or Digital Versatile Disc freely within the domain, even when the right on the disc are more restrictive. Because the domain-specific rights are bound to the domain, there is no risk that users are able to access the content item outside the domain. In an embodiment the right associated with the content item is a right that can be exercised a predetermined number of times, and the number of domain-specific rights derived from the right associated with the content item corresponds to the predetermined number. This provides an easy mapping of content-bound rights to domain-bound rights. The one or more domain-specific rights derived from the right associated with the content item could then be rights that can be exercised a predetermined number of times, preferably one time. This has the advantage that use of the domain-specific rights is very limited, allowing a great amount of control over access to the content item. Further, the problem that the domain-specific right may exist while the right associated with the content item has expired or has become invalid for another reason is now minimized. The predetermined number of times the one or more domain-specific rights can be exercised could be indicated by the right associated with the content item, or be a characteristic of the domain or of the device through which the content item is imported into the domain. For instance the predetermined number could be proportional or inversely proportional to the size of the domain. A large domain could have a large predetermined number to make the content usable on many locations, or maybe a small predetermined number to discourage users to form very large domains. Import devices that provide large predetermined numbers could be sold at higher prices. In an embodiment the content item is permitted to be copied freely and a single specimen of the right associated with the content item is permitted to exist in the domain. This provides great flexibility on where the content item can be accessed, but it prevents users from exercising rights beyond what they are allowed to. In an embodiment every device in the domain has one or more domain identifiers and only communicates with other devices having at least one identical domain identifier. This is a surprisingly effective way to create a domain of mutually authenticated devices. Preferably there is a single domain identifier for every domain. A device can be a member of multiple domains, thus holding multiple domain identifiers. There could also be subdomains within the domain, and then devices hold the domain identifier for the “main” domain and the domain identifiers for the subdomains. A new device that successfully authenticates itself to a device in the domain receives one or more of the one or more domain identifiers, preferably from a central controller device. This is optionally done conditional upon approval by a majority of the devices in the domain. If a particular device leaves or is removed from the domain, its domain identifier for that domain is deleted. The domain identifier may comprise a list of device identifiers for devices that are members of the domain. This list can be compiled easily and so implementation of the domain identifier is straightforward. The domain identifier may comprise the device identifier of the central controller device. Preferably the right associated with the content item comprises one of a render right, a transport right, a derivative work right and a utility right. The domain-specific right then preferably comprises one of a render right, a derivative work right and a utility right. It is a ether object of the invention to provide a system comprising a set of mutually authenticated devices, said set making up a domain, the system comprising a central rights manager arranged for deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. Preferably every device in the domain has one or more domain identifiers and is arranged to only communicate with other devices having at least one identical domain identifier. In a variant of this embodiment a device in the domain is arranged to authenticate a new device and upon successful authentication to supply the one or more domain identifiers to the new device. The device arranged to authenticate the new device could be a central controller device and the one or more domain identifiers then comprise the device identifier of the central controller device. BRIEF DESCRIPTION OF THE FIGURES These and other aspects of the invention will be apparent from and elucidated with reference to the illustrative embodiments shown in the drawings, in which: FIG. 1 schematically shows a system comprising devices interconnected via a network; FIG. 2 shows the schematic division of the system 100 of FIG. 1 into a CA domain and a CP domain; FIG. 3 shows a flow chart for an illustrative embodiment of a process to check in a device into the CP domain of FIG. 2; and FIG. 4 shows a flow chart for an illustrative embodiment of a process to check in digital rights into the CP domain of FIG. 2. Throughout the figures, same reference numerals indicate similar or corresponding features. Some of the features indicated in the drawings are typically implemented in software, and as such represent software entities, such as software modules or objects. System Architecture FIG. 1 schematically shows a system 100 comprising devices 101-105 interconnected via a network 110. In this embodiment, the system 100 is an in-home network. A typical digital home network includes a number of devices, e.g. a radio receiver, a tuner/decoder, a CD player, a pair of speakers, a television, a VCR, a tape deck, and so on. These devices are usually interconnected to allow one device, e.g. the television, to control another, e.g. the VCR. One device, such as e.g. the tuner/decoder or a set top box (STB), is usually the central device, providing central control over the others. Content, which typically comprises things like music, songs, movies, TV programs, pictures, books and the likes, but which also includes interactive services, is received through a residential gateway or set top box 101. Content could also enter the home via other sources, such as storage media as discs or using portable devices. The source could be a connection to a broadband cable network, an Internet connection, a satellite downlink and so on. The content can then be transferred over the network 110 to a sink for rendering. A sink can be, for instance, the television display 102, the portable display device 103, the mobile phone 104 and/or the audio playback device 105. The exact way in which a content item is rendered depends on the type of device and the type of content. For instance, in a radio receiver, rendering comprises generating audio signals and feeding them to loudspeakers. For a television receiver, rendering generally comprises generating audio and video signals and feeding those to a display screen and loudspeakers. For other types of content a similar appropriate action must be taken. Rendering may also include operations such as decrypting or descrambling a received signal, synchronizing audio and video signals and so on. The set top box 101, or any other device in the system 100, may comprise a storage medium S1 such as a suitably large hard disk, allowing the recording and later playback of received content. The storage medium S1 could be a Personal Digital Recorder (PDR) of some kind, for example a DVD+RW recorder, to which the set top box 101 is connected. Content can also enter the system 100 stored on a carrier 120 such as a Compact Disc (CD) or Digital Versatile Disc (DVD). The portable display device 103 and the mobile phone 104 are connected wirelessly to the network 110 using a base station 111, for example using Bluetooth or IEEE 802.11b. The other devices are connected using a conventional wired connection. To allow the devices 101-105 to interact, several interoperability standards are available, which allow different devices to exchange messages and information and to control each other. One well-known standard is the Home Audio/Video Interoperability (HAVi) standard, version 1.0 of which was published in January 2000, and which is available on the Internet at the address http://www.havi.org/. Other well-known standards are the domestic digital bus (D2B) standard, a communications protocol described in IBC 1030 and Universal Plug and Play (http://www.upnp.org). It is important to ensure that the devices 101-105 in the home network do not make unauthorized copies of the content. To do this, a security framework, typically referred to as a Digital Rights Management (DPM) system is necessary. In one such framework, the home network is divided conceptually in a conditional access (CA) domain and a copy protection (CP) domain. Typically, the sink is located in the CP domain. This ensures that when content is provided to the sink, no unauthorized copies of the content can be made because of the copy protection scheme in place in the CP domain. Devices in the CP domain may comprise a storage medium to make temporary copies, but such copies may not be exported from the CP domain. This framework is described in European patent application 01204668.6 (attorney docket PHNL010880) by the same applicant as the present application. Regardless of the specific approach chosen, all devices in the in-home network that implement the security framework do so in accordance with the implementation requirements. Using this framework, these devices can authenticate each other and distribute content securely. Access to the content is managed by the security system. This prevents the unprotected content from leaking “in the clear” to unauthorized devices and data originating from untrusted devices from entering the system. FIG. 2 shows the schematic division of the system 100 of FIG. 1 into a CA domain and a CP domain. In FIG. 2, the system 100 comprises a source, a sink, and two storage media S1 and S2. Most content enters the in-home network in the CA domain through the set-top box 101 (the source). Typically, the sinks, for instance the television system 102 and the audio playback device 105, are located in the CP domain. This ensures that when content is provided to the sink, no unauthorized copies of the content can be made because of the copy protection scheme in place in the CP domain. A CA→CP gateway is provided between the CA and the CP domains. This gateway is responsible for letting content enter the CP domain. This process may require transcoding and/or (re-)encrypting the content, translating digital rights associated with the content to a format supported in the CP domain, and so on. The CP domain comprises a storage medium S2, on which (temporary) copies of the content can be stored in accordance with the copy protection rules. These copies can be used for example for time-shifted playback of the content, but these copies may not be easily exported from the CP domain. A device becomes part of the CP domain by connecting it to another device already in the CP domain, or by connecting it to the bus connecting these devices. To prevent rapid changing of CP domains, changing CP domains could be discouraged e.g. by ensuring that it must remain in that particular CP domain for a certain period of time, for example one day. Authorized Domain Functions and Design Principles The main functionality required for creation and maintenance of an AD comprises the following: AD identification (This might also be considered as an AD management function) Device check-in (this could also be called: device registration) Device check-out (this could also be called: device de-registration) Rights check-in Rights check-out Content check-in Content check-out Management of the AD: Content access Storage of rights in the domain Some of the chosen design principles are: No centralized management of the AD. No a-priori restrictions in number of devices and amounts of content in the AD. The following functional requirements were identified: No a-priori restrictions on content access within the domain. Only controlled content and/or rights exchange at the domain borders. Only compliant devices are allowed in the domain (non-compliant devices are not considered). The following non-functional requirements were identified: The solution should work for portable mostly off-line devices. The solution for an AD should be compliant with the typical DRM system architecture, i.e. the usage of digital rights is the basis for controlling access to content. Authorized Domain (AD) Identification One of the issues when implementing authorized domains is how to maintain an information structure that allows determining whether a device is part of a domain. It is important that content is not easily transferred from a device within the domain to a device outside the domain. Such checking out of content should be done under controlled circumstances, and may be restricted to'particular devices. For example, a DVD+RW writer could be permitted to make copies of the content on a DVD rewritable disc, but a Personal Video Recorder inside the domain should not let a device outside the domain read unencrypted content stored on its built-in hard disk. We now present various ways to allow determining whether a device is a member of a particular authorized domain. Others are of course also possible. In a first embodiment, an authorized domain is identified by means of a unique domain_id. This identifier is then stored in every device that is a member of the domain. If there is a need to have an overview of the complete set of domain member devices, an explicit list of device_ids that constitute the domain can be maintained. This list can be stored centrally in the domain. Determining whether a device is a member of a particular authorized domain can now be done by simply checking whether the identifier for that particular domain has been stored in the device in question. The device must be also be compliant, of course. In a second embodiment, an authorized domain is identified by means of the set of device_ids that constitute the domain. This set of device_ids is stored in one designated device within the domain (or, alternatively, outside the domain). Note that in this solution no explicit domain_id exists. This solution, however, seems less practical. In case two portable devices desire to communicate, while they have no connection with the central list, they cannot determine if the other also is a member of the AD. In a variation of this embodiment the set of device_ids is stored in every device part of the domain. This solves the above problem that arises when two portable devices desire to communicate, but introduces a lot of management complexity and imposes relatively large storage requirements in all devices. In a further variation of this embodiment the set of device_ids is stored in a number of specific devices part of the domain. Again, this introduces a lot of management complexity and imposes relatively large storage requirements in all devices. Device Check-In Another important issue is how and when to check-in a compliant device. “Checking in” or “registration” refers to the process by which a device is accepted as part of an authorized domain. Only compliant devices should be accepted, to prevent content leaking from the authorized domain due to a malicious noncompliant device. An illustrative embodiment of this process is given as a flow chart in FIG. 3. The check-in process is initiated by a user who, in step 301, connects the compliant device he wishes to add to another device that is already in the authorized domain. This is preferably a central server or controller for the authorized domain, if such a device exists. Other systems, for example SmartRight, allow initiating a check-in process by connecting the device to be added to any device already in the authorized domain. Of course “connecting” is not restricting to establishing physical connections using cables. Wireless connections, for example using BlueTooth or IEEE 802.11b can also be established. After a network connection has been established, the next step 302 involves authentication of the new device by the device to which it is connected. If this authentication is successful, as determined in step 303, the new device becomes part of the authorized domain in step 304. Otherwise, the new device is rejected in step 305. Possibly also other conditions are checked, e.g. in case only a limited number of devices are allowed in the domain, another step would be to check that this limited number is not yet exceeded. In case a central unique domain_id is used, as explained above, the new device in step 306 receives the domain_id from the central controller or from the device to which it is connected. If desired, any other device in the authorized domain could also supply the domain_id to the new device. One could for example designate particular types of devices has been allowed to distribute domain_ids to newly added devices. As an extension, the newly added device could obtain the domain_id from any device in the domain, but the majority of the devices already in the domain should give permission. This way no single device (which could be corrupted by an adversary or make errors in for example its authentication procedure) can accept other devices into the domain. In another embodiment a domain originator transmits the domain_id to the newly added device. In this embodiment, all compliant devices store a device_id and are equipped with storage space for a domain_id. The domain_id of the domain originator will be his device_id. Any other device added to the authorized domain then receives the domain_id from the domain originator. Initially (in the factory), for a device, the domain_id will be set to the device_id. Any individual device then could be considered as an AD with a size of 1 device and the device is automatically the domain originator for that AD. When an AD grows, the originator device will lend his device_id to other devices as domain_id. The domain originator device can later on be recognized as the device with device_id=domain_id. Typically the originator device should be a large static device, e.g. the television set in the living room and not e.g. a portable device. If two such large static devices are connected in one authorized domain, then a negotiation process may be needed to determine which one of the two should become the domain originator. Such a negotiation process can be implemented by requesting the user to designate the domain originator. As this protocol requires the user to connect a device to the domain originator, the domain originator should be recognizable, by indicating this in the user interface of the device, for example, by showing an indicator on a display screen, activating a particular LED, and so on. The user could also add a physical indication, such as a special antenna or decorative element, or by changing its appearance in some other way, to the domain originator. A device may only be checked in if the device is compliant and the device belongs to the household. Whether a device is compliant can easily be checked with known (authentication) mechanisms. The problems lie in determining if a device belongs to a household, i.e. to prevent that whole the world becomes member of the same domain. After all, the principle of authorized domains was introduced to allow some flexibility in handling content by consumers, not to allow unlimited content distribution worldwide. The SmartRight system imposes a limitation on the number of devices in the domain. This solution is suitable for the case where all devices belonging to the domain are centrally registered. A problem with this solution is that it is badly scalable, and is not in line with our design principles. Another solution is to impose a limitation for the number of sessions for playing back a certain piece of content from the AD domain controller. A problem with this solution that it is not very suitable for off-line portable devices, and is not in line with our design principles. This solution is described in European patent application serial number 02009651.7 (attorney docket PHNL020372) by the same applicant as the present application. Yet another solution imposes a limitation on the number of authorized domain rights (e.g. playback rights, see below for a more extensive discussion of authorized domain rights) in the domain. This way, for example a playback right can only be used once at a time. This solution can be implemented de-centrally and therefore fits our design principles. A possible disadvantage, however, is that we now have a copy management scheme within a copy management scheme. (This solution preferably should work together with a device registration scheme.) In another embodiment an external third party enables the device to work within a specific domain. Such message can be sent over a broadcast channel, the Internet, or using storage media like floppy discs, flash cards, smart cards, etc. Although this is a valid approach, the implementation is very different from the model expressed in this document and will not be addressed further. Device Check-Out Another important aspect of authorized domains is how and when to check-out a compliant device. “Checking out” or “deregistration” refers to the process by which a device that is part of the authorized domain can leave the authorized domain. If an authorized domain is identified by means of a unique domain_id, then checking out a device in the authorized domain can be implemented by deleting the domain_id stored in the device. When a device checks out from an authorized domain we have a situation where in fact two authorized domains exist: the original authorized domain and the device that just left, which can be considered as an authorized domain in itself. At this point a distribution of the (XAD) rights (see later for explanation of type of rights) between these two authorized domains has to take place (AD rights belonging to checked-out XAD rights must be deleted, e.g. by sending a revocation message into the domain.). This will be implemented by means of (user-) controlled rights check-out and check-in. Digital Rights Management Content inside the authorized domain is still subject to digital rights management rules. The digital rights associated with content are typically received together with the content as it enters the authorized domain. For example, the rights could be present in a license file downloaded together with the content from a Website, or be part of the MPEG-2 stream received over a cable network. Rights can also be purchased separately. A consumer could for example purchase a carrier such as a DVD disc in a store. The content on this disc can only be played back if he separately purchases a playback right, for example on the website of the content owner. The playback right in question could be limited in time, forcing the consumer to purchase new playback rights at regular intervals. It is to be expected that the rights are distributed in proprietary formats, although of course rights might also already be distributed in AD format. Rights may also originate from other ADs, i.e. inter-AD communication. This makes it necessary to convert the rights to the format used inside the authorized domain. This is referred to as “checking in a right”. Some requirements on rights check-in are: Only accept rights that can be enforced by the AD. Only accept rights in case obligations are acceptable (We will only consider the case were there are a limited number of identifiable obligations as this allows easy and simple implementation using enumeration.). Only accept rights if content related to right is acceptable (certain content, e.g. adult movies, might be unacceptable in a household with children). AD rights management preferably involves three types of actions: AD rights identification: How to find out to which domain a right belongs? Check-in of rights in to the AD: How to add a right to a domain? Checkout of rights from the AD: How to delete/transfer a right from a domain? Right identification may operate in different ways: i. A common AD key may encrypt the rights in the domain. Only devices which posses the common key can use the content key in the right. ii. A right may contain an AD identifier. Compliant devices will only “use” rights with the correct AD identifier. iii. A right is implicitly bound to the domain, i.e. once entered it cannot leave the domain. It is protected by devices and on secure interfaces. An advantage of method i and ii is that it is very clear to which domain rights belong. A disadvantage, however, is that rights need to be changed (different identifier/different encryption), whenever changes occur in the set of devices in the domain and when rights are checked-in/out. A right can only be checked in if it is compliant to the domain and was allowed to be “checked-out” from its origin. The typical origin of a right will be a DRM or pay-TV system. Rights check-out may only occur when allowed by the right. Correct handling of rights is ensured by the compliance of devices handling the right. An illustrative embodiment of a process to check in digital rights in accordance with the present invention is given in the flow chart of FIG. 4. The first step 401 is to determine whether the rights are in a proprietary format. If so, the next step 402 is to convert the rights from the proprietary format to the AD format. If conversion is not possible, another entity should convert or interpret the right for the AD. If this also fails the conversion has failed and the right will be refused. Having obtained the digital rights in the AD format, the next steps 403, 404, 405, 407 and 408 are to check whether: a) the right is legal, i.e. is it approved by the right/license authority (step 403), b) the transaction is legal, i.e. am I allowed to receive/accept this right (step 404), c) the right can be enforced by the AD (step 405); if not refuse or downgrade the right (step 406), d) the obligations are acceptable to the AD or the AD owner (step 407), e) the right refers to content that the AD is willing to accept (step 408). If all these checks are passed, the right is added in step 409 to the AD under the control of the Rights Manager in the AD. This Rights Manager may not be a single identifiable entity, but can be completely distributed. Of course nothing prevents the system to also maintain hold of the rights on the content in the original DRM system. So when the rights were downgraded, the user could still make use of the complete rights using the original DRM system. We will now further concentrate on point a) and b). Items c), d), e) are more related to the contents of the rights and content and less to domain management and will therefore not be further elaborated on. In the case II under a), we consider a right legal if 1) it contains an authenticity mark by the right/license authority or by another approved party (or device) and 2) it originates from an approved/compliant device. We will not further elaborate on this here, as techniques to achieve this are known. In the case II under b), we first need to know the different origins of rights. Some example ways to obtain rights are: i. Rights can be imported via a wired or wireless domain interface. ii. Rights can piggyback on a (packaged) medium iii. Rights can piggyback on device iv. Rights can be generated in the domain itself. International patent application WO 02/065255 (attorney docket PHNL010113) describes how rights can be generated when importing content. Some extensions are described in European patent application serial number 02076209.2 (attorney docket PHNL020246). Given these different origins of rights, we consider a transaction legal if: transmitting the right in question to the present domain is allowed, i.e. the right is not bound to a specific domain, or the right originates from a compliant transmission/communication channel (e.g. Secure Authenticated Channel, SAC), a compliant device, a compliant medium, or from a compliant right generating device (e.g. a compliant A/D converter). Given the points above we have rights that are bound to a domain and that we have rights which can be transferred to and between domains. We therefore introduce two types of rights: XAD rights (or cross-AD rights) and AD rights. AD rights belong to one AD. XAD rights can be transferred between ADs (if allowed). The following type of rights can be recognized: Render rights, e.g. view, play, print. Transport rights, e.g. copy, move, loan. Derivative work rights, e.g. extract, embed, edit. Utility rights, e.g. backup, cache, data integrity The following attributes can be attached to rights: Consideration: Whatever the user has to give in return. Extents: How long; how many, where, etc. User attributes, Subscribers, age, sex, etc. An AD right can be any type of right, except for a transport type of right. That is, an AD right cannot be a right for transport to other ADs. Within the AD render rights may for example be copied. An XAD right can be any type of right. AD rights are only meant for use within the authorized domain and are derived from the XAD right. Initially XAD rights originate from the rights owner. If an XAD right is checked-in in to an authorized domain, AD rights can be derived from this. AD rights may be multiplied at will in the domain, but they may never leave the domain. The XAD right will be used to control inter domain communication. For ease of management reasons only one copy of the XAD right is preferably allowed (unless copies are made for back-up reasons). However, if XAD rights leave the domain, the derived AD rights in the original domain must be deleted. This can be done by sending a revocation messages from the device taking along the XAD right. Now we have the inventive solution for rights check-in: Only allow the checking in of XAD rights and then only if they originate from a compliant transmission/communication/device/medium/generator. Now we also have the inventive solution for rights check-out: only allow checking out XAD rights from a domain. Export of AD rights from the domain is forbidden. Content Management Content typically comprises things like music, songs, movies, TV programs, pictures, books and the likes, but could also include interactive services. We distinguish between three types of content: Encrypted content (digital format) Un-encrypted but watermarked content (both analog as digital format) Unprotected content (both analog as digital format) In an authorized domain digital rights control the use of content. Without a right, content is useless in the domain. The operation check-in of digital protected content in the AD is therefore not relevant to the present invention and will not be discussed further. In case we have watermarked and unencrypted content, the watermark should be checked by the importing device to see if content check-in is allowed and under what conditions. In case that check-in is allowed, the content is imported and an accompanying right is generated. After importing the content, it is preferably encrypted to protect it. In case of unprotected content, the content shall be imported and an accompanying right will be generated. An alternative approach is to let the authorized domain enforce the limitations set upon the content; some rights are granted and some are not. In the case of unprotected content (content in which by law or license no usage restrictions can be detected), such an enforcement subsystem is not needed. As such the content can move freely without restrictions and does not have to be imported. With regards to content check-out, we observe that typically digital format content is encrypted and cannot be used elsewhere (without the right). Flowing away of content in analog format can anyhow not be prevented. Such content can of course contain watermarks, or watermarks can be added to the analogue content. A special case of using watermarks is to always indicate copy-never, thereby preventing reinsertion of analogue content. The issue of content check-out will not be further discussed here. When the content rights are checked-out, the content may need to be re-encrypted. As the protection of the content and the enforcement of the AD is primarily done by controlling the rights, one could say that the content did not enter the AD, only the rights do. Authorized Domain Management Content can only be accessed in the domain if the correct AD right is available. The AD right is derived from an available XAD right, as explained above. An AD right is valid in the complete domain, and is non-transferable between domains. The AD right may be allowed to multiply inside the domain. That means that any device in the domain that needs the right will have unconditional access to the right. Rights can be stored anywhere in the domain. A method therefore must be present to locate and obtain such a right. Different strategies can be applied for this. These strategies can generally be divided into centralized storage methods and decentralized storage methods. In the case of centralized storage of rights there is a central rights manager that will be contacted to obtain a specific right. In the case of decentralized storage of the rights a distributed search mechanism is used to locate and obtain the right within the domain. Note that in practice rights should be located on devices that are mostly/always on and that rights are most likely stored on the same device as the content. For some (AD) rights it is acceptable to have multiple instances/copies of the right (in the domain), for example the play unlimited right (and can be stored anywhere in the domain). Typically, rights containing some counting mechanism to restricted e.g. the number of times to play or copy cannot be replicated in a system without additional precautions. One way of addressing part of this problem is by generating a number of “one shot use rights”. In the case of “copy once”, one “copy right” will be generated. This right will be consumed (deleted) when the content is copied to another domain. As the right represents a one time action, is should be protected against copying but may move freely within the domain. It can be advantageous to store the rights with the content. This would make it easy to locate the right (if the content is available, the right is also available). Another advantage is that the storage space required for the rights scales with the storage available for storing content. The major disadvantage is that it becomes difficult to support rights with some kind of counting mechanism. Packaged media, such as Digital Versatile Discs (DVDs) or compact discs, deserve special mention. We assume that a packaged (ROM) medium will have serial copy management on board (which is the source of the XAD rights), unless it is possible to include a counter mechanism on e.g. a disc to support rights like copy once. An example of such a mechanism can be realized using Chip-in-Disc type mechanisms, such as described in international patent application WO 02/17316 (attorney docket PHNL010233). In a preferred embodiment, a packaged medium may only contain XAD rights. If the medium contains AD rights it might be impossible to delete them afterwards if the corresponding XAD right is removed from the domain. Also, consumers expect that packaged media (e.g. DVD+RW) play anywhere, and in any compliant device. In case of “copy-no-more” we could require that the disc only playback (i.e. renders) on the domain originator device, i.e. the device for which holds device_id=domain_id or on the disc reader (Thus not playable inside the whole domain!). This might stimulate original media sales. Other use rules are possible depending on the setting of the serial copy management bits. To summarize, some advantageous embodiments, which may each be combined with one or more others or deployed stand-alone, of the present invention are: 1. Using domain_ids in devices to identify devices in a domain. In this case all AD compliant devices need to have storage space to store a domain_id number. 2. To limit domain size, a device is checked-in at the domain originator device and when it is in close proximity to this device. 3. The size of the domain is limited by limiting the amount of playback rights in the domain. 4. Two type of rights in the AD: XAD rights for transfer between domains and AD rights for use inside domain. 5. When checking-out a device, its domain_id is deleted, for example by making it equal to the device_id again, and the AD rights residing on the device are deleted as well. This prevents the attack of exporting content from the domain by checking-out a device. 6. When checking-out a device containing XAD rights, a revocation message for corresponding AD rights is sent into the domain, or use hart beat (white list) mechanism. In this case portable devices (not always connected to the network) need to obtain renewed AD rights at regular intervals. This mechanism hinders the attack of trying to leave behind content/rights in a domain by checking out a device. It also prevents illegal distribution of content by checking in a device, storing content on it, and subsequently checking out the device and checking in the device in another authorized domain. 7. To stimulate sales of original packaged media, only allow derivation of AD rights from the XAD (serial copy management right) on a packaged medium if it the medium indicates “one-generation-copy” allowed (and not “no-more-copies”). This means that it is not possible to derive AD rights from a “no-more-copies” XAD right and that the content on the medium can only be played in the domain if the medium is present in the domain. 8. A limited number of use rights is implemented by generating “one shot rights” or “rights tokens”. It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims. The system 100, representing a home network, is of course not the only situation in which authorized domains are useful. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word “comprising” does not exclude the presence of elements or steps other than those listed in a claim. The word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements. The invention can be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In the device claim enumerating several means, several of these means can be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
<SOH> INTRODUCTION TO THE INVENTION <EOH>In recent years, the amount of content protection systems is growing in a rapid pace. Some of these systems only protect the content against illegal copying, while others are also prohibiting the user to get access to the content. The first category is called Copy Protection (CP) systems. CP systems have traditionally been the main focus for consumer electronics (CE) devices, as this type of content protection is thought to be cheaply implemented and does not need bi-directional interaction with the content provider. Some examples are the Content Scrambling System (CSS), the protection system of DVD ROM discs and DTCP, the protection system for IEEE 1394 connections. The second category is known under several names. In the broadcast world, systems of this category are generally known as conditional access (CA) systems, while in the Internet world they are generally known as Digital Rights Management (DRM) systems. Some type of CP systems can also provide services to interfacing CA or DRM systems. Examples are the systems currently under development by the DVB-CPT subgroup and the TV-Anytime RMP group. The goal is a system in which a set of devices can authenticate each other through a bi-directional connection. Based on this authentication, the devices will trust each other and this will enable/allow them to exchange protected content. The accompanying licenses describe which rights the user has and what operations he is allowed to perform on the content. The license is protected by means of some general network secret, which is only exchanged between the devices within a certain household. This network of devices is called an Authorized Domain (AD). The concept of authorized domains tries to find a solution to both serve the interests of the content owners (that want protection of their copyrights) and the content consumers (that want unrestricted use of the content). The basic principle is to have a controlled network environment in which content can be used relatively freely as long as it does not cross the border of the authorized domain. Typically, authorized domains are centered around the home environment, also referred to as home networks. Of course, other scenarios are also possible. A user could for example take a portable television with him on a trip, and use it in his hotel room to access content stored on his Personal Video Recorder at home. Even though the portable television is outside the home network, it is a part of the user's authorized domain. A home network can be defined as a set of devices that are interconnected using some kind of network technology (e.g. Ethernet, IEEE 1394, BlueTooth, 802.11b, . . . ). Although network technology allows the different devices to communicate, this is not enough to allow devices to interoperate. To be able to do this, devices need to be able to discover and address the functions present in the other devices in the network. Such interoperability is provided by home networking middleware (HN-MW). Examples of home networking middleware are Jini, HAVi, UPnP, AVC. The use of network technology and HN-MW allows one to view a set of individual devices as one large virtual device. From a HN-MW point of view, a network can be seen as a set of functions that can be used and connected. Such a system provides a user with capabilities to address any content or service from anywhere in the home network. HN-MW can be defined as a system that provides two services. It allows an application in the network to locate devices and functions in the network. Furthermore, some kind of mechanism, such as remote procedure calls (RPC), defines how to use these functions. From a HN-MW point of view, systems related to handling secure content appear in several ways. Certain functions in the network require access to protected content. Other functions in the network provide functionality that can be used by the elements in the network handling content security. Furthermore, security frameworks like OPIMA can use the HN-MW to locate each other and communicate in an interoperable way. Of course authorized domains can also be implemented in other ways. For a more extensive introduction to the use of DRM in home networks, see F. L. A. J. Kamperman, S. A. F. A. van den Heuvel M. H. Verberkt, Digital Rights Management in Home Networks, Philips Research, The Netherlands, IBC 2001 conference publication vol. I, pages 70-77. Various systems already exist that implement the concept of authorized domains to some extent. Examples of such systems are SmartRight (Thomson Multimedia), xCP (4C, mainly IBM), and NetDRM (Matshushita). The SmartRight system has, amongst others, the following properties: Smart cards can be inserted in all devices. The system uses authentication of those smart cards. The system uses a common network secret. New smart cards added to the domain will receive the network secret. All smart cards can open the licenses (=rights) in the domain. The xCP system has, amongst others, the following properties: Uses common network secret (key space). Key spaces based on MKB structure. When devices are added, the key spaces are merged. Also a new common secret (Media_key) is then generated. All licenses are re-encrypted with the new secret. A central domain manager decides if merger is allowed. The NetDRM system has, amongst others, the following properties: A central server to register device to domain. This server can be at home or in the outside network. Uses network (domain) secret. Secret is distributed from central server, which could also be in the home. Licenses are typically stored in the outside network, but may also be stored locally. Virtual Private Networks (VPNs) could to some extent be considered similar, but their purpose and therefore their implementation is different. Roughly it can be said that the purpose of VPNs is to keep internally generated content in the network (typically accessible in the whole network), while authorized domains try to keep externally generated content (such as purchased copyrighted content) in the domain (typically accessible in the whole domain).
<SOH> SUMMARY OF THE INVENTION <EOH>It is an object of the invention to provide a method of controlling access to a content item in a domain comprising a set of mutually authenticated devices, which is flexible with respect to handling content and rights associated with content. This object is achieved according to the invention in a method comprising deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. Preferably the devices in the domain receive the domain-specific rights from a central rights manager device in the domain, although decentralized rights distribution or other solutions are also possible. The number of domain-specific rights may be limited to a predetermined amount This may apply to all domain-specific rights or just to those of the ‘playback’ type. This allows unlimited copying but limits simultaneous playback. In an embodiment the one or more domain-specific rights are revoked if the right associated with the content item is revoked or removed from the domain. This way it is not possible to exercise the domain-specific rights if there exists no valid corresponding right associated with the content item. The content item may be stored on a removable storage medium together with the right associated with the content item. In that case, the one or more domain-specific rights might be derived only if the removable storage medium indicates that making a one-generation copy is permitted. Alternatively, they are derived only if the removable storage medium indicates that making a single copy of the content item is permitted. This way of deriving domain-specific rights is in line with the permissions (rights) indicated on the removable storage medium. Another option is to derive the one or more domain-specific rights even though the removable storage medium indicates that making a copy of the content item is not permitted, or is no longer permitted (referred to as “copy no more” content). These options make it possible to use content on a removable storage medium such as a Compact Disc or Digital Versatile Disc freely within the domain, even when the right on the disc are more restrictive. Because the domain-specific rights are bound to the domain, there is no risk that users are able to access the content item outside the domain. In an embodiment the right associated with the content item is a right that can be exercised a predetermined number of times, and the number of domain-specific rights derived from the right associated with the content item corresponds to the predetermined number. This provides an easy mapping of content-bound rights to domain-bound rights. The one or more domain-specific rights derived from the right associated with the content item could then be rights that can be exercised a predetermined number of times, preferably one time. This has the advantage that use of the domain-specific rights is very limited, allowing a great amount of control over access to the content item. Further, the problem that the domain-specific right may exist while the right associated with the content item has expired or has become invalid for another reason is now minimized. The predetermined number of times the one or more domain-specific rights can be exercised could be indicated by the right associated with the content item, or be a characteristic of the domain or of the device through which the content item is imported into the domain. For instance the predetermined number could be proportional or inversely proportional to the size of the domain. A large domain could have a large predetermined number to make the content usable on many locations, or maybe a small predetermined number to discourage users to form very large domains. Import devices that provide large predetermined numbers could be sold at higher prices. In an embodiment the content item is permitted to be copied freely and a single specimen of the right associated with the content item is permitted to exist in the domain. This provides great flexibility on where the content item can be accessed, but it prevents users from exercising rights beyond what they are allowed to. In an embodiment every device in the domain has one or more domain identifiers and only communicates with other devices having at least one identical domain identifier. This is a surprisingly effective way to create a domain of mutually authenticated devices. Preferably there is a single domain identifier for every domain. A device can be a member of multiple domains, thus holding multiple domain identifiers. There could also be subdomains within the domain, and then devices hold the domain identifier for the “main” domain and the domain identifiers for the subdomains. A new device that successfully authenticates itself to a device in the domain receives one or more of the one or more domain identifiers, preferably from a central controller device. This is optionally done conditional upon approval by a majority of the devices in the domain. If a particular device leaves or is removed from the domain, its domain identifier for that domain is deleted. The domain identifier may comprise a list of device identifiers for devices that are members of the domain. This list can be compiled easily and so implementation of the domain identifier is straightforward. The domain identifier may comprise the device identifier of the central controller device. Preferably the right associated with the content item comprises one of a render right, a transport right, a derivative work right and a utility right. The domain-specific right then preferably comprises one of a render right, a derivative work right and a utility right. It is a ether object of the invention to provide a system comprising a set of mutually authenticated devices, said set making up a domain, the system comprising a central rights manager arranged for deriving one or more domain-specific rights from a right associated with the content item, the one or more domain-specific rights being bound to the domain and allowing the devices in the domain access to the content item. Preferably every device in the domain has one or more domain identifiers and is arranged to only communicate with other devices having at least one identical domain identifier. In a variant of this embodiment a device in the domain is arranged to authenticate a new device and upon successful authentication to supply the one or more domain identifiers to the new device. The device arranged to authenticate the new device could be a central controller device and the one or more domain identifiers then comprise the device identifier of the central controller device.
20041117
20171212
20050922
94378.0
0
ABRISHAMKAR, KAVEH
Digital rights management method and system
UNDISCOUNTED
0
ACCEPTED
2,004
10,515,220
ACCEPTED
Integrated programmable system for controlling the operation of electrical and/or electronic appliances of a premises
There is disclosed an integrated programmable system for controlling the operation of a number of electrical and/or electronic appliances of a premises, the application being controllable electrically, electronically, wirelessly, by infrared and/or by radio frequency, the system including a central data processing apparatus, e.g. a home server, or a central controller, connected with a common digital communication backbone, and the central data processing apparatus is connectable with the appliances via the digital communication backbone.
1. An integrated programmable system for controlling the operation of a plurality of electrical and/or electronic appliances of a premises, wherein said plurality of appliances are controllable electrically, electronically, wirelessly, by infrared and/or by radio frequency, wherein said system includes a central data processing apparatus connected with a digital communication backbone, wherein said central data processing apparatus is adapted to be connected with said appliances via said digital communication backbone. 2. A system according to claim 1 further characterized in that said system includes sound producing means connected to a plurality of sources of audio signals for selectively outputting sound upon receipt of audio signals from at least one of said sources or outputting audible alarm prompts upon receipt of audio signals from said system. 3. A system according to claim 2 further characterized in that audio signals from said system are prioritized above audio signals from said sources of audio signals. 4. A system according to claim 1 further characterized in that said data processing apparatus comprises a computer server. 5. A system according to claim 1 further characterized in that said communication backbone includes at least a network hub, switch or router. 6. A system according to claim 1 further characterized in including at least one controller for controlling the operation of said plurality of electrical and/or electronic appliances in a predetermined manner. 7. A system according to claim 6 further characterized in including a plurality of said controllers which are spaced apart from one another. 8. A system according to claim 1 further characterized in being adapted to be connected with said electrical and/or electronic appliances via at least two different standard interfaces. 9. A system according to claim 1 further characterized in that said system is adapted to connect at least two said appliances together by Home Audio Video interoperability (HAVi) standard. 10. A system according to claim 1 further characterized in being adapted to be connected with at least one said appliance via Universal Plug and Play (UPnP) architecture. 11. A system according to claim 1 further characterized in incorporating a unified devices abstraction layer with at least one translator for translating proprietary means of controlling individual devices into standard interfaces, and thereby to allow said system to control devices in a uniform manner. 12. A system according to claim 1 further characterized in that said system is adapted to be connected with at least one said appliance via a standard serial bus interface. 13. A system according to claim 1 further characterized that said system is adapted to be connected with at least a lighting device via at least one electrical power control module. 14. A system according to claim 2 further characterized in that said sound producing member comprises a speaker. 15. A system according to claim 2 further characterized in that said plurality of audio signal sources include said central data processing apparatus, an audio system, an audio-visual system, and a microphone. 16. A system according to claim 1 further characterized in being adapted to be connected with a security system. 17. A system according to claim 16 further characterized in that said system is adapted to be connected with and to connect a plurality of components of said security system via said common communication backbone. 18. A system according to claim 16 further characterized in that said security system includes at least a motion detector. 19. A system according to claim 16 further characterized in that said security system includes at least a speaker. 20. A system according to claim 16 further characterized in that said security system includes means for dialing at least one pre-determined telephone number.
This invention relates to an integrated programmable system for controlling the operation of electrical and/or electronic appliances of a premises, e.g. a house, a flat, or an office, and in particular such a system allowing the end user to program the mode and manner of operation of such appliances as he wishes. With the advance of technology, home automation is a goal long sought to be achieved. Home automation will offer more freedom and autonomy to the disabled or elderly. Other members of the family will also benefit from the comfort and convenience offered by home automation. Existing approaches to home automation are, however, proprietary in nature, and are non-extensible solutions that cannot accommodate the growth of the market. Each company or school has its own system and basic structure, which is not compatible with those of other companies or schools. In short, the systems and basic protocols are all vendor-specific. In addition, existing home electrical appliances and electronic systems suffer from the following drawbacks and limitations: a. The appliances are mostly self-contained and thus functionally separate from one another. b. All functionalities and limitations of the appliances are pre-defined by the manufacturers/vendors. c. Very few appliances are “cross-applicational”, for example a motion detector connected to a standard security control panel cannot usually be used for occupancy energy saving or occupancy alarm purpose. d. Various appliances may have some common functions. For example, an alarm clock which rings, a radio clock which tunes to a station at a certain pre-set time, a sprinkler control panel which turns on periodically, an occupancy energy saver which turns off lights after a predetermined period of no activity, and a VCR which records television programs all contain an internal clock. At a minimum, this is unnecessary duplication of resources. These internal clocks are also not synchronized with one another, adding to the difficulty of having multiple appliances work in concert with one another, e. It is very difficult and sometimes impossible to add new functions to appliances which are not originally envisaged by the manufacturers/vendors. f. Routing audio and/or video signals to different locations in the premises cannot be easily achieved without installing more wires. Usually, wiring is necessary between any possible pair of audio and/or video source and destination, resulting in a large number of wires for a full-scale installation. g. Most appliances have their own respective remote control devices, which results in a large number of remote control devices being scattered around the premises, causing confusion and inconvenience. h. In some situations, co-ordination of several devices is required. For example, for watching a DVD movie, the television has to be switched to AV mode, DVD video input and the appropriate digital audio mode have to be selected for the amplifier, the DVD player is then switched on to play the DVD disc, the shades have to be lowered and the lights to be dimmed. A user thus has to perform all these functions before he can sit down to, enjoy the DVD movie, and in reverse when he finishes watching the DVD movie, and wants to watch television again. It can thus be fairly said that all the existing electrical and/or electronic appliances operate on a stand-alone basis, with very limited, if any, capacity for integration with one another for concerted operation. In particular, there is no way for central control and operation of such appliances. Even if in cases where integration of a number of such appliances of the same manufacturer is allowed, such is all pre-designed and pre-determined by the manufacturer, and is thus a closed platform. It is thus not up to the end user to integrate the functions of the appliances as he or she wishes, according to his or her own need in view of the physical environment. Furthermore, in conventional security systems, security zones are set and are usually geographically oriented, e.g. one zone per room. Sensor devices in various zones are connected to a central security panel. Each particular zone may be individually armed or disarmed. Upon triggering of any device, and if the zone is armed, a pre-determined action is taken, e.g. an alarm is given. There is, however, no assessment of the situation, i.e. each trigger of the relevant sensor is considered to be a security event requiring action. It is not possible to assign a rating on the importance of the alarm signals given by each individual sensor device. For example, it is usually difficult to program a control panel to trigger an alarm signal only when a detector and a sensor are both activated within a short term of each other, and even with more advanced control panels, more devices and complex relationships are rarely supported. False alarms are thus common. It is also difficult to exclude a particular sequence of activities or a particular device from a security profile unless the device is wired in its own zone, in which case it can be individually disarmed. It is thus usually impossible to set the system such that, for example, it ignores the sequence of events in which the bedroom door is opened, followed by motion in the stairs and motion in the kitchen (which collectively signify someone getting up for a drink), but sounds alarms in a reversed sequence of events, which collectively signify a burglar breaking in from the kitchen and going into the bedroom. The conventional systems thus force the users to accept either an indiscriminating all-secured scenario or an all-unsecured scenario. It is thus an object of the present invention to provide an integrated programmable system for controlling the operation of electrical and/or electronic appliances of a premises, e.g. a house, an office, a factory, etc., in which the aforesaid shortcomings are mitigated, or at least to provide a useful alternative to the public. According to the present invention, there is provided an integrated programmable system for controlling the operation of a plurality of electrical and/or electronic appliances of a premises, wherein said plurality of appliances are controllable electrically, electronically, wirelessly, by infrared and/or by radio frequency, wherein said system includes a central data processing apparatus connected with a digital communication backbone, wherein said central data processing apparatus is adapted to be connected with said appliances via said digital communication backbone, characterized in that said system includes sound producing means connected to a plurality of sources of audio signals for selectively outputting sound upon receipt of audio signals from at least one of said sources or outputting audible alarm prompts upon receipt of audio signals from said system. Embodiments of the present invention will now be described, by way of examples only, with reference to the accompanying drawings, in which: FIG. 1 is a first schematic diagram of a two-layered distributed network architecture design of an integrated programmable system according to the present invention for controlling the operation of electrical and/or electronic appliances of a premises; FIG. 2 is a second schematic diagram of the system shown in FIG. 1; FIG. 3 is a third schematic diagram of the system shown in FIG. 1; FIG. 4 is a schematic diagram showing the physical architecture of the system shown in FIG. 1; FIG. 5 is a schematic diagram showing the networking of various electrical and/or electronic appliances in the system shown in FIG. 1; FIG. 6 is a schematic diagram showing reproduction of audio signals in the system shown in FIG. 1; FIG. 7 shows a known way of achieving audio distribution; FIG. 8 is a schematic diagram of an integrated security system forming part of the system shown in FIG. 1; FIG. 9 is a schematic diagram of an integrated elderly monitoring system forming part of the system shown in FIG. 1; FIG. 10 is a schematic diagram of an integrated occupancy energy saving system forming part of the system shown in FIG. 1; FIG. 11 is a schematic diagram of an integrated automatic sprinkler system forming part of the system-shown in FIG. 1; FIG. 12 is a flow chart of the operation of the central server in the system shown in FIG. 1; and FIG. 13 is a flow chart of the operation of the smart controller in the system shown in FIG. 1. Referring firstly to FIG. 1, such shows, at a first level of understanding, a schematic diagram of an integrated programmable system for controlling the operation of electrical and/or electronic appliances of a premises, e.g. a house, according to the present invention. The fundamental design principles are: 1. The premises is constructed and viewed as a programmable platform, in which every aspect of the premises which are served by an electrical and/or electronic appliance are controllable via one or more programs written to the platform architecture. 2. Rerouting or rewiring connections to physical hardware does not require changing of the system configuration. 3. To minimize as much as possible hard-wired scenarios. 4. The system consists of a number of simplistic (dumb) components, each providing only one or a few simple generic services, and working in co-operation under the guidance and coordination of a central intelligence. 5. The components themselves do not preferably have intelligence. 6. Operations and desired features are implemented by mixing and/or matching of different services performed by the individual components. 7. All components are controlled and described by custom-built translators that expose standard interfaces to the central intelligence, so that the central intelligence does not have to be aware of the details of the specific service/hardware providers. 8. The system is controllable via a number of different user interfaces, e.g. Web browser, televisions with remote control apparatus, personal digital assistants (PDA), touch screens, cellular phones, etc. As can be seen in FIG. 1, broadly speaking, an integrated programmable system, generally designated as 100, for controlling the operation of electrical and/or electronic appliances of a premises consists of a two-layered, distributed network architecture design, with an outer appliance layer 102 and an inner control layer 104. The appliance layer 102 includes various electrical and/or electronic appliances and devices, including, but not limited to, security sensors, monitoring devices, audio and/or visual equipment, telephony equipment, lighting apparatus, display devices, control devices, switches, and mechanical devices etc. All such appliances are connected to a central home server 106 in the control layer 104, either directly or indirectly, via a common digital communication backbone. The home server 106 allows the end user to control, adjust and program the criteria and manner of operation of the various appliances. The common digital communication backbone includes a central cable (bus) which connects all the appliances with the central control layer 104. The common digital communication backbone may be a single foil-shielded twisted-pair (FTP) CAMSe cable, which runs through the whole premises. Also incorporated in the control layer 104 are a number of smart controllers 108 each for directly controlling and monitoring the operation of one or more of the various electrical and/or electronic appliances in the appliance layer 102. The various smart controllers 108 are connected with the digital communication backbone and with one another via one or more network hubs, switches or routers 110, and via which the system 100 may also be connected with the Internet. The smart controllers 108 may be implemented as book-sized form-factor industrial personal computers (PC). The actual hardware is PC-based, with a high-speed central processing unit (CPU), 256M random-access-memory (RAM) and a small (say 20-40 GB) hard disk drive, and a number of hardware devices implemented in the motherboard itself (e.g. 100Base-T network, analog audio input/output, and 3D graphics). Each smart controller 108 runs a Microsoft® Embedded XP operating system. In each smart controller 108 is usually installed a PCI-based digital input/output (I/O) card with 24 to 84 digital inputs, although the system also supports many other brands of PCI-based, cPCI-based, ISA-based or RS232/RS485-based digital I/O modules on the market. Each digital I/O module card accepts switch inputs from a multitude of sensor devices connected to opto-isolated terminals on this card with straight electrical wires. Regulated power supplies provide 12V and 24V DC power, via electric wires, to these devices and equipment, e.g. motion detectors, smoke detectors, glass-break detectors, door and window contacts, gas and water sensors, etc. Contact switches are wired in serial with 12V DC supply into each input channel of the digital I/O card so that, when a device triggers (e.g. the relay switch closes), electricity at 12 volts will be supplied to the particular I/O channel. Various devices and equipment may be connected directly to the smart controller 108 in the following manner: communicating thermostats (which supports serial protocols) that control the heating, ventilating and air conditioning (HVAC) systems are connected to the smart controller's RS232 serial port, either directly or via a RS485 converter; fingerprint scanners are connected to the smart controller 108 via either USB port or parallel port; infrared receivers and infrared routers/emitters are connected to the RS232 serial ports of the smart controller 108; some commercial equipment (e.g. plasma TVs and weather stations) also have built-in serial communication ports that can be connected to the RS232 serial ports of the smart controller 108; microphones are connected to the audio input ports, and hardware is available on the sound cards to compress these audio streams into digital format (e.g. MP3) for transmission to other smart controllers or to the home server 106 either for playback or recording purposes; pan-tilt-zoom video cameras are connected to the RS232 serial ports of the smart controller 108 for control, and their video outputs are connected either to the USB ports or to composite video input ports of one or more video capture cards installed in the smart controller 108. These video capture cards may contain hardware necessary to compress the video streams into digital format (e.g. MPEG2) for transmission, or the compression may be performed in software. Each connection to a device or equipment is unique, described by an address. A central database in the home server 106 stores all the addresses of the device or equipment connected to the system 100. A device address contains all the necessary information to enable the system 100 to connect to that particular device or equipment and to communicate with it. Such information may include the serial port number to which the device/equipment is connected, communications protocol speed, equipment model number, signal timings, data formats, etc. FIG. 2 shows the architectural structure of the system 100 at a more detailed level. The system 100 includes a Unified Devices Abstraction Layer (UDAL) 112, which corresponds, functional-wise, to part of the home server 106 shown in FIG. 1 and discussed above. The hardware equipment may be connected to the UDAL 112 via various standard interfaces. For example: a. traditional and Internet telephony apparatus may be connected with the UDAL 112 via Telephony Application Programming Interface (TAPI) and Personal Computer-Private Branch Exchange (PC-PBX); b. audio and/or visual and/or gaming apparatus may be connected with the UDAL 112 via DirectX or DirectShow, in which DirectX is a set of application program interface (API) developed by Microsoft Inc.; c. lighting apparatus, various electrical and/or electronic apparatus, control apparatus, etc. may be connected with the UDAL 112 via: 1. X-10 electrical power control modules traded by X-10 Inc., of the US. Such modules are devices that plug into an electrical outlet and allow a user to remotely control the power to a lamp or an appliance that is plugged into them. There are also X-10 modules that may be installed in place of wall switches to control lights, and some can be used to set back a thermostat; 2. Universal Plug and Play (UPnP), a network architecture that provides compatibility among networking equipment, software and peripherals of the various vendors that are part of the Universal Plug and Play Forum; 3. CEBus Standard, a non-proprietary protocol based upon an open standard (ELA 600) set down by the CEBus Industry Council, which allows every CEBus HomePnP™ device to communicate with every other CEBus HomePnP™ device over the power line without the need for new wires. Such CEBus HomePnP™ devices can be networked with a central controller for larger and more extensive automation projects; 4. Jini, a software from Sun Microsystems; 5. remote device management interfaces provided by emWare, Inc. of the US; 6. Home Audio Video interoperability (HAVi), a vendor-neutral audio-video standard allowing different home entertainment and communication devices (such as VCRs, televisions, stereos, security systems, video monitors) to be networked together and controlled from a primary device, e.g. a personal computer. Using IEEE 1394 as the interconnection medium, HAVi allows products from different vendors to comply with one another based on defined connection and communication protocols and API. One of the key features of HAVi is its ability to easily add new devices to the network. When a new device is installed, the system will configure itself to accommodate it. Other services provided by the distributed application system include: addressing scheme and message transfer, lookup for discovering resources, posting and receiving local or remote events, streaming and controlling isochronous data streams; 7. proprietary interfaces; 8. standard serial bus interfaces, e.g. RS232, 422, 485, USB, and FireWire™. FireWire™ is the name given by Apple Computer Inc. to products supporting the IEEE 1394 standard, which is a very fast external bus standard that supports data transfer rates of up to 400 Mbps; 9. relays and switches; and 10. digital and analog input/output interfaces. As there are, at least in theory, unlimited types of devices or equipment, and different ways to communication with or control them, it is necessary for the smart controller system software to translate communication protocols and commands for individual devices or equipment into a uniform schema for easy adaptation into the system 100. Such program logics form the Unified Device Abstraction Layer, and the uniform schema format is the Unified Device Space. A possible Unified Device Space format may be a simple device name plus a property name, as in the following Table 1: Device Name Property Name Meaning TV PowerOn Status of the power button TV Channel The current channel number TV Volume Audio volume Air Conditioner CurrentTemp Current room temperature Air Conditioner TargetTemp Target temperature Air Conditioner PowerOn Status of the power button Air Conditioner FanOn Status of the fan button The system software translates actual device status and setting values into this Unified Device Space format. For instance, the TV may be a “legacy device”, i.e. one that does not have built-in digital communication capabilities. A light sensor may be connected to the digital I/O board to detect whether the TV power LED is turned on. If so, it will set the “PowerOn” property of the “TV” device to be true. A physical current sensor may be connected to an analog voltage meter to detect the volume level. In order to turn on/off the TV or to change channel/volume, an infrared emitter device may be called on to emit the relevant infrared remote-control codes. The air conditioner may be controlled by a communicating thermostat. In this case, finding out the current temperature and power status, etc. can be effected by sending the relevant text command via the serial cable connected to the thermostat through its RS232 port and waiting for a response, in a format specified by the air conditioner's communications protocol. In the first case, i.e. the case with the “legacy” TV, the system software translates a number of physical measurements into logic values represented in the Unified Device Space. In the second case, the system software translates the air conditioner's communications protocol into values in the Unified Device Space. The benefit of the Unified Device Space is that, within the present system 100, all other system modules can work with a uniform way of controlling, measuring and detecting devices and their statuses and settings. To a system customization script (see below), the user simply has to issue: SetDeviceProperty (“TV”, “PowerOn”, True) SetDeviceProperty (“A/C”, “PowerOn”, True) to turn on both the TV and air conditioner. The system software automatically translates these Unified Device Space commands into the appropriate infrared codes sent by the infrared emitter to the TV, as well as the appropriate text commands sent via RS232 to the thermostat of the air conditioner. As to the common digital communication backbone, such may be of the Transmission Control Protocol (TCP)/Internet Protocol (IP) or FR/ATM (Frame Relay/Asynchronous Transfer Mode) or a virtual private network (VPN), over a cable under 100Base-T (Fast Ethernet) standard (IEEE 802.3u), a wireless local area network (LAN), or fibre optics. The system 100 may be connected with the Internet via integrated services digital network (ISDN) standard, cables, digital subscriber lines (DSL), etc. The system 100 includes a Primary User Interface which allows an end user to interact with the Unified Devices Abstraction Layer, including the home server 106 of the system 100, and via Direct3D, which is an application program interface for manipulating and displaying three-dimensional objects, for programming, setting, resetting and/or changing the manner of operation of the various components and appliances connected with the system 100. Some other acronyms appearing in FIG. 2 have the following meanings: “WAP” stands for Wireless Application Protocol, which is a secure specification that allows users to access information instantly via handheld wireless devices, such as mobile phones, pagers, two-way radios. “HTM” stands for Hyper Text Markup Language, which is the authoring language used for creating documents on the World Wide Web. HTML defines the structure and layout of a Web document by using a variety of tags and attributes. “XML” stands for Extensible Markup Language, which is a specification specifically designed for Web documents. It allows designers to create their own customized tags, enabling the definition, transmission, validation, and interpretation of data between applications and between organizations. “ASP” stands for Active Server Pages, which is a specification for a dynamically created Web page with a ASP extension that utilizes ActiveX scripting. When a browser requests an ASP page, the Web server generates a page with HTML code and sends it back to the browser. “ADO” stands for ActiveX Data Objects, which is Microsoft's high-level interface for data objects. ADO is very general and can be used for accessing all sorts of different types of data, including web pages, spreadsheets, and other types of documents. “IIS” stands for Internet Information Service, which is Microsoft's Web server that runs on Windows NT platforms. “VBScript” stands for Visual Basic Scripting Edition, a scripting language. VBScript is based on the Visual Basic programming language, but is much simpler. It enables Web authors to include interactive controls, such as buttons and scrollbars, on their Web pages. FIG. 3 shows the integration of the hardware protocols, the Unified Devices Abstraction Layer, also representing the common communication backbone, the system core engine, and the control interface. With particular reference to the control interface, it can be seen that the system 100 may be controlled by operating over the Internet, a WAP phone, a computer, a remote-control device, a touch screen, or a personal data assistant (PDA) etc. With the advance of technology, some other protocols and/or interfaces may be incorporated into the existing system. FIG. 4 shows a schematic diagram of the system 100 at a yet further different level. The system 100 includes a central controller 120, which corresponds to the home server 106 shown in FIG. 1. The central controller 120 is connected with a number of the smart controllers 108, via a high-speed digital backbone 124, corresponding to the common digital communication backbone. Each smart controller 108 is connected with a number of electrical and/or electronic appliances, i.e. hardware devices 126, via physical wiring of various types. Most such hardware devices 126 are connected to smart controllers 108 that are physically located closest to them. Such hardware devices 126 may, however, be connected directly to the central controller 120. For the purpose of this invention, a smart controller 108 has processing power, its own operating system, application software, a number of virtual devices 128, software devices 129, and other converter hardware to communicate with the hardware devices 126 connected with it. A software device is a device that exists only in software and has no necessary hardware to match. Such may include speech generators, which exist in software implementation only, which take simple text and generate sound signals. These sound signals may then be fed to an amplifier to produce the sound. A virtual device is an appliance which pretends to be an actual hardware device, even though in reality it only simulates such a device by performing appropriate actions on another hardware device. An example of virtual device usage can be found in a PABX system. The PABX hardware supports a number of central-office phone lines, plus a number of extension phones. If virtual devices are designed for such a PABX system, it may include virtual phone devices that simulate regular simple phone lines, even though in reality it calls upon the PABX system to perform the duties. The user of such a virtual phone device may not need to know that the phone is not a regular phone line, but part of a PABX system. The central home server 106 consists of a high-speed PC-based system with a hard disk storage of 160 GB and RAM of 512 MB, connected to the digital communication backbone. It runs the Microsoft® Server 2003 operating system, and is physically connected to all other smart controllers 108 in the same system 100 via a TCP/IP network. Inside the home server 106 is also run the Microsoft® Data Engine (MSDE), which is a relational database engine storing all the device setup information (addresses) for the entire system 100. The home server 106 is also connected to an X10 automation controller, via RS232, that is in turn plugged into the electrical mains. The X10 automation controller acts as a bridge to control a number of devices and equipment which understand the X10 power-line carrier protocol. The home server 106 also contains the Microsoft (E Internet Information Server (IIS), together with a web-application writing in ASP (ActiveX Server Pages) that allows a user to control the system via a standard web browser. The home server 106 has sufficient hard disk space to store digitized audio files (for whole-premises audio), digitized video files (for video-on-demand), video and audio recordings (e.g. from close circuit TV cameras, telephony answering messages, etc.), and other system set-up files in network-shared folders. The smart controllers 108 may request these files when they need to play back audio or video in a particular room or house area. The homer server 106 may also act double as a smart controller for a number of rooms and areas in the premises. The home server 106 automatically runs system software upon start-up that does the following: detects and establishes communications with each smart controller 108 in the network; maintains a collection of customization scripts (stored in the database) written in scripting languages (VisualBasic, VBScript or JavaScript) that will be triggered upon particular system events; maintains a snapshots of all the devices and equipment in the system 100, together with the current values of all states and settings of each device or equipment. These values are kept in Unified Device Space format, so that any smart controller or customization script may read from the database without knowing the physical details of the device or equipment; waits until notified by the smart controllers 108 that a particular state or setting of a particular device or equipment has changed value; when notified of a change, identifies if any customization script should be run due to that change, and, if so, executes the script; when a script calls for a particular device or equipment to perform a particular action, e.g. turn the power on, sends a request in Unified Device Space format, to the smart controller that is handling that particular device or equipment; logs any necessary change notifications in the database for historical reference; and keeps an internal clock that wakes up periodically to check whether any scheduled event (defined via customization script) should be run. As an example, when an occupant of the premises wants to enter the premises closed by a locked door, he/she places his/her finger on a fingerprint scanner connected to a smart controller 108. The smart controller 108 will then poll the fingerprint scanner for images periodically and detects the new image. It understands that this represents a change of value for a particular status of the fingerprint scanner, i.e. the previous image was blank. It then sends a notification to the home server 106, in Unified Device Space format, notifying it that the device “Fingerprint” has changed the property “Image” to the new image. Upon receipt of this notification, the homer server 106 will check through its database and notices that, when the “Image” property has changed for the device “Fingerprint”, then the customized script “CheckFingerprint” should be run. It then executes the script “CheckFingerprint”, which first checks the fingerprint with fingerprints stored in the database, to determine a match. If a match is found, it sends a request to set the “Open” property of the device “DoorLock” to “true”. The smart controller 108 handling the door lock, upon receiving this commands, translates the command into the appropriate physical action, which is to turn on a digital output channel in the Digital I/O board to energize a relay switch that sends 12 volts to the electric door strike, opening the door. The following is a sample script suitable for controlling the opening or otherwise of the front gate of the premises, upon scanning of a fingerprint image by the fingerprint scanner, receipt of data from a smart card, or entry of code via a keypad, as well as other actions of various devices and equipment of the system following opening of the front gate. ‘ Check identity of person Dim Name As String Select Case TriggerSource Case “FINGERPRINT” ‘ Fingerprint scanned Name = IntelliHome.LookupUser(UserID) If Not (Name Is Nothing) Then ‘ Track location IntelliHome.LocationTracking(“FRONTYARD”) = UserID Else ‘ Fingerprint not found IntelliHome.Devices(“FRONTYARD_Speakers”, “TextToSpeech”) = “Fingerprint not recognized. Access denied.” Return End If Case “CARD” Case “KEYPAD” ‘ Keypad code entry or access card Dim CanEnter As Boolean = False ‘ Is the key code (or access card) allowed to open the front gate? If IntelliHome.CheckSecurity(KeyValue, “OPENFRONTGATE”) Then Dim contact As Integer = IntelliHome.LookupCode(KeyValue) If contact >= 0 Then Name = IntelliHome.LookupUser(contact) IntelliHome.LocationTracking(“FRONTYARD”) = contact Else Name = “ ” End If CanEnter = True End If If Not CanEnter Then If Trigger.TriggerProperty = “CARD” Then IntelliHome.Devices(“FRONTYARD_Speakers”, “TextToSpeech”) = “Invalid access card. Access denied.” Else IntelliHome.Devices(“FRONTYARD_Speakers”, “TextToSpeech”) = “Invalid entry code. Access denied.” End If Return End If Case Else Return End Select ‘ Disarm perimeter - but retain security of inside IntelliHome.Devices(“FRONTYARD_Speakers”, “TextToSpeech”) = “Welcome home, ” & Name & “. Perimeter is disarmed. Please enter.” IntelliHome.DisarmSecurity(“FRONTYARD”) ‘ Disarm security in the front yard IntelliHome.DisarmSecurity(“GARDEN”) ‘ Disarm security in the back garden IntelliHome.DisarmSecurity(“GARAGE”) ‘ Disarm security in the garage ‘ Open front gate IntelliHome.Devices(“FRONTYARD_FrontGate”, “Open”) = True ‘ Turn on lights if after 6 pm or too dark Dim LightsOn As Boolean = False If System.DateTime.Now.Hour < 7 Or System.DateTime.Now.Hour > 17 Or IntelliHome.Devices(“LightSensor”, “Light”) > 0.5 Then IntelliHome.Devices(“FRONTYARD_FloodLights”, “On”) = True LightsOn = True End If ‘ Turn lights off and close the gate after one minute System.Threading.Thread.Sleep(60000) If LightsOn Then IntelliHome.Devices(“FRONTYARD_FloodLights”, “On”) = False ‘ Close front gate IntelliHome.Devices(“FRONTYARD_FrontGate”, “Open”) = True FIG. 5 shows a schematic diagram of the system 100 at a still further different level. As can be seen, various electrical and/or electric components and devices are connected via a central digital common communication backbone with the home server 106, via various standard interfaces, e.g. HAVi, digital/analog and input/output modules, X-10, telephone lines, and serial bus, e.g. 232 (RS232) interfaces. FIG. 6 shows a schematic diagram of a digital distributed audio module, forming part of the system 100. The central controller 120, which corresponds to the home server 106 shown in FIG. 1, contains an archive of pre-recorded audio files in compressed digital formats, e.g. MP3, WMA, RA, SND, PCM, WAN, MIDI, etc. The central controller 120 is connected to each smart controller 108 via the digital network backbone 124. Each smart controller 108, among other features, is connected to sound generating hardware for producing audio recording from the digital stream. In particular, the smart controller 108 is connected to one or more speakers 130 via an amplifier 132. To enhance the flexibility and/or the audio quality, a local Hi-Fi system 134 may be connected to the speaker 130 via a relay switch 136. The system is so designed that audio signals from the smart controller 108 will always take precedence over those from the local Hi-Fi system 134, in particular because some audio prompts from the smart controller 108, e.g. alarms, must be heard. The speakers are connected to an amplifier, which is in turn connected to the digital audio output port of the smart controller 108. Audio signals produced by the smart controllers 108 (e.g. music, or system alert messages) is amplified and outputted via the speakers. If the smart controller 108 controls more than one set of speakers, then separate digital sound cards are installed in the smart controllers 108, each sound card being connected to a separate amplifier connected to each set of speakers. There may be a separate local high-end Hi-Fi system in some rooms, e.g. the entertainment room. In this case, both the speaker line outputs from the amplifier connected to the smart controller 108 and the speaker line outputs from the local Hi-Fi system are connected to the inputs of a relay switch (the local system to the normally-closed input, and the smart controller 108 to the normally-open input), with the output of the relay switch connected to the actual speakers. The relay switch is activated by an audio signal sensor, which is connected to the analog audio output of the smart controller 108. By way of such an arrangement, when no audio signal is played by the smart controller 108, the relay switch will stay in the normally-closed position, which connects the local Hi-Fi system to the speakers. Upon audio signals generated by the smart controller 108, the audio signal sensor will energize the relay switch, which will then switch to the normally-open position, disconnecting the local Hi-Fi system and connecting the smart controller amplifier with the speakers. Thus, any audio output from the smart controller 108 will override audio output from the local system. This is crucial as certain system-generated audio output (e.g. alert messages, warning messages) must be heard and should thus override any other audio streams currently playing. When the smart controller 108 stops outputting audio signals, the audio signal sensor will de-energize, and the relay switch will return to the normally-closed position, thus disconnecting the smart controller 108 and re-connecting the local Hi-Fi system with the speakers. The benefits of such an arrangement include: the number of physical wires is reduced, in particular as a digital communication backbone is used for carrying almost all types of programs and audio signals; such enables the use of the same set of hardware for all audio generation purposes; pre-recorded audio pieces are shared among all zones; different audio pieces may be played in each different zone, at its own respective pace; the same audio piece may be played in different zones, which are geographically remote from each other; and local Hi-Fi systems are seamlessly integrated into this arrangement. In contrast, FIG. 7 shows a schematic diagram of a known way of achieving audio distribution module, which is both costly and less flexible. Source devices, e.g. DVD players 140, CD changers 144, radio tuners 142, MD decks, etc. are located at a central location. Audio signals from the source devices are fed into a matrix switch 146, either amplified or pre-amplified. The matrix switch 146 is mapped to a number of zones, each representing a room or a particular designation of audio signals. Speaker wires extend out of the matrix switch 146, one set for each zone, directly to the speaker(s) 148 in the particular zone. The matrix switch 146 is controlled by various control devices, e.g. remote controls, wall panels, etc. At any one time, a particular program source is connected (switched) to a particular zone, enabling the speaker(s) 148 in the zone to receive the output of the program source. Separate routing technologies have to be used for controlling separate program source devices, e.g. infrared remote devices use infrared radiation to transmit remote control signals to one of the source devices, and radio frequency remote control apparatus may control a device via radio frequency signals. FIG. 8 shows a schematic diagram of a programmable security feature, forming part of the system 100. In this security system, a motion detector 150 for detecting motion is connected via the common digital communication backbone with the central server 120 of the integrated programmable system, which is in turn connected with (a) a speaker, which maybe the speaker 130 of the digital distributed audio module shown in FIG. 6, for producing pre-recorded audio message; (b) lights 152, (c) a telephone 154 directly for dialing a pre-determined telephone number, and/or (d) a telephone 156 via a speech generator 158 for producing synthesized audio message and transmitting same through the telephone 156. By way of such an arrangement, the security feature may be constructed of components of other existing systems, e.g. a motion detector of a security system, a speaker of an audio-visual system, existing lighting system, and a telephone of a telephony system, etc. FIG. 9 shows an integrated elderly monitoring feature, forming part of the system shown in FIG. 1. In this elderly monitoring feature, a clock 160, a motion detector 162, and a microphone 164 are connected, via the common communication backbone, to the central server 120 of the system 100. The central server 120 contains a programmable logic 166 which has been pre-set such that, if neither motion nor sound is detected for a pre-determined period of time (as counted by the clock 160), alarming signals will be outputted by speakers 168 which may, again, be the speaker 130 of the digital distributed audio module shown in FIG. 6. FIG. 10 shows an integrated occupancy energy saving feature, forming part of the system shown in FIG. 1, consisting of a clock 170 and a motion detector 172 connected, via the common communication backbone to the central server 120 of the system 100. The central server 120 contains a logic 174 which has been pre-set such that, if neither motion nor sound is detected for a pre-determined period of time (as counted by the clock 170), lights 176 also connected with the system will be switched off, so as to save energy consumption. It should be understood that the clock 170 in this occupancy energy saving system may be the same as the clock 160 in the integrated elderly monitoring feature discussed above. FIG. 11 shows an integrated automatic sprinkler system, forming part of the system shown in FIG. 1. The sprinkler system includes a clock 180 and an electronic weather station 182 connected, via the common communication backbone to the central server 120 of the system 100. The central server 120 contains a logic 184 which has been pre-set such that, if no rain falls when a pre-determined time (as counted by the clock 180) is reached, a sprinkler 186 also connected to the system will be activated. FIG. 12 is a flow chart showing the operation of the central server 120 discussed above. When the system 100 is activated, it is first initialized (step 302). The device database 304 is loaded (step 306), followed by loading of triggers and scripts (step 308). The smart controllers 108 are then connected (step 310). The system 100 will then check if there has been any change in or to the UDAL (step 312). If so, the device database 304 will be updated (step 314), and if the history is to be stored (step 316), the archive will be written (step 318). The system 100 will then check if trigger has been fired (step 320). If yes, it will spawn script (step 322), but if not, it will check other modules (step 324), and if a positive result is detected, the specific module action will be carried out (step 326), e.g. by sending appropriate control commands. If, on the other hand, there is no change in or to the UDAL, the system will check for control command (step 328). If the result is positive, UDAL value change will be sent to the smart controllers 108 (step 330). If not, a clock in the system will check if it is time for some scheduled events (step 332). If yes, it will spawn the appropriate script (step 322), but if not, the system 100 will resume checking if there has been any change in or to the UDAL (step 312). As to FIG. 13, such is a flow chart showing the operation of the smart controller 108 discussed above. When the system 100 is activated, the system will be initialized (step 402), and local and device UDAL maps will be loaded (step 404) from the database 406. The device settings will also be loaded (step 408) from the database 406. The smart controller 108 is then connected to the system 100 (step 410). The controllers 108 then scan through the central database and identify all devices and equipment connected to each respective controller 108 and gets their addresses. All connected devices are also initialized (step 412). Each device/equipment is initialized with the information provided by its respective address. This is done via a separate piece of program logic specifically developed for each type/brand/model of device or equipment. Some devices or equipment, e.g. sound cards for audio generation, are installed inside the smart controller 108. These devices/equipment are controlled in the same manner as devices/equipment external to the smart controller 108, although in the case of devices/equipment installed inside the smart controller 108, communication is usually much more reliable and instantaneous, since they do not have to send signals to the smart controller 108 via physical wires. All device states are then updated (step 414). Translators exist to call specific control protocols to get the status of their states (step 416). The smart controller 108 will maintain communication with the devices/equipment. The equipment may send a notification message automatically when a state or a setting has changed, e.g. the state of a thermostat will change when there is a change in the temperature. The equipment, e.g. digital I/O modules, may on the other hand require periodic polling to discover its current status and settings, which are then compared with the system's internal copy of the states and settings in order to discover whether any of them has changed. The system 100 will then continuously check if there has been any change in the state of the various devices and equipment (step 418). If there has been any change in a state or setting of a device/equipment, the smart controller 108 to which the device/equipment is connected will send information to the home server 106, such that other programs or other smart controllers may act on this information. The device state will be mapped to the UDAL value (step 420), and the UDAL value will then be updated in the server (step 422). After this updating (step 422), or if there has not been any change in the state, the system will then check if there has been any UDAL change (step 424). If there has been any UDAL change, the UDAL value will be mapped to the device state (step 426), and the device state set accordingly (step 428). The translators will then convert the state change to specific control protocol (step 430) for operation of the appliances or devices connected with the smart controllers 108. In particular, the translators can translate proprietary means of controlling individual devices into standard interfaces, thereby to allow the system 100 to control and accommodate with electrical and/or electronic devices in a uniform manner. When instructed by the system 100, the smart controller 108 will act upon such request to control or initiate actions on the device/equipment. The particular means to accomplish such actions depend on the brand and model of the equipment, and the communication protocol used by that piece of equipment. The smart controller 108 also puts up a user interface from the graphics chip, with its output connected directly to a visual output, e.g. a TV set, to enable the user to control the system 100 using the TV. With the present invention, it is possible to construct and implement a threat-based security system. In such a system, “event” is defined as change in the state of an input service, e.g. a sensor; “group” is defined as a collection of similar events which are regarded as forming a coherent set, e.g. in a security zone; “threat” is determined by reference to the amount and nature of security danger represented by an event, given the sequence and threat levels of previous events; and “action” is the activity to be carried out when a particular type of threat has exceeded a predetermined threshold level, which may be governed by the sequence and nature of previous detected events. In such a system, events are detected when a particular state of an input service/sensor has changed, e.g. a window sensor changes from being closed to being open. The event so detected is that mapped to a set of groups that contain that particular type of event, e.g. window being opened. Each mapped group has an intrinsic priority level, and the group list is then sorted according to the priority levels, allowing more general groups to be overridden by more specific groups, e.g. allowing all window openings to be monitored except a particular window. The group of the highest priority is then mapped to a set of threats that would trigger when the group is activated. Each threat will generate a corresponding threat level number and a threat type, depending on the particular event and the sequence of previous events, if any. For example, a window being opened may be particularly suspicious if followed by motion detected by a motion detector close to the window. However, the suspicion level will be less if opening of the window follows motion inside the house, which may indicate someone in the house opening the window for fresh air. The highest threat level is taken as the threat level of this particular event, since the event may mean different levels of threat for different areas/situations, and only the highest threat level is considered. The system will monitor the current threat level, and the threat level of the current event will be added to the current threat level, under which the degree of threat to the premises is continuously monitored and assessed. If, at any time, the resultant current threat level exceeds a pre-determined level, then one or more predetermined actions will be taken, e.g. an alarm is triggered and/or lights in the garden are turned on. The current threat level will be reduced by a predetermined percentage after the passing of a pre-set period of time between the events, such that events happening between a long period of time are considered to pose less threat than events happening between very short period of time, say, one happening immediately after the other. As an example, the following Table 1 gives the hypothetical threat level assigned to a list of exemplary events detected by sensors of the security system: TABLE 1 Detected Events Threat Level Motion in the garden 1 Kitchen window opened 2 Kitchen window opened within five (5) 3 minutes of motion in the garden Motion in the kitchen 2 Motion in the kitchen within two (2) minutes 4 of kitchen window opened Motion in the master bedroom 2 Motion in the study where a safe is kept 4 Let us assume that the system is set such that: a. an alarm will be sounded if at any one point, the current threat level reaches at least 10; b. the current threat level will automatically fall by 10% with the passing of every 5 minutes in which no new event is detected by the system. In this example, if motion is detected in the garden, the threat level will be 1. If no event is detected for five minutes, the threat level will fall to 0.9, and subsequently to 0.81 if no event is detected for another five minutes. Assume that within 2 minutes of motion in the garden, the kitchen window is detected as opened, the threat level will be 4 (i.e. 1+3). If, then, within 30 seconds of opening of the kitchen window, motion is detected in the kitchen, the threat level will rise to 8 (i.e. 4+4). If, within, five minutes, motion is detected either the master bedroom or the study where a safe is kept, the threat level will rise to 10 or 12. In either case, an alarm will be sounded. If, however, motion is detected in the master bedroom after, say, 6 minutes, the threat level will only be 9.2 (i.e. 8×90%+2), thus not enough to set off the alarm. If, on the other hand, motion is instead detected in the study where a safe is kept after, say, 10 minutes, the threat level will be 10.48 (i.e. 8×90%×90%+4), in which case the alarm will still be set off. Take another example, if the sequence of events is different, say motion in the study where the safe is kept, followed within five minutes by motion in the kitchen, then followed within five minutes by opening of the kitchen, then followed within five minutes by motion in the garden, the threat level will only be 9, which is not enough to set off the alarm. The advantages and characteristics of such a threat-based security systems include: a. instead of focusing solely on the triggering of the individual devices/sensors, the actual events, which are of more concern to occupants of the premises, are also focused upon; b. an event is made up of a number of device triggering in a particular predetermined order; c. both the triggering of the devices and the sequence order of such triggering are taken into account; and d. the threat levels are continuously monitored and assessed, depending on whether certain events have been recorded, and if so, when that event was recorded. With such an arrangement, each individual event may be categorized in a more intelligent manner, based on the actual degree of threat that it poses. It is, of course, the case that some events are more significant that others. False alarms will be reduced. Security breach events can be distinguished from mere warnings, thus focusing security attention to the actually important incidents. Different response actions can be triggered, depending on the degree of threat, thus ensuring that appropriate actions be taken in response to the relevant incidents. With the above arrangement of an integrated programmable system according to the present invention, the following functions can be achieved: a. identity recognition; b. personalized settings for temperature, lighting, music, audio and/or visual equipment; c. baby and elderly monitoring; d. notification of significant events, e.g. by audio signals; e. hazard detection and warning; f. flexible control and monitoring of the system via touch pads, infrared remote control apparatus, mobile phones, computers or through the Internet; g. integration with popular existing electrical and/or electronic appliance interfaces, e.g. X10, emWare, UPnP/Home API, Jini, HAVi, etc.; h. complete control over lighting of the entire premises, including preset scene lighting, and remote control of lights in another room or area; i. automatic, scheduled or on-demand recording of video and television shows; j. a common timing apparatus-for (1) keeping calendar and schedules for home members; (2) reminders and event tracking; (3) automatic timed/scheduled events based on environmental situations, e.g. sprinklers on only when not raining; (4) playing pre-set messages or execute pre-determined actions at pre-determined time; (5) intelligent alarm clocks, e.g. also turning on the radio to a pre-set station for reporting the weather and traffic condition; k. video surveillance and security monitoring of all windows and doors, with motion/smoke detectors activated; l. intelligent actions upon penetration of security boundary, security triggers or fire threat, e.g. sounding alarms, notifying occupants via telephone or the Internet, or reporting to the police or fire station; m. creating non-repetitive at-home scenes automatically for discouraging break-ins; n. allowing, after identification via remote video, entry of visitors, workmen or deliverymen, and fall video monitoring of their activities in the premises; o. announcement of identity of telephone caller; p. tailored greetings and message boxes for identified telephone callers; q. specific barring or diversion of particular telephone caller(s); r. message box for individual and event play back; s. telephony system being accessed via WAP or normal phone for remote control, message centre access and status monitoring; t. plug-in Internet and World Wide Web access throughout the entire premises; u. remote control, video surveillance and status monitoring via the Internet; and v. intra-premises e-mail services. It can be seen that various existing and future electrical and/or electronic appliances may be integrated into this system because of the use of existing standard interfaces. It is also up to the end user to incorporate new appliances into the system according to his or her own need, taking into account the physical environment of the premises. Since the system can be connected with such appliances via different existing standard interfaces, a large variety of such appliances can be integrated, thus greatly enhancing the ability of the system to accommodate different sorts of appliances of different manufacturers. Simply stated, a system according to the present invention is an open platform with virtually unlimited possibility of extension and modification. It should be understood that the above only illustrates examples whereby the present invention may be carried out, and that various modifications and/or alterations may be made thereto without departing from the spirit of the invention. Although the above examples are illustrated with home-oriented examples, it should of course be understood that the invention is equally applicable to other premises, e.g. offices, factories, hospitals, etc. It should also be understood that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any appropriate sub-combinations.
20041122
20070109
20051103
63726.0
6
POPE, DARYL C
INTEGRATED PROGRAMMABLE SYSTEM FOR CONTROLLING THE OPERATION OF ELECTRICAL AND/OR ELECTRONIC APPLIANCES OF A PREMISES
SMALL
0
ACCEPTED
2,004
10,515,227
ACCEPTED
Solid oxide type fuel cell-use electrode support substrate and production method therefor
Disclosed is an electrode support substrate for a fuel cell which is even, gives a small fluctuation in gas permeability, and is capable of carrying out printing of an anodic electrode with high adhesiveness, and which comprises a ceramic sheet having a porosity of 20 to 50%, a thickness of 0.2 to 3 mm and a surface area of 50 cm2 or more wherein the variation coefficient of measured values of the gas permeable amounts of areas measured by the method according to JIS K 6400 ranges from 5 to 20% and further the surface roughness measured with a laser optical manner three-dimensional shape measuring device may be 1.0 to 40 μm as the maximum roughness depth (Rmax) thereof.
1. A electrode support substrate for solid oxide type fuel cell characterized in comprising a ceramic sheet having a porosity of 20 to 50%, a thickness of 0.2 to 3 mm and a surface area of 50 cm2 or more, and the variation coefficient of measured values of the gas permeable amounts of any area of 4 cm2 selected optionally from the whole of the surface area of the substrate, the values being measured by the method according to JIS K 6400, is from 5 to 20%. 2. The electrode support substrate according to claim 1, wherein a surface roughness thereof measured with a laser optical manner three-dimensional shape measuring device is 1.0 to 40 μm as the maximum roughness depth (Rmax: German Standard “DIN 4768”). 3. The electrode support substrate according to claim 1, wherein height of burrs thereof measured with a laser optical manner three-dimensional shape measuring device is ½ or less of the thickness of the sheet. 4. The electrode support substrate according to claim 1, wherein largest height(s) of undulations and/or projections measured with a laser optical manner three-dimensional shape measuring device is/are ⅓ or less of a thickness of the sheet. 5. A producing process of the electrode support substrate of sheet form for solid oxide type fuel cell according to claim 1 characterized in comprising steps: using a slurry for producing of green sheet becoming a ceramic precursor, including an conductive component powder, an skeleton component powder, a pore-forming agent powder and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. 6. The process according to claim 5, wherein particle size distribution of the slurry has a peak in each of ranges of 0.2 to 2 μm and 3 to 50 μm, and a content ratio by mass of fine particles in the range of 0.2 to 2 μm to coarse particles in the range of 3 to 50 μm is in a range of 20/80 to 90/10. 7. The process according to claim 5 for producing the electrode support substrate for solid oxide type fuel cell comprising the porous ceramic, wherein there is used the slurry including 5 to 30 parts by mass of the binder and 2 to 40 parts by mass of the pore-forming agent powder with respect to 100 parts by mass of the total of the conductive component powder and the skeleton component powder. 8. The process according to claim 5, wherein the green sheet is punched into given shape by use of a punching blade having a waver-form blade edge, and then is fired. 9. The process according to claim 8, wherein the punching blade is used of which the angle (α1), (α2), (θ1) and (θ2) thereof satisfy the following relationship: α1=30 to 120°, 20°≦α2=θ1+θ2≦70°, and θ1≦θ2, the angle (α1) meaning of angle being viewed from the side face of the wave-form blade, the angle (α2) meaning of blade edge angle of the cross section of the blade, the angle (θ1) meaning of angle made between the surface thereof on the side of the sheet becoming a product and a center line (x) passing through the blade edge, the angle (θ2) meaning of angle made between the surface thereof on the side of the rest of the sheet and the center line (x) passing through the blade edge. 10. The electrode support substrate according to claim 2, wherein height of burrs thereof measured with a laser optical manner three-dimensional shape measuring device is ½ or less of the thickness of the sheet. 11. The electrode support substrate according to claim 2, wherein largest height(s) of undulations and/or projections measured with a laser optical manner three-dimensional shape measuring device is/are ⅓ or less of a thickness of the sheet. 12. The electrode support substrate according to claim 3, wherein largest height(s) of undulations and/or projections measured with a laser optical manner three-dimensional shape measuring device is/are ⅓ or less of a thickness of the sheet. 13. A producing process of the electrode support substrate of sheet form for solid oxide type fuel cell according to claim 2 characterized in comprising steps: using a slurry for producing of green sheet becoming a ceramic precursor, including an conductive component powder, an skeleton component powder, a pore-forming agent powder and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. 14. A producing process of the electrode support substrate of sheet form for solid oxide type fuel cell according to claim 3 characterized in comprising steps: using a slurry for producing of green sheet becoming a ceramic precursor, including an conductive component powder, an skeleton component powder, a pore-forming agent powder and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. 15. A producing process of the electrode support substrate of sheet form for solid oxide type fuel cell according to claim 4 characterized in comprising steps: using a slurry for producing of green sheet becoming a ceramic precursor, including an conductive component powder, an skeleton component powder, a pore-forming agent powder and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. 16. The process according to claim 6 for producing the electrode support substrate for solid oxide type fuel cell comprising the porous ceramic, wherein there is used the slurry including 5 to 30 parts by mass of the binder and 2 to 40 parts by mass of the pore-forming agent powder with respect to 100 parts by mass of the total of the conductive component powder and the skeleton component powder. 17. The process according to claim 6, wherein the green sheet is punched into given shape by use of a punching blade having a waver-form blade edge, and then is fired. 18. The process according to claim 7, wherein the green sheet is punched into given shape by use of a punching blade having a waver-form blade edge, and then is fired.
TECHNICAL FIELD The present invention relates to an electrode support substrate for a solid oxide type fuel cell. In particular, the present invention relates to an electrode support substrate for a fuel cell, which is even in the size and the distribution situation of pores all over the surface of the substrate, which is even and good in the permeability/diffusibility of gas and which makes it possible that when an electrode or an electrolyte is formed on a single face of the electrode support substrate by screen printing or the like, the printed electrode or electrolyte is made excellent in evenness and adhesion, and to a useful process for producing the same. In this specification, an electrode support substrate includes an electrode-forming substrate having, on a single face thereof, a formed anodic electrode layer or a solid electrolyte film. The substrate has a function as an anodic electrode in itself and is a support substrate for constituting a cell by forming a solid electrolyte layer and a cathodic electrode layer successively on the support substrate itself. In the present invention, these are referred to as electrode support substrates. BACKGROUND ART In recent years, attention has been paid to fuel cells as clean energy sources. The use purposes thereof are mainly power generation for home use, power generation for business, power generation for automobiles, and others, and researches for improving the cells and making the cells practicable have been rapidly advanced. A typical structure of solid oxide type fuel cells is basically a stack obtained by stacking a large number of cells wherein an anodic electrode is formed on one face side of a planar solid electrolyte self-supporting film and a cathodic electrode is formed on the other face side. In order to make the power generation performance of the fuel cells high, it is effective to make the solid electrolyte self-supporting film dense and thin. This is based on the following reason. The solid electrolyte self-supporting film needs to have denseness for blocking the mixing of a fuel gas which is a power generation source with air surely, and an excellent ionic conductivity capable of suppressing electric conductance loss as much as possible. For this purpose, the film is required to be as thin and dense as possible. Moreover, a large stacking-load is imposed on the solid electrolyte self-supporting film since a fuel cell has a structure wherein a cell having an anodic electrode, a solid electrolyte self-supporting film and a cathodic electrode and a separator for separating and circulating a fuel gas and air are alternately stacked many times. Additionally, the operation temperature thereof is about 700 to 1000° C.; thus, the fuel cells receive considerable thermal stress. Accordingly, the fuel cells are required to have high-level strength and thermal stress resistance. From the viewpoint of such required properties, a ceramic sheet made mainly of zirconia is mainly used as the material of the solid electrolyte self-supporting film for a solid oxide type fuel cell. A cell, wherein anodic and cathodic electrodes are formed on both faces of the sheet by screen printing or the like, is used. The present inventors have been advancing research on such planar solid electrolyte self-supporting films for solid oxide type fuel cells for some time, and the research has been advanced so as to aim to make the thickness as small as possible for the purpose of decreasing ionic conductance loss while keeping physical properties and shape properties resisting stacking-load or thermal stress (preventing cracks based on local stress by decreasing undulations, projections, burrs and others) and, further, so as to aim to make the surface roughness appropriate for the purpose of heightening evenness and adhesion of the printed electrode. Previously, the present inventors suggested techniques disclosed in JP-A 2000-281438, JP-A 2001-89252, JP-A 2001-10866 and others. These techniques made it possible that the solid electrolyte self-supporting film is largely thin and dense, and further the strength which resists stacking-load generated when cells are stacked, the thermal stress resistance, together with the adhesion and evenness of printed electrodes, are largely improved by improving the shape property, that is, decreasing undulations, projections, burrs and others. Subsequently, the present inventors have been advancing research in order to improve the performance of fuel cells. This time, research has been made to aim to modify the property of electrode support substrates for support film type cells instead of the modification of the property of ceramic sheets used as solid electrolyte self-supporting films. This is based on the following reason. Ceramic solid electrolyte self-supporting films are more easily cracked by stacking-load as the films are made thinner; therefore, there is naturally generated a limitation in making the films thin and there is generated a limitation in decreasing in the ionic conductance loss. In order to obtain cells having structure strength suitable for practical use in the case that thin solid electrolyte films are used therein, electrode support substrates are jointed, as supporting members for the cells, in between the cells or their electrodes are caused to have a sufficient thickness. The substrates have electrical conductivity for electric conduction. Furthermore, the substrates are made of porous ceramic material through which a fuel gas that becomes a power generation source, air, or exhaust gas (carbon dioxide, water vapor and others) generated by burning these gases can permeate and diffuse, which is different from the above-mentioned solid electrolyte self-supporting films. In recent years, the following method has also been investigated. A method of forming an anodic electrode on a porous electrode support substrate by screen printing, forming a solid electrolyte film thereon by coating or the like, and further forming a cathodic electrode thereon by screen printing or the like to produce a cell, thereby making the solid electrolyte film still thinner so as to decrease electric conductance loss still more. The most important theme when such a method is realized is that a cell has even and excellent gas permeability/diffusibility throughout its electrode support substrate. This is because this support substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate. Further, the substrate is desired to have an even distribution state of the pores in such a manner that the gas can permeate and diffuse evenly through the whole of the substrate. Another property desired for the electrode support substrate is that a superior printing adaptability is given to the surface thereof so that an electrode wherein the number of defects is as small as possible can be printed. As described above, the electrode support substrate is required to have an appropriate electrical conductivity. Further, the substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate. Thus, numerous openings are present in the surface thereof. Therefore, in order to make superior electrode-printing possible in spite of the presence of such openings, it is indispensable to clarify surface properties peculiar to the porous electrode support substrate since the surface properties prescribed about the above-mentioned dense solid electrolyte film cannot be applied, as they are, to the porous electrode support substrate. Still another property desired for the electrode support substrate is that the shape property of the support substrate itself is improved so that burrs, projections, undulations and others, which become stress-concentrated spots when they receive stacking-load or thermal shock, are made as small as possible. This is based on the following reason. As described above, the electrode support substrate is required to have an appropriate electrical conductivity. Further, the substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate; thus, numerous openings are present in the surface thereof. Therefore, in order to restrain the support substrate, even admitting that the substrate is such a porous sheet, from being cracked or damaged by local stress concentration caused when it receives stacking-load, it is necessary to restrain the generation of burrs, which are formed at its internal and external circumferential edges at the time of punching, and projections or undulations, which may be formed inside the substrate, as much as possible. Furthermore, the electrode support substrate which is intended in the present invention must be a porous body through which a gas can permeate and diffuse. Therefore, the shape property effective for the printability of a dense sheet, such as a solid electrolyte film, and effective for the prevention of stress concentration thereon cannot be applied, as it is, to the electrode support substrate. The present invention has been made, paying attention to a situation as described above. An object thereof is to provide an electrode support substrate to which electrode or a solid electrolyte film may be applied by screen printing. The substrate has the following characteristics. The entire surface of the substrate is stable against a fuel gas and others; the substrate has superior gas permeability/diffusibility. The substrate is able to form a printed electrode and a solid electrolyte film that are even and closely adhesive. The substrate has such a shape property that even if a plurality of the substrates are laminated into a cell stack and each of the substrates receives a large stacking-load, the substrate is not easily cracked or damaged by local stress concentration. DISCLOSURE OF THE INVENTION The subject matter of the electrode support substrate of the present invention for a fuel cell, which has solved the above-mentioned problems, is that the substrate comprises a ceramic sheet having a porosity of 20 to 50%, a thickness of 0.2 to 3 mm and a surface area of 50 cm2 or more, and the variation coefficient of measured values of the gas permeable amounts of any area of 4 cm2 selected optionally from the whole of the surface area of substrate, the values being measured by the method according to JIS K 6400, is from 5 to 20%. The electrode support substrate of the present invention for a fuel cell preferably satisfies the following as a requirement for obtaining superior adhesion and evenness when an anodic electrode and so on are printed and formed on the surface of substrate, as well as the above-mentioned requirement: the surface roughness measured with a laser optical manner three-dimensional shape measuring device is 1.0 to 40 μm as the maximum roughness depth (Rmax: German Standard “DIN 4768”) thereof. Furthermore, the electrode support substrate of the present invention for a solid oxide type fuel cell is used in a multi-layered and laminated state, as described above; therefore, in order to suppress cracking or breaking based on stacking-load as much as possible when the substrate is used, it is desired that height of burrs measured with the laser optical manner three-dimensional shape measuring device is ½ or less of the thickness of the sheet. Further, it is desired that largest height(s) of undulations and/or projections measured with the same laser optical manner three-dimensional shape measuring device is/are ⅓ or less of the thickness of the sheet. The producing process of the present invention is placed as a producing process making it possible to obtain surely an electrode support substrate for a fuel cell, in particular, an electrode support substrate for a fuel cell which satisfies the above-mentioned properties. Above process has a feature in: using, as a slurry for producing a green sheet which becomes a ceramic precursor, a slurry which comprises an conductive component powder, an skeleton component powder, a pore-forming agent powder, and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. When the producing process is carried out, it is desired to use, as the slurry for producing the green sheet, a slurry wherein its particle size distribution has a peak in each of ranges of 0.2 to 2 μm and 3 to 50 μm and the content ratio by mass of fine particles in the range of 0.2 to 2 μm to coarse particles in the range of 3 to 50 μm is in a range of 20/80 to 90/10. Further, it is preferred to use a slurry containing 5 to 30 parts by mass of the binder and 2 to 40 parts by mass of the pore-forming agent powder with respect to 100 parts by mass of the total of the conductive component powder and the skeleton component powder. In order to obtain the electrode support substrate satisfying the above-mentioned preferred height of burr and preferred height of undulation and/or projection, which is intended in the present invention, it is desired that when the green sheet is punched into a shape used as product, a punching blade having a waver-form blade edge is used. It is more preferred to use the punching blade which the angle (α1), (α2), (θ1) and (θ2) thereof satisfy the following relationship: α1=30 to 120°, 20°≦α2=θ1+θ2≦70°, and θ1≦θ2, the angle (α1) meaning of angle being viewed from the side face of the wave-form blade, the angle (α2) meaning of blade edge angle of the cross section of the blade, the angle (θ1) meaning of angle made between the surface thereof on the side of the sheet becoming a product and a center line (x) passing through the blade edge, the angle (θ2) meaning of angle made between the surface thereof on the side of the rest of the sheet and the center line (x) passing through the blade edge. According to this, height of undulations and/or projections and/or burrs can be favorably suppressed into as low a value as possible. BRIEF DESCRIPTION OF THE INVENTION FIG. 1 is a frequency graph illustrating a preferred particle size distribution of a slurry, for producing a green body, which is preferably used upon producing an electrode support substrate for a fuel cell according to the present invention; FIG. 2 is an explanatory sectional view illustrating the shape of a burr formed on an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device; FIG. 3 is an explanatory enlarged view illustrating a projection which may be generated in the surface of an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device; and FIG. 4 is an explanatory view illustrating an undulation which may be generated in the whole of an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device. FIG. 5 is a view showing an example of the particle size distribution of a slurry which is preferably used upon producing a green body which becomes a precursor of an electrode substrate according to the present invention; FIG. 6 is an explanatory side view illustrating the blade edge shape of a preferred punching blade used to punch a green sheet upon producing an electrode substrate for a fuel cell according to the present invention; FIG. 7 is an explanatory sectional view illustrating the blade edge shape of a preferred punching blade used to punch a green sheet upon producing an electrode substrate for a fuel cell according to the present invention; FIG. 8 is an explanatory sectional view illustrating a preferred example expect FIG. 7 of a punching blade used in the present invention; FIG. 9 is an explanatory schematic sectional view showing the structure of a punching machine adopted preferably in the present invention and a punching work example; FIG. 10 is an explanatory schematic sectional view showing the structure of the punching machine adopted preferably in the present invention and the punching work example; FIG. 11 is an explanatory schematic sectional view showing the structure of the punching machine adopted preferably in the present invention and the punching work example; and FIG. 12 is an explanatory view showing an outline of a gas permeation resistance measuring device used in examples of the present invention. 1: blade edge portion, h: height of blade, p: pitch of blade edge, t: thickness of blade, and α1, α2, θ1 and θ2: angle of blade edge BEST MODE FOR CARRYING OUT THE INVENTION The present inventors have been advancing research for providing an electrode support substrate which can surely obtain a printed electrode that is particularly dense, even and closely adhesive while gas permeability/diffusibility necessary for a practical electrode support substrate is kept under the above-mentioned themes to be solved. As a result, it has been found out that a ceramic sheet having a porosity of 20 to 50%, a thickness of 0.2 to 3 mm and a surface area of 50 cm2 or more, as a ceramic constituting a substrate. The substrate satisfies the following: the variation coefficient of measured values of the gas permeable amounts of any areas of 4 cm2 selected optionally from the whole of the surface area, the values being measured by the method according to JIS K 6400, is from 5 to 20% is substantially even in the state of pore distribution throughout the substrate for supporting an electrode, and can exhibit stable and superior gas permeability/diffusibility. The electrode support substrate of the present invention is essentially a porous substrate having electrical conductivity, superior thermal shock resistance and mechanical strength and further having sufficient gas permeability/diffusibility, as described above. The specific structure of the electrode support substrate which can satisfy these requirements will be described in detail hereinafter. The electrode support substrate comprises, as main constituting materials, a conductive component for giving electrical conductivity, and a ceramic material which becomes a skeleton component of a substrate. The conductive component is a component essential for giving electrical conductivity to the substrate. Examples of the component which becomes a component of an anodic electrode support substrate include metals oxides which are changed to conductive metals under reducing atmosphere when the fuel cell operates, such as iron oxide, nickel oxide and cobalt oxide; metal oxides which exhibit electrical conductivity in reducing atmosphere, such as ceria, yttria-doped ceria, samaria-doped ceria, prasea-doped ceria, and gadolia-doped ceria; and noble metals which exhibit electrical conductivity, such as platinum, palladium, and ruthenium. These may be used alone, or may be used in combination of two or more which are appropriately selected therefrom if necessary. Of these conductive components, nickel oxide has the highest wide-usability, considering cost or electrical conductive characteristics. The skeleton component is a component important for keeping strength necessary for an electrode support substrate, in particular, strength which resists thermal shock and stacking-load and further important for relieving difference in thermal expansion from the solid electrolyte. In the case that the solid electrolyte is zirconia, a single material or a composite material from zirconia, alumina, magnesia, titania, aluminum nitride, mullite and others are used. Of these, stabilized zirconia has the highest wide-usability. Preferred examples of the stabilized zirconia include solid solutions obtained by dissolving, into zirconia, one or more oxides selected from the following as a stabilizer or stabilizers: oxides of alkaline earth metals, such as MgO, CaO, SrO and BaO; oxides of rear earth elements, such as Y2O3, La2O3, CeO2, Pr2O3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb2O3, Dy2O3, Er2O3, Tm2O3, and Yb2O3; and Sc2O3, Bi2O3, and In2O3. Additional preferred examples include dispersion strengthened zirconia wherein a dispersing strengthening agent such as alumina, titania, Ta2O5 or Nb2O5 is added to the above-mentioned solid solutions. There can also be used a ceria based or bismuth based ceramic wherein one or more of the following are added to CeO2 or Bi2O3: CaO, SrO, BaO, Y2O3, La2O3, Ce2O3, Pr2O3, Nb2O3, Sm2O3, Eu2O3, Gd2O3, Tb2O3, Dr2O3, Ho2O3, Er2O3, Yb2O3, PbO, WO3, MoO3, V2O5, Ta2O5 and Nb2O5; or a gallate based ceramic such as LaGaO3. Of these, particularly preferable are zirconia stabilized with 2.5 to 12% by mole of yttria, or zirconia stabilized with 3 to 15% by mole of scandia. The content blend between the conductive component and the skeleton component is important for giving appropriate electrical conductivity and strength property to the resultant electrode support substrate. When the amount of the conductive component becomes relatively large, the electrical conductivity of the substrate is improved but the strength property lowers since the amount of the skeleton component becomes relatively small. Conversely, when the amount of the conductive component becomes relatively small, the strength property becomes high because of an increase in the amount of the skeleton component. Thus, the blend ratio between the two should be appropriately decided under the consideration of the balance between the above-mentioned matters. The ratio is changed on the basis of the kind of the conductive component, and others, but it is preferable in the present invention, which mainly aims at an anodic electrode support substrate, that the ratio of the skeleton component amount to the conductive component amount is in the range of 60-20 to 40-80% by mass, more generally 50-30 to 50-70% by mass. The electrode support substrate of the present invention comprises a conductive component and a skeleton component, as described above. The mechanical strength and thermal stress resistance thereof are kept by the skeleton component, and electrical conductivity is given to the substrate by the conductive component. The electrode support substrate, which is made of them, needs to have pores through which a fuel gas or a burning exhaust gas permeates or diffuses, as described above. In order to pass these gases smoothly under low pressure loss, it is indispensable that the substrate has a porosity of 20% or more as a whole under oxidizing atmosphere. If the porosity is less than 20%, the gases permeate or diffuse insufficiently so that the efficiency of power generation falls. The porosity is more preferably 25% or more, even more preferably 30% or more. However, if the porosity is too large, the strength property and thermal stress resistance of the substrate lower so that the following tendencies are generated: when the substrate is integrated into a stack, the substrate is easily cracked or deteriorated by staking-load, thermal shock or the like; or the distribution state of the conductive component becomes thin so that the substrate has an insufficient electrical conductivity. Therefore, it is advisable that the porosity is restrained into 50% or less at highest, preferably 45% or less, more preferably 40% or less. It is indispensable that the thickness of the electrode support substrate of the present invention is in the range of 0.2 to 3 mm. If the thickness is less than 0.2 mm, the substrate is too thin so that the substrate does not easily keep strength for a practical electrode support substrate. On the other hand, if the substrate is made excessively thick to make the thickness into more than 3 mm, the strength is improved but when a large number of the electrode support substrates are laminated to be made practicable as a cell stack, the whole of the laminated structure becomes thick. The structure is not easily suitable for a desire that the structure is made compact as a power generator. When the electrode support substrate is made practicable as a substrate for a fuel cell, the thickness thereof is more preferably 0.3 mm or more and 2 mm or less. The size of the electrode support substrate according to the present invention, which depends on the use purpose or scale thereof, is important for ensuring electric power generation at a level satisfactory for practical use. For this purpose, the substrate should ensure a necessary and minimum surface area. It is desired that the substrate ensures a sheet area (surface area on a single side thereof) of 50 cm2 or more, more preferably 100 cm2 or more. It is essential that the electrode support substrate satisfies the following: under the conditions that the above-mentioned porosity, thickness and surface area are satisfied, the above-mentioned variation coefficient of the measured values of the gas permeable amounts of any plural areas of 4 cm2 selected optionally from the whole of the surface area of the substrate ranges from 5 to 20%, and the substrate exhibits substantially even gas permeability/diffusibility as a whole. In order to pass a fuel gas or a reaction-produced gas rapidly into the electrode support substrate, it is naturally preferred that the whole of the substrate has even gas permeability/diffusibility as a whole. For this purpose, it is desired that the distribution state of pores throughout the substrate is even. However, only by measuring the porosity of the whole, it is impossible to specify whether the pores are pores continuing to the inside of the substrate or pores which are closed inside the substrate. Thus, the porosity may be insufficient as information on permeability. Permeability is an important factor as a physical property of any electrode support substrate. The permeability thereof has been repeatedly investigated, so as to find out: when the gas permeable amounts of any specified areas in the entire surface area of a substrate fluctuate, a fuel gas is unevenly distributed in the entire surface of the substrate to generate locally regions where electric power generation is large and regions where electric power generation is small, so that a temperature distribution is generated to cause the generation of a crack in the substrate; and the specification of the fluctuation causes the electrode support substrate to exhibit excellent property for a practical electrode support substrate. The size of any electrode support substrate for a solid oxide type fuel cell is expected to be from about 50 to 1000 cm2, more generally about 100 to 500 cm2 for practical use. Therefore, a standard for checking the evenness of the distribution state of pores throughout the substrate has been defined as 4 cm2, which is {fraction (1/10)} or less of the minimum area 50 cm2 of the substrate, considering the minimum area. In the case that the area to be measured is made smaller, the distribution state of the pores throughout the substrate can be observed. Thus, this case is preferred. However, even if an area having each side of 1.5 cm length (area: 2.25 cm2) was measured, a significant different between the measurement results and the measurement results about 4 cm2 was not recognized. In the measurement of the gas permeability distribution, it is preferable that at least five spots are selected optionally from the entire surface of a supplied substrate and then the gas permeable amounts thereof are measured. In the present invention, the variation coefficient of measured values of the gas permeable amounts obtained by this method is specified as 5 to 20%. Any one of the gas permeable amounts is a value measured according to gas permeable amount measuring method of JIS K 6400 (1997) about soft urethane foam testing methods. Specifically, a stationary flow differential pressure measuring method is adopted which comprises cutting a substrate into a piece 3 cm square (area: 9 cm2) with a diamond cutter, reducing the pressure on a single surface side (low pressure side) of this test piece, introducing air onto the other surface side thereof, and measuring the gas permeable amount by an increase in the pressure on the low pressure side. Both ends of the test piece are used by 0.5 cm, respectively, to hold the test piece, thereby yielding an effective gas permeable area of 4 cm2. As the resultant gas permeable amount data of the supplied substrate, the variation coefficient is used which is obtained by obtaining the standard deviation for representing the fluctuation or scattering of measured values of the gas permeable amount relatively, and then dividing it by the average thereof. In the present invention, the variation coefficient is specified as 5 to 20%, more preferably 5 to 15%, even more preferably 5 to 13%. For reference, if the variation coefficient exceeds 20%, the substrate is cracked or broken in almost all cases. It appears that this is based on the following reason: when a fuel gas permeates through the inside of the substrate, the gas cannot pass evenly to be unevenly distributed so that the fuel gas reaching the vicinity of the electrolyte becomes uneven dependently on spots; consequently, regions where electric power generation is large and regions where this is small can be locally generated so that a temperature distribution is generated. If the gas permeable amount in the substrate is completely constant over the entire surface thereof, the variation coefficient is 0%. However, the variation coefficient obtained by the above-mentioned method is 5% at lowest; therefore, this is decided as the lower limit for practical use. In the present invention, it is desired that the distribution state of the pores throughout the substrate is even and further it is preferable that the size of the pores is 3 μm or more and 20 μm or less as the average diameter thereof. If the average diameter of the pores is less than 3 μm, the gas permeability/diffusibility are insufficient so that the same problems as in the case that the porosity is insufficient may be caused. Conversely, if the average diameter is too large, the strength tends to deteriorate and the electrical conductivity tends to be insufficient in the same manner as in the case that the porosity is excessive. Therefore, it is preferable to suppress the diameter into 20 μm or less. The porosity of the substrate, the variation coefficient of measured values of the gas permeable amounts, and the preferable average diameter of the pores can be adjusted by the kind and the blend amount of a pore-forming agent used when the substrate is produced, the particle size construction of starting material powder, the temperature at the time of firing a green sheet which will become a substrate precursor, and others. Specific methods thereof will be described later. As described, an anodic electrode or an electrolyte layer is formed on a single surface of the electrode support substrate of the present invention by screen printing or the like. In order to make the electrode or electrolyte printing even and sure with close adhesion, it is necessary to control the surface thereof into an appropriate surface roughness. The present inventors have made it evident by experiments that the maximum roughness depth (Rmax: German Standard “DIN 4768”) thereof is set to 1.0 μm or more and 40 μm or less. Furthermore, in the electrode support substrate of the invention, which is porous in order to ensure the gas permeability/diffusibility thereof, whether the surface property is good or bad cannot be precisely estimated according to the surface roughness obtained by using a contact type surface roughness meter which is generally adopted for dense sheets. Thus, it is desired that the surface is made to satisfy the above-mentioned Rmax on the basis of the surface roughness measured with a laser optical manner three-dimensional shape measuring device. If the Rmax is less than 1.0 μm, the surface is too smooth so that the electrode printing tends to be insufficient in close adhesion. Thus, it is feared that the printed electrode layer is peeled from the substrate by thermal shock receiving when the fuel cell is handled or operated. Additionally, the gas permeability/diffusibility tend to turn insufficient. On the other hand, if the Rmax exceeds 40 μm, the thickness of the electrode layer becomes uneven when the electrode is printed, or a part of the electrode-constituting material is embedded in concave portions in the surface. Thus irregularities are formed in the electrode layer surface to result in an increase in electric conductance loss. Furthermore, a crack may be generated in the electrode layer when the electrode-constituting material is fired or the resultant cell is used as a fuel cell. In order to decrease the electric conductance loss as much as possible and heighten the close adhesion of the printed electrode layer, the Rmax is more preferably 0.2 μm or more and 30 μm or less, even more preferably 20 μm or less. The reason why the laser optical manner three-dimensional shape measuring device, which is of a non-contact type, is used in the present invention to evaluate the surface roughness is based on the following. In the case of the electrode support substrate of the invention, which is porous and has a surface on which innumerable pores are opened, the surface roughness is not smoothly and easy measured with any surface roughness meter of a contact type, such as a stylus type, since the stylus is caught by the pores; moreover, the surface roughness cannot be precisely measured in the contact manner since the pores opened in the surface are relatively deep. At any rate, in the present invention, the variation coefficient of measured values of the gas permeable amounts, which is obtained by the above-mentioned method, is from 5 to 20%, and further the maximum roughness depth (Rmax) is preferably made into an appropriate range. Thereby make it possible to print an electrode on surface of substrate, substrate is porous and have even in thickness, which has even gas permeability/diffusibility in the entire surface thereof not to cause any uneven gas flow or any extreme temperature distribution when the electrode is operated, and which has a highly close adhesion. In order to ensure such evenness of the gas permeability/diffusibility and an appropriate surface roughness, it is necessary to control properly the particle size construction of starting material powder used to produce a green sheet which will become a precursor of the ceramic which constitutes the electrode support substrate, conditions for producing or firing the green sheet, and others. These will be described later. Since a large number of the electrode support substrates of the invention are laminated in the upper and lower directions so as to be integrated into a stack as described above, the stack is subjected to a large stacking-load and further receives thermal shock or thermal stress based on heat generated when the stack is operated. Therefore, even if a slight number of burrs or projections are present on the lamination faces, stress is concentrated on the portions thereof so that cracking or breaking may be caused. When such cracking or breaking is generated in the substrates, the cracking spreads to the anodic electrodes and others formed on the surfaces so that the electrical conductivity thereof is blocked. If the cracking or breaking spreads to the solid electrolyte film, the effect of shielding the fuel gas and others is lost so that the stack comes not to act as a fuel cell. If the burrs, projections or undulations on the substrate surface(s) become large, the anodic layers and the solid electrolyte layer(s) formed on the surfaces become uneven and further the adhesion of the layers to the substrates becomes poor. It is therefore desired that the burrs generated to the circumferential edges of the substrates are made as small as possible and further the projections or undulations on the substrate surfaces are preferably made as small as possible, thereby restraining local stress concentration generated in the lamination state into as small a value as possible. The present inventors has made it evident by experiments that: a substrate sheet wherein height of burrs in the circumferential edge thereof, measured with a laser optical manner three-dimensional shape measuring device, is ½ or less of the thickness of the sheet, the height of the largest projection measured with the same laser optical manner three-dimensional shape, measuring device, is preferably ⅓ or less of the sheet thickness, and the height of the largest undulation, measured with the same laser optical manner three-dimensional shape measuring device, is ⅓ or less of the sheet thickness. The substrate sheet exhibit stable and have superior resistance against stacking-load, thermal shock resistance, and thermal stress resistance. Further the substrate sheet can have superior performance about printing adaptability when an electrode is formed or a solid electrolyte film is formed thereon. If the height of the burrs in the substrate circumferential edge exceeds ½ of the sheet thickness, at the time of using this substrate as one element and integrating the substrate into a stack, stress based on integrating force or stacking-load is concentrated onto the large burr. Consequently, before the stack is operated as a fuel cell, the substrate is broken or cracked together with the electrode layers or solid electrolyte films thereon. Alternatively, the stress-concentrated portions are cracked or broken by receiving thermal hysteresis when the stack is operated even if cracks and others are not generated at the time of the integration. Thus, the power generation performance of the fuel cell is remarkably decreased. However, it has been made evident that: a substrate wherein the burr height is ½ or less of the sheet thickness, more preferably ⅓ or less thereof, even more preferably ¼ or less thereof is hardly cracked or broken even if the substrate receives stacking-load or thermal stress at a practical level; and this substrate can use as substrate for a fuel cell which can maintain a given power-generating performance for a long term. The burr height in the present invention means the difference between the highest portion and the lowest portion in a section in a perpendicular line direction from the external circumferential (or internal circumferential) edge of a cut face of a substrate, and can be obtained with a laser optical manner three-dimensional shape measuring device, which is of a non-contact type, as illustrated, for example, in FIG. 1. At any rate, when the burr height obtained by the above-mentioned method is restrained into ½ or less of the sheet thickness in the present invention, local stress concentration based on load or thermal shock in the laminated state is suppressed into a minimum so that the generation of cracking or breaking can be suppressed into a minimum. In order to obtain such a surface roughness, it is important to contrive a blade shape when a green sheet which becomes a ceramic precursor constituting the electrode substrate is subjected to punching work. This will be described later. In the present invention, it is desired to make the height of the largest projection or the largest undulation on the substrate surface, besides the burr height, as small as possible. The standard thereof is as follows: in order to restrain stress concentration when stacking-load is received and restrain cracking or breaking similarly and further make even an electrode layer or a solid electrolyte film formed on the electrode surface, the largest projection height, measured with the same laser optical manner three-dimensional shape measuring device, is desirably set to ⅓ or less of the sheet thickness, more preferably ¼ or less thereof, even more preferably ⅕ or less thereof and the largest undulation height is desirably set to ⅓ or less of the sheet thickness, more preferably ¼ or less thereof, even more preferably ⅕ or less. The projections mean convex portions which are basically independently generated on the surface of the electrode sheet and have a diameter of about 2 to 15 mm (more generally 5 to 10 mm), for example, as illustrated in FIG. 2, and the undulations mean distortion which is easily generated on the electrode sheet, in particular, a circumferential edge portion thereof and which is continuous into a wave form, for example, as illustrated in FIG. 3. These can be obtained by radiating a laser ray onto the surface of the sheet and analyzing the light reflected thereon three-dimensionally. The shape of the ceramic sheet which constitutes the electrode support substrate of the present invention may be any shape, such as a circle, ellipse, rectangle, or rectangle having a roundish corner, and may be a shape wherein such a sheet has therein one or more holes which have a shape of a similar circle, ellipse, rectangle or rectangle having a roundish corner, or some other shape. The area of the sheet is not particularly limited, and is generally 50 cm2 or more, more preferably 100 cm2 or more, even more preferably 200 cm2 or more under the consideration of practical use. When the holes are present in the sheet, this area means the total area including the area of the holes. The following describes a process for producing an electrode support substrate according to the present invention. About the electrode support substrate of the present invention, a powder made of a metal or metal oxide which becomes the above-mentioned conductive component, a metal oxide powder which becomes the skeleton component, and a pore-forming agent powder blended for making pores are homogeneously mixed with an organic or inorganic binder, a dispersing medium (solvent), an optional dispersing agent, an optional plasticizer and others in the same method as described above, so as to prepare a paste. The resultant paste is applied onto a flat and smooth sheet (such as a polyester sheet) by any method such as a doctor blade method, a calendar roll method or an extruding method, so as to have an appropriate thickness. The resultant is dried to volatilize and remove the dispersing medium (solvent), thereby yielding a green sheet. The pore-forming agent used herein may be an agent of any kind if the agent is burned up under the above-mentioned firing conditions. The following is used: a natural organic powder such as wheal powder, corn starch, sweet potato powder, potato powder or tapioca powder, a crosslinked fine particle aggregate made of (meth)acrylic resin or the like, a thermally-decomposing or sublimating resin powder of melamine cyanurate, or a carbonous powder such as carbon black or activated carbon Of these, preferable are corn starch, the acrylic crosslinked fine particle aggregate, carbon black and so on since they can carry and contain a large amount of the conductive component as described later. The shape of these pore-forming agent powders is desirably a spherical shape or a rugby ball shape in order to cause a large amount of the conductive component to be carried and contained therein and promote an even distribution of the conductive component into the ceramic substrate obtained by firing. Preferably, the powder or fine particle aggregate itself has pores or capillaries so as to cause the conductive component to be contained in the powder or the fine particle aggregate. A preferable particle size of the powder or the crosslinked fine particle aggregate which become the pore-forming agent is 0.5 to 100 μm, more preferably 3 to 50 μm as the average particle size thereof measured with a laser diffraction type particle size distribution meter (trade name: “SALD-1100”, manufactured by Shimadzu Corp.), and is 0.1 to 10 μm, more preferably 1 to 5 μm as the 10% by volume diameter thereof. Particularly preferable is a fine particle aggregate of 0.5 to 100 μm average particle size, wherein crosslinked polymer fine particles of 0.01 to 30 μm average particle size aggregate with each other, the fine particle aggregate being obtained by emulsion-polymerizing a (meth)acrylic monomer, as disclosed in, for example, JP-A 2000-53720. In the present invention, the pore-forming agent may be mixed with each of the above-mentioned starting powders to prepare slurries for forming the green sheet. It is however effective to mix or compound the pore-forming agent and the above-mentioned conductive component and subsequently mix the resultant with the other staring materials. That is, the following method can be adopted: (1) a method of blending the conductive component powder or a precursor compound thereof with the pore-forming agent at a given ratio, and wet-mixing or dry-mixing the blended components, thereby sticking the conductive powder or the precursor compound evenly onto the surface of the pore-forming powder, (2) a method of sticking the conductive component powder or a precursor compound evenly onto the surface of the pore-forming agent by a spray method or the like, and (3) a method of incorporating the conductive component powder or a precursor compound thereof into pores or gaps in a fine particle aggregate for forming pores. More specifically, it is possible to modify a method as disclosed in JP-A 07-22032 (1995) and adopt a method of mixing the pore-forming agent powder with a precursor compound which can generate an conductive component by thermal decomposition, and volatilizing the solvent while dry-pulverizing the mixture in a mill or the like, or volatilizing the solvent while wet-pulverizing the mixture, or some other method. It is preferable to adopt a method as disclosed in JP-A 2000-53720 or JP-A 2001-81263 or some other method. It is emulsion-polymerized a (meth)acrylic polymerizable monomer mixture to produce a fine particle aggregate of 0.5 to 100 μm average particle size wherein crosslinked polymer fine particles of 0.01 to 30 μm average particle size adhere to each other. The fine particle aggregate mix with a precursor compound which can generate an conductive component by thermal decomposition, causing these to enter gaps in the fine particle aggregate, and then drying the resultant to volatilize and remove the solvent. When the pore-forming agent into which the conductive component is incorporated is used in this way, the following advantageous effects can be obtained: the pore-forming agent is burned up when the green sheet is fired, so that pores are made in the portions thereof when the conductive component is also present in the portions, the pores are present near the conductive component after the firing; and even if the conductive component is oxidized to undergo volume expansion at the time of making the substrate practicable as an electrode support substrate for a fuel cell, the above-mentioned pore portions absorb strain generated by the volume expansion so that the generation of breaking or cracking, which may easily be caused in the electrode support substrate, is prevented. As a result, in particular, the thermal shock resistance and the thermal stress resistance of the electrode support substrate can be made high. The pore-forming agent is an important component, which is burned up at the time of the heating and firing as described above so as to give gas permeability/diffusibility to the electrode support substrate. In order to ensure a porosity of 20% or more and 50% or less, which is desired for the porous body in the present invention, it is desired that the blend amount of the pore-forming agent is set to 2 parts or more and 40 parts or less, more preferably 5 parts or more and 30 parts or less by mass for 100 parts by mass of the total of the conductive component powder and the skeleton component powder. If the blend amount of the pore-forming agent is insufficient, pores made by thermal decomposition when the green sheet is heated and fired tend to be short so that an electrode support substrate having satisfactory gas permeability/diffusibility is not easily obtained. Conversely, if the blend amount of the pore-forming agent is too large, the number of the pores made at the time of the heating and firing becomes excessively large so that the sintered product becomes sufficient in strength and further a flat substrate is not easily obtained. In this case, it is possible to advance the sintering and lower the porosity by making the sintering temperature high or extending the sintering time. However, this is not economical since a long time is required for the sintering and further energy consumption also increases to a large extent. The kind of the binder used in the production of the green sheet is not particularly limited, and a binder selected appropriately from organic binders which have been known hitherto can be used. Examples of the organic binders include ethylene type copolymer, styrene type copolymer, acrylate or methacrylate type copolymer, vinyl acetate type copolymer, maleic acid type copolymer, vinyl butyral type resin, vinyl alcohol type resin, waxes, and ethyl celluloses. Of these, the following examples are given from the viewpoints of the formability into a green sheet, punchability, strength, thermal decomposability when they are fired, and others: polymers obtained by polymerizing or copolymerizing at least one of alkyl acrylates having an alkyl group having 10 or less carbon atoms, such as methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, isobutyl acrylate, cyclohexyl acrylate, and 2-ethylhexyl acrylate; alkyl methacrylates having an alkyl group having 20 or less carbon atoms, such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, octyl methacrylate, 2-ethylhexyl methacrylate, decyl methacrylate, dodecyl methacrylate, lauryl methacrylate, and cyclohexyl methacrylate; acrylates or methacrylates having a hydroxyalkyl group, such as hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxy methacrylate, and hydroxypropyl methacrylate; aminoalkyl acrylates or aminoalkyl methacrylates, such as dimethylaminoethyl acrylate, and dimethylaminoethyl methacrylate; carboxyl-containing monomers, such as acrylic acid, methacrylic acid, maleic acid, and monoisopropyl maleate. These may be used alone. Alternatively, if necessary, these may be used in an appropriate combination of two or more thereof. Of these, particularly preferable are acrylate or methacrylate type copolymers having a number-average molecular weight of 5,000 to 200,000, more preferably 10,000 to 100,000. Of these, the following is recommendable as preferred one: copolymer comprising, as a monomer component, isobutyl methacrylate and/or 2-ethylhexyl methacrylate in an amount of 60% or more by mass. About the use ratio between the starting powders (the total of the conductive component, the skeleton component, and the pore-forming agent) and the binder, the amount of the latter is 5 parts or more and 30 parts or less, more preferably 10 parts or more and 20 parts or less by mass for 100 parts by mass of the former. If the used amount of the binder is short, the strength or the flexibility of the green sheet becomes insufficient. Conversely, if the amount is too large, the viscosity of the slurry is not easily adjusted and further the binder component is actively decomposed or released into a large amount when the green sheet is fired. Thus, the surface property of the green sheet does not become even with ease. As the dispersing medium used in the production of the green sheet, the following is appropriately selected and used: an alcohols such as methanol, ethanol, 2-propanol, 1-butanol, 1-hexanol or 1-hexanol; a ketone such as acetone or 2-butanone; an aliphatic hydrocarbons such as pentane, hexane, or heptane; an aromatic hydrocarbons such as benzene, toluene, xylene, or ethylbenzene; an acetates such as methyl acetate, ethyl acetate, or butyl acetate; or the like. These dispersing medium may be used alone. Alternatively, if necessary, these may be used in an appropriate combination of two or more thereof. The most ordinary ones of these dispersing medium are 2-propanol, toluene, ethyl acetate and so on. In the preparation of the slurry for producing the green sheet, the pore-forming agent powder into which the above-mentioned conductive component powder or a precursor compound thereof is incorporated, the skeleton powder, and an conductive component powder which may be optionally replenished are homogeneously mixed with the binder, the dispersing medium, an optional dispersing agent for promoting the dissociation or dispersion of the starting powders, an optional plasticizer and others, so as to prepare the slurry in a homogeneous dispersion state. As the dispersing agent used therein, the following is used: a polymer electrolyte such as polyacrylic acid or polyacrylic ammonium; an organic acid such as citric acid or tartaric acid; a copolymer made from isobutylene and styrene or maleic anhydride, or an ammonium salt or amine salt thereof; a copolymer made from butadiene and maleic anhydride. The plasticizer has an effect of making the flexibility of the green sheet high, and specific examples thereof include phthalates such as dibutyl phthalate and dioctyl phthalate; and glycols such as propylene glycol and glycol esters. The starting powder which becomes the skeleton of the electrode support substrate according to the invention is preferably one wherein the average particle size is 0.1 μm or more and 3 μm or less and the particle size of the 90% volume thereof is 6 μm or less; more preferably one wherein the average particle size is 0.1 μm or more and 1.5 μm or less and the particle size of the 90% volume is 3 μm or less; and even more preferably one wherein the average particle size is 0.2 μm or more and 1 μm or less and the particle size of the 90% volume is 2 μm or less. The powder used as the starting material of the conductive component is preferably one wherein the average particle size is 0.6 μm or more and 15 μm or less and the particle size of the 90% volume is 30 μm or less; more preferably one wherein the average particle size is 0.6 μm or more and 3 μm or less and the particle size of the 90% volume is 20 μm or less; and even more preferably one wherein the average particle size is 0.6 μm or more and 1.5 μm or less and the particle size of the 90% volume is 10 μm or less. In particular, in the case that nickel oxide powder is used as the constituent material of the conductive component, it is preferable to use a powder wherein the particle size of the 90% volume is 6 μm or less, more preferably 3 μm or less and the amount of contained coarse particles is made as small as possible. In the case that a powder wherein the average particle size exceeds 3 μm and the particle size of the 90% volume exceeds 6 μm is used as the starting powder which constitutes the skeleton component and further a powder wherein the average particle size exceeds 15 μm and the particle size of the 90% volume exceeds 30 μm is used as the starting powder which becomes the constituent material of the conductive component, desired thermal shock resistance and mechanical strength are not easily obtained since the green sheet is pre-fired to be made porous and further gaps between the particles become pores. On the other hand, in the case that a powder wherein the average particle size is less than 0.1 μm is used as the constituent material of the skeleton component and further a powder wherein the average particle size is less than 0.6 μm is used as the constituent material of the conductive component, pores in the sintered body becomes too small even if the pore-forming agent is used together. As a result, the gas permeability/diffusibility thereof is liable to become insufficient. However, in order to obtain surely an electrode support substrate satisfying an appropriate surface roughness, that is, the requirement that the maximum roughness depth (Rmax) is 1.0 μm or more and 40 μm or less as the surface roughness measured with a laser optical manner three-dimensional shape measuring device while the variation coefficient of measured values of the gas permeable amounts is kept into the range of 5 to 20%, which is the most important in the invention, it is desired to adopt a process of: using a slurry for producing of green sheet becoming a ceramic precursor, including an conductive component powder, an skeleton component powder, a pore-forming agent powder and a binder, defoamed under reduced pressure after milling to adjust the viscosity thereof to 40 to 100 poise (25° C.), and kept at room temperature while rotating stirring fans therein at a rotating speed of 5 to 30 rpm for 20 to 50 hours; fashioning the slurry into a sheet by a doctor blade method to obtain a green sheet; cutting the green sheet into a given shape; and then firing the green sheet having the given shape. This is based on the following reason. When this process is adopted, air bubbles present in the slurry adjusted into the given viscosity are effectively removed so that air bubbles remaining in the slurry, in particular, fine air bubbles having a level of 1 μm can be reduced as much as possible. Further the pore-forming agent powder, which is thermally decomposed at the time of the firing so as to make pores in the substrate, can be more evenly dispersed into the slurry. Thereby it makes the distribution of air permeability in the substrate plane slight. Moreover, the effect of ripening the slurry is also obtained with ease so that the slurry can be made more stable. It is advisable to adjust the viscosity of the slurry into 40 to 100 poise (25° C.). If the viscosity is less than 40 poise, the fluidity of the slurry is too high so that a substrate having a thickness of 1 mm or more, in particular 2 mm or more, is not easily formed. Conversely, if the viscosity exceeds 100 poise, the viscosity is too high so that air bubbles remaining in the slurry, in particular, fine air bubbles having a level of 1 μm are not easily reduced. From such a viewpoint, the slurry viscosity is more preferably from 50 to 80 poise (25° C.). If the rotating speed of the stirring fans is below 5 rpm, air bubbles present in the slurry is insufficiently removed and further it is difficult to disperse the pore-forming agent powder evenly into the slurry. Consequently, it is indispensable to extend the above-mentioned keeping time to 50 hours or more. Thus, this case is not practicable. On the other hand, if the rotating speed is over 30 rpm, air is easily incorporated into the slurry while the slurry is stirred. Inversely, air bubbles are easily generated. From such a viewpoint, a more preferred rotating speed is from 5 to 20 rpm. The shape of the stirring fans is not particularly limited. Preferable are stirring fans each having an anchor shape, which causes air mixture to be reduced. If the time for keeping the rotation of the stirring fans is less than 20 hours, air bubbles present in the slurry is insufficiently removed and further it is difficult to disperse the pore-forming agent powder evenly into the slurry. Conversely, if the time is made excessively long so as to be over 50 hours, a long time is required for the process. Thus, this case is unsuitable for practical use. In order to make a scattering in the permeability between lots of the green sheets small in the above-mentioned process, it is advisable to use, as the slurry for producing the green sheets which become ceramic precursors, a slurry obtained by: adding, to the viscosity-adjusted slurry which comprises the conductive component powder, the skeleton component powder, the pore-forming agent powder, and the binder and obtained by defoaming the components under reduced pressure after milling the components to set the viscosity thereof into the range of 40 to 100 poises (25° C.) and then keeping the resultant at room temperature while rotating the stirring fans in the slurry at a rotating speed of 5 to 30 rpm for 20 to 50 hours, a slurry which is subjected to the same milling, has the same composition and has a viscosity not adjusted; defoaming the resultant mixture slurry under reduced pressure to adjust the viscosity into the range of 40 to 100 poise (25° C.); and then keeping the resultant at room temperature while rotating the stirring fans in the slurry at a rotating speed of 5 to 30 rpm for 20 to 50 hours. In order to make a scattering in the green sheet lots smaller in this case, it is preferable to add 95 to 105 parts by mass of the total of the conductive component powder and the skeleton component powder in the slurry the viscosity of which is not adjusted to 100 parts by mass of the total of the conductive component powder and the skeleton component powder in the viscosity-adjusted slurry. An instrument used for the defoaming under reduced pressure is preferably a concentrating and stirring defoaming machine having a refrigerator and a collecting tank for collecting solvent and having an internal volume of 10 liters or more, preferably 30 liters or more, more preferably 50 liters or more. According to a separable flask having an internal volume of less than 10 liters and having a cock for reducing pressure, or some other flask, which is used in ordinary laboratories, a substrate having a sufficient quality intended in the present invention is not easily obtained, probably, because of scale effect. For satisfying the above-mentioned properties, important is the size distribution of particles in the slurry state used in the production of a green sheet which becomes a ceramic precursor which becomes an electrode support substrate, and it is important to use a slurry having one peak in each of the ranges of 0.2 to 2 μm and of 3 to 50 μm in the particle size distribution of the starting slurry for producing the green sheet. In other words, the surface roughness of a support substrate is affected, to some extent, by the above-mentioned particle size construction of the used starting materials. If coarse materials are used, the surface roughness of the resultant sintered body becomes relatively coarse. If fine materials are used, the surface roughness thereof becomes relatively dense. If a material having the above-mentioned preferable particle size construction is used as each of the conductive component material powder and the skeleton component material powder which constitute the electrode support substrate, this substrate can easily have the above-mentioned proper porosity and a maximum roughness depth (Rmax) in the preferred range. However, the present inventors have repeatedly made research so as to find out following. A more important matter for obtaining a sintered body satisfying, in particular, the above-mentioned variation coefficient of measured values of the gas permeable amounts and Rmax defined in the present invention is the particle size distribution of solid components contained in the slurry for obtaining a ceramic molded body which becomes a sintering material rather than the above-mentioned particle size construction of the starting powders themselves. Moreover, when a slurry having one peak in each of the ranges of 0.2 to 2 μm and of 3 to 50 μm in the particle size distribution thereof is used to produce a green sheet and then the sheet is fired, a sintered body (electrode support substrate) having a porosity of 20 to 50% and a Rmax of 1.0 to 40 μm can be more surely obtained. When the slurry is prepared, there is adopted a method of treating the above-mentioned starting material blended suspension including the starting powders in a ball mill or the like to knead and pulverize the powders. Dependently on conditions for the kneading (examples of which include the kind of a dispersing agent, and the added amount thereof), a part of the starting powders aggregates secondarily in this slurry-preparing step and a part thereof is crushed. Therefore, the particle size construction of the starting powders is not kept as it is in the particle size construction of solid components in the slurry. Thus, when the electrode support substrate of the present invention is produced, it is important to adjust the particle size distribution of the slurry-state solid components used to produce a green sheet which is not fired, as a factor which produces the largest effect on the porosity and the surface roughness of the electrode support substrate, to satisfy the above-mentioned requirements. The particle size distributions of the solid components in the starting powders and in slurry are values measured by the following methods. The particle size distribution of the starting powders is a measured value after using a laser diffraction manner particle size distribution meter “SALD-1100”, manufactured by Shimadzu Corp., using, as a dispersing medium, an aqueous solution wherein 0.2% by mass of sodium metaphosphoric acid is added as a dispersing agent to distilled water, adding 0.01 to 1% by mass of each of the starting powders to about 100 cm3 of the dispersing medium, and treating the resultant with ultrasonic waves for 3 to 10 minutes to disperse the powders. The particle size distribution of the solid components in each slurry is a measured value after using a solvent having the same composition as the solvent in the slurry, as a dispersing medium, adding the slurry to 100 cm3 of the dispersing medium into a concentration of 0.1 to 1% by mass, and treating the resultant with ultrasonic waves for 3 to 10 minutes in the same way to disperse the solid components. It is obtained as a particle size distribution frequency graph as illustrated, for example, in FIG. 4. When the slurry having one peak in each of the ranges of 0.2 to 2 μm and of 3 to 50 μm in the particle size distribution thereof in the slurry state as described above is used to form a green sheet, the formed green sheet is a green body wherein relatively fine particles having of 0.2 to 2 μm size are filled into gaps between relatively coarse particles of 3 to 50 μm size. When this is fired, a sintered body having the preferred surface roughness can be obtained. In order to ensure the above-mentioned preferable surface roughness, the content ratio by mass of the fine particles of 0.2 to 2 μm size to the coarse particles of 3 to 50 μm size, in the slurry state thereof, is more preferably from 20/80 to 90/10, even more preferably from 40/60 to 80/20. The average particle size of the whole is preferably from 0.2 to 5 μm, more preferably from 0.3 to 3 μm. Means for adjusting the particle size distribution in the slurry state into the preferable range is not particularly limited, and examples of ordinary methods thereof are as following methods: (i) a method of pre-firing a part of powders which are starting materials at 900 to 1400° C. for 1 to 20 hours to make the particle size thereof large, and then mixing the part with the powders that are not fired, (ii) a method of separating the addition of starting powders into two stages when the starting powders and others are mixed in a ball mill, and adding a part thereof after a given time passes, thereby suppressing the degree of the pulverization, and (iii) a method of kneading starting powders and others in two kinds of ball mills having balls different in diameter to prepare two slurries of different particle sizes, and then mixing the two slurries. The above-mentioned methods may be adopted alone. Alternatively, if necessary, two or more out of the methods can be appropriately combined to be carried out. For the electrode support substrate of the present invention, the following method is adopted: a method of laying and spreading a slurry obtained as described above, which is comprised a ceramic starting powder, a binder, and a dispersing medium, into an appropriate thickness onto a supporting plate or a carrier sheet by a doctor blade method, a calendering method, an extrusion method or some other method so as to be molded into a sheet form, drying this, volatilizing the dispersing medium to yield a green sheet, adjusting the sheet into pieces of an appropriate size by cutting, punching or the like. The resulting sheet of an appropriate size put one of the pieces on a porous setter on a shelf board or put one of the pieces between setters as disclosed in Re-Publication Patent WO 99/59936, and heat and fire the piece in this state, at about 1100 to 1500° C., preferably about 1200 to 1450° C., most preferably about 1250 to 1500° C. in the case of an anodic electrode support substrate, under the atmosphere of air for about 1 to 5 hours. As the porous setter, there is preferably used a setter, for producing a porous ceramic sheet, which is made of a sheet-form ceramic body comprising 40 to 90% by mass of a (Ni) unit having a high gas permeability so as to emit smoothly gas which is generated in a large amount from the binder or the pore-forming agent when the green sheet is fired. In the case that the electrode support substrate of the present invention is made practicable for a fuel cell, it is advisable to set the thickness of the sheet to 0.3 mm or more, more preferably 0.5 mm or more and set to 3 mm or less, more preferably 1 mm or less in order to suppress electric conductance loss as much as possible while satisfying required strength. Incidentally, the burr height, which is very important for preventing cracking or breaking when the electrode support substrate receives stacking-load or the like in the present invention, is remarkably changed by the edge shape of a punching blade used when the green sheet is punched into a given size. It has been found out that when a punching blade wherein the shape of its edge is wave-form is used, the height of burrs formed on the punched-line of the green sheet can be suppressed into a remarkably smaller value than in the case of using an ordinary straight punching blade. The reasons for this would be as follows. In the case that a straight punching blade is used, the whole of the blade edge contacts the green sheet in a linear form when the green sheet is cut with the blade. Simultaneously, tensile stress is linearly generated in the punching direction so that the cut face of the green sheet comes to be curled in the punching direction. Consequently, large burrs are easily formed. On the other hand, in the case that a wave-form punching blade is used, some parts of the blade edge (that is, the highest points of the wave form) contact the green sheet in the form of points. Therefore, the tensile stress in the punching direction is relieved so that the degree of the curl becomes small. Thus, the burr height would be remarkably lowered. For example, FIG. 5 is an explanatory view for illustrating a punching blade 1 used preferably in the present invention. A blade edge portion 1a is made into the form of the teeth of a saw. As described above, in order to suppress the curl as much as possible at the time of punching the green sheet to make the burr height small, it is desired to form the blade edge portion 1a as sharp as possible to make the blade edge portion which firstly contacts the green sheet surface as small as possible. Further, it set the angle α1 of the blade edge (which means the angle of the wave-form blade edge portion when the blade is viewed from the side thereof) into the range of about 30 to 120 degrees, more preferably about 45 to 90 degrees, set the height h of the blade into the range of about 0.5 to 2 mm, more preferably about 0.5 to 1 mm, and set the pitch p into the range of about 0.2 to 7 mm, more preferably about 0.2 to 4 mm. A preferred sectional structure of the punching blade 1 is as illustrated in FIG. 6. The angle α2 of the blade edge (which means the tip angle of any section in the thickness direction of the blade) is preferably from 20 to 70 degrees, more preferably from 20 to 50 degrees, and the thickness t of the edge is preferably from 0.3 to 1 mm, more preferably from 0.4 to 0.7 mm. For example, as illustrated in FIG. 7, the structure of the blade edge is preferably made as follows: for a green sheet G to be punched, the standing-up angle θ1 on its Gx side (ordinarily, its internal circumferential side) which will be a punched product is made acuter than the standing-up angle θ2 on its cut-off side GY side (ordinarily, its external circumferential side). The angle θ1 is preferably from 10 to 25 degrees, more preferably from 10 to 20 degrees, and the angle θ2 is preferably from 10 to 35 degrees, more preferably from 10 to 30 degrees. By use of the punching blade 1 having a blade edge structure satisfying such angles, burrs formed on the external circumferential edge on the punched-product side can be made even smaller. In the illustrated example, the blade edge portion having a recurring structure of the same pitch and the same shape is shown. However, the shape of the blade edge portion and the recurring units thereof are not limited to the illustrated example. Of course, it is allowable to modify the shape, the size or the like appropriately and carry out punching as far as the blade structure is a structure suitable for suppressing burrs. At the time of the punching, it is preferable to drop down the punching blade 1 as perpendicularly as possible to a surface of the green sheet. In this case, it is desirable to sandwich and fix the green sheet between soft and elastic supporting plates not to be out of position. For example, FIGS. 8 to 11 are explanatory schematic sectional views illustrating the structure of a punching member A used in the present invention, and a punching method using this. A punching blade 1 is fixed to a blade holder 2 with a hard member 3 and further a projecting plate 4 made of a soft rubber or the like is fitted to the front end portion side of the hard member 3. The blade 1 is set not to penetrate through the projecting plate 4, so as not to project from the front end face thereof as far as the projecting plate 4 is not deformed by compression (see FIG. 8). In the illustrated example, illustrated is a structure wherein an elastic plate 6 is laminated also on the upper face of the hard plate 5 in a sheet supporting member B arranged oppositely to the punching member A in order to ensure the fixation of a green sheet even more when the sheet is punched. However, the elastic plate 6 is not necessarily essential. The green sheet G which is an object to be punched is arranged on the supporting member B and then a punching work is performed. When the green sheet G is punched, the punching member A is caused to approach the surface of the green sheet G put on the sheet supporting member B in the direction substantially perpendicular to the surface, from the state illustrated in FIG. 8. The punching blade 1 fitted into in the punching member A is set not to project from the front face of the projecting plate 4 as described above. Therefore, when the punching member A is caused to approach the green sheet G as described above, the upper face of the sheet G firstly contacts the projecting plate 4 so that the green sheet G is sandwiched from the upper and lower sides between the projecting plate 4 and the elastic plate 6 (see FIG. 9). Thereafter, the punching member A is further dropped down. As a result, the projecting plate 4 which is made of the elastic material is compressed and deformed so that the punching blade 1 comes to project out toward the green sheet G. Simultaneously, the green sheet G is urged from both sides thereof by elastic force resulting from the elastic deformation of the projecting plate 4 and elastic force, based on the plastic plate 6, from the lower face side of the sheet. Thus, the sheet G is supported and fixed, and in this state the blade 1 advances to punch the sheet (see FIG. 10). After the punching blade 1 penetrates through the green sheet G so that the sheet is punched, the punching member A is backed up to move the blade 1 backwards from the green sheet G punched portion. In this step, similarly, the sandwich and fixation state is maintained by elastic forces of the projecting plate 4 and the elastic plate 6 until the punching blade 1 is withdrawn from the green sheet G, and the state is cancelled after the punching blade 1 is withdrawn (see FIG. 11. in the figure, y represents the punched portion). In other words, a fall in the punching dimensional accuracy, based on positional slippage, is prevented and additionally the generation of burrs is restrained as much as possible since the punching and withdrawing which follow the forward and backward movement of the punching blade 1 are performed in the state that the green sheet G is elastically sandwiched and fixed. Thus, when the present invention is carried out, a blade having a waver-form blade edge portion is used as a device for punching a green sheet, whereby the height of burrs formed in the punched-out portion can be made as low as possible. As a result, when the resultant substrate receives stacking-load or the like, stress concentration on the burrs thereof can be suppressed as much as possible and the generation of cracking or breaking can be suppressed into a minimum. In particular, the green sheet which becomes a precursor of the electrode support substrate according to the present invention comprises a large amount of a pore-forming agent in order to ensure given porosity, and the green sheet is softer than any green sheet used in the production of a dense sintered body. Therefore, burrs generated when the green sheet is punched into a given size easily become large. However, a punching blade and a punching method as described above are adopted, whereby the burrs can be controlled as slightly as possible. Clacking or breaking caused when the sheet substrate receives stacking-load or the like may also be caused on the basis of large projections, undulations and so on that are present on the substrate surface besides the burrs. Therefore, in order to make the cracking resistance or breaking resistance thereof even higher, the projections or undulations should be made as small as possible as well as the burr height is decreased. About a standard thereof, each of the largest projection height and the largest undulation height is ⅓ or less of the thickness of the sheet, more preferably ¼ or less thereof, even more preferably ⅕ or less thereof, as described above. The reason why the burr height, the largest projection height and the largest undulation height are defined as the ratio thereof to the sheet thickness as described above is that these values tend to be relatively larger as the sheet thickness is larger. It appears that the largest cause that the projections are generated when the porous electrode support substrate according to the present invention is produced is as follows. In the case that a granular alien substance is present on the shelf board or setter used when the green sheet is fired, the alien substance is caught in the green sheet, which is put thereon, so that the sheet is hindered from being evenly shrunk in a flat state. It also appears that the largest cause that the undulations are generated is as follows. When the binder or pore-forming agent in the green sheet is burned up so that the sheet is sintered, the content thereof is too large or when the green sheets are put on each other and fired, the burning does not evenly advance with ease. Thus, a scattering in the decomposed amount or burned amount thereof per unit time is generated so that the amount of generated decomposition gas becomes uneven. The shrinkage amount (about 10 to 30% of the length) of the green sheet generated when the sheet is fired is larger in the circumferential edge portion than in the central portion of the sheet. Therefore, the undulations are easily generated in the circumferential edge portion. Thus, means for suppressing the projections into a minimum may be a method of performing removal and cleaning sufficiently so that adhering particles, fallen particles and others may not be present on the shelf board or setter used in the firing. A specific and effective example of means for suppressing the undulations in a minimum may be a method of suppressing the use of the binder or the pore-forming agent into a minimum and further firing the green sheets in the state that a porous setter is put as a spacer in between the green sheets and a spacer for a weight is put onto the topmost portion, in particular when the green sheet are laminated and fired, so as to emit decomposition gas evenly from the binder or the like. When the electrode support substrate of the present invention is used as a member for a solid electrolyte type fuel cell, an anodic electrode and a thin electrolyte film are formed on a single surface of the substrate. The method for forming the electrode or the thin electrolyte film is not particularly limited. The following can be appropriately used: a gas phase method, such as plasma spraying such as VSP, flame spraying, PVD (physical vapor deposition), magnetron sputtering, or electron beam PVD; or a wet method such as screen printing, sol-gel process, or slurry coating. The thickness of the anodic electrode is usually from 3 to 300 μm, preferably from 5 to 100 μm, and the thickness of the electrolyte layer is usually from 3 to 100 μm, preferably from 5 to 30 μm. EXAMPLES The following describes the present invention more specifically, giving working examples and comparative examples. However, the present invention is not basically limited by the following working examples, and may be carried out with appropriate modification within a scope suitable for the subject matters which have been described above and will be described below. All of them are included in the technical scope of the present invention. Example 1 (Formation of Setters) The following were mixed to produce a mixed powder as a starting material: 40% by mass of 8% by mole yttrium oxide stabilized zirconia powder (hereinafter referred to as the “8YSZ”) wherein the average particle size thereof was 0.5 μm and the particle size of the 90% volume thereof was 1.2 μm; and 60% by mass of nickel oxide powder obtained by decomposing nickel carbonate powder thermally wherein the average particle size was 4.5 μm and the particle size of the 90% volume was 8 μm. To 100 parts by mass of this mixed powder were added 12 parts by mass of an acrylic binder made of a copolymer obtained by use of 79.5% by mass of isobutyl methacrylate, 20% by mass of 2-ethylhexyl methacrylate and 0.5% by mass of methacrylic acid as monomer units, 40 parts by mass of toluene and ethyl acetate (ratio by mass: 2/1) as solvents, and 2 parts by mass of dibutyl phthalate as a plasticizer. The mixture was kneaded in a ball mill and then defoamed, and the viscosity thereof was adjusted, thereby yielding a slurry of 40 poise viscosity. This slurry was fashioned into a sheet form by a doctor blade method, thereby forming green sheets, for setters, having a thickness of about 0.5 mm. This was cut into a given size. Subsequently, the resultants were put on a shelf board made of alumina and having a thickness of 20 mm, and fired at 1400° C. for 5 hours to yield porous setters 17 cm square and about 0.4 mm thick, the porosity thereof being 15%. (Formation of Electrode Support Substrate) (1) Formation of Green Sheet for Electrode Support Substrate Commercially available 3% by mole yttria-stabilized zirconia powder (trade name “HSY-3.0”, manufactured by Daichi Kigenso Kagaku Kogyo Co., Ltd., particle size construction: particle size of the 50% by volume=0.41 μm; and particle size of the 90% by volume=1.4 μm) (hereinafter referred to as the “3YSZ”) was pre-fired at 1200° C. under the atmospheric of air for 3 hours. The following were put into a ball mill wherein alumina balls of 15 mm diameter were put: 20 parts by mass of the pre-fired powder (particle size construction: particle size of the 50% by volume=14 μm; and particle size of the 90% by volume=29 μm), 20 parts by mass of the above-mentioned zirconia powder not pre-fired, 60 parts by mass of nickel oxide powder (manufactured by Kishida Chemical Co., Ltd., particle size construction: particle size of the 50% by volume=0.6 μm; and particle size of the 90% by volume=2.7 μm), 10 parts by mass of corn starch (manufactured by Kanto Chemical Co., Inc.), 15 parts by mass of a methacrylic acid based copolymer (molecular weight: 30,000, glass transition temperature: −8° C.) as a binder, 2 parts by mass of dibutyl phthalate as a plasticizer, and 50 parts by mass of a mixed solvent of toluene and isopropyl alcohol (ratio by mass: 3/2) as a dispersing medium. The mixture was kneaded at about 60 rpm for 20 hours to prepare a slurry. The particle size distribution of the resultant slurry was measured with a laser diffraction manner particle size distribution meter (trade name “SALD-1100”, manufactured by Shimadzu Corp.), and the resultant frequency graph of the particle size distribution was observed. As a result, two peaks were observed in a section of 0.2 to 0.3 μm and a section of 4 to 5 μm, and the content ratio of fine particles in the range of 0.2 to 2 μm and coarse particles in the range of 3 to 50 μm was 82/18. This slurry was put into a pressure-reducing defoaming machine, concentrated and defoamed to adjust the viscosity into 50 poise (25° C.). Anchor-shaped stirring fans immersed in the slurry were rotated at a rotating speed of 10 rpm for 24 hours, and finally the slurry was passed through a 200-mesh filter. The resultant was applied onto a polyethylene terephthalate (PET) film by a doctor blade method. At this time, a gap based on a blade was adjusted to form a green sheet having a thickness of about 0.59 mm. (2) Punching and Firing of Green Sheet for Electrode Support Substrate The green sheet obtained as described above was punched into a piece 15 cm square by the method as illustrated in FIGS. 8 to 11 using a punching blade (manufactured by Nakayama Shiki Zairyo Co., Ltd.) having a wave-form blade edge (in the form of the teeth of a saw as illustrated in FIGS. 5 to 7) and having blade edge angles α1 and α2 of 60° and 45°, respectively, blade edge angles θ1 and θ2 of 15° and 30°, respectively, a blade width t of 0.7 mm, a blade height h of 1 mm, and a pitch p of 1.1 mm. The upper and lower faces of the punched substrate green sheet were sandwiched between the setters produced as described above so as not to force out the circumferential edge of the green sheet therefrom. Then the resultant was put onto a shelf board (trade name: “Dialight DC-M”, manufactured by Tokai Konetsu Kogyo Co., Ltd.) having a thickness of 20 mm and fired at 1300° C. for 3 hours to yield an electrode support substrate about 12.5 cm square and about 0.5 mm thick. Example 2 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, a slurry having no adjusted viscosity, obtained by treatment with a ball mill in the same way as in Example 1, and a slurry having a viscosity adjusted to 50 poise with the pressure-reducing defoaming machine were prepared. The slurry having no adjusted viscosity was added to the slurry having the adjusted viscosity. At this time, the addition was performed to make the total mass of the 3YSZ powder and the nickel oxide powder in the slurry having the adjusted viscosity equal to the total mass of the 3YSZ powder and the nickel oxide powder in the slurry having no adjusted viscosity. Next, the viscosity of the mixed slurry was adjusted to 50 poise (25° C.) by pressure-reducing defoaming in the same way. The slurry was kept at room temperature while stirring fans in the slurry were rotated at a rotating speed of 12 rpm for 20 hours. The resultant green-sheet-producing slurry was used and fashioned into a sheet form. Thus, a green sheet having a thickness of about 0.59 mm was yielded. Subsequently, in the same way as in Example 1, punching and firing were performed to yield an electrode support substrate about 12.5 cm square and about 0.5 mm thick. Example 3 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, the viscosity of the slurry was adjusted to 60 poise by pressure-reducing defoaming. The slurry was kept at room temperature while the stirring fans were rotated at a rotating speed of 18 rpm for 30 hours. Subsequently, a gap based on the doctor blade was adjusted to form a green sheet having a thickness of 0.35 mm. In the very same way as in Example 1 except the above, an electrode support substrate about 12.5 cm square and about 0.3 mm thick was yielded. Example 4 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, 10 parts by mass of corn starch (manufactured by Kanto Chemical Co., Inc.), 15 parts by mass of a binder made of methacrylic copolymer and 2 parts by mass of dibutyl phthalate as a plasticizer, the latter two of which were the same as in Example 1, were used for 15 parts by mass of pre-fired powder (particle size concentration: diameter of the 50% volume=20 μm; and diameter of the 90% volume=41 μm) obtained by pre-firing 8YSZ powder (particle size concentration: diameter of the 50% volume=0.5 μm; and diameter of the 90% volume=1.2 μm) at 1200° C. under the atmosphere of air for 3 hours, and 15 parts by mass of the above-mentioned powder not pre-fired, and 70 parts by mass of nickel oxide (manufactured by Seido Chemical Industry Co., Ltd., particle size concentration: diameter of the 50% volume=0.8 μm; and diameter of the 90% volume=2.1 μm). In the same way as in Example 1 except the above, a green sheet for a substrate was formed, and subsequently punching and firing were performed in the same way to yield an electrode support substrate about 12.5 cm square and about 0.5 mm thick. Example 5 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, 10 parts by mass of corn starch (manufactured by Kanto Chemical Co., Inc.), 15 parts by mass of a binder made of methacrylic copolymer and 2 parts by mass of dibutyl phthalate as a plasticizer, the latter two of which were the same as in Example 1, were used for 20 parts by mass of pre-fired powder obtained by pre-firing commercially available 3YSZ powder (ditto) at 1200° C. under the atmosphere of air for 3 hours, 10 parts by mass of the above-mentioned powder not pre-fired, and 70 parts by mass of nickel oxide (manufactured by Kishida Chemical Co., Ltd.). In the same way as in Example 1 except the above, a green sheet for a substrate was formed, and subsequently punching and firing were performed in the same way to yield an electrode support substrate about 12.5 cm square and about 0.5 mm thick. Example 6 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, 20 parts by mass of corn starch (manufactured by Kanto Chemical Co., Inc.), 15 parts by mass of a binder made of methacrylic copolymer and 2 parts by mass of dibutyl phthalate as a plasticizer, the latter two of which were the same as in Example 1, were used for 15 parts by mass of pre-fired powder obtained by pre-firing commercially available 3YSZ powder (ditto) at 1200° C. under the atmosphere of air for 3 hours, and 15 parts by mass of the above-mentioned powder not pre-fired, and 70 parts by mass of nickel oxide (manufactured by Seido Chemical Industry Co., Ltd.). In the same way as in Example 1 except the above, a green sheet for a substrate was formed, and subsequently punching and firing were performed in the same way to yield an electrode support substrate about 12.5 cm square and about 0.5 mm thick. Comparative Example 1 In Example 1, the viscosity was adjusted to 50 poise (25° C.), and immediately after this the slurry was passed through a 200-mesh filter without keeping the slurry at room temperature while stirring the slurry. Subsequently, the slurry was applied onto a PET film by a doctor blade method so as to form a green sheet about 0.59 mm thick similarly. Furthermore, in the same way as in Example 1, an electrode support substrate about 12.5 cm square and about 0.5 mm thick was produced. Comparative Example 2 In Example 1, the viscosity was adjusted to 120 poise (25° C.), and subsequently stirring fans were immersed into the slurry. The stirring fans in the slurry were rotated at a rotating speed of 10 rpm for 10 hours. Thereafter, the slurry was passed through a 200-mesh filter and then the slurry was applied onto a PET film by a doctor blade method so as to form a green sheet about 0.59 mm thick similarly. Furthermore, in the same way as in Example 1, an electrode support substrate about 12.5 cm square and about 0.5 mm thick was produced. Comparative Example 3 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, the same materials were used except that the 1200° C. pre-fired powder made of the commercially available 3YSZ powder (ditto) was not used and 40 parts by mass of the 3YSZ powder (ditto) were used. The materials were put into a ball mill in which zirconia balls of 5 mm diameter were charged, and kneaded at about 50 rpm for 3 hours to prepare a slurry. In the same way as in the item 1) of Example 1 except the above, a green sheet of about 0.59 mm thickness was formed. Furthermore, in the same way as in Example 1, an electrode support substrate about 12.5 cm square and about 0.5 mm thick was formed. Comparative Example 4 In the item “(1) Formation of green sheet for electrode support substrate” in Example 1, the same materials were used except that the 3YSZ powder (ditto) was not used and the following were used: 40 parts by mass of 3YSZ powder pre-fired at 1200° C. for 3 hours and 60 parts by mass of powder obtained by pre-firing nickel oxide powder (manufactured by Kishida Chemical Co., Ltd.) at 1100° C. in the atmosphere of air for 3 hours (particle size concentration: diameter of the 50% volume=17 μm; and diameter of the 90% volume=30 μm). The materials were put into a ball mill in which alumina balls of 20 mm diameter were charged, and kneaded at about 40 rpm for 10 hours to prepare a slurry. In the same way as in the item 1) of Example 1 except the above, a green sheet of about 0.59 mm thickness was formed. Furthermore, in the same way as in Example 1, an electrode support substrate about 12.5 cm square and about 0.5 mm thick was formed. Comparative Example 5 In Comparative Example 1, the conditions for ripening the slurry was changed as follows: 2 rpm×2 hours. In the item “(2) Punching of Green Sheet for Substrate”, a single edge blade (manufactured by Nakayama Shiki Zairyo Co., Ltd.) having a straight blade edge having a thickness t of 0.7 mm and an blade edge angle α2 of 45° was used to punch the sheet into a piece 15 cm square. In the very same way except the above, punching and firing were performed to form an electrode support substrate. Comparative Example 6 In the item “(1) Formation of green sheet for electrode support substrate” in Comparative Example 1, 25 parts by mass of the binder made of the methacrylic acid based copolymer were used and further the conditions for ripening the slurry was changed as follows: 2 rpm×54 hours. Additionally, in the item 2) Firing of Green Sheet for Substrate therein, the electrode-substrate-forming green sheet was fired without putting any setter thereon and further the following was used as the setter for underlay: a setter wherein about ten adhering particles having a diameter of about 0.5 to 2 mm were observed per 100 Cm2. In the same way as the above-mentioned example except the above, an electrode support substrate was formed. Performance Tests Each of the electrode support substrates obtained in Examples 1 to 6 and Comparative Examples 1 to 6 was used to make the following performance evaluating tests. The results are shown in Tables 1 to 6. (1) Gas Permeable Test The electrode support substrate about 12.5 cm square and about 0.5 mm thick, which was obtained as described above, was cut into 16 pieces 3 cm square with a diamond cutter fitted to a ceramic grinder (manufactured by Marutoh Co., Ltd.). These were used as permeability testing pieces. Any one of the testing pieces was set to a permeability testing machine (trade name: “KES-F8-AP1”, manufactured by Kato Tech Co., Ltd.), to which an assistant member for holding a sample was fitted. This testing machine is a machine which has a mechanism wherein a constant flow rate of air is sent to the test piece by piston movement of a plunger and a cylinder to emit the air into the atmosphere or absorb air therefrom, and which is capable of measuring the pressure loss based on the sample with a differential pressure semiconductor gauge within 10 seconds per cycle and showing the gas permeation resistance (the reciprocal number of the gas permeability) of the sample directly with a digital panel meter. The size of the sample piece was 3 cm square, and both ends thereof were necessary by 0.5 mm for holding the sample piece. Therefore, the effective area thereof was 2 cm square (area: 4 cm2). The outline of the machine is illustrated in FIG. 12 (in this figure, S represents the sample; 11, a compressor; 12, a flow rate meter; and 13, a differential pressure meter). About each of the 16 sample pieces, the gas permeability thereof was measured. The average value and the standard deviation were obtained, and further the variation coefficient was obtained. (2) Measurement of Porosity The porosities of the electrode support substrate obtained as described above were measured with an automatic porosimeter (trade name: “Autopore III9240”, manufactured by Shimadzu Corp.). (3) Surface Roughness A laser optical manner non-contact three-dimensional shape measuring device (trade name: “Micro-focus Expert UBM-14 model”, manufactured by UBM Co.) was used to measure the maximum roughness depths (Rmax) of the front and rear faces (the side contacting the PET surface when the green sheet was formed is referred as the front side) of each of the electrode support substrates at a pitch of 0.1 mm. Simultaneously, burrs on the circumferential edge of each of the electrode support substrates, and projections and undulations on the surface were measured. (4) Load Test Each of the sample substrates was arranged on an alumina underlying-plate in the state that the substrate was sandwiched between two alumina plates (trade name: “SSA-S1”, manufactured by Nikkato Co., Ltd.), the surfaces of which were smooth and had kept parallelism, and then a load of 0.2 kg/cm2 was applied onto the entire surface of the substrate. In this state, the temperature of the substrate was raised from room temperature to 1000° C. over 10 hours, and kept at 1000° C. for 1 hour, and then dropped to room temperature. This operation was repeated ten times to obtain the generation frequency of cracking or breaking. It was judged with the naked eye whether or the cracking or breaking was generated. (5) Observation of Cell Printed Interface The states of the interfaces between each of the electrode support substrates and an anodic electrode and between each of the electrode support substrates and an electrolyte layer were observed from an SEM photograph thereof. (Formation of Cell) (a) Preparation of Paste To 100 parts by mass of 10% by mole scandia- and 1% by mole ceria-stabilized zirconia powder (manufactured by Daichi Kigenso Kagaku Kogyo Co., Ltd.) were added 350 parts by mass of turpentine oil and 2 parts by mass of ethylcellulose as a binder. Then, the mixture was kneaded in a planetary mill for 2 hours to yield a slurry. The slurry was used as an electrolyte paste. To 50 parts by mass of 3YSZ powder (ditto) and 50 parts by mass of nickel oxide (manufactured by Kishida Chemical Co., Ltd.) were added 350 parts by mass of turpentine oil and 2 parts by mass of ethylcellulose as a binder. Then, the mixture was kneaded in a planetary mill for 2 hours to yield a slurry. The slurry was used as an anode paste. To 100 parts by mass of La0.8Sr0.2MnO3 powder (manufactured by Seimi Chemical Co., Ltd.) were added 350 parts by mass of turpentine oil and 2 parts by mass of ethylcellulose as a binder. Then, the mixture was kneaded in a planetary mill for 2 hours to yield a slurry. The slurry was used as a cathode paste. (b) Formation of Cell Next, the anode paste was printed onto one surface of the above-mentioned electrode support substrate by screen printing. The resultant was dried at 100° C. for 1 hour and fired at 1350° C. for 2 hours to form an anode layer on the electrode support substrate, thereby forming an anode-layer-attached electrode support substrate (AS-A). The electrolyte paste was printed on the anode layer of the anode-layer-attached electrode support substrate (AS-A) by screen printing. The resultant was dried at 100° C. for 1 hour and fired at 1350° C. for 2 hours to form a half cell wherein the anode layer and an electrolyte layer were formed on the electrode support substrate (AS-A-E). Finally, the cathode paste was applied onto the electrolyte layer of this half cell by screen printing. The resultant was dried at 100° C. for 1 hour and fired at 1300° C. for 2 hours to form a cell wherein the anode layer, the electrolyte layer and a cathode layer were formed on the electrode support substrate (AS-A-E-C). The electrode area of the cell was about 121 cm2. (c) An electrolyte layer, an anode layer, and a cathode layer were formed on the electrode support substrate about 12.5 cm square and about 0.5 mm thick, obtained in each of the Examples and the Comparative Examples, by screen printing in accordance with the method described in the item (Formation of cell), so as to produce an anode-layer-attached electrode support substrate (AS-A) and a half cell (AS-A-E). The surface of each thereof was observed with the naked eye. Further the state of the printed interface was observed from an SEM photograph thereof. In this way, the state of the interface between the electrode support substrate and the anode layer, the state of the interface between the anode layer and the electrolyte layer, and the state of the electrolyte layer were examined. (6) Power Generation Test Furthermore, in a single cell power generation test device using the cell (AS-A-E-C) produced in accordance with the method described in the item (Formation of cell), humidified hydrogen and air were used as a fuel and an oxidizer, respectively, to make a power generation test at a power generation temperature of 800° C. for 24 hours. The highest power density at the initial of the test and the highest power density after 24 hours from the start of the test were obtained so as to calculate the decreasing rate of the highest power. The results are shown in Tables 1 to 6 TABLE 1 Example 1 Example 2 Example 3 Composition NiO/3YSZ + NiO/3YSZ + NiO/3YSZ + pre-sintered pre-sintered pre-sintered 3YSZ/starch 3YSZ/starch 3YSZ/starch 60/20 + 20/10 60/20 + 20/10 60/20 + 20/10 Peak sections in slurry 0.2 to 0.3 μm and 0.2 to 0.3 μm and 0.2 to 0.3 μm and particle size distribution 4 to 5 μm 4 to 5 μm 4 to 5 μm Content ratio of fine 82/18 82/18 82/18 particles to coarse particles Slurry viscosity (poise) 50 50 60 Conditions for keeping 10 rpm × 24 hours 12 rpm × 20 hours 18 rpm × 30 hours slurry at room temperature Green sheet thickness (mm) 0.59 0.59 0.35 Punching die Wave form Wave form Wave form Support substrate thickness 0.5 0.5 0.3 (mm) Porosity (%) 25 23 27 Burr height/substrate 0.30 0.27 0.34 thickness Undulation 0.13 0.11 0.17 height/substrate thickness Projection height/substrate 0.15 0.12 0.17 thickness TABLE 2 Example 4 Example 5 Example 6 Composition NiO/8YSZ + NiO/3YSZ + NiO/3YSZ + pre-sintered pre-sintered pre-sintered 8YSZ/starch 3YSZ/starch 3YSZ/starch 70/15 + 15/10 70/20 + 10/10 70/15 + 15/20 Peak sections in slurry 0.2 to 0.3 μm and 0.2 to 0.3 μm and 0.2 to 0.3 μm and particle size distribution 5 to 6 μm 4 to 5 μm 4 to 5 μm Content ratio of fine 86/14 82/18 Dec-88 particles to coarse particles Slurry viscosity (poise) 50 70 50 Conditions for keeping 10 rpm × 24 hours 10 rpm × 24 hours 10 rpm × 24 hours slurry at room temperature Green sheet thickness (mm) 0.59 0.59 0.59 Punching die Wave form Wave form Wave form Support substrate thickness 0.5 0.5 0.5 (mm) Porosity (%) 28 28 32 Burr height/substrate 0.41 0.32 0.36 thickness Undulation 0.11 0.15 0.13 height/substrate thickness Projection height/substrate 0.12 0.17 0.14 thickness TABLE 3 Comparative Comparative Comparative Example 1 Example 2 Example 3 Composition NiO/3YSZ + NiO/3YSZ + NiO/3YSZ/starch pre-sintered pre-sintered 60/40/10 3YSZ/starch 3YSZ/starch 60/20 + 20/10 60/20 + 20/10 Peak sections in slurry 0.2 to 0.3 μm and 0.2 to 0.3 μm and Only 0.2 to particle size distribution 4 to 5 μm 4 to 5 μm 0.3 μm Content ratio of fine 82/18 82/18 — particles to coarse particles Slurry viscosity (poise) 50 120 40 Conditions for keeping Nothing 10 rpm × 10 hours 50 rpm × 3 hours slurry at room temperature Green sheet thickness (mm) 0.59 0.59 0.59 Punching die Wave form Wave form Wave form Support substrate thickness 0.5 0.5 0.5 (mm) Porosity (%) 25 29 28 Burr height/substrate 0.33 0.37 0.39 thickness Undulation 0.14 0.19 0.21 height/substrate thickness Projection height/substrate 0.15 0.26 0.12 thickness TABLE 4 Comparative Comparative Comparative Example 4 Example 5 Example 6 Composition Pre-sintered NiO/3YSZ + NiO/3YSZ + NiO/pre-sintered pre-sintered pre-sintered 3YSZ/starch 3YSZ/starch 3YSZ/starch 60/40/10 60/20 + 20/10 60/20 + 20/10 Peak sections in slurry Only 7 to 0.2 to 0.3 μm and 0.2 to 0.3 μm and particle size distribution 8 μm 4 to 5 μm 4 to 5 μm Content ratio of fine — 82/18 82/18 particles to coarse particles Slurry viscosity (poise) 80 50 50 Conditions for keeping 40 rpm × 10 hours 2 rpm × 2 hours 2 rpm × 54 hours slurry at room temperature Green sheet thickness (mm) 0.59 0.59 0.59 Punching die Wave form Linear Wave form Support substrate thickness 0.5 0.5 0.5 (mm) Porosity (%) 37 26 26 Burr height/substrate 0.24 0.68 0.42 thickness Undulation 0.14 0.31 0.35 height/substrate thickness Projection height/substrate 0.19 0.28 0.38 thickness TABLE 5 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Crack generation 0 0 0 0 5 0 frequency (%/in 20 sheets) Surface roughness (μm) Front face Rmax 4.15 2.89 3.74 18.13 5.57 3.11 Rear face Rmax 3.97 3.13 3.61 22.09 3.96 3.83 Gas permeability test (mL/min-kPa) Gas permeability 33 28 62 41 30 30 maximum value Gas permeability 19 18 45 23 19 19 minimum value Average value 23 23 54 32 15 24 Standard deviation 2.1 1.7 8.3 3.7 1.9 2.5 Variation coefficient 9 7 15 12 13 10 Anode formation Interface between Close adhesion Close adhesion Close adhesion Close adhesion Close adhesion Close adhesion substrate and anode Electrolyte formation Interface between Close adhesion Close adhesion Close adhesion Close adhesion Close adhesion Close adhesion anode and electrolyte State of electrolyte Substantially Substantially Substantially Substantially Substantially Substantially thickness even even even even even even Power generation performance Highest-power 8 6 7 11 14 9 decreasing rate (%) Crack after the test Not generated Not generated Not generated Not generated Not generated Not generated TABLE 6 Comparative Comparative Comparative Comparative Comparative Comparative Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Crack generation 0 5 10 45 26 36 frequency (%/in 20 sheets) Surface roughness (μm) Front face Rmax 4.36 3.84 4.75 47.3 3.42 3.86 Rear face Rmax 4.19 4.33 4.96 45.8 3.06 4.11 Gas permeability test (mL/min-kPa) Gas permeability 35 30 33 43 35 33 maximum value Gas permeability 12 9 15 17 14 13 minimum value Average value 20 21 21 24 23 19 Standard deviation 6.6 5.5 5.9 5.5 7.1 4.2 Variation coefficient 33 26 28 23 31 22 Anode formation Interface between Close adhesion Close adhesion Exfoliation Partial Close adhesion Partial substrate and anode exfoliation exfoliation Electrolyte formation Interface between Close adhesion Close adhesion Close adhesion Partial Close adhesion Close adhesion anode and electrolyte exfoliation State of electrolyte Substantially Substantially Substantially Uneven Substantially Substantially thickness even even even even even Power generation performance Highest-power 35 23 28 31 18 20 decreasing rate (%) Crack after the test Generated Generated Generated Generated Generated Generated INDUSTRIAL APPLICABILITY The present invention is constructed as described above, and comprises a ceramic sheet having appropriate porosity, thickness and surface area. In particular, the variation coefficient of measured values of the gas permeable amounts thereof is set into a given range and further the surface roughness measured with a laser optical manner three-dimensional shape measuring device is controlled, as the maximum roughness depth thereof, into a specific range, thereby making it possible to provide an electrode support substrate wherein a dense, even and highly-adhesive printed electrode can be formed while even and superior gas permeability/diffusibility can be ensured, the substrate having performances eminent for a solid oxide type fuel cell. Furthermore, the height of burrs, and the height(s) of undulations and/or projections, which are measured with the same laser optical manner three-dimensional shape measuring device, are specified, thereby making it possible to provide an electrode support substrate for giving a high-performance fuel cell capable of suppressing cracking or braking based on local stress concentration when stacking-load is applied to the cell and capable of resisting thermal shock, thermal stress and others.
<SOH> BACKGROUND ART <EOH>In recent years, attention has been paid to fuel cells as clean energy sources. The use purposes thereof are mainly power generation for home use, power generation for business, power generation for automobiles, and others, and researches for improving the cells and making the cells practicable have been rapidly advanced. A typical structure of solid oxide type fuel cells is basically a stack obtained by stacking a large number of cells wherein an anodic electrode is formed on one face side of a planar solid electrolyte self-supporting film and a cathodic electrode is formed on the other face side. In order to make the power generation performance of the fuel cells high, it is effective to make the solid electrolyte self-supporting film dense and thin. This is based on the following reason. The solid electrolyte self-supporting film needs to have denseness for blocking the mixing of a fuel gas which is a power generation source with air surely, and an excellent ionic conductivity capable of suppressing electric conductance loss as much as possible. For this purpose, the film is required to be as thin and dense as possible. Moreover, a large stacking-load is imposed on the solid electrolyte self-supporting film since a fuel cell has a structure wherein a cell having an anodic electrode, a solid electrolyte self-supporting film and a cathodic electrode and a separator for separating and circulating a fuel gas and air are alternately stacked many times. Additionally, the operation temperature thereof is about 700 to 1000° C.; thus, the fuel cells receive considerable thermal stress. Accordingly, the fuel cells are required to have high-level strength and thermal stress resistance. From the viewpoint of such required properties, a ceramic sheet made mainly of zirconia is mainly used as the material of the solid electrolyte self-supporting film for a solid oxide type fuel cell. A cell, wherein anodic and cathodic electrodes are formed on both faces of the sheet by screen printing or the like, is used. The present inventors have been advancing research on such planar solid electrolyte self-supporting films for solid oxide type fuel cells for some time, and the research has been advanced so as to aim to make the thickness as small as possible for the purpose of decreasing ionic conductance loss while keeping physical properties and shape properties resisting stacking-load or thermal stress (preventing cracks based on local stress by decreasing undulations, projections, burrs and others) and, further, so as to aim to make the surface roughness appropriate for the purpose of heightening evenness and adhesion of the printed electrode. Previously, the present inventors suggested techniques disclosed in JP-A 2000-281438, JP-A 2001-89252, JP-A 2001-10866 and others. These techniques made it possible that the solid electrolyte self-supporting film is largely thin and dense, and further the strength which resists stacking-load generated when cells are stacked, the thermal stress resistance, together with the adhesion and evenness of printed electrodes, are largely improved by improving the shape property, that is, decreasing undulations, projections, burrs and others. Subsequently, the present inventors have been advancing research in order to improve the performance of fuel cells. This time, research has been made to aim to modify the property of electrode support substrates for support film type cells instead of the modification of the property of ceramic sheets used as solid electrolyte self-supporting films. This is based on the following reason. Ceramic solid electrolyte self-supporting films are more easily cracked by stacking-load as the films are made thinner; therefore, there is naturally generated a limitation in making the films thin and there is generated a limitation in decreasing in the ionic conductance loss. In order to obtain cells having structure strength suitable for practical use in the case that thin solid electrolyte films are used therein, electrode support substrates are jointed, as supporting members for the cells, in between the cells or their electrodes are caused to have a sufficient thickness. The substrates have electrical conductivity for electric conduction. Furthermore, the substrates are made of porous ceramic material through which a fuel gas that becomes a power generation source, air, or exhaust gas (carbon dioxide, water vapor and others) generated by burning these gases can permeate and diffuse, which is different from the above-mentioned solid electrolyte self-supporting films. In recent years, the following method has also been investigated. A method of forming an anodic electrode on a porous electrode support substrate by screen printing, forming a solid electrolyte film thereon by coating or the like, and further forming a cathodic electrode thereon by screen printing or the like to produce a cell, thereby making the solid electrolyte film still thinner so as to decrease electric conductance loss still more. The most important theme when such a method is realized is that a cell has even and excellent gas permeability/diffusibility throughout its electrode support substrate. This is because this support substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate. Further, the substrate is desired to have an even distribution state of the pores in such a manner that the gas can permeate and diffuse evenly through the whole of the substrate. Another property desired for the electrode support substrate is that a superior printing adaptability is given to the surface thereof so that an electrode wherein the number of defects is as small as possible can be printed. As described above, the electrode support substrate is required to have an appropriate electrical conductivity. Further, the substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate. Thus, numerous openings are present in the surface thereof. Therefore, in order to make superior electrode-printing possible in spite of the presence of such openings, it is indispensable to clarify surface properties peculiar to the porous electrode support substrate since the surface properties prescribed about the above-mentioned dense solid electrolyte film cannot be applied, as they are, to the porous electrode support substrate. Still another property desired for the electrode support substrate is that the shape property of the support substrate itself is improved so that burrs, projections, undulations and others, which become stress-concentrated spots when they receive stacking-load or thermal shock, are made as small as possible. This is based on the following reason. As described above, the electrode support substrate is required to have an appropriate electrical conductivity. Further, the substrate must be a porous substrate having pores sufficient for allowing a fuel gas and others to permeate and diffuse through the substrate; thus, numerous openings are present in the surface thereof. Therefore, in order to restrain the support substrate, even admitting that the substrate is such a porous sheet, from being cracked or damaged by local stress concentration caused when it receives stacking-load, it is necessary to restrain the generation of burrs, which are formed at its internal and external circumferential edges at the time of punching, and projections or undulations, which may be formed inside the substrate, as much as possible. Furthermore, the electrode support substrate which is intended in the present invention must be a porous body through which a gas can permeate and diffuse. Therefore, the shape property effective for the printability of a dense sheet, such as a solid electrolyte film, and effective for the prevention of stress concentration thereon cannot be applied, as it is, to the electrode support substrate. The present invention has been made, paying attention to a situation as described above. An object thereof is to provide an electrode support substrate to which electrode or a solid electrolyte film may be applied by screen printing. The substrate has the following characteristics. The entire surface of the substrate is stable against a fuel gas and others; the substrate has superior gas permeability/diffusibility. The substrate is able to form a printed electrode and a solid electrolyte film that are even and closely adhesive. The substrate has such a shape property that even if a plurality of the substrates are laminated into a cell stack and each of the substrates receives a large stacking-load, the substrate is not easily cracked or damaged by local stress concentration.
<SOH> BRIEF DESCRIPTION OF THE INVENTION <EOH>FIG. 1 is a frequency graph illustrating a preferred particle size distribution of a slurry, for producing a green body, which is preferably used upon producing an electrode support substrate for a fuel cell according to the present invention; FIG. 2 is an explanatory sectional view illustrating the shape of a burr formed on an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device; FIG. 3 is an explanatory enlarged view illustrating a projection which may be generated in the surface of an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device; and FIG. 4 is an explanatory view illustrating an undulation which may be generated in the whole of an electrode substrate, which is measured with a laser optical manner three-dimensional shape measuring device. FIG. 5 is a view showing an example of the particle size distribution of a slurry which is preferably used upon producing a green body which becomes a precursor of an electrode substrate according to the present invention; FIG. 6 is an explanatory side view illustrating the blade edge shape of a preferred punching blade used to punch a green sheet upon producing an electrode substrate for a fuel cell according to the present invention; FIG. 7 is an explanatory sectional view illustrating the blade edge shape of a preferred punching blade used to punch a green sheet upon producing an electrode substrate for a fuel cell according to the present invention; FIG. 8 is an explanatory sectional view illustrating a preferred example expect FIG. 7 of a punching blade used in the present invention; FIG. 9 is an explanatory schematic sectional view showing the structure of a punching machine adopted preferably in the present invention and a punching work example; FIG. 10 is an explanatory schematic sectional view showing the structure of the punching machine adopted preferably in the present invention and the punching work example; FIG. 11 is an explanatory schematic sectional view showing the structure of the punching machine adopted preferably in the present invention and the punching work example; and FIG. 12 is an explanatory view showing an outline of a gas permeation resistance measuring device used in examples of the present invention. detailed-description description="Detailed Description" end="lead"? 1 : blade edge portion, h: height of blade, p: pitch of blade edge, t: thickness of blade, and α 1 , α 2 , θ 1 and θ 2 : angle of blade edge
20050201
20080401
20050630
58870.0
0
LEWIS, BEN
SOLID OXIDE TYPE FUEL CELL-USE ELECTRODE SUPPORT SUBSTRATE AND PRODUCTION METHOD THEREFOR
UNDISCOUNTED
0
ACCEPTED
2,005
10,515,307
ACCEPTED
Production of high purity and ultra-high purity gas
Trace amounts of carbon monoxide and optionally hydrogen are removed from gaseous feed streams by passing the feed stream through a carbon monoxide adsorbent (33) prior to passing it through a supported metal catalyst (34). The invention saves significant capital and operational costs over existing processes.
1. An adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, said apparatus comprising at least one adsorption vessel containing a CO adsorbent layer, the CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein a) when said feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, CH4 and mixtures thereof, said adsorbent is ion exchanged with a Group IB element; or b) when said feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, said adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+. 2. The apparatus of claim 1, wherein said apparatus contains two or more of said adsorption vessels. 3. The apparatus of claim 1, wherein said adsorption vessel is selected from the group consisting of vertical flow vessels, horizontal flow vessels, lateral flow vessels or radial flow vessels. 4. The adsorption apparatus of claim 1, wherein said apparatus further contains an adsorbent selective for the adsorption of water, and wherein the water selective adsorbent layer is upstream of said CO adsorbent layer. 5. The adsorption apparatus of claim 1, wherein said apparatus further contains a catalyst layer for the catalytic oxidation of H2 to H2O, and wherein said catalyst layer is downstream of said CO adsorbent layer. 6. The adsorption apparatus of claim 5, wherein said apparatus further contains an auxiliary adsorbent for the removal of water, and wherein said auxiliary adsorbent is downstream of said catalyst layer. 7. The apparatus of claim 1, wherein said ΔCO working capacity is greater than or equal to 0.03 mmol/g. 8. The apparatus of claim 4, wherein the water selective adsorbent is one or more of alumina or NaX zeolite. 9. The apparatus of claim 5, wherein the H2 catalyst is a supported metal catalyst. 10. The apparatus of claim 9, wherein said supported metal catalyst is comprises one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce and is supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide. 11. The apparatus of claim 1, wherein said apparatus further contains: a) at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2, b) a catalyst layer for the catalytic conversion of H2 to H2O that is downstream of said CO adsorbent layer; and c) one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. 12. The apparatus of claim 11, wherein said one or more additional adsorbents are selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof. 13. The apparatus of claim 1, wherein the CO adsorbent has a ΔCO/AN2 separation factor of greater than or equal to 1×10−3. 14. The apparatus of claim 1, wherein when said feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, H2, CH4 and mixtures thereof, said CO adsorbent is selected from the group consisting of AgX zeolite, Ag-Mordenite, Cu-clinoptilolite, AgA zeolite and AgY zeolite. 15. The apparatus of claim 1, wherein when said feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, said CO adsorbent is selected from the group consisting of AgX zeolite, Ag-Mordenite, AgA zeolite and AgY zeolite. 16. The apparatus of claim 1, wherein said CO adsorbent is AgX zeolite. 17. The apparatus of claims 1, wherein when said feed gas further contains air, said apparatus is an air prepurifier. 18. The apparatus of claim 1, wherein said CO adsorbent is AgX having 100% of its cations associated with Ag. 19. A process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, said process comprising contacting said feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein a) when said feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, H2, CH4 and mixtures thereof, said adsorbent is a zeolite exchanged with a Group IB element; or b) when said feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, said adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+. 20. The process of claim 19, further comprising recovering said CO depleted gas stream, wherein CO is present in said CO depleted gas stream at a concentration of less than 100 ppb. 21. The process of claim 19, further comprising recovering said CO depleted gas stream, wherein CO is present in said CO depleted gas stream at a concentration of less than 5 ppb. 22. The process of claim 19, wherein said CO concentration in said feed stream is less than 1 ppm CO. 23. The process of claim 19, wherein said CO concentration in said feed stream is less than 0.5 ppm CO. 24. The process of claim 19, wherein said feed gas further comprises water (H2O), and said process further comprises contacting said feed stream with a water selective adsorbent that is located upstream of said CO adsorbent. 25. The process of claim 19, wherein said feed gas further comprises hydrogen, and said process further comprises contacting said CO depleted feed stream with a catalyst layer for the catalytic oxidation of H2 to H2O to produce a H2 depleted and H2O enriched gas, and wherein said catalyst layer is located downstream of said CO adsorbent layer. 26. The process of claim 25, wherein said process further comprises the step of contacting said H2O enriched gas with an adsorbent for the removal of water, and wherein the H2O adsorbent layer is located downstream of said catalyst layer to produce a gas that is depleted in CO, H2 and H2O. 27. The process of claim 19, wherein said ΔCO working capacity is greater than or equal to 0.03 mmol/g. 28. The process of claim 19, wherein the CO adsorbent has aΔCO/AN2 separation factor that is greater than or equal to 1×10−3. 29. The process of claim 19, wherein the CO adsorbent has a ΔCO/AN2 separation factor that is greater than or equal to 1×10−2. 30. The process of claim 24, wherein the water selective adsorbent is one or more of alumina or NaX. 31. The process of claim 25, wherein the catalyst is a supported metal catalyst. 32. The process of claim 31, wherein said supported metal catalyst is comprises one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce and is supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide. 33. The process of claim 19, wherein said process further comprises passing said feed gas over: a) at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2, b) a catalyst layer for the catalytic conversion of H2 to H2O that is downstream of said CO adsorbent layer; and c) one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. 34. The process of claim 33, wherein said one or more additional adsorbents are selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof. 35. The process of claim 19, wherein said process is selected from the group consisting of pressure swing adsorption, temperature swing adsorption, or a combination thereof. 36. The process of claim 19, wherein said process takes place in an adsorber vessel selected from a vertical flow vessel, a horizontal flow vessel or a radial flow vessel. 37. The process of claim 25, wherein the hydrogen depleted gas contains less than 100 ppb hydrogen. 38. The process of claim 25, wherein the hydrogen depleted gas contains less than 5 ppb hydrogen. 39. The process of claim 19, wherein the adsorption step of said process is operated at a temperature of zero to fifty degrees Celsius. 40. The process of claim 19, wherein when said feed gas further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, H2, CH4 and mixtures thereof said CO adsorbent is selected from the group consisting of AgX, Ag-Mor, Cu-clinoptilolite, AgA zeolite and AgY zeolite. 41. The process of claim 19, wherein when said feed gas further contains at least one gas selected from the group consisting of air and oxygen and mixtures thereof said CO adsorbent is selected from the group consisting of AgX, Ag-Mor, AgA zeolite and AgY zeolite. 42. The process of claim 19, wherein said CO adsorbent is AgX having greater than 50% of its cations associated with Ag. 43. The process of claim 19, wherein said CO adsorbent is AgX having 100% of its cations associated with Ag. 44. The process of claim 19, wherein said feed stream contains air, and wherein said CO depleted gas stream is passed to a cryogenic distillation column. 45. The process of claim 19, further comprising recovering said CO depleted gas stream, wherein CO is present in said CO depleted gas stream at a concentration of less than 1 ppb. 46. The process of claim 19, wherein the CO partial pressure in said feed stream is less than 0.1 mmHg. 47. The process of claim 19, wherein the CO partial pressure in said feed stream is less than 0.005 mmHg. 48. A process for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and hydrogen said process comprising contacting said feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein said adsorbent is a zeolite exchanged with a Group IB element. 49. An adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, and hydrogen, said apparatus comprising at least one adsorption vessel containing a CO adsorbent layer, the CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein said adsorbent is a zeolite exchanged with a Group IB element. 50. An air prepurification adsorption apparatus for the removal of CO from an air feed stream containing CO in an amount of less than 50 ppm, said apparatus comprising at least one adsorption vessel containing a CO adsorbent layer, the CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein said adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+. 51. The apparatus of claim 50, wherein said apparatus further comprises at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2. 52. The apparatus of claim 49 or claim 50, further comprising a catalyst layer for the catalytic conversion of H2 to H2O that is downstream of said CO adsorbent layer; and one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. 53. The apparatus of claim 49 or claim 50, wherein said CO adsorbent is AgX. 54. A process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and air said process comprising contacting said feed stream in an adsorber vessel with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein said adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+. 55. The process claim 54, wherein said process further comprises passing said feed stream over at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2 to produce a H2O and or CO2 depleted feed stream. 56. The process of claim 54, wherein said process further comprises, passing said feed stream over a catalyst layer that is downstream of said CO adsorbent layer for the catalytic conversion of H2 to H2O layer and one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer to produce a feed stream that is depleted in CO, H2 and one or more of H2O, CO2, N2O and hydrocarbons. 57. The process of claim 54, wherein said CO adsorbent is AgX. 58. The process of claim 54, wherein the depleted feed stream is passed to a cryogenic distillation column for the separation of air.
PRIORITY This application claims the benefit of U.S. provisional applications Ser. No. 60/384,612, filed May 31, 2002 and Ser. No. 60/385,148, filed Jun. 3, 2002. The contents of each application are herein incorporated by reference. FIELD OF THE INVENTION This invention relates to the removal of impurities from feed air streams and more particularly to the removal of hydrogen (H2) and carbon monoxide (CO) from feed air streams. BACKGROUND OF THE INVENTION Carbon monoxide (CO) and hydrogen (H2) can be present in air at concentrations of up to about 50 ppm and 10 ppm respectively, although typical concentrations in air are on the order of 1 ppm CO and 1 ppm H2. Normal cryogenic distillation processes used to produce ultra high purity (UHP) nitrogen (N2) do not remove hydrogen and remove only a small portion of the CO. Unless removed by alternative means, these molecules will contaminate the product nitrogen at a concentration up to about two and a half times their concentration in the feed air. Since the electronic industry demands very high purity nitrogen product (typically having on the order of 5 ppb CO or less and 5 ppb H2 or less), CO and H2 have to be removed from feed air. Air also contains other contaminants such as water (H2O), carbon dioxide (CO2) and hydrocarbons. In cold sections of the distillation separation process (such as heat exchangers and separation columns), water and CO2 can solidify and block the heat exchangers or other parts in the distillation columns. Acetylene and other hydrocarbons in air also present a potential problem because they can accumulate in the liquid oxygen (O2) and create an explosion hazard. It is therefore desirable to remove these impurities prior to the cryogenic distillation of air. Air prepurification can be accomplished using pressure swing adsorption (PSA), temperature swing adsorption (TSA) or a combination of both (TSA/PSA) incorporating either a single adsorbent or multiple adsorbents. When more than one adsorbent is used, the adsorbents may be configured as discrete layers, as mixtures, composites or combinations of these. Impurities such as H2O and CO2 are commonly removed from air using one or more adsorbent layers in a combined TSA/PSA process. A first layer of activated alumina or zeolite is commonly used for water removal and a second layer of zeolite such as 13X molecular sieve is used for CO2 removal. Prior art, such as U.S. Pat. No. 4,711,645, teaches the use of various adsorbents and methods for removal of CO2 and water vapor from air. These adsorbents are ineffective for the removal of CO and H2, thus allowing CO and H2 to pass through to the distillation equipment. There are three principal strategies in the prior art to remove CO and/or H2 from air to produce UHP nitrogen: removal upstream of the prepurifier adsorber, removal within the prepurifier adsorber using an oxidation catalyst and removal from the nitrogen product after cryogenic air separation. In the first approach, CO and H2 are usually removed by high temperature catalytic oxidation over a supported noble metal or hopcalite catalyst upstream of the prepurifier beds. The products from oxidizing CO and H2, namely CO2 and H2O, are removed along with the ambient CO2 and H2O in the prepurifier beds (F. C. Venet, et al., “Understand the Key Issues for High Purity Nitrogen Production,” Chem. Eng. Prog., pp 78-85, January 1993). This approach requires significant power and additional capital, adding substantially to the cost of the process. U.S. Pat. No. 5,656,557 discloses a process wherein the compressed air is further heated to 350° C. prior to entering a catalyst tower containing palladium (Pd) and/or platinum (Pt) supported catalyst for converting CO, H2 and hydrocarbons to H2O and CO2. The processed air is then cooled to 5° C. to 10° C. prior to entering the prepurifier where the H2O and CO2 are removed. Part of the effluent from the prepurifier may be used as air containing less than 1 ppm total impurities, while the remaining air is separated cryogenically to produce N2 and O2. French patent FR 2 739 304 describes a method of removing CO and H2 from air which involves; 1) contacting the compressed hot moist gas from the compressor with a bed of CO oxidation catalyst; 2) cooling the resulting intermediate air stream to ambient temperature; 3) contacting this CO free stream with an adsorbent to adsorb CO2 and H2O; and 4) contacting the resulting stream with a H2 trapping adsorbent. The CO catalyst can be copper (Cu) or a Pt group metal supported on alumina, silica or zeolite. The H2 trapping adsorbent can be osmium (Os), iridium (Ir), Pd, ruthenium (Ru), rhodium (Rh) or Pt supported on alumina, silica or zeolite. U.S. Pat. No. 6,074,621 describes a similar process as FR 2 739 304 except for the cooling step after the CO oxidation catalyst. U.S. Pat. No. 5,693,302 discloses a method of removing CO and H2 from a composite gas by passing over particles containing gold and Pd supported by TiO2. U.S. Pat. No. 5,662,873 describes a similar process using a catalyst consisting of silver and at least one element from Pt family supported on alumina, silica or zeolite. A second technology employed in the prior art is an ambient temperature process for CO and H2 removal from air. U.S. Pat. No. 5,110,569 discloses a process for removing CO and optionally hydrogen from air by 1) removing water 2) catalytically oxidizing CO to CO2 and optionally H2 to H2O and 3) removing the oxidation products. Oxidation catalysts for CO can be a mixture of manganese and copper oxides such as hopcalite or Carulite. Nickel oxide is also stated to be an effective CO catalyst. The oxidation catalyst for H2 is typically supported palladium. U.S. Pat. No. 5,238,670 discloses a method of removing CO and/or H2 from air at a temperature between 0° C. and 50° C. by 1) removing water from air until it has a water content lower than 150 ppm and 2) removing CO and H2 on a bed of particles containing at least one metallic element selected from Cu, Ru, Rh, Pd, Os, Ir and Pt deposited by ion-exchange or impregnation on zeolite, alumina or silica. European patent application EP 0 454 531 describes a similar method which suggests removing both H2O and CO2 prior to the impregnated bed of particles. Traces of H2O and CO2 are removed downstream of the impregnated particle bed. U.S. Pat. No. 6,048,509 discloses a method for removing CO and H2 from air at ambient temperature wherein air containing H2O, CO2, CO and optionally H2 passes through following steps; 1) contacting the gas with a CO catalyst consisting of Pd or Pt and at least one member selected from the group consisting of iron (Fe), cobalt (Co), nickel (Ni), manganese (Mn), Cu, chromium (Cr), tin (Sn), lead (Pb), and cerium (Ce) supported on large pore alumina; 2) contacting the CO free gas with an adsorbent for water removal; 3) contacting the resulting gas with a CO2 adsorbent for CO2 removal and optionally; 4) contacting the gas with a H2 catalyst which consists of Pt or Pd supported on activated alumina or zeolite. The water formed in the last step of hydrogen oxidation is either adsorbed on the H2 catalyst support or it is removed by a H2O adsorbent, which is either physically mixed with the H2 catalyst or placed downstream of it. U.S. Pat. No. 6,093,379 describes a method where a prepurifier bed with a first layer of water adsorbent and a second layer of CO2 adsorbent operating at ambient temperature is augmented by a third layer of catalyst/adsorbent to remove both CO and H2. The third layer is exposed to substantially H2O-free and CO2-free air at ambient temperature. The dual catalyst/adsorbent is placed in the third layer in the most downstream end of the prepurifier beds. The dual catalyst/adsorbent layer oxidizes CO, adsorbs the resulting CO2, and chemisorbs H2. This dual catalyst/adsorbent is a precious metal such as Pd on a support having a zero point charge (ZPC) of greater than 8. U.S. Pat. No. 6,511,640 discloses a method wherein a prepurifier is configured to contain various materials layered in series beginning with an adsorbent at the feed inlet for H2O removal. The second layer, an oxidation catalyst to convert CO to CO2, is followed by an adsorbent for CO2 removal. An oxidation catalyst is placed in the next layer to convert H2 to H2O, while the final layer is used for adsorbing H2O. The CO catalyst disclosed is hopcalite, while the H2 catalyst is Pd supported on activated alumina. A third common strategy for producing UHP N2 in the prior art is the treatment of the cryogenically separated N2 product to remove H2, CO, O2 and other contaminants penetrating the prepurifier and air separation unit. U.S. Pat. No. 4,579,723 discloses the use of a Ni or Cu supported catalyst or getter to oxidize the contaminants to CO2 and H2O, which are subsequently removed in an adsorber. European patent EP 0 835 687 teaches regeneration of catalyst beds with a high temperature N2 purge. Adsorption of CO has been applied in the prior art predominantly for recovery of CO in bulk separations, e.g. in cases where the concentration (partial pressure) of CO is relatively high (typically=1%) and where CO is the more strongly adsorbed component in the gas mixture. Cuprous compounds, either in cationic form in zeolites or dispersed on a porous support, have been widely applied in the recovery of CO from gas mixtures containing CO and N2, methane (CH4), H2 and/or CO2. Materials containing copper in the single oxidation state (denoted as Cu+, Cu(I) or cuprous) display high CO adsorption capacity, while adsorbents containing Cu(II) do not. Adsorbents are commonly synthesized, treated or modified with a Cu(II) compound and then subsequently exposed to a reducing agent such as H2 at elevated temperature to convert the Cu(II) to Cu(I). Xie et al. (“Highly Efficient Adsorbent for Separation of Carbon Monoxide,” Fundamentals of Adsorption, Proc. IVth Int. Conf. On Fundamentals of Adsorption, Kyoto, May 17-22, 1992, pp. 737-741) describes an adsorbent formed by dispersing CuCl on a zeolite support by mixing the dry powders at elevated temperature. High purity CO separated to high recovery is demonstrated for feed streams containing 9.0% CO/91% N2 and 30.7% CO/65.3% H2/4% CH4. U.S. Pat. No. 4,917,711 discloses adsorbents and processes utilizing supported CuCl. U.S. Pat. No. 5,531,809 discloses VSA processes using CuCl dispersed on alumina for recovery of CO from synthesis gas exiting a steam-methane reformer. G. K. Pearce (“The Industrial Practice of Adsorption,” in: Separation of Gases, 5th BOC Priestley Conf., Birmingham, UK Sep. 19-21, 1989, Spec. Publ. No. 80, Royal Soc. Of Chemistry, Cambridge, 1990) provides a description on the use of Cu(I)Y zeolite for the recovery of CO from CO/N2 and CO/H2 feed streams containing percentage (%) levels of CO. U.S. Pat. No. 4,473,276 discloses Cu(I)Y and Cu-Mordenite along with other exchanged zeolites having a silica to alumina ratio (SiO2/Al2O3)=10 for the recovery of CO. U.S. Pat. No. 4,019,879 discloses recovery of CO from streams containing H2O and/or CO2 using Cu+ containing zeolites with 20=SiO2/Al2O3=200, e.g. ZSM-5, -8, -11, etc. Another class of adsorbents having potential for CO adsorption is one in which the materials contain silver (Ag+). Y. Huang (“Adsorption in AgX and AgY Zeolites by Carbon Monoxide and Other Simple Molecules,” J. Catal., 32, pp. 482-491, 1974) provides CO and N2 isotherms for AgX and AgY zeolites to partial pressures only as low as 0.1 to 1.0 torr for the lowest temperature (0° C. and 25° C.) isotherms. The adsorption capacity for CO is significantly greater than that of N2 at 25° C. and 100 torr. U.S. Pat. No. 4,743,276 discloses mordenite, A, Y and X type zeolites exchanged with various amounts of Ag for the bulk separation (recovery) of CO from refinery and petro-chemical off-gases. U.S. Pat. No. 4,019,880 relates to the recovery of CO from gas streams containing also H2O and/or CO2 using Ag exchanged zeolites with 20=SiO2/Al2O3=200, e.g. ZSM-5, -8, -11, etc. The invention applies to feed streams containing at least 10 ppm CO at temperatures 0° C.-300° C. The claimed process results in a CO-depleted effluent, e.g. air. U.S. Pat. No. 4,944,273 discloses zeolites with 1=Si/Al=100 and doped with Ca, Co, Ni, Fe, Cu, Ag, Pt or Ru for adsorption of oxides of nitrogen (NOx) and CO as part of NOx and CO sensors, particularly in exhaust gases of automotive vehicles. U.S. Pat. No. 3,789,106 discloses that mordenite charged with copper is effective in removing CO from H2 at CO partial pressure below 3 mmHg. The effectiveness was determined by subjecting the adsorbent to CO concentrations greater than or equal to 100 ppm and measuring capacity at saturation. The above prior art relating to adsorption of CO is almost totally silent with respect to purification of CO from mixed gas streams, particularly those containing less than 10 ppm CO in O2 and N2. OBJECTS OF THE INVENTION It is therefore an object of the invention to provide an improved method for the removal of trace amounts of CO and at least one of H2, H2O, CO2, hydrocarbons and N2O from feed gas streams, preferably air. SUMMARY OF THE INVENTION The invention relates to the removal of CO and optionally H2 from air and/or other gases or gas mixtures using a combination of adsorptive separation and catalytic conversion, and provides unexpected savings in capital and power costs over existing technologies. In one preferred embodiment, at least 90% of each of CO2 and H2O are first removed from the feed gas (preferably air) to produce a CO2 and H2O depleted gas. In a particularly preferred embodiment, the CO2 and H2O depleted gas contains less than 1.0 ppm (more preferably less than 0.25 ppm) CO2 and less than 1.0 ppm (more preferably less than 0.10 ppm) H2O. A substantial amount of CO is then removed from the CO2 and H2O depleted gas through the use of a CO adsorbent to produce a CO depleted gas containing, in a preferred embodiment, less than 100 ppb CO, more preferably less than 5 ppb CO. Optionally H2 and any remaining CO may then be removed using a catalyst. Because of this unique combination of catalysis and adsorption, the process of the present invention provides surprisingly superior CO and H2 removal efficiency over the prior art processes. A preferred apparatus for the practice of the invention comprises an adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm. The apparatus comprises at least one adsorption vessel containing a CO adsorbent layer, the CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein a) when the feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, CH4 and mixtures thereof, the adsorbent is ion exchanged with a Group IB element, and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, Cu-clinoptilolite, AgA zeolite and AgY zeolite, and b) when the feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, the apparatus is preferably an air prepurifier, and the adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+, and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, AgA zeolite and AgY zeolite. In a further embodiment the apparatus contains two or more adsorption vessels that are selected from the group consisting of vertical flow vessels, horizontal flow vessels, lateral flow vessels or radial flow vessels. In a further embodiment the adsorption apparatus further contain an adsorbent, preferably one or more of alumina or NaX zeolite, selective for the adsorption of water that is upstream of said CO adsorbent layer. In a further embodiment the apparatus further contains a catalyst layer, preferably a metal supported catalyst comprising one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide, for the catalytic oxidation of H2 to H2O that is downstream of said CO adsorbent layer. In a further embodiment the apparatus further contains an auxiliary adsorbent, preferably one or more of alumina or NaX, for the removal of water that is downstream of said catalyst layer. In a further embodiment the ΔCO working capacity is greater than or equal to 0.03 mmol/g. In a further embodiment, the apparatus further contains one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein the additional adsorbents preferably are selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof, and are located downstream of the catalyst layer. In a further embodiment the CO adsorbent has a ΔCO/ΔN2 separation factor of greater than or equal to 1×10−3. In a further embodiment the CO adsorbent is AgX having at least 50%, preferably 100% of its cations associated with Ag. A preferred process for the practice of the invention comprises a process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, or even less than 1.0 ppm or 0.5 ppm. The process, which is preferably an air prepurification process, comprises contacting the feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g, preferably greater than or equal to 0.03 mmol/g, to produce a CO depleted gas stream, that may be recovered; and wherein a) when the feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, H2, CH4 and mixtures thereof, the adsorbent is a zeolite exchanged with a Group IB element and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, Cu-clinoptilolite, AgA zeolite and AgY zeolite, and b) when the feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, the adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+, and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, AgA zeolite and AgY zeolite. In a further embodiment, the process comprises recovering the CO depleted gas stream, wherein CO is present in the CO depleted gas stream at a concentration of less than 100 ppb, preferably less than 5 ppb, most preferably less than 1 ppb. In a further embodiment, said feed gas further comprises water (H2O), and the process further comprises contacting the feed stream with a water selective adsorbent, preferably alumina or NaX, that is located upstream of said CO adsorbent. In a further embodiment, the feed gas further comprises hydrogen, and the process further comprises contacting the CO depleted feed stream with a catalyst layer that is preferably a metal supported catalyst comprising one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide, for the catalytic oxidation of H2 to H2O to produce a H2 depleted and H2O enriched gas, and wherein the catalyst layer is located downstream of said CO adsorbent layer. The hydrogen depleted gas preferably contains less than 100 ppb hydrogen, and more preferably less than 5 ppb hydrogen. In another embodiment, the process further comprises the step of contacting the catalytically produced H2O enriched gas with an adsorbent for the removal of water (preferably alumina or NaX) that is located downstream of said catalyst layer to produce a gas that is depleted in CO, H2 and H2O. In another embodiment the CO adsorbent has aΔCO/AN2 separation factor that is greater than or equal to 1×10−3, preferably greater than or equal to 1×10−2. In another embodiment, the process further comprises passing said feed gas over a) at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2, b) a catalyst layer for the catalytic conversion of H2 to H2O that is downstream of said CO adsorbent layer; and c) one or more additional adsorbents, preferably selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof, for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. In an alternative embodiment, the process is selected from the group consisting of pressure swing adsorption, temperature swing adsorption, or a combination thereof, and the process takes place in an adsorber vessel selected from a vertical flow vessel, a horizontal flow vessel or a radial flow vessel. In a preferred embodiment the adsorption step of the process is operated at a temperature of zero to fifty degrees Celsius. In a preferred process the CO adsorbent is AgX having at least 50%, more preferably 100% of its cations associated with Ag. In a preferred embodiment the feed stream contains air, and the CO depleted gas stream is passed to a cryogenic distillation column. In an alternative embodiment the CO partial pressure in the feed stream is less than 0.1 mmHg, or even less than 0.005 mmHg. An alternative embodiment relates to a process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and hydrogen, the process comprising contacting the feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein the adsorbent is a zeolite exchanged with a Group IB element. In a preferred embodiment, the invention comprises an adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, and hydrogen, the apparatus comprising at least one adsorption vessel containing a CO adsorbent layer having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein said adsorbent is a zeolite exchanged with a Group IB element. In a particularly preferred embodiment, the invention comprises an air prepurification adsorption apparatus for the removal of CO from an air feed stream containing CO in an amount of less than 50 ppm, the apparatus comprising at least one adsorption vessel containing a CO adsorbent layer having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein the adsorbent is a zeolite (preferably AgX), having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+. In a preferred embodiment, the air prepurification apparatus further comprises at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2. In a preferred embodiment, the prepurification apparatus further comprises a catalyst layer for the catalytic conversion of H2 to H2O that is downstream of the CO adsorbent layer; and one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. In an alternative embodiment, the invention comprises a process for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and air said process comprising contacting said feed stream in an adsorber vessel with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein the adsorbent is a zeolite having a SiO2/Al2O3 ratio of <20, and is ion-exchanged with a Ag+ or Au+, preferably AgX. This process may further comprise a) passing the feed stream over at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H2O and CO2 to produce a H2O and or CO2 depleted feed stream b) passing the feed stream over a catalyst layer that is downstream of said CO adsorbent layer for the catalytic conversion of H2 to H2O layer and one or more additional adsorbents for the adsorption of one or more of H2O, CO2, N2O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer to produce a feed stream that is depleted in CO, H2 and one or more of H2O, CO2, N2O and hydrocarbons, and, optionally, passing the depleted feed stream to a cryogenic distillation column for the separation of air. Combinations of any of the above embodiments are contemplated to be within the scope of the invention. BRIEF DESCRIPTION OF THE DRAWING Other objects, features and advantages will occur to those skilled in the art from the following description of preferred embodiment(s) and the accompanying drawings, in which: FIG. 1 is a schematic diagram of a breakthrough test apparatus; FIG. 2 is a graph of CO and H2 breakthrough curves for the AgX adsorbent of Table II; FIGS. 3-6 are schematic diagrams of preferred adsorbent arrangements in an adsorbent vessel/bed. FIG. 7 is a schematic diagram of a prepurification apparatus useful for carrying out the invention. DETAILED DESCRIPTION OF THE INVENTION The invention relates to the removal of CO and optionally H2 from a feed gas containing ppm levels of CO and ppm levels of H2. The invention is particularly applicable to removing CO from feed gas streams having 1 ppm or less CO therein; in particular, feed gas streams having CO partial pressures of less than 0.1 mmHg or even as low as 0.005 mmHg or lower. The feed gas is typically air, and may also contain other contaminants including at least one of CO2, H2O, N2O and hydrocarbons such as acetylene. The removal of these components typically takes place in a prepurification process prior to air separation by cryogenic means, though the invention may also be applied to remove CO and, optionally hydrogen impurities after cryogenic distillation of air. The invention may be practiced with feed gas streams containing as much as 50 ppm CO and 10 ppm H2 in the feed, though feed gas streams containing less than 1 ppm or even less than 0.5 ppm CO and 1 ppm or even less than 0.5 ppm H2 may also be used. Practice of the invention with such feed streams can produce a product gas stream containing less than 5 ppb CO and less than 5 ppb H2, though gas streams containing 1 ppb CO and 1 ppb H2 can also be achieved. The use of a CO adsorbent followed by a H2 catalyst in accordance with a preferred embodiment of the invention reduces the H2 catalyst requirement, eliminates the need for high temperature activation, maximally protects the H2 catalyst from poisoning by locating it at the clean end of the adsorber and reduces capital and operation costs as compared to existing prepurification techniques. The result is that the effluent from the inventive adsorber/adsorption process (e.g. the feed to a cryogenic distillation column (or “cold box”) of an air separation unit (ASU)) contains less than 5 parts per billion (ppb) CO and less than 5 ppb H2. In one preferred embodiment of the invention, an adsorbent bed is configured to first remove from a feed stream containing CO, H2, CO2 and H2O impurities, substantially all of the H2O and optionally all of the CO2 prior to removing CO on a CO adsorbent. The CO2, H2O and CO depleted gas is then passed through a catalyst bed to remove any remaining CO and the H2. The thus purified gas is then passed to an ASU to produce UHP nitrogen. For the purpose of this disclosure, a “high purity” gas means a gas having individual contaminant levels of less than about 100 ppb (parts per billion) and an “ultra high purity” (UHP) gas means a gas having individual contaminant levels less than about 10 ppb, preferably less than about 5 ppb and most preferably less than 1 ppb, depending upon the intended application of the gas. Thus the present invention produces a gas depleted of H2 and CO in a two step process: 1) Removal of CO by adsorption from a feed stream containing trace amounts of CO at temperatures in the range of 0 to 50 degrees Celsius (C.) on a suitable adsorbent in the presence of high N2 and/or O2 concentrations to produce an effluent gas containing less than 5 ppb CO; and 2) optional removal of trace amounts of H2 from a feed stream in the presence of high N2 and/or O2 concentrations by a combination of adsorption and/or absorption and/or catalysis at temperatures in the range of 0 to 50 degrees C. to produce an effluent gas containing less than 5 ppb H2. In accordance with one embodiment of the invention, an appropriate CO adsorbent is selected that has sufficient ΔCO working capacity to remove most or all of the CO from the feed stream. An ideal CO adsorbent would have good CO loading (ΔCO or working capacity) in the presence of high N2 and/or O2 concentrations. It is also desirable to have low N2 loading to maximize CO selectivity and to minimize the cooling effect of N2 desorption during depressurization. In a preferred embodiment the adsorbent also has a high ΔCO/AN2 working separation factor at the local stream conditions. One method for estimating adsorbent performance is by determining the working capacity of each of the primary adsorbates, i.e. N2 and CO. This is the methodology applied in the present invention. The separation factor α, as defined below, is a preferred way to evaluate the adsorbent effectiveness. This methodology is discussed in detail in U.S. Pat. No. 6,152,991, the contents of which are herein incorporated by reference. Separation factor α is defined as follows: α = Δ ⁢ ⁢ CO Δ ⁢ ⁢ N 2 = w CO ⁡ ( y , p , T ) ads - w CO ⁡ ( y , p , T ) des w N 2 ⁡ ( y , p , T ) ads - w N 2 ⁡ ( y , p , T ) des ( 1 ) where separation factor α is defined as the ratio of the working capacities. The numerator in this equation is the working capacity of CO, which is equal to the difference in loading w between adsorption and desorption conditions. The adsorption and desorption conditions are characterized by composition y, pressure p and temperature T. In TSA air prepurification, maximum regeneration temperatures may vary from about 100° C. to about 350° C. As a result, it is expected that the adsorbates (particularly atmospheric gases) will be completely thermally desorbed from the adsorbents. Under such conditions, Equation (1) can be simplified as follows: α = Δ ⁢ ⁢ CO Δ ⁢ ⁢ N 2 = w CO ⁡ ( y , p , T ) ads w N 2 ⁡ ( y , p , T ) ads ( 2 ) When a contaminant is removed in a shallow adsorbent layer in a TSA process and significant resistance to mass transfer exists, the selectivity is redefined according to Equation (3): Δ ⁢ ⁢ X CO Δ ⁢ ⁢ X N 2 = m in w s ⁢ ∫ 0 t b ⁢ ( y in - y out ) ⁢ ⅆ t X N 2 ⁡ ( y , P , T ) ADS ( 3 ) The numerator in Equation (3) represents the working capacity of the adsorbent for the contaminant. min represents the molar feed flow into the bed, yin and yout are the inlet and outlet mole fractions of the minor component, respectively. ws is the mass of adsorbent and tb is the breakthrough time corresponding to a predetermined concentration. The denominator is the equilibrium capacity of the major component at the conditions at the end of the adsorption step, i.e. assuming complete desorption of all components. Application of Equation (3) is preferred when the length of the mass transfer zone is an appreciable fraction (e.g. more than about 10%) of the overall depth of the adsorbent layer. This method is preferred over other methods because the working capacities are determined at the partial pressure of each individual component at the relevant process conditions, e.g. in the case of prepurification the CO and N2 partial pressures in the feed air are typically <0.1 mmHg and >1000 mmHg, respectively. Coadsorption effects are also incorporated into the determination of the loading. Since in air prepurification the feed concentration of N2O is overwhelming compared to CO, the coadsorption effect of CO upon N2 is negligible. Thus, the denominator of Equation (2) and Equation (3) may be obtained directly from the measured pure-component N2 isotherm. Conversely, the coadsorption of N2 would have a very significant effect upon the adsorption of CO. If accurate low concentration pure-component isotherm data for CO is available or attainable, then Equation (2) may be applied to assess equilibrium working capacity and selectivity. However, it is preferred to determine the working capacity for CO directly under N2 coadsorption conditions and with mass transfer effects included. This may be done using a breakthrough test method, which is well known to those skilled in the art. Breakthrough tests provide the equilibrium capacity of a component at saturation, and the breakthrough capacity and time at some defined breakthrough level, e.g. 100 ppb. Thus, the ΔCO working capacity and selectivity are preferably determined using the terms of Equation (3). Since the coadsorption of nitrogen is incorporated into the ΔCO working capacity, ΔCO determined by the breakthrough method (numerator of Equation (3)) is the dominant factor in selecting an appropriate Co adsorbent for the purpose of the invention. One skilled in the art will appreciate that adsorbents satisfying the criteria for acceptable working characteristics for CO relative to N2 will perform even more favorably in other gas mixtures where the bulk component adsorbs less strongly than N2. Examples of such CO-containing gas mixtures include those with one or more of He, H2, Ar, Ne, Xe, Kr, O2 and CH4, and the invention may also be applied to the separation of CO from these gases or gas mixtures. In order to evaluate the potential effectiveness of CO adsorbents at conditions typical of air separation processes, CO and/or H2 breakthrough tests were performed. Breakthrough tests were performed at 7.9 bara (114.7 psia), either 10° C. or 27° C. and an inlet gas flowrate of approximately 21 slpm (78.7 mol/m2 s) using an adsorption column length of 5.9 cm or 22.9 cm. Variations to these conditions are noted in the examples. The feed conditions are representative of conditions at the inlet of an air prepurifier for a typical cryogenic air separation plant. Complete breakthrough curves were generated for CO and/or H2 in some of the tests, while only partial breakthroughs were determined in those cases using high capacity materials. Initial breakthrough was established at 100 ppb CO and 20 ppb H2. Initial breakthrough and/or saturation loading (capacity in mmol/g) were then determined according to the mass balances as indicated in the numerator of Equation (3). CO and H2 loading determined at the initial breakthrough represent a dynamic or working capacity—incorporating both coadsorption and mass transfer effects. Breakthrough tests were conducted in the following manner using an apparatus for which the key elements are shown in the schematic of FIG. 1. Challenge gases from cylinders (3,4) containing a mixture of the contaminant gas in N2 were metered through flow controllers (7,8) (at flow rates on the order of 0-5 standard liters per minute (slpm)) where they were mixed in a gas mixer (9) with high purity diluents N2 or helium (He). In some cases the diluent was synthetic air wherein O2 from source 2 was combined with N2 from source 1. This diluent was provided at a prescribed flowrate (e.g. 0-30 slpm) through flow controllers (5,6) to achieve the desired feed concentration of contaminant(s). This mixed challenge gas was then fed through a heat exchange loop and to the test bed 10 containing the adsorbent. Both the test bed 10 and heat exchange loop were located within a thermal bath (not shown), the temperature of which was controlled via a water chiller and thermocouples. Temperature control systems are well known in the art and typically consist of a heat exchange loop, thermal bath, water chiller and thermocouples. Any number of variations of the temperature control system can be effectively applied to maintain the test bed at a constant temperature as would be readily familiar to one of ordinary skill in the art. The gas pressure during the test was controlled through a control valve/pressure controller 11. A portion of the effluent was passed through valve 12 to one or more analyzers 13 to monitor the breakthrough concentrations of CO and/or H2 as a function of time. A Servomex 4100 Gas Purity Analyzer equipped with both CO and CO2 sensors was used in Example 1. In Examples 2-4 a Trace Analytical (RGA5) Analyzer was used for trace CO and H2 measurement. All zeolites were obtained from commercial sources (identified below), but some were further modified by the inventors by ion exchange. Mordenite and Type Y zeolites were extrudates, Type X and Type A zeolites were beads and clinoptilolite and chabazite were granular for the examples of this invention. A laboratory ion-exchange column was used to create highly exchanged zeolites. In the column procedure, the zeolite was packed inside the column and ion exchange solution was pumped upwards through the bed at a flow rate of 0.5 ml/minute. The column was heated between 70-90° C. to promote exchange. At least a ten-fold excess of solution was used to ensure that high levels of ion exchange are obtained. The product was collected by filtration and washed thoroughly with deionized water. Powder X-ray diffraction and inductively coupled plasma (ICP) chemical analysis were used to verify the integrity of the samples as well as determine the level of ion exchange. For the Ag, Cu and zinc (Zn) samples, a 0.1 molar (M) solution of the respective nitrate salt was used. For sodium (Na) exchange, a 1.0M sodium chloride salt solution was used. The zeolites were typically in their Na exchanged forms prior to exchange with Ag, Cu or Zn. For clinoptilolite, a TSM-140 sample was selected and exchanged first with Na before Ag, Cu or Zn was introduced. Zeolites 13X HP, 13X APG and Na mordenite were obtained from UOP and zeolite 4A was purchased from Aldrich. For lower exchange levels of Ag on 13X HP (e.g. <85%), a batch procedure was used. In the batch process the zeolite was immersed in a fixed volume of solution as opposed to having fresh solution pumped into a column on a regular basis. Silver nitrate solution having a concentration of 0.025-0.1M was used. The zeolites were stirred in a solution of silver nitrate at 50-90° C. The solution strength was chosen to reflect the level of exchange desired. After a period of 6-8 hours stirring at temperature, the solution was either refreshed up to a total of three times, or the sample was collected by filtration and washed thoroughly with deionised water. Refreshing the solution increased the exchange level. Powder X-ray diffraction and ICP chemical analyses were performed to examine the crystallinity and ion exchange level of the product samples. Methods for ion exchange of zeolites are well known to those of ordinary skill in the art. The column and batch methods described above are in no way limiting to the invention. Different procedures may be used in order to achieve desired exchange levels for the cations and zeolites in accordance with the present invention. The invention will now be described with reference to the following comparative examples. These examples are not intended to limit the scope of the invention in any way. EXAMPLE 1 Outside the Scope of the Invention The natural adsorbents (clinoptilolite and chabazite) were obtained from Steelhead Specialty Minerals, WA. Synthetic zeolites were obtained from various manufacturers: Zeolyst (HZSM5), Zeochem (CaX) and UOP (13X, LiX, 5AMG). All of the adsorbents were thermally activated at 350° C., 1.0 bara pressure and under N2 purge for approximately 16 hours before each test. After regeneration the adsorbents were allowed to cool to 27° C. This group of adsorbents presents a cross section of adsorbent characteristics known to effect adsorption properties, e.g. Si/Al, micropore channel opening size, zeolite structure type, number and type of cations, etc. Breakthrough tests were performed at the conditions described above to saturation using 1.0 ppm CO in N2 or He. Breakthrough time was determined at 100 ppb CO. The results are summarized in Table I. TABLE I Flow T yco Bed tb(2) Xco(3) Adsorbent slpm ?C Carrier(1) ppm cm min mmol/g Clinoptilolite 20.4 27 N2 1.0 22.9 <2 1.4 × 10−5 TSM-140 21 27 He 1.0 22.9 30 1.2 × 10−3 Chabazite 21 27 N2 1.0 22.9 <2 2.2 × 10−5 TSM-300 21 27 He 1.0 22.9 114 4.5 × 10−3 LiX 21 27 N2 1.0 22.9 <2 2.5 × 10−5 (SiO2/ Al2O3 = 2.0) 5A MG 5.5 10 N2 1.0 22.9 <6 3.1 × 10−5 CaX (Z100) 5.5 10 N2 1.0 22.9 <4 3.9 × 10−5 HZSM5 21 27 air 2.0 5.9 <2 — (CBV3024E) (1)typical H2 concentrations in carrier gases .0.25 ppm (2)breakthrough determined at yco = 100 ppb (3)equilibrium saturation capacity of CO The competitive effect of N2 upon CO saturation capacity (XCO) is evident in that XCO for CO/N2 feed was reduced by a factor of 100 or more compared to that for CO/He feed for the small pore natural zeolites. Breakthrough times of CO in N2 were reduced by factors of 15 to more than 50 compared to CO in He. The high partial pressure of N2 relative to that of CO is a critical factor in determining adsorbent effectiveness in CO removal. All of the adsorbents in Table I have CO/N2 breakthrough times of only a few minutes. Although breakthrough time can be extended with longer adsorbent beds, none of these adsorbents is likely to provide a practical solution for air prepurifiers with adsorption cycle times of one hour or more. N2 isotherms were measured at 27° C. using well known gravimetric balance methods for chabazite and clinoptilolite. The N2 capacity from the isotherms and the CO saturation capacity from Table I were combined in Equation 2 to result in equilibrium separation factors for the adsorbents in Table I (ΔCO/ΔN2)<2×10−5. EXAMPLE 2 Several zeolites containing exchanged Ag, Cu and Zn cations were tested as described above to evaluate the working CO capacity. AgX (P/N 38,228-0) was obtained from Aldrich, while clinoptilolite (TSM-140) and mordenite (large-pore from UOP) were exchanged in small-scale laboratory columns. The extent of exchange was determined by inductively coupled plasma (ICP) analysis. Exchanged samples were air-dried and then activated overnight in a dry N2 purge at 350° C. Breakthrough tests were conducted using a 5.9 cm long column filled with adsorbent and subjected to 2.0 ppm CO in synthetic air (79% N2/21% O2) at 27° C. and 7.9 bar, flowing at a rate of approximately 21 slpm (78.7 mol/m2s). The amount of H2 in the feed for each test is given in Table II along with the results of the breakthrough tests. The breakthrough time (tb) and the working capacity (XCO) were determined at a CO breakthrough concentration of 100 ppb. TABLE II Xco % CO Size @yco = removal % US YH2 100 ppb tb @yco = Adsorbent exch. mesh ppm mmol/g hr 100 ppb AgX 100 10 × 14 3.0 0.052 5.4 98.8 Ag-Mor 89 1.8 mm* 3.0 0.034 3.2 98.3 Cu- 100 8 × 14 0.5 0.037 3.0 99.3 clinoptilolite Zn- 86 8 × 14 0.6 — <0.2 — clinoptilolite Ag- 89 8 × 14 0.4 — <0.5 — clinoptilolite *extrudate diameter AgX, Ag-mordenite and Cu-clinoptilolite all display CO working capacities in excess of 0.03 mmol/g, and consequently meet the criteria of the invention. Zn-clinoptilolite and Ag-clinoptilolite had working capacities less than 0.01 mmol/g and consequently are outside the scope of the invention. Conservatively compared to the CO saturation capacities in Table I, the CO working capacities in Table II (including dynamic effects) for these adsorbents are more than 1000 times greater than those in Table I. Furthermore, breakthrough times are several hours for relatively short beds, i.e. the resultant CO working capacity allows the adsorbent to be easily integrated with current prepurifier cycles and with a minimum of additional adsorbent. Cu-, Zn- and Ag-exchanged clinoptilolite show little or no removal capacity for H2. Although H2 breaks through almost immediately in AgX and Ag-mordenite, some modest holdup of H2 is evident as can be seen from FIG. 2. FIG. 2 gives the breakthrough history for both CO and H2 using AgX (Aldrich P/N 38,228-0). Although a CO breakthrough concentration of 100 ppb was chosen for the purpose of adsorbent evaluation, one skilled in the art will appreciate that the amount of CO impurity in the product can be adjusted by selecting either a shorter adsorption step or by increasing the amount of adsorbent. Beds were regenerated after each breakthrough test in air at 200° C. for 3.0 hr followed by a ambient temperature purge in dry N2 for 3.0 hr, all at a flow of 2.2 slpm and a pressure of about 1.7 bar (25 psia). The results in FIG. 2 are for the tenth breakthrough of this bed. There was no noticeable deterioration in CO removal capacity with cycling—even in the presence of the strong H2 reducing agent. Desorption was monitored after the sixth breakthrough by purging the bed with N2 at 27° C. and 50° C. prior to the standard regeneration. Only CO was detected in the effluent, and more than 87% of the adsorbed CO was desorbed. The remaining CO was desorbed in the normal regeneration procedure. N2 isotherms were measured for AgX (Aldrich P/N 38,228-0) at 0° C. and 27° C. as described above. The N2 capacity at 27° C. at a N2 partial pressure of 6.25 bar was determined as 0.81 mmol/g. The corresponding Co partial pressure for the test stream of Table II is 1.2×10−2 mmHg. Using Equation 3 and the results in Table II, the working separation factor ΔCO/ΔN2=6.4×10−2. The results in Table II for Cu-clinoptilolite are for the first breakthrough after activation. After regeneration following the conditions cited above, the performance was significantly degraded in the second breakthrough. The performance in Table II was restored after re-activating in N2 at 350° C. It is believed that regeneration in air at elevated temperature resulted in the oxidation of Cu+ to Cu++. Reactivation in N2 returned the Cu to the lower oxidation state Cu+. Thus, this adsorbent may be more effectively applied in an alternative embodiment of the invention which applies the inventive concept to post-purification of cryogenically separated N2 where little or no O2 is present. EXAMPLE 3 Samples of commercially available AgX (Ag400B3), Ag-mordenite (Ag900E16) and AgY (Ag600E16) were obtained from C*CHEM, A Division of Molecular Products, Inc., Lafayette, Colo. AgX was also prepared by exchanging 13X HP zeolite with Ag to various Ag-exchange levels (designated AgX (HP)). AgA was prepared by exchanging 4A zeolite with Ag. These materials and the corresponding Ag exchange levels are given in Table III along with the breakthrough time and CO working capacity. TABLE III Ag- Xco exch. Size @yco = 100 ppb tb % CO Adsorbent % US Mesh mmol/g hr removal AgX 100 10 × 18 0.051 5.5 99.0 (Ag400B3) AgX (HP) 95 10 × 18 0.13 13.3 99.1 AgA 94 8 × 12 0.019 2.2 98.4 Ag-Mor 40 2.0 mm* 0.0096 0.85 97.9 AgY 61 1.7 mm* 0.018 1.4 98.8 *extrudate diameter Breakthrough tests were performed at the same conditions as those of Example 2, except that 3.0 ppm H2 was present in the feed for all tests. The results of Table III are for the first breakthrough after activation. The AgX (Ag400B3) performance agrees well with that of AgX in Table II. Although the AgX (HP) appears to have a significantly improved CO working capacity over the commercial AgX, much of this advantage was lost after several breakthrough/regeneration cycles. After the fourth cycle, the breakthrough time for AgX (HP) was reduced to 7.3 hr and the CO working capacity fell to 0.073 mmol/g. The amount of degradation, however, was rapidly decreasing and a final working capacity greater than that of AgX (Ag400B3) was projected. Such improvement may be the result of either the base zeolite starting material (13X HP), macropore geometry of the exchanged zeolite and/or differences in the final state and/or location of the silver cation in the zeolite. Different Ag-exchange levels varying from 10% to 100% were prepared using the 13XHP base material. CO working capacity was found to be approximately linearly proportional to Ag-exchange level. Thus, higher Ag-exchange level is preferred for the adsorption of CO, with 100% exchange being most preferred. The commercial AgY and Ag-mordenite adsorbents performed much better than conventional zeolites in CO adsorption, but were less effective than AgX. The significantly different CO working capacity for the Ag-mordenites in Tables II and III are consistent with the higher Ag-exchange level of the laboratory prepared Ag-mordenite in Table II, with the lower level of exchanged material (in Table III) having a ΔCO working capacity of <0.01 mmol/g, and therefore being outside the scope of the invention. EXAMPLE 4 In this example, a bed is constructed from a 7.6 cm layer of the AgX of Example 2 followed by a 15.2 cm layer of palladium supported on porous alumina (Pd/Al2O3) oxidation catalyst typical of the prior art. A second bed was constructed of the same overall length (22.9 cm) using only the Pd/Al2O3 oxidation catalyst. The oxidation catalyst (E221, 0.5 wt % Pd supported on the surface of activated alumina beads) was obtained from Degussa Corporation. Breakthrough tests were performed at the same conditions as those in Example 3. The results are compared in Table IV. Breakthrough time of H2 were recorded at 1 ppb, 5 ppb and 20 ppb. TABLE IV tb XH2 (H2) mmol/g hr tb tb @ yH2 = yH2 = (CO) (CO2) yH2 = Bed yH2 = 1 ppb 5 ppb 20 ppb hr hr 20 ppb 7.6 cm AgX + 21.3 23.2 26.5 >30.7 17.3 0.218 15.2 cm 0.5% PdAl2O3 22.9 cm 3.9 4.9 13.0 >21.5 3.0 0.072 0.5% PdAl2O3 Surprisingly, replacing one third of the catalyst bed with AgX for adsorption of CO resulted in H2 breakthrough times of two to five times greater than for the catalyst used alone. The effective capacity of the catalyst at 20 ppb H2 breakthrough was more than tripled when CO was removed prior to H2 oxidation. There was essentially no breakthrough of CO in either bed over the duration of the test, i.e. 30.7 hours (hr) for the layered bed and 21.5 hr for the catalyst only bed. Finally, the CO2 breakthrough time (at yCO2=100 ppb) was more than five times greater when CO was adsorbed in AgX. As is evident from the information above, the use of AgX to replace part of the CO/H2 oxidation catalyst results in unexpected advantages in purifying the stream of CO and H2 while minimizing CO2 as an oxidation by-product. Based upon the examples above, a preferred CO adsorbent for the practice of the invention has a ΔCO working capacity ≧0.01 mmol/g, preferably ≧0.03 mmol/g. In a more preferred embodiment, the CO adsorbent has a ΔCO/ΔN2 separation factor α, as given by Equation 3, equal to or greater than 1×10−3, preferably greater than 1×10−2. In the case of small pore zeolites (e.g. natural zeolites clinoptilolite, chabazite, etc.), the pore opening or kinetic diameter of the zeolite “window” must be larger than the kinetic diameter of the CO molecule (0.376 nm). Zeolites exchanged with Group IB cations (Cu, Ag, Au (gold)) attaining an oxidation state +1 are preferred adsorbents for CO for the application of the invention. Ag-exchanged zeolites (>50% exchange) are preferred and highly exchanged AgX (>85% exchange) are most preferred. While not disclosed above in the examples, gold is believed to be useful in the practice of the invention given its similarity in chemical structure to Cu and Ag. Since the Group IB metals acting as charge balancing cations in exchanged zeolites provide enhanced CO adsorption capacity, zeolites requiring a higher number of charge balancing cations are preferred in the practice of the invention. Such zeolites are characterized by a SiO2/Al2O3 ratio of <20. Using the method of this invention, a TSA adsorber and system can be designed for the reduction of the concentrations of CO and, optionally one or more H2O, CO2, and H2 from an incoming feed stream to levels of 100 ppb or less, or even 5 ppb or less in the effluent or product gas. Preferably the vessel is used in a TSA prepurifier for an air feed stream. One such vessel design is described below with reference to FIG. 3. The arrow (see also in FIGS. 4-6) indicates the direction of gas flow through the adsorber bed/vessel. A TSA prepurifier system incorporating such a vessel is disclosed below with reference to FIG. 7. Returning to FIG. 3, vessel 30 is shown. Vessel 30 contains a first layer of H2O adsorbent (31) such as alumina, silica gel or molecular sieve or mixture of these to remove substantially all of H2O entering the vessel. A second layer (32) of CO2 adsorbent such as 13X (NaX) or 5A or mixture of these is used to remove substantially all of CO2. The CO2 adsorbent layer can also remove any residual water remaining from the H2O adsorbent layer. A third layer (33) of CO adsorbent is placed downstream of the CO2 adsorbent. (By the term “downstream” we mean closer to the effluent or product end of the adsorber vessel.) A substantially H2O-free and CO2-free gas stream enters this CO adsorbent layer. The CO adsorbent layer can be designed to remove more than 50%, preferably more than 95% of the CO in the feed, thus producing a product gas containing <100 ppb CO and most preferably removing more than 99.8% of the CO in the feed, thus producing a product gas stream containing <5 ppb CO. A feed stream, which is substantially free of H2O, CO2 and CO, enters the catalyst layer 34. This catalyst removes H2 and any remaining small amounts of CO using a combination of adsorption and/or absorption and oxidation. One or more optional adsorbent layers 35 may be placed downstream of the CO adsorbent and catalyst layer to remove any CO2 and H2O oxidation products formed but not adsorbed in the catalyst. The optional layer(s) may also be selected to remove hydrocarbons, N2O and/or other trace contaminants. FIGS. 4-6 show alternative embodiments for integrating a CO adsorbent layer into an adsorber vessel for use in gas separations such as prepurification. Of course combinations of these embodiments are within the scope of the invention. The required adsorbent and catalyst layer thickness vary according to the process conditions of experienced by the adsorber during the separation process. These can vary widely from one system/process to another. The depth of the layers depicted in FIGS. 3-6 are not intended to imply or suggest any particular or relative amounts of adsorbent and/or catalyst. The most important process conditions are molar flux of air, cycle time, feed temperature and pressure and gas composition. A person ordinarily skilled in designing a prepurifier should, for example, be able to design the adsorbent and catalyst layers for each prepurifier according to the adsorbent/catalyst properties and the prepurifier process conditions. These methods are illustrated in detail in various textbooks such as Ruthven (Principles of Adsorption and Adsorption Processes, 1984). While FIG. 3 has been described above, FIGS. 4-6 will now be described below. With reference to FIG. 4, an embodiment is contemplated using vessel 40 for the removal of H2O (in layer 41), CO2 (in layer 42) and CO (in layer 43). In this embodiment a catalyst layer for H2 removal is not required. With reference to FIG. 5, a vessel 50 is shown wherein the H2O and CO2 adsorbents are combined in a single layer 51 either as a single adsorbent, a mixture of different adsorbents or through the use of composite adsorbents, followed by a CO adsorbent layer 52 and catalyst layer 53 for H2 removal. A further adsorbent layer (similar in function to layer 35 illustrated in FIG. 3) for clean-up and/or removal of other components (e.g. hydrocarbons) as with layer 35) may also be used, but is not shown. With reference to FIG. 6, vessel 60 contains a CO adsorbent layer 62 placed prior to the CO2 adsorbent layer 63, with both being downstream of H2O adsorbent layer 61. If removal of H2 is required an additional catalyst layer (not shown) may be used after the CO layer. Additional layers for clean-up and removal of other components (e.g. hydrocarbons) may be added. The catalyst used for the removal of H2 and remaining CO is a supported metal catalyst. One or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce may be deposited on a support chosen from alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide or calcium oxide. At least one of these metals is deposited on the support by techniques well known in the art. The most preferred catalyst for this invention is Pt and/or Pd supported on alumina. The optional adsorbent layer described above may be at least one of alumina, silica gel or zeolite. A zeolite layer is preferred. Most preferably, 13X (with 13X APG, available from UOP, Des Plaines, Ill. USA being most preferred) is used in this layer when CO2 and H2O oxidation products are to be removed. This optional H2O and CO2 removal layer can either be placed downstream of the catalyst layer or can be physically mixed with the catalyst layer. The adsorbent selected for the optional layer depends upon the contaminants to be removed, e.g. clinoptilolite for removal of trace N2O and CO2 as described in copending commonly assigned patent application PCT Serial No. O2/40591 “Method for Removal of N2O from Gaseous Streams”; and/or NaY, alumina or SELEXORB (a composite of NaY/alumina available from ALCOA, USA) for the removal of hydrocarbons. The invention offers the advantage that existing prepurifiers can be easily retrofitted by placing the CO adsorbent and optional catalyst at the downstream end of the prepurifier. The invention may also be applied to create “high purity” product when ultra high purity product is not required, i.e. when the standard purity of existing air separation plants is not sufficient, but electronics grade UHP is not necessary. In such applications, any of the embodiments, processes and configurations of the invention may be used to purify a feed mixture and remove CO and/or H2 contaminants to <100 ppb, individually. The process is carried out preferably in a cyclic process such as pressure swing adsorption (PSA), temperature swing adsorption (TSA), vacuum swing adsorption (VSA) or a combination of these. The process of the invention may be carried out in single or multiple adsorption vessels operating in a cyclic process that includes at least the steps of adsorption and regeneration. The adsorption step is carried out at pressure range of 1.0 to 25 bar and preferentially from about 3 to 15 bar. The temperature range during the adsorption step is −70° C. to 80° C. When a PSA process is used, the pressure during the regeneration step is in the range of about 0.20 to 5.0 bar, and preferably 1.0 to 2.0 bar. For a TSA process, regeneration is carried out at a temperature usually in the range of about 50° C. to 400° C., preferably between 100° C. to 300° C. One possible process is described herein with reference to FIG. 7. Feed air is compressed in compressor 70 and cooled by chilling means 71 prior to entering one of two adsorbers (76 and 77) where at least the contaminants H2O, CO2 and CO are removed from the air. The adsorbers 76 and 77 each have the same adsorbent bed configuration, which may, for example be one as described with reference to FIGS. 3-6 above. The purified air exits the adsorber and then enters the air separation unit (ASU) where it is then cryogenically separated into its major components N2 and O2. In special designs of the ASU, Ar, Kr and Xe may also be separated and recovered from the air. While one of the beds is adsorbing the contaminants from air, the other is being regenerated using purge gas. A dry, contaminant-free purge gas may be supplied from the product or waste stream from the ASU or from an independent source to desorb the adsorbed contaminants and thereby regenerate the adsorber and prepare it for the next adsorption step in the cycle. The purge gas may be N2, O2, a mixture of N2 and O2, air or any dry inert gas. In the case of thermal swing adsorption (TSA), the purge gas is first heated in heater 82 prior to being passed through the adsorber in a direction countercurrent to that of the feed flow in the adsorption step. TSA cycles may also include a pressure swing. When only pressure swing adsorption (PSA) is utilized, there is no heater. The operation of a typical TSA cycle is now described in reference to FIG. 7 for one adsorber 76. One skilled in the art will appreciate that the other adsorber vessel 77 will operate with the same cycle, only out of phase with the first adsorber in such a manner that purified air is continuously available to the ASU. This operation of this out of phase cycle is indicated with reference to the numbers in parentheses. Feed air is introduced to compressor 70 where it is pressurized. The heat of compression is removed in chilling means 71, e.g. a mechanical chiller or a combination of direct contact after-cooler and evaporative cooler. The pressurized, cool and H2O-saturated feed stream then enters adsorber 76 (77). Valve 72 (73) is open and valves 74 (75), 78 (79) and 80 (81) are closed as the adsorber vessel 76 (77) is pressurized. Once the adsorption pressure is reached, valve 78 (79) opens and purified product is directed to an ASU for cryogenic air separation. When the adsorber 76 (77) has completed the adsorption step, valves 78 (79) and 72 (73) are closed and valve 74 (75) is opened to blow down the adsorber 76 (77) to a lower pressure, typically near ambient pressure. Once depressurized, valve 80 (81) is opened and heated purge gas is introduced into the product end of the adsorber 76 (77). At some time during the purge cycle, the heater is turned off so that the purge gas cools the adsorber to near the feed temperature. One of ordinary skill in the art will further appreciate that the above description represents only an example of a typical prepurifier cycle, and there are many variations of such a typical cycle that may be used with the present invention. For example, PSA may be used alone wherein both the heater 82 and the chilling means 71 may be removed. Pressurization may be accomplished with product gas, feed gas or a combination of the two. Bed-to-bed equalization may also be used and a blend step may be incorporated where a freshly regenerated bed is brought on line in the adsorption step with another adsorber nearing completion of its adsorption step. Such a blend step serves to smooth out pressure disturbances due to bed switching and also to minimize any thermal disturbances caused when the regenerated bed is not completely cooled to the feed temperature. Furthermore, the invention may be practiced with a prepurifier cycle not limited to two adsorber beds. The method of the invention can be applied in horizontal, vertical or radial flow vessels. The method of regeneration depends upon the type of cyclic process. For a TSA process, regeneration of the adsorbent bed is achieved by passing heated gas countercurrently through the bed. Using the thermal pulse method, a cooling purge step follows the hot purge step. The heated regeneration gas may also be provided at a reduced pressure (relative to the feed) so that a combined TSA/PSA process is affected. This reduced pressure may be above or below ambient pressure. In cryogenic air separation processes, the regeneration gas is typically taken from the product or waste N2 or O2 streams. In some cases, passing an inert or weakly adsorbed purge gas countercurrently through the bed can further clean the adsorbent bed. In a PSA process, the purge step usually follows the countercurrent depressurization step. In case of a single vessel system, the purge gas can be introduced from a storage vessel, while for multiple bed system, purge gas can be obtained from another adsorber that is in the adsorption phase. The adsorption system can have more steps than the two basic fundamental steps of adsorption and desorption. For example, top to top equalization or bottom to bottom equalization can be used to conserve energy and increase recovery. In a preferred embodiment of the invention, as applied to air prepurification, essentially all of water vapor and substantially all of the CO2 are removed from air on at least one layer of activated alumina or zeolite, or by multiple layers of activated alumina and zeolite prior to passing the air stream through the CO adsorbent layer. Optionally, the CO selective adsorbent layer may be extended and used to remove part or all of the CO2 from air. Alternately, in an adsorption vessel, a first layer of adsorbent can be used to remove water vapor and a next layer comprised of a mixture of the CO selective adsorbent and 13X (or other zeolite) can be used to remove both CO2 and CO from the air. Such an adsorbent mixture may be composed of physically separate adsorbents or of different adsorbents bound together in the form of a composite. In applications requiring only a small amount of CO adsorbent (e.g. low CO concentrations in the feed, etc.), it may be advantageous to mix the CO adsorbent with another adsorbent (such as 13X) in order to affect a thicker layer of mixed adsorbent rather than a very thin layer of the CO adsorbent alone. The advantage of the thicker mixed layer being ease of installation and less critical tolerance on the overall layer thickness. The method of the invention can be used to remove one or both of CO and H2 from air, N2 and other weakly adsorbing bulk gases. Weaker adsorbing gases to be purified of CO can be identified initially from the electronic properties of such gases. Using the criteria of CO/N2 selectivity and CO working capacity defined above for selecting an appropriate adsorbent insures that the system will work as well or better in removing CO from more weakly adsorbed gases such as N2, helium (He), neon (Ne), H2, xenon (Xe), krypton (Kr), argon (Ar), O2 and methane (CH4) and others with similar properties. Further, while a preferred application of the invention is in prepurification prior to cryogenic air separation, the invention as described herein may also be applied to remove CO and/or hydrogen present in nitrogen gas after cryogenic distillation. The size of H2O and CO2 removal layers upstream (by the term “upstream” we mean being located closer to the feed end of the adsorber vessel) of CO adsorbent would depend upon the H2O and CO2 concentration in the gas to be purified. Inert gases such as N2 may contain ppm levels of O2, if they contain any oxygen at all. Therefore the mechanism for CO and H2 removal in the CO adsorbent and the catalyst would be a combination of adsorption/chemisorption and absorption. For the removal of CO only by adsorption, an optional clean-up layer may be eliminated as shown in FIG. 4 described above. In the absence of oxygen, the oxidation products CO2 and H2O would not form, therefore an optional clean up layer as shown in FIG. 3 may not be needed. The method of this invention can also be used for post purification of N2 in the cryogenic plants. As indicated above, the adsorbent beds/vessels used in the method of the invention can have variety of configurations such as vertical flow beds, horizontal flow beds or radial flow beds and can be operated in a pressure swing adsorption mode, temperature swing adsorption mode, vacuum swing adsorption mode or a combination of these. The adsorbents in this method may be shaped by a series of methods into various geometrical forms such as beads, granules and extrudates. This might involve addition of a binder to zeolite powder in ways well known to those skilled in the art. These binders might also be necessary for tailoring the strength of the adsorbents. Binder types and shaping procedures are well known and the current invention does not put any constraints on the type and percentage amount of binders in the adsorbents. The CO adsorbent could also potentially adsorb some hydrocarbons and nitrogen oxides from air. To ensure complete removal of hydrocarbons, the CO adsorbent can be physically mixed with a hydrocarbon selective adsorbent. The method suggested in this invention can be used for cleanup of any gas containing contaminant levels of CO alone or in combination with H2, H2O, CO2, hydrocarbons and N2O. The term “comprising” is used herein as meaning “including but not limited to”, that is, as specifying the presence of stated features, integers, steps or components as referred to in the claims, but not precluding the presence or addition of one or more other features, integers, steps, components, or groups thereof. Specific features of the invention are shown in one or more of the drawings for convenience only, as each feature may be combined with other features in accordance with the invention. Alternative embodiments will be recognized by those skilled in the art and are intended to be included within the scope of the claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>Carbon monoxide (CO) and hydrogen (H 2 ) can be present in air at concentrations of up to about 50 ppm and 10 ppm respectively, although typical concentrations in air are on the order of 1 ppm CO and 1 ppm H 2 . Normal cryogenic distillation processes used to produce ultra high purity (UHP) nitrogen (N 2 ) do not remove hydrogen and remove only a small portion of the CO. Unless removed by alternative means, these molecules will contaminate the product nitrogen at a concentration up to about two and a half times their concentration in the feed air. Since the electronic industry demands very high purity nitrogen product (typically having on the order of 5 ppb CO or less and 5 ppb H 2 or less), CO and H 2 have to be removed from feed air. Air also contains other contaminants such as water (H 2 O), carbon dioxide (CO 2 ) and hydrocarbons. In cold sections of the distillation separation process (such as heat exchangers and separation columns), water and CO 2 can solidify and block the heat exchangers or other parts in the distillation columns. Acetylene and other hydrocarbons in air also present a potential problem because they can accumulate in the liquid oxygen (O 2 ) and create an explosion hazard. It is therefore desirable to remove these impurities prior to the cryogenic distillation of air. Air prepurification can be accomplished using pressure swing adsorption (PSA), temperature swing adsorption (TSA) or a combination of both (TSA/PSA) incorporating either a single adsorbent or multiple adsorbents. When more than one adsorbent is used, the adsorbents may be configured as discrete layers, as mixtures, composites or combinations of these. Impurities such as H 2 O and CO 2 are commonly removed from air using one or more adsorbent layers in a combined TSA/PSA process. A first layer of activated alumina or zeolite is commonly used for water removal and a second layer of zeolite such as 13X molecular sieve is used for CO 2 removal. Prior art, such as U.S. Pat. No. 4,711,645, teaches the use of various adsorbents and methods for removal of CO 2 and water vapor from air. These adsorbents are ineffective for the removal of CO and H 2 , thus allowing CO and H 2 to pass through to the distillation equipment. There are three principal strategies in the prior art to remove CO and/or H 2 from air to produce UHP nitrogen: removal upstream of the prepurifier adsorber, removal within the prepurifier adsorber using an oxidation catalyst and removal from the nitrogen product after cryogenic air separation. In the first approach, CO and H 2 are usually removed by high temperature catalytic oxidation over a supported noble metal or hopcalite catalyst upstream of the prepurifier beds. The products from oxidizing CO and H 2 , namely CO 2 and H 2 O, are removed along with the ambient CO 2 and H 2 O in the prepurifier beds (F. C. Venet, et al., “Understand the Key Issues for High Purity Nitrogen Production,” Chem. Eng. Prog., pp 78-85, January 1993). This approach requires significant power and additional capital, adding substantially to the cost of the process. U.S. Pat. No. 5,656,557 discloses a process wherein the compressed air is further heated to 350° C. prior to entering a catalyst tower containing palladium (Pd) and/or platinum (Pt) supported catalyst for converting CO, H 2 and hydrocarbons to H 2 O and CO 2 . The processed air is then cooled to 5° C. to 10° C. prior to entering the prepurifier where the H 2 O and CO 2 are removed. Part of the effluent from the prepurifier may be used as air containing less than 1 ppm total impurities, while the remaining air is separated cryogenically to produce N 2 and O 2 . French patent FR 2 739 304 describes a method of removing CO and H 2 from air which involves; 1) contacting the compressed hot moist gas from the compressor with a bed of CO oxidation catalyst; 2) cooling the resulting intermediate air stream to ambient temperature; 3) contacting this CO free stream with an adsorbent to adsorb CO 2 and H 2 O; and 4) contacting the resulting stream with a H 2 trapping adsorbent. The CO catalyst can be copper (Cu) or a Pt group metal supported on alumina, silica or zeolite. The H 2 trapping adsorbent can be osmium (Os), iridium (Ir), Pd, ruthenium (Ru), rhodium (Rh) or Pt supported on alumina, silica or zeolite. U.S. Pat. No. 6,074,621 describes a similar process as FR 2 739 304 except for the cooling step after the CO oxidation catalyst. U.S. Pat. No. 5,693,302 discloses a method of removing CO and H 2 from a composite gas by passing over particles containing gold and Pd supported by TiO 2 . U.S. Pat. No. 5,662,873 describes a similar process using a catalyst consisting of silver and at least one element from Pt family supported on alumina, silica or zeolite. A second technology employed in the prior art is an ambient temperature process for CO and H 2 removal from air. U.S. Pat. No. 5,110,569 discloses a process for removing CO and optionally hydrogen from air by 1) removing water 2) catalytically oxidizing CO to CO 2 and optionally H 2 to H 2 O and 3) removing the oxidation products. Oxidation catalysts for CO can be a mixture of manganese and copper oxides such as hopcalite or Carulite. Nickel oxide is also stated to be an effective CO catalyst. The oxidation catalyst for H 2 is typically supported palladium. U.S. Pat. No. 5,238,670 discloses a method of removing CO and/or H 2 from air at a temperature between 0° C. and 50° C. by 1 ) removing water from air until it has a water content lower than 150 ppm and 2) removing CO and H 2 on a bed of particles containing at least one metallic element selected from Cu, Ru, Rh, Pd, Os, Ir and Pt deposited by ion-exchange or impregnation on zeolite, alumina or silica. European patent application EP 0 454 531 describes a similar method which suggests removing both H 2 O and CO 2 prior to the impregnated bed of particles. Traces of H 2 O and CO 2 are removed downstream of the impregnated particle bed. U.S. Pat. No. 6,048,509 discloses a method for removing CO and H 2 from air at ambient temperature wherein air containing H 2 O, CO 2 , CO and optionally H 2 passes through following steps; 1) contacting the gas with a CO catalyst consisting of Pd or Pt and at least one member selected from the group consisting of iron (Fe), cobalt (Co), nickel (Ni), manganese (Mn), Cu, chromium (Cr), tin (Sn), lead (Pb), and cerium (Ce) supported on large pore alumina; 2) contacting the CO free gas with an adsorbent for water removal; 3) contacting the resulting gas with a CO 2 adsorbent for CO 2 removal and optionally; 4) contacting the gas with a H 2 catalyst which consists of Pt or Pd supported on activated alumina or zeolite. The water formed in the last step of hydrogen oxidation is either adsorbed on the H 2 catalyst support or it is removed by a H 2 O adsorbent, which is either physically mixed with the H 2 catalyst or placed downstream of it. U.S. Pat. No. 6,093,379 describes a method where a prepurifier bed with a first layer of water adsorbent and a second layer of CO 2 adsorbent operating at ambient temperature is augmented by a third layer of catalyst/adsorbent to remove both CO and H 2 . The third layer is exposed to substantially H 2 O-free and CO 2 -free air at ambient temperature. The dual catalyst/adsorbent is placed in the third layer in the most downstream end of the prepurifier beds. The dual catalyst/adsorbent layer oxidizes CO, adsorbs the resulting CO 2 , and chemisorbs H 2 . This dual catalyst/adsorbent is a precious metal such as Pd on a support having a zero point charge (ZPC) of greater than 8. U.S. Pat. No. 6,511,640 discloses a method wherein a prepurifier is configured to contain various materials layered in series beginning with an adsorbent at the feed inlet for H 2 O removal. The second layer, an oxidation catalyst to convert CO to CO 2 , is followed by an adsorbent for CO 2 removal. An oxidation catalyst is placed in the next layer to convert H 2 to H 2 O, while the final layer is used for adsorbing H 2 O. The CO catalyst disclosed is hopcalite, while the H 2 catalyst is Pd supported on activated alumina. A third common strategy for producing UHP N 2 in the prior art is the treatment of the cryogenically separated N 2 product to remove H 2 , CO, O 2 and other contaminants penetrating the prepurifier and air separation unit. U.S. Pat. No. 4,579,723 discloses the use of a Ni or Cu supported catalyst or getter to oxidize the contaminants to CO 2 and H 2 O, which are subsequently removed in an adsorber. European patent EP 0 835 687 teaches regeneration of catalyst beds with a high temperature N 2 purge. Adsorption of CO has been applied in the prior art predominantly for recovery of CO in bulk separations, e.g. in cases where the concentration (partial pressure) of CO is relatively high (typically=1%) and where CO is the more strongly adsorbed component in the gas mixture. Cuprous compounds, either in cationic form in zeolites or dispersed on a porous support, have been widely applied in the recovery of CO from gas mixtures containing CO and N 2 , methane (CH 4 ), H 2 and/or CO 2 . Materials containing copper in the single oxidation state (denoted as Cu + , Cu(I) or cuprous) display high CO adsorption capacity, while adsorbents containing Cu(II) do not. Adsorbents are commonly synthesized, treated or modified with a Cu(II) compound and then subsequently exposed to a reducing agent such as H 2 at elevated temperature to convert the Cu(II) to Cu(I). Xie et al. (“Highly Efficient Adsorbent for Separation of Carbon Monoxide,” Fundamentals of Adsorption, Proc. IV th Int. Conf. On Fundamentals of Adsorption, Kyoto, May 17-22, 1992, pp. 737-741) describes an adsorbent formed by dispersing CuCl on a zeolite support by mixing the dry powders at elevated temperature. High purity CO separated to high recovery is demonstrated for feed streams containing 9.0% CO/91% N 2 and 30.7% CO/65.3% H 2 /4% CH 4 . U.S. Pat. No. 4,917,711 discloses adsorbents and processes utilizing supported CuCl. U.S. Pat. No. 5,531,809 discloses VSA processes using CuCl dispersed on alumina for recovery of CO from synthesis gas exiting a steam-methane reformer. G. K. Pearce (“The Industrial Practice of Adsorption,” in: Separation of Gases, 5 th BOC Priestley Conf., Birmingham, UK Sep. 19-21, 1989, Spec. Publ. No. 80, Royal Soc. Of Chemistry, Cambridge, 1990) provides a description on the use of Cu(I)Y zeolite for the recovery of CO from CO/N 2 and CO/H 2 feed streams containing percentage (%) levels of CO. U.S. Pat. No. 4,473,276 discloses Cu(I)Y and Cu-Mordenite along with other exchanged zeolites having a silica to alumina ratio (SiO 2 /Al 2 O 3 )=10 for the recovery of CO. U.S. Pat. No. 4,019,879 discloses recovery of CO from streams containing H 2 O and/or CO 2 using Cu + containing zeolites with 20=SiO 2 /Al 2 O 3=200 , e.g. ZSM-5, -8, -11, etc. Another class of adsorbents having potential for CO adsorption is one in which the materials contain silver (Ag + ). Y. Huang (“Adsorption in AgX and AgY Zeolites by Carbon Monoxide and Other Simple Molecules,” J. Catal., 32, pp. 482-491, 1974) provides CO and N 2 isotherms for AgX and AgY zeolites to partial pressures only as low as 0.1 to 1.0 torr for the lowest temperature (0° C. and 25° C.) isotherms. The adsorption capacity for CO is significantly greater than that of N 2 at 25° C. and 100 torr. U.S. Pat. No. 4,743,276 discloses mordenite, A, Y and X type zeolites exchanged with various amounts of Ag for the bulk separation (recovery) of CO from refinery and petro-chemical off-gases. U.S. Pat. No. 4,019,880 relates to the recovery of CO from gas streams containing also H 2 O and/or CO 2 using Ag exchanged zeolites with 20=SiO 2 /Al 2 O 3 =200, e.g. ZSM-5, -8, -11, etc. The invention applies to feed streams containing at least 10 ppm CO at temperatures 0° C.-300° C. The claimed process results in a CO-depleted effluent, e.g. air. U.S. Pat. No. 4,944,273 discloses zeolites with 1=Si/Al=100 and doped with Ca, Co, Ni, Fe, Cu, Ag, Pt or Ru for adsorption of oxides of nitrogen (NO x ) and CO as part of NO x and CO sensors, particularly in exhaust gases of automotive vehicles. U.S. Pat. No. 3,789,106 discloses that mordenite charged with copper is effective in removing CO from H 2 at CO partial pressure below 3 mmHg. The effectiveness was determined by subjecting the adsorbent to CO concentrations greater than or equal to 100 ppm and measuring capacity at saturation. The above prior art relating to adsorption of CO is almost totally silent with respect to purification of CO from mixed gas streams, particularly those containing less than 10 ppm CO in O 2 and N 2 .
<SOH> SUMMARY OF THE INVENTION <EOH>The invention relates to the removal of CO and optionally H 2 from air and/or other gases or gas mixtures using a combination of adsorptive separation and catalytic conversion, and provides unexpected savings in capital and power costs over existing technologies. In one preferred embodiment, at least 90% of each of CO 2 and H 2 O are first removed from the feed gas (preferably air) to produce a CO 2 and H 2 O depleted gas. In a particularly preferred embodiment, the CO 2 and H 2 O depleted gas contains less than 1.0 ppm (more preferably less than 0.25 ppm) CO 2 and less than 1.0 ppm (more preferably less than 0.10 ppm) H 2 O. A substantial amount of CO is then removed from the CO 2 and H 2 O depleted gas through the use of a CO adsorbent to produce a CO depleted gas containing, in a preferred embodiment, less than 100 ppb CO, more preferably less than 5 ppb CO. Optionally H 2 and any remaining CO may then be removed using a catalyst. Because of this unique combination of catalysis and adsorption, the process of the present invention provides surprisingly superior CO and H 2 removal efficiency over the prior art processes. A preferred apparatus for the practice of the invention comprises an adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm. The apparatus comprises at least one adsorption vessel containing a CO adsorbent layer, the CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein a) when the feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, CH 4 and mixtures thereof, the adsorbent is ion exchanged with a Group IB element, and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, Cu-clinoptilolite, AgA zeolite and AgY zeolite, and b) when the feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, the apparatus is preferably an air prepurifier, and the adsorbent is a zeolite having a SiO 2 /Al 2 O 3 ratio of <20, and is ion-exchanged with a Ag + or Au + , and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, AgA zeolite and AgY zeolite. In a further embodiment the apparatus contains two or more adsorption vessels that are selected from the group consisting of vertical flow vessels, horizontal flow vessels, lateral flow vessels or radial flow vessels. In a further embodiment the adsorption apparatus further contain an adsorbent, preferably one or more of alumina or NaX zeolite, selective for the adsorption of water that is upstream of said CO adsorbent layer. In a further embodiment the apparatus further contains a catalyst layer, preferably a metal supported catalyst comprising one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide, for the catalytic oxidation of H 2 to H 2 O that is downstream of said CO adsorbent layer. In a further embodiment the apparatus further contains an auxiliary adsorbent, preferably one or more of alumina or NaX, for the removal of water that is downstream of said catalyst layer. In a further embodiment the ΔCO working capacity is greater than or equal to 0.03 mmol/g. In a further embodiment, the apparatus further contains one or more additional adsorbents for the adsorption of one or more of H 2 O, CO 2 , N 2 O and hydrocarbons, wherein the additional adsorbents preferably are selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof, and are located downstream of the catalyst layer. In a further embodiment the CO adsorbent has a ΔCO/ΔN 2 separation factor of greater than or equal to 1×10 −3 . In a further embodiment the CO adsorbent is AgX having at least 50%, preferably 100% of its cations associated with Ag. A preferred process for the practice of the invention comprises a process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, or even less than 1.0 ppm or 0.5 ppm. The process, which is preferably an air prepurification process, comprises contacting the feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g, preferably greater than or equal to 0.03 mmol/g, to produce a CO depleted gas stream, that may be recovered; and wherein a) when the feed stream further contains at least one gas selected from the group consisting of nitrogen, He, Ne, Ar, Xe, Kr, H 2 , CH 4 and mixtures thereof, the adsorbent is a zeolite exchanged with a Group IB element and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, Cu-clinoptilolite, AgA zeolite and AgY zeolite, and b) when the feed stream further contains at least one gas selected from the group consisting of oxygen and air and mixtures thereof, the adsorbent is a zeolite having a SiO 2 /Al 2 O 3 ratio of <20, and is ion-exchanged with a Ag + or Au + , and is preferably selected from the group consisting of AgX zeolite, Ag-Mordenite, AgA zeolite and AgY zeolite. In a further embodiment, the process comprises recovering the CO depleted gas stream, wherein CO is present in the CO depleted gas stream at a concentration of less than 100 ppb, preferably less than 5 ppb, most preferably less than 1 ppb. In a further embodiment, said feed gas further comprises water (H 2 O), and the process further comprises contacting the feed stream with a water selective adsorbent, preferably alumina or NaX, that is located upstream of said CO adsorbent. In a further embodiment, the feed gas further comprises hydrogen, and the process further comprises contacting the CO depleted feed stream with a catalyst layer that is preferably a metal supported catalyst comprising one or more of the metals Os, Ir, Pt, Ru, Rh, Pd, Fe, Co, Ni, Cu, Ag, Au, Zn, Sn, Mn, Cr, Pb, Ce supported on a substrate selected from the group consisting of alumina, silica, natural or synthetic zeolites, titanium dioxide, magnesium oxide and calcium oxide, for the catalytic oxidation of H 2 to H 2 O to produce a H 2 depleted and H 2 O enriched gas, and wherein the catalyst layer is located downstream of said CO adsorbent layer. The hydrogen depleted gas preferably contains less than 100 ppb hydrogen, and more preferably less than 5 ppb hydrogen. In another embodiment, the process further comprises the step of contacting the catalytically produced H 2 O enriched gas with an adsorbent for the removal of water (preferably alumina or NaX) that is located downstream of said catalyst layer to produce a gas that is depleted in CO, H 2 and H 2 O. In another embodiment the CO adsorbent has aΔCO/AN 2 separation factor that is greater than or equal to 1×10 −3 , preferably greater than or equal to 1×10 −2 . In another embodiment, the process further comprises passing said feed gas over a) at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H 2 O and CO 2 , b) a catalyst layer for the catalytic conversion of H 2 to H 2 O that is downstream of said CO adsorbent layer; and c) one or more additional adsorbents, preferably selected from the group consisting of alumina, silica gel, clinoptilolite, zeolites, composites thereof and mixtures thereof, for the adsorption of one or more of H 2 O, CO 2 , N 2 O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. In an alternative embodiment, the process is selected from the group consisting of pressure swing adsorption, temperature swing adsorption, or a combination thereof, and the process takes place in an adsorber vessel selected from a vertical flow vessel, a horizontal flow vessel or a radial flow vessel. In a preferred embodiment the adsorption step of the process is operated at a temperature of zero to fifty degrees Celsius. In a preferred process the CO adsorbent is AgX having at least 50%, more preferably 100% of its cations associated with Ag. In a preferred embodiment the feed stream contains air, and the CO depleted gas stream is passed to a cryogenic distillation column. In an alternative embodiment the CO partial pressure in the feed stream is less than 0.1 mmHg, or even less than 0.005 mmHg. An alternative embodiment relates to a process for the removal for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and hydrogen, the process comprising contacting the feed stream with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein the adsorbent is a zeolite exchanged with a Group IB element. In a preferred embodiment, the invention comprises an adsorption apparatus for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm, and hydrogen, the apparatus comprising at least one adsorption vessel containing a CO adsorbent layer having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein said adsorbent is a zeolite exchanged with a Group IB element. In a particularly preferred embodiment, the invention comprises an air prepurification adsorption apparatus for the removal of CO from an air feed stream containing CO in an amount of less than 50 ppm, the apparatus comprising at least one adsorption vessel containing a CO adsorbent layer having a ΔCO working capacity greater than or equal to 0.01 mmol/g; and wherein the adsorbent is a zeolite (preferably AgX), having a SiO 2 /Al 2 O 3 ratio of <20, and is ion-exchanged with a Ag + or Au +. In a preferred embodiment, the air prepurification apparatus further comprises at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H 2 O and CO 2 . In a preferred embodiment, the prepurification apparatus further comprises a catalyst layer for the catalytic conversion of H 2 to H 2 O that is downstream of the CO adsorbent layer; and one or more additional adsorbents for the adsorption of one or more of H 2 O, CO 2 , N 2 O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer. In an alternative embodiment, the invention comprises a process for the removal of CO from a feed stream containing CO in an amount of less than 50 ppm and air said process comprising contacting said feed stream in an adsorber vessel with a CO adsorbent having a ΔCO working capacity greater than or equal to 0.01 mmol/g to produce a CO depleted gas stream; and wherein the adsorbent is a zeolite having a SiO 2 /Al 2 O 3 ratio of <20, and is ion-exchanged with a Ag + or Au + , preferably AgX. This process may further comprise a) passing the feed stream over at least one adsorbent layer upstream of said CO adsorbent for the adsorption of one or more of H 2 O and CO 2 to produce a H 2 O and or CO 2 depleted feed stream b) passing the feed stream over a catalyst layer that is downstream of said CO adsorbent layer for the catalytic conversion of H 2 to H 2 O layer and one or more additional adsorbents for the adsorption of one or more of H 2 O, CO 2 , N 2 O and hydrocarbons, wherein said additional adsorbents are downstream of said catalyst layer to produce a feed stream that is depleted in CO, H 2 and one or more of H 2 O, CO 2 , N 2 O and hydrocarbons, and, optionally, passing the depleted feed stream to a cryogenic distillation column for the separation of air. Combinations of any of the above embodiments are contemplated to be within the scope of the invention.
20060509
20090428
20060921
60254.0
B01D5000
0
LAWRENCE JR, FRANK M
PRODUCTION OF HIGH PURITY AND ULTRA-HIGH PURITY GAS
UNDISCOUNTED
0
ACCEPTED
B01D
2,006
10,515,569
ACCEPTED
Method and device for efficient frame erasure concealment in linear predictive based speech codecs
The present invention relates to a method and device for improving concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder (106) to a decoder (110), and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received. For that purpose, concealment/recovery parameters are determined in the encoder or decoder. When determined in the encoder (106), the concealment/recovery parameters are transmitted to the decoder (110). In the decoder, erasure frame concealment and decoder recovery is conducted in response to the concealment/recovery parameters. The concealment/recovery parameters may be selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. The determination of the concealment/recovery parameters comprises classifying the successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset, and this classification is determined on the basis of at least a part of the following parameters: a normalized correlation parameter, a spectral tilt parameter, a signal-to-noise ratio parameter, a pitch stability parameter, a relative frame energy parameter, and a zero crossing parameter.
1. A method of concealing frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, comprising: determining, in the encoder, concealment/recovery parameters; transmitting to the decoder concealment/recovery parameters determined in the encoder; and in the decoder, conducting frame erasure concealment and decoder recovery in response to the received concealment/recovery parameters. 2. A method as defined in claim 1, further comprising quantizing, in the encoder, the concealment/recovery parameters prior to transmitting said concealment/recovery parameters to the decoder. 3. A method as defined in claim 1, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 4. A method as defined in claim 3, wherein determination of the phase information parameter comprises determining a position of a first glottal pulse in a frame of the encoded sound signal. 5. A method as defined in claim 1, wherein conducting frame erasure concealment and decoder recovery comprises conducting decoder recovery in response to a determined position of a first glottal pulse after at least one lost voice onset. 6. A method as defined in claim 1, wherein conducting frame erasure concealment and decoder recovery comprises, when at least one onset frame is lost, constructing a periodic excitation part artificially as a low-pass filtered periodic train of pulses separated by a pitch period. 7. A method as defined in claim 6, wherein: the method comprises quantizing the position of the first glottal pulse prior to transmission of said position of the first glottal pulse to the decoder; and constructing a periodic excitation part comprises realizing the low-pass filtered periodic train of pulses by: centering a first impulse response of a low-pass filter on the quantized position of the first glottal pulse with respect to the beginning of a frame; and placing remaining impulse responses of the low-pass filter each with a distance corresponding to an average pitch value from the preceding impulse response up to the end of a last subframe affected by the artificial construction. 8. A method as defined in claim 4, wherein determination of the phase information parameter further comprises encoding, in the encoder, the shape, sign and amplitude of the first glottal pulse and transmitting the encoded shape, sign and amplitude from the encoder to the decoder. 9. A method as defined in claim 4, wherein determining the position of the first glottal pulse comprises: measuring the first glottal pulse as a sample of maximum amplitude within a pitch period; and quantizing the position of the sample of maximum amplitude within the pitch period. 10. A method as defined in claim 1, wherein: the sound signal is a speech signal; and determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 11. A method as defined in claim 10, wherein classifying the successive frames comprises classifying as unvoiced every frame which is an unvoiced frame, every frame without active speech, and every voiced offset frame having an end tending to be unvoiced. 12. A method as defined in claim 10, wherein classifying the successive frames comprises classifying as unvoiced transition every unvoiced frame having an end with a possible voiced onset which is too short or not built well enough to be processed as a voiced frame. 13. A method as defined in claim 10, wherein classifying the successive frames comprises classifying as voiced transition every voiced frame with relatively weak voiced characteristics, including voiced frames with rapidly changing characteristics and voiced offsets lasting the whole frame, wherein a frame classified as voiced transition follows only frames classified as voiced transition, voiced or onset. 14. A method as defined in claim 10, wherein classifying the successive frames comprises classifying as voiced every voiced frames with stable characteristics, wherein a frame classified as voiced follows only frames classified as voiced transition, voiced or onset. 15. A method as defined in claim 10, wherein classifying the successive frames comprises classifying as onset every voiced frame with stable characteristics following a frame classified as unvoiced or unvoiced transition. 16. A method as defined in claim 10, comprising determining the classification of the successive frames of the encoded sound signal on the basis of at least a part of the following parameters: a normalized correlation parameter, a spectral tilt parameter, a signal-to-noise ratio parameter, a pitch stability parameter, a relative frame energy parameter, and a zero crossing parameter. 17. A method as defined in claim 16, wherein determining the classification of the successive frames comprises: computing a figure of merit on the basis of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter; and comparing the figure of merit to thresholds to determine the classification. 18. A method as defined in claim 16, comprising calculating the normalized correlation parameter on the basis of a current weighted version of the speech signal and a past weighted version of said speech signal. 19. A method as defined in claim 16, comprising estimating the spectral tilt parameter as a ratio between an energy concentrated in low frequencies and an energy concentrated in high frequencies. 20. A method as defined in claim 16, comprising estimating the signal-to-noise ratio parameter as a ratio between an energy of a weighted version of the speech signal of a current frame and an energy of an error between said weighted version of the speech signal of the current frame and a weighted version of a synthesized speech signal of said current frame. 21. A method as defined in claim 16, comprising computing the pitch stability parameter in response to open-loop pitch estimates for a first half of a current frame, a second half of the current frame and a look-ahead. 22. A method as defined in claim 16, comprising computing the relative frame energy parameter as a difference between an energy of a current frame and a long-term average of an energy of active speech frames. 23. A method as defined in claim 16, comprising determining the zero-crossing parameter as a number of times a sign of the speech signal changes from a first polarity to a second polarity. 24. A method as defined in claim 16, comprising computing at least one of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter using an available look-ahead to take into consideration the behavior of the speech signal in the following frame. 25. A method as defined in claim 16, further comprising determining the classification of the successive frames of the encoded sound signal also on the basis of a voice activity detection flag. 26. A method as defined in claim 3 wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and determining concealment/recovery parameters comprises calculating the energy information parameter in relation to a maximum of a signal energy for frames classified as voiced or onset, and calculating the energy information parameter in relation to an average energy per sample for other frames. 27. A method as defined in claim 1, wherein determining, in the encoder, concealment/recovery parameters comprises computing a voicing information parameter. 28. A method as defined in claim 27, wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal; said method comprises determining the classification of the successive frames of the encoded sound signal on the basis of a normalized correlation parameter; and computing the voicing information parameter comprises estimating said voicing information parameter on the basis of the normalized correlation. 29. A method as defined in claim 1, wherein conducting frame erasure concealment and decoder recovery comprises: following receiving a non erased unvoiced frame after frame erasure, generating no periodic part of a LP filter excitation signal; following receiving, after frame erasure, of a non erased frame other than unvoiced, constructing a periodic part of the LP filter excitation signal by repeating a last pitch period of a previous frame. 30. A method as defined in claim 29, wherein constructing the periodic part of the LP filter excitation signal comprises filtering the repeated last pitch period of the previous frame through a low-pass filter. 31. A method as defined in claim 30, wherein: determining concealment/recovery parameters comprises computing a voicing information parameter; the low-pass filter has a cut-off frequency; and constructing the periodic part of the excitation signal comprises dynamically adjusting the cut-off frequency in relation to the voicing information parameter. 32. A method as defined in claim 1, wherein conducting frame erasure concealment and decoder recovery comprises randomly generating a non-periodic, innovation part of a LP filter excitation signal. 33. A method as defined in claim 32, wherein randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises generating a random noise. 34. A method as defined in claim 32, wherein randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises randomly generating vector indexes of an innovation codebook. 35. A method as defined in claim 32, wherein: the sound signal is a speech signal; determination of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and randomly generating the non-periodic, innovation part of the LP filter excitation signal further comprises: if the last correctly received frame is different from unvoiced, filtering the innovation part of the excitation signal through a high pass filter; and if the last correctly received frame is unvoiced, using only the innovation part of the excitation signal. 36. A method as defined in claim 1, wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; conducting frame erasure concealment and decoder recovery comprises, when an onset frame is lost which is indicated by the presence of a voiced frame following frame erasure and an unvoiced frame before frame erasure, artificially reconstructing the lost onset by constructing a periodic part of an excitation signal as a low-pass filtered periodic train of pulses separated by a pitch period. 37. A method as defined in claim 36, wherein conducting frame erasure concealment and decoder recovery further comprises constructing an innovation part of the excitation signal by means of normal decoding. 38. A method as defined in claim 37, wherein constructing an innovation part of the excitation signal comprises randomly choosing entries of an innovation codebook. 39. A method as defined in claim 36, wherein artificially reconstructing the lost onset frame comprises limiting a length of the artificially reconstructed onset so that at least one entire pitch period is constructed by the onset artificial reconstruction, said reconstruction being continued until the end of a current subframe. 40. A method as defined in claim 39, wherein conducting frame erasure concealment and decoder recovery further comprises, after artificial reconstruction of the lost onset, resuming a regular CELP processing wherein the pitch period is a rounded average of decoded pitch periods of all subframes where the artificial onset reconstruction is used. 41. A method as defined in claim 3, wherein conducting frame erasure concealment and decoder recovery comprises: controlling an energy of a synthesized sound signal produced by the decoder, controlling energy of the synthesized sound signal comprising scaling the synthesized sound signal to render an energy of said synthesized sound signal at the beginning of a first non erased frame received following frame erasure similar to an energy of said synthesized signal at the end of a last frame erased during said frame erasure; and converging the energy of the synthesized sound signal in the received first non erased frame to an energy corresponding to the received energy information parameter toward the end of said received first non erased frame while limiting an increase in energy. 42. A method as defined in claim 3, wherein: the energy information parameter is not transmitted from the encoder to the decoder; and conducting frame erasure concealment and decoder recovery comprises, when a gain of a LP filter of a first non erased frame received following frame erasure is higher than a gain of a LP filter of a last frame erased during said frame erasure, adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame. 43. A method as defined in claim 42 wherein: adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame comprises using the following relation: E q = E 1 ⁢ E LP0 E LP1 where E1 is the energy at the end of the current frame, ELP0 is the energy of an impulse response of the LP filter to the last non erased frame received before the frame erasure, and ELP1 is the energy of the impulse response of the LP filter to the received first non erased frame following frame erasure. 44. A method as defined in claim 41, wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and when the first non erased frame received after a frame erasure is classified as ONSET, conducting frame erasure concealment and decoder recovery comprises limiting to a given value a gain used for scaling the synthesized sound signal. 45. A method as defined in claim 41, wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and said method comprising making a gain used for scaling the synthesized sound signal at the beginning of the first non erased frame received after frame erasure equal to a gain used at the end of said received first non erased frame: during a transition from a voiced frame to an unvoiced frame, in the case of a last non erased frame received before frame erasure classified as voiced transition, voice or onset and a first non erased frame received after frame erasure classified as unvoiced; and during a transition from a non-active speech period to an active speech period, when the last non erased frame received before frame erasure is encoded as comfort noise and the first non erased frame received after frame erasure is encoded as active speech. 46. A method of concealing frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, comprising: determining, in the encoder, concealment/recovery parameters; and transmitting to the decoder concealment/recovery parameters determined in the encoder. 47. A method as defined in claim 46, further comprising quantizing, in the encoder, the concealment/recovery parameters prior to transmitting said concealment/recovery parameters to the decoder. 48. A method as defined in claim 46, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 49. A method as defined in claim 48, wherein determination of the phase information parameter comprises determining a position of a first glottal pulse in a frame of the encoded sound signal. 50. A method as defined in claim 49, wherein determination of the phase information parameter further comprises encoding, in the encoder, the shape, sign and amplitude of the first glottal pulse and transmitting the encoded shape, sign and amplitude from the encoder to the decoder. 51. A method as defined in claim 49, wherein determining the position of the first glottal pulse comprises: measuring the first glottal pulse as a sample of maximum amplitude within a pitch period; and quantizing the position of the sample of maximum amplitude within the pitch period. 52. A method as defined in claim 46, wherein: the sound signal is a speech signal; and determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 53. A method as defined in claim 52, wherein classifying the successive frames comprises classifying as unvoiced every frame which is an unvoiced frame, every frame without active speech, and every voiced offset frame having an end tending to be unvoiced. 54. A method as defined in claim 52, wherein classifying the successive frames comprises classifying as unvoiced transition every unvoiced frame having an end with a possible voiced onset which is too short or not built well enough to be processed as a voiced frame. 55. A method as defined in claim 52, wherein classifying the successive frames comprises classifying as voiced transition every voiced frame with relatively weak voiced characteristics, including voiced frames with rapidly changing characteristics and voiced offsets lasting the whole frame, wherein a frame classified as voiced transition follows only frames classified as voiced transition, voiced or onset. 56. A method as defined in claim 52, wherein classifying the successive frames comprises classifying as voiced every voiced frames with stable characteristics, wherein a frame classified as voiced follows only frames classified as voiced transition, voiced or onset. 57. A method as defined in claim 52, wherein classifying the successive frames comprises classifying as onset every voiced frame with stable characteristics following a frame classified as unvoiced or unvoiced transition. 58. A method as defined in claim 52, comprising determining the classification of the successive frames of the encoded sound signal on the basis of at least a part of the following parameters: a normalized correlation parameter, a spectral tilt parameter, a signal-to-noise ratio parameter, a pitch stability parameter, a relative frame energy parameter, and a zero crossing parameter. 59. A method as defined in claim 58, wherein determining the classification of the successive frames comprises: computing a figure of merit on the basis of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter; and comparing the figure of merit to thresholds to determine the classification. 60. A method as defined in claim 58, comprising calculating the normalized correlation parameter on the basis of a current weighted version of the speech signal and a past weighted version of said speech signal. 61. A method as defined in claim 58, comprising estimating the spectral tilt parameter as a ratio between an energy concentrated in low frequencies and an energy concentrated in high frequencies. 62. A method as defined in claim 58, comprising estimating the signal-to-noise ratio parameter as a ratio between an energy of a weighted version of the speech signal of a current frame and an energy of an error between said weighted version of the speech signal of the current frame and a weighted version of a synthesized speech signal of said current frame. 63. A method as defined in claim 58, comprising computing the pitch stability parameter in response to open-loop pitch estimates for a first half of a current frame, a second half of the current frame and a look-ahead. 64. A method as defined in claim 58, comprising computing the relative frame energy parameter as a difference between an energy of a current frame and a long-term average of an energy of active speech frames. 65. A method as defined in claim 58, comprising determining the zero-crossing parameter as a number of times a sign of the speech signal changes from a first polarity to a second polarity. 66. A method as defined in claim 58, comprising computing at least one of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter using an available look-ahead to take into consideration the behavior of the speech signal in the following frame. 67. A method as defined in claim 58, further comprising determining the classification of the successive frames of the encoded sound signal also on the basis of a voice activity detection flag. 68. A method as defined in claim 48 wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and determining concealment/recovery parameters comprises calculating the energy information parameter in relation to a maximum of a signal energy for frames classified as voiced or onset, and calculating the energy information parameter in relation to an average energy per sample for other frames. 69. A method as defined in claim 46, wherein determining, in the encoder, concealment/recovery parameters comprises computing a voicing information parameter. 70. A method as defined in claim 68, wherein: the sound signal is a speech signal; determination, in the encoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal; said method comprises determining the classification of the successive frames of the encoded sound signal on the basis of a normalized correlation parameter; and computing the voicing information parameter comprises estimating said voicing information parameter on the basis of the normalized correlation. 71. A method for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, comprising: determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, conducting erased frame concealment and decoder recovery in response to concealment/recovery parameters determined in the decoder. 72. A method as defined in claim 71, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 73. A method as defined in claim 71, wherein: the sound signal is a speech signal; and determination, in the decoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 74. A method as defined in claim 71, wherein determining, in the decoder, concealment/recovery parameters comprises computing a voicing information parameter. 75. A method as defined in claim 71, wherein conducting frame erasure concealment and decoder recovery comprises: following receiving a non erased unvoiced frame after frame erasure, generating no periodic part of a LP filter excitation signal; following receiving, after frame erasure, of a non erased frame other than unvoiced, constructing a periodic part of the LP filter excitation signal by repeating a last pitch period of a previous frame. 76. A method as defined in claim 75, wherein constructing the periodic part of the excitation signal comprises filtering the repeated last pitch period of the previous frame through a low-pass filter. 77. A method as defined in claim 76, wherein: determining, in the decoder, concealment/recovery parameters comprises computing a voicing information parameter; the low-pass filter has a cut-off frequency; and constructing the periodic part of the LP filter excitation signal comprises dynamically adjusting the cut-off frequency in relation to the voicing information parameter. 78. A method as defined in claim 71, wherein conducting frame erasure concealment and decoder recovery comprises randomly generating a non-periodic, innovation part of a LP filter excitation signal. 79. A method as defined in claim 78, wherein randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises generating a random noise. 80. A method as defined in claim 78, wherein randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises randomly generating vector indexes of an innovation codebook. 81. A method as defined in claim 78, wherein: the sound signal is a speech signal; determination, in the decoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and randomly generating the non-periodic, innovation part of the LP filter excitation signal further comprises: if the last received non erased frame is different from unvoiced, filtering the innovation part of the LP filter excitation signal through a high pass filter; and if the last received non erased frame is unvoiced, using only the innovation part of the LP filter excitation signal. 82. A method as defined in claim 78, wherein: the sound signal is a speech signal; determination, in the decoder, of concealment/recovery parameters comprises classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; conducting frame erasure concealment and decoder recovery comprises, when an onset frame is lost which is indicated by the presence of a voiced frame following frame erasure and an unvoiced frame before frame erasure, artificially reconstructing the lost onset by constructing a periodic part of an excitation signal as a low-pass filtered periodic train of pulses separated by a pitch period. 83. A method as defined in claim 82, wherein conducting frame erasure concealment and decoder recovery further comprises constructing an innovation part of the LP filter excitation signal by means of normal decoding. 84. A method as defined in claim 83, wherein constructing an innovation part of the LP filter excitation signal comprises randomly choosing entries of an innovation codebook. 85. A method as defined in claim 82, wherein artificially reconstructing the lost onset comprises limiting a length of the artificially reconstructed onset so that at least one entire pitch period is constructed by the onset artificial reconstruction, said reconstruction being continued until the end of a current subframe. 86. A method as defined in claim 85, wherein conducting frame erasure concealment and decoder recovery further comprises, after artificial reconstruction of the lost onset, resuming a regular CELP processing wherein the pitch period is a rounded average of decoded pitch periods of all subframes where the artificial onset reconstruction is used. 87. A method as defined in claim 72, wherein: the energy information parameter is not transmitted from the encoder to the decoder; and conducting frame erasure concealment and decoder recovery comprises, when a gain of a LP filter of a first non erased frame received following frame erasure is higher than a gain of a LP filter of a last frame erased during said frame erasure, adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame using the following relation: E q = E 1 ⁢ E LP0 E LP1 where E1 is the energy at the end of the current frame, ELP0 is the energy of an impulse response of the LP filter to the last non erased frame received before the frame erasure, and ELP1 is the energy of the impulse response of the LP filter to the received first non erased frame following frame erasure. 88. A device for conducting concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, comprising: means for determining, in the encoder, concealment/recovery parameters; means for transmitting to the decoder concealment/recovery parameters determined in the encoder; and in the decoder, means for conducting frame erasure concealment and decoder recovery in response to received concealment/recovery parameters determined by the determining means. 89. A device as defined in claim 88, further comprising means for quantizing, in the encoder, the concealment/recovery parameters prior to transmitting said concealment/recovery parameters to the decoder. 90. A device as defined in claim 88, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 91. A device as defined in claim 90, wherein the means for determining the phase information parameter comprises means for determining the position of a first glottal pulse in a frame of the encoded sound signal. 92. A device as defined in claim 88, wherein the means for conducting frame erasure concealment and decoder recovery comprises means for conducting decoder recovery in response to a determined position of a first glottal pulse after at least one lost voice onset. 93. A device as defined in claim 88, wherein the means for conducting frame erasure concealment and decoder recovery comprises means for constructing, when at least one onset frame is lost, a periodic excitation part artificially as a low-pass filtered periodic train of pulses separated by a pitch period. 94. A device as defined in claim 93, wherein: the device comprises means for quantizing the position of the first glottal pulse prior to transmission of said position of the first glottal pulse to the decoder; and the means for constructing a periodic excitation part comprises means for realizing the low-pass filtered periodic train of pulses by: centering a first impulse response of a low-pass filter on the quantized position of the first glottal pulse with respect to the beginning of a frame; and placing remaining impulse responses of the low-pass filter each with a distance corresponding to an average pitch value from the preceding impulse response up to the end of a last subframe affected by the artificial construction. 95. A device as defined in claim 91, wherein the means for determining the phase information parameter further comprises means for encoding, in the encoder, the shape, sign and amplitude of the first glottal pulse and means for transmitting the encoded shape, sign and amplitude from the encoder to the decoder. 96. A device as defined in claim 91, wherein the means for determining the position of the first glottal pulse comprises: means for measuring the first glottal pulse as a sample of maximum amplitude within a pitch period; and means for quantizing the position of the sample of maximum amplitude within the pitch period. 97. A device as defined in claim 88, wherein: the sound signal is a speech signal; and the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 98. A device as defined in claim 97, wherein the means for classifying the successive frames comprises means for classifying as unvoiced every frame which is an unvoiced frame, every frame without active speech, and every voiced offset frame having an end tending to be unvoiced. 99. A device as defined in claim 97, wherein the means for classifying the successive frames comprises means for classifying as unvoiced transition every unvoiced frame having an end with a possible voiced onset which is too short or not built well enough to be processed as a voiced frame. 100. A device as defined in claim 97, wherein the means for classifying the successive frames comprises means for classifying as voiced transition every voiced frame with relatively weak voiced characteristics, including voiced frames with rapidly changing characteristics and voiced offsets lasting the whole frame, wherein a frame classified as voiced transition follows only frames classified as voiced transition, voiced or onset. 101. A device as defined in claim 97, wherein the means for classifying the successive frames comprises means for classifying as voiced every voiced frames with stable characteristics, wherein a frame classified as voiced follows only frames classified as voiced transition, voiced or onset. 102. A device as defined in claim 97, wherein the means for classifying the successive frames comprises means for classifying as onset every voiced frame with stable characteristics following a frame classified as unvoiced or unvoiced transition. 103. A device as defined in claim 97, comprising means for determining the classification of the successive frames of the encoded sound signal on the basis of at least a part of the following parameters: a normalized correlation parameter, a spectral tilt parameter, a signal-to-noise ratio parameter, a pitch stability parameter, a relative frame energy parameter, and a zero crossing parameter. 104. A device as defined in claim 103, wherein the means for determining the classification of the successive frames comprises: means for computing a figure of merit on the basis of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter; and means for comparing the figure of merit to thresholds to determine the classification. 105. A device as defined in claim 103, comprising means for calculating the normalized correlation parameter on the basis of a current weighted version of the speech signal and a past weighted version of said speech signal. 106. A device as defined in claim 103, comprising means for estimating the spectral tilt parameter as a ratio between an energy concentrated in low frequencies and an energy concentrated in high frequencies. 107. A device as defined in claim 103, comprising means for estimating the signal-to-noise ratio parameter as a ratio between an energy of a weighted version of the speech signal of a current frame and an energy of an error between said weighted version of the speech signal of the current frame and a weighted version of a synthesized speech signal of said current frame. 108. A device as defined in claim 103, comprising means for computing the pitch stability parameter in response to open-loop pitch estimates for a first half of a current frame, a second half of the current frame and a look-ahead. 109. A device as defined in claim 103, comprising means for computing the relative frame energy parameter as a difference between an energy of a current frame and a long-term average of an energy of active speech frames. 110. A device as defined in claim 103, comprising means for determining the zero-crossing parameter as a number of times a sign of the speech signal changes from a first polarity to a second polarity. 111. A device as defined in claim 103, comprising means for computing at least one of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter using an available look-ahead to take into consideration the behavior of the speech signal in the following frame. 112. A device as defined in claim 103, further comprising means for determining the classification of the successive frames of the encoded sound signal also on the basis of a voice activity detection flag. 113. A device as defined in claim 90, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and the means for determining concealment/recovery parameters comprises means for calculating the energy information parameter in relation to a maximum of a signal energy for frames classified as voiced or onset, and means for calculating the energy information parameter in relation to an average energy per sample for other frames. 114. A device as defined in claim 88, wherein the means for determining, in the encoder, concealment/recovery parameters comprises means for computing a voicing information parameter. 115. A device as defined in claim 114, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal; said device comprises means for determining the classification of the successive frames of the encoded sound signal on the basis of a normalized correlation parameter; and the means for computing the voicing information parameter comprises means for estimating said voicing information parameter on the basis of the normalized correlation. 116. A device as defined in claim 88, wherein the means for conducting frame erasure concealment and decoder recovery comprises: following receiving a non erased unvoiced frame after frame erasure, means for generating no periodic part of a LP filter excitation signal; following receiving, after frame erasure, of a non erased frame other than unvoiced, means for constructing a periodic part of the LP filter excitation signal by repeating a last pitch period of a previous frame. 117. A device as defined in claim 116, wherein the means for constructing the periodic part of the LP filter excitation signal comprises a low-pass filter for filtering the repeated last pitch period of the previous frame. 118. A device as defined in claim 117, wherein: the means for determining concealment/recovery parameters comprises means for computing a voicing information parameter; the low-pass filter has a cut-off frequency; and the means for constructing the periodic part of the excitation signal comprises means for dynamically adjusting the cut-off frequency in relation to the voicing information parameter. 119. A device as defined in claim 88, wherein the means for conducting frame erasure concealment and decoder recovery comprises means for randomly generating a non-periodic, innovation part of a LP filter excitation signal. 120. A device as defined in claim 119, wherein the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises means for generating a random noise. 121. A device as defined in claim 119, wherein the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises means for randomly generating vector indexes of an innovation codebook. 122. A device as defined in claim 119, wherein: the sound signal is a speech signal; the means for determining concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal further comprises: if the last correctly received frame is different from unvoiced, a high-pass filter for filtering the innovation part of the excitation signal; and if the last correctly received frame is unvoiced, means for using only the innovation part of the excitation signal. 123. A device as defined in claim 88, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; the means for conducting frame erasure concealment and decoder recovery comprises, when an onset frame is lost which is indicated by the presence of a voiced frame following frame erasure and an unvoiced frame before frame erasure, means for artificially reconstructing the lost onset by constructing a periodic part of an excitation signal as a low-pass filtered periodic train of pulses separated by a pitch period. 124. A device as defined in claim 123, wherein the means for conducting frame erasure concealment and decoder recovery further comprises means for constructing an innovation part of the excitation signal by means of normal decoding. 125. A device as defined in claim 124, wherein the means for constructing an innovation part of the excitation signal comprises means for randomly choosing entries of an innovation codebook. 126. A device as defined in claim 123, wherein the means for artificially reconstructing the lost onset comprises means for limiting a length of the artificially reconstructed onset so that at least one entire pitch period is constructed by the onset artificial reconstruction, said reconstruction being continued until the end of a current subframe. 127. A device as defined in claim 126, wherein the means for conducting frame erasure concealment and decoder recovery further comprises, after artificial reconstruction of the lost onset, means for resuming a regular CELP processing wherein the pitch period is a rounded average of decoded pitch periods of all subframes where the artificial onset reconstruction is used. 128. A device as defined in claim 90, wherein the means for conducting frame erasure concealment and decoder recovery comprises: means for controlling an energy of a synthesized sound signal produced by the decoder, the means for controlling energy of the synthesized sound signal comprising means for scaling the synthesized sound signal to render an energy of said synthesized sound signal at the beginning of a first non erased frame received following frame erasure similar to an energy of said synthesized signal at the end of a last frame erased during said frame erasure; and means for converging the energy of the synthesized sound signal in the received first non erased frame to an energy corresponding to the received energy information parameter toward the end of said received first non erased frame while limiting an increase in energy. 129. A device as defined in claim 90, wherein: the energy information parameter is not transmitted from the encoder to the decoder; and the means for conducting frame erasure concealment and decoder recovery comprises, when a gain of a LP filter of a first non erased frame received following frame erasure is higher than a gain of a LP filter of a last frame erased during said frame erasure, means for adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame. 130. A device as defined in claim 129, wherein: the means for adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame comprises means for using the following relation: E q = E 1 ⁢ E LP0 E LP1 where E1 is the energy at the end of the current frame, ELP0 is the energy of an impulse response of the LP filter to the last non erased frame received before the frame erasure, and ELP1 is the energy of the impulse response of the LP filter to the received first non erased frame following frame erasure. 131. A device as defined in claim 128, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and when the first non erased frame received after a frame erasure is classified as ONSET, the means for conducting frame erasure concealment and decoder recovery comprises means for limiting to a given value a gain used for scaling thee synthesized sound signal. 132. A device as defined in claim 128, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and said device comprises means for making a gain used for scaling the synthesized sound signal at the beginning of the first non erased frame received after frame erasure equal to a gain used at the end of said received first non erased frame: during a transition from a voiced frame to an unvoiced frame, in the case of a last non erased frame received before frame erasure classified as voiced transition, voice or onset and a first non erased frame received after frame erasure classified as unvoiced; and during a transition from a non-active speech period to an active speech period, when the last non erased frame received before frame erasure is encoded as comfort noise and the first non erased frame received after frame erasure is encoded as active speech. 133. A device for conducting concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, comprising: means for determining, in the encoder, concealment/recovery parameters; and means for transmitting to the decoder concealment/recovery parameters determined in the encoder. 134. A device as defined in claim 133, further comprising means for quantizing, in the encoder, the concealment/recovery parameters prior to transmitting said concealment/recovery parameters to the decoder. 135. A device as defined in claim 133, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 136. A device as defined in claim 135, wherein the means for determining the phase information parameter comprises means for determining the position of a first glottal pulse in a frame of the encoded sound signal. 137. A device as defined in claim 136, wherein the means for determining the phase information parameter further comprises means for encoding, in the encoder, the shape, sign and amplitude of the first glottal pulse and means for transmitting the encoded shape, sign and amplitude from the encoder to the decoder. 138. A device as defined in claim 136, wherein the means for determining the position of the first glottal pulse comprises: means for measuring the first glottal pulse as a sample of maximum amplitude within a pitch period; and means for quantizing the position of the sample of maximum amplitude within the pitch period. 139. A device as defined in claim 133, wherein: the sound signal is a speech signal; and the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 140. A device as defined in claim 139, wherein the means for classifying the successive frames comprises means for classifying as unvoiced every frame which is an unvoiced frame, every frame without active speech, and every voiced offset frame having an end tending to be unvoiced. 141. A device as defined in claim 139, wherein the means for classifying the successive frames comprises means for classifying as unvoiced transition every unvoiced frame having an end with a possible voiced onset which is too short or not built well enough to be processed as a voiced frame. 142. A device as defined in claim 139, wherein the means for classifying the successive frames comprises means for classifying as voiced transition every voiced frame with relatively weak voiced characteristics, including voiced frames with rapidly changing characteristics and voiced offsets lasting the whole frame, wherein a frame classified as voiced transition follows only frames classified as voiced transition, voiced or onset. 143. A device as defined in claim 139, wherein the means for classifying the successive frames comprises means for classifying as voiced every voiced frames with stable characteristics, wherein a frame classified as voiced follows only frames classified as voiced transition, voiced or onset. 144. A device as defined in claim 139, wherein the means for classifying the successive frames comprises means for classifying as onset every voiced frame with stable characteristics following a frame classified as unvoiced or unvoiced transition. 145. A device as defined in claim 139, comprising means for determining the classification of the successive frames of the encoded sound signal on the basis of at least a part of the following parameters: a normalized correlation parameter, a spectral tilt parameter, a signal-to-noise ratio parameter, a pitch stability parameter, a relative frame energy parameter, and a zero crossing parameter. 146. A device as defined in claim 145, wherein the means for determining the classification of the successive frames comprises: means for computing a figure of merit on the basis of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter; and means for comparing the figure of merit to thresholds to determine the classification. 147. A device as defined in claim 145, comprising means for calculating the normalized correlation parameter on the basis of a current weighted version of the speech signal and a past weighted version of said speech signal. 148. A device as defined in claim 145, comprising means for estimating the spectral tilt parameter as a ratio between an energy concentrated in low frequencies and an energy concentrated in high frequencies. 149. A device as defined in claim 145, comprising means for estimating the signal-to-noise ratio parameter as a ratio between an energy of a weighted version of the speech signal of a current frame and an energy of an error between said weighted version of the speech signal of the current frame and a weighted version of a synthesized speech signal of said current frame. 150. A device as defined in claim 145, comprising means for computing the pitch stability parameter in response to open-loop pitch estimates for a first half of a current frame, a second half of the current frame and a look-ahead. 151. A device as defined in claim 145, comprising means for computing the relative frame energy parameter as a difference between an energy of a current frame and a long-term average of an energy of active speech frames. 152. A device as defined in claim 145, comprising means for determining the zero-crossing parameter as a number of times a sign of the speech signal changes from a first polarity to a second polarity. 153. A device as defined in claim 145, comprising means for computing at least one of the normalized correlation parameter, spectral tilt parameter, signal-to-noise ratio parameter, pitch stability parameter, relative frame energy parameter, and zero crossing parameter using an available look-ahead to take into consideration the behavior of the speech signal in the following frame. 154. A device as defined in claim 145, further comprising means for determining the classification of the successive frames of the encoded sound signal also on the basis of a voice activity detection flag. 155. A device as defined in claim 135, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and the means for determining concealment/recovery parameters comprises means for calculating the energy information parameter in relation to a maximum of a signal energy for frames classified as voiced or onset, and means for calculating the energy information parameter in relation to an average energy per sample for other frames. 156. A device as defined in claim 133, wherein the means for determining, in the encoder, concealment/recovery parameters comprises means for computing a voicing information parameter. 157. A device as defined in claim 156, wherein: the sound signal is a speech signal; the means for determining, in the encoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal; said device comprises means for determining the classification of the successive frames of the encoded sound signal on the basis of a normalized correlation parameter; and the means for computing the voicing information parameter comprises means for estimating said voicing information parameter on the basis of the normalized correlation. 158. A device for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, comprising: means for determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, means for conducting erased frame concealment and decoder recovery in response to concealment/recovery parameters determined by the determining means. 159. A device as defined in claim 158, wherein the concealment/recovery parameters are selected from the group consisting of: a signal classification parameter, an energy information parameter and a phase information parameter. 160. A device as defined in claim 158, wherein: the sound signal is a speech signal; and the means for determining, in the decoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset. 161. A device as defined in claim 158, wherein the means for determining, in the decoder, concealment/recovery parameters comprises means for computing a voicing information parameter. 162. A device as defined in claim 158, wherein the means for conducting frame erasure concealment and decoder recovery comprises: following receiving a non erased unvoiced frame after frame erasure, means for generating no periodic part of a LP filter excitation signal; following receiving, after frame erasure, of a non erased frame other than unvoiced, means for constructing a periodic part of the LP filter excitation signal by repeating a last pitch period of a previous frame. 163. A device as defined in claim 162, wherein the means for constructing the periodic part of the excitation signal comprises a low-pass filter for filtering the repeated last pitch period of the previous frame. 164. A device as defined in claim 163, wherein: the means for determining, in the decoder, concealment/recovery parameters comprises means for computing a voicing information parameter; the low-pass filter has a cut-off frequency; and the means for constructing the periodic part of the LP filter excitation signal comprises means for dynamically adjusting the cut-off frequency in relation to the voicing information parameter. 165. A device as defined in claim 158, wherein the means for conducting frame erasure concealment and decoder recovery comprises means for randomly generating a non-periodic, innovation part of a LP filter excitation signal. 166. A device as defined in claim 165, wherein the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises means for generating a random noise. 167. A device as defined in claim 165, wherein the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal comprises means for randomly generating vector indexes of an innovation codebook. 168. A device as defined in claim 165, wherein: the sound signal is a speech signal; the means for determination, in the decoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; and the means for randomly generating the non-periodic, innovation part of the LP filter excitation signal further comprises: if the last received non erased frame is different from unvoiced, a high-pass filter for filtering the innovation part of the LP filter excitation signal; and if the last received non erased frame is unvoiced, means for using only the innovation part of the LP filter excitation signal. 169. A device as defined in claim 165, wherein: the sound signal is a speech signal; the means for determining, in the decoder, concealment/recovery parameters comprises means for classifying successive frames of the encoded sound signal as unvoiced, unvoiced transition, voiced transition, voiced, or onset; the means for conducting frame erasure concealment and decoder recovery comprises, when an onset frame is lost which is indicated by the presence of a voiced frame following frame erasure and an unvoiced frame before frame erasure, means for artificially reconstructing the lost onset by constructing a periodic part of an excitation signal as a low-pass filtered periodic train of pulses separated by a pitch period. 170. A device as defined in claim 169, wherein the means for conducting frame erasure concealment and decoder recovery further comprises means for constructing an innovation part of the LP filter excitation signal by means of normal decoding. 171. A device as defined in claim 170, wherein the means for constructing an innovation part of the LP filter excitation signal comprises means for randomly choosing entries of an innovation codebook. 172. A device as defined in claim 169, wherein the means for artificially reconstructing the lost onset comprises means for limiting a length of the artificially reconstructed onset so that at least one entire pitch period is constructed by the onset artificial reconstruction, said reconstruction being continued until the end of a current subframe. 173. A device as defined in claim 172, wherein the means for conducting frame erasure concealment and decoder recovery further comprises, after artificial reconstruction of the lost onset, means for resuming a regular CELP processing wherein the pitch period is a rounded average of decoded pitch periods of all subframes where the artificial onset reconstruction is used. 174. A device as defined in claim 159, wherein: the energy information parameter is not transmitted from the encoder to the decoder; and the means for conducting frame erasure concealment and decoder recovery comprises, when a gain of a LP filter of a first non erased frame received following frame erasure is higher than a gain of a LP filter of a last frame erased during said frame erasure, means for adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame using the following relation: E q = E 1 ⁢ E LP0 E LP1 where E1 is the energy at the end of the current frame, ELP0 is the energy of an impulse response of the LP filter to the last non erased frame received before the frame erasure, and ELP1 is the energy of the impulse response of the LP filter to the received first non erased frame following frame erasure. 175. A system for encoding and decoding a sound signal, comprising: a sound signal encoder responsive to the sound signal for producing a set of signal-encoding parameters; means for transmitting the signal-encoding parameters to a decoder; said decoder for synthesizing the sound signal in response to the signal-encoding parameters; and a device as recited in claim 88, for concealing frame erasure caused by frames of the encoded sound signal erased during transmission from the encoder to the decoder. 176. A decoder for decoding an encoded sound signal comprising: means responsive to the encoded sound signal for recovering from said encoded sound signal a set of signal-encoding parameters; means for synthesizing the sound signal in response to the signal-encoding parameters; and a device as recited in claim 158, for concealing frame erasure caused by frames of the encoded sound signal erased during transmission from an encoder to the decoder. 177. An encoder for encoding a sound signal comprising: means responsive to the sound signal for producing a set of signal-encoding parameters; means for transmitting the set of signal-encoding parameters to a decoder responsive to the signal-encoding parameters for recovering the sound signal; and a device as recited in claim 133, for conducting concealment of frame erasure caused by frames erased during transmission of the signal-encoding parameters from the encoder to the decoder.
FIELD OF THE INVENTION The present invention relates to a technique for digitally encoding a sound signal, in particular but not exclusively a speech signal, in view of transmitting and/or synthesizing this sound signal. More specifically, the present invention relates to robust encoding and decoding of sound signals to maintain good performance in case of erased frame(s) due, for example, to channel errors in wireless systems or lost packets in voice over packet network applications. BACKGROUND OF THE INVENTION The demand for efficient digital narrow- and wideband speech encoding techniques with a good trade-off between the subjective quality and bit rate is increasing in various application areas such as teleconferencing, multimedia, and wireless communications. Until recently, a telephone bandwidth constrained into a range of 200-3400 Hz has mainly been used in speech coding applications. However, wideband speech applications provide increased intelligibility and naturalness in communication compared to the conventional telephone bandwidth. A bandwidth in the range of 50-7000 Hz has been found sufficient for delivering a good quality giving an impression of face-to-face communication. For general audio signals, this bandwidth gives an acceptable subjective quality, but is still lower than the quality of FM radio or CD that operate on ranges of 20-16000 Hz and 20-20000 Hz, respectively. A speech encoder converts a speech signal into a digital bit stream which is transmitted over a communication channel or stored in a storage medium. The speech signal is digitized, that is, sampled and quantized with usually 16-bits per sample. The speech encoder has the role of representing these digital samples with a smaller number of bits while maintaining a good subjective speech quality. The speech decoder or synthesizer operates on the transmitted or stored bit stream and converts it back to a sound signal. Code-Excited Linear Prediction (CELP) coding is one of the best available techniques for achieving a good compromise between the subjective quality and bit rate. This encoding technique is a basis of several speech encoding standards both in wireless and wireline applications. In CELP encoding, the sampled speech signal is processed in successive blocks of L samples usually called frames, where L is a predetermined number corresponding typically to 10-30 ms. A linear prediction (LP) filter is computed and transmitted every frame. The computation of the LP filter typically needs a lookahead, a 5-15 ms speech segment from the subsequent frame. The L-sample frame is divided into smaller blocks called subframes. Usually the number of subframes is three or four resulting in 4-10 ms subframes. In each subframe, an excitation signal is usually obtained from two components, the past excitation and the innovative, fixed-codebook excitation. The component formed from the past excitation is often referred to as the adaptive codebook or pitch excitation. The parameters characterizing the excitation signal are coded and transmitted to the decoder, where the reconstructed excitation signal is used as the input of the LP filter. As the main applications of low bit rate speech encoding are wireless mobile communication systems and voice over packet networks, then increasing the robustness of speech codecs in case of frame erasures becomes of significant importance. In wireless cellular systems, the energy of the received signal can exhibit frequent severe fades resulting in high bit error rates and this becomes more evident at the cell boundaries. In this case the channel decoder fails to correct the errors in the received frame and as a consequence, the error detector usually used after the channel decoder will declare the frame as erased. In voice over packet network applications, the speech signal is packetized where usually a 20 ms frame is placed in each packet. In packet-switched communications, a packet dropping can occur at a router if the number of packets become very large, or the packet can reach the receiver after a long delay and it should be declared as lost if its delay is more than the length of a jitter buffer at the receiver side. In these systems, the codec is subjected to typically 3 to 5% frame erasure rates. Furthermore, the use of wideband speech encoding is an important asset to these systems in order to allow them to compete with traditional PSTN (public switched telephone network) that uses the legacy narrow band speech signals. The adaptive codebook, or the pitch predictor, in CELP plays an important role in maintaining high speech quality at low bit rates. However, since the content of the adaptive codebook is based on the signal from past frames, this makes the codec model sensitive to frame loss. In case of erased or lost frames, the content of the adaptive codebook at the decoder becomes different from its content at the encoder. Thus, after a lost frame is concealed and consequent good frames are received, the synthesized signal in the received good frames is different from the intended synthesis signal since the adaptive codebook contribution has been changed. The impact of a lost frame depends on the nature of the speech segment in which the erasure occurred. If the erasure occurs in a stationary segment of the signal then an efficient frame erasure concealment can be performed and the impact on consequent good frames can be minimized. On the other hand, if the erasure occurs in an speech onset or a transition, the effect of the erasure can propagate through several frames. For instance, if the beginning of a voiced segment is lost, then the first pitch period will be missing from the adaptive codebook content. This will have a severe effect on the pitch predictor in consequent good frames, resulting in long time before the synthesis signal converge to the intended one at the encoder. SUMMARY OF THE INVENTION The present invention relates to a method for improving concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: determining, in the encoder, concealment/recovery parameters; transmitting to the decoder the concealment/recovery parameters determined in the encoder; and in the decoder, conducting erasure frame concealment and decoder recovery in response to the received concealment/recovery parameters. The present invention also relates to a method for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, conducting erased frame concealment and decoder recovery in response to the determined concealment/recovery parameters. In accordance with the present invention, there is also provided a device for improving concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: means for determining, in the encoder, concealment/recovery parameters; means for transmitting to the decoder the concealment/recovery parameters determined in the encoder; and in the decoder, means for conducting erasure frame concealment and decoder recovery in response to the received concealment/recovery parameters. According to the invention, there is further provided a device for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: means, for determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, means for conducting erased frame concealment and decoder recovery in response to the determined concealment/recovery parameters. The present invention is also concerned with a system for encoding and decoding a sound signal, and a sound signal decoder using the above defined devices for improving concealment of frame erasure caused by frames of the encoded sound signal erased during transmission from the encoder to the decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received. The foregoing and other objects, advantages and features of the present invention will become more apparent upon reading of the following non restrictive description of illustrative embodiments thereof, given by way of example only with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic block diagram of a speech communication system illustrating an application of speech encoding and decoding devices in accordance with the present invention; FIG. 2 is a schematic block diagram of an example of wideband encoding device (AMR-WB encoder); FIG. 3 is a schematic block diagram of an example of wideband decoding device (AMR-WB decoder); FIG. 4 is a simplified block diagram of the AMR-WB encoder of FIG. 2, wherein the down-sampler module, the high-pass filter module and the pre-emphasis filter module have been grouped in a single pre-processing module, and wherein the closed-loop pitch search module, the zero-input response calculator module, the impulse response generator module, the innovative excitation search module and the memory update module have been grouped in a single closed-loop pitch and innovative codebook search module; FIG. 5 is an extension of the block diagram of FIG. 4 in which modules related to an illustrative embodiment of the present invention have been added; FIG. 6 is a block diagram explaining the situation when an artificial onset is constructed; and FIG. 7 is a schematic diagram showing an illustrative embodiment of a frame classification state machine for the erasure concealment. DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS Although the illustrative embodiments of the present invention will be described in the following description in relation to a speech signal, it should be kept in mind that the concepts of the present invention equally apply to other types of-signal, in particular but not exclusively to other types of sound signals. FIG. 1 illustrates a speech communication system 100 depicting the use of speech encoding and decoding in the context of the present invention. The speech communication system 100 of FIG. 1 supports transmission of a speech signal across a communication channel 101. Although it may comprise for example a wire, an optical link or a fiber link, the communication channel 101 typically comprises at least in part a radio frequency link. The radio frequency link often supports multiple, simultaneous speech communications requiring shared bandwidth resources such as may be found with cellular telephony systems. Although not shown, the communication channel 101 may be replaced by a storage device in a single device embodiment of the system 100 that records and stores the encoded speech signal for later playback. In the speech communication system 100 of FIG. 1, a microphone 102 produces an analog speech signal 103 that is supplied to an analog-to-digital (A/D) converter 104 for converting it into a digital speech signal 105. A speech encoder 106 encodes the digital speech signal 105 to produce a set of signal-encoding parameters 107 that are coded into binary form and delivered to a channel encoder 108. The optional channel encoder 108 adds redundancy to the binary representation of the signal-encoding parameters 107 before transmitting them over the communication channel 101. In the receiver, a channel decoder 109 utilizes the said redundant information in the received bit stream 111 to detect and correct channel errors that occurred during the transmission. A speech decoder 110 converts the bit stream 112 received from the channel decoder 109 back to a set of signal-encoding parameters and creates from the recovered signal-encoding parameters a digital synthesized speech signal 113. The digital synthesized speech signal 113 reconstructed at the speech decoder 110 is converted to an analog form 114 by a digital-to-analog (D/A) converter 115 and played back through a loudspeaker unit 116. The illustrative embodiment of efficient frame erasure concealment method disclosed in the present specification can be used with either narrowband or wideband linear prediction based codecs. The present illustrative embodiment is disclosed in relation to a wideband speech codec that has been standardized by the International Telecommunications Union (ITU) as Recommendation G.722.2 and known as the AMR-WB codec (Adaptive Multi-Rate Wideband codec) [ITU-T Recommendation G.722.2 “Wideband coding of speech at around 16 kbit/s using Adaptive Multi-Rate Wideband (AMR-WB)”, Geneva, 2002]. This codec has also been selected by the third generation partnership project (3GPP) for wideband telephony in third generation wireless systems [3GPP TS 26.190, “AMR Wideband Speech Codec: Transcoding Functions,” 3GPP Technical Specification]. AMR-WB can operate at 9 bit rates ranging from 6.6 to 23.85 kbit/s. The bit rate of 12.65 kbit/s is used to illustrate the present invention. Here, it should be understood that the illustrative embodiment of efficient frame erasure concealment method could be applied to other types of codecs. In the following sections, an overview of the AMR-WB encoder and decoder will be first given. Then, the illustrative embodiment of the novel approach to improve the robustness of the codec will be disclosed. Overview of the AMR-WB Encoder The sampled speech signal is encoded on a block by block basis by the encoding device 200 of FIG. 2 which is broken down into eleven modules numbered from 201 to 211. The input speech signal 212 is therefore processed on a block-by-block basis, i.e. in the above-mentioned L-sample blocks called frames. Referring to FIG. 2, the sampled input speech signal 212 is down-sampled in a down-sampler module 201. The signal is down-sampled from 16 kHz down to 12.8 kHz, using techniques well known to those of ordinary skilled in the art. Down-sampling increases the coding efficiency, since a smaller frequency bandwidth is encoded. This also reduces the algorithmic complexity since the number of samples in a frame is decreased. After down-sampling, the 320-sample frame of 20 ms is reduced to a 256-sample frame (down-sampling ratio of 4/5). The input frame is then supplied to the optional pre-processing module 202. Pre-processing module 202 may consist of a high-pass filter with a 50 Hz cut-off frequency. High-pass filter 202 removes the unwanted sound components below 50 Hz. The down-sampled, pre-processed signal is denoted by sp(n), n=0, 1, 2, . . . , L−1, where L is the length of the frame (256 at a sampling frequency of 12.8 kHz). In an illustrative embodiment of the preemphasis filter 203, the signal sp(n) is preemphasized using a filter having the following transfer function: P(z)=1−μz−1 where μ is a preemphasis factor with a value located between 0 and 1 (a typical value is μ=0.7). The function of the preemphasis filter 203 is to enhance the high frequency contents of the input speech signal. It also reduces the dynamic range of the input speech signal, which renders it more suitable for fixed-point implementation. Preemphasis also plays an important role in achieving a proper overall perceptual weighting of the quantization error, which contributes to improved sound quality. This will be explained in more detail herein below. The output of the preemphasis filter 203 is denoted s(n). This signal is used for performing LP analysis in module 204. LP analysis is a technique well known to those of ordinary skill in the art. In this illustrative implementation, the autocorrelation approach is used. In the autocorrelation approach, the signal s(n) is first windowed using, typically, a Hamming window having a length of the order of 30-40 ms. The autocorrelations are computed from the windowed signal, and Levinson-Durbin recursion is used to compute LP filter coefficients, ai, where i=1, . . . , p, and where p is the LP order, which is typically 16 in wideband coding. The parameters ai are the coefficients of the transfer function A(z) of the LP filter, which is given by the following relation: A ⁡ ( z ) = 1 + ∑ i = 1 p ⁢ a i ⁢ z - i LP analysis is performed in module 204, which also performs the quantization and interpolation of the LP filter coefficients. The LP filter coefficients are first transformed into another equivalent domain more suitable for quantization and interpolation purposes. The line spectral pair (LSP) and immitance spectral pair (ISP) domains are two domains in which quantization and interpolation can be efficiently performed. The 16 LP filter coefficients, ai, can be quantized in the order of 30 to 50 bits using split or multi-stage quantization, or a combination thereof. The purpose of the interpolation is to enable updating the LP filter coefficients every subframe while transmitting them once every frame, which improves the encoder performance without increasing the bit rate. Quantization and interpolation of the LP filter coefficients is believed to be otherwise well known to those of ordinary skill in the art and, accordingly, will not be further described in the present specification. The following paragraphs will describe the rest of the coding operations performed on a subframe basis. In this illustrative implementation, the input frame is divided into 4 subframes of 5 ms (64 samples at the sampling frequency of 12.8 kHz). In the following description, the filter A(z) denotes the unquantized interpolated LP filter of the subframe, and the filter Â(z) denotes the quantized interpolated LP filter of the subframe. The filter Â(z) is supplied every subframe to a multiplexer 213 for transmission through a communication channel. In analysis-by-synthesis encoders, the optimum pitch and innovation parameters are searched by minimizing the mean squared error between the input speech signal 212 and a synthesized speech signal in a perceptually weighted domain. The weighted signal sw(n) is computed in a perceptual weighting filter 205 in response to the signal s(n) from the pre-emphasis filter 203. A perceptual weighting filter 205 with fixed denominator, suited for wideband signals, is used. An example of transfer function for the perceptual weighting filter 205 is given by the following relation: W(z)=A(z/γ1)/(1−γ2z−1) where 0<γ2<γ1≦1 In order to simplify the pitch analysis, an open-loop pitch lag TOL is first estimated in an open-loop pitch search module 206 from the weighted speech signal sw(n). Then the closed-loop pitch analysis, which is performed in a closed-loop pitch search module 207 on a subframe basis, is restricted around the open-loop pitch lag TOL which significantly reduces the search complexity of the LTP parameters T (pitch lag) and b (pitch gain) The open-loop pitch analysis is usually performed in module 206 once every 10 ms (two subframes) using techniques well known to those of ordinary skill in the art. The target vector x for LTP (Long Term Prediction) analysis is first computed. This is usually done by subtracting the zero-input response s0 of weighted synthesis filter W(z)/Â(z) from the weighted speech signal sw(n). This zero-input response s0 is calculated by a zero-input response calculator 208 in response to the quantized interpolation LP filter Â(z) from the LP analysis, quantization and interpolation module 204 and to the initial states of the weighted synthesis filter W(z)Â(z) stored in memory update module 211 in response to the LP filters A(z) and Â(z), and the excitation vector u. This operation is well known to those of ordinary skill in the art and, accordingly, will not be further described. A N-dimensional impulse response vector h of the weighted synthesis filter W(z)/Â(z) is computed in the impulse response generator 209 using the coefficients of the LP filter A(z) and Â(z) from module 204. Again, this operation is well known to those of ordinary skill in the art and, accordingly, will not be further described in the present specification. The closed-loop pitch (or pitch codebook) parameters b, T and j are computed in the closed-loop pitch search module 207, which uses the target vector x, the impulse response vector h and the open-loop pitch lag TOL as inputs. The pitch search consists of finding the best pitch lag T and gain b that minimize a mean squared weighted pitch prediction error, for example e(j)=∥x−b(j)y(j)∥2 where j=1, 2, . . . , k between the target vector x and a scaled filtered version of the past excitation. More specifically, in the present illustrative implementation, the pitch (pitch codebook) search is composed of three stages. In the first stage, an open-loop pitch lag TOL is estimated in the open-loop pitch search module 206 in response to the weighted speech signal sw(n). As indicated in the foregoing description, this open-loop pitch analysis is usually performed once every 10 ms (two subframes) using techniques well known to those of ordinary skill in the art. In the second stage, a search criterion C is searched in the closed-loop pitch search module 207 for integer pitch lags around the estimated open-loop pitch lag TOL (usually ±5), which significantly simplifies the search procedure. A simple procedure is used for updating the filtered codevector yT (this vector is defined in the following description) without the need to compute the convolution for every pitch lag. An example of search criterion C is given by: C = x t ⁢ y T y T t ⁢ y T where t denotes vector transpose Once an optimum integer pitch lag is found in the second stage, a third stage of the search (module 207) tests, by means of the search criterion C, the fractions around that optimum integer pitch lag. For example, the AMR-WB standard uses ¼ and ½ subsample resolution. In wideband signals, the harmonic structure exists only up to a certain frequency, depending on the speech segment. Thus, in order to achieve efficient representation of the pitch contribution in voiced segments of a wideband speech signal, flexibility is needed to vary the amount of periodicity over the wideband spectrum. This is achieved by processing the pitch codevector through a plurality of frequency shaping filters (for example low-pass or band-pass filters). And the frequency shaping filter that minimizes the mean-squared weighted error e(j) is selected. The selected frequency shaping filter is identified by an index j. The pitch codebook index T is encoded and transmitted to the multiplexer 213 for transmission through a communication channel. The pitch gain b is quantized and transmitted to the multiplexer 213. An extra bit is used to encode the index j, this extra bit being also supplied to the multiplexer 213. Once the pitch, or LTP (Long Term Prediction) parameters b, T, and j are determined, the next step is to search for the optimum innovative excitation by means of the innovative excitation search module 210 of FIG. 2. First, the target vector x is updated by subtracting the LTP contribution: x′=x−byT where b is the pitch gain and yT is the filtered pitch codebook vector (the past excitation at delay T filtered with the selected frequency shaping filter (index j) filter and convolved with the impulse response h). The innovative excitation search procedure in CELP is performed in an innovation codebook to find the optimum excitation codevector ck and gain g which minimize the mean-squared error E between the target vector x′ and a scaled filtered version of the codevector ck, for example: E=λx′−gHck∥2 where H is a lower triangular convolution matrix derived from the impulse response vector h. The index k of the innovation codebook corresponding to the found optimum codevector ck and the gain g are supplied to the multiplexer 213 for transmission through a communication channel. It should be noted that the used innovation codebook is a dynamic codebook consisting of an algebraic codebook followed by an adaptive prefilter F(z) which enhances special spectral components in order to improve the synthesis speech quality, according to U.S. Pat. No. 5,444,816 granted to Adoul et al. on Aug. 22, 1995. In this illustrative implementation, the innovative codebook search is performed in module 210 by means of an algebraic codebook as described in U.S. Pat. No. 5,444,816 (Adoul et al.) issued on Aug. 22, 1995; U.S. Pat. No. 5,699,482 granted to Adoul et al., on Dec. 17, 1997; U.S. Pat. No. 5,754,976 granted to Adoul et al., on May 19, 1998; and U.S. Pat. No. 5,701,392 (Adoul et al.) dated Dec. 23, 1997. Overview of AMR-WB Decoder The speech decoder 300 of FIG. 3 illustrates the various steps carried out between the digital input 322 (input bit stream to the demultiplexer 317) and the output sampled speech signal 323 (output of the adder 321). Demultiplexer 317 extracts the synthesis model parameters from the binary information (input bit stream 322) received from a digital input channel. From each received binary frame, the extracted parameters are: the quantized, interpolated LP coefficients Â(z) also called short-term prediction parameters (STP) produced once per frame; the long-term prediction (LTP) parameters T, b, and j (for each subframe); and the innovation codebook index k and gain g (for each subframe). The current speech signal is synthesized based on these parameters as will be explained hereinbelow. The innovation codebook 318 is responsive to the index k to produce the innovation codevector ck, which is scaled by the decoded gain factor g through an amplifier 324. In the illustrative implementation, an innovation codebook as described in the above mentioned U.S. Pat. Nos. 5,444,816; 5,699,482; 5,754,976; and 5,701,392 is used to produce the innovative codevector ck. The generated scaled codevector at the output of the amplifier 324 is processed through a frequency-dependent pitch enhancer 305. Enhancing the periodicity of the excitation signal u improves the quality of voiced segments. The periodicity enhancement is achieved by filtering the innovative codevector ck from the innovation (fixed) codebook through an innovation filter F(z) (pitch enhancer 305) whose frequency response emphasizes the higher frequencies more than the lower frequencies. The coefficients of the innovation filter F(z) are related to the amount of periodicity in the excitation signal u. An efficient, illustrative way to derive the coefficients of the innovation filter F(z) is to relate them to the amount of pitch contribution in the total excitation signal u. This results in a frequency response depending on the subframe periodicity, where higher frequencies are more strongly emphasized (stronger overall slope) for higher pitch gains. The innovation filter 305 has the effect of lowering the energy of the innovation codevector ck at lower frequencies when the excitation signal u is more periodic, which enhances the periodicity of the excitation signal u at lower frequencies more than higher frequencies. A suggested form for the innovation filter 305 is the following: F(z)=−αz+1−αz−1 where α is a periodicity factor derived from the level of periodicity of the excitation signal u. The periodicity factor α is computed in the voicing factor generator 304. First, a voicing factor rv is computed in voicing factor generator 304 by: rv=(Ev−Ec)/(Ev+Ec) where Ev is the energy of the scaled pitch codevector bvT and EC is the energy of the scaled innovative codevector gck. That is: E v = b 2 ⁢ v T t ⁢ v T = b 2 ⁢ ⁢ ∑ n = 0 N - 1 ⁢ v T 2 ⁡ ( n ) and E c = g 2 ⁢ c k t ⁢ c k = g 2 ⁢ ⁢ ∑ n = 0 N - 1 ⁢ c k 2 ⁡ ( n ) Note that the value of rv lies between −1 and 1 (1 corresponds to purely voiced signals and −1 corresponds to purely unvoiced signals). The above mentioned scaled pitch codevector bvT is produced by applying the pitch delay T to a pitch codebook 301 to produce a pitch codevector. The pitch codevector is then processed through a low-pass filter 302 whose cut-off frequency is selected in relation to index j from the demultiplexer 317 to produce the filtered pitch codevector vT. Then, the filtered pitch codevector vT is then amplified by the pitch gain b by an amplifier 326 to produce the scaled pitch codevector bvT. In this illustrative implementation, the factor α is then computed in voicing factor generator 304 by: α=0.125(1+rV) which corresponds to a value of 0 for purely unvoiced signals and 0.25 for purely voiced signals. The enhanced signal cf is therefore computed by filtering the scaled innovative codevector gck through the innovation filter 305 (F(z)). The enhanced excitation signal u′ is computed by the adder 320 as: u′=cf+bvT It should be noted that this process is not performed at the encoder 200. Thus, it is essential to update the content of the pitch codebook 301 using the past value of the excitation signal u without enhancement stored in memory 303 to keep synchronism between the encoder 200 and decoder 300. Therefore, the excitation signal u is used to update the memory 303 of the pitch codebook 301 and the enhanced excitation signal u′ is used at the input of the LP synthesis filter 306. The synthesized signal s′ is computed by filtering the enhanced excitation signal u′ through the LP synthesis filter 306 which has the form 1/Â(z), where Â(z) is the quantized, interpolated LP filter in the current subframe. As can be seen in FIG. 3, the quantized, interpolated LP coefficients Â(z) on line 325 from the demultiplexer 317 are supplied to the LP synthesis filter 306 to adjust the parameters of the LP synthesis filter 306 accordingly. The deemphasis filter 307 is the inverse of the preemphasis filter 203 of FIG. 2. The transfer function of the deemphasis filter 307 is given by D(z)=1/(1−μz−1) where μ is a preemphasis factor with a value located between 0 and 0.1 (a typical value is μ=0.7). A higher-order filter could also be used. The vector s′ is filtered through the deemphasis filter D(z) 307 to obtain the vector sd, which is processed through the high-pass filter 308 to remove the unwanted frequencies below 50 Hz and further obtain sh. The oversampler 309 conducts the inverse process of the downsampler 201 of FIG. 2. In this illustrative embodiment, over-sampling converts the 12.8 kHz sampling rate back to the original 16 kHz sampling rate, using techniques well known to those of ordinary skill in the art. The oversampled synthesis signal is denoted ŝ. Signal ŝ is also referred to as the synthesized wideband intermediate signal. The oversampled synthesis signal ŝ does not contain the higher frequency components which were lost during the downsampling process (module 201 of FIG. 2) at the encoder 200. This gives a low-pass perception to the synthesized speech signal. To restore the full band of the original signal, a high frequency generation procedure is performed in module 310 and requires input from voicing factor generator 304 (FIG. 3). The resulting band-pass filtered noise sequence z from the high frequency generation module 310 is added by the adder 321 to the oversampled synthesized speech signal ŝ to obtain the final reconstructed output speech signal sout on the output 323. An example of high frequency regeneration process is described in International PCT patent application published under No. WO 00/25305 on May 4, 2000. The bit allocation of the AMR-WB codec at 12.65 kbit/s is given in Table 1. TABLE 1 Bit allocation in the 12.65-kbit/s mode Parameter Bits / Frame LP Parameters 46 Pitch Delay 30 = 9 + 6 + 9 + 6 Pitch Filtering 4 = 1 + 1 + 1 + 1 Gains 28 = 7 + 7 + 7 + 7 Algebraic Codebook 144 = 36 + 36 + 36 + 36 Mode Bit 1 Total 253 bits = 12.65 kbit/s Robust Frame Erasure Concealment The erasure of frames has a major effect on the synthesized speech quality in digital speech communication systems, especially when operating in wireless environments and packet-switched networks. In wireless cellular systems, the energy of the received signal can exhibit frequent severe fades resulting in high bit error rates and this becomes more evident at the cell boundaries. In this case the channel decoder fails to correct the errors in the received frame and as a consequence, the error detector usually used after the channel decoder will declare the frame as erased. In voice over packet network applications, such as Voice over Internet Protocol (VoIP), the speech signal is packetized where usually a 20 ms frame is placed in each packet. In packet-switched communications, a packet dropping can occur at a router if the number of packets becomes very large, or the packet can arrive at the receiver after a long delay and it should be declared as lost if its delay is more than the length of a jitter buffer at the receiver side. In these systems, the codec is subjected to typically 3 to 5% frame erasure rates. The problem of frame erasure (FER) processing is basically twofold. First, when an erased frame indicator arrives, the missing frame must be generated by using the information sent in the previous frame and by estimating the signal evolution in the missing frame. The success of the estimation depends not only on the concealment strategy, but also on the place in the speech signal where the erasure happens. Secondly, a smooth transition must be assured when normal operation recovers, i.e. when the first good frame arrives after a block of erased frames (one or more). This is not a trivial task as the true synthesis and the estimated synthesis can evolve differently. When the first good frame arrives, the decoder is hence desynchronized from the encoder. The main reason is that low bit rate encoders rely on pitch prediction, and during erased frames, the memory of the pitch predictor is no longer the same as the one at the encoder. The problem is amplified when many consecutive frames are erased. As for the concealment, the difficulty of the normal processing recovery depends on the type of speech signal where the erasure occurred. The negative effect of frame erasures can be significantly reduced by adapting the concealment and the recovery of normal processing (further recovery) to the type of the speech signal where the erasure occurs. For this purpose, it is necessary to classify each speech frame. This classification can be done at the encoder and transmitted. Alternatively, it can be estimated at the decoder. For the best concealment and recovery, there are few critical characteristics of the speech signal that must be carefully controlled. These critical characteristics are the signal energy or the amplitude, the amount of periodicity, the spectral envelope and the pitch period. In case of a voiced speech recovery, further improvement can be achieved by a phase control. With a slight increase in the bit rate, few supplementary parameters can be quantized and transmitted for better control. If no additional bandwidth is available, the parameters can be estimated at the decoder. With these parameters controlled, the frame erasure concealment and recovery can be significantly improved, especially by improving the convergence of the decoded signal to the actual signal at the encoder and alleviating the effect of mismatch between the encoder and decoder when normal processing recovers. In the present illustrative embodiment of the present invention, methods for efficient frame erasure concealment, and methods for extracting and transmitting parameters that will improve the performance and convergence at the decoder in the frames following an erased frame are disclosed. These parameters include two or more of the following: frame classification, energy, voicing information, and phase information. Further, methods for extracting such parameters at the decoder if transmission of extra bits is not possible, are disclosed. Finally, methods for improving the decoder convergence in good frames following an erased frame are also disclosed. The frame erasure concealment techniques according to the present illustrative embodiment have been applied to the AMR-WB codec described above. This codec will serve as an example framework for the implementation of the FER concealment methods in the following description. As explained above, the input speech signal 212 to the codec has a 16 kHz sampling frequency, but it is downsampled to a 12.8 kHz sampling frequency before further processing. In the present illustrative embodiment, FER processing is done on the downsampled signal. FIG. 4 gives a simplified block diagram of the AMR-WB encoder 400. In this simplified block diagram, the downsampler 201, high-pass filter 202 and preemphasis filter 203 are grouped together in the preprocessing module 401. Also, the closed-loop search module 207, the zero-input response calculator 208, the impulse response calculator 209, the innovative excitation search module 210, and the memory update module 211 are grouped in a closed-loop pitch and innovation codebook search modules 402. This grouping is done to simplify the introduction of the new modules related to the illustrative embodiment of the present invention. FIG. 5 is an extension of the block diagram of FIG. 4 where the modules related to the illustrative embodiment of the present invention are added. In these added modules 500 to 507, additional parameters are computed, quantized, and transmitted with the aim to improve the FER concealment and the convergence and recovery of the decoder after erased frames. In the present illustrative embodiment, these parameters include signal classification, energy, and phase information (the estimated position of the first glottal pulse in a frame). In the next sections, computation and quantization of these additional parameters will be given in detail and become more apparent with reference to FIG. 5. Among these parameters, signal classification will be treated in more detail. In the subsequent sections, efficient FER concealment using these additional parameters to improve the convergence will be explained. Signal Classification for FER Concealment and Recovery The basic idea behind using a classification of the speech for a signal reconstruction in the presence of erased frames consists of the fact that the ideal concealment strategy is different for quasi-stationary speech segments and for speech segments with rapidly changing characteristics. While the best processing of erased frames in non-stationary speech segments can be summarized as a rapid convergence of speech-encoding parameters to the ambient noise characteristics, in the case of quasi-stationary signal, the speech-encoding parameters do not vary dramatically and can be kept practically unchanged during several adjacent erased frames before being damped. Also, the optimal method for a signal recovery following an erased block of frames varies with the classification of the speech signal. The speech signal can be roughly classified as voiced, unvoiced and pauses. Voiced speech contains an important amount of periodic components and can be further divided in the following categories: voiced onsets, voiced segments, voiced transitions and voiced offsets. A voiced onset is defined as a beginning of a voiced speech segment after a pause or an unvoiced segment. During voiced segments, the speech signal parameters (spectral envelope, pitch period, ratio of periodic and non-periodic components, energy) vary slowly from frame to frame. A voiced transition is characterized by rapid variations of a voiced speech, such as a transition between vowels. Voiced offsets are characterized by a gradual decrease of energy and voicing at the end of voiced segments. The unvoiced parts of the signal are characterized by missing the periodic component and can be further divided into unstable frames, where the energy and the spectrum changes rapidly, and stable frames where these characteristics remain relatively stable. Remaining frames are classified as silence. Silence frames comprise all frames without active speech, i.e. also noise-only frames if a background noise is present. Not all of the above mentioned classes need a separate processing. Hence, for the purposes of error concealment techniques, some of the signal classes are grouped together. Classification at the Encoder When there is an available bandwidth in the bitstream to include the classification information, the classification can be done at the encoder. This has several advantages. The most important is that there is often a look-ahead in speech encoders. The look-ahead permits to estimate the evolution of the signal in the following frame and consequently the classification can be done by taking into account the future signal behavior. Generally, the longer is the look-ahead, the better can be the classification. A further advantage is a complexity reduction, as most of the signal processing necessary for frame erasure concealment is needed anyway for speech encoding. Finally, there is also the advantage to work with the original signal instead of the synthesized signal. The frame classification is done with the consideration of the concealment and recovery strategy in mind. In other words, any frame is classified in such a way that the concealment can be optimal if the following frame is missing, or that the recovery can be optimal if the previous frame was lost. Some of the classes used for the FER processing need not be transmitted, as they can be deduced without ambiguity at the decoder. In the present illustrative embodiment, five (5) distinct classes are used, and defined as follows: UNVOICED class comprises all unvoiced speech frames and all frames without active speech. A voiced offset frame can be also classified as UNVOICED if its end tends to be unvoiced and the concealment designed for unvoiced frames can be used for the following frame in case it is lost. UNVOICED TRANSITION class comprises unvoiced frames with a possible voiced onset at the end. The onset is however still too short or not built well enough to use the concealment designed for voiced frames. The UNVOICED TRANSITION class can follow only a frame classified as UNVOICED or UNVOICED TRANSITION. VOICED TRANSITION class comprises voiced frames with relatively weak voiced characteristics. Those are typically voiced frames with rapidly changing characteristics (transitions between vowels) or voiced offsets lasting the whole frame. The VOICED TRANSITION class can follow only a frame classified as VOICED TRANSITION, VOICED or ONSET. VOICED class comprises voiced frames with stable characteristics. This class can follow only a frame classified as VOICED TRANSITION, VOICED or ONSET. ONSET class comprises all voiced frames with stable characteristics following a frame classified as UNVOICED or UNVOICED TRANSITION. Frames classified as ONSET correspond to voiced onset frames where the onset is already sufficiently well built for the use of the concealment designed for lost voiced frames. The concealment techniques used for a frame erasure following the ONSET class are the same as following the VOICED class. The difference is in the recovery strategy. If an ONSET class frame is lost (i.e. a VOICED good frame arrives after an erasure, but the last good frame before the erasure was UNVOICED), a special technique can be used to artificially reconstruct the lost onset. This scenario can be seen in FIG. 6. The artificial onset reconstruction techniques will be described in more detail in the following description. On the other hand if an ONSET good frame arrives after an erasure and the last good frame before the erasure was UNVOICED, this special processing is not needed, as the onset has not been lost (has not been in the lost frame). The classification state diagram is outlined in FIG. 7. If the available bandwidth is sufficient, the classification is done in the encoder and transmitted using 2 bits. As it can be seen from FIG. 7, UNVOICED TRANSITION class and VOICED TRANSITION class can be grouped together as they can be unambiguously differentiated at the decoder (UNVOICED TRANSITION can follow only UNVOICED or UNVOICED TRANSITION frames, VOICED TRANSITION can follow only ONSET, VOICED or VOICED TRANSITION frames). The following parameters are used for the classification: a normalized correlation rx, a spectral tilt measure et, a signal to noise ratio snr, a pitch stability counter pc, a relative frame energy of the signal at the end of the current frame Es and a zero-crossing counter zc. As can be seen in the following detailed analysis, the computation of these parameters uses the available look-ahead as much as possible to take into account the behavior of the speech signal also in the following frame. The normalized correlation rx is computed as part of the open-loop pitch search module 206 of FIG. 5. This module 206 usually outputs the open-loop pitch estimate every 10 ms (twice per frame). Here, it is also used to output the normalized correlation measures. These normalized correlations are computed on the current weighted speech signal sw(n) and the past weighted speech signal at the open-loop pitch delay. In order to reduce the complexity, the weighted speech signal sw(n) is downsampled by a factor of 2 prior to the open-loop pitch analysis down to the sampling frequency of 6400 Hz [3GPP TS 26.190, “AMR Wideband Speech Codec: Transcoding Functions,” 3GPP Technical Specification]. The average correlation rx is defined as {tilde over (r)}x=0.5(rx(1)+rx(2))(1) where rx(1), rx(2) are respectively the normalized correlation of the second half of the current frame and of the look-ahead. In this illustrative embodiment, a look-ahead of 13 ms is used unlike the AMR-WB standard that uses 5 ms. The normalized correlation rx(k) is computed as follows: r x ⁡ ( k ) = r x ⁢ ⁢ y r x ⁢ ⁢ x , r y ⁢ ⁢ y , where r x ⁢ ⁢ y = ∑ i = 0 Lk - 1 ⁢ x ⁡ ( t k + i ) · x ⁡ ( t k + i - p k ) r x ⁢ ⁢ x = ∑ i = 0 Lk - 1 ⁢ x 2 ⁡ ( t k + i ) r y ⁢ ⁢ y = ∑ i = 0 Lk - 1 ⁢ x 2 ⁡ ( t k + i - p k ) ( 2 ) The correlations rx(k) are computed using the weighted speech signal sw(n). The instants tk are related to the current frame beginning and are equal to 64 and 128 samples respectively at the sampling rate or frequency of 6.4 kHz (10 and 20 ms). The values pk=TOL are the selected open-loop pitch estimates. The length of the autocorrelation computation Lk is dependant on the pitch period. The values of Lk are summarized below (for the sampling rate of 6.4 kHz): Lk=40 samples for pk≦31 samples Lk=62 samples for pk≦61 samples Lk=115 samples for pk>61 samples These lengths assure that the correlated vector length comprises at least one pitch period which helps for a robust open-loop pitch detection. For long pitch periods (p1>61 samples), rx(1) and rx(2) are identical, i.e. only one correlation is computed since the correlated vectors are long enough so that the analysis on the look-ahead is no longer necessary. The spectral tilt parameter et contains the information about the frequency distribution of energy. In the present illustrative embodiment, the spectral tilt is estimated as a ratio between the energy concentrated in low frequencies and the energy concentrated in high frequencies. However, it can also be estimated in different ways such as a ratio between the two first autocorrelation coefficients of the speech signal. The discrete Fourier Transform is used to perform the spectral analysis in the spectral analysis and spectrum energy estimation module 500 of FIG. 5. The frequency analysis and the tilt computation are done twice per frame. 256 points Fast Fourier Transform (FFT) is used with a 50 percent overlap. The analysis windows are placed so that all the look ahead is exploited. In this illustrative embodiment, the beginning of the first window is placed 24 samples after the beginning of the current frame. The second window is placed 128 samples further. Different windows can be used to weight the input signal for the frequency analysis. A square root of a Hamming window (which is equivalent to a sine window) has been used in the present illustrative embodiment. This window is particularly well suited for overlap-add methods. Therefore, this particular spectral analysis can be used in an optional noise suppression algorithm based on spectral subtraction and overlap-add analysis/synthesis. The energy in high frequencies and in low frequencies is computed in module 500 of FIG. 5 following the perceptual critical bands. In the present illustrative embodiment each critical band is considered up to the following number [J. D. Johnston, “Transform Coding of Audio Signals Using Perceptual Noise Criteria,” IEEE Jour. on Selected Areas in Communications, vol. 6, no. 2, pp. 314-323]: Critical bands {100.0, 200.0, 300.0, 400.0, 510.0, 630.0, 770.0, 920.0, 1080.0, 1270.0, 1480.0, 1720.0, 2000.0, 2320.0, 2700.0, 3150.0, 3700.0, 4400.0, 5300.0, 6350.0} Hz. The energy in higher frequencies is computed in module 500 as the average of the energies of the last two critical bands: {overscore (E)}h=0.5(e(18)+e(19)) (3) where the critical band energies e(i) are computed as a sum of the bin energies within the critical band, averaged by the number of the bins. The energy in lower frequencies is computed as the average of the energies in the first 10 critical bands. The middle critical bands have been excluded from the computation to improve the discrimination between frames with high energy concentration in low frequencies (generally voiced) and with high energy concentration in high frequencies (generally unvoiced). In between, the energy content is not characteristic for any of the classes and would increase the decision confusion. In module 500, the energy in low frequencies is computed differently for long pitch periods and short pitch periods. For voiced female speech segments, the harmonic structure of the spectrum can be exploited to increase the voiced-unvoiced discrimination. Thus for short pitch periods, {overscore (E)}1 is computed bin-wise and only frequency bins sufficiently close to the speech harmonics are taken into account in the summation, i.e. E _ l = 1 cnt · ∑ i = 0 24 ⁢ e b ⁡ ( i ) ( 4 ) where eb(i) are the bin energies in the first 25 frequency bins (the DC component is not considered). Note that these 25 bins correspond to the first 10 critical bands. In the above summation, only terms related to the bins closer to the nearest harmonics than a certain frequency threshold are non zero. The counter cnt equals to the number of those non-zero terms. The threshold for a bin to be included in the sum has been fixed to 50 Hz, i.e. only bins closer than 50 Hz to the nearest harmonics are taken into account. Hence, if the structure is harmonic in low frequencies, only high energy term will be included in the sum. On the other hand, if the structure is not harmonic, the selection of the terms will be random and the sum will be smaller. Thus even unvoiced sounds with high energy content in low frequencies can be detected. This processing cannot be done for longer pitch periods, as the frequency resolution is not sufficient. The threshold pitch value is 128 samples corresponding to 100 Hz. It means that for pitch periods longer than 128 samples and also for a priori unvoiced sounds (i.e. when {overscore (r)}+re<0.6), the low frequency energy estimation is done per critical band and is computed as E _ l = 1 10 · ∑ i = 0 9 ⁢ e ⁡ ( i ) ( 5 ) The value re, calculated in a noise estimation and normalized correlation correction module 501, is a correction added to the normalized correlation in presence of background noise for the following reason. In the presence of background noise, the average normalized correlation decreases. However, for purpose of signal classification, this decrease should not affect the voiced-unvoiced decision. It has been found that the dependence between this decrease re and the total background noise energy in dB is approximately exponential and can be expressed using following relationship re=2.4492·10−4·e0.1596·NdB−0.022 where NdB stands for N dB = 10 · log 10 ⁡ ( 1 20 ⁢ ⁢ ∑ i = 0 19 ⁢ n ⁡ ( i ) ) - g dB Here, n(i) are the noise energy estimates for each critical band normalized in the same way as e(i) and gdB is the maximum noise suppression level in dB allowed for the noise reduction routine. The value re is not allowed to be negative. it should be noted that when a good noise reduction algorithm is used and gdB is sufficiently high, re is practically equal to zero. It is only relevant when the noise reduction is disabled or if the background noise level is significantly higher than the maximum allowed reduction. The influence of re can be tuned by multiplying this term with a constant. Finally, the resulting lower and higher frequency energies are obtained by subtracting an estimated noise energy from the values and {overscore (E)}1 and {overscore (E)}1 calculated above. That is Eh={overscore (E)}h−fc·Nh (6) E1{overscore (E)}1−fc·Nl (7) where Nh and Nl are the averaged noise energies in the last two (2) critical bands and first ten (10) critical bands, respectively, computed using equations similar to Equations (3) and (5), and fc is a correction factor tuned so that these measures remain close to constant with varying the background noise level. In this illustrative embodiment, the value of fc has been fixed to 3. The spectral tilt et is calculated in the spectral tilt estimation module 503 using the relation: e t = E l E h ( 8 ) and it is averaged in the dB domain for the two (2) frequency analyses performed per frame: et=10·log10 (et(0)·et (1)) The signal to noise ratio (SNR) measure exploits the fact that for a general waveform matching encoder, the SNR is much higher for voiced sounds. The snr parameter estimation must be done at the end of the encoder subframe loop and is computed in the SNR computation module 504 using the relation: snr = E sw E e ( 9 ) where Esw is the energy of the weighted speech signal sw(n) of the current frame from the perceptual weighting filter 205 and Ee is the energy of the error between this weighted speech signal and the weighted synthesis signal of the current frame from the perceptual weighting filter 205′. The pitch stability counter PC assesses the variation of the pitch period. It is computed within the signal classification module 505 in response to the open-loop pitch estimates as follows: pc=|p1−p0|+|p2−p1| (10) The values p0, p1, p2 correspond to the open-loop pitch estimates calculated by the open-loop pitch search module 206 from the first half of the current frame, the second half of the current frame and the look-ahead, respectively. The relative frame energy Es is computed by module 500 as a difference between the current frame energy in dB and its long-term average Es={overscore (E)}f−Elt where the frame energy {overscore (E)}f is obtained as a summation of the critical band energies, averaged for the both spectral analysis performed each frame: Ef=10log10(0.5Ef(0)+Ef (1))) E f ⁡ ( j ) = ∑ i = 0 19 ⁢ e ⁡ ( i ) The long-term averaged energy is updated on active speech frames using the following relation: Elt=0.99Elt+0.01Ef The last parameter is the zero-crossing parameter zc computed on one frame of the speech signal by the zero-crossing computation module 508. The frame starts in the middle of the current frame and uses two (2) subframes of the look-ahead. In this illustrative embodiment, the zero-crossing counter zc counts the number of times the signal sign changes from positive to negative during that interval. To make the classification more robust, the classification parameters are considered together forming a function of merit fm. For that purpose, the classification parameters are first scaled between 0 and 1 so that each parameter's value typical for unvoiced signal translates in 0 and each parameter's value typical for voiced signal translates into 1. A linear function is used between them. Let us consider a parameter px, its scaled version is obtained using: ps=kp·px+cp and clipped between 0 and 1. The function coefficients kp and cp have been found experimentally for each of the parameters so that the signal distortion due to the concealment and recovery techniques used in presence of FERs is minimal. The values used in this illustrative implementation are summarized in Table 2: TABLE 2 Signal Classification Parameters and the coefficients of their respective scaling functions Parameter Meaning kp cp {overscore (r)}x Normalized Correlation 2.857 −1.286 {overscore (e)}t Spectral Tilt 0.04167 0 snr Signal to Noise Ratio 0.1111 −0.3333 pc Pitch Stability counter −0.07143 1.857 Es Relative Frame Energy 0.05 0.45 zc Zero Crossing Counter −0.04 2.4 The merit function has been defined as: f m = 1 7 ⁢ ( 2 · r _ x s + e _ t s + snr s + p ⁢ ⁢ c s + E s s + z ⁢ ⁢ c s ) where the superscript s indicates the scaled version of the parameters. The classification is then done using the merit function fm and following the rules summarized in Table 3: TABLE 3 Signal Classification Rules at the Encoder Previous Frame Class Rule Current Frame Class ONSET fm = 0.66 VOICED VOICED VOICED TRANSITION 0.66 > fm = 0.49 VOICED TRANSITION UNVOICED fm < 0.49 UNVOICED TRANSITION fm > 0.63 ONSET UNVOICED 0.63 = fm > 0.585 UNVOICED TRANSITION fm = 0.585 UNVOICED In case of source-controlled variable bit rate (VBR) encoder, a signal classification is inherent to the codec operation. The codec operates at several bit rates, and a rate selection module is used to determine the bit rate used for encoding each speech frame based on the nature of the speech frame (e.g. voiced, unvoiced, transient, background noise frames are each encoded with a special encoding algorithm). The information about the coding mode and thus about the speech class is already an implicit part of the bitstream and need not be explicitly transmitted for FER processing. This class information can be then used to overwrite the classification decision described above. In the example application to the AMR WB codec, the only source-controlled rate selection represents the voice activity detection (VAD). This VAD flag equals 1 for active speech, 0 for silence. This parameter is useful for the classification as it directly indicates that no further classification is needed if its value is 0 (i.e. the frame is directly classified as UNVOICED). This parameter is the output of the voice activity detection (VAD) module 402. Different VAD algorithms exist in the literature and any algorithm can be used for the purpose of the present invention. For instance the VAD algorithm that is part of standard G.722.2 can be used [ITU-T Recommendation G.722.2 “Wideband coding of speech at around 16 kbit/s using Adaptive Multi-Rate Wideband (AMR-WB)”, Geneva, 2002]. Here, the VAD algorithm is based on the output of the spectral analysis of module 500 (based on signal-to-noise ratio per critical band). The VAD used for the classification purpose differs from the one used for encoding purpose with respect to the hangover. In speech encoders using a comfort noise generation (CNG) for segments without active speech (silence or noise-only), a hangover is often added after speech spurts (CNG in AMR-WB standard is an example [3GPP TS 26.192, “AMR Wideband Speech Codec: Comfort Noise Aspects,” 3GPP Technical Specification]). During the hangover, the speech encoder continues to be used and the system switches to the CNG only after the hangover period is over. For the purpose of classification for FER concealment, this high security is not needed. Consequently, the VAD flag for the classification will equal to 0 also during the hangover period. In this illustrative embodiment, the classification is performed in module 505 based on the parameters described above; namely, normalized correlations (or voicing information) rx, spectral tilt et, snr, pitch stability counter pc, relative frame energy Es, zero crossing rate zc, and VAD flag. Classification at the Decoder If the application does not permit the transmission of the class information (no extra bits can be transported), the classification can be still performed at the decoder. As already noted, the main disadvantage here is that there is generally no available look ahead in speech decoders. Also, there is often a need to keep the decoder complexity limited. A simple classification can be done by estimating the voicing of the synthesized signal. If we consider the case of a CELP type encoder, the voicing estimate rv computed as in Equation (1) can be used. That is: rv=(Ev−Ec)/(Ev+Ec) where Ev is the energy of the scaled pitch codevector bvT and Ec is the energy of the scaled innovative codevector gck. Theoretically, for a purely voiced signal rv=1 and for a purely unvoiced signal rv=−1. The actual classification is done by averaging rv values every 4 subframes. The resulting factor frv (average of rv values of every four subframes) is used as follows TABLE 4 Signal Classification Rules at the Decoder Previous Frame Class Rule Current Frame Class ONSET frv > −0.1 VOICED VOICED VOICED TRANSITION −0.1 = frv = −0.5 VOICED TRANSITION UNVOICED frv < −0.5 UNVOICED TRANSITION UNVOICED frv > −0.1 ONSET −0.1 = frv = −0.5 UNVOICED TRANSITION frv < −0.5 UNVOICED Similarly to the classification at the encoder, other parameters can be used at the decoder to help the classification, as the parameters of the LP filter or the pitch stability. In case of source-controlled variable bit rate coder, the information about the coding mode is already a part of the bitstream. Hence, if for example a purely unvoiced coding mode is used, the frame can be automatically classified as UNVOICED. Similarly, if a purely voiced coding mode is used, the frame is classified as VOICED. Speech Parameters for FER Processing There are few critical parameters that must be carefully controlled to avoid annoying artifacts when FERs occur. If few extra bits can be transmitted then these parameters can be estimated at the encoder, quantized, and transmitted. Otherwise, some of them can be estimated at the decoder. These parameters include signal classification, energy information, phase information, and voicing information. The most important is a precise control of the speech energy. The phase and the speech periodicity can be controlled too for further improving the FER concealment and recovery. The importance of the energy control manifests itself mainly when a normal operation recovers after an erased block of frames. As most of speech encoders make use of a prediction, the right energy cannot be properly estimated at the decoder. In voiced speech segments, the incorrect energy can persist for several consecutive frames which is very annoying especially when this incorrect energy increases. Even if the energy control is most important for voiced speech because of the long term prediction (pitch prediction), it is important also for unvoiced speech. The reason here is the prediction of the innovation gain quantizer often used in CELP type coders. The wrong energy during unvoiced segments can cause an annoying high frequency fluctuation. The phase control can be done in several ways, mainly depending on the available bandwidth. In our implementation, a simple phase control is achieved during lost voiced onsets by searching the approximate information about the glottal pulse position. Hence, apart from the signal classification information discussed in the previous section, the most important information to send is the information about the signal energy and the position of the first glottal pulse in a frame (phase information). If enough bandwidth is available, a voicing information can be sent, too. Energy Information The energy information can be estimated and sent either in the LP residual domain or in the speech signal domain. Sending the information in the residual domain has the disadvantage of not taking into account the influence of the LP synthesis filter. This can be particularly tricky in the case of voiced recovery after several lost voiced frames (when the FER happens during a voiced speech segment). When a FER arrives after a voiced frame, the excitation of the last good frame is typically used during the concealment with some attenuation strategy. When a new LP synthesis filter arrives with the first good frame after the erasure, there can be a mismatch between the excitation energy and the gain of the LP synthesis filter. The new synthesis filter can produce a synthesis signal with an energy highly different from the energy of the last synthesized erased frame and also from the original signal energy. For this reason, the energy is computed and quantized in the signal domain. The energy Eq is computed and quantized in energy estimation and quantization module 506. It has been found that 6 bits are sufficient to transmit the energy. However, the number of bits can be reduced without a significant effect if not enough bits are available. In this preferred embodiment, a 6 bit uniform quantizer is used in the range of −15 dB to 83 dB with a step of 1.58 dB. The quantization index is given by the integer part of: i = 10 ⁢ ⁢ log 10 ⁡ ( E + 0.001 ) + 15 1.58 ( 15 ) where E is the maximum of the signal energy for frames classified as VOICED or ONSET, or the average energy per sample for other frames. For VOICED or ONSET frames, the maximum of signal energy is computed pitch synchronously at the end of the frame as follow: E = max i = L - t E L - 1 ⁢ ( s 2 ⁡ ( i ) ) ( 16 ) where L is the frame length and signal s(i) stands for speech signal (or the denoised speech signal if a noise suppression is used). In this illustrative embodiment s(i) stands for the input signal after downsampling to 12.8 kHz and pre-processing. If the pitch delay is greater than 63 samples, tE equals the rounded close-loop pitch lag of the last subframe. If the pitch delay is shorter than 64 samples, then tE is set to twice the rounded close-loop pitch lag of the last subframe. For other classes, E is the average energy per sample of the second half of the current frame, i.e. tE is set to L/2 and the E is computed as: E = 1 t E ⁢ ⁢ ∑ i = L - t E L - 1 ⁢ s 2 ⁡ ( i ) ( 17 ) Phase Control Information The phase control is particularly important while recovering after a lost segment of voiced speech for similar reasons as described in the previous section. After a block of erased frames, the decoder memories become desynchronized with the encoder memories. To resynchronize the decoder, some phase information can be sent depending on the available bandwidth. In the described illustrative implementation, a rough position of the first glottal pulse in the frame is sent. This information is then used for the recovery after lost voiced onsets as will be described later. Let T0 be the rounded closed-loop pitch lag for the first subframe. First glottal pulse search and quantization module 507 searches the position of the first glottal pulse τ among the T0 first samples of the frame by looking for the sample with the maximum amplitude. Best results are obtained when the position of the first glottal pulse is measured on the low-pass filtered residual signal. The position of the first glottal pulse is coded using 6 bits in the following manner. The precision used to encode the position of the first glottal pulse depends on the closed-loop pitch value for the first subframe T0. This is possible because this value is known both by the encoder and the decoder, and is not subject to error propagation after one or several frame losses. When T0 is less than 64, the position of the first glottal pulse relative to the beginning of the frame is encoded directly with a precision of one sample. When 64=T0<128, the position of the first glottal pulse relative to the beginning of the frame is encoded with a precision of two samples by using a simple integer division, i.e. τ/2. When T0=128, the position of the first glottal pulse relative to the beginning of the frame is encoded with a precision of four samples by further dividing τ by 2. The inverse procedure is done at the decoder. If T0<64, the received quantized position is used as is. If 64=T0<128, the received quantized position is multiplied by 2 and incremented by 1. If T0=128, the received quantized position is multiplied by 4 and incremented by 2 (incrementing by 2 results in uniformly distributed quantization error). According to another embodiment of the invention where the shape of the first glottal pulse is encoded, the position of the first glottal pulse is determined by a correlation analysis between the residual signal and the possible pulse shapes, signs (positive or negative) and positions. The pulse shape can be taken from a codebook of pulse shapes known at both the encoder and the decoder, this method being known as vector quantization by those of ordinary skill in the art. The shape, sign and amplitude of the first glottal pulse are then encoded and transmitted to the decoder. Periodicity Information In case there is enough bandwidth, a periodicity information, or voicing information, can be computed and transmitted, and used at the decoder to improve the frame erasure concealment. The voicing information is estimated based on the normalized correlation. It can be encoded quite precisely with 4 bits, however, 3 or even 2 bits would suffice if necessary. The voicing information is necessary in general only for frames with some periodic components and better voicing resolution is needed for highly voiced frames. The normalized correlation is given in Equation (2) and it is used as an indicator to the voicing Information. It is quantized in first glottal pulse search and quantization module 507. In this illustrative embodiment, a piece-wise linear quantizer has been used to encode the voicing information as follows: i = r x ⁡ ( 2 ) - 0.65 0.03 + 0.5 , for ⁢ ⁢ r X ⁡ ( 2 ) < 0.92 ( 18 ) i = 9 + r x ⁡ ( 2 ) - 0.92 0.01 + 05 , for ⁢ ⁢ r X ⁡ ( 2 ) ≥ 0.92 ( 19 ) Again, the integer part of i is encoded and transmitted. The correlation rx(2) has the same meaning as in Equation (1). In Equation (18) the voicing is linearly quantized between 0.65 and 0.89 with the step of 0.03. In Equation (19) the voicing is linearly quantized between 0.92 and 0.98 with the step of 0.01. If larger quantization range is needed, the following linear quantization can be used: i = r _ x - 0.4 0.04 + 0.5 ( 20 ) This equation quantizes the voicing in the range of 0.4 to 1 with the step of 0.04. The correlation {overscore (r)}x is defined in Equation (2a). The equations (18) and (19) or the equation (20) are then used in the decoder to compute rx(2) or {overscore (r)}x. Let us call this quantized normalized correlation rq. If the voicing cannot be transmitted, it can be estimated using the voicing factor from Equation (2a) by mapping it in the range from 0 to 1. rq=0.5·(f+1) (21) Processing of Erased Frames The FER concealment techniques in this illustrative embodiment are demonstrated on ACELP type encoders. They can be however easily applied to any speech codec where the synthesis signal is generated by filtering an excitation signal through an LP synthesis filter. The concealment strategy can be summarized as a convergence of the signal energy and the spectral envelope to the estimated parameters of the background noise. The periodicity of the signal is converging to zero. The speed of the convergence is dependent on the parameters of the last good received frame class and the number of consecutive erased frames and is controlled by an attenuation factor α. The factor α is further dependent on the stability of the LP filter for UNVOICED frames. In general, the convergence is slow if the last good received frame is in a stable segment and is rapid if the frame is in a transition segment. The values of a are summarized in Table 5. TABLE 5 Values of the FER concealment attenuation factor α Last Good Received Number of successive Frame erased frames α ARTIFICIAL ONSET 0.6 ONSET, VOICED =3 1.0 >3 0.4 VOICED TRANSITION 0.4 UNVOICED TRANSITION 0.8 UNVOICED =1 0.6 θ + 0.4 >1 0.4 A stability factor θ is computed based on a distance measure between the adjacent LP filters. Here, the factor θ is related to the ISF (Immittance Spectral Frequencies) distance measure and it is bounded by 0≦θ≦1, with larger values of θ corresponding to more stable signals. This results in decreasing energy and spectral envelope fluctuations when an isolated frame erasure occurs inside a stable unvoiced segment. The signal class remains unchanged during the processing of erased frames, i.e. the class remains the same as in the last good received frame. Construction of the Periodic Part of the Excitation For a concealment of erased frames following a correctly received UNVOICED frame, no periodic part of the excitation signal is generated. For a concealment of erased frames following a correctly received frame other than UNVOICED, the periodic part of the excitation signal is constructed by repeating the last pitch period of the previous frame. If it is the case of the 1 st erased frame after a good frame, this pitch pulse is first low-pass filtered. The filter used is a simple 3-tap linear phase FIR filter with filter coefficients equal to 0.18, 0.64 and 0.18. If a voicing information is available, the filter can be also selected dynamically with a cut-off frequency dependent on the voicing. The pitch period Tc used to select the last pitch pulse and hence used during the concealment is defined so that pitch multiples or submultiples can be avoided, or reduced. The following logic is used in determining the pitch period Tc. if ((T3<1.8 Ts) AND (T3>0.6 Ts)) OR (Tcnt=30), then Tc=T3, else Tc=Ts. Here, T3 is the rounded pitch period of the 4th subframe of the last good received frame and Ts is the rounded pitch period of the 4th subframe of the last good stable voiced frame with coherent pitch estimates. A stable voiced frame is defined here as a VOICED frame preceded by a frame of voiced type (VOICED TRANSITION, VOICED, ONSET). The coherence of pitch is verified in this implementation by examining whether the closed-loop pitch estimates are reasonably close, i.e. whether the ratios between the last subframe pitch, the 2nd subframe pitch and the last subframe pitch of the previous frame are within the interval (0.7, 1.4). This determination of the pitch period Tc means that if the pitch at the end of the last good frame and the pitch of the last stable frame are close to each other, the pitch of the last good frame is used. Otherwise this pitch is considered unreliable and the pitch of the last stable frame is used instead to avoid the impact of wrong pitch estimates at voiced onsets. This logic makes however sense only if the last stable segment is not too far in the past. Hence a counter Tcnt is defined that limits the reach of the influence of the last stable segment. If Tcnt is greater or equal to 30, i.e. if there are at least 30 frames since the last Ts update, the last good frame pitch is used systematically. Tcnt is reset to 0 every time a stable segment is detected and Ts is updated. The period Tc is then maintained constant during the concealment for the whole erased block. As the last pulse of the excitation of the previous frame is used for the construction of the periodic part, its gain is approximately correct at the beginning of the concealed frame and can be set to 1. The gain is then attenuated linearly throughout the frame on a sample by sample basis to achieve the value of α at the end of the frame. The values of α correspond to the Table 5 with the exception that they are modified for erasures following VOICED and ONSET frames to take into consideration the energy evolution of voiced segments. This evolution can be extrapolated to some extend by using the pitch excitation gain values of each subframe of the last good frame. In general, if these gains are greater than 1, the signal energy is increasing, if they are lower than 1, the energy is decreasing. α is thus multiplied by a correction factor fb computed as follows: fb={square root}{square root over (0.1b(0)+0.2b(1)+0.3b(2)+0.4b(3))} (23) where b(0), b(1), b(2) and b(3) are the pitch gains of the four subframes of the last correctly received frame. The value of fb is clipped between 0.98 and 0.85 before being used to scale the periodic part of the excitation. In this way, strong energy increases and decreases are avoided. For erased frames following a correctly received frame other than UNVOICED, the excitation buffer is updated with this periodic part of the excitation only. This update will be used to construct the pitch codebook excitation in the next frame. Construction of the Random Part of the Excitation The innovation (non-periodic) part of the excitation signal is generated randomly. It can be generated as a random noise or by using the CELP innovation codebook with vector indexes generated randomly. In the present illustrative embodiment, a simple random generator with approximately uniform distribution has been used. Before adjusting the innovation gain, the randomly generated innovation is scaled to some reference value, fixed here to the unitary energy per sample. At the beginning of an erased block, the innovation gain gs is initialized by using the innovation excitation gains of each subframe of the last good frame: gs=0.1g(0)+0.2g(1)+0.3g(2)+0.4g(3) (23a) where g(0), g(1), g(2) and g(3) are the fixed codebook, or innovation, gains of the four (4) subframes of the last correctly received frame. The attenuation strategy of the random part of the excitation is somewhat different from the attenuation of the pitch excitation. The reason is that the pitch excitation (and thus the excitation periodicity) is converging to 0 while the random excitation is converging to the comfort noise generation (CNG) excitation energy. The innovation gain attenuation is done as: gs1=α·gs0+(1−α)·gn (24) where gs1 is the innovation gain at the beginning of the next frame, gs0 is the innovative gain at the beginning of the current frame, gn is the gain of the excitation used during the comfort noise generation and a is as defined in Table 5. Similarly to the periodic excitation attenuation, the gain is thus attenuated linearly throughout the frame on a sample by sample basis starting with gs0 and going to the value of gs1 that would be achieved at the beginning of the next frame. Finally, if the last good (correctly received or non erased) received frame is different from UNVOICED, the innovation excitation is filtered through a linear phase FIR high-pass filter with coefficients −0.0125, −0.109, 0.7813, −0.109, −0.0125. To decrease the amount of noisy components during voiced segments, these filter coefficients are multiplied by an adaptive factor equal to (0.75-0.25 rv), rv being the voicing factor as defined in Equation (1). The random part of the excitation is then added to the adaptive excitation to form the total excitation signal. If the last good frame is UNVOICED, only the innovation excitation is used and it is further attenuated by a factor of 0.8. In this case, the past excitation buffer is updated with the innovation excitation as no periodic part of the excitation is available. Spectral Envelope Concealment, Synthesis and Updates To synthesize the decoded speech, the LP filter parameters must be obtained. The spectral envelope is gradually moved to the estimated envelope of the ambient noise. Here the ISF representation of LP parameters is used: l1(j)=αl0(j)+(1−α)ln(j), j=0, . . . , p−1 (25) In equation (25), l1(j) is the value of the jth ISF of the current frame, 106) is the value of the jth ISF of the previous frame, ln(j) is the value of the jth ISF of the estimated comfort noise envelope and p is the order of the LP filter. The synthesized speech is obtained by filtering the excitation signal through the LP synthesis filter. The filter coefficients are computed from the ISF representation and are interpolated for each subframe (four (4) times per frame) as during normal encoder operation. As innovation gain quantizer and ISF quantizer both use a prediction, their memory will not be up to date after the normal operation is resumed. To reduce this effect, the quantizers' memories are estimated and updated at the end of each erased frame. Recovery of the Normal Operation After Erasure The problem of the recovery after an erased block of frames is basically due to the strong prediction used practically in all modern speech encoders. In particular, the CELP type speech coders achieve their high signal to noise ratio for voiced speech due to the fact that they are using the past excitation signal to encode the present frame excitation (long-term or pitch prediction). Also, most of the quantizers (LP quantizers, gain quantizers) make use of a prediction. Artificial Onset Construction The most complicated situation related to the use of the long-term prediction in CELP encoders is when a voiced onset is lost. The lost onset means that the voiced speech onset happened somewhere during the erased block. In this case, the last good received frame was unvoiced and thus no periodic excitation is found in the excitation buffer. The first good frame after the erased block is however voiced, the excitation buffer at the encoder is highly periodic and the adaptive excitation has been encoded using this periodic past excitation. As this periodic part of the excitation is completely missing at the decoder, it can take up to several frames to recover from this loss. If an ONSET frame is lost (i.e. a VOICED good frame arrives after an erasure, but the last good frame before the erasure was UNVOICED as shown in FIG. 6), a special technique is used to artificially reconstruct the lost onset and to trigger the voiced synthesis. At the beginning of the 1st good frame after a lost onset, the periodic part of the excitation is constructed artificially as a low-pass filtered periodic train of pulses separated by a pitch period. In the present illustrative embodiment, the low-pass filter is a simple linear phase FIR filter with the impulse response hlow={−0.0125, 0.109, 0.7813, 0.109, −0.0125}. However, the filter could be also selected dynamically with a cut-off frequency corresponding to the voicing information if this information is available. The innovative part of the excitation is constructed using normal CELP decoding. The entries of the innovation codebook could be also chosen randomly (or the innovation itself could be generated randomly), as the synchrony with the original signal has been lost anyway. In practice, the length of the artificial onset is limited so that at least one entire pitch period is constructed by this method and the method is continued to the end of the current subframe. After that, a regular ACELP processing is resumed. The pitch period considered is the rounded average of the decoded pitch periods of all subframes where the artificial onset reconstruction is used. The low-pass filtered impulse train is realized by placing the impulse responses of the low-pass filter in the adaptive excitation buffer (previously initialized to zero). The first impulse response will be centered at the quantized position rq (transmitted within the bitstream) with respect to the frame beginning and the remaining impulses will be placed with the distance of the averaged pitch up to the end of the last subframe affected by the artificial onset construction. If the available bandwidth is not sufficient to transmit the first glottal pulse position, the first impulse response can be placed arbitrarily around the half of the pitch period after the current frame beginning. As an example, for the subframe length of 64 samples, let us consider that the pitch periods in the first and the second subframe be p(0)=70.75 and p(1)=71. Since this is larger than the subrame size of 64, then the artificial onset will be constructed during the first two subframes and the pitch period will be equal to the pitch average of the two subframes rounded to the nearest integer, i.e. 71. The last two subframes will be processed by normal CELP decoder. The energy of the periodic part of the artificial onset excitation is then scaled by the gain corresponding to the quantized and transmitted energy for FER concealment (As defined in Equations 16 and 17) and divided by the gain of the LP synthesis filter. The LP synthesis filter gain is computed as: g LP = ∑ i = 0 63 ⁢ h 2 ⁡ ( i ) ( 31 ) where h(i) is the LP synthesis filter impulse response Finally, the artificial onset gain is reduced by multiplying the periodic part with 0.96. Alternatively, this value could correspond to the voicing if there were a bandwidth available to transmit also the voicing information. Alternatively without diverting from the essence of this invention, the artificial onset can be also constructed in the past excitation buffer before entering the decoder subframe loop. This would have the advantage of avoiding the special processing to construct the periodic part of the artificial onset and the regular CELP decoding could be used instead. The LP filter for the output speech synthesis is not interpolated in the case of an artificial onset construction. Instead, the received LP parameters are used for the synthesis of the whole frame. Energy Control The most important task at the recovery after an erased block of frames is to properly control the energy of the synthesized speech signal. The synthesis energy control is needed because of the strong prediction usually used in modem speech coders. The energy control is most important when a block of erased frames happens during a voiced segment. When a frame erasure arrives after a voiced frame, the excitation of the last good frame is typically used during the concealment with some attenuation strategy. When a new LP filter arrives with the first good frame after the erasure, there can be a mismatch between the excitation energy and the gain of the new LP synthesis filter. The new synthesis filter can produce a synthesis signal with an energy highly different from the energy of the last synthesized erased frame and also from the original signal energy. The energy control during the first good frame after an erased frame can be summarized as follows. The synthesized signal is scaled so that its energy is similar to the energy of the synthesized speech signal at the end of the last erased frame at the beginning of the first good frame and is converging to the transmitted energy towards the end of the frame with preventing a too important energy increase. The energy control is done in the synthesized speech signal domain. Even if the energy is controlled in the speech domain, the excitation signal must be scaled as it serves as long term prediction memory for the following frames. The synthesis is then redone to smooth the transitions. Let g0 denote the gain used to scale the 1st sample in the current frame and g1 the gain used at the end of the frame. The excitation signal is then scaled as follows: us(i)=gAGC(i)·u(i), i=0, . . . , L−1 (32) where us(i) is the scaled excitation, u(i) is the excitation before the scaling, L is the frame length and gAGC(i) is the gain starting from g0 and converging exponentially to g1: gAGC(i)=fAGCgAGC(i−1)+(1−AGC)g1 i=0, . . . , L−1 with the initialization of gAGC(−1)=g0, where fAGC is the attenuation factor set in this implementation to the value of 0.98. This value has been found experimentally as a compromise of having a smooth transition from the previous (erased) frame on one side, and scaling the last pitch period of the current frame as much as possible to the correct (transmitted) value on-the-other-side. This is important because the transmitted energy value is estimated pitch synchronously at the end of the frame. The gains g0 and g1 are defined as: g0={square root}{square root over (E−1/E0)} (33a) g1={square root}{square root over (Eq/E1)} (33b) where E−1 is the energy computed at the end of the previous (erased) frame, E0 is the energy at the beginning of the current (recovered) frame, E1 is the energy at the end of the current frame and Eq is the quantized transmitted energy information at the end of the current frame, computed at the encoder from Equations (16, 17). E−1 and E1 are computed similarly with the exception that they are computed on the synthesized speech signal s′. E−1 is computed pitch synchronously using the concealment pitch period Tc and E1 uses the last subframe rounded pitch T3. E0 is computed similarly using the rounded pitch value To of the first subframe, the equations (16, 17) being modified to: E = max i = 0 t E ⁢ ( s ′ ⁢ ⁢ 2 ⁡ ( i ) ) for VOICED and ONSET frames. tE equals to the rounded pitch lag or twice that length if the pitch is shorter than 64 samples. For other frames, E = 1 t 0 ⁢ ∑ i = 0 t E ⁢ s ′ ⁢ ⁢ 2 ⁡ ( i ) with tE equal to the half of the frame length. The gains g0 and g1 are further limited to a maximum allowed value, to prevent strong energy. This value has been set to 1.2 in the present illustrative implementation. Conducting frame erasure concealment and decoder recovery comprises, when a gain of a LP filter of a first non erased frame received following frame erasure is higher than a gain of a LP filter of a last frame erased during said frame erasure, adjusting the energy of an LP filter excitation signal produced in the decoder during the received first non erased frame to a gain of the LP filter of said received first non erased frame using the following relation: If Eq cannot be transmitted, Eq is set to E1. If however the erasure happens during a voiced speech segment (i.e. the last good frame before the erasure and the first good frame after the erasure are classified as VOICED TRANSITION, VOICED or ONSET), further precautions must be taken because of the possible mismatch between the excitation signal energy and the LP filter gain, mentioned previously. A particularly dangerous situation arises when the gain of the LP filter of a first non erased frame received following frame erasure is higher than the gain of the LP filter of a last frame erased during that frame erasure. In that particular case, the energy of the LP filter excitation signal produced in the decoder during the received first non erased frame is adjusted to a gain of the LP filter of the received first non erased frame using the following relation: E q = E 1 ⁢ E LP0 E LP1 where ELPO is the energy of the LP filter impulse response of the last good frame before the erasure and ELP1 is the energy of the LP filter of the first good frame after the erasure. In this implementation, the LP filters of the last subframes in a frame are used. Finally, the value of Eq is limited to the value of E−1 in this case (voiced segment erasure without Eq information being transmitted). The following exceptions, all related to transitions in speech signal, further overwrite the computation of g0. If artificial onset is used in the current frame, g0 is set to 0.5 g1, to make the onset energy increase gradually. In the case of a first good frame after an erasure classified as ONSET, the gain g0 is prevented to be higher that g1. This precaution is taken to prevent a positive gain adjustment at the beginning of the frame (which is probably still at least partially unvoiced) from amplifying the voiced onset (at the end of the frame). Finally, during a transition from voiced to, unvoiced (i.e. that last good frame being classified as VOICED TRANSITION, VOICED or ONSET and the current frame being classified UNVOICED) or during a transition from a non-active speech period to active speech period (last good received frame being encoded as comfort noise and current frame being encoded as active speech), the g0 is set to g1. In case of a voiced segment erasure, the wrong energy problem can manifest itself also in frames following the first good frame after the erasure. This can happen even if the first good frame's energy has been adjusted as described above. To attenuate this problem, the energy control can be continued up to the end of the voiced segment. Although the present invention has been described in the foregoing description in relation to an illustrative embodiment thereof, this illustrative embodiment can be modified as will, within the scope of the appended claims without departing from the scope and spirit of the subject invention.
<SOH> BACKGROUND OF THE INVENTION <EOH>The demand for efficient digital narrow- and wideband speech encoding techniques with a good trade-off between the subjective quality and bit rate is increasing in various application areas such as teleconferencing, multimedia, and wireless communications. Until recently, a telephone bandwidth constrained into a range of 200-3400 Hz has mainly been used in speech coding applications. However, wideband speech applications provide increased intelligibility and naturalness in communication compared to the conventional telephone bandwidth. A bandwidth in the range of 50-7000 Hz has been found sufficient for delivering a good quality giving an impression of face-to-face communication. For general audio signals, this bandwidth gives an acceptable subjective quality, but is still lower than the quality of FM radio or CD that operate on ranges of 20-16000 Hz and 20-20000 Hz, respectively. A speech encoder converts a speech signal into a digital bit stream which is transmitted over a communication channel or stored in a storage medium. The speech signal is digitized, that is, sampled and quantized with usually 16-bits per sample. The speech encoder has the role of representing these digital samples with a smaller number of bits while maintaining a good subjective speech quality. The speech decoder or synthesizer operates on the transmitted or stored bit stream and converts it back to a sound signal. Code-Excited Linear Prediction (CELP) coding is one of the best available techniques for achieving a good compromise between the subjective quality and bit rate. This encoding technique is a basis of several speech encoding standards both in wireless and wireline applications. In CELP encoding, the sampled speech signal is processed in successive blocks of L samples usually called frames, where L is a predetermined number corresponding typically to 10-30 ms. A linear prediction (LP) filter is computed and transmitted every frame. The computation of the LP filter typically needs a lookahead, a 5-15 ms speech segment from the subsequent frame. The L-sample frame is divided into smaller blocks called subframes. Usually the number of subframes is three or four resulting in 4-10 ms subframes. In each subframe, an excitation signal is usually obtained from two components, the past excitation and the innovative, fixed-codebook excitation. The component formed from the past excitation is often referred to as the adaptive codebook or pitch excitation. The parameters characterizing the excitation signal are coded and transmitted to the decoder, where the reconstructed excitation signal is used as the input of the LP filter. As the main applications of low bit rate speech encoding are wireless mobile communication systems and voice over packet networks, then increasing the robustness of speech codecs in case of frame erasures becomes of significant importance. In wireless cellular systems, the energy of the received signal can exhibit frequent severe fades resulting in high bit error rates and this becomes more evident at the cell boundaries. In this case the channel decoder fails to correct the errors in the received frame and as a consequence, the error detector usually used after the channel decoder will declare the frame as erased. In voice over packet network applications, the speech signal is packetized where usually a 20 ms frame is placed in each packet. In packet-switched communications, a packet dropping can occur at a router if the number of packets become very large, or the packet can reach the receiver after a long delay and it should be declared as lost if its delay is more than the length of a jitter buffer at the receiver side. In these systems, the codec is subjected to typically 3 to 5% frame erasure rates. Furthermore, the use of wideband speech encoding is an important asset to these systems in order to allow them to compete with traditional PSTN (public switched telephone network) that uses the legacy narrow band speech signals. The adaptive codebook, or the pitch predictor, in CELP plays an important role in maintaining high speech quality at low bit rates. However, since the content of the adaptive codebook is based on the signal from past frames, this makes the codec model sensitive to frame loss. In case of erased or lost frames, the content of the adaptive codebook at the decoder becomes different from its content at the encoder. Thus, after a lost frame is concealed and consequent good frames are received, the synthesized signal in the received good frames is different from the intended synthesis signal since the adaptive codebook contribution has been changed. The impact of a lost frame depends on the nature of the speech segment in which the erasure occurred. If the erasure occurs in a stationary segment of the signal then an efficient frame erasure concealment can be performed and the impact on consequent good frames can be minimized. On the other hand, if the erasure occurs in an speech onset or a transition, the effect of the erasure can propagate through several frames. For instance, if the beginning of a voiced segment is lost, then the first pitch period will be missing from the adaptive codebook content. This will have a severe effect on the pitch predictor in consequent good frames, resulting in long time before the synthesis signal converge to the intended one at the encoder.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a method for improving concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: determining, in the encoder, concealment/recovery parameters; transmitting to the decoder the concealment/recovery parameters determined in the encoder; and in the decoder, conducting erasure frame concealment and decoder recovery in response to the received concealment/recovery parameters. The present invention also relates to a method for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, conducting erased frame concealment and decoder recovery in response to the determined concealment/recovery parameters. In accordance with the present invention, there is also provided a device for improving concealment of frame erasure caused by frames of an encoded sound signal erased during transmission from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: means for determining, in the encoder, concealment/recovery parameters; means for transmitting to the decoder the concealment/recovery parameters determined in the encoder; and in the decoder, means for conducting erasure frame concealment and decoder recovery in response to the received concealment/recovery parameters. According to the invention, there is further provided a device for the concealment of frame erasure caused by frames erased during transmission of a sound signal encoded under the form of signal-encoding parameters from an encoder to a decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received, comprising: means, for determining, in the decoder, concealment/recovery parameters from the signal-encoding parameters; in the decoder, means for conducting erased frame concealment and decoder recovery in response to the determined concealment/recovery parameters. The present invention is also concerned with a system for encoding and decoding a sound signal, and a sound signal decoder using the above defined devices for improving concealment of frame erasure caused by frames of the encoded sound signal erased during transmission from the encoder to the decoder, and for accelerating recovery of the decoder after non erased frames of the encoded sound signal have been received. The foregoing and other objects, advantages and features of the present invention will become more apparent upon reading of the following non restrictive description of illustrative embodiments thereof, given by way of example only with reference to the accompanying drawings.
20041123
20100406
20050714
92111.0
5
LERNER, MARTIN
METHOD AND DEVICE FOR EFFICIENT FRAME ERASURE CONCEALMENT IN LINEAR PREDICTIVE BASED SPEECH CODECS
UNDISCOUNTED
0
ACCEPTED
2,004
10,515,808
ACCEPTED
Aiding in a satellite positioning system
The invention relates to an aided Global Positioning System (GPS) subsystem within a wireless device. The wireless device includes a wireless processing section capable of receiving signals from a wireless network and a GPS subsystem having a radio frequency (RF) front-end capable of receiving a GPS satellite signal. The wireless processing section of the wireless device receives an external clock and determines the offset between the clock in the wireless processing section and that of the external clock. The GPS subsystem then receives the offset information from the wireless processing section, information related to the nominal frequency of the wireless processing section clock and the wireless processing section clock. Using this information and the GPS clock in the GPS subsystem, the GPS subsystem determines an acquiring signal, which is related to a frequency offset between the GPS clock and the network clock. The GPS subsystem then acquires GPS satellite signals in an acquiring unit though the use of the acquiring signal.
1. An aided Global Positioning System (GPS) subsystem within a wireless device, wherein the wireless device has a wireless processing section capable of receiving signals from a wireless network and the GPS subsystem has a radio frequency (RF) front-end capable of receiving a GPS satellite signal, the aided GPS subsystem comprising: a GPS clock; and a GPS processor section that receives the GPS clock and at least one signal from the wireless processing section, and in response produces at least one acquiring signal that is utilized by an acquiring unit to acquire the GPS satellite signal. 2. The aided GPS subsystem of claim 1, wherein the at least one signal from the wireless processing section may include a digital message. 3. The aided GPS subsystem of claim 1, wherein the GPS processing section includes: a GPS clock processor that receives the GPS clock and the at least one signal from the wireless processing section and produces an offset signal representative of the difference between the GPS clock and a network clock that is external to the wireless device; and a GPS carrier and code generator that produces the at least one acquiring signal in response to receiving the offset signal from the GPS clock processor. 4. The aided GPS subsystem of claim 3, wherein the at least one signal from the wireless processing section may include a digital message. 5. The aided GPS subsystem of claim 3, wherein the GPS clock processor includes an offset counter that receives the GPS clock and the at least one signal from the wireless processing section and produces an offset counter output signal that is representative of the difference between the GPS clock and a clock within the wireless processing section. 6. The aided GPS subsystem of claim 5, wherein the at least one signal form the wireless processing section includes information about the clock within the wireless processing section. 7. The aided GPS subsystem of claim 6, wherein the information about the clock within the wireless processing section includes the clock signal. 8. The aided GPS subsystem of claim 7, wherein the information about the clock within the wireless processing section further includes a message having information about the nominal frequency of the clock. 9. The aided GPS subsystem of claim 5 further including an offset combiner that produces a second offset signal in response to combining the offset counter output signal with a first offset signal from the wireless processor, the first offset signal representing the difference between the clock within the wireless processing section and the network clock. 10. The aided GPS subsystem of claim 9, wherein the GPS carrier and code generator includes: a Doppler prediction model that produces Doppler correction values; and an offset combiner unit that combines the Doppler correction values with the second offset signal and produces a total offset signal that is utilized by the GPS carrier and code generator in producing the at least one acquiring signal. 11. The aided GPS subsystem of claim 3, wherein the GPS carrier and code generator includes: a Doppler prediction model that produces Doppler correction values; and an offset combiner unit that combines the Doppler correction values with a second offset signal and produces a total offset signal that is utilized by the GPS carrier and code generator in producing the at least one acquiring signal. 12. An aided Global Positioning System (GPS) subsystem within a wireless device, wherein the wireless device has a wireless processing section capable of receiving signals from a wireless network and the GPS subsystem has a radio frequency (RF) front-end capable of receiving a GPS satellite signal, the aided GPS subsystem comprising: a GPS clock; means for receiving the GPS clock and at least one signal from the wireless processing section; and means for producing in response to the receiving means at least one acquiring signal that is utilized by an acquiring unit to acquire the GPS satellite signal. 13. The aided GPS subsystem of claim 12, wherein the at least one signal from the wireless processing section may include a digital message. 14. The aided GPS subsystem of claim 12, wherein the GPS processing section includes: means for receiving the GPS clock and the at least one signal from the wireless processing section; means for producing an offset signal representative of the difference between the GPS clock and a network clock that is external to the wireless device; and means for producing the at least one acquiring signal in response to receiving the offset signal from the receiving means. 15. The aided GPS subsystem of claim 14, wherein the offset signal producing means includes an offset counter that receives the GPS clock and the at least one signal from the wireless processing section and produces an offset counter output signal that is representative of the difference between the GPS clock and a clock within the wireless processing section. 16. The aided GPS subsystem of claim 15 further including an offset combiner that produces a second offset signal in response to combining the offset counter output signal with a first offset signal from the wireless processor, the first offset signal representing the difference between the clock within the wireless processing section and the network clock. 17. The aided GPS subsystem of claim 16, wherein the producing acquiring signal means includes: means for producing Doppler correction values; and means for combining the Doppler correction values with the second offset signal and produces a total offset signal that is utilized by a GPS carrier and code generator in producing the at least one acquiring signal. 18. A method for aiding a Global Positioning System (GPS) subsystem within a wireless device, wherein the wireless device has a wireless processing section capable of receiving signals from a wireless network and the GPS subsystem has a radio frequency (RF) front-end capable of receiving a GPS satellite signal, the method comprising: receiving a GPS clock, wireless processing section clock, message having information related to the wireless processing section clock nominal frequency, and a message having information related to an offset between the wireless processing section clock and a network clock external to the wireless device; determining an acquiring signal in response to receiving the GPS clock, wireless processing section clock, wireless processing section clock nominal frequency message, and the offset message, wherein the acquiring signal is related to a frequency offset between the GPS clock and the network clock. acquiring the GPS satellite signal in an acquiring unit that utilizes the acquiring signal. 19. The method of claim 18, wherein the acquiring signal includes a digital message having information related to the frequency offset between the GPS clock and the network clock. 20. The method of claim 18, wherein determining the acquiring signal further includes: determining an offset between the GPS clock and the wireless processing section clock; and determining the frequency offset between the GPS clock and network clock from the offset between the GPS clock and wireless processing section and the offset between the wireless processing section clock and the network clock. 21. The method of claim 20, wherein determining the acquiring signal further includes combining the frequency offset between the GPS clock and the network clock with a Doppler correction value. 22. The method of claim 21 further including adjusting a numerically controlled oscillator (NCO) with the combined frequency offset between the GPS clock and the network clock with the Doppler correction value. 23. The method of claim 22, wherein acquiring includes utilizing a correlator to acquire the received GPS satellite signal. 24. The method of claim 22, wherein acquiring includes utilizing a matched filter to acquire the received GPS satellite signal. 25. A signal-bearing medium having software for aiding a Global Positioning System (GPS) subsystem within a wireless device, wherein the wireless device has a wireless processing section capable of receiving signals from a wireless network and the GPS subsystem has a radio frequency (RF) front-end capable of receiving a GPS satellite signal, the signal-bearing medium comprising: logic for receiving a GPS clock, wireless processing section clock, message having information related to the wireless processing section clock nominal frequency, and a message having information related to an offset between the wireless processing section clock and a network clock external to the wireless device; logic for determining an acquiring signal in response to receiving the GPS clock, wireless processing section clock, wireless processing section clock nominal frequency message, and the offset message, wherein the acquiring signal is related to a frequency offset between the GPS clock and the network clock. logic for acquiring the GPS satellite signal in an acquiring unit that utilizes the acquiring signal. 26. The signal-bearing medium of claim 25, wherein the logic for acquiring the GPS satellite signal includes a digital message having information related to the frequency offset between the GPS clock and the network clock. 27. The signal-bearing medium of claim 25, wherein determining logic the acquiring signal further includes: logic for determining an offset between the GPS clock and the wireless processing section clock; and logic for determining the frequency offset between the GPS clock and network clock from the offset between the GPS clock and wireless processing section and the offset between the wireless processing section clock and the network clock. 28. The signal-bearing medium of claim 27, wherein the logic for determining the acquiring signal further includes combining the frequency offset between the GPS clock and the network clock with a Doppler correction value. 29. The signal-bearing medium of claim 28 further including logic for adjusting a numerically controlled oscillator (NCO) with the combined frequency offset between the GPS clock and the network clock with the Doppler correction value. 30. The signal-bearing medium of claim 29, wherein the acquiring logic includes logic for utilizing a correlator to acquire the received GPS satellite signal. 31. The signal-bearing medium of claim 29, wherein the acquiring logic includes logic for utilizing a matched filter to acquire the received GPS satellite signal.
CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 10/155,614, filed May 22, 2002, titled Search Domain Reducing Frequency Transfer in a Multi-mode Global Positioning System Used With Wireless Networks, which is a continuation-in-part of U.S. patent application Ser. No. 09/795,871, filed Feb. 28, 2001, titled Information Transfer in a Multi-mode Global Positioning System Used with Wireless Networks, now U.S. Pat. No. 6,427,120, which claims priority under Section 119(e) to U.S. Provisional Application Ser. No. 60/225,076, filed Aug. 14, 2000, all of which are incorporated into this application by reference. BACKGROUND OF THE INVENTION 1. Field of Invention The invention relates to Satellite Positioning System (SPS) receivers, and in particular to increasing the accuracy of SPS receivers by providing the receivers with information to correct for the frequency offset between the oscillators of the receivers and those of the satellites. 2. Related Art Satellite Positioning System (SPS) receivers, such as Global Positioning System (GPS), also known as NAVSTAR, receivers, receive radio transmissions from satellite-based radio navigation systems and use those received transmissions to determine the location of the SPS receiver. The location of the SPS receiver may be determined by applying the well-known concept of intersection if the distances from the SPS receiver to three SPS satellites having known satellite locations. Generally, each satellite in a satellite-based radio navigation system broadcasts a radio transmission, that contains its location information, and orbit information. More specifically, each of the orbiting satellites in the GPS system contains four highly accurate atomic clocks: two Cesium and two Rubidium. These clocks provide precision timing pulses used to generate two unique binary codes (also known as a pseudo random noise “PRN,” or pseudo noise “PN” code) that are transmitted to earth. The PN codes identify the specific satellite in the constellation. The satellite also transmits a set of digitally coded ephemeris data that completely defines the precise orbit of the satellite. The ephemeris data indicates where the satellite is at any given time, and its location may be specified in terms of the satellite ground track in precise latitude and longitude measurements. The information in the ephemeris data is coded and transmitted from the satellite providing an accurate indication of the exact position of the satellite above the earth at any given time. Although atomic clocks are very precise with a stability of about 1 to 2 parts in 1013 over a period of one day, a slight error (generally known as clock drift) may occur in the clocks over time resulting in satellite clock errors of about 8.64 to 17.28 ns per day with corresponding range errors of 2.59 to 5.18 meters. In order to compensate for the error, the accuracy of the satellite atomic clocks are continuously monitored from ground stations in the GPS control system and any detected errors and drift in the clock of the satellites may be calculated and transmitted by the satellites as part of a navigation message in the form of three coefficients of a second-degree polynomial. In the case of GPS, there is nominally a constellation of 24 operational satellites above the Earth. Each satellite has individual PN codes, a nearly circular orbit with an inclination of 55° to the equator with a height of 10,898 nautical miles (20,200 kilometers) above Earth and an orbital period of approximately 12 hours. Each GPS satellite transmits a microwave radio signal composed of two carrier frequencies modulated by two digital codes and a navigation messages. The two carrier frequencies are referred to as the “L1” and “L2” carriers and are transmitted at 1,572.42 megahertz (MHz) and 1,227.60 MHz, respectively. The two GPS codes are called the coarse acquisition (C/A-code) and precision (P-code). Each code consists of a stream of binary digits, zeros and ones, known as bits or “chips.” Both the C/A-code and P-code are generally referred to as a PN code because they look like random noise-like signals. Presently, the C/A-code is modulated only on the L1 carrier while the P-code is modulated on both L1 and L2 carriers. The C/A-code has a chipping rate of 1.023 MHz because it is a stream of 1,023 binary digits that repeats itself every millisecond. Each satellite is assigned a unique C/A-code, which enables a GPS receiver to identify which satellite is transmitting a particular code. The C/A-code range measurement is relatively less precise when compared to the P-code but it is also less complex and available to all users. The P-code is mostly limited in use to the United States government and military. Each satellite also transmits a GPS navigation message that is a data stream added to both the L1 and L2 carriers as binary bi-phase modulation at 50 kilo-bits per second (kbps). The navigation message contains, along with other information, the coordinates of the GPS satellites as a function of time, the satellite health status, the satellite clock corrections, the satellite almanac, and atmospheric data. Each satellite transmits its own navigation message with information on the other satellites, such as the approximate location and health status. By receiving these radio signals emitted from the satellites, a GPS receiver may calculate its distance from the satellite by determining how long it took the GPS receiver to receive the signal transmitted from the satellite. For example, a GPS receiver could calculate its two-dimensional position (longitude and latitude or X and Y) by determining its distance from three satellites. Similarly, the GPS receiver could calculate its three-dimensional position (longitude, latitude and altitude or X, Y and Z) by measuring its distance from four satellites. Unfortunately, this approach assumes that the distances measured from the GPS receiver to the satellites are very accurate and there is no bias error. In practice, however, the distance measured between the GPS receiver and each satellite typically has a constant unknown bias, because the GPS receiver clock (GPS-CLK) is usually different from the GPS satellite clocks. In order to resolve this bias error one more satellite transmission is typically needed to calculate the location of the GPS receiver. Generally, to receive the signals transmitted by the satellites, the GPS-CLK of the GPS receiver should be synchronized with that of the GPS satellites. Any errors in the synchronization between the clocks will cause inaccuracies the measurement of the location of the GPS receiver. Atomic clocks, like those found in the GPS satellites, are very expensive typically costing a few thousand dollars for a Rubidium clock and a few tens of thousands of dollars for a Cesium clock. They are therefore not practical for use in typical consumer GPS receivers. Inexpensive, less accurate clocks, such as crystal clocks, are generally utilized in GPS receivers as GPS-CLKs. However, unless the inaccuracy of the GPS-CLK is determined and corrected for, synchronization with that of the atomic clocks of the satellites will be partially off and the resulting distance measurement calculated by the GPS receiver will be partially inaccurate. Thus, the error of the GPS-CLK is yet another unknown variable that must be determined to accurately determine the location of the GPS receiver. Besides accuracy, another problem associated with the error of the GPS-CLK relative to the GPS satellite clocks is the resulting acquisition time for the GPS receiver commonly known as the time to first fix (TTFF). For many applications, such as E911, a GPS receiver must be able to provide a position solution in a short period of time after the GPS receiver is powered on. Unfortunately, the GPS-CLK can have large frequency drift during the first couple minutes after being powered on. The large frequency drift can cause significant degradation on TTFF performance and may even result in lack of navigation fix in weak signal environments. In addition to the frequency drift in the GPS-CLK, there are a number of other factors that can affect TTFF performance. Although there are a large number of GPS satellites positioned above the earth's atmosphere, it is not always possible for a GPS receiver to receive accurate transmissions from the required number of GPS satellites necessary to calculate the position of the GPS receiver. Any number of problems may prevent a GPS receiver from receiving the necessary number of signals, or from receiving accurate signals because of transmission or receiver errors. These problems can result in high TTFF times. For example, a GPS receiver may not be able to receive the necessary number of GPS transmissions due to physical obstructions in the atmosphere or on the earth. Alternatively, even though a GPS receiver may be able to receive the necessary signals, the signal could be inaccurate due to any of the following: (i) error in the satellite clock; (ii) error in the receiver clock; (iii) error in computed satellite position; (iv) atmospheric errors caused by the ionosphere or the troposphere; (v) multipath errors caused by the receipt of reflective signals; (vi) receiver measuring errors and/or (vii) selective errors, or man made errors. These inaccuracies could lead to TTFF times that may be over thirty seconds because the GPS receiver needs to obtain the ephemeris data from the GPS system itself, and the GPS receiver typically needs a strong signal to acquire the ephemeris data reliably. Since the inception of GPS, methods have been, and are still being, developed to reduce errors and to enhance the accuracy of the GPS systems. Further, many different methods are being implemented to provide alternative means for providing the GPS receiver with information concerning unknown variables or inaccuracies in the system such that it is not always required for the system to receive satellite transmission signals from all the satellites or to receive accurate transmission data. One technique that has been introduced to assist with overcoming errors in the GPS system is differential GPS. With differential GPS, a receiver having a known location receives the GPS signals and calculates its position from the received signals. The calculated position is then compared to the actual known position of the receiver. The differential between the known position and the calculated position can then be used to calculate errors in the transmission signals. These errors can then be transmitted to receivers in unknown locations (“mobile receivers”) and used by the mobile receivers to compute their own location with better accuracy. Differential GPS is typically used to correct for errors other than receiver or multipath errors. However, in a similar manner as differential GPS, correction data may be sent to the GPS receiver to correct for receiver errors. For example, one method that has been used to correct for errors in the GPS-CLK has been to send a precision carrier frequency signal to the GPS receiver from a second source, such as a base station. In this application, the GPS receiver is designed to receive the precision carrier frequency signal and then calibrate and/or lock the GPS-CLK to that of the precision carrier frequency. This method, however, typically involves the use of additional complicated circuitry that first locks and/or calibrates the GPS-CLK to the precision carrier frequency and then maintains dynamic synchronization between the GPS-CLK and precision carrier frequency. A need therefore exists for a method of compensating for errors created by the drift of the GPS-CLK to increase positional accuracy and improve TTFF in a dynamic manner without utilizing additional complex circuitry and without significantly modifying the existing hardware. SUMMARY The invention relates to aiding a Global Positioning System (GPS) subsystem within a wireless device. The wireless device includes a wireless processing section capable of receiving signals from a wireless network and a GPS subsystem having a radio frequency (RF) front-end capable of receiving a GPS satellite signal. The wireless processing section of the wireless device receives an external clock and determines the offset between the clock in the wireless processing section and that of the external clock. The GPS subsystem then receives the offset information from the wireless processing section, information related to the nominal frequency of the wireless processing section clock and the wireless processing section clock. Using this information and the GPS clock in the GPS subsystem, the GPS subsystem determines an acquiring signal, which is related to a frequency offset between the GPS clock and the network clock. The GPS subsystem then acquires GPS satellite signals in an acquiring unit though the use of the acquiring signal. Other systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims. BRIEF DESCRIPTION OF THE DRAWINGS The invention can be better understood with reference to the following figures. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. In the figures, like reference numerals designate corresponding parts throughout the different views. FIG. 1 is an example implementation of a GPS system using a wireless device having a GPS receiver located within the wireless device. FIG. 2 is an example implementation of a block diagram of the wireless device shown in FIG. 1. FIG. 3 is general block diagram of an offset circuit within the GPS subsystem shown in FIG. 2 for generating GPS-STD-OFFSET. FIG. 4 illustrates a basic block diagram of the GPS subsystem of FIG. 2. FIG. 5 is a block diagram of an example implementation of the GPS processor section of FIG. 4. FIG. 6 is a block diagram of an example implementation of the GPS frequency source. FIG. 7 is a simplified block diagram of an example implementation of the GPS RF front-end utilizing direct conversion. FIG. 8 illustrates a simple block diagram of an example implementation of the acquiring unit. FIG. 9 shows a block diagram for another example implementation of the RF front-end and the acquisition unit, which is in signal communication with the RF front-end via the ADC. FIG. 10 shows a block diagram for yet another example implementation of the RF front-end and the acquisition unit, which is in signal communication the RF front-end via the ADC. FIG. 11 shows a block diagram for an example implementation of the GPS carrier and code generator. FIG. 12 shows a block diagram of an example implementation of the GPS clock processor. FIG. 13 is a flow chart illustrating the process preformed by the GPS subsystem. DETAILED DESCRIPTION FIG. 1 is an example implementation of a GPS system 100 using a wireless device 102 having a GPS receiver (not shown) located within the wireless device 102. As shown in FIG. 1, during operation, the wireless device 102 is in signal communication with a wireless network 104 via a basestation 106 and wireless transmission path 108 and is in signal communication with at least one satellite of the GPS satellite constellation 110 via signal communication path 112. The wireless device 102 includes both a GPS receiver (not shown) and a wireless processing section (not shown). The GPS receiver within the wireless device 102 may receive GPS signals from the GPS satellite constellation 110 via signal communication path 112 and the wireless processing section of the wireless device 102 may receive wireless communication signals from the wireless network 104 via signal communication path 108 and base station 106. In some implementations, the wireless device 102 may also send wireless communication signals to the wireless network 104 via signal communication path 108 and base station 106. The wireless device 102 may be a wireless handset such as a cellular telephone (also known as a cellphone, mobile telephone or mobile phone) or any other type of mobile device, including, but not limited to, personal digital assistants (PDAs), pagers, computer, two-way radio, trunked radio, specialized mobile radio (SMR) or any other device for which it is desirable to determine location information. In the case of a cellular telephone, the wireless device 102 may utilize a cellular transceiver that operates at any radio frequency (RF) band utilizing any transmission schemes including but not limited to CDMA, CDMA-2000, W-CDMA, TDMA, FDMA, GSM, UMTS, AMPS, Bluetooth, Wi-Fi and/or any combination or extension of these transmission schemes or similar schemes. FIG. 2 is an example implementation of a block diagram of the wireless device 102 shown in FIG. 1. As seen in FIG. 2, the wireless device 102 includes both a wireless processing section 200 and a GPS subsystem 202. The wireless processing section 200 performs the processing functions for the wireless applications and may include a wireless transceiver. For example, in the case of a cellular telephone, the wireless device 102 would include a call processing section with a cellular transceiver. The GPS subsystem includes a GPS receiver (not shown) for receiving satellite transmissions 204 from satellites 205 and a GPS engine (not shown) that performs the position computation functions for the wireless device 102. By integrating the technology of the wireless device 102 with that of the GPS subsystem 202, the wireless device 102 provides two major service systems: that of a wireless device, such as cellular telephone service, and that of the GPS receiver to provide location information of the wireless device 102. It is appreciated by those skilled in the art that this integration provides for numerous advantages including meeting the E911 requirements of the Federal Communication Commission (FCC). Within the wireless device 102, or, alternatively, between the wireless device 102 and an external accessory device (not shown) to the wireless device 102, communications between the wireless processing section 200 and GPS subsystem 202 take place. These communications allow signals to be transferred from the wireless processing section 200 to GPS section 202, and may take place on a serial or parallel communications link 206 (such as RS-232 serial communication link) and hardware lines 208, but other connections may be also utilized if desired. For example, in another example implementation, the wireless processing section 200 and the GPS subsystem 202 may share the same digital processor (not shown) and/or other circuitry. In such a case, the communication between the wireless processing section 200 and the GPS subsystem 202 may be made by inter-task communication, and certain data transfers, such as any time or frequency transfers between the wireless processing section 200 and the GPS subsystem 202, would not use hardware lines 208, but would be internal to the circuitry or, potentially, no transfer would be required depending on the circuit design. As illustrated by FIG. 2, the GPS satellites 205 transmit spread spectrum signals 204 that are received at the wireless device 102. For purposes of illustration, satellite 205 represents a constellation of satellites 205 in the GPS system. If the wireless device 102 is capable of receiving strong enough signals 204, the GPS subsystem 202 in the wireless device 102 can compute the position of the wireless device 102 as is typically done in a standalone GPS system. Oftentimes, however, the GPS subsystem 202 is not able to receive strong enough signals 204, or is not able to receive signals 204 from enough available GPS satellites 205 to autonomously compute the position of the wireless handset 102. This results in high time to first fix (TTFF) values. The wireless devices 102 may still, however, be able to communicate to the base station 106. Thus, the base station 106 can communicate information via signals 108 to wireless device 102 that allow the wireless device 102 to improve its TTFF and compute its location, or in certain applications (although not required for the implementation of the invention) to communicate information from the wireless device 102 to the base station 106, to allow a server (not shown) at the wireless network 104, in signal communication with the base station 106, to compute the position of the wireless device 102. When the base station 106 transmits information to the wireless device 102 to allow the wireless device 102 to compute its position, it is typically known as “aided GPS.” As further illustrated by FIG. 2, the base station 106 and both the wireless processing section 200 and the GPS subsystem 202 of the wireless device 102 have internal clocks that are produced by internal clock circuits. For illustrative purposes, the clock of the wireless processing section 200 shall be referred to as the “WPS-CLK” 210 and the clock of the GPS subsystem 202 shall be referred to as the “GPS-CLK” 212. Typically, the WPS-CLK 210 and GPS-CLK 212 are inexpensive clocks produced by crystal oscillators that are not highly accurate when compared to the atomic clocks of the GPS satellites 205. Thus, to reduce the TTFF and accurately calculate the position of the wireless device 102, the error in the GPS-CLK 212 should be accounted for. In contrast to the WPS-CLK 210 and GPS-CLK 212, the base station 106 clock is a highly accurate. In the case of a CDMA wireless network, the base station 106 clock would be synchronized with the atomic clocks of the GPS satellites 205. For purposes of illustration, this base station 106 clock shall be referred to as the “BS-CLK” 214 or the “Standard Clock” (STD-CLK) 214. In operation, the STD-CLK 214 is transmitted, via signal communication path 108, to the wireless processing section 200 of wireless handset 102. As explained in more detail below, the wireless processing section 200 of the wireless handset 102 calculates a first offset value (referred to as “STD-WPS-OFFSET”) that corresponds to the difference in frequency between the STD-CLK 214 and that WPS-CLK 210. The STD-WPS-OFFSET is then communicated to the GPS subsystem 202, which uses the STD-WPS-OFFSET, along with WPS-CLK 210 and GLS-CLK 212 to estimate a second offset value (referred to as “GPS-STD-OFFSET”) between the GPS-CLK 212 and that of the STD-CLK 214. The GPS-STD-OFFSET is then utilized by the GPS subsystem 202 to acquire the received GPS signals from the GPS satellites 204. FIG. 3 is general block diagram of an offset circuit 300 within the GPS subsystem 202 shown in FIG. 2 for generating GPS-STD-OFFSET. The offset circuit 300 may include an offset counter 302 and an offset combiner 304 in signal communication with the offset counter 302. The offset circuit 300 is in signal communication with a wireless sub-processor 306 located in the wireless processing section 200. The wireless sub-processor 306 receives the STD-CLK 214 and WPS-CLK 210, and in response produces a WPS initialization message that includes information about the nominal frequency (referred to as “N-WPS-CLK”) of the WPS-CLK 210 and a WPS periodic message that includes information about the STD-WPS-OFFSET. The N-WPS-CLK information is passed to the offset counter 302 via first offset bus 308 and the STD-WPS-OFFSET is passed to the offset combiner 304 via the second offset bus 310. The offset counter 302 receives the N-WPS-CLK information via first bus 308, GPS-CLK 212 and WPS-CLK 210. In response, the offset counter 302 generates an offset signal (or message) that includes information about the difference in frequency between WPS-CLK 210 and GPS-CLK 212 (referred to as “GPS-WPS-OFFSET”) and passes that offset signal to the offset combiner 304 via third offset bus 312. The offset combiner 304 then combines the information for the STD-WPS-OFFSET and GPS-WPS-OFFSET and produces the STD-GPS-OFFSET which is passed to the rest of the GPS subsystem 202 via message bus (or signal path) 314. FIG. 4 illustrates a basic block diagram of the GPS subsystem 202 of FIG. 2. In FIG. 4, the GPS subsystem 202 includes the GPS-CLK 212 and a GPS processor section 400 that receives at least one signal from the wireless processing section 200 via signal bus 402. The wireless processing section 200 receives communication data from the wireless network 104 (FIG. 1) including STD-CLK 214 (FIG. 2). The wireless processing section 200 then generates the STD-WPS-OFFSET message that represents the frequency difference between the WPS-LO 210 and the STD-CLK 214. The STD-WPS-OFFSET message is transferred to the GPS processor section 400 via signal bus 402. The GPS processor section 400, in response to receiving the STD-WPS-OFFSET and the GPS-CLK 212, generates a STD-GPS-OFFSET that assists in the acquiring of the received GPS satellite signals when input into an acquiring unit (not shown) within the GPS processor section 400. FIG. 5 is a block diagram of an example implementation of the GPS processor section 400 of FIG. 4. As shown in FIG. 5, the GPS processor section 400 may include a radio frequency (RF) front-end 500, GPS clock processor 502, GPS code and carrier generator 504, analog-to-digital converter (ADC) 506 and acquiring unit 508. A GPS frequency source 510 sends a frequency reference to the RF front-end 500, GPS code and carrier generator 504 and ADC 506. The RF front-end 500 may be a standard GPS RF front-end. In operation, the RF front-end 500 receives the GPS satellite signals and demodulates (also known as downconverting) them to remove the carrier frequency from the data transmitted on the GPS satellite signals. The demodulation is accomplished by mixing the received GPS satellite signals with the GPS frequency source 510. The resulting demodulated GPS satellite signals are then passed from the RF front-end 500 to the ADC 506. At the ADC 506, the demodulated GPS satellite signals are typically digitized into a bit-stream of samples by a number of well-known sampling techniques. The resultant bit-stream of samples is then transferred to the acquiring unit 508. It is appreciated by one skilled in the art that the GPS frequency source 510 may be a local oscillator (LO) (not shown) that includes a voltage-controlled oscillator (VCO) (not shown) or voltage-controlled crystal oscillator (VCXO) (not shown) in a phase-locked loop (PLL) (not shown) that is locked to GPS-CLK 212 by many well known techniques. The acquiring unit 508 receives the bit-stream of samples from the ADC 506 finishes demodulating the bit-stream of samples (if the RF front-end 500 only downconverted the received satellite signals into an intermediate frequency “IF”) and decodes it by typically utilizing a bank of correlators (not shown) or a matched filter (not shown). If the acquiring unit 508 downconverts the bit-stream of samples from the IF frequency, the acquiring unit 508 may have a mixing stage that mixes a Doppler corrected frequency signal from the GPS code and carrier generator 504 with the bit-stream of samples. The result from the mixer would be a new bit-stream of samples corrected for carrier Doppler shift. The correlators or matched filter correlate the bit-stream of samples from the ADC 506 with the different satellite codes PN codes. The acquiring unit 508 produces a detection signal when the corresponding PN code of a satellite is correlated against the bit-stream samples of the received satellite signal. The PN codes are produced by the GPS code and carrier generator 504. The GPS code generator 504 may include a numerically controlled oscillator (NCO) (not shown) that produces a PN code and other circuitry (not shown) that corrects for Doppler shift both for the carrier and code. The GPS clock processor 502 is capable of determining the STD-GPS-OFFSET. Once the STD-GPS-OFFSET has been generated by the GPS clock processor 502, it is passed to the GPS code and carrier generator 504. The GPS code and carrier generator 504 then combines the STD-GPS-OFFSET with the corrections for Doppler shift and utilizes the combined result to remove the IF carrier and produce the PN codes for the acquiring unit 508. The GPS code and carrier generator 504 attempts to correct the effects of Doppler shift in both the carrier and the code of the received satellite signal. In general, satellite motion has an impact on the processing of the signals at the GPS receiver because the input frequency shifts as a result of the Doppler effect. The satellite motion causes a Doppler frequency shift on the carrier frequency and on the coarse/acquisition (C/A) code. The angular velocity and speed of the satellite can be calculated from the approximate radius of the satellite orbit and is approximately 1.458×10−4 radians/second and 3,874 meters/second. The Doppler frequency shift is caused by the satellite velocity component toward the GPS receiver. Typically, the maximum Doppler velocity occurs when the satellite is at the horizon position and from the orbit speed the maximum Doppler velocity along the horizontal direction is approximately 2,078 miles per hour. This speed is equivalent to a high-speed military aircraft. Therefore, the Doppler frequency shift caused by a land vehicle is often very small, even if the motion is directly toward the satellite to produce the highest Doppler effect. For the L1 frequency, which is modulated by the C/A signal, the maximum Doppler frequency shift is approximately 4.9 KHz. Therefore, for a stationary observer, the maximum Doppler frequency shift is around ±5 KHz. To create a Doppler frequency shift of ±5 KHz by the vehicle alone, the vehicle must move toward the satellite at about 2,078 miles/hour. As such, if the GPS receiver is used in a low-speed vehicle, the Doppler shift can be approximated as ±5 KHz. FIG. 6 is a block diagram of an example implementation of the GPS frequency source 510 of FIG. 5. The GPS frequency source 510 may include the GPS-CLK 212 and a PLL 600. It is appreciated that typically the GPS-CLK 212 may be produced by a timing circuit (not shown) with a crystal oscillator 602. The PLL 600 may be implemented by a number of approaches that are well known to one of ordinary skill in the art. As an example, the basic components of the PLL 600 include a phase detector (not shown), a loop filter (not shown) and a VCO (not shown) whose frequency is controlled by an external voltage and that is locked on to frequency of the GPS-CLK 212. In this example implementation, the GPS carrier and code generator 504 and the GPS clock processor 502 use the GPS-CLK 212 as the base reference and generate their own respective frequencies. The RF front-end 500 and ADC 506 use the frequency from the PLL 600 because they are typically related in a synchronous manner or use frequency values that are multiples of one another. FIG. 7 is a simplified block diagram of an example implementation of the GPS RF front-end 500 utilizing direct conversion. The RF front-end 500 may include an antenna 700 and a mixer 702. The mixer 702 is in signal communication with the PLL 600 and ADC 506. The mixer 702 is basically multiplier that demodulates (or downconverts, i.e., removes the carrier frequency signal) a received satellite signal, on signal path 704, by taking a product of the received satellite signal with the frequency signal provided by the PLL 600. If the frequency of the received satellite signal carrier 704 and the frequency of the PLL 600 are synchronous, i.e., are of the same frequency, the output of the mixer is a direct current (DC) component signal with a second order harmonic that may be filtered out with a low pass filter (not shown). As an example, if the signal on signal path 704 is “x(t)cos(ωt),” where “ω” is the angular frequency and “t” is the time, and the PLL 600 produces a demodulation signal 606 of “cos(ωt)” that is fed into the mixer 702, the resulting output 708 of the mixer would be x(ωt)cos2(ωt) which equals x ⁡ ( t ) 2 ⁢ ( 1 + cos ⁢ ⁢ ( 2 ⁢ ⁢ ω ⁢ ⁢ t ) ) ⁢ ⁢ or ⁢ ⁢ x ⁡ ( t ) 2 + cos ⁢ ⁢ ( 2 ⁢ ⁢ ω ⁢ ⁢ t ) 2 . If the frequency of the received satellite signal carrier 704 and the frequency of the PLL 600 are not synchronous, then there is no DC component. As another example, if the signal on the signal path 704 is “x(t)cos(ωt)” and the PLL 600 produces a demodulation signal 606 “cos(ω1t),” the resulting output 608 of the mixer would be x(t)cos(ωt) cos(ω1t). If “ω1” is close to ω but off by a small amount “Δω,” the relationship may be represented as ω=ω1±Δω. In this case, x(t)cos(ωt) cos(ω1t) would equal x(t)cos(ωt) cos(ωt±Δωt). This problem may be overcome by adjusting the frequency of the PLL 600 to be synchronous with the satellite signal carrier frequency. Adjusting for frequency at the PLL 600 does not, however, account for Doppler shift, which also affects the perceived frequency of the received satellite carrier signal in a dynamic fashion. Rather than correcting for frequency at the demodulating stage at the RF-front end, the correction could be made at the acquiring stage, i.e., at the acquiring unit 508, which would include the correction for Doppler shift. FIG. 8 illustrates a simple block diagram of an example implementation of the acquiring unit 508. At the acquiring unit 508 the Doppler shift error and PLL 600 are corrected by an adjustment in the GPS code and carrier generator 504 and in a change in frequency generated by the PLL 600. The acquiring unit 508 may include a plurality of correlators or matched filters. For simplicity, the acquiring unit 508 is illustrated with one correlator 800, however it is appreciated by one skilled in the art that numerous banks of correlators will most likely be present. In operation, the acquiring unit 508 receives from the ADC 506 a bit-stream of samples possibly corresponding to a received satellite signal. The acquiring unit 508 places the bit-stream of samples into a bank of correlators or matched filters and receives a PN code from the GPS code and carrier generator 504. The PN code is then shifted through the bank of correlators and an output is produced that signifies when a satellite signal has been received by the wireless device 102. Typically, the PN code received from the GPS code and carrier generator 504 has been adjusted to compensate for any Doppler shift for the respective satellites. However, in this situation the GPS code and carrier generator 504 and the PLL 600 has also compensated for any frequency errors in the GPS-CLK 212. FIG. 9 shows a block diagram of another example implementation of the RF front-end 900 and the acquisition unit 902, which is in signal communication with the RF front-end 900 via the ADC 904. In this example, the RF front-end 900 is a multi-stage receiver that first downconverts a received satellite signal at the antenna 906 to an intermediate frequency (IF) signal 908, such as 96 KHz, via mixer 910 and then to a baseband (i.e., demodulate to zero) signal 912 via mixer 914. The baseband signal 912 may then be passed through the ADC 904 to the acquisition unit 902. In the acquisition unit 902, the ADC sample baseband signal is corrected for Doppler carrier shift via mixer 916 and passed to a bank of correlators 918 or a matched filter (not shown). The frequency sources 918 and 920 may be produced by frequency generator 922 that either multiplies or divides (in any one of many well known techniques) the frequency signal produced by the PLL 924 which is locked to the GPS-CLK 212. Similarly, the GSP carrier and code generator 926, which utilizes the GPS-CLK 212, may produce signals 928 and 930 that compensate for the carrier Doppler shift and drive the correlators 918 or matched filer (not shown). FIG. 10 shows a block diagram for yet another example implementation of the RF front-end 1000 and the acquisition unit 1002, which is in signal communication the RF front-end 1000 via the ADC 1004. In this example the RF front-end 1000 only has mixer stage. The received satellite signal is received at antenna 1006 and mixed with an IF frequency 1008 at mixer 1010. The IF frequency 1008 is produced by frequency generator 1012 and it mixes with the received satellite signal in mixer 1010 to downconvert the received satellite signal to an intermediate downconverted signal 1014 such as 96 KHz. The intermediate downconverted signal 1014 is passed through the ADC 1004 to the acquisition unit 1002. The ADC 1004 digitizes the intermediate downconverted signal in a bit-stream of samples and passes it to the acquisition unit 1002. At the acquisition unit 1002, the bit-stream of samples are feed into a second mixer 1016 which mixes the samples with a carrier Doppler corrected signal 1018 which produces a downconverted bit-stream of samples that have been corrected for carrier Doppler shift. The output of mixer 1016 is feed into a bank of correlators 1020 or matched filters and produces a detection signal if a satellite has been acquired. As before, the frequency generator 1012 is related to the PLL frequency 1026 and both the PLL and GPS carrier and code generator 1022 are related to the GPS-CLK 212. FIG. 11 shows a block diagram for an example implementation of the GPS carrier and code generator 504. The GPS carrier and code generator 504 may include a Doppler prediction model 1100, an offset combiner 1102, a NCO register 1104 and a NCO 1106. In operation, the Doppler prediction model 1100 produces a number of Doppler correction values that are combined with the STD-GPS-OFFSET. These correction values are input into the NCO register 1104 that controls the NCO 1106. The NCO 1106 then sends the Doppler corrected carrier signal and PN code to the acquisition unit 508. FIG. 12 shows a block diagram of an example implementation of the GPS clock processor 502. The GPS clock processor 502 may include an offset counter 1200 and an offset combiner 1202. As an example, the offset counter 1200 may receive a signal 1204 from the GPS-CLK 212 and at least one signal 1212 from the wireless processing section 200. The offset counter 1200 then produces an offset signal that represents GPS-WPS-OFFSET. The offset signal may be transmitted as a message via signal path 1206 to the offset combiner 1202. The offset combiner 1202 then combines the information from the offset signal received, via signal path 1206, with a message received from the wireless processing section 200, via signal path 1208, that represents STD-WPS-OFFSET. The output of the offset combiner 1202 is an offset signal 1210 that represents STD-GPS-OFFSET. This offset signal 1210 is input into the combiner 1102 of FIG. 11. As an example of operation, the offset counter 1200 is utilized to measure the relative frequency offset between the WPS-CLK 210 and GPS-CLK 212. A gate signal to the offset counter 1200 may be generated by the GPS-CLK 212 via signal path 1204. The pulse width, which may also be referred to as gate time, is determined by counting a fixed number of GPS-CLK 212 clock pulses. The offset counter 1200 also receives, via signal path 1212, the WPS-CLK 210. The offset counter 1200 then counts the pulses from the WPS-CLK 210 clock during the gate time. In general, the offset counter 1200 should count number WPS-CLK 210 clock pulses (the “predicted count” or “count predicted”) to be equal to the frequency of the WPS-CLK 210 multiplied by the gate time or in other words: count_predicted=frequency×gate_time. For example, the offset counter 1200 should accumulate 25 million pulses from a frequency source, such as an oscillator, with a hypothetical WPS-CLK 210 frequency of 25 MHz during a one-second interval. Therefore, a frequency offset (freq_offset) may be determined as the quantity of the actual count reading (count_reading) minus the count predicted, the quantity divided by product of the WPS-CLK 210 frequency by the gate time. Written as a mathematical relationship the frequency offset is: freq_offset=(count_reading−count_predicted)/(frequency×gate_time). It is appreciated by those of skill in the art, that in order to compute the predicted count, one needs the nominal GPS-CLK 212 and WPS-CLK 210 clock frequencies. The GPS-CLK 212 clock frequency is imposed via signal path 1204. To avoid a compilation time parameter in the GPS subsystem 202 source code, the wireless processing section 200 specifies the WPS-CLK 210 nominal frequency. Typically this is done by sending a periodic frequency calibration message that includes the WPS-CLK 210 nominal frequency parameter, N-WPS-CLK, from the wireless processing section 200 to the offset counter 1200 via signal path 1214. The GPS clock processor 502 may then compute the relative frequency error without prior knowledge of the WPS-CLK 210 clock characteristics. To reduce the complexity of the offset counter 1200 hardware, the overall counting range of the offset counter 1200 may be much smaller than the total counting number, provided that the offset counter 1200 counts modulo its range, and its value range is smaller than the total range of the offset counter 1200. For example, if the total range is 5 parts per million (ppm), the WPS-CLK 210 frequency is 20 MHz, and the gating time is 1 second, the offset counter 1200 range may be as small as 5e−6 times 20e6=100. The difference between the predicted count and the actual count reading is utilized to compute the GPS-CLK 212 frequency offset as follows. First, the difference between the predicted count and the actual count is not only due to the WPS-CLK 210 frequency error (δfwps-lo), but also to the gate time error and offset counter 1200 resolution. Supposing the offset counter 1200 gate time is t seconds that is controlled by the GPS-CLK 212 clock, the error of gate time (δt) caused by the GPS-CLK 212 clock frequency (δfgps-lo) is & δt=δfgps-lo×t. Then, the freq_offset=δfwps-lo+δfgps-lo+counting_error/(t×fwps-lo). The value that the offset counter 1200 measures is (δfgps-lo+δfwps-lo). Theoretically, the GPS-CLK 212 clock cannot be calibrated better than WPS-CLK 210 clock and extending the gate time may improve the measurement accuracy of (δfgps-lo+δfwps-lo). However, using too long a gate time is typically impractical. Therefore, the minimum gate time is generally predetermined such that the relative frequency offset estimate error is within the desired design limits. FIG. 13 is a flow chart illustrating the process performed by the GPS subsystem 200. The process begins 1300 by GPS clock processor 502, FIG. 5, receiving 1302, FIG. 13, GPS-CLK, WPS-CLK and STD-WPS-OFFSET. Then the GPS clock processor 502 determines the GPS-WPS-OFFSET and combines 1306 the GPS-WPS-OFFSET with STD-WPS-OFFSET to generate STD-GPS-OFFSET. The STD-GPS-OFFSET is then passed to the GPS carrier and code generator 504 where the STD-GPS-OFFSET is combined 1308 with Doppler prediction to create a correction signal. The correction signal is used to adjust 1310 the NCO in the GPS carrier and code generator. The NCO output is then feed 1312 into the acquisition unit 508 and in response the acquisition unit acquires 1314 a received satellite signal using the correction signal. The process then ends 1316. The process in FIG. 14 may be performed by hardware or software. If in hardware, the process may be performed by a controller (not shown) in either the wireless processing section 200 or GPS processor section 400. The controller may selectively be any general-purpose processor such as an Intel XXX86, Motorola 68XXX or PowerPC, or other equivalent or GPS and/or cellular specialized processor capable of running software instructions (not shown) resident on the controller. Alternatively, a GPS-specific circuit or oriented device may selectively also be utilized. It is appreciated that the controller may also be selectively integrated into a signal semiconductor chip such as an Application Specific Integrated Chip (ASIC) or Reduced Instruction Set Computer (RISC), or may be implemented via a Digital Signal Processor (DSP) chip. If the process is performed by software, the software may reside in software memory (not shown) in the wireless device 102 (either in the wireless processing section 200 and/or GPS subsystem 202) or at a server on wireless 104. The software in software memory may include an ordered listing of executable instructions for implementing logical functions (i.e., “logic” that may be implement either in digital form such as digital circuitry or source code or in analog form such as analog circuitry or an analog source such an analog electrical, sound or video signal), may selectively be embodied in any computer-readable (or signal-bearing) medium for use by or in connection with an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that may selectively fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions. In the context of this document, a “computer-readable medium” and/or “signal-bearing medium” is any means that may contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device. The computer readable medium may selectively be, for example but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, device, or propagation medium. More specific examples “a non-exhaustive list” of the computer-readable medium would include the following: an electrical connection “electronic” having one or more wires, a portable computer diskette (magnetic), a RAM (electronic), a read-only memory “ROM” (electronic), an erasable programmable read-only memory (EPROM or Flash memory) (electronic), an optical fiber (optical), and a portable compact disc read-only memory “CDROM” (optical). Note that the computer-readable medium may even be paper or another suitable medium upon which the program is printed, as the program can be electronically captured, via for instance optical scanning of the paper or other medium, then compiled, interpreted or otherwise processed in a suitable manner if necessary, and then stored in a computer memory. As previously discussed, the GPS system of the invention may be incorporated into any number of wireless mobile applications. Similarly, the GPS system can be used in connection with any number of geo-location services that have the capability to receive frequency information. Such GPS system can be used in connection with mobile devices that operate in network aided mode or network based services modes, or that operate in multi-mode, thereby having the ability to simultaneously switch between standalone mode, network aided mode, network based services, or other modes that allow the device to receive frequency information from the a secondary source, such as a base station. While various embodiments of the invention have been described, it will be apparent to those of ordinary skill in the art that many more embodiments and implementations are possible within the scope of this invention. Accordingly, the invention is not to be restricted except in light of the attached claims and their equivalents.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of Invention The invention relates to Satellite Positioning System (SPS) receivers, and in particular to increasing the accuracy of SPS receivers by providing the receivers with information to correct for the frequency offset between the oscillators of the receivers and those of the satellites. 2. Related Art Satellite Positioning System (SPS) receivers, such as Global Positioning System (GPS), also known as NAVSTAR, receivers, receive radio transmissions from satellite-based radio navigation systems and use those received transmissions to determine the location of the SPS receiver. The location of the SPS receiver may be determined by applying the well-known concept of intersection if the distances from the SPS receiver to three SPS satellites having known satellite locations. Generally, each satellite in a satellite-based radio navigation system broadcasts a radio transmission, that contains its location information, and orbit information. More specifically, each of the orbiting satellites in the GPS system contains four highly accurate atomic clocks: two Cesium and two Rubidium. These clocks provide precision timing pulses used to generate two unique binary codes (also known as a pseudo random noise “PRN,” or pseudo noise “PN” code) that are transmitted to earth. The PN codes identify the specific satellite in the constellation. The satellite also transmits a set of digitally coded ephemeris data that completely defines the precise orbit of the satellite. The ephemeris data indicates where the satellite is at any given time, and its location may be specified in terms of the satellite ground track in precise latitude and longitude measurements. The information in the ephemeris data is coded and transmitted from the satellite providing an accurate indication of the exact position of the satellite above the earth at any given time. Although atomic clocks are very precise with a stability of about 1 to 2 parts in 10 13 over a period of one day, a slight error (generally known as clock drift) may occur in the clocks over time resulting in satellite clock errors of about 8.64 to 17.28 ns per day with corresponding range errors of 2.59 to 5.18 meters. In order to compensate for the error, the accuracy of the satellite atomic clocks are continuously monitored from ground stations in the GPS control system and any detected errors and drift in the clock of the satellites may be calculated and transmitted by the satellites as part of a navigation message in the form of three coefficients of a second-degree polynomial. In the case of GPS, there is nominally a constellation of 24 operational satellites above the Earth. Each satellite has individual PN codes, a nearly circular orbit with an inclination of 55° to the equator with a height of 10,898 nautical miles (20,200 kilometers) above Earth and an orbital period of approximately 12 hours. Each GPS satellite transmits a microwave radio signal composed of two carrier frequencies modulated by two digital codes and a navigation messages. The two carrier frequencies are referred to as the “L1” and “L2” carriers and are transmitted at 1,572.42 megahertz (MHz) and 1,227.60 MHz, respectively. The two GPS codes are called the coarse acquisition (C/A-code) and precision (P-code). Each code consists of a stream of binary digits, zeros and ones, known as bits or “chips.” Both the C/A-code and P-code are generally referred to as a PN code because they look like random noise-like signals. Presently, the C/A-code is modulated only on the L1 carrier while the P-code is modulated on both L1 and L2 carriers. The C/A-code has a chipping rate of 1.023 MHz because it is a stream of 1,023 binary digits that repeats itself every millisecond. Each satellite is assigned a unique C/A-code, which enables a GPS receiver to identify which satellite is transmitting a particular code. The C/A-code range measurement is relatively less precise when compared to the P-code but it is also less complex and available to all users. The P-code is mostly limited in use to the United States government and military. Each satellite also transmits a GPS navigation message that is a data stream added to both the L1 and L2 carriers as binary bi-phase modulation at 50 kilo-bits per second (kbps). The navigation message contains, along with other information, the coordinates of the GPS satellites as a function of time, the satellite health status, the satellite clock corrections, the satellite almanac, and atmospheric data. Each satellite transmits its own navigation message with information on the other satellites, such as the approximate location and health status. By receiving these radio signals emitted from the satellites, a GPS receiver may calculate its distance from the satellite by determining how long it took the GPS receiver to receive the signal transmitted from the satellite. For example, a GPS receiver could calculate its two-dimensional position (longitude and latitude or X and Y) by determining its distance from three satellites. Similarly, the GPS receiver could calculate its three-dimensional position (longitude, latitude and altitude or X, Y and Z) by measuring its distance from four satellites. Unfortunately, this approach assumes that the distances measured from the GPS receiver to the satellites are very accurate and there is no bias error. In practice, however, the distance measured between the GPS receiver and each satellite typically has a constant unknown bias, because the GPS receiver clock (GPS-CLK) is usually different from the GPS satellite clocks. In order to resolve this bias error one more satellite transmission is typically needed to calculate the location of the GPS receiver. Generally, to receive the signals transmitted by the satellites, the GPS-CLK of the GPS receiver should be synchronized with that of the GPS satellites. Any errors in the synchronization between the clocks will cause inaccuracies the measurement of the location of the GPS receiver. Atomic clocks, like those found in the GPS satellites, are very expensive typically costing a few thousand dollars for a Rubidium clock and a few tens of thousands of dollars for a Cesium clock. They are therefore not practical for use in typical consumer GPS receivers. Inexpensive, less accurate clocks, such as crystal clocks, are generally utilized in GPS receivers as GPS-CLKs. However, unless the inaccuracy of the GPS-CLK is determined and corrected for, synchronization with that of the atomic clocks of the satellites will be partially off and the resulting distance measurement calculated by the GPS receiver will be partially inaccurate. Thus, the error of the GPS-CLK is yet another unknown variable that must be determined to accurately determine the location of the GPS receiver. Besides accuracy, another problem associated with the error of the GPS-CLK relative to the GPS satellite clocks is the resulting acquisition time for the GPS receiver commonly known as the time to first fix (TTFF). For many applications, such as E911, a GPS receiver must be able to provide a position solution in a short period of time after the GPS receiver is powered on. Unfortunately, the GPS-CLK can have large frequency drift during the first couple minutes after being powered on. The large frequency drift can cause significant degradation on TTFF performance and may even result in lack of navigation fix in weak signal environments. In addition to the frequency drift in the GPS-CLK, there are a number of other factors that can affect TTFF performance. Although there are a large number of GPS satellites positioned above the earth's atmosphere, it is not always possible for a GPS receiver to receive accurate transmissions from the required number of GPS satellites necessary to calculate the position of the GPS receiver. Any number of problems may prevent a GPS receiver from receiving the necessary number of signals, or from receiving accurate signals because of transmission or receiver errors. These problems can result in high TTFF times. For example, a GPS receiver may not be able to receive the necessary number of GPS transmissions due to physical obstructions in the atmosphere or on the earth. Alternatively, even though a GPS receiver may be able to receive the necessary signals, the signal could be inaccurate due to any of the following: (i) error in the satellite clock; (ii) error in the receiver clock; (iii) error in computed satellite position; (iv) atmospheric errors caused by the ionosphere or the troposphere; (v) multipath errors caused by the receipt of reflective signals; (vi) receiver measuring errors and/or (vii) selective errors, or man made errors. These inaccuracies could lead to TTFF times that may be over thirty seconds because the GPS receiver needs to obtain the ephemeris data from the GPS system itself, and the GPS receiver typically needs a strong signal to acquire the ephemeris data reliably. Since the inception of GPS, methods have been, and are still being, developed to reduce errors and to enhance the accuracy of the GPS systems. Further, many different methods are being implemented to provide alternative means for providing the GPS receiver with information concerning unknown variables or inaccuracies in the system such that it is not always required for the system to receive satellite transmission signals from all the satellites or to receive accurate transmission data. One technique that has been introduced to assist with overcoming errors in the GPS system is differential GPS. With differential GPS, a receiver having a known location receives the GPS signals and calculates its position from the received signals. The calculated position is then compared to the actual known position of the receiver. The differential between the known position and the calculated position can then be used to calculate errors in the transmission signals. These errors can then be transmitted to receivers in unknown locations (“mobile receivers”) and used by the mobile receivers to compute their own location with better accuracy. Differential GPS is typically used to correct for errors other than receiver or multipath errors. However, in a similar manner as differential GPS, correction data may be sent to the GPS receiver to correct for receiver errors. For example, one method that has been used to correct for errors in the GPS-CLK has been to send a precision carrier frequency signal to the GPS receiver from a second source, such as a base station. In this application, the GPS receiver is designed to receive the precision carrier frequency signal and then calibrate and/or lock the GPS-CLK to that of the precision carrier frequency. This method, however, typically involves the use of additional complicated circuitry that first locks and/or calibrates the GPS-CLK to the precision carrier frequency and then maintains dynamic synchronization between the GPS-CLK and precision carrier frequency. A need therefore exists for a method of compensating for errors created by the drift of the GPS-CLK to increase positional accuracy and improve TTFF in a dynamic manner without utilizing additional complex circuitry and without significantly modifying the existing hardware.
<SOH> SUMMARY <EOH>The invention relates to aiding a Global Positioning System (GPS) subsystem within a wireless device. The wireless device includes a wireless processing section capable of receiving signals from a wireless network and a GPS subsystem having a radio frequency (RF) front-end capable of receiving a GPS satellite signal. The wireless processing section of the wireless device receives an external clock and determines the offset between the clock in the wireless processing section and that of the external clock. The GPS subsystem then receives the offset information from the wireless processing section, information related to the nominal frequency of the wireless processing section clock and the wireless processing section clock. Using this information and the GPS clock in the GPS subsystem, the GPS subsystem determines an acquiring signal, which is related to a frequency offset between the GPS clock and the network clock. The GPS subsystem then acquires GPS satellite signals in an acquiring unit though the use of the acquiring signal. Other systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims.
20051003
20070626
20060504
95321.0
G01C2136
1
ARTHUR JEANGLAUD, GERTRUDE
AIDING IN A SATELLITE POSITIONING SYSTEM
UNDISCOUNTED
1
CONT-ACCEPTED
G01C
2,005
10,515,836
ACCEPTED
Screen/mixer
A device (10) for sieving and/or mixing is disclosed which includes a base (12) and a container (13) mounted thereon for rotation about an axis which is substantially horizontal. The container has a peripheral wall (14) extending angularly about and longitudinally relative to the axis, and an opening (25) extending longitudinally relative to the axis to provide for movement of material into and out of said space. Means to drive the container angularly about the axis are provided so that any material which is introduced into the container may be processed as required by rotation thereof. The peripheral wall is configured with an internal baffle to prevent material from being delivered when the container is rotated one way, but delivers material from within said space through the opening when the container is moved angularly about its axis in the opposite direction being a predetermined direction of rotation for delivery.
1. A device for sieving and/or mixing including: a base; a container mounted on the base for rotation about an axis which is substantially horizontal, said container having a peripheral wall extending angularly about and longitudinally relative to said axis, and an opening extending longitudinally relative to said axis to provide for movement of said material with respect to said space; means to drive said container angularly about said axis so that any material which is introduced into the container may be processed as required by rotation thereof; and wherein said peripheral wall delivers material from within said space through said opening when said container is moved angularly about said axis in a predetermined direction. 2. A device according to claim 1 wherein the base is be free standing so that the device functions as a stand alone piece of equipment. 3. A device according to claim 1 wherein the base is itself in the form of a suitable support mechanism or otherwise has suitable mounting means for attachment to some other apparatus. 4. A device according to claim 3 wherein the device is mountable on the front of a front-end loader, prime mover or other similar vehicle (including agricultural and earth moving equipment), from which it derives its drive means. 5. A device according to any one of the preceding claims, in which said peripheral wall includes a tray portion in the form of a blade or having a cutting edge, located radially outwardly of said opening and adjacent said opening. 6. A device according to claim 5 in which the tray has a simple straight leading edge. 7. A device according to claim 5 in which the tray is provided in known fashion with teeth or the like to facilitate entering or breaking up material prior to causing it to enter the container. 8. A device according to any one of the preceding claims in which the device functions as a sieve, with said peripheral wall having perforations in at least a portion thereof through which sieved particle material is to pass. 9. A device according to claim 8, in which said peripheral wall includes a mesh portion and a tray portion. 10. A device according to any one of the preceding claims, in which the container is provided with a catch tray which is located radially outwardly of and extending externally from the peripheral wall in the lower region thereof and opposite the opening, which acts so as to prevent material (in the case of utilising the device as a sieve), from merely passing straight through the back of the container (the back being understood as relative to the front where the opening is located). 11. A device according to any one of the preceding claims in which the peripheral wall comprises one or more removable segments or panels, so that one or more segments or panels can be interchanged between solid panels suitable for mixing operations and mesh panels or the like suitable for sieving. 12. A device according to any one of the preceding claims in which said peripheral wall retains said material within said space so that said material is processed (sieved or mixed as the case may be) within that space when the container is rotated in a direction opposite to said predetermined direction in which it will deliver material out of the container. 13. A device according to claim 12, in which retention of the material is facilitated by an internal baffle extending from the peripheral wall radially inwardly in the region of the opening and from that side of the opening opposite the external tray, so that on rotation of the container in the direction opposite to the predetermined direction in which material is delivered from the opening, material is prevented from falling from the opening as the container rotates in that opposite direction. 14. A device according to any of claims 1 to 11, in which there is provided suitable closing means to close the opening in the peripheral wall, so that said peripheral wall acts in conjunction with the closing means to retain said material within said space so that said material is processed (sieved or mixed as the case may be) within said space when the closed container is rotated in either a direction opposite to said predetermined direction and depending on the particular arrangement, in either direction. 15. A device according to claim 14 in which the closing means functions as a baffle to prevent material leaving the container when rotated opposite the predetermined direction of rotation, band is additionally hinged to act not only as a baffle but as a door as required. 16. A device according to either claim 14 or 15, wherein opposing hydraulic drives cause the door to open when the container is rotated in the predetermined direction to facilitate delivery, whilst causing the door to closing when the container is rotated in the opposite direction. 17. A device including: a base; a container mounted on the base for rotation about an axis that has a direction of extension that is at least partly horizontal, said container having a peripheral wall extending angularly about and longitudinally relative to said axis, and an opening extending longitudinally relative to said axis to provide for movement of said material with respect to said space; means to drive said container angularly about said axis; and wherein said peripheral wall includes a tray portion located radially outwardly of said opening and adjacent said opening.
TECHNICAL FIELD The present invention relates to devices that can sieve and/or mix granular material. BACKGROUND OF INVENTION Typically, devices that sieve granular material, also known as screens, are discrete pieces of apparatus and are generally not portable. In respect of mixers, such as cement and concrete mixers, the devices are either very large truck-mounted drums or alternatively small trailer type mixers. In respect of the smaller trailer type mixers, the inclination of the drum needs to be changed in order to deliver the contents from within the drum. It would be advantageous in many situations, if such a device were able to be used in conjunction with a front end loader apparatus or similar equipment including earth moving or agricultural equipment, so that material could be scooped up as required, processed and deposited elsewhere as required. In such arrangements, it would also be advantageous if the device operated in essentially one plane or having only one form of motion (eg rotation), without the need to have to tip or to be inclined so as to empty the contents of the device, thereby reducing the complexity of any associated drive means. OBJECT OF THE INVENTION It is an object of the present invention to provide an alternative sieving device or mixer relative to the above-discussed devices, overcoming some or all of the inherent problems and taking into account where appropriate the above identified proposed advantages. At the very least, the device of the invention is an alternative to presently known means for sieving and/or mixing material. DISCLOSURE OF THE INVENTION There is disclosed herein a device for sieving and/or mixing including: a base; a container mounted on the base for rotation about an axis which is substantially horizontal, said container having a peripheral wall extending angularly about and longitudinally relative to said axis, and an opening extending longitudinally relative to said axis to provide for movement of said material with respect to said space; means to drive said container angularly about said axis so that any material which is introduced into the container may be processed as required by rotation thereof; and wherein said peripheral wall delivers material from within said space through said opening when said container is moved angularly about said axis in a predetermined direction. The base may be free standing so that the device functions as a stand alone piece of equipment, it or may itself be in the form of a suitable support mechanism or otherwise have suitable mounting means for attachment to some other apparatus. Thus, in one preferred form of the invention, the device is able to be mounted on the front of a front-end loader, prime mover or other similar and suitable vehicle (including agricultural and earth moving equipment), from which it may derive its drive means. More preferably, especially for use with such vehicles, said peripheral wall includes a tray portion in the form of a blade or having a cutting edge, located radially outwardly of said opening and adjacent said opening. The primary purpose of the tray is to act as a scoop so that when the device is pushed into the material to be sieved or mixed (using the motive power of the front end loader or similar apparatus), the material is caused to enter the container in a scooping fashion. The tray may have a simple straight leading edge, or be provided in known fashion with teeth or the like to facilitate entering or breaking up material prior to causing it to enter the container. Preferably, said device is a sieve, with said peripheral wall having perforations in at least a portion thereof through which sieved particle material is to pass. Preferably, said peripheral wall includes a mesh portion and a tray portion, the tray portion functioning as described above. Preferably, the container is provided with a catch tray which is located radially outwardly of and extending externally from the peripheral wall in the lower region thereof and opposite the opening, which acts so as to prevent material (in the case of utilising the device as a sieve), from merely passing straight through the back of the container (the back being understood as relative to the front where the opening is located). Thus material will be retained in the device, prior to any rotation of the container, notwithstanding that some material may initially pass through a portion of the perforated wall, it being prevented from leaving the device altogether by virtue of the catch tray, even when the device is being moved to another location where the sieved material is to be deposited. Although a region of the peripheral wall in this case could be provided without perforations, the catch tray thus maximises the available sieve area within the peripheral wall proper. With advantage, the peripheral wall comprises one or more removable segments or panels, so that one or more segments or panels can be interchanged, for example between solid panels suitable for mixing operations and mesh panels or the like suitable for sieving. In this way, a number of alternate mesh sizes may also be employed for different sieving specifications in order to achieve different results. In one preferred embodiment, said peripheral wall retains said material within said space so that said material is processed (sieved or mixed as the case may be) within that space when the container is rotated in a direction opposite to said predetermined direction in which it will deliver material out of the container. It will be appreciated that “retains” means, in the case where sieving is performed, retaining that material which will not pass through the sieve. In this embodiment retention of the material is preferably facilitated by an internal baffle extending from the peripheral wall radially inwardly in the region of the opening and from that side of the opening opposite the external tray, so that on rotation of the container in the direction opposite to the predetermined direction in which material is delivered from the opening, material is prevented from falling from the opening as the container rotates in that opposite direction. In other words, once material is collected in the container, for example by pushing the device into a pile of material to be processed, simply rotating the container one way will cause the material to be retained (or more accurately in the case of sieving, will cause that portion of material which does not pass through the sieve to be retained), whilst simply reversing the direction of rotation of the container, will cause the remaining or otherwise retained material to be delivered out of the container. It will of course be appreciated that this will generally involve three locations to complete a cycle (for sieving at least), namely a pick-up location, processing location and a deposit location. Thus in a typical sieving process, the device is first brought into contact with a pile of material to processed simply by pushing the open side of the container into the pile in a typical scooping action reminiscent of many such operations with front end-loaders etc. Then the device is moved to a second location, where the container is rotated opposite the predetermined rotation for delivery, during which time finer material is allowed to fall through the screens or perforations of the device. After the finer material has fallen through, then the device is moved to a third location where the rotation of the container is reversed and the larger retained material is let fall from the opening. A typical mixing operation is similar except that the second location is not required, ie where sieved material is allowed to fall, as all the material will remain when mixing. Alternatively, in a second embodiment, there is provided suitable closing means to close the opening in the peripheral wall, so that said peripheral wall acts in conjunction with the closing means to retain said material within said space so that said material is processed (sieved or mixed as the case may be) within said space when the closed container is rotated in either a direction opposite to said predetermined direction, or in this case, depending on the particular arrangement, in either direction. Again “retains” here means in the case of sieving, retaining material which will not pass through the sieve. It will also be understood that in this embodiment, the closing means may in fact be reminiscent of the internal baffle described in the previous embodiment, but which is hinged for example to act not only as a baffle but as a door if require. Thus in one form of the invention, the longitudinal opening of the container is permanently available or open, for example in a fixed or static arrangement. In this embodiment, the material once sieved or mixed (ie remaining material in the case of sieving) is only able to be delivered from within the container via the opening when the container is rotated in the predetermined direction, whilst the said material to be sieved or mixed otherwise remains inside the space of the container when it is rotated in the opposite direction (except that which passes through the sieve if that operation is performed). Put simply, rotating the container one way retains material, reversing the rotation causes it to empty. In the second embodiment, the longitudinal opening is able to be closed, for example by a door or flap, so that once material has been collected in the container and the opening closed, the container may in principle be rotated in either direction to sieve or mix the material. However, with advantage, two counteracting drives, eg hydraulic drives, may be utilised. The first and more powerful causes the container to rotate opposite the predetermined delivery direction, whilst the second acts in the opposite direction on the door or flap effectively acting like a brake to keep the door closed, when the container rotates in that direction. However, reversing the direction of the main drive to the container, so that it rotates in the predetermined direction for delivery, will causing both drives to act in the same direction, thereby causing the door to be opened, thereby facilitating delivery from within the container. Such drive arrangements are possible especially utilising hydraulic means, although other suitable clutch means may be utilised. It will also be understood that rotation of the container as described includes not only simple continuous rotation, but also intermittent rotation, and in some cases where rocking, vibrating or shaking are required (especially desirable during sieving), appropriate intermittent back and forth rotation might be effected. Thus, rotation may include, during the course of an operation to mix or sieve, any one or more of such motions as described. Thus for example even a simple scooping of material and shaking of the material (without necessarily performing full revolutions of the container is envisaged in some circumstances. There is further disclosed herein: a base; a container mounted on the base for rotation about an axis that has a direction of extension that is at least partly horizontal, said container having a peripheral wall extending angularly about and longitudinally relative to said axis, and an opening extending longitudinally relative to said axis to provide for movement of said material with respect to said space; means to drive said container angularly about said axis; and wherein said peripheral wall includes a tray portion located radially outwardly of said opening and adjacent said opening. BRIEF DESCRIPTION OF THE DRAWINGS Preferred forms of the present invention will now be described by way of example with reference to the accompanying drawings wherein: FIG. 1 is a schematic side elevation of a device to sieve particle matter; FIG. 2 is a schematic perspective view of a modification of the device of FIG. 1; FIG. 3 is a schematic side elevation of a mixing device; FIG. 4 is a schematic side elevation of the device of FIG. 1 mounted on a front end loader or other suitable prime mover; FIG. 5 is a schematic side elevation of a modification of the device of FIG. 4, and FIG. 6 is a series of schematic diagrams showing the sequence of operation of one embodiment of the invention operating as a sieve. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring generally to the Figures and in particular FIG. 1, there is schematically depicted a sieve 10. The sieve 10 may be mounted on an associated stand or base, or may be adapted to be attached to a front end loader or other prime mover 11 (FIG. 4). The prime mover 11 may be any suitable piece of agricultural equipment or alternatively a piece of earth moving equipment. The sieve 10 includes a base 12 which rotatably supports a container 13. The container 13 is mounted on the base 12 for rotation about a generally horizontal axis. The container 13 has a peripheral wall 14 including an arcuate mesh segment 15 extending to an external collecting tray segment 16. In that respect, the tray segment 16 has a rearwardly extending portion 17 acting as a catch tray, generally coextensive with a portion of the mesh segment 15, but spaced a little away therefrom except in the region along which the two in fact join. The base 12 includes a pair of generally parallel coextensive arms 18 which directly support the container 13. Mounted within one of the arms 18 is a drive assembly 19. The drive assembly 19 includes chains 21 that drive a series of sprockets including sprockets 22 and 23, with the sprocket 23 being coupled to the container 13 to drive the container in this case. Any suitable drive arrangement may be employed in known fashion. The motor 20 may be operated in either rotational direction. In operation of the above sieve 10, the tray segment 16 is loaded with particle material to be sieved. Thereafter, the motor 20 is activated to cause rotation of the container 13 in the direction of the arrow 24. For example, the container 13 could be continually rotated in the direction of the arrow 24 so that material smaller than a predetermined size will fall through the mesh segment 15. Alternatively, the container 13 may be merely inverted and then angularly oscillated so that again the smaller material falls through the mesh segment 15. When the sieving operation is complete the operator reverses the direction of the motor 20 so that it rotates in the opposite direction to the arrow 24. The material then contained within the container 13 will exit the container 13 by means of the opening 25. In that respect, it should be appreciated that the opening 25 extends generally parallel to the rotational axis. The wall 14 also extends generally parallel to the rotational axis and extends angularly about the rotational axis. The peripheral wall 14 further includes an internal baffle 26 spaced from the tray 16, with the opening 25 being located between the tray 16 and baffle 26. In respect of the portion 17 it should be appreciated that it is spaced radially outward from the segment 15 relative to the rotational axis. In the modification of FIG. 2, the drive assembly 19 is replaced with a pair of hydraulic or pneumatic cylinders 27 which cause rotation or angular oscillation of the container 13 by means of crank members 28. In FIG. 3 there is schematically depicted a modification of the container 13. In this embodiment the peripheral wall 14 is not a mesh material but would preferably be sheet material. The container 13 could be used to mix materials such as cement and concrete. Mixing would occur by rotation of the container 13 in the direction of the arrow 24. Reverse direction would then deliver the mixed material out through the opening 25. In the modification of FIG. 5, the container 13 of the sieve 10 is modified by removal of the internal baffle 26 and the inclusion of a door 29. The door 29 is movable by means of one or more hydraulic or pneumatic cylinders 30, between a closed position closing the opening 25, and an open position exposing the opening 25. In respect of this embodiment it should be appreciated that although it is described and illustrated as being a sieve 10, it could also be adapted as a mixer as described with reference to FIG. 3. In respect of the above preferred embodiments it should be appreciated that the tray portion 16 is located radially outwardly of said opening and adjacent said opening so that the container 13 may be moved to engage a supply of material to be sieved or mixed, and then the container 13 moved while retaining the material on the tray portion 16, rearward extension 17 preventing material from falling through until rotation is commenced. Referring to FIG. 6, there is depicted diagrammatically a series of steps a to 1 for a typical sieving process, in which steps a to i show rotation of the device 10 in a clockwise direction (opposite the predetermined direction of rotation for delivery and steps j to l show rotation in a counter clockwise direction (according to the predetermined direction of rotation for delivery). From a resting position in step a where for example material 32 is loaded into the device 10 by pushing it in the direction of arrow “31”, the device 10 is rotated clockwise (steps b to i) which causes the material 32 to be sieved, smaller material 33 falling through the mesh segment 15 of the container 13. As shown in steps g to i material intended to be retained 34 is prevented from falling through the opening 25 by virtue of the internal baffle 26. Once the material 32 is sufficiently sieved, the motor (not shown) is reversed and in steps j to l, the remaining material 34 is caused to be delivered from the opening 25. Throughout the specification any use of the word “comprise” and its derivatives is intended to have an inclusive rather than exclusive meaning unless the context requires otherwise. INDUSTRIAL APPLICABILITY The invention has industrial applicability at least in relation to devices for sieving and/or mixing. The foregoing describes only one embodiment of the present invention, and modifications obvious to those skilled in the art can be made thereto without departing from the scope of the present invention.
<SOH> BACKGROUND OF INVENTION <EOH>Typically, devices that sieve granular material, also known as screens, are discrete pieces of apparatus and are generally not portable. In respect of mixers, such as cement and concrete mixers, the devices are either very large truck-mounted drums or alternatively small trailer type mixers. In respect of the smaller trailer type mixers, the inclination of the drum needs to be changed in order to deliver the contents from within the drum. It would be advantageous in many situations, if such a device were able to be used in conjunction with a front end loader apparatus or similar equipment including earth moving or agricultural equipment, so that material could be scooped up as required, processed and deposited elsewhere as required. In such arrangements, it would also be advantageous if the device operated in essentially one plane or having only one form of motion (eg rotation), without the need to have to tip or to be inclined so as to empty the contents of the device, thereby reducing the complexity of any associated drive means.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>Preferred forms of the present invention will now be described by way of example with reference to the accompanying drawings wherein: FIG. 1 is a schematic side elevation of a device to sieve particle matter; FIG. 2 is a schematic perspective view of a modification of the device of FIG. 1 ; FIG. 3 is a schematic side elevation of a mixing device; FIG. 4 is a schematic side elevation of the device of FIG. 1 mounted on a front end loader or other suitable prime mover; FIG. 5 is a schematic side elevation of a modification of the device of FIG. 4 , and FIG. 6 is a series of schematic diagrams showing the sequence of operation of one embodiment of the invention operating as a sieve. detailed-description description="Detailed Description" end="lead"?
20041129
20090922
20050811
65875.0
0
HAGEMAN, MARK C
SCREEN/MIXER
SMALL
0
ACCEPTED
2,004
10,515,868
ACCEPTED
Crisp polypeptides as contraceptives and inhibitors of sperm capacitation
Included in the present invention are methods of inhibiting sperm capacitation, inhibiting the phosphorylation of a protein at tyrosine residues, inhibiting an acrosomal reaction, and inhibiting fertilization of an egg by sperm with the administration of a CRISP polypeptide.
1. A method of inhibiting sperm capacitation comprising contacting said sperm with a CRISP polypeptide. 2. A method of inhibiting sperm capacitation in an individual comprising administering a CRISP polypeptide to said individual. 3. A method for inhibiting the fertilization of an egg by sperm in an individual, comprising the administration of a CRISP polypeptide to said individual. 4. A method of inhibiting the phosphorylation of a protein at tyrosine residues comprising contacting said protein with a CRISP polypeptide. 5. The method of claim 4, wherein said protein is on the surface of mammalian sperm. 6. A method of inhibiting an acrosomal reaction comprising contacting the acrosomal reaction with a CRISP polypeptide. 7. The method of claim 2, wherein said CRISP polypeptide is administered orally. 8. The method of claim 2, wherein said CRISP polypeptide is administered parenterally. 9. The method of claim 2, wherein said CRISP polypeptide is administered transdermally. 10. The method of claim 2, wherein said CRISP polypeptide is administered in a composition comprising a pharmaceutically acceptable carrier. 11. The method of claim 2, wherein said individual is a mammalian male. 12. The method of claim 2, wherein said individual is a mammalian female. 13. The method of claim 12, wherein said CRISP polypeptide is administered intravaginally. 14. The method of claim 12, wherein said CRISP polypeptide is administered as a time released, vaginal implant. 15. The method of claim 12, wherein said CRISP polypeptide is administered to the vagina of the mammalian female in an amount capable of inhibiting sperm capacitation, rendering said sperm incapable of fertilization. 16. The method of claim 1 wherein the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7), and biologically active analogs thereof. 17. The method of claim 1 wherein the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1), or a biologically active analog thereof. 18. The method of claim 1 wherein the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). 19. The method of claim 1 wherein the CRISP polypeptide has about at least 40% structural identity to rat CRISP-1 (SEQ ID NO:2), or a biologically active analog thereof. 20. The method of claim 1 wherein the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). 21. A contraceptive composition comprising a CRISP polypeptide in an amount effective to inhibit sperm capacitation, inhibit phosphorylation of a protein at tyrosine residues, inhibit an acrosome reaction, and/or inhibit the fertilization of an egg by sperm. 22. The contraceptive composition of claim 21 wherein the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7) and biologically active analogs thereof. 23. The contraceptive composition of claim 21 wherein the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1), or a biologically active analog thereof. 24. The contraceptive composition of claim 21 wherein the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). 25. The contraceptive composition of claim 21 wherein the CRISP polypeptide has at least about 40% structural identity to rat CRISP-1 (SEQ ID NO:2), or a biologically active analog thereof. 26. The contraceptive composition of claim 21 wherein the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). 27. The contraceptive composition of claim 21 further comprising a spermicidal or antiviral agent.
This application claims the benefit of the U.S. Provisional Application Ser. No. 60/383,628, filed May 28, 2002, which is incorporated herein by reference in its entirety. STATEMENT OF GOVERNMENT RIGHTS This invention was made with government support under a grant from the National Institutes of Health, Grant No. HD 11962. The U.S. Government has certain rights in this invention. BACKGROUND An effective, safe and easily reversible male contraceptive with universal acceptability remains an elusive goal. Although a variety of approaches for achieving male contraception have been tried, no single mode of male contraception is without its immediate drawbacks for efficacy or compliance. Even seemingly simple interventions have not proven to be widely acceptable. For example, surgical or non-surgical vasectomy, methods that interrupt sperm transport in the male reproductive tract, are not without their complications or long-term risk. More complex approaches, such as regimens for the hormonal control of male fertility, have also not been fully satisfactory. Such methods have focused on the suppression of spermatogenesis to the point of azoospermia, a goal that has been difficult to achieve. The use of the immune response to block contraception has been an important front in efforts to develop more sophisticated contraceptive systems. Unfortunately, such approaches have thus far failed, as male autoimmunity against sperm does not suppress sperm production in men; this is known because such autoimmunity can occur after vasectomy. Thus, inhibiting sperm fertilizing-ability without affecting the hormonal balance in either the male or female remains an important goal in the field of reproductive biology. The present invention achieves this goal. SUMMARY OF THE INVENTION The present invention includes a method of inhibiting sperm capacitation including contacting sperm with a CRISP polypeptide. Also included in the present invention is a method of inhibiting sperm capacitation in an individual including the administration of a CRISP polypeptide to the individual. In another aspect, the present invention also includes a method for inhibiting fertilization of an egg by sperm in an individual, comprising the administration of a CRISP polypeptide to the individual. In another aspect, the present invention includes a method of inhibiting the phosphorylation of a protein at tyrosine residues including contacting the protein with a CRISP polypeptide. In some embodiments of the present invention, the protein may be on the surface of mammalian sperm. A further aspect of the present invention includes a method of inhibiting an acrosomal reaction including contacting the acrosomal reaction with a CRISP polypeptide. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered orally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered parenterally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered transdermally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered in a composition including a pharmaceutically acceptable carrier. In some embodiments of the methods of the present invention, the individual may be a mammalian male. In some embodiments of the methods of the present invention, the individual may be a mammalian female. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered intravaginally, including administered as a time released, vaginal implant. In other embodiments of the methods of the present invention, the CRISP polypeptide is administered to the vagina of the mammalian female in an amount capable of inhibiting sperm capacitation, rendering said sperm incapable of fertilization. In other embodiments of the methods of the present invention, the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7), and biologically active analogs thereof. In yet other embodiments of the methods of the present invention, the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1) or a biologically active analog thereof. In some embodiments of the methods of the present invention, the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). In other embodiments of the methods of the present invention, the CRISP polypeptide has about at least 40% structural identity to rat CRISP-1 (SEQ ID NO:2) of a biologically active analog thereof. In some embodiments of the methods of the present invention, the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). Also included in the present invention is a contraceptive composition including a CRISP polypeptide in an amount effective to inhibit sperm capacitation, inhibit phosphorylation of a protein at tyrosine residues, inhibit an acrosome reaction, and/or inhibit fertilization of an egg by sperm. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7) and biologically active analogs thereof. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1) and biologically active analogs thereof. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to rat CRISP-1 (SEQ ID NO:2), and biologically active analogs thereof. In other embodiments of the contraceptive composition of the present invention, the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). In some embodiments of the contraceptive composition of the present invention, the contraceptive composition further includes a spermicidal or an antiviral agent. DETAILED DESCRIPTION OF THE DRAWINGS FIG. 1. Immunoblot of solubilized rat sperm collected from the end of the epididymis and incubated in a defined capacitation medium in vitro for 5 hours under controlled conditions. A sample of sperm was taken at the beginning of incubation to provide the time zero conditions (lane 1). Aliquots of collected sperm were incubated under the following various conditions: 5 hours under non-capacitation conditions (lane 2); 5 hours under capacitating conditions (lane 3); and 5 hours under capacitating conditions with increasing concentrations of CRISP-1 (lanes 4, 5, and 6). In FIG. 1A, the immunoblot is stained with an anti-phosphotyrosine antibody. FIG. 1B shows the same gel stained with an anti-CRISP-1 antibody. FIG. 2. The requirement of incubating rat sperm with bovine serum albumin (BSA) to achieve the tyrosine phosphorylation associated with capacitation. Rat epididymal sperm were isolated in BWW with (+BSA) or without (−BSA) 15 mg/ml lipid-rich BSA for 5 hours. Aliquots of sperm were checked for tyrosine phosphorylation at 1, 3, and 5 hour time points by western blot analysis using an anti-phosphotyrosine antibody (FIG. 2A). A steady accumulation of tyrosine phosphorylation was observed in the presence of BSA, with negligible phosphorylation in BWW alone. To determine if extraction of cholesterol was the action of the BSA that led to the tyrosine phosphorylation, sperm were incubated with 15 mg/ml BSA with (Ch) or without (B) the addition of 30 μM cholesterol sulfate and tyrosine phosphorylation compared to levels seen in sperm incubated in BWW alone (C). The addition of exognenous cholesterol sulfate eliminated the BSA-induced phosphorylation of sperm proteins (FIG. 2B). FIG. 3. The comparative activity of lipid-rich BSA and Fraction V BSA in the induction of protein tyrosine phosphorylation of rat and mouse sperm. Rat epididymal sperm were incubated in increasing concentrations of lipid-rich (LR) or Fraction V (F5) BSA and protein tyrosine phosphorylation was determined after 5 hours (FIG. 3A). Both lipid-rich and Fraction V BSA showed maximal induction of phosphorylation at 15 mg/ml, but phosphorylation was greatest in lipid-rich BSA at each concentration. Since Fraction V BSA is routinely used for capacitation studies in other species, 4 mg/ml lipid-rich or Fraction V BSA were tested in capacitation incubations with mouse sperm (FIG. 3B). With mouse sperm, both lipid-rich and Fraction V are equipotent at inducing protein tyrosine phosphorylation. FIG. 4. The requirement of extracellular Ca++ for induction of capacitation in rat sperm. Sperm were incubated in BWW solution with (+Ca++) or without (−Ca++) 1.7 mM Ca++. At hourly time points out to 4 hours, sperm were tested for the presence of tyrosine-phosphorylated proteins. The presence of extracellular calcium ion was required for maximal phosphorylation. FIG. 5. The requirement of extracellular bicarbonate ion for induction of capacitation in rat sperm. Sperm were incubated in BWW solution with (+) or without (−) 25 mM HCO3− for 4 hours and then tested for the presence of tyrosine-phosphorylated proteins. The presence of bicarbonate ion in the media was required for tyrosine phosphorylation of sperm proteins. Omission of bicarbonate resulted in phosphorylation levels the same as BWW alone (C). FIG. 6. Quantitative kinetics of cholesterol extraction and protein tyrosine phosphorylation of sperm proteins. Rat epididymal sperm were incubated in 1 or 2 mM methyl-β-cyclodextran (MBCD) and extracted cholesterol measured at time intervals out to 2 hours (FIG. 6A). The levels of cholesterol were determined by the Amplex Red Cholesterol assay and the results normalized to cholesterol extracted in BWW alone. Protein tyrosine phosphorylation was measured by western blot at hourly time points during extraction with MBCD (FIG. 6B). Cholesterol extraction reached a plateau with 1 mM MBCD at 30 minutes and with 2 mM MBCD between 60 and 120 minutes (later time points not shown). Maximal phosphorylation lagged behind maximal cholesterol extraction with both concentrations of MBCD. FIG. 7. The effect of incubation of rat epididymal sperm with exogenous purified Crisp-1 on the level of protein tyrosine phosphoryation. Sperm were incubated under capacitating conditions with 15 mg/ml lipid-rich BSA for 5 hours in the presence of increasing concentrations (μg/ml) of purified proteins DE (FIG. 7A). Analysis of cells prior to capacitation incubation are shown as control (C). At 400 μg/ml protein tyrosine phosphorylation was nearly completely inhibited. The same Western blot was stripped and probed with antibody CAP-A (FIG. 7B) and 4E9 (FIG. 7C). Protein detected by CAP-A demonstrates that Crisp-1 re-associates with the sperm in a dose dependent fashion that correlates with the inhibition of capacitation (FIG. 7B). Antibody CAP-A detects all forms of Crisp-1 including processed forms of proteins D and E. Monoclonal antibody 4E9 detects only forms of Protein E (FIG. 7C). Comparison of the staining with 4E9, which stains only a processed form of protein E extracted from the sperm surface, and CAP-A demonstrates that only an unprocessed form of protein D re-associates with sperm to inhibit phosphorylation. The unprocessed Crisp-1 detected by CAP-A is lost with time when the sperm are removed from the exogenous pure Crisp-1 solution, suggesting that unprocessed Crisp-1 associates in a receptor-ligand fashion while processed Crisp-1 is covalently attached to the sperm surface. FIG. 8. The effect of incubation of rat epididymal sperm with exogenous purified Crisp-1 on the level of progesterone induced acrosome reaction. Sperm were incubated under capacitating conditions for 1 hours in the presence or absence of 400 μg/ml Crisp-1. Progesterone (P4) at 1 μM was added to sperm after 30 minutes of incubation to induce the acrosome reaction. DMSO, the solvent used for the P4 stock solution, was added to control cells. Addition of P4 to capacitated sperm (+BSA+P4) caused a statistically significant (*P<0.05) increase in acrosome reacted sperm compared to capacitated sperm (+BSA or +BSA+DMSO). This increase is completely abolished by addition of exogenous Crisp-1 (+BSA+P4+CRISP-1), as evidenced by the statistically significant decrease (*P<0.05) in acrosome reacted sperm. Columns are shown with values at base. The percent acrosome reacted sperm in the +BSA+P4 group was significantly higher (*P<0.05) than all other groups and there was no significant difference in the percent acrosome reacted sperm between any of the other groups. Data are presented as means +/−SEM. FIG. 9. The reversibility of protein tyrosine phosphoryation inhibition by exogenous purified Crisp-1 in rat epididymal sperm. Sperm were incubated under capacitating conditions with 15 mg/ml lipid-rich BSA for 5 hours in the presence (lane 4) or absence (lane 3) of 200 μg/ml Crisp-1. At 5 hours sperm were washed free of exogenous Crisp-1 and incubated for an additional 3 (lane 5) or 19 (lane 6) hours. Sperm at time zero and after 5 hours in BWW without BSA are shown in lanes 1 and 2, respectively. Sperm proteins were analyzed by western blot analysis for protein tyrosine phosphorylation (FIG. 9A) and Crisp-1 (FIG. 9B). As shown previously, 200 μg/ml Crisp-1 has an inhibitory effect on sperm protein tyrosine phosphorylation. The inhibition of protein tyrosine phosphorylation was reversed with the removal of Crisp-1. Exogenous Crisp-1 associated with sperm after 5 hours incubation is lost from the surface of sperm with time. An aliquot of purified Crisp-1 used in the sperm incubations is shown in lane 7. FIG. 10. Effect of exogenous administration of cAMP analog, dibromo-cAMP (db-cAMP), and the phosphodiesterase inhibitor IBMX on the protein tyrosine phosphorylation associated with capacitation. To determine if BSA, Ca++, and HCO3− act upstream of cAMP in the signaling cascade that leads to protein tyrosine phosphorylation (FIG. 10A), sperm were incubated in the presence (lanes 4, 6, 8) or absence (lanes 3, 5, 7) of db-cAMP/IBMX without BSA (lanes 3, 4), Ca++ (lanes 5, 6), or HCO3− (lanes 7, 8). Control phosphorylation in BWW or BWW with BSA are shown in lanes 1 and 2, respectively. In each case, exogenous cAMP and IBMX overcome the block to phosphorylation caused by omission of BSA, Ca++, or HCO3− from the capacitation medium, indicating that cAMP acts downstream for the effect of these three required constituents of capacitation. The ability of cAMP to overcome the inhibition of phosphorylation by Crisp-1 was tested by incubating sperm under capacitating conditions with and without db-cAMP/IBMX in the presence of 400 μg/ml pure Crisp-1 (lanes 3 & 4, respectively, FIG. 10B). Control sperm in BWW only or BWW with BSA are shown in lanes 1 and 2, respectively. The results show that the block to phosphorylation caused by Crisp-1 is also upstream of the effect of cAMP on protein tyrosine phosphorylation. FIG. 11. Amino acid sequence of human CRISP-1 (SEQ ID NO:1), rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6) and mouse CRISP-3 (SEQ ID NO7). FIG. 12. cDNA sequences encoding human CRISP-1 (SEQ ID NO:8), rat CRISP-1 (SEQ ID NO:9), mouse CRISP-1 (SEQ ID NO:10), human CRISP-2 (SEQ ID NO:11), rat CRISP-2 (SEQ ID NO:12), human CRISP-3 (SEQ ID NO:13) and mouse CRISP-3 (SEQ ID NO:14). DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS With the present invention it has been demonstrated that a CRISP polypeptide inhibits sperm capacitation, inhibits protein phosphorylation at tyrosine residues, and inhibits the acrosomal reaction. Thus, CRISP polypeptides can be used in improved methods of contraception, without affecting or interfering with the hormonal or immune systems. The CRISP polypeptides of the present invention include naturally occurring CRISP polypeptides and biologically active analogs thereof. Naturally occurring CRISP polypeptides comprise a family of Cysteine-RIch Secretory Proteins that are expressed in numerous organs in male animals, particularly in the reproductive tract. CRISP polypeptides are not generally expressed in female animals, with the exception of neutrophils, and possibly in tumors. In the male, CRISP-1 is expressed primarily in the epididymis, CRISP-2 is expressed primarily in the testis and CRISP-3 is expressed primarily in salivary glands. Prostate and seminal vesicles also have low expression of some of these proteins. Sperm require passage through the epididymis before they are able to fertilize an egg. This passage is an obligatory maturational process in the male and during this time, CRISP-1, a secretory product of the epididymis, is added to the sperm surface. When sperm are ejaculated into the female reproductive tract they under go a process called “capacitation,” which is required as the final maturational step before interaction between sperm and egg. It is well recognized that sperm that are not capacitated win not fertilize. Thus, the identification of agents that inhibit capacitation will lead to development of improved contraceptives. The CRISP family of polypeptides has been extensively characterized and the amino acid sequences of the CRISP-1, CRISP-2 and CRISP-3 polypeptides from a number of species are known. The CRISP-1 polypeptides from human (Kratzschmar et al., Eur. J. Biochem. 236(3):827-36, 1996), rat (Klemme et al., Gene 240(2):279-88, 1999; Charest et al., Mol. Endocrinol. 2 (10), 999-1004, 1988; Brooks et al., Eur. J. Biochem 161(1):13-18, 1986), and mouse (Eberspaecher et al., Mol. Reprod. Dev. 42:157-172, 1995; Haendler et al., Endocrinology 133 (1), 192-198, 1993) have been characterized. The human CRISP-1 amino acid sequence (SEQ ID NO:1) is available as Genbank Accession Number CAA64524, the rat CRISP-1 amino acid sequence (SEQ ID NO:2) is available as Genbank Accession Number AAD41529, and the mouse CRISP-1 amino acid sequence (SEQ ID NO:3) is available as Genbank Accession A49202, all of which are shown in FIG. 11. The cDNA sequence encoding human CRISP-1 (SEQ ID NO:8) is available as Genbank Accession Number X95237, the cDNA sequence encoding rat CRISP-1 (SEQ ID NO:9) is available as Genbank Accession Number NM—022859, and the cDNA sequence encoding mouse CRISP-1 (SEQ ID NO:10) is available as Genbank Accession Number L05559, all of which are shown in FIG. 12. The CRISP-2 polypeptides from human (Kratzschmar et al., Eur. J. Biochem. 236 (3), 827-836, 1996) and rat (O'Bryan et al., Mol. Reprod. Dev. 50 (3), 313-322, 1998) have been characterized. The human CRISP-2 amino acid sequence (SEQ ID NO:4), available as Genbank Accession Number P16562, and the rat CRISP-2 amino acid sequence (SEQ ID NO:5), available as Genbank Accession Number AAD48090, are shown in FIG. 11. The cDNA sequence encoding human CRISP-2 (SEQ ID NO:11) is available as Genbank Accession Number X95239 and the cDNA sequence encoding rat CRISP-2 (SEQ ID NO:12) is available as Genbank Accession Number AF078552, all of which are shown in FIG. 12. The CRISP-3 polypeptides from human (Kratzschmar et al., Eur. J. Biochem. 236 (3), 827-836, 1996) and mouse (Haendler et al., Endocrinology 133 (1), 192-198 (1993)) have been characterized. The human CRISP-3 amino acid sequence (SEQ ID NO:6), available as Genbank Accession Number P54108, and the mouse CRISP-3 amino acid sequence (SEQ ID NO:7), available as Genbank Accession Number Q03402, are shown in FIG. 11. The cDNA sequence encoding human CRISP-3 (SEQ ID NO:13) is available as Genbank Accession Number X95240 and the cDNA sequence encoding mouse CRISP-3 (SEQ ID NO:14) is available as Genbank Accession Number L05560, all of which are shown in FIG. 12. The CRISP polypeptides of the present invention may be derived from a variety of species, including, but not limited to, human, primate, rat, mouse, bovine, and horse. The CRISP polypeptides of the present invention include, but are not limited to, CRISP-1, CRISP-2 and CRISP-3 polypeptides. For example, the CRISP polypeptides of the present invention include, but are not limited to, human CRISP-1 (SEQ ID NO:1), rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO: 6), and mouse CRISP-3 (SEQ ID NO:7). “Polypeptide” as used herein refers to a polymer of amino acids and does not refer to a specific length of a polymer of amino acids. Thus, for example, the terms peptide, oligopeptide, protein, and enzyme are included within the definition of polypeptide, whether naturally occurring or synthetically derived, for instance, by recombinant techniques or chemically or enzymatically synthesized. This term also includes post-expression modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations, and the like. The following abbreviations are used throughout the application: A=Ala=Alanine T=Thr=Threonine V=Val=Valine C=Cys=Cysteine L=Leu=Leucine Y=Tyr=Tyrosine I=Ile=Isoleucine N=Asn=Asparagine P=Pro=Proline Q=Gln=Glutamine F=Phe=Phenylalanine D=Asp=Aspartic Acid W=Trp=Tryptophan E=Glu=Glutamic Acid M=Met=Methionine K=Lys=Lysine G=Gly=Glycine R=Arg=Arginine S=Ser=Serine H=His=Histidine As used herein, a CRISP polypeptide also includes “biologically active analogs” of naturally occurring CRISP polypeptides. For example, the CRISP polypeptides of the present invention include, but are not limited to, biologically active analogs of human CRISP-1 (SEQ ID NO:1), rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), or mouse CRISP-3 (SEQ ID NO:7). As used herein to describe a CRISP polypeptide, the term “biologically active” means to inhibit protein tyrosine phosphorylation, inhibit sperm capacitation, inhibit an acrosome reaction, and/or inhibit fertilization of an egg by sperm. Biological activity of a CRISP polypeptide can be easily assessed using the various assays described herein as well as other assays well known to one with ordinary skill in the art. An inhibition in biological activity can be readily ascertained by the various assays described herein, and by assays known to one of skill in the art. An inhibition in biological activity can be quantitatively measured and described as a percentage of the biological activity of a comparable control. The biological activity of the present invention includes an inhibition that is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, at least about 100%, at least about 110%, at least about 125%, at least about 150%, at least about 200%, at least or about 250% of the activity of a suitable control. A “biologically active analog” of a CRISP polypeptide includes polypeptides having one or more amino acid substitutions that do not eliminate biological activity. Substitutes for an amino acid in the polypeptides of the invention may be selected from other members of the class to which the amino acid belongs. For example, it is well-known in the art of protein biochemistry that an amino acid belonging to a grouping of amino acids having a particular size or characteristic (such as charge, hydrophobicity and hydrophilicity) can be substituted for another amino acid without altering the activity of a protein, particularly in regions of the protein that are not directly associated with biological activity. Substitutes for an amino acid may be selected from other members of the class to which the amino acid belongs. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and tyrosine. Polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. Examples of such preferred conservative substitutions include Lys for Arg and vice versa to maintain a positive charge; Glu for Asp and vice versa to maintain a negative charge; Ser for Thr so that a free —OH is maintained; and Gln for Asn to maintain a free NH2. Likewise, biologically active analogs of a CRISP polypeptide containing deletions or additions of one or more contiguous or noncontiguous amino acids that do not eliminate the biological activity of the CRISP polypeptide are also contemplated. A “biologically active analog” of a CRISP polypeptide includes “fragments” and “modifications” of a CRISP polypeptide. As used herein, a “fragment” of a CRISP polypeptide means a CRISP polypeptide that has been truncated at the N-terminus, the C-terminus, or both. The CRISP protein family is characterized by sixteen-conserved cysteine residues located within the C-terminus of the polypeptide. A “fragment” of a CRISP polypeptide may include 1, 2, 3, 4, 5 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 of the conserved cysteine residues of the CRISP protein family. A fragment may range for about 5 to about 250 amino acids in length. For example it may be about 5, about 10, about 20, about 25, about 50, about 75, about 100, about 125, about 150, about 175, about 200, about 225, or about 250 amino acids in length. Fragments of a CRISP polypeptide with potential biological activity can be identified by many means. One means of identifying such fragments of a CRISP polypeptide with biological activity is to compare the amino acid sequences of a CRISP polypeptide from rat, mouse, human and/or other species to one another. Regions of homology can then be prepared as fragments. A “modification” of a CRISP polypeptide includes CRISP polypeptides or fragments thereof chemically or enzymatically derivatized at one or more constituent amino acid, including side chain modifications, backbone modifications, and N- and C-terminal modifications including acetylation, hydroxylation, methylation, amidation, and the attachment of carbohydrate or lipid moieties, cofactors, and the like. Modified polypeptides of the invention may retain the biological activity of the unmodified polypeptide or may exhibit a reduced or increased biological activity. The CRISP polypeptides and biologically active analogs thereof of the present invention include native (naturally occurring), recombinant, and chemically or enzymatically synthesized polypeptides. For example, the CRISP polypeptides of the present invention may be prepared following the procedures for the isolation of CRISP-1 polypeptide from rat sperm detailed by Hall and Tubbs (Prep. Biochem. Biotechnol. 27(4):239-51, 1997). For example, the CRISP polypeptides of the present invention can be prepared recombinantly, by well known methods, including, for example, preparation as fusion proteins in bacteria and insect cells. As used herein, the term “isolated” means that a polynucleotide or polypeptide is either removed from its natural environment or synthetically derived, for instance by recombinant techniques, or chemically or enzymatically synthesized. An isolated polynucleotide denotes a polynucleotide that has been removed from its natural genetic milieu and is thus free of other extraneous or unwanted coding sequences, and is in a form suitable for use within genetically engineered protein production systems. Isolated polynucleotides of the present invention are free of other coding sequences with which they are ordinarily associated, but may include naturally occurring 5′ and 3′ untranslated regions such as promoters and terminators. Preferably, the polynucleotide or polypeptide is purified, i.e., essentially free from any other polynucleotides or polypeptides and associated cellular products or other impurities. As used herein, “structural similarity” refers to the identity between two polypeptides. Structural similarity is generally determined by aligning the residues of the two polypeptides to optimize the number of identical amino acids along the lengths of their sequences; gaps in either or both sequences are permitted in making the alignment in order to optimize the number of identical amino acids, although the amino acids in each sequence must nonetheless remain in their proper order. For example, polypeptides may be compared using the Blastp program of the BLAST 2 search algorithm, as described by Tatusova et al. (FEMS Microbiol. Lett., 174; 247-250, 1999) and available on the world wide web at ncbi.nlm.nih.gov/BLAST/. The default values for all BLAST 2 search parameters may be used, including matrix=BLOSUM62; open gap penalty=1, extension gap penalty=1, gap x_dropoff=50, expect=10, wordsize=3, and filter on. In the comparison of two amino acid sequences using the BLAST search algorithm, structural similarity may be referred to by percent “identity” or may be referred to by percent “similarity.” “Identity” refers to the presence of identical amino acids and “similarity” refers to the presence of not only identical amino acids but also the presence of conservative substitutions. The CRISP polypeptides of the present invention include polypeptides with at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% structural identity to a known rat, mouse or human CRISP polypeptide. The CRISP polypeptides of the present invention also include polypeptides with at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% structural similarity to a known rat, mouse or human CRISP polypeptide. For example, the CRISP polypeptides of the present invention may include, but are not limited to, polypeptides with at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% structural identity to human CRISP-1 (SEQ ID NO:1), rat CRISP-1 (SEQ ID NO:2), or mouse CRISP-1 (SEQ ID NO:3). For example, the CRISP polypeptides of the present invention may also include, but are not limited to, polypeptides with at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% structural similarity to human CRISP-1 (SEQ ID NO:1), rat CRISP-1 (SEQ ID NO:2), or mouse CRISP-1 (SEQ ID NO:3). According to the present invention, a CRISP polypeptide, including biologically active analogs thereof, can be administered to a subject in an effective amount sufficient to inhibit protein phosphorylation at tyrosine residues, inhibit sperm capacitation, inhibit an acrosome reaction, and/or inhibit the fertilization of an egg by sperm. The CRISP polypeptides of the present invention may be administered to a male or female individual. The individual may be a mammal, including, but not limited to a mouse, rat, primate, bovine, or human. For example, in one embodiment of the present invention, a CRISP-1 polypeptide, or a biologically active analog thereof, can be administered to a subject in an effective amount sufficient to inhibit protein phosphorylation at tyrosine residues, inhibit sperm capacitation, inhibit an acrosome reaction, and/or inhibit the fertilization of an egg by sperm. As used herein an “acrosome reaction” or “acrosomal reaction” includes the sequence of structural changes that occur in spermatozoa when in the vicinity of an oocyte. Such structural changes serve to facilitate entry of a spermatozoon into the oocyte and include the fusion of portions of the outer membrane of the acrosome with the plasma membrane of the sperm head, creating openings through which the enzymes of the acrosome are released. See, for example, Wasserman et al., Nat. Cell Biol. 3:9-14, 2001. By the term “effective amount” of an agent as provided herein is meant a nontoxic but sufficient amount of the agent or composition to provide the desired effect. Thus, in the context of the present invention, an “effective amount” of a CRISP polypeptide is an amount sufficient to inhibit protein phosphorylation at a tyrosine residue, inhibit sperm capacitation, inhibit an acrosome reaction, and/or affect contraception. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the condition being treated, and the particular agent and its mode of administration, and the like. Thus, it is not possible to specify an exact “effective amount.” However, an appropriate effective amount may be determined by one of ordinary skill in the art using only routine experimentation. Therapeutically effective concentrations and amounts may be determined for each application herein empirically by testing the compounds in known in vitro and in vivo systems, such as those described herein; dosages for humans or other animals may then be extrapolated therefrom. In some embodiments of the present invention, a CRISP polypeptide may be delivered by intravaginal administration. For such administration, a CRISP polypeptide may be provided as a cream gel, foam, emulsion, suppository, and the like. In certain embodiments of the present invention, CRISP polypeptides may be contained within a time released vaginal implant. In some embodiments of the present invention, a CRISP polypeptide may be delivered by oral administration. For such oral administration, a CRISP polypeptide may be provided as a liquid, a tablet, a pill, a capsule, a gel coated tablet, a syrup, or some other oral administration method. In certain embodiments of the present invention, CRISP polypeptides may be contained within a bio-erodible matrix for time-controlled release. In some embodiments of the present invention, a CRISP polypeptide may be delivered by transdermal administration. For such administration, a CRISP polypeptide may be provided as a cream, a transdermal patch, and the like. In certain embodiments of the present invention, CRISP polypeptides may be contained within a time released composition. In some embodiments of the present invention, a CRISP polypeptide may be delivered by parenteral administration. For such administration, a CRISP polypeptide may by provided in an aqueous solution, for example, the solution should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous, intraperitoneal, and intratumoral administration. In this connection, sterile aqueous media that can be employed will be known to those of skill in the art in light of the present disclosure (see for example, “Remington's Pharmaceutical Sciences” 15th Edition). Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person responsible for administration will, in any event, determine the appropriate dose for the individual subject. Moreover, for human administration, preparations should meet sterility, pyrogenicity, and general safety and purity standards as required by the FDA. In some aspects, the present invention includes contraceptive compositions including an effective amount of a CRISP polypeptide, or a biologically active analog thereof, in an amount effective to inhibit sperm capacitation, inhibit protein tyrosine phosphorylation, inhibit an acrosome reaction, and/or effect contraception. These contraceptive compositions may contain one or more active agents. For example, such contraceptive compositions may include, one or more CRISP polypeptides. Such contraceptive compositions may include one or more additional active agents that are not a CRISP polypeptide. Such active agents may include, but are not limited to, spermicidal agents and/or antiviral agents. The CRISP polypeptides of the present invention may be administered at once, or may be divided into a number of smaller doses to be administered at intervals of time. It is understood that the precise dosage and duration of treatment is a function of the desired therapeutic outcome and may be determined empirically using known testing protocols or by extrapolation from in vivo or in vitro test data. It is to be noted that concentrations and dosage values may also vary with the severity of the condition to be treated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that the concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed compositions and methods. The agents of the present invention may be administered to the subject in combination with other modes of contraception. The agents of the present invention can be administered before, during or after the administration of the other therapies. The CRISP polypeptides of the present invention may be formulated in a composition along with a “carrier.” As used herein, “carrier” includes any and all solvents, dispersion media, vehicles, coatings, diluents, antibacterial and antifungal agents, isotonic and absorption delaying agents, buffers, carrier solutions, suspensions, colloids, and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. By “pharmaceutically acceptable” is meant a material that is not biologically or otherwise undesirable, i.e., the material may be administered to an individual along with a CRISP polypeptide without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained. A “subject” or an “individual” is an organism, including, for example, a mammal. A mammal may include, for example, a rat, mouse, a primate, a domestic pet, such as, but not limited to, a dog or a cat, livestock, such as, but not limited to, a cow, a horse, and a pig, or a human. Subject also includes model organisms, including, for example, animal models, used to study fertilization of an egg by sperm, sperm capacitation, protein tyrosine phosphorylation, or the acrosome reaction. A “control” sample or subject is one in which a CRISP pathway has not been manipulated in any way. As used herein in vitro is in cell culture, ex vivo is a cell that has been removed from the body of a subject and in vivo is within the body of a subject. Unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one. The present invention also includes an isolated molecule, the molecule being present on the sperm plasma membrane and binds to a CRISP polypeptide. The molecule may be an isolated component of a calcium channel or a receptor involved in calcium channel signaling. For example, the isolated molecule may be a molecule being present on the sperm plasma membrane and binds to a CRISP-1 polypeptide, or a biologically active analog, fragment, or modification thereof. This molecule that binds to a CRISP-1 polypeptide may be an isolated component of a calcium channel or a receptor involved in calcium channel signaling. EXAMPLES The present invention is illustrated by the following example. It is to be understood that the particular example, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein. Example 1 Role of CRISP Proteins in the Regulation of Sperm Capacitation and Use in Contraception The results of Example 1 are shown in FIG. 1. Rat sperm were collected from the end of the epididymis and incubated in a defined capacitation medium in vitro for 5 hours under controlled conditions. A sample of sperm was taken at the beginning of incubation to provide the time zero conditions (lane 1 of FIG. 1). Aliquots of collected sperm were incubated under the following various conditions: For 5 hours under non-capacitation conditions (lane 2 of FIG. 1) For 5 hours under capacitating conditions (lane 3 of FIG. 1) For 5 hours under capacitating conditions with increasing concentrations of CRISP-1 (lanes 4, 5 and 6 of FIG. 1). At the end of incubation, sperm were solubilized and solubilized sperm proteins were separated by SDS gel electrophoresis. Proteins were then transblotted onto a membrane and treated with a primary anti-phosphotyrosine antibody. The results of this anti-phosphotyrosine western blot are shown in FIG. 1A. After recording the results with the anti-phosphotyrosine antibody, the transblot was striped of antibodies and re-probed with an antibody against CRISP-1. The results of this anti-CRISP-1 western blot are shown as FIG. 1B. FIG. 1A shows phosphotyrosine distribution in sperm under the various incubation conditions. Under non-capacitating conditions, there appears to be some phosphorylation activity. This phosphorylation activity is significantly increased under capacitation conditions, with numerous different proteins exhibiting phosphorylation. Phosphorylation activity is inhibited on many proteins by the addition of CRISP-1. FIG. 1B shows the same gel stained with an anti-CRISP-1 antibody. In lane 1 (time zero) one can see two bands (the D form and the E form of CRISP-1). Under both non-capacitating and capacitating conditions, the D form of CRISP-1 is lost from sperm (see lanes 2 and 3). When CRISP-1 is added back (see lanes 4, 5 and 6), the D form re-appears in a dose-dependent fashion. The E form, which is also present in the added CRISP-1 protein, remains constant under all experimental conditions. Thus, the addition of CRISP-1 to the capacitating incubation medium inhibits protein tyrosine phosphorylation, a universal indicator of capacitation. Example 2 Inhibition of Capacitation-Associated Tyrosine Phophorylation Signaling in Rat Sperm by Epididymal Protein Crisp-1 In mammals, development of fertilizing ability and progressive motility by sperm, the process of post-testicular maturation, begin as sperm are moved through the male reproductive tract and are completed when sperm are deposited in the female reproductive tract and undergo capacitation. In the male post-testicular duct system, sperm acquire new proteins and glycoproteins on their surfaces and undergo numerous biochemical changes during their passage through the ducts that make them capable of vigorous, directed movement and able to fertilize an egg (Yanagimachi R. Mammalian Fertilization. The Physiology of Reproduction 1994: 186-317). Crisp-1 (DE, AEG) is a glycoprotein couplet (comprised of protein D and protein E, hereinafter referred to collectively as Crisp-1) that is secreted by the epididymal epithelium (Brooks and Higgins, Journal of Reproduction & Fertility 1980; 59: 363-375; Moore et al, Molecular Reproduction & Development 1994; 37: 181-194) and associates with the sperm surface (Rochwerger and Cuasnicu, Molecular Reproduction & Development 1992; 31: 3441; Xu et al, Mol Reprod Dev 1997; 46: 377-382.). A portion of the Crisp-1 on the sperm surface, in particular Protein E, is proteolytically-processed (Roberts et al, Biology of Reproduction 2002; 67: 525-533). Crisp-1 is one of many epididymis-secreted proteins that associate with sperm (Faye et al, Biol Reprod 1980, 23: 423-432; Kohane et al, Biol Reprod 1980, 23: 737-742; Moore, J Exp Zool 1981, 215: 77-85 (1981); Wong and Tsang, Biol Reprod 1982, 27: 1239-1246; Tezon et al, Biol Reprod 1985, 32: 591-597; Iusem et al, Biol Reprod 1989, 40: 307-316; Vreeburg et al., Bull Assoc Anat (Nancy) 1991, 75: 171-173; Rankin et al., Biology of Reproduction 1992, 46: 747-766; Boue et al, Biol Reprod 1996, 54: 1009-1017). The mechanism(s) of the interaction (e.g., covalent bonds, charge effects, hydrophobic bonds) between the sperm plasma membrane and extracellular epididymal molecules is unknown, but is likely to be varied. In contrast seminal vesicle secretions that are known to participate in capacitation in mice (Huang et al., Biol Reprod 2000, 63: 1562-1566 (2000); Huang et al., Biochem J 1999, 343 Pt 1: 241-248; Luo et al, J Biol Chem 2001 276: 6913-6921) and bulls (Huang et al, Biol Reprod 2000, 63: 1562-1566 (2000); Huang et al, Biochem J 1999, 343 Pt 1: 241-248; Luo et al., J Biol Chem 2001, 276: 6913-6921) are added to the cell surfaces after ejaculation by binding to sperm plasma membrane phospholipid head groups. In rats there is evidence that seminal vesicle proteins are added to the sperm surface (Manco and Abrescia, Gamete Res 1988, 21: 71-84; Manco et al., Eur J Cell Biol 1988, 47: 270-274), possibly by transglutaminase activity in semen (Paonessa et al., Science 1984, 226: 852-855), and it has been reported also that a prostate-derived protein binds to rat spermatozoa (Sansone and Abrescia, J Exp Zool 1991, 259: 379-385). Thus, addition of proteins and glycoproteins derived from different parts of the duct to sperm surfaces occurs throughout the male excurrent duct system. Under normal conditions ejaculated sperm are unable to fertilize an egg until they have resided in the female tract for a number of hours (the time varies from species to species (Bedford, Biol Reprod 1970, 2: Suppl 2:128-158; Davis, Proc Natl Acad Sci USA 1981, 78: 7560-7564), and have undergone capacitation. Capacitation was independently, and virtually simultaneously, described in two laboratories (Austin, Australian Journal of Scientific Research, B 1951, 4: 581-589; Chang, Nature 1951, 168: 697) as the time required for sperm to penetrate an egg after having been deposited in the female reproductive tract. Residence in the female tract is required for capacitation in vivo, resulting in the acquisition of hyperactivated motility in many, but not all species; the loss or changes in some constituents of the plasma membrane, including proteins and glycoproteins and in the acquisition of the ability to undergo the acrosome reaction. During the more than half century since its discovery, capacitation has been the subject of intense investigation, particularly since it is possible to capacitate sperm in vitro and use them to fertilize an egg. Common themes about what happens during capacitation are beginning to emerge. In all species that have been examined, it is necessary for cholesterol to be removed from the membrane, which can be accomplished in vitro by incubating sperm in a medium containing serum albumin (Davis, Proc Soc Exp Biol Med 1976, 151: 240-243; Davis et al., Proc Natl Acad Sci USA 1980, 77: 1546-1550) or other cholesterol-binding agents such as cyclodextrins (Choi and Toyoda, Biol Reprod 1998, 59: 1328-1333; Visconti et al., Biol Reprod 1999, 61: 76-84). Cholesterol removal results in a cAMP-dependent tyrosine phosphorylation of a number of proteins, both in the sperm plasma membrane and in intracellular structures such as the axoneme and fibrous sheath. Initiation and completion of capacitation is absolutely dependent on extracellular Ca++ and HCO3−, in addition to a cholesterol sequestering agent. In this example we report the results of experiments designed to elucidate the conditions required for in vitro capacitation of rat spermatozoa and the effects of Crisp-1, an epididymal secretory protein, on capacitation. We demonstrate that protein tyrosine phosphorylation, a hallmark of capacitation in other species' sperm, occurs during five hours of in vitro incubation and that this phosphorylation is dependent upon cAMP. HCO3−, Ca++, and the removal of cholesterol from the membrane. We also show that Crisp-1, added to the sperm surface in the epididymis in vivo, is lost during capacitation and that addition of exogenous Crisp-1 to the incubation medium inhibits tyrosine phosphorylation in a dose dependent manner, and thus inhibits capacitation and ultimately the acrosome reaction. We further show that the inhibition of capacitation by Crisp-1 is upstream of the production of cAMP by the sperm. Materials and Methods Chemicals and Reagents: Anti-Phosphotyrosine (4G10) monoclonal IgG conjugated to horseradish peroxidase (HRP) was purchased from Upstate Biotechnology Inc. (Lake Placid, N.Y.). ALEXA FLUOR 488 goat anti-rabbit IgG, AMPLEX Red Cholesterol Assay Kit and Slow-Fade were purchased from Molecular Probes (Eugene, Oreg.). Cold water fish skin gelatin (40% solution) was purchased from Electron Microscopy Sciences (Washington, Pa.). SUPER SIGNAL West Pico Chemiluminescent Substrate was purchased from Pierce Chemical Co. (Rockford, Ill.). ALBUMAX I lipid-rich bovine serum albumin (BSA) was purchased from Gibco BRL (Grand Island, N.Y.). Original and modified BWW were purchased from Irvine Scientific (Santa Ana, Calif.). All other chemicals and reagents were purchased from Sigma-Aldrich (St. Louis, Mo.). Generation of the CAP-A anti-peptide polyclonal antibody and the 4E9 monoclonal antibody have been previously described (Moore et al., Molecular Reproduction & Development 1994, 37:181-194; Roberts et al., Biology of Reproduction 2002, 67: 525-533). Media: The base media used for collection and experimental incubation of sperm was original formula BWW medium (Biggers et al, Methods in Mammalian Embryology 1971, 86-116). BWW minus calcium or bicarbonate was prepared according to the recipe reported by Biggers, et. al. (1971) (Biggers et al, Methods in Mammalian Embryology 1971, 86-116). Sperm were capacitated in BWW with 15 mg/ml ALBUMAX I lipid-rich BSA, unless otherwise noted. Other cholesterol acceptor molecules included Fraction V BSA and methyl-β-cyclodextrin, and were added to BWW in some experiments. Sperm Collection and Preparation: Spague-Dawley male retired breeder rats were euthanized by CO2 asphyxiation and epididymes were surgically removed. Radial slits were made in each of the cauda epididymes followed by a 5 minute incubation in 1 ml of BWW buffered with 21 mM HEPES on an orbital shaker to facilitate the swim out of sperm into the media. The sperm suspensions were placed in a 1.5 ml microcentrifuge tube, leaving behind the epididymes, and gently shaken by hand to ensure an even concentration of sperm. Sperm counts were performed using a hemacytometer. Aliquots of approximately 3.5×106 sperm were diluted into 0.5 ml of capacitation medium that was pre-equilibrated overnight at 37° C. in 5% CO2. The incubation wells were overlayed with 0.5 ml of mineral oil and incubated for times indicated (in figure legends) at 37° C. in 5% CO2. Subjective assessment of sperm motility showed minimal decreases during capacitation incubation. All animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Minnesota. SDS-PAGE and Western Blotting: Samples were prepared for SDS-PAGE analysis using a modification of the protocol described by Visconti et. al., (1995). Briefly, sperm were collected from under oil and centrifuged at 16,000×g in microcentrifuge tubes for 5 minutes immediately following the capacitation incubation. The sperm pellet was washed twice with 1 ml of phosphate buffered saline (PBS) and resuspended in 100 μl of 1× Laemmli sample buffer (Laemmli. Nature 1970, 227: 680-685). The samples were vortexed for 15 seconds, heated to 95° C. for 5 minutes and centrifuged at 16,000×g to remove insoluble material. Supernatants were transferred to new tubes, reduced by the addition of β-mercaptoethanol (to a final concentration of 2.5%) and heated again to 95° C. for 5 minutes. 20 μl of each sample, equivalent to 7×105 sperm, were subjected to polyacrylamide gel electrophoresis (PAGE) on tris-glycine gels (7.5%, 12% or 15%, depending on the experiment). Proteins were transferred to Immobilon P membrane (Millipore, Bedford, Mass.) at 100 volts for 1 hour at 4° C. For detection of tyrosine-phosphorylated proteins, blots were blocked with 6.5% fish skin gelatin in TBS-T (Tris Buffererd Saline with 0.1% Tween 20) for 30 minutes followed by incubation with anti-phosphotyrosine-HRP antibody (1:15,000), in blocking solution, for 1 hour at room temperature. The blots were washed with TBS-T, followed by incubation with HRP substrate (Super Signal West Pico) for 5 minutes. Blots were exposed to X-ray film for 5 to 30 seconds. Western blot detection of the protein D and E forms of Crisp-1 with anti-peptide antibody CAP-A and monoclonal antibody 4E9 were done as previously described (Moore et al., Molecular Reproduction & Development 1994, 37: 181-194; Roberts et al., Biology of Reproduction 2002, 67: 525-533.). Immunocytochemistry: Sperm were stained immunocytochemically with anti-peptide antibody CAP-A and monoclonal antibody 4E9 essentially as previously described (Moore et al., Molecular Reproduction & Development 1994; 37: 181-194). Briefly, sperm were washed 3× in BWW to remove media, fixed with Bouin's fixative for 30 minutes and washed extensively with PBS. Cells were blocked for 30 minutes with 1% BSA/PBS and antibodies were added for an hour incubation at room temperature. The anti-peptide antibody CAP-A was used at a dilution of 1:200 while mAb 4E9 was used at 1:1000. Sperm were washed 3× with PBS and Alexa-Fluor 488 anti-rabbit antibody was added to the CAP-A tubes while anti-mouse—FITC was added to the 4E9 tubes. After incubation for 1 hour in Alexa-Fluor second antibody at room temperature, cells were washed with PBS mounted on slides in Slow-Fade® and viewed using a Nikon fluorescent microscope. Cholesterol Assay: Total lipids were extracted from BWW containing MBCD after incubation with sperm essentially as described by Bligh and Dyer (Bligh and Dyer, Canadian Journal of Biochemistry and Physiology 1959, 37: 911-917). Briefly, after incubating sperm with BWW/MBCD, sperm were removed by centrifugation and 0.8 ml of supernatant was recovered. Chloroform and methanol were added to the supernatant, with vortexing, to a final ratio of chloroform to methanol to aqueous supernatant of 2:2:1.8. After vigorous vortexing, the final mixture was centrifuged for 5 minutes at 600×g and one ml of the organic (lower) phase was removed to a new tube. The lipids in the organic phase were dried under a stream of desiccated nitrogen and stored at −20° C. Cholesterol was measured in the extracted lipid samples using the Amplex Red Cholesterol Assay Kit, according to the manufacturers instructions. Briefly, dried lipid samples were resuspended in 50 μl of reaction buffer and mixed 1:1 with working solution containing 300 μM Amplex Red reagent, 2 U/ml horseradish peroxidase, 2 U/ml cholesterol oxidase and 2 U/ml cholesterol esterase in wells of a 96-well microtiter plate. A standard curve was prepared using the cholesterol reference standard provided with the kit. All samples were incubated for 2 hrs at 37° C. Fluorescence of reaction product was measured at various time points in a FL600 Microplate Reader (BIOTEK Instruments, Inc., Winooski, Vt.) with an excitation filter of 530 nm and an emission filter of 590 nm. Acrosome reaction and staining: The acrosome reaction and assessment of acrosomal status was performed essentially as described by Bendahmane et al. (Bendahmane et al., Arch Biochem Biophys 2002, 404: 38-47). Following incubation under capacitating or non-capacitating conditions for 30 minutes, progesterone (P4), dissolved in DMSO, was added to a final concentration of 1 μM. After an additional 30 minutes of incubation, sperm were fixed in 4% paraformaldehyde, washed and dried on slides. To visualize the acrosome, the sperm were stained with 0.22% Coomassie blue G-250 solution for 2 minutes, rinsed with distilled water and allowed to air dry. Slides were coverslipped using Permount mounting media and observed under a Nikon brightfield microscope at a magnification of 600×. For each condition within an experiment, 500 cells were assessed for acrosomal status. Statistical Analysis: All experiments reported in the manuscript were repeated a minimum of three times. Raw data from the acrosome reaction experiments were subjected to the Tukey analysis for determination of statistically significant differences (P<0.05) between pairs of all treatment groups. Results Initial studies were carried out to characterize the dependence of rat sperm capacitation on the presence of a cholesterol binding molecule, Ca++ and HCO3−; the three components shown to be requirements of capacitation in most other species. Capacitation conditions for rat sperm were tested using tyrosine phosphorylation of sperm proteins as an indication of the extent of the capacitation process. FIG. 2A demonstrates, by western blot with an antibody against phosphotyrosine, the dependence of capacitation on incubation with a lipid-accepting molecule, in this experiment bovine serum albumin (BSA). In the presence of 15 mg/ml lipid rich BSA, protein tyrosine phosphorylation on sperm proteins increased over 5 hours of incubation. Cholesterol was determined to be the lipid responsible for capacitation since incubation with exogenous cholesterol sulfate inhibited protein tyrosine phosphorylation (FIG. 2B). Initial capacitation experiments were carried out in solution of a 15 mg/ml lipid-rich BSA (Gibco-BRL), a concentration of BSA routinely used in our BWW solution for in vitro fertilization. Because most capacitation experiments are conducted using fraction V BSA, we compared the efficacy of using lipid-rich or fraction V BSA at various concentrations. FIG. 3A demonstrates that lipid-rich BSA was superior to fraction V for inducing tyrosine phosphorylation in rat sperm at all concentrations investigated. In fact, incubation of sperm with fraction V BSA gave very low levels of tyrosine phosphorylation in rat sperm. When the same comparison was performed using mouse sperm, where fraction V BSA is routinely used, the efficacy of tyrosine phosphorylation was the same (FIG. 3B). These results suggest that different BSA preparations have different effects on sperm depending on the species. The basis for this difference is not clear. The dependence of rat sperm capacitation on exogenous Ca++ is shown in FIG. 4. Incubation in the absence of exogenously added Ca++ for 4 hours was accompanied by minimal tyrosine phosphorylation compared to sperm incubated in the presence of 1.7 mM Ca++. The level of tyrosine phosphorylation in the absence of exogenous Ca++ was higher than that seen in the absence of BSA, which may be attributable to trace amounts of Ca++ in the medium or to the availability of Ca++ from intracellular sources. Likewise, capacitation was shown to be dependent on the presence of bicarbonate ion in the medium by assessing protein tyrosine phosphorylation in the presence and absence of HCO3− (FIG. 5). Solutions in this experiment were buffered with HEPES buffer to insure that the requirement of bicarbonate was not simply due to its buffering capacity in the medium. To examine the relationship between cholesterol removal from the sperm plasma membrane and the protein tyrosine phosphorylation events associated with capacitation, sperm were incubated with two doses of the cholesterol-binding molecule methyl-β-cyclodextran (MBCD). During incubation with MBCD, cholesterol was removed from the sperm in a dose-dependent fashion. MBCD at 2 mM removed twice as much cholesterol as 1 mM MBCD (FIG. 6A). When protein tyrosine phosphorylation was measured, phosphorylation in 2 mM MBCD was increased in both kinetics and total amount over that observed with 1 mM MBCD (FIG. 6B). Protein tyrosine phosphorylation lagged behind the removal of cholesterol from the sperm plasma membrane, as indicated by the fact that cholesterol removal was at a plateau within 30 minutes with 1 mM MBCD (FIG. 6A) yet no increase in phosphorylation was observed until 2 hours (FIG. 6B). These results indicated that protein tyrosine phosphorylation is dependent on cholesterol removal in a dose dependent fashion, but that the kinetics of cholesterol removal is not rate limiting to the phosphorylation process. The removal of cholesterol from cell membranes has been shown to affect the organization of lipid micro-domains, or rafts, which in turn can affect signaling events in the cell (Simons, Nat Rev Mol Cell Biol 2000, 1: 31-39). To determine if the removal of cholesterol from rat epididymal sperm might be associated with changes in lipid rafts, sperm were stained with the β subunit of cholera toxin (βCT), which binds to the ganglioside GM1 (a lipid known to be present in many lipid rafts) before and after cholesterol removal. Rat epididymal sperm were incubated in BWW with or without BSA or MBCD to facilitate the removal of cholesterol from the sperm plasma membrane. After 5 hours the sperm were fixed and stained with a fluorescent-tagged β-subunit of cholera toxin, which binds to the sugar moiety of GM1. In control sperm at time zero or after 5 hours in BWW only, GM1 staining is tightly confined to the post-acrosomal and head cap regions of the sperm. After removal of cholesterol by BSA or MBCD, GM1 staining begins to diffuse over the equatorial region and acrosome, and increased staining is seen on the sperm tail. Immediately after isolation of sperm from the rat epididymis the sperm show very specific staining with βCT over the equatorial segment and the head cap region. This staining pattern remained constant after 5 hours of incubation in BWW devoid of a cholesterol-binding molecule. However, after 5 hours of incubation with 15 mg/ml BSA or 1 mM MBCD, βCT staining became diffuse over the entire sperm head and became visible on the sperm tail. Virtually all of the sperm observed (>99%) underwent this redistribution. This result indicates that lipid microdomains on sperm are disrupted by removal of cholesterol, and raft components, such as GM1, are redistributed on the surface of the sperm. This redistribution correlates with sperm capacitation, implicating raft-associated signaling events in the capacitation process. Crisp-1 is a sperm maturation protein secreted in two forms, proteins D and E (Roberts et al., Biology of Reproduction 2002, 67: 525-533., Cameo and Blaquier, Journal of Endocrinology 1976, 69: 47-55; Xu and Hamilton, Mol Reprod Dev 1996, 43: 347-357) by the epididymal epithelium, both of which become bound to the sperm surface during epididymal transit (Moore et al., Molecular Reproduction & Development 1994, 37: 181-194., Brooks and Tiver, Journal of Reproduction & Fertility 1983, 69: 651-657). Studies have shown that the majority of Crisp-1 is lost from sperm during incubation after ejaculation or after incubation of sperm isolated from the epididymis (Tubbs et al., J Androl 2002, 23: 512-521). Staining of the protein D and E forms of Crisp1 by anti-peptide antibody CAP-A and monoclonal antibody 4E9 in the presence or absence of MBCD reveals that CAP-A binds to both the D and E forms of Crisp-1 and localizes to the entire surface of the sperm. With time the staining of sperm with CAP-A becomes less intense in both the absence and, even more so, in the presence of MBCD. The intensity of staining with antibody 4E9, which recognizes only the E form of Crisp-1, does not change with time in BWW and decreases only marginally when the sperm are incubated for 4 hours with MBCD. Staining, with antibodies that differentiate the binding of the protein D and E form of Crisp-1, demonstrates that the majority of the protein D and E forms of Crisp-1 is lost during capacitation incubation, with or without a cholesterol binding agent. However, the protein E form of Crisp-1 remains confined to the tail of the sperm without detectable loss or redistribution during the capacitation process. Since the loss of the protein D form of Crisp-1 occurs during the time frame of sperm capacitation, it is possible that the presence of exogenous Crisp-1 may inhibit the capacitation process. FIG. 7A shows the effect on protein tyrosine phosphorylation of incubating sperm under capacitating conditions in the presence of increasing concentrations of purified Crisp-1. At a dose of 400 μg/ml, Crisp-1 inhibits almost completely the protein tyrosine phosphorylation associated with capacitation. Re-probing of these western blots with anti-peptide antibody CAP-A, which recognizes all forms of the Crisp-1 proteins, showed that the endogenous D-form of Crisp-1 (protein D at 32 kDa) is lost from the sperm during capacitation and that exogenous protein D becomes associated with the sperm coincident with the inhibition of capacitation (FIG. 7B). When this western blot was probed with a monoclonal antibody 4E9, which recognizes only the E-form of Crisp-1 (protein E at −28 kDa), the blot showed that protein E is not lost from the sperm surface during capacitation and no additional protein E associates with sperm during the incubation with exogenous Crisp-1 (FIG. 7C). It has been recently reported that the protein E form of Crisp-1 is processed as it associates with sperm in the epididymis and that a portion of the protein D form of Crisp-1 may also be processed as it associates with sperm (Roberts et al., Biology of Reproduction 2002, 67: 525-533). Comparison of FIGS. 7B and 7C demonstrates the presence of a processed form of Crisp-1 that is not recognized by the 4E9 antibody. This observation suggests that the processed forms of Crisp-1 attach permanently to the sperm while the unprocessed form of protein D interacts dynamically with the sperm plasma membrane to reversibly prevent capacitation-associated tyrosine phosphorylation. If the tyrosine phosphorylation events suppressed by Crisp-1 represent the suppression of capacitation, then Crisp-1 should also be able to inhibit the ability of the cells to undergo an induced acrosome reaction. To test this, rat sperm were capacitated for one hour with 15 mg/ml BSA in the presence or absence of 400 μg/ml Crisp-1 and the acrosome reaction induced with 1 μM progesterone (P4). FIG. 8 shows a significant increase (P<0.05) in the acrosome reaction in capacitated sperm after incubation with P4. This increase was completely suppressed by addition of exogenous Crisp-1. The suppression of the acrosome reaction by Crisp-1 was statistically significant (P<0.05). This result indicates that Crisp-1 is inhibiting capacitation in rat sperm. The dynamic nature of the interaction between Crisp-1 (unprocessed form) and the sperm surface suggests that the inhibition of protein tyrosine phosphorylation by Crisp-1 may be reversible. To test this possibility, sperm were incubated under capacitating conditions in the presence 200 μg/ml Crisp-1 for 5 hours and then removed to capacitation media devoid of Crisp-1. As the data of FIG. 9A demonstrate, significant suppression of protein tyrosine phosphorylation was observed at 5 hours by Crisp-1. After 3 additional hours of incubation in the absence of Crisp-1, protein tyrosine phosphoryation had resumed and continued out to 24 hours. The resumption of phosphorylation activity correlates with the loss of Crisp-1 from the sperm (FIG. 9B). Previous studies on the requirements for capacitation in mouse sperm have shown that Ca++, HCO3−, and removal of cholesterol from the sperm plasma membrane are all required for the protein tyrosine phosphorylation events of capacitation (Visconti et al., Development 1995, 121: 1129-1137). However, the absence of any of these three could be compensated for by the addition of cAMP analogs, demonstrating that cAMP signaling in the sperm is intermediary to protein tyrosine phosphorylation (Visconti et al., Development 1995, 121: 1139-1150). FIG. 10 demonstrates that a similar signaling pathway exists for rat sperm. When sperm were incubated in the presence of the cAMP analog db-cAMP and the phophodiesterase inhibitor IBMX, protein tyrosine phosphorylation occurred in the absence of any of the three molecules required for capacitation (FIG. 10A). Furthermore, stimulation of the cAMP pathway by db-cAMP and IBMX also overcame the inhibition of capacitation caused by exogenous Crisp-1 (FIG. 10B). These results indicate that the signaling pathway leading to capacitation is similar between mouse and rat, and that Crisp-1 inhibits capacitation by intervening in an event upstream of the stimulation of cAMP production by the sperm. Discussion This study provides the first characterization of the requirements for capacitation of rat sperm using tyrosine-phosphorylation of sperm proteins as the indication that the capacitation signaling cascade has been activated. As with previous work in other laboratories, primarily using mouse sperm, we have shown that rat sperm capacitation requires the presence of a cholesterol-binding agent, such as BSA, calcium ion, and bicarbonate ion (Visconti et al., Development 1995, 121: 1129-1137; Visconti et al., J Androl 1998, 19: 242-248). Further, the action of all three of these required molecules likely leads to the production of cAMP, as evidenced by the ability of exogenous db-cAMP with the phosphodiesterase inhibitor IBMX to overcome the absence of BSA, Ca++ or HCO3−, consistent with the results of studies of mouse sperm capacitation (Visconti et al., Development 1995, 121: 1129-1137). Most, if not all, mammalian sperm require cholesterol removal from the plasma membrane in order for capacitation to occur. However, the mechanism by which cholesterol removal facilitates capacitation in sperm is not known. One likely possibility is that removal of cholesterol from lipid microdomains, or rafts, facilitates the movement of signaling molecules in the plasma membrane, allowing critical interactions that lead to the activation of adenylate cyclase and subsequent tyrosine phosphorylation of target proteins. Several recent studies have provided evidence for the existence of lipid rafts on mouse and guinea pig sperm (Travis et al., Dev Biol 2001, 240: 599-610; Trevino et al., FEBS Lett 2001, 509: 119-125.; Honda et al., J Biol Chem 2002, 277: 16976-16984). We demonstrate here that rat sperm contain discrete regions of staining for binding of cholera toxin β subunit, which binds to the ganglioside GM1, a common lipid component of membrane rafts. Furthermore, the discrete localization of GM1 is lost during cholesterol extraction with either BSA or MBCD, suggesting that molecules within the sperm plasma membrane begin to diffuse upon removal of cholesterol. A similar diffusion of lipids in the sperm plasma membrane has been reported in boar sperm during in vitro capacitation (Gadella et al., J Cell Sci 1995, 108 (Pt 3):935-946)). Our data also show that the degree of tyrosine phosphorylation in rat sperm is dependent upon the extent of cholesterol extraction. The data of FIG. 6 demonstrate that doubling the amount of MBCD used to extract cholesterol from the sperm membrane increases the maximal degree of tyrosine phosphorylation at the 5 hour time point. Increasing MBCD also increases the kinetics of phosphorylation. Taken together these findings suggest that, if liberation of signaling molecules to move in the plasma membrane is the mechanism by which cholesterol extraction works, removing more cholesterol facilitates more interactions and with faster kinetics. However, it is also clear that removal of cholesterol under the conditions of our experiments is not rate limiting to subsequent tyrosine phosphorylation. Using 1 mM MBCD, extraction of cholesterol reached a plateau within 30 minutes, but an increase in tyrosine phosphorylation was not detected until 2 hours and is not maximal until 3 hours. The delay between cholesterol removal and tyrosine phosphorylation is consistent with a requirement for physical redistribution of signaling molecules within the plasma membrane. The requirement for bicarbonate ion in rat sperm capacitation is consistent with a role for the bicarbonate-dependent soluble adenylate cyclase that has been implicated in the capacitation process in sperm from other mammalian species (Sinclair et al., Mol Reprod Dev 2000, 56: 6-11; Wuttke et al., Jop 2001, 2: 154-158; Flesch et al., J Cell Sci 2001, 114: 3543-3555). A previous study using boar sperm demonstrated that without bicarbonate ion in the media, cholesterol was not lost from the plasma membrane during incubation in the presence of BSA (Flesch et al., J Cell Sci 2001, 114: 3543-3555). The authors of this study proposed that the role of bicarbonate ion was to activate the bicarbonate-dependent adenylate cyclase, which in turn caused the cAMP-dependent activation of flipase, which was required for cholesterol removal from the plasma membrane. In the work presented here, the absence of bicarbonate was overcome by addition of cAMP analog and IBMX, consistent with a capacitation requirement for cAMP downstream of the requirement for bicarbonate ion. However, cholesterol removal from the membrane proceeded normally in the absence of bicarbonate ion, supporting a mechanism of capacitation where cAMP acts downstream of cholesterol removal from the membrane. Both capacitation and the acrosome reaction are calcium ion dependent functions of mammalian sperm (Visconti et al., J Reprod Immunol 2002, 53: 133-150); Breitbart, Mol Cell Endocrinol 2002, 187: 139-144). Our results demonstrate that exogenous calcium is required for the tyrosine phosphorylation accompanying capacitation, consistent with this requirement shown in earlier studies for other mammalian species (Visconti et al., Development 1995, 121: 1129-1137; Dorval et al., Biol Reprod 2002, 67: 1538-1545). The specific calcium-dependent molecular events of capacitation have not been determined, but the ability to overcome the absence of calcium in the medium with exogenous cAMP analogs suggests that the calcium-dependent events in the sperm are upstream of the activation of adenylate cyclase. In addition to the requirement for Ca++, HCO3−, and a cholesterol-binding agent in capacitation, a requirement for the disassociation of Crisp-1 from the sperm membrane for capacitation to proceed in rat sperm has also been demonstrated. It has been demonstrated by immunocytochemistry that a portion of the Crisp-1 staining is lost from the sperm with incubation, primarily from the head region and by western blot analysis that it is the 32 kDa form of Crisp-1 that is lost from the sperm membrane (FIG. 7). The addition of exogenous Crisp-1 inhibits protein tyrosine phosphorylation in a reversible manner, suggesting that Crisp-1 interacts with a specific protein or lipid on the sperm surface, in a dynamic ligand-receptor fashion, and inhibits the capacitation process. Given this effect of Crisp-1 on rat sperm capacitation and the high concentration of Crisp-1 in epididymal fluid, it is likely that Crisp-1 acts as a capacitation inhibiting factor. Crisp-1 was also shown to inhibit the P4 induced acrosome reaction, supporting the conclusion that Crisp-1 inhibits capacitation and that protein tyrosine phosphorylation is required for capacitation in the rat. The level of induced acrosome reaction is low compared with that seen in other species but is consistent with a previous report for rat sperm (Bendahmane et al., Arch Biochem Biophys 2002, 404: 38-47). The very high level of spontaneous acrosome reactions that occur in rat sperm with time during capacitation, over 75% by 3 hours, make it difficult to measure the induced acrosome reaction at extended time points where phosphorylation is more easily measured. The mechanism by which Crisp-1 inhibits the progression of rat sperm to capacitation is unknown. However, potential mechanisms of action can be inferred from similarities of this protein to proteins of known function. The primary amino acid sequence of Crisp-1 is highly similar to that of many toxins, in particular the toxin helothermine produced by the lizard Heloderma horridum (Morrissette et al., Biophysical Journal 1995, 68: 2280-2288). Helothermine is known to act as an inhibitor of calcium flux through the ryanodine receptor, a regulated calcium channel in muscle cells (Morrissette et al., Biophysical Journal 1995, 68: 2280-2288). Since calcium is required for capacitation, Crisp-1 may prevent the uptake of needed calcium via channels in the sperm plasma membrane. Ryanodine receptors have been reported to be present in testicular germ cells and sperm, but their exact localization remains unclear (Gianni et al., Journal of Cell Biology 1995, 128: 893-904; Trevino et al., Zygote 1998, 6: 159-172). However, it is certainly plausible that Crisp-1 acts on the sperm by interacting with a ryanodine receptor or a ryanodine receptor-like channel in the sperm plasma membrane. It appears that Crisp-1 is the only secretory protein of the epididymis to possess capacitation inhibitory activity. However, proteins or factors in secretions of the male reproductive tract with apparent capacitation inhibitory activity have been reported from several species (Huang et al., Biol Reprod 2000, 63: 1562-1566 (2000); Aonuma et al., Chem Pharm Bull (Tokyo) 1976, 24:907-911; Eng and Oliphant, Biol Reprod 1978, 19: 1083-1094; Kanwar et al., Fertil Steril 1979, 31: 321-327; Tomes et al., Mol Hum Reprod 1998, 4: 17-25). The mouse seminal vesicle autoantigen has been shown to inhibit protein tyrosine phosphorylation associated with sperm capacitation and human seminal plasma has been shown to contain a factor(s) with similar activity (Huang et al., Biol Reprod 2000, 63: 1562-1566 (2000); Tomes et al., Mol Hum Reprod 1998, 4: 17-25). Although little is known of the mechanism of capacitation suppression reported in seminal plasma and secretory proteins of the seminal vesicles, it appears that suppression of premature capacitation is an important function of fluids of the male excurrent reproductive tract. In addition to the 32 kDa form of Crisp-1 that interacts in a reversible way with the sperm plasma membrane to inhibit capacitation, a second smaller molecular weight form is also found on sperm; this form is strongly attached and is not removed during incubation under capacitating conditions. It has been previously shown that both the D and E forms of Crisp-1 are processed (Roberts et al., Biology of Reproduction 2002, 67: 525-533). The processed E form of Crisp-1 is recognized by monoclonal antibody 4E9 and localizes to the sperm tail; its function there is unknown (Roberts et al., Biology of Reproduction 2002, 67: 525-533). Crisp-1 has been implicated as playing a role in sperm-egg fusion. A number of studies in rat, mouse and human systems have shown that fusion of sperm to the plasma membrane of zona pellucida-free eggs is inhibited in the presence of Crisp-1 (Rochwerger et al., Developmental Biology 1992, 153: 83-90); Cohen et al., Biol Reprod 2000, 63: 462-468, Cohen et al., Biol Reprod 2001, 65: 1000-1005). Further, preincubation of zona pellucida-free eggs with Crisp-1, followed by immunocytochemistry with an antibody specific to Crisp-1, demonstrates specific binding sites for Crisp-1 on the surface of eggs (Rochwerger et al., Developmental Biology 1992, 153: 83-90). Taken together, these studies suggest that Crisp-1 can inhibit sperm-egg fusion and are consistent with the hypothesis that Crisp-1 is involved in sperm-egg fusion. However, there are no known fusogenic domains contained within the amino acid sequence of Crisp-1 and nothing in the predicted tertiary structure of the protein suggests a role in membrane fusion. Therefore, it is unlikely that Crisp-1 mediates the sperm-egg fusion event directly. Given the ability of Crisp-1 to block the signaling cascade leading to capacitation, as shown in the present example, a possible role for Crisp-1 in sperm-egg fusion may involve regulation of signaling events, particularly those associated with protein tyrosine phosphorylation. Processed Crisp-1 remaining on the sperm plasma membrane could interact with signaling molecules on the egg surface to initiate or otherwise regulate the fusion event. The complete disclosures of all patents, patent applications including provisional patent applications, and publications, and electronically available material (e.g., GenBank amino acid and nucleotide sequence submissions) cited herein are incorporated by reference. The foregoing detailed description and examples have been provided for clarity of understanding only. No unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described; many variations will be apparent to one skilled in the art and are intended to be included within the invention defined by the claims. Sequence Listing Free Text SEQ ID NO: 1-7 are amino acid sequences. SEQ ID NO: 8-14 are cDNA sequences.
<SOH> BACKGROUND <EOH>An effective, safe and easily reversible male contraceptive with universal acceptability remains an elusive goal. Although a variety of approaches for achieving male contraception have been tried, no single mode of male contraception is without its immediate drawbacks for efficacy or compliance. Even seemingly simple interventions have not proven to be widely acceptable. For example, surgical or non-surgical vasectomy, methods that interrupt sperm transport in the male reproductive tract, are not without their complications or long-term risk. More complex approaches, such as regimens for the hormonal control of male fertility, have also not been fully satisfactory. Such methods have focused on the suppression of spermatogenesis to the point of azoospermia, a goal that has been difficult to achieve. The use of the immune response to block contraception has been an important front in efforts to develop more sophisticated contraceptive systems. Unfortunately, such approaches have thus far failed, as male autoimmunity against sperm does not suppress sperm production in men; this is known because such autoimmunity can occur after vasectomy. Thus, inhibiting sperm fertilizing-ability without affecting the hormonal balance in either the male or female remains an important goal in the field of reproductive biology. The present invention achieves this goal.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention includes a method of inhibiting sperm capacitation including contacting sperm with a CRISP polypeptide. Also included in the present invention is a method of inhibiting sperm capacitation in an individual including the administration of a CRISP polypeptide to the individual. In another aspect, the present invention also includes a method for inhibiting fertilization of an egg by sperm in an individual, comprising the administration of a CRISP polypeptide to the individual. In another aspect, the present invention includes a method of inhibiting the phosphorylation of a protein at tyrosine residues including contacting the protein with a CRISP polypeptide. In some embodiments of the present invention, the protein may be on the surface of mammalian sperm. A further aspect of the present invention includes a method of inhibiting an acrosomal reaction including contacting the acrosomal reaction with a CRISP polypeptide. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered orally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered parenterally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered transdermally. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered in a composition including a pharmaceutically acceptable carrier. In some embodiments of the methods of the present invention, the individual may be a mammalian male. In some embodiments of the methods of the present invention, the individual may be a mammalian female. In some embodiments of the methods of the present invention, the CRISP polypeptide may be administered intravaginally, including administered as a time released, vaginal implant. In other embodiments of the methods of the present invention, the CRISP polypeptide is administered to the vagina of the mammalian female in an amount capable of inhibiting sperm capacitation, rendering said sperm incapable of fertilization. In other embodiments of the methods of the present invention, the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7), and biologically active analogs thereof. In yet other embodiments of the methods of the present invention, the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1) or a biologically active analog thereof. In some embodiments of the methods of the present invention, the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). In other embodiments of the methods of the present invention, the CRISP polypeptide has about at least 40% structural identity to rat CRISP-1 (SEQ ID NO:2) of a biologically active analog thereof. In some embodiments of the methods of the present invention, the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). Also included in the present invention is a contraceptive composition including a CRISP polypeptide in an amount effective to inhibit sperm capacitation, inhibit phosphorylation of a protein at tyrosine residues, inhibit an acrosome reaction, and/or inhibit fertilization of an egg by sperm. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to a polypeptide selected from the group consisting of human CRISP-1 (SEQ ID NO:1, rat CRISP-1 (SEQ ID NO:2), mouse CRISP-1 (SEQ ID NO:3), human CRISP-2 (SEQ ID NO:4), rat CRISP-2 (SEQ ID NO:5), human CRISP-3 (SEQ ID NO:6), mouse CRISP-3 (SEQ ID NO:7) and biologically active analogs thereof. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to human CRISP-1 (SEQ ID NO:1) and biologically active analogs thereof. In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide is human CRISP-1 (SEQ ID NO:1). In some embodiments of the contraceptive composition of the present invention, the CRISP polypeptide has at least about 40% structural identity to rat CRISP-1 (SEQ ID NO:2), and biologically active analogs thereof. In other embodiments of the contraceptive composition of the present invention, the CRISP polypeptide is rat CRISP-1 (SEQ ID NO:2). In some embodiments of the contraceptive composition of the present invention, the contraceptive composition further includes a spermicidal or an antiviral agent.
20050523
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DESAI, ANAND U
CRISP POLYPEPTIDES AS CONTRACEPTIVES AND INHIBITORS OF SPERM CAPACITATION
SMALL
0
ACCEPTED
2,005
10,515,870
ACCEPTED
Method of enabling a wireless information device to access location data
A method of enabling a first wireless information device to access absolute location data in which the first wireless information device does not possess its own absolute location finding system but is instead able to receive, over a wireless network, absolute location data from a second wireless information device that does have its own absolute location finding system. The present invention hence enables wireless information devices to share absolute location data: for example, a mobile telephone with GPS capability can be used as a local ‘beacon’ to broadcast its absolute location to any nearby devices over a personal area wireless network (e.g. a Bluetooth network) so that those nearby devices can use that location data. Hence, a camera with no location finding system of its own could obtain location data from a nearby GPS equipped mobile telephone over a Bluetooth PAN and watermark its images with location data.
1. A method of enabling a first wireless information device to access absolute geographic data (i.e. location, speed or direction), in which the first wireless information device docs not possess its own absolute graphic finding system but is instead able to receive over a wireless network, absolute geographic data from a second wireless information device that docs have its own absolute geographic fig system; in which the second wireless information device is programmed to enable any authorised component, whether on the second wireless device or tee first wireless information device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the second wireless information device that meet those parameters. 2. The method of claim 1 in which the wireless network is a short range personal area network. 3. The method of claim 1 in which the second wireless information device is a mobile telephone. 4. The method of claim 1 in which the absolute location finding system of the second wireless information device is a wireless based system, such as a GPS or time of arrival system. 5. The method of claim 1 in which a publish and subscribe API is used to enable any such authorised component, whether running on the second wireless information device or the first wireless information device, to subscribe to location data published by any of the location finding systems running on the second wireless information device. 6. The method of claim 1 in which the first bless information device is able to receive, over the wireless network, speed data from the second wireless information device, to indicate the speed at which it is travelling. 7. The method of claim 1 in which the first wireless information device is able to receive, over the wireless network, direction data from the second wireless information device, to indicate the direction at which it is traveling. 8. The method of claim 1 in which the fist wireless information device is a still or video camera. 9. The method of claim 1 in which the first wireless information device is a tag used for asset tracking. 10. The method of claim 1 in which the fist wireless information device is a digital music player. 11. The method of claim 1 in which the first wireless information device can relay the location data obtained from the second wireless information device to another wireless information device. 12. A wireless information device programmed with its own absolute geographic finding system and capable of sharing absolute geographic data with a second wireless information device that does not possess its own absolute geographic finding stem but is instead able to receive, over a wireless network absolute geographic data from the wireless information device; in which the wireless information device is programmed to enable any authorised component, whether running on the device or the second device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the device that meet those parameters. 13. The device of claim 12, being a mobile telephone. 14. The device of claim 12 in which the absolute location finding system of the wireless information device is a wireless based system, such as a GPS or time of a system. 15. The device of claim 12 in which a publish and subscribe API is used to enable any such authorised component, whether running on the device or externally to it, to subscribe to location data published by any of the location finding systems running on the wireless information device. 16. The device of claim 12 being able to send, over the wireless network, speed data to the second wireless information device, to indicate die speed at which it is traveling. 17. The device of claim 12 being able to send, over the wireless network, direction data to the second wireless information device, to indicate the direction in which it is travelling.
BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a method of enabling a wireless information device to access location data. The term ‘wireless information device’ used in this patent specification should be expansively construed to cover any kind of device with one or two way wireless communication capabilities and includes without limitation radio telephones, smart phones, communicators, personal computers, computers and wireless enabled application specific devices such as cameras, video recorders, asset tracking systems etc. It includes devices able to communicate in any manner over any kind of network, such as GSM or UMTS, CDMA and WCDMA mobile radio, Bluetooth, IrDA etc. 2. Description of the Prior Art As mobile Internet devices and third generation mobile networks become more pervasive, location based services are thought to be a major growth area. Providing information, context and services based on location awareness enables the potential for new capabilities and simplified interfaces for the user, as well as new revenue streams for operators and service providers. The technology required for provision of automated location information to mobile devices has been in continual development for several decades. Whilst the majority has its roots in military, naval and aviation applications, modern consumer technology is also rising to meet the challenges, specifically in the metropolitan environment. Typical examples of location technology that are being adopted for use in wireless information devices include GPS and basestation triangulation technology that can very accurately measure the time of signal arrival. A device able to determine its absolute location has, conventionally, had to include its own location finding components (e.g. a GPS receiver and related software). These location finding systems are usually regarded as establishing an “absolute location”; this means the physical location in an absolute reference frame, such as WGS-84, as opposed to logical location (e.g. close to a specific location beacon). Reference may be made to U.S. No. 2001/048746, which shows a mobile telephone with GPS capabilities that is able to share GPS location data with other devices over a short range wireless link; this obviates the need for those other devices to have their own GPS capability. SUMMARY OF THE PRESENT INVENTION In a fist aspect there is a method of enabling a first wireless information device to access absolute geographic data (i.e. location, speed or direction), in which the fist wireless information device docs not possess its own absolute geographic finding system but is instead able to receive, over a wireless network absolute geographic data from a second wireless information device that does have its own absolute geographic finding system; in which the second wireless information device is programmed to enable any authorised component, whether running on the second wireless device or the first wireless information device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the second wireless information device that meet those parameters. The present invention hence enables wireless information devices to share absolute location data: for example, a mobile telephone with GPS capability can be used as a local ‘beacon’ so broadcast its absolute location to any nearby devices over a wireless PAN (personal area network, e.g. a Bluetooth network) so that those nearby devices can use that location data. Hence, a camera with no location finding system of its own could obtain location data from a nearby GPS equipped mobile telephone over a Bluetooth PAN and watermark its images with location data. ‘Absolute location’ In this context means the physical location in an absolute reference frame, such as WGS-84, as opposed to logical location (e.g. close to a specific location beacon). The second wireless information device could be a simple RF ID tag used in asset tracking whenever the tag is dose enough to a device that is broadcasting absolute location data it stores a second of that absolute location, hence building up a record of its journey. The second wireless information device does not have to be a portable device, but may be a simple, fixed location beacon programmed with its absolute location. It may also be unable to independently obtain that location, but be simply programmed with it (e.g. may be connected to a WAN and be sent its absolute location over that WAN). Other kinds of data that accompany location data can also be shared between the first and second devices across the wireless network for example; if the second wireless information device has a GPS receiver, than not only are absolute location co-ordinates generated, but also speed and direction co-ordinates as well. With the present invention, any or all of absolute location, speed and direction (or indeed any other absolute geographic indicator) can be shard between devices. The present invention therefore introduces the concept of ‘distributed absolute geographic awareness’—i.e. distributing or sharing absolute geographic data: absolute location, speed in that absolute reference frame used to establish location or direction in that absolute reference frame (and any combination of the three). It hence leverages the ability of just one device to actually obtain and that absolute geographic data, or of one device to obtain one kind of absolute geographic data, and another device to obtain a different kind. In a second aspect, there is a wireless information device programmed with its own absolute geographic finding system and capable of sharing absolute geographic data with a second wireless information device that does not possess its own absolute geographic finding system but is instead able to receive, over a wireless network, absolute geographic data from the wireless information device; in which the wireless information device is programmed to enable any authorised component, whether running on the device or the second device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the device that meet those parameter. BRIEF DESCRIPTION OF THE DRAWING The present invention will be described with reference to accompanying drawing FIG. 1, which shows an architecture for a wireless information device that can implement the present investigation. DETAILED DESCRIPTION An implementation of the present invention enables absolute location data sharing between (a) any kind of device that is both cognisant of its absolute location and is capable of transmitting that data location and (b) any kind of wireless device that is capable of receiving that transmitted location data and that might, for whatever reason, benefit from being able to use knowledge of its absolute location. In most practical implementations, the data transmission will be over a transient personal area wireless network, such as a Bluetooth network. Further, most mobile telephones will have some form of absolute location finding capability in the near future and hence make an ideal location beacon for transmitting absolute location data to nearby devices. To give an indication of the breadth of potential applications of the present invention, the following further examples of use are given: Use Cases 1. An interesting use case is that of enabling a MP3/OggVorbis digital music playing device to pick up a user's absolute location using the present invention (e.g. from that user's location enabled mobile telephone) and to play a favourite song that reminds the user or connects him to that location. This requires the music playing device to be able to store and update a database with locations and music songs associated with each location. 2. Another simpler idea is that when you take a photo with your camera it embeds a location fix in the postcard which can then be transmitted over the network using Obex that includes a location object in there. 3. Other use cases cover asset tracking and fleet management services where, for example, when a courier delivers a parcel, the signatory effectively watermarks its signature with the location of delivery. For fleet management, a wireless information device could discover (or calculate) it's position from the vehicle's on-board location system. 4. Another use case is that of location-relaying where many devices in a “wireless-chain”, relay the location fix obtained from an other. In that scenario, only one such device can obtain the absolute location fix (from GPS or Galileo satellites for example) and the others relay it; so that for example in a building many devices get to know about their location together with an error which can be calculated from the number of hops. In that scenario, triangulation is also possible using multiple sources. 5. An interesting use case is that of asset tracking with restricted operational range. For example if a laptop should not leave a predefined area/premises etc. Then it can be programmed to seek such location beacons and completely lock or destruct (automatically or after communication to base) if such location identification is made. The value there of that laptop (or other device for that matter) not to have it's own location system is that it can pick up location beacons from many other device and after authentication (or not) make the appropriate decisions and actions. 6. As noted earlier, it is possible to share non-location data as well. For example, an on-car GPS navigation system could share speed data with to an on-car data recorder, that would alert the user if it's speed was excessive. The on-car data recorder could use location information from the GPS system to establish the road the car was travelling on (for example, in conjunction with conventional GPS navigation software, such as the TomTom Navigator) and, using a database of applicable speed limits for all roads, establish if the car is speeding or not. The GPS navigation system could also share location data with an on-car road charging system: the congestion charging system can work out if the car's location corresponds to a charge area (e.g. toll road, congestion area) and then ensure that the appropriate debit or charge or payment is made. The method used to share absolute location data is relatively straightforward. For example, one way to distribute absolute location information to the personal area network over Bluetooth is to have devices inquiring the location-aware device's, SDP (service discovery protocol) records—using a universally unique identifier (UUID)—for the particular service that provides the location information. In fact, the location-aware device can make this process much simpler and faster by including the location fix in it's SDP service records and thus returning the result to the interested parties embedded in the SDP response (as opposed to returning the relevant info for the remote device to connect to the location service). Another way (which would require more battery power) would be for a Bluetooth device to periodically broadcast/multicast such location fixes using raw Bluetooth Link Layer AUX packets and thus allow anyone who might listen to pick them up. A standardised location data format, akin to the vCard format for personal contact information, would be possible. Currently, applications that need location information are tightly bound into the technology that provides the location data. This may require developers to understand in detail how GPS and GSM triangulation location technologies operate, which is onerous. The present invention can be implemented using a location technology “insulation layer” in the second wireless information device OS which separates and hence decouples applications and any system servers from the underlying location technologies. Hence, location technologies (e.g. a GPS plug-in or a GSM triangulation plug-in) provide location data to the insulation layer (a server in a Symbian OS implementation). This server insulation layer then gives access to the location data to any client (e.g. an application or system server) that needs it over a generic API. Critically, the client need not be limited to a client on the second wireless information device itself, but can reside on a completely different device that does not have its own location finding system. There are further advantages to a location insulation layer approach: Application developers can develop location based apps without needing to understand the specifics of any location technology such as GPS or even define the kind of location technology that should be providing the location data; they merely need to be able to use the API. Location technology developers can develop location technology without needing to understand the specifics of any application or system server; the location technology can be implemented as plug-ins, which are potentially hot swappable; Any application or resource on the device that needs location data can now readily obtain it; location data is made available across the entire OS. Multiple location technologies could be running on one device, with the insulation layer deciding which technology to use at any time—the application need know nothing about a hot-swap over between technologies; The location information can be readily supplied to different system servers—e.g. a system server which decided which bearer/protocol to communicate over could be fed location information and use that as part of its decision making; hence, when within range of a Bluetooth pod, it could change to Bluetooth; when out of range, it could revert to GSM etc. A device can be readily made to dial out its location information (e.g. to the police) if the device receives an appropriate trigger message that the device is stolen. A publish and subscribe API can be used to enable any such authorised server, whether running on the second wireless information device or the first wireless information device, to subscribe to location data published by any of the location finding systems running on the second wireless information device Appendix 1 Appendix 1 comprises a more detailed description of a suitable architecture, plus a discussion of some important design principles for a location aware operating system. 1. Source Data Processing The location aware device can use one or more different location sensing technologies; where more than one is used, a technique for combining location data from multiple sources into a single estimate of location may be employed. This is particularly useful where the different sources have differing characteristics, in terms of acquisition technique and accuracy. The aim of such processing is to improve the new accuracy of a location fix, above that of any individual source. Kalman filtering is often used to combine, GPS and INS data, as the strengths of each compensate the weaknesses of the other very well, resulting in output data of higher accuracy than anyone of them can provide at any given instant in time. 2. Security, Privacy Security of location information is based around “Who”, “Where”, and “When”. These are listed in order of importance for protection. The location aware device should guard the most securely whom it represents. “Where” that person is can reasonably be shared with others also in the locality (although arguably so long as the “who” is not shared) as explained above, and time can be shared with anyone (restricting the other two). However, as this information is the most dangerous when more than one is known (in particular, all three, and for a range of times), securing all three, from leakage to remote parties, is the most sure-fire way of avoiding this most sensitive combination falling into the wrong hands. So each of the three should only issued on a “need to know” basis—providing open services in a personal device should only be done on the explicit instruction of the user. 3. Location Discovery vs. Navigation Another way of partitioning services is between location discovery (static), and navigating through space (dynamic). A third class is the intersection of these two (continuously discovering whilst moving). Discovery covers many areas, such as 1. Own location (“where am I?”) 2. Other location (“Where am I going?”) 3. Person location (“Buddy finder”) 4. Information filtering (“present traffic info before going out of home on Monday morning”) 5. action/event filtering (‘don't beep loudly when in the cinema or boss' office’) 6. Service location (“Find my nearest . . . ”) 7. Other property of a location (local time-zone, traffic conditions, weather, etc.) The last two are to many degrees interchangeable, as you can view a local service as a property of a location, and a service may itself provide other information (properties) about that location. 4. Location Awareness: Architecture Considerations App Engines Location knowledge is primarily an application service, although it is important to appreciate that the applications that use the location data can be distributed across several devices, connected over a wireless PAN. Contacts and Agenda applications can benefit greatly from location data, and there is also potential for journaling. Location based searching for local as well as remote content is facilitated. One could imagine a “location” stamp anywhere there is currently a “time” stamp—e.g. on documents (e.g. to establish where electronically signed; on photographs for evidential reasons, with the location data being watermarked to be tamper evident). One might also want to log symbolic location information, or to tie this info into contacts, e.g. My Contacts & My Locations, for commonly used locations. A “World” mapping application could get auto updates from location. It actually re-publishes some of the information that may be available from a location server, e.g. time zone and local dialling code. If these were standardised into location server, the ‘World’ app server could just relay them through (or perhaps disappear altogether). 5. Power Management—Polling Concerns Initial usage models will generally assume that location information is only sought through direct user intervention. This solves many security and power consumption issues. This has the downside, however, that the time to first fix (ITFF) could be quite high, as when the user initiates location acquisition activity, the device must bootstrap it's knowledge from nothing. If any future hardware supports a “tell me when I move (more than X meters)” notification interface, then the TTFN could be reduced significantly. This is based on the assumption the user moves (more than X meters) fairly infrequently in terms of device on time. For network based location technologies, this could greatly reduce battery drain for autonomous applications. 6. Architecture—Component Level View To better understand the architecture, we present a component view based on areas of responsibility. The philosophy behind the suggested APIs and Architecture for Symbian Location Awareness/LBS is: “make it easy for most and possible for the others” Thus, we have the distinction between the different offered APIs and the separation of plug-ins from the plug-in framework. The overall structure is shown in the attached figure. The main components are described in the following section. 6.1 Location API Responsibilities: Present a clean and simple interface by which most clients can use the location primitives offered by the context server. Such an API will provide the Location primitives to the upper layers of the platform like applications, application engines and application protocols. Offer services to obtain location fixes based on various QoS parameters requested by its client and present the data in a simple and consistent format (most likely WGS-84 and possibly Cell-ID strings). Clients: Applications and the application frameworks Collaborations: With the Context Server 6.2 Advanced Location Client API Responsibilities: Present a complete and generic interface by which clients can request a variable number of attributes from the Context server and thus make use of any capabilities that a particular location technology may have to offer. Also allows for bi-directional data transfer. Clients: Advanced and/or technology dependent applications and the app framework. Collaborations: With the Context Server 6.3 Location Awareness Server Responsibilities: To encapsulate and mediate resource sharing of the location acquisition resources/technologies. The server is responsible for routing client calls to the correct technology plug-in, based on the caller's QOS requirements, as well as police the interaction based on the platform security model. It hosts the location acquisition technology plug-ins and provides the framework needed to interface them. Enforces per transaction policing efficiently so that on every call from the client it checks every process' capabilities mask. Clients: The Location Clients Collaborations: With the location acquisition technology plug-ins. Publish and Subscribe interface in the Kernel. File Server, DBMS Server ESock and whatever resources and servers that the technology plugins may need. 6.4 Plug-ins Framework Responsibilities: To enable and facilitate re-use among plug-ins and facilitate plug-in development. Clients: Plug-ins and the Context Server Collaborations: Base components 6.5 Plug-in Message Passing Framework Responsibilities: Allow different location acquisition plug-ins to intercept and exchange messages so that we can have plug-in functionality reuse with loose coupling (e.g. AGPS using GPS) and for a listen/hook interface in order to log all events if a product wants it; or for fusion scenarios where one plug-in may provide location fixes by combining other technologies. Clients: Plug-ins and the Location Server Collaborations: Location Server Base components other plug-ins 6.6 Quality of Position Services Responsibilities: Select a positioning technology which fulfils the QoP parameters provided by a client through the Location Client API. Allow the client to obtain location fixes without specifying a particular location acquisition technology plug-in. Basic set of QoP parameters shall include: horizontal accuracy, vertical accuracy, time to fix, cost, power consumption. Clients: Plug-ins and the Location Client API Collaborations: Location Server Location acquisition technology plug-ins. 6.7 Location Acquisition Technology Plug-ins Responsibilities: To interface with the location acquisition technologies and the Location Server. Each plug-in is responsible for providing the communication mechanisms and protocols needed to interface with a particular technology and hardware. Plug-ins are also concerned with providing static technology specific capabilities, as well as runtime capabilities (e.g. no GPS signal etc) to the server necessary for the location QoS decision making in the server. The cost option of a plug-in is provided by the operator/user not the plug-in itself as it may change according to operator, time, subscription and possibly even location (roaming etc). Clients: Location Server and other plug-ins indirectly Collaborations: Context server other plug-ins through the framework ETel (SMS,GSM/GPRS,UMTS) C32 server, UART/some serial or bus abstraction drivers etc. 6.8 Application Framework Responsibilities: Conversion of map data Interfacing to DBMS (e.g. Landmarks DB, persistence, log viewing) Privacy related settings and service filtering. Clients: Apps and other frameworks. Collaborations: Between Location Server app engines and GUI 7. Client API Recommendations Location Acquisition Technology Modularity Architecture In the internal architecture underlying the Location Server the vision is to allow for technology specific server plug-ins to act as the hardware proxies for the location acquisition hardware, utilising their full capabilities. For these reasons and because a varying plethora of such hardware is expected to be used by licensees and users, the interface between the server and these plug-in will allow for ‘load time’ capabilities discovery. In effect a plug-in will present as many published interfaces as it needs. This can be achieved by making use of a simple capabilities discovery protocol and polymorphic factory managed plug-in dlls. Using this scheme will also allow applications and 3rd parties to make use of specific hardware capabilities without needing to extend the server or plug-in interfaces. As a minimum we believe that the technology plug-ins may expose interfaces like: NMEA 0183 v2.0 or some subset of Power Management Cell-ID Basic Lon,Lat,Alt Basic Anchor, waypoint operations QoS Capabilities Advertisement Internally to the technology plug-in modules, developers may choose any number of methods to communicate with the hardware. For example to harness all of the device's potential one developer may choose use the proprietary device specific protocols (to communicate with the device) whereas other may decide for time-to-market reasons to use simpler means (like NMEA for GPS receivers). In any case the interfaces exposed will insulate from the internals that may change in later revisons of these modules. In the case of a 3rd party harnessing the full potential of an advanced GPS device, they would communicate using the receiver's proprietary protocol and translate raw data to NMEA sentences as needed if exposing an NMEA interface. At the same time all modules will be expected to use the ‘Location QoS Capabilities’ interface to register their static and run-time capabilities with the server (which does not preclude them being stored in a DB). This registration allows the Location Server to dynamically select technology plug-ins to satisfy client requests with particular QoS requirements. 7. Plug-in Settings Installed Location Server plug-in modules will need a level of configurability that will demand some settings to be stored and retrieved on persistent storage. Configuration of these settings will be exposed to the user by means of control applets. To achieve a secure and caged access to these settings, they will most likely (unless a P&S mechanism is chosen) be stored and structured in a databse, hosted by the DBMS Server. A framework for the plug-ins will be provided to access these settings on the DBMS server through the Location Server.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention relates to a method of enabling a wireless information device to access location data. The term ‘wireless information device’ used in this patent specification should be expansively construed to cover any kind of device with one or two way wireless communication capabilities and includes without limitation radio telephones, smart phones, communicators, personal computers, computers and wireless enabled application specific devices such as cameras, video recorders, asset tracking systems etc. It includes devices able to communicate in any manner over any kind of network, such as GSM or UMTS, CDMA and WCDMA mobile radio, Bluetooth, IrDA etc. 2. Description of the Prior Art As mobile Internet devices and third generation mobile networks become more pervasive, location based services are thought to be a major growth area. Providing information, context and services based on location awareness enables the potential for new capabilities and simplified interfaces for the user, as well as new revenue streams for operators and service providers. The technology required for provision of automated location information to mobile devices has been in continual development for several decades. Whilst the majority has its roots in military, naval and aviation applications, modern consumer technology is also rising to meet the challenges, specifically in the metropolitan environment. Typical examples of location technology that are being adopted for use in wireless information devices include GPS and basestation triangulation technology that can very accurately measure the time of signal arrival. A device able to determine its absolute location has, conventionally, had to include its own location finding components (e.g. a GPS receiver and related software). These location finding systems are usually regarded as establishing an “absolute location”; this means the physical location in an absolute reference frame, such as WGS-84, as opposed to logical location (e.g. close to a specific location beacon). Reference may be made to U.S. No. 2001/048746, which shows a mobile telephone with GPS capabilities that is able to share GPS location data with other devices over a short range wireless link; this obviates the need for those other devices to have their own GPS capability.
<SOH> SUMMARY OF THE PRESENT INVENTION <EOH>In a fist aspect there is a method of enabling a first wireless information device to access absolute geographic data (i.e. location, speed or direction), in which the fist wireless information device docs not possess its own absolute geographic finding system but is instead able to receive, over a wireless network absolute geographic data from a second wireless information device that does have its own absolute geographic finding system; in which the second wireless information device is programmed to enable any authorised component, whether running on the second wireless device or the first wireless information device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the second wireless information device that meet those parameters. The present invention hence enables wireless information devices to share absolute location data: for example, a mobile telephone with GPS capability can be used as a local ‘beacon’ so broadcast its absolute location to any nearby devices over a wireless PAN (personal area network, e.g. a Bluetooth network) so that those nearby devices can use that location data. Hence, a camera with no location finding system of its own could obtain location data from a nearby GPS equipped mobile telephone over a Bluetooth PAN and watermark its images with location data. ‘Absolute location’ In this context means the physical location in an absolute reference frame, such as WGS-84, as opposed to logical location (e.g. close to a specific location beacon). The second wireless information device could be a simple RF ID tag used in asset tracking whenever the tag is dose enough to a device that is broadcasting absolute location data it stores a second of that absolute location, hence building up a record of its journey. The second wireless information device does not have to be a portable device, but may be a simple, fixed location beacon programmed with its absolute location. It may also be unable to independently obtain that location, but be simply programmed with it (e.g. may be connected to a WAN and be sent its absolute location over that WAN). Other kinds of data that accompany location data can also be shared between the first and second devices across the wireless network for example; if the second wireless information device has a GPS receiver, than not only are absolute location co-ordinates generated, but also speed and direction co-ordinates as well. With the present invention, any or all of absolute location, speed and direction (or indeed any other absolute geographic indicator) can be shard between devices. The present invention therefore introduces the concept of ‘distributed absolute geographic awareness’—i.e. distributing or sharing absolute geographic data: absolute location, speed in that absolute reference frame used to establish location or direction in that absolute reference frame (and any combination of the three). It hence leverages the ability of just one device to actually obtain and that absolute geographic data, or of one device to obtain one kind of absolute geographic data, and another device to obtain a different kind. In a second aspect, there is a wireless information device programmed with its own absolute geographic finding system and capable of sharing absolute geographic data with a second wireless information device that does not possess its own absolute geographic finding system but is instead able to receive, over a wireless network, absolute geographic data from the wireless information device; in which the wireless information device is programmed to enable any authorised component, whether running on the device or the second device, to define quality of position parameters and to be sent location data from one or more absolute location finding systems running on the device that meet those parameter.
20050413
20121211
20050825
69117.0
0
HOLLIDAY, JAIME MICHELE
METHOD OF ENABLING A WIRELESS INFORMATION DEVICE TO ACCESS LOCATION DATA
UNDISCOUNTED
0
ACCEPTED
2,005
10,515,909
ACCEPTED
Card
The invention relates to a card having a card base body (20) and a plastic layer (30) joined thereto. According to the invention, the delimiting edge(s) of the plastic layer (30) is/are set back from the card edge(s) and comprise(s) projections that terminate with the edge(s) of the card base body (20) in a flush manner.
1-5. (canceled) 6. A card comprising a base body and a plastic layer welded to the base body, the plastic layer having at least one boundary edge that is set back from an edge of the base body, and further having projections, which terminate flush with the edge of the base body. 7. The card according to claim 6, wherein the base body and the plastic layer each have a rectangular shape, the edges of the rectangle of the plastic layer are set back from the edges of the rectangle of the base body, at least two of the projections being provided on each edge of the plastic layer. 8. The card according to claim 7, wherein the projections have a rounded shape. 9. The card according to claim 6, wherein the plastic layer is printed on a side facing the base body. 10. The card according to claim 6, wherein the plastic layer is printed on a side facing away from the base body. 11. The card according to claim 7, wherein the base body and the plastic layer have rounded corners.
The invention pertains to a card, comprising at least one layer of laminate and a layer of plastic, preferably printed, which is bonded to the laminate. A card of this type is described in, for example, EP 0 669 214 B1. This card comprises a finished base card, which has been die-cut to the final dimensions. A printed plastic layer, also with its final dimensions, is laid on the base card and attached to it by welding. The base card consisting of at least one layer of laminate and the printed plastic layer arranged on top of it have the same final dimensions. In many cases, these types of cards are also produced by laminating a base card and, for example, a piece of printed plastic film together and by die cutting the composite card thus obtained to bring it to its final dimensions. In the case of this card as well, the edges of the plastic film terminates precisely at the edge of the card. Terminating the edges of the plastic film so that its edges are flush with the edges of the card is problematic with respect to the production of these cards. Either the plastic film must be of exactly the same size as the card and be positioned very precisely thereon, or the plastic film and the card must undergo a final die cutting operation. Terminating the edges of the plastic film so that its edges are flush with the edges of the card is also problematic because of the possibility that frequent use of the card can lead to damage to the plastic film precisely in the area of the edges. Such damage can even make it possible for the plastic film to peel off at least partially from the card. Information printed on the plastic film can therefore be lost, for example, and damage of this type to the card is also undesirable from an aesthetic standpoint. The invention is therefore based on the problem of improving a card of the general type in question so that it can be produced easily, so that the previously described problems can be eliminated, and especially so that the plastic layer on the card cannot be damaged or peeled off even under conditions of frequent use. This task is accomplished according to the invention with a card of the type described above in that the boundary edge/edges of the plastic layer is/are set back from the edge/edges of the card and has/have projections, which terminate flush with the edge/edges of the card. Because the plastic layer has a smaller surface area that the card, damage to the plastic layer is prevented precisely in the edge areas of the card subject to especially severe stress. The projections make it possible to position the plastic layer precisely on the card during the production process, and a much smaller degree of precision is required than for the cards according to the state of the art, for which the plastic layer is precut to the final dimensions of the card. Both the card and the plastic layer preferably also have a rectangular shape with preferably rounded corners, where the edges of the plastic layer are set back from the edges of the card and where at least two projections are provided on each of the four sides of the rectangle formed by the plastic layer. This design of the plastic layer makes it possible to position it on the laminate layer in an especially advantageous manner. The projections advantageously have a rounded form. The rounded form makes it possible for the plastic layer to make more-or-less point-wise contact with the edges of the laminate layer, which reduces the danger of damage to the plastic layer and the danger of its separation to a minimum. The plastic layer can be printed in a mirror-reversed manner on the side facing the card body or in a non-mirror-reversed manner on the side facing away from the card body. The card base body and the plastic layer are preferably welded together, with the result that it is practically impossible for the plastic layer to come loose from the card base body. Additional advantages and features of the invention are the object of the following description and of the drawings, which show an exemplary embodiment of the invention. The FIGURE shows a schematic diagram of a card according to the invention. A card, designated overall by the number 10, has a card base body 20, which comprises at least one layer of laminate, and a plastic layer 30, which is welded or laminated to the base body. The minimum of one layer of laminate forming the card base body 20 has an essentially rectangular shape with 4 edges 21, 22, 23, 24, each of which forms one side of the rectangle. The plastic layer 30 also has a rectangular shape conforming to that of the card base body 20 with the edges 31, 32, 33, 34, which also form the sides of a rectangle. Projections 35 are provided on each of the edges 31, 32, 33, 34 of the plastic layer, such as a printed piece of PVC film. Two such projections, for example, can be provided on each of the four sides. These projections are used to position the plastic layer on the card base body 20 during the production of the card 10. These projections 35 have a rounded, possibly circular, shape. Because of this rounded, possibly circular, shape, it is ensured that, in practice, the projections of the plastic layer 30 terminate flush with the edges 21, 22, 23, 24 of the card base body 20 at only a single point in each case. This prevents damage to the plastic layer as a result of, for example, scuffing, which can occur especially when the card 10 is subjected to very intensive use. Setting the edges 31, 32, 33, 34 of the plastic layer 30 back from the edges 21, 22, 23, 24 of the base body 20 of the card is also a very effective way of preventing the plastic layer 30 welded or laminated to the card base body 20 from coming loose from the card base body 20. The plastic layer 30 can be printed on the side facing the base body 20 or on the side facing away from it. It can also be provided, however, merely as protection for the previously printed card base body 20. The plastic layer 30 and the card base body 20 are welded together to prevent the plastic layer 30 from coming loose from the card base body 20.
20050204
20080219
20050602
94902.0
0
THOMAS, ALEXANDER S
CARD
SMALL
0
ACCEPTED
2,005
10,515,926
ACCEPTED
Method and apparatus for optical mode conversion
A mode conversion apparatus including a dynamic waveguide section associated with a plurality of control elements that, when activated, are able to produce a periodic refractive-index perturbation pattern in the dynamic waveguide section, wherein the periodic refractive-index perturbation pattern is able to convert at least a fraction of an input signal from a first guided mode of the dynamic waveguide section into a second guided mode of the dynamic waveguide section.
1. A mode conversion apparatus comprising a dynamic waveguide section associated with a plurality of control elements that, when activated, are able to produce a periodic refractive-index perturbation pattern in said dynamic waveguide section, wherein said periodic refractive-index perturbation pattern is able to convert at least a fraction of an input signal from a first guided mode of said dynamic waveguide section into a second guided mode of said dynamic waveguide section. 2. The apparatus of claim 1 wherein said control elements are selectively activated to produce said periodic refractive-index perturbation pattern. 3. The apparatus of claim 1 wherein said control elements are controllably activated to produce said periodic refractive-index perturbation pattern. 4. The apparatus of claim 1 further comprising an input section able to guide at least said first guided mode. 5. The apparatus of claim 4 wherein said input section comprises an adiabatic waveguide expander. 6. The Apparatus of claim 5 wherein said adiabatic waveguide expander comprises a tapered waveguide. 7. The apparatus of claim 1 further comprising an output section able to guide at least one of said first and second guided modes. 8. The apparatus of claim 6 wherein said output waveguide comprises an adiabatic waveguide constrictor. 9. The Apparatus of claim 7 wherein said adiabatic waveguide constrictor comprises a tapered waveguide. 10. The apparatus of claim 1 wherein said dynamic section has a width sufficient to simultaneously guide both said first and second guided modes. 11. The apparatus of claim 1 wherein said plurality of control elements comprise an arrangement of heating elements able to produce, in response to electric power applied thereto, a predetermined increase in temperature at regions of said dynamic waveguide section substantially corresponding to said periodic refractive-index perturbation pattern. 12. The apparatus of claim 11 wherein said arrangement of heating elements comprises strips of an at least partially resistive material sequentially connected by strips of a substantially conducting material. 13. The apparatus of claim 11 wherein said arrangement of heating elements comprises a periodic configuration of strips of a substantially conducting material attached to a layer of an at least partially resisting material. 14. The apparatus of claim 11 wherein said heating elements are arranged in an apodization pattern able to produce a predetermined coupling between said first and second guided modes, wherein said coupling varies along the length of said dynamic section. 15. The apparatus of claim 14 wherein a transverse position of said heating elements relative to a center of said dynamic section varies according to a predetermined scheme. 16. The apparatus of claim 11 wherein said heating elements are arranged in a chirping scheme to create a predetermined variation of the period of said periodic perturbation pattern along the length of said dynamic section. 17. The apparatus of claim 16 wherein a width of said heating elements varies according to a predetermined scheme along the length of said dynamic section. 18. An optical filter comprising an apparatus as in claim 1, wherein said conversion is effective only within a pre-determined range of wavelengths of said input signal. 19. A variable optical attenuator comprising an apparatus as in claim 1, further comprising an attenuator input section associated with an input of said apparatus and an attenuator output section associated with an output of said apparatus, wherein said attenuator input and output sections are able to guide said first guided mode, and wherein said output section does not guide said second guided mode. 20. The apparatus of claim 19 wherein said first guided mode is a zero-order mode. 21. The apparatus of claim 19 wherein said attenuator input section and said attenuator output section are tapered. 22. A variable optical attenuator comprising: an attenuator input section able to guide an input signal in a first guided mode; a dynamic waveguide section associated with a plurality of control elements that, when activated, are able to produce a periodic refractive-index perturbation pattern in said dynamic waveguide section, wherein said periodic refractive-index perturbation pattern is able to convert a fraction of said input signal from said first guided mode into a second guided mode; and an attenuator output section able to guide said first guided mode and prevented from guiding said second guided mode. 23. The apparatus of claim 22 wherein said first guided mode is a zero-order mode. 24. A method of mode conversion comprising: selectively activating a periodic refractive-index perturbation pattern of a dynamic waveguide section to convert at least a fraction of an input signal from a first guided mode of said dynamic waveguide section into a second guided mode of said dynamic waveguide section. 25. The method of claim 24 wherein selectively activating comprises controllably activating said periodic refractive-index perturbation pattern to convert a predetermined fraction of said first guided mode into said second guided mode. 26. A Dynamic Gain Equalizer comprising a plurality of filters as in claim 18, each having a maximum response at a pre-determined wavelength and a wavelength response representing a basic function, respectively, such that said Dynamic Gain Equalizer has a predetermined wavelength filtering function.
FIELD OF THE INVENTION The present invention relates generally to the field of optical devices and, more specifically, to optically converting a mode order of a light signal. BACKGROUND OF THE INVENTION In the field of integrated optics, there may be a need to use a mode conversion device, such as a mode converter (MC). European Patent Application EP-0513919-A1 to Van Der Tol describes a passive device for mode conversion of a first mode into a second pre-defined mode. The device is described to include a periodic geometrical structure consisting of a periodic sequence of two wave-guiding subsections within each period, wherein the lengths of the subsections and the number of periods being matched to a pre-determined conversion fraction may be designed to allow coupling of a first pre-defined guided mode to a second pre-defined guided mode. Similar devices are also described in U.S. Pat. No. 5,703,977 to Pedersen et al and in European Patent Application EP0645650A1 to Van Der Tol. In such passive devices, the fraction of light being converted is pre-determined by the geometry of the device and, therefore, the activation and operation of such devices cannot be selectively adjusted or controlled. U.S. Pat. No. 5,574,808 to Van Der Tol et al describes a mechanism for activating and de-activating a mode-conversion device. The described device is activated by activating an electrode designed to disrupt the coupling between guided modes of the device, thereby to convert the coupling of a signal from a first guided mode to a second guided mode. SUMMARY OF EMBODIMENTS OF THE INVENTION Exemplary embodiments of the present invention provide a Mode Converter (MC), which may operate in conjunction with one or more single-mode and/or multi-mode waveguides. The MC according to embodiments of the invention may have at least two states of operation, namely, “On” and “Off”. When the MC is at the “Off” state, a mode of order i enters the MC and the same mode of order i may exit the MC. In contrast, when the MC is set to the “On” state, the mode of order i entering the MC may be at least partially converted to a mode of order j exiting the MC. According to some of these exemplary embodiments, only a certain portion of the mode of order I may be converted into the mode of order j, such that two mode-orders, for example, i and j, may exit the MC. The relative portion of converted light may be controllably varied, if desired. In other exemplary embodiments, the signal carried by mode order i is converted substantially entirely to mode order j. Exemplary embodiments of the invention enable dynamic and/or selective and/or tunable mode conversion of a fraction of a signal component propagating according to a first guided mode, or substantially the entire signal component, into a signal component propagating at least partially according to a desired second guided mode. In accordance with exemplary embodiments of the invention, a MC may include an input section, a dynamic waveguide section, and an output section. The dynamic waveguide section may be surrounded by a top cladding, a bottom cladding, a base substrate and a set of control elements, e.g., heating elements, which may be attached to an outer surface of the top or bottom cladding surrounding the dynamic waveguide section. In exemplary embodiments of the invention, a thermo-optical effect may be utilized to achieve selective and/or dynamic and/or tunable refractive-index perturbation. The heating elements may be implemented in the form of electrodes, for example, strips of material having a suitable electrical resistance supplied with electrical current to produce a predetermined increase in temperature, thereby tunably controlling the temperature distribution along the dynamic section of the device. According to exemplary embodiments of the invention, the magnitude of electrical power supplied to the heating elements may be controllably and/or selectively varied to allow controllable tuning of the conversion between the first guided mode and the desired second guided mode. Supplying the heating elements with greater electrical power per unit length may increase the temperature more sharply and, thus, may result in a higher coupling coefficient between the first and second guided modes. The coupling coefficient may influence the fraction of light converted between the modes. Thus, the power supplied to the heating elements may be dynamically tunable to provide at least a partial conversion between the first guided mode and the desired second guided mode. According to embodiments of the invention, the MC may be combined with additional elements, e.g., with appropriate input and output waveguides, to form a Variable Optical Attenuator (VOA), which may provide controllable attenuation of an optical signal. In further exemplary embodiments of the invention, the MC may be adapted for use as a wavelength filter, which may be tunable to convert signals only within a predetermined wavelength range. According to some exemplary variations of this embodiment, a set of one or more mode converters may be adapted to provide a Dynamic Gain Equalizer (DGE), which may be used in optical networks, for example, to “flatten” the spectra of optical signals. BRIEF DESCRIPTION OF THE DRAWINGS The subject matter regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of the specification. The invention, however, both as to organization and method of operation, together with objects, features and advantages thereof, may best be understood by reference to the following detailed description when read with the accompanied drawings in which: FIG. 1A is a schematic, simplified plane view illustration of a mode converter in accordance with exemplary embodiments of the present invention; FIG. 1B is a schematic, simplified, front view, cross-sectional, illustration of the mode converter of FIG. 1A; FIG. 1C is a schematic illustration of graph depicting temperature increase as a function of location in a cross-section of a waveguide, in a vicinity of a heating element, according to exemplary embodiments of the invention; FIG. 2A is a schematic graph depicting light intensity and area undergoing refractive-index perturbation, respectively, as a function of position within a mode converter having a relatively narrow dynamic section in accordance with an exemplary embodiment of the invention; FIG. 2B is a schematic graph depicting light intensity and area undergoing refractive-index perturbation, respectively, as a function of position within a mode converter having a relatively wide dynamic section in accordance with an exemplary embodiment of the invention; FIG. 3A is a schematic, top view, cross-sectional illustration of a mode converter according to an exemplary embodiment of the invention, depicting conversion between a zero-order mode and a first-order mode; FIG. 3B is a schematic illustration of a graph depicting a fraction of light converted from the zeroorder mode to the first-order mode by the mode converter of FIG. 3A as a function of a temperature increase selectively applied to portions of the mode converter; FIGS. 4A and 4B are schematic illustrations of two exemplary configurations, respectively, of heating elements of a mode converter in accordance with embodiments of the present invention; FIG. 5 is a schematic, simplified, plane view illustration of a Variable Optical Attenuator (VOA) including a mode converter in accordance with exemplary embodiments of the present invention; FIG. 6 is a schematic illustration of a graph depicting a wavelength response curve of a mode converter, and a wavelength response curve of a wavelength filter including an adapted mode converter, in accordance with exemplary embodiments of the present invention; FIG. 7A is a schematic, simplified, plane view illustration of a heating element arrangement for apodization of a mode converter in accordance with exemplary embodiments of the present invention; FIG. 7B is a schematic illustration of a graph depicting coupling strength as a function of location along a dynamic section associated with the heating element arrangement of FIG. 7A; FIG. 7C is a schematic, simplified plane view illustration of a heating element arrangement for chirping of a mode converter in accordance with exemplary embodiments of the present invention; FIG. 7D is a schematic illustration of a graph depicting grating period as a function of location along a dynamic section associated with the heating element arrangement of FIG. 7C; FIG. 8 is a schematic illustration of a Dynamic Gain Equalizer (DGE) constructed using a set of mode converters, in accordance with an embodiment of the present invention; and FIG. 9 is a schematic illustration of a graph depicting response versus wavelength of the DGE of FIG. 8. It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn accurately or to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity or several physical components included in one element. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. It will be appreciated that these figures present examples of embodiments of the present invention and are not intended to limit the scope of the invention. DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those of ordinary skill in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, components and circuits may not have been described in detail so as not to obscure the present invention. According to embodiments of the invention, a Mode Converter (MC) may operate in conjunction with one or more single mode and/or multi-mode waveguides, and may have at least two states of operation, e.g., “On” and “Off”. When the MC is at the “Off”state, the mode of order i enters the MC and the same mode of order i exits the MC. When the MC is at the “On” state, the mode of order i entering the MC may be at least partially converted into a mode of order j that exits the MC. According to some of these embodiments, the mode of order i may be partially converted into the mode of order j, such that two mode-orders, e.g. i and j, exit the MC. The fraction converted between the two modes may be controlled as described below. In other exemplary embodiments, the signal carried by mode order i is converted substantially entirely to mode order j. Exemplary embodiments of the present invention enable dynamic, tunable, mode conversion of a fraction of a signal component propagating according to a first guided mode, or substantially the entire signal component, into a signal component propagating according to a desired second guided mode. Reference is made to FIGS. 1A and 1B, which schematically illustrate a MC 100 in accordance with exemplary embodiments of the present invention MC 100 may include an input section 101, a dynamic waveguide section 102 and an output section 103. Input section 101 may be implemented in the form of an adiabatic waveguide expander, and output section 103 may be implemented in the form of an adiabatic waveguide constrictor, as explained in detail below. According to exemplary embodiments of the invention, input section 101 may support up to N guided modes. An input end 104 of input section 101 may have a width sufficient to support a required amount of N guided modes, yet sufficiently narrow to avoid unnecessary mixing between the N guided modes. In embodiments of the invention, the effective refractive index, which relates to a propagation constant of the signal, of a signal carried by a mode of a waveguide having a waveguide-core and a waveguide-cladding, may be smaller than the refractive index of the waveguide-core and larger than the refractive index of the waveguide-cladding. For given refractive indices of the waveguide-core and to waveguide-cladding, a waveguide supporting a larger number of mode-orders, e.g., a relatively wider waveguide, may result in a smaller difference between the propagation constants corresponding to each of the supported mode orders, respectively. The smaller the difference between the propagation constants corresponding to different mode orders, the higher the coupling, which may result in unnecessary mixing, between the different mode orders, for example, due to variations in the waveguide structure. According to exemplary embodiments of the invention, input section 101 may be shaped as an adiabatic waveguide expander, for example, having a tapered structure, whereby the width of the waveguide gradually increases to substantially the width of dynamic section 102 at an interface 106 between input section 101 and dynamic section 102. Output section 103 may be shaped as an adiabatic waveguide restrictor, for example, having a tapered structure substantially analogous to the input section structure, yet in a reversed direction, whereby the waveguide is gradually decreased from the width of dynamic section 102 to a relatively narrow width at output end 110, for example, to the width of input end 104. The length of the input and output sections may be adapted to allow a desired adiabatic expansion and constriction, respectively, of the waveguide. Adiabatic expansion/constriction in this context means that an i-th mode of input waveguide 101 at its input end 104 may become the i-th mode at interface 105, and vice-versa, substantially without affecting any other modes. The degree of adiabaticity of the expansion/constriction may increase with the length of the tapered sections. The adiabatic expansion/constriction of input section 101 and output section 103 may be achieved in the form of various tapered structures known in the art, including but not limited to linear, polynomial, exponential, or hyperbolic tapered structures. In an exemplary embodiment of the invention, dynamic section 102 may be surrounded by a top cladding 106, a bottom cladding 107, a base substrate 109, and a plurality of control elements, e.g., heating elements 108, which elements may be attached, e.g., located on, the outer surface of top cladding 106. The top and bottom cladding may be formed of any material suitable to line or cover dynamic section 102, for example, a plastic or glass sheath that may surround dynamic section 102 and may be fused to the waveguide. The cladding may reflect light guided by dynamic section 102 thereby to prevent unnecessary loss of light and strengthen the guided light intensity. According to embodiments of the invention, the refractive index of the material of dynamic section 102 at normal temperature may be generally higher than the refractive index of claddings 106 and 107. Base substrate 109 may be formed of any material known in the art, for example, silicon. Base substrate 109 may act as a heat sink, and may be held at a substantially constant temperature by use of a Thermo-Electric Cooler (TEC) or any other device adapted to keep the substrate at a substantially constant temperature. Embodiments of the present invention allow for dynamic, tunable, effective refractive-index perturbation. Such perturbation may be implemented by several methods including but not limited to charge carrier injection, acousto-optic effect, electro optical effect, optical-optic effect, or thermo-optic effect. Refractive-index perturbation, in accordance with embodiments of the invention, may be achieved by creating a periodical refractive-index pattern including a periodic concatenation of two subsections with different refractive indices. According to exemplary embodiments of the invention, refractive-index perturbation as described herein, or any other suitable perturbation scheme, may be applied by elements 108 to a region of dynamic section 102, while other regions of dynamic section 102 may remain unaffected. In exemplary embodiments of the present invention, a thermo optical effect may be utilized to achieve dynamic refractive index perturbation. Heating elements 108, which may act as thermo-optical refractive index modifiers, may be implemented in the form of electrodes, for example, strips of material having predetermined electrical resistance. By controllably and/or selectively supplying electrical current to the electrodes, an increase in temperature in the vicinities of each of the electrodes results in a predetermined temperature distribution across dynamic section 102. An example of such temperature distribution is illustrated schematically by isothermal lines 150 in FIG. 1C. The thermo-optical effect evoked by the controllable and/or selective temperature increase may create a refractive index perturbation in regions of dynamic section 102 covered by heating elements 108, while regions not covered by heating elements 108 may not undergo any refractive index perturbation. Thus, a periodic refractive index perturbation may be achieved by implementing a periodic arrangement of heating elements 108. FIG. 2A schematically depicts graphs of light intensity and area undergoing refractive-index perturbation, respectively, as a function of position within a mode converter having a relatively narrow dynamic section in accordance with an exemplary embodiment of the invention, and FIG. 2B schematically depicts graphs of light intensity and area undergoing refractive-index perturbation, respectively, as a function of position within a mode converter having a relatively wide dynamic section in accordance with an exemplary embodiment of the invention. According to perturbation theory, a coupling coefficient between two modes may be estimated by the following equation: Coupling coefficient=∫ψ1Δψ2dxdy (1) wherein ψ1 and ψ2 are transverse profiles of a zero-order mode and a first-order mode, respectively, and Δ is a refractive index perturbation term. Since the zero-order mode, ψ1, and refractive index perturbation term, Δ, are constantly positive, the sign of the coupling coefficient depends on the sign of the first-order mode, ψ2. To analyze the significance of Equation 1, two cases may be examined, as illustrated schematically in FIGS. 2A and 2B, respectively. If a refractive-index perturbation field 201 affects a relatively large portion of dynamic section 102, as illustrated in FIG. 2A, the field may influence both a positive part 203 and a negative part 204 of a first order mode 202, thereby allowing the coupling obtained in positive part 203 to be partially canceled by the negative contribution of negative part 204. In contrast, if an index perturbation field 205 affects only a relatively small part of dynamic section 102 and affects only a positive part 207 of a first-order mode 206, as illustrated in FIG. 2B, no cancellation between positive part 207 and a negative part 208 may take place, whereby sufficient coupling may be obtained to allow conversion from a zero-order mode 209 to first-order mode 206. According to embodiments of the invention, the width of dynamic section 102 may be designed to provide a degree of coupling sufficient for conversion of a signal from the first guided mode to the desired second guided mode. A required width of the dynamic section may be determined according to the desired order of the second mode and according to the slope of the index perturbation profile created by the heating elements, e.g., the steeper the slope of the perturbation profile and the lower the order of the desired second mode, the narrower the dynamic section required to provide the degree of coupling sufficient to allow the conversion from the first guided mode to the desired second guided mode. According to embodiments of the invention, the refractive-index perturbation may be performed periodically along the dynamic section. A grating period, Λ0, i.e., the period of the refractive-index perturbation, may be proportional to the width of the dynamic section, e.g., the wider the dynamic section the larger the grating period, as explained below. According to embodiments of the invention, in order to increase the coupling coefficient between the first guided mode and the desired second guided mode, the grating period may be reciprocal to a phase difference between the first guided mode and the second guided mode, as described above. The phase of each of the mode-orders is proportional to the effective refractive index of the mode-order, respectively. Since the difference between the refractive indices is reciprocally proportional to the width of the waveguide, as described above, the grating period may be proportional to the width of the waveguide, i.e., a wider waveguide will correspond to a larger grating period. Therefore, the grating period, Λ0, may be calculated using the following equation: Λ 0 = λ 0 n 1 ⁡ ( λ 0 ) - n 2 ⁡ ( λ 0 ) ( 2 ) wherein λ0 is the wavelength of the signal, and n1(λ0) and n2(λ0) are the refractive indices corresponding to the first guided mode and the second guided mode, respectively. According to embodiments of the invention, the conversion of the first guided mode into the second guided mode may be preformed gradually, such that each period of the perturbation converts a portion of the first guided mode into the second guided mode. Therefore, a number of successive grating periods may be used to convert a desired aggregated fraction of at least part of the first guided mode into the second guided mode. According to embodiments of the invention, the heating elements may be dynamically activated, e.g., by controlling the electric power supplied to the control elements, to control the portion of the first guided mode which is converted into the second guided mode at each grating period, as described above. According to embodiments of the invention, the refractive index perturbation profile may change the mode-coupling coefficient between the first guided mode and other mode orders. By controlling the refractive index perturbation profile, e.g., by tunable activation of the control elements, the conversion of a desired fraction of the light signal from the first guided mode to the desired second guided mode may be controlled. According to embodiments of the invention, the magnitude of electrical power supplied to heating elements 108 (FIG. 1) may be varied to allow a tunable degree of coupling between the two modes. Heating elements 108 (FIG. 1) may be supplied with a predetermined electric power per unit length of the heating elements so as to create a refractive-index perturbation profile corresponding to the coupling coefficient required for conversion between the two modes. According to some embodiments of the invention, the heating elements may be selectively activated, e.g., by selectively, controllably supplying electric power to some of the control elements, so as to create a grating period corresponding to a desired aggregated conversion fraction, as described above. FIG. 3A is a schematic, top-view, cross-sectional illustration of a mode converter according to an exemplary embodiment of the invention, showing conversion between a zero-order mode and a first-order mode, and FIG. 3B is a schematic illustration of a graph depicting a fraction of light converted from the zero-order mode to the first-order mode as a function of a temperature increase selectively applied to portions of the mode converter of FIG. 3A. Referring again to FIG. 1, according to some exemplary embodiments of the invention, MC 100 may have a total length, Ltotal, of between 500 μm and 50000 μm, for example, about 6000 μm; input end 104 may have a width of between 4 μm and 60 μm, for example, about 12 μm, and a height of 0.5 μm to 8 μm, for example, about 6 μm; dynamic section 102 may have a width of between 6 μm and 100 μm, for example, about 24 μm, and a height of between 0.5 μm and 8 μm, for example, about 6 μm; and output end 110 may have a width of between 4 μm and 60 μm, for example, about 12 μm, and a height of between 0.5 μm and 8 μm, for example, about 6 μm. Further, in exemplary embodiments of the invention, top cladding 106 may have a height of between 6 μm and 30 μm, for example, about 10 μm, and bottom cladding 107 may have a height of between 6 μm and 30 μm, for example, about 15 μm. Additionally, in exemplary embodiments of the invention, there may be a refractive index difference, Δn, between the dynamic section and the cladding of between 0.005 and 3.0, for example, about 0.01. In exemplary embodiments of the invention, the MC may also include heating elements 108 (FIG. 1) spaced in a repetitive grating period, Λ0, of between 50 μm and 10000 μm, for example, about 2715 μm. In this exemplary embodiment of the invention, adiabatic expansion and constriction of the waveguide may be achieved by hyperbolic tapering, wherein the tapered length of the input section and the output section, respectively, Ltapering may be between 50 μm and 6000 μm, for example, about 800 μm. A power level, P, for example, 0.05 Watts (W) to 5.0 W, e.g., about 2.1 W, may be supplied to the heating elements to create a corresponding maximal temperature increase of between 10 and 500 degrees Kelvin (°K), for example, about 150° K, in the vicinity of each of the electrodes, as described above. This temperature increase may allow conversion of a predetermined fraction of the signal from the zero-order mode to the first-order mode, as illustrated in FIG. 3A. For example, in order to achieve a conversion of about 99% between the zero-order mode and the first-order mode, a temperature increase of 150°K may be required, as illustrated in FIG. 3B. The temperature increase may be tuned by controlling the power supplied to the electrodes, as described above. Thus, any desired fraction of the zero-order mode may be converted into the first-order mode, by creating an appropriate temperature increase corresponding to the desired fraction of conversion, as illustrated in FIG. 3B. According to other embodiments of the invention, different configurations, e.g. height and width of the different MC sections, Λ0, Ltapering, P, or any other parameter defining the MC, may be designed in order to allow at least partial, tunable mode conversion between any two desired mode-orders. According to exemplary embodiments of the invention, MC 100 (FIG. 1) may provide selective, dynamic control, i.e., tunability, of the fraction of light converted between two modes, thereby providing dynamic switching between “On” and “Off” states of the MC in relation to desired modes. When at the “Off” state, the MC may not require electric power and may represent a simple tapered waveguide, providing sufficiently low cross-talk, e.g. minimal unnecessary mixing between modes, as described above. When at the “On” state, a desired fraction of light carried by a chosen guided mode, e.g., a zero-order mode, may be selectively converted to another guided mode, e.g., a first-order mode, by controlling the power supplied to heating elements 108 (FIG. 1). Reference is now made to FIGS. 4A and 4B, which illustrate two exemplary configurations of heating elements 108 (FIG. 1) of a MC in accordance with embodiments of the invention. According to embodiments of the invention, heating elements 108 (FIG. 1) may be configured in different ways to provide a desired periodical refractive-index pattern, for example, the configuration illustrated in FIGS. 4A and 4B. The configuration shown in FIG. 4A may be produced by etching a desired pattern out of a resisting material layer, leaving a plurality of strips 402 that may be used as heating elements 108 (FIG. 1). Strips 402 may be sequentially connected to each other by strips 404 of a suitable conducting material, for example, using Aluminum strips. To produce the configuration of FIG. 4B, a layer of electrically-resistant material 406 may initially be covered with a layer of conducting material 408, which may subsequently be etched in accordance with the desired pattern. In the resultant pattern, portions of layer 406 not covered with conducting layer 408 act as heating elements 108 (FIG. 1), whereas portions covered with non-etched conducting material 408 do not produce heat in response to an applied voltage. According to embodiments of the invention, MC 100 may be combined with additional elements in order to create a Variable Optical Attenuator (VOA), which may provide controllable, e.g., tunable, attenuation of an optical signal, as discussed below. Reference is now made to FIG. 5, which is a schematic, simplified, plane view illustration of a VOA 500 including MC 100 in accordance with exemplary embodiments of the present invention. In order to implement VOA 500, according to exemplary embodiments of the invention, a VOA input section 502 and a VOA output section 504 may be added to the input and output ends, respectively, of a MC such as MC 100. In some embodiments of the invention, VOA input section 502 may be adapted to provide adiabatic expansion from a width of an input waveguide (not shown), for example a narrow waveguide designed to support only one mode, e.g., a zero-order mode, of an input signal, to the width of MC input section 102, which may support higher-order modes. VOA output section 504 may be designed to provide adiabatic constriction from the width of MC output section 103, which is may support higher-order modes, to the width of an output waveguide (not shown), which may support only one mode, for example, the same order mode supported by the input waveguide. According to embodiments of the invention, attenuation of the input light signal may be achieved by using MC 100 to convert a desired fraction of the input light signal from the input mode into a higher-order mode. Thus, a partially converted light signal, exiting the MC, may include the converted fraction of the higher-order mode and a non-converted fraction of the input-order mode. However, because the output waveguide may be designed to support only the input-order mode, all the power carried by the higher-order mode may be diffracted, dispersed, or otherwise dissipated by a cladding of the output waveguide. Therefore, the final output of VOA 500 is an attenuated signal retaining the mode order of the input signal. According to embodiments of the invention, the MC may be tunably controlled, as described above, to provide mode conversion of the desired fraction of the light signal. The larger the converted fraction, the smaller the non-converted fraction and, therefore, more conversion results in less power of the light signal exiting the VOA. In other words, a larger conversion fraction results in a higher attenuation level of the VOA. Thus, the maximal attenuation level achievable by VOA 500 may depend on the efficiency at which the MC of the VOA may convert the input-order mode into the higher-order mode. According to some of these embodiments, a number of VOA devices 500 may be cascaded to obtain a desired aggregated attenuation level. Implementation of such cascading will be apparent to those of ordinary skill in the art. According to embodiments of the invention, in order to provide a desired mode conversion, heating elements 108 (FIG. 1) may be used to provide a periodic refractive index perturbation pattern, as described above. According to exemplary embodiments of the invention, this feature may be utilized by an adaptation of the MC described above for use as a wavelength filter, as explained below. A wavelength response of the MC may be defined as a correlation between the conversion ability of the MC and the wavelength of an input signal. In exemplary embodiments of the invention, the MC may be adapted to operate as a wavelength filter, for example, by using various techniques that improve the wavelength response of the MC, for example, apodization or chirping, as described below. FIG. 6 schematically illustrates a graph depicting a wavelength response curve 601 of a mode converter as described above, compared with a wavelength response curve 602 of a MC adapted to operate as a wavelength filter, in accordance with exemplary embodiments of the present invention. The areas confined under curves 602 and 601 may define the wavelength-ranges of signals that may be converted by each of the mode converters. As described above with reference to Equation 2, the grating period, Λ0, of the MC may relate to the wavelength of the input signal, Λ0. Thus, by controllably tuning the grating period of MC 100 (FIG. 1), as described above, a tunable wavelength response may be obtained. A Full-Width-Half-Maximum (FWHM) of a wavelength response curve of a MC may depend on the coupling strength of the MC. The stronger the coupling, the larger the FWHM of the wavelength response curve. Accordingly, a weaker coupling may result in a relatively smaller FWHM. Thus, a relatively small FWHM may provide a relatively sensitive wavelength filter, allowing conversion of signals having a pre-determined range of wavelengths. However, a weaker coupling may require a larger number of grating periods to achieve full mode-conversion, as described above. A larger number of grating periods may require a longer MC, which may have a wavelength response as illustrated by curve 601. As shown in FIG. 6, curve 601 may have a relatively narrow peak and relatively high lobes. Thus, the MC may allow conversion of a relatively wide range of signals having a relatively wide range of wavelengths, respectively. As further shown in FIG. 6, wavelength response curve 602 may have a wider and flattened peak and suppressed side-lobes in comparison to response curve 601. The suppressed lobs of curve 602 imply MC 100 (FIG. 1), when further adapted to operate as a wavelength filter, for example, using apodization and/or chirping techniques as described below, may convert a relatively narrow range of signals having a relatively narrow range of wavelength, respectively. Thus, a wavelength filter using a mode converter in accordance with embodiments of the invention may allow a more accurate, tunable, conversion of signals within a pre-determined range of wavelengths, centered at a wavelength λ0, and may not allow conversion of signals outside the predetermined wavelength range, as described below. FIG. 7A schematically illustrates an exemplary arrangement 702 of heating elements 108 that may produce an apodization effect, in accordance with exemplary embodiments of the invention, and FIG. 7B schematically illustrates a graph depicting coupling strength as a function of location along dynamic section 102 associated with the heating element arrangement of FIG. 7A. Apodization, in this context, means that a perturbation field applied by heating elements 108 may not be homogeneous, so that the mode-coupling strength may vary with length. In arrangement 702, the positions of heating elements 108 relative to the center of dynamic section 102 may be varied to produce the desired apodization effect. The apodization effect may be used to create a varying coupling strength, within a range 703, along dynamic section 102, as illustrated schematically in FIG. 7B. It will be appreciated by persons skilled in the art that arrangement 702 may allow conversion substantially only of signals whose wavelengths correspond to coupling levels within range 703, as described above. FIG. 7C illustrates an arrangement 704 of heating elements 108 to achieve a desired chirping effect, in accordance with exemplary embodiments of the invention, and FIG. 7D schematically illustrates a graph depicting grating period as a function of location along dynamic section 102 associated with the heating element arrangement of FIG. 7C. Chirping, according to embodiments of the invention, may be based on slight period variations along the length of the dynamic section. In arrangement 704, the width of heating elements 108 may be varied along the length of the dynamic section to produce a desired chirping effect. The chirping effect may be used to create a varying grating period, within a range 705, along dynamic section 102, as illustrated schematically in FIG. 7D. It will be appreciated by persons skilled in the art that arrangement 704 may allow conversion substantially only of signals whose wavelengths correspond to grating periods within range 705, as described above. According to further embodiments of the invention, one or more mode converters as described herein may be adapted to perform the function of a Dynamic Gain Equalizer (DGE), which may be used in optical networks, e.g., for “spectrum flattening” of an optical signal. In exemplary embodiments of the invention, the DGE may provide a predetermined wavelength filtering function, for example, to compensate for a wavelength dependent response of an amplifier. A filter function over a given spectrum may be implemented by dividing the spectrum to N sections, each having a representative, e.g., central wavelength, λi. Then, by appropriately combining N basic filter functions, each centered at a different wavelength λi, wherein at least one filter function is implemented using a mode converter as described above with reference to FIG. 6, a more complex filter function may be approximated, as is known in the art. It will be appreciated that the larger the number of basic functions, the better the approximation that may be achieved. According to an exemplary embodiment of the invention, a DGE may be implemented by combining N mode converters, such as MC 100 (FIG. 1), wherein each MC 100 may have a grating period corresponding to a maximum response at λi and a wavelength response representing a basic function. FIG. 8 schematically illustrates a DGE 800 constructed using a set of mode converters 100, in accordance with an embodiment of the present invention, and FIG. 9 schematically illustrates a graph depicting response versus wavelength of DGE 800. According to an exemplary embodiment of the invention, DGE 800 may include a combination of six mode converters 100 (FIG. 1), which may be connected in a row, each having a grating period corresponding to a spectrum centered at a different wavelength, λi, together providing an expanded transmission spectrum covering a desired wavelength range, for example, a C-band 902. As is known in the art, a C-band represents a range of wavelengths commonly used in Optical communications, for example, between approximately 1.525 micrometers and approximately 1.57 micrometers. While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made. Embodiments of the present invention may include other apparatuses for performing the operations herein. Such apparatuses may integrate the elements discussed, or may comprise alternative components to carry out the same purpose. It will be appreciated by persons skilled in the art that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.
<SOH> BACKGROUND OF THE INVENTION <EOH>In the field of integrated optics, there may be a need to use a mode conversion device, such as a mode converter (MC). European Patent Application EP-0513919-A1 to Van Der Tol describes a passive device for mode conversion of a first mode into a second pre-defined mode. The device is described to include a periodic geometrical structure consisting of a periodic sequence of two wave-guiding subsections within each period, wherein the lengths of the subsections and the number of periods being matched to a pre-determined conversion fraction may be designed to allow coupling of a first pre-defined guided mode to a second pre-defined guided mode. Similar devices are also described in U.S. Pat. No. 5,703,977 to Pedersen et al and in European Patent Application EP0645650A1 to Van Der Tol. In such passive devices, the fraction of light being converted is pre-determined by the geometry of the device and, therefore, the activation and operation of such devices cannot be selectively adjusted or controlled. U.S. Pat. No. 5,574,808 to Van Der Tol et al describes a mechanism for activating and de-activating a mode-conversion device. The described device is activated by activating an electrode designed to disrupt the coupling between guided modes of the device, thereby to convert the coupling of a signal from a first guided mode to a second guided mode.
<SOH> SUMMARY OF EMBODIMENTS OF THE INVENTION <EOH>Exemplary embodiments of the present invention provide a Mode Converter (MC), which may operate in conjunction with one or more single-mode and/or multi-mode waveguides. The MC according to embodiments of the invention may have at least two states of operation, namely, “On” and “Off”. When the MC is at the “Off” state, a mode of order i enters the MC and the same mode of order i may exit the MC. In contrast, when the MC is set to the “On” state, the mode of order i entering the MC may be at least partially converted to a mode of order j exiting the MC. According to some of these exemplary embodiments, only a certain portion of the mode of order I may be converted into the mode of order j, such that two mode-orders, for example, i and j, may exit the MC. The relative portion of converted light may be controllably varied, if desired. In other exemplary embodiments, the signal carried by mode order i is converted substantially entirely to mode order j. Exemplary embodiments of the invention enable dynamic and/or selective and/or tunable mode conversion of a fraction of a signal component propagating according to a first guided mode, or substantially the entire signal component, into a signal component propagating at least partially according to a desired second guided mode. In accordance with exemplary embodiments of the invention, a MC may include an input section, a dynamic waveguide section, and an output section. The dynamic waveguide section may be surrounded by a top cladding, a bottom cladding, a base substrate and a set of control elements, e.g., heating elements, which may be attached to an outer surface of the top or bottom cladding surrounding the dynamic waveguide section. In exemplary embodiments of the invention, a thermo-optical effect may be utilized to achieve selective and/or dynamic and/or tunable refractive-index perturbation. The heating elements may be implemented in the form of electrodes, for example, strips of material having a suitable electrical resistance supplied with electrical current to produce a predetermined increase in temperature, thereby tunably controlling the temperature distribution along the dynamic section of the device. According to exemplary embodiments of the invention, the magnitude of electrical power supplied to the heating elements may be controllably and/or selectively varied to allow controllable tuning of the conversion between the first guided mode and the desired second guided mode. Supplying the heating elements with greater electrical power per unit length may increase the temperature more sharply and, thus, may result in a higher coupling coefficient between the first and second guided modes. The coupling coefficient may influence the fraction of light converted between the modes. Thus, the power supplied to the heating elements may be dynamically tunable to provide at least a partial conversion between the first guided mode and the desired second guided mode. According to embodiments of the invention, the MC may be combined with additional elements, e.g., with appropriate input and output waveguides, to form a Variable Optical Attenuator (VOA), which may provide controllable attenuation of an optical signal. In further exemplary embodiments of the invention, the MC may be adapted for use as a wavelength filter, which may be tunable to convert signals only within a predetermined wavelength range. According to some exemplary variations of this embodiment, a set of one or more mode converters may be adapted to provide a Dynamic Gain Equalizer (DGE), which may be used in optical networks, for example, to “flatten” the spectra of optical signals.
20041124
20070515
20050721
98365.0
0
WONG, ERIC K
METHOD AND APPARATUS FOR OPTICAL MODE CONVERSION
UNDISCOUNTED
0
ACCEPTED
2,004
10,515,972
ACCEPTED
Industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive dielectric materials
Industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive dielectric materials comprises a radio-frequency voltage generator and an applicator device for applying radio-frequency electromagnetic fields. The applicator device comprises a plurality of electrodes electrically connected to the electrical generator for generating between then a radio-frequency electromagnetic field with electrical and magnetic components arranged in a preferential direction. The applicator device further comprises at least one pair of equipotential electrodes substantially aligned in the preferential direction and material transportation means for housing and transporting semiconductive dielectric material within the applicator device in a direction substantially parallel to the preferential direction.
1. Applicator device for applying radio-frequency electromagnetic fields to semiconductive dielectric materials, of the type comprising a plurality of electrodes (12, 13, 14, 15) which are connected, in use, to an electrical generator (10) for generating between them a radio-frequency electromagnetic field comprising electrical and magnetic-components arranged in a preferential direction, and material transportation mean (32) for housing and transporting semiconductive dielectric material, at least one pair of equipotential electrodes (12, 14) being arranged substantially in alignment in the preferential direction, the transportation means (32) transporting the material, within the applicator device (1), in a direction substantially parallel to the preferential direction, characterized in that each electrode (12, 13, 14, 15) comprises an electrically-conductive plate in which at least one opening (30) is formed, and the transportation means (32) being inserted in the opening (30) in order to extend through the plates in the preferential direction, application means (40) being engaged with at least one of the pairs of electrodes (12, 13, 14, 15) and disposed in the vicinity of the transportation means (32). 2. Applicator device according to claim 1, characterized in that it comprises at least one first pair of electrodes (13, 15) which can be connected electrically to the earth potential in use, at least one second pair of electrodes (12, 14) which can be connected electrically to the electrical generator (10) in use, and connecting elements (16) connected to the second pair of electrodes (12, 14) so as to keep both of the electrodes at the same potential, the second pair of electrodes (12, 14) being arranged between the electrodes of the first pair of electrodes (13, 15). 3. Applicator device according to claim 3, characterized in that the application means comprise metal cylinders (40). 4. Applicator device according to claim 3, characterized in that the length of the metal cylinders (40) is predominant in comparison with their diameter. 5. Applicator device according to claim 3, characterized in that it comprises reinforcing mean (50) arranged around the transportation mean (32) for preventing deformation of the transportation means (32) in use owing to thermal shock of the material contained therein. 6. Applicator device according to claim 5, characterized in that the reinforcing means comprise cylinders made of insulating material (50) disposed between the application mean (40). 7. Applicator device according to claim 6, characterized in that it can contain several transportation means (32) connectable to one another in series or in parallel. 8. Applicator device according to any one of the preceding claims, characterized in that it further comprises support means (22, 24, 26) for supporting the pairs of electrodes, the support means enabling the relative distance of the electrodes to be varied selectively, in use. 9. Industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive materials, of the type comprising a radio-frequency voltage generator (10) and an applicator device (1) for the application of radio-frequency electromagnetic fields to semiconductive dielectric materials, characterized in that the applicator device is defined by any one of the preceding claims. 10. Industrial apparatus according to claim 9, characterized in that selectively adjustable phase-modification means are disposed between at least one pair of electrodes (12, 13) for displacing the phase of the electrical potentials of the at least one pair of electrodes relative to one another in use. 11. Industrial apparatus according to claim 9, characterized in that each electrode of the applicator device can be connected to a load-adaptation network constructed by means of passive resistive, inductive, and/or capacitive electrical elements, and disposed between the electrical generator (10) and the applicator device (1). 12. Industrial apparatus according to claim 9, characterized in that the voltage generator can generate a radio-frequency voltage or current with a frequency of between 1 kHz and 1 GHz at its terminals. 13. Industrial apparatus according to claim 9, characterized in that it comprises at least one first pair of electrodes (13, 15) electrically connected to an earth potential, at least one second pair of electrodes (12, 14) electrically connected to the voltage generator (10), and connecting elements (16) connected to the second pair of electrodes (12, 14) in a manner such as to keep both of the electrodes at the same potential, the second pair of electrodes (12, 14) being disposed between the electrodes of the first pair of electrodes (13, 15), each electrode (12, 13, 14, 15) comprising an electrically-conductive plate in which at least one opening (30) is formed, and the transportation means (32) being inserted in the opening (30) in order to extend through the plates in the preferential direction. 14. Applicator device according to claim 8, characterized in that the support means comprises vertical plates (18). 15. Applicator device according to claim 15, characterised in that the electrode plates (12, 13, 14, 15) are horizontally displaced with respect to the vertical plates (18). 16. Applicator device according to claim 3, characterised in that the metal cylinder (40) are disposed between the first two electrode plates (13, 14). 17. Applicator device according to claim 3, characterized in that the metal cylinder (40) are disposed between the second two electrode plates (14, 15). 18. Applicator device according to any of the preceding claim, characterised is that the distance between the upper two electrode plate (12, 13) is greater than the distance between the first electrode plate (12, 14) of each electrode. 19. Applicator device according to any of the preceding claim, characterised in that the distance between the lower two electrode plate (14, 15) is greater than the distance between the first electrode plate (12, 14) of each electrode.
The present invention relates to an industrial apparatus and to an applicator device for applying radio-frequency electromagnetic fields to semiconductive dielectric materials. In particular, but in non-limiting manner, the apparatus can be used for heat-treating fluid food products, which are preferably of low viscosity and transportable by transportation means. More particularly, the apparatus can be used very advantageously in pasteurization or sterilization treatments of milk and its derivatives, as well as of fruit juices, beer, beverages of various types, shakes, soups, purees, flavouring syrups and tomato sauces. In many technological processes, and in particular in those in the food field, products may be subjected to a heat treatment in order to dry, dehydrate, defrost, cook, pasteurize, sterilize or otherwise treat them thermally. The heat to be supplied to the product may be transferred by means of external heat sources by utilizing convection, conduction or radiation effects, or may be generated directly within the product. In the latter case, an oscillating electromagnetic field can be used to produce a field of electrical currents in the product to be treated; by interacting with the material constituting the product, this field brings about a rise in its internal temperature. The electromagnetic field which can be applied may have various intensities and various oscillation frequencies. Known apparatus which performs heating of this type comprises a radio-frequency generator which, when supplied with the mains voltage, produces an oscillating voltage of variable amplitude and of predetermined frequency at its output terminals. The apparatus further comprises an applicator device with capacitive or inductive behaviour which transforms the oscillating voltage of the generator into electromagnetic fields having predominantly electrical or magnetic components of the oscillating field, respectively. The above-mentioned frequencies are typically within ranges established by international standards, the central values of which are 6.78-13.56-27.12-40.68-433.92 MHz. The intensity of the oscillating electromagnetic fields thus generated depends on the amplitude of the radio-frequency voltage which is applied to the terminals of the applicator device and on the construction of the applicator device, which can increase or reduce the intensity of the field in the zones provided for housing the product to be treated. There are known devices of various types which apply radio-frequency electromagnetic fields to products having different physical, dimensional and electrical characteristics. The most widespread applications relate to heat treatments of paper, fabrics, textile materials in general, particularly after dyeing, hides, rubber, wood, plastics laminates and food products. In most of these cases, the heating of the products takes place by dielectric losses due to the displacement currents which are induced in them by the electromagnetic field applied, rather than by the conduction currents. Each of these devices has a structure and technical characteristics suitable for the frequency used and for the type of application required. Moreover, the same devices may have a structure such as to give rise to electromagnetic fields of predetermined intensities, delivering specific powers to the product on the basis of the particular heat treatment required. For example, the Applicant's European patent application EP 0946104 describes an industrial apparatus for heating food products by means of a radio-frequency oscillating electromagnetic field. This apparatus can cook meat-based food products such as, for example, ham and the like, which have considerable mass and volume and are preferably placed in moulds. One of the main limitations to the use of radio-frequency technology for heat treatment is that it is difficult to bring the products to be treated to high temperatures within extremely short times without thereby causing undesired effects detrimental to the products. For example, but in non-limiting manner, during pasteurization or sterilization processes, or during the defrosting of purees of food products, it is necessary to supply high powers within a short time and, in particular, high powers per unit volume of product, for continuous flows. This operation is particularly difficult, especially for semiconductive dielectric products, since their considerable electrical conductivity limits the effect of the dielectric losses, that is, the effect due to the displacement currents induced therein by the electromagnetic field applied. Moreover, if the volume of product transported through the radio-frequency treatment zone per unit of time is particularly high, undesired chemical and organoleptic effects may arise in the products if the radio-frequency treatment time is not sufficiently short. In some known solutions, it is possible to deliver high specific powers to the products in a short period of time with the use of high voltages and currents in the devices. However, these solutions lead to difficult management and complex control. In fact, the supply of high powers may lead to undesired electrical discharges between various points of the applicator devices, leading to damage thereto and to the product housed therein and, even more disadvantageously, may lead to uneven heating and/or burning of portions of the product. Processes for pasteurization and/or sterilization of fluid food products should, in theory, comprise a first stage of instantaneous heating of the product to the pasteurization and/or sterilization temperatures, a subsequent stage characterized by a standing time reduced to zero and, finally, a stage of instantaneous cooling to the starting temperature. Since a process of this type cannot be achieved by known technology, the best conditions must be sought in dependence on the apparatus available in order to construct a plant which enables a process as similar as possible to the theoretical one to be achieved. Thus, in the field of the heat treatment of milk, one of the most widespread pasteurization processes consists of a stage in which the milk is heated to a temperature below its boiling point, a stage in which the product is kept in these conditions for a predetermined period of time, and a cooling stage. The period of time at constant temperature must be long enough to kill pathogenic and sporiferous micro-organisms of all types which are present and a proportion of micro-organisms which are not pathogenic but which can nevertheless bring about changes of various types in the product. Some examples of known heat treatments are slow pasteurization (comprising, amongst other things, a stage of heating to 63°-65° C. and a maintenance stage of about 30 minutes) and quick pasteurization, known as H.T.S.T. (comprising, amongst other things, a stage of heating to 72° C. and a maintenance stage of about 20 seconds). Both processes serve to pasteurize milk intended for consumption or for the production of dairy products such as cheese, cream, butter, curd cheese and the like. Another known type of method for the heat treatment of milk is that used when the product is intended for direct consumption. In this process, which is known as U.H.T., the milk is heated to temperatures much higher than the pasteurization temperature, which are maintained for a period of time much shorter than in the processes described above, for example, 155° C. for about 2-5 seconds. In this case, the object is to eliminate as far as possible everything which leads to a reduction in the shelf life of the product since, in this case, the milk must have a shelf life of at least 120 days when kept at ambient temperature. In U.H.T. treatment, the heating stage is usually achieved in two steps: first of all by an indirect exchange, for example, by means of external heat sources, such as plate-like hot-water heat-exchangers, and then by a direct exchange, for example, by the admission of steam into the milk at high temperature (known as the “uperization” stage). Both of the treatments described above have some disadvantages. The use of steam at high temperature enables the product to be brought to the required temperatures quickly but at the same time leads to an alteration in its physical and organoleptic characteristics. In fact, the steam admitted not only changes the percentage of water in the milk, but also leads to depletion of the nutritional substances since, once the required temperature has been reached, the same amount of steam which was injected is extracted, together with some substances which were originally contained in the milk. It is therefore an invasive technique in which an external element, the steam, is used to achieve extremely quick heating times which cannot be achieved by other known techniques. In contrast, indirect exchange treatment does not modify the chemical characteristics of the product, since it is not an invasive process, but is not as effective in reaching the required temperatures within a short time, thus causing serious and undesired side effects in the pasteurized milk. In the said processes, it is also known that, for a given maximum treatment temperature, the milk-sterilization effect can also be achieved with a limited duration of the maintenance stage, which is responsible for the organoleptic degradation of the product, if the required temperatures are reached within the shortest possible time. It is clear that, with known techniques, there are physical limitations to this which are connected with the technologies used. For example, indirect exchange of heat by means of heat exchangers requires sufficiently long periods of contact between the product and the heating means for the product to be heated completely and uniformly in order to ensure complete treatment thereof. It is known that, over the years, the temperatures necessary to achieve correct sterilization of milk are continually increasing because of new contaminations connected with new pathogenic agents, spores, enzymes, bacteria, or micro-organisms. These harmful substances are in fact becoming ever more heat-resistant and hence difficult to inactivate. However, excessive heat treatment clearly conflicts with the ever greater requirement by the public for products with flavours, odours and colours which are as close as possible to their natural properties. These reasons have forced and are forcing many companies producing sterilization plant or fluid foods to investigate, implement and use ever newer and more sophisticated technological processes connected with the improvement of plant, with the use of heat sources which make use of convection, conduction or radiation effects. In this connection, it is widely believed that the known technologies have reached such a high degree of development that they can now be considered “mature techniques” which are ever more difficult to improve. The main object of the present invention is to overcome the disadvantages of known apparatus by providing an industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive dielectric materials which can treat large quantities of product very quickly without bringing about particular changes in its physical, chemical and organoleptic characteristics. Another object of the present invention is to provide an industrial apparatus for the heat treatment of semiconductive dielectric materials which can apply radio-frequency electromagnetic fields of considerable intensity with the use of limited voltages and currents in the apparatus so as to be easy to manage and control, avoiding unnecessary loadless power dissipation and localized heating, and consequently burning, of the product. A further object of the present invention is to provide an industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive dielectric materials which can easily apply fields of greater or lesser intensity for times adjustable over an extremely wide range and which can thus be used in various technological processes which may even involve products other than food products. Not least, another object of the present invention is to provide an industrial apparatus which is easy and inexpensive to manufacture, easy to inspect, easily accessible for cleaning and maintenance operations, and easy to dismantle. To achieve the objects indicated above, the subject of the invention is apparatus having the characteristics indicated in the appended claims. According to a particularly advantageous characteristic of the present invention, the industrial apparatus comprises means for housing and transporting the products to be treated, which means can be connected easily and quickly to the means used for transporting the products in production lines. The apparatus of the present invention can thus be inserted in production lines for fluid products, preferably of low viscosity, transported in sterile pipes, without altering the layout and configuration of the existing devices or even the cross-section and/or configuration of the lines and pipes for transporting the products. Another advantage of the present invention is that products flowing through production lines at extremely fast speeds can be treated industrially without the provision of additional applicator devices and/or plants. As well as having large dimensions and therefore being difficult to use and to maintain, these additional devices generally require large volumes of product in the radio-frequency treatment zones and therefore involve treatment times which are so long that they cause undesired chemical/organoleptic effects in the products. Further characteristics and advantages of the present invention will become clear from the following detailed description of a preferred embodiment, given with reference to the appended drawings, provided purely by way of non-limiting example, in which: FIG. 1 is a schematic side view of the apparatus of the present invention, and FIG. 2 is a schematic view of the apparatus of the present invention, sectioned on the line II-II of FIG. 1. With reference now to the drawings, an industrial apparatus for applying radio-frequency electromagnetic fields to semiconductive dielectric materials comprises an electrical generator 10 of generally known type which produces at its terminals an oscillating voltage of predetermined amplitude and with a predetermined frequency within the typical radio-frequency range, for example, but in non-limiting manner, from a few kHz to a few hundred MHz. The voltage produced by the radio-frequency generator 10 supplies an applicator device 1, the configuration of which enables a radio-frequency electromagnetic field of considerable intensity to be generated inside it. The material to be subjected to heat treatment, for example, but in non-limiting manner, semiconductive food products, preferably milk during pasteurization or sterilization treatments, is passed through the applicator device 1 in a manner such that the electromagnetic field heats it to a predetermined temperature and for a predetermined period of time. It is very important for milk, as for most food products which are transported in a production line, to be contained in sterile pipes to prevent any contact with the air and, in general, with external agents which might damage its chemical and physical properties. The industrial apparatus of the present invention comprises inlet means and outlet means which are connected in sealed manner to the pipes for transporting the material so as not to cause the above-mentioned problems. This characteristic further facilitates the insertion of the apparatus of the present invention in industrial production lines, since it does not require modification either of the structure or of the layout or even of the configuration of the devices present therein. The applicator device 1 of the present invention comprises at least one pair of electrodes and, preferably, as shown in the drawings, two pairs of electrodes 12, 13 and 14, 15, the surfaces of which are formed, for example, but in non-limiting manner, by plates of electrically-conductive material, preferably stainless steel, arranged opposite and parallel to one another. Each pair of electrodes comprises a first plate 12, 14, electrically connected to one terminal of the generator 10 and a second plate 13, 15, electrically connected to a terminal of different potential such as, for example, the other terminal of the generator 10, or preferably, to earth. The first plates 12, 14 of each pair of electrodes are electrically connected to one another, for example, by means of two connecting elements 16, also made of electrically-conductive material and disposed at their ends so as to be equipotential, that is, so as to be kept at the same electrical potential. The other two plates 13, 15, which are connected to earth, are arranged facing and opposite the first two, equipotential plates 12, 14. In use, a first electromagnetic field generated between the plate 12 and the plate 13 has flow lines which are oriented in a preferential direction substantially perpendicular to the surfaces of the plates. Similarly, a second electromagnetic field generated between the plate 14 and the plate 15 has flow lines which are also oriented substantially in the said preferential direction. Finally, the pair of equipotential electrodes 12, 14 connected to the generator 10 defines a plane substantially perpendicular to the said preferential direction. Naturally, the number, shape and dimensions of the electrodes 12, 13, 14, 15 and of the connecting elements 16, as well as the above-described electrical connections, may vary widely from those shown in the appended drawings, without thereby departing from the scope and from the objects of the present invention. Each plate 12, 13, 14, 15 comprises a plurality of openings 30 in which are inserted means for housing and transporting food products, for example, but in non-limiting manner, a duct made of insulating material, preferably a pipe 32 made of plastics material. The food product thus passes through the applicator device 1 in a preferential direction substantially parallel to that of the lines of the electromagnetic field generated in the applicator device 1, and the two electrodes 12, 14 are arranged substantially in alignment in the preferential direction. Application means, for example, but in non-limiting manner, metal cylinders 40, are engaged with each plate, for example, but in non-limiting manner, are fitted in the openings 30 in a manner such as to encircle the pipes 32 transporting the product to be treated. The inside diameter of the transporting pipes 32, and consequently of the metal cylinders 40, may advantageously be selected on the basis of the cross-sections of the pipes used in the production treatment lines. Any irregularities between the internal surfaces of the various pipes are thus eliminated, preventing accidental deposition of portions of product subjected to treatment. Prolonged deposition and consequent deterioration of such portions of product could in fact lead to organic contamination of the product subject to treatment, for example, rendering its sterilization impossible. The metal cylinders 40 also have a reinforcing function for preventing damage to the transporting pipes 32. The thermal shock which the material subject to treatment undergoes in the equipotential ducts tends to change its volume, creating a bulge in the transporting pipe 32. Since the transporting pipes are preferably made of insulating material and generally of flexible plastics material, repeated deformation of their walls could lead to changes in the pressure inside the pipes, a loss of elasticity, or even tearing of the plastics material, with consequent leakages of the material. The metal cylinders 40 comprise respective abutment elements, for example, but in non-limiting manner, abutment projections 42 which enable a minimum distance, beyond which it is not possible to move the plates of the electrodes 12, 13, 14, 15 towards one another, to be preset. This minimum distance prevents undesired side effects which might arise at particular operating frequencies of the apparatus if the electrodes were moved too close together. The applicator device 1 also comprises further means for reinforcing the transporting pipe 32, for example, but in non-limiting manner, cylinders 50 made of insulating material, preferably Teflon, which enclose the portions of the transporting pipe 32 disposed between the abutment projections 42. The plastics cylinders 50 thus increase the retaining quality of the transporting pipes 32 should products be transported at high pressure inside the industrial apparatus. The transporting means 32, the application means 40, and the reinforcing means 50 may be formed with different dimensions and geometrical shapes, according to the type of product or the technological processes in which the present invention is used. This is important to ensure adequate flexibility of the industrial apparatus and hence its applicability to various technological processes. In the embodiment shown in the drawings, the applicator device 1 comprises support means, for example, but in non-limiting manner, two “L”-shaped metal plates 18 which also enable one of the two plates of the first pair of electrodes to be connected to the earth potential. The remaining plates 12, 13, 14 are supported on the second plate 15 of one of the electrodes by support elements made of insulating materials, preferably Teflon, so as not to interfere with the electromagnetic field present between the two pairs of electrodes. Each support element comprises, for example, a threaded bar 22 connected to the two second plates 13, 15 of the pairs of electrodes by means of locating elements 24. Further pairs of locating elements 26 are engaged on the bar 22 and support the first plates 12, 14, respectively, in a manner such that their relative distance can be varied. Naturally, the support elements may comprise or be replaced by other means of known type which a person skilled in the art could easily identify, once their function has been understood from the present description and as long as they enable the relative distance between the plates 12, 13, 14, 15 of the applicator device 1 to be varied. A particular advantage of these support elements is in fact that it is possible to vary the intensity of the electromagnetic field applied to the product, as well as its treatment time, by varying the volume of the product which is subjected to the action of the radio-frequency electromagnetic field per unit of time. As shown in FIG. 1, a layer of insulating material 44 is applied to the plates 13 and 15 so as to prevent the formation of any electric arcs between the ends of the metal ducts and between the pairs of electrodes. The insulating layers 44 are not shown in FIG. 2, for greater clarity of illustration. In use, when the electrical generator 10 produces an oscillating voltage of predetermined amplitude and with a predetermined frequency at its terminals, a first electromagnetic field is generated between the plate 12 and the plate 13 and has flow lines which are oriented in a preferential direction substantially perpendicular to the surfaces of the plates. Similarly, a second electromagnetic field is generated between the plate 14 and the plate 15 and has flow lines which are also oriented substantially in the preferential direction. The food product is housed and transported in the pipes 32 and passes through the applicator device 1 in a preferential direction substantially parallel to that of the lines of the electromagnetic field generated in the applicator device 1. The metal cylinders 40 enable the opposite, or different, potentials of the electrodes to be carried along the walls of the pipes 32. The product under treatment is thus subjected to the effect of an electromagnetic field the field lines of which are applied substantially in the direction in which the product flows and which is rendered particularly intense by the equipotentiality and by the length of the metal ducts. The lines of an electric field in fact never intersect one another and the electric field lines generated inside the equipotential metal ducts, the length of which is predominant in comparison with their diameter, therefore have a considerable intensity and must close either onto surfaces of the same shape as that mentioned above or even different surfaces, provided that they are of different potential. This electromagnetic field produces currents substantially of two types in the product housed in the device, that is: a first type known as displacement currents and a second type known as conduction currents. The first is due to the dielectric displacement of the substances constituting the product, which is caused by the oscillations of the alternating electromagnetic field applied (like a type of molecular oscillation). It thus acts on portions of product which are not free ionic charges, bringing about molecular oscillations, and the molecular friction between the various molecules thus produces heat (dielectric heating). The second type is due to the conduction of the free ionic charges which are present in the product, such as to render it semiconductive, and is caused by the radio-frequency potential difference applied to the product since the capacitive effect of the walls of the pipe 32 allows the radio-frequency current to pass through it. By thus acting on ionic charges which are free to move in the product, this current causes heating by the Joule effect. The two currents are both at the typical frequency of the radio-frequency generator which supplies the applicator device 1. Clearly, the two currents are electrically out of phase with one another by 90° since one is capacitive and the other is resistive. Naturally, the lengths of the metal ducts enable a larger electromagnetic field to be applied to the product. The distance between the pairs of electrodes 12, 13 and 14, 15 and hence of metal ducts 40 advantageously enables the treatment times of the product to be reduced since there is a smaller volume of product disposed between the metal ducts having different electrical potentials. A configuration of this type is particularly advantageous for the heat treatment of semiconductive materials such as, for example, milk, with radio-frequency electromagnetic fields. In fact, the heat treatment takes place in very short times and much more homogeneously than in any other known device, even when the material passes through the applicator device 1 at fast speeds, as in the case of a continuous line for transporting milk. Moreover, the ability of the applicator device 1 to concentrate high-intensity electromagnetic fields in a small space enables the generator 10 to supply the applicator device 1 with voltages low enough to eliminate the risks of undesired electrical discharges which could damage the pipes transporting the material or cause burning of the product, without thereby limiting the intrinsic characteristic of heating the material very rapidly to high temperatures within very short periods of time. Naturally, the applicator device 1 may also comprise more than one pipe so as to increase the volume of material to be subjected to heat treatment within the same period of time, or several pipes of different cross-section, so as to fit the dimensions of the pipes transporting material at the input and/or the output of the industrial apparatus of the present invention. An important technical characteristic of the present invention is that the electrodes 12, 13, 14, 15 and the metal ducts 40 connected thereto, that is, the ends of the applicator device 1, are all connected to earth. This prevents the flow of undesired electrical currents through the product under treatment, outside the applicator device 1, which currents are greater the more conductive the product is, causing undesired side effects such as electromagnetic interference with probes immersed in the product, or difficulties in screening, that is, in containing the radio-frequency electromagnetic field within the apparatus. Moreover, the entire apparatus is electrically insulated from the production line and from its component devices and, for obvious safety reasons, avoids any dispersal of current to the exterior. Moreover, since the electrical potential of the material to be treated is in practice at the earth potential outside the ends of the applicator device 1, metal tubing, particularly stainless-steel tubing, can advantageously be connected to the pipe 32, thus enabling the device to be incorporated perfectly well in production lines in which stainless steel tubing is often used. Another advantage of the interposition of insulating material at the ends of the applicator device is the solving of problems of screening and of limiting leakage currents and interference in electrical devices connected to the apparatus such as, for example, probes, inverters, PLCs and the like. Phase-modifying means formed, for example, but in non-limiting manner, by inductances 52, which are necessary for adapting the load of the device to the radio-frequency generator 10, may be disposed between the generator 10 and the earth, that is, between the second plates 13 and 15 and the pair of equipotential plates 12, 14. The inductances 52 may be formed, for example, but in non-limiting manner, by tubes, preferably of silvered copper, of a thickness greater than the depth of penetration of the working radio-frequency currents of the apparatus. Moreover, one or more adjustment elements may advantageously be connected to each inductance so as to form longer or shorter paths for the currents and for the respective magnetic flux linkage, on the basis of their position, thus adjusting the phase-modifying current and hence the radio-frequency voltage range necessary for the type of product to be treated. This characteristic is particularly useful since it renders the use of the apparatus extremely flexible for products possibly having notably different electrical and dielectric characteristics. The phase-modifying means also perform the load-adaptation function and have been designed in accordance with the criterion of converting the impedance from the value obtained from the system comprising the radio-frequency applicator device 1 with the product housed therein, to the utilizable impedance of the generator, in order to maximize the transfer of power between the generator and the load. The circulation of radio-frequency currents in the structure of the applicator device can also be reduced to the values which are strictly necessary for the generation of the electromagnetic field in the pipes 32 by the interposition of a suitable load-adaptation network between the generator 10 and the applicator device 1, as well as by the above-mentioned phase-modifying means. Undesired radiation of radio-frequency power outside the physical limits of the applicator device can thus be prevented, thus also limiting loadless losses which would otherwise arise, leading to unnecessary power dissipation and more or less localized hot spots inside the device. The radio-frequency generator 10 may comprise a system of known type for adjusting the power delivered, for example, by limiters of the amplitude of the mains voltage supplied to the generator, or a system for transforming impedance by means of a capacitive, inductive, mutual inductive, or impedance-transformation coupling between the generator and the applicator device. These systems for regulating the power of the generator can advantageously be controlled by electronic devices which, by detecting the temperature of the product at the input and/or at the output of the applicator device by means of temperature sensors, can keep the output product temperature stable or vary it by providing feedback to the generator power-regulation system. An alternative feedback system may be, for example, that of keeping the radio-frequency power delivered to the product stable at a predetermined value with variations either of the speed of the product or of the type of product treated. Naturally, the controls described above are only some of the feedback controls which may be used for the present invention. Similarly, electronic supervision and control devices which are normally used in automation and are commonly present in production lines such as, for example PLC or PC devices and the like, may also be incorporated in the apparatus of the present invention. Naturally, the principle of the invention remaining the same, the forms of embodiment and details of construction may be varied widely without thereby departing from the scope of the present invention.
20050804
20080212
20060511
61615.0
A23L332
0
SIMONE, TIMOTHY F
INDUSTRIAL APPARATUS FOR APPLYING RADIO-FREQUENCY ELECTROMAGNETIC FIELDS TO SEMICONDUCTIVE DIELECTRIC MATERIALS
UNDISCOUNTED
0
ACCEPTED
A23L
2,005
10,516,058
ACCEPTED
Functional optical devices and methods for producing them
A functional optical device has cores which are trenches, different portions of the cores being formed from different core materials. The optical device can be formed by forming trenches 5,7,9 within a substrate (normally a substrate 1 covered by a cladding layer 3), covering at least part of at least one trench 7 with a cover 11, depositing a first cladding material to fill the trenches 5,9 which are not covered, removing the cover 11, depositing a second cladding layer 15 of a second cladding material to fill the trenches 7 which were previously covered, removing core material outside the trenches 5,7,9 and applying a cladding layer to cover the trenches.
1. A method of producing an optical device, the method including the steps of: forming trenches within a cladding layer; covering certain areas of the trenches with a cover comprising a photoresist material, wherein the cover is formed by a liftoff process; depositing a first core layer of a first core material to fill the trenches which are not covered; removing the cover; depositing a second core layer of a second core material to fill the trenches which were previously covered; removing the first and second core materials outside the trenches in a single process step; and applying a cladding layer to cover the trenches. 2. A method according to claim 1 in which the core material outside the trenches is removed by polishing. 3. An optical device comprising at least two optical paths of different geometrical lengths, light passing along the two optical paths interacting, characterised in that each of the optical paths is being formed as a trench within a cladding layer including at least one optical path comprising a first and second region composed of different core materials and having different refractive index variation with temperature, the core materials in the first and second region chosen such that the interaction between the light passing along the paths is temperature independent. 4. An optical device according to claim 3 which is an interferometer. 5. An optical device according to claim 3 which is an arrayed-waveguide grating having a plurality of optical paths. 6. An optical device according to claim 5, each path intersecting with a region within which the cores are of a different material from the cores outside the region, the intersection of the optical paths with the region varying with the geometrical length of the optical paths. 7. An optical device according to claim 3 which is produced by a method according to claim 1. 8. An optical device according to claim 3 which is produced by a method according to claim 2.
FIELD OF THE INVENTION The present invention relates to optical devices of the kind which transform light transmitted through them (“functional optical devices”). The invention further relates to methods for producing the functional optical devices. BACKGROUND OF INVENTION Recently there has been a growth in demand for improved functional optical devices, especially for use in DWDM (dense wavelength division multiplexing) systems. It has become necessary to provide improved functional optical devices such as Mux (multiplexer) devices, DeMux (demultiplexer) devices, amplifiers, optical switches and VOA (variable optical attenuator) devices. It is known to form such devices as PLC (planar lightwave circuits), in which light moves along paths defined by cores extending over a substrate in a plane parallel to the surface of the substrate. Conventional PLC fabrication methods produce cores which are either ridge structures or trench structures. Ridge-type cores are ridges of a selected core material upstanding from a layer of cladding material formed over the substrate. Trench-type cores are formed by depositing a selected material within a pre-formed trench in a layer of cladding material which itself overlies the substrate. Generally, ridge structures are more common than trench structures. The fabrication method of a ridge-type core is typically as follows. Firstly, a substrate such as Si is covered by a cladding layer of a cladding material (such as SiO2), and then a layer of core material (such as SiO2 including GeO2). which is to be formed into the core. A mask is applied in selected regions over the core layer, and the exposed portions of the core layer are etched by an etching process such as reactive ion etching (RIE), to leave the ridges of the core material. After the mask is removed, a further cladding layer is provided over the surface of the device, so that the ridges are fully embedded between two cladding layers. Although this method is successful, it is difficult to modify it to produce a device in which different portions of the core are formed of different materials, since depositing each core material requires a series of process steps. Additionally, it is difficult to control the thickness of the two different core materials at regions when they meet. One example of a device having two different core materials is U.S. Pat. No. 6,201,918, which describes a device in which a Mach-Zehnder interferometer having two optical fiber arms is processed by splicing an optical path changing segment into one of the arms. SUMMARY OF THE INVENTION The present invention aims to provide new and useful optical devices, and new and useful methods for producing optical devices. In general terms the present invention proposes that an optical device is formed having one or more cores which are trenches, different portions of the core(s) being formed from different materials. The invention is based on the realisation that it is easier to form trenches of different materials than to form ridges of different materials. This factor more than compensates for the factors because of which ridge-type cores are normally preferred to trench-type cores. The optical devices may be formed by the steps of forming trenches within a cladding layer (normally a cladding layer which is located on a substrate), covering certain areas of the trenches, depositing a first core layer of a first core material to fill the trenches which are not covered, removing the cover, depositing a second core layer of a second core material to fill the trenches which were previously covered, removing core material outside the trenches, and applying a cladding layer to cover the trenches. Preferably, the core material outside the trenches is removed by polishing. Previously polishing techniques were not capable of polishing the whole surface of an optical device with an accuracy on the level of the dimensions of desired trenches (e.g. 6 micrometers), which is one reason why ridge-type cores are conventionally preferred to trench-type cores. However, the present inventors observe that advances in polishing techniques have removed this factor, making trench-type cores more acceptable. It is to be understood that the present invention is not limited to the case in which there are exactly two different core materials. Rather, the present invention makes it possible to form optical devices in which any number of different materials are used to form different portions of the cores. Each material is deposited into the respective portion(s) of the trenches at a time when all the other portions of the trenches are either already filled by a previously deposited core material or covered. The present invention makes it possible to form a variety of devices having cores composed of different materials. Examples of such devices are given below, and include, but are not limited to amplifier devices, interferometer devices such as Mach-Zehnder interferometers, arrayed-waveguide gratings, thermo-optic switches, variable optical attenuators, and gain flattening devices. In particular the present invention makes it possible to provide optical devices which have predefined thermal characteristics. For example, in some optical devices according to the invention, optical paths of differing geometrical lengths include portions of different respective core materials (so that they have different optical path lengths, i.e. the product of the geometrical length and the refractive index value). The various core materials are selected to have different thermal properties, such that although the paths have different geometrical lengths, the optical path lengths vary with temperature in the same way (i.e. the differing core materials compensate for the differing geometrical lengths of the optical paths). In this way it is possible to ensure that the performance of the overall optical device is not temperature dependent. Alternatively, in other devices a temperature dependence is actually desirable. The present invention makes it possible to tailor this temperature dependence by appropriate selection of different core materials. Specifically, a first expression of the invention is a method of producing an optical device, the method including the steps of: forming trenches within a cladding layer; covering certain areas of the trenches; depositing a first core layer of a first core material to fill the trenches which are not covered; removing the cover; depositing a second core layer of a second core material to fill the trenches which were previously covered; removing core material outside the trenches; and applying a cladding layer to cover the trenches. A second expression of the invention is an optical device having one of more cores defining one or more optical paths, each core being formed as a trench within a cladding layer, different portions of the core or cores being composed of different core materials. BRIEF DESCRIPTION OF THE FIGURES Preferred features of the invention will now be described, for the sake of illustration only, with reference to the following figures in which: FIG. 1, which is composed of FIGS. 1(a) to FIG. 1(e) shows steps in the formation of an optical device which is an embodiment of the invention; FIG. 2 shows a PLC amplifier device which is an embodiment of the invention; FIG. 3 shows a Mach-Zehnder interferometer which is an embodiment of the invention; FIG. 4 shows an arrayed-waveguide grating which is an embodiment of the invention; FIG. 5 shows a thermo-optic switch which is an embodiment of the invention; FIG. 6 shows a variable optical attenuator which is an embodiment of the invention; FIG. 7 shows another Mach-Zehnder interferometer which is an embodiment of the invention; FIG. 8, which is composed of FIGS. 8(a) and 8(b), shows the temperature variation with time of a known Mach-Zehnder interferometer, and of the one of FIG. 7; FIG. 9 shows a waveguide device which is a further embodiment of the invention; FIG. 10 shows a cross-sectional view of the waveguide device of FIG. 9; FIG. 11, which is composed of FIG. 11(a) and 11(b) shows experimental results of wavelength temperature dependence (dλ/dT) for comparative examples of a Mach-Zehnder interferometer, respectively having core compositions of (a) 10GeO2-90OSiO2 and (b) 8GeO2-5B2O3-87SiO2; and FIG. 12, which is composed of FIG. 12(a) and 12(b) shows experimental results of wavelength temperature dependence (dλ/dT) for Mach-Zehnder interferometers, both having the first core material of 8GeO2-5B2O3-87SiO2, and the second core material of 10GeO2-90SiO2, which are embodiments of the invention, respectively having geometric lengths of the second core material of (a) Lcore2=15 mm and (b) Lcore2=17 mm. DETAILED DESCRIPTION OF THE EMBODIMENTS A method of forming an optical device according to the invention is shown in FIGS. 1(a) to 1(e). Below, a method is shown of producing a waveguide with differing core materials, such as one into which have been introduced a dopant such as GeO2 which increases refractive index, and/or a dopant such as B2O3 which is effective to reduce the temperature dependence of the refractive index. The method employs a substrate layer 1, which may for example be a Si wafer having a diameter of 3 inches (7.5 cm) and 1 mm thickness. Firstly, the substrate layer 1 (e.g. Si), shown in FIG. 1(a) in cross-section, is covered by an under cladding layer 3. The under cladding layer 3 may be a silica glass film, which is formed by plasma enhanced chemical vapour deposition (referred to here as PECVD). The gas material is tetraethoxysilane (Si(OC2H5)4, referred to here as TEOS) and oxygen (O2). Trenches 5, 7, 9 within the under cladding layer 3 may be formed using a photolithographic method which is widely used in semiconductor industry. For the silica glass film etching, reactive ion etching (here referred to as RIE) technology is adopted using fluorine-containing gas. For this, in order to form the trenches with a precise square form, an inductively coupled plasma (here referred to as ICP) RIE apparatus, such as an RIE-200iPC apparatus produced by the Samco company, is useful. As the fluorine containing gas, trifluoromethane (CHF3) is used at about 5 mTorr. Radio frequency electric power of 103 Watts at 13.56 MHz is supplied to the coil. A film of Cr of thickness 100 nm prepared by sputtering is used as a mask. After the formation of the trenches, the Cr mask remaining on the cladding layer 3 is removed by oxygen plasma etching using the same RIE apparatus. Alternatively, the substrate itself can be used as the under cladding layer when the substrate material is applicable for cladding (e.g. if it is silica). These trenches 5, 7, 9 are shown in FIG. 1(a) in an end-on view, and with a square cross-section. Typically, the trenches may have a depth of about 6 micrometers and a width of about 6 micrometers, although of course other dimensions are possible. As shown in FIG. 1(b) a cover 11 is deposited over a portion of the under cladding layer 3 by known techniques, such as a lift off process using a photoresist material as the cover. The cover 11 covers one or more portions of one or more of the trenches (in FIG. 1(b) it is shown covering trench 7) but exposes other portions of the trenches (in FIG. 1(b) it is shown exposing the trenches 5, 9). A first core layer 13 of a first core material is then deposited, filling the exposed trenches 5, 9. The core may be a Ge-B co-doped silica glass film deposited using the PECVD technique. In order to get high quality core glass, an ICP CVD apparatus, such as a PD-160iP apparatus produced by the Samco company, is useful. Any of the following may be used as the raw material gas: TEOS, tetramethoxygermane (Ge(OCH3)4, here referred to as TMOG) and triethoxyborane (B(OC2H5)3). Instead of triethoxyborane, trimethoxyborane (B(OCH3)3) may be used as the boron-containing raw material gas. By controlling the flow rate of the raw material gas, the amount of dopant contained in the grown film varies. In order to obtain the desired composition of the deposited glass film, it is advantageous to adjust the CVD conditions, such as the gas pressure in the vacuum chamber and ICP power. The gas pressure during the deposition process may be 5.0 pa. The radio frequency power at 13.56 MHz supplied to the ICP device and to the substrate electrode may respectively be set to 900 and 300W. The substrate temperature may be 250° C. By controlling the flow rate of the raw material gas, a film can be obtained having a composition of germanium oxide 12.5 mole %, boron oxide (B2O3) 6.2 mole %, and silicon oxide 81.3 mole %. The deposition time was 120 minutes, and the obtained film thickness was 7 μm. As shown in FIG. 1(c) the cover 11 is then removed (again by any known technique, such as an O2 plasma etching method), thus exposing the trench 7. A second core layer 15 of a second core material is then deposited, filling the exposed trench 7, as shown in FIG. 1(d). As shown in FIG. 1(e), the portions of the core layers 13, 15 which are outside the trenches 5, 7, 9 are removed, by polishing, leaving cores in the trenches 5, 7, 9. Specifically, trenches 5, 9 are filled with the first core material 13, while trench 7 is filled with the second core material 15. An upper cladding layer (not shown) may then be deposited over the surface of the device, so as to cover all the cores. Note that the polishing should be performed with a high degree of accuracy. This is because if, alternatively, the polishing is uneven such that one side of the substrate surface is polished by a few micrometers more than the other side, then the cores on the first side of the substrate may be partially removed. The remaining trenches will then be of different depths. Note that the deposition of the various materials can be accomplished in various ways according to any known technique(s). For example, any one of the layers may be formed by chemical vapour deposition (CVD), or alternatively by flame hydrolysis deposition (FHD) employing one of the reactions: SiCl4+2H2+O2-<SiO2+4HCl, GeCl4+2H2+O2->GeO2+4HCl, or Si(OC2H5)4+H2O->SiO2+organic compounds. Apart from these materials, materials such as tantalum oxide, titanium oxide, silicon nitride, tantalum nitride, silicon carbide, tantalum carbide, titanium carbide can be used. The method according to the invention for forming waveguides having differing core materials can be used to produce various functional optical devices, such as amplifier devices, devices with a wavelength division multiplexing function, and light beam spot-size converters. In the following text, preferred examples of such devices are given. Note, however, that the present invention is not limited to these devices, which are presented for the purposes of illustration. A first device which is an embodiment of the invention is shown in FIG. 2, which is a top view of an erbium doped waveguide amplifier (EDWA) device 20 according to the invention. As in known devices, the device 20 has an entry portion 21 for receiving a signal (from the left) which is concentrated into an amplification region 23 in which laser amplification occurs, to generate an output signal in region 25. Excitation light is input through inputs 27, 29 to amplification region 23 by couplers 22, 24. The present invention makes it possible to form the cores in the amplification region 23 of an erbium doped material, while the cores in the other regions 21, 22, 24, 25, 27, 29 are not doped. This is advantageous because it means that losses in regions 21, 22, 24, 25, 27, 29 are reduced. An example of this embodiment was prepared using FHD (flame hydrolysis deposition). After fabricating the trenches by RIE, a first core material for the regions 21, 22, 24, 25, 27, 29 is formed by depositing Ge-doped silica glass soot on the cladding layer to fill up the trench, and consolidating it into a transparent glass film. The starting materials in this case were silicon tetrachloride (SiCl4) and germanium tetrachloride (GeCl4). Another possibility would be to use a different dopant which increases the refractive index, such as phosphorous which can be obtained from phosphorous oxy-trichloride (POCl3). The second (erbium doped) core material can be obtained by performing a soot deposition step and then following it with an erbium doping step in which the soot is subjected to a solution soaking method using an aqueous solution of Erbium trichloride (ErCl3). We can level of the erbium doping by adjusting the concentration of erbium aqueous solution, and the soaking time to the solution. A second device which is an embodiment of the invention is shown in FIG. 3 which shows a top view of a Mach-Zehnder interferometer 30 having two optical paths 31, 32 defined by respective cores. Light which is input to one of the optical paths at the left of FIG. 3 is partially transmitted to the other of the optical paths at the coupler 33, and light on the two paths interacts at the coupler 34. The couplers 33, 34 may for example be directional couplers. Between these sections, the two light paths have respective geometrical lengths L1 and L2, which are different. As is well known to an expert, this means that the light which will be transmitted by the device has a wavelength λ which is equal to the refractive index multiplied by ΔL defined as L1-L2 and divided by an integer. The optical path lengths of each of the two paths are determined by the product of n×L where n is the refractive index of the path and L is its geometrical length. In this embodiment all the cores are formed of the same material, except that the part of the cores in the region marked 35 are formed of a different material. Thus, each of the paths has a different length but also a different refractive index (which we can write respectively as n1 and n2). The two refractive indexes can be chosen in dependence on the lengths L1 and L2 such that, although each of the refractive indexes varies with temperature (with either a positive or a negative Δn/ΔT), the output of the interferometer is independent of the temperature, since the effects of the varying refractive indices are cancelled between the paths. Thus, a temperature independent Mach-Zehnder interferometer can be achieved. In this embodiment, cancellation of the effects of the varying refractive indices is important. It is obvious that cancellation is obtained even if the region marked 35 is positioned on the opposite arm, namely the shorter arm. The following example is shown for this case. We have constructed such a device by the following steps. First, trenches with selected dimensions were directly formed within Cr masked (3000 Å) silica substrate (Asahi, AQ, 1 mm thickness) by selective plasma etching (Samco, RIE-200iPC). CHF3 and C3F8 were used as etching gas at a process pressure of 0.4 Pa. The Cr mask was then removed by O2 plasma etching using the same system. A Ge—SiO2 or Ge—B—SiO2 film was deposited by an inductively coupled plasma chemical vapor deposition (ICP-CVD, Samco PD-160iP). Tetraethoxysilane, tetramethoxygermane, and triethoxyborane were used as the source materials for SiO2, GeO2, and B2O3 growth, respectively. The trench gap filling results were observed by SEM. Component analysis and depth profile study were applied using TOF-SIMS. The refractive indexes of the films were checked by a prism coupler. We could control the refractive indexes by adjusting the Si, Ge, and B content in the film. The sample was then annealed at 1000° C. in an atmosphere for 2 hrs after deposition to stabilize the refractive index of the core materials. The core materials outside the trenches are removed by planar surface polishing (Nanofactor, NF300) with accuracy of 0.2 μm. The trenches were over-cladded using another silica glass substrate by perfect optical contact followed by 1000° C. thermal bonding. The polished surface is smooth enough for this cladding method to be applied. As a result, buried waveguides with symmetrical structure which might reduce the polarization dependent loss were obtained in very short time and with low cost. As discussed above, certain areas of the trenches were covered during the first core material deposition. The covering could be performed by a lift off process using certain material as a photoresist. However, we were short of good photoresist material, so instead we used sharp-edged glass chip with selected length. The trenches that were not covered were filled with the first kind of material by the ICP-CVD process. The cover was then removed. The second core material was deposited by the ICP-CVD process to fill the trenches which were previously covered. After an annealing process, the samples were polished to remove the films outside the trenches and cladding material was applied to the surface by optical contact and thermal bonding. The Mach-Zehnder interferometer filter was designed as shown in FIG. 3 (and employing geometric principles used in U.S. Pat. No. 6,201,918), with double directional 3 dB couplers at 1.55 μm range. The core dimension is 7.5 μm and the corresponding refractive index of the core was 1.4632 at 0.6328 μm. The two light paths had a geometric length difference of ΔL≈1 mm, resulting in a pass-band pitch of 200 GHz (1.6 nm). As a comparison, Mach-Zehnder interferometer devices were made using only one kind of core material. Silica based materials with different doping ratios of Ge (8-10 mol. %) and B (1-5 mol. %) were used to test wavelength temperature dependence (dλ/dT) for the device with one core material. Then, embodiments with two kinds of core material were prepared to test the dλ/dT characteristics. The device characteristics were measured using a tunable laser source (Agilent 81689 A) with a wavelength range from 1.525 to 1.575 μm, and a power sensor (Agilent 81634 A). The temperature of the Mach-Zehnder interferometer filters was controlled to be −20, 0, 30, 51 and 80° C. by a temperature chamber (Yamato IW 241) during measurement. The wavelength temperature dependence (dλ/dT) of the filter device was calculated as the pass-band peak shift against temperature change. The wavelength temperature dependence (dλ/dT) of the Mach-Zehnder interferometer with one core material at the temperature range from −20° C. to 80° C. is shown in Table 1. As shown the GeO2 and B2O3 doping of the core materials effectively changes the refractive index and dλ/dT; our data also shows that the refractive index decreases from 1.4640 to 1.4632 and dλ/dT decreases from 9.5 pm/° C. to 8.1 pm/° C. when the B2O3 concentration increases from 0 to 5 mol. % while the GeO2 concentration remains at 8 mol. %. The lowest optical propagation loss of ˜0.1 dB/cm at 1550 nm of our Mach-Zehnder interferometer devices were obtained. The higher propagation loss of 1.53 dB/cm might be caused by particle contamination in the waveguides during the fabrication process, which can be reduced by applying a sample cleaning technology in our process. The trench type Ge—B—SiO2 planar waveguides exhibit reasonably low loss for the wavelengths of interest in integrated optics, and thus have promising applications. TABLE 1 Propagation Core composition n (@632.8 nm) dλ/dT@1550 nm loss @1550 10GeO2—90SiO2 1.4652 9.7 0.23 8GeO2—92SiO2 1.4640 9.5 0.12 8GeO2—1B2O3— 1.4640 9.4 0.18 91SiO2 8GeO2—2B2O3— 1.4638 9.2 0.54 90SiO2 8GeO2—4B2O3— 1.4635 8.9 1.53 88SiO2 8GeO2—5B2O3— 1.4632 8.1 0.11 87SiO2 Due to the results summarized in Table 1, the two compositions of 8GeO2-5B2O3-87SiO2 and 10GeO2-90SiO2 were chosen to be core material 1 and core material 2, respectively, to prepare the Mach-Zehnder interferometer filters of FIG. 3 (but with the region 35 positioned on the path 32, i.e. on the opposite shorter arm) by the multi-core fabrication method described above to test the athermal property. They have significant different dλ/dT of 8.1 pm/° C. and 9.7 pm/° C. as shown respectively in FIGS. 11(a) and 11(b), which correspond to different refractive index temperature dependences of dλ/dT and dn2/dT, respectively. The reason we chose 8GeO2-5B2O3-87SiO2 as core material 1 is that its refractive index 1.4632 is close to the designed refractive index value at coupling area. For the devices consist of two different core material sections with different values of dn1/dT, dn2/dT, and a certain relationship between their lengths, the athermal condition is: (dn1/dT)ΔL=[(dn2/dT)−(dn1/dT)]Lcore2. Here Lcore2 is the geometric length for core material 2 (10GeO2-90SiO2) section at the shorter path. Although the optical path length of each of the core material varies with temperature, the effects of the varying optical path lengths can be made to cancel by choosing a suitable value for the length Lcore2; thus the output of the device is independent of the temperature. Because the substituted region 35 of the second core material still has the waveguide structure, we can adjust the geometric length Lcore2 without worrying that it will generate extra propagation loss. We tried different Lcore2 from 7.6 mm to 17 mm, different values of dλ/dT from 3.75 to −2.85 pm/° C. with temperature from −20° C. to 80° C. were obtained in our experiments as shown in Table 2. The theoretically estimated values of dλ/dT with different Lcore2 are also listed for comparison, which agree fairly well with the experimental results. TABLE 2 Geometric length dλ/dT@1550 nm (pm/° C.) Propagation loss Lcore2 (mm) Estimated Measured @1550 (dB/cm) 7.6 3.89 3.75 0.64 9.6 2.21 2.00 1.77 15 0.75 0.54 1.73 17 −2.93 −2.85 0.61 Our best athermal result of the prepared Mach-Zehnder interferometer filter shows the dλ/dT of 0.5 pm/° C. when Lcore2≈15 mm, as shown in FIG. 12(a). This is small enough even for the 50 GHz pitch filters. The measured 3-dB bandwidth of 1.6 nm is close to the designed channel separation. By increasing the geometric length Lcore2 to 17 mm, even a negative value of −2.85 pm/° C. for dλ/dT was obtained, as shown in FIG. 12(b)! This shows that it is possible for us to control the dλ/dT from positive to negative value for different functional purposes. The excess loss can be reduced to be negligible by optimizing the fabrication technology. A third device which is an embodiment of the invention is shown in top-view in FIG. 4, an AWG device 40. The device has an input region 45 and an output region 46, spaced apart by an array region 47 in which each of the paths flexes. The device 40 has two coupling sections 48, 49, for example slab waveguides. A light signal containing two wavelength components with respective wavelengths λ1 and λ2 is launched into some path in the input region 45, and transmitted through the device obtaining one path of the output region 46 has wavelength λ1 and another wavelength λ2. Most of the cores are composed of a first core material, but the portion of the cores which intersect within the substantially triangular region 4 are of a second (different) core material from the material outside the triangular region 4. Note that this means that the different light paths, which are of different respective geometrical lengths in the region 4, include different respective geometrical lengths of the second core material (i.e. the intersection of the optical paths with the region 4 varies with the geometrical length of the paths). An appropriate selection of the two core materials provides temperature compensation of the kind described above, whereby the functionality of the AWG is temperature independent. The arrangement of FIG. 4 is appropriate when Δn/ΔT of the cores in the region 4 is lower than the Δn/ΔT of the cores outside the region 4. If the opposite were true, the triangle 4 could be formed vertically inverted (i.e. to point upwards in FIG. 4) so that the longer paths would have a shorter geometrical length of intersection with the region 4. An array waveguide diffraction grating using the above structure is made as follows. Using a synthetic quartz glass (SiO2) substrate of thickness 1 mm and diameter 76 mm (3 inches) as a direct cladding, trenches are formed using RIE in an optical waveguide pattern forming an array waveguide diffraction grating. The waveguide regions 45, 46, 47 shown in FIG. 4 were formed with a width of 6 μm, and a depth of 6 μm, and the narrowest spacing (i.e. the width of the cladding formed between two adjacent channels) is appeared as 4 μm at the region of FIG. 4 in which the array waveguide 47 meets the coupling sections 48, 49. The coupling sections are slab waveguides having a width of 5 mm, a length of 12 mm and a depth of 4 μm. The second core material of the triangular region 4 in FIG. 4, and the first core material of the other trenches are formed by PECVD. Annealing process after deposition is effective to improve the qualities of the glass, such as suppressing fractuation of the refractive index, and removing impurities such as hydrogen. The annealing conditions are 1100° C. and 30 minutes. This temperature is higher than the glass transition temperature of the core glass, but lower than the softening temperature of the cladding glass which is SiO2. The surface of the embodiment is polished to remove the films outside the trenches and cladding material was applied to the surface by optical contact and thermal bonding. The thermal bonding was carried out for 30 minutes at 1100° C. The upper cladding layer may alternatively be formed by deposition. Two patterns of AWG were formed at the same time on a single substrate, so in order to get the AWG devices from this substrate, it was necessary to be diced into a chip having a AWG circuit. Then, the respective waveguides of the input region 45 and output region 46 are connected to respective fibres. Signals are input and output using these fibres. When these fibres are provided, the device is completed. An AWG device was produced in this way, having a operating wavelength range of 1.551 μm band and with a channel spacing of 0.8 nm (corresponding to an interval of 100 GHZ), and having 41 channels. The characteristics of this device were measured by connecting one input port near the middle of the input region 45 to a tunable laser source, and measuring the light signal output from one output port of the output region 46. In order to measure the temperature characteristics, the whole device was installed in an temperature control chamber, and the temperature was raised in steps, and once the temperature had stabilized sufficiently the wavelength of the output light signal was measured. In the case of raising the temperature from −20° C. to 80° C., the total change of the output wavelength of the AWG device with the structure of the embodiment was found to be adequately low. Specifically, it was 0.05 nm. Note that according to reported data, the change of the output wavelength in prior art AWG is 0.012 nm/° C., from which one can estimate that the change between −20° C. and 80° C. was 1.2 nm. Due to this value, even if the channel spacing is 1.6 nm, precise control of the temperature of the device is required for practical applications, in case the change in the output wavelength becomes too high. Note that U.S. Pat. No. 6,304,687 shows an AWG device in which an array of waveguides is interrupted by a triangular resin section which exhibits a negative Δn/ΔT placed in an array region of an AWG in a configuration similar to the positioning of the triangular region 4 in the array region 47. Although there are no core paths in this region, light is able to propagate within the resin from one side to the other, and different light paths include different lengths of resin. Thus, an appropriate selection of the resin material makes it possible to achieve temperature compensation in a way similar to the embodiment described above. However, this device is subject to severe losses, since light is undirected while propagating within the resin triangle. The present embodiment is not subject to this disadvantage, since all light paths have light guiding structures (i.e. cores and cladding material) along substantially their entire lengths, albeit of differing materials in different locations. Whereas the embodiments above attempt to achieve temperature independent operation, other known functional optical devices actually utilize the temperature dependence. For example, a fourth device which is an embodiment of the invention, a thermo-optic light switch 50, is shown in FIG. 5. This device consists of symmetric Mach-Zehnder interferometer (MZ-I). In this case a resistor 51 has a temperature controlled by external leads 52, 54, so that the temperature along the portion shown within rectangle 53 can be varied in relation to that along other portions. This means that the temperature along part of the light path 55 can be varied in relation to that along a second light path 56. According to the temperature of the portion 53, light input to one of the light paths (say path 55) is transmitted either to the opposite end of the same light path or to the opposite end of the other light path. The resistor 51 is set close to the core to detect the temperature change sensitively. In this embodiment, over cladding with thickness of 20 μm after polishing is performed by FHD method. And then, the resistor 51 is prepared by sputtering of Cr on the cladding layer. There are two directional couplers 57, 59, and in these regions it is desirable that there is small temperature dependence. By using this MZ-I device, a switching operation can be achieved by changing the temperature along the portion shown within rectangle 53. The present invention thus proposes that a device 50 includes a portion of a different core material (one having a high temperature dependence) in the region of the optical path near the resistor 51 (e.g. the portion shown within rectangle 53), and material of relatively lower temperature dependence in other places to achieve stable coupling condition against temperature change. The core materials may be selected from those shown in Table 1. For example, the material having high temperature dependence can be 90SiO2-10GeO2, and the one having a relatively lower temperature dependence may be 87SiO2-8GeO2-5B2O3. In other variations of the embodiment, the GeO2 may be replaced with materials such as tantalum oxide, titanium oxide, silicon nitride, tantalum nitride, silicon carbide, tantalum carbide, or titanium carbide. Note that in the absence of heat generated by the resistor 51 the ΔL of the two paths is zero (it is symmetric), in contrast with the Mach-Zehnder interferometer of FIG. 3 which is intrinsically asymmetric. A fifth device which is an embodiment of the invention is shown in FIG. 6, and is a variable optical attenuator (VOA) 60. The device includes a single optical path 61 defined by a trench-type core and having an entry portion 62, an exit portion 63 and between them a portion 64 at which the temperature is controlled by a resistor 65 operated by external leads 66, 67. The core material in the region 64 is thermochromic, and the core material in regions 62, 63 is not thermochromic. This makes it possible that the regions 62, 63 of the device should have low losses, as compared to known devices in which the core is entirely formed from thermochromatic material. A sixth device 70 which is an embodiment of the invention is shown in FIG. 7. Again it is a Mach-Zehnder interferometer, but in this case it is one designed to be controllable, and thus operates as a VOA device. Specifically, a first path extends between an input 71 and an output 73, while a second path extends between an input 72 and an output 74. The different paths have different respective geometrical lengths L1, L2 between couplers 75, 76. The first path is heated in a heat-receiving section of its length by a resistor 78 controlled by electrodes. All these features are known in prior art Mach-Zehnder interferometer-type VOAs. However, in contrast to known systems the device 70 includes a region 77 of geometrical length L in which the core of the second path is of a different material from that of the rest of the device, and specifically one core material has a refractive index which increases to a great extent with increasing temperature, and the other core material has a refractive index which increases less than that of the first material. For example, the refractive index of the core material in the region 77 may increase less with increasing temperature compared to the material which composes the rest of the cores. Writing the increase in the refractive index of one path as Δn1 and the increase of the refractive index of the other path as Δn2, the critical measure is Δn1-Δn2. To understand the operation of the invention consider firstly what the operation of the device 70 would be if the region 77 were not present. In this case, since L1 and L2 have a geometric length difference ΔL, the device 70 will only pass light having a wavelength λ given by mλ=nΔL where m is an integer and n is the refractive index. Upon a current being applied to the resistor 78, the temperature of the heat receiving section of the first path will increase, changing its refractive index, and thus changing the wavelength which is passed, resulting in a change of the transmitted power, so that the device acts as a VOA. Unfortunately, heat will also conduct in time to the lower path, changing its refractive index in the same way, and thus reducing the difference between the optical lengths of the paths. To address this, the current applied to the resistor 78 must be raised to increase the temperature of the upper path. As this cycle continues, the ambient temperature TA of the device, which is the temperature of the second path, rises linearly with time, for example as shown in FIG. 8(a) (in which the vertical axis indicates the rise in temperature caused by the resistor 78 during the operation of the device), and the temperature T1 which is required to be applied to the heat receiving section of the first path by the resistor 78 rises. This gradually rising temperatures may cause the device to overheat, unless a cooling device, such as cooling fins, is used, thus increasing the size and cost of the device. By contrast, since in the embodiment the region 77 is present, when heat spreads from the first path to the region 77 it changes the refractive index in the direction opposite to the change it causes in the first path. In other words, depending on the value L, the temperature dependence of the optical length of the second path varies. It may for example be zero, or it may be opposite to that of the first path. Thus, heat transmission from the first path to the second path need not prevent the Mach-Zehnder interferometer 70 from working, and it is not necessary to further increase the temperature of the first path to maintain the operation of the device 70. Thus, the device may be operated with the first path remaining at a lower temperature than in the known devices described above, which in turn means that less heat is transmitted to the first path. The device 70 may thus avoid the need for cooling fins to be present. The temperature dependence of the ambient temperature TA may thus be as shown in FIG. 8(b). Lines 81, 82, 83, 84 show, for four respective increasing values of L, the corresponding temperature at which the temperature of the heat-receiving section of the first path is maintained by the resistor 78. Line 82 is the case that the L is a length (e.g. 18 mm) such that the resistor 78 should maintain the temperature of the first path at the same value irrespective of the ambient temperature, while lines 83, 84 show the operation of the device for two higher values of L, and line 81 shows the operation of the device for a smaller value of L. Note that the initial rate of increase of temperature shown in line 81 is lower than that of T1 in FIG. 8(a). Gradually, all the curves TA, 81, 82, 83 and 84 eventually reach constant values as an equilibrium state is reached. As an example of this embodiment, the Mach-Zehnder interferometer-type VOA device may be an asymmetric one operating at a wavelength of 1.55 μm. The geometrical lengths between the couplers 75, 76 may be around 42 mm, and they may have a difference of ΔL=4.24 μm. Both the two core materials may have a refractive index of n=1.4632, but each may have a different temperature dependence, such as Δn1=9×10−6 and Δn2=8.01×10−6 respectively. The first core material may be deposited in the whole of the core area, except the region 77. The second core material may be deposited in the region 77, where the waveguide length may be L=18 mm. We prepares a device having these characteristics, and with a heater 78 having a length of 2 mm near to the longer path in FIG. 7. Using this device, when the temperature difference between the heater and the ambient temperature was required to be 20° C. in order to adjust into the desirable output power from the device, we found that the difference in temperature remains constant as shown as line 82 in FIG. 8(b) even though the ambient temperature gradually increased. Note that many variations of the device 70 are possible within the scope of the invention. In particular, it is not necessary that the region 77 is provided on the opposite optical path from the resistor 78. For example, the region 77 may actually be the heat-receiving section of the first optical path. We now turn to a further embodiment of the invention. This embodiment is motivated by the known difficulty of coupling two different optical devices. For example, it is often desired to couple two devices which each contain an optical path (e.g. two devices each containing an optical fibre), with the end of one fibre being connected to the end of the other fibre. The two fibres may have different respective widths (and therefore different refractive indices, even if the material they are formed from has the same propagation constant). In such situations a technique known as TEC (thermally expanded core) is used, in which atoms of a material such as Ge are allowed to diffuse outside of the core at the end of the fibre of narrower width, to thereby increase its effective width and thus decrease refractive index at the end, so that the sizes and refractive indices of the two fibres are made equal at the interface between them. However, TEC has a number of drawbacks, one of which is that it is not readily applicable to connecting a waveguide to an array of fibres, since the width of the end surface of the waveguide is too great (typically 1 mm, compared to 125 μm for a single fibre) for Ge diffusion to be convenient. To address this, consider a further embodiment of the invention shown in FIG. 9, which is a device 90 (such as a waveguide) which includes cores 91 (for illustration only two are shown, but usually the number of cores will be greater than 2, e.g. 10) and which is to be coupled to another optical device 92 including one or more fibres 93. In particular, in order to make the waveguide device small adopting small bending radius of the waveguide patterns, one should attempt to keep the bending loss from becoming large. For this reason, the waveguides having large refractive index difference between the core and the cladding and small size of the core, so-called super-high delta waveguides, are very useful. In this case, the coupling loss at the connection between the waveguide and a conventional single mode optical fibre (with a core diameter of 8 μm) will become very big. This is the typical difficulty of coupling two different optical devices. In this embodiment, the waveguide includes a functional portion 94 in which the cores 91 must have a smaller width of 4 μm and a refractive index of 1.4799, whereas the fibres 93 in a typical fiber array 92 have a greater diameter of 8 μm and are composed of a material having a smaller refractive index. In the embodiment, each of the cores 91 terminates by a respective waveguide 95 through a transition region 96 of the device 90 which is to be coupled to the device 92. Each waveguide 95 is of a different material having a refractive index of 1.4632 and a width of 7.5 μm, which is matched to that of the fibres 93. At a transition region 96 of the device 90, core width is gradually spread from 4 μm to 7.5 μm. FIG. 10 is a cross-sectional view of part of the device 90 shown in FIG. 9 (in FIG. 10 the view is in a direction parallel to the surface of the device 90), showing a possible structure of the transition between the cores in the functional portion 91 and in the coupling waveguide 95. Both are covered by a cladding layer 97. This structure may be achieved by the methods described above. Because of this, the coupling loss with the optical fibre array 92 is very much reduced, and the miniaturisation of the waveguide device became possible. The application of this embodiment is not limited to coupling to a conventional optical fibre. Instead, the embodiment may be adapted to suit the mode field diameter of the output waveguide 93 of any other optical device 92. All of the devices 20, 30, 40, 50, 60, 70, 90 are preferably formed by the method of the invention described above in relation to FIG. 1. In particular, indeed it is considered that this is presently the only commercially realistic way in which they can be formed, the invention is not limited in this respect. Although preferred embodiments of the invention have been described above, many variations are possible within the scope of the invention as will be clear to a skilled reader. For example, although all the devices shown have only two different core materials in different regions, the invention is not limited in this respect and devices according to the invention may include core regions formed of any number of different respective core materials.
<SOH> BACKGROUND OF INVENTION <EOH>Recently there has been a growth in demand for improved functional optical devices, especially for use in DWDM (dense wavelength division multiplexing) systems. It has become necessary to provide improved functional optical devices such as Mux (multiplexer) devices, DeMux (demultiplexer) devices, amplifiers, optical switches and VOA (variable optical attenuator) devices. It is known to form such devices as PLC (planar lightwave circuits), in which light moves along paths defined by cores extending over a substrate in a plane parallel to the surface of the substrate. Conventional PLC fabrication methods produce cores which are either ridge structures or trench structures. Ridge-type cores are ridges of a selected core material upstanding from a layer of cladding material formed over the substrate. Trench-type cores are formed by depositing a selected material within a pre-formed trench in a layer of cladding material which itself overlies the substrate. Generally, ridge structures are more common than trench structures. The fabrication method of a ridge-type core is typically as follows. Firstly, a substrate such as Si is covered by a cladding layer of a cladding material (such as SiO 2 ), and then a layer of core material (such as SiO 2 including GeO 2 ). which is to be formed into the core. A mask is applied in selected regions over the core layer, and the exposed portions of the core layer are etched by an etching process such as reactive ion etching (RIE), to leave the ridges of the core material. After the mask is removed, a further cladding layer is provided over the surface of the device, so that the ridges are fully embedded between two cladding layers. Although this method is successful, it is difficult to modify it to produce a device in which different portions of the core are formed of different materials, since depositing each core material requires a series of process steps. Additionally, it is difficult to control the thickness of the two different core materials at regions when they meet. One example of a device having two different core materials is U.S. Pat. No. 6,201,918, which describes a device in which a Mach-Zehnder interferometer having two optical fiber arms is processed by splicing an optical path changing segment into one of the arms.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention aims to provide new and useful optical devices, and new and useful methods for producing optical devices. In general terms the present invention proposes that an optical device is formed having one or more cores which are trenches, different portions of the core(s) being formed from different materials. The invention is based on the realisation that it is easier to form trenches of different materials than to form ridges of different materials. This factor more than compensates for the factors because of which ridge-type cores are normally preferred to trench-type cores. The optical devices may be formed by the steps of forming trenches within a cladding layer (normally a cladding layer which is located on a substrate), covering certain areas of the trenches, depositing a first core layer of a first core material to fill the trenches which are not covered, removing the cover, depositing a second core layer of a second core material to fill the trenches which were previously covered, removing core material outside the trenches, and applying a cladding layer to cover the trenches. Preferably, the core material outside the trenches is removed by polishing. Previously polishing techniques were not capable of polishing the whole surface of an optical device with an accuracy on the level of the dimensions of desired trenches (e.g. 6 micrometers), which is one reason why ridge-type cores are conventionally preferred to trench-type cores. However, the present inventors observe that advances in polishing techniques have removed this factor, making trench-type cores more acceptable. It is to be understood that the present invention is not limited to the case in which there are exactly two different core materials. Rather, the present invention makes it possible to form optical devices in which any number of different materials are used to form different portions of the cores. Each material is deposited into the respective portion(s) of the trenches at a time when all the other portions of the trenches are either already filled by a previously deposited core material or covered. The present invention makes it possible to form a variety of devices having cores composed of different materials. Examples of such devices are given below, and include, but are not limited to amplifier devices, interferometer devices such as Mach-Zehnder interferometers, arrayed-waveguide gratings, thermo-optic switches, variable optical attenuators, and gain flattening devices. In particular the present invention makes it possible to provide optical devices which have predefined thermal characteristics. For example, in some optical devices according to the invention, optical paths of differing geometrical lengths include portions of different respective core materials (so that they have different optical path lengths, i.e. the product of the geometrical length and the refractive index value). The various core materials are selected to have different thermal properties, such that although the paths have different geometrical lengths, the optical path lengths vary with temperature in the same way (i.e. the differing core materials compensate for the differing geometrical lengths of the optical paths). In this way it is possible to ensure that the performance of the overall optical device is not temperature dependent. Alternatively, in other devices a temperature dependence is actually desirable. The present invention makes it possible to tailor this temperature dependence by appropriate selection of different core materials. Specifically, a first expression of the invention is a method of producing an optical device, the method including the steps of: forming trenches within a cladding layer; covering certain areas of the trenches; depositing a first core layer of a first core material to fill the trenches which are not covered; removing the cover; depositing a second core layer of a second core material to fill the trenches which were previously covered; removing core material outside the trenches; and applying a cladding layer to cover the trenches. A second expression of the invention is an optical device having one of more cores defining one or more optical paths, each core being formed as a trench within a cladding layer, different portions of the core or cores being composed of different core materials.
20041129
20070320
20050804
63005.0
0
CONNELLY, MICHELLE R
FUNCTIONAL OPTICAL DEVICES AND METHODS FOR PRODUCING THEM
UNDISCOUNTED
0
ACCEPTED
2,004
10,516,432
ACCEPTED
Method for controlling a device for treating the human eye
The invention relates to a method for controlling a device for the treatment or refractive correction of the human eye by means of an electronic computer. The aim of the invention is to create a method for controlling a device for treating the human eye, which provides a simple overview of the influence of all of the parameters. To this end, once the operating parameters have been determined, a graphical simulation of the operating procedure is carried out in the form of a graphical visualization.
1-13. (canceled) 14. A method for controlling a device for an ablation of a part of a human eye using laser irradiation, the control being exercised using an electronic data processing system, the method comprising: determining optic and geometrical data of the eye; and performing a graphic simulation of the ablation in the form of a graphic visualization. 15. The method as recited in claim 14, further comprising inputting a plurality of treatment parameters manually using a central input/output device. 16. The method as recited in claim 15, further comprising determining a plurality of operating parameters, wherein the determining includes at least one of: a) establishing a topography data of the eye; b) establishing a refraction data of the eye; c) establishing a higher-order aberration data of the eye using wave-front measurement; d) establishing a pachymetry data of the eye; e) establishing a pupillometry data; f) point-accurate overlaying of all the measurement data from a) through e) in a fixed coordinates system of the eye; g) calculating a height data of deviations relative to a reference surface; h) calculating a height data difference relative to the reference surface; g) calculatiing an adapted height data difference relative to the reference surface; h) calculating ablation coordinates for the device, wherein the device includes a laser. 17. The method as recited in claim 16, wherein the establishing of the refraction data includes establishing at least one of a subjective and an objective refraction data. 18. The method as recited in claim 16, further comprising calculating a height data of deviations of a cornea surface of the eye relative to a reference surface using at least one of the topography data and the refraction data. 19. The method as recited in claim 18, further comprising determining a tissue to be abraded from the cornea of the eye using the height data of the deviations of the cornea surface. 20. The method as recited in claim 16, further comprising determining a result using the topography data, the result including at least one of a K value, a curvature map, a topography map, and a power map, and wherein the controlling the device for the ablation is performed using the result. 21. The method as recited in claim 16, wherein the establishing of the refraction data of the eye includes establishing at least one of spherical refraction data and cylindrical refraction data. 22. The method as recited in claim 16, wherein the reference surface is an ellipsoid. 23. The method as recited in claim 16, wherein a refraction reference surface of the refraction data is a spheroid. 24. The method as recited in claim 14, wherein the device for ablation includes at least one of a laser and a wave-front measurement device. 25. A device for treating a human eye using laser irradiation, the device comprising: a aberrometry apparatus configured to measure an aberrometry of the eye; a topography apparatus configured to measure a topography of the eye; a pachymetry apparatus configured to measure a pachymetry of the eye; an overlaying apparatus configured to provide a point-accurate, centred overlaying of the aberrometry, topography, and pachymetry; a laser unit; and an electronic data-processing apparatus configured to link the aberrometry, topography, pachymetry and further patient data to ablation values using a processing model. 26. The device as recited in claim 24, further comprising a pupillometry apparatus for measuring a pupillometry of the eye. 27. The device as recited in claim 25, wherein the aberrometry apparatus, the topography apparatus, the pachymetry apparatus, and the pupillometry apparatus are disposed in a measuring equipment arrangement configured to allow measurement of aberrometry, topography, pupillometry and pachymetry using a fixing. 28. The device as recited in claim 24, wherein the device is configured to display an ablation of the eye graphically as an ablation map.
The present invention relates to a method for controlling a device for the ablation of parts of the human eye, in particular the cornea, by means of laser irradiation, the control being exercised by an electronic data-processing system which provides data to a device for treating the human eye by means of laser irradiation, and a device for treating the human eye by means of laser irradiation. In ophthalmic surgery a series of methods are known which make possible, with or without additional invasive procedures, an abrasion of parts of the cornea surface to correct sight defects. In particular the PRK, LASIK and LASEK methods may be named here. Traditionally, fine tuning of the refractive correction is carried out in the case of sphere and cylinder on the basis of subjective phoropter measurements, because the best possible standard correction can thereby take place in individually secured manner without taking higher aberrations into account. In the meantime, higher aberrations can be subjectively evaluated with the help of a so-called phase-plate phoropter which is known for example from DE10103763, or adaptive phoropters, and used for refractive correction. A problem when carrying out such treatment procedures is the fact that slight changes in the treatment parameters can have a marked effect on the success of the treatment. Reliance is usually placed here on the experience of the doctor in attendance, the assumption being that he is aware of the significance of the effect of all the parameters. The object of the present invention is therefore to provide a method for controlling a device for treating the human eye which provides a simple overview of the effect of all the parameters. This problem is solved by a method according to claim 1. It is provided according to the invention that once the optical and geometric eye data have been established a graphic simulation of the ablation is carried out in the form of a graphic visualization. During the graphic visualization, in particular the pachymetry of the cornea before and after the treatment procedure is represented graphically. The optical and geometric eye data are in particular thickness (pachymetry) and also the curvature of the cornea (topography). These data can be summarized for each eye in a pachymetry map and a topography map. In this way, the doctor in attendance can graphically anticipate the result of the treatment procedure and in particular recognize problem areas. In addition, problems that can be expected, such as too small a residual thickness of the cornea in part areas, can be established by the computer software used and displayed as a warning. In particular for the correction of several sight defects, an optimum parameter configuration can be discovered with the help of the method according to the invention, for example by varying one or more parameters. This makes it possible to optimize the ablation for example to a minimum abrasion of the cornea. All the parameters can be entered or automatically recorded by means of the computer software which contains all the reciprocal relationships and which can thus calculate a correction which takes all the relevant factors into account. However the weighting and selection of the parameters is not unequivocal, but determined by various patient-specific objectives; e.g. best sight during the day, best sight at dusk, smallest corneal abrasion or similar. The computer software preferably includes an operating interface with the help of which, using the weighting presented previously, the doctor can swiftly arrive at an optimum correction. A mode can also be selected which makes possible a manual adjustment of all parameters, e.g. via scroll boxes or similar displayed on the operating interface. The effect of the parameter changes is illustrated directly via a graphic simulation of the correction. All the treatment parameters that are to be entered manually are preferably entered by means of a central input/output device. This can be for example a computer screen connected to a keyboard or a so-called touch screen. In a development of the method according to the invention it is provided that the establishment of the operating parameters comprises one or more of the following process steps: establishment of topography data of the eye; establishment of refraction data of the eye; establishment of higher-order aberration data by wave-front measurement; establishment of pachymetry data; establishment of the pupillometry of the eye (preferably for various lighting conditions); point-accurate overlaying of all established measurement data in a fixed coordinates system of the eye; calculation of height data of the deviations relative to a reference surface; calculation of a height data difference relative to the reference surface; calculation of an adapted height data difference relative to the reference surface; calculation of ablation coordinates for the laser. K values and/or a curvature map and/or a topography map and/or a power map are preferably obtained from the topography data. The spherical and/or cylindrical refraction correspondingly form part of the data for controlling the ablation device. The reference surface is freely selectable as regards the topography data, preferably an ellipsoid, in the case of the ellipsoid the reference surface of the refraction data is correspondingly a spheroid. When establishing the pupillometry, i.e. in particular the diameter of the pupil, parameters of the various lighting conditions are preferably included, as the pupil diameter changes depending on the lighting. The deviation of the centre of the pupil can thus shift by up to 0.5 mm under different lighting conditions. Additional parameters such as special patient wishes regarding visual acuity distribution or similar are included in the adapted height data difference. As a result of the overlaying of these measurement data in a fixed coordinates system of the eye, the overall correction of the eye can be shown in one representation. In a development of the method according to the invention it is provided that in a further intermediate step, height data deviations of the cornea surface relative to a reference surface are calculated from the topography and/or refraction data. The height data are stored as a height data map of the deviations and can be visualized graphically. In a development of the method according to the invention it is provided that in a further intermediate step the tissue to be abraded from the cornea is determined from the height data of the deviations of the cornea surface. In a preferred version the device for treating the human eye includes a laser and/or means for wave-front measurement. The problem named at the outset is also solved by a device for treating the human eye by means of laser irradiation comprising an apparatus for measuring aberrometry, an apparatus for measuring topography, an apparatus for measuring pachymetry, optionally an apparatus for measuring pupillometry, an apparatus for point-accurate, centred overlaying of the measurement data of all the measuring equipment of a laser unit and also an electronic data-processing apparatus which by using a treatment model can link the measurement values and further patient data to ablation values. This device preferably also includes an apparatus for measuring the pupillometry of the eye, i.e. a pupillometer. The device preferably includes a measuring equipment arrangement which allows the measurement of aberrometry, topography, pupillometry and pachymetry by means of a fixing, i.e. in a point-accurate reference of the measurement data to a centred fixed coordinates system of the eye. For this, the device has a combination of the necessary measuring instruments which make possible a measurement of the eye to be treated via a common eyepiece or overlay all separate measurement data centred vis-à-vis a location-specific coordinates system and display them together in their interaction. This is preferably carried out by determining the optical axis or the visual axis of the eye during the measurements using each individual measuring apparatus and then using these to display all the measurement data point-accurate, centred, overlaid. For this, the application of marks to the eye can be envisaged, for example colour dots to which each measuring apparatus or each measurement with the individual integrated measuring apparatus can orientate itself and refer. It is also possible to use the texture of the iris, in particular the unchangeable areas of the iris, or the texture of the veins in the sclera, as fixed parameters during the measurement. The treatment model is realized as a software module. By treatment model is meant that the software can calculate, on the basis of the measured or manually entered parameters, the ablation for each individual point of the cornea surface. A weighting of all the measurement values or parameters is carried out by the software. The software thus represents a central recording and evaluation tool. The ablation for each point of the cornea surface produces an ablation map, i.e. a “chart” with which the surface can be displayed. The device is preferably capable of displaying the ablation for each point graphically summarized as an ablation map. The measuring instruments can also be arranged at least partly separately, their measurement results having to be imported manually into the device, or connected to the device by means of a data bus such as e.g. a serial cable so that their data can be automatically imported. Advantageous designs of the invention are explained further in the drawings. There is shown in: FIG. 1 a flowchart of the method; FIG. 1 shows a flowchart of the method according to the invention. Initially, the optical data of the eye are recorded in a first step. For this the topography is initially established in the form of K values, a curvature map, a topography map and a power map of the cornea. Pupil data and centring data such as the line of view (visual axis of the eye) are also included. In a next step, objective and subjective refraction data, namely the spherical and cylindrical refraction of the patient, are established. Objective refraction data are data which are established exclusively by measuring with a measuring apparatus. This can be for example by means of a refractometer or aberrometer. Subjective refraction data are data which are based on the feedback from the patient, who reports whether a potential correction is found to be “better” or worse. This is achieved for example by using a phoropter which displays potential correction scenarios on which the patient comments. With refractive correction of the cornea based on aberrometric wave-front data it must be taken into account that an aberrometer measurement is an objective measuring process. However, due to the physiological process of vision, the quality of the individual sight is ultimately fixed, not only by the objective optical quality of the optical system, the eye, but additionally by the subjectively evaluated visual faculty. With the device according to the invention and the method according to the invention, it is provided to also allow, in addition to aberrometry, topography, pachymetry, pupillometry, fixing/centring, registration (this is a point-accurate allocation of the measurement data of the eye to position the therapeutic correction, e.g. via local marks on the cornea or significant structures of the eye such as veins or iris structures) and phoropter, a subjective evaluation of the refraction with the help of a phase-plate or adaptive phoropter and an acuity projector to play a part. In a simplified method the subjective evaluation of the higher-order aberrations can be excluded, e.g. by means of Zernike polynomials, using the sphere and cylinder values determined with a refractometer and/or subjectively evaluated with a phoropter as a base data set for the refractive correction. In addition this base data set is supplemented by the objectively measured data of higher-order Zernike polynomials which are corrected by the spherical equivalent portions from the wave-front data. The higher aberration orders have a particular role in the production of aspherical lens profiles or correction profiles. The simplified method represented above can also be carried out directly on the basis of height data instead of the wave-front/data calculation based on Zernike polynomials. These aberrometer-aided height data are customary in the measurement data output of topography equipment and are obtained in aberrometers with the help of “zonal reconstruction”. Compared with data exchange on the basis of Zernike polynomials, they guarantee a higher spatial resolution of the wave front. Uncertainties with regard to the correct wave-front reconstruction in polynomial description can be largely avoided depending on the resolution of the zonal reconstruction. So-called “repair cases” can thus be realized based on a complete data set of the overall optical system. Also on the basis of these wave-front height data, it must be taken into account within the framework of the described simplified method that in addition to the base data set the wave-front data can also be supplemented as equivalent portions without the spherical and cylindrical base portions. In individually optimized treatment based on the method according to the invention, a higher quality of the refractive correction of the cornea is achieved in particular by combining the produced measurement data of the whole wave front and the topography of the cornea based on a polynomial breakdown, e.g. according to Zernike or Taylor and/or the height data. In this way, the refractive correction can be designed in consideration of the special characteristics of the different optical part-systems of the eye. Particular consideration is given to the cornea which delivers the main refracting power of the eye at approx. 80% and simultaneously forms the ablation target for refractive laser surgery. Thus in a simplified model the projection effects of the ablative laser spot on the spherical surface of the cornea can be taken into account for a radius of approx. 7.8 mm over a keratometric radius measurement of the cornea. A still more precise control of the ablation in consideration of the projective fluence variations of the laser spot on the cornea is obtained when the topography is taken into account. Thus not only can the ablation be controlled by the method according to the invention, in consideration of a keratometrically established radius of the cornea in order to balance out the projective fluence variations of the laser spot in particular at the margins of the ablation, but the topography data which describe the surface more accurately can also be used for this. The higher-order aberrations are objectively established by means of a wave-front measurement. Known devices and methods for wave-front measurement can be used for this. In a further step, height data of the deviations of the cornea surface relative to a reference surface are calculated from the thus-established refraction or topography data. They are established from refraction data, applying the standard algorithms, for example the Munnerlyn formulae. A sphere is used as assumed reference surface. In a further step the height data are derived from the topography data. The curvature of the reference surface is established using the refraction data. Here too the data are calculated using standard algorithms such as Munnerlyn formulae. The K values are also taken into account here. An ellipsoid is used as assumed reference surface. In a further step, the refraction data are linked to the data of the wave-front measurement. The curvature of the reference surfaces is established using the refractive data. The subjective refractions are calculated applying standard algorithms such as the Munnerlyn formulae and overlaying the thus-established data with high-order (HO) data. A sphere is used as assumed reference surface. In a third step the refraction data are linked to the topography data and the data of the wave-front measurement. Here too these values are overlaid with high order data in consideration of the K values applying standard algorithms such as the Munnerlyn formulae. An ellipsoid is used here as assumed reference surface. The difference in the topography data vis-à-vis the data established with the wave front measurement is problematic. In a further step the height data difference relative to the reference surface is now calculated. A chart (data map) is calculated with height data relative to the deviations to the reference surface. The height difference relative to the reference surface, and thus the tissue to be abraded is given for each point of the cornea surface. When applying the LASIK procedure, the flap thickness, the flap diameter and the direction of the fold (hinge side) of the flap are determined. Furthermore, data relating to pachymetry, the thickness of the cornea, are included in the form of a pachymetry map. The effects of pachymetry on the ablation depth are determined. In addition, further patient data such as the age and the cylinder data of the patient are included. Effects on the correction of the refraction and correction of the cylinder axis are also calculated from these. Depending on the method to be carried out, for example PRK or LASIK, process-typical effects on the nomograms and the refraction are established. In addition certain optimizations are taken into account, e.g. TSA, Night Vision, ASAP grade. A reference surfaces fit is brought about in each zone with a Z shifting. With the parameters shown above, patient-adapted (customized) height data differences relative to the reference surface are established from the height data difference relative to the reference surface. This results in an adapted data map with height data of the deviation relative to the reference surface. The ablation algorithms are realized with these data. This produces as a result the output of the residual thickness, the ablation volume and the residual defect. In addition to the previously established data the influences of the laser parameters, in particular the energy density distribution, the firing frequency, the spot geometry and also the resolution accuracy of the scanner are taken into account. In addition the data with regard to smoke and thermal problems are incorporated. In addition, reflection and projection data are established, in particular the change in energy density distribution and reflection losses. This yields correction data for the ablation target data. Finally, ablation coordinates for the laser are issued, in this case coordination data for specific lasers (for example MEL 70). The established and calculated data can be issued on a computer screen in the form of a graphic simulation. The simulation displays the cornea to be treated for example in different colours or similar in top view or in section so that the doctor in attendance can assess the whole procedure in advance. Thus it is possible with this device or the electronic data-processing system which consists either of a networked or compact integrated measuring equipment system to record all the objective and subjective data of the optical refraction and geometry of the eye is such a way that they are stored or displayed overlaid centred and point-accurate in a fixed coordinates system of the eye.
20050729
20101123
20060323
73951.0
A61F9008
0
FARAH, AHMED M
METHOD FOR CONTROLLING A DEVICE FOR TREATING THE HUMAN EYE
UNDISCOUNTED
0
ACCEPTED
A61F
2,005
10,516,791
ACCEPTED
Container for collecting and disposing of animal excreta
A hand-held portable container (1) for collecting and disposing of animal excreta comprising a shell (5,101) having an opening for receiving excreta, the shell (5,101) having an impaling means including a plurality of tines (8) disposed within the shell (5,101) for impaling excreta. The tines (8) are provided by teeth (105) tapered so that the edges of the teeth (105) closet to the opening of the shell (5,101) are thin enough to allow at least partial penetration of excreta received into the opening. An aerosol cartridge (4,136) is mounted in a housing (3,131) of the container (1) and the cartridge includes a freezing component for freezing the excreta to the tines of the shell.
1. A hand-held portable container (1) for collecting and disposing of animal excreta comprising a shell (5, 101) having an opening for receiving excreta, the shell (5, 101) having an impaling means including a plurality of tines (8) disposed within the shell (5, 101) for impaling excreta. 2. A hand-held portable container (1) as claimed in claim 1, wherein the tines (8) are provided by teeth (105) tapered so that the edges of the teeth (105) closest to the opening of the shell (5, 101) are thin enough to allow at least partial penetration of excreta received into the opening. 3. A hand-held portable container (1) as claimed in claim 1, wherein the teeth (105) extend radially inwardly from the shell (5, 101). 4. A hand-held portable container (1) as claimed in claims 2 or 3, wherein the teeth (105) are symmetrically disposed about the central axis of the shell (5, 101). 5. A hand-held portable container (1) as claimed in any one of the preceding claims, wherein the shells (5, 101) are nestable with one another. 6. A hand-held portable container (1) as claimed in any one of the preceding claims, wherein the container (1) comprises a housing (3,131) having one or more shells (5, 101) releasably mounted thereon. 7. A hand-held portable container (1) as claimed in claim 6, wherein one or more shells (5, 101) are held on one end of the housing (3, 131) by a collet (141). 8. A hand-held portable container (1) as claimed in claim 6, wherein the shells (5, 101) are held in place by friction. 9. A hand-held portable container (1) as claimed any one of the preceding claims, wherein the shell (5, 101) has a flared open end. 10. A hand-held portable container (1) as claimed in claim 6, wherein an aerosol cartridge (4, 136) is mounted in the housing (3, 131). 11. A hand-held portable container (1) as claimed in claim 10, wherein the aerosol includes a freezing component 12. A hand-held portable container (1) as claimed in claims 6 to 11, wherein the housing (3, 131) comprises two identical semi-cylindrical plastics mouldings (133). 13. A hand-held portable container (1) as claimed in claims 6 to 12, wherein a second end of the housing accommodates means for actuating an aerosol cartridge (4, 136) so that a predetermined portion of aerosol is dispensed. 14. A hand-held portable container (1) as claimed in claims 6 to 13, wherein the actuating means comprises a button (150) housed in the second end of the housing and being depressible so as to dispense aerosol from the aerosol cartridge (4, 136). 15. A hand-held portable container (1) as claimed in claim 14, wherein the button (150) is normally urged out of the housing (3, 131) by a biasing means on the nozzle of the aerosol cartridge (4, 136). 16. A hand-held portable container (1) as claimed in claims 14 or 15, wherein the travel of the button (150) is selected to accommodate a wide range of aerosol cartridges (4, 136). 17. A hand-held portable container (1) as claimed in claims 10 to 16, wherein the shells (5, 101) have an aperture for receiving the aerosol from the aerosol cartridge (4, 136). 18. A hand-held portable container (1) as claimed in claim 17, wherein the aperture (104) is disposed centrally of the shell (5, 101) and is substantially aligned with the dispensing nozzle in use. 19. A hand-held portable container (1) as claimed in claim 18, wherein the impaling means is removably mounted on the shell. 20. A hand-held portable container (1) as claimed in claim 19, wherein the impaling means comprises a base located outside the shell and a plurality of tines outstanding therefrom, extending through and disposed within the shell, the shell having a plurality of apertures aligned with the fines for slidable engagement therewith. 21. A method of collecting animal excreta comprising the steps of contacting the excreta with a solid body, dispensing aerosol including a freezing component around the excreta and solid body so as to form a bond between the excreta and the solid body and subsequently lifting the solid body so as to remove the excreta from the surface it was deposited on. 22. A hand-held portable container substantially as hereinbefore described and with reference to FIGS. 1 to 3 of the accompanying drawings. 23. A hand-held portable container substantially as hereinbefore described and with reference to FIGS. 4 to 19 of the accompanying drawings. 24. A method of collecting animal excreta substantially as hereinbefore described and with reference to the accompanying drawings.
This invention relates to a container for collecting and disposing of animal excreta and in particular to a hand held apparatus for collecting dog's excreta. Various cities and towns throughout the world have introduced legislation making it a public offence for a dog owner to allow a dog to foul the pavements or public parks without removing the excreta thereafter. An apprehended person walking the animal is often subject to a fixed penalty fine. In any event, this is an unhygienic practice particularly in parks or areas where children are prone to be playing. The impact of both the deterrent of a fine and increased public awareness in relation to hygiene has produced a need for an apparatus to remove excreta from pavements, grass and other surfaces upon which a dog excretes during exercise or during any other time spent outdoors. A variety of apparatuses have been developed to assist pet owners with the task of removing excreta from a surface shortly after it has been deposited by a pet. WO 89/08744 discloses a refuse collector having a receiver for the refuse and a vacuum cleaner unit for collecting the refuse and transmitting it to the receiver. A source of refrigerant gas is provided to be directed onto the refuse to partly freeze it before it is collected and transmitted to the receiver. DE 3238062 discloses a container in which a cooling medium is accommodated to harden the surface of domestic animal faeces making it easier to lift and carry. The container is designed for both lifting and storing the faeces of the domestic animal. DE 29816807 discloses a device having a portable container with a cold spray enabling the dog excrement to be cooled before collection and disposal. The device enables the excrement to acquire a firm consistency prior to collection and disposal. The present invention provides an alternative construction of container for collecting and disposing of excreta deposited by a pet/domestic animal. Accordingly, there is provided a hand-held portable container for collecting and disposing of animal excreta comprising a shell having an opening for receiving excreta, the shell having an impaling means including a plurality of tines disposed within the shell for impaling excreta. The plurality of tines cause minimal dispersion of the excreta when an operator presses the tines down into it. The tines increase the surface area of the container which comes into contact with the excreta increasing the likelihood of a successful removal of all of the excreta from the surface it has been deposited on. Preferably, the tines are provided by teeth tapered so that the edges of the teeth closest to the opening of the shell are thin enough to allow at least partial penetration of excreta received into the opening. Ideally, the teeth extend radially inwardly from the shell. Preferably, the teeth are symmetrically disposed about the central axis of the shell. Ideally, the shells are nestable with one another. This reduces the space required for shells during storage, transportation and use. Ideally, the container comprises a housing having one or more shells releasably mounted thereon. Preferably, the housing comprises a hollow elongate element for receiving an aerosol cartridge. Ideally, the one or more shells are releasably mounted on a first end of the housing. Ideally, the or each shell is held on the first end of the housing by a collet Alternatively, the shells are held in place by friction. Preferably, the shell has a flared open end. This allows the shell to receive excreta of varying size and forms. Ideally, the aerosol includes a freezing component for freezing at least the outer skin of the excreta. This improves the bond between the tines and the excreta increasing the likelihood of a successful removal of the excreta, at the first attempt. Preferably, the housing comprises two identical semi-cylindrical plastics mouldings. This reduces the manufacturing costs of the housing. Preferably, a second end of the housing accommodates means for actuating an aerosol cartridge so that a predetermined portion of aerosol is dispensed. Ideally, the actuating means comprises a button housed in the second end of the housing and being depressible so as to dispense aerosol from the aerosol cartridge. Preferably, the button has a predetermined travel so that a desired quantity of aerosol is dispensed when the button is depressed along the full distance of its travel. Ideally, the second end of the housing defines a slot and the button has a flange housed within the slot so that the travel of the button is delimited by the width of the slot. Preferably, the button is normally urged out of the housing by the biasing means on a nozzle of the cartridge. Ideally, the travel of the button is selected to accommodate a wide range of aerosol cartridges. Preferably, the surface of the button in contact with the aerosol cartridge is substantially hemispherical. Preferably, an outer surface of the housing for receiving a hand is adapted to increase friction between the users hand and the housing. Ideally, a rib and groove formation is provided on at least a portion of the outer surface of the housing. Preferably, means for engaging the nozzle of the aerosol cartridge are provided on the first end of the housing so that a predetermined optimum quantity of aerosol is dispensed when the button is fully depressed once. Ideally, a seat is provided for supporting the dispensing end of the cartridge. Preferably, the engagement means depresses the nozzle of the aerosol cartridge in response to the button being depressed so that aerosol is dispensed. Ideally, a plurality of shells are releasably mounted on the first end of the housing. Preferably, the shells have an aperture for receiving the aerosol from the cartridge. Ideally, the aperture is disposed centrally of the shell and is substantially aligned with the dispensing nozzle in use. Preferably, an upstanding collar is disposed on the outside of the shell surrounding the aperture. Ideally, the collar is suitably dimensioned for engaging the nozzle of the aerosol cartridge in order to dispense aerosol in response to the button being depressed. In a first embodiment, the impaling means is integrally formed with the shell. In a second embodiment, the impaling means is removably mounted on the shell. In the second embodiment, the impaling means comprises a base located outside the shell and a plurality of tines outstanding therefrom, extending through and disposed within the shell, the shell having a plurality of apertures aligned with the tines for slidable engagement therewith. In a third embodiment, sharp tines penetrate the shell without the need of apertures. The shell facilitates their cleaning upon withdrawal. Ideally, the shell comprises a base and a wall outstanding from the periphery of the base. In a fourth embodiment, the container comprises a housing having one or more shells releasably mounted thereon and a fluid delivery means being mounted on the housing for communicating fluid from an aerosol cartridge mounted on the housing to the area around the fines. In any embodiment, a lid is provided for engagement with the shell for covering the tines and any excreta impaled thereon prior to disposal. This improves the hygienic aspect of the container. Preferably, the lid has a covering plate and a flange projecting substantially orthogonally from the plate. Ideally, the flange extends around the external surface of the shell at or about the shell's free edge to prevent contamination from excreta lodged adjacent to the free edge. In any embodiment, the shell, lid and tines are formed from plastic. In any embodiment, the shell and lid are formed from cardboard and the tines are formed from wood. In the second embodiment, the base of the impaling means is formed from cardboard and the tines are formed from wood. In the second embodiment, the base of the impaling means and the tines are formed from plastic. In the second embodiment, the housing is integrally formed with the base of the impaling means on the side of the base opposite the side which carries the tines. In a fifth embodiment, the housing has a substantially c-shaped resilient clip mounted thereon for receiving the aerosol cartridge. In the fourth or fifth embodiment, the fluid delivery means comprises a dispensing head for engagement with a nozzle of the aerosol cartridge and a pipe extending between the dispensing head and the area around the tines. In the fourth or fifth embodiment, the shell defines an aperture for receiving a free end of the pipe. In the fourth or fifth embodiment, the dispensing head has an annular shoulder formed for engagement with an annular flange on the nozzle to open the aerosol cartridge when an operator presses on the dispensing head allowing aerosol to flow out of the cartridge through the pipe to the area around the tines. It will of course be appreciated that an elongate handle in the form of a walking stick can extend from the housing, the handle having a means for remotely activating the dispensing head for opening the aerosol cartridge. Ideally, the free end of the pipe is located centrally of and extends through the aperture in the shell for communicating the aerosol to the area around the tines. In the second embodiment, the free end of the pipe is located centrally of and extends through the base of the impaling means and the aperture in the shell. In a sixth embodiment, the shell is releasably mounted on a housing having two main faces, one face carrying a means for fastening an aerosol cartridge thereon and the other face having a surrounding wall outstanding from the periphery thereof defining a cavity for receiving the shell. In the sixth embodiment, the shell and the cavity are dimensioned to form an interference fit therebetween. This allows the shell to be easily inserted into and removed from the cavity before and after use respectively. In the sixth embodiment, a screw is provided in a threaded bore extending through the wall outstanding from the face of the housing for engaging the shell housed in the cavity. In any embodiment of the invention, the wooden or plastic tines are replaced by metal tines having an integrally formed temperature reducing means. The reduced temperature of the metal fines results in freezing of the excreta in the area around the tines and providing a strong bond between the excreta and the tines. Preferably, a battery-powered light bulb or semi-conductor lamp and a switch are mounted on the housing. Ideally, transparent glass covers the light bulb to the front of the container and a red glass is provided for transmitting the light at the rear of the container. Accordingly, the present invention also provides a method of collecting animal excreta comprising the steps of contacting the excreta with a solid body, dispensing aerosol including a freezing component around the excreta and solid body so as to form a bond between the excreta and the solid body and subsequently lifting the solid body so as to remove the excreta from the surface it was deposited on. The present invention will now be described with reference to the accompanying drawings, which show, by way of example only, two embodiments of an apparatus for collecting and disposing of animal excreta in accordance with the invention. In the drawings:— FIG. 1 is an internal perspective view of a shell; FIG. 2 is an external perspective view of the shell of FIG. 1; FIG. 3 is a partial cutaway perspective view of a first embodiment of a container; FIG. 4 is an elevation view of a second embodiment of the container; FIG. 5 is a side view of FIG. 4; FIG. 6 is a plan view of FIG. 4 and FIG. 5; FIG. 7 is an elevation view of the second embodiment of the container with an aerosol cartridge mounted thereon; FIG. 8 is side view of FIG. 7; FIG. 9 is a plan view of FIG. 7 and FIG. 8; FIG. 10 is an elevation view of a second embodiment of a shell; FIG. 11 is a side view of FIG. 10; FIG. 12 is a plan view of FIG. 10 and FIG. 11; FIG. 13 is an elevation view of a lid for the shell of FIGS. 10 to 12; FIG. 14 is a side view of the lid of FIG. 13; FIG. 15 is a plan view of the lid of FIG. 13 and FIG. 14; FIG. 16 is an elevation view of a lid for the housing of FIGS. 7 to 9; FIG. 17 is a side view of the lid of FIG. 16; FIG. 18 is a plan view of the lid of FIG. 16 and FIG. 17; and FIG. 19 is an exploded view of the second embodiment of the container. Referring to the drawings and initially to FIG. 1, there is shown a shell indicated generally by the reference numeral 101. The shell 101 has a circular base 102 and a wall 103 upstanding from the base 102. The base 102 has a central aperture 104. Ten tapered teeth 105 are integrally formed with the base 102 and upstanding wall 103. The edges 106 of the teeth 105 closest to the opening of the shell 101 are thin enough to allow penetration of excreta received into the opening. The teeth 105 extend radially inwardly from the base 102 and wall 103 and cover a substantial portion of the space enclosed by the shell 101. Referring now to FIG. 2, cavities 108 are defined on the external surface 109 of the shell 101 by the radially inwardly extending teeth 105 of FIG. 1. An integrally formed collar 110 upstanding from the base 102 in a direction opposite to the wall 103 encloses the aperture 104. The end of the wall 103 distal from the base 102 defines a minor support rim or flange 111 on the external surface of the wall 103. (See FIGS. 1 and 2). Referring to FIG. 3, there is shown the shell 101 of FIGS. 1 and 2 mounted on housing 131. The housing 131 is a hollow elongate element 132. The element 132 has two identical semi-cylindrical sections 133 (only one shown) fastened together by any suitable fasteners along the split line of the element 132 via bores 134 correspondingly located in each semi-cylindrical section 133. An aerosol cartridge 136 is accommodated within the housing 131 with the end of the cartridge 136 carrying a dispensing nozzle (not shown) juxtaposed the shell 101. A seat 137 is provided on the first end of the housing 131 juxtaposed the shell 101. The seat 137 provided on this end of the housing 131 is for supporting the tapered neck 138 of the cartridge 136. This end also has an abutment element (not shown) for engaging the nozzle (not shown) of the cartridge 136. A collet 141 also extends from this end of the housing 131 for releasably fastening the shell 101 thereon. The second end of the housing 131 has a slot 142 extending at least partially around the internal surface of the housing 131 perpendicular to the longitudinal axis of the housing 131. A cylindrical button 150 has a peripheral flange 151 and is held in this end of the housing 131 by the peripheral flange 151 which is housed within the slot 142 and movable relative to the slot 142. The cartridge 136 urges the button 150 out of the housing 131 under normal circumstances due to the biasing force of the biasing element acting on the nozzle of the cartridge 136. A rib and groove formation 153 is provided on the outer surface of the housing 131. In use, an operator locates one or more shells 101 onto the first end of the housing 131. In order to collect and dispose of excreta, the operator lowers the housing 131 and shell 101 towards the excreta with the open end of the shell 101 facing the excreta. The edges 106 of the teeth 105 are forced down into the excreta. At this point, the operator presses the button 150 forcing the nozzle of the cartridge 136 to engage the abutment element. This releases a predetermined amount of aerosol through the upstanding collar 110 and aperture 104 into the space in the shell 101 around the impaled excreta. A short period of time is allowed for the frozen excreta to bond with the teeth 105. The operator raises the housing 131 and shell 101 lifting the excreta off the surface it was deposited on. The operator can place a lid on the shell 101 and remove the sealed shell 101 from the housing 131 in order to discard the shell 101 and excreta. Referring to FIGS. 4 to 9 and FIG. 19, there is shown a container for collecting and disposing of excreta indicated generally by the reference numeral 1. The container 1 has a housing 3 for receiving an aerosol cartridge 4 therein. A shell 5 is releasably mounted on the housing 3, the shell 5 having a base 7 and a plurality of tines 8 outstanding substantially orthogonally from the base 7. The housing 3 also carries a fluid delivery apparatus 11 for delivering fluid from the aerosol cartridge 4 to the area around the tines 8. The housing 3 has an open-ended tube 12 for receiving an aerosol cartridge 4 manufactured from plastic and integrally formed with a substantially oblong elongate element 14 having the tube 12 extending along one side 15 thereof. The opposite side 16 of the element 14 carries a surrounding wall 17 outstanding therefrom and defining a cavity 21. The cavity 21 is dimensioned for receiving the shell 5 holding it in position by an interference fit therebetween. The shell 5 has a surrounding wall 22 outstanding from the base 7 in the same direction as the tines 8. The base 7 and surrounding wall 22 are formed from cardboard and the tines 8 are formed from wood and are presented as wooden stakes. A lid 25 (see FIGS. 16 to 18) formed for engagement with the outstanding wall 22 of the container 5 is provided to enclose the tines and any matter impaled thereon. The lid 25 has a base 41 and a surrounding wall 42 outstanding from the base 41. A second lid 27 (see FIGS. 13 to 15) formed for engagement with the surrounding wall 17 is also provided with a base 43 and a surrounding wall 44 outstanding from the base 43 and the lid 25 is enclosed by the lid 27 when both lids are mounted on their respective surrounding walls 22, 17. The lid 27 provides further protection against contamination from excreta which adheres to the free edge of the shell 5. The fluid delivery apparatus 11 (see FIG. 19) has a dispensing head 31 for engagement with the nozzle 32 of the aerosol cartridge 4 and a pipe 33 for transferring the aerosol to the area surrounding the tines 8. The dispensing head 31 has an annular shoulder 34 formed for engagement with an annular flange 35 surrounding the base of the nozzle 32. The free end 37 of the pipe 33 is located centrally of and extends through the base 7 of the shell 5. Referring to FIGS. 10 to 13, the tines 8 are shown in rows and columns outstanding from the base 7 of the shell 5 forming an array of wooden stakes to penetrate excreta. In this embodiment, the tines 8 extend perpendicularly from the base 7. In use, a person who is walking a pet which has fouled the walking area takes hold of the container 1 by the housing 3. With the other hand, an operator removes both lids, outer lid 27 and then inner lid 25 exposing the outstanding tines 8. The lids 25, 27 are placed on the ground on their bases 41 and 43 respectively so that the lids can be rejoined to their corresponding parts without lifting them again. The operator now moves the container 1 towards the excreta, tines 8 first. The tines 8 are pressed down into the excreta until the outstanding wall 22 contacts the surface upon which the excreta is supported. The aerosol cartridge 4 is now opened for a few seconds by applying force to the nozzle 32 allowing the aerosol to flow through the pipe 33 and into the area enclosed by the base 7, wall 22 and the surface upon which the excreta is supported. The freezing component of the aerosol freezes at least the skin of the excreta which bonds to the tines 8 and the core of the excreta. The lifting operation can now be repeated in order to lift additional mounds of excreta. After the first mound has been successfully frozen and lifted, the apparatus can be placed over an additional mound. The inner core of the original mound merges and bonds with the second mound. Parts of the second mound are pierced by the tines and the new combined mound is frozen again. The operator lifts the container 1 away from the support surface and the excreta is removed from the surface. The operator now moves the container 1 into alignment with the lid 25 and lowers the container 1 tines 8 first onto the lid 25 sealing the excreta within the shell 5. The shell 5 may now be detached from the cavity 21 of the container 1 and disposed of in a bin. Alternatively, if no such waste disposal facility is available, the operator can place the main lid 27 onto the container 1 until a suitable bin is located. Variations and modifications can be made without departing from the scope of the invention described above and as claimed hereinafter.
20041203
20070227
20051027
90108.0
0
KRAMER, DEAN J
CONTAINER FOR COLLECTING AND DISPOSING OF ANIMAL EXCRETA
SMALL
0
ACCEPTED
2,004
10,516,804
ACCEPTED
Rotor blade for a wind power plant
The invention concerns a rotor blade of a wind power installation and a wind power installation. One advantage of the present invention is to provide a rotor blade having a rotor blade profile, and a wind power installation, which has better efficiency than hitherto. A rotor blade of a wind power installation, wherein the rotor blade has a thickness reserve approximately in the range of between 15% and 40%, preferably in the range of between about 23% and 28%, and wherein the greatest profile thickness is between about 20% and 45%, preferably between about 32% and 36%.
1. A wind power installation comprising at least one rotor blade which is mounted to a rotor hub, and a hub cladding, characterized in that provided on the outside of the hub cladding is a part of a rotor blade, which is fixedly connected to the hub cladding but which is not an integral constituent part of the rotor blade of the wind power installation. 2. The rotor blade according to claim 1 characterized in that the rotor blade has a thickness reserve approximately in the range of between 15% and 40%, preferably in the range of between about 23% and 28%, and wherein the greatest profile thickness is between about 20% and 45%, preferably between about 32% and 36%. 3. The rotor blade according to claim 1 characterized in that the cross-section of the rotor blade is described by a mean camber line whose greatest camber is in a range of between 50° and 70°, preferably approximately in the range of between 60° and 65°. 4. The rotor blade according to claim 1 characterized in that the greatest camber is between about 3% and 10%, preferably between about 4% and 7%. 5. The rotor blade according to claim 1 characterized in that said cross-section is preferably provided in the lower third of the rotor blade, which adjoins the rotor blade connection. 6. The rotor blade according to claim 1 characterized in that the rotor blade has an increased-pressure side and a reduced-pressure side, wherein the increased-pressure side has a part with a concave curvature and that an almost straight portion is provided on the reduced-pressure side. 7. The wind power installation according to claim 6 characterized in that the profile of the part of the rotor blade which is provided on the hub cladding substantially corresponds to the profile of the rotor blade in the region near the hub. 8. The wind power installation according to claim 7 characterized in that the part of the rotor blade which is provided on the hub cladding is stationary and is substantially so oriented that in the position of the rotor blade at the nominal wind speed below the nominal wind speed it is directly beneath the region near the hub of the rotor blade of the wind power installation. 9. The wind power installation comprising at least one rotor blade according to claim 1. 10. The wind power installation in particular according to claim 9 wherein the wind power installation has a rotor which accommodates at least one rotor blade which is of its greatest profile depth in the region of the rotor blade hub, wherein the ratio of the profile depth to the rotor diameter assumes the value which is in the range of between about 0.04 and 0.1, and is preferably approximately of a value of between 0.055 and 0.7, for example 0.061. 11. The wind power installation in particular according to claim 9 comprising a machine housing which accommodates a generator and a rotor connected to the generator, wherein the rotor includes at least two rotor blades, wherein the rotor has a hub which is provided with a cladding (spinner), wherein the ratio of the profile depth of a rotor blade to the diameter of the spinner is of a value which is greater than 0.4, preferably in a range of values of between 0.5 and 1. 12. The wind power installation in particular according to claim 1 comprising a rotor which preferably has more than one rotor blade, wherein the rotor blade is of a trapezoidal shape which is more or less approximated to the optimum aerodynamic shape and the rotor blade has its greatest width in the region of the rotor blade root and the edge of the rotor blade root, which faces towards the pod of the wind power installation, is such that the configuration of the edge is substantially matched to the external contour of the pod (in the longitudinal direction). 13. The wind power installation according to claim 12 characterized in that the lower edge of the rotor blade, which faces towards the pod, in the root region, is almost parallel to the external contour of the pod upon rotation of the rotor blade into the feathered position. 14. The wind power installation according to claim 13 characterized in that the spacing of the lower edge of the rotor blade, which faces towards the pod, and the external contour of the pod, in the feathered position, is less than 50 cm, preferably less than 20 cm. 15. The wind power installation according to claim 1 characterized in that the rotor blade is tilted in the root region out of the main blade plane. 16. The wind power installation according to claim 1 characterized in that the rotor blade is of a two-part configuration in the root region, wherein there is a separating line which is directed in the longitudinal direction of the rotor blade. 17. The wind power installation according to claim 16 characterized in that both parts of the rotor blade are fitted together only shortly before installation of the rotor blade in the wind power installation. 18. The wind power installation according to claim 16 characterized in that the parts of the rotor blade are separated during transport of the rotor blade. 19. The wind power installation in particular according to claim 1 characterized in that the wind power installation has at least one rotor blade which is characterized by a reduced-pressure side and an increased-pressure side, wherein the ratio of the length of the reduced-pressure side to the length of the increased-pressure side is less than a value of 1.2, preferably less than 1.1 and in particular is in a range of values of between 1 and 1.03.
BACKGROUND OF THE INVENTION 1. Field of the Invention The invention concerns a rotor blade of a wind power installation, and a wind power installation. As state of the art in this respect attention should be directed generally to the book ‘Windkraftanlagen’, Erich Hau, 1996. That book contains some examples of wind power installations, rotor blades of such wind power installations as well as cross-sections of such rotor blades from the state of the art. Page 102, FIG. 5.34, illustrates the geometrical profile parameters of aerodynamic profiles in accordance with NACA. It is to be seen in that respect that the rotor blade is described by a profile depth which corresponds to the length of the chord, a greatest camber (or camber ratio) as the maximum rise of a median line over the chord, a camber reserve, that is to say the location with respect to the profile depth where the greatest camber is provided within the cross-section of the rotor blade, a greatest profile thickness as the largest diameter of an inscribed circle with the center point on the median line and the thickness reserve, that is to say the location with respect to the profile depth where the cross-section of the rotor blade assumes its greatest profile thickness. In addition the leading-edge radius and the profile co-ordinates of the underside and the top side are brought into consideration to describe the cross-section of the rotor blade. The nomenclature known from the Erich Hau book is to be retained inter alia for the further description of the cross-section of a rotor for the present application. 2. Description of the Related Art Rotor blades are to be optimized in regard to a large number of aspects. On the one hand they should be quiet while on the other hand they should also afford a maximum dynamic power so that, even with a quite slight wind, the wind power installation begins to run and the nominal wind speed, that is to say the speed at which the nominal power of the wind power installation is also reached for the first time, is already reached at wind strengths which are as low as possible. If then the wind speed rises further, nowadays when considering pitch-regulated wind power installations the rotor blade is increasingly set into the wind so that the nominal power is still maintained, but the operative surface area of the rotor blade in relation to the wind decreases in order thereby to protect the entire wind power installation or parts thereof from mechanical damage. It is crucial however that great significance is attributed to the aerodynamic properties of the rotor blade profiles of the rotor blade of a wind power installation. BRIEF SUMMARY OF THE INVENTION One advantage of the present invention is to provide a rotor blade having a rotor blade profile and a wind power installation, which involve better efficiency than hitherto. The advantage may be attained by a rotor blade having a rotor blade profile with the features as set forth in one of the independent claims. Other advantageous developments are described in the appendant claims. The specific co-ordinates of a rotor blade profile according to the invention are set forth in a Table 1. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS The invention is illustrated hereinafter by a number of drawings in which: FIG. 1 shows a perspective view from the front of a wind power installation according to the invention, FIG. 2 shows a perspective view of a wind power installation according to the invention from the rear and the side, FIG. 3 shows a view of a wind power installation according to the invention from the side, FIGS. 4-8 show views of a rotor blade according to the invention from various directions, FIG. 9 shows a view on an enlarged scale of a wind power installation according to the invention, FIG. 10 shows a view of a rotor blade according to the invention, FIGS. 11-17 and 19 show various views of a wind power installation according to the invention, and FIG. 18 shows a cross-section of a rotor blade according to the invention (in the region near the hub). DETAILED DESCRIPTION OF THE INVENTION FIG. 18 shows the rotor blade profile described in accordance with one illustrated embodiment. In particular, in the region of the rotor blade which adjoins the rotor blade connection, (for connection to the hub) the profile is of a selected size and shape. The profile described in the present embodiment is provided in the first third of the rotor blade 1, with respect to the overall length of the rotor blade 1. In this respect the overall length L of a rotor blade 1 may definitely be in the range of between 10 m and 70 m, depending on the nominal power which a wind power installation is to involve. Thus, for example, the nominal power of a wind power installation from the corporation Enercon of type E-112 (diameter about 112 m) is 4.5 MW while the nominal power of a wind power installation from Enercon of type E-30 is 300 KW. What is particularly characteristic in terms of the profile of the rotor blade 1 according to the invention is that the greatest profile thickness is between about 25% and 40%, preferably between 32% and 36%, of the length of a rotor blade chord 9. In FIG. 18, the greatest profile thickness is about 34.6% of the length of the rotor blade chord 9. The chord 9 extends from the center 2 of the rotor blade trailing edge 3 to the foremost point 4 of the rotor blade leading edge 5. The thickness reserve TR, that is to say the location in relation to the blade length where the greatest profile thickness occurs, is between about 20% and 30% of the length of the chord, preferably between 23% and 28%, and about 25.9% in the illustrated example. The greatest thickness is ascertained perpendicularly to the chord 9 and the reserve TR is related to the rotor blade leading edge. In addition, FIG. 18 shows mean camber line 7. The camber line 7 results from half the respective thickness of the rotor blade 1 at a point. Accordingly, the camber line 7 does not extend in a straight line, but instead extends between oppositely disposed points on an increased-pressure side 10 of the rotor blade 1 and a reduced-pressure side 11 of the rotor blade 1. The camber line 7 intersects the chord 9 at the trailing edge 3 of the rotor blade 1 and the leading edge 5 of the rotor blade 1. The camber reserve CR in the cross-section of a rotor blade 1 is located between about 55% and 70% of the length of the chord 9, and preferably between about 59% and 63%. In the illustrated example the camber reserve CR is located at about 61.9% of the length of the chord 9. The amount of camber 11 at the camber reserve CR can be between about 4% and 8% of the length of the chord, and preferably between about 5% and 7% of the length of the chord. In the illustrated example, the camber “C” is about 5.87% of the length of the chord. It is further particularly striking in terms of the profile of the rotor blade 1 that the reduced-pressure side 11 of the rotor blade 1 ‘cuts’ the chord twice at points 12 and 13. That is to say in that the reduced-pressure side 11 of the profile is of a concave configuration, while in the front region of the profile, the increased-pressure side 10 is of a convex configuration. In the region where the increased-pressure side 10 is of a convex configuration, in the corresponding, oppositely disposed region on the reduced-pressure side 11, this region 14 is delimited by an almost straight line. While it might be previously known for the reduced-pressure side 11 to be provided with a concave curvature or for the increased-pressure side 11 to be provided with a straight-line boundary as individual components, the combination of having one opposite the other is a new feature according to invention. In particular, the combination of those two measures is significant in the profile of the rotor blade 1 according to the invention and is characteristic in respect of the rotor blade profile according to the invention. The rotor blade trailing edge 3 of the illustrated profile is also noticeably thick. This thickness, however, does not cause any problem in regard to the creation of sound at the trailing edge 3 of the rotor blade 1 because the illustrated profile is in the inner third of the rotor circle and there the orbital speed is not very high. One embodiment of the x-y-coordinates of the profile is shown in FIG. 18 and is reproduced in Table 1. The profile of the rotor blade 1 can be made substantially as described herein. Of course, variations from Table 1 are possible and the invention can still be obtained; use of the exact x-y values in Table 1 is not required. As shown in FIG. 1, to improve the aerodynamic shape of the rotor blade, it is of such a configuration, in the general region of the rotor blade root 15, that there it is of its greatest width W and thus the rotor blade 1 is of a trapezoidal shape (in plan) which is more or less approximated to the optimum aerodynamic shape. Preferably in the region of the rotor blade root 15, the rotor blade 1 is of such a configuration that the edge 16 of the rotor blade root 15, which is towards a pod 18 of a wind power installation (FIG. 15), is adapted to the external contour of the pod cladding 20 of the pod 18 in at least one angular position, for example it is adapted in such a way that a very small spacing S, for example a spacing S of between about 5 mm and 100 mm, exists between the pod cladding 20 and the edge 16 of the rotor blade root 15 which is towards the wind power installation and the external contour of the pod cladding 20 when the rotor blade 1 is positioned in the nominal wind position. A rotor blade 1 with the above-indicated properties affords a significantly higher increase in power of about up to 10%. By virtue of that increase in power, a wind power installation operating at a wind speed below the nominal wind speed, can achieve a higher power output. In addition, the wind power installation reaches its nominal power output earlier than hitherto. Accordingly, the rotor blades 1 can also be rotated to a pitched position, which can reduce sound emission and the mechanical loading on the installation. In that respect the invention is based on the realisation realization that the rotor blade shape which is common nowadays is investigated in a wind tunnel admittedly using different wind speeds but with an air flow which is always uniform. In nature, it is rare that the wind blows uniformly, but rather the wind is subject to a stochastic law. Standard rotor blade profiles, as a consequence of gusts, involve detachment of the flow precisely in the inner region of the blade near the rotor hub 17 where the blade no longer has an aerodynamically clean and optimum configuration. This flow detachment phenomena is propagated a distance along the rotor blade 1 in the direction towards the rotor blade tip. As a result, the flow can become detached from the rotor blade 1 in a bubble-shaped region and thus result in corresponding power losses. In the case of the present invention and in regard to the above-described situation, it is possible to achieve a considerable increase in power output by virtue of a rotor blade 1 which is of a clean configuration in the inner region of the rotor blade according to the embodiments of the present invention. If now a known standard profile were to be used instead of the empirically ascertained blade profile, which is described herein, then, to afford an aerodynamically clean configuration for the rotor blade, approximately double the profile depth relative to the length of the chord of the rotor blade could be required in the region of the rotor blade near the hub 17. The profile thickness in the front region permits the transmission of air loads and permits the rotor blade to attain a lift value CA greater than 2. As is known from the state of the art, rotor blades are usually constructed to entail a saving of material to the greatest possible extent in the inner region. Typical examples in that respect are disclosed in the state of the art, which has already been referred to above, in ‘Windkraftanlagen’, Erich Hau, 1996, on pages 114 and 115. It can be seen therein that the greatest profile depth is always attained at a certain distance from the rotor blade connection, that is to say in the region near the rotor blade connection, in which respect material is saved in those rotor blades in accordance with the state of the art. If, however, a shape approximating a trapezoidal shape is used, then the greatest width of a rotor blade is not at a spacing relative to the rotor blade connection but precisely in the region of the rotor blade connection itself. That structure then therefore does not save the greatest possible amount of material in the inner region of the rotor blades. The approach to saving in material, as described above, has been developed by considering the static manner of the flow conditions in regard to calculating/developing the rotor blades 1. In addition, current calculation programs for rotor blades divide the rotor blade 1 into individual portions and calculate each rotor blade portion in itself in order to derive an evaluation for the overall rotor blade. As noted above, wind does not blow uniformly and statically over a given-surface area region, but markedly exhibits a stochastic behavior. The low peripheral speed of the rotor blade 1 in the inner region near the rotor hub 19 influences the wind speed and may cause the angle of incidence to change in that region in response to and dependent on the instantaneous wind speed. As a consequence, detachment of the flow from the rotor blade 1 can frequently occur in the inner region of the rotor blade 1. A hysteresis effect is operative in such a situation. When the previous wind speed occurs again, that is to say after a gust is past, the flow is not the same at the rotor blade 1 again. Rather, the wind speed firstly has to fall further (the angle of incidence must therefore be further changed) until the air again bears against the surface of the rotor blade 1. If, however, the wind speed does not decrease, it may certainly happen that, for a prolonged period of time, in spite of the afflux flow of the wind to the rotor blade 1, a relevant force is exerted on the rotor blade 1 because the flow has not yet come to bear against (i.e., flow cleanly over) the rotor blade surface again. The risk of flow detachment can be reduced by the embodiments of the rotor blade described herein. For example, the detachment risk is reduced by the relatively thick profile. The thick profile of rotor blade 1 provides an increase in power can also be well explained by virtue of due to the hysteresis effect, once flow detachment has occurred, the power losses are maintained over a considerable period of time for rotor blades in accordance with the state of the art. A further part of the increase in power can be explained by virtue of the fact that the wind follows the path of least resistance. Thus, if the rotor blade is very thin in the inner region near the hub 17 because of saving material, then this can be viewed as a ‘slip hole’ in the harvesting area of the rotor circle (i.e., around and proximate to the pod 18), through which air preferentially flows. In this case, it is possible to see that the common calculation programs based on uniform distribution over the rotor circle area may not be sufficiently accurate. In one embodiment as best illustrated in FIGS. 3 and 11, the ‘slip hole’ can be ‘closed’ by virtue of the trapezoidal configuration of the rotor blade 1 in the region near the hub 17, then an improved distribution of air flow over the entire circular surface area can be achieved. In addition, the efficiency of the outer region of the rotor blade is also increased somewhat. Accordingly, ‘closing’ the ‘slip hole’ makes a contribution to the higher power output of the rotor blade 1. Another insufficiency of the current calculation programs is that they consider the rotor blade portion directly adjoining the ‘slip hole’ as a full-value rotor blade portion which it cannot be, because of the particular flow conditions, which results in frequent flow breakdowns. FIGS. 3 and 11 show a wind power installation according one illustrated embodiment. The three rotor blades 1 have an almost seamless transition with respect to the external configuration of the pod cladding 21 and with respect to the hub cladding 19 when the rotor blades 1 are in a nominal wind position. FIG. 9 illustrates that if the wind increases above nominal wind speed, then the rotor blades 1 are moved slowly to change their pitch to the wind by pitch control or pitch regulation and a large spacing “S” develops between the lower edge 16 of the rotor blade 1 and the hub cladding 19 and pod cladding 21, respectively. FIG. 11, however, shows that when the contour of the hub cladding 19 and the contour of the pod cladding 21 substantially correspond to the edge profile of the rotor blade 1 in the region near the hub 19 and which, when the rotor blade 1 is set in an angle of incidence at the nominal speed, is directly below the rotor blade so that there is only a small gap “S” between the structure and the rotor blade in the region near the hub. When the rotor blade 1 is in the feathered position, with reduced surface area towards the wind, the rotor blade 1 is parallel to the lower edge 16 that is towards the pod 18 and the spacing between the lower edge 16 and the external contour of the pod cladding 21 is at a minimum, preferably being less than 50 cm or even less than 20 cm. When the rotor blade 1 is set into the wind, it involves a large surface area even in the very near region of the rotor blade (the slip hole is very small). The above-mentioned reference Erich Hau shows that the rotor blade in the state of the art decreases regularly in the region near the hub 17 (the rotor blades are there less wide than at their widest location). Conversely, the widest location of the rotor blade 1 according to at least one embodiment of the invention is in the region near the hub 17 so that the wind can be utilized to the best possible extent. Referring back to the rotor blade profile shown in FIG. 18, the leading edge radius 5 is approximately 0.146 of the profile depth. The reduced-pressure side 10 has a longer, almost straight region. In this region, at between 38% and 100% of the profile depth, the radius is about 1.19 times the length of the profile depth. Between 40% and 85% of the profile depth, the radius is about 2.44 times the profile depth. And, between 42% and 45% of the profile depth, the radius is about 5.56 times of the profile depth. In the region between 36% and 100% of the profile depth, the maximum deviation from an ideal straight line is about 0.012 of the profile length. This value is an important variable as the curvature radius varies and the greatest curvature radius is already specified in the respective regions. In the illustrated embodiment of FIG. 18, the length of the reduced-pressure side 10 is about 1.124 of the length of the profile depth while the length of the increased-pressure side 11 is 1.112 of the length of the profile depth. This means that the reduced-pressure side 10 is only immaterially longer than the increased-pressure side 11. It is advantageous if the ratio of the reduced-pressure side 10 length to the increased-pressure side 11 length is less than 1.2, preferably less than 1.1 or in a range of values of between 1 and 1.03. It can be seen from the illustrated Figures that the rotor blade 1 has its greatest profile depth directly at the spinner or hub 17, that is to say at the outside of the pod 18 of the wind power installation. For a wind power installation with a rotor diameter of 30 m, the profile depth at the spinner 17 is between about 1.8 to 1.9, preferably 1.84. If then the spinner 17 is approximately of a diameter of 3.2 mm, the ratio of the profile depth of the rotor blade 1 at the spinner to the spinner diameter is about 0.575. It is further advantageous if the ratio of the profile depth to the spinner diameter is greater than a value of 0.4 or in a range of values of about 0.4 to 1. In the above-specified example, the ratio of the profile depth to the rotor diameter is about 0.061. The ‘slip hole’ can be made as small as possible if the ratio of the profile depth to the rotor diameter is greater than a value of between 0.05 and 0.01. In another example, a rotor blade 1 with a profile cross-section similar to the one shown in FIG. 18, the first third of the profile, has a profile depth at the spinner of about 4.35 mm, a spinner diameter of 5.4 m and a rotor diameter of about 71 m. Thus, the value of the profile depth to the spinner diameter is 0.806 and the ratio of the profile depth to the rotor diameter is again 0.061. The above-indicated values relate to a triple-blade rotor with pitch regulation. As described, a rotor blade 1 according to another embodiment of the invention can have its greatest profile depth in the region near the hub 17 and the rotor blade 1 can further include the rotor blade portion 30. FIG. 15 illustrates the rotor blade portion 30, which is a physically separable component With respect to the rotor blade 1, but is considered to a functional part of the rotor blade 1 with respect to carrying air loads. The rotor blade portion 30, although not an integral part of the rotatable rotor blade 1, can be an integral, constituent part of the hub cladding 19 or affixed to the hub cladding 19 of the hub 17, which is further a part of the pod 18, in a variety of ways (e.g., joined, screwed and so forth). In addition the lower edge of the rotor blade portion 30, that is to say the edge which faces towards the pod of the wind power installation, can be substantially adapted to or matched to the external contour of the hub cladding 19 and/or pod cladding 21 in the longitudinal direction. Accordingly in this case, when a rotor blade 1 is in the feathered position, (practically no longer where hardly any surface area which faces towards the wind), the rotor blade 1 is parallel to the lower edge 16 that is towards the pod 18 and the spacing between the lower edge 16 and the external contour of the pod is at a minimum, preferably being less than 50 cm or even better less' than 20 cm. As is known, it is precisely when dealing with very large rotor blades 1 that a very great rotor blade width is involved in the region near the hub 17. In order for such rotor blades 1 to be transported, the rotor blade 1 can be of a two-part configuration, in which the two parts are separated during transport and re-assembled after transport. In such an embodiment, the two parts are connected together before being installed on the wind power installation, for example by way of screw connections and/or secure connections (e.g., adhesive). Large rotor blades may be accessible from the interior for being fitted together so that such a rotor blade can have of a unitary assembled appearance on the exterior and the separation lines are scarcely visible or not visible at all. As initial measurements show, the rotor blade 1 according to embodiments of the present invention can markedly have an increased efficiency in comparison with previous rotor blades. As can be seen from FIGS. 4-8, the rotor blades 1 have their greatest profile depth in the region near the hub 17 In addition, the rotor blade portions, along their respective edge profiles, are configured to substantially conform to the contour of the hub cladding 17 and/or the pod cladding 21. Accordingly, at least for the position in which the rotor blade 1 assumes an angle that corresponds to wind speeds up to the nominal wind range, there may be a very small spacing relative to the pod cladding 21. FIG. 16 illustrates a seamless transition between the feathering portion of the rotor blade 1 and the non-feathering portion 30 is indicated in by the lack of any demarcation line between the blade portions 1 and 30. The rotor blade portion 30, which as previously stated, is not an integral constituent part of the overall rotor blade 1 is affixed to the pod 18, or more specifically to the hub cladding 19 of the hub 17. The rotor blade portion 30 located on the outside of the pod is fixed thereto and arranged at an angle corresponding to the angular position of a rotor blade 1 up to the nominal wind speed. Thus, at wind speeds up to the nominal wind, there are minimal gaps between the lower edge 16 of the rotor blade 1, the rotor blade portion 30, and the pod 18, respectively. The rotor blade portion 30 can be screwed to the pod 18 or can also be glued or joined in one piece to the pod 18. FIG. 19 illustrates that there is only a quite small ‘slip hole’ for the wind that cannot be seen from a distance by virtue of the configuration of the rotor blades 1 in relation to the rotor blade portion 30. FIG. 18 shows a cross-section through a rotor blade according to the invention as taken along line A-A in FIG. 17, that is to say the profile of the rotor blade in the region near the hub. FIG. 17 also includes an indication of what is to be understood by the diameter D of the spinner. The rotor diameter is described by the diameter of the circular area which is covered by the rotor when it rotates. As can be seen from FIG. 15 and other Figures the rotor blade portion 30 of the rotor blade 1 which is not an integral constituent part of the rotatable rotor blade 1 is an integral constituent part of the outside cladding 19 of at least the hub 17. The respective portion 30 can be screwed to the pod or can also be glued or joined in one piece to the pod. Referring back to FIG. 11, a wind and/or weather sensor 31 is attached to the pod 18 according to one illustrated embodiment. The sensor 31 can measure a variety of parameters such as wind velocity, direction, temperature, etc. This information may be recorded or transmitted. TABLE 1 X-Y-COORDINATES x y 1.000000 0.013442 0.983794 0.020294 0.958357 0.030412 0.930883 0.040357 0.899462 0.050865 0.863452 0.062358 0.823890 0.074531 0.781816 0.086987 0.737837 0.099513 0.692331 0.111993 0.645363 0.124434 0.597614 0.136709 0.549483 0.148731 0.503007 0.160228 0.481036 0.170758 0.425769 0.179639 0.397598 0.186588 0.374996 0.191889 0.356186 0.195840 0.339750 0.198668 0.324740 0.200524 0.310542 0.201512 0.296731 0.201704 0.232999 0.201174 0.269154 0.200007 0.255115 0.198267 0.240876 0.195985 0.226479 0.193185 0.212006 0.189892 0.197571 0.186146 0.183315 0.181995 0.169384 0.177505 0.155924 0.172745 0.143051 0.167780 0.130850 0.162675 0.119369 0.157478 0.108625 0.152229 0.098610 0.146953 0.089297 0.141664 0.080653 0.136362 0.072636 0.131036 0.065201 0.125679 0.058312 0.120269 0.051931 0.114786 0.046015 0.109229 0.040531 0.103598 0.035457 0.097893 0.030772 0.092113 0.026461 0.086252 0.022520 0.080332 0.018937 0.074321 0.015688 0.068240 0.012771 0.062095 0.010196 0.055378 0.007926 0.049601 0.005911 0.043298 0.004164 0.036989 0.002755 0.030661 0.001709 0.024300 0.000953 0.017915 0.000415 0.011534 0.000088 0.005186 0.000000 0.000000 0.000197 −0.007376 0.000703 −0.013612 0.001550 −0.019816 0.002704 −0.025999 0.004080 −0.032162 0.005649 −0.038281 0.007477 −0.044316 0.009639 −0.050245 0.012124 −0.056078 0.014883 −0.061829 0.017905 −0.067491 0.021204 −0.073045 0.024779 −0.078485 0.028618 −0.083809 0.032721 −0.089004 0.037087 −0.094062 0.041711 −0.098973 0.046594 −0.103723 0.051740 −0.108301 0.057150 −0.112695 0.062824 −0.116897 0.068769 −0.120893 0.074991 −0.124669 0.081500 −0.128219 0.088310 −0.131521 0.095450 −0.134551 0.102955 −0.137294 0.110872 −0.139735 0.119262 −0.141872 0.128192 −0.143724 0.137734 −0.145316 0.147962 −0.146667 0.158934 −0.147800 0.170663 −0.148727 0.183106 −0.149431 0.196155 −0.149877 0.209657 −0.150001 0.223475 −0.149715 0.237539 −0.148932 0.251855 −0.147579 0.266497 −0.145597 0.281578 −0.142949 0.297206 −0.139628 0.313400 −0.135651 0.330088 −0.131016 0.347173 −0.125692 0.364627 −0.119588 0.382602 −0.112537 0.401480 −0.104293 0.421912 −0.094548 0.444568 −0.083182 0.468376 −0.071217 0.491608 −0.060017 0.514034 −0.049898 0.535806 −0.040854 0.557225 −0.032760 0.578580 −0.025495 0.600131 −0.018956 0.622095 −0.013059 0.644620 −0.007755 0.667811 −0.003015 0.691690 0.001179 0.716104 0.004827 0.740707 0.007908 0.364985 0.010392 0.788448 0.012236 0.810817 0.013425 0.832004 0.013957 0.852100 0.013834 0.871284 0.013058 0.889797 0.011606 0.907926 0.009441 0.925997 0.006502 0.944381 0.002701 0.963552 −0.002134 0.984409 −0.008335 1.000000 −0.013442 0.000197 −0.007376 0.000703 −0.013612 0.001550 −0.019816 0.002704 −0.025999 0.004080 −0.032162 0.005649 −0.038281 0.007477 −0.044316 0.009639 −0.050245 0.012124 −0.056078 0.014883 −0.061829 0.017905 −0.067491 0.021204 −0.073045 0.024779 −0.078485 0.028618 −0.083809 0.032721 −0.089004 0.037087 −0.094062 All of the above U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety. From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The invention concerns a rotor blade of a wind power installation, and a wind power installation. As state of the art in this respect attention should be directed generally to the book ‘Windkraftanlagen’, Erich Hau, 1996. That book contains some examples of wind power installations, rotor blades of such wind power installations as well as cross-sections of such rotor blades from the state of the art. Page 102, FIG. 5.34, illustrates the geometrical profile parameters of aerodynamic profiles in accordance with NACA. It is to be seen in that respect that the rotor blade is described by a profile depth which corresponds to the length of the chord, a greatest camber (or camber ratio) as the maximum rise of a median line over the chord, a camber reserve, that is to say the location with respect to the profile depth where the greatest camber is provided within the cross-section of the rotor blade, a greatest profile thickness as the largest diameter of an inscribed circle with the center point on the median line and the thickness reserve, that is to say the location with respect to the profile depth where the cross-section of the rotor blade assumes its greatest profile thickness. In addition the leading-edge radius and the profile co-ordinates of the underside and the top side are brought into consideration to describe the cross-section of the rotor blade. The nomenclature known from the Erich Hau book is to be retained inter alia for the further description of the cross-section of a rotor for the present application. 2. Description of the Related Art Rotor blades are to be optimized in regard to a large number of aspects. On the one hand they should be quiet while on the other hand they should also afford a maximum dynamic power so that, even with a quite slight wind, the wind power installation begins to run and the nominal wind speed, that is to say the speed at which the nominal power of the wind power installation is also reached for the first time, is already reached at wind strengths which are as low as possible. If then the wind speed rises further, nowadays when considering pitch-regulated wind power installations the rotor blade is increasingly set into the wind so that the nominal power is still maintained, but the operative surface area of the rotor blade in relation to the wind decreases in order thereby to protect the entire wind power installation or parts thereof from mechanical damage. It is crucial however that great significance is attributed to the aerodynamic properties of the rotor blade profiles of the rotor blade of a wind power installation.
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>One advantage of the present invention is to provide a rotor blade having a rotor blade profile and a wind power installation, which involve better efficiency than hitherto. The advantage may be attained by a rotor blade having a rotor blade profile with the features as set forth in one of the independent claims. Other advantageous developments are described in the appendant claims. The specific co-ordinates of a rotor blade profile according to the invention are set forth in a Table 1.
20050804
20080415
20060511
75864.0
B63H106
0
WIEHE, NATHANIEL EDWARD
ROTOR BLADE FOR A WIND POWER PLANT
UNDISCOUNTED
0
ACCEPTED
B63H
2,005
10,516,920
ACCEPTED
Method for the production of butadiene from n-butane
The invention relates to a process for preparing butadiene from n-butane comprising the steps (A) providing an n-butane-containing feed gas stream, (B) feeding the n-butane-containing feed gas stream into a first dehydrogenation zone and nonoxidatively catalytically dehydrogenating n-butane to 1-butene, 2-butene and optionally butadiene to obtain a first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, (C) feeding the first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, into a second dehydrogenation zone and oxidatively dehydrogenating 1-butene and 2-butene to butadiene to give a second product gas stream comprising butadiene, n-butane and steam, with or without secondary components, (D) recovering butadiene from the second product gas stream.
1. A process for preparing butadiene from n-butane comprising the steps of (A) providing an n-butane-containing feed gas stream, (B) feeding the n-butane-containing feed gas stream into a first dehydrogenation zone and nonoxidatively catalytically dehydrogenating n-butane to 1-butene, 2-butene and optionally butadiene to obtain a first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, (C) feeding the first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, into a second dehydrogenation zone and oxidatively dehydrogenating 1-butene and 2-butene to butadiene to give a second product gas stream comprising butadiene, n-butane and steam, with or without secondary components, (D) recovering butadiene from the second product gas stream. 2. The process as claimed in claim 1, wherein the provision of the n-butane-containing feed gas stream comprises the steps of (A1) providing a liquefied petroleum gas (LPG) stream, (A2) removing propane and optionally methane, ethane and pentanes from the LPG stream to obtain a butane-containing stream, (A3) removing isobutane from the butane-containing stream to obtain the n-butane-containing feed gas stream and optionally isomerizing the removed isobutane to an n-butane/isobutane mixture and recycling the n-butane/isobutane mixture into the isobutane removal. 3. The process as claimed in claim 1 or 2, wherein the nonoxidative catalytic dehydrogenation (B) of n-butane is carried out as an autothermal catalytic dehydrogenation. 4. The process as claimed in any of claims 1 to 3, wherein the oxidative dehydrogenation (C) is carried out in more than one stage. 5. The process as claimed in any of claims 1 to 4, wherein the recovery (D) of butadiene from the second product gas stream comprises the steps: (D1) cooling the product gas stream with water to condense out steam and any high-boiling organic secondary components; (D2) removing the low-boiling secondary components contained in the second product gas stream which are selected from the group consisting of hydrogen, carbon monoxide, carbon dioxide, nitrogen, methane, ethane, ethene, propane and propene, to obtain a stream comprising butadiene and n-butane, with or without 1-butene and 2-butene, and with or without oxygenates as further secondary components; (D3) optionally removing the oxygenates to obtain a stream comprising butadiene and n-butane, with or without 1-butene and 2-butene; (D4) separating the stream comprising butadiene and n-butane, with or without 1-butene and 2-butene, into a stream comprising n-butane, with or without 1-butene and 2-butene, and a stream comprising butadiene; (D5) optionally recycling the stream comprising n-butane, with or without 1-butene and 2-butene, into the nonoxidative catalytic dehydrogenation (B).
Butadiene is prepared predominantly by thermal cleavage (cracking) of saturated hydrocarbons, customarily starting from naphtha as the raw material. Cracking of naphtha results in a hydrocarbon mixture of methane, ethane, ethene, acetylene, propane, propene, propyne, allene, butenes, butadiene, butynes, methylallene, C5 and higher hydrocarbons. Acetylenically unsaturated hydrocarbons in the cracking gas such as acetylene, propyne, 1-butyne, 2-butyne, butenyne and diacetylene may interfere, for example, in a subsequent dimerization of butadiene in a Diels-Alder reaction to vinylcyclohexane, since even traces of these compounds can poison the copper dimerization catalyst. Butynes and allenes likewise react with butadiene in a Diels-Alder reaction and lead to by-product formation. Triply unsaturated C4 hydrocarbons are generally also troublesome in other uses of butadiene. The butynes in particular, which can only be removed distillatively or extractively from butadiene with great difficulty, present problems. It is therefore necessary when using butadiene from crackers to precede the butadiene dimerization with a hydrogenation stage in which the butynes are selectively partially hydrogenated to the corresponding butenes. A further disadvantage is that when cracking naphtha or other hydrocarbon mixtures, a complex hydrocarbon mixture is obtained. For instance, when butadiene is obtained in the cracking process, relatively large amounts of ethene or propene are inevitably obtained as coproducts. Alternatively, butadiene can be prepared starting from n-butane by catalytic dehydrogenation. However, a disadvantage of this process is the low butadiene yield, since the catalytic dehydrogenation of n-butane results predominantly in 1-butene and 2-butene. It is an object of the present invention to provide a process for preparing butadiene from n-butane which does not have the disadvantages of the prior art and allows high butadiene yields to be obtained. We have found that this object is achieved by a process for preparing butadiene from n-butane comprising the steps of (A) providing an n-butane-containing feed gas stream, (B) feeding the n-butane-containing feed gas stream into a first dehydrogenation zone and nonoxidatively catalytically dehydrogenating n-butane to 1-butene, 2-butene and optionally butadiene to obtain a first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, (C) feeding the first product gas stream comprising n-butane, 1-butene and 2-butene, with or without butadiene and secondary components, into a second dehydrogenation zone and oxidatively dehydrogenating 1-butene and 2-butene to butadiene to give a second product gas stream comprising butadiene, n-butane and steam, with or without secondary components, (D) recovering butadiene from the second product gas stream. In a first process part A, an n-butane-containing feed gas stream is provided. Customarily, the raw material is an n-butane-rich gas mixture such as liquefied petroleum gas (LPG). LPG substantially comprises C2-C5-hydrocarbons. The composition of LPG may vary widely. Advantageously, the LPG used comprises at least 10% by weight of butanes. In one variant of the process according to the invention, the provision of the n-butane-containing dehydrogenation feed gas stream comprises the steps of (A1) providing a liquefied petroleum gas (LPG) stream, (A2) removing propane and optionally methane, ethane and pentanes from the LPG stream to obtain a butane- (n-butane- and isobutane-) containing stream, (A3) removing isobutane from the butane-containing stream to obtain the n-butane-containing feed gas stream and optionally isomerizing the removed isobutane to an n-butane/isobutane mixture and recycling the n-butane/isobutane mixture into the isobutane removal. Propane and any methane, ethane and pentanes are removed in one or more customary rectification columns. For example, low boilers (methane, ethane, propane) can be removed overhead in a first column and high boilers (pentanes) removed at the column bottom in a second column. A stream comprising butanes (n-butane and isobutane) is obtained from which isobutane is removed, for example in a customary rectification column. The remaining n-butane-containing stream is used as the feed gas stream for the subsequent butane dehydrogenation. Preference is given to subjecting the removed isobutane stream to isomerization. To this end, the isobutane-containing stream is fed into an isomerization reactor. The isomerization of isobutane to n-butane can be carried out as described in GB-A 2 018 815. An n-butane/isobutane mixture is obtained which is fed into the n-butane/isobutane separating column. In a process part (B), the n-butane-containing feed gas stream is fed into a first dehydrogenation zone and subjected to a nonoxidative catalytic dehydrogenation. n-Butane is partially dehydrogenated in a dehydrogenation reactor over a dehydrogenating catalyst to 1-butene and 2-butene, and small amounts of butadiene may also be formed. In addition, hydrogen and small amounts of methane, ethane, ethene, propane and propene are formed. Depending on the dehydrogenation method, carbon oxides (CO, CO2), water and nitrogen may also be present in the product gas mixture of the nonoxidative catalytic n-butane dehydrogenation. In addition, unconverted n-butane is present in the product gas mixture. The nonoxidative catalytic n-butane dehydrogenation may be carried out with or without oxygen-containing gas as a cofeed. A feature of the nonoxidative method compared to an oxidative method is the presence of hydrogen in the effluent gas. In the oxidative dehydrogenation, no substantial amounts of free hydrogen are formed. In principle, the nonoxidative catalytic n-butane dehydrogenation may be carried out in all reactor types and methods known from the prior art. A comparatively comprehensive description of dehydrogenation processes suitable according to the invention may also be found in “Catalytica® Studies Division, Oxidative Dehydrogenation and Alternative Dehydrogenation Processes” (Study Number 4192 OD, 1993, 430 Ferguson Drive, Mountain View, Calif. 94043-5272, USA). A suitable reactor form is a fixed bed tubular or tube bundle reactor. In these reactors, the catalyst (dehydrogenation catalyst and, when working with oxygen as the cofeed, optionally a special oxidation catalyst) is disposed as a fixed bed in a reaction tube or in a bundle of reaction tubes. The reaction tubes are customarily heated indirectly by the combustion of a gas, for example a hydrocarbon such as methane, in the space surrounding the reaction tubes. It is favorable to apply this indirect form of heating only to about the first 20 to 30% of the length of the fixed bed and to heat the remaining bed length to the required reaction temperature by the radiant heat released in the course of indirect heating. Customary reaction tube internal diameters are from about 10 to 15 cm. A typical dehydrogenation tube bundle reactor comprises from about 300 to 1 000 reaction tubes. The internal temperature in the reaction tubes is customarily in the range from 300 to 1 200° C., preferably in the range from 500 to 1 000° C. The working pressure is customarily from 0.5 to 8 bar, frequently from 1 to 2 bar, when a small steam dilution is used (similar to the Linde process for propane dehydrogenation), or else from 3 to 8 bar when using a high steam dilution (similar to the steam active reforming process (STAR process) for dehydrogenating propane or butane of Phillips Petroleum Co., see U.S. Pat. No. 4,902,849, U.S. Pat. No. 4,996,387 and U.S. Pat. No. 5,389,342). Typical gas hourly space velocities (GSHV) are from 500 to 2 000 −1, based on the hydrocarbon used. The catalyst geometry may, for example, be spherical or cylindrical (hollow or solid). The nonoxidative catalytic n-butane dehydrogenation may also be carried out under heterogeneous catalysis in a fluidized bed, as described in Chem. Eng. Sci. 1992 b, 47 (9-11) 2313. Advantageously, two fluidized beds are operated in parallel, of which one is generally in the process of regeneration. The working pressure is typically from 1 to 2 bar, the dehydrogenation temperature generally from 550 to 600° C. The heat required for the dehydrogenation is introduced into the reaction system by preheating the dehydrogenation catalyst to the reaction temperature. The admixing of an oxygen-containing cofeed allows the preheater to be dispensed with and the required heat can be generated directly in the reactor system by combustion of hydrogen in the presence of oxygen. Optionally, a hydrogen-containing cofeed may additionally be admixed. The nonoxidative catalytic n-butane dehydrogenation may be carried out in a tray reactor with or without oxygen-containing gas as cofeed. This reactor comprises one or more successive catalyst beds. The number of catalyst beds may be from 1 to 20, advantageously from 1 to 6, preferably from 1 to 4 and in particular from 1 to 3. The catalyst beds are preferably flowed through radially or axially by the reaction gas. In general, such a tray reactor is operated using a fixed catalyst bed. In the simplest case, the fixed catalyst beds are disposed axially in a shaft furnace reactor or in the annular gaps of concentric cylindrical grids. A shaft furnace reactor corresponds to one tray. Carrying out the dehydrogenation in a single shaft furnace reactor corresponds to a preferred embodiment, where the oxygen-containing cofeed may be used. In a further preferred embodiment, the dehydrogenation is carried out in a tray reactor having three catalyst beds. In a method without oxygen-containing gas as cofeed, the reaction gas mixture is subjected to a degree of heating in the tray reactor on its way from one catalyst bed to the next catalyst bed, for example by passing it over heat exchanger plates heated by hot gases or by passing it through tubes heated by hot combustion gases. In a preferred embodiment of the process according to the invention, the nonoxidative catalytic n-butane dehydrogenation is carried out autothermally. To this end, the reaction gas mixture of the n-butane dehydrogenation is additionally admixed with oxygen in at least one reaction zone and the hydrogen and/or hydrocarbon present in the reaction gas mixture is at least partially combusted which directly generates in the reaction gas mixture at least a portion of the heat required for dehydrogenation in the at least one reaction zone. In general, the amount of oxygen-containing gas added to the reaction gas mixture is chosen in such a manner that the amount of heat required for the dehydrogenation of n-butane is generated by the combustion of the hydrogen present in the reaction gas mixture and any hydrocarbons present in the reaction gas mixture and/or carbon present in the form of coke. In general, the total amount of oxygen fed in, based on the total amount of butane, is from 0.001 to 0.5 mol/mol, preferably from 0.005 to 0.2 mol/mol, more preferably from 0.05 to 0.2 mol/mol. Oxygen may be used either as pure oxygen or as an oxygen-containing gas in the mixture with inert gases, for example in the form of air. The inert gases and the gases resulting from the combustion generally provide additional dilution and therefore support the heterogeneously catalyzed dehydrogenation. The hydrogen combusted to generate heat is the hydrogen formed in the catalytic n-butane dehydrogenation and also any hydrogen additionally added to the reaction gas mixture as hydrogen-containing gas. The quantity of hydrogen present should preferably be such that the H2/O2 molar ratio in the reaction gas mixture immediately after the oxygen is fed in is from 1 to 10 mol/mol, preferably from 2 to 5 mol/mol. In multistage reactors, this applies to every intermediate feed of oxygen-containing and any hydrogen-containing gas. The hydrogen is combusted catalytically. The dehydrogenation catalyst used generally also catalyzes the combustion of the hydrocarbons and of hydrogen with oxygen, so that in principle no additional specialized oxygenation catalyst is required. In one embodiment, operation is effected in the presence of one or more oxidation catalysts which selectively catalyze the combustion of hydrogen to oxygen in the presence of hydrocarbons. The combustion of these hydrocarbons with oxygen to give CO, CO2 and water therefore proceeds only to a minor extent. The dehydrogenation catalyst and the oxidation catalyst are preferably present in different reaction zones. When the reaction is carried out in more than one stage, the oxidation catalyst may be present only in one, in more than one or in all reaction zones. Preference is given to disposing the catalyst which selectively catalyzes the oxidation of hydrogen at the points where there are higher oxygen partial pressures than at other points in the reactor, in particular near the feed point for the oxygen-containing gas. The oxygen-containing gas and/or hydrogen-containing gas may be fed in at one or more points in the reactor. In one embodiment of the process according to the invention, there is intermediate feeding of oxygen-containing gas and of hydrogen-containing gas upstream of each tray of a tray reactor. In a further embodiment of the process according to the invention, oxygen-containing gas and hydrogen-containing gas are fed in upstream of each tray except the first tray. In one embodiment, a layer of a specialized oxygenation catalyst is present downstream of every feed point, followed by a layer of the dehydrogenation catalyst. In a further embodiment, no specialized oxidation catalyst is present. The dehydrogenation temperature is generally from 400 to 1 100° C., the pressure in the last catalyst bed of the tray reactor is generally from 0.2 to 5 bar, preferably from 1 to 3 bar. The GSHV is generally from 500 to 2 000 h−1, and in a high-load operation, even up to 100 000 h−1, preferably from 4 000 to 16 000 h−1. A preferred catalyst which selectively catalyzes the combustion of hydrogen comprises oxides and/or phosphates selected from the group consisting of oxides and/or phosphates or germanium, tin, lead, arsenic, antimony and bismuth. A further preferred catalyst which catalyzes the combustion of hydrogen comprises a noble metal of transition group VIII and/or I of the periodic table. The dehydrogenation catalysts used generally comprise a support and an active composition. The support generally consists of a heat-resistant oxide or mixed oxide. The dehydrogenation catalysts preferably comprise a metal oxide selected from the group consisting of zirconium oxide, zinc oxide, aluminum oxide, silicon dioxide, titanium dioxide, magnesium oxide, lanthanum oxide, cerium oxide and mixtures thereof, as support. The mixtures may be physical mixtures or else chemical mixed phases of magnesium aluminum oxide or zinc aluminum oxide mixed oxides. Preferred supports are zirconium dioxide and/or silicon dioxide, and particular preference is given to mixtures of zirconium dioxide and silicon dioxide. The active composition of the dehydrogenation catalysts generally comprises one or more metals of transition group VIII of the periodic table, preferably platinum and/or palladium, more preferably platinum. Furthermore, the dehydrogenation catalysts may comprise one or more elements of main group I and/or II of the period table, preferably potassium and/or cesium. The dehydrogenation catalysts may further comprise one or more elements of transition group III of the period table including the lanthanides and actinides, preferably lanthanum and/or cerium. Finally, the dehydrogenation catalysts may comprise one or more elements of main group III and/or IV of the periodic table, preferably one or more elements selected from the group consisting of boron, gallium, silicon, germanium, tin and lead, more preferably tin. In a preferred embodiment, the dehydrogenation catalyst comprises at least one element of transition group VIII, at least one element of main group I and/or II, at least one element of main group III and/or IV and at least one element of transition group III including the lanthanides and actinides, of the periodic table. For example, all dehydrogenation catalysts which are disclosed by WO 99/46039, U.S. Pat. No. 4,788,371, EP-A 705 136, WO 99/29420, U.S. Pat. No. 5,220,091, U.S. Pat. No. 5,430,220, U.S. Pat. No. 5,877,369, EP 0 117 146, DE-A 199 37 106, DE-A 199 37 105 and DE-A 199 37 107 may be used according to the invention. Particularly preferred catalysts for the above-described variants of autothermal n-butane dehydrogenation are the catalysts according to examples 1, 2, 3 and 4 of DE-A 199 37 107. Preference is given to carrying out the n-butane dehydrogenation in the presence of steam. The added steam serves as a heat carrier and supports the gasification of organic deposits on the catalysts, which counteracts carbonization of the catalysts and increases the on stream time of the catalysts. The organic deposits are converted to carbon monoxide, carbon dioxide and possibly water. The dehydrogenation catalysts may be regenerated in a manner known per se. For instance, steam may be added to the reaction mixture or an oxygen-containing gas may be passed from time to time over the catalyst bed at elevated temperature and the deposited carbon burnt off. Dilution with steam shifts the equilibrium toward the products of dehydrogenation. After the regeneration with steam, the catalyst is optionally reduced with a hydrogen-containing gas. The n-butane dehydrogenation provides a gas mixture which, in addition to butadiene, 1-butene, 2-butene and unconverted n-butane, comprises secondary components. Customary secondary components include hydrogen, steam, nitrogen, CO and CO2, methane, ethane, ethene, propane and propene. The composition of the gas mixture leaving the first dehydrogenation zone may be highly variable depending on the dehydrogenation method. For instance, in the preferred autothermal dehydrogenation with feeding in of oxygen and in addition of hydrogen, the product gas mixture comprises a comparatively high content of steam and carbon oxides. In methods without feeding in of oxygen, the product gas mixture of the nonoxidative dehydrogenation has a comparatively high hydrogen content. The product gas stream of the nonoxidative autothermal n-butane dehydrogenation typically comprises from 0.1 to 15% by volume of butadiene, from 1 to 15% by volume of 1-butene, from 1 to 20% by volume of 2-butene, from 20 to 70% by volume of n-butane, from 5 to 70% by volume of steam, from 0 to 5% by volume of low-boiling hydrocarbons (methane, ethane, ethene, propane and propene), from 0 to 30% by volume of hydrogen, from 0 to 30% by volume of nitrogen and from 0 to 5% by volume of carbon oxides. According to the invention, the nonoxidative catalytic dehydrogenation is followed by an oxidative dehydrogenation (oxydehydrogenation) as process part C. In principle, this may be carried out in all reactor types and methods known from the prior art, for example in a fluidized bed, in a tray furnace or a fixed bed tubular or tube bundle reactor. Preference is given to using the latter in the process according to the invention. To carry out the oxydehydrogenation, a gas mixture is required which has a molar oxygen: n-butene ratio of at least 0.5. Preference is given to an oxygen: n-butene ratio of from 0.55 to 50. To adjust this ratio, the product gas mixture which generally results from the catalytic dehydrogenation is mixed with oxygen or an oxygen-containing gas, for example air. The oxygen-containing gas mixture obtained is then fed to the oxydehydrogenation. The catalysts which are particularly suitable for the oxydehydrogenation of the n-butenes to 1,3-butadiene are generally based on an Mo—Bi—O multimetal oxide system which generally additionally comprises iron. In general, the catalyst system also comprises additional components from groups 1 to 15 of the periodic table, for example potassium, magnesium, zirconium, chromium, nickel, cobalt, cadmium, tin, lead, germanium, lanthanum, manganese, tungsten, phosphorus, cerium, aluminum or silicon. Useful catalysts and their preparation are described, for example, in U.S. Pat. No. 4,423,281 (Mo12BiNi8Pb0.5Cr3K0.2Ox and Mo12BibNi7Al3Cr0.5K0.5Ox), U.S. Pat. No. 4,336,409 (Mo12BiNi6Cd2Cr3P0.5Ox), DE-A 26 00 128 (Mo12BiNi0.5Cr3P0.5Mg7.5K0.1Ox+SiO2) and DE-A 24 40 329 (Mo12BiCo4.5Ni2.5Cr3P0.5K0.1Ox), which are explicitly incorporated herein by way of reference. The stoichiometry of the active composition of a variety of multimetal oxide catalysts suitable for the oxydehydrogenation of the n-butenes to 1,3-butadiene can be subsumed under the general formula (I) Mo12BiaFebCocNidCreX1fKgOx (I) where the variables are defined as follows: X1=W, Sn, Mn, La, Ce, Ge, Ti, Zr, Hf, Nb, P, Si, Sb, Al, Cd and/or Mg; a=from 0.5 to 5, preferably from 0.5 to 2; b=from 0 to 5, preferably from 2 to 4; c=from 0 to 10, preferably from 3 to 10; d=from 0 to 10; e=from 0 to 10, preferably from 0.1 to 4; f=from 0 to 5, preferably from 0.1 to 2; g=from 0 to 2, preferably from 0.01 to 1; and x=a number which is determined by the valency and frequency of the elements in (I) other than oxygen. In the process according to the invention, preference is given to using an Mo—Bi—Fe—O multimetal oxide system for the oxydehydrogenation, and particular preference is given to a Mo—Bi—Fe—Cr—O or Mo—Bi—Fe—Zr—O metal oxide system. Preferred systems are described, for example, in U.S. Pat. No. 4,547,615 (Mo12BiFe0.1Ni8ZrCr3K0.2Ox and Mo12BiFe0.1Ni8AlCr3K0.2Ox), U.S. Pat. No. 4,424,141 (Mo12BiFe3Co4.5Ni2.5P0.5K0.1Ox+SiO2), DE-A 25 30 959 (MO12BiFe3CO4.5Ni2.5Cr0.5K0.1Ox, Mo13.75BiFe3Co4.5Ni2.5Ge0.5K0.8Ox, Mo12BiFe3Co4.5Ni2.5Mn0.5K0.1Ox and Mo12BiFe3Co4.5Ni2.5La0.5K0.1Ox), U.S. Pat. No. 3,911,039 (MO12BiFe3CO4.5Ni2.5Sn0.5K0.1Ox), DE-A 25 30 959 and DE-A 24 47 825 (Mo12BiFe3Co4.5Ni2.5W0.5K0.1Ox). The preparation and characterization of the catalysts mentioned are described comprehensively in the documents cited to which reference is hereby explicitly made. The oxydehydrogenation catalyst is generally used as shaped bodies having an average size of over 2 mm. Owing to the pressure drop to be observed when performing the process, smaller shaped bodies are generally unsuitable. Examples of useful shaped bodies include tablets, cylinders, hollow cylinders, rings, spheres, strands, wagon wheels or extrudates. Special shapes, for example “trilobes” and “tristars” (see EP-A-0 593 646) or shaped bodies having at least one notch on the exterior (see U.S. Pat. No. 5,168,090) are likewise possible. In general, the catalysts used may be used as an unsupported catalyst. In this case, the entire shaped catalyst body consists of the active composition, including any auxiliary, such as graphite or pore former and also further components. In particular, it has proven advantageous to use the Mo—Bi—Fe—O catalyst preferably used for the oxydehydrogenation of n-butenes to butadiene as an unsupported catalyst. Furthermore, it is possible to apply the active compositions of the catalysts to a support, for example an inorganic, oxidic shaped body. Such catalysts are generally referred to as coated catalysts. The oxydehydrogenation of the n-butenes to butadiene is generally carried out at a temperature of from 220 to 490° C. and preferably from 250 to 450° C. For practical reasons, a reactor entrance pressure is generally chosen which is sufficient to overcome the flow resistances in the plant and the subsequent workup. This reactor entrance pressure is generally from 0.005 to 1 MPa above atmospheric pressure, preferably from 0.01 to 0.5 MPa above atmospheric pressure. By its nature, the gas pressure applied in the entrance region of the reactor substantially falls over the entire catalyst bed and inert fractions. The coupling of the nonoxidative catalytic, preferably autothermal dehydrogenation with the oxidative dehydrogenation of the n-butenes formed provides a very much higher yield of butadiene based on n-butane used. The nonoxidative dehydrogenation can also be operated in a gentler manner. Comparable yields would only be achievable with an exclusively nonoxidative dehydrogenation at the cost of distinctly reduced selectivities. In addition to butadiene and unconverted n-butane, the second product gas stream leaving the oxydehydrogenation comprises steam. As secondary components it generally comprises carbon monoxide, carbon dioxide, oxygen, nitrogen, methane, ethane, ethene, propane and propene, with or without hydrogen and also oxygen-containing hydrocarbons, known as oxygenates. In general, it only comprises very small proportions of 1-butene and 2-butene. For example, the product gas stream leaving the oxydehydrogenation may comprise from 1 to 20% by volume of butadiene, from 0 to 1% by volume of 1-butene, from 0 to 1% by volume of 2-butene, from 0 to 50% by volume of butane, from 2 to 50% by volume of steam, from 0 to 5% by volume of low-boiling hydrocarbons (methane, ethane, ethene, propane and propene), from 0 to 20% by volume of hydrogen, from 0 to 90% by volume of nitrogen, from 0 to 5% by volume of carbon oxides and from 0 to 3% by volume of oxygenates. Butadiene is recovered in a process part D from the second product gas stream obtained in the oxydehydrogenation. The recovery of butadiene from the second product gas stream may comprise the following steps: (D1) cooling the product gas stream with water to condense out steam and any high-boiling organic secondary components; (D2) removing the low-boiling secondary components contained in the second product gas stream which are selected from the group consisting of hydrogen, carbon monoxide, carbon dioxide, nitrogen, methane, ethane, ethene, propane and propene, to obtain a stream comprising butadiene and n-butane, with or without 1-butene and 2-butene, and with or without oxygenates as further secondary components; (D3) optionally removing the oxygenates to obtain a stream comprising butadiene and n-butane, with or without 1-butene and 2-butene; (D4) separating the stream comprising butadiene and n-butane, with or without 1-butene and 2-butene, into a stream comprising n-butane, with or without 1-butene and 2-butene, and a stream comprising butadiene; (D5) optionally recycling the stream comprising n-butane, with or without 1-butene and 2-butene, into the nonoxidative catalytic dehydrogenation (B). After leaving the dehydrogenation stages, the hot gas mixture whose temperature is generally from 220 to 490° C. is customarily cooled with water. This condenses out steam and any high-boiling organic secondary components. The low-boiling secondary components such as hydrogen, carbon monoxide, carbon dioxide, nitrogen, methane, ethane, ethene, propane and propene present in the dehyrogenation gas mixture in addition to butadiene, n-butane and any 1-butene and 2-butene are subsequently removed from the C4 hydrocarbons. The low-boiling secondary components may be removed by customary rectification. The low-boiling secondary components may also be removed in an absorption/desorption cycle using a high-boiling absorbent. In this way, substantially all low-boiling secondary components (nitrogen, hydrogen, methane, ethane, ethene, propane, propene, carbon oxides, oxygen) are removed from the n-butane dehydrogenation product gas stream. To this end, the C4-hydrocarbons are absorbed in an inert absorbent in an absorption stage to obtain a C4-hydrocarbon-laden absorbent and an offgas comprising the remaining secondary components. In a desorption stage, the C4-hydrocarbon and traces of secondary components are released again from the absorbent. Inert absorbents used in the absorption stage are generally high-boiling nonpolar solvents in which the hydrocarbon which is to be removed has a distinctly higher solubility than the remaining components of the product gas mixture. The absorption may be effected by simply passing the product gas mixture through the absorbent. However, it may also be effected in columns or in rotary absorbers. Operation may be effected in cocurrent, countercurrent or crosscurrent. Examples of useful absorption columns include tray columns having bubble, centrifugal and/or sieve trays, columns having structured packings, for example sheet metal packings having a specific surface area of from 100 to 1 000 m2/m3 such as Mellapak® 250 Y, and randomly packed columns. However, useful absorption columns also include trickle and spray towers, graphite block absorbers, surface absorbers such as thick-film and thin-film absorbers and also rotary columns, plate scrubbers, cross-space scrubbers and rotary scrubbers. Useful absorbents are comparatively nonpolar organic solvents, for example aliphatic C8-to C18-alkenes, or aromatic hydrocarbons such as the middle oil fractions from paraffin distillation, or ethers having bulky groups, or mixtures of these solvents, to each of which a polar solvent such as 1,2-dimethyl phthalate may be added. Further useful absorbents include esters of benzoic acid and phthalic acid with straight-chain C1-C8-alkanols, such as n-butyl benzoate, methyl benzoate, ether benzoate, dimethyl phthalate, diethyl phthalate, and also heat carrier oils, such as biphenyl and diphenyl ether, their chlorine derivatives and also triarylalkenes. A useful absorbent is a mixture of biphenyl and diphenyl ether, preferably in the azeotropic composition, for example the commercially available Diphyl®. Frequently, this solvent mixture comprises dimethyl phthalate in an amount of 0.1 to 25% by weight. Further useful absorbents are octanes, nonanes, decanes, undecanes, dodecanes, tridecanes, tetradecanes, pentadecanes, hexadecanes, heptadecanes and octadecanes, or fractions obtained from refinery streams which have linear alkanes mentioned as main components. For desorption, the laden absorbent is heated and/or decompressed to a lower pressure. Alternatively, desorption may also be effected by stripping or in a combination of decompression, heating and stripping in one or more process steps. The absorbent regenerated in the desorption stage is recycled into the absorption stage. A stream consisting substantially of butadiene and n-butane remains which may also comprise 1-butene and 2-butene and also oxygenates as further secondary components. Such oxygenates include, for example, furan and maleic anhydride. The oxygenates may be removed from the C4 hydrocarbons in a further separating stage which may likewise be configured as an absorption/desorption stage or as a rectification. The remaining stream which customarily consists predominantly of butadiene and n-butane and, in addition, may also comprise small amounts of 1-butene and 2-butene may be separated in a further separating stage in a stream comprising n-butane and any 1-butene and 2-butene, and a stream comprising butadiene. The separation may be effected, for example, by butadiene scrubbing. Butadiene scrubbing may be effected as described in Weissermehl/Arpe, Industrielle Organische Chemie, 5th Edition 1998, p. 120/121, or Hydrocarbon Processing, Mar. 2002, p. 50B. The stream comprising n-butane and any 1-butene and 2-butene may at least partially be recycled into the nonoxidative catalytic dehydrogenation (B). Process part (D) preferably comprises at least the steps (D1), (D2) and (D4). More preferably, it comprises the steps (D1) to (D5). The invention is illustrated hereinbelow with reference to the drawing. The FIGURE shows the process flow diagram of a preferred embodiment of the process according to the invention. A feed stream 1 of liquefied petroleum gas (LPG) which consists substantially of propane, n-butane and isobutane and, in addition, may also comprise methane, ethane or pentanes, is fed to a rectification column 2 and separated into a stream 3 composed substantially of propane and any methane and ethane, and a stream 4 composed substantially of n-butane and isobutane and any pentanes. In the rectification column 5, any pentanes 6 are removed. The butane mixture 7 is separated in the rectification column 8 into isobutane 9 and n-butane 12, and isobutane is isomerization in the isomerization reactor 10 to an n-butane/isobutane mixture 11 which is fed back into the rectification column 8. n-Butane is fed as the feed gas stream 12 into the first dehydrogenation stage 15 in which a nonoxidative catalytic dehydrogenation of butane to 1-butene, 2-butene and butadiene takes place. This is preferably carried out under autothermal conditions while feeding in oxygen or air as cofeed 13 and optionally hydrogen as cofeed 14. Preference is given to carrying out the first dehydrogenation stage with backmixing in a fluidized bed or with partial gas recycling, for example as described in German patent application P 102 11 275.4, unpublished at the Priority date of the present invention. The product gas stream 16 leaving the first dehydrogenation stage which, in addition to butadiene, 1-butene, 2-butene and unconverted n-butane, comprises steam and customary secondary components such as hydrogen, carbon oxides, nitrogen, hydrogen, methane, ethane, ethene, propane and propene is fed to a second dehydrogenation stage 18, in which while feeding in oxygen or air as cofeed 17, an oxydehydrogenation of 1-butene and 2-butene to butadiene takes place. The second dehydrogenation stage is preferably carried out in a tube bundle reactor. The second dehydrogenation stage may itself be carried out in more than one stage, for example in two stages. In the two-stage configuration of the oxydehydrogenation, the second dehydrogenation stage consists of a first oxydehydrogenation stage 18 and a second oxydehydrogenation stage 18a, into each of which air or oxygen is fed as cofeed 17 or 17a. The product gas stream 19a leaving the second dehydrogenation stage (in the one-stage configuration of the oxydehydrogenation, this is the product gas stream 19) comprises, in addition to butadiene and unconverted n-butane, steam and secondary components such as hydrogen, carbon oxides, nitrogen, methane, ethane, ethene, propane and/or propene, with or without small residues of 1-butene and 2-butene and with or without oxygen and oxygen-containing hydrocarbons (oxygenates). The product gas stream 19a, optionally after precooling in heat exchangers, is cooled in the cooling and condensation unit 20 which may be configured, for example, as a water fluidized bed or as a falling-film condenser, to such an extent that water and high-boiling organic by-products such as high-boiling hydrocarbons and oxygenates condense out and are discharged from the process as stream 21. The uncondensed product gas components are fed to the separating stage 23 as stream 22 in which a removal of low boilers and uncondensable secondary components 24 (when present in product gas stream 19a: hydrogen, carbon oxides, nitrogen, methane, ethane, ethene, propane, propene and oxygen) takes place. The separating stage 23 may be configured as a rectification column or as an absorption/desorption unit. The stream 25 comprising the C4 products of the dehydrogenation, unconverted n-butane and any oxygenates such as furan and maleic anhydride is optionally fed to a further separating stage 26 which may be configured as a rectification column or an absorption/desorption unit. In the separating stage 26, oxygenates and any remaining water traces are removed and discharged from the process as stream 27. The stream 28 composed of butadiene and n-butane which may also comprise small proportions of 1-butene and 2-butene is fed to a further separating stage 29, for example a butadiene scrubbing, and separated there into a stream 31 composed of n-butane and any 1-butene and 2-butene and a stream 30 composed of butadiene. The stream 31 may at least partially be recycled into the nonoxidative catalytic dehydrogenation stage 15. The invention is illustrated by the examples hereinbelow. EXAMPLES Example 1 Preparation of a Dehydrogenation Catalyst Precursor A solution of 11.993 g of SnCl2.2H2O and 7.886 g of H2PtCl6.6H2O in 600 ml of ethanol is poured over 1 000 g of a spalled ZrO2/SiO2 mixed oxide having a ZrO2/SiO2 weight ratio of 95:5 from Norton (USA). The mixed oxide has the following specifications: Sieve fraction 1.6 to 2 mm; BET surface area: 86 m2/g; pore volume: 0.28 ml/g (from mercury porosimetry measurement). The supernatant ethanol is taken off on a rotary evaporator using a water jet pump vacuum (20 mbar). Drying is then effected at 100° C. for 15 h followed by calcining at 560° C. for 3 h, each under stationary air. A solution of 7.71 g of CsNO3, 13.559 g of KNO3 and 98.33 g of La(NO3)3.6H2O in 2 500 ml of H2O is then poured over the dry solid. The supernatant water is taken off on a rotary evaporator using a water jet pump vacuum (20 mbar). Drying is then effected at 100° C. for 15 h followed by calcining at 560° C. for 3 h, each under stationary air. The resulting catalyst precursor has a composition of Pt0.3Sn0.6Cs0.5K0.5La3.0 (indices represent weight ratios) on (ZrO2)95 (SiO2)5 as carrier indices represent weight ratios). Example 2 Charging of a Dehydrogenation Zone A Reactor and Activation of the Catalyst Precursor 20 ml of the catalyst precursor obtained from example 1 are used to charge a vertical tubular reactor (reactor length: 800 mm; wall thickness: 2 mm; internal diameter: 20 mm; reactor material: internally alonized, i.e. aluminum oxide-coated, steel tube; heating: electrical using an oven from HTM Reetz, LOBA 1100-28-650-2 at a longitudinal midpoint length of 650 mm). The length of the catalyst bed is 75 mm. The catalyst bed is disposed at the longitudinal midpoint of the tubular reactor. The remaining reactor volume above and below is filled with steatite spheres as an inert material (diameter 4-5 mm) which are supported from below on the catalyst base. The reactor tube is then charged at an external wall temperature along the heating zone of 500° C. with 9.3 l/h (stp) of hydrogen over 30 min. At the same wall temperature, the hydrogen stream is initially replaced over 30 min by a stream of 80% by volume of nitrogen and 20% by volume of air at 23 l/h (STP) and then over 30 min by an identical stream of pure air. While retaining the wall temperature, purging is then effected with an identical stream of N2 over 15 min and finally reduction is once again effected with 9.3 l/h (STP) of hydrogen over 30 min. The activation of the catalyst precursor is then completed. Example 3 Preparation of an Oxydehydrogenation Catalyst 1750.9 g of aqueous cobalt nitrate solution having a free HNO3 content of 0.2% by weight and a Co content of 12.5% by weight (=3.71 mol of Co) are initially charged in a heatable glass 10 L solid reactor. 626.25 g of solid Fe(NO3)3.9H2O having an Fe content of 14.2% by weight (=1.59 mol of Fe) are dissolved with stirring at room temperature in the initially charged cobalt nitrate solution. 599.5 g of bismuth nitrate solution having a free HNO3 content of 3% by weight and a Bi content of 11.1% by weight (=0.32 mol of Bi) are added to the solution obtained at room temperature. 106.23 g of solid Cr(NO3)3.9H2O (=0.27 mol of Cr) are then added. After heating to 60° C. and further stirring, a red solution (solution A) is obtained. In a heatable 3 l stirred glas vessel, 2 000 ml of water are initially charged. 2.38 g of KOH (=0.042 mol of K) and 1 124.86 g of (NH4)6Mo7O24.4H2O (=6.37 mol of Mo) are then added and are dissolved at 60° C. The solution obtained exhibits slight turbidity (solution B). Solution B is then pumped into solution A while stirring the latter. 102.05 g of SiO2 sol having an SiO2 content of 50% by weight (“Ludox ™” from DuPont =0.85 mol of Si) are added to the dark yellow suspension obtained at 60° C. The suspension obtained is stirred at 60° C. for 30 minutes and then spray-dried (entrance temperature 370° C., exit temperature 110 to 112° C.). The spray powder obtained is admixed with 4% weight of graphite and then tableted to solid tablets having a diameter of 5 mm and a height of 3 mm. The solid tablets are heat treated at 480° C. for 6 hours in a muffle furnace on a wire sieve (mesh size 3.5 mm) flowed through by air with air flowing through at a rate of 100 l/h. The calcined tablets are comminuted through a wire sieve to give catalyst spall having an average granulate diameter of from 2 to 3 mm. The oxydehydrogenation catalyst has the nominal composition Mo12Bi0.6Fe3Co7Cr0.5Si1.6K0.08Ox (indices represent atomic ratios). Example 4 Charging of a Dehydrogenation Zone B Reactor 95 ml of catalyst precursor obtained for example 3 are used to charge a vertical tubular reactor (reactor length: 100 cm; wall thickness: 2 mm; internal diameter: 13 mm, reactor material: internally alonized steel tube with a thermowell disposed therein having an external diameter of 2 mm which contains a moveable thermal element; heating: electrical with three different heating zones over the reactor length of 100 cm using heating collars from Winkler, Heidelberg, and a maximum isothermal length of 82 cm is achieved over the middle region of the reactor). The length of the catalyst bed is 82 cm. The catalyst bed is in the isothermal region of the tubular reactor. The remaining reactor volume above and below is charged with steatite spheres as an inert material (diameter 2-3 mm), and the entire reactor tube charge is supported from below on a catalyst base of height 5 cm. Example 5 Dehydrogenation of n-Butane in the Dehydrogenation Zone A Reactor The dehydrogenation zone A reactor for example 2 is charged at an external wall temperature along the heating zone of 500° C. with a mixture of 20 l/h (stp) of n-butane, 3.5 l/h (stp) of air, 1.4 l/h (stp) of hydrogen and 10 l/h (stp) of steam as the reaction gas mixture. The n-butane, air and hydrogen are metered by means of a mass flow regulator from Brooks, while the water is initially metered into an evaporator in liquid form by means of a Kontron HPLC pump 420, evaporated in it and then mixed with the n-butane and the air. The temperature of the charge gas mixture in the charge is 150° C. By means of an REKO pressure regulator at the reactor exit, the exit pressure of the tubular reactor is set to 1.5 bar. An analytical amount of the product gas mixture A obtained is decompressed to atmospheric pressure and cooled to condense out the steam present. The remaining gas is analyzed by means of GC (HP 6890 with Chem.-Station, detectors: FID; TCD; separating columns: Al2O3/KCI (Chrompack), Carboxen 1010 (Supelco)). In a corresponding manner, the charging gas mixture is also analyzed. After an operating time of three days, the analysis results reported in table 1 were obtained: TABLE 1 Charging gas mixture [% Product gas mixture by volume] [% by volume] Methane 0.07 Ethane 0.05 Ethene <0.01 Propane 0.10 Propene 0.05 H2 4.0 16.3 O2 2.0 <0.01 N2 8.0 6.8 CO 0.03 CO2 0.28 Isobutane 0.11 n-Butane 57.4 33.2 trans-butene 5.7 cis-Butene 4.8 Isobutene 0.08 1-Butene 4.1 Butadiene 0.52 H2O 28.6 27.7 An n-butane conversion of 32 mol % based on single pass and a selectivity of n-butene formation of 94 mol % corresponds to these values. The selectivity of the butadiene formation corresponds to 3.3%. Example 6 Dehydrogenation of n-Butane in the Dehydrogenation Zone A Reactor and Subsequent Oxydehydrogenation in the Dehydrogenation Zone B Reactor. The dehydrogenation zone B reactor from example 4 is heated to a temperature at which the n-butene conversion on single throughput of the reaction gas mixture is >99 mol %, and the internal temperature of the reactor is controlled by means of the thermal elements disposed in the internal thermowell. The charge consists of a mixture of 150 l/h (stp) of air (=20° C.) and the 34.4 l/h (stp) of product gas mixture A from example 5 (=500° C.). The air is metered in by means of a mass flow regulator from Brooks. The temperature of the charging gas mixture is brought to the reactor external wall temperature. By means of a pressure regulator at the reaction tube exit, the exit pressure of the reactor is set to 1.3 bar. Downstream of the pressure regulator, the product gas mixture B obtained (temperature =330° C.) is decompressed to atmospheric pressure and analyzed by means of GC (HP 6890 with Chem-Station; detectors: TCD; FID; separating column: Poraplot Q (Chrompack), Carboxen 1010 (Supelco)). The charging gas mixture is analyzed in an identical manner. After an operating time of 3 days, the results reported in table 2 are obtained. TABLE 2 Charging gas mixture Product gas mixture [% by volume] [% by volume] Methane 0.02 0.01 Ethane 0.01 0.01 Ethene <0.01 <0.01 Propane 0.02 0.02 Propene 0.01 <0.01 H2 3.5 3.5 O2 15.7 11.1 N2 64.3 63.5 CO 0.01 1.3 CO2 0.06 1.3 Isobutane 0.02 0.02 n-Butane 7.1 7.0 trans-Butene 1.2 <0.01 cis-Butene 1.0 <0.01 Isobutene 0.02 <0.01 1-Butene 0.9 <0.01 Butadiene 0.11 2.6 H2O 6.0 9.6 An n-butene conversion of 99 mol % based on single pass and a selectivity of butadiene formation of 80 mol % corresponds to these values. The overall yield of butadiene over both dehydrogenation zones A and B based on n-butane used is 25%. 4. Comparative Example The charging gas mixture described in example 5 is passed directly into the dehydrogenation zone B reactor. Under identical reaction conditions, there is no conversion of the n-butane to butenes or butadiene.
20041207
20060425
20050804
72241.0
0
TESKIN, FRED M
METHOD FOR THE PRODUCTION OF BUTADIENE FROM N-BUTANE
UNDISCOUNTED
0
ACCEPTED
2,004
10,516,934
ACCEPTED
Suspension arm and method for making same
A motor vehicle front suspension arm including three bores corresponding respectively to an articulation of the arm to a wheel support, to a front articulation, and a rear articulation of a hinge formed between the arm and the vehicle body. The suspension arm includes a single-piece sheet metal part and the bores corresponding to the articulations of the hinge have substantially perpendicular axes.
1-15. (canceled) 16. A front suspension arm of a motor vehicle, comprising: three bores corresponding respectively to a coupling of the arm to a wheel support, to a front coupling and a rear coupling of a hinge formed between that arm and a chassis of the vehicle, formed by a single sheet metal part, and wherein the bores corresponding to the hinge couplings have appreciably perpendicular axes. 17. A suspension arm according to claim 16, wherein centers of the front coupling and rear coupling of the hinge are situated in a same longitudinal plane. 18. A suspension arm according to claim 16, wherein a center of the front coupling of the hinge is situated in back of a transverse plane passing through a center of the coupling of the arm on the wheel support. 19. A suspension arm according to claims 16, wherein the single sheet metal part is formed by a stamped sheet presenting a flat center part, a first side connecting the coupling of the arm to the wheel support and the rear coupling of the hinge, a second side connecting the coupling of the arm to the wheel support and the front coupling of the hinge, and a third side connecting the front and rear couplings of the hinge. 20. A suspension arm according to claim 19, further comprising an appreciably vertical joining plane connecting the second side to a periphery of the bore corresponding to the front coupling of the hinge. 21. A suspension arm according to claim 19, further comprising an appreciably horizontal joining plane connecting the third side to a periphery of the bore corresponding to the front coupling of the hinge. 22. A suspension arm according claim 19, wherein the first side is provided with a vertical wall. 23. A suspension arm according to claim 19, wherein the second side is provided with a raised edge, a height of which gradually varies. 24. A suspension arm according to claim 23, wherein the raised edge of the second side bears a dropped edge at a right angle, directed toward an outside of the arm. 25. A suspension arm according to claim 24, wherein indexing bores are borne by the dropped edge. 26. A suspension arm according to claim 24, further comprising means for determining a stable position of the vehicle borne by the dropped edge. 27. A suspension arm according to claim 19, further comprising a groove formed along the flat center part of a single part of the arm. 28. A suspension arm according to claim 19, further comprising a flange made in an uninterrupted connection of the bore corresponding to the front coupling of the hinge, the flange being oriented toward the rear coupling of the hinge. 29. A method of obtaining a motor vehicle suspension arm according to claim 28, comprising stamping of a single sheet metal part having three couplings with a chassis and a wheel support comprising: forming a triangular flat surface presenting at two ends a bore of vertical axis; creating a raised edge and a dropped edge borne at a right angle by the raised edge on a side situated between the front coupling of the hinge and the wheel support coupling, creating a vertical wall on a side situated between the rear coupling of the hinge and the wheel support coupling, forming smooth shapes and joining planes complementing adjacent sides to generate the front coupling of the hinge of an appreciably horizontal axis, creating a flange in an extension of the bore corresponding to the front coupling of the hinge, in a direction of the rear coupling of that hinge, marking and indexing the dropped edge. 30. A method of mounting a suspension arm according to claim 29, comprising placing elastic elements forming the coupling of the arm on the chassis and a wheel support, wherein the elastic element forming the front coupling of the hinge created between the arm and the chassis is mounted in a direction opposite the flange.
This invention concerns the lower suspension arms placed in front of a vehicle and, in particular, single-sheet “rectangle” type arms. Arms of this type come in a single part with a mounting area on the steering knuckle and two mounting areas constituting a hinge between the arm and the chassis of the vehicle. The front coupling and the rear coupling of that hinge present appreciably parallel axes. Depending on the vehicles on which the arms must be installed, the two hinge couplings are of horizontal axis or the two hinge couplings are of vertical axis. Such an arrangement does not permit a radial flexibility of the rear coupling of the hinge, commonly called point B. It would, in fact, be necessary to set a large-sized elastic stud in place while that point B is situated in a restricted space. One of the objectives of the invention is therefore to satisfy these imperatives of flexibility of the hinge coupling, within a context of a single-sheet arm. In that connection, the invention proposes a front suspension arm of a motor vehicle, containing three bores corresponding respectively to a coupling of the arm to a wheel support, to a front coupling and a rear coupling of a hinge formed between that arm and the chassis of the vehicle. That suspension arm is characterized in that it is formed by a single sheet metal part and in that the bores corresponding to the hinge couplings have appreciably perpendicular axes. According to another characteristic of this invention, the centers of the front and rear couplings of the hinge are situated in a same longitudinal plane. For the purpose of proposing a suspension gear, the space for which is minimal, the center of the front coupling of the hinge is situated in back of a transverse plane passing through the center of the coupling of the arm on the wheel support. According to one characteristic of this invention, the single part is formed by a stamped sheet presenting a flat center part, a first side connecting the coupling of the arm to the wheel support and the rear coupling of the hinge, a second side connecting the coupling of the arm to the wheel support and the front coupling of the hinge and a third side connecting the two couplings of the hinge. Making the arm in the area close to the front coupling imposes intense stresses owing to the horizontal orientation of that coupling. With a view to presenting an arm satisfying stress resistance criteria, a appreciably vertical joining plane connects the second side to the periphery of the bore corresponding to the front coupling of the hinge, and a appreciably horizontal joining plane connects the third side to the periphery of that bore. In order to stabilize the section of the arm in case of braking or longitudinal shock and respectively to stiffen the arm under turning stress, the first side is provided with a vertical wall and the second side is respectively provided with a raised edge, the height of which progressively varies, on which raised edge a dropped edge bears at a right angle, directed toward the outside of the arm. According to another characteristic of this invention, indexing means are borne by the dropped edge. According to another characteristic of this invention, means of determining the stable position of the vehicle are borne by the dropped edge. According to another characteristic of this invention, a groove is formed along the center part of the single part of the arm. To make possible the mounting and holding of the elastic means ensuring the coupling of the arm on the chassis, within a context of a single-part arm, a flange is made in the uninterrupted connection of the bore corresponding to the front coupling of the hinge, that flange being oriented toward the rear coupling of the hinge. That orientation generates a direction of mounting of the elastic element having to ensure the front coupling of the hinge, that elastic element being mounted with “counter-flange” to ensure better resistance to braking stresses. The invention also concerns the method of obtaining such a suspension arm, involving the stamping of a single sheet metal part having three couplings with the chassis and a wheel support, characterized in that it consists at least of the formation of a triangular flat surface presenting at two ends a bore of vertical axis, the creation of a raised edge and of a dropped edge borne at a right angle by that raised edge on the side situated between the front coupling of the hinge and the wheel support coupling, the creation of a vertical wall on the side situated between the rear coupling of the hinge and the wheel support coupling, the formation of smooth shapes and joining planes complementing the adjacent sides in order to generate the front coupling of the hinge of appreciably horizontal axis, the creation of a flange in the extension of the bore corresponding to the front coupling of the hinge, in the direction of the rear coupling, and the marking and indexing of the dropped edge. Other characteristics and advantages of the invention will be apparent on reading the detailed description which follows, for the understanding of which the attached drawings will be referred to, in which: FIG. 1 is a view in perspective of a suspension arm according to the invention. FIG. 2 is a side-face view, from inside the vehicle, of a suspension arm as represented on FIG. 1. In the description which follows, a longitudinal, vertical and transverse orientation will be adopted on a non-restrictive basis, without limitation, according to the orientation traditionally used in motor vehicles and indicated by the trihedron L, V, T of FIG. 1. A front lower suspension arm 1, as represented on FIG. 1, consists of a single part 2 connecting the area of coupling 3 on the wheel support and two areas of coupling 4 and 5 forming a hinge between the arm 1 and the chassis of the vehicle. Those three areas form an appreciably right-angled triangle, the hypotenuse of which connects the center of the coupling 3 on the wheel support to the center of the rear coupling 5 of the hinge. The sides of that right-angled triangle are such that the distance between the two centers of couplings 4 and 5, constituting the hinge between the arm and the chassis, is less than the distance between the center of front coupling 4 of the hinge and the center of coupling 3 of the arm 1 on the wheel support, in a ratio of approximately 2/3. The arm 1 is stamped so as to present at each end of the hypotenuse a bore of vertical axis corresponding on the one hand to the rear coupling 5 of the hinge between the arm 1 and the chassis and on the other to the coupling 3 of the arm 1 on the wheel support. At the end corresponding to the front coupling 4 of the hinge, the arm 1 presents a bore of appreciably longitudinal axis. The two couplings 4 and 5 of the arm 1 on the chassis therefore present appreciably perpendicular axes, the center of each of those couplings being situated in the same longitudinal plane. The center part 6 of the arm 1 corresponds to an arc joining the two ends 3 and 5 of the hypotenuse, of width greater than the larger diameter of the two bores present at those ends, such as the bore corresponding to the rear coupling 5 of the hinge. The stamped sheet forms around that bore a first coaxial round 51 in the uninterrupted connection of the center part 6 of the arm 1. Likewise, the stamped sheet forms a second coaxial round 31 around the bore corresponding to the coupling 3 on the wheel support, but the diameter of which, less than the first round 51, imparts a recess 32 in relation to the width of the arc-shaped center part 6 of the arm 1. A groove 7 is made at the bottom of the stamping, along the arc-shaped center part 6. In known manner, such a groove 7 makes it possible, by improving the surface evenness, to avoid creasing of the sheets and the risks of destabilization of the arm 1 when it is subjected to various stresses. Each end of that groove 7 is situated at a distance, predetermined by calculation, from the bores present at the two ends 3 and 5 of the hypotenuse. A first side 8 is formed by the edge of the arc-shaped center part 6 of the arm 1, situated inside the curve of that arc. This first side 8 is provided with a vertical wall 9. The latter extends from the recess 32 made in proximity to the coupling 3 on the wheel support to the transverse plane passing through the center of the rear coupling 5 of the hinge. Such a wall 9 is dimensioned to best stabilize the section of the arm 1 upon operation of that arm 1 under compression due to a braking or longitudinal shock. As such a situation then entails a considerable rise in stress in that edge 8 directed toward the rear of the vehicle, it is a question of avoiding the buckling of the part 2. The height of that wall 9 can, for example, be 40 millimeters. A second side 10, situated between the coupling 3 on the wheel support and the front coupling 4 of the hinge, is also provided with a raised edge 11. While the wall 9, symmetrically opposite the groove 7 of the arm 1, is of constant height, the raised edge 11 has a gradually increasing height, from zero height close to the coupling 3 of the wheel support to a height, equivalent to the opposite wall 9, close to the front coupling 4 of the hinge. That raised edge 11, of vertical orientation, bears at its free end a dropped edge 12 at right angle to the raised edge 11 and directed toward the front of the vehicle. That dropped edge 12 thus makes possible a stiffening of the assembly on compression of the arm 1 due to a turning stress, capable of generating a considerable stress between the front link with the chassis and the link to the wheel support. The flat surface it presents also makes possible the integration of different functions. Each suspension arm 1 of the same gear, left and right, thus symmetrically presents, on the one hand, a marking area 13 for the traceability of machined parts and, on the other, a fastening hole 14 for a control rod, necessary to indicate in known manner the stable position of the vehicle and thus regulate the direction of the headlights of the vehicle. The left suspension arm 1 also possesses on that dropped edge 12 a keying slot, not represented, making possible an indexing of the front gear on assembly of the vehicle. The bore corresponding to the front coupling 4 of the hinge, of appreciably longitudinal axis, is provided on its periphery with a third coaxial round 41. A flange 42, made by stamping and oriented toward the rear of the vehicle, is borne by that third round 41 in the uninterrupted connection of the corresponding bore. The center of the front coupling 4 of the hinge is set back from the transverse plane passing through the center of the coupling 3 on the wheel support. For example, a recess of 70 millimeters makes it possible to obtain a more compact and therefore less cumbersome arm. Owing to the geometric characteristics of the embodiment of the arm 1 described above, the front coupling 4 of the hinge is situated outside the circle defined by the arc-shaped center part 6 of the arm 1. The upper part of the third coaxial round 41 therefore extends in an appreciably transverse plane to the junction of the raised edge 12. The joining plane 43 thus formed is situated in a vertical plane. The lower part of the third coaxial round 41 extends in an appreciably longitudinal plane to the junction of a third side 16 defined by the arc-shaped center part 6 between the two couplings 4 and 5, constituting the hinge. The joining plane 44 thus formed is situated in a horizontal plane. Obtaining of the arm 1 by stamping makes it possible to obtain in that area even profiles passing from a vertical section to a horizontal section smoothly. Stamping also makes it possible to obtain a flange 42 without a then welded gusset. The arm 1 then comes entirely within a single-piece context and makes possible a fitting of the elastic element, ensuring the front coupling 4 of the hinge with “counter-flange”, that is, a fitting toward the front of the vehicle, while the flange 42 is oriented toward the rear coupling 5 of the hinge. That type of fitting makes possible a better resistance to braking stresses. This arrangement around the front coupling 4 of the hinge necessitates reducing the longitudinal stresses at that coupling point. The appreciably perpendicular arrangement—in the hinge formed between the arm 1 and the chassis—of the rear coupling 5 in relation to the front coupling 4 makes it possible to increase the longitudinal stress contribution of the point corresponding to the rear coupling 5 of the hinge. For example, on braking, there is the equation: → ⁢ → → F XE = - Σ ⁢ ⁢ ( F xA + F xB ) The possibility of rendering the rear coupling point 5 of the hinge stiffer makes possible an increase of FxB and therefore, depending on the constancy of FxE, a reduction of FxA. Such a single-sheet suspension arm 1 is the result of a particular method of stamping capable of obtaining an arm 1, on the one hand, in that particular geometry where the front coupling 4 and rear coupling 5 of the hinge formed between the suspension arm 1 and the chassis of the vehicle are of appreciably perpendicular axis and, on the other hand, validated in terms of stiffness and stress resistance, notably in case of braking or turning, and without resorting to a multiple part technology. It is advisable to work the junction 43 between the dropped edge 12 and the part of the arm situated in proximity to the front coupling 4 of the hinge, as well as the junction 44 between that part of the arm and the arc-shaped center part 6 of the arm 1. Smooth shapes make it possible not to generate too many stresses on passage between vertical and horizontal section planes. The invention is not at all limited to the embodiment described and illustrated, which has been given only by way of example.
20041214
20070925
20051013
63839.0
0
CULBRETH, ERIC D
SUSPENSION ARM AND METHOD FOR MAKING SAME
UNDISCOUNTED
0
ACCEPTED
2,004
10,517,071
ACCEPTED
Saw sensor device using slit acoustic wave and method thereof
The present invention discloses an SAW sensor device using a slit acoustic wave and a method thereof. The SAW sensor device using the slit acoustic wave includes a piezoelectric medium having a thin membrane at its one portion, a medium at the other portion, and a narrow slit which the slit acoustic wave passes through at its inside, an input IDT formed at the outer portion in the narrow slit of the piezoelectric medium, for transducing an electric input signal into the slit acoustic wave, and an output IDT formed at the outer portion opposite to the input IDT, for receiving the propagated slit acoustic wave and transducing the wave into an electric signal, whereby an external pressure transmitted to the device is sensed. The SAW sensor device using the slit acoustic wave and the method thereof can obtain intensity of the external pressure and viscosity and dielectric permittivity of liquid passing through the narrow slit by using correlations of frequency and velocity shifts of the slit acoustic wave generated in a resonator of the narrow slit.
1. An SAW sensor device using a slit acoustic wave, comprising: a piezoelectric medium having a thin membrane at its one portion, a medium at the other portion, and a narrow slit which the slit acoustic wave passes through at its inside; an input IDT formed at the outer portion in the narrow slit of the piezoelectric medium, for transducing an electric input signal into the slit acoustic wave; and an output IDT formed at the outer portion opposite to the input IDT, for receiving the propagated slit acoustic wave and transducing the wave into an electric signal, whereby an external pressure transmitted to the device is sensed. 2. The SAW sensor device according to claim 1, wherein a width of the narrow slit is varied according to the pressure transmitted to the thin membrane, and a velocity of the slit acoustic wave propagated in the narrow slit is shifted according to variations of the width of the narrow slit. 3. The SAW sensor device according to claim 1, wherein the velocity of the slit acoustic wave is shifted according to a property of the medium of the piezoelectric medium. 4. An SAW sensor device using a slit acoustic wave, comprising: a piezoelectric medium having a narrow slit which the slit acoustic wave passes through at its inside, and being divided into an upper portion and a lower portion from the narrow slit, for sensing liquid in the device; an input IDT formed at one side of the piezoelectric medium, for transducing an electric input signal into the slit acoustic wave; an output IDT formed at the opposite side to the input IDT in the piezoelectric medium, for receiving the propagated slit acoustic wave, and transducing the wave into an electric signal; an input liquid port for inputting the liquid into the narrow slit of the piezoelectric medium; and an output liquid port for outputting the liquid of the narrow slit of the piezoelectric medium. 5. The SAW sensor device according to claim 4, wherein, when the liquid flows in the narrow slit, dielectric permittivity and viscosity of the liquid are sensed by measuring a velocity and frequency of the slit acoustic wave of the liquid of the narrow slit. 6. A method for sensing an external pressure of an SAW sensor device, comprising the steps of: (a) when a thin membrane does not receive a pressure, calculating a frequency and velocity of electric signals of an input IDT and an output IDT in a narrow slit, and comparing the resultant values; (b) when the thin membrane receives an external pressure, calculating a frequency and velocity of electric signals of the input IDT and the output IDT, and comparing the resultant values; and (c) sensing intensity of the external pressure in consideration of velocity and frequency shifts due to the external pressure transmitted to the thin membrane. 7. The method according to claim 6, wherein step (c) for sensing the intensity of the external pressure is performed by previously setting frequency and velocity shift value data under the external pressure to an external device, and comparing the data values. 8. A method for sensing liquid of an SAW sensor device, comprising the steps of: (a) measuring a phase velocity of a slit acoustic wave proceeding in an empty slit, and calculating a frequency; (b) when the liquid flows in the narrow slit through an input liquid port, measuring a phase velocity of the slit acoustic wave in the narrow slit, and calculating a frequency; and (c) sensing dielectric permittivity and viscosity of the liquid passing through the narrow slit in consideration of velocity and frequency shifts. 9. The method according to claim 8, wherein step (b) for measuring the phase velocity of the slit acoustic wave and calculating the frequency calculates the velocity and frequency of the slit acoustic wave when the liquid is filled in an output liquid port. 10. The method according to claim 8, wherein step (c) for sensing the dielectric permittivity and viscosity of the liquid is performed by previously setting dielectric permittivity and viscosity data of all kinds of liquids in an external device, and comparing the data values.
TECHNICAL FIELD The present invention relates to a surface acoustic wave (SAW) device, and more particularly to an SAW sensor device using a slit acoustic wave which can sense intensity of an external pressure and viscosity and dielectric permittivity of liquid by using correlations of frequency and velocity shifts of the slit acoustic wave generated in a resonator, like using a surface acoustic wave generated in a resonator of an SAW device, and a method thereof. BACKGROUND ART Recently, mobile communication apparatuses such as cellular phones and portable information terminals have been rapidly distributed due to development of a mobile communication system. Thus, there are increasing demands for miniaturization and high performance of the apparatuses and their components. In addition, two kinds, namely analog and digital type wireless communication systems are used for cellular phones, and a frequency for the wireless communication varies from a band of 800 MHz˜1 GHz to a band of 1.5 GHz to 2.0 GHz. A dielectric resonator duplexer has been generally used as an antenna duplexer for the mobile communication system in consideration of low loss, power efficiency and temperature stability. However, an SAW (Slit Acoustic Wave) duplexer is newly recommended on the basis of recent low loss design of an SAW filter, development of a power efficiency material, and development of a medium having a stabilized temperature property. When the dielectric duplexer is compared with the SAW duplexer, the SAW duplexer has equal or more excellent properties to/than the dielectric duplexer, except for power efficiency. Especially, the SAW duplexer is absolutely advantageous in shape and size. Nevertheless, the SAW duplexer is still more expensive than the dielectric resonator type duplexer. When mass production of the SAW duplexer is achieved according to the property of an SAW manufacturing process using a semiconductor process, the SAW duplexer will have a competitive price. FIG. 1 is a schematic diagram illustrating a general SAW filter. As illustrated in FIG. 1, the SAW filter includes a single crystal medium 101, an input inter-digital transducer (IDT) and an output IDT 103. When the single crystal medium 101 is a piezoelectric single crystal medium such as quartz, LiTaO3 and LiNbO3, the input IDT 102 and the output IDT 103 are comprised of thin metal membranes. In FIG. 1, an electric signal transmitted to the input IDT 102 is transduced into a mechanical wave by the piezoelectric single crystal medium 101, and propagated to the output IDT 103 through the single crystal medium 101. The wave transmitted to the output IDT 103 is re-transduced into an electric signal according to piezoelectric effects, and then outputted. That is, the SAW filter generally used in a mobile communication terminal for filtering high frequency signals is a manual device for selectively passing wanted frequency signals by patternizing a transducer on the piezoelectric single crystal medium with thin metal membranes, and connecting the transducer to I/O terminals. A frequency response total transfer function of the resonator of the SAW filter is provided as a composite function of material properties such as physical properties of a piezoelectric material, purity of a crystal and properties of a thin metal membrane, and device variables including variables considered in electrode design. There have been known that a limit of a minimum value of a resonance frequency range is determined by a size of the device, and that a limit of a maximum value thereof is influenced by a line width of an electrode and loss of electric wave. Because the resonator has a very narrow bandwidth frequency response and a long impulse response, it can embody wanted properties by precisely manufacturing an electrode according to an electrode design. As described above, the properties of the SAW device are intended to be applied to the other application fields, especially in the sensor field. DISCLOSURE OF THE INVENTION An object of the invention is to solve at least the above problems and/or disadvantages and to provide at least the advantages described hereinafter. Accordingly, one object of the present invention is to solve the foregoing problems by providing an SAW sensor device using a slit acoustic wave which can sense intensity of an external pressure and viscosity and dielectric permittivity of liquid passing through a narrow slit, by using correlations of frequency and velocity shifts of the slit acoustic wave generated in a resonator, like using a surface acoustic wave generated in a resonator of an SAW device, and a method thereof. The foregoing and other objects and advantages are realized by providing an SAW sensor device using a slit-acoustic wave, including: a piezoelectric medium having a thin membrane at its one portion, a medium at the other portion, and a narrow slit which the slit acoustic wave passes through at its inside; an input IDT formed at the outer portion in the narrow slit of the piezoelectric medium, for transducing an electric input signal into the slit acoustic wave; and an output IDT formed at the outer portion opposite to the input IDT, for receiving the propagated slit acoustic wave and transducing the wave into an electric signal, whereby an external pressure transmitted to the device is sensed. A width of the narrow slit is varied according to the pressure transmitted to the thin membrane, and a velocity of the slit acoustic wave propagated in the narrow slit is shifted according to variations of the width of the narrow slit. In addition, the velocity of the slit acoustic wave is shifted according to a property of the medium of the piezoelectric medium. According to another aspect of the invention, an SAW sensor device using a slit acoustic wave includes: a piezoelectric medium having a narrow slit which the slit acoustic wave passes through at its inside, and being divided into an upper portion and a lower portion from the narrow slit; an input IDT formed at one side of the piezoelectric medium, for transducing an electric input signal into the slit acoustic wave; an output IDT formed at the opposite side to the input IDT in the piezoelectric medium, for receiving the propagated slit acoustic wave, and transducing the wave into an electric signal; an input liquid port for inputting the liquid into the narrow slit of the piezoelectric medium; and an output liquid port for outputting the liquid of the narrow slit of the piezoelectric medium, whereby liquid in the device is sensed. When the liquid flows in the narrow slit, dielectric permittivity and viscosity of the liquid are sensed by measuring a velocity and frequency of the slit acoustic wave of the liquid of the narrow slit. According to another aspect of the invention, a method for sensing an external pressure of an SAW sensor device includes the steps of: (a) when a thin membrane does not receive a pressure, calculating a frequency and velocity of electric signals of an input IDT and an output IDT in a narrow slit, and comparing the resultant values; (b) when the thin membrane receives an external pressure, calculating a frequency and velocity of electric signals of the input IDT and the output IDT, and comparing the resultant values; and (c) sensing intensity of the external pressure in consideration of velocity and frequency shifts due to the external pressure transmitted to the thin membrane. Step (c) for sensing the intensity of the external pressure is performed by previously setting frequency and velocity shift value data under the external pressure in an external device, and comparing the data values. According to another aspect of the invention, a method for sensing liquid of an SAW sensor device includes the steps of: (a) measuring a phase velocity of a slit acoustic wave proceeding in an empty slit, and calculating a frequency; (b) when the liquid flows in the narrow slit through an input liquid port, measuring a phase velocity of the slit acoustic wave in the narrow slit, and calculating a frequency; and (c) sensing dielectric permittivity and viscosity of the liquid passing through the narrow slit in consideration of velocity and frequency shifts. Step (b) for measuring the phase velocity of the slit acoustic wave and calculating the frequency calculates the velocity and frequency of the slit acoustic wave when the liquid is filled in an output liquid port. Step (c) for sensing the dielectric permittivity and viscosity of the liquid is performed by previously setting dielectric permittivity and viscosity data of all kinds of liquids in an external device, and comparing the data values. In accordance with the present invention, the intensity of the external pressure and the viscosity and dielectric permittivity of the liquid can be sensed by using correlations of the frequency and velocity shifts of the slit acoustic wave generated in a resonator, like using a surface acoustic wave generated in a resonator of an SAW device. Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention. The objects and advantages of the invention may be realized and attained as particularly pointed out in the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS The invention will be described in detail with reference to the following drawings in which like reference numerals refer to like elements wherein: FIG. 1 is a schematic diagram illustrating a general SAW filter; FIG. 2 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a pressure sensor by using a slit acoustic wave in accordance with a first embodiment of the present invention; and FIG. 3 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a liquid sensor by using a slit acoustic wave in accordance with a second embodiment of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION The following detailed description will present an SAW sensor device using a slit acoustic wave and a method thereof according to preferred embodiments of the invention in reference to the accompanying drawings. FIG. 2 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a pressure sensor by using a slit acoustic wave in accordance with a first embodiment of the present invention. Referring to FIG. 2, the SAW sensor device operated as the pressure sensor by using the slit acoustic wave includes a piezoelectric medium 203 having a thin membrane 205 at its upper portion, a medium at its lower portion, and a narrow slit 204 which the slit acoustic wave passes through at its inside, an input IDT 201 formed at the outer portion in the narrow slit 204 of the piezoelectric medium 203, for transducing an electric input signal into the slit acoustic wave, and an output IDT 202 formed at the outer portion opposite to the input IDT 201, for receiving the propagated slit acoustic wave and transducing the wave into an electric signal. The operation principle of the SAW sensor device operated as the pressure sensor in accordance with the present invention will now be explained. The input IDT 201 transduces an electric signal into a vibration type signal which is a slit acoustic wave, and the slit acoustic wave is propagated along the piezoelectric medium 203. That is, in the SAW sensor device, when a metal electrode is formed on a medium showing high insulation and piezoelectricity is generated on the metal electrode, the medium temporarily hogs. A physical wave is generated by using the operation. Because a velocity of a wave transmitted on the surface of the SAW sensor device is lower than that of an electric wave, the SAW sensor device is used as a filter for temporarily delaying an electric signal, or passing a specific frequency signal. Accordingly, the slit acoustic wave, a specific frequency signal propagated along the piezoelectric medium 203 shows a state of a wave transmitted along the surface of the medium in the same concept as a surface acoustic wave of a general SAW device. Here, waves are divided into transverse waves and longitudinal waves according to properties of the piezoelectric medium 203. In addition, such waves are attenuated under various conditions such as medium properties. On the other hand, the upper side thin membrane 205 of the narrow slit 204 in the piezoelectric medium 203 is comprised of a thin piezoelectric medium deformed due to an external pressure, and the slit acoustic wave can proceed in the narrow slit 204. In the slit acoustic wave propagated along the piezoelectric medium 203, the vibration type signal is transduced into an electric signal by the output IDT 202. Here, when an external pressure is transmitted to the thin membrane 205, the thin membrane 205 hogs. A width (t) of the narrow slit 204 is varied, and thus a phase velocity of the slit acoustic wave proceeding in the narrow slit 204 is also shifted. In addition, an additional stress is generated on the piezoelectric medium 203, to shift the velocity of the slit acoustic wave. That is, the phase velocity of the slit acoustic wave is dependent upon the width (t) of the narrow slit 204. Therefore, correlations of the width (t) of the narrow slit 204 and the velocity of the slit acoustic wave are obtained on the basis of the facts that the width (t) of the narrow slit 204 is varied according to intensity of the external pressure and that the velocity of the slit acoustic wave is shifted due to variations of the width (t) of the narrow slit 204, thereby sensing intensity of the external pressure. The process for operating the SAW sensor device as the pressure sensor will now be described in detail. When the thin membrane 205 does not receive a pressure, a frequency and velocity of an electric signal of the input IDT 201 are calculated, a frequency and velocity of an electric signal of the output IDT 202 are calculated, and the resultant values are compared with each other (S21). Here, the frequency and velocity of the input and output signals are rarely shifted. When the thin membrane 205 receives an external pressure, a frequency and velocity of an electric signal of the input IDT 201 are calculated, a frequency and velocity of an electric signal of the output IDT 202 are calculated, and the resultant values are compared with each other (S22). At this time, the frequency and velocity of the input and output signals are shifted. In addition, the correlations can be obtained by using the formula ‘f=v/λ’. Here, ‘f’, ‘v’ and ‘λ’ respectively represent frequency, velocity and wavelength. Thus, the velocity shift causes the frequency shift, which is dependent upon the external pressure. That is, when the thin membrane 205 receives an external pressure, the narrow slit 204 hogs, which influences the slit acoustic wave proceeding in the narrow slit 204. Accordingly, the frequency and velocity of the signals of the input IDT 201 and the output IDT 202 are shifted. The frequency and velocity shift value data under the external pressure are previously set in an external device in the form of a database (S23). Therefore, the intensity of the external pressure can be sensed by comparing the velocity and frequency values shifted due to the external pressure transmitted to the thin membrane 205 with the velocity and frequency shift data values of the database (S24), so that the SAW sensor device can be operated as the pressure sensor. SECOND EXAMPLE FIG. 3 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a liquid sensor by using a slit acoustic wave in accordance with a second embodiment of the present invention. As depicted in FIG. 3, the SAW sensor device operated as the liquid sensor includes a piezoelectric medium 301 having a narrow slit 304 which the slit acoustic wave passes through at its inside, and being divided into an upper portion and a lower portion from the narrow slit 304, an input IDT 302 formed at one side of the piezoelectric medium 301, for transducing an electric input signal into the slit acoustic wave, an output IDT 303 formed at the opposite side to the input IDT 302 in the piezoelectric medium 301, for receiving the propagated slit acoustic wave, and transducing the wave into an electric signal, an input liquid port 305 for inputting the liquid into the narrow slit 305 of the piezoelectric medium 301, and an output liquid port 306 for outputting the liquid of the narrow slit 304 of the piezoelectric medium 301. The operation principle of the SAW sensor device operated as the liquid sensor in accordance with the present invention will now be explained. The slit acoustic wave transduced in the input IDT 302 is transmitted by the piezoelectric medium 301, and re-transduced into an electric signal in the output IDT 303. The slit acoustic wave passing through the narrow slit 304 of the piezoelectric medium 301 passes a specific frequency. When the slit acoustic wave is propagated in the narrow slit 304 of the piezoelectric medium 301, a phase velocity of the slit acoustic wave is dependent upon dielectric permittivity of liquid in the narrow slit 304. That is, when there are presumed that a velocity of a slit acoustic wave proceeding in an empty slit is v0 and a velocity of a slit acoustic wave proceeding in a slit with liquid is v1, the phase velocity of the slit acoustic wave is shifted according to dielectric permittivity of the liquid. In addition, loss of wave power is generated according to viscosity of the liquid, which shifts the phase velocity. Because the phase velocity of the slit acoustic wave is shifted according to the viscosity and dielectric permittivity of the liquid, the SAW sensor device is operated as the liquid sensor by using the correlations. This operation will now be described in detail. In order to obtain the viscosity and dielectric permittivity of the liquid, the phase velocity v0 of the slit acoustic wave proceeding in the empty slit 304 is measured (S304), and a frequency f0 is calculated (S31). Here, the correlations of the velocity and frequency can be obtained by using the formula ‘f=v/λ’. When the liquid flows in the narrow slit 304 through the input liquid port 305, the phase velocity v1 of the slit acoustic wave in the narrow slit 304 is measured, and a frequency f1 is calculated (S32). Here, the velocity and frequency of the slit acoustic wave when the liquid is filled in the output liquid port 306 are calculated. Therefore, the dielectric permittivity and viscosity of the liquid passing through the narrow slit 304 can be obtained in consideration of velocity shifts v0 and v1 and frequency shifts f0 and f1. That is, dielectric permittivity and viscosity value data of all kinds of liquids due to the phase velocity and frequency shifts of the slit acoustic wave are previously set in an external device in the form of a database (S33). Here, the dielectric permittivity and viscosity of the liquid can be sensed by searching similar values to the dielectric permittivity and viscosity value data of all kinds of liquids previously set in the external device (S34), so that the SAW device can be operated as the liquid sensor. Industrial Applicability As discussed earlier, in accordance with the present invention, the SAW sensor device using the slit acoustic wave and the method thereof can sense the intensity of the external pressure by using the correlations of the frequency and velocity shifts of the slit acoustic wave generated in the resonator, like using the surface acoustic wave generated in the resonator of the SAW device. In addition, the SAW sensor device using the slit acoustic wave and the method thereof can obtain the viscosity and dielectric permittivity of the liquid passing through the narrow slit by using the correlations of the frequency and velocity shifts of the slit acoustic wave generated in the resonator of the SAW device slit. While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. The foregoing embodiments and advantages are merely exemplary and are not to be construed as limiting the present invention. The present teaching can be readily applied to other types of apparatuses. The description of the present invention is intended to be illustrative, and not to limit the scope of the claims. Many alternatives, modifications, and variations will be apparent to those skilled in the art. In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures.
<SOH> BACKGROUND ART <EOH>Recently, mobile communication apparatuses such as cellular phones and portable information terminals have been rapidly distributed due to development of a mobile communication system. Thus, there are increasing demands for miniaturization and high performance of the apparatuses and their components. In addition, two kinds, namely analog and digital type wireless communication systems are used for cellular phones, and a frequency for the wireless communication varies from a band of 800 MHz˜1 GHz to a band of 1.5 GHz to 2.0 GHz. A dielectric resonator duplexer has been generally used as an antenna duplexer for the mobile communication system in consideration of low loss, power efficiency and temperature stability. However, an SAW (Slit Acoustic Wave) duplexer is newly recommended on the basis of recent low loss design of an SAW filter, development of a power efficiency material, and development of a medium having a stabilized temperature property. When the dielectric duplexer is compared with the SAW duplexer, the SAW duplexer has equal or more excellent properties to/than the dielectric duplexer, except for power efficiency. Especially, the SAW duplexer is absolutely advantageous in shape and size. Nevertheless, the SAW duplexer is still more expensive than the dielectric resonator type duplexer. When mass production of the SAW duplexer is achieved according to the property of an SAW manufacturing process using a semiconductor process, the SAW duplexer will have a competitive price. FIG. 1 is a schematic diagram illustrating a general SAW filter. As illustrated in FIG. 1 , the SAW filter includes a single crystal medium 101 , an input inter-digital transducer (IDT) and an output IDT 103 . When the single crystal medium 101 is a piezoelectric single crystal medium such as quartz, LiTaO 3 and LiNbO 3 , the input IDT 102 and the output IDT 103 are comprised of thin metal membranes. In FIG. 1 , an electric signal transmitted to the input IDT 102 is transduced into a mechanical wave by the piezoelectric single crystal medium 101 , and propagated to the output IDT 103 through the single crystal medium 101 . The wave transmitted to the output IDT 103 is re-transduced into an electric signal according to piezoelectric effects, and then outputted. That is, the SAW filter generally used in a mobile communication terminal for filtering high frequency signals is a manual device for selectively passing wanted frequency signals by patternizing a transducer on the piezoelectric single crystal medium with thin metal membranes, and connecting the transducer to I/O terminals. A frequency response total transfer function of the resonator of the SAW filter is provided as a composite function of material properties such as physical properties of a piezoelectric material, purity of a crystal and properties of a thin metal membrane, and device variables including variables considered in electrode design. There have been known that a limit of a minimum value of a resonance frequency range is determined by a size of the device, and that a limit of a maximum value thereof is influenced by a line width of an electrode and loss of electric wave. Because the resonator has a very narrow bandwidth frequency response and a long impulse response, it can embody wanted properties by precisely manufacturing an electrode according to an electrode design. As described above, the properties of the SAW device are intended to be applied to the other application fields, especially in the sensor field.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>The invention will be described in detail with reference to the following drawings in which like reference numerals refer to like elements wherein: FIG. 1 is a schematic diagram illustrating a general SAW filter; FIG. 2 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a pressure sensor by using a slit acoustic wave in accordance with a first embodiment of the present invention; and FIG. 3 is a schematic cross-sectional diagram illustrating an SAW sensor device operated as a liquid sensor by using a slit acoustic wave in accordance with a second embodiment of the present invention. detailed-description description="Detailed Description" end="lead"?
20041203
20081202
20050721
92130.0
0
DOUGHERTY, THOMAS M
SAW SENSOR DEVICE USING SLIT ACOUSTIC WAVE AND METHOD THEREOF
UNDISCOUNTED
0
ACCEPTED
2,004
10,517,189
ACCEPTED
Mounting device for a disk drive unit, releasable fastener and method of testing a disk drive unit
A disk drive unit mounting device is adapted to carry one or plural disk drive units. The mounting device includes a temperature control module and a carrier module secured together y a releasable fastener device so that the temperature control module controls the temperature of the disk drive unit. The temperature control module has an air flow control device for controlling the flow of air across the disk drive unit appropriately according to the required temperature for the disk drive unit. The mounting device may be used in testing disk drive units.
1. A mounting device for a disk drive unit, the mounting device comprising: a carrier module constructed and arranged to receive at least one disk drive unit, the carrier module having an air input port, the carrier module being arranged to direct air from the air input port over a disk drive unit received in the carrier module; a temperature control module comprising an air flow control device, the temperature control module having an air output port; and, a releasable fastener for releasably fastening the carrier module to the temperature control module with the air input port of the carrier module in register with the air output port of the temperature control module, wherein the temperature control module is arranged to provide air to said air input port for controlling the temperature of a said disk drive unit received in the carrier module to be at a predetermined temperature during operation of the disk drive unit. 2. A mounting device according to claim 1, wherein the carrier module has an air outlet port and the temperature control module has an air inlet port, the arrangement being such that when the releasable fastener fastens the carrier module to the temperature control module the air outlet port of the carrier module is in register width with the air inlet port of the temperature control module. 3. A mounting device according to claim 2, wherein the temperature control module has a fan and is arranged to recirculate air from the air outlet port of the carrier module to the air output port of the temperature control module. 4. A mounting device according to claim 1, wherein the releasable fastener comprises a manually releasable hinge pivotally connecting the carrier module and the temperature control module along one edge of the carrier module and the temperature control module and a lever latch for securing the carrier module to the temperature control module along an edge of the carrier module and temperature control module opposite the said one edge. 5. A mounting device according to claim 4, wherein the manually releasable hinge has a pin portion, a receptacle portion and a hook member, the pin portion being secured to and supported substantially parallel to and spaced from a wall of one of said the carrier module and temperature control module, the receptacle portion being formed on the other of the carrier module and the temperature control module, the receptacle portion being constructed and arranged to engage said pin portion, the receptacle portion having a curved wall for abutment by the pin portion and the receptacle formation defining an opening such that the pin portion may be brought into engagement with the curved wall of the receptacle portion via the opening, and the hook member being constructed and arranged to engage the carrier module and the temperature control module to retain the pin portion in engagement with the curved wall of the receptacle portion. 6. A mounting device according to claim 1, wherein the carrier module is constructed and arranged to simultaneously receive plural disk drive units. 7. A mounting device according to claim 6, comprising air flow passages arranged to divide air flow from the output port of the temperature control module for application to each of plural disk drive units received in the carrier module. 8. A mounting device according to claim 6, having air flow passages arranged to combine the air flow from each of plural disk drive units received in the carrier module to provide a single air flow from the carrier module. 9. A mounting device according to claim 7, wherein the passages are arranged to divide the air flow such that air flows in the same direction around each disk drive unit. 10. A mounting device according to claim 7, comprising a baffle that provides said air flow passages, the baffle having a first side having at least one opening for receiving an incoming air flow from the temperature control module, and a second side having plural openings for supplying air to each of plural disk drive units received in the carrier module, the baffle having a deflection structure constructed and arranged to divide the incoming air flow between said plural disk drive units. 11. A mounting device according to claim 10, wherein the second side of the baffle has plural further openings for receiving air from that has flowed over plural disk drive units received in the carrier module, and the first side of the baffle has at least one opening for passing said air to the temperature control module. 12. A mounting device for disk drive units according to claim 11, wherein at said second side of said baffle, said openings and said further openings are interleaved, whereby each of the plural disk drive units has a similar flow of air. 13. A mounting device for disk drive units according to claim 1, wherein the temperature control module has an electrical connection device, the carrier module has a first electrical connector for engaging a disk drive unit received in the carrier module, and the carrier module has a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are fastened together. 14. A mounting device for disk drive units according to claim 1, wherein the temperature control module has an electrical connection device, and the carrier module has plural first electrical connectors for engaging respective disk drive units received in the carrier module and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are fastened together. 15. A releasable fastener for fastening together first and second members, the fastener comprising a pin portion for mounting on a first member, a receptacle portion for mounting on a second member and a hook member for engagement with a said first and second member, the receptacle portion being constructed and arranged to engage said pin portion, the receptacle portion having a concave curved wall and defining an opening such that the pin portion may be brought into engagement with the curved wall of the receptacle formation via the opening, and the hook member being constructed and arranged to retain the pin portion engaged with the curved wall of the receptacle portion. 16. A releasable fastener according to claim 15, wherein the arrangement is such that the hook member is under tension when engaged with a said first and second member. 17. A method of testing a disk drive unit in a test device comprising a temperature control module and a carrier module constructed and arranged to support said disk drive unit, wherein the carrier module has an air input port and is arranged to direct air from the air input port over a said disk drive unit received in the carrier module and the temperature control module comprises an air flow control device and has an air output port, the method comprising: releasably fastening the carrier module to the temperature control module, such that the air input port of the carrier module is in register with the air output port of the temperature control module; disposing said disk drive unit in said carrier module; and, causing the temperature control module to provide air to said air input port to control the temperature of said disk drive unit disposed in the carrier module to be at a predetermined temperature during operation of the disk drive unit. 18. A method of testing a disk drive unit according to claim 17, comprising the step of controlling the flow of air across the disk drive unit to cause air to recirculate directly across the disk drive unit, or to cause chilled air obtained by passing at least a portion of the air that has passed over the disk drive unit through a heat exchanger to flow across the disk drive unit, or to cause a mixture of directly recirculating air and chilled air to flow across the disk drive unit. 19. A method of testing a disk drive unit according to claim 17, wherein the temperature control module and the carrier module each have a respective part of a manual release hinge and the step of releasably fastening comprises engaging the two parts of the hinge, mutually pivotally moving the carrier module and the temperature control module until they abut one another and securing the carrier module to the temperature control module via a lever latch. 20. method of testing a disk drive unit according to claim 17, wherein the carrier module has locations constructed and arranged to simultaneously receive plural disk drive units, and the disposing step comprises disposing at least two disk drive units in respective ones of said locations. 21. A method of testing a disk drive unit according to claim 17, comprising dividing air flow from the outlet of the temperature control module and applying a part of said divided air flow to each of plural disk drive units received in the carrier module, and combining the air flow from each of the disk drive units to provide said outlet from the carrier module. 22. A method of testing a disk drive unit according to claim 21, wherein the dividing step comprises dividing the air flow such that it flows in the same direction around each disk drive unit. 23. A method of testing a disk drive unit according to claim 17, comprising providing plural types of carrier module, each type of module being suitable for a respective one of plural different types of disk drive unit. 24. A method of testing a disk drive unit according to claim 17, wherein the temperature control module has an electrical connection device, the carrier module has a first electrical connector secured thereto for engaging a disk drive unit received in the carrier module, and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are secured together, and said step of disposing comprises connecting the electrical connection device of the disk drive unit to said first electrical connector. 25. A method of testing a disk drive unit according to claim 24, wherein each of said different types of disk drive unit has an electrical connection device which is at least one of differently disposed or differently configured to electrical connection devices of others of said types of disk drive units, the temperature control module has an electrical connection device, each type of carrier module has a respective first electrical connector secured thereto for engaging the electrical connection device of the corresponding type of disk drive unit received in the carrier module, and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are secured together, and said step of disposing comprises connecting the electrical connection device of the disk drive unit to said first electrical connector.
The present invention relates to a mounting device for a disk drive unit, to a releasable fastener and to a method of testing a disk drive unit. During manufacture of disk drive units, it is necessary to test the disk drive units to ensure that they meet the required specification. As part of the testing operation, it is necessary to control the temperature of the disk drive units. The temperature of the disk drive units is varied across a wide range during testing. In many known testing apparatus, the temperature of plural disk drive units is controlled by using cooling or heating air which is common to all of the disk drive units. In our WO-A-01/41148, the entire content of which is hereby incorporated by reference, there is disclosed a carrier for a disk drive unit that enables the temperature of the disk drive unit to be controlled during testing or normal operation by the use of a temperature control device that causes air at a required temperature to be passed over the disk drive unit. This arrangement allows the temperature of the disk drive unit to be controlled independently of the temperature of disk drive units mounted in other carriers in a rack containing plural such carriers. While this carrier is valuable, there are certain applications in which it has non-optimal performance. First, the structure of the carrier means that the carrier is dedicated to a particular type and model of disk drive unit, and thus the carrier cannot be used for disk drive units having a different connectivity or configuration. Secondly, in the event of a fault in the carrier itself, the whole carrier must be removed for repair or replacement. Thirdly, the carrier is specifically adapted for housing only one disk drive unit at a time, which means that a test device for a number of disk drive units may be undesirably large. According to a first aspect of the present invention, there is provided a mounting device for a disk drive unit, the mounting device comprising: a carrier module constructed and arranged to receive at least one disk drive unit, the carrier module having an air input port, the carrier module being arranged to direct air from the air input port over a disk drive unit received in the carrier module; a temperature control module comprising an air flow control device, the temperature control module having an air output port; and, a connection device for releasably fastening the carrier module to the temperature control module with the air input port of the carrier module in register with the air output port of the temperature control module, wherein the temperature control module is arranged to provide air from the air input port for controlling the temperature of a said disk drive unit received in the carrier module to be at a predetermined temperature during operation of the disk drive unit. By providing a temperature control module, which may have a standard or fixed configuration, together with a carrier module matching that configuration, and a connection device for releasably fastening the two together, one carrier module may be readily interchanged for another. Thus carrier modules may be provided for different types of disk drive unit. A carrier module for one type of disk drive unit may be readily removed from the temperature control module and exchanged for a carrier module for the same or another type of disk drive unit. Carrier modules configured to simultaneously house two or more disk drive units may be provided. The device is particularly useful for carrying one or more disk drive units whilst the or each disk drive unit is being tested during manufacture, though the device can also be used to carry one or more disk drive units during normal use of the disk drive units by an end user. The air flow control device may include an air-moving device such as a fan, and/or flow control valves together with a device of devices for sensing the temperature of air in the carrier module. A heater may allow the air output from the temperature control module to be heated, and a cooler may allow that air to be cooled before inlet into the carrier module to achieve a desired air temperature in the carrier module. The mounting device enables the temperature of a disk drive unit in the carrier module to be controlled to be at a predetermined temperature during operation of the disk drive unit. It will be understood that, in practice, the temperature will be controlled to be within certain limits of a predetermined temperature and the phrase “predetermined temperature” shall be construed accordingly. The mounting device can be located with other similar devices each carrying their own respective disk drive units. In that case, embodiments of the present invention in which each carrier module houses only one disk drive unit allow the temperature of individual disk drive units to be controlled independently. Other embodiments in which two or more disk drive units are housed in a single carrier module allow the temperature of the two or more disk drive units to be controlled together. This in turn means that if for example a rack of plural such mounting devices is being used, disk drive units in the different mounting devices can be at different temperatures at the same time, which is particularly advantageous when used in a test application in that it allows for fully independent testing of the disk drive units including insertion and removal of the disk drive units into respective carriers. The temperature control module comprises an air flow control device for causing air to flow across a disk drive unit received in the carrier. As will be discussed further below, the air can be for cooling or warming the disk drive unit and/or for keeping the temperature of the disk drive unit constant. Preferably the carrier module has an air outlet port and the temperature control module has an air inlet port, the arrangement being such that when the connection device fastens the carrier module to the temperature control module the air outlet port of the carrier module is aligned with the air inlet port of the temperature control module. By providing an air outlet port of the carrier module aligned with the air inlet port of the temperature control module, embodiments of the invention allow for air flow to occur all around a disk drive unit and under controlled conditions. It would of course be possible to exhaust air from the carrier module to the atmosphere, but this has a number of disadvantages. For example, in use the disk drive units generate heat, and where air is extracted by the temperature control module rather than being exhausted, this heat can be employed by recirculating the air during testing to reduce the energy applied by the test device. Another example of a disadvantage of exhausting air is that the control of air flow within the carrier module would be less precise than where a positive extraction occurs. Advantageously the temperature control module has a fan and is arranged to selectively recirculate air from the air inlet port to the air outlet port. Recirculation allows for energy to be conserved within the mounting device, by preventing heated or cooled air from being fed into a facility containing the mounting device, and thus reduces environmental loads on that facility. A heat exchanger may be accessible by the temperature control module for selectively receiving and cooling at least a portion of the air that has passed over a disk drive unit received in the carrier module thereby to provide chilled air, the air flow control device being selectively operable to cause air to recirculate directly across a disk drive unit received in the carrier module, or to cause at least a portion of the air that has passed over a disk drive unit received in the carrier to pass through the heat exchanger to provide chilled air and to cause said chilled air to flow across a disk drive unit received in the carrier module, or to cause a mixture of directly recirculated air and chilled air to flow across a disk drive unit received in the carrier module. The temperature control module may be selectively operable to cause air to cause fresh air from outside the carrier to flow across a disk drive unit received in the carrier, or to cause a mixture of recirculated air and fresh air from outside the carrier to flow across a disk drive unit received in the carrier. Typically, causing air to recirculate across a disk drive unit will cause the temperature of the disk drive unit to rise until heat loss from the carrier matches the power consumption of the disk drive unit. Fresh air will normally be at a temperature, which is lower than the temperature of the disk drive unit and thus will tend to cool the disk drive unit. Otherwise, a heat exchanger can be used to provide chilled air. The air flow means can be operated to cause a mixture of recirculated air and fresh or chilled air to flow across the disk drive unit, allowing for intermediate temperatures to be obtained and maintained. The temperature control module may comprise a selectively operable heater in the air flow path to a disk drive unit received in the carrier module for selectively heating air prior to said air flowing across a disk drive unit received in the carrier module. This allows the temperature of the disk drive unit to be raised or to be raised more quickly than otherwise. Preferably the connection device comprises a manually releasable hinge pivotally connecting the carrier module and the temperature control module along one edge thereof, and a lever latch for securing the carrier module to the temperature control module along an edge opposite the said one edge. Although other types of manual connect/release connectors are possible, a manual release hinge allows the carrier and temperature control modules to be connected together and separated without the need for tools. The hinge function allows embodiments to be created in which faces of the modules are not in contact at the time of such connection and separation. The modules can then be mutually pivoted until the faces come into contact, which facilitates connections to be made between them. The use of a lever latch enables embodiments to be created in which the modules are only capable of being locked together when in correct alignment. The tension of the closed lever latch provides resilience, which urges the faces of the modules together. The use of a lever latch also provides a mechanical advantage for drawing together the modules during assembly, and particularly for drawing the electrical connectors of the device into cooperative engagement. In disassembling the modules, it is an advantage to provide a controlled force to disengage the electrical connectors, if possible damage is to be avoided. In the preferred embodiment, the lever latch further provides this controlled disengaging force. Preferably, the manually releasable hinge has a pin portion, a receptacle portion and a hook member, the pin portion being secured to and supported substantially parallel to and spaced from a wall of one of said the carrier module and temperature control module, the receptacle portion being formed on the other of the carrier module and the temperature control module, the receptacle portion being constructed and arranged to engage said pin portion, the receptacle portion having a curved wall for abutment by the pin portion and the receptacle formation defining an opening such that the pin portion may be brought into engagement with the curved wall of the receptacle portion via the opening, and the hook member being constructed and arranged to engage the carrier module and the temperature control module to retain the pin portion in engagement with the curved wall of the receptacle portion. The particular structure allows a hinge to be made which provides accurate self-alignment of the two modules, and which thus facilitates connection of the carrier module to the temperature control module. Preferably, the carrier module is constructed and arranged to simultaneously receive plural disk drive units. The ability to use the carrier module simultaneously for two or more disk drive units allows more disk drive units to be accommodated within a certain volume. As two or more disk drive units are subjected to the same conditions in embodiments of the invention using such carrier modules, this enables the performance of disk drive units to be compared with one another. Advantageously the mounting device has air flow passages for dividing air flow from the output port of the temperature control module for application to each of plural disk drive units received in the carrier module. Advantageously again the mounting device has air flow passages for combining the air flow from each of plural disk drive units received in the carrier module to provide said outlet from the carrier module. Preferably the passages are arranged to divide the air flow such that it flows in the same direction around each disk drive unit. Embodiments of the invention that have such passages allow for precisely the same temperature conditions to be applied to each disk drive. Preferably the mounting device has a baffle that provides said air flow passages, the baffle having a first side having at least one opening for receiving an incoming air flow from the temperature control module, and a second side having plural openings for supplying air to each of plural disk drive units received in the carrier module, the baffle having a deflection structure constructed and arranged to divide the incoming air flow between said plural disk drive units. Preferably again, the second side of the baffle has plural further openings for receiving air from the disk drive units and the first side of the baffle has at least one opening for passing said air from the disk drive units to a temperature control module. Advantageously, at said second side of said baffle, said openings and said further openings are interleaved, whereby each of the plural disk drive units has a similar flow of air. Advantageously the temperature control module has an electrical connection device, the carrier module has a first electrical connector for engaging a disk drive unit received in the carrier module, and the carrier module has a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are fastened together. In embodiments where plural disk drive units may be simultaneously received in the carrier module, preferably the temperature control module has an electrical connection device, and the carrier module has plural first electrical connectors for engaging respective disk drive units received in the carrier module and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are fastened together. Where different types of carrier modules are provided, each for a different type of disk drive unit, and each different type of disk drive unit has a differently configured or located electrical connection device, preferably the temperature control module has an electrical connection device, each type of carrier module has a respective first electrical connector and disposed and configured to engage each disk drive unit of a respective type received in the carrier module, and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and any of said types of carrier module are secured together. Each of the apparatus described above may comprise a controller for independent control of the temperature control modules associated with the disk drive unit carrier modules. According to a second aspect of the present invention, there is provided a releasable fastener for fastening together first and second members, the fastener comprising a pin portion for mounting on a first member, a receptacle portion for mounting on a second member and a hook member for engagement with a said first and second member, the receptacle portion being constructed and arranged to engage said pin portion, the receptacle portion having a concave curved wall and defining an opening such that the pin portion may be brought into engagement with the curved wall of the receptacle formation via the opening, and the hook member being constructed and arranged to retain the pin portion engaged with the curved wall of the receptacle portion. Preferably, the arrangement is such that the hook member is under tension when engaged with a said first and second member. According to a third aspect of the present invention, there is provided a method of testing a disk drive unit in a test device comprising a temperature control module and a carrier module constructed and arranged to support said disk drive unit, wherein the carrier module has an air input port and is arranged to direct air from the air input port over a said disk drive unit received in the carrier module and the temperature control module comprises an air flow control device and has an air output port, the method comprising: releasably fastening the carrier module to the temperature control module, such that the air input port of the carrier module is in register with the air output port of the temperature control module; disposing said disk drive unit in said carrier module; and, causing the temperature control module to provide air from said air output port to said air input port to control the temperature of said disk drive unit disposed in the carrier module to be at a predetermined temperature during operation of the disk drive unit. The method may comprise the step of controlling the flow of air across the disk drive unit to cause air to recirculate directly across the disk drive unit, or to cause chilled air obtained by passing at least a portion of the air that has passed over the disk drive unit through a heat exchanger to flow across the disk drive unit, or to cause a mixture of directly recirculating air and chilled air to flow across the disk drive unit. The method may comprise the step of, independently for each disk drive unit, controlling the flow of air across the disk drive unit to cause air to recirculate across the disk drive unit, or to cause fresh air to flow across the disk drive unit, or to cause a mixture of recirculated air and fresh air to flow across the disk drive unit. In an advantageous embodiment, the temperature control module and the carrier module each have a respective part of an manual release hinge and the step of releasably fastening comprises engaging the two parts of a said hinge, mutually pivotally moving the carrier module and the temperature control module until they abut one another and securing the carrier module to the temperature control module via a lever latch. In a preferred embodiment, the carrier module has locations constructed and arranged to simultaneously receive plural disk drive units, and the disposing step comprises disposing at least two disk drive units in respective ones of said locations. Advantageously the method comprises dividing air flow from the outlet of the temperature control module and applying a part of said divided air flow to each of plural disk drive units received in the carrier module, and combining the air flow from each of the disk drive units to provide said outlet from the carrier module. Preferably the dividing step comprises dividing the air flow such that it flows in the same direction around each disk drive unit. In a preferred embodiment, the method comprises providing plural types of carrier module, each type of module being suitable for a respective one of plural different types of disk drive unit. In some embodiments the temperature control module has an electrical connection device, the carrier module has a first electrical connector secured thereto for engaging a disk drive unit received in the carrier module, and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are secured together, and said step of disposing comprises connecting the electrical connection device of the disk drive unit to said first electrical connector. In preferred embodiments each of said different types of disk drive unit has an electrical connection device which is at least one of differently disposed or differently configured to electrical connection devices of others of said types of disk drive units, the temperature control module has an electrical connection device, each type of carrier module has a respective first electrical connector secured thereto for engaging the electrical connection device of the corresponding type of disk drive unit received in the carrier module, and a second electrical connector arranged to engage the electrical connection device of the temperature control module when the temperature control module and the carrier module are secured together, and said step of disposing comprises connecting the electrical connection device of the disk drive unit to said first electrical connector. Embodiments of the present invention will now be described by way of example with reference to the accompanying drawings, in which: FIG. 1 is an exploded perspective view of an example of a mounting device for a disk drive unit in accordance with one aspect of the present invention; FIG. 2 is a perspective view of a part of the device of FIG. 1, with parts removed for clarity; FIG. 3 is a perspective view of the temperature control module of the device of FIG. 1 with covers and parts removed for clarity; FIG. 4 is a view similar to that of FIG. 3 showing the connection of a heat exchanger for cooling purposes; FIG. 5 is a rear perspective view of the carrier module of the device of FIG. 1; FIG. 6 is a perspective view of an example of an interface unit of the device of FIG. 1 shown from one side, being the side abutting the temperature control module; FIG. 7 is a perspective view of the interface unit of FIG. 6 shown from the other side, being the side for receiving the disk drive units; FIG. 8 is a cut-away view of the interface unit of FIG. 7 showing the air flow passages; FIG. 9a shows the air flow from the interface unit from the temperature control module side; FIG. 9b shows the air flow from the interface unit from the carrier module side; FIG. 10 is a partial view of the temperature control module of FIG. 1 showing the pin portion of a manual release hinge; FIG. 11 is a partial view of the carrier module of FIG. 1 showing the receptacle portion of the manual release hinge; FIG. 12 is a partial view of the temperature control module of FIG. 1 showing the tension strap portion of the manual release hinge; and, FIG. 13 is a partial view of the temperature control module and carrier module of FIG. 1 showing an assembled manual release hinge. Referring to FIG. 1, a mounting device 1 for a disk drive unit has a first module 2 secured to a second module 3, the two modules 2,3 being secured end-to-end. The modules 2,3 are each of box-like construction and generally of rectangular section. The first module is a temperature control module 2 and the second is a carrier module 3 for, in this example, two disk drive units 102,202 (see FIG. 2) carried in disk drive unit supports 203,204. The carrier module 3 has an air input port 130 (see FIG. 5) in the end that engages the temperature control module 2, and includes walls 138-145 (see FIG. 8) forming a baffle defining air flow passages for directing air from the input port 130 over the disk drive units 102,202 disposed within the carrier module. The temperature control module 2 includes an air control device, including in this example a centrifugal fan 105 (see FIG. 3) and mode controller 260 (see FIG. 3), and has an air output port 9. The air output port 9 is in the rectangular end wall 90 that abuts the carrier module 3. The carrier module also has a generally rectangular end wall 28, best seen in FIG. 5, the arrangement being that the end walls 28,90 sealingly abut one another when the modules 2,3 are secured together. Referring to FIG. 1, the temperature control module 2 also has an air inlet port 111. The carrier module 3 has an air outlet port 131a-131c (see FIG. 5), the inlet 111 and outlet 131a-131c ports being aligned when the modules are secured together. A connection device secures the modules together in a releasable fashion, so that the air input port 130 is aligned with the air output port 9. The connection device of this embodiment includes a pair of manual release hinges 6a, 6b, a pair of tension straps 170 and a pair of lever latches 7. It is desirable to have fastenings that enable rapid connection and disconnection of the two modules 2,3, preferably without the need for tools, and the connection device of this embodiment allows these desiderata to be met. The temperature control module 2 has a top wall 103 which has forms receptacle portions 16-7 of the manual release hinges 6a, 6b (see FIG. 11). The temperature control module 2 also has opposing side walls 15 that at their lower front portions define engagement points 77,78 for the lever latches 7. At the end portions of the side walls 15 of the temperature control module 2, and above the engagement points 77, 78, the walls 15 have a corrugated portion 19 to enable a reduced thickness of material to be used. The carrier module 3 has a top wall 104, which at its rear has pin portions 150-2 (see FIG. 10) of the manually released hinges 6a, 6b, as counterpart formations to the receptacle parts in the top wall 103 of the temperature control module 2. The top wall 104 of the carrier module 3 is engaged by one end of the tension straps 170 which allow linkage of the carrier and temperature control modules 2,3. The manually released hinges 6a, 6b enable releasable fastening of the temperature control module 2 to the carrier module 3, final securing of the two being via the lever latches 7 at the lower parts of the sides of the two modules 2,3. The final securing is under tension of the tension straps, which thereby prevents vibrations to be prevented. It would of course be possible to provide instead other connection devices, for example aligning pins projecting from one of the modules and mating holes or recesses in the other, and a clip or latch for maintaining the desired sealing connection. As will be further described later herein, the temperature control module 2 controls the temperature of the disk drive units 102,202 to be at a predetermined temperature during operation of the disk drive units 102,202. Operation of the disk drive unit 102, 202 includes operation during testing of the disk drive units 102, 202. As will also be seen in FIG. 5, an interface unit 8 forming the rear wall of the carrier module 3 is provided at the rear of the carrier module 3. The interface unit 8 allows for electrical connection between the temperature control module 2 and the disk drive units 102,202. The interface unit 8 also has the walls 138-145 that define the air passages for conducting air between the temperature control module 2 and the surfaces of the disk drive units 102,202, as will be later described herein. The carrier module 3 has mechanical latches 4,5 at the front which can be released to allow two disk drive units 102,202 to be inserted into or removed from the carrier module 3. The disk drive units 102,202 will typically be a complete unit having one or more rotatable magnetic disks on which data can be stored, one or more read/write heads mounted on one or more read/write arms, at least one motor for moving the arm or arms, and appropriate internal electrical connections. In the described embodiment used for testing, the mechanical latches 4,5 are operable by a mechanical handling device for loading disk drive units 102,202 for testing and unloading disk drive units 102,202 when tested. The location of the disk drive units 102, 202 in the carrier module 3 is best seen in FIG. 2. The disk drive units 102,202 are disposed one above the other, and are engaged both mechanically and electrically with the interface unit 8 with openings of the interface unit providing air flow over the disk drive units 102,202. In this embodiment, air flow is in the same sense around each of the two disk drive units 102,202. To that end the interface unit has an upper edge 108 over which air flows to the upper side 109 of the upper disk drive unit 102 and a lower recessed edge 120 for return of air from the lower surface 210 of the lower disk drive unit 202. There are also three central slots 121-3, of which one 121 forms a return for air from the lower surface 110 of the upper disk drive unit 102. The other two slots 122,123 are disposed side by side and below the first slot 121 to provide flow over the upper surface 209 of the lower disk drive unit 202. Referring to FIG. 3, the temperature control module 2 is, as has previously been described, a generally box-like structure with a rectangular section, and has a generally rectangular end wall 90. The wall 90 defines a generally central slot-like air inlet 111 from the interface unit 8 of an attached carrier module 3, and in combination with the top wall 103, defines an air outlet 9 to such an interface unit 8. Below the slot-like air intake 111 is a recess 91, which houses electrical connectors 113. The electrical connectors 113 are sockets and serve to carry signals from a base unit (not shown) to which the rear face of the temperature control module 2 is mounted, and disk drive units 102,202 mounted to a carrier module 3 connected to the temperature control module 3. The base unit may include a support framework for several temperature control modules, together with cooling devices, power supplies and test computers. Internally, the temperature control module 2 has an air flow control device that includes a centrifugal fan 105 that rotates about a vertical axis in the orientation shown in the drawings. It would alternatively be possible to use other types of fan, such as an axial fan or indeed a compressor. In the present embodiment, the air flow control device also includes a mode controller 260 which routes the air flow differently according to the test conditions required. The mode controller here allows for air to be simply recirculated with no added or removed heat, to be recirculated with added heat or to be cooled by diversion through a cooling device, in the manner described in our patent application WO-A-01/41148. In the present embodiment, the mode controller is a baffle 260 in the form of an upstanding semi-circular wall which can be pivoted about a vertical axis by a motor 268, also as described in our co-pending patent application WO-A-01/41148. However, other devices such as blend doors, or valves could be used instead. Although not shown, the temperature control module 2 of the currently described embodiment, in which the mounting device is used to test disk drive units 102,202, includes a processing device operated as an embedded processor to run programs that provide testing routines and regimes for disk drive units 102,202 in the associated carrier module 3. This arrangement enables communication between a main processor and the individual disk drive units 102,202 to be much less than would be needed if the main processor were directly controlling the disk drive units 102,202. The centrifugal fan 105 is contained within a generally circular housing 10 which directs the air flow exiting the fan 105 towards an air output port 9 of the temperature control module 3. The air inlet 111 is to the inlet side of the fan 105, at the centre of its lower side and the fan 105 has a generally tangential air outlet 12 at its upper side and directed towards the air output port 9. A heater coil 112 is disposed across the fan outlet; the function of this will be later described herein. Two portions of a side wall 15 of the temperature control module 2 are absent towards the rear of the temperature control module 2 to provide two adjacent openings 16,17 in the side wall 15 at a position near the fan 105. The side wall 15 has a short wall portion 18 between the openings 16,17 that is directed generally inwardly of the carrier 1 towards the fan 105. As schematically shown in FIG. 4, the heat exchanger 18 is fixed to the temperature control module 2 over the openings 16,17 in the side wall 15 so that air exiting the temperature control module 2 through the front opening 16 passes through the heat exchanger 18, where the air is cooled, and back into the temperature control module 2 via the rear opening 17. Referring to FIG. 5, the carrier module 3 has the interface unit 8 at its rear, the interface unit 8 together with the upper wall 104 defining a slot-shaped opening 130 into the interface unit 8 for air from an associated temperature control module 3. Three generally rectangular apertures 131a-131c forming an air outlet are disposed across the centre line of the rear wall of the interface unit 8 so as to line up with the slot 111 of a temperature control module, which it will be recalled extracts air. The apertures 131a-131c comprise a central aperture 131a, which as will be described later herein conducts air which has passed over the top disk drive unit 102, and two side apertures 131b, 131c, which as will be later described herein conduct air that has passed over the lower disk drive unit 202. The central aperture 131a is disposed on and about a vertical axis of symmetry of the carrier module 3, and the side apertures 131b, 131c are disposed at the same level as the central aperture 131a, but to each side of it. As best seen in FIGS. 1,2 and 5, each lever latch 7 has a lever member 71 pivotally secured via a pivot 72 to the lower rear edge of the carrier module 3. The lever member 71 can rotate freely on its pivot 72. The lever member has an elongate straight portion 73 which extends at one end into a curved portion 75 that contains a hole 106 for cooperation with the pivot 72 into a nose portion 74. The nose portion 74 is disposed in the plane of the straight portion 73 but transverse to the extent of the straight portion 73. The straight portion 73 is eccentric of the pivot 72. The straight portion 73 extends from the pivot 72 by about five times the extent of the nose portion 74, to give a mechanical advantage in use. The lever member 71 cooperates with a socket 76 on the lower front edge of the temperature control module 2. The socket 76 has a curved wall 77 extending to a downward-facing notch 78 for receiving the nose portion 74. Referring now to FIG. 6, the interface unit 8 is an assembly of first and second printed circuit boards 28, 29 spaced apart by a structure 138 which has the walls 138-145 that define air passages through the interface unit. Releasable electrical connection between the first and second printed circuit boards 28, 29 is made via a plug and socket arrangement 30 disposed between corresponding edges of the boards 28, 29. The plug device 31 projects from the second circuit board 29 and the plug device 32 is secured to the first printed circuit board 28. Where it is desirable to operate or test different types of disk drive unit each requiring a different type of second printed circuit board, the use of the plug and socket arrangement 30 enables easy interchange between the different types of second printed circuit board, providing each type is fitted with compatible plug devices 32. The first printed circuit 28 defines the apertures 131a-131c and part of the slot 130, and also has electrical connection devices 132 to allow electrical signals to be conveyed to and from disk drive units engaged with the second printed circuit board 29. The connection devices 132 in the described embodiment are plug-type devices that connect to the counterpart sockets 113 of the temperature control module 3. Referring to FIG. 7, the front face of the second printed circuit board 29 defines the openings 108, 120-3 described previously herein with respect to FIG. 2. The second printed circuit board 29 also has two electrical sockets 134, 135, one above the other, for electrical connection of the disk drive units 102,202. First 136 and second 137 pairs of support pins are disposed approximately level with the sockets 134, 135 for supporting the disk drive units. Referring now to FIG. 8, the structural member 138 consists of a generally rectangular frame having two opposing short side walls 140,141 and two opposing long cross walls 142,143. The top cross wall 142 is slightly inset from the top of the side walls 140,141, so as to form the first air delivery passage 108. It has a leading knife-edge 146 for splitting incoming air into two parts, one directed upwardly and one downwardly. A bridge piece 144 crosses the frame about one-third of the way down the side walls 140,141. The bridge piece 144 divides the frame into two parts, an upper part through which air has flows forwardly into the paper as shown, and a lower part through which air flows out of the paper as shown. The upper part has a V shaped deflecting wall 145 to direct the part of the air deflected downwardly by the knife edge 146 once again downwardly and out of the second and third slots 122,123. The wall of the bridge piece 144 is shaped so as evenly to distribute this air across the slots 122, 123. The bridge piece 144 has a central passage 147 that directly connects the slot 120 with the centre aperture 131a. The bridge portion 144 also defines between itself and the lower cross wall 143 a chamber 149 which opens through the first printed circuit board 28 as outer apertures 131b, 131c and, through the second printed circuit board, as the slot 121. The shape of the bridge portion 144 and of the various apertures and walls is determined to give even flows across two identical disk drive units. The flows are more clearly seen in FIGS. 9a and 9b. In these figures, flow to the upper disk drive unit is referenced 150, and that to the lower disk drive unit 151. The return flow from the upper disk drive unit is referenced 152, and from the lower disk drive unit 153. Referring again to FIG. 2 shows the flows with the two disk drive units 102,202 in place. Typically, different types of disk drive unit will require one or both of different electrical sockets 134,135 and different air flow passages. This can be achieved by either changing the second printed circuit board alone, or by also changing the structural member 138 and the associated baffle. Turning now to FIG. 10, as has previously been mentioned, the top wall 104 of the carrier module 3 is generally planar, and has formations which form the pin portions 150-2 of manually released hinges 6a, 6b. Two side wall portions 150,151 stand up from the top wall 104 and project out from the edge of the top wall 104 to define a channel therebetween. The channel has a base wall 152 between the side wall portions 150,151 which rises from the top wall 104 and has a distal portion which is parallel to and raised from the top wall 104. The distal end of the base wall 152 extends into a pin portion 153, whose wall follows a circular-cylindrical contour. The pin portion 153 has a longitudinal axis at least substantially parallel to the plane of the top wall 104, and raised with respect to that plane. The distal ends of the side wall portions 150,151 extend via waist regions 154 into the pin portion 153, whose axial length is substantially the spacing between the side walls 150,151. The waist regions 154 are thinner than the base wall thickness and thus the pin wall extends angularly further around the pin portion 153 in the end regions of the pin portion 153 than in the central region. At the proximal end of the base wall 152, there is a slot 155 in the top wall 104 to allow insertion of the tension strap 170. Referring now to FIG. 11, the receptacle portions 160-7 of the manually releasable hinges will now be described. The edge region 163 of the top wall 103 of the temperature control module 2 has walls 160,161 that stand perpendicularly up from the plane of the wall 103. The walls 160,161 are in positions along the temperature control module 2 which correspond to the position of the walls 150,151 of the pin portion 153 on the carrier module 3, and are spaced by substantially the same amount as the spacing of the walls 150,151. The top wall 103 forms a recess 164 in the edge. The recess 164 has a width for receiving the pin portion 153, and a surface 165 which has a first convex curved portion 166 extending into a circular concave portion 167. The convex curved portion is for leading a pin portion 153 into engagement with the circular concave portion 167 and extends from a start point at around half the thickness of the wall 103 to an end point inset further from the edge and below the top surface of the top wall 103 by around one third the wall thickness. The circular concave portion 167 extends from the end point by substantially 180 degrees to the surface of the top wall 103, so as to provide a pivot for the pin portion 153. The walls 160, 161 extend somewhat over the sides of the circular concave portion 167 at the level of the surface of the wall 104 to define housing notches which serve to prevent the pin portion from disengaging from the circular concave portion 167. Inset from the edge 163 and beyond the walls 160, 161 an aperture 168 is formed in the top wall 103 for receiving the end of a tension strap 170. FIG. 12 shows a tension strap 170 engaged in the slot 155 of the top wall 104 of the carrier module 3. The tension strap 170 is of plastics material, and consists of a thin straight bar portion 171 extending at a first end into a first hook portion 172 which engages in the slot 155. The other end of the bar portion of the tension strap extends into a second hook portion 173, which is more sharply radiussed than the first hook portion 172. The second hook portion 173 comes into a gripping engagement with the edge of the aperture 168 during rotation of the carrier module 3 as will be further described below. The strap 170 has a width for passing between the upstanding walls 150, 151 of the carrier module 3 and the walls 160, 161 of the temperature control module 3. In the embodiment, the length of the pin portion 153 is such as to provide a sliding fit between the sides of the recess 164 and the tension strap width is such as to provide a sliding fit between the walls 150,151 and 160, 161. This ensures that the carrier module 3 and temperature control module 2 are self-aligned. To assemble the temperature control and carrier modules 2,3 the temperature control module 2 is supported substantially vertically with the air output port 9 and air inlet port 111 facing up and the receptacle portions 160-167 of the manually-releasable hinges 6a, 6b towards the operator. The carrier module 3 is lowered more or less in line with the axis of the temperature control module 2 until the pin portions 150-4 of the manually-releasable hinges 6a, 6b engage with the hinge receptacle portions 160-7. The carrier module 3 is then pivoted towards the operator until the tension straps 170 engage their slots 168. Next the carrier module 3 is rotated away from the operator until the latch lever members 71 are disposed with the noses 74 engaging in the notches 78. At this point the operator turns the latch lever members about their pivots 72 to pull the two modules 2,3 together. Once this is done the straight parts 73 of the levers are disposed within the envelope of the carrier module 3. The assembly of the two modules 2,3 is then secured to a base unit and extends substantially horizontally. FIG. 13 shows the hinge and tension straps in the connected state. During this assembly process, the electrical connections between plugs 132 and sockets 113 are made, and due to the method of connection, substantially no side forces are exerted on the plugs or sockets. Once the assembly is completed, the air inlet 111 and outlet 9 of the temperature control module 2 and the apertures 131a-131c and slot 130 of the carrier module 3 are aligned in register with one another. The wall around the inlet and outlet of the temperature control module 2 and the wall around the apertures 131a-131c and slot 130 of the carrier module 3 are urged together by the action of the tension straps 170 and the lever latches 7 to prevent leakage of air. The connection between the two modules 2,3 is easily made and released, but once in the fastened state, the modules are secured together with a high degree of rigidity. To mutually separate the two modules 2,3, the assembly is removed from the base unit and the operator then rotates the straight parts 73 of the lever latches, counterclockwise as seen in FIG. 1. The straight parts 73 move out of the envelope of the carrier module 3, and noses 74 are urged against the rear wall of the notches 78, to separate the two modules. This technique allows a controlled separation force to be exerted between the two modules while the hinge connection remains made. In operation of the support device for testing, the disk drive units are typically operated with a range of different voltage levels, and at a range of different temperatures while monitoring drive performance. For some tests, the dissipation of the drive unit or units provides the heat needed, and for these tests the air flow is simply recirculated. Where higher temperatures are needed, the air at the output of the temperature control module 2 is heated by activating the heater coil 112. Where it is desired to operate at sub-ambient temperatures or temperatures below that achieved by direct recirculation, the air is fed through the cooling heat exchanger 18. In the described embodiment, the embedded processor provides power supply conditioning to yield the different voltage levels, and provides control of the temperature regimes while monitoring performance. To do this, program data are loaded in from a main processor, and the embedded processor then needs to report only faults and exceptions. Once a test run is completed on disk drive units 102,202 an automatic handler extracts the disk drive units 102,202 from the carrier module 3 and loads new drive units 102,202 for testing. Embodiments of the present invention have been described with particular reference to the examples illustrated. However, it will be appreciated that variations and modifications may be made to the examples described within the scope of the present invention.
20041207
20070116
20051006
99401.0
0
DATSKOVSKIY, MICHAIL V
MOUNTING DEVICE FOR A DISK DRIVE UNIT, RELEASABLE FASTENER AND METHOD OF TESTING A DISK DRIVE UNIT
UNDISCOUNTED
0
ACCEPTED
2,004
10,517,190
ACCEPTED
Method for continuously and dynamically mixing at least two fluids, and micromixer
The invention relates to a method for continuously and dynamically mixing at least two fluids. Said method comprises the following steps: a) the rotor (1) of a micromixer is rotatably driven, said micromixer comprising a rotor (1) which is provided with a shaft (2) encompassing blades (3) that are arranged in groups (3a-3g), a stator (4) which is provided with at least one inlet (5) for a first fluid, at least one inlet (6) for a second fluid, and an outlet (7); b) the fluids are fed into the micromixer; and c) a micromixture of the fluids is collected at the outlet (7) of the micromixer. The inventive method is particularly suitable for rapid and/or complex kinetic chemical reactions such as anionic polymerization. The invention also relates to a micromixer for carrying out said method.
1. Method for continuously and dynamically mixing at least two fluids, comprising the following steps: a) driving in rotation the rotor (1) of a micromixer comprising: a rotor (1) comprising a shaft (2) equipped with blades (3) distributed in groups (3a-3g), the blades (3) of each group (3a-3g) being arranged around the shaft (2) in the same plane perpendicular to the longitudinal axis of the shaft (2), and the groups (3a-3g) of blades (3) being spaced out from each other along the longitudinal axis of the shaft (2); a stator (4) in the form of a hollow cylinder which is able to receive the rotor (1), this stator (4) comprising, at one end of its longitudinal axis, at least one inlet (5) for a first fluid, at least one inlet (6) for a second fluid and, at the other end of its longitudinal axis, an outlet (7) for the micromixture of the fluids; b) introducing the fluids into the micromixer; and c) recovering at the outlet (7) of the micromixer a micromixture of the fluids. 2. Method according to claim 1, characterized in that the rotor (1) is driven in rotation at a speed equal to 30,000 r.p.m. at most and preferably greater than 5000 r.p.m. and less than 20,000 r.p.m. 3. Method according to claim 1, characterized in that the first and second fluids are introduced in at least two places (5, 6) diametrically opposed with respect to the axis of the rotor (1). 4. Method according to claim 1, characterized in that it is used with a fluid temperature comprised between −100° C. and 300° C. and preferably comprised between −80° C. and 110° C. 5. Method according to claim 1, characterized in that it is implemented with fluid pressures comprised between 0.1 and 100 bars absolute and preferably comprised between 1 and 50 bars absolute. 6. Method according to claim 1, characterized in that the fluids are introduced into the mixer at a flow rate between 1 g/h and 10,000 kg/h and preferably between 1 kg/h and 5,000 kg/h. 7. Method according to claim 1, characterized in that the ratio of the mass flow rates is comprised between 0.01 and 100, preferably between 0.1 and 10. 8. Method according to claim 1, characterized in that the fluids have a viscosity comprised between 1 mPa.s and 103 Pa.s and preferably comprised between 10 mPa.s and 10 Pa.s. 9. Method according to claim 1, characterized in that it is implemented with residence times of the fluids in the micromixer greater than 1 ms, and preferably, comprised between 5 ms and 10 s. 10. Method according to claim 1, characterized in that the fluids are reactive fluids. 11. Method according to claim 10, characterized in that the fluids are liquids which produce anionic polymerization reactions. 12. Method according to claim 11, characterized in that at least one of the fluids comprises at least one (meth)acrylic monomer. 13. Method according to claim 12, characterized in that the (meth)acrylic monomer is chosen from the group constituted by acrylic anhydride, methacrylic anhydride, acrylates of methyl, ethyl, propyl, n- and tert-butyl, ethylhexyl, nonyl, 2-dimethyl amino ethyl and methacrylates of methyl, ethyl, propyl and n- and tert-butyl, ethylhexyl, nonyl and 2-dimethyl amino ethyl. 14. Polymerization method, comprising the following steps: (i) driving in rotation the rotor (1) of a micromixer comprising: a rotor (1) comprising a shaft (2) equipped with blades (3) distributed in groups (3a-3g), the blades (3) of each group (3a-3g) being arranged around the shaft (2) in the same plane perpendicular to the longitudinal axis of the shaft (2), and the groups (3a-3g) of blades (3) being spaced out from each other along the longitudinal axis of the shaft (2); a stator (4) in the form of a hollow cylinder which is able to receive the rotor (1), this stator (4) comprising, at one end of its longitudinal axis, at least one inlet (5) for a first fluid, at least one inlet (6) for a second fluid and, at the other end of its longitudinal axis, an outlet (7) for the micromixture of the fluids; (ii) introduction of at least two fluids, at least one of which is reactive, into the micromixer; (iii) recovery at the outlet (7) of the micromixer of a micromixture of the fluids; (iv) polymerization of the reactive fluid or fluids, this polymerization being able to occur outside the micromixer or begin inside this micromixer and continue outside this micromixer. 15. Polymerization method according to claim 14, in which at least one of the fluids comprises at least one (meth)acrylic monomer. 16. Polymerization method according to claim 15, characterized in that the (meth)acrylic monomer is chosen from the group constituted by acrylic anhydride, methacrylic anhydride, acrylates of methyl, ethyl, propyl, n- and tert-butyl, ethylhexyl, nonyl, 2-dimethyl amino ethyl and methacrylates of methyl, ethyl, propyl and n- and tert-butyl, ethylhexyl, nonyl and 2-dimethyl amino ethyl. 17. Micromixer comprising: a rotor (1) comprising a shaft (2) equipped with blades (3) distributed in groups (3a-3g), the blades (3) of each group (3a-3g) being arranged around the shaft (2) in the same plane perpendicular to the longitudinal axis of the shaft (2), and the groups (3a-3g) of blades (3) being spaced out from each other along the longitudinal axis of the shaft (2); and a stator (4) approximately in the form of a hollow cylinder which is able to receive the rotor (1), this stator (4) comprising, at one end of its longitudinal axis, at least one inlet (5) for a first fluid, at least one inlet (6) for a second fluid and, at the other end of its longitudinal axis, an outlet (7) for the micromixture of the fluids; 18. Micromixer according to claim 17, characterized in that the stator (4) also comprises a plurality of disks (8), these disks (8) being stacked and arranged inside the stator (4), each disk having in its centre a recess (9) housing a group (3a-3g) of blades (3). 19. Micromixer according to claim 18, characterized in that the recess (9) of each disk (8) has the shape of a circular hole, one part of which is occupied by extensions of the disk (8) forming counter-blades (10). 20. Micromixer according to claim 19, characterized in that the counter-blades (10) of the disks (8) have the same shape and the same dimensions as the blades (3) of the rotor (1) and have a thickness less than that of the body (12) of the disk (8). 21. Micromixer according to claim 17, characterized in that the inlets (5, 6) of the stator are diametrically opposed. 22. Micromixer according to claim 17, characterized in that it also comprises a fluid distributor 17 in the form of a washer, this distributor (17) comprising at least one inlet for a first fluid and at least one inlet for a second fluid, these inlets communicating respectively with the inlets (5, 6) of the stator (4).
The present invention relates to a method for continuously and dynamically mixing at least two fluids. This method is particularly suitable for rapid and/or complex kinetic chemical reactions such as anionic polymerizations. The invention also relates to a micromixer which is able to implement this method. Currently, one of the most commonly used techniques for mixing two or more liquids consists of using a closed, semi-closed or open vessel, equipped with a mechanical stirrer of propeller, turbine or similar type, and injecting one or more of the reagents into the vessel. The mixing can be carried out due to the energy dissipated by the mechanical stirring. Unfortunately, in certain cases, these devices do not allow micromixing times to be achieved which are sufficiently short for rapid and complex reactions to be implemented, and above all, they are unsuitable in the case of polymerization reactions where the viscosity increases rapidly over time. The static mixers, placed in line in a conduit or at the inlet of a reactor, allow a good mixing of the liquids. Nevertheless, they are, most of the time, used as premixers before entering into a reactor or when the constraints of time or viscosity are not redhibitory. These devices are good for homogenizing solutions, but are not really suitable for certain polymerization reactions, in particular rapid reactions, because the risks of blocking up are significant. This is the case, in particular, for polymerizations with high levels of solid. The tangential jet mixers (which can be used in particular for anionic polymerizations as described in EP-A-0749987) or RIM (“Reaction Injection Molding”) mixing heads are confined jet mixers, i.e. with jets in contact with the wall of the mixer. They are very efficient, but cause blockages when high polymer contents are involved, or require the injection of products by pumps which are resistant to high pressures (several hundreds of bars). Moreover the RIM mixing heads require discontinuous operation. The mixer by impact of free jets (i.e. without the jets being in contact with the walls of the mixer) is known and has been described for creating emulsions or in liquid-liquid extraction methods, for example by Abraham TAMIR, “Impinging-Stream Reactors. Fundamentals and Applications”, Chap. 12: Liquid-Liquid Methods, Elsevier (1994). Devices with free jet impact have also been described for precipitation or polymerization. They are constituted by two jets orientated according to a given angle and the impact of which causes a rapid micromixing; cf. Amarjit J., Mahajan and Donald J. Kirwan “Micromixing Effects in a Two Impinging-Jets Precipitator, Aiche Journal, Vol. 42, no. 7, pages 1801-1814 (July 1996); Tadashi Yamaguchi, Masayuki Nozawa, Narito Ishiga and Akihiko Egastira “A Novel Polymerisation Method by Means of Impinging Jets”, Die Angewandte Makromolekulare Chemie 85 (1980) 197-199 (no. 1311). The drawback of these systems is that they only allow the mixing of two fluids and that the jets are all of the same diameter and, consequently, if the mixture is to be effective, the respective flow rates in each jet must be the same. In the case of a polymerization reaction, the monomer arriving in a first jet and the initiator solution in a second jet with the same flow rate as the first, it is thus seen that the quantity of solvent in the system is necessarily relatively large, which means that recycling operations, which are generally costly, have to be envisaged downstream of the polymerization method. Then a method was developed which is described in the French patent application published under the no. 2 770 151 for continuously mixing by free jet impact at least 2 fluids and recovering the mixture in the form of a resulting jet, so as to overcome the limitations which have just been described. However, the drawback of this system is that it requires a very precise adjustment of the injection device in order that the jets of fluids correctly come into contact at a given point. In the international patent application published under the no. WO 97/10273 a device is described for dispersing isocyanate-terminated polyurethane prepolymers comprising a dynamic mixer allowing an average residence time of 10 to 120 seconds to be achieved. However, this type of mixer is not suitable for the more rapid reactions whose average residence time in the mixer must be much shorter, in order to allow a mixing of the reagents in a sufficiently short time compared to the reaction half-life. As when the reaction and mixing rates are of the same order of magnitude, strong competition arises between these two methods. Thus, as this international application shows, a slow reaction does not require a very rapid mixing method, while the development of a rapid reaction is greatly disturbed by a slow mixing. The object of the European patent application published under the no. EP 824 106 is a method for the preparation of cellulose particles which have cationic and/or anionic groups, in which a dynamic mixer is used comprising a stator and a rotor equipped with blades of cylindrical shape. The drawback of such a mixer is that the aggregates of matter are subjected to multiple velocity gradients which stretch and contract them in a random way, causing very significant concentration gradients. The present invention thus aims to propose a method and a mixer for dynamically and continuously mixing at least two fluids. It advantageously applies to the mixing of reactive fluids and in particular, to the anionic polymerization of at least one (meth)acrylic monomer. Thus, the subject of the invention is a method comprising the following steps: a) driving in rotation the rotor of a micromixer comprising: a rotor comprising a shaft equipped with blades distributed in groups, the blades of each group being arranged around the shaft in the same plane perpendicular to the longitudinal axis of the shaft, and the groups of blades being spaced out from each other along the longitudinal axis of the shaft; a stator in the form of a hollow cylinder which is able to receive the rotor, this stator comprising, at one end of its longitudinal axis, at least one inlet for a first fluid, at least one inlet for a second fluid and, at the other end of its longitudinal axis, an outlet for the micromixture of the fluids; b) introducing the fluids into the micromixer; and c) recovering at the outlet of the micromixer a micromixture of the fluids. A subject of the invention is also a micromixer comprising: a rotor comprising a shaft equipped with blades distributed in groups, the blades of each group being arranged around the shaft in the same plane perpendicular to the longitudinal axis of the shaft, and the groups of blades being spaced out from each other along the longitudinal axis of the shaft; and a stator in the form of a hollow cylinder which is able to receive the rotor, this stator comprising, at one end of its longitudinal axis, at least one inlet for a first fluid, at least one inlet for a second fluid and, at the other end of its longitudinal axis, an outlet for the micromixture of the fluids. Such a micromixer has the double advantage of not inducing a large pressure loss and being able to be easily adjusted so as to adapt to changes in the operating conditions such as the flow rates and viscosities. In fact it only requires changing the speed of rotation of the rotor, the shape of the blades or counter-blades, or their number. Moreover, the effectiveness of the mixing does not diminish along the longitudinal axis of the rotor as is the case in a standard mixer in the shape of a tube. Moreover, the micromixer according to the invention is very effective even when the viscosities are high. According to another aspect of the invention, a polymerization method is proposed, in which the method of dynamically and continuously mixing and the micromixer according to the invention are used. This method comprises the following steps: (i) driving in rotation the rotor of a micromixer comprising: a rotor comprising a shaft equipped with blades distributed in groups, the blades of each group being arranged around the shaft in the same plane perpendicular to the longitudinal axis of the shaft, and the groups of blades being spaced out from each other along the longitudinal axis of the shaft; a stator in the form of a hollow cylinder which is able to receive the rotor, this stator comprising, at one end of its longitudinal axis, at least one inlet for a first fluid, at least one inlet for a second fluid and, at the other end of its longitudinal axis, an outlet for the micromixture of the fluids; (ii) introduction of at least two fluids, at least one of which is reactive, into the micromixer; (iii) recovery at the outlet of the micromixer of a micromixture of the fluids; (iv) polymerization of the reactive fluid or fluids, this polymerization being able to occur outside the micromixer or begin inside this micromixer and continue outside this micromixer. Other characteristics and advantages of the invention will now be described in detail in the following description which refers to the figures, in which: FIG. 1 represents schematically and in an exploded front view, a micromixer according to the invention; FIG. 2 represents schematically and in a top view, a rotor of the micromixer of FIG. 1; FIG. 3 represents schematically and in a top view, a disk of the stator of the micromixer of FIG. 1; FIG. 4 represents schematically and in a top view, the assembly of the disk of FIG. 3 and of the rotor of FIG. 2; FIG. 5 represents schematically and in partial section, a micromixer according to the invention; FIGS. 6 and 7 are curves showing the influence of the speed of rotation of the rotor of the micromixer according to the invention, on the quality of product obtained, at constant flow rates; FIGS. 8 and 9 are curves showing the influence of the flow rates of the fluids on the quality of product obtained, at a constant speed of rotation of the rotor of the micromixer according to the invention; FIGS. 10 and 11 are curves showing the influence of the type of mixer used on the quality of product obtained, at constant flow rates. DETAILED DESCRIPTION OF THE INVENTION Mixing Method According to the Invention The method for dynamically and continuously mixing according to the invention has been described in a general way above. It can be implemented for mixing more than two fluids. However, for the sake of simplicity, it will now be described for an implementation with two fluids. According to the invention, the rotor can be driven in rotation at a speed which can reach up to 30,000 r.p.m. Preferably, a speed of rotation of the rotor greater than 5,000 r.p.m is chosen, in order to obtain a homogeneous mixing and less than 20,000 r.p.m, so as to limit overheating phenomena. The introduction of the first and second fluids preferably occurs in at least two places which are diametrically opposed with respect to the axis of the rotor of the micromixer. The method according to the invention is generally used with a fluid temperature comprised between −100° C. and 300° C. It is preferably used with temperatures comprised between −80° C. and 110° C. It can be implemented with fluid pressures comprised between 0.1 and 100 bars absolute. Preferably, it is used with pressures comprised between 1 and 50 bars absolute. The fluids can be introduced into the mixer at a flow rate between 1 g/h and 10,000 kg/h. Preferably, the flow rate of the fluids is comprised between 1 kg/h and 5,000 kg/h. The ratio of the mass flow rates of the fluids can be very variable. It is generally comprised between 0.01 and 100, preferably between 0.1 and 10. The method according to the invention can allow mixing of fluids whose viscosity is comprised between 1 mpa.s and 103 Pa.s. Preferably, this viscosity is comprised between 10 mPa.s and 10 Pa.s. The method according to the invention is used with residence times for the fluids in the micromixer generally greater than 1 ms. Preferably, the operating conditions are adjusted so that the residence time is comprised between 5 ms and 10 s. Polymerization Method According to the Invention The mixing method which has just been described is particularly suitable for the micromixing of reactive fluids. It preferably applies to reactive liquids. It can thus advantageously be implemented for the production of an intimate mixture of liquids which is to produce chemical reactions with rapid and/or complex kinetics, such as anionic polymerizations, or polymerizations with high levels of solid. Thus, the mixing method according to the invention can constitute a part of a more global polymerization method. This polymerization method according to the invention in particular applies to the mixture of reactive fluids intended for anionic polymerization, at least one of which comprises at least one (meth)acrylic monomer. As (meth)acrylic monomer, there can thus be mentioned in particular acrylic anhydride, methacrylic anhydride, methyl, ethyl, propyl, n- and tert-butyl acrylates, ethylhexyl, nonyl, 2-dimethyl amino ethyl and methyl, ethyl, propyl and n- and tert-butyl methacrylates, ethylhexyl, nonyl and 2-dimethyl amino ethyl. The actual polymerization can occur outside the micromixer according to the invention, or it can begin inside the micromixer and continue outside this micromixer, for example in an appropriate reactor. The method according to the invention can be used in any polymerization installation. In particular the one illustrated by FIG. 1 on page 14 of the aforementioned patent application EP 749 987 can be mentioned. The method according to the invention can in particular be used for the preparation of polymers according to the methods described in European patent applications published under the numbers EP 749 987, EP 722 958 and EP 524 054. Micromixer According to the Invention The micromixer according to the invention is able to implement the method which has just been described. This micromixer has been described in a general way above. For more details about its structure reference can be made to FIGS. 1 to 6 which give an illustration of the structure of this micromixer. In FIG. 1 in particular, it is seen that the micromixer according to the invention comprises a rotor 1 comprising a shaft 2 of approximately cylindrical shape equipped with blades 3. These blades 3 are distributed in groups 3a, 3b, 3c, 3d, 3e, 3f and 3g, the blades of each group are arranged around the shaft 2, in the same plane perpendicular to the longitudinal axis of the shaft 2, and the groups of blades being spaced out from each other along the longitudinal axis of the shaft 2. This can be seen clearly in FIG. 1, where each group 3a to 3g has the appearance of a disk. In FIG. 2, a top view of the rotor is shown. Thus a group 3a of six blades 3 is seen. The blades are arranged regularly around the shaft, in a star and each is inclined at 60 degrees with respect to its two nearest neighbours. The blades are approximately identical to each other and are in the form of a cutting edge. One of their longitudinal sides forms a tangent at the circumference of the shaft 2. The free end of each blade 3 can be tapered. A 60 degree rotation of the shaft allows one blade to occupy the place that one of its two neighbours occupied before this rotation. The blades 3 of a group of blades 3a are preferably aligned respectively with the blades of another group of blades 3b along the longitudinal axis of the rotor, so that in a top view and looking in the direction of the longitudinal axis of the rotor 1 (FIG. 2), only one group of blades can be seen, the others being hidden beneath them. The rotor 1 is intended to cooperate with a stator 4 which is seen firstly in FIG. 1. This stator 4 has approximately the form of a hollow cylinder. It has dimensions which make it able to house at least partly the rotor 1. As is seen in FIG. 5, the stator 4 comprises at one end of its longitudinal axis, an inlet 5 for a first fluid, an inlet 6 for a second fluid and at the other end of its longitudinal axis, an outlet 7 for the micromixture of fluids. Preferably, the inlet 6 is diametrically opposed with respect to the inlet 5. According to one embodiment of the invention, the stator 4 comprises disks 8 which are seen out of the stator in FIG. 1. When the stator 4 is mounted, as is seen in FIG. 5, the disks 8 are stacked inside. The specific shape of the disks 8 can be seen in FIG. 3. Each disk 8 has in its centre a recess 9 which allows it to house a group of blades 3a or 3b to 3g, while allowing the latter to turn together with the rotor 1. The recess 9 has the shape of a circular hole, one part of which is occupied by extensions 10 of the disk 8. These extensions 10 project with respect to the wall 11 of the disk 8 delimiting the recess 9. These extensions 10 of the disks 8 have approximately the same shape and the same dimensions as the blades 3 of the rotor 1. That is why in the remainder of the present description they are called counter-blades 10. Each disk 8 thus comprises its group of six counter-blades 10 arranged in a regular manner on the circumference of the wall 11. Each counter-blade is inclined at 60 degrees with respect to its two nearest neighbours. As for the blades 3 of the rotor 1, a 60 degree rotation of a disk 8 allows a counter-blade 10 to occupy the place that one of its two neighbours occupied before this rotation. The counter-blades 10 of a group of counter-blades 10 are also preferably aligned respectively with the counter-blades of another group of counter-blades 10 along the longitudinal axis of the stator, so that in a top view and looking in the direction of the longitudinal axis of the stator 4 (FIG. 3), only one group of counter-blades 10 can be seen, the others being hidden beneath them. FIG. 4 shows, in a top view, a group of blades 3 of the rotor 1 around which a disk 8 has been placed. With reference to FIG. 5, it is noted that the counter-blades 10 have a thickness less than that of the body 12 of the disk 8 which they extend. The disks 8 are in contact with each other, stacked inside the stator 4, so that each group of blades 3 (with the exception of the first and the last) is inserted between two groups of counter-blades 10. Thus, when the shaft 2 of the rotor 1 turns, each group of blades 3 can turn freely, i.e. without being impeded by the adjacent groups of counter-blades 10. The blades 3 and the counter-blades 10 are preferably inclined in opposite directions so that, during rotation of the rotor, they come close to each other like the blades of shears, and thus cause shearing of the fluids. Moreover, looking from the inlet 5 of the micromixer towards its outlet 7, it is noted that a space 13 is provided, in longitudinal direction, between each group of blades 3 and the group of counter-blades 10 which precedes it (except in the case of the first group of blades situated close to the inlet of the stator) and another space 14 is also provided between each group of blades 3 and the group of counter-blades 10 which follows it (except in the case of the last group of blades situated close to the outlet of the stator). Moreover, as is seen in FIG. 4, when the rotor/stator assembly is seen in cross section, it is noted that the sum of the surface areas of the shaft 2, the blades 3 and the counter-blades 10 is less than the surface area of the circular hole delimited by the wall 11 of the disk 8, so that there are still spaces 15 allowing the circulation in the longitudinal direction of the fluids being mixed. The spaces 15 have a minimum size in the case of FIG. 4, where the side of each blade 3 which is tangential to the shaft 2 is arranged parallel to the longitudinal sides of a counter-blade 10. The spaces 15 have a maximum size when, looking in the direction of the axis of the shaft 2, the blades 3 are superposed on the counter-blades 10 and hide them. As can be deduced from FIG. 5, a bore 16 can be provided through the thicknesses of the disks 8 and in the stator 4, in order to be able to introduce a rod or a screw (not represented) in order to immobilize the disks 8 and make them integral with the stator 4. Generally, the stator 4 also comprises a fluid distributor 17 approximately in the form of a washer and situated at the level of the feed of the stator 4 and upstream of the disks 8, if referring to the general direction of circulation of the fluids. One end of the distributor 17 is in annular contact with the first disk 8. The distributor 17 comprises at least one opening for the first fluid and at least one other opening for the second fluid, these openings being cut in the washer radially and communicating respectively with the entries 5 and 6 of the stator 4. Thus, the fluids entering through the entries 5 and 6 are taken through the openings of the distributor 17 close to the shaft 2 of the rotor 1. Generally, the central hole 18 of the distributor 17 has a diameter approximately the same as that of the circular hole of a disk 18 delimited by the wall 11 of this disk. It follows that when the rotor 1 is mounted in the stator 4, a first group of blades 3 of the rotor 1 can optionally be inserted inside the central hole 18 and turn freely therein. At its lower end, i.e. the one opposite the one which is in contact with a disk 18, the distributor 17 optionally has a bore 19 intended to receive a ring seal 20 which is also in contact with the shaft 2 of the rotor 1. The stator 4 is generally-fixed onto a support 21 in a standard way using a bolt (not represented). Operation of the Micromixer The rotor 1 is generally driven in rotation in a standard way by means for driving in rotation such as an electric motor (not represented). However, a motor capable of maintaining a constant speed of rotation, independent of the resisting torque to which it can be subjected, (e.g. milling machine motor), is preferably chosen. The direction of rotation of the rotor is that of the inclination of the blades 3. As is seen by observing FIG. 5, the micromixer is fed through the inlet 5 using a first fluid and through the inlet 6 using a second fluid. The openings of the distributor 17 take the fluids towards the centre, into the central hole 18. The fluids are then confined between the shaft 2 and the walls of the central hole 18 and are in contact with a first group of blades 3. Under the effect of the pressure of the fluids and of the rotation of the shaft 2, the first blades, in cooperation with the first counter-blades, shear the fluids which progress through the spaces 14, then 15 and 13. The fluids then rapidly encounter other blades 3 and counter-blades 10 until outlet 7 of the mixer where they are intimately mixed. The intimate mixture of the fluids can then be used in numerous applications. For example, it can be introduced into a tubular reactor or similar, and chemical reactions can occur, as described previously. EXAMPLES The following examples illustrate the present invention without however limiting its scope. In these examples, the polymerization installation used is the one represented schematically in FIG. 1, page 14 of the aforementioned European patent application no. EP 749 987 and in which, as mixer M, a micromixer according to the invention is used having the following characteristics: internal volume of the micromixer: 1.62 ml diameter of the rotor shaft in the mixing zone: 5.4 mm thickness of the blades of the rotor: 1 mm thickness of the counter-blades of the disks: 1 mm space, measured in the direction of the longitudinal axis of the rotor, between a counter-blade of the rotor and each of the adjacent rotor blades: 0.4 mm (thickness of the disks of the stator: 2.8 mm) number of groups of blades: 7 number of disks: 6 The triblocks (triblock copolymers) ABC 100, ABC 101 and ABC 104 as identified in Examples 1 to 6 are prepared according to the operating method described in the European patent application published under the number EP 524 054 or in the aforementioned application EP 749 987. The following abbreviations were used: PS: polystyrene BP: polybutadiene PMMA: poly(methylmethacrylate) SB: diblock(diblock copolymer)poly(styrene-b-butadiene) SBM: triblock (triblock terpolymer formed by a polystyrene block, a polybutadiene block and a poly(methyl methacrylate) block ABC 100: PS-b-PB-b-PMMA (terpolymer formed by a polystyrene block, a polybutadiene block and a poly(methyl methacrylate) block, with a mass composition (32/35/33) and having an average molecular mass by numbers of the polystyrene block, Mn (PS), of 27,000 g/mol ABC 101: PS-b-PB-b-PMMA with a mass composition (20/30/50) and having an average molecular mass by numbers Mn (PS) of 20,000 g/mol ABC 104: PS-b-PB-b-PMMA with a mass composition (20/30/50) and having an average molecular mass by numbers Mn (PS) of 20,000 g/mol Q(SB): flow rate in kg/h of the poly(styrene-b-butadiene)-butadienyl lithium solution, at the inlet of the micromixer, Q(M): flow rate of the methyl methacrylate solution at the inlet of the micromixer in kg/h V0: 0 r.p.m. V1: approximately 7,600 r.p.m. V2: approximately 11,200 r.p.m. V3: approximately 15,000 r.p.m. V4: approximately 18,500 r.p.m. 114T: example according to the prior art, in which the standard tangential jet mixer as described in EP 749 987 is used Ve: elution volume The average molecular mass in numbers of the PS block was determined by steric exclusion chromatography (SEC) in polystyrene equivalent, after sampling this block during the experiment. The mass fractions of PS, PB and PMMA were determined by proton NMR. The products contain a homopolystyrene (PS) fraction and a diblock copolymer fraction poly(styrene-b-butadiene) (SB), these fractions resulting from a non-quantitative blocking efficiency under the synthesis conditions used. In all cases, the glass transition temperature (Tg) of the PB block is approximately −90° C. The PMMA blocks are syndiotactic at more than 70% and have a Tg of 135° C. In Examples no. 1 to 6, the results of SEC are superposed in order for the tests carried out to be better visualized. Example 1 The influence of the speed of rotation of the rotor of the micromixer according to the invention on the quality of an synthesized ABC 100 triblock is studied. For this purpose, at one inlet of the micromixer, a solution of poly(styrene-b-butadiene)-butadienyl lithium and at the diametrically opposed inlet of the micromixer, a solution of methyl methacrylate is introduced. The flow rates are kept constant, namely, 40 kg/h for Q(SB) and 20 kg/h for Q(M). After polymerization in the tubular reactor, measurement by SEC is carried out of the intensity of the I(RD) detection as a function of the elution volume Ve. The results are shown in the form of curves in FIG. 6, each curve corresponding to a speed of rotation of the rotor. No notable difference is observed between the synthesized ABC 100 when passing from V1 to V4. In all cases, the presence of residual SB in the product obtained is noted. But the proportion of SB in the synthesized ABC 100 is significantly higher at V0 than for V1, V2, V3, or V4. This can be explained by the fact that when chemical reactions are in play, it is the bringing into contact of the reagents, the mixing on the molecular level which is important. However, the polmerization kinetics of methacrylates under these conditions is extremely rapid. Moreover, it is known that the efficiency of mixing required for a reactor depends on the relationship between the characteristic time of the reaction considered and the mixing time on the molecular level. In the case of mixing at V0, the volume energy dissipated in the micromixing zone is smaller, which results in the contact between the reagents being less intimate. A heterogeneous distribution of the reagents results which causes unwanted reaction terminations. In other words, the peaks are narrower for V1 to V4, which shows that the dynamic micromixer according to the invention is more effective at a speed greater than V0. Example 2 The influence of the speed of rotation of the rotor of the micromixer according to the invention on the quality of a synthesized ABC 101 triblock is studied. For this purpose, the operation is carried out as in Example 1. The results are shown in FIG. 7. The same conclusions as in Example 1 are reached, namely: no notable difference is observed between the synthesized ABC 101 when passing from V1 to V4.; in all cases, the presence of residual SB in the product obtained is noted; the proportion of SB in the synthesized ABC 100 is significantly higher at V0 (static mixer) than for V1, V2, V3, or V4, which again shows that the dynamic micromixer according to the invention performs better than a static mixer. Example 3 In this example, in a micromixer according to the invention, the influence of the total flow rate Q (SB)+Q(M), with a constant flow rate ratio Q(SB)/Q(M) and a constant speed of rotation of the rotor, on the quality of a synthesized ABC 100 triblock is studied. In a first case, the sum of the flow rates Q(SB) and Q(M), respectively, 30 kg/h and 15 kg/h, is equal to 45 kg/h. In a second case, the sum of the flow rates Q(SB) and Q(M), respectively, 40 kg/h and 20 kg/h, is equal to 60 kg/h. The results are shown in FIG. 8. It is noted that the increase in the total flow rate leads to better results. Example 4 The same study as in Example 3 is undertaken, but synthesizing an ABC 101 triblock instead of the previous ABC 100 triblock. The results are shown in FIG. 9. It is noted that for this product, ABC 101, the variation in the total flow rate has very little influence on the quality of the synthesized product, from the time when this flow rate has reached a minimum value which is sufficient to allow a characteristic micromixing time which is shorter than the reaction time. Example 5 In this example, the results obtained with three types of mixers were compared, namely: a tangential jet mixer (114T); a static mixer (speed V0); and the mixer according to the invention (speed V2). In the three cases, ABC 104 was synthesized with constant flow rates, Q(SB)=30 kg/h and Q(M)=15 kg/h. The results are shown in FIG. 10. The following is noted: on the one hand, a significant improvement in the rate of coupling (which results in a fall in the quantity of residual SB diblock in the SBM), when using a tangential jet or dynamic mixer rather than a static mixer, and on the other hand, a notable improvement in the quality of the coupling when passing from a tangential jet mixer to the mixer according to the invention. These results are expressed by different dispersities of population of the different chains, i.e. by different polymolecularity indexes (Ip): Ip=2.45 for the static mixer; Ip=2.01 for the tangential jet mixer; Ip=1.80 for the dynamic mixer according to the invention. Example 6 In this example, the operation is carried out as in Example 5, except that higher total flow rates were used, namely, 60 kg/h instead of 45 kg/h. The results are shown in FIG. 11. The same conclusions are reached as in Example 5. A significant improvement in the Ip is also noted in the case of the static mixer. Specifically: Ip=2.02 for the static mixer; Ip=1.98 for the tangential jet mixer; Ip=1.80 for the dynamic mixer according to the invention. Nevertheless, the dynamic mixer according to the invention is clearly performs better than the tangential jet mixer and a fortiori than the static mixer.
20041207
20071030
20051027
75225.0
1
HARLAN, ROBERT D
METHOD FOR CONTINUOUSLY AND DYNAMICALLY MIXING AT LEAST TWO FLUIDS, AND MICROMIXER
UNDISCOUNTED
0
ACCEPTED
2,004
10,517,405
ACCEPTED
Rotary motion mechanism
A rotary motion mechanism including a rotatable element geometrically lockable at two points (e.g., limits) of travel, and a linear motion element linked to the rotatable element, the linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of the rotatable element.
1. A rotary motion mechanism comprising: a rotatable element geometrically lockable at two points of travel; and a linear motion element linked to said rotatable element, said linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of said rotatable element. 2. The mechanism according to claim 1 wherein said points of travel comprise limits of travel. 3. The mechanism according to claim 1 wherein said two points of travel are defined by structure formed in said rotatable element. 4. The mechanism according to claim 3 wherein said structure comprises a plurality of grooves adapted for receiving therein a portion of said linear motion element, wherein one of said grooves defines a first point of travel of said rotatable element when said portion of said linear motion element is received therein, and another of said grooves defines a second point of travel of said rotatable element when said portion of said linear motion element is received therein. 5. The mechanism according to claim 4 wherein said rotatable element is rotatable about a pivot and at least two of said grooves are offset from said pivot. 6. The mechanism according to claim 4 wherein said linear motion element is adapted to cause said rotatable element to rotate when said portion of said linear motion element is not positioned in said grooves that define the points of travel. 7. The mechanism according to claim 4 wherein said plurality of grooves comprises a groove that is not one of said grooves that define the points of travel. 8. The mechanism according to claim 7 wherein said linear motion element is adapted to cause said rotatable element to rotate when said portion of said linear motion element is positioned in the groove that is not one of said grooves that define the points of travel. 9. The mechanism according to claim 7 wherein said grooves comprise at least three grooves formed generally in a clover shape in said rotatable element. 10. The mechanism according to claims 1 wherein said rotatable element comprises a hook. 11. The mechanism according to claims 1 wherein said linear motion element comprises a link arm coupled with said rotatable element. 12. The mechanism according to claim 11 wherein said link arm comprises a first pin at one end thereof that engages a slot formed in said linear motion element, and a second pin at a second end thereof receivable in any of said grooves formed in said rotatable element. 13. The mechanism according to claim 12 wherein said first pin is constrained to travel in a first channel, and said second pin is constrained to travel in a second channel. 14. A mechanical system comprising: a rotatable element geometrically lockable at two points of travel; a linear motion element linked to said rotatable element, said linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of said rotatable element; and a linkage apparatus adapted to move said linear motion element in said linear motion. 15. The system according to claim 14 and further comprising an element actuable by rotation of said rotatable element. 16. The system according to claim 14 wherein said system comprises a portion of a door lock system.
FIELD OF THE INVENTION The present invention relates generally to mechanisms for transferring linear motion to rotary motion. BACKGROUND OF THE INVENTION Many devices are known for transferring linear motion to rotary motion. For example, the linkage in an internal combustion engine between the pistons and the crankshaft transfers the linear reciprocating motion of the pistons to the rotary motion of the crankshaft. Some mechanisms that transfer linear to rotary motion, such as in the example of the linkage in the engine, are dedicated to continuous motion. Other mechanisms, instead of providing continuous motion, constrain the motion between limits of travel. Some push-pull or toggle mechanisms are examples of such mechanisms. However, the known mechanisms lack the ability to geometrically lock at the limits of travel. SUMMARY OF THE INVENTION The present invention seeks to provide an improved mechanism for transferring linear motion to rotary motion, wherein the rotary motion is constrained between two points of travel, and wherein there is geometrical locking at the points of travel. There is thus provided in accordance with a preferred embodiment of the present invention a rotary motion mechanism including a rotatable element geometrically lockable at two points (e.g., limits) of travel, and a linear motion element linked to the rotatable element, the linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of the rotatable element. In accordance with a preferred embodiment of the present invention the two points of travel are defined by structure formed in the rotatable element. Further in accordance with a preferred embodiment of the present invention the structure comprises a plurality of grooves adapted for receiving therein a portion of the linear motion element, wherein one of the grooves defines a first point of travel of the rotatable element when the portion of the linear motion element is received therein, and another of the grooves defines a second point of travel of the rotatable element when the portion of the linear motion element is received therein. Still further in accordance with a preferred embodiment of the present invention the rotatable element is rotatable about a pivot and at least two of the grooves are offset from the pivot. In accordance with a preferred embodiment of the present invention the linear motion element is adapted to cause the rotatable element to rotate when the portion of the linear motion element is not positioned in the grooves that define the points of travel. Further in accordance with a preferred embodiment of the present invention the plurality of grooves comprises a groove that is not one of the grooves that define the points of travel. Still further in accordance with a preferred embodiment of the present invention the linear motion element is adapted to cause the rotatable element to rotate when the portion of the linear motion element is positioned in the groove that is not one of the grooves that define the points of travel. Additionally the grooves comprise at least three grooves formed generally in a clover shape in the rotatable element. In accordance with a preferred embodiment of the present invention the rotatable element comprises a hook. Further in accordance with a preferred embodiment of the present invention the linear motion element comprises a link arm coupled with the rotatable element. Still further in accordance with a preferred embodiment of the present invention the link arm comprises a first pin at one end thereof that engages a slot formed in the linear motion element, and a second pin at a second end thereof receivable in any of the grooves formed in the rotatable element. Additionally in accordance with a preferred embodiment of the present invention the first pin is constrained to travel in a first channel, and the second pin is constrained to travel in a second channel. There is also provided in accordance with a preferred embodiment of the present invention a mechanical system including a rotatable element geometrically lockable at two points of travel, a linear motion element linked to the rotatable element, the linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of the rotatable element, and a linkage apparatus adapted to move the linear motion element in the linear motion. The system may include an element actuable by rotation of the rotatable element. BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be understood and appreciated more fully from the following detailed description taken in conjunction with the drawings in which: FIGS. 1A-1E are simplified front view illustrations of a rotary motion mechanism, constructed and operative in accordance with a preferred embodiment of the present invention, wherein the mechanism is progressively rotated from a first point of travel to a second point of travel, and the mechanism is geometrically locked in place at both points of travel; and FIGS. 2A-2E are simplified pictorial illustrations of the rotary motion mechanism, corresponding respectively to FIGS. 1A-1E. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Reference is now made to FIGS. 1A-1E and 2A-2E, which illustrate rotary motion mechanism 10, constructed and operative in accordance with a preferred embodiment of the present invention. The rotary motion mechanism 10 may include a rotatable element 12. Although the invention is not limited to the example illustrated in the figures, the rotatable element 12 may comprise a pivot 14 about which the rotatable element 12 may rotate, and two or more recesses or grooves offset from the pivot 14. In the illustrated embodiment, three grooves 16, 17 and 18 are formed generally in a clover shape in the rotatable element 12. The rotatable element 12 may comprise a hook 20. The rotary motion mechanism 10 may include a linear motion element 22. Although the invention is not limited to the example illustrated in the figures, the linear motion element 22 may comprise a tongue 24 that protrudes from a body 26 that pivots about a pivot 28. A groove or slot 30 may be formed in body 26. The linear motion element 22 may comprise a link arm 32, which is preferably coupled with the rotatable element 12. Although the invention is not limited to the example illustrated in the figures, the link arm 32 may comprise a bar with a first pin 34 at one end thereof that engages slot 30 of the linear motion element 22, and another second pin 36 at another end thereof that engages any of the grooves 16, 17 or 18. First pin 34 may be constrained to travel in a slot or first channel 38 (FIGS. 1D and 1E), and second pin 36 may be constrained to travel in a slot or second channel 40 (FIGS. 1A, 1B and 1C). Channels 38 and 40 may be formed in a base or substrate 42, which may also serve as the base for the pivots 14 and 28. In FIGS. 1A and 2A, second pin 36 (i.e., a portion of link arm 32) is fully received in groove 16, thereby geometrically locking rotatable element 12, that is, preventing rotation of rotatable element 12. Thus, the rotary motion mechanism 10 is at a first point (for example, limit) of travel and geometrically locked in place. Reference is now made to FIGS. 1B and 2B, which illustrate initial actuation of the rotary motion mechanism 10. Tongue 24 may be lifted by a linkage apparatus 43 (shown only in FIG. 1B and omitted in the rest of the drawings for the sake of clarity) generally in the direction of an arrow 44, thereby causing the linear motion element 22 to pivot about pivot 28 generally in the direction of an arrow 46. Linkage apparatus 43 may comprise a rod, bar or other similar device, for example. Alternatively, tongue 24 may be lifted by a hand, finger or foot, for example. As the linear motion element 22 pivots, groove 30 pushes first pin 34 and the link arm 32 generally in the direction of an arrow 47 (along first channel 38). This causes second pin 36 to move out of groove 16, along second channel 40, towards a junction 48 of grooves 17 and 18. FIGS. 1B and 2B show second pin 36 abutting against junction 48. Until this point, rotatable element 12 has not yet started to rotate about pivot 14. As tongue 24 continues to move in the direction of arrow 44, and linear motion element 22 continues to pivot about pivot 28, link arm 32 continues to move generally in the direction of arrow 47. As shown in FIGS. 1C and 2C, this urges second pin 36 into groove 17 and causes rotatable element 12 to rotate generally in the direction of an arrow 49 about pivot 14. In FIGS. 1D and 2D, tongue 24 continues to move in the direction of arrow 44, and linear motion element 22 continues to pivot about pivot 28 in the direction of arrow 46, second pin 36 continues to move along second channel 40 and rotatable element 12 continues to pivot about pivot 14 in the direction of arrow 49. This motion moves second pin 36 out of groove 17 towards groove 18. Finally, in FIGS. 1E and 2E, tongue 24 continues to move in the direction of arrow 44, and linear motion element 22 continues to pivot about pivot 28 in the direction of arrow 46, until second pin 36 slides into groove 18. Once this happens, second pin 36 is locked in groove 18, thereby geometrically locking rotatable element 12, that is, preventing further rotation of rotatable element 12. Thus, the rotary motion mechanism 10 is at a second point (for example, limit) of travel and geometrically locked in place. The rotary motion mechanism 10 may be brought back to the orientation of FIG. 1, by moving tongue 24 generally in the direction opposite to arrow 44 and reversing the above-described process. The rotary motion mechanism 10 may be implemented in a mechanical system that comprises rotary and linear motion. The mechanical system may comprise a wide range of devices, and may include an element actuable by rotation of rotatable element 12, such as the hook 20, for example. For example, the rotary motion mechanism 10 may be part of a door lock system installed in a door, and hook 20 may be adapted to protrude from an escutcheon 60 into a door frame (not shown). Geometrically locking hook 20 at the second point of travel may substantially increase the locked security of the door. Other examples of devices may include a plowing mechanism, wherein it is desired to lock the plowing mechanism at two different points of travel, such as one orientation for plowing the ground and another orientation lifted above the ground. It is appreciated that these are just two examples of many other implementations of the rotary motion mechanism 10 of the invention. It will be appreciated by person skilled in the art that the present invention is not limited by what has been particularly shown and described herein above. Rather the scope of the present invention is defined only by the claims that follow:
<SOH> BACKGROUND OF THE INVENTION <EOH>Many devices are known for transferring linear motion to rotary motion. For example, the linkage in an internal combustion engine between the pistons and the crankshaft transfers the linear reciprocating motion of the pistons to the rotary motion of the crankshaft. Some mechanisms that transfer linear to rotary motion, such as in the example of the linkage in the engine, are dedicated to continuous motion. Other mechanisms, instead of providing continuous motion, constrain the motion between limits of travel. Some push-pull or toggle mechanisms are examples of such mechanisms. However, the known mechanisms lack the ability to geometrically lock at the limits of travel.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention seeks to provide an improved mechanism for transferring linear motion to rotary motion, wherein the rotary motion is constrained between two points of travel, and wherein there is geometrical locking at the points of travel. There is thus provided in accordance with a preferred embodiment of the present invention a rotary motion mechanism including a rotatable element geometrically lockable at two points (e.g., limits) of travel, and a linear motion element linked to the rotatable element, the linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of the rotatable element. In accordance with a preferred embodiment of the present invention the two points of travel are defined by structure formed in the rotatable element. Further in accordance with a preferred embodiment of the present invention the structure comprises a plurality of grooves adapted for receiving therein a portion of the linear motion element, wherein one of the grooves defines a first point of travel of the rotatable element when the portion of the linear motion element is received therein, and another of the grooves defines a second point of travel of the rotatable element when the portion of the linear motion element is received therein. Still further in accordance with a preferred embodiment of the present invention the rotatable element is rotatable about a pivot and at least two of the grooves are offset from the pivot. In accordance with a preferred embodiment of the present invention the linear motion element is adapted to cause the rotatable element to rotate when the portion of the linear motion element is not positioned in the grooves that define the points of travel. Further in accordance with a preferred embodiment of the present invention the plurality of grooves comprises a groove that is not one of the grooves that define the points of travel. Still further in accordance with a preferred embodiment of the present invention the linear motion element is adapted to cause the rotatable element to rotate when the portion of the linear motion element is positioned in the groove that is not one of the grooves that define the points of travel. Additionally the grooves comprise at least three grooves formed generally in a clover shape in the rotatable element. In accordance with a preferred embodiment of the present invention the rotatable element comprises a hook. Further in accordance with a preferred embodiment of the present invention the linear motion element comprises a link arm coupled with the rotatable element. Still further in accordance with a preferred embodiment of the present invention the link arm comprises a first pin at one end thereof that engages a slot formed in the linear motion element, and a second pin at a second end thereof receivable in any of the grooves formed in the rotatable element. Additionally in accordance with a preferred embodiment of the present invention the first pin is constrained to travel in a first channel, and the second pin is constrained to travel in a second channel. There is also provided in accordance with a preferred embodiment of the present invention a mechanical system including a rotatable element geometrically lockable at two points of travel, a linear motion element linked to the rotatable element, the linear motion element being adapted to move in response to a linear motion imparted thereto and to cause rotation of the rotatable element, and a linkage apparatus adapted to move the linear motion element in the linear motion. The system may include an element actuable by rotation of the rotatable element.
20041208
20070501
20060316
64615.0
G05G100
0
LUGO, CARLOS
ROTARY MOTION MECHANISM
SMALL
0
ACCEPTED
G05G
2,004
10,517,732
ACCEPTED
Herbicidal composition
A herbicidal composition comprising, in addition to customary inert formulation excipients, as a mixture of at least one acetamide herbicide and a lipophilic additive comprising at least one member selected from the group consisting of C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids.
1. A herbicidal synergistic composition comprising, in addition to customary inert formulation excipients, a mixture of a) at least one acetamide and b) a synergistically active amount of a lipophilic additive comprising at least one member selected from the group consisting of C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids. 2. The herbicidal composition of claim 1 wherein the ratio (wt/wt) of a) to b) is 90:1 to 1.5:1. 3. The herbicidal composition of claim 1 wherein the acetamide comprises at least one member selected from the group consisting of diphenamid, napropamide, naproanilide, acetochlor, alachlor, butachlor, dimethachlor, dimethenamid, dimethenamid-P, fentrazamide, metazachlor, metolachlor, pethoxamid, pretilachlor, propachlor, propisochlor, S-metolachlor, thenylchlor, flufenacet and mefenacet. 4. The herbicidal composition of claim 3 wherein the acetamide comprises a mixture of the (S) and (R) isomers of metolachlor in the ratio of 50-100% (S) to 50-0% (R). 5. The herbicidal composition of claim 1 wherein the lipophilic additive is saturated. 6. The herbicidal composition of claim 5 wherein the lipophilic additive comprises stearic acid. 7. The herbicidal composition of claim 5 wherein the lipophilic additive comprises stearyl alcohol. 8. The herbicidal composition of claim 1 wherein the lipophilic additive comprises a hydrocarbon fluid. 9. The herbicidal composition of claim 8 wherein the hydrocarbon fluid contains less than 2.0 wt. % aromatic component. 10. The herbicidal composition of claim 8 wherein the hydrocarbon fluid contains greater than 50 wt. % paraffins. 11. The herbicidal composition of claim 8 wherein 50-100% wt. % of the paraffins present in the hydrocarbon fluid are iso-paraffins. 12. The herbicidal composition of claim 11 wherein 90-100% wt. % of the paraffins present in the hydrocarbon fluid are iso-paraffins. 13. The herbicidal composition of claim 8 wherein at least 95 wt. % of the carbon structures of the hydrocarbon fluids have a carbon number distribution of from C13 to C20. 14. The herbicidal composition of claim 8 wherein the hydrocarbon fluid comprises a synthetic iso-paraffin fluid. 15. The herbicidal composition of claim 1 further comprising a safener. 16. The herbicidal composition of claim 1 further comprising a co-herbicide. 17. The herbicidal composition of claim 1 wherein the herbicidal composition is a soil-applied, preemergent herbicidal composition. 18. A method of controlling undesired plant growth in the presence of cultivated plants, which comprises treating the cultivated plants, plant parts, seed or the locus thereof with a herbicidally effective amount of the herbicidal composition according to claim 1. 19. The method according to claim 18, wherein the cultivated plants are selected from the group consisting of cereals, rape, sugar beet, sugar cane, rice, maize, plantation crops, soybeans and cotton. 20. The method of claim 18 wherein the cultivated plants comprise transgenic plants or herbicidally tolerant plants created by conventional breeding. 21. The method according to claim 18 wherein the herbicidally effective amount of the composition is applied to the soil as a preemergent herbicide. 22. The method of claim 18, which further comprises treating the cultivated plants, plant parts, seed or the locus thereof with a co-herbicide. 23. The method of claim 22, which comprises treating the cultivated plants, plant parts, seed or the locus thereof at separate times with the herbicidal composition and the co-herbicide. 24. The method of claim 18, which further comprises treating the cultivated plants, plant parts, seed or the locus thereof with a safener. 25. The method of claim 24, which comprises treating the cultivated plants, plant parts, seed or the locus thereof at separate times with the herbicidal composition and the safener.
BACKGROUND OF THE INVENTION The present invention relates to novel herbicidal synergistic compositions containing a combination of at least one acetamide herbicide and at least one lipophilic additive suitable for selectively controlling weeds in crops of cultivated plants, typically in crops of cereals, rape, sugar beet, sugar cane, rice, maize, plantation crops, soybeans and cotton. The invention further relates to a method for controlling weeds in crops of cultivated plants and to the use of said novel composition therefor. BRIEF SUMMARY OF THE INVENTION Acetamides are a known class of selective herbicides. Acetamides, as used herein, include those classes of herbicides commonly referred to as acetamides as well as chloroacetamides and oxyacetamides. Surprisingly, it has now been found that combinations of at least one acetamide herbicide and at least one lipophilic additive exert a synergistic effect that is able to control the majority of weeds preferably occurring in crops of cultivated plants, without substantial injury to the cultivated plants. Lipophilic additives suitable for use in the present invention include C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids as defined herein. Further, the compositions of the present invention perform more consistently across varying environmental conditions compared to similar formulations absent the lipophilic additive. DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel synergistic composition for the selective control of weeds that, In addition to customary inert formulation excipients, comprises as active ingredients a mixture of a) at least one acetamide herbicide and b) a synergistically effective amount of a lipophilic additive comprising at least one member selected from the group consisting of C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids. Representative acetamide herbicides include diphenamid, napropamide, naproanilide, acetochlor, alachlor, butachlor, dimethachlor, dimethenamid, dimethenamid-P, fentrazamide metazachlor, metolachlor, pethoxamid, pretilachlor, propachlor, propisochlor, S-metolachlor, thenylchlor, flufenacet and mefenacet. As used herein, the term acetamide includes mixtures of the two or more acetamides as well as mixtures of optical isomers of the acetamides. For example, mixtures of the (R) and (S) isomers of metolachlor wherein the ratio of (S)-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide to (R)-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide is in the range of from 50-100% to 50-0%, preferably 70-100% to 30-0% and more preferably 80-100% to 20-0%. The lipophilic additives of the present invention comprise at least one member selected from the group consisting of C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids. In a preferred embodiment, the lipophilic additives are saturated. Preferred fatty acids include stearic acid. A preferred fatty alcohol is stearyl alcohol. The hydrocarbon fluids suitable for use as the lipophilic additives of the present invention include mixtures of paraffins, naphthenes and aromatics. Preferably, the hydrocarbon fluids contain less than 2.0 wt. %, more preferably 0.5 wt. % or less, most preferably 0-0.2 wt. % aromatic component. Preferred hydrocarbon fluids contain greater than 50 wt. % paraffins. Preferably 50-100 wt. %, more preferably 90-100 wt. % of the paraffins present are iso-paraffins. Preferably, at least 95 wt. %, more preferably at least 98 wt. %, of the carbon structures of the hydrocarbon fluids have a carbon number distribution from C13 to C20. Preferred hydrocarbon fluids have an initial boiling point of at least 200° C., preferably at least 250° C. and a final boiling point of 325° C. or less. Preferred hydrocarbon fluids for use in the present invention contain less than 2.0 wt. %, more preferably 0.5 wt. % or less, most preferably 0-0.2 wt. % aromatic component; greater than 50 wt. % paraffins and 50-100 wt. %, more preferably 90-100 wt. % of the paraffins present are iso-paraffins. More preferred hydrocarbon fluids for use in the present invention contain less than 2.0 wt. %, more preferably 0.5 wt. % or less, most preferably 0-0.2 wt. % aromatic component; greater than 50 wt. % paraffins; 50-100 wt. %, more preferably 90-100 wt. % of the paraffins present are iso-paraffins and at least 95 wt. %, more preferably at least 98 wt. %, of the carbon structures of the hydrocarbon fluids have a carbon number distribution from C13 to C20. Still more preferred hydrocarbon fluids for use in the present invention contain less than 2.0 wt. %, more preferably 0.5 wt. % or less, most preferably 0-0.2 wt. % aromatic component; greater than 50 wt. % paraffins; 50-100 wt. %, more preferably 90-100 wt. % of the paraffins present are Iso-paraffins; at least 95 wt. %, more preferably at least 98 wt. %, of the carbon structures of the hydrocarbon fluids have a carbon number distribution from C13 to C20; an initial boiling point of at least 200° C., preferably at least 250° C. and a final boiling point of 325° C. or less. Particularly preferred hydrocarbon fluids for use as the lipophilic additives of the present invention are synthetic iso-paraffin fluids such as Isopar® V available from Exxon Chemical Company. The lipophilic additives of the present invention are not generally thought of as herbicides. Therefore, it is entirely surprising that the combination of the acetamides with the lipophilic additives exceeds the expected action against the weeds to be controlled and thus in particular enhances the activity range of the acetamides in two respects: On the one hand, the concentration of the acetamide herbicide is reduced while the effectiveness of said herbicide is retained. On the other hand, the novel herbicidal composition also achieves a high degree of weed control where the single compounds have become no longer agriculturally effective at low concentrations. The consequence is a substantial broadening of the activity spectrum against weeds and an additional increase in the selectivity for the cultivated plants that is necessary and desirable in the event of unintentional overapplication of herbicide. In addition, the novel composition permits greater flexibility with respect to subsequent crops while retaining the excellent control of weeds in crops of cultivated plants. The composition of the invention may be used against a large number of agronomically important weeds, including Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Phaseolus, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum halepense, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Panicum, Brachiara, Viola, and Veronica. For purposes of the present invention, the term “weeds” includes undesirable crop species such as volunteer crops. The compositions of the invention are preferably used in soil-applied preemergence applications. The composition of the invention is suitable for selectively controlling weeds in crops of cultivated plants, typically cereals, rape, sugar beet, sugar cane, rice, maize, plantation crops and in crops of soybeans and cotton. Crops of cultivated plants will also be understood as meaning those crops that have been made tolerant to herbicides or classes of herbicides by conventional plant breeding or genetic engineering methods (for example transgenic crops). The composition of the invention contains the acetamide herbicide and the lipophilic additive in a ratio (wt/wt) of 90:1 to 1.5:1. Preferred ratios of the acetamide to the lipophilic additives are 60:1 to 5:1. It has been found that particularly effective compositions are those of metolachlor including mixtures containing the optical isomers of metolachlor, for example S-metolachlor, with the hydrocarbon fluid lipophilic additives. Preferred acetamides include mixtures of metolachlor (S) and (R) isomers wherein the ratio of (S)-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide to (R)-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide is in the range of from 50-100% to 50-0%, preferably 70-100% to 30-0% and more preferably 80-100% to 20-0%. The compositions of the present invention may contain co-herbicides. Co-herbicides suitable for use in the present invention include PSII inhibitors, PSI inhibitors, ALS inhibitors, HPPD inhibitors, ACCase inhibitors, Cell Division inhibitors, PDS inhibitors, lipid metabolism inhibitors and PPGO inhibitors. Representative co-herbicides include atrazine, halosulfuron-methyl, terbuthylazine, dicamba, fluthiacet-methyl, pyridate, butafenacil, NOA 402989, terbutryn, simazine, prosulfuron, primisulfuron, imazapyr, sethoxydim, flufenacet, cloransulam, diclosulam, metribuzin, isopropazol, isoxaflutole, iodosulfuron-methyl-sodium, isoxachlortole, sulfentrazone, mesotrione, flurtamone, sulcotrione, azafenidin, metosulam, flumetsulam, florasulam, pendimethalin, trifluralin, MON4660, 8-(2,6-diethyl-4-methyl-phenyl)-tetrahydropyrazolo[1,2-d][1,4,5]oxadiazepine-7,9-dione, 4-Hydroxy-3-[2-(2-methoxyethoxymethyl)-6-trifluoromethylpyridine-3-carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, flumiclorac-pentyl, bentazone, AC304415, bromoxynil, BAS145138, nicosulfuron, cyanazine, rimsulfuron, imazaquin, amitrole, thifensulfuron, thifensulfuron-methyl, bilanafos, metobenzuron, diuron, MCPA, MCPB, MCPP, 2,4-D, diflufenzopyr, clopyralid, clopyralid-olamine, fluroxypyr, quinmerac, dimethametryn, esrocarb, pyrazosulfuron-ethyl, benzofenap, clomazone, carfentrazone-ethyl, butylate, EPTC, aclonifen, fomesafen, flumioxazin, paraquat, glyphosate, glufosinate, S-glufosinate, sulfosate, imazamox, imazethapyr and the agriculturally acceptable salts and esters thereof. It has been found that particularly effective mixtures of active ingredients include the following combinations: acetamide+atrazine, acetamide+glyphosate, acetamide+atrazine+glyphosate, acetamide+metribuzin, acetamide+mesotrione, acetamide+prometryn, acetamide+quinmerac, acetamide+dimethametryn, acetamide+esprocarb, acetamide+pyrazosulfuron-ethyl, acetamide+benzofenap, acetamide+pendimethalin, acetamide+terbuthylazine and acetamide+4-Hydroxy-3-[2-(2-methoxyethoxymethyl)-6-trifluoromethylpyridine-3-carbonyl]-bicyclo[3.2.1]oct-3-en-2-one. Preferred amongst these combinations of active ingredients are those wherein the acetamide comprises at least one member selected from the group consisting of acetochlor, alachlor, dimethenamid, dimethenamid-P, metolachlor, S-metolachlor, fentrazamide, pethoxamid, flufenacet and mefenacet. In addition to the acetamide herbicide, the lipophilic additive and optionally at least one compound from amongst the co-herbicides set forth above, the synergistic compositions according to the invention may contain at least one safener. Suitable safeners include benoxacor, cloquintocet, dichlormid, fenclorim, flurazole, fluxofenim, furilazole, mefenpyr and the agriculturally acceptable salts and esters thereof such as cloquintocet-mexyl and mefenpyr-diethyl. Particulary preferred safeners include benoxacor. The abovementioned acetamides, co-herbicides and safeners are described and characterized in “The Pesticide Manual”, Twelfth Edition, 2000, Crop Protection Publications or in other customary agronomical publications. The rate of application can vary within a wide range and will depend on the nature of the soil, the type of application (application to the seed furrow; no-tillage application etc.), the crop plant, the weed to be controlled, the prevailing climatic conditions, and on other factors governed by the type and timing of application and the target crop. In general, the mixture of active ingredients according to the invention can be applied in a rate of application of 300 to 4,000 g of mixture of active ingredients/ha. The co-herbicides and safeners may be applied to the plants, plant parts, seeds or locus thereof at the same time or at separate times as the acetamide/lipophilic additive mixtures of the present invention. The present invention is also directed to a method of controlling undesired plant growth in the presence of cultivated plants, which comprises treating the cultivated plants, plant parts, seed or the locus thereof with a herbicidally effective amount of at least one acetamide herbicide and at least one lipophilic additive as described herein. In the composition according to the invention, the weight ratio of the acetamide to at least one compound from amongst the co-herbicides set forth above is from 1:10 to 1:0.001. If the composition comprises a safener, the weight ratio of acetamide to safener is preferably 5:1 to 30:1. The composition of the present invention can be formulated in a variety of ways. For example, it can take the physical form of a dustable powder, gel, a wettable powder, a water dispersible granule, a water-dispersable or water-foaming tablet, a briquette, an emulsifiable concentrate, a microemulsifiable concentrate, an oil-in-water emulsion, a water-in-oil emulsion, a dispersion in water, a dispersion in oil, a suspoemulsion, a soluble liquid (with either water or an organic solvent as the carrier), an impregnated polymer film, or other forms known in the art. These formulations may be suitable for direct application or may be suitable for dilution prior to application, said dilution being made either with water, liquid fertilizer, micronutrients, biological organisms, oil or solvent. The compositions are prepared by admixing the active Ingredient with adjuvants including diluents, extenders, carriers, and conditioning agents to provide compositions in the form of finely-divided particulate solids, granules, pellets, solutions, dispersions or emulsions. Thus, it is believed that the active ingredient could be used with an adjuvant such as a finely-divided solid, a mineral oil, a liquid of organic origin, water, various surface active agents or any suitable combination of these. The active ingredient may also be contained in very fine microcapsules in polymeric substances. Microcapsules typically contain the active material enclosed in an inert porous shell which allows escape of the enclosed material to the surrounds at controlled rates. Encapsulated droplets are typically about 0.1 to 500 microns in diameter. The enclosed material typically constitutes about 25 to 95% of the weight of the capsule. The active ingredient may be present as a monolithic solid, as finely dispersed solid particles in either a solid or a liquid, or it may be present as a solution in a suitable solvent. Shell membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, other polymers familiar to one skilled in the art, chemically-modified polymers and starch xanthates. Alternative very fine microcapsules may be formed wherein the active ingredient is dispersed as finely divided particles within a matrix of solid material, but no shell wall surrounds the microcapsule. Suitable agricultural adjuvants and carriers that are useful in preparing the compositions of the invention are well known to those skilled in the art. The formulations, i.e., the acetamides and the lipophilic additives and where applicable the agents, preparations, or compositions containing one or more than one liquid or solid formulation excipient are prepared in a known manner, e.g., by homogeneously mixing and/or grinding the compounds with said formulation assistants, typically liquid carriers or solid carriers. The compositions of the present invention may be prepared by incorporating the lipophilic additive into a pre-mix or concentrate with the acetamide or adding the lipophilic additive and the acetamide separately as a tank mix when the product is diluted into, for example, water prior to application. Liquid carriers that can be employed include water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropyleneglycol dibenzoate, diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octyl amine acetate, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, propylene glycol mono-methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerine, N-methyl-2-pyrrolidinone, and the like. Water is generally the carrier of choice for the dilution of concentrates. Suitable solid carriers include talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, Fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like such as described in the CFR 180.1001. (c) & (d). A broad range of surface-active agents are advantageously employed in both solid and liquid compositions, especially those designed to be diluted with carrier before application. Depending on the herbicides to be formulated, suitable surface-active compounds are nonionic, cationic and/or anionic surfactants and surfactant mixtures having good emulsifying, dispersing and wetting properties. Examples of suitable surfactants and surfactant mixtures are given in U.S. Pat. Nos. 5,958,835; 6,063,732 and 6,165,939, the disclosures of which are incorporated fully herein by reference. Also the surfactants customarily used for the art of formulation and described, inter alia, in “Mc Cutcheon's Detergents and Emulsifiers Annual” MC Publishing Corp., Ridgewood N.J., 1981, Stache, H., “Tensid-Taschenbuch” (Handbook of Surfactants), Carl Hanser Verlag, Munich/Vienna, 1981, and M. and J. Ash, “Encyclopedia of Surfactants”, Vol I-III, Chemical Publishing Co., New York, 1980-81 are suitable for manufacture of the herbicides according to the invention. The anionic surfactants suitable for use in the invention may be any known in the art. The anionic surfactants may be polyarylphenol polyalkoxyether sulfates and/or phosphates; C8-18 alcohol polyalkoxyether phosphates, carboxylates, and/or citrates; alkyl benzenesulfonic acids; C8-20 alkyl carboxylates including fatty acids; C8-20 alcohol sulfates; C8-20 alcohol phosphate mono- and diesters; C8-20 alcohol and (C8-20 alkyl)phenol polyoxyethylene ether carboxylates, sulfates and sulfonates; C8-20 alcohol and (C8-20 alkyl)phenol polyoxyethylene phosphate mono- and diesters; C8-20 alkylbenzene sulfonates, naphthalene sulfonates and formaldehyde condensates thereof; lignosulfonates; C8-20 alkyl sulfosuccinates and sulfosuccinamates; C8-20 acyl glutamates, sarcosinates, isethionates and taurates; water-soluble soaps and mixtures thereof. Exemplary polyarylphenol polyalkoxyether sulfates and phosphates include polyarylphenol polyethoxyether sulfates and phosphates, polyarylphenol polypropoxyether sulfates and phosphates, polyarylphenol poly(ethoxy/propoxy)ether sulfates and phosphates, and salts thereof. The term “aryl” includes, for example, phenyl, tolyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl, styryl, pyridyl, quinolinyl, and mixtures thereof. Exemplary polyarylphenol polyethoxyether sulfates and phosphates include distyrylphenol polyethoxyether sulfates and phosphates, and tristyrylphenol polyethoxyether sulfates and phosphates. The polyarylphenol polyalkoxether sulfates and phosphates may have a degree of alkoxylation (e.g., ethoxylation) of between about 1 and about 50, preferably between about 2 and about 40, more preferably between about 5 and about 30. Commercially available polyarylphenol polyalkoxyether sulfates and phosphates include, for example, SOPROPHOR® 4 D 384 (Rhodia Corporation, Cranbury, N.J.) (tristyrylphenol (EO)16 sulfate ammonium salt), SOPROPHOR® 3 D 33 (Rhodia Corporation, Cranbury, N.J.) (tristyrylphenol (EO)16 phosphate free acid), SOPROPHOR® FLK (Rhodia Corporation, Cranbury, N.J.) (tristyrylphenol (EO)16 phosphate potassium salt), DEHSCOFIX® 904 (Albright & Wilson Americas, Inc., Glen Allen, Va.) (tristyrylphenol polyethoxylated ether phosphate triethanolamine salt) and SOPROPHOR® RAM/384 (tristyrylphenol polyethoxylated ether sulfate neutralized with polyethoxylated oleylamine). In other embodiments, the polyarylphenol polyalkoxyether sulfates and phosphates may be mono-arylphenol polyalkoxyether sulfates and phosphates, such as styrylphenol polyethoxyether sulfates and phosphates. Exemplary C8-18 alcohol polyethoxyether phosphates, carboxylates and citrates include STEPFAC® 8180 (Stepan Corporation, Northfield, Ill.) (tridecylalcohol (EO)3 phosphate), STEPFAC® 8181 (Stepan Corporation, Northfield, Ill.) (tridecylalcohol (EO)6 phosphate), STEPFAC® 8182 (Stepan Corporation, Northfield, Ill.) (tridecylalcohol (EO)12 phosphate), EMCOL® CN-6 (CK Witco Corporation, Greenwich, Conn.) (tridecylalcohol (EO)6 carboxylate). The C8-18 alcohol polyethoxyether phosphates, carboxylates and citrates may have a degree of ethoxylation of between about 1 and about 25, preferably between about 1 and about 20. Exemplary alkylbenzene sulfonic acids and salts thereof Include dodecylbenzene sulfonic acid, and metal (for example sodium or calcium), ammonia or amine salts of the alkylbenzene sulfonic acids, including dodecylbenzene sulfonic acid. Amine neutralized versions include primary amines, diamines, triamines and alkanol amines. Additional preferred anionic surfactants include (C8-12 alkyl)phenol polyoxyethylene ether sulfates, and (C8-12 alkyl)phenol polyoxyethylene phosphate mono- and diesters, accompanied in each case by monovalent counterions. In one embodiment the monovalent counterion for a (C8-12 alkyl)phenol polyoxyethylene ether sulfate or a (C8-12 alkyl)phenol polyoxyethylene phosphate is a protonated polyoxyethylene C12-20 alkylamine surfactant. More specifically, polyoxyethylene tallowamine salt of a nonylphenol polyoxyethylene ether sulfate, nonylphenol polyoxyethylene phosphate, and a blend of such nonylphenol polyoxyethylene phosphate with polyoxyethylene tallowamine. Suitable water-soluble soaps are the alkali metal salts, alkaline earth metal salts, ammonium salts or substituted ammonium salts of higher fatty acids (C10-C22), e.g. the sodium or potassium salts of oleic or stearic acid, or of natural fatty acid mixtures which can be obtained, inter alia, from coconut oil or tallow oil. Further suitable soaps are also the fatty acid methyl taurin salts. The anionic surfactants are optionally neutralized with a basic compound. The basic compounds may be any known in the art that are capable of neutralizing the anionic surfactants. Basic compounds include, for example, inorganic bases, C8-18 alkyl amine polyalkoxylates, alkanol amines, alkanol amides, and mixtures thereof. Exemplary inorganic bases include ammonium hydroxides, sodium hydroxides, potassium hydroxides, calcium hydroxides, magnesium hydroxides, zinc hydroxides, and mixtures thereof. The C8-18 alkyl amine polyalkoxylates may be, for example, C8-18 alkyl amine polypropoxylates and/or C8-18 alkyl amine polyethoxylates. Exemplary C8-18 alkyl amine polyalkoxylates include tallow amine polyalkoxylates, cocoamine polyalkoxylates, oleylamine polyalkoxylates, and stearylamine polyalkoxylates. The C8-18 alkyl amine polyethoxyates may have from about 2 to about 50 moles of ethylene oxide per molecule, more preferably from about 2 to about 20 moles of ethylene oxide per molecule. Exemplary C8-18 alkyl amine polyethoxylates include tallow amine ethoxylates (2 moles EO or 8 moles EO), cocoamine ethoxylates, oleylamine ethoxylates, and stearylamine ethoxylates. Exemplary alkanol amines include diethanol amine and triethanol amine. Exemplary alkanol amides include oleic diethanolamide and linoleic diethanolamide, and the diethanolamides of other C8-18 fatty acids. The anionic surfactants may be neutralized to the inflection point in the titration curve with one or more basic compounds. One skilled in the art will recognize that the pH of the inflection will vary according to the acid and base strengths of the components being used, but will generally fall within the range of about pH 4 to about pH 9, preferably about pH 5 to about pH 7. For example, the compositions of the invention may comprise at least one polyarylphenol polyalkoxyether sulfate, polyarylphenol polyalkoxyether phosphate, C8-18 alcohol polyalkoxyether phosphates, C8-18 alcohol polyalkoxyether carboxylates, C8-18 alcohol polyalkoxyether citrates, and/or alkyl benzenesulfonic acids neutralized to the inflection point in the titration curve with one or more basic compounds. The basic compound used to neutralize the different anionic surfactants may be the same or different. In still other embodiments, the compositions of the invention comprise mixtures of at least two anionic surfactants selected from polyarylphenol polyalkoxyether sulfates, polyarylphenol polyalkoxyether phosphates, C8-20 alkyl carboxylates including fatty acids, C8-20 alcohol sulfates, C8-20 alcohol phosphate mono- and diesters, C8-20 alcohol and (C8-20 alkyl)phenol polyoxyethylene ether carboxylates, sulfates and sulfonates, C8-20 alcohol and (C8-20 alkyl)phenol polyoxyethylene phosphate mono- and diesters, C8-20 alkylbenzene sulfonates, naphthalene sulfonates and formaldehyde condensates thereof, lignosulfonates, C8-20 alkyl sulfosuccinates and sulfosuccinamates, and/or C8-20 acyl glutamates, sarcosinates, isethionates and taurates neutralized to the inflection point in the titration curve with one or more basic compounds. The basic compound used to neutralize the different anionic surfactants may be the same or different. When neutralized, the anionic surfactants and basic compounds are preferably used in a ratio of about 1:1. One basic compound may be used to neutralize one or more anionic surfactants. In other embodiments, more than one basic compound may be used to neutralize one or more anionic surfactants. Exemplary nonionic surfactants include ethylene oxide-propylene oxide block copolymers; ethylene oxide-butylene oxide block copolymers; C2-6 alkyl adducts of ethylene oxide-propylene oxide block copolymers; C2-6 alkyl adducts of ethylene oxide-butylene oxide block copolymers; polypropylene glycols; polyethylene glycols; polyarylphenol polyethoxy ethers; polyalkylphenol polyethoxy ethers; polyglycol ether derivatives of aliphatic or cycloaliphatic alcohols or of saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols; mono-, di- and tri(C12-20 alkyl)esters of polyoxyethylene sorbitan; alkoxylated vegetable oils; alkoxylated acetylenic diols; alkyl polyglycosides and mixtures thereof. The ethylene oxide-propylene oxide block copolymers may comprise alkyl or alkyphenol ether bases, such as butyl ether, methyl ether, propyl ether, ethyl ether, or mixtures thereof. Commercially available nonionic surfactants include, for example, TOXIMUL® 8320 (Stepan Corporation, Northfield, Ill.) (butyl ether derivative of EO/PO block copolymer), WITCONOL® NS-500LQ (CK Witco Corporation, Greenwich, Conn.) (butyl ether derivative of EO/PO block copolymer) and WITCONOL® NS-108LQ (CK Witco Corporation, Greenwich, Conn.) (nonylphenol ether derivative of EO/PO block copolymer). Any alkyl polyglycoside known in the art can be used in the invention. The alkyl polyglycoside of the invention may have formula (I): R1O(R2O)b(Z)a (I) R1 is a monovalent organic radical having from about 6 to about 30 carbon atoms. R1 is preferably a C8-22 alkyl or alkenyl group, more preferably a C8-11 alkyl group. R2 is a divalent alkylene radical having from about 2 to about 4 carbon atoms. R2 is preferably ethylene or propylene, more preferably ethylene. b is 0 to about 100. b is preferably 0 to about 12, more preferably 0. Z is a saccharide residue having about 5 to about 6 carbon atoms. Z may be glucose, mannose, fructose, galasctose, talose, gulose, altrose, allose, apiose, gallose, idose, ribose, arabinose, xylose, lyxose, or a mixture thereof. Z is preferably glucose. a is an integer from 1 to about 6. a is preferably from 1 to about 3, more preferably about 2. Preferred compounds of formula (I) are compounds of formula (II): where n is the degree of polymerization and is from 1 to 3, preferably 1 or 2, and R5 is a branched or straight chain alkyl group having from 4 to 18 carbon atoms or a mixture of alkyl groups having from 4 to 18 carbon atoms. Exemplary alkyl polyglycosides include APG® 325 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 9 to 11 carbon atoms and has an average degree of polymerization of 1.6), PLANTAREN® 2000 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 8 to 16 carbon atoms and has an average degree of polymerization of 1.4), PLANTAREN® 1300 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 12 to 16 carbon atoms and has an average degree of polymerization of 1.6), AGRIMUL® PG 2067 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 8 to 10 carbon atoms and has an average degree of polymerization of 1.7), AGRIMUL® PG 2069 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 9 to 11 carbon atoms and has an average degree of polymerization of 1.6), AGRIMUL® PG 2076 (Cognis Corporation, Cincinnati, Ohio) (an alkyl polyglycoside in which the alkyl group contains 8 to 10 carbon atoms and has an average degree of polymerization of 1.5), ATPLUS® 438 (Uniqema, Inc., Wilmington, Del.) (an alkylpolysaccharide in which the alkyl group contains 9 to 11 carbon atoms), and ATPLUS® 452 (Uniqema, Inc., Wilmington, Del.) (an alkylpolysaccharide in which the alkyl group contains 8 to 10 carbon atoms). Cationic surfactants are preferably quaternary ammonium salts carrying, as N-substituent, at least one C8-C22 alkyl radical and, as further substituents, unsubstituted or halogenated lower alkyl, benzyl or hydroxy-lower alkyl radicals. The salts are preferably in the form of halides, methyl sulfates or ethyl sulfates, for example stearyl trimethylammonium chloride or benzyl bis(2-chloroethyl)ethylammonium bromide. The amount of surfactant(s) depends on the particular active ingredients selected for the composition and the absolute and relative amounts of these desired. Suitable amounts of stabilizing system components selected from the classes or specific examples provided herein can be determined by routine experimentation, the test being that substantially no phase separation, sedimentation or flocculation Is exhibited by the composition following storage at 20-25° C. for a period of 24 hours, or, for preferred embodiments, following a longer period of storage over a broader range of temperatures as indicated above. Typically the total concentration of all surfactants in the composition as a whole is about 1% to about 10% by weight, for example about 1.5% to about 5% by weight, excluding the weight of counterions, if present. In computing relative amounts of surfactants present in a composition, the weight of water or other diluent supplied with a surfactant, if known, should be excluded. For example, WITCONATE® 79S of CK Witco Corporation contains 52% dodecylbenzene sulfonic acid triethanolamine salt. In a composition containing 1% WITCONATE® 79S, the concentration of dodecylbenzene sulfonic acid triethanolamine salt should be computed as 0.52%. Other adjuvants commonly utilized in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emolients, lubricants, sticking agents, dispersing agents, thickening agents, freezing point depressants, antimicrobial agents, and the like. The compositions can also contain other compatible components, for example, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like. The herbicidal compositions will usually comprise from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of a mixture of the acetamide and the lipophilic additive, from 1 to 99.9% by weight of a solid or liquid formulation assistant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant. Whereas it is customarily preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations. The compositions may also comprise further ingredients, such as: stabilisers, e.g. where appropriate epoxidised vegetable oils (epoxidised coconut oil, rapeseed oil, or soybean oil); antifoams, typically silicone oil; preservatives; viscosity regulators; binders; and tackifiers; as well as fertilisers or other chemical agents. Particularly preferred formulations are made up as follows (%=per cent by weight; compound mixture means a mixture of the acetamide, the lipophilic additive and any co-herbicide, if present): Emulsifiable Concentrates: Compound mixture: 1 to 95%, preferably 60 to 90% Surfactant: 1 to 30%, preferably 5 to 20% Liquid carrier: 1 to 80%, preferably 1 to 35% Dusts: Compound mixture: 0.1 to 10%, preferably 0.1 to 5% Solid carrier: 99.9 to 90%, preferably 99.9 to 99% Suspension Concentrates: Compound mixture: 5 to 75%, preferably 10 to 50% Water: 94 to 24%, preferably 88 to 30% Surfactant: 1 to 40%, preferably 2 to 30% Wettable Powders: Compound mixture: 0.5 to 90%, preferably 1 to 80% Surfactant: 0.5 to 20%, preferably 1 to 15% Solid carrier: 5 to 95%, preferably 15 to 90% Granulates: Compound mixture: 0.1 to 30%, preferably 0.1 to 15% Solid carrier: 99.5 to 70%, preferably 97 to 85% BIOLOGICAL EXAMPLES The synergistic effect of the combinations of the acetamides with the lipophilic additives is demonstrated in the following Examples. The formulations tested are set forth in Table 1. All formulations contained benoxacor safener in a ratio of S-metolachlor to benoxacor of 20:1. The formulation types for the test formulations were either emulsifiable concentrates (EC) or oil-in-water emulsions (EW) and were prepared by techniques known to one skilled in the art. TABLE 1 Formulations Wt. % Lipophilic Wt. % Formulation Surfactant Example Active Ingredient A.I. Additive Additive Type System 1 S-metolachlor 68.5 Isopar ® V 12.4 EC A 2 S-metolachlor 55.2 Stearic acid 1.8 EC B 3 S-metolachlor 43.4 Stearyl alcohol 5.0 EW C Std* S-metolachlor 82.4 None — EC A A: 45% nonylphenol polyoxyethylene ether sulfate, polyoxyethylene tallowamine salt 25% polyoxyethylene polyoxypropylene nonylphenol ether 30% aromatic petroleum hydrocarbon B: 50% polyoxyethylene lauryl alcohol ether 50% polyoxyethylene polyoxypropylene nonylphenol ether C: 50% polyoxyethylene nonylphenol ether 32% dodecylbenzenesulfonic acid, triethanolamine salt 18% water Seeds of test species Echinochloa crus-galli were sown in plastic pots in a standard soil. Pots were immediately watered and placed in a greenhouse under controlled growing conditions. Between 18 and 24 hours after seeding the soil surface was sprayed with aqueous solutions of the test formulations at doses ranging between 3.75 and 150 g ai/ha at an application volume of 150 l/ha. Pots were subsequently maintained in a greenhouse under controlled growing conditions. After a test period of 12 to 14 days, growth of the test species was evaluated. Plant growth in each pot was visually compared to plant growth in pots that were not sprayed with a test solution. Herbicidal activity was recorded on a scale of 0 to 100: 100% means complete damage of test species, 0% means no damage. A value of 90% represents good herbicidal action. Herbicidal activity data were used to calculate a linear regression plot of herbicidal activity against the log of herbicide dose for each test formulation. From the linear regression analysis, the herbicide dose (g ai/ha) required for 90% damage of the test species (ED90) was calculated for each test formulation. The herbicidal activity of each test formulation was compared to the herbicidal activity of a standard formulation (that is, one not containing a lipophilic additive according to the present invention) applied in the same greenhouse test by calculating the ratio (ED90 for the standard formulation/ED90 for test formulation). When the value of the activity ratio is>1.0 then the test formulation has greater herbicidal activity than the standard formulation. The Performance Factor is the average of the above-described ratios over the number of trials indicated in Table 2 as (#). TABLE 2 Pre-emergent herbicidal activity of test formulations Lipophilic Performance Example Additive Factor 1 Isopar ® V 1.24 (5) 2 Stearic acid 1.12 (6) 3 Stearyl 1.21 (3) alcohol Std* None 1 It is clear, upon examination of Table 2 that the compositions of the present invention exhibit superior performance compared to the standard formulation as evidenced by the Performance Factors greater than 1. Although only a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to novel herbicidal synergistic compositions containing a combination of at least one acetamide herbicide and at least one lipophilic additive suitable for selectively controlling weeds in crops of cultivated plants, typically in crops of cereals, rape, sugar beet, sugar cane, rice, maize, plantation crops, soybeans and cotton. The invention further relates to a method for controlling weeds in crops of cultivated plants and to the use of said novel composition therefor.
<SOH> BRIEF SUMMARY OF THE INVENTION <EOH>Acetamides are a known class of selective herbicides. Acetamides, as used herein, include those classes of herbicides commonly referred to as acetamides as well as chloroacetamides and oxyacetamides. Surprisingly, it has now been found that combinations of at least one acetamide herbicide and at least one lipophilic additive exert a synergistic effect that is able to control the majority of weeds preferably occurring in crops of cultivated plants, without substantial injury to the cultivated plants. Lipophilic additives suitable for use in the present invention include C13-C20 fatty acids, C13-C20 fatty alcohols and hydrocarbon fluids as defined herein. Further, the compositions of the present invention perform more consistently across varying environmental conditions compared to similar formulations absent the lipophilic additive. detailed-description description="Detailed Description" end="lead"?
20050609
20120117
20051020
71629.0
0
PRYOR, ALTON NATHANIEL
HERBICIDAL COMPOSITION
UNDISCOUNTED
0
ACCEPTED
2,005
10,517,843
ACCEPTED
Craniofacial implant
A composite surgical implant that is made of a planar sheet of a thermoplastic resin that includes a top surface (400), a bottom surface (410), and a surgical grade metal mesh (405) contained therein. The implant may be bent by hand, wherein upon the displacement of the implant, the implant will generally maintain the shape to which it has been displaced.
1. A composite surgical implant comprising a planar sheet of a thermoplastic resin having a top surface and a bottom surface, and a surgical grade metal mesh contained therein, and said implant is able to be bent or displaced by manipulation by hand, wherein upon the displacement of said implant, said implant will generally maintain the shape to which it has been displaced. 2. The implant recited in claim 1 wherein said metal comprises titanium. 3. The implant recited in claim 1 wherein said top surface further comprises a smooth barrier surface. 4. The implant recited in claim 3, wherein said bottom surface comprises a smooth barrier surface. 5. The implant recited in claim 3 wherein said bottom surface comprises a porous surface. 6. The implant recited in claim 5 wherein the pores of said porous surface are sized to allow for fibrovascular ingrowth. 7. The implant as recited in claim 1 wherein said thermoplastic resin comprises polyethylene. 8. The implant as recited in claim 5 wherein said porous surface comprising high density polyethylene. 9. The implant as recited in claim 1, further comprising porous surfaces to allow for fibrovascular ingrowth. 10. The implant recited in claim 1 further comprising means for attachment to bone. 11. The implant as recited in claim 9 wherein said means comprise openings in said mesh that will receive and engage the head of a surgical screw or surgical bone anchor. 12. A method of making a surgical implant comprising placing a metallic mesh material in the bottom of a mold introducing thermoplastic resin fines into said receptacle to allow said fines to fill the bottom of said mold and the interstitial spaces of the said mesh, placing a sheet of thermoplastic resin over said fines and said mesh, placing a mold top over said sheet and applying heat and pressure to said components contained in said mold to allow said fines to partially melt and to fuse to one another whereby an implant is constructed having a smooth barrier surface and an opposite porous surface. 13. The method of making an implant as recited in claim wherein said first step comprises placing a thin sheet on the bottom surface of the cavity of said mold, whereby the implant created comprises barriers on opposite sides of said mesh. 14. A method of reconstruction of a bone defect comprising, bending a surgical implant having a top and bottom surface comprised of thermoplastic resin and a metallic mesh contained therein to conform to the profile of said defect, and mechanically attaching said implant to bone in proximity with said defect. 15. The method of reconstruction recited in claim 14 wherein said defect is in a human 16. The method of reconstruction recited in claim 14 wherein said defect is on the cranium. 17. The method of reconstruction recited in claim 14 wherein said defect is in the orbit. 18. The method f reconstruction recited in claim 17 wherein said implant further comprises a top smooth barrier surface and a bottom porous surface and said implant is positioned in said orbit with said top smooth barrier surface oriented toward the orbital void. 19. The method of reconstruction as recited in claim 14 wherein said securing step comprises introduction of mechanical fasteners through said mesh of said implant and into said bone tissue. 20. The method of reconstruction as recited in claim 19 wherein said mechanical fasteners comprise surgical screws. 21. The method of reconstruction recited in claim 14 further comprising a step of cutting said implant to conform to the shape of said defect.
The applicant claims the benefit U.S. Application Nos. 60/463,036 and 60/496,684. BACKGROUND OF THE INVENTION Craniofacial and especially orbital wall and floor defects may result from trauma, cancer, resection, or congenital defects. Such defects are typically treated surgically using bone grafts or synthetic implants. Congenital defects or fractures of the complex and relatively thin bone structures surrounding and supporting the human eye present difficult internal bone repair and fixation problems. In instances when the eye is subject to trauma, the margin or rim of the orbit may diffuse the force of the impact. However, compression of the orbital contents sometimes may occur and fracture the relatively fragile orbit floor and/or the lateral and medial orbital walls. Also injury at the lateral orbital rim may produce a fracture within the orbit. When the orbit is fractured standard bone-grafting techniques for orbital reconstruction may not result in predictable eye function and positioning. Often the support of the globe is deficient as a result of under correction of the defect, over correction, or inadequate reconstruction of the orbital volume. Further, the bone graph may be subject to resorption that may result in result in a less than optimal support. The accurate anatomical reconstruction of the bony orbit is essential to maintain normal function and appearance of the eye following orbital fractures. Because most of the bone of the internal orbit surfaces is thin, it is difficult to adequately stabilize the fractured bone fragments without the use of autogenous or alloplastic materials. Autologous bone grafts have been considered an optimal treatment method for orbital floor and wall reconstruction. However, this material is sometimes difficult to obtain and difficult to shape the bone graft material to properly fit within the orbit. There are problems relating to the tissue donor site morbidity. As discussed above, autogenous bone grafts have frequently been used by craniomaxillofacial surgeons for the reconstruction of the internal orbit. Bone may be harvested from the calvarium and other autogenous materials including iliac bone, split rib bone. Cartilage has also been used as a bone graft material. However, autogenous bones sometimes result in an unacceptable amount of resorption. A variety of alloplastic materials have been used for orbital reconstruction and craniofacial applications including, silicone rubber, Teflon, Supramid, tantalum mesh, Vitallium mesh, titanium mesh, polyethylene, and methyl methacrylate Perforated biocompatible metallic strips and metallic panels may be used for rigid internal fixation of fractures in trauma surgery and as a plate material for bone immobilization and stabilization. Metal implants can be used for bone graft support material in reconstructive surgery. Synthetic implant materials have the advantage of no donor site morbidity, ease of use, relative low cost and ready availability. While there are advantages of synthetic implants, some characteristics may be regarded as disadvantages. Silicone rubber has a smooth surface, but does not allow fibrovascular ingrowth into the implant. Further, although it is flexible, it does not readily conform to the profile of the region where it is required or maintain a new shape when shaped to fit a particular location. For example, in connection with the reconstruction of the orbit, a silicone rubber implant is not an attractive option because upon shaping it to the desired profile, it will tend to be biased back to its original shape. While a silicone rubber implant does not maintain its shape, in a case where the soft tissues of the orbit have been traumatized, an implant with a smooth superior surface is desirable to prevent attachment of the tissues to the implant upon healing. Attachment of these tissues to the wall of the implant may result in restriction of movement of the eye, causing diplopia, dizziness, and headaches, as well as a cosmetic anomaly on upgaze, downgaze or lateral gaze. Implants having a porous structure such as porous polyethylene with predetermined pore sizes allow for fibrovascular ingrowth. In some circumstances fibrovascular ingrowth is desirable because it integrates the implant within the tissues, and reduces the possibility that that the synthetic material will be rejected. Further, fibrovascular ingrowth on the inferior or sinus side of the implant, allows for mucosalization of the implant surface, and, since the opposite side of the implant may be a barrier, the sinus is effectively isolated from the soft tissues of the orbit. This arrangement is considered desirable because it increases the ability of the implant to ward off infection and minimizes the chance of a sinus infection from entering through the orbit. Fibrovascular ingrowth is also thought to minimize the chance of implant migration or displacement. Porous polyethylene is somewhat flexible and thin sheets appropriate for orbital floor and wall reconstruction can be bent to an appropriate shape. However, this material tends to return to its original shape. Further, porous polyethylene does not have a smooth superior surface, so it may result in restriction of the orbital tissues due to fibrous ingrowth when used for orbital reconstruction. Pure titanium is the material of choice in craniofacial reconstructive surgery, especially when the implant is intended to be permanent. As an implant material, pure titanium is preferred because its low density and elastic modules are less than some of the stainless steel or cobalt-chromium alloys that have been used as implant materials. Titanium is corrosion resistant and, when provided in thin sheets, is pliable. Titanium implants many be cut and shaped to the appropriate configuration at the time of surgery. Titanium mesh is easily moldable in situ and easily fixed to bone, but does not have smooth surfaces, nor does it allow for fibrovascular ingrowth. An easily molded material is desirable so that the surgeon can create the correct shape to properly reconstruct the orbital walls or orbital floor. Titanium mesh can be molded to the desired shape by hand and it will retain the shape due to the malleability and strength of the titanium material. While there are a number of options for an implant material for orbital reconstruction, there remains a need for a material that is easily moldable by hand and will retain its shape after molding, has a smooth impenetrable surface on one side, and a porous surface on the opposite side, and is made from highly biocompatible materials. Preferably it is desirable to provide an implant that can be trimmed and bent to shape to fit the shape of the orbital wall or orbital floor reconstruction, and placed in the orbit with the smooth surface on the inside, against the periosteum and soft tissues and with the porous side directed toward the sinus region. Further, it would be desirable to provide a material that can be fixed to the orbital bones with surgical screws or to the surrounding tissues with sutures. It is an object of the present invention to provide a unique implant for the repair of orbital defects and fixation of orbital fractures. It is a further object of the invention to provide a unique composite implant structure which can be shaped for use during a surgical procedures relating to the repair of the orbit and be readily cut, reshaped or bent to conform to the orbital walls and affixed to the orbit or the orbital margin. It is another object of the invention to provide an implant structure that forms a barrier between the sinus and the soft tissues of the orbit. It is a further object of the invention to provide a craniofacial implant that may be sued in other applications wherein it is desirable to maintain the shape of the implant. Other objects and advantages of the invention will be apparent from the following summary and detailed description of the orbital repair implant structure of the invention taken with the accompanying drawing figures. SUMMARY OF THE INVENTION The present invention is directed to an improved implant and method of reconstruction of craniofacial defects, and in particular for orbital defects. The implant is a composite structure comprised of a surgical grade metal provided in a planar sheet form that is encased within a thermoplastic resin. In a first embodiment, one surface of the implant is smooth and impervious so that when the implant is placed within the body, it may form a barrier. In an alternative embodiment of the invention, while one side of the implant has a smooth surface, the opposite side of the implant is comprised of porous polyethylene that allows for fibrous tissue ingrowth. In a method of reconstruction, the implant that is described herein is cut and then shaped to conform to the profile of a defect to be treated. The implant is then secured to bony tissue using surgical screws or an alternative mechanical fastener. Because the implant contains a mesh it will maintain its shape. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a top plan view of a first embodiment of an implant according to the invention wherein top side of the implant is a barrier surface. FIG. 2 is a side view in elevation of the first embodiment of the invention showing the barrier surface and the bottom porous surface. FIG. 3 is a bottom view of the first embodiment of the invention. FIG. 4 is a perspective view of the first embodiment of the invention. FIG. 5 is a side sectional view of an implant within a mold used to assemble the invention. FIG. 6. is a top view of a mold depicted in FIG. 5 with the top cover removed. FIG. 7 is a top view of an alternative mold that can be used to create the invention with the top cover removed. FIG. 8 is a side sectional view of the mold depicted in FIG. 7 FIG. 9 is a top view of titanium mesh that may be employed with any of the embodiments of the invention. FIG. 10 is an enlarged view of a section of the titanium mesh depicted in FIG. 9. FIG. 11 is a side sectional view of an implant having opposite barrier surfaces that a center section. FIG. 12 is a side view in elevation of the implant depicted in FIG. 11. FIG. 13 is a side sectional view of the implant depicted in FIGS. 1-3. FIG. 14 depicts a sectional view of a cranial defect. FIG. 15 is a side sectional view of the implant shown in FIGS. 1-3 within a cranial defect. FIG. 16 is yet another embodiment of the invention wherein the implant has opposite barrier surfaces. FIG. 17 is a side view in elevation of the implant depicted in FIG. 16. FIG. 18 is a side sectional view of a further embodiment of the invention wherein the metal mesh is formed with an implant with opposite porous surfaces. FIG. 19 is an exploded view of an implant having three layers. FIG. 20 is a perspective illustration of an implant according to the invention shown in an orbital reconstruction application. DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTS The present invention is directed to novel implants for craniofacial surgery, methods for making said implant and a method of reconstructing orbital and cranial defects with the implants described. As described herein, a preferred application for the implant is for the reconstruction of orbital defects that may have resulted from trauma or disease or birth defects. Other craniofacial applications are also contemplated. Now referring to FIG. 1, a first embodiment of the invention comprises a sheet of titanium mesh 20, with porous polyethylene formed in the interstices of the mesh and completely covering the bottom surface 27 of the implant. A solid sheet of polyethylene film 23 covers the top side of the implant. The mesh 20 provides for strength and serves to retain the shape of the implant in a rigid and fixed position. It should be understood that a mesh as used herein encompass any flat sheet of surgical grade metal that has perforations or passages formed through the sheet. The passages in the sheet help enable the sheet to be shaped or bent in more than one dimension and then retain the desired shape. It is contemplated that the mesh could be formed in a variety of manners including woven screens, or be etched from plates, or be formed from sold plates that are cut and then expanded to form a substrate having passages. The first specific embodiment of the invention is illustrated in FIG. 1 where a smooth barrier material 23 lies on top of the titanium mesh material 20 with porous polyethylene 25 formed in the interstices and under the titanium mesh 20. As best seen in FIG. 4, the top surface 23 of the implant has some transparency so that the mesh 20 may be seen through the polyethylene film layer 23. While FIG. 1 shows the mesh 105 extended to the periphery of the implant, it is contemplated that in some embodiments the mesh may not extend to the edge of the implant structure. In yet other embodiments, the mesh may extend from the implant structure. In this later regard, it may be advantageous to extend the mesh from the implant structure to provide for a metal projection to be employed for the attachment of the implant during the surgical procedure. While in the embodiments depicted herein, the mesh is depicted in the center of the implant structure, it is contemplated that the mesh may be positioned adjacent to the top thin sheet layer or other locations within the implant depending on the respective application. Now referring to FIG. 5, to manufacture the implant as depicted in FIG. 1, a mesh 40 is selected and positioned on tabs 50 that project form the sidewalls 45 and 48 of the bottom of the mold section 42. Next, polyethylene fines are introduced into the mold so that they fill the void below the mesh 40, the spaces between the titanium mesh 40 and cover the top surface of mesh 40. Last, a thin sheet or continuous film of solid polyethylene 55 is placed on the top of a suitable mold. The solid barrier sheet 55 extends beyond the edges of the cavity section of the mold and extends to the mold surface 63 thereby maintaining the sheet on one side of the mold. FIG. 7 depicts an alternative arrangement for a mold wherein the mesh may be received on a shelf 70 that is suspended over the cavity using a shelf 70 around the mold cavity that holds the mesh sheet in position. As best seen in FIG. 8 shelf region 70 that extend into the void area 78 of mold 75 supports the edges of the mesh. A polyethylene sheet 90 is positioned above polyethylene fines 92 that fill the cavity 78. The passages through the mesh are identified by reference number 52. It should be understood that the dimensions, including the depth of the cavity from top surface 85 of bottom mold section 75, and the length and width of the mold may be altered depending on the particular application intended for the implant. As illustrated by FIG. 8, the fines 92 come into contact with both the smooth polyethylene sheet 90 and the mesh 80. Once the mold is filled as described above, the top section 98 is placed over the components and the materials are subjected to heat and pressure, as is known in the current art, to form a porous polyethylene material. The heat and pressure causes the fines to be sintered together and to be affix the polyethylene sheet and titanium mesh. The resulting structure has titanium mesh embedded within a porous matrix and a solid smooth polyethylene film that is attached both to the titanium mesh and/or to the porous polyethylene structure. The sheet or film of polyethylene is impervious to water and serves as a barrier. In a preferred embodiment of the invention described above, the polyethylene film is approximately 0.1 mm thick, the titanium mesh is approximately 0.35 mm thick and the porous polyethylene is approximately 0.9 mm thick, inclusive of the imbedded titanium mesh. Thus the overall thickness of the material is approximately 1 mm. Now referring to FIG. 9, in a preferred embodiment of the invention, the titanium mesh consists of a series of annular rings 107 that are attached to adjacent annular rings by bridges 110 also made of titanium. As best seen in FIG. 10, the annular rings have countersunk holes 115 that will receive the head of surgical screw. This structure allows for flexibility of the titanium component within the implant and the countersunk holes allow for easy fixation of the implant to the bone using appropriately sized surgical screws. In the preferred embodiment of the invention, the titanium is of sufficient strength in relation to the thickness of the polyethylene components (the solid sheet and the porous matrix) so that the implant will hold its shape after being bent by the surgeon. It is therefore contemplated that during a surgical procedure the surgeon may bend the implant to conform to the shape of the defect that is being treated. In a preferred embodiment the surgeon can bend the implant by hand during the procedure. The implant as described above can also be cut with conventional plate cutters that are routinely used for cutting titanium surgical plates or mesh. While preferred embodiments of the titanium mesh are illustrated by FIGS. 9 and 10, other titanium mesh products that can be used in connection with the invention are commercially available from sources that include Stryker Instruments, Synthes Maxillofacial, Leibinger, KLS-Martin, L. P. and Walter-Lorenz Surgical. FIG. 11 depicts yet another embodiment of the invention in which the titanium 150 is placed between two opposite polyethylene barrier sheets 153 and 155. A porous matrix 160 is sandwiched between the barrier sheets 153 and 155. use. The configuration of this implant provides a bendable sheet that has a smooth polyethylene surface on both the top and bottom surface. The implant will retain its shape after it has been bent to conform to the contours of defect to be treated. The implant has strength properties that are inherent to titanium, and it has a non-porous barrier surface that is not amenable to tissue attachment to the implant. The thickness of the sheets of polyethylene may be selected to result in an implant having the desired thickness. In the alternative, the thickness of the implant may be adjusted by variation of the porous matrix layer 160. Like the previous embodiments, the implant may be bent by the surgeon and it will maintain its shape. Now referring to FIG. 13, a side sectional view of the implant depicted in FIGS. 1-4 shows the mesh 20 formed along the interface 175 between the porous layer and the sold polyethylene layer 23. As seen in FIG. 14, a defect in the cranium 178 has a floor 180 and a wall 182. In order to address this defect, the implant is bent to conform to the contour of the defect and cut to the shape of the defect. The implant is placed within the defect and the bottom porous layer is brought into contact with the bone on the floor and sidewalls. The implant may be secured into place with screw or sutures. Because the bottom surface and the sidewalls of the implant are porous, fibrovascular ingrowth into the implant is encouraged and this ingrowth serves to further stabilize the implant and diminish the possibility of rejection. The smooth barrier surface prevents the dermis from attachment and thereby allows the skin to slide over the implant area. In yet a further alternative embodiment of the invention, the structure involves the providing of a titanium mesh plate within a porous polyethylene matrix wherein all sides have porous surfaces. FIG. 18 depicts a sectional view wherein the mesh 300 is formed with a porous polyethylene matrix. This implant may be suitable for those applications where a smooth barrier surface is not indicated. For example, an implant having porous surfaces that allow for fibrovascular ingrowth on opposite sides may be indicated in cranial applications and for temporal implants for soft tissue replacement. In the preferred embodiments of the invention described above, the pore size of the porous polyethylene is sized large enough to allow for fibrovascular ingrowth. This pore size range would preferably be in the range of 100-250 microns, but could vary in the range of 20-500 microns. While polyethylene sheets and high density porous polyethylene matrix are preferred, it is also contemplated that other synthetic resins and combinations can be used in connection with the invention. For example PETE, PTFE and/or nylon may be selected as the thermoplastic resin. It is also should be understood that the Figures depicted herein are not necessarily drawn to scale. For example, the barrier in FIGS. 1-4 may be formed with a sheet having a much smaller width than the drawings may suggest. In a preferred embodiment the invention as depicted in FIGS. 1-4 is approximately 5 mm wide by 10 mm in length and has a thickness of approximately 1 mm. However, other dimensions are contemplated. FIG. 5 is a sectional view of the implant according to the invention located within a mold. As depicted therein, the mesh is located adjacent to the barrier layer on the top of the mold. The barrier layer is formed of a solid sheet of polyethylene and the porous section is made by sintering together polyethylene fines under heat and pressure. The sold sheet may be made by introducing polyethylene fines to a press having opposite smooth metal sheets and heating the surfaces causing the fines to completely fuse together. When the implant has cooled, the structure may be removed from the mold because both the tabs 50 and the implant material have some flexibility. Now referring to FIG. 6, a contemplated arrangement depicting a plurality of tabs 50 provided on the lower section of mold 61 is shown. The titanium sheet will rest on or is supported by the tabs 50 provided around the periphery of the mold. The tabs are placed a distance from the top surface of the mold that is slightly less than the width of the mesh, so that when the top of the mold that retains the barrier sheet is placed over the mold bottom, the thin barrier sheet may come into contact with the mesh. FIG. 7 depicts an alternative arrangement wherein the mold is provided with a shelf to retain the titanium mesh in position near the top of the mold. FIG. 16 depicts yet a further embodiment of the implant wherein the top surface 214 and bottom surface 126 are polyethylene sheets. The mesh 220 is contiguous with the internal surfaces of both the top sheet 214 and the lower sheet 216. This implant has a top barrier surface 221 and bottom barrier surface 223 and is indicated in those applications where fibrovascular ingrowth is not desired. FIG. 19 shows an exploded perspective schematic view of the embodiment according to the invention. Top layer 400 may comprise a barrier surface or porous surface. The mesh 405 may be any metallic material suitable for surgical applications that and that is malleable and will retain its shape. Bottom layer 410 may be a barrier surface or a porous surface. This embodiment depicts mesh 405 at the interface between the layers 400 and 410. FIG. 20 depicts an implant 500 made according to the invention in position on the orbit floor of an orbit 507. In addition to the repair and reconstruction of orbital defects, the implants according to the invention may be advantageously employed with other surgery such as the repair of lost bone flaps resulting from neurological procedures, repair of the mastoid area after a mastoidectomy, fixation for LeFort procedures, fixation for sliding genioplasty. It is further contemplated that the planar sheets may be bent into tubular shapes and used for orthopedic applications. A planar sheet bent in a U shaped configuration may be useful in connection with spinal fixation procedures or the repair of herniated disks. The invention having been described in detail with respect to preferred embodiments above, it will now be apparent from the foregoing to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and the invention, therefore, as defined in the appended claims is intended to cover all such changes and modifications as fall within the true spirit of the invention.
<SOH> BACKGROUND OF THE INVENTION <EOH>Craniofacial and especially orbital wall and floor defects may result from trauma, cancer, resection, or congenital defects. Such defects are typically treated surgically using bone grafts or synthetic implants. Congenital defects or fractures of the complex and relatively thin bone structures surrounding and supporting the human eye present difficult internal bone repair and fixation problems. In instances when the eye is subject to trauma, the margin or rim of the orbit may diffuse the force of the impact. However, compression of the orbital contents sometimes may occur and fracture the relatively fragile orbit floor and/or the lateral and medial orbital walls. Also injury at the lateral orbital rim may produce a fracture within the orbit. When the orbit is fractured standard bone-grafting techniques for orbital reconstruction may not result in predictable eye function and positioning. Often the support of the globe is deficient as a result of under correction of the defect, over correction, or inadequate reconstruction of the orbital volume. Further, the bone graph may be subject to resorption that may result in result in a less than optimal support. The accurate anatomical reconstruction of the bony orbit is essential to maintain normal function and appearance of the eye following orbital fractures. Because most of the bone of the internal orbit surfaces is thin, it is difficult to adequately stabilize the fractured bone fragments without the use of autogenous or alloplastic materials. Autologous bone grafts have been considered an optimal treatment method for orbital floor and wall reconstruction. However, this material is sometimes difficult to obtain and difficult to shape the bone graft material to properly fit within the orbit. There are problems relating to the tissue donor site morbidity. As discussed above, autogenous bone grafts have frequently been used by craniomaxillofacial surgeons for the reconstruction of the internal orbit. Bone may be harvested from the calvarium and other autogenous materials including iliac bone, split rib bone. Cartilage has also been used as a bone graft material. However, autogenous bones sometimes result in an unacceptable amount of resorption. A variety of alloplastic materials have been used for orbital reconstruction and craniofacial applications including, silicone rubber, Teflon, Supramid, tantalum mesh, Vitallium mesh, titanium mesh, polyethylene, and methyl methacrylate Perforated biocompatible metallic strips and metallic panels may be used for rigid internal fixation of fractures in trauma surgery and as a plate material for bone immobilization and stabilization. Metal implants can be used for bone graft support material in reconstructive surgery. Synthetic implant materials have the advantage of no donor site morbidity, ease of use, relative low cost and ready availability. While there are advantages of synthetic implants, some characteristics may be regarded as disadvantages. Silicone rubber has a smooth surface, but does not allow fibrovascular ingrowth into the implant. Further, although it is flexible, it does not readily conform to the profile of the region where it is required or maintain a new shape when shaped to fit a particular location. For example, in connection with the reconstruction of the orbit, a silicone rubber implant is not an attractive option because upon shaping it to the desired profile, it will tend to be biased back to its original shape. While a silicone rubber implant does not maintain its shape, in a case where the soft tissues of the orbit have been traumatized, an implant with a smooth superior surface is desirable to prevent attachment of the tissues to the implant upon healing. Attachment of these tissues to the wall of the implant may result in restriction of movement of the eye, causing diplopia, dizziness, and headaches, as well as a cosmetic anomaly on upgaze, downgaze or lateral gaze. Implants having a porous structure such as porous polyethylene with predetermined pore sizes allow for fibrovascular ingrowth. In some circumstances fibrovascular ingrowth is desirable because it integrates the implant within the tissues, and reduces the possibility that that the synthetic material will be rejected. Further, fibrovascular ingrowth on the inferior or sinus side of the implant, allows for mucosalization of the implant surface, and, since the opposite side of the implant may be a barrier, the sinus is effectively isolated from the soft tissues of the orbit. This arrangement is considered desirable because it increases the ability of the implant to ward off infection and minimizes the chance of a sinus infection from entering through the orbit. Fibrovascular ingrowth is also thought to minimize the chance of implant migration or displacement. Porous polyethylene is somewhat flexible and thin sheets appropriate for orbital floor and wall reconstruction can be bent to an appropriate shape. However, this material tends to return to its original shape. Further, porous polyethylene does not have a smooth superior surface, so it may result in restriction of the orbital tissues due to fibrous ingrowth when used for orbital reconstruction. Pure titanium is the material of choice in craniofacial reconstructive surgery, especially when the implant is intended to be permanent. As an implant material, pure titanium is preferred because its low density and elastic modules are less than some of the stainless steel or cobalt-chromium alloys that have been used as implant materials. Titanium is corrosion resistant and, when provided in thin sheets, is pliable. Titanium implants many be cut and shaped to the appropriate configuration at the time of surgery. Titanium mesh is easily moldable in situ and easily fixed to bone, but does not have smooth surfaces, nor does it allow for fibrovascular ingrowth. An easily molded material is desirable so that the surgeon can create the correct shape to properly reconstruct the orbital walls or orbital floor. Titanium mesh can be molded to the desired shape by hand and it will retain the shape due to the malleability and strength of the titanium material. While there are a number of options for an implant material for orbital reconstruction, there remains a need for a material that is easily moldable by hand and will retain its shape after molding, has a smooth impenetrable surface on one side, and a porous surface on the opposite side, and is made from highly biocompatible materials. Preferably it is desirable to provide an implant that can be trimmed and bent to shape to fit the shape of the orbital wall or orbital floor reconstruction, and placed in the orbit with the smooth surface on the inside, against the periosteum and soft tissues and with the porous side directed toward the sinus region. Further, it would be desirable to provide a material that can be fixed to the orbital bones with surgical screws or to the surrounding tissues with sutures. It is an object of the present invention to provide a unique implant for the repair of orbital defects and fixation of orbital fractures. It is a further object of the invention to provide a unique composite implant structure which can be shaped for use during a surgical procedures relating to the repair of the orbit and be readily cut, reshaped or bent to conform to the orbital walls and affixed to the orbit or the orbital margin. It is another object of the invention to provide an implant structure that forms a barrier between the sinus and the soft tissues of the orbit. It is a further object of the invention to provide a craniofacial implant that may be sued in other applications wherein it is desirable to maintain the shape of the implant. Other objects and advantages of the invention will be apparent from the following summary and detailed description of the orbital repair implant structure of the invention taken with the accompanying drawing figures.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to an improved implant and method of reconstruction of craniofacial defects, and in particular for orbital defects. The implant is a composite structure comprised of a surgical grade metal provided in a planar sheet form that is encased within a thermoplastic resin. In a first embodiment, one surface of the implant is smooth and impervious so that when the implant is placed within the body, it may form a barrier. In an alternative embodiment of the invention, while one side of the implant has a smooth surface, the opposite side of the implant is comprised of porous polyethylene that allows for fibrous tissue ingrowth. In a method of reconstruction, the implant that is described herein is cut and then shaped to conform to the profile of a defect to be treated. The implant is then secured to bony tissue using surgical screws or an alternative mechanical fastener. Because the implant contains a mesh it will maintain its shape.
20050712
20100202
20051229
59297.0
1
GANESAN, SUBA
CRANIOFACIAL IMPLANT
UNDISCOUNTED
0
ACCEPTED
2,005
10,517,865
ACCEPTED
Composition of polymer having functional substance encapsulated, process for producing the same, ink-jet recording ink, method of forming image with the same, and image-forming apparatus
A polymer composition including a functional material, the composition containing at least a block polymer encapsulating a material of a predetermined function and a solvent, wherein a property of the polymer in the composition is changed in response to a stimulus, whereby the block polymer encapsulating the material agglomerates together, or an ink composition usable as an inkjet ink containing at least a block polymer encapsulating a coloring material and a solvent, wherein a property of the polymer in the composition is changed in response to a stimulus, whereby the block polymer encapsulating the coloring material agglomerates together. The change of the property of the block polymer in response to a stimulus is a change from the lyophilic nature to the lyophobic nature, or the lyophilic nature to the lyophobic nature.
1. A composition comprising a block polymer encapsulating a functional material of a predetermined function and a solvent, wherein a property of the block polymer is changed in response to a received stimulus, whereby the block polymer encapsulating the functional material agglomerates together. 2. The composition according to claim 1, wherein the composition comprises micelles of the block polymer encapsulating the functional material of a predetermined function and a solvent, wherein the property of the block polymer is changed in response to the received stimulus, whereby the micelles of the block polymer agglomerate together. 3. The composition according to claim 1, wherein the block polymer is an AB, ABC or ABA block polymer where A, B and C each represent a block segment. 4. The composition according to claim 3, wherein at least one of the block segments of the block polymer has a vinyl ether structure. 5. The composition according to claim 1, wherein the functional material of the predetermined function is a coloring material. 6. The composition according to claim 3, wherein at least one of the segments of the block polymer has an oxyalkylene structure at a side chain. 7. The composition according to claim 1, wherein the change of the property of the block polymer in response to the stimulus is a change from lyophilic to the lyophobic, or from lyophilic to lyophobic. 8. The composition according to claim 1, wherein the stimulus to the block polymer is at least one selected from the group consisting of a change in temperature, irradiation with an electromagnetic wave, a change in pH of the composition and a change in a concentration of the composition. 9. The composition according to claim 4, wherein at least one of the block segments of the block polymer has a vinyl ether structure expressed by the following General Formula (1): wherein R1 is selected from the group consisting of a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, —(CH(R2)—CH(R3)—O)1—R4 and —(CH2)m—(O)n—R4, and 1 and m are independently selected from integers of 1 to 12 and n is 0 or 1, and R2 and R3 are independently a hydrogen atom or CH3, and R4 is a hydrogen atom, a straight, branched or cyclic alkyl group having 1 to 6 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —CHO, —CH2CHO, —CO—CH═CH2, —CO—C (CH3)═CH2 or CH2COOR5, and if R4 is not a hydrogen atom, the hydrogen atom on the carbon atom may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms or F, Cl or Br, and the carbon atom in the aromatic ring may be replaced with a nitrogen atom, and R5 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. 10. The composition according to claim 1, wherein a molecular weight distribution of the block polymer is 2.0 or less. 11. The composition according to claim 1, wherein at least one of the segments of the block polymer has a glass transition temperature of 20° C. or lower. 12. A method for production of a composition comprising a block polymer encapsulating a functional material of a predetermined function and a solvent, wherein a property of the block polymer is changed in response to a stimulus, whereby the block polymer encapsulating the functional material agglomerates together, the method comprising the steps of: completely dissolving the block polymer in a solvent; and encapsulating the functional material with the block polymer by causing a change in a solvent environment. 13. The production method according to claim 12, wherein the change in the solvent environment is at least one selected from the group consisting of a change in temperature, irradiation with an electromagnetic wave, a change in pH of the composition and a change in a concentration of the composition. 14. An image formation method wherein an image is formed through a process that a composition comprising a block polymer encapsulating a functional material of a predetermined function and a solvent is applied to a medium, and a property of the block polymer is changed in response to a received stimulus, whereby the block polymer encapsulating the functional material agglomerates together. 15. The image formation method according to claim 14, wherein an image is formed on a medium through a process in which the composition comprising micelles of the block polymer encapsulating the functional material of a predetermined function and the solvent is applied to a medium, and the property of the block polymer is changed in response to a received stimulus, whereby the micelles composed of the block polymer encapsulating the functional material agglomerate together. 16. The image formation method according to claim 14, wherein the stimulus is at least one selected from the group consisting of a change in temperature, irradiation with an electromagnetic wave, a change in pH of the composition and a change in concentration of the composition. 17. An image formation apparatus comprising means for applying a composition to a medium to form an image on the medium, wherein the composition comprises a block polymer encapsulating a functional material of a predetermined function and a solvent, the composition undergoes a process in which a property of the block polymer is changed in response to a received stimulus, whereby the block polymer encapsulating the functional material agglomerates together. 18. An image formation apparatus wherein the image formation apparatus is used for using a composition containing a micelle composed of a block polymer encapsulating a functional material of a predetermined function and a solvent to form an image through a process in which a property of the block polymer is changed in response to a stimulus, whereby the micelle composed of the block polymer encapsulating the functional material agglomerates together. 19. The image formation apparatus according to claim 17 wherein the stimulus is at least one selected from the group consisting of a change in temperature, irradiation with an electromagnetic wave, a change in pH of the composition and a change in concentration of the composition. 20. The image formation method according to claim 14, wherein the functional material of the predetermined function is a coloring material. 21. The image formation method according to claim 14, wherein the stimulus is a change in pH, and the size of particles in the composition comprising the block polymer encapsulating the functional material is increased by the change in pH, whereby an image is formed on a medium.
TECHNICAL FIELD The present invention relates to a composition containing a block polymer encapsulating a material of a predetermined function and a solvent, a method for production of the same, and an image formation method and an image formation apparatus using the composition. BACKGROUND ART Aqueous dispersions containing functional materials have been widely used for agricultural chemicals such as herbicides and insecticides and drugs such as anticancer drugs, antiallergic drugs and anti-inflammatory drugs as functional materials. Meanwhile, coloring materials such as ink and toner containing a colorant in a form of solid particles are well known. In recent years, digital printing technologies represented by electrophotography and inkjet printing have been making great progress, and the significance of these technologies as an image formation technology is recognized more and more in office and home. Among them, the inkjet technology has remarkable features such as compactness and low power consumption as a direct recording method. In addition, image quality has been rapidly improved owing to refinement of nozzles and the like. One example of the inkjet technology is a method in which ink supplied from an ink tank is heated by a heater in a nozzle to form a bubble therein by boiling, and the ink is discharged from the nozzle to form an image on a recording medium. Another method is a method in which a piezo element is vibrated to discharge ink from a nozzle. Since an aqueous dye solution is usually used in ink used in these methods, bleeding may occur when colors are superimposed, and a phenomenon called feathering may occur along paper fibers at a recording location on the recording medium. For the purpose of alleviating these problems, use of pigment dispersion ink is proposed (U.S. Pat. No.5,085,698). However, many improvements are still desired. DISCLOSURE OF THE INVENTION In view of the above situations, the present invention provides a composition characterized in that a block polymer encapsulating a functional material agglomerates together in response to a stimulus applied. Particularly, the present invention provides a composition suitable for an inkjet ink that alleviates bleeding and feathering and is excellent in fixation. The present invention provides an image formation method and an image formation apparatus using the composition described above. The first aspect of the present invention relates to a composition comprising a block polymer encapsulating a functional material of a predetermined function and a solvent, wherein the property of the block polymer changes in response to the applied stimulus, whereby the block polymer encapsulating the functional material agglomerates together. The second aspect of the present invention is a method for production of the composition that agglomerates together in response to a stimulus, the method comprises the steps of: completely dissolving a block polymer in a solvent; and encapsulating the functional material in the block polymer by a change in the solvent environment. The third aspect of the present invention is an image formation method characterized in that an image is formed on the medium through a process that the composition is applied to a medium, and the property of the block polymer is changed in response to a received stimulus, whereby the block polymer encapsulating the functional material agglomerates together. The block polymer preferably forms micelles. Particularly, in a polymer-containing composition containing a material having a functional material included in an amphipathic block polymer having a hydrophobic segment and a nonionic hydrophilic segment and a solvent, it is preferable that the particle size of the material is increased by a change in pH for fixation on a recording medium. The fourth aspect of the present invention is an image formation apparatus that comprises means for applying the composition to a medium, and is used for forming an image on the medium. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows an outlined mechanism of an image recording apparatus of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. The inventors of the present invention studied the above-described situations and technical problems and completed the present invention. The first aspect of the present invention is a composition comprising a block polymer encapsulating a functional material of a predetermined function and a solvent, characterized in that a property of the block polymer will change in response to a stimulus applied, whereby the block polymer encapsulating the functional material agglomerates together. Hereinafter such a composition is referred to as “the composition”. Preferably, such a composition contains micelles of a block polymer encapsulating a functional material of a predetermined function and a solvent, characterized in that a property of the block polymer will change in response to a stimulus applied to cause aggregation of the block polymer micelles. The “material being encapsulated in a block polymer” refers to such a state that a material is enclosed in the block polymer, e.g., a coloring material exists in hydrophobic core portions of the micelles of the block polymer in water. The solvent (liquid medium) contained in the composition of the present invention is not specifically limited as long as it can dissolve, suspend or disperse the components of the composition. In the present invention, the solvent includes organic solvents such as various kinds of straight, branched or cyclic aliphatic hydrocarbons, aromatic hydrocarbons and heteroaromatic hydrocarbons, aqueous solvents and water. In order to accelerate drying on a recording medium such as paper, monohydric alcohols such as methanol, ethanol and isopropyl alcohol may be used. The second aspect of the present invention is a method for production of the composition characterized in that the polymer is completely dissolved in a solvent, and then the solvent environment is changed to make the material included in the block polymer. More preferably, the change in solvent environment in the production method is at least one selected from change in temperature, irradiation with an electromagnetic wave, change in pH of the composition and change in the concentration of the composition. The range of temperature change preferably includes the phase transition temperature of the composition. Regarding the exposure to electromagnetic waves, the wavelength of the electromagnetic wave is preferably in the range of 100 to 800 nm. The range of pH change is preferably from pH 3 to pH 12. The range of the concentration change preferably covers a concentration at which the composition undergoes phase transition. The third aspect of the present invention is an image formation method for forming an image by applying ink onto a recording medium, characterized in that a dispersion composition containing a block polymer encapsulating a coloring material is used as ink and a property of the polymer will change in response to a stimulus to cause agglomeration of the block polymer molecules. Preferably, the image formation method is characterized in that the dispersion composition contains a block polymer that forms micelles to encapsulate the coloring material and an image is formed through a process in which a property of the polymer changes in response to a stimulus applied to cause aggregation of the micelles of the polymer. More preferably, the stimulus applied in the image formation method is at least- one selected from temperature change, irradiation of electromagnetic wave, pH change and change in concentration of the composition. The range of temperature change preferably includes the phase transition temperature of the composition. Regarding the exposure to electromagnetic waves, the wavelength of the electromagnetic wave is preferably in the range of 100 to 800 nm. The range of pH change is preferably from pH 3 to pH 12. The range of the concentration change preferably covers a concentration at which the composition undergoes phase transition. The fourth aspect of the present invention is an image formation apparatus to be used for image formation using a dispersion composition that contains a block polymer encapsulating a pigment through a process in which a property of the polymer changes in response to a stimulus applied to cause agglomeration of the pigment-encapsulating block polymer. Preferably, it is an image formation apparatus to be used for image formation using a dispersion composition that contains block polymer micelles encapsulating a pigment through a process in which a property of the polymer changes in response to a stimulus applied to cause agglomeration of the micelles of the block polymer. More preferably, the stimulus applied in the image formation method is at least one selected from temperature change, irradiation of electromagnetic wave, pH change and change in concentration of the composition. The range of temperature change preferably includes the phase transition temperature of the composition. Regarding the exposure to electromagnetic waves, the wavelength of the electromagnetic wave is preferably in the range of 100 to 800 nm. The range of pH change is preferably from pH 3 to pH 12. The range of the concentration change preferably covers a concentration at which the composition undergoes phase transition. The block polymer for use in the present invention is preferably an amphipathic block polymer. It is preferably an amphipathic block polymer having a hydrophobic segment and a nonionic hydrophilic segment, in other words, the block polymer contains at least one hydrophobic segment and at least one nonionic hydrophilic segment. Types of block structures include the followings. Representative ones are block polymers of AB type having different block segments, tri-block polymers of ABA having the same block segments at both ends, and tri-block polymers of ABC type having different block segments. There are also block polymers of ABCD type having different block segments, block polymers of ABCA type and block polymers having a larger number of block segments. In the case of tri-block polymers of ABC type or block polymers having three or more block segments, at least one hydrophobic segment and at least one nonionic hydrophilic segment should be included in the block segments, and the other block segment may be a block segment having an ionic functional group. The block polymers described above can be previously known block polymers such as acrylate or methacrylate block polymers, block polymers of polystyrene and other polymers of addition polymerization or condensation polymerization, and block polymers of polyoxyethylene and polyoxyalkylene. More preferable one is a block polymer having a polyalkenyl ether structure as a repeating unit structure, and further more preferable one is a compound having a polyvinyl ether structure as a repeating unit structure. Each block segment of the block polymer compound of the present invention may be composed of a single type of repeating units or may be composed of two or more types of repeating units. Examples of block segments composed of two or more types of repeating units include random copolymers and graduation copolymers having composition ratios gradually changed. The block polymer compound of the present invention may be a polymer where a block polymer of three or more block segments is bonded to another polymer by grafting. The number average molecular weight (Mn) of the block polymer compound of the present invention is 200 to 10,000,000, preferably 1,000 to 1,000,000. If the number average molecular weight is greater than 10,000,000, entanglement within a polymer chain and between polymer chains may become so severe that the polymer is hard to be dispersed in a solvent. If the number average molecular weight is less than 200, the molecular weight is so small that a steric effect of the polymer may not be obtained. The polymerization degree of each block segment is preferably from 3 to 10,000. More preferable is from 5 to 5,000. Further more preferable is from 10 to 4,000. For improvement of dispersion stability and improvement of inclusion properties (encapsulating properties), it is preferable that molecules of the block polymer are more flexible because the polymer can physically entangle with the surface of the functional material to increase affinity. As described in detail later, the flexibility is preferable in the point that a covering layer is easily formed on a recording medium. For this purpose, the glass transition temperature Tg of the main chain of the block polymer is preferably 20° C. or lower, more preferably 0° C. or lower, further more preferably −20° C. or lower. In this respect, a polymer having a polyvinyl ether structure is preferably used because the polymer generally has a low glass transition temperature and has flexible properties. Most of the example repeating unit structures described above have a glass transition temperature of about −20° C. or lower. Polyvinyl ether that is characteristically used in the present invention is described. The features of the composition of the present invention, that is high dispersion stability, alleviation of bleeding and feathering and excellence in fixation, are mostly due to the polymer material having a polyvinyl ether structure used in the dispersion. As described above, stimulus responsivity in the present invention means that the shape or physical properties change drastically in response to environmental stimuli such as exposure to an electromagnetic wave, application of an electric field, temperature change, pH change, addition of a chemical material or concentration change of the composition. A polymer having a polyvinyl ether structure can provide stimulus responsibility to the composition. In such a composition, it is preferable the polymer also serves as a stabilizer of a pigment dispersion. Thus, polyvinyl ether preferably has both hydrophilic and hydrophobic portions, i.e. an amphipathic structure. Specifically, a polymer obtained by copolymerization of a hydrophilic monomer and a hydrophobic monomer can be a preferred example. Such a polymer having a polyvinyl ether structure has more preferable dispersion properties because the polyvinyl ether structure generally has a low transition temperature and flexibility, and its hydrophobic portion tends to physically entangle or has affinity with solid particles. Various methods for synthesis of a polymer having a polyvinyl ether structure have been reported (for example, Japanese Patent Application Laid-Open No. H11-080221), among which a method by cationic living polymerization by Aoshima et al. (Japanese Patent Application Laid-Open Nos. H11-322942 and H11-322866) is representative. By synthesizing polymers by cationic living polymerization, various polymers such as homopolymers, copolymers of 2 or more monomers and block polymers, graft polymers and graduation polymers can be synthesized with the same length (molecular weight). Polyvinyl ether can have various functional groups on the side chain. Cationic polymerization can be carried out by the HI/I2 system, HCl/SnCl4 system or the like. The first object of the addition of a polymer having a polyvinyl ether structure in the present invention is to provide stimulus responsivity, but other functions such as dispersion of solid particles (pigment etc.) may be also provided. Typical stimuli and polymers of a polyvinyl structure responsive to the stimuli will be illustrated below. Responses of the composition to changes in temperature include changes in solubility, thermal polymerization, changes in polarity, phase transition (sol-gel transition, liquid crystals) and the like. The range of the temperature change preferably covers the phase transition temperature of the composition, and more preferably covers a critical gel temperature. Polyvinyl ether structures responsive to a temperature stimulus are, for example, alkoxy vinyl ether derivatives such as poly(2-methoxyethyl vinyl ether) and poly(2-ethoxyethyl vinyl ether), and copolymers having these polymer compounds as the main components. Particularly, a block polymer of poly((2-methoxyethyl vinyl ether)-b-(2-ethoxyethyl vinyl ether)) causes a rapid change in viscosity at 20° C. Here b indicates being a block polymer. Next stimulus responsivity is responsivity to exposure to an electromagnetic wave. The wavelength of the electromagnetic wave is more preferably in the range of 100 to 800 nm. Responses to a stimulus of exposure to an electromagnetic wave include, for example, solubility change, photo-polymerization, photochromism, photoisomerization, photodimerization, phase transition (sol-gel transition, liquid crystals). Polyvinyl ether structures responsive to the stimulus may include, for example, vinyl ether derivatives having functional groups for polymerization, such as poly(2-vinyloxyethyl methacrylate) and copolymers having such a polymer compound as the main component. Regarding the response to a stimulus of pH change, it is preferable for the composition to respond to changes in the range of pH 3 to 12. Responses to a stimulus of pH change may include, for example, changes in solubility, hydrogen bonding and coordination bonding and polarity and phase transition (sol-gel transition, liquid crystals). Structures of the polymers having a polyvinyl ether structure, to be contained in a dispersion responsive to the stimuli, may include, for example, copolymers and polymer blends of alkoxy vinyl ether derivatives such as poly(2-methoxyethyl vinyl ether) and poly(2-ethoxyethyl vinyl ether) and polycarboxylic acid such as polymethacrylic acid. Further stimulus examples may include concentration change in an aqueous ink. The stimulus is given by, for example, vaporization or absorption of water of the aqueous ink or a change in concentration of a polymer dissolved in the composition. For the stimulus, the concentration change preferably covers the phase transition concentration of the composition, and more preferably it covers a critical gel concentration. Response of the composition to the stimulus of concentration change includes, for example, hydrogen bonding, hydrophobic interaction and phase transition (sol-gel transition, liquid crystals). One example polymer is an alkoxy vinyl ether derivative such as poly(2-methoxyethyl vinyl ether) or poly(2-ethoxyethyl vinyl ether) or the like, aryl oxyvinyl ether derivative such as poly(2-phenoxyethyl vinyl ether) or copolymer having such a polymer as the main component. Of these stimuli, two or more of types of stimuli can be combined. The function of stimulus response can be provided by a polymer having a polyvinyl ether structure. In the present invention, other polymers can be used to improve the function. For example, a polymer not having a polyvinyl ether structure can be used to provide stimulus responsivity, and a polymer having a polyvinyl ether structure is used to provide other functions (e.g. dispersion stability). Examples of other polymers having stimulus responsivity include those described below, but the present invention is not limited thereto. By adding into the composition a polymer other than a polymer having a polyvinyl ether structure (e.g. polymer having stimulus responsivity described above), stimulus responsivity can be added or improved. A first example is such a polymer that causes phase transition when the composition is heated to cause change in the composition. Specific examples of such a polymer include poly(meta)acrylamide, poly N-alkyl substituted(meta)acrylamide such as poly-N-isopropyl(meta)acrylamide, poly N-vinylisobutylamide, poly(meta)acrylic acid or metal salts thereof, poly-2-hydroxyethyl(meta)acrylate, poly-N-(meta)acrylpiperidine, poly(2-ethyloxazolin), polyvinyl alcohol or partially saponified products thereof, polyethylene oxide, copolymers of polyethylene oxide and polypropylene oxide, poly(ethyleneglycolmonomethacrylate), poly(ethyleneglycolmonoacrylate), substituted cellulose derivatives such as methylcellulose, ethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose and copolymers and polymer blends having these polymer compounds as the main components. A second example is such a polymer that undergoes structure change by photoreaction to cause phase transition when the composition is exposed to the electromagnetic wave, to cause a change in the composition. Specific examples of the polymer include polymer compounds having groups such as photochromic groups. Specifically, they include various kinds of polymers, for instance, triphenylmethane derivatives that undergoes ion cleavage by light, poly(meta)acrylamides having a spiropyran derivative or spirooxazine derivative group, poly N-alkyl substituted (meta)acrylamides such as poly-N-isopropyl(meta)acrylamide and N-vinylisobutylamides. A third example is such a polymer that causes phase transition when the composition of the composition is changed by a change in pH. Specific examples of such a polymer include poly(meta)acrylic acid or metal salts thereof, polyvinylsulfonic acid, polyvinylbenzenesulfonic acid, poly(meta)acrylamidealkylsulfonic acid, polymaleic acid or metal salts thereof, or copolymers based on monomer components constituting these polymer compounds, polyvinyl alcohol-polyacrylic acid composites or metal salts thereof, poly(ethyleneglycolmonomethacrylate), metal salts of carboxymethylcellulose, metal salts of carboxyethylcellulose, and copolymers and polymer blends having as main components these polymer compounds. A fourth example is such a polymer that causes phase transition, when the concentration of the polymer dissolved in the composition is changed. Specific examples of such a polymer include polymer compounds having a lower critical solution temperature (LCST) such as poly(meta)acrylamide, poly N-alkyl-substituted(meta)acrylamide, polyvinyl methyl ether and polymethacrylic acid as aqueous solutions (Japanese Patent publication No. S61-7948, Japanese Patent Application Laid-Open No. H3-237426 and Japanese Patent Application Laid-Open No. H8-82809), polyvinyl alcohol, polyvinyl alcohol-polyacrylic acid complexes or metal salts thereof, poly(ethyleneglycol monomethacrylate), inorganic polymers such as alkoxy siloxane, and copolymers and polymer blends having as main components these polymer compounds. The structure of the block polymer in the composition is not specifically limited but particularly, a polymer having a vinyl ether structure in at least one of the segments is more preferable. Block polymer retains respective properties of the repeating monomer units of the blocks or units, and can exhibit these properties in a coexistent manner. These polymers can more effectively function than random polymers, since block or unit portions having stimulus responsivity can function effectively. Further, these polymers enable dispersion of solid particles an aqueous medium used to disperse the polymer. In this case, a part of the polymer should have an affinity for the aqueous solvent used. In the case of the polymer having a polyvinyl ether structure, various block forms such as AB, ABA and ABC are possible as described above, and the polymer preferably has two or more different types of hydrophilic blocks. The polymer can have ionic sites at its end. The repeating unit structure of the polymer having the polyvinyl ether structure is not specifically limited, but preferable is expressed by the following General Formula (1): wherein R1 is selected from the group consisting of a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, phenyl(Ph), pyridyl(Pyr), Ph-Ph, Ph-Pyr, —(CH(R2) )—CH(R3)—O)1—R4 and —(CH2)m—(O)n—R4, hydrogen on the aromatic ring may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms, and carbon in the aromatic ring may be replaced with nitrogen. 1 is selected from integers of 1 to 18, m is selected from integers of 1 to 36, and n is 0 or 1. R2 and R3 are independently H or CH3. R4 is H, a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —CHO, —CH2CHO, —CO—CH═CH2, —CO—C (CH3)═CH2 or CH2COOR5, and if R4 is not hydrogen, hydrogen on the carbon atom may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms or F, Cl or Br, and carbon in the aromatic ring may be replaced with nitrogen. R5 is H or an alkyl group having 1 to 5 carbon atoms. Preferably, R1 is selected from the group consisting of a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, —(CH(R2)—CH(R3)—O)1—R4 and —(CH2)m—(O)n—R4. l and m are independently selected from integers of 1 to 12, and n is 0 or 1. R2 and R3 are independently H or CH3. R4 is H, a straight, branched or cyclic alkyl group having 1 to 6 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —CHO, —CH2CHO, —CO—CH═CH2, —CO—C(CH3)═CH2 or CH2COOR5, and if R4 is not hydrogen, hydrogen on the carbon atom may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms. F, Cl or Br, and carbon in the aromatic ring may be replaced with nitrogen. R5 is H or an alkyl group having 1 to 5 carbon atoms. In the present invention, the straight or branched alkyl group is methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, n-hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, octadecyl or the like. The cyclic alkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl or the like. Substitution of alkyl may be single or plural. A preferable repeating unit structure of the polymer having a polyvinyl ether structure is expressed by the following general formula (2): wherein R6 is selected from the group consisting of a straight, branched or cyclic alkyl group, Ph, Pyr, Ph-Ph, Ph-Pyr, —(CH2—CH2—O)1—R7 and —(CH2)m—(O)n—R7, hydrogen on the aromatic ring may be replaced with a straight or branched alkyl group having carbon atoms 1 to 4, and carbon in the aromatic ring may be replaced with nitrogen. l is selected from integers of 1 to 18, m is selected from integers of 1 to 36, and n is 0 or 1. R7 is comprised of H, a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —CHO, —CH2CHO, —CO—CH═CH2, —CO—C(CH3)═CH2 or CH2COOR8, and if R7 is not hydrogen, hydrogen on the carbon atom may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms or F, Cl or Br, and carbon in the aromatic ring may be replaced with nitrogen. R8 is H or an alkyl group having 1 to 5 carbon atoms. Preferably, R6 is selected from the group consisting of a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —(CH2—CH2—O)1—R7 and —(CH2)m—(O)n—R7, hydrogen on the aromatic ring may be replaced with a straight or branched alkyl group having carbon atoms 1 to 4, and carbon in the aromatic ring may be replaced with nitrogen. l is selected from integers of 1 to 18, m is selected from integers of 1 to 36, and n is 0 or 1. R7 is comprised of H, a straight, branched or cyclic alkyl group having 1 to 18 carbon atoms, Ph, Pyr, Ph-Ph, Ph-Pyr, —CHO, —CO—CH═CH2 or —CO—C(CH3)═CH2, and if R7 is not hydrogen, hydrogen on the carbon atom may be replaced with a straight or branched alkyl group having 1 to 4 carbon atoms or F, Cl or Br, and carbon in the aromatic ring may be replaced with nitrogen. More preferably, regarding the repeating unit molecular structure of the polymer that has the polyvinyl ether structure in the composition described above, the following vinyl ether monomers can be recited, but not limited thereto. Block polymers having a polyvinyl ether structure made from these vinyl ether monomers can be suitably used in the present invention. The polymer that can be used in the present invention is not limited to stimulus-responsive polymers having a polyvinyl ether structure made from the vinyl ether monomers described above. Examples of these polymers are recited below, but not limited thereto. Preferably, the numbers of repeating units of polyvinyl ether (x, y and z in (II-a) to (II-g) described above) are independently 1 to 10,000 and more preferably, the total of the numbers ((x+y+z) in (II-a) to (II-f) described above) is 10 to 40,000. If each segment in the block polymer having a polyvinyl ether structure is composed of two or more types of monomers, each segment may be a random polymer, gradient polymer or graft polymer. Other components of the present invention will be described below. The solvent in the composition of the present invention is preferably water or an aqueous solvent. [Water] Water contained in the composition of the present invention is preferably ion exchanged water free from metal ions and the like, pure water or ultrapure water. [Aqueous Solvent] For the aqueous solvent, polyhydric alcohols such as ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol and glycerin, polyhydric alcohol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monoethyl ether and diethylene glycol monobutyl ether, nitrogen-containing solvents such as N-methyl-2-pyrolidone, substituted pyrolidone and triethanolamine, and the like may be used. For the purpose of accelerating drying on the recording medium, monohydric alcohol such as methanol, ethanol and isopropyl alcohol may be used. In the present invention, the content of water and aqueous solvent described above is 20 to 95 wt % based on the total weight of the composition. It is more preferably 30 to 90 wt %. [Coloring Material] The coloring material useful in the present invention may be pigment or dye depending on applications of the composition of the present invention. The coloring material that is used in the composition of the present invention is preferably 0.1 to 50 wt % based on the weight of the composition. Specific examples of the pigment and dye for use in the composition of the present invention will now be described. The pigment may be either an organic pigment or inorganic pigment and for the pigment that is used in ink, a black pigment and pigments of primary three colors, cyan, magenta and yellow, are preferably used. Pigments of other colors, colorless or light-colored pigments, metalescent pigments and the like may be also used. Pigments newly synthesized for the present invention may also be used. Commercially available black, cyan, magenta and yellow pigments will be described with examples below. Examples of black pigments include, but not limited to, Raven 1060, Raven 1080, Raven 1170, Raven 1200, Raven 1250, Raven 1255, Raven 1500, Raven 2000, Raven 3500, Raven 5250, Raven 5750, Raven 7000, Raven 5000 ULTRA II, Raven 1190 ULTRA II (all of the above, from Columbian Carbon Company), Black Pearls L, MOGUL-L, Regal 400R, Regal 660R, Regal 330R, Monarch 800, Monarch 880, Monarch 900, Monarch 1000, Monarch 1300, Monarch 1400 (all of the above, from Cabot Corporation), Color Black FW1, Color Black FW2, Color Black FW200, Color Black 18, Color Black S160, Color Black S170, Special Black 4, Special Black 4A, Special Black 6, Printex 35, Printex U, Printex 140U, Printex V, Printex 140V (all of the above, from Degussa AG), No. 25, No. 33, No. 40, No. 47, No. 52, No. 900, No. 2300, MCF-88, MA600, MA7, MA8, and MA100 (all of the above, from Mitsubishi Chemical Corporation). Examples of cyan pigments include, but not limited to, C. I. Pigment Blue-1, C. I. Pigment Blue-2, C. I. Pigment Blue-3, C. I. Pigment Blue-15, C. I. Pigment Blue-15:2, C. I. Pigment Blue-15:3, C. I. Pigment Blue-15:4, C. I. Pigment Blue-16, C. I. Pigment Blue-22, and C. I. Pigment Blue-60. Examples of magenta pigments include, but not limited to, C. I. Pigment Red-5, C. I. Pigment Red-7, C. I. Pigment Red-12, C. I. Pigment Red-48, C. I. Pigment Red-48:1, C. I. Pigment Red-57, C. I. Pigment Red-112, C. I. Pigment Red-122, C. I. Pigment Red-123, C. I. Pigment Red-146, C. I. Pigment Red-168, C. I. Pigment Red-184, C. I. Pigment Red-202, and C. I. Pigment Red-207. Examples of yellow pigments include, but not limited to, C. I. Pigment Yellow-12, C. I. Pigment Yellow-13, C. I. Pigment Yellow-14, C. I. Pigment Yellow-16, C. I. Pigment Yellow-17, C. I. Pigment Yellow-74, C. I. Pigment Yellow-83, C. I. Pigment Yellow-93, C. I. Pigment Yellow-95, C. I. Pigment Yellow-97, C. I. Pigment Yellow-98, C. I. Pigment Yellow-114, C. I. Pigment Yellow-128, C. I. Pigment Yellow-129, C. I. Pigment Yellow-151, and C. I. Pigment Yellow-154. In the composition of the present invention, pigments self-dispersing in water (self-dispersing pigment) may also be used. Self dispersing pigments include those utilizing steric hindrance of a polymer adsorbed on the surface of the pigment and those utilizing electrostatic repulsion, and commercially available such pigments include CAB-0-JET200 and CAB-0-JET300 (manufactured by Cabot Co., Ltd.) and Microjet Black CW-l(manufactured by Orient Chemical Co., Ltd.). The pigment content in the composition of the present invention is preferably 0.1 to 50 wt % based on the weight of the composition. If the pigment content is less than 0.1 wt %, a sufficient image density cannot be obtained, and if the pigment content is greater than 50 wt %, fixation of the image may be deteriorated. More preferably, the pigment content is in the range of 0.5 wt % to 30 wt %. Dyes that can be used in the composition of the present invention may be known dyes including water soluble dyes such as a direct dye, acid dye, basic dye or reactive dye or food dyes, or insoluble dyes such as a disperse dye. Oil-soluble dyes may also be suitably used. Examples of oil-soluble dyes include C. I. Solvent Blue-33, -38, -42, -45, -53, -65, -67, -70, -104, -114, -115, and -135; C. I. Solvent Red-25, -31, -86, -92, -97, -118, -132, -160, -186, -187, and -219; and C. I. Solvent Yellow-1, -49, -62, -74, -79, -82, -83, -89, -90, -120, -121, -151, -153, and -154. Examples of water-soluble dyes include direct dyes such as C. I. Direct Black-17, -19, -22, -32, -38, -51, -62, -71, -108, -146, and -154; C. I. Direct Yellow-12, -24, -26, -44, -86, -87, -98, -100, -130, and -142; C. I. Direct Red-1, -4, -13, -17, -23, -28, -31, -62, -79, -81, -83, -89, -227, -240, -242, and -243; C. I. Direct Blue-6, -22, -25, -71, -78, -86, -90, -106, and -199; C. I. Direct Orange-34, -39, -44, -46, and -60; C. I. Direct Violet-47 and -48; C. I. Direct Brown-109; and C. I. Direct Green-59; acid dyes such as C. I. Acid Black-2, -7, -24, -26, -31, -52, -63, -112, -118, -168, -172, and -208; C. I. Acid Yellow-11, -17, -23, -25, -29, -42, -49, -61, and -71; C. I. Acid Red-1, -6, -8, -32, -37, -51, -52, -80, -85, -87, -92, -94, -115, -180, -254, -256, -289, -315, and -317; C. I. Acid Blue-9, -22, -40, -59, -93, -102, -104, -113, -117, -120, -167, -229, -234, and -254; C. I. Acid Orange-7 and -19; and C. I. Acid Violet-49; reactive dyes such as C. I. Reactive Black-1, -5, -8, -13, -14, -23, -31, -34, and -39; C. I. Reactive Yellow-2, -3, -13, -15, -17, -18, -23, -24, -37, -42, -57, -58, -64, -75, -76, -77, -79, -81, -84, -85, -87, -88, -91, -92, -93, -95, -102, -111, -115, -116, -130, -131, -132, -133, -135, -137, -139, -140, -142, -143, -144, -145, -146, -147, -148, -151, -162, and -163; C. I. Reactive Red-3, -13, -16, -21, -22, -23, -24, -29, -31, -33, -35, -45, -49, -55, -63, -85, -106, -109, -111, -112, -113, -114, -118, -126, -128, -130, -131, -141, -151, -170, -171, -174, -176, -177, -183, -184, -186, -187, -188, -190, -193, -194, -195, -196, -200, -201, -202, -204, -206, -218, and -221; C. I. Reactive Blue-2, -3, -5, -8, -10, -13, -14, -15, -18, -19, -21, -25, -27, -28, -38, -39, -40, -41, -49, -52, -63, -71, -72, -74, -75, -77, -78, -79, -89, -100, -101, -104, -105, -119, -122, -147, -158, -160, -162, -166, -169, -170, -171, -172, -173, -174, -176, -179, -184, -190, -191, -194, -195, -198, -204, -211, -216, and -217; C. I. Reactive Orange-5, -7, -11, -12, -13, -15, -16, -35, -45, -46, -56, -62, -70, -72, -74, -82, -84, -87, -91, -92, -93, -95, -97, and -99; C. I. Reactive Violet-1, -4, -5, -6, -22, -24, -33, -36, and -38; C. I. Reactive Green-5, -8, -12, -15, -19, and -23; and C. I. Reactive Brown-2, -7, -8, -9, -11, -16, -17, -18, -21, -24, -26, -31, -32, and -33; and C. I. Basic Black-2; C. I. Basic Red-1, -2, -9, -12, -13, -14, and -27; C. I. Basic Blue-1, -3, -5, -7, -9, -24, -25, -26, -28, and -29; C. I. Basic Violet-7, -14, and -27; and C. I. Food Black-1 and -2. Examples of the coloring materials described above are especially preferable for the composition of the present invention, but the coloring material that is used in the composition of the present invention is not specifically limited to the coloring materials described above. The content of the dye that is used in the composition of the present invention is preferably 0.1 to 50 wt % based on the weight of the composition. If the content of the dye is less than 0.1 wt %, a sufficient image density cannot be obtained, and if the content is greater than 50 wt %, fixation of the image may be deteriorated. More preferably, the content of the dye is in the range of 0.5 wt % to 30 wt %. In the present invention, the pigment and the dye may be used in conjunction. [Additives] To the composition of the present invention, various kinds of additives, assistants and the like may be added as required. One of additives of the composition is a dispersion stabilizer for stabilizing a pigment in a solvent. The composition of the present invention has a function of dispersing solid particles such as a pigment with a polymer having a polyvinyl ether structure, but if dispersion is in sufficient, other dispersion stabilizer may be added. As other dispersion stabilizer, a resin having both hydrophilic and hydrophobic portions or a surfactant can be used. Resins having both hydrophilic and hydrophobic portions include, for example, copolymers of hydrophilic monomers and hydrophobic monomers. Hydrophilic monomers include acrylic acid, methacrylic acid, maleic acid, fumaric acid, the monocarboxylates described above, vinyl sulfonic acid, styrene sulfonic acid, vinyl alcohol, acrylamide and methacryloxyethyl phosphate, and hydrophobic monomers include styrene, styrene derivatives such as α-methyl styrene, vinylcyclohexane, vinyl naphthalene derivatives, acrylates and methacrylates. For the copolymer, various copolymers such as random, block and graft copolymers may be used. Of course, hydrophilic and hydrophobic monomers are not limited to those described above. For the surfactant, anionic, nonionic, cationic and ampholytic surfactants may be used. Anionic surfactants include fatty acid esters, alkyl sulfates, alkyl aryl sulfonates, alkyl diaryl ether disulfonates, dialkyl sulfosuccinates, alkyl phosphates, formalin naphthalenesulfonate condensates, polyoxyethylene alkyl phosphates and glycerol borate fatty acid esters. Nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene oxypropylene block copolymers, sorbitan fatty acid esters, glycerin fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene alkyl amines, fluorine surfactants and silicon surfactants. Cationic surfactants include alkyl amine salts, quaternary ammonium salts, alkyl pyridinium salts and alkyl imidazolium salts. Ampholytic surfactants include alkyl betaines, alkyl amine oxides and phosphatidyl choline. Similarly, the surfactant is not limited to those described above. A composition containing the additives described above is provided, for example, as a composition different from the ink composition of the present invention, and it may be brought in contact, as required, with the ink composition to give a stimulus. Specifically, in the case of inkjet ink, for example, an ink tank containing an ink composition of the present invention and an ink tank containing a composition containing additives are prepared, and the compositions are discharged onto the same recording material separately and thus contacted with each other. Alternatively, a composition containing additives is provided to a recording medium in advance, to which the ink composition of the present invention is applied for contact with each other. To the composition of the present invention, an aqueous solvent may be added as required. Particularly, if the composition is used in inkjet ink, the aqueous solvent is used for prevention of drying and solidification of the ink at a nozzle portion, and can be used alone or in mixture. For the aqueous solvent, those described above apply directly. In the case of ink, the content of the solvent is 0.1 to 60 wt %, preferably 1 to 25 wt % based on the total weight of the ink. Other additives for ink include, for example, a pH adjuster for stabilizing the ink in the feeding pipe in a recording apparatus, a penetration agent promoting penetration of the ink into the recording medium and accelerating apparent drying, anti-mold agent preventing growth of mold in the ink, a chelating agent blocking metal ions in the ink and preventing precipitation of metals at the nozzle portion, precipitation of insoluble matters in the ink and the like, an antifoaming agent preventing foaming in during circulation and movement of a recording liquid or during production of the recording liquid, an antioxidant, a fungicide, a viscosity adjuster, a conducting agent, an ultraviolet absorber, a water soluble dye, a disperse dye, an oil-soluble dye and the like. Inkjet ink (aqueous dispersion ink), which is a preferred embodiment of the ink composition of the present invention, will be described specifically below. [Method for Production of Inkjet Ink] A method for production of the composition is characterized by a step of encapsulating a coloring material in the block polymer where the block polymer is fully dissolved in a solvent, and then the solvent environment is changed to cause inclusion of the coloring material in the block polymer. More preferably, in the production step, the change in solvent environment is selected from change in pH, change in temperature and change in solvent hydrophilicity or a combination of two or more of the changes. An example of the production method of inkjet ink of the present invention will be described below. To a block polymer having a vinyl ether structure in at least one segment, a solvent that can fully dissolve the polymer is added. The solvent is selected depending on the solubility of the polymer. For example, in the case of (II-a), each segment is responsive to heat, so that hydrophilicity and hydrophobicity can be controlled with temperature, and the solvent may be water if the temperature is 20° C. or lower. When the polymer has a hydrophobic group as (II-e) being only one example, the solvent may be toluene, chloroform or methanol. A solution of the block polymer is prepared in this way, then a coloring material is added and dispersed using a dispersion apparatus, and then the solvent environment is changed to encapsulate the coloring material. An example of the composition-producing method where the change in solvent environment is selected from change in pH, temperature and hydrophilicity of the solvent or combination of two or more thereof is as follows: a block polymer II-a is dissolved in water at 20° C. or lower, a pigment is then added and dispersed, and the resultant solution is heated to 25° C., whereby a segment comprised of 2-ethoxyethyl vinyl ether becomes hydrophobic and the block polymer becomes amphipathic, and micelles are formed in water and the coloring material is included therein. In the case of (II-e), a pigment is added and dispersed in a solvent in which a block polymer has been dissolved, and water is added to increase hydrophilicity of the solvent mixture, whereby the segment comprised of isobutyl vinyl ether causes phase separation to form micelles in which the coloring material is included. If required, coarse particles are then removed by centrifugal separation or the like. If necessary, a water soluble solvent may added to the product followed by stirring, mixing and filtration. Dispersion apparatuses include, for example, an ultrasonic homogenizer, a laboratory homogenizer, a colloid mill, a jet mill and a ball mill, and they may be used alone or in combination. The composition can be produced in the same manner when a self-dispersing pigment or oil-soluble dye is used. [Image Formation Method and Image Formation Apparatus] The aqueous dispersion ink in the present invention can be used with various image formation apparatuses of various printing methods such as the inkjet method and electrophotography, to form images by such an apparatus. If the composition is used as an inkjet ink, it can be used in the following manner in the present invention. The ink agglomerates with changes in solvent environment described below. When the composition uses the block polymer (II-a), for example, an image can be formed using temperature as the change solvent environment. Due to the difference of the ink temperature in the tank and on the recording medium, the inkjet ink of the present invention cause phase separation resulting in rapid thickening or coagulation of insoluble components. Change in ink properties can improve blurring and feathering, and excellent fixation can be achieved. The change in ink properties is not limited to the above thickening or coagulation of insoluble components. Similarly, an image can be formed changing the solvent environment by irradiation with electromagnetic wave, changing pH of the composition or changing concentration. The change in temperature preferably covers the phase transition temperature of the composition. Regarding exposure to electromagnetic wave, the wavelength of the electromagnetic wave is preferably in the range of 100 to 800 nm. Regarding the change in pH, it is preferably in the range of pH 3 to pH 12. The change in the composition concentration preferably spans the concentration at which the composition causes phase transition. For the method for giving a stimulus for changing the solvent environment, various methods can be applied. One preferred method is a method in which a composition giving a stimulus and the ink composition described above are mixed together or made to contact each other. For example, to cause a change in solvent environment by changing pH, a composition having a corresponding pH can be mixed with the ink composition by using the ink jet method. As described in Japanese Patent Application Laid-Open No. S64-63185, a composition giving a stimulus can be applied to the entire surface of an area on which an image is formed by using an inkjet head, and as described in Japanese Patent Application Laid-Open No. H8-216392, the amount of a composition giving a stimulus can be controlled to form a better image. The block polymer in the composition described above is preferably amphipathic, and a preferable solvent is water. With such a composition, micelles of the block polymer are formed to disperse a pigment excellently. And since most of the block polymer molecules are not dissolved but dispersed in a micelle state, a relatively low viscosity can be achieved. For the block polymer in the present invention, polymers described above can be used, but a block polymer having a polyvinyl ether structure described above is preferable. In the present invention, the composition is brought into contact with a composition that gives a stimulus to the block polymer portion, whereby the micelles form a network structure together to thicken the ink for excellent fixation. Thus, the image formation method using the composition of the present invention can achieve excellent fixation. When the inkjet ink of the present invention and the stimulating composition are brought into contact, they may be applied as separate compositions. For example, the inkjet composition and the stimulating composition are put in separate packages, and contacted each other as required. In the case of inkjet ink, for example, an image can be formed by a method in which an ink tank containing the composition of the present invention and an ink tank containing the stimulating composition are prepared independently, and the compositions are separately discharged onto the same recording medium and contacted each other to form an image. Alternatively, a stimulating composition is previously provided to a recording medium by means such as coating or spraying, and the ink composition of the present invention is then discharged onto the recording medium where the compositions contact with each other and form an image. It is also preferable that a mechanism for giving a stimulus is provided in the recording medium in advance. In an example of such a method, a pH responsive ink, specifically an acid responsive ink, is used to perform recording on a sheet of acid paper. In this case, the recording medium has a function of giving a stimulus to the stimulus-responsive ink of the present invention. This recording medium is included in the present invention. That is, the present invention relates to a recording medium having a function of giving a stimulus. In the present invention, the recording medium may be of any known form. For example, the recording medium can be plain paper, heat sensitive paper or acid paper. Inkjet printers using the inkjet ink of the present invention include various inkjet recording apparatuses such as a piezo inkjet system using a piezoelectric element and a thermal inkjet system utilizing thermal energy to make a bubble in the ink to perform recording. For the apparatus of the present invention, in the case of inkjet ink, for example, the amount of ink discharged from a discharge port of a discharge head is preferably in the range of 0.1 to 100 picoliter. The composition of the present invention may also be used in an indirect recording apparatus using a recording system in which ink is printed on an intermediate transfer material, and then transferred to a recording medium such as paper. The composition may also be applied for an apparatus using an intermediate transfer material by a direct recording system. The ink composition of the present invention may be also used in an image formation method and apparatus system in the electrophotographic recording system. An example image formation apparatus comprises a photosensitive drum on which a latent image is formed, means for forming a latent image on the photosensitive drum such as a light exposure means, ink-applying means, a transfer mechanism and a recording medium. For formation of an image by this apparatus, a latent image is first formed on the photosensitive drum, the composition of the present invention is applied to the latent image area or areas other than the latent image, and the obtained image is transferred onto the recording medium by the transfer mechanism and fixed thereon. The outline of an inkjet recording apparatus will be described below with reference to FIG. 1. However, FIG. 1 is only one example of the configuration and does not limit the invention of this application. FIG. 1 is a block diagram showing the configuration of the inkjet recording apparatus. FIG. 1 shows recording onto a recording medium by moving a head. In FIG. 1, an X direction driving motor 56 and a Y direction driving motor 58 for driving a head 70 in X and Y directions is connected to a CPU 50 controlling the overall operation of a production apparatus through an X motor driving circuit 52 and a Y motor driving circuit 54. The X direction driving motor 56 and the Y direction driving motor 58 are driven through the X motor driving circuit 52 and the Y motor driving circuit 54 according to instructions by the CPU to determine a position of the head 70 relative to the recording medium. As shown in FIG. 1, in addition to the X direction driving motor 56 and the Y direction driving motor 58, a head driving circuit 60 is connected to the head 70, the CPU 50 controls the head driving circuit 60, and drives the head 70, i.e. discharges inkjet ink, and so on. An X encoder 62 and a Y encoder 64 for detecting the position of the head are connected to the CPU 50, and information of the position of the head 70 is input to the CPU 50. A control program is input to a program memory 66. Based on this control program and information of the positions of the X encoder 62 and the Y encoder 64, the CPU 50 moves the head 70, and places the head to a desired position on a recording medium to discharge inkjet ink. In this way, a desired image is formed on the recording medium. In the case of an image recording apparatus capable of loading a plurality of inkjet inks, a desired image can be formed on the recording medium by performing the above operation for each inkjet ink predetermined times. After inkjet ink is discharged, the head 70 can be moved to a position at which removal means (not shown) for removing excessive ink deposited on the head is disposed, and cleaned by wiping or the like. For the specific method of cleaning, a conventional method can be used directly. When image formation is completed, the recording medium on which an image has been formed is replaced by a new recording medium with a mechanism for conveyance of recording media (not shown). In the present invention, the embodiment described above can be modified or altered without departing from the spirit of the invention. For example, an example in which the head 70 is moved along X and Y axes has been described above, but a configuration is also possible in which the head 70 is moved only along the X axis (or Y axis), the recording medium is moved along the Y axis (or X axis), and an image is formed with the former and the latter interlocked with each other. In the present invention, means (e.g. electrothermal converter, laser light, etc.) for generating heat energy as an energy source used for discharging inkjet ink is provided, and a head discharging inkjet ink with the heat energy brings about an excellent effect. According to such a system, fineness of image formation can be enhanced. By using the inkjet ink of the present invention, further excellent images can be formed. For the typical configuration and principle of the apparatus comprising the means for generating heat energy, basic principles disclosed in U.S. Pat. Nos. 4,723,129 and 4,740,796 specifications are preferably used. This system is applicable to both so called the on-demand type and the continuous type, but the on-demand type is especially effective because at least one drive signal matching discharge information and giving a rapid increase in temperature exceeding nuclear boiling of a liquid is applied to an electrothermal converter retaining the liquid and placed in correspondence with a channel, whereby the electrothermal converter is caused to generate heat energy, and film boiling is created on the heated surface of the head, so that a bubble is formed in the liquid corresponding to the drive signal on a one-to-one basis. The liquid is discharged through a discharge opening by the growth and shrinkage of a bubble to form at least one droplet. This drive signal more preferably has a pulse shape because bubbles grow or shrink appropriately in an instant, and therefore discharge of a liquid with excellent responsivity can be achieved. For the drive signal having a pulse shape, those described in U.S. Pat. Nos. 4,463,359 and 4,345,262 specifications are suitable. If conditions described in U.S. Pat. No. 4,313,124 specification for an invention relating to a temperature-rise rate of the thermal action surface are employed, further excellent discharge can be performed. For the configuration of the head, the present invention includes a configuration described in U.S. Pat. Nos. 4,558,333 and 4,459,600 disclosing a configuration in which a thermal action portion is placed in a curved area, in addition to the configuration of a combination of a discharge port, a liquid channel and an electrothermal converter (linear liquid channel or orthogonal liquid channel) as disclosed in the specifications described above. In addition, the present invention is effective even with a configuration based on Japanese Patent Application Laid-Open No. 59-123670 disclosing a configuration in which for a plurality of electrothermal converters, a common slit is a discharge portion of the electrothermal converters or Japanese Patent Application Laid-Open No. 59-138461 in which a hole absorbing pressure waves of heat energy is brought into correspondence with the discharge portion. That is, according to the present invention, inkjet ink can be discharged reliably and efficiently irrespective of the form of the head. Further, the present invention can effectively applied to a full line type head having a length matching the largest width of the recording medium in the image formation apparatus of the present invention. The head may have either a configuration in which a plurality of heads are combined to meet the length or configuration as one head integrally formed. In addition, the present invention is effective even if among serial types, a head fixed on an apparatus main body, or a replaceable chip type head which is mounted on the apparatus main body so that electrical connection can be established with the apparatus main body and ink can be supplied from the apparatus main body is used. Further, the apparatus of the present invention may comprise droplet removing means. If the means is added, a further excellent discharge effect can be realized. As a configuration of the apparatus of the present invention, addition of preliminary auxiliary means is preferable because the effect of the present invention can be still further stabilized. Specific examples of the means may include capping means for the head, pressure or suction means, preliminary heating means for heating using an electrothermal converter or other heating element or a combination thereof, and preliminary discharge means for performing discharge other than discharge of ink. The apparatus that is the most effective for the present invention is an apparatus carrying out the film boiling method described above. EXAMPLES The present invention will be described in detail below with Examples, but the present invention is not limited to the Examples. In the following Examples, a method for synthesizing a block polymer of the present invention is described as well as ink compositions dispersing an oil-soluble dye therein as examples of aqueous dispersions. In the Examples of synthesis of polymers and dye-dispersion ink, only several specific examples are described, but the present invention is not limited to these examples. Example 1 <Synthesis of Block Polymer> Synthesis of a block polymer having a terminal carboxylic acid made of 2-ethoxyethyl vinyl ether (EOVE), 2-methoxyethyl vinyl ether (MOVE) and HO(CH2)5COOH Poly[EOVE(2-ethoxyethyl vinyl ether)-b-MOVE(methoxymethyl vinyl ether)]—O—(CH2)5COOH (b is a symbol indicating being block polymer) was synthesized according to the following procedure. A glass container provided with a three-way stopcock was flashed with nitrogen, and the glass container was then heated at 250° C. under an atmosphere of nitrogen gas to remove adsorbed water. When the system reached the room temperature, 12 mmol of EOVE, 16 mmol of ethyl acetate, 0.1 mmol of 1-isobutoxyethyl acetate and 11 ml of toluene were added, and the reaction system was cooled. When the system temperature reached 0° C., 0.2 mmol of ethyl aluminum sesquichloride (equimolar mixture of diethyl aluminum chloride and ethyl aluminum dichloride) was added, and polymerization was started. The molecular weight was monitored with time by gel permeation column chromatography (GPC), and completion of polymerization of A component (EOVE) was confirmed. Then, 12 mmol of B component (MOVE) was added, and polymerization was performed. Completion of polymerization of B component was confirmed by GPC, and 30 mmol of HO(CH2)5COOEt was then added to stop the polymerization reaction. The reaction mixture solution was diluted with dichloromethane, and washed with 0.6 M hydrochloric acid three times, and then distilled with water three times. The resultant organic phase was concentrated to solidify on an evaporator to obtain a block polymer of poly[EOVE-b-MOVE]—O(CH2)5COOEt. The synthesized compound was identified by GPC and NMR. The end portion was identified by confirming existence of a terminus in the spectrum of high molecular weight materials by the NMR DOSY method. Mn was 2.1×104, and Mw/Mn was 1.4. Mn represents a number average molecular weight, and Mw represents a weight average molecular weight. The ester portion at the end of the obtained poly[EOVE-b-MOVE]—O(CH2)5COOEt was hydrolyzed and identified by NMR to confirm that poly[EOVE-b-MOVE]—O(CH2)5COOH was obtained. 26 parts by weight of the thus obtained block polymer having a carboxylic acid terminus were stirred at 0° C. for 3 days together with 200 parts by weight of an aqueous sodium hydroxide solution of pH 11 to prepare a solution of sodium carboxylate polymer where the polymer was fully dissolved. The polymer was extracted with methylene chloride. After drying, the solvent was distilled away to isolate the polymer. Then, 97 parts by weight of ion exchanged water were added to 4 parts by weight of the polymer, and the block polymer was dissolved at 0° C. using a homogenizer. Then, 30 parts by weight of yellow oil-soluble dye (trade name: Yellow 3150 manufactured by Orient Chemical Co., Ltd.) were dissolved in 70 parts by weight of toluene. 20 parts by weight of the coloring material solution were added to 65 parts by weight of the block polymer aqueous solution, and dispersed/mixed using a homogenizer at 0° C. The resultant mixture was heated to 25° C. to form micelles composed of the block polymer encapsulating the liquid coloring material. Finally, 10 parts by weight of diethylene glycol and 5 parts by weight of 2-pyrolidone were added, and mixed using a homogenizer. Then coarse particles were filtered away to prepare an ink composition of the present invention. The structure including the liquid coloring material was observed using electron microscope observation. When the ink composition was contacted with a 5 wt % aqueous polymethacrylic acid solution adjusted to pH 2, yellow agglomerates were formed to confirm that the ink composition was responsive to a stimulus. Example 2 A 5 wt % aqueous polymethacrylic acid solution adjusted to be pH 2 as used in Example 1 was sprayed onto a sheet of plain paper. Then printing was carried out by spraying the ink composition produced in Example 1 onto the paper. One minute after the spraying of the ink composition, a blank plain paper was pressed against the printed area under a load of 4.9×104 N/m2 to evaluate the fixation strength on the basis whether or not the blank plain paper was smeared with the ink. Ink smear on the blank plain paper was not observed. The same test was conducted five times, and the same result was obtained for each test. Comparative Example 1 6 parts by weight of yellow oil-soluble dye (trade name: Yellow 3150 manufactured by Orient Chemical Co., Ltd.) were dissolved in 94 parts by weight of toluene, and printing and evaluation of fixation strength were carried out in the same manner as in Example 2. The ink attached onto the blank plain paper was observed. Example 3 <Synthesis of Block Polymer> Synthesis of diblock polymer composed of isobutyl vinyl ether and CH2═CHOCH2CH2OPhPh (IBVE-r-VEEtPhPH: A block) and 2-methoxyethyl vinyl ether (MOVE: B block) A glass container provided with a three-way stopcock was flashed with nitrogen gas, and then heated at 250° C. under a nitrogen atmosphere to remove adsorbed water. The system was returned to room temperature, to which 6 mmol of IBVE, 6 mmol of VEEtPhPh, 16 mmol of ethyl acetate, 0.1 mmol of 1-isobutoxyethyl acetate and 11 ml of toluene were added. Then the reaction system was cooled to 0° C., 0.2 mmol of ethyl aluminum sesquichloride (equimolar mixture of diethyl aluminum chloride and ethyl aluminum dichloride) was added thereto to start polymerization. The molecular weight was monitored with time by gel permeation chromatography (GPC), and completion of polymerization of A block was confirmed. Then, 24 mmol of MOVE for B block was added and polymerization was continued. Completion of polymerization of B block was confirmed by monitoring using GPC, and then the polymerization reaction was stopped by adding 0.3% by mass of an aqueous ammonia/methanol solution to the system. The reaction mixture solution was diluted with dichloromethane, and washed with 0.6 M hydrochloric acid three times, and then with distilled water three times. The resultant organic phase was concentrated to dryness on an evaporator. The resultant material was dried under vacuum, and then repeatedly dialyzed against methanol using a semipermeable cellulose membrane to remove monomers and obtain a diblock polymer as a desired product. The compound was identified by NMR and GPC. Mn was 32500, and Mw/Mn was 1.24. The polymerization ratio was A:B ═100:200. The polymerization ratio of two types of monomers in A block was 1:1. Example 4 15 parts by mass of the AB type diblock polymer obtained in Example 3 were, dissolved in 150 parts by mass of dimethyl formamide, and the resultant solution was gradually converted into a water phase using 400 parts by mass of distilled water to obtain an aqueous polymer dispersion. Example 5 1 ml of the aqueous polymer dispersion obtained in Example 4, 4 ml of a 0.1 mol/l aqueous NaOH solution and 75 ml of distilled water were mixed, to which a 0.1 mol/l aqueous HCl solution was gradually added measuring pH and DLS (dynamic light scattering). The results are shown below. Amount of 0.1 N Particle size HCl aq added (ml) pH (nm) 0 11.3 102 2.0 10.6 99 3.5 8.9 89 4.0 6.8 75 4.5 3.3 84 6.0 2.8 91 As described above, the nonionic hydrophilic polymer extended its chain in both acidic and alkaline solutions with increase in micelle diameter. Example 6 15 parts by mass of the AB type diblock polymer obtained in Example 3 and 7 parts by mass of oil blue N (C.I. Solvent Blue-14 manufactured by Aldrich Co., Ltd.) were co-dissolved in 150 parts by mass of dimethyl formamide, and the resultant solution was gradually converted into a water phase using 400 parts by mass of distilled water. Thus an ink composition was obtained. Oil blue N was not separately precipitated even after the ink composition was left standing for 10 days. Comparative Example 2 2 parts by mass of a black self-dispersing pigment (trade name: CAB-0-JET300 manufactured by Cabot Co., Ltd.), 0.5 parts by mass of a surfactant (Nonion E-230 manufactured by NOF Corporation), 5 parts by mass of ethylene glycol and 92.5 parts by mass of ion exchanged water were mixed to prepare an ink composition. The ink composition was filled in a print head of an inkjet printer (trade name: BJF800 manufactured by Canon Inc.) to perform solid printing. One minute after printing, the printed area was strongly rubbed with a line marker five times. Black tailing was observed after the first run. Example 7 An aqueous hydrochloric acid solution of pH 3 was sprayed onto a sheet of plain paper to produce a recording medium. The ink composition obtained in Example 6 was filled in a print head of an inkjet printer (trade name: BJF800 manufactured by Canon Inc.) to perform solid printing on the recording medium. One minute after printing, the printed area was strongly rubbed with a line marker five times but no blue tailing was observed. Thus fixation of the ink composition was very good. Comparative Example 3 The ink composition obtained in Example 6 was filled in a print head of an inkjet printer (trade name: BJF800 manufactured by Canon Inc.) to perform solid printing on a sheet of plain paper. One minute after printing, the printed area was strongly rubbed with a line marker five times. Blue tailing was observed after the fourth run. Industrial Applicability As described above, according to the present invention, a composition excellent in fixation, particularly an inkjet ink, can be provided. The composition comprises at least a block polymer encapsulating a material of a predetermined function and a solvent, and is characterized in that a property of the block polymer in the composition is changed in response to a stimulus, whereby the block polymer encapsulating the material agglomerate together. The present invention can provide print images excellent in fixation according to an image formation method using the composition and an image formation apparatus that is used in the method.
<SOH> BACKGROUND ART <EOH>Aqueous dispersions containing functional materials have been widely used for agricultural chemicals such as herbicides and insecticides and drugs such as anticancer drugs, antiallergic drugs and anti-inflammatory drugs as functional materials. Meanwhile, coloring materials such as ink and toner containing a colorant in a form of solid particles are well known. In recent years, digital printing technologies represented by electrophotography and inkjet printing have been making great progress, and the significance of these technologies as an image formation technology is recognized more and more in office and home. Among them, the inkjet technology has remarkable features such as compactness and low power consumption as a direct recording method. In addition, image quality has been rapidly improved owing to refinement of nozzles and the like. One example of the inkjet technology is a method in which ink supplied from an ink tank is heated by a heater in a nozzle to form a bubble therein by boiling, and the ink is discharged from the nozzle to form an image on a recording medium. Another method is a method in which a piezo element is vibrated to discharge ink from a nozzle. Since an aqueous dye solution is usually used in ink used in these methods, bleeding may occur when colors are superimposed, and a phenomenon called feathering may occur along paper fibers at a recording location on the recording medium. For the purpose of alleviating these problems, use of pigment dispersion ink is proposed (U.S. Pat. No.5,085,698). However, many improvements are still desired.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 shows an outlined mechanism of an image recording apparatus of the present invention. detailed-description description="Detailed Description" end="lead"?
20041210
20080916
20051006
75327.0
0
CAIN, EDWARD J
POLYMER COMPOSITION INCLUDING FUNCTIONAL MATERIAL, METHOD FOR PRODUCTION OF THE SAME, INKJET INK, AND IMAGE FORMATION METHOD AND IMAGE FORMATION APPARATUS USING THE SAME
UNDISCOUNTED
0
ACCEPTED
2,004
10,517,996
ACCEPTED
Anchor with smaller second fluke
The present invention provides an improved anchor which is capable of being readily laid, irrespective of the holding or anchorage involved. The anchor includes a first fluke or base member (2), an elongate shank member (9) to which at least one anchor line or chain may be attached, and a second fluke (20) from and disposed substantially parallel to the first fluke (2) but is of a smaller size than the first fluke (2).
1. An improved anchor, comprising: a first fluke or base member, one end thereof constituting a leading end of said anchor and being adapted to assist in anchorage/embedding of said anchor within a given holding; an elongate shank member fixedly attached to said first fluke, said shank member being adapted to receive, and releasably retain, at least one anchor line; a second fluke associated with said shank member and adapted to be fixedly connected thereto, said second fluke being spaced apart from said first fluke and disposed substantially parallel thereto, and wherein said second fluke is of a smaller size than said first fluke. 2. The anchor as claimed in claim 1, wherein said first fluke or base member has a substantial triangular shape when viewed in plan, with a vertex of said triangular shape constituting the leading end of said anchor, said first fluke or base member being formed from two opposed wing members, each substantially triangularly shaped when viewed in plan, said opposed wing members being joined along a line constituting a centre-line for said anchor, said opposed wing members being disposed at an angle to one another such that, when viewed in end elevation, said first fluke or base member has a substantial V-shape, and wherein each of said opposed wing members includes, at a leading end thereof, a down-turned portion which constitutes part of said leading end of said anchor for assisting in digging in or bedding in of said anchor in the holding. 3. The anchor as claimed in claim 2, comprising stabilizing means releasably attached to said first fluke or base member, said stabilizing means comprising a member which is substantially semi-circular in shape, said stabilizing means serving to ensure that said anchor readily assumes an operating configuration and is restored to said operating configuration even after having been disturbed therefrom. 4. The anchor as claimed in claim 3, wherein said second fluke is fixedly secured to both the uppermost surface of said shank and to said stabilizing means. 5. The anchor as claimed in claim 4, comprising means for re-setting thereof, said means for re-setting including a slot extending substantially longitudinally of said shank member and along at least a part of the length of said shank member, said slot being adapted to receive, and releasably retain, a shackle means for the anchor line. 6. The anchor as claimed in claim 5, wherein said stabilizing means is attached to both said first fluke or base member and said shank member. 7. The anchor as claimed in claim 6, wherein said stabilizing means is fixedly secured to said shank member at a leading end of said shank member and to opposite sides of said first fluke or base member. 8. The anchor as claimed in claim 7, wherein each wing member comprises, at a trailing end thereof remote from said down-turned portion, a further member extending upwardly and at an angle to each respective wing member. 9. The anchor as claimed in claim 8, wherein said angle is other the 90°. 10. The anchor as claimed in claim 9, wherein each said wing member comprises at least one discontinuity therein. 11. The anchor as claimed in claim 10, wherein said further member of each said wing member comprises at least one discontinuity therein. 12. The anchor as claimed in claim 11, wherein each wing member has a free edge constituting a side of said anchor and being beveled. 13. The anchor as claimed in claim 12, including a bracing member extending between said further members of said wing members, and at the rear of said further members. 14. The anchor as claimed in claim 13, wherein said shank member is fixedly attached to both said first fluke or base member and said bracing member. 15. The anchor as claimed in claim 14, wherein said stabilizing means is in the form of a tubular member having a substantially semi-circular shape with opposed free ends being fixedly attached to said bracing member. 16. The anchor as claimed in claim 15, wherein said shank member comprises an arm portion extending substantially parallel to said base member, and a leg portion connect to said base member. 17. The anchor as claimed in claim 16, wherein said leg portion of said shank member comprises at least one discontinuity therein. 18. The anchor as claimed in claim 17, wherein said shackle means is free to move along said slot of said shank member responsive to changes in disposition of said anchor relative to the holding. 19. The anchor as claimed in claim 18, comprising means for preventing said shackle means, and an anchor line connected thereto, from being disposed on an underside of said arm portion of said shank member whereby to avoid fouling of said anchor by the anchor line. 20. The anchor as claimed in claim 19, wherein said means for avoiding fouling is at least one projection extending laterally from said arm portion of said shank member and located in the vicinity of a free end of said arm portion. 21. The anchor as claimed in claim 20, including at least one notch in an underside of said leg portion of said shank member. 22. The anchor as claimed in claim 21, comprising at least one slot in an underside of said leg portion of said shank member.
FIELD OF THE INVENTION The present invention relates, in general terms, to improvements in anchors or means for anchoring. More particularly, but not exclusively, the invention relates to an improved form of anchor suitable for use in a variety of different contexts, for achieving effective anchoring regardless of the nature of the holding (be it sand, rock, coral or the like), whilst preferably at the same time allowing for ready release and re-setting of the anchor as and when desired. For ease of explanation, throughout the ensuing specification reference will be made to an especially preferred embodiment of an anchor in accordance with the present invention, to be utilised for the purposes of anchoring a boat or the like water-borne vessel at any give locale. It should be realised, however, that an anchor in accordance with the present invention is equally suited for other purposes than for the mooring of boats, as by way of example the permanent or temporary mooring of buoys, drilling rigs and/or the like. In particular the present invention relates to an improvement in the anchor disclosed in the present applicant's Australian Patent No. 734943. THE PRIOR ART The situation often arises wherein there is a need to anchor or moor boats, buoys, drilling rigs and/or any other form of vessel or water-borne body, either permanently or temporarily, in a given position or at a given locale. That need may, in turn, give rise to problems in that, dependent upon circumstances and the actual location, it has become necessary to anchor or moor such vessels or other bodies in different types of holdings. An anchor which might be particularly suitable for one type of holding, as for example sand or mud, need not be appropriate for another, different type of holding, as for example rock or coral. It has sometimes been the practice for the vessel owner/user to utilise a different form of anchor dependent upon the nature of the holding. Up until recently, prior to the advent of the present applicant's SARCA (Registered Trade Mark) anchor, the subject of Australian Patent No. 734943, there had not been available a multi-use, multi-purpose anchor. In the result, and in order to achieve the best or optimum anchoring result, a different form of anchor would often need to be deployed dependent upon the nature of the holding. That fact alone gave rise to problems, regardless of the size of the water-borne vessel, craft or the like to be anchored or moored. By way of example only, it was not particularly efficient to have the vessel or craft operator required to change the anchor to a different type dependent upon circumstances and the nature of the holding expected below, this especially taking into consideration the possible problems associated with the task of physically replacing one type of anchor for another. In this day and age, where it has become a reasonably common practice to have inexperienced persons in charge of vessels, such a task can be extremely difficult, with the consequences of its not being done properly potentially dangerous. Conventional anchors, if disturbed, can tend to roll over and thereafter be disposed on the ocean/sea/river/lake bottom (or other holding) incorrectly, in effect the wrong way up. In reality prior art anchors, when so disturbed, would lie on their side and have a tendency to stay that way. Quite clearly when so disposed or deployed the efficiency of operation of the overall anchor can be expected to be significantly reduced, a totally unacceptable result. Furthermore, when so deployed there may be a tendency for the anchor to be dragged across the holding, giving rise to disturbance of sand, mud, dislodgment of rock unwanted, destruction of coral etc. Such can have a deleterious effect on the overall environment and, if the relevant vessel is being used, for example, for purposes of angling or fishing, such a disturbance to the holding/ocean bottom is again undesirable, since it can be expected to disturb the local sea-life, thereby reducing the chances of anything being caught. A further problem/disadvantage associated with anchors in accordance with the known art has related to the tendency or possibility of such anchors inadvertently working their way free from the holding, regardless of the nature of such holding. Once an anchor works itself free from its holding, then the vessel associated therewith is totally susceptible to the vagaries of the tides, weather, etc. This can be especially unfortunate if, for example, the crew or passenger(s) of the vessel or craft are not aware of the fact that the anchor has worked loose, as for example if they are suitably inexperienced sleeping or otherwise occupied. An unanchored vessel can drift alarmingly, dependent upon the tides and prevailing weather conditions, leaving itself liable to all sorts of consequences, as for example beaching, being swept onto rocks or reefs, etc, all such consequences involving significant danger to the occupants of the vessel. The present invention seeks to overcome the problems and disadvantages associated with the prior art by providing a form of anchor which lends itself to ready use regardless of the nature of the holding, includes fewer component parts and is hence both easier and cheaper to manufacture, exhibits an inherent ability to right itself or assume/resume the desired configuration even when disturbed, and yet affords increased safety and security, not to mention ease of overall operation/installation. In accordance with one aspect of the present invention there is provided an improved anchor, including: a first fluke or base member, one end thereof constituting a leading end of said anchor and being adapted to assist in anchorage/embedding of said anchor within a given holding; an elongate shank member fixedly attached to said first fluke, said shank member being adapted to receive, and releasably retain, at least one anchor line; a second fluke associated with said shank member and adapted to be fixedly connected thereto, said second fluke being spaced apart from said first fluke and disposed substantially parallel thereto, and wherein said second fluke is of a smaller size than said first fluke. In accordance with a further aspect of the present invention there is provided an improved anchor, said anchor including: a first fluke preferably having a substantially triangular-shape when viewed in plan, a vertex of said first fluke being adapted to assist in anchorage of said anchor within a given holding; an elongate shank member fixedly attached to said first fluke, said shank member being adapted to received, and releasably retain, at least one anchor line; a second fluke associated with said shank member and being adapted to be fixedly connected thereto, said second fluke being spaced apart from said first fluke and disposed substantially parallel thereto; and stabilising means adapted to be attached to said shank member and to both said first and second flukes, wherein said second fluke is of lesser size than said first fluke. In accordance with another aspect of the present invention there is provided an improved re-settable anchor including: a first fluke preferably having a substantially triangular shape when view in plan, a vertex of said first fluke being adapted to assist in anchorage of said anchor within a given holding; an elongate shank member fixedly attached to said first fluke, said shank member being adapted to receive, and releasably retain, at least one anchor line; a second fluke associated with said shank member and adapted to be fixedly connected thereto, said second fluke being spaced apart from said first fluke and disposed substantially parallel thereto; stabilising means adapted to be attached to said first fluke, said shank and preferably said second fluke, and wherein said second fluke is of a lesser size than said first fluke. DESCRIPTION OF THE DRAWINGS In order that the invention may be more clearly understood and put into practical effect reference will now be made to a preferred embodiment of an anchor in accordance with the invention. The ensuing description is given by way of non-limitative example only and is with reference to the accompanying drawings, wherein: FIG. 1 is a front perspective view, of a preferred embodiment of an anchor in accordance with the present invention; FIG. 2 is a rear perspective view of the anchor of FIG. 1; FIG. 3 is a top plan view of the anchor of FIGS. 1 and 2; FIG. 4 is a underneath view of the anchor of FIGS. 1 to 3; FIG. 5 is a front perspective or end view of a preferred embodiment of the anchor in accordance with the invention; and FIG. 6 is a side elavational view of the anchor of FIGS. 1 to 5. With particular reference now to the drawings, an anchor in accordance with the present invention, generally designated 1, is preferably of a shape which is substantially symmetrical about a central and vertically disposed plane (see for example FIGS. 3 and 5). The anchor 1 includes a base member or primary fluke 2 which, in the preferred embodiment illustrated, is formed from opposed substantially triangular-shape wing members 3 and 4 (when viewed in plan). Each of these wing members 3 and 4 has, at or in the vicinity of the vertex thereof, a downwardly turned portion 5, shaped so as to extend downwardly from the overall plane of each wing member 3, 4 whereby to provide, at the leading end of the primary fluke 2 (and therefore of the anchor), a portion whose function is to facilitate digging in of the overall anchor into the relevant holding, thereby to ensure proper anchorage therein. At the other end of each wing member 3, 4, in other words that end remote from the tip or vertex and associated downwardly turned portion 5, there is provided a further member 6 projecting upwardly and rearwardly from the overall plane of the associated wing member 3, 4 at an angle other than 90 degrees. In the preferred embodiment illustrated each wing member 3, 4 has the longest side thereof constituting a free side edge of the overall anchor 1. The wing members 3, 4 are joined together along one side thereof at an angle one to the other. In the preferred embodiment illustrated each wing member 3, 4 is non-planar, with the wing members 3, 4 in fact being disposed at an angle to one another such that, when viewed in end elevation, the base member or primary fluke 2 formed thereby is substantially V-shaped. The primary fluke 2 is preferably formed from a single sheet of a suitable metal, in any known manner and using any known apparatus. It must be realised, however, that the actual method of construction does not constitute a part of the invention. As shown in the drawings, the respective wing members 3, 4 of the primary fluke 2, and preferably the rearwardly projecting members 6 thereof, each include therein one or more elongate slots or discontinuities 7. Such slots 7 have been found to assist in rapid sinking of the anchor, by allowing the passage of water therethrough. When it is desired to release an anchor from its holding, the existence of these slots 7 assists in breaking of the suction effect which acts to keep that anchor in place, thereby facilitating release of the overall anchor as and when desired. The very existence of these slots 7 can also give rise to a type of pumping action, more especially when the anchor is in use in rough seas and/or windy weather, in turn allowing for movement of sand, mud and the like from under the anchor whereby to afford an overall better anchorage. Extending substantially laterally of the anchor 1 towards the rear or non-toe end thereof is a bracing member 8. Such bracing member 8 may be either formed integrally with the primary fluke 2 or, more preferably, be associated therewith as by welding. In the especially preferred embodiment illustrated that bracing member 8 extends substantially laterally of the overall anchor. The bracing member 8 is of a substantially planar shape, with opposed fixed ends being affixed to the uppermost free edge or side of the associated rearwardly projecting member 6 in any suitable manner, as for example by welding. In the preferred embodiment illustrated the anchor 1 in accordance with the present invention includes a shank member, generally designated 9, which is fixably attached to both the primary fluke 2 and the bracing member 8 by any suitable means, as for example by welding. In the especially referred embodiment illustrated the shank member 9 includes an elongate arm portion 10 preferably extending substantially parallel to the primary fluke 2 of the anchor 1 and spaced therefrom, and a leg member 11 attached to the primary fluke 2. Preferably the leg member 11 will be so shaped as to be in physical connection or contact—as for example by welding—with both the bracing member 8 and the primary fluke 2, the overall shank member 9 will be located substantially centrally of the primary fluke 2, or in other words of the overall anchor. The leg member 11 of the shank member 9 has a substantial void or discontinuity 12 therein. Such void or discontinuity 12 serves to reduce the overall weight of the anchor 1, yet at the same time increases the effectiveness thereof. Again in the preferred embodiment illustrated an anchor in accordance with the present invention includes means, which are preferably releasably connectable thereto, which assist in balancing or self-righting of the overall anchor. Preferably such can take the form of a shaped hoop-like member 13, of a substantial semi-circular configuration as shown, which can be either releasably or permanently affixed to the primary fluke 2 in any known manner and using any suitable means. According to one preferred embodiment of the present invention, not shown, the self-righting means 13 may be releasably attached to the primary fluke 2. In an alternative embodiment, not shown, the hoop-like member 13 will be fixed to the anchor using any suitable means, as for example welding. In the preferred embodiment illustrated the arm portion 10 of the shank member 9 includes a shaped slot 14 extending longitudinally thereof, such slot 14 being adapted to receive, and preferably releasably retain, a shackle or the like means, as for example a D-shackle. The arrangement is such as to operate in the manner described in detail in the present applicant's Australian Patent No. 734943, whereby to allow for automatic re-setting of the anchor as and when necessary. The present applicant's arrangement further includes a secondary fluke, spaced apart from the primary fluke 2 and disposed substantially parallel thereto. In one embodiment, not shown, the secondary fluke may be associated with the uppermost free surface of the elongate arm member 10 of the shank member 9, being connected thereto in any known manner, as for example by welding. In an especially preferred embodiment, however, as illustrated for example in FIG. 1, the secondary fluke 20 is adapted, in use, to extend between the self-righting means 13 and the shank member 9. In that regard in the preferred embodiment illustrated the self-righting means 13 is affixed, at its uppermost extremity thereof, to a rear portion of the shank member 9 by any suitable means and in any suitable manner, as for example by welding. The secondary fluke 20 then extends between that self-righting means 13 and the shank member 9, adapted in use to be disposed substantially parallel to the primary fluke 2. In use, the anchor in accordance with the present invention is intended to be embedded in the relevant holding. In the instance, however, of the anchor becoming disengaged from its holding, then the D-shackle will act to run along the slot 14 until such time as it impacts with the end thereof. In that regard it should be understood that, whilst this procedure of course occupies a finite time, in real terms the D-shackle impacts with the end of the slot 14 with quite a substantial force. In one embodiment, not shown, strategically placed along the length of the arm portion 10 of the shank 9, at or in the vicinity of the free end thereof, may be a protrusion 21 of any given type and shape (as for example a pin or the like). This protrusion 21 acts, in use, to prevent the D-shackle from moving along or falling down the shank 9, more particularly along the underside thereof. In that regard it should be realised that, if such was allowed to happen, then a consequence thereof would be that the shackle and its associated chain, cable, chainrope or the like (collectively referred to as anchor line and not shown), could become jammed or fouled on the shank 9, hence preventing correct orientation of the overall anchor 1. In an alternative embodiment, the slot 14 is substantially flat along the entire length thereof, with no sloping intermediate or joining section. Furthermore, and rather than employing a protrusion to prevent jamming or fouling of the D-shackle and its associated chain, a shaped member 21 is provided at or in the vicinity of the end of the shank 9. This shaped member also acts to prevent the D-shackle from travelling around the free end of the shank 9. By virtue of the overall shape and configuration of the anchor 1, which can be seen to have the bulk of its weight at the end thereof remote from the free end of the shank 9, the impact of the D-shackle against the end of the slot 14 causes (or more correctly forces) the anchor 1 to be tipped up. When in that position or configuration, the D-shackle then runs in the reverse direction along the slot 14, to return to the other end thereof, causing the overall anchor 1 to be brought back, lifting the back of the anchor 1, thereby allowing the overall anchor 1 to re-set itself in the holding. It should be realised that this entire operation takes place automatically, without any need for human intervention. This is in marked contrast to the prior art procedures previously employed, which required retraction of the anchor to the surface, and then subsequent re-setting thereof. The arrangement in accordance with the present invention, utilising or employing the secondary fluke 10, is responsible for a number of important practical advantages when compared with the known art. Firstly, tests have shown that an anchor 1 in accordance with the present invention, when thrown over the side of a vessel, will right itself to ensure that it first lands on the surface of the relevant holding the right way up, thereby to ensure embedding thereof, regardless of the actual spatial disposition of the anchor 1 when first thrown. Such means that an improved and appropriate anchorage will be achieved regardless of the “skill” or experience of the person actually responsible for laying out the anchor 1 itself. In actual fact there is no skill or real prior experience needed in order to achieve a satisfactory result. This is in contrast to the prior art arrangements. The present applicant's arrangement, by its very configuration, is substantially proof against the possibility of becoming entangled or caught-up on weed or the like sometimes resident on a give holding. The secondary fluke 20 acts to prevent mud and other extraneous and unwanted material from building up on the self-righting hoop means 13 and associated shank 9 of the anchor 1, thereby ensuring that the anchor can be readily released from the holding as and when desired. In the present applicant's arrangement the primary fluke 2 is also cut away so as to be of a smaller overall size when compared with similar prior art arrangements. This allows the toe end of the anchor 1 to dig in to a given holding quicker and more readily. In the past there have occurred instances wherein an anchor 1 has been dragged upside down through mud or the like making up the holding. The present applicant's arrangement, with its spaced-apart first and second flukes 2 and 20, is so configured that water pressure will act to assist in lifting of the overall anchor 1 from mud or the like, even in the instance of it somehow having been disposed the wrong way up therein. The prior art anchors, as for example that the subject of the present applicant's Australian Patent No. 734943, have been found to suffer from the practical disadvantage that, in use, can accumulate substantially amounts of weed and the like material. Such a build-up or accumulation can result in the anchor not being able to right itself properly. The self-righting means (hoop), when not protected by a secondary fluke as in the arrangement of the present invention, can reasonably readily attach itself—or be “hooked” over—a piece of reef, for example, preventing readily release and self-righting. When the anchor is located upside down, for example, in a holding such as soft mud, the secondary fluke in effect acts as a lifting device as the overall anchor is dragged by the vessel. Mud is actually pushed forward, ahead of the secondary fluke itself, the result being that the anchor is lifted out of the mud, allowing it to turn over and set itself properly, or be released if required. Further, when the anchor 1 is buried in a sand holding, the secondary fluke enhances the overall holding power, giving rise to an increase in downward force acting on the overall anchor. This additional downward-acting force due to the existence of the secondary fluke has been found to increase the performance of the overall anchor to such an extent that it can actually pivot through a full 3600 without pulling out or separating from the holding. As such, the present anchor is especially suited for mooring purposes. Finally it should be understood that the aforegoing description refers merely to preferred embodiments of the present applicant's arrangement and that variations and modifications wills be possible thereto without departing from the spirit and scope of the invention, the ambit of which is to be determined from the following claims.
<SOH> FIELD OF THE INVENTION <EOH>The present invention relates, in general terms, to improvements in anchors or means for anchoring. More particularly, but not exclusively, the invention relates to an improved form of anchor suitable for use in a variety of different contexts, for achieving effective anchoring regardless of the nature of the holding (be it sand, rock, coral or the like), whilst preferably at the same time allowing for ready release and re-setting of the anchor as and when desired. For ease of explanation, throughout the ensuing specification reference will be made to an especially preferred embodiment of an anchor in accordance with the present invention, to be utilised for the purposes of anchoring a boat or the like water-borne vessel at any give locale. It should be realised, however, that an anchor in accordance with the present invention is equally suited for other purposes than for the mooring of boats, as by way of example the permanent or temporary mooring of buoys, drilling rigs and/or the like. In particular the present invention relates to an improvement in the anchor disclosed in the present applicant's Australian Patent No. 734943.
20041215
20060926
20051110
64292.0
0
OLSON, LARS A
ANCHOR WITH SMALLER SECOND FLUKE
SMALL
0
ACCEPTED
2,004
10,518,021
ACCEPTED
Fiber-reinforced concrete cask, supporting frame for molding thereof and process for produicng the concrete cask
The object of this invention is to provide a fiber-reinforced concrete cask that ensures easy working, enables reducing working cost, excels in strength, durability and heat resistance and enables minimizing cracking; a process for fabrication of the same; and a supporting frame for molding the concrete cask. In particular, concrete cask (10) formed through injecting and solidification of concrete (11) is characterized in that sheets of reinforcement fibers having a thermal expansion coefficient equal to or lower than that of concrete (11) are provided on at least the outer circumferential surface and the inner circumferential surface of the concrete cask (10) and that the inner circumferential surface of outer sheet (21) and the outer circumferential surface of inner sheet (22) are connected with each other by strings of reinforcement fibers (23). Preferably, carbon fibers are used as the reinforcement fibers.
1. A fiber reinforced concrete cask formed by injecting and solidifying concrete wherein reinforcement fiber sheets are disposed at least on an outside circumference surface of said cask, said reinforcement fiber sheets have a coefficient of thermal expansion equivalent to or less than a coefficient of thermal expansion of the concrete, and said support frame is sewn together into a cylindrical bag shape and made from reinforcement fiber sheets. 2. The fiber reinforced concrete cask according to claim 1, wherein said reinforcement fiber sheets are disposed on both the outside circumference surface and the inside circumference surface of said concrete cask, and said reinforcement fiber sheets on said outside and inside circumference surfaces are connected with strings. 3. The fiber reinforced concrete cask according to claim 1, wherein said reinforcement fiber sheets are carbon fibers. 4. A fiber reinforced concrete cask formed by injecting concrete into and solidifying within a cylindrical bag support frame formed from reinforcement fiber sheets that have a coefficient of thermal expansion equivalent to or less than the coefficient of thermal expansion of the concrete. 5. The fiber reinforced concrete cask according to claim 4, wherein said reinforcement fiber sheets are carbon fibers. 6. A support frame for forming the concrete cask, wherein said support frame is made from reinforcement fiber sheets having a coefficient of thermal expansion that is equivalent to or less than a coefficient of thermal expansion of the concrete, and said support frame is sewn together into a cylindrical bag shape and made from reinforcement fiber sheets. 7. The support frame for forming the concrete cask according to claim 6, wherein said support frame has a double walled structure made from said reinforcement fiber sheets comprising an outside sheet and an inside sheet joined together, and said outside sheet and inside sheet are joined by strings. 8. The support frame for forming the concrete cask according to claim 6, wherein said support frame has an injection port in the lower part of said support frame. 9. (canceled) 10. The support frame for forming the concrete cask according to claim 9, wherein said support frame has an injection port in the lower part of said support frame. 11. A method for the fabrication of a concrete cask, comprising the processes for: forming a support frame for injection of the concrete, using reinforcement fiber sheets having a coefficient of thermal expansion equivalent to or less than a coefficient of thermal expansion of the concrete, and injecting the concrete into said support frame. 12. The method for the fabrication of the concrete cask according to claim 11, wherein said support frame is made from reinforcement fiber sheets comprising an outside sheet and an inside sheet joined together by reinforcement fiber strings in said process for forming said support frame. 13. The method for the fabrication of the concrete cask according to claim 11, further comprising processes following said process for forming said support frame: filling said formed support frame with a fluid that will maintain a shape of said support frame, and injecting the concrete from the bottom of said support frame in said concrete injecting process to replace said fluid, which is pre-filled into said support frame to hold said shape, with the concrete. 14. The method for the fabrication of the concrete cask according to claim 11, wherein said process for injecting the concrete is performed so that the tensile forces remain in said reinforcement fiber sheets of said support frame from the pressure exerted upon said sheets during said injecting process.
FIELD OF TECHNOLOGY The present invention relates to a fiber reinforced concrete cask such is used for the transport and storage of radioactive materials, as well as a support frame for molding thereof, and a process for fabrication of the concrete cask. BACKGROUND TECHNOLOGY When storing or transporting radioactive substances, generated by nuclear power plants such as spent fuel having a high level of radioactivity and decay heat, the container used to hold this material must have a high radioactivity shielding capability, high seal performance, and have adequate cooling capabilities and structural strength. In general, concrete reinforced with steel rods or sheets has been used to fabricate such containers, but problems remain in the current implementations. One of the problems is the difference in the coefficients of thermal expansion between the concrete and the steel reinforcing materials. Internally or externally reinforcing concrete using steel materials improves the strength of the container, but since the coefficient of thermal expansion of the steel materials is greater than that of the concrete, if the materials inside the container emit heat, cracks in the concrete could be generated to damage the container. Further, since the heat conductivity of concrete is lower than that of the metal, the additional problem being difficult to dispel heat generated inside the container to the outside exacerbates the above cited differences in their coefficients of thermal expansion even more to increase crack formation. At this point, JP2000-162384A discloses a concrete cask which prevents the concrete cask container itself from reaching high temperatures. As is shown in FIG. 4, the concrete cask 51 is comprised of concrete 55 formed to a cylindrical shape with a bottom, and an inner metal cylinder 56 on the inside circumference of container unit 53. Then, canister 52 is inserted into the container and the top opening is sealed by lid 54. A space 57 for the circulation of cooling air is disposed between the outside surface of canister 52 and container unit 53 and cooling air supply passages 58 and cooling air exhaust passages 59 are formed to connect thereto. Thus, the structure enables cooling air to exhaust the heat from the inside of the container unit to the outside to thereby improve the durability and heat resistance of the container. It is further disclosed to use a metal such as stainless steel, which has a coefficient of thermal expansion approximately equivalent to that of the concrete, to form the inner metal cylinder 56 as a reinforcing material for the concrete cask, as a means to minimize any damage to the cask and help it maintain its strength. Further, JP2000-265435A discloses the use of polyethylene or other fiber sheets as a support frame instead of using steel as a reinforcing material to thereby simplify fabrication and reduce fabrication costs for concrete structures. According to this cited invention, a jacket would be formed from an outer sheet and inner sheet with a space disposed between them, and then the jacket would be immersed into the sea so as to introduce sea water into the space in the jacket, which would then be filled with concrete, which would displace the water, and be subsequently allowed to solidify to complete the structure. However, just as is the case with the above cited JP2000-162384A, by simply forming passages for the flow of cooling air, when used to contain a high temperature heat emitting material with a high heat output, differences in the coefficients of thermal expansion of the materials could not be absorbed, and cracking would be inevitable. Further, not only does the use of stainless steel materials as disclosed make the fabrication more difficult, but it also entails much higher material costs. On the other hand, while concrete structures according to the foregoing Patent Publication 2000-265435 would be suitable for holding low temperature materials, the use of polyethylene, or other fiber sheets for the support frame poses problems in the areas of both strength and heat resistance. DISCLOSURE OF THE INVENTION The present invention was developed after reflecting upon the problems associated with the prior art. The object of this invention is to provide a fiber-reinforced concrete cask that ensures easy working, enables reducing working cost, excels in strength, durability and heat resistance and enables minimizing cracking; a process for fabrication of the same; and a support frame for molding the concrete cask. To resolve the above problems the present invention is characterized in that the fiber reinforced concrete cask is formed by injecting and solidifying concrete wherein reinforcement fiber sheets are disposed at least on an outside circumference surface of said cask, and said reinforcement fiber sheets have a coefficient of thermal expansion equivalent to or less than that of the concrete. In this case, the reinforcement fiber sheets are preferably disposed on both the outside circumference surface and the inside circumference surface of said concrete cask, and said reinforcement fiber sheets on said outside and inside circumference surfaces are connected with strings. Further, the reinforcement fiber sheets are preferably carbon fibers. According to the invention disclosed above, it is possible to fabricate concrete casks having superior durability and heat resistance without the cracking or dissociation from the reinforcement material seen in the prior art that was caused by expansion or pulling away from the concrete of the steel reinforcement materials or frames utilized in the casks that were caused by heat generation from the cask's contents. Additionally, the present invention is characterized in that the fiber reinforced concrete cask is formed by injecting concrete into and solidifying within a cylindrical bag support frame formed from reinforcement fiber sheets that have a coefficient of thermal expansion equivalent to or less than that of the concrete. What is meant by the aforementioned “cylindrical bag,” are bag-shaped cylindrical structures that include hollow cylindrical shapes, hollow cylindrical shapes with a bottom (a cylindrical container), and structures where the base plate includes true cylindrical forms. Further, through the use of carbon fibers that have a negative coefficient of thermal expansion as the foregoing reinforcement fibers, such carbon fibers contract in response to rising temperatures from the heat generated inside the cask to exert compression force upon the concrete, which is weak with respect to tensile forces, but strong with respect to compression forces, thereby making it possible to dramatically improve the strength of the concrete. It is necessary that the foregoing reinforcement fibers are strong enough to withstand the injection of the concrete, and that the fibers have sufficiently high heat resistance to withstand the heat from heat-emitting materials. It is further preferable that the aforementioned strings are formed from reinforcement fibers such as carbon fibers. Further still, the present invention is characterized in that the support frame is made from reinforcement fiber sheets having a coefficient of thermal expansion that is equivalent to or less than that of the concrete. Also, it is further preferable in this invention that the support frame has a double walled structure made from said reinforcement fiber sheets comprising an outer sheet and an inner sheet joined together, and said outer sheet and inner sheet are joined by strings, and the support frame is sewn together into a cylindrical bag shape, and made from reinforcement fiber sheets. As previously stated, what is meant by “cylindrical bag” shaped includes bag-shaped cylindrical structures that include hollow cylindrical shapes, hollow cylindrical shapes with a bottom (a cylindrical container), and structures where the base plate includes true cylindrical forms. According to this invention, it is possible to form a support frame for the concrete cask that will deliver the aforementioned operational effects of this invention. It is further preferable that a concrete injecting input opening is located in the lower part of the foregoing support frame according to the present invention. The preferred method for the fabrication of a concrete cask according to the present invention is characterized in that it includes the processes: forming a support frame for injection of the concrete, using reinforcement fiber sheets having a coefficient of thermal expansion equivalent to or less than that of the concrete, and injecting the concrete into said support frame. The process for forming the foregoing support frame includes preferably the joining of the outer sheet and inner sheet of reinforcement fibers comprising said support frame with strings. By doing so, although tensile forces remain in the sheets of the support frame from the pressure exerted upon them during the injection of the concrete, since the concrete exhibits no resiliency after it has cured, said sheets then contract, which puts a compressive pre-stress on the concrete from the outside. This makes it possible to effectively use a concrete structure which is characteristically weak to the tensile force but strong to the compression force. It is further preferable following the process to form the foregoing support frame, to include a process for filling said formed support frame with a fluid that will maintain a shape of said support frame, and a process for injecting the concrete from a bottom of said support frame in said concrete injecting process to replace said fluid previously filled into said support frame to hold said shape, with the concrete. The fluid used to maintain the shape of the foregoing support frame should be, for ease of operations, one with a lower specific gravity than the concrete and easy-care such as water, air, etc. According to this invention, by pre-filling the support frame with a fluid to hold its shape and by replacing it with concrete, it is possible to fabricate the concrete cask to accurate dimensions without the necessity of taking the trouble to prepare a mold frame such as a steel frame. To wit, the present invention not only makes it possible to ease fabrication and lower fabrication costs, but the invention can provide the concrete cask which additionally makes it possible to improve the strength, durability and heat resistance and to minimize any crack generation. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a perspective view of an embodiment of a fiber reinforced concrete cask according to the present invention. FIG. 2 shows sectional views: (a) a sectional view along line A-A of FIG. 1, and (b) a sectional view along line B-B of FIG. 2(a). FIG. 3 is a diagram showing the fabrication process for this embodiment of a fiber reinforced concrete cask according to the present invention. FIG. 4 shows a perspective outer view of a concrete cask according to the prior art. A PREFERRED EMBODIMENT OF THE PRESENT INVENTION Embodiments of the present invention will be described below with the reference of the attached drawings. In these embodiments, unless otherwise stated, any specific mention of such details as the dimensions, materials, or relative positioning of any of the component parts should not be construed as to limit the scope of this invention; they are merely included for purposes of explanation. FIG. 1 shows a perspective view of an embodiment of a fiber reinforced concrete cask according to the present invention; FIG. 2 shows sectional views: (a) a sectional view along line A-A of FIG. 1, and (b) a sectional view along line B-B of FIG. 2(a); and FIG. 3 is a diagram showing the fabrication process for this embodiment of a fiber reinforced concrete cask according to the present invention. This embodiment of a fiber reinforced concrete cask would be used as a container to store or transport radioactive material generated in a nuclear power plant such as spent fuel, recycled fuel, etc. In FIG. 1 and FIGS. 2(a) and (b), fiber reinforced concrete cask 10 according to the present embodiment is comprised of support frame 20, formed by sewing together an outer sheet 21 and a smaller diameter inner sheet 22 into a cylindrical shaped bag having a bottom, and concrete 11 contained in the bag. Although not shown in the figures, its structure is such that it can contain a canister holding radioactive materials. Further, in order to facilitate shape retention of the foregoing support frame 20, a plurality of strings 23 join the inside circumference of the foregoing outer sheet 21 with the outside circumference of inner sheet 22. Reinforcement fibers are used in the foregoing outer sheet 21, inner sheet 22 and strings 23. Said reinforcement fibers, at least for outer sheet 21, must have a coefficient of thermal expansion equivalent to or less than that of thermal expansion of the concrete. To wit, if the concrete used to fill support frame 20 has a thermal expansion coefficient ranging from about 0.5 to 1.5×10−5/° C., the reinforcement fibers used for support frame 20 must have a coefficient of thermal expansion equal to or less than approximately 1.5×10−5/° C. It is preferable that the reinforcement fibers can be high strength, heat resistant fibers having a negative coefficient of thermal expansion, such as carbon fibers. It is, of course, preferable to use high strength fibers with the aforementioned properties for the foregoing inner sheet 22 and the strings 23 as well. Further, the foregoing support frame 20 should have an injection port 12 in the lower part thereof as well as a fluid outlet port 13 in the upper part thereof. The foregoing injection port 12 should be of a structure which can be connected to the supply hose of the concrete to be injected into the support frame, and when the concrete is injected, the supply hose and the foregoing injection port 12 are sealed off with a hose clamp. On the other hand, the fluid outlet port 13 should preferably be equipped with a cock or other type of valve to facilitate the below described expelling of the shape retention fluid, and to make it possible to seal off the inside of the foregoing support frame with the forgoing valve. Further, a plurality of strings 23, which help the foregoing support frame 20 hold its shape, should be installed in the circumferential and in the height directions of said support frame 20; the number installed should be the number required for the support frame to retain its shape when it is filled with concrete. Further, flange 15 is fabricated in the top inside circumference of the foregoing concrete cask 10, which can accommodate the insertion of lid member 14. Said flange 15 is preferably formed as a projection on the inside circumference of the foregoing inner sheet 22 by filling it with concrete 11, and lid member 14 can be formed by filling a bag-shaped lid frame made from reinforcement fibers with concrete 11 in a manner similar to that described above for support frame 20. Also, in the present embodiment, concrete cask 10 is a unitized hollow cylinder having a bottom, but the body of the hollow cylindrical shape and the bottom of the cylinder and the lid also may be comprised of 3 respective blocks, or an even greater number of blocks, that are individually fabricated and joined together to form a unitized concrete cask. Further, it is also preferable that there are air supply ports and exhaust ports established in the sides of concrete cask 10 to accommodate the supply and exhausting of the air that is circulated in the space between the inside circumferential wall of said concrete cask and the outside of the canister contained within concrete cask 10. Using the above described structure, even if heat generated inside the foregoing canister causes concrete 11 to expand, the support frame 20, which has a coefficient of thermal expansion that is less than that of said concrete, protects the concrete and generates the special effect of increasing its compression strength as a tradeoff for weakened tensile strength. Further, by using carbon fibers as the foregoing reinforcement fibers, it is possible to provide concrete casks 10 having excellent strength and heat resistance. Next, the fabrication method for the fiber reinforced concrete cask of the present embodiment will be described with reference to FIG. 3. First, as shown in FIG. 3(a), the outer sheet and inner sheet of carbon or other reinforcement fibers are sewn together. The reinforcement fibers, as explained above, must have a coefficient of thermal expansion that is equivalent to or less than that of concrete, and additionally, they must be strong and resistant to heat. Sheets of reinforced fibers woven to the required size, or rectangular shaped sheets blocks of the appropriate size are sewn together to create cylindrical shaped sheets. The diameter of the inner sheet is smaller than the diameter of the outer sheet by an amount equivalent to the desired thickness of the cask. It would also be possible to bind with adhesives or fuse the reinforcement fiber sheets instead of sewing them together. Also, the outside circumferential surface of inner sheet 22 is joined with the inside circumferential surface of outer sheet 21 by a plurality of strings 23, also made from reinforcement fibers, and in addition, a bottom made from circle-shaped reinforcement fiber sheet is sewn together with the sheets, and a ring-shaped reinforcement fiber sheet is sewn to the top of the sheets for fabricating the bag-shaped support frame. Then, as shown in FIG. 3(b), a support frame shape retention fluid 16 is injected through injection port 12 in the bottom of the foregoing support frame 20. To facilitate operations, said fluid should be one which has a lower specific gravity than the concrete such as air or water and also easy-care, and it should be one which easily separates out from the concrete. Then, as shown in FIG. 3(c), with the support frame 20 filled with said fluid 16, stays 26 are attached to facilitate its shape retention as well as to prevent its falling over. Next, as shown in FIG. 3(d), a concrete supply pump is connected to the foregoing injection port 12 and concrete 11 is injected. At the same time, the valve at the fluid outlet port 13 installed on the top of support frame 20 is opened to allow the fluid 16 to be expelled. Thus, as concrete 11 is inserted from the bottom, the lower specific gravity fluid is output from the top, until concrete has replaced all of fluid 16 inside support frame 20 as shown in FIG. 3(e). When the concrete injecting into said support frame 20 has been completed, the injection of concrete is halted and it is allowed to cure for the required period of time. Thus, with the solidification of concrete 11 inside support frame 20, the fabrication of the concrete cask is completed. The use of this method makes it possible to simplify fabrication and reduce fabrication costs in producing concrete casks that provide excellent heat resistance and strength. When using water as the fluid 16 for retaining the shape of the support frame, it is preferable to use a type of concrete materials for concrete 11 that exhibits very little separation in aqueous environments. EFFECTS OF THE INVENTION According to this invention disclosed above, it is possible to fabricate concrete casks having superior durability and heat resistance without the cracking or dissociation from the reinforcement material seen in the prior art that was caused by expansion or pulling away from the concrete of the steel reinforcement materials or frames utilized in the casks that were caused by heat generation from the cask's contents. Further, through the use of carbon fibers that have a negative coefficient of thermal expansion as the foregoing reinforcement fibers, such carbon fibers contract in response to rising temperatures from the heat generated inside the cask to exert compression force upon the concrete, which is weak with respect to tensile forces, but strong with respect to compression forces, thereby making it possible to dramatically improve the strength of the concrete. By doing so, although tensile forces remain in the sheets of the support frame from the pressure exerted upon them during the injection of the concrete, since the concrete exhibits no resiliency after it has cured, said sheets then contract, which puts a compressive pre-stress on the concrete from the outside. This makes it possible to effectively use a concrete structure which is characteristically weak to the tensile force but strong to the compression force. To wit, the present invention not only makes it possible to ease fabrication and lower fabrication costs, but the invention can provide the concrete cask which additionally makes it possible to improve the strength, durability and heat resistance and to minimize any crack generation.
<SOH> BACKGROUND TECHNOLOGY <EOH>When storing or transporting radioactive substances, generated by nuclear power plants such as spent fuel having a high level of radioactivity and decay heat, the container used to hold this material must have a high radioactivity shielding capability, high seal performance, and have adequate cooling capabilities and structural strength. In general, concrete reinforced with steel rods or sheets has been used to fabricate such containers, but problems remain in the current implementations. One of the problems is the difference in the coefficients of thermal expansion between the concrete and the steel reinforcing materials. Internally or externally reinforcing concrete using steel materials improves the strength of the container, but since the coefficient of thermal expansion of the steel materials is greater than that of the concrete, if the materials inside the container emit heat, cracks in the concrete could be generated to damage the container. Further, since the heat conductivity of concrete is lower than that of the metal, the additional problem being difficult to dispel heat generated inside the container to the outside exacerbates the above cited differences in their coefficients of thermal expansion even more to increase crack formation. At this point, JP2000-162384A discloses a concrete cask which prevents the concrete cask container itself from reaching high temperatures. As is shown in FIG. 4 , the concrete cask 51 is comprised of concrete 55 formed to a cylindrical shape with a bottom, and an inner metal cylinder 56 on the inside circumference of container unit 53 . Then, canister 52 is inserted into the container and the top opening is sealed by lid 54 . A space 57 for the circulation of cooling air is disposed between the outside surface of canister 52 and container unit 53 and cooling air supply passages 58 and cooling air exhaust passages 59 are formed to connect thereto. Thus, the structure enables cooling air to exhaust the heat from the inside of the container unit to the outside to thereby improve the durability and heat resistance of the container. It is further disclosed to use a metal such as stainless steel, which has a coefficient of thermal expansion approximately equivalent to that of the concrete, to form the inner metal cylinder 56 as a reinforcing material for the concrete cask, as a means to minimize any damage to the cask and help it maintain its strength. Further, JP2000-265435A discloses the use of polyethylene or other fiber sheets as a support frame instead of using steel as a reinforcing material to thereby simplify fabrication and reduce fabrication costs for concrete structures. According to this cited invention, a jacket would be formed from an outer sheet and inner sheet with a space disposed between them, and then the jacket would be immersed into the sea so as to introduce sea water into the space in the jacket, which would then be filled with concrete, which would displace the water, and be subsequently allowed to solidify to complete the structure. However, just as is the case with the above cited JP2000-162384A, by simply forming passages for the flow of cooling air, when used to contain a high temperature heat emitting material with a high heat output, differences in the coefficients of thermal expansion of the materials could not be absorbed, and cracking would be inevitable. Further, not only does the use of stainless steel materials as disclosed make the fabrication more difficult, but it also entails much higher material costs. On the other hand, while concrete structures according to the foregoing Patent Publication 2000-265435 would be suitable for holding low temperature materials, the use of polyethylene, or other fiber sheets for the support frame poses problems in the areas of both strength and heat resistance.
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 shows a perspective view of an embodiment of a fiber reinforced concrete cask according to the present invention. FIG. 2 shows sectional views: (a) a sectional view along line A-A of FIG. 1 , and (b) a sectional view along line B-B of FIG. 2 ( a ). FIG. 3 is a diagram showing the fabrication process for this embodiment of a fiber reinforced concrete cask according to the present invention. FIG. 4 shows a perspective outer view of a concrete cask according to the prior art. detailed-description description="Detailed Description" end="lead"?
20050607
20080401
20050929
93578.0
0
LOGIE, MICHAEL J
FIBER-REINFORCED CONCRETE CASK, SUPPORTING FRAME FOR MOLDING THEREOF AND PROCESS FOR PRODUICNG THE CONCRETE CASK
UNDISCOUNTED
0
ACCEPTED
2,005
10,518,134
ACCEPTED
Lock comprising two locking rods, in particular for vehicles
In a lock of this type at least one locking rod (11, 12) is displaced in a longitudinal direction, said rod being driven using an actuator by means of a rotor (20). To produce said lock in a cost-effective manner, the internal section of the locking rod is flexible, thus having the properties of a flexural section (15). The locking rod (11, 12), together with the flexural section (15) and the rotor (20) are configured in one piece from plastic. This special connection permits a transfer between the rotor (20) and the locking rod or rods (11, 12) that is devoid of play.
1. Lock, especially for vehicles, for locking a movable part such as a pivoting door (41) to a stationary part such as a housing (42), with at least one longitudinally movable (65, 66) locking bar (11, 12), which is driven by an actuator acting by way of a rotor (20); where the locking bar (11, 12), the rotor (20), and an elastic element located in between are designed as a one-piece part; with a longitudinal guide (31, 32) for the locking bar (11, 12); and with a locking opening (43) in the stationary part (42), into which the outer end (13) of the locking bar (12, 13) travels to produce a locking effect, wherein the elastic element is formed by the inner section of the locking bar (11, 12) itself and provides a bendable flexing section (15) on the locking bar (11, 12); in that the flexing section (15) is also accommodated in the longitudinal guide (31, 32) of the locking bar (11, 12); in that at least a certain part of this longitudinal guide (31, 32) in the area of the flexing section (15) has a curved course (55) essentially coaxial to the axis of rotation (23) of the rotor (20); and in that the rotor (20) is molded at a circumferential point (21, 22) onto the lateral flank of the flexing section (15) of the locking bar (11, 12). 2. Lock according to claim 1, wherein, in the area of the flexing section (15), the part of the longitudinal guide (31, 32) adjacent to the curved guide piece (55) is essentially tangential (57) to the rotation (25) of the rotor (20) 3. Lock according to claim 1, wherein at least a certain part of the flexing section (15) is seated tangentially on the free end of the arm (26, 27) of the rotor (20). 4. Lock according to claim 1, wherein the locking bar or bars (11, 12) have a cranked part (16). 5. Lock according to claim 4, wherein the end (13) of the bar responsible for the locking action extends in a direction which is essentially radial (24) with respect to axis of rotation (23) of the rotor (20); and in that the locking bar (11, 12) has a central angled section (18), which proceeds at an angle to the longitudinal movement (65, 66) of the bar, which angled section bridges the radial distance (37) to the inner flexing section (15) of the locking bar (11, 12). 6. Lock according to claim 1, wherein the pivot bearing (35) of the rotor (20) is seated on a carrier (33), and in that the carrier (33) is designed to form a one-piece part with the guide (31, 32) for the locking bar or bars (11, 12). 7. Lock according to claim 6, wherein the pivot bearing of the rotor (20) consists of a bearing pin (35), and in that the bearing pin (35) is designed to form a one-piece part with the carrier and the guide (31, 32). 8. Lock according to claim 1, wherein the longitudinal guides (11, 12) are designed in the form of channels. 9. Lock according to claim 8, wherein the guide channel (31, 32) extends over essentially the entire length of the locking bar (11, 12), all the way to the outer end (13) responsible for the locking action. 10. Lock according to claim 9, wherein the guide channel (31, 32) has a channel piece (58), which also encloses the angled section (18) of the locking bar (11, 12); and in that this channel piece (58) has an open width (56) which is greater than or equal to the stroke (60) of the locking bar (11, 12) during its longitudinal movement (65, 66). 11. Lock according to claim 10, wherein the lateral channel walls (36) of the channel piece (58) limit the longitudinal stroke (16) of the locking bar or bars (11, 12). 12. Lock according to claim 1, wherein the longitudinal guides (31, 32) are provided in certain areas with flanges (34), which serve to attach the lock to the movable or resting part (41, 42). 13. Lock according to claim 1, wherein the lock consists of two structural units (10, 30), which, although consisting of multiple elements, are designed to form a single piece, namely, a movable unit (10), comprising the locking bar or bars (11, 12) with their flexing sections (15), onto which the rotor (20) is molded; and a stationary unit (30), comprising the pivot bearing (35) for the rotor (20); the longitudinal guide or guides (31, 32) for the locking bars (11, 12); and possibly the carrier (33), which is installed between the bars, and the fastening flange (34). 14. Lock according to claim 1, wherein the locking bar or bars (11, 12) consist of two different materials, where the material in the area of the flexing section or sections (15) is designed to bend more easily than the material of the remaining bar (14). 15. Lock according to claim 1, wherein the flexing section or sections (15) of the locking bars (11, 12), together with the rigid remaining bar (14) and the rotor (20), are all made of the same material, which is dimensionally stable in and of itself, with the difference that the flexing section or sections (15) have a profiling (46), which makes this area flexible. 16. Lock according to claim 15, wherein the locking bar (11, 12) has a maximum outside profile width (44) in the flexing section (15) which is essentially the same as the width of the rigid sections (14) of the bar; and in that the flexing section (15) has longitudinal profiling (46), which reduces the cross section of the locking bar (11, 12) in certain areas. 17. Lock according to claim 16, wherein, when seen from above, the longitudinal profiling (46) of the flexing sections (15) consists of H-shaped pieces (49) arranged in a row in a polymer-like manner. 18. Lock according to claim 16, wherein the essentially rigid sections (14) of the locking bar (11, 12) have a fissured cross section (51, 52), which extends uniformly over essentially the entire length of the section. 19. Lock according to claim 18, wherein the fissured cross section has the profile of a cross (51, 52), the ends of the crossbeams being supported against the inside surfaces of the longitudinal guides (31, 32).
The invention pertains to a lock of the type indicated in the introductory clause of claim 1. At least one longitudinally movable locking bar is provided, which moves in a direction determined by a longitudinal guide. The locking bar is driven by an actuator, which operates by way of a rotor. The outer end of the bar engages in a locking opening in the stationary part of the lock. In the known lock of this type (WO 95/27115 A1), the two locking bars and the rotor are made as a single piece of plastic, but elastic tabs are used to connect the rotor to the bars. In the assembled lock, these tabs are intended to exert elastic force on the locking bars to keep them in their locking position. This is achieved by producing the two locking bars, the two tabs, and the rotor located between the bars in a stretched-out state and by bringing the tabs into a bent position upon installation in the door, as a result of which they act as leaf springs. A manipulator, which presses against a transverse wall molded onto one of the locking bars and which pivots the rotor by way of the associated tab out of the locking position, is used as an actuator for moving the locking bar. To increase the flexibility of the tabs at the points where they are connected to the rotor, the tabs are made very thin. This negatively affects the strength of the lock; the tabs can break easily at these sensitive connecting points. If this happens, the known lock becomes unusable. The longitudinal guides for the two locking bars consist of strips a certain distance apart, which enclose between them a cross section of the locking bar. No guides are provided in the area of the elastic tabs or in the area of the rotor. In a lock of a different type (DE 44 00 628 A1), so-called “film hinges” are provided between rigid sections of the locking bars, two rotors, and the connecting bars; these hinges produce a flexible connection between these parts, which are rigid in and of themselves. Film hinges of this type are susceptible to breakage. If a film hinge breaks, the lock is unusable. In a lock with three bars (DE 23 19 315 A), the two locking bars which move in opposite direction are attached to the bearing ends of two connecting rods, which are connected by elastic bands to a rotor, which can be turned by a key. The rotor, the two elastic bands, and the connecting rods are produced as a single unit out of plastic. When the rotor is turned, the connecting rods can execute a limited pivoting movement inside the lock housing, whereas their bearing ends are guided longitudinally in grooves in the lock housing. The elastic bands extend along radial slots in the rotor and merge with the inner ends of the associated connecting rods. These transition points tend to break easily, however, because of their thinness and because of the load exerted on them during the pivoting movements. The connecting rods have a grooved profile adjacent to their ends, into which the rotor can fit when the connecting rods pivot to the maximum extent. In the minimum pivot position of the connecting rods, their ends are designed to be supported on flattened circumferential areas on the rotor, in which case the elastic bands are bent at a right angle. The locking bars in this case are components which are independent in any case of the gear assembly, and they must be produced separately and then connected in an articulated manner to the two bearing ends of the gear assembly. Play must be allowed between the connecting rods and the locking bars and between the bearing ends and the housing grooves, but this play causes noise when the vehicle is moving. The invention is based on the task of developing a low-cost lock of the type indicated in the introductory clause of claim 1, which operates reliably, withstands strong loads, and survives many actuating cycles without damage. This is achieved according to the invention by the features listed in claim 1, to which the following special meaning attaches. In the invention, the inner section of the locking bar is used as an elastic element. This inner section of the locking bar is designed to be flexible and will therefore be referred to in the following as the “flexing section”. The flexing section obtains its flexibility through the longitudinal guide of the locking bar, which has a curved course in the area of the rotor. This curvature of the longitudinal guide produces the desired bending of the flexing section upon actuation of the rotor. The rotor itself is molded at a circumferential point onto the lateral flank of the flexing section. The molded connection is not subject to any bending stress and can therefore be made thick enough to be sufficiently sturdy. There is therefore no fear that this connecting point between the flexing section of the locking bar and the circumference of the rotor will break. Upon actuation of the rotor, the flexing section of the locking bar travels to a varying extent into the curved area of the longitudinal guide. The length of the bent part of the flexing section therefore changes. Additional measures and advantages of the invention can be derived from the subclaims, from the following description, and from the drawings. The invention is illustrated in the drawings on the basis of an exemplary embodiment: FIG. 1 shows a longitudinal section through the housing with the most essential parts of the inventive lock, which is shown in its locking position; FIG. 2 shows a view corresponding to FIG. 1, in which the lock is in its released position; FIG. 3 shows an enlarged view of the central area of this lock, designated “III” in FIG. 1; and FIGS. 4, 5, and 6 show cross sections through the lock along lines IV-IV, V-V, and VI-VI, respectively, of FIG. 3. The exemplary embodiment illustrated in the drawings represents a lock, which, with respect to its most important components, can be divided into two units 10 and 30, which, even though they comprise several elements, are each formed as a single unit. The one unit 10 comprises two locking bars 11, 12, and a rotor 20, located between the bars. Because these components are movable when actuated, they will be referred to in brief below as the “movable unit”. To accept this movable unit 10, a housing-like part is used, which, as can be seen in FIG. 1, can be divided into the following components. First, there is a first guide 31 and a second guide 32 for the two locking bars 11, 12. Between the guides is a carrier 33. Mounting flanges 34 can also be provided on the guides 31, 32 to attach this second unit 30. On the carrier 33 there is a bearing pin 35, which serves as a pivot bearing for the rotor 20. All these components 31 to 35 are designed to form a single unit in the present case, thus forming a common structural unit 30. Because, upon actuation of the lock, the elements of this structural unit 30 remain stationary, this unit will be referred to in brief in the following as the “stationary unit”. As can be seen in FIG. 1, the movable unit 10 is integrated into the stationary unit 30. This integration is accomplished after the two units 10, 30 have been fabricated. For this purpose, the housing-like components of the stationary unit 30 can be opened, e.g., by means of a removable cover, so that the movable unit 10 can be introduced as a whole into the stationary unit 30. After units 10 and 30 have thus been combined, a preassembled combination unit 40 is obtained, which can be attached as a whole either to the movable part or to the stationary part of a door or hatch in a vehicle. In the present case, as FIG. 1 illustrates, the combination unit 40 is attached to the door 41 of a glove compartment. The stationary part 42 consists in the present case of parts of the glove compartment housing. Locking openings 43 are provided in the housing, into which the ends 13 of the bars engage when the lock moves into the locking position shown in FIG. 1. Here, as usual, the locking ends of the bars are located at the outer ends of the bars. In the present case, the two locking bars 11, 12 are designed as mirror images of each other. It is therefore sufficient to describe their design on the basis of only the one locking bar 11, which will be done with the help of FIG. 2. The description applies analogously to the second locking bar 12. In the illustrated exemplary embodiment according to FIG. 2, the locking bar 11 can be divided into two main sections 14, 15, the dimensional stabilities of which differ from each other. Whereas the inner section 15 is designed to be flexible, the adjacent, remaining section 14 is essentially rigid. Because of its deformability, the inner section 15 will therefore be referred to in brief as the “flexing section”. The remaining section 14 of the locking bar is provided with a cranked part 16, which is provided here in the center of the remaining section 14 and therefore divides this section into three subsections 17, 18, 19. The first subsection 17 is adjacent to the outer end of the flexing section 15 and forms a linear extension of it; as can be seen in the enlarged view of FIG. 3, this subsection is essentially tangential to the rotational movement of the rotor, to be described in greater detail later. This movement is illustrated here by the rotational arrow 25. The third subsection 19 of the rigid remaining section projects straight out at a lateral offset from but parallel to the first subsection 17. The subsection 19 is oriented in such a way that it lies in the radial plane indicated in dash-dot line in FIG. 1, which passes through the axis of rotation 23, marked in the figure, of the rotor 20. The result is that, even though the initial subsections 17 of the two locking bars 11, 12 are laterally offset from each other as indicated at 37 in FIG. 2, their ends 13 nevertheless lie in the previously mentioned radial plane 24. The previously mentioned cranks 16 allow the subsections 18 to bridge this lateral offset 37. This is achieved by angling the course of these subsections 18, for which reason this section 18 is referred to in brief in the following as the “angled section”. The way in which the three elements 11, 12, 20 of the movable unit 10 are held together can be seen most clearly in FIG. 3. This is done, first, in that the two diametrically opposing circumferential points 21, 22 of the rotor 20 are molded onto the flexing sections 15 of the two bars 11, 12. This is done by means of the two radial arms 26, 27, which proceed from a common hub 28 and which are a component of the rotor 20. The previously mentioned circumferential points 21, 22 are in the present case formed by the free ends of these arms, onto which the flexing sections 15 are molded. The flexing sections continue tangentially from there in the form of the straight subsections 17 of the locking bars 11, 12. The two arms 26, 27 lie on the same diameter. One possibility of fabricating the movable unit 10 consists in forming the flexing sections 25 of the two locking bars 11, 12 out of one type of material and the remaining sections 14 out of a different material. In this case, the material used for the flexing sections 25 would be more flexible than that used for the rigid remaining sections 14. The rotor 20 between the bars would also be molded of this rigid material. The production of components from two different materials by injection molding is known and is referred to as the “two component process”. According to an exemplary embodiment, it is easier in terms of production to use the same material for both the flexing sections 25 and the remaining sections 14 plus the rotor 20, this material being rigid in and of itself. In this case, the different dimensional rigidities are obtained by providing the components with different profilings. This can be explained best by reference to FIGS. 36. A comparison of FIG. 4 with FIG. 6 shows that the width 44 and the height 45 of the profile in the flexing section 25 are essentially the same as those in the rigid sections 17. The deformability of the flexing section 25 is achieved by a special longitudinal profiling 46 of the flexing section 15. In this area, the cross section is reduced in certain areas, namely, at 47. Here there is a web 47, as can be seen in FIG. 4, which extends down the center of the profile. This web 47 connects two transverse plates 48, the outside edges of which, as can be seen in FIG. 5, are in contact with the inside surfaces of the associated guides 31, 32, to be described in greater detail below. One can think of this longitudinal profiling 46 as consisting of a row of H-shaped pieces 48, which are connected to each other in a polymer-like manner by central webs 47 on both sides. As previously mentioned, the adjacent subsection 17 already belongs to the remaining, rigid part of the bar, the structure of which can be derived from FIG. 6. Here the bar has a fissured cross section 50, which extends over the entire length of the previously described remaining section 14. In the present case, a cross-shaped profile is provided, consisting of the crossbars 51, 52, which extend in the width and height directions. By dividing the cross section 50 into elements in this way, a large geometrical moment of inertia is obtained with minimal use of material, which ensures the desired rigidity of these remaining sections 14. Instead of the previously described structure of the movable unit 10, it would also be possible, as an alternative, to provide a flexible connection between the main sections 14 of the two locking bars 11, 12, which are rigid in and of themselves, and the connecting points 21, 22 with the rotor 20. One could, in fact, consider the transition area of the flexing section 15 characterized by the number 53 in FIG. 3 as already representing a “flexible connection” of this type. This connection could alternatively consist of a so-called “film hinge” between the rotor 20 and the rigid initial section 17 of the rigid locking bar 11, 12. One could then either dispense completely with the guides 31, 32 or limit these guides to certain areas of support for the rigid remaining sections 14 of the two locking bars. As can be seen in FIGS. 46, each guide 31, 32 consists of a channel 54, which encloses the previously described cross sections 48, 50 on all sides. In the present case, as will be explained in greater detail on the basis of the second guide 32 of FIG. 2, the guide is designed in the following special way. Each of the two guides 32 has, first, a curved section 55, which is concentric to the axis of rotation 23 of the rotor. The curved section 55 is made just long enough to accommodate the flexing section 15 after the movable unit 10 and thus the ends 13 of the bars have been brought into the release position, as illustrated by the auxiliary line 10.2 in FIG. 2. In this situation, the rotor 20 has completed the previously mentioned rotational movement 25 away from the starting position shown in FIG. 1. The movable unit 10 is in its locking position in FIG. 1, as marked by the auxiliary line 10.1. In this case, the previously described connecting piece 53 of the flexing section 15 projects into the adjacent channel piece 57 according to FIG. 1, which, as can be seen in FIG. 2, is tangential to the curved section 55. This channel piece 57 serves primarily to accommodate the initial rigid section 17 of the associated locking bar 12, 11. This is followed by a channel piece 58, which accepts the previously described angled section 18 and therefore has a larger open width 56. The width 56 is greater than/equal to the length of the stroke 60 shown in FIG. 2 between the two end positions 10.1, 10.2 of the movable unit 10. If necessary, the lateral channel walls 36 can serve to limit this longitudinal stroke 60. This expanded third channel section 58 is followed, finally, by a last section 59, which serves as a longitudinal guide for the outermost section 19 of the locking bar, at the end of which the previously mentioned bar end 13 is located. This last channel section 59 lies on the previously described radial plane 24 of FIG. 1, which passes through the rotor 20. The one-piece movable unit 10 is subject to the action of a restoring force, which tries to move the two locking bars 11, 12 in opposite directions as indicated by the force arrows 61, 62 of FIG. 1. The restoring spring used for this purpose can act at any desired point. Because of the special one-piece design of the entire unit 10, it is recommended for this purpose that a common shank spring 38 be used, the first shank 29 of which is supported on the rotor 20, whereas the second shank 39 is supported on the carrier 33. This shank spring 38 wraps around the bearing pin 35, which, as previously mentioned, is seated on the carrier 33 and forms an integral part of the stationary unit 30. The carrier 33 ensures that the two guides 31, 32 are held in position, and it is also provided with mounting holes 63. Similar mounting holes 63 are also located in the mounting flanges 34, which, according to FIG. 2, are provided at the end of each of the guides 32, that is, on the last channel sections 59. A common actuator, which is not shown but which can consist of, for example, a handle to be pulled or turned, is provided for the two locking bars. It is sufficient for the actuator to act on one of the two locking bars 12 or 11, because they are both connected to the rotor 20, which synchronizes the movement of the two bars 11, 12. Because of the special one-piece design of the movable unit, this synchronized movement is free of play and free of rattling. In the present case, the attack point for the actuating end of an actuator of this type is a shoulder 64, which is seated in an axially fixed position on the second locking bar 12. In the normally present locking position 10.1 of the movable unit 10, the shoulder 64 is located in its rest position, marked by the auxiliary line 64.1 in FIGS. 1 and 3. By means of the previously mentioned actuator, the shoulder is moved as illustrated in FIG. 2 into its working position, indicated by the auxiliary line 64.2. As a result, the locking bars are moved in opposite directions, as indicated by the motion arrows 65, 66, and enter the associated channels 31, 32 of the stationary unit 30. To make it possible for the mounted rotor 20 to rotate in the guides 31, 32, openings 67, 68 are provided in the walls of the guides for the two arms 26, 27. In a similar manner, a cutout 69 is provided in the guide 32 to allow the longitudinal displacement of the shoulder 64; this cutout is made long enough to allow the longitudinal movement 70 shown in FIG. 2 between the two positions 64.1 and 64.2 of FIG. 2. LIST OF REFERENCE NUMBERS 10 first structural unit, one-piece movable unit 10.1 locking position of 10 (FIGS. 1, 3) 10.2 release position of 10 (FIG. 2) 11 first locking bar of 10 12 second locking bar of 10 13 ends of locking bars 11, 12 14 rigid main sections of 11, 12, remaining sections (FIG. 2) 15 flexible main sections of 11, 12, inner flexing sections (FIG. 2) 16 cranked sections of 11, 12 17 first subsection of 14, inner section (FIG. 20 18 second subsection of 14, central angled section (FIG. 2) 19 third subsection of 14, outer section (FIG. 2) 20 rotor 21 first circumferential point of 20 (FIG. 3) 22 second circumferential point of 20 (FIG. 3) 23 axis of rotation of the rotor 20 (FIGS. 1, 2) 24 radial plane passing through 23, for 19 (FIG. 1) 25 arrow of the rotation of 20 (FIG. 3) 26 first radial arm of 20 at 21 (FIG. 3) 27 second arm of 20 at 22 (FIG. 3) 28 hub of 20 29 first shank of spring 38, on 20 (FIG. 3) 30 second structural unit, stationary unit 31 first guide of 30, for 11 32 second guide of 30, for 12 33 carrier between 31 and 32 (FIG. 3) 34 mounting flanges on 31, 32 (FIG. 1) 35 bearing pin for 20 (FIG. 3) 36 inner channel wall at 58 (FIG. 2) 37 lateral offset between sections 17 of 11 and 12 (FIG. 2) 38 shank spring for 61, 62 (FIG. 3) 39 second shank of spring 38, on 33 (FIG. 3) 40 combination unit consisting of 10 and 30 (FIG. 1) 41 movable part, door 42 stationary part, housing 43 locking opening in 42 for 13 (FIG. 1) 44 outside width of profile of 25 or 17 (FIGS. 4, 5) 45 outside height of profile of 25 or 17 (FIGS. 4, 5) 46 longitudinal profiling of 15 (FIG. 3) 47 web of 46 in 15 (FIG. 3) 48 transverse plate of 46 in 15 (FIG. 3) 49 H-shaped piece consisting of 47, 48 (FIG. 3) 50 fissured cross section of 14, 17 (FIG. 6) 51 first crossbar of 50 (FIG. 6) 52 second crossbar of 50 (FIG. 6) 53 flexible connection at 15 (FIG. 3) 54 channel for 31, 32 (FIGS. 5, 6) 55 first channel piece of 32 or 31, curved section (FIG. 2) 56 open width of 58 (FIG. 2) 57 second channel piece, for 17, tangential piece (FIG. 2) 58 third channel piece, for 18, expanded channel piece (FIG. 2) 59 fourth channel piece, for 19, last channel piece (FIG. 2) 60 stroke of 13 (FIG. 2) 61 force arrow for 11 (FIG. 1) 62 force arrow for 12 (FIG. 1) 63 mounting holes in 33 and 34 for 30 and 40 (FIG. 1) 64 shoulder on 12 (FIG. 1) 64.1 rest position of 64 (FIGS. 1, 2) 64.2 working position of 64 (FIG. 2) 65 arrow of the inward travel of 11 (FIG. 2) 66 arrow of the inward travel of 12 (FIG. 2) 67 cutout in 31 for 26 (FIG. 3) 68 cutout in 32 for 27 (FIG. 3) 69 cutout in 32 for 34 (FIG. 3) 70 longitudinal movement of 64 (FIG. 2)
20041215
20070417
20051013
64615.0
1
LUGO, CARLOS
LOCK COMPRISING TWO LOCKING RODS, IN PARTICULAR FOR VEHICLES
UNDISCOUNTED
0
ACCEPTED
2,004
10,518,223
ACCEPTED
Pharmaceutical preparation and method of treatment of human malignancies with arginine deprivation
The present invention provides an isolated and substantially purified recombinant human arginase having sufficiently high enzymatic activity and stability to maintain Adequate Arginine Depletion in a patient. The present invention also provides a pharmaceutical composition comprising the modified invention enzyme and method for treatment of diseases using the pharmaceutical composition.
1. An isolated recombinant human arginase I, comprising substantially the same amino acid sequence as set forth in SEQ ID NO: 9 and having a purity of 80-100%. 2. The recombinant human arginase I according to claim 1 further comprising six histidines attached to the amino terminal end thereof. 3. The recombinant human arginase I according to claim 1 having a specific activity of at least 250 I.U./mg. 4. The recombinant human arginase I according to claim 3 having a specific activity of 500 to 600 I.U./mg. 5. The recombinant human arginase I according to claim 4, comprising a modification that results in an in vitro plasma half-life of at least approximately 3 days. 6. An isolated recombinant human arginase I according to claim 1, having a purity of at least 90%. 7. The recombinant human arginase I according to claim 5, wherein said modification is pegylation. 8. The recombinant human arginase I according to claim 7, wherein said pegylation results from covalently attaching at least one polyethylene glycol (PEG) moiety to said arginase using a coupling agent. 9. The recombinant human arginase I according to claim 8, wherein said coupling agent is selected from the group consisting of 2,4,6-trichloro-s-triazine (cyanuric chloride, CC) and succinimide propionic acid (SPA). 10. A method of producing recombinant protein comprising: (a) cloning a gene encoding said protein; (b) constructing a recombinant Bacillus subtilis strain for expression of said protein; (c) fermenting said recombinant Bacillus subtilis cells using fed-batch fermentation; (d) heat-shocking said recombinant Bacillus subtilis cells to stimulate expression of said recombinant protein; and (e) purifying said recombinant protein from the product of said fermentation. 11. The method according to claim 10 wherein said Bacillus subtilis is a prophage. 12. The method according to claim 10 wherein said protein is human arginase I. 13. The method according to claim 12 wherein said human arginase I comprises six histidines linked to the amino-terminus thereof, and said purifying step comprises affinity chromatography in a chelating column. 14. The method according to claim 12 wherein said fermenting step is performed using a feeding medium consisting essentially of 180-320 g/L glucose, 2-4 g/L MgSO4.7H2O, 45-80 g/L tryptone, 7-12 g/L K2HPO4 and 3-6 g/L KH2PO4. 15. A pharmaceutical composition comprising an isolated and substantially purified arginase. 16. The pharmaceutical composition according to claim 15 wherein said recombinant human arginase is human arginase I. 17. The pharmaceutical composition according to claim 15 wherein said recombinant human arginase is human arginase I, further comprising eentaifing six additional histidines attached to the amino terminal end thereof. 18. The pharmaceutical composition according to claim 15, wherein said composition is further formulated in a pharmaceutically acceptable carrier. 19. The pharmaceutical composition according to claim 15, wherein the formulation of said pharmaceutical composition is in a form suitable for oral use, for a sterile injectable solution or a sterile injectable suspension. 20. The pharmaceutical composition according to claim 16, wherein said recombinant human arginase I has a specific enzyme activity of at least 250 I.U./mg. 21. The pharmaceutical composition according to claim 20, wherein said recombinant human arginase I has a specific enzyme activity of 500 to 600 I.U./mg. 22. The pharmaceutical composition according to claim 16, wherein said recombinant human arginase I has a half-life in patient plasma of at least 3 days. 23. The pharmaceutical composition according to claim×22, wherein said recombinant human arginase I has a half-life in patient plasma of approximately at least 1 day. 24. A method of treatment of human malignancies, comprising administering human arginase I. 25. A method of treatment of human malignancies comprising administering the pharmaceutical composition of claim 15. 26. The use according to method of claim 25, wherein said human malignancies are selected from the group consisting of: liver tumor, breast cancer, colon cancer and rectal cancer. 27. A method of treatment of human malignancies comprising administering recombinant human arginase to a patient. 28. A method of treatment of human malignancies in a patient comprising administering a pharmaceutical composition that reduces the physiological arginine level in said patient to below 10 μM for at least 3 days.
FIELD OF INVENTION The present invention is related to pharmaceutical compositions containing arginase and use therefor. In particular, the present invention is related to pharmaceutical compositions that have the capability of reducing the arginine level in patients with tumours and its use for treatment of human malignancies. The present invention also relates to a method of producing a recombinant protein. BACKGROUND OF INVENTION Arginase I (EC 3.5.3.1; L-arginine amidinohydrolase), is a key mammalian liver enzyme that catalyses, the final step in the urea formation in the Urea cycle, converting arginine into ornithine and urea. Rat liver extract, which has a high content of arginase, was found to have anti-tumour properties in vitro when it was accidentally added to tumour cell culture medium (Burton et al., 1967, Cytolytic action of corticosteroids on thymus and lymphoma cells in vitro. Can J. Biochem. 45, 289-297). Subsequent experiments showed that the anti-tumour properties of the enzyme were due to depletion of arginine, which is an essential amino acid in the culture medium. At below 8 μM levels of arginine, irreparable cell death in cancer cells occurred (Storr & Burton, 1974, The effects of arginine deficiency on lymphoma cells. Br. J. Cancer 30, 50-59). A more novel aspect of arginine centers on its role as the direct precursor for the synthesis of the potent signalling molecule nitric oxide (NO), which functions as a neurotransmitter, smooth muscle relaxant, and vasodilator. Biosynthesis of NO involves a Ca++, NADPH-dependent reaction catalysed by nitric oxide synthase (NOS). Another recognized role of arginine is that it acts as a precursor, via ornithine, of the polyamines, spermidine and spermine, which participate in diverse physiologic processes including cell proliferation and growth (Wu & Morris, 1998, Arginine metabolism: nitric oxide and beyond. Biochem. J. 336, 1-17). Arginine also serves as a substrate for several important enzymes, including nitric oxide synthase (NOS). There are three types of NOSs, nNOS, eNOS and iNOS, all convert arginine to nitric oxide and citrulline. The facial flushes induced by NO, for instance, is mediated through nNOS, the neuronal type of NOS. iNOS, the inducible NOS is produced by macrophages and the NO so produced from arginine during septicaemia causes vasodilation in endotoxic shock. eNOS, the endothelial NOS, is produced by endothelial cells in blood vessels. It converts arginine into NO, which then causes de-aggregation of platelets in the endothelial surfaces through cGMP mechanism. NO produced from eNOS in the local endQthelial lining has a half-life of about 5 seconds and diffusion distance of about 2 microns. The productions of these enzymes are controlled by different NOS genes (NOS1, NOS2, NOS3) encoded in chromosomes 12, 17 & 7, respectively. These genes share strikingly similar genomic structures in size of exons and the location of the splice junctions. The in vitro anti-tumour activities of arginine depletion were confirmed recently by a group in Scotland, UK (Scott et al., 2000, Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignanat cells. Br. J. Cancer 83, 800-810; Wheatley et al., 2000, Single amino acid (arginine) restriction: Growth and Death of cultured HeLa and Human Diploid Fibroblasts. Cellular Physiol. Biochem. 10, 37-55). Of the 24 different tumour cell lines tested, which included common cancers such as breast, colorectal, lung, prostate and ovaries, all died within 5 days of arginine depletion. Using flow-cytometry studies, the group was able to show that normal cell lines would enter into quiescence for up to several weeks in G0 phase of the cell cycle without any apparent harm. Tumour cells, however, would proceed pass the “R” point in the G1 phase and enter the S phase with deficiency of arginine. Without arginine, which is an irreplaceable amino acid, protein synthesis is deranged. Some cell lines were shown to die from apoptosis. More excitingly, repeated depletions can bringforth tumour kill without “resistance” being developed (Lamb et al., 2000, Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of Cdk4 expression in cultured human diploid fibroblasts. Experimental Cell Research 225, 238-249). Despite the promising in vitro data, attempts with arginine depletion to treat cancer in vivo were unsuccessful. The original Storr group attempted to treat tumour-bearing rats with intraperitoneal liver extracts and met with no success (Storr & Burton, 1974, The effects of arginine deficiency on lymphoma cells. Br. J. Cancer 30, 50-59). It is now generally recognized that under normal physiological condition, the blood plasma arginine level and indeed that of other amino acids too, are kept between the normal ranges (100-120 μM) with muscle being the main regulator. In the face of amino acid deficiency, intracellular protein breakdown pathways are activated (proteasomal and lysosomal) releasing amino acids into the circulation (Malumbres & Barbacid, 2001, To cycle or not to cycle: a critical decision in cancer. Nature Reviews, 1, 222-231). This amino acid homeostatic mechanism keeps the various amino acid levels at constant ranges. Thus, previous attempts to deplete arginine with various physical methods or arginine degrading enzymes have failed because of the body's amino acid homeostatic mechanism. To overcome the problem on the body's natural homeostatic tendencies, Tepic et al. in U.S. Pat. No. 6,261,557 described a therapeutic composition and method for treatment of cancer in which an arginine decomposing enzyme is used in combination with a protein breakdown inhibitors such as insulin in order to prevent the muscles of the body from replenishing the depleted arginine. Although insulin can act as a protein breakdown inhibitor, it also has far-reaching physiological effects on the human body that may cause fatal problems if blood glucose levels of the patient are not strictly maintained within the narrow normal range. It is therefore an object to the present invention to find improved method of treatment and compositions for the treatment of cancer. SUMMARY OF INVENTION Accordingly, the present invention provides, in one aspect, an isolated and substantially purified recombinant human arginase I (hereinafter referred to as “Arginase” for ease of description unless otherwise stated) having a purity of 80-100%. In the preferred embodiment, the Arginase has a purity of between 90-100%. In the most preferred embodiment, the Arginase according to the present invention is at least 99% pure. In the example described below, the Arginase is more than 99.9% pure based on densitometry tracing after SDS-PAGE separation. In another preferred embodiment, the Arginase of the present invention is modified to have sufficiently high enzymatic activity and stability to maintain “adequate arginine deprivation” (hereinafter referred to as “AAD”) in a patient for at least 3 days. One preferred method of modification is an amino-terminal tag of six histidines. Another preferred modification is pegylation to increase the stability of the enzyme and minimise immunoreactivity illicited by the patient thereto. In the example described below, the Arginase has a plasma 12-life of at least about 3 days and specific activity of at least about 250 I.U./mg. In another aspect of the present invention, a method is provided for producing a recombinant protein comprising the steps of (a) cloning a gene encoding the protein; (b) constructing a recombinant Bacillus subtilis strain for expression of said protein (c) fermenting said recombinant B. subtilis cells using fed-batch fermentation; (d) heat-shocking said recombinant B. subtilis cells to stimulate expression of said recombinant protein; and (e) purifying said recombinant protein from the product of said fermentation. In the preferred embodiment, a prophage is used as the recombinant strain. Using the fed-batch method of fermentation and prophage described above for the cloning and expression of human recombinant arginase, there is more than a 4-fold increase in maximum optical density at wavelength of 600 nm (OD) reached, and more than 5 times improvement in both the yield and productivity of the Arginase as shown in Example 3 in the next section. In a further embodiment, the fermenting step can be scaled up for producing the recombinant protein. In a further embodiment, the fermenting step is performed using a well-defined feeding medium of 180-320 g/L glucose, 2-4 g/L MgSO4.7H2O, 45-80 g/L tryptone, 7-12 g/L K2HPO4 and 3-6 g/L KH2PO4. The use of a well-defined medium prevents undesirable material from being purified together with the recombinant protein, making the method safe and efficient for the production of pharmaceutical grade recombinant material. In yet another preferred embodiment, the human Arginase gene is provided with an additional coding region that encodes six additional histidines at the amino-terminal end thereof, and the purifying step comprises a chelating column chromatography step. In a further preferred embodiment, the Arginase enzyme is further modified by pegylation to improve stability. In another aspect of the present invention, there are further provided pharmaceutical compositions comprising Arginase. In the preferred embodiment, the Arginase has sufficiently high enzymatic activity and stability to maintain AAD in a patient for at least 3 days. In the most preferred embodiment, the Arginase is further modified by pegylation to improve stability and minimise immunoreactivity. According to another aspect of the present invention, a pharmaceutical composition is further formulated using Arginase. In yet another aspect of the present invention, a method for treatment of a disease is provided comprising administering a formulated pharmaceutical composition of the present invention to a patient to maintain the arginine level in such a patient to below 10 LM for at least 3 days without the need for other protein breakdown inhibitors. In one of the preferred embodiments, no insulin is administered exogenously for non-diabetic patients. Furthermore, the most preferred treatment method of the present invention involves the monitoring of the patient's blood for platelet count (preferably maintained above 50,000×109) and prothrombin time (maintained no more than 2 times normal). No nitric oxide producer is exogenously administered unless these levels of platelet count and prothrombin time are not reached. In another preferred embodiment of this aspect of the present invention, pegylated Arginase is given as short infusion of over 30 minutes at 3,000-5,000 I.U./kg in short infusion. arginine levels and Arginase activity are taken before Arginase infusion and daily thereafter. If AAD is not achieved on day 2, the dose of the next infusion of Arginase is under the discretion of the treating physician. The maximum tolerated duration of AAD is defined as the period of time during which blood pressure is under control (with or without medication as deem appropriate by the treating physician), platelet count above 50,000×109 and prothrombin time less than 2× normal. As with arginine levels, complete blood count (CBC) and prothrombin time (PT) are taken daily. Liver chemistry is monitored at least twice weekly during the treatment. The experimental data provided in the following detailed description shows that arginase, if provided at sufficiently potent form, is useful for the treatment of maligancies. Although recombinant human arginase I is the specific embodiment of an arginase that is used for the present disclosure, it is clear that other forms of arginase and/or from other sources may be used in accordance with the present invention. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows plasmid map of pAB101. This plasmid carries the gene encoding Arginase (arg) and only replicates in E. coli but not in B. subtilis. FIGS. 2A, 2B and 2C show nucleotide sequence and its deduced amino acid sequence of the human Arginase I. FIG. 2A shows the nucleotide sequence (SEQ ID NO: 1) from EcoRI/MunI to XbaI sites of plasmid pAB101. Nucleotide (nt) 1-6, EcoRI/MunI site; nt 481-486, -35 region of promoter 1; nt 504-509, -10 region of promoter 1; nt 544-549, -35 region of promoter 2; nt 566-571, -10 region of promoter 2; nt 600-605, ribosome binding site; nt 614-616, start codon; nt 632-637, NdeI site; nt 1601-1603, stop codon; nt 1997-2002, XbaI site. FIG. 2B shows the encoding nucleotide sequence (SEQ ID NO: 2) and its corresponding encoded amino acid sequence (SEQ ID NO: 3) of a modified human Arginase. Nucleotide 614-1603 from FIG. 2A is a encoding region for the amino acid sequence of the modified Arginase. The 6×His (SEQ ID NO: 4) tag at the N-terminus is underlined. Translation stop codon is indicated by asterisk. FIG. 2C shows the encoding nucleotide sequence (SEQ ID NO:8) and its corresponding encoded amino acid sequence (SEQ ID NO:9) of the normal human Arginase I. FIG. 3 is a schematic drawing of the construction of a B. subtilis prophage allowing expression of Arginase. FIGS. 4A and 4B show the time-course for fermentation in a 2-liter fermentor by the recombinant Bacillus subtilis strain LLC101. FIG. 4A shows the results obtained from the batch fermentation. FIG. 4B shows the results obtained from the fed-batch fermentation. FIGS. 5A and 5B show history plots of the fermentation showing the changes of parameters such as temperature, stirring speed, pH and dissolved oxygen values. FIG. 5A shows the history plot from the batch fermentation. FIG. 5B shows the history plot from the fed-batch fermentation. FIGS. 6A and 6B show the results of biochemical purification of human Arginase at 3 h after heat shock by the first 5-ml HiTrap Chelating column. FIG. 6A shows the FPLC running parameters and protein elution profile. FIG. 6B shows the SDS-PAGE (12%) analysis of 5 μl of each of the fractions 11-31 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 7A and 7B show results of purification of the human Arginase at 3 h after heat shock by the second 5-ml HiTrap Chelating column. FIG. 7A shows the FPLC running parameters and protein elution profile. FIG. 7B shows the SDS-PAGE (12%) analysis of 1 μl of each of the fractions 9-39 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 8A and 8B show results of purification of the human Arginase at 6 h after heat shock by the first 5-ml HiTrap Chelating column. FIG. 8A shows FPLC running parameters and protein elution profile. FIG. 8B shows the SDS-PAGE (12%) analysis of 2.5 μl of each of the fractions 10-32 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 9A and 9B show results of purification of the human Arginase at 6 h after heat shock by the second 5-ml HiTrap Chelating column. FIG. 9A shows FPLC runing parameters and protein elution profile. FIG. 9B shows the SDS-PAGE (12%) analysis of 2 μl of each of the fractions 8-E6 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,40. FIG. 10 shows the time-course of bacterial cell growth when heat shock was performed at a higher cell density. Heat shock was performed at 8 h when the culture density (OD600nm) was about 25. FIG. 11 is the history plot of the fed-batch fermentation when heat shock was performed at a higher cell density. This plot shows the changes of parameters such as temperature, stiring speed, pH and dissolved oxygen values. FIGS. 12A and 12B show the results of purification of the human Arginase at 6 h after heat shock (at a higher cell density of OD 25) by the first 5-ml HiTrap Chelating column. FIG. 12A shows FPLC running parameters and protein elution profile. FIG. 12B shows results of SDS-PAGE (12%) analysis of 5 μl of each of the fractions 16-45 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. Lane “crude”: 5 μl of the crude cell extract before loading the column. FIGS. 13A and 13B show the results of purification of the human Arginase at 6 h after heat shock (at a higher cell density of OD 25) by the second 5-ml HiTrap Chelating column. FIG. 13A shows FPLC running parameters and protein elution profile. FIG. 13B shows the SDS-PAGE (12%) analysis of 5 μl of each of the fractions 7-34 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 14A and 14B show the results of purification of the human Arginase at 6 h after heat shock (at a higher cell density of OD 25) by the first 1-ml HiTrap SP FF column. FIG. 14A shows FPLC running parameters and protein elution profile. FIG. 14B shows the SDS-PAGE (12%) analysis of 5 μl of each of the fractions A11-B7 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 15A and 15B show the purification of the human Arginase at 6 h after heat shock (at a higher cell density of OD 25) by the second 1-ml HiTrap SP FF column. FIG. 15A shows the FPLC running parameters and protein elution profile. FIG. 15B shows the SDS-PAGE (12%) analysis of 5 μl of each of the fractions A6-B12 collected from the column. The protein gel was stained with coomassie brilliant blue and destained to show the protein bands. Lane M: low-range molecular weight marker (1 μg per band; Bio-Rad), with MW (Daltons): 97,400; 66,200; 45,000; 31,000; 21,500; 14,400. FIGS. 16A and 16B are the SDS-PAGE (15%) analysis of the human Arginase modified with MnPEG-SPA (MW 5,000) using the Arginase:PEG mole ratio of 1:50. FIG. 16A shows the results when reactions were performed on ice. Lane 1: low-range protein marker; Lane 2: Arginase (5.35 μg) without PEG added (control); Lane 3: 1 h after reaction; Lane 4: 0.5 h after reaction; Lane 5: 2 h after reaction; Lane 6: 3 h after reaction; Lane 7: 4 h after reaction; Lane 8: 5 h after reaction; Lane 9: 23 h after reaction. FIG. 16B shows the results when reactions were performed at room temperature. Lane 1: low-range protein marker, Lane 2: Arginase (5.35 μg) without PEG added (control); Lane 3: 1 h after reaction; Lane 4: 0.5 h after reaction; Lane 5: 2-h after reaction; Lane 6: 3 h after reaction; Lane 7: 4 h after reaction; Lane 8: 5 h after reaction; Lane 9: 23 h after reaction. FIGS. 17A and 17B are the SDS-PAGE (15%) analysis of the human Arginase modified with mPEG-SPA (MW 5,000) using the Arginase:PEG mole ratio of 1:20. FIG. 17A shows the results when reactions were performed on ice. Lane 1: low-range protein marker; Lane 2: Arginase (5.35 μg) without PEG added (control); Lane 3: 1 h after reaction; Lane 4: 0.5 h after reaction; Lane 5: 2 h after reaction; Lane 6: 3 h after reaction; Lane 7: 4 h after reaction; Lane 8: 5 h after reaction; Lane 9: 23 h after reaction. FIG. 17B shows the results when reactions were performed at room temperature. Lane 1: low-range protein marker; Lane 2: Arginase (5.35 μg) without PEG added (control); Lane 3: 1 h after reaction; Lane 4: 0.5 h after reaction; Lane 5: 2 h after reaction; Lane 6: 3 h after reaction; Lane 7: 4 h after reaction; Lane 8: 5 h after reaction; Lane 9: 23 h after reaction. FIG. 18A is the SDS-PAGE (15%) analysis of the human Arginase modified with mPEG-CC (MW 5,000). The reactions were performed on ice. Lane 1: low-range protein marker; Lane 2: Arginase (5.35 μg) without PEG added (control); Lane 3: 2 h after reaction with Arginase:PEG mole ratio of 1:50; Lane 4: empty; Lane 5: 23 h after reaction with Arginase:PEG mole ratio of 1:50; Lane 6: 2 h after reaction with Arginase:PEG mole ratio of 1:20; Lane 7: 5 h after reaction with Arginase:PEG mole ratio of 1:20; Lane 8: 23 h after reaction with Arginase:PEG mole ratio of 1:20. FIG. 18B shows the SDS-PAGE (12%) analysis of the native and the pegylated Arginase which are highly active and stable. Lane 1: Low-range protein marker (Dio-rad); Lane 2: Native Arginase (1 μg); Lane 3: Pegylated Arginase (1 μg); Lane 4: Pegylated Arginase after ultra-dialysis (1.5 μg). FIGS. 19A and 19B show the measurement of the isolated recombinant human Arginase purity. FIG. 19A shows that for Lane 1: 5 μg of purified E. coli-expressed recombinant human Arginase obtained from methods described by Ikemoto et al. (Ikemoto et al., 1990, Biochem. J. 270, 697-703). Lane 2: 5 μg of purified B. subtilis-expressed recombinant human Arginase obtained from methods described in this report. FIG. 19B shows the analysis of densities of protein bands shown in FIG. 19A with the Lumianalyst 32 program of Lumi-imagerm (Roche Molecular Biochemicals). Upper panel: results from lane 1 of FIG. 19A. Lower panel: results from lane 2 of FIG. 19A. FIG. 20 is a diagram to show the stability of the pegylated Arginase in vitro in human blood plasma. FIGS. 21 and 22 show the half-life determination in vivo of pegylated Arginase obtained from the method described in example 8A. FIG. 21 shows the in vivo activity of the pegylated Arginase produced according to the present invention using the activity test described in Example 9A. FIG. 22 is a plot from which the first half-life and the second half-life of the pegylated Arginase are determined. FIG. 23 is a comparison of arginine depletion in four groups of laboratory rats administered intraperitoneally with different dosages of pegylated recombinant human Arginase (500 I.U., 1000 I.U., 1500 I.U., and 3000 I.U.). FIG. 24 shows the comparison of survival rate, average tumour size and tumour growth rate of tumours between 2 groups of nude mice which have tumours induced by implantation with Hep3B cells. One group was treated with Arginase with dosage of 500 I.U. intraperitoneally while the other control group was not treated with Arginase. FIGS. 25A and 25B show the comparison of average tumour size and average tumour weight between 2 groups of nude mice which have tumours induced by implantation with PLC/PRF/5 cells. One group was treated with Arginase with dosage of 500 I.U. intraperitoneally while the other control group was not treated with Arginase. FIGS. 26A and 26B show the comparison of average tumour size and average tumour weight of 2 groups of nude mice which have tumours induced by implantation with HuH-7 cells. One group was treated with Arginase with dosage of 500 I.U. intraperitoneally while the other control group was not treated with Arginase. FIG. 27 shows the comparison of average tumour size of 2 groups of nude mice which have tumours induced by implantation with MCF-7 cells. One group was treated with Arginase with dosage of 500 I.U. intraperitoneally while the other control group was not treated with Arginase. FIG. 28 and FIG. 29 show in vivo arginine and CEA levels respectively of the patient during treatment as described in Example 12. DETAILED DESCRIPTION As used herein, the term “pegylated Arginase” refers to Arginase I of present invention modified by pegylation to increase the stability of the enzyme and minimise immunoreactivity. As used herein, the phrase “substantially the same”, whether used in reference to the nucleotide sequence of DNA, the ribonucleotide sequence of RNA, or the amino acid sequence of protein, refers to sequences that have slight and non-consequential sequence variations from the actual sequences disclosed herein. Species with sequences that are substantially the same are considered to be equivalent to the disclosed sequences and as such are within the scope of the appended claims. In this regard, “slight and non-consequential sequence variations” means that sequences that are substantially the same as the DNA, RNA, or proteins disclosed and/or claimed herein are functionally equivalent to the sequences disclosed and/or claimed herein. Functionally equivalent sequences will function in substantially the same manner to produce substantially the same compositions as the nucleic acid and amino acid compositions disclosed and claimed herein. In particular, functionally equivalent DNAs encode proteins that are the same as those disclosed herein or proteins that have conservative amino acid variations, such as substitution of a non-polar residue for another non-polar residue or a charged residue for a similarly charged residue. These changes include those recognized by those of skill in the art not to substantially alter the tertiary structure of the protein. The term “sufficiently high enzymatic activity” refers to the enzyme specific activity of the recombinant human Arginase for at least 250 I.U./mg, preferably at least 300-350 I.U./mg, more preferably at least 500 I.U./mg. In the preferred embodiment, the Arginase has a specific activity of 500-600 I.U./mg. The term “stability” refers to in vitro stability of the Arginase. More preferably, the stability refers to in vivo stability. The rate of decrease of enzyme activity is inversely proportional to the plasma stability of the isolated, purified recombinant human Arginase. The half-life of such a human Arginase in plasma is calculated. As used herein, the term “adequate arginine deprivation” (AAD) refers to in vivo arginine level at or below 10 μM. The term “disease” refers to any pathological conditions, including but not limited to liver diseases and cancer. As used herein, the term “half-life” (½-life) refers to the time that would be required for the concentration of the Arginase in human plasma in vitro, to fall by half. In early 2001, three cases of spontaneous transient remission of hepatocellular carcinoma (HCC) were observed by one of the inventors of the present invention. All three patients had spontaneous rupture of HCC with resulting haemoperitoneum. In one case, the plasma arginine was found to be as low as 3 μM and arginine level in the ascitic fluid at 7 μM. These patients all had spontaneous remission of their liver tumour with normalization of alpha-fetoprotein (AFP) after ruptured liver lesions in the absence of any treatment using any pharmaceutical drugs. One patient had remission of his HCC for over 6 months. In accordance with the present invention, it is believed that such prolonged remission is caused by arginine depletion due to the spontaneous and sustained release of endogenous Arginase into the peritoneum from the rupture of the liver. Thus, the inventors inferred that prolonged arginine depletion was the causative factor leading to remission of HCC. A series of experiments was then designed by the inventor of the present invention to show that endogenous hepatic Arginase can be released from the liver after transhepatic arterial embolisation causing systemic arginine deprivation. This has now been filed in the U.S. provisional patent application No. 60/351,816, which is incorporated by reference herewith. In the experiments designed by the inventor, moderate and measurable amount of endogenous hepatic arginase was found to be released into the systemic circulation in patients with unresectable metastatic HCC after hepatic arterial embolisation treatment using lipiodol and gel foam that caused a temporary hepatic perfusion defect. High dose insulin infusion was incorporated into the treatment regime to induce a state of hypoaminoacidemia. In a series of 6 cases of HCC treated, 4 had extra hepatic remission of liver cancer suggesting the treatment effects are systemic. One patient had sustained complete remission, both radiological with CT and PET in his liver and extrahepatic disease (celiac adenopathy). His AFP level dropped to normal within 3 weeks and sustained for over 4 months. Interval CT at 4 months showed no demonstrable tumour both hepatic or extrahepatic. The other 3 patients all had remission of their extra hepatic disease (one pulmonary, one mesenteric/retroperitoneal/bone and one retroperitoneal adenopathy) on PET scan at 4 weeks after embolisation. On testing their Arginase activities and arginine levels, all had adequate arginine depletion for a period of time lasting from 2 hours to 2 days. In fact the duration of AAD correlated well with the degree and duration of remission of the tumour, both hepatic and extra-hepatic. Although the transhepatic arterial embolisation technique was performed in conjunction with high doses of insulin infusion, the inventors, in accordance with the present invention, subsequently came to the realisation that the need for the administration of insulin was due to the fact that insufficient arginase activities may be released into the system of the patient such that any protein degradation from the muscle would have a compensatory effect from the arginine deprivation and render the treatment ineffective. In accordance with the present invention, the inventors realised that in order to improve the treatment and to eliminate the need for administration of insulin in conjunction with the arginine deprivation treatment, arginase activity has to be present in sufficiently high amounts in the patient's system in order to counteract any protein degradation from the muscle. In accordance with the present invention, the inventors therefore set out to produce an Arginase enzyme that had sufficiently high enzymatic activities and stability to maintain “adequate arginine deprivation” hereinafter referred to as “AAD”) of below 10 μM in the patient without the need to administrate high dose of insulin. Thus, in addition to augmenting the endogenous Arginase, the highly stable and active Arginase according to the present invention provides the additional benefit of allow AAD to be attained without the administration of a protein degradation inhibitor, which has undesirable side effects on the patient. Systemic depletion of arginine may cause other undesirable side effect related to nitric oxide deficiency. These include hypertension due to absence of vasodilator effect of NO on vascular endothelium, platelet aggregation and thrombocytopenia secondary to lack of NO and depletion of early clotting factors related to temporary cessation of cell division. The inventor recognized, however, that in nitric oxide knock out mice the animals are not hypertensive and have normal life expectance with normal platelet counts. Thus, in accordance with another aspect of the present invention and in patients with thrombocytopenia, no overt haemorrhagic tendency is seen until platelet count is well below 50,000×109. In patients with thrombotic tendency, therapy entails prolonging the prothrombin time for up to 2× normal. The following detailed examples teach how to make and use a highly stable and active Arginase according to the present invention. Example 1 describes the construction of the recombinant strain of Bacillus subtilis LLC101 containing the human Arginase I gene. This is followed by two examples of fermentation of the recombinant B. subtilis. In the initial fermentation experiments of the recombinant LLC101 cells, batch fermentation and fed-batch fermentation were conducted in a 2-L fermentor. It was found that under batch conditions sufficiently high cell density could not be attained. Only under the fed-batch conditions provided in accordance with the present invention would cell density be increased to above 10 OD (optical density). These experiments and results are shown in Examples 2A and 2B. A comparison of the 2 fermentation methods is shown in Example 3. Fed-batch fermentation operation was thus chosen for production of isolated and purified recombinant human Arginase. The fed-batch fermentation was scaled up in a 100-L fermentor. The experiments and results are shown in Example 2C. The LLC101 strain is a heat sensitive strain that causes expression of the Arginase upon heat shock at 50° C. In the initial optimisation experiments, the heat shock treatment was performed at varying cell densities to obtain the optimal conditions under which maximum Arginase would be produced. Examples 5 and 6 describe the purification process and the yield of purified Arginase thus obtained of two different fed-batch fermentation runs with heat shock at two different OD (optical density at 600 nm), 12.8 and 25. The experimental data showed that although all heat shocks were applied during the exponential growth phase of the LLC101, introduction of heat shock at a lower cell density, e.g., 12.8 OD, produced better results. Conditions for maximum expression of Arginase after heat shock was also optimised by varying the time of harvest after heat shock. Example 4 shows results from harvesting the cells three hours after heat shock and using a fed-batch fermentation process. Example 5 describes a purification of Arginase 6 hours after heat shock at a cell density of 12.8 OD. Example 6 describes the purification of Arginase 6 hours after heat shock at a higher cell density of 250D. Example 7 shows a comparison of the data to compare the yield of the Arginase under various harvesting and purification conditions. These data show that harvesting cells 6 h after heat shock at a lower cell density of 12.8 produced a higher Arginase yield of 162 mg/L. The Arginase was modified to improve stability. Example 8A shows one protocol for the pegylation of the Arginase using cyanuric chloride (cc) as the cross-linker at an ratio of 1:140 (Arginase:PEG) mole ratio. Example 8B describes a different pegylation protocol in which a much lower proportion of cross-linker is added into the reaction mixture with the enzyme. Both cc and succinimide of propionic acid (SPA) were tested as cross-linker. Experimental results show that the method as described in Example 8B using SPA provided a pegylated Arginase with a 12-life of 3 days and a specific activity of approximately 255 I.U./mg as discussed in Examples 9 and 10. Example 8C describes a method for preparing a highly active pegylated Arginase, which has a specific activity of about 592 I.U./mg. Using the method as described above, a highly stable and active Arginase has been produced. It has sufficiently high activity and stability to allow treatment of patients without significant use of a protein degradation inhibitor because any replenishment of arginine by the muscle would be quickly removed by the systemic Arginase. Thus, adequate arginine deprivation of below 10 μM can be achieved without high doses of exogenously administered insulin. Various treatment protocols using the Arginase according to the present invention is described in Example 11. Example 12 illustrates the clinical data of a patient administered with Arginase to further support the treatment protocol shown in Example 11. Examples 13 to 14 are two animal studies on rats investigating dose responses and safety doses of the Arginase according to the present invention. Examples 15 to 18 are another series of animal studies on nude mice to investigate the responses of tumours induced by different human cancer cell lines upon arginine depletion induced by administration of modified Arginase. All references cited above are incorporated by reference herein. The practice of the invention is exemplified in the following non-limited Examples. The scope of the invention is defined solely by the appended claims, which are in no way limited by the content or scope of the Examples. EXAMPLES Example 1 Construction of the Recombinant Strain LLC101 (a) Isolation of the Gene Encoding Human Arginase I The gene sequence of human Arginase I was published in 1987 (Haraguchi, Y. et al., 1987, Proc. Natl. Acad. Sci. 84, 412-415) and primers designed therefrom. Polymerase chain reaction (PCR) was performed to isolate the gene encoding a human Arginase using the Expand High Fidelity PCR System Kit (Roche). Primers Arg1 (5′-CCAAACCATATGAGCGCCAAGTCCAGAACCATA-3′) (SEQ ID NO: 5) and Arg2 (5′-CCAAACTCTAGAATCACA=TTTGAATGACATGGACAC-3′) (SEQ ID NO: 6), respectively, were purchased from Genset Singapore Biotechnology Pte Ltd. Both primers have the same melting temperature (Tm) of 72 degree C. Primer Arg1 contains a NdeI restriction enzyme recognition site (underlined) and primer Arg2 contains a XbaI site (underlined).These two primers (final concentration 300 nM of each) were added to 5 μl of the human liver 5′-stretch plus cDNA library (Clontech) in a 0.2-ml micro-tube. DNA polymerase (2.6 units, 0.75 μl), the four deoxyribonucleotides (4 μl of each; final concentration 200 μM of each) and reaction buffer (5 μl) and dH2O (17.75 μl) were also added. PCR was performed using the following conditions: pre-PCR (94 degree C., 5 min), 25 PCR cycles (94 degree C., 1 min; 57 degree C., 1 min; 72 degree C., 1 min), post-PCR (72 degree C., 7 min). PCR product (5 μl) was analyzed on a 0.8% agarose gel and a single band of 1.4 kb was observed. This DNA fragment contains the gene encoding Arginase. (b) Isolation of Plasmid pSG1113 Plasmid pSG1113, which is a derivative of plasmid pSG703 (Thomewell, S. J. et al., 1993, Gene, 133, 47-53), was isolated from the E. coli DH5a clone carrying pSG1113 by using the Wlizard Plus Minipreps DNA Purification System (Promega) following the manufacturer's instruction. This plasmid, which only replicates in E. coli but not in B. subtilis, was used as the vector for the subcloning of the Arginase gene. (c) Subcloning the 1.4 kb PCR Product into Plasmid pSG1113 to Form Plasmid pAB101 The PCR product, prepared using the above protocol, was treated with restriction endonucleases NdeI and XbaI (Promega) in a reaction medium composed of 6 mM Tris-HCl (pH 7.9), 6 mM MgCl2, 150 mM NaCl, 1 mM DTT at 37 degree C. for 1.5 h. After completion of the treatment, the reaction mixture was subjected to agarose gel (0.8%) electrophoresis, and the 1.4 kb DNA fragment was recovered from the gel by using the Qiaex II Gel Extraction Kit (Qiagen). Separately, the plasmid pSG1113 was treated with the same restriction endonucleases in the same way. After completion of the treatment, the reaction mixture was subjected to agarose gel (0.8%) electrophoresis, and a DNA fragment having a size of about 3.5 kb was recovered from the gel. This DNA fragment was joined by using T4 DNA ligase to the above 1.4 kb DNA fragment. The ligation mixture was used to transform E. coli XLI-Blue using the conventional calcium method (Sambrook, J. et al., Molecular Cloning, A Laboratory Manual, second edition, Cold Spring Harbor Laboratory Press, New York, 1989) and plated on nutrient agar plate containing 100 μg/ml ampicillin. Colonies were screened for a plasmid with the appropriate insert by restriction analysis. The plasmid constructed was designated pAB101 (FIG. 1). OR1 is the E. coli origin of replication and bla is the ampicillin resistant marker gene. DNA sequencing was performed with primers Arg1 (SEQ ID NO: 5), Arg2 (SEQ ID NO:6) and Arg6 (5′-CTCTGGCCATGCCAGGGTCCACCC-3′) (SEQ ID NO: 7) to confirm the identity of the gene encoding Arginase (FIG. 2). (d) Construction of the Novel Recombinant B. subtilis Prophage Strain LLC101 The plasmid pAB101 was extracted and purified from the clone carrying the pAB101 by using the Wizard Plus Minipreps DNA Purification System (Promega). In the plasmid pAB101 (FIG. 1), the Arginase gene (arg) was flanked by the 0.6 kb MunI-NdeI p105 phage DNA fragment (labelled as “p105”) and the cat gene (FIG. 1 and FIG. 3). This plasmid DNA (1 μg) was used to transform competent B. subtilis 1A304(+105MU331) according to the known method (Anagnostopoulos C. and Spizizen J., 1961, J. Bacteriol. 81, 741-746). The B. subtilis strain 1A304(φ105MU331) was obtained from J. Errington (Thornewell, S. et al., 1993, Gene 133, 47-53). The strain was produced according to the publications by Thornewell, S. et al., 1993, Gene 133, 47-53 and by Baillie, L. W. J. et al., 1998, FEMS Microbiol. Letters 163, 43-47, which are incorporated herein in their entirety. Plasmid pAB101 (shown linearized in FIG. 3) was transformed into the B. subtilis strain 1A304 (φ105MU331) with selection for the CmR marker, and the transformants were screened for an Ers phenotype. Such transformants should have arisen from a double-crossover event, as shown in FIG. 3, placing transcription of the Arginase gene (arg) under the control of the strong phage promoter (Leung and Erington, 1995, Gene 154, 1-6). The thick lines represent the prophage genome, broken lines the B. subtilis chromosome, and thin lines plasmid DNA. The genes are shown in FIG. 3 as shaded arrows pointing in the direction of transcription and translation. Regions of homology are bounded by broken vertical lines and homologous recombination events by ‘X’. Fifty-two chloramphenicol resistant (CmR) colonies were obtained from plating 600 μl of the transformed cells on an agar plate containing chloramphenicol (5 μg/ml). Ten of these colonies were selected randomly and streaked onto an agar plate containing erythromycin (20 μg/ml) and one of these colonies did not grow, indicating that it was erythromycin sensitive (Ers). This chloramphenicol resistant but erythromycin sensitive colony was thus isolated and named as LLC101. In the chromosome of this newly constructed prophage strain, the erythromycin resistance gene (ermC) was replaced by the Arginase gene (arg) by a double crossover event in a process of homologous recombination. The 0.6 kb MunI-NdeI φ105 phage DNA fragment (labelled as “φ105”) and the cat gene provided the homologous sequences for the recombination. In this way, the Arginase gene was targeted to the expression site in the prophage DNA of B. subtilis 1A304(φ105MU331) and the Arginase gene was put under the control of the strong thermoinducible promoter (Leung, Y. C. and Errington, J., 1995, Gene 154, 1-6). Fermentation of B. subtilis LLC101 Cells Example 2A Batch Fermentation in a 2-Liter Fermentor The B. subtilis LLC101 strain is maintained on a Nutrient Agar (beef extract 1 g/L, peptone 10 g/L, NaCl 5 g/L and agar 20 g/L) plate, supplemented with 5 mg/L of chloramphenicol. To prepare the innoculum for batch and fed-batch fermentation, a few colonies of the aforementioned strain were transferred from a freshly prepared Nutrient Agar plate into two 1-L flasks, each containing 80 mL of fermentation medium containing glucose 5 g/L, tryptone 10 g/L, yeast extract 3 g/L, sodium citrate 1 g/L, KH2PO4 1.5 g/L, K2HPO4 1.5 g/L, and (NH4)2SO4 3 g/L. The bacterial cell culture was cultivated at 37° C. and pH 7.0 on an orbital shaker rotating at 250 r.p.m. The cultivation was terminated when OD600nm reached 5.5-6.0 at about 9-11 h growth time. Then the 160-nL culture broth was introduced into the 2-L fermentor containing 1440-mL fermentation medium (glucose 5 g/L, tryptone 10 g/L, yeast extract 3 g/L, sodium citrate 1 g/L, KH2PO4 1.5 g/L, K2HPO4 1.5 g/L, and (NH4)2SO4 3 g/L). The batch fermentation was carried out at a temperature of 37° C. The pH was controlled at 7.0 by adding sodium hydroxide and hydrochloric acid. The dissolved oxygen concentration was controlled at 20% air saturation with the adjustment of stirring speed. Heat shock was performed at 3.25 h when the culture density (OD600nm) was about 3.9. During the heat shock, the temperature of the fermentor was increased from 37 degree C. to 50 degree C. and then cooled immediately to 37 degree C. The complete heating and cooling cycle took about 0.5 h. The OD of the culture reached a maximum of about 6.4 at 3.5 h after heat shock. Cells were harvested for separation and purification of Arginase at 6 h after heat shock. The aforementioned strain produced active human Arginase in an amount of about 30 mg/L of the fermentation medium at 6 h after heat shock. The time-course of the fermentation is plotted in FIG. 4A. The history plot of this batch fermentation showing the changes of parameters such as temperature, stirring speed, pH and dissolved oxygen values is depicted in FIG. 5A. Example 2B Fed-Batch Fermentation in a 2-Liter Fermentor The Fed-batch fermentation was carried out at 37 degree C., pH 7.0 and dissolved oxygen 20% air saturation. The inoculation procedure was similar to that of the batch fermentation described in Example 2A. Initially, the growth medium was identical to that used in the batch fermentation described in Example 2A. The feeding medium contained 200 g/L glucose, 2.5 g/L MgSO4.7H2O, 50 g/L tryptone, 7.5 g/L K2HPO4 and 3.75 g/L KHzPO4. The medium feeding rate was controlled with the pH-stat control strategy. In this strategy, the feeding rate was adjusted to compensate the pH increase caused by glucose depletion. This control strategy was first implemented when the glucose concentration decreased to a very low level at about 4.5-h fermentation time. If pH>7.1, 4 mL of feeding medium was introduced into the fermentor. Immediately after the addition of glucose, the pH value would decrease below 7.1 rapidly. After approximate 10 min, when the glucose added was completely consumed by the bacterial cells, the pH value would increase to a value greater than 7.1, indicating that another 4 mL of feeding medium was due to be added into the fermentor. Heat shock was performed at 5-6 h when the culture density (OD600nm) was between 12.0 and 13.0. During the heat shock, the temperature of the fermentor was increased from 37 degree C. to 50 degree C. and then cooled immediately to 37 degree C. The complete heating and cooling cycle took about 0.5 h. Cells were harvested for separation and purification of Arginase at 3 h and 6 h after heat shock. The aforementioned strain produced active human Arginase in an amount of at least about 162 mg per L of the fermentation medium at 6 h after heat shock. The time-course of the fermentation is plotted in FIG. 4B. The history plot of this fed-batch fermentation showing the changes of parameters such as temperature, stirring speed, pH and dissolved oxygen values is indicated in FIG. 5B. Example 2C Fed-Batch Fermentation in a 100-Liter Fermentor The Fed-batch fermentation was scaled up in a 100-L fermentor. The fermentation was carried out at 37 degree C., pH 7.0, dissolved oxygen 20% air saturation. A 10% inoculum was used. Initially, the growth medium was identical to that used in the batch fermentation described in Example 2A. The feeding medium contained 300 g/L glucose, 3.75 g/L MgSO4.7H2O, 75 g/L tryptone, 11.25 g/L K2HPO4 and 5.625 g/L KH2PO4. The medium feeding rate was controlled with a pH-stat control strategy similar to that used in the fed-batch fermentation described in Example 2B. Heat shock was performed at about 7.5 h when the culture density (OD600nm) was between 11.5 and 12.5. During the heat shock, the temperature of the fermentor was increased from 37 degree C. to 50 degree C., maintained at 50 degree C. for 7 s and then cooled immediately to 37 degree C. The complete heating and cooling cycle took about 0.5 h. Cells were harvested for separation and purification of Arginase at 2 h and 4 h after heat shock. The aforementioned strain produced active human Arginase in an amount of at least about 74 mg and 124 mg per L of the fermentation medium at 2 h and 4 h, respectively, after heat shock. These data show that harvesting cells 4 h after heat shock produced a higher Arginase yield than harvesting cells 2 h after heat shock in a 100-L fermentor. Example 3 Comparison of Batch and Fed-Batch Fermentation Table 1 below compares the results of batch and fed-batch fermentation. The comparison demonstrates that the fed-batch fermentation was much superior to the batch operation in terms of culture OD, Arginase yield and productivity. TABLE 1 Batch Fed-batch Fermentation Fermentation The OD at the start of heat 3.9 12.8 shock Maximum OD reached 6.0 26.8 Arginase Yield (mg/L) 30 162 Arginase Productivity (mg/L-h) 2.5 13.5 Example 4 Purification of Arginase at 3H After Heat Shock After Fed-Batch Fermentation at Low Cell Density Fed-batch fermentation in a 2-liter fermentor was performed as described in Example 2B. The cell density of the fed-batch culture was monitored at 30 or 60 min interval and the temperature of the culture raised to 50° C. for heat shock at 5.5 hours after the fermentation started when the OD of the culture reached 12.8 (see FIG. 4B and FIG. 5B). The cell culture (470 ml) collected at 3 h after heat shock was centrifuged at 5,000 rpm for 20 min at 4 degree C. to pellet the cells. The wet weight of the cells was 15.1 g. The culture supernatant liquor was discarded and the cell pellet was stored at −80 degree C. The cells are stable at this temperature for a few days. To extract intracellular proteins, the cell pellet was resuspended in 140 ml solubilization buffer [50 mM Tris-HCl (pH 7.4), 0.1 M NaCl, 5 mM MlSO4, lysozyme (75 μg/ml)]. After incubation at 30 degree C. for 15 min, the mixture was sonicated for eight times, each time lasted for 10 s (the total time was 80 s), at 2 min intervals using the Soniprep 150 Apparatus (MSE). About 500 units of deoxyribonuclease I (Sigma D 4527) was added and the mixture was incubated at 37 degree C. for 10 min to digest the chromosomal DNA. After centrifugation at 10,000 rpm for 20 min at 4 degree C., the supernatant, containing the crude protein extract, was assayed for the presence of the Arginase activity and analyzed by SDS-PAGE (Laemmli, 1970, Nature, 227, 680-685). A 5-ml HiTrap Chelating column (Pharmacia) was equilibrated with 0.1 M NiCl2 in dH2O, for 5 column volumes. The crude protein extract (140 ml) was loaded onto the column. Elution was performed with a linear gradient (0-100%) at a flow rate of 5 ml/min for 15 column volumes under the following conditions: Buffer A=start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]; Buffer B=start buffer containing 0.5 M imidazole. The elution profile is shown in FIG. 6A and the protein gel is shown in FIG. 6B. Fractions 13-20 were pooled (16 ml) and diluted ten times with start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]. This was loaded onto a second 5-ml HiTrap Chelating column (Pharmacia), repeating the same procedure as above. The elution profile is shown in FIG. 7A and the protein gel is shown in FIG. 7B. Fractions 12-30 containing Arginase were pooled (38 ml) and salt was removed using a 50-ml HiPrep 26/10 desalting column (Pharmacia) with the following conditions: flow rate=10 mVmin, buffer=10 mM Tris-HCl (pH 7.4) and length of elution=1.5 column volume. The protein concentration was measured by the method of Bradford (Bradford, M. M., 1976, Anal. Biochem., 72, 248-254). A total of 56.32 mg of Arginase was purified from 470 ml cell culture. The yield of purified Arginase was estimated to be 119.8 mg/l cell culture or 3.73 mg/g wet cell weight. Example 5 Purification of Arginase at 6H After Heat Shock After Fed-Batch Fermentation at Low Cell Density Fed-batch fermentation in a 2-liter fermentor was performed as described in Example 4. The cell culture (650 ml) collected at 6 h after heat shock at OD 12.8 was centrifuged at 5,000 rpm for 20 min at 4 degree C. to pellet the cells. The wet weight of the cells was 24 g. The culture supernatant liquor was discarded and the cell pellet was stored at −80° C. The cells are stable at this temperature for a few days. To extract intracellular proteins, the cell pellet was resuspended in 140 ml solubilization buffer [50 mM Tris-HCl (pH 7.4), 0.1 M NaCl, 5 mM MnSO4, lysozyme (75 μg/ml)]. After incubation at 30 degree C. for 15 min, the mixture was sonicated for eight times, each time lasted for 10 s (the total time was 80 s), at 2 min intervals using the Soniprep 150 Apparatus (MSE). About 500 units of deoxyribonuclease I (Sigma D 4527) was added and the mixture was incubated at 37 degree C. for 10 min to digest the chromosomal DNA. After centrifugation at 10,000 rpm for 20 min at 4 degree C., the supernatant, containing the crude protein extract, was assayed for the presence of the Arginase activity and analyzed by SDS-PAGE (Laemmli, 1970, Nature, 227, 680-685). A 5-ml HiTrap Chelating column (Pharmacia) was equilibrated with 0.1 M NiCl2 in dH2O, for 5 column volumes. The crude protein extract (140 ml) was loaded onto the column. Elution was performed with a linear gradient (0-100%) at a flow rate of 5 m/min for 15 column volumes under the following conditions: Buffer A=start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]; Buffer B=start buffer containing 0.5 M imidazole. The elution profile is shown in FIG. 8A and the protein gel is shown in FIG. 8B. Fractions 13-24 were pooled (24 ml) and diluted ten times with start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]. This was loaded onto a second 5-ml HiTrap Chelating column (Phalmacia), repeating the same procedure as above. The elution profile is shown in FIG. 9A and the protein gel is shown in FIG. 9B. Fractions 12-24 containing Arginase were pooled (26 ml) and salt was removed using a 50-ml HiPrep 26/10 desalting column (Pharmacia) with the following conditions: flow rate=10 ml/min, buffer=10 mM Tris-HCl (pH 7.4) and length of elution=1.5 column volume. The protein concentration was measured by the method of Bradford (Bradford, M. M., 1976, Anal. Biochem., 72, 248-254). A total of 85.73 mg of Arginase was purified from 650 ml cell culture. The yield of purified Arginase was estimated to be 132 mg/l cell culture or 3.57 mg/g wet cell weight Example 6 Purification of Arginase at 6H After Heat Shock at a Higher Cell Density In this particular fed-batch fermentation, the process was similar to the above example except that the heat shock was performed at 8 h when the culture density (OD600nm) was about 25. During the heat shock, the temperature of the fermentor was increased from 37 degree C. to 50 degree C. and then cooled immediately to 37 degree C. The complete heating and cooling cycle took about 0.5 h. A portion of the cell culture (760 ml) was harvested for separation and purification of Arginase at 6 h after heat shock. The time-course of bacterial cell growth in this fermentation is plotted in FIG. 10. The history plot of this fed-batch fermentation showing the changes of parameters such as temperature, stirring speed, pH and dissolved oxygen values is indicated in FIG. 11. The cell culture (760 ml) collected at 6 h after heat shock was centrifuged at 5,000 rpm for 20 min at 4 degree C. to pellet the cells. The wet weight of the cells was 32 g. The culture supernatant liquor was discarded and the cell pellet was stored at −80 degree C. The cells are stable at this temperature for a few days. To extract intracellular proteins, the cell pellet was resuspended in 280 ml solubilization buffer [50 mM Tris-HCl (pH 7.4), 0.1 M NaCl, 5 mM MnSO4, lysozyme (75 μg/ml)]. After incubation at 30 degree C. for 15 min, the mixture was sonicated for eight times, each time lasted for 10 s (the total time was 80 s), at 2 min intervals using the Soniprep 150 Apparatus (MSE). About 500 units of deoxyribonuclease I (Sigma D 4527) was added and the mixture was incubated at 37 degree C. for 10 min to digest the chromosomal DNA. After centrifugation at 10,000 rpm for 20 min at 4 degree C., the supernatant, containing the crude protein extract, was assayed for the presence of the Arginase activity and analyzed by SDS-PAGE (Laemmli, 1970, Nature, 227, 680-685). A 5-ml HiTrap Chelating column (Pharmacia) was equilibrated with 0.1 M NiCl2 in dH2O, for 5 column volumes. The crude protein extract (280 ml) was loaded onto the column. Elution was performed with a linear gradient (0-100%) at a flow rate of 5 ml/min for 15 column volumes under the following conditions: Buffer A=start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]; Buffer B=start buffer containing 0.5 M imidazole. The elution profile is shown in FIG. 12A and the protein gel is shown in FIG. 12B. Fractions 17-31 were pooled (30 ml) and diluted ten times with start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]. This was loaded onto a second 5-ml HiTrap Chelating column (Pharmacia), repeating the same procedure as above. The elution profile is shown in FIG. 13A and the protein gel is shown in FIG. 13B. Fractions 10-20 containing Arginase were pooled (22 ml) and salt was removed using a 50-ml HiPrep 26/10 desalting column (Pharmacia) with the following conditions: flow rate=10 ml/min, buffer=10 mM Tris-HCl (pH 7.4) and length of elution=1.5 column volume. The sample was then loaded onto a 1-ml HiTrap SP FF column (Pharmacia). Elution was performed with the following conditions: flow rate=1 ml/min, Buffer A=10 mM Tris-HCl (pH 7.4), Buffer B=10 mM Tris-HCl (pH 7.4) containing 1 M NaCl, linear gradient (0-100%), length of elution=30 column volumes. The elution profile is shown in FIG. 14A and the protein gel is shown in FIG. 14B. Fractions A12-B7 were pooled (7 ml) and diluted ten times with start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCl]. This sample was loaded onto a second 1-ml HiTrap SP FF column (Pharmacia), repeating the same procedure as above, except that the elution was performed with a segmented gradient. The elution profile is shown in FIG. 15A and the protein gel is shown in FIG. 15B. Fractions A7-B12 were pooled (7 ml) and desalted as above using a 50-ml HiPrep 26/10 desalting column (Pharmacia). The protein concentration was measured by the method of Bradford (Bradford, M. M., 1976, Anal. Biochem., 72, 248-254). A total of 41.61 mg of Arginase was purified from 760 ml cell culture. The yield of purified Arginase was estimated to be 55.5 mg/l cell culture or 1.3 mg/g wet cell weight. Example 7 Comparison of Yield of Arginase Harvested and Purified Under Various Conditions Table 2 below compares the yield of the Arginase produced under various harvesting and purification conditions. These data show that harvesting cells 6 h after heat shock at a lower cell density of 12.8 produced a higher Arginase yield of 132 mg/L after purification. TABLE 2 Arginase Yield (mg/L) Harvested 3 h after Harvested 6 h after Fed-batch Fermentation heat shock heat shock Heat shock at OD 12.8 120 132 Heat shock at OD 25 — 55.5 Example 8A Preparation of the Pegylated Enzyme Using Cyanuric Chloride (CC) Activated Methoxypolyethylene Glycol 50 mg Arginase was dissolved in 20 ml PBS buffer solution (pH 7.4) to a final concentration of 2.5 mg/ml. Heat activation of Arginase was carried out at 60° C. for 10 minutes. After activation, the temperature of the enzyme was allowed to bring back to room temperature. 1 g cyanuric chloride activated methoxypolyethylene glycol (mPEG-CC) (MW=5000, Sigma) was added to Arginase at mole ratio 1:140 (Arginase:PEG). A magnetic stirring bar was used to stir the mixture until all of the polyethylene glycol (PEG) was dissolved. When all of the PEG was dissolved, pH of the PEG-Arginase mixture was adjusted to 9.0 with 0.1 N NaOH, pH was further maintained at 9.0 for the next 30 minutes with furter additions of NaOH. Pegylation was stopped by adjusting pH back to 7.2 with addition of 0.1 N HCl. The pegylated Arginase was dialyzed against 2-3 liters of PBS buffer solution, pH 7.4, at 4° C., with the use of a Hemoflow F40S capillary dialyzer (Fresenius Medical Care, Germany) to remove excess PEG. After dialysis, pegylated Arginase was recovered and the final concentration was readjusted. The pegylated Arginase was filtered through a 0.2 pmn filter into a sterilized container and was stored at 4° C. The ½-life of this enzyme in a human patient was tested to be about 6 hours (see FIG. 21). Example 8B Preparation of Arginase Expressed in B. subtilis and Using Either CC or SPA at a Lower Peg Ratio Pegylation was first developed by Davis, Abuchowski and colleagues (Davis, F. F. et al., 1978, Enzyme Eng. 4, 169-173) in the 1970s. In contrast to modifying the formulation of a drug, chemical attachment of poly(ethylene glycol) PEG moieties to therapeutic proteins (a process known as “pegylation”) represents a new approach that may enhance important drug properties (Harris, J. M. et al., 2001, Clin. Pharmacokinet. 40, 539-551). In 1979, Savoca et al. attached methoxypolyethylene glycol (mPEG) of 5,000 Daltons covalently to bovine liver Arginase using 2,4,6-trichloro-s-triazine (cyanuric chloride) as the coupling agent (Savoca, K. V. et al., 1979, Biochimica et Biophysica Acta 578, 47-53). The conjugate (PEG-Arginase) only retained 65% of its original enzymatic activity. They reported that the blood-circulating life of PEG-Arginase in mice was extended over that of bovine Arginase. The half-life of injected bovine Arginase was less than 1 h, whereas that of the PEG-enzyme was 12 h. Their data also indicated that bovine Arginase modified by PEG was rendered both non-immunogenic and non-antigenic when tested in mice. Recombinant human Arginase (1.068 mg) was dissolved in 125 mM borate buffer solution (pH 8.3) on ice or at room temperature. Activated mPEG, succinimide of mPEG propionic acid (mPEG-SPA; MW 5,000; Shearwater Corporation) or mPEG activated with cyanuric chloride (mPEG-CC; MW 5,000; Sigma), was added into the solution at Arginase:PEG mole ratios of 1:50 or 1:20. This was performed in two stages. At the first stage, half of the PEG was added into the Arginase solution little by little and mixed for 30 min gently on ice to prevent the pH getting out of the recommended range of 8.0-8.5. The other half of the PEG was added to this solution and further mixed gently for 0.5-23 h. The mixture was then dialyzed against dH2O by changing with dH2O at least 3 times at 4 degree C. using dialysis membrane with cut-off value of below 10,000. Both MnPEG-SPA and mPEG-CC use amino groups of lysines and the N-terminus of the protein as the site of modification. When Arginase was modified on ice or at room temperature with MPEG-SPA (MW 5,000) using an Arginase:PEG mole ratio of 1:50, most of the enzyme molecules were modified after 1 h of reaction (FIG. 16). The sample appeared the same even after 23 h of reaction. Arginase molecules were attached with different numbers of PEG molecules and generated molecules of various molecular weights. As expected, when a lower mole ratio of 1:20 was used for the pegylation reaction, a higher proportion of Arginase was found in the non-pegylated form (FIG. 17). However, for both of the mole ratios of Arginase:PEG used, longer reaction time and the use of room temperature instead of ice did not seem to affect the extent of pegylation. With MPEG-SPA (MW 5,000), a mole ratio of 1:50 and 1 h of reaction, the Arginase retained as much as 72-76% of its original enzymatic activity (see Table 3 below), which is higher than that reported for the bovine Arginase (65%; Savoca, K. V. et al., 1979, Biochimica et Biophysica Acta 578, 47-53). When Arginase was modified on ice with mPEG-CC (MW 5,000) using an Arginase:PEG mole ratio of 1:50, the reaction was quite slow and it took 23 h to complete the pegylation (FIG. 18A). Moreover, most of the enzyme molecules were converted to a narrow spectrum of very high molecular weights. The reaction was much slower if a lower mole ratio of 1:20 was used, as indicated in FIG. 18A. Example 8C Preparation of Highly Active Pegylated Arginase Fed-batch fermentation in a 15-L B. Braun Biostat C stainless steel fermentor was performed as described in Example 4. The cell culture (8.4 L) collected at 4.5 h after heat shock at OD 12-13 was centrifuged at 5,000 rpm for 20 min at 4 degree C. to pellet the cells. The culture supernatant liquor was discarded and the cell pellet was stored at −80° C. The cells are stable at this temperature for a few days. To extract intracellular proteins, the cell pellet was resuspended in 1250 ml solubilization buffer [50 mM Tris-HCl (pH 7.4), 0.1 M NaCl, 5 mM MnSO4, lysozyme (75 μg/ml)]. After incubation at 30 degree C. for 20 min, the mixture was divided into 300-ml portions in beakers, and each portion was sonicated for 12 times, each time lasted for 10 s (the total time was 120 s), at 2 min intervals using the Soniprep 150 Apparatus (MSE). About 5000 units of deoxyribonuclease I (Sigma D 4527) was added and the mixture was incubated at 37 degree C. for 15 min to digest the chromosomal DNA. After centrifugation twice, each at 9,000 rpm for 30 min at 4 degree C., the supernatant, containing the crude protein extract, was assayed for the presence of the Arginase activity and analyzed by SDS-PAGE (Laemmli, 1970, Nature, 227, 680-685). The crude protein extract (1195 ml) was filtered and divided into 2 portions, each contained 597.5 ml. Each portion was then loaded onto a 130-ml Ni-NTA superflow (Qiagen) column (Pharmacia). Elution was performed with a linear gradient (0-100%) at a flow rate of 5 ml/min under the following conditions: Buffer A=start buffer [0.02 M sodium phosphate buffer (pH 7.4), 0.5 M NaCd]; Buffer B=start buffer containing 0.5 M imidazole. Fractions containing pure Arginase were pooled and buffer exchanged at 35 ml/min at 4 degree C. with PBS buffer, pH 7.4 using the Pellicon XL device (polyether-sulphone membrane cut-off=8 kDa) and the lab-scale tangential flow filtration system (Millipore). The protein concentration was measured by the method of Bradford (Bradford, M. M., 1976, Anal. Biochem., 72, 248-254). A total of 788 mg of Arginase was purified from 8.4 L cell culture. The yield of purified Arginase was estimated to be 94 mg/l cell culture. The measured specific activity was as high as 518 I.U./mg. Pegylated Arginase with high specific activity was prepared in PBS buffer. The purified Arginase (specific activity=518 I.U./mg) was in PBS buffer before carrying out pegylation. The mPEG-SPA, MW 5,000 (5.82 g) was added into 555 ml of the purified Arginase (813.64 mg, 1.466 mg/ml) solution slowly in a 1-L beaker and then stirred for 2 h 40 min at room temperature (mole ratio of Arginase: rnPEG-SPA=1: 50). The mixture was then dialyzed extensively by ultra-dialysis against 15 L of PBS buffer using the F50(S) capillary dialyser (Fresenius Medical Care) to remove all the unincorporated PEG. The mPEG-SPA uses amino groups of lysines and the N-terminus of the protein as the site of modification. The measured specific activity of the pegylated Arginase is as high as 592 I.U./mg. The results from SDS-PAGE analysis of the native and the pegylated Arginase are shown in FIG. 18B. The pegylated Arginase was shown to be highly stable, in terms of Arginase activity and protein concentration, when stored in PBS buffer at 1 mg/ml for at least 3 weeks at room temperature. When stored at 4 degree C. in PBS buffer at 1 mg/ml, it is stable for at least 6 months without decrease in specific activity. TABLE 3 Activity (%) of Arginase when pegylated with various activated PEG at different mole ratios and temperatures. Activity (%) of Activity (%) Arginase of Arginase (pegylated at Activity (%) of (pegylated at Activity (%) of Activity (%) Activity (%) of room Arginase room Arginase Arginase Arginase Time (h) temperature (pegylated on temperature (pegylated on (pegylated on (pegylated on Allowed for with ice with with ice with ice with ice with the Arginase:mPEG- Arginase:mPEG- Arginase:mPEG- Arginase:mPEG- Arginase:mPEG- Arginase:mPEG- Pegylation SPA SPA ratio of SPA SPA ratio of CC ratio of CC ratio of Reaction ratio of 1:20) 1:20) ratio of 1:50) 1:50) 1:20) 1:50) 0 100 100 100 100 100 100 1 83 76 76 72 ND ND 2 79 76 72 68 68 64 5 83 74 74 72 65 65 23 75 72 72 64 66 66 ND: Not determined. 100% activity of Arginase is equivalent to 336 I.U./mg of protein. Example 9A ½-Life Determination In Vivo of Arginase Obtained from Example 8A The pegylated Arginase was injected into a patient. A 3 ml blood sample in EDTA was taken from patient on a daily basis. The tube was pre-cooled to 4° C. on melting ice to prevent ex-vivo enzymatic reaction. The blood was then immediately spun down at 14000 rpm for 2 minutes to remove red blood cells. 1.5 ml supernatant (plasma) was pipetted out and transferred to a new eppendorf tube. The plasma was then incubated at 37° C. for 30 minutes. After incubation, arginine was added as a substrate in concentration of 100 μM. Enzyme reaction was carried out at 37° C. for 0, 10, 30, 60 minutes. At each time interval, reaction was stopped by taking out 300 μl reaction sample to a new eppendorf tube containing 300 μl 10% trichloroacetic acid. Samples were taken and spun at maximum speed (14000 rpm) for 10 minutes. Supernatant was pipetted out and filtered with 0.45 μm filter. Finally, samples at different time intervals were analysed with amino acid analyzer (Hitachi, L8800). The results are shown in FIG. 21. Two batches of pegylated Arginase were prepared as described in Example 8A during the studies. The first batch of pegylated Arginase was prepared with Arginase:PEG mole ratio of 1:140. The second batch of pegylated Arginase was prepared with Arginase:PEG mole ratio of 1:70. The pegylation protocol and condition used for preparing the two batches were identical (see Example 8A). At time zero, 50 mg of the first batch of pegylated Arginase was infused. After 12 hours, another 50 mg of the first batch of pegylated Arginase was infused. The third Arginase infusion was done at hour 24 during which another 50 mg of the first batch of pegylated Arginase was used. From hour 26 to hour 72, continuous infusion of the first batch of pegylated Arginase (100 mg/day) was carried out instead of intermittent infusion (50 mg/dosage). From hour 72 to hour 144, continuous infusion of the second batch of pegylated Arginase was carried out at a rate of 100 mg/day. Continuous Arginase infusion was stopped at hour 144, and the measurement of the half-life started from this point. The results of the half-life determination are shown in FIG. 22. Time zero in FIG. 22 is equivalent to hour 144 in FIG. 21. The results suggested that the half-life of the activity of the Arginase could be divided into two phases. The first half-life of the pegylated enzyme was about 6 hours. It took about 6 hours to reduce the relative activity from 100% to 50% (see FIG. 22). However, the second half-life was about 21 days. It took about 21 days to reduce the relative activity from 50% to 25%. This dual half-life effects might be due to a number of factors including the use of higher amount of mnPEG-CC in the pegylation and the specific infusion protocol used. Example 9B ½-Life Determination of Pegylated Arginase In Vitro Using the Method in Human Blood Plasma Purified Arginase (1 mg) was dissolved in 1 ml of 125 mM borate buffer solution (pH 8.3) on ice. Activated PEG (mnPEG-SPA, MW 5,000) (7.14 mg) was added into the protein solution slowly at a mole ratio of Arginase:PEG=1:50. The mixture was stirred on ice for 2.5 h, following the method as described in Example 8B. Pegylated Arginase (305.6 μl) at a concentration of 1 mg/ml was added into human plasma (1 ml) and the final concentration of pegylated Arginase was 0.24 mg/ml. The mixture was divided into 20 aliquots in eppendorf tubes (65 μl mixture in each eppendorf tube) and then incubated at 37° C. A 1-2 μl portion of the mixture from each eppendorf tube was used to test the Arginase activity. Results are shown in FIG. 20. The ½-life was determined to be approximately 3 days. It took about 3 days to reduce the relative activity from 100% to 50%. This is determined by using the curve in FIG. 20. Example 10 Characterization of B. subtilis-Expressed Human Arginase and Pegylated, Isolated and Purified Recombinant Human Arginase (a) Measurement of Purity of Arginase by SDS-PAGE and Lumi-Imaging Purified E. coli-expressed Arginase obtained from methods described by Ikemoto et al. (Ikemoto et al., 1990, Biochem. J. 270, 697-703) was compared to purified B. subtilis-expressed recombinant human Arginase obtained from methods described in the present invention (FIGS. 19A and 19B). Analysis of densities of total protein bands shown in FIG. 19A with the Lumianalyst 32 program of Lumi-imager™ (Roche Molecular Biochemicals) indicated that the process developed in the present invention produced an Arginase that is to more than 99.9% pure (FIG. 19B). However, an Arginase that is between 80-100% pure may also serve as the active ingredient to prepare a pharmaceutical composition. In the preferred embodiment, recombinant Arginase of 80-100% purity is used. In the more preferred embodiment, the recombinant Arginase according to the present invention is 90-100% pure using SDS-PAGE followed by lumi-inaging. (b) Measurement of Specific Activity by Coupled Reactions The rate of the release of urea from 1-arginine by Arginase was monitored in a system containing urease, L-glutamate dehydrogenase and NADPH (Ozer, N., 1985, Biochem. Med. 33, 367-371). To prepare the master mix, 0.605 g Tris, 0.0731 g a-ketoglutarate and 0.4355 g arginine were dissolved in 40 ml dH2O. The pH was adjusted to 8.5 with 1 M HCl and then 0.067 g urease was added to the mixture. The pH was furter adjusted to 8.3 with HCl before 0.0335 g glutamate dehydrogenase and 0.0125 g NADPH were added. The final volume was adjusted to 50 ml with dH2O to form the master mix. The master mix (1 ml) was pipetted into a quartz cuvette. For measuring Arginase activity, 1-5 μg Arginase was added and the decrease in absorbance at 340 nm (A340) was followed for 1-3 min at 30 degree C. One I.U. of Arginase was defined as the amount of enzyme that released 1 μmol of urea for 1 min under the given conditions. The specific activity of the purified recombinant human Arginase of the present invention was calculated to be 518 I.U./mg of protein, which was significantly higher than the reported values for purified human erythrocyte Arginase (204 I.U./mg of protein; Ikemoto et al., 1989, Ann. Clin. Biochem. 26, 547-553) and the E. coli-expressed isolated and purified recombinant human Arginase (389 I.U./mg of protein; Ikemoto et al., 1990, Biochem. J. 270, 697-703). With mPEG-SPA (MW 5,000), a mole ratio of 1:50 and 2 h 40 min of reaction, the pegylated Arginase retained as much as 114% of its original enzymatic activity (see Example 8C). That means the specific activity of the pegylated human Arginase was 592 I.U./mg. With MPEG-CC (MW 5,000), the pegylated human Arginase retained 64-68% of its original enzymatic activity (Table 3), similar to that of the pegylated bovine Arginase (Savoca, K. V. et al., 1979, Biochimica et Biophysica Acta 578, 47-53,). (c) Structural Characterization of the Native Arginase by Electrospray LC/MS The B. subtilis-expressed and purified recombinant human Arginase, according to the amino aid sequence shown in FIG. 2B, contains 329 amino acid residues at a theoretical molecular weight of 35,647.7 Da Simultaneous HPLC/UV and mass spectral analysis of the native Arginase provided a molecular weight of 35,634 Da. The observed molecular weight for the native Arginase was found to correspond well with the theoretical molecular weight of 35,647.7 Da derived from the expected amino acid sequence of a 6×His-tagged human Arginase (FIG. 2B). The purity was found to be 98% by HPLC/UV based on LC/MS and 100% by LC/MS based on HPLC/UV detection at 215 nr relative responses. (d) Structural Characterization of the Native Arginase and the Pegylated Arginase by Gel Filtration Chromatography Studied by gel filtration chromatography in a HiLoad 16/60 superdex gel filtration column (Pharmacia) at the protein concentration of about 2.8 mg/ml in PBS buffer, the molecular weight of the native Arginase was found to be about 78 kDa and that of the pegylated Arginase (prepared in Example 8C) was about 688 kDa. As the molecular weight of monomeric Arginase is about 36 kDa, the results suggested that the native Arginase exists as a dimer in PBS buffer. (e) Secondary Structural Studies Circular dichroism (CD) was used to analyze the secondary structures of the purified Arginases in a JASCO model J810 CD spectrometer. At equal protein concentrations in 10 mM potassium phosphate buffer (pH 7.4), the CD spectrum of the native Arginase was found to be very similar to that of the pegylated Arginase (prepared in Example 8C) when scanned from 195 nm to 240 un, indicating that the native form and the pegylated form of Arginase have nearly identical secondary structures. (f) Determination of VI Point Using a Bio-Rad Model 111 mini IEF cell, the isoelectric point (pI) of the native Arginase (prepared in Example 8C) was found to be 9.0, which is consistent with the published value of 9.1 in literature (Christopher and Wayne, 1996, Comp. Biochem. Physiol. 114B, 107-132). (g) Functional Characterization and Determination of Kinetic Properties Using the method reported by Ikemoto et al. (1990, Biochem. J. 270, 697-703) for measuring Arginase activities, the native Arginase gave a Km of 1.9±0.7 mM, a Vmax of 518 μmol urea min−1 mM−1, a kcat of 2.0±0.5 s−1, and a kcat/Km of 1.3±0.4 mM−1 s−1. The Km value of the purified native Arginase was found to be similar to the published value (2.6 mM) of the human liver Arginase in literature (Carvajal, N. et al., 1999). Moreover, about 1 mM of Mn2+ ions and a temperature of 30-50 degree C. are required to achieve maximum activity for the native Arginase. The pegylated Arginase gave a Km of 2.9±0.3 nM and a Vmax of 360 μmol urea min−1 mM−1. The Km value of the pegylated Arginase is similar to that of the native Arginase, suggesting that the binding affinity towards arginine is retained after pegylation. Moreover, about 1 mM of Mn2+ ions, a temperature of 40-50 degree C., and a pH of 10 are required to achieve maximum activity for the pegylated Arginase. The functional properties of Arginase before and after pegylation are similar, which indicates that the covalent attachment of mPEG-SPA molecules to Arginase improves its properties as a whole. Example 11 Treatment Protocol Using Exogenously Adminstered Arginase Blood samples of patients are taken daily throughout treatment for arginine levels, Arginase activities, complete blood picture and flill clotting profile. Renal and liver functions are taken at least every other days, sooner if deemed necessary. Vital signs (BP, Pulse, Respiratory rate, Oximeter reading) are taken every 15 minutes for 1 hour after commencement of Arginase infusion then hourly until stable. Thereafter, at the discretion of the treating physician. 20 minutes before Arginase infusion, premedication with dipheneramine 10 mg iv. and hydrocortisone 100 mg iv. to be given before each fresh infusion of Arginase or at the discretion of the treating physician. On day One Arginase is infuised over 30 minutes. Thereafter, Arginase is infused weekly for at least 8 weeks. This may be continued if anti-tumour activity is observed. Example 12 Example of Treatment Protocol Using Exogenously Administered Arginase A 54-year old Chinese lady with metastatic rectal carcinoma with extensive pulmonary metastases that failed all standard treatments was treated with pegylated recombinant Arginase in early August 2001. Her main symptoms were cough, poor appetite and constipation. Her cancer marker CEA was 1100 U/ml. Informed consent for treatment with pegylated recombinant Arginase was obtained prior to treatment. Treatment Methodology 850 mg of lyophilised recombinant Arginase I was administered. The drug was reconstituted in PBS and pegylated. The pegylated enzyme was found to be of fall activity. Results Results are shown in FIGS. 28 and 29. FIG. 28 shows satisfactory depletion of arginine between 1-5 μM for 5 days (also see FIG. 21). FIG. 29 shows a decrease of CEA levels from 1100 to 800 in 4 weeks. 1) Unlike chemotherapy this treatment resulted in no marrow suppressive effects or hair loss. 2) It can deplete arginine in a controlled manner, keeping the arginine levels within the therapeutic range (1-8 μM) for the desired period of 5 days, which in vitro data suggest provide optimal tumour kill. 3) No major side effects and the patient tolerated the treatment with only slight headache which may not be directly due to treatment. 4) Both biochemical and radiological improvement of the disease was observed after treatment, with CEA dropping by 30% and clearing up of upper zone disease on chest X ray. Example 13 In Vivo Arginne Depletion in Laboratory Rats with Arginase In this example, four groups of rats (two in each group, one male and one female) were given dosages of various amounts of Arginase obtained from example 8C on day 0. Blood samples were drawn from their tail veins on day 0 before intraperitoneal injection of the recombinant human Arginase, day 1 to day 6, then every 2 days. As shown in FIG. 23, undetectable arginine level was achieved in all groups and appeared to be dose dependent with 500 I.U. giving only after one day of arginine depletion. With 1000 I.U. (500 I.U. administered in the mormnig and another 500 I.U. administered in the afternoon), there was a 4-day period with complete arginine depletion. With single dose of 1500 I.U. administered, there was 6-day arginine depletion. By doubling this dose to 3000 I.U., the duration of complete arginine depletion did not appear to be prolonged to any further extent. Therefore, 1500 I.U. of pegylated Arginase administered intraperitoneally appears to be the optimal dose for arginine depletion with undetectable arginine level for 6 days. Example 14 Comparison of Changes in Level of Components in Blood Between Normal Rats and Rats with Zero Arginine Level Induced by Arginase from Day 1 to Day 5 Intracardiac arterial blood samples were taken from a group of 5 rats on day 0 before administering Arginase. The day 0 samples served as the untreated control. The level of total protein, albumin, globulin, SGOT/AST, SGPT/ALT, haemoglobin, fibrinogen A.P.T.T./second, prothrombin/second, number of white blood cells (WBC) and platelets were measured by Pathlab Medical Laboratory. Ltd, 2nd Floor Henan Building, 90-92 Jaffe Road, Wanchai, Hong Kong. The rats then were injected with single dose of 1500 I.U. of Arginase intraperitoneally. Zero arginine level were achieved in all rats. From day 1 to day 5, one rat was sacrificed on each day and intracardiac arterial blood sample was taken and measured by PathLab Medical Laboratory. Results show that all proteins were within the normal ranges as cited by PathLab Medical Laboratory. Example 15 The Response Upon Arginine Depletion in Hep3B Tumour-Bearing Nude Mice A human hepatoma cell line (Hep3B2.1-7) was inoculated subcutaneously into the right flank of six BALB/c nude mice to induce growth of the tumour. Three randomly picked mice were administered intraperitoneally once a week with 500 I.U. pegylated Arginase obtained from the method described in example 8C while the other three mice were not given any Arginase treatment to serve as the control. The implanted mice were observed once every two days for the growth of the solid tumour in situ by digital calliper measurements to determine tumour size which is calculated according to the formula: Tumour size (mm)=average of two perpendicular diameters and one diagonal diameter. The number of mice that died in each group was also recorded on a daily basis. As shown in FIG. 24, the rate of increase in size of the tumour per day in control group was approximately 6 times the rate increase in group treated with pegylated Arginase for the first 20 days of the experiment. 2 mice in the control group were dead within 24 days while the mice treated with pegylated Arginase can survive for at least 75 days. Example 16 The Response Upon Arginine Depletion in PLC/PRF/5 Tumour-Bearing Nude Mice In this example, a solid tumour of human hepatoma (PLC/PRF/5) was implanted subcutaneously into the back of ten BALB/c nude mice to induce growth of tumour. Five randomly picked mice were administered intraperitoneally once a week with 500 I.U. pegylated Arginase obtained from the method described in example 8C while the other five mice were given 200 μl phosphate buffer saline (PBS) intraperitoneally to serve as the control. The implanted mice were observed once every two days for the growth of the solid tumour in situ by digital calliper measurements to determine tumour size and mass. Tumour size is measured as described in example 15 while tumour mass is calculated according to the formula: Tumour mass (mg)=length×width2/2 (assuming a specific gravity of 1.0 g/cm3) (where length is the longest perpendicular diameter and width is the shortest perpendicular diameter) As shown in FIG. 25A, the rate of increase in size of the tumour per day was approximately 6.5 mm/day in the control group and the rate of increase in size of tumour in the group treated with pegylated Arginase is approximately 5.3 mm/day for the first 39 days of the experiment. As shown in FIG. 25B, the rate of increase in mass of the tumour per day was approximately 1.8 times higher in the control group than that of the treated group. Example 17 The Response Upon Arginine Depletion in HuH-7 Tumour-Bearing Nude Mice In this example, a solid tumour of human hepatoma (HuH-7) was implanted subcutaneously into the back of ten BALB/c nude mice to induce growth of tumour. Five randomly picked mice were administered intraperitoneally once a week with 500 I.U. pegylated Arginase obtained from the method described in example 8C while the other five mice were given 200 μl phosphate buffer saline (PBS) per week intraperitoneally to serve as the control. The implanted mice were observed once every two days for the growth of the solid tumour in situ by digital calliper measurements to determine tumour size and mass as described in examples 15 and 16. As shown in FIG. 26A, the rate increase in size of the tumour per day was approximately 6.0 mm/day in control group and the rate of increase in size of tumour in the group treated with pegylated Arginase is approximately 5.6 mm/day for the first 18 days of the experiment. As shown in FIG. 26B, the rate of increase in mass of the tumour per day was approximately 1.4 times higher in the control group than that of the treated group. Example 18 The Response Upon Arginine Depletion in MCF-7 Tumour-Bearing Nude Mice In this example, a human breast cancer cell line (MCF-7) was inoculated subcutaneously into the right flank of four BALB/c nude mice to induce growth of tumour. Three randomly picked mice were administered intraperitoneally once a week with 500 I.U. pegylated Arginase obtained from the method described in Example 8C while the last one mouse were not given any arginine treatment to serve as the control. The implanted mice were observed once every two days for the growth of the solid tumour in situ by digital calliper measurements to determine tumour size as described in Example 15. As shown in FIG. 27, the tumour inoculated in the mice treated with pegylated Arginase disappeared within 20 days of the experiment It must be noted that as used herein and in the appended claims, the singular forms “a,” “and,” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “a pharmaceutical preparation” includes mixtures of different preparations and reference to “the method of treatment” includes reference to equivalent steps and methods known to those skilled in the art and so forth. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to describe and disclose specific information for which the reference was cited in connection with. The invention having been fully described, modifications within its scope will be apparent to those of ordinary skill in the art. All such modifications are within the scope of the invention. Formulations of the pharmaceutical composition of the present invention can be used in the form of a solid, a solution, an emulsion, a dispersion, a micelle, a liposome, and the like, wherein the resulting formulation contains one or more of the modified human arginase in the practice of the present invention, as active ingredients, in a mixture with an organic or inorganic carrier or excipient suitable for enteral or parenteral applications. The active ingredients may be the arginase, for example, with the usual non-toxic, pharmaceutically acceptable carriers for tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, and any other form suitable for use in manufacturing preparations, in solid, semisolid, or liquid form. In addition auxiliary, stabilizing, thickening and coloring agents and perfumes may be used. The active ingredients of one or more arginase are included in the pharmaceutical formulation in an amount sufficient to produce the desired effect upon the target process, condition or disease. Pharmaceutical formulations containing the active-ingredients contemplated herein may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Formulations intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical formulations. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract, thereby providing sustained action over a longer period. They may also be coated to form osmotic therapeutic tablets for controlled release. In some cases, formulations for oral use may be in the form of hard gelatin capsules wherein the active ingredients are mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, kaolin, or the like. They may also be in the form of soft gelatin capsules wherein the active ingredients are mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil. The pharmaceutical formulations may also be in the form of a sterile injectable solution or suspension. This suspension may be formulated according to known methods using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,4-butanediol. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides, fatty acids (including oleic acid), naturally occurring vegetable oils like sesame oil, coconut oil, peanut oil, cottonseed oil, or synthetic fatty vehicles, like ethyl oleate, or the like. Buffers, dextrose solutions preservatives, antioxidants, and the like, can be incorporated or used as solute to dissolve the soluble enzyme as required. The pharmaceutical formulations may also be an adjunct treatment together with other chemotherapeutic agents. In the claims, an arginase that has an amino acid sequence substantially the same as the sequence shown in SEQ ID No. 9 means that the sequence is at least 30% identical to that shown in SEQ ID No. 9 or that using the Arginase activity assay as described herein, there is no significant difference in the enzymatic activity between the enzyme of SEQ ID No. 9 and the one that is substantially similar. The six histidines are provided for ease of purification, and the additional methionine group provided at the amino terminus thereof is to allow translation to be initiated It is clear to one skilled in the art that other forms of purification may also be used, and therefore a “substantially similar” arginase does not need to have any homology with the MHH H sequence of SEQ ID No. 3. In some bacterial strains there may be at least 40% homology with SEQ. SEQ ID No. 9. Some mammalian arginase may be 70% homology with SEQ ID No. 9.
<SOH> BACKGROUND OF INVENTION <EOH>Arginase I (EC 3.5.3.1; L-arginine amidinohydrolase), is a key mammalian liver enzyme that catalyses, the final step in the urea formation in the Urea cycle, converting arginine into ornithine and urea. Rat liver extract, which has a high content of arginase, was found to have anti-tumour properties in vitro when it was accidentally added to tumour cell culture medium (Burton et al., 1967, Cytolytic action of corticosteroids on thymus and lymphoma cells in vitro. Can J. Biochem. 45, 289-297). Subsequent experiments showed that the anti-tumour properties of the enzyme were due to depletion of arginine, which is an essential amino acid in the culture medium. At below 8 μM levels of arginine, irreparable cell death in cancer cells occurred (Storr & Burton, 1974, The effects of arginine deficiency on lymphoma cells. Br. J. Cancer 30, 50-59). A more novel aspect of arginine centers on its role as the direct precursor for the synthesis of the potent signalling molecule nitric oxide (NO), which functions as a neurotransmitter, smooth muscle relaxant, and vasodilator. Biosynthesis of NO involves a Ca ++ , NADPH-dependent reaction catalysed by nitric oxide synthase (NOS). Another recognized role of arginine is that it acts as a precursor, via ornithine, of the polyamines, spermidine and spermine, which participate in diverse physiologic processes including cell proliferation and growth (Wu & Morris, 1998, Arginine metabolism: nitric oxide and beyond. Biochem. J. 336, 1-17). Arginine also serves as a substrate for several important enzymes, including nitric oxide synthase (NOS). There are three types of NOSs, nNOS, eNOS and iNOS, all convert arginine to nitric oxide and citrulline. The facial flushes induced by NO, for instance, is mediated through nNOS, the neuronal type of NOS. iNOS, the inducible NOS is produced by macrophages and the NO so produced from arginine during septicaemia causes vasodilation in endotoxic shock. eNOS, the endothelial NOS, is produced by endothelial cells in blood vessels. It converts arginine into NO, which then causes de-aggregation of platelets in the endothelial surfaces through cGMP mechanism. NO produced from eNOS in the local endQthelial lining has a half-life of about 5 seconds and diffusion distance of about 2 microns. The productions of these enzymes are controlled by different NOS genes (NOS1, NOS2, NOS3) encoded in chromosomes 12, 17 & 7, respectively. These genes share strikingly similar genomic structures in size of exons and the location of the splice junctions. The in vitro anti-tumour activities of arginine depletion were confirmed recently by a group in Scotland, UK (Scott et al., 2000, Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignanat cells. Br. J. Cancer 83, 800-810; Wheatley et al., 2000, Single amino acid (arginine) restriction: Growth and Death of cultured HeLa and Human Diploid Fibroblasts. Cellular Physiol. Biochem. 10, 37-55). Of the 24 different tumour cell lines tested, which included common cancers such as breast, colorectal, lung, prostate and ovaries, all died within 5 days of arginine depletion. Using flow-cytometry studies, the group was able to show that normal cell lines would enter into quiescence for up to several weeks in G0 phase of the cell cycle without any apparent harm. Tumour cells, however, would proceed pass the “R” point in the G1 phase and enter the S phase with deficiency of arginine. Without arginine, which is an irreplaceable amino acid, protein synthesis is deranged. Some cell lines were shown to die from apoptosis. More excitingly, repeated depletions can bringforth tumour kill without “resistance” being developed (Lamb et al., 2000, Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of Cdk4 expression in cultured human diploid fibroblasts. Experimental Cell Research 225, 238-249). Despite the promising in vitro data, attempts with arginine depletion to treat cancer in vivo were unsuccessful. The original Storr group attempted to treat tumour-bearing rats with intraperitoneal liver extracts and met with no success (Storr & Burton, 1974, The effects of arginine deficiency on lymphoma cells. Br. J. Cancer 30, 50-59). It is now generally recognized that under normal physiological condition, the blood plasma arginine level and indeed that of other amino acids too, are kept between the normal ranges (100-120 μM) with muscle being the main regulator. In the face of amino acid deficiency, intracellular protein breakdown pathways are activated (proteasomal and lysosomal) releasing amino acids into the circulation (Malumbres & Barbacid, 2001, To cycle or not to cycle: a critical decision in cancer. Nature Reviews, 1, 222-231). This amino acid homeostatic mechanism keeps the various amino acid levels at constant ranges. Thus, previous attempts to deplete arginine with various physical methods or arginine degrading enzymes have failed because of the body's amino acid homeostatic mechanism. To overcome the problem on the body's natural homeostatic tendencies, Tepic et al. in U.S. Pat. No. 6,261,557 described a therapeutic composition and method for treatment of cancer in which an arginine decomposing enzyme is used in combination with a protein breakdown inhibitors such as insulin in order to prevent the muscles of the body from replenishing the depleted arginine. Although insulin can act as a protein breakdown inhibitor, it also has far-reaching physiological effects on the human body that may cause fatal problems if blood glucose levels of the patient are not strictly maintained within the narrow normal range. It is therefore an object to the present invention to find improved method of treatment and compositions for the treatment of cancer.
<SOH> SUMMARY OF INVENTION <EOH>Accordingly, the present invention provides, in one aspect, an isolated and substantially purified recombinant human arginase I (hereinafter referred to as “Arginase” for ease of description unless otherwise stated) having a purity of 80-100%. In the preferred embodiment, the Arginase has a purity of between 90-100%. In the most preferred embodiment, the Arginase according to the present invention is at least 99% pure. In the example described below, the Arginase is more than 99.9% pure based on densitometry tracing after SDS-PAGE separation. In another preferred embodiment, the Arginase of the present invention is modified to have sufficiently high enzymatic activity and stability to maintain “adequate arginine deprivation” (hereinafter referred to as “AAD”) in a patient for at least 3 days. One preferred method of modification is an amino-terminal tag of six histidines. Another preferred modification is pegylation to increase the stability of the enzyme and minimise immunoreactivity illicited by the patient thereto. In the example described below, the Arginase has a plasma 12-life of at least about 3 days and specific activity of at least about 250 I.U./mg. In another aspect of the present invention, a method is provided for producing a recombinant protein comprising the steps of (a) cloning a gene encoding the protein; (b) constructing a recombinant Bacillus subtilis strain for expression of said protein (c) fermenting said recombinant B. subtilis cells using fed-batch fermentation; (d) heat-shocking said recombinant B. subtilis cells to stimulate expression of said recombinant protein; and (e) purifying said recombinant protein from the product of said fermentation. In the preferred embodiment, a prophage is used as the recombinant strain. Using the fed-batch method of fermentation and prophage described above for the cloning and expression of human recombinant arginase, there is more than a 4-fold increase in maximum optical density at wavelength of 600 nm (OD) reached, and more than 5 times improvement in both the yield and productivity of the Arginase as shown in Example 3 in the next section. In a further embodiment, the fermenting step can be scaled up for producing the recombinant protein. In a further embodiment, the fermenting step is performed using a well-defined feeding medium of 180-320 g/L glucose, 2-4 g/L MgSO 4 .7H 2 O, 45-80 g/L tryptone, 7-12 g/L K 2 HPO 4 and 3-6 g/L KH 2 PO 4 . The use of a well-defined medium prevents undesirable material from being purified together with the recombinant protein, making the method safe and efficient for the production of pharmaceutical grade recombinant material. In yet another preferred embodiment, the human Arginase gene is provided with an additional coding region that encodes six additional histidines at the amino-terminal end thereof, and the purifying step comprises a chelating column chromatography step. In a further preferred embodiment, the Arginase enzyme is further modified by pegylation to improve stability. In another aspect of the present invention, there are further provided pharmaceutical compositions comprising Arginase. In the preferred embodiment, the Arginase has sufficiently high enzymatic activity and stability to maintain AAD in a patient for at least 3 days. In the most preferred embodiment, the Arginase is further modified by pegylation to improve stability and minimise immunoreactivity. According to another aspect of the present invention, a pharmaceutical composition is further formulated using Arginase. In yet another aspect of the present invention, a method for treatment of a disease is provided comprising administering a formulated pharmaceutical composition of the present invention to a patient to maintain the arginine level in such a patient to below 10 LM for at least 3 days without the need for other protein breakdown inhibitors. In one of the preferred embodiments, no insulin is administered exogenously for non-diabetic patients. Furthermore, the most preferred treatment method of the present invention involves the monitoring of the patient's blood for platelet count (preferably maintained above 50,000×10 9 ) and prothrombin time (maintained no more than 2 times normal). No nitric oxide producer is exogenously administered unless these levels of platelet count and prothrombin time are not reached. In another preferred embodiment of this aspect of the present invention, pegylated Arginase is given as short infusion of over 30 minutes at 3,000-5,000 I.U./kg in short infusion. arginine levels and Arginase activity are taken before Arginase infusion and daily thereafter. If AAD is not achieved on day 2, the dose of the next infusion of Arginase is under the discretion of the treating physician. The maximum tolerated duration of AAD is defined as the period of time during which blood pressure is under control (with or without medication as deem appropriate by the treating physician), platelet count above 50,000×10 9 and prothrombin time less than 2× normal. As with arginine levels, complete blood count (CBC) and prothrombin time (PT) are taken daily. Liver chemistry is monitored at least twice weekly during the treatment. The experimental data provided in the following detailed description shows that arginase, if provided at sufficiently potent form, is useful for the treatment of maligancies. Although recombinant human arginase I is the specific embodiment of an arginase that is used for the present disclosure, it is clear that other forms of arginase and/or from other sources may be used in accordance with the present invention.
20041215
20110531
20051103
86169.0
0
CHOWDHURY, IQBAL HOSSAIN
PHARMACEUTICAL PREPARATION AND METHOD OF TREATMENT OF HUMAN MALIGNANCIES WITH ARGININE DEPRIVATION
UNDISCOUNTED
0
ACCEPTED
2,004
10,518,302
ACCEPTED
Epimerized derivatives of k5 polysaccharide with a very high degree of sulfation
A new method is described for the oversulfation of epiK-N sulfate to obtain an epiK5-amine-O-oversulfate with very high sulfation degree which, by subsequent N-sulfation, provides new epiK5-N,O-oversulfate-derivatives with a sulfation degree of at least 4, basically free of activity on the coagulation parameters and useful in the cosmetic or pharmaceutical field. Also described are new low molecular weight epiK5-N-sulfates useful as intermediates in the preparation of the corresponding LMW-epiK5-N,O-oversulfate-derivatives.
1-70. (canceled) 71. A process for the preparation of an epiK5-N,O-oversulfate-derivative, which comprises (a) treating an epiK5-N-sulfate-derivative, in acidic form, with tertiary or quaternary organic base, letting the reaction mixture to stand for a time period of 30-60 minutes at a pH of approximately 7 and its salt is isolated with said organic base; (b) treating said salt of organic base of said epiK5-N-sulfate-derivative with an O-sulfation reagent in the conditions of O-oversulfation; (c) treating a salt of tertiary or quaternary organic base of epiK5-amine-O-oversulfate-derivative thus obtained with a reagent of N-sulfation and isolating the epiK5-N,O-oversulfate-derivative thus obtained. 72. Process according to claim 71, wherein said epiK5-N,O-oversulfate-derivative is isolated in sodium salt form and optionally transformed into another chemically or pharmaceutically acceptable salt. 73. Process according to claim 71, wherein in step (a) tetrabutylammonium hydroxide is used as an organic base. 74. Process according to claim 71, wherein in step (b) the O-oversulfation is carried out in dimethylformamide using 2-4 moles of O-sulfation reagent per available OH per disaccharide at a temperature of 40-60° C. for 15-20 hours. 75. Process according to claim 71, wherein an epiK5-N-sulfate-derivative is used as starting material having a mean molecular weight from approximately 1,000 to approximately 25,000. 76. Process according to claim 75, characterized in that said starting epiK5-N-sulfate-derivative is 40-60% C5-epimerized. 77. Process according to claim 71, wherein said starting epiK5-N-sulfate-derivative has a mean molecular weight from approximately 1,500 to approximately 25,000. 78. Process according to claim 77, starting epiK5-N-sulfate-derivative has a mean molecular weight between 10,000 and 25,000. 79. Process according to claim 71, wherein said starting material has a mean molecular weight from approximately 1,000 to approximately 12,000. 80. Process according to claim 79, wherein said starting material has a mean molecular weight from approximately 1,500 to approximately 8,000. 81. Process according to claim 71, wherein an epiK5-N-sulfate-derivative is used as starting material consisting of a chain mixture in which at least 90% of said chains have the formula I in which the uronic units are 20-60% consisting of iduronic acid, n is an integer from 2 to 100 and the corresponding cation is chemically or pharmaceutically acceptable. 82. Process according to claim 81, wherein said starting material consists of a chain mixture in which at least 90% of said chains have the formula I, in which the uronic units are 40-60% consisting of iduronic acid. 83. Process according to claim 81, wherein, in the formula I, n represents an integer from 3 to 100. 84. Process according to claim 81, wherein said starting material consists of a chain mixture in which at least 90% of said chains have the formula I′ in which the uronic units are 20-60% consisting of iduronic acid, q is an integer from 2 to 20 and the corresponding cation is chemically or pharmaceutically acceptable. 85. Process according to claim 84, wherein said starting material consists of a chain mixture in which at least 90% of said chains have the formula I′, in which n is an integer from 3 to 15. 86. Process according to claim 81, wherein said starting material consists of a chain mixture in which the preponderant species has the formula I′a in which the uronic units are 60-40% consisting of glucuronic acid and 40% to 60% of iduronic acid, p is an integer from 4 to 8 and the corresponding cation is chemically or pharmaceutically acceptable. 87. Process according to claim 86, wherein the mean molecular weight of said starting material is from approximately 2000 to approximately 4000. 88. Process according to claim 86, wherein said starting material consists of a chain mixture in which the preponderant species has the formula I′b in which X is hydroxymethyl, m is 4, 5 or 6 and the glucuronic and iduronic units are present alternately, starting with a glucuronic or iduronic unit. 89. Process according to claim 71, wherein said starting material comes from a N-deacetylation and from a N-sulfation of a K5 that is basically free of lipophilic substances. 90. An epiK5-N,O-oversulfate-derivative having an iduronic acid content of 20-60%, a mean molecular weight from approximately 2,000 to approximately 45,000 and a sulfation degree of at least 4, or one of its chemically or pharmaceutically acceptable salts, said derivative being basically inactive on the coagulation parameters. 91. An epiK5-N,O-oversulfate-derivative according to claim 90, whose mean molecular weight is between approximately 15,000 and approximately 45,000. 92. An epiK5-N,O-oversulfate-derivative according to claim 90, whose mean molecular weight is between approximately 4,500 and approximately 8,500. 93. An epiK5-N,O-oversulfate-derivative according to claim 90, wherein said degree of sulfation is from 4 to 4.6. 94. An epiK5-N,O-oversulfate-derivative according to claim 90, which is 100% 6-O-sulfated and 50-80% 3-O-sulfated in its glucosamine units, 5-10% O-monosulfated in glucuronic units, 10-15% 3-O-monosulfated in iduronic units and 2,3-di-O-sulfated in the remaining uronic units. 95. An epiK5-N,O-oversulfate-derivative according to claim 90 consisting of a chain mixture in which at least 90% of said chains have the formula III in which the uronic units are 20-60% consisting of iduronic acid, R, R′, R″ represent hydrogen or SO3−, R being SO3− in at least 40% of said chain mixture, Z is a SO3− group, n is an integer from 2 to 100, the degree of sulfation is at least 4 and the corresponding cation is chemically or pharmaceutically acceptable. 96. An epiK5-N,O-oversulfate-derivative according to claim 95, consisting of a chain mixture in which at least 90% of said chains have the formula III, in which the uronic units are 40-60% iduronic acid. 97. An epiK5-N,O-oversulfate-derivative according to claim 95, consisting of a chain mixture in which at least 90% of said chains have the formula III, in which n is an integer from 3 to 100. 98. An epiK5-N,O-oversulfate-derivative according to claim 95, which is a LMW-epiK5-N,O-oversulfate consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which the uronic units are 20-60% consisting of iduronic acid, q is an integer from 2 to 20, R, R′ and R″ represent hydrogen or a SO3− group, Z is SO3−, for a sulfation degree of from 4 to 4.6, and the corresponding cation is one chemically or pharmaceutically acceptable ion. 99. A LMW-epiK5-N,O-oversulfate according to claim 98, consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which q is an integer from 3 to 15. 100. A LMW-epiK5-N,O-oversulfate according to claim 99, consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which the uronic units are 40-60% consisting of iduronic acid. 101. A LMW-epiK5-N,O-oversulfate according to claim 100, whose iduronic acid content is 50-55%. 102. A LMW-epiK5-N,O-oversulfate according to claim 98, consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which R is at least 40% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in glucuronic acid and 10-15% SO3− in iduronic acid. 103. A LMW-epiK5-N,O-oversulfate according to claim 102, having a mean molecular weight from approximately 2,000 to approximately 16,000. 104. A LMW-epiK5-N,O-oversulfate according to claim 103, having a molecular weight from approximately 4,500 to approximately 9,000. 105. A LMW-epiK5-N,O-oversulfate according to claim 102, consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which R is 50-80% SO3−. 106. A LMW-epiK5-N,O-oversulfate according to claim 101, consisting of a chain mixture in which the preponderant species has the formula III′a in which the uronic units are 20-60% consisting of iduronic acid, p is an integer from 4 to 8, Z is SO3−, R, R′ and R″ are hydrogen or SO3−, for a degree of sulfation from 4 to 4.6 and the corresponding cation is chemically or pharmaceutically acceptable. 107. A LMW-epiK5-N,O-oversulfate according to claim 102, consisting of a chain mixture in which the preponderant species has the formula III′b in which R, R′ and R″ are hydrogen or SO3−, Z is SO3−, X″ is OH or OSO3−, m is 4, 5 or 6, for a degree of sulfation from 4 to 4.6, the glucuronic and iduronic units are present alternately, starting with a glucuronic or iduronic unit, and the corresponding cation is a chemically or pharmaceutically acceptable ion. 108. An epiK5-N,O-oversulfate-derivative according to claim 90, wherein said chemically or pharmaceutically acceptable salt is an alkaline metal, alkaline-earth metal, ammonium, (C1-C4)tetraalkylammonium, aluminum or zinc salt. 109. An epiK5-N,O-oversulfate-derivative according to claim 108, wherein said chemically or pharmaceutically acceptable salt is the salt of sodium, calcium or tetrabutylammonium. 110. An epiK5-amine-O-oversulfate-derivative whose iduronic acid content is 20-60% of the total of the uronic acids, having a mean molecular weight from approximately 3,500 to approximately 40,000 and a sulfation degree of from 3.55 to 4, or one of its chemically or pharmaceutically acceptable salts. 111. An epiK5-amine-O-oversulfate-derivative according to claim 110, consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are 20-60% consisting of iduronic acid, n is an integer from 2 to 100, R, R′ and R″ are hydrogen or SO3−, the degree of sulfation is from 3.55 to 4 and the corresponding cation is chemically or pharmaceutically acceptable. 112. An epiK5-amine-O-oversulfate-derivative according to claim 111, of formula II, wherein n represents an integer from 3 to 100. 113. An epiK5-amine-O-oversulfate-derivative according to claim 111, consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are 40-60% consisting of iduronic acid, with a mean molecular weight from approximately 2,000 to approximately 40,000, R is at least 40%, SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in monosulfate glucuronic acid and 10-15% SO3− in monosulfate iduronic acid. 114. An epiK5-amine-O-oversulfate-derivative according to claim 111, which is a LMW-epiK5-amine-O-oversulfate consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are 40-60% consisting of iduronic acid, R is at least 40%, SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in glucuronic acid and 10-15% SO3− in iduronic acid, n is an integer from 3 to 15, with a mean molecular weight from approximately 4,000 to approximately 8,000 and the corresponding cation is chemically or pharmaceutically acceptable. 115. A LMW-epiK5-amine-O-oversulfate according to claim 134, consisting of a chain mixture in which the preponderant species has the formula II′a in which the uronic units are 20-60% consisting of iduronic acid, p is an integer from 4 to 8, R, R′ and R″ are hydrogen or SO3−, bearing a sulfated 2,5-anhydromannitol unit of structure (a′) wherein R is hydrogen or SO3− at the reducing end of the majority of said chains. 116. A LMW epiK5-amine-O-oversulfate according to claim 115, consisting of a chain mixture in which the preponderant species is a compound of formula II′b in which the uronic units are 40-60% consisting of iduronic acid, m is 4, 5 or 6, R, R′ and R″ are hydrogen or SO3−, X″ is OH or OSO3−, for a sulfation degree of at least 3.4, the iduronic units being present alternately, starting with a glucuronic or iduronic unit. 117. A LMW-epiK5-N-sulfate virtually free of NH2 and N-acetyl groups, having an iduronic acid content from 20 to 60% and a mean molecular weight from approximately 1,500 to approximately 12,000, or one of its chemically or pharmaceutically acceptable salts. 118. A LMW-epiK5-N-sulfate according to claim 117, whose iduronic acid content is from 40 to 60% and the mean molecular weight is from approximately 1,500 to approximately 10,000. 119. A LMW-epiK5-N-sulfate according to claim 117, whose iduronic acid content is 50-55% and the mean molecular weight is from approximately 1,500 to approximately 7,500. 120. A LMW-epiK5-N-sulfate according to claim 117, consisting of a chain mixture in which at least 90% of said chains have the formula I′ in which the uronic units are 20-60% consisting of iduronic acid, q is an integer from 2 to 20, bearing a 2,5-anhydromanno unit of structure (a) wherein X is formyl or hydroxymethyl, at the reducing end of the majority of said chains, and the corresponding cation is chemically or pharmaceutically acceptable. 121. A LMW-epiK5-N-sulfate according to claim 120, consisting of a chain mixture in which at least 90% of said chains have the formula I′, in which the uronic units are 40-60% iduronic acid. 122. A LMW-epiK5-N-sulfate according to claim 120, consisting of a chain mixture in which at least 90% of said chains have the formula I′, in which n is an integer from 3 to 15. 123. A LMW-epiK5-N-sulfate according to claim 120, consisting of a chain mixture in which the preponderant species has the formula I′a in which the uronic units are 60-40% consisting of glucuronic acid and 40% to 60% iduronic acid, p is an integer from 4 to 8 and the corresponding cation is chemically or pharmaceutically acceptable. 124. A LMW-epiK5-N-sulfate according to claim 121, consisting of a chain mixture in which the preponderant species has the formula I′b in which X is hydroxymethyl, m is 4, 5 or 6, the corresponding cation is a chemically or pharmaceutically acceptable ion and the glucuronic and iduronic units are present alternately, starting with a glucuronic or iduronic unit. 125. A LMW-epiK5-N-sulfate according to claim 117, wherein said salt is selected from the group consisting of alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc salts. 126. A LMW-epiK5-N-sulfate according to claim 125, wherein said salt is sodium, calcium or tetrabutylammonium salt. 127. A process for the preparation of a LMW-epiK5-N-sulfate, which comprises subjecting a K5-N-sulfate, in any one order, (i) to C5-epimerization with a D-glucuronyl C5-epimerase isolated, purified and in solution or immobilized on a solid support, at a pH of approximately 7, at a temperature of approximately 30° C. and for a time period of 12-24 hours in the presence of at least one bivalent ion selected among calcium, magnesium, barium and manganese; and (ii) to nitrous depolymerization optionally followed by reduction. 128. Process according to claim 127, which is carried out in the order (i)-(ii). 129. Process according to claim 127, which is carried out in the order (ii)-(i). 130. Process according to claim 129, wherein the product obtained upon termination of the depolymerization is a LMW-K5-N-sulfate which is directly subjected to C5-epimerization. 131. Process according to claim 130, wherein said LMW-K5-N-sulfate has a mean molecular weight of more than 4,000. 132. A pharmaceutical composition including, as an active ingredient, a pharmacologically active amount of an epiK5-N,O-oversulfate-derivative according to claim 90, in mixture with a pharmaceutical excipient. 133. A cosmetic composition including an effective amount of an epiK5-N,O-oversulfate-derivative according to claim 90, in mixture with a cosmetic excipient. 134. A LMW-epiK5-amine-O-oversulfate consisting of mixture of chains in which at least 90% of said chains have the formula II′ in which 20-60% of the uronic acid units are those of iduronic acid, q is an integer from 2 to 20, R, R′ and R″ are hydrogen or SO3−, bearing a sulfated 2,5-anhydromannitol unit of structure (a′) wherein R is hydrogen or SO3−, at the reducing end of the majority of said chains, for a sulfation degree of at least 3.4, and the corresponding cation is a chemically or pharmaceutically acceptable ion.
OBJECT OF THE INVENTION The present invention concerns new derivatives of K5 polysaccharide with a very high degree of sulfation, a process for their preparation, highly O-sulfated new intermediates useful in their synthesis and pharmaceutical compositions containing said derivatives of K5 polysaccharide as active ingredients basically free of activity on coagulation. In particular, the invention refers to a process for the preparation of epiK5-N,O-oversulfates starting with a K5 polysaccharide, previously N-deacetylated, N-sulfated and C5-epimerized at least 20%, through O-oversulfation in suitable conditions and subsequent N-sulfation, to said epiK5-N,O-oversulfates of antiangiogenetic and antiviral activity and to new low molecular weight intermediates of epi-K5-N-sulfates. BACKGROUND OF THE INVENTION The glycosaminoglycans such as heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate and hyaluronic acid are biopolymers that are industrially extracted from various animal organs. In particular, heparin, mainly obtained by extraction from the intestinal mucous membrane of pigs or bovine lung, is a polydispersed copolymer with a molecular weight distribution from approximately 3,000 to approximately 30,000 D consisting of a chain mixture basically consisting of a uronic acid (glucuronic acid or iduronic acid) and of an amino sugar (glucosamine) linked by α-1→4 or β-1→4 bonds. In heparin, the uronic unit can be O-sulfated in position 2 and the glucosamine unit is N-acetylated or N-sulfated, 6-O-sulfated, and 3-O-sulfated in approximately 0.5% of the glucosamine units present. The properties and natural biosynthesis of heparin in mammals have been described by Lindahl et al., 1986 in Lane, D. and Lindahl, U. (Editors) “Heparin. Chemical and Biological Properties; Clinical Applications”, Edward Arnold, London, Pages 159-190, by Lindahl, U, Feingold D. S. and Roden L, 1986 TIBS, 11, 221-225 and by Conrad H. E. “Heparin Binding Proteins”, Chapter 2: Structure of Heparinoids. Academic Press, 1998. The biosynthesis of heparin occurs starting with its precursor N-acetyl-heparosan consisting of a chain mixture consisting of the repetitive disaccharide unit glucuronyl-β1-4-N-acetylglucosamine. Said precursor undergoes enzymatic modifications which partially hydrolyse the N-acetyl group, substituting it with an SO3− group, epimerize the carboxyl in position 5 of a part of the glucuronic units converting them into iduronic units and introducing O-sulfate groups to get a product which, once extracted industrially, has approximately double the number of sulfate groups as regards carboxyl ones per disaccharide unit. These enzymatic modifications lead to, besides, the formation of the pentasaccharide region of a bond to antithrombin III (ATIII), called active pentasaccharide, which is the structure necessary for the high affinity bond of heparin to the ATIII and fundamental for anticoagulant and antithrombotic activity of the heparin itself. This pentasaccharide, present inside only some of the chains which form heparin, contains a sulfated glucosamine unit in position 3 and a glucuronic acid spaced out between disaccharides containing iduronic acids. In nature, the formation of the active pentasaccharide is made possible by the epimerization reaction of the carboxyl of a part of the glucuronic units into iduronic units carried out by the glucuronyl-C5-epimerase (C5-epimerization) and by suitable sulfation which also leads to the introduction of a sulfate group onto the hydroxyl in position 3 of the glucosamine. More particularly, in nature the formation of the active pentasaccharide is made possible by the fact that the C5-epimerization occurs in clusters, i.e. on portions of chains, and extensively, which results in a product that contains more iduronic units than glucuronic ones. Commercial heparin, in fact, contains approximately 70% of iduronic units and 30% of glucuronic units. Alongside the main anticoagulant and antithrombotic activities, heparin also exercises antilipaemic, antiproliferative, antiviral, antitumorous and antimetastatic activities, but its use as a drug is hindered by the side effects due to the anticoagulant action which can cause bleeding. PRIOR ART It is known that the capsular K5 polysaccharide isolated from Escherichia coli, described by Vann W. F. et al., in European Journal of Biochemistry, 1981, 116, 359-364 (“Vann 1981”), consists of a chain mixture consisting of the repetitive disaccharide unit glucuronyl-β-1→4-N-acetyl glucosamine and therefore shows the same repetitive sequence (A) of the N-acetyl-heparosan precursor of heparin. The capsular K5 polysaccharide, referred to hereafter as “K5 polysaccharide” or more simply “K5”, was chemically modified by Lormeau et al. as described in U.S. Pat. No. 5,550,116 and by Casu et al. as described in Carbohydrate Research, 1994, 263, 271-284. K5-O-sulfates having antitumorous, antimetastatic, antiviral, in particular anti-HIV activities are described in EP 333243 and WO 98/34958. The K5 was also modified chemically and enzymatically in order to obtain products having the same type of in vitro biological activity on coagulation as that of heparin as extracted from animal organs (extractive heparin). The attainment of the products having an activity on coagulation of the same type as that of extractive heparin occurs by processes which imitate that occurring in nature and envisage the entire key step of C5-epimerization with D-glucuronyl C5 epimerase. The processes described in IT 1230785, WO 92/17507, WO 96/14425 and WO 97/43317 utilize K5 as the starting material. K5 originating from fermentation is subjected to N-deacetylation followed by N-sulfation and on the K5-N-sulfate thus obtained C5-epimerization with C5-epimerase in solution is performed, obtained either by chromatography of a solution of microsomal enzymes from mouse mastocytoma (IT 1230 785) or from bovine liver (WO 92/17507, WO 96/14425 and WO 97/43317). The D-glucuronyl C5 epimerase from bovine liver was purified by Campbell, P. et al. in J. Biol. Chem., 1994, 269/43, 26953-26958 (“Campbell 1994”) who also supplied its composition in amino acids and described its use in solution for the transformation of a K5-N-sulfate into the corresponding 30% epimerized product, demonstrating the formation of iduronic acid by HPLC method followed by total nitrous depolymerization to disaccharide. The document WO 98/48006 describes the DNA sequence which codes for the D-glucuronyl C5 epimerase and a recombinant D-glucuronyl C5 epimerase, obtained from a recombinant expression vector containing said DNA, afterwards purified by Campbell et al. as shown by Jin-Ping L. et al. in J. Biol. Chem. 2001, 276, 20069-20077 (“Jin-Ping 2001”). The complete C5-epimerase sequence was described by Crawford B. E. et al. in J. Biol. Chem., 2001, 276(24), 21538-21543 (Crawford 2001). The document WO 01/72848 describes a method for the preparation of N-deacetylated N-sulfate derivatives of K5 polysaccharide, at least 40% epimerized of iduronic acid as regards the total of the uronic acids, having a molecular weight from 2,000 to 30,000, containing from 25 to 50% of high affinity chains for ATIII and having an anticoagulant and antithrombotic activity expressed as HCII/antiXa ratio from 1.5 to 4. Said document describes the oversulfation of a K5-N-sulfate, 40-60% epimerized and shows that the product obtained, whose 13C-RMN is illustrated, has a sulfate group content per disaccharide unit of 2-3.5. Repeating the aforesaid oversulfation in the conditions described and examining the 13C-RMN it was ascertained that the product obtained is actually a free amine whose 6-O-sulfate content is 80-95%, that of 3-O-sulfate on the amino sugar is 30%, but whose sulfation degree is 3.2. It was also observed that in the conditions of oversulfation described in WO 01/72848 a degree of sulfation higher than 3.2 was not obtained. The document U.S. 2002/0062019 describes a process for the preparation of epiK5-N,O-sulfates, active in the control of coagulation, having a degree of sulfation from 2.3 to 2.9 and a molecular weight from 2,000 to 30,000, or from 4,000 to 8,000, or from 18,000 to 30,000. The aforesaid process involves the steps: (p-a) an N-deacetylation of K5 polysaccharide and an N-sulfation of the resulting K5-amine, (p-b) an epimerization of K5-N-sulfate, (p-c) an O-oversulfation of epiK5-N-sulfate, (p-d) a partial O-desulfation, (p-e) a selective 6-O-sulfation, (p-f) an N-sulfation of the product thus obtained, any product obtained upon termination of one of the steps (p-b)-(p-f) able to be subjected to depolymerization. Said document describes an epiK5-N,O-sulfate having a molecular weight of 7,400, obtained by the aforesaid steps (p-a)-(p-f) followed by a nitrous depolymerization at the end of step (p-f), with a degree of sulfation from 2.3 to 2.9. The same document also describes a moiety of K5 with a molecular weight of approximately 5,000 which can also be subjected to steps (p-a)-(p-f). In order to standardize the terminology and render the text more comprehensible, in the present description conventional terms or expressions will be used, in the singular or plural. In particular: by “K5” or “K5 polysaccharide” is meant the capsular polysaccharide from Escherichia coli obtained by fermentation, i.e. a chain mixture consisting of disaccharide units (A) optionally containing a double bond at the non-reducing end as shown above, in any case, prepared and purified according to the methods described in literature, in particular according to Vann 1981, according to Manzoni M. et al., Journal of Bioactive Compatible Polymers, 1996, 11, 301-311 (“Manzoni 1996”) or according to the method described in WO 01/72848 and in WO 02/068447; it is obvious for a person skilled in the art that what is shown hereafter can be applied to any N-acetylheparosan; by “C5-epimerase” is meant the D-glucuronyl C-5 epimerase, extractive or recombinant, in any case prepared, isolated and purified, in particular as described in Campbell 1994, in WO 98/48006, in Jin-Ping L. et al. in J. Biol. Chem. 2001, 276, 20069-20077 (Jin-Ping 2001”) or in Crawford 2001; by K5-amine is meant at least 95% N-deacetylated K5, but in which N-acetyl groups are undetectable with a normal NMR apparatus; by “K5-N-sulfate” is meant at least 95% N-deacetylated and N-sulfate K5, normally 100%, since N-acetyl groups are undetectable with a normal NMR apparatus, as described hereafter; by “epiK5” is meant the K5 and its derivatives in which 20-60% of the glucuronic units is C5-epimerized to iduronic units by “epiK5-N-sulfate” is meant K5-N-sulfate in which 20-60% of the glucuronic units is C5-epimerized to iduronic units; by “epiK5-amine-O-oversulfate” is meant an epiK5-amine-O-sulfate with a sulfation degree of at least 3.4; by “epiK5-N,O-oversulfate” is meant an epiK5-amine-O-sulfated completely N-sulfated with a sulfation degree of at least 4; In addition: the conventional terms and expressions herein defined above refer to a K5 as isolated after fermentation, generally with a molecular weight distribution from approximately 1,500 to approximately 50,000 with a mean molecular weight of 10,000-25,000, advantageously of 15,000-25,000; the conventional terms and expressions herein defined above, when preceded by the acronym “LMW” (low molecular weight), for example LMW-K5-N-sulfate, LMW-epiK5-N-sulfate, indicate low molecular weight products, obtained by fractionation or by depolymerization of K5-N-sulfate and consisting of or derived from K5-N-sulfates having a mean molecular weight from approximately 1,500 to approximately 12,000, calculated on a 100% N-sulfated product; the conventional terms and expressions as herein defined above, when followed by “-derivative” indicate as a whole both the derivatives from native K5 and those of low molecular weight; by the term “approximately”, referring to the molecular weight, is meant the molecular weight measured by viscometry±the theoretical weight of a disaccharide unit, including the weight of the sodium, calculated as 461 in the case of an epiK5-N-sulfate-derivative and 806 in the case of an epiK5-N,O-oversulfated-derivative with a sulfation degree of 4.26; by the expression “preponderant species”, is meant the compound which, in the mixture constituting the LMW-epiK5-N-sulfate, the LMW-epiK5-amine-O-oversulfate or the LMW-epiK5-N,O-oversulfate, is the most represented type, determined by the peak of the curve of the molecular weight measured by HPLC; unless otherwise specifically stated, by “degree of sulfation” is meant the SO3−/COO− ratio, expressible also as the number of sulfate groups per disaccharide unit, measured with the conductometric method described by Casu B. et al. in Carbohydrate Research, 1975, 39, 168-176 (Casu 1975), the same utilized in WO 01/72848; by “conditions of O-oversulfation” is meant an extreme O-sulfation performed, for example, according to the Method C described by B. Casu et al. in Carbohydrate Research, 1994, 263, 271-284 (Casu 1994); by the term “alkyl” is meant a linear or branched alkyl, whereas “tetrabutylammonium” denotes the tetra-n-butylammonium group. SUMMARY OF THE INVENTION It has now surprisingly been found that, unlike that which occurs with the processes described in IT 1230785, WO 92/17507, WO 96/14425, WO 97/43317, WO 01/72848 and U.S. 2002/0062019, starting with an epiK5-N-sulfate it is possible to obtain an epiK5-amine-O-oversulfate with a greater degree of sulfation than every other epiK5-amine-O-sulfate described in literature, for example in WO 01/72848, by preparing the salt with tertiary or quaternary organic base of said epiK5-N-sulfate taking care to let the reaction mixture to stand for a time period of 30-60 minutes maintaining the pH at approximately 7 with the same organic base and then treating the salt obtained with an O-sulfation reagent in the conditions of O-oversulfation. Subjecting the epiK5-amine-O-oversulfates thus obtained to N-sulfation, new epiK5-N,O-oversulfates are obtained which, unlike the products described in IT 1230785, WO 92/17507, WO 96/14425, WO 97/43317, WO 01/72848 and U.S. 2002/0062019, are free of activity on coagulation and useful for the preparation of medicines, particularly pharmaceutical compositions of antiangiogenetic and antiviral activity or of cosmetic compositions. By depolymerization with nitrous acid of said epiK5-N,O-oversulfates new LMW-epiK5-N,O-oversulfates are obtained, free of activity on coagulation, and with antiangiogenetic and antiviral activity. In preparing N,O-sulfate N-deacetylated derivatives of K5 polysaccharide, at least 40% epimerized of iduronic acid as regards the total of the uronic acids and having low molecular weight according to the method described in WO 01/72848, it was ascertained that the depolymerization of the product of high molecular weight obtained at the end of the final N-sulfation step of the process can give varying results since it generally produces some depolymerized products showing much lower activity, than that of high molecular weight products from which they arise, on all the coagulation parameters. It is assumed this takes place because degradation with nitrous acid is influenced by the presence of the sulfate groups. In particular the sulfates in position 3 of the glucosamine result in heterogenous products, as described by Nagasawa et al. in Thrombosis Research, 1992, 65, 463-467 (Nagasawa 1992). It has now been found that subjecting an epiK5-N-sulfate to nitrous depolymerization in which the iduronic acid content as regards the total of uronic acids is 20-60%, advantageously of 40-60%, preferably around 50%, LMW-epiK5-N-sulfates are obtained which constitute new effective intermediates for the preparation of LMW-epiK5-N,O-oversulfates having a high degree of activity on different biological parameters, with or without activity on coagulation parameters. In particular, it was found that it is possible to depolymerize an epiK5-N-sulfate so as to obtain new LMW-epiK5-N-sulfates of mean molecular weight from approximately 2,000 to approximately 4,000, more particularly specific LMW-epiK5-N-sulfates consisting of mixtures in which the predominant compound is a decasaccharide or a dodecasaccharide or a tetradecasaccharide. Also these LMW-epiK5-N-sulfates, otherwise unobtainable, have interesting biological properties and are useful intermediates for the preparation of LMW-epiK5-N,O-oversulfated of antiviral and/or antiangiogenetic activity and surprisingly free of activity on coagulation. By subjecting a LMW-epiK5-N-sulfate to the aforesaid method of salification with a tertiary or quaternary organic base, taking care to let the reaction mixture to stand for a time period of 30-60 minutes maintaining the pH at approximately 7 with the same organic base and then treating the salt obtained with an O-sulfation reagent in the conditions of O-oversulfation, new LMW-epiK5-amine-O-oversulfates are obtained. By subjecting the LMW-epiK5-amine-O-oversulfate to N-sulfation, new N-sulfated and O-oversulfated derivatives (LMW-epiK5-N,O-oversulfates) are obtained, surprisingly free of activity on coagulation and of antiviral and/or antiangiogenetic activity, useful for the preparation of pharmaceutical or cosmetic compositions. These LMW-epiK5-N-sulfates are obtained starting with a K5-N-sulfate with an epimerization reaction with an isolated and purified recombinant C5-epimerase, immobilized on a solid support, at a temperature of approximately 30° C. and at a pH of approximately 7 for 12-24 hours in the presence of a bivalent cation selected among calcium, magnesium, barium and manganese and a subsequent nitrous depolymerization reaction of the epimerized product thus obtained, or vice versa. Surprisingly, from observations made on the course of the epimerization reaction in the aforesaid conditions, it is possible to assume that, contrary to that occurring in nature in the biosynthesis of heparin, ordinary and not “cluster” type C5-epimerization of the substrate occurs every 2 glucuronic acid units which leads to epi-K5-N-sulfate-derivatives characterized by a repetitive tetrasaccharide unit consisting of two glucosamine units separated by a glucuronic unit and followed by an iduronic unit or vice versa. DETAILED DESCRIPTION Thus, according to one of its aspects, the present invention provides a process for the preparation of epiK5-N,O-oversulfate-derivatives, characterized in that (a) a K5-N-sulfate-derivative, in acidic form, is treated with a tertiary or quaternary organic base, letting the reaction mixture to stand for a time period of 30-60 minutes, maintaining the pH of the solution at a value of 7 by addition of the same tertiary or quaternary organic base, and its salt is isolated with said organic base; (b) said salt of organic base of said epiK5-N-sulfate-derivative is treated with an O-sulfation reagent in the conditions of O-oversulfation; (c) the epi-K5-amine-O-oversulfate-derivative thus obtained is treated with a reagent of N-sulfation and the epiK5-N,O-oversulfate-derivative is isolated. Generally, the epiK5-N,O-oversulfate-derivative is isolated in sodium salt form and optionally said sodium salt is transformed into another chemically or pharmaceutically acceptable salt. In this context, the term “chemically acceptable” refers to a cation usable in chemical synthesis, such as the sodium, ammonium, (C1-C4)tetraalkylammonium ion, or for the purification of the product, whereas “pharmaceutically acceptable” is self-explanatory. Advantageous cations are those derived from alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc. Preferred cations are the sodium, calcium and tetrabutylammonium ions. According to an advantageous manner of procedure, step (a) is carried out by passing a solution of the sodium salt of epiK5N-sulfate-derivative, i.e. of K5 polysaccharide, previously N-deacetylated, N-sulfated, normally 100%, and 20-60% C5-epimerized and optionally depolymerized with nitrous acid, having a mean molecular weight from approximately 1,000 to approximately 25,000, advantageously from approximately 1,500 to approximately 25,000, through an acid ionic exchange resin, for example of the type IR-120H+, collecting the eluate also including the washing water of the resin and neutralizing the eluate with tertiary or quaternary organic base, preferably with an aqueous solution of tetrabutylammonium hydroxide. The solution is let to stand for 1 hour, maintaining its pH at 7 by addition of the same base and the salt thus obtained is isolated by lyophilization. In step (b), the O-oversulfation occurs by using an excess of O-sulfating agent and working at a temperature from 20 to 70° C. for a time period of up to 24 hours in an aprotic polar solvent. Advantageously, the salt with a tertiary or quaternary organic base of the epiK5-N-sulfate-derivative, i.e. of K5 polysaccharide, previously N-deacetylated, N-sulfated preferably 100%, and 20-60% C5-epimerized and optionally depolymerized with nitrous acid, having a mean molecular weight from approximately 1,000 to approximately 25,000, advantageously from approximately 1,500 to approximately 25,000 as isolated in step (a), is dissolved in dimethylformamide and treated with 2-10 moles of an O-sulfation reagent for every free hydroxyl at a temperature of 40-60° C. for 10-20 hours. As an O-sulfation reagent is advantageously used the pyridine.SO3 adduct in a quantity of 2.5-5 moles, preferably 2.5-4 moles per free hydroxyl per disaccharide and the reaction is advantageously carried out at 50-60° C., preferably at 55° C., overnight. The product obtained upon termination of the reaction is isolated by addition of 0.1-1 volume of water and neutralization, preferably with sodium hydroxide, precipitation with a saturated sodium chloride solution in acetone, filtration and possible ultrafiltration. The product thus obtained is generally the sodium salt of an epiK5-amine-O-oversulfate-derivative having an iduronic acid content of 20-60% of the total of the uronic acids, having a mean molecular weight from approximately 3,500 to approximately 40,000, advantageously from approximately 4,500 to approximately 40,000 and a sulfation degree of at least 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8. The sodium salt thus obtained can be converted into another salt. By way of example an exchange with the calcium ion can be performed working with ultrafiltration membranes. In step (c), the epiK5-amine-O-oversulfated-derivative with a very high degree of sulfation is N-sulfated using the known N-sulfation methods in literature. In practice, the N-sulfation is performed by treating an aqueous solution containing the epiK5-amine-O-oversulfated-derivative originating from step (b) with sodium carbonate and an agent of N-sulfation, for example a (C1-C4)trialkylamine.SO3 or pyridine.SO3 adduct, maintaining the mixture at 30-50° C. for 8-24 hours and isolating the desired epiK5-N,O-oversulfate-derivative, for example by diafiltration. Optionally the step of N-sulfation is repeated until obtaining more than 95% substitution, preferably complete. The new epiK5-N,O-oversulfate-derivatives thus obtained are generally in their sodium salt form. Said sodium salt can be converted into another chemically or pharmaceutically acceptable salt. Particularly advantageous salts are those of alkaline metals, alkaline-earth metals, of ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc. Preferred are the salts of sodium, calcium and tetrabutylammonium. The starting epiK5-N-sulfates subjected to step (a) of the process of the present invention are derived from a K5 polysaccharide, previously N-deacetylated, N-sulfated virtually 100%, and 20-60% C5-epimerized, advantageously 40-60%, and optionally depolymerized with nitrous acid, having a mean molecular weight from approximately 1,000 to approximately 25,000, advantageously from approximately 1,500 to approximately 25,000. Preferably, said starting material is an epi-K5-N-sulfate having a mean molecular weight between 10,000 and 25,000 or a LMW-epiK5-N-sulfate having a mean molecular weight from approximately 1,000 to approximately 12,000, advantageously from approximately 1,000 to approximately 10,000, preferably between approximately 1,500 and approximately 8,000. The epiK5-N-sulfates, prepared by C5-epimerization of K5-N-sulfates, are well known in literature and widely described for example in WO 92/17507, WO 01/72848, WO 98/14425, WO 97/43317 or U.S. 2002/0062019. Their preparation by C-5 epimerization of the glucuronic unit of K5-N-sulfate with a D-glucuronyl C5 epimerase was described in documents cited herein above. A LMWepiK5-N-sulfate having an iduronic unit content of approximately 20%, obtained by N-deacetylation, N-sulfation and C5-epimerization of a moiety of K5 having a mean molecular weight of 5,000 is described in WO 92/17507. However such LMW-K5-N-sulfate contains a considerable quantity of acetyl groups. An epiK5-N-sulfate with an iduronic acid content of 40-60%, particularly advantageous as a starting material, is that obtained by epimerization of a K5-N-sulfate virtually free of acetyl groups, in turn prepared from particularly pure K5, in particular not containing lipophilic substances, described in WO 02/068477. According to a preferential manner of procedure, by epimerization a K5-N-sulfate is used obtained from a K5 free of lipophilic substances like that described in WO 02/068477 and the C5 epimerization is performed with a D-glucuronyl C5-epimerase that is isolated, purified and immobilized on a solid support, at a pH of approximately 7, at a temperature of approximately 30° C. and for a time period of 12-24 hours in the presence of at least one bivalent ion selected among calcium, magnesium, barium and manganese. The LMW-epiK5-N-sulfates having a higher content of iduronic units, in particular 40-60%, preferably 50-55%, are new, particularly advantageous products as starting materials in the preparation of LMW-epiK5-N,O-oversulfate-derivatives. The LMW-epiK5-N-sulfates as shown above are prepared by a process characterized in that a K5-N-sulfate is subjected, in any one order, (i) to C5-epimerization with a D-glucuronyl C5-epimerase that is isolated, purified and in solution or immobilized on a solid support, at a pH of approximately 7, at a temperature of approximately 30° C. and for a time period of 12-24 hours in the presence of at least one bivalent ion selected among calcium, magnesium, barium and manganese; and (ii) to a nitrous depolymerization optionally followed by reduction, normally with sodium borohydride. The expression “in any order” shows that the process can be indifferently carried out both in the direction (i)-(ii), i.e. in the sequence shown above, as well as in reverse direction, i.e. also in the direction (ii)-(i), subjecting the K5-N-sulfate at first to the nitrous depolymerization reaction, optionally followed by reduction with sodium borohydride, and afterwards to C5-epimerization in the aforesaid conditions. The preferred order is in the direction (i)→(ii). The sequence (ii)-(i) is preferably utilized starting with LMW-K5-N-sulfates having a mean molecular weight of more than 4,000, preferably starting with approximately 6,000. For example, one can determine the amount of sodium nitrite which, starting with 1 g of epiK5-N-sulfate, allows the attainment of a LMW-epiK5-N-sulfate with a molecular weight of more than 4,000, in particular of at least 6,000, so as to obtain useful intermediates for the preparation of LMWepiK5-N,O-oversulfates. In fact, in this case, in step (ii) the percentage of optimum epimerization is obtained. According to a preferential aspect of the invention, the C5-epimerase is immobilized on an inert solid support. The C5-epimerase, preferably recombinant, isolated and purified for example according to Campbell 1994, WO 98/48006, Jin-Ping 2001 or Crawford 2001, is immobilized on an inert support in the presence of the substrate, i.e. in the presence of starting K5-N-sulfate-derivative or in the presence of LMW-K5-N-sulfate, advantageously having a mean molecular weight of more than 4,000, preferably of at least 6,000. The immobilization is performed according to conventional methods, for example as described in WO 01/72848. The C-5epimerization reaction is carried out by recirculating 20-1,000 ml of a 25 mM HEPES solution at a pH of approximately 0.7 containing 0.001-10 g of substrate (K5-N-sulfate or LMW-K5-N-sulfate, preferably with a molecular weight of more than 4,000, in particular of at least 6,000) and a cation selected among calcium, magnesium, barium and manganese at a concentration of between 10 and 60 mM through a column containing from 1.2×107 to 3×1011 cpm of the immobilized enzyme, maintaining the pH at approximately 7 at approximately 30° C., at a flow of 30-220 ml/hour for a time period of 12-24 hours, advantageously 15-24 hours. Preferably said solution is recirculated at a flow of approximately 200 ml/hour overnight (15-20 hours). The product obtained is purified and separated according to known methods, for example by ultrafiltration and precipitation with ethanol. The product thus obtained is either consisting of epiK5-N-sulfate (and in such case is dissolved in water and subjected to depolymerization) or LMW-epiK5-N-sulfate (in such case it constitutes the end product). The percentage of epimerization, in practice the amount of iduronic units as regards the glucuronic ones, is calculated using 1H-RMN according to the method described in WO 96/4425. The nitrous depolymerization reaction is carried out according to known methods by the depolymerization of heparin, for example according to the method described in EP 37319, in WO 82/03627 or according to the method by depolymerization of a K5-N-sulfate described in EP 544592, but starting with a K5-N-sulfate or an epiK5-N-sulfate containing from 0 to no more than 10%, preferably no more than 5%, of acetyl groups. Preferably, the depolymerization, performed with sodium nitrite and hydrochloric acid on an epiK5-N-sulfate virtually free of acetyl groups, is followed by in situ reduction with sodium borohydride. In practice, a cold aqueous solution of epiK5-N-sulfate is brought to acid pH (approximately 2) with hydrochloric acid and, still cold, treated with sodium nitrite maintaining the temperature (approximately 4° C.) and the pH (approximately 2) constant and, upon termination of depolymerization (approximately 15-30 minutes) the solution is neutralized with sodium hydroxide and treated, still at approximately 4° C., with an aqueous solution of sodium borohydride. Upon termination of the reduction (approximately 4 hours) the excess sodium borohydride is destroyed with hydrochloric acid, the solution is neutralized with sodium hydroxide and the depolymerized (and reduced) product is isolated according to known methods, for example by straightforward precipitation with ethanol or acetone. The product obtained upon termination of depolymerization can be either a LMW-epiK5-N-sulfate (in such case it constitutes the end product) or a LMW-K5-N-sulfate (and in such case is directly subjected to C5-epimerization as herein shown above, after isolation or also in solution without being previously isolated), in particular when it has a mean molecular weight of more than 4,000, preferably of at least 6,000, or is utilized to prepare antiangiogenetic and antiviral activity LMW-K5-N,O-oversulfated. By appropriately controlling the depolymerization reaction, in particular using different amounts of sodium nitrite/hydrochloric acid, are obtained LMW-K5-N-sulfates or LMW-epiK5-N-sulfates having a mean molecular weight in the entire interval from approximately 1,500 to approximately 12,000, advantageously from approximately 1,500 to approximately 10,000, preferably from approximately 1,500 to approximately 7,500, calculated at the 13C-RMN spectrum through the integration of the signal attributed to the C2 of 2,5-anhydromannitol with that of the anomeric carbon of the glucosamine inside the polysaccharide chain. According to a general manner of procedure, starting for example with 1 g of epiK5-N-sulfate, the starting product is dissolved in 100-200 ml of deionized water and thermostated at 4° C. Then an amount of sodium nitrite is added so as to obtain the desired mean molecular weight, for example from approximately 2,000 to approximately 4,000. Therefore, starting with an epiK5-N-sulfate having a molecular weight of 20,000 measured with the HPLC method equipped with a BioRad BioSil 250 column and using a heparin standard of known molecular weight, will require the addition of 330 to 480 mg of sodium nitrite dissolved in a 0.2% aqueous solution. The solution containing the epiK5-N-sulfate and the sodium nitrite, kept at 4° C., is brought to pH 2 through the addition of 0.1 N HCl cooled to 4° C. It is left to react under slow agitation for 20-40 minutes, then is neutralized with 0.1 N NaOH. The product obtained is brought to room temperature and treated with reducing agent such as for example sodium borohydride (250-500 mg dissolved in 50-100 ml of water) and left to react for 4-8 hours. The excess sodium borohydride is eliminated bringing the pH to 5-5.5 with 0.1 N HCl and let to stand for a further 2-4 hours. In the end it is neutralized with 0.1 N NaOH and the product is recovered by precipitation with acetone or ethanol after having concentrated the product by evaporation at reduced pressure. Similarly, the amount of sodium nitrite can be determined which, starting with 1 g of K5-N-sulfate or epiK5-N-sulfate, allows the attainment of a LMW-K5-N-sulfate or a LMW-epiK5-N-sulfate with a mean molecular weight from approximately 4,000 to approximately 12,000, advantageously from approximately 4,000 to approximately 7,500, in particular of 6,000-7,500. The LMW-epiK5-N-sulfate thus obtained, with an iduronic acid content from 20 to 60%, advantageously from 40 to 60%, preferably of 50-55% and virtually free of NH2 and N-acetyl groups, having a mean molecular weight from approximately 1,500 to approximately 12,000, advantageously from approximately 1,500 to approximately 10,000, preferably from approximately 1,500 to approximately 7,500 and their chemically or pharmaceutically acceptable salts constitute new products useful as particularly interesting starting materials in the preparation of LMW-epiK5-N,O-oversulfates, but also themselves useful as active ingredients of pharmaceutical or cosmetic compositions and constitute an additional aspect of the present invention. Advantageously, the starting materials in the preparation of the epiK5-N,O-oversulfate-derivatives of the present invention are epiK5-N-sulfate-derivatives consisting of a chain mixture in which at least 90% of said chains have the formula I in which the uronic units are 20-60% consisting of iduronic acid, n is a integer from 2 to 100, advantageously from 3 to 100 and the corresponding cation is chemically or pharmaceutically acceptable. More advantageously, said starting epiK5-N-sulfate-derivatives are consisting of a chain mixture in which at least 90% of said chains have the formula I in which the uronic units are 40-60% consisting of iduronic acid, n is a integer from 2 to 100, advantageously from 3 to 100 and the corresponding cation is chemically acceptable. Preferred starting materials are LMW-epiK5-N-sulfates as shown above, consisting of a chain mixture in which at least 90% of said chains have the formula I in which the uronic units are 20-60% comprised advantageously 40-60%, preferably 50-55%, of iduronic acid, n is a integer from 2 to 20, advantageously from 3 to 15 and the corresponding cation is chemically acceptable. In practice, said preferred LMW-epiK5-N-sulfates are consisting of a chain mixture in which at least 90% of said chains have the formula I′ in which the uronic units are 20-60% comprised, advantageously 40-60%, preferably 50-55% of iduronic acid, q is a integer from 2 to 20, advantageously from 3 to 15, and the corresponding cation is chemically or pharmaceutically acceptable. In this context, the term “chemically” refers to a cation usable in chemical synthesis, such as sodium, ammonium, (C1-C4)tetroalkylammonium ions, or for the purification of the product. Advantageous cations are those derived from alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc. Preferred cations are the sodium, calcium and tetrabutylammonium ions. Particularly interesting are the LMW-epiK5-N-sulfates consisting of a chain mixture in which at least 90% of said chains have the formula I′ herein above, obtained by nitrous depolymerization of the corresponding epiK5-N-sulfates shown above and subsequent possible reduction for example with sodium borohydride. Among these, are preferred the LMW-epiK5-N-sulfates consisting of a chain mixture in which the preponderant species has the formula I′a in which the uronic units are 60-40% consisting of glucuronic acid and 40% to 60% of iduronic acid, p is a integer from 4 to 8. The mean molecular weight of these products is from approximately 2000 to approximately 4000 and the corresponding cation is chemically or pharmaceutically acceptable. The origin of these epiK5-N-sulfates from a step of nitrous depolymerization involves, at the reducing end of the majority of the chains in said chain mixture, the presence of a 2,5-anhydromannose unit or, in the case of reduction with for example sodium borohydride, of 2,5-anhydromannitol of structure (a) in which X represents a formyl group or a hydroxymethyl group. Therefore, the reducing end of the majority (60-70% of the chains) is actually represented by the structure (b) in which X is as defined above. The presence of the structure (a) does not have any influence on the chemical characteristics of the epiK5-N-sulfates and their derivatives since any sulfations would lead to a possible introduction of one or two sulfate groups which would not however significantly move the sulfation degree of the O-sulfated derivatives. It is however preferable that the nitrous depolymerization is followed by reduction for example with sodium borohydride since, according to the process of the present invention, said LMW-epiK5-N-sulfates are subjected to sulfation and acylation reactions whose influence, of the 2,5-anhydromannose radical of structure (a), is unknown on the formyl group in which X represents formyl. Besides, the presence of structure (a) does not influence the biological activity of the products, as demonstrated by Østergaard P. B. et al. in Thrombosis Research, 1987, 45, 739-749 (Østergaard 1987) for the heparins of low molecular weight. Particularly advantageous LMW-epiK5-N-sulfates according to the present invention are consisting of chain mixtures in which the preponderant species is a compound of formula I′b in which X is formyl or, preferably, hydroxymethyl, m is 4, 5 or 6, the corresponding cation is one chemically or pharmaceutically acceptable ion and the glucuronic and iduronic units are present alternately, starting with a glucuronic or iduronic unit. In such case the glucuronic/iduronic ratio is from 45/55 to 55/45, i.e. approximately 50/50. The use of the C5-epimerase, preferably recombinant, preferably immobilized on a solid support in the conditions shown above therefore allows not the “cluster” epimerization of K5-N-sulfate-derivatives into epiK5-N-sulfate-derivatives as occurs in nature, but the ordinary type. Thus, according to another of its aspects, the present invention provides the use of the isolated and purified C5-epimerase, for the conversion of a K5-N-sulfate-derivative into a corresponding epiK5-N-sulfate-derivative characterized by a repetitive tetrasaccharide unit consisting of two glucosamine units separated by a glucuronic unit and followed by an iduronic unit or separated by an iduronic unit and followed by a glucuronic unit. Said epimerization occurs optimally if carried out on a K5-N-sulfate-derivative having a mean molecular weight of more than 4,000, preferably from 6,000 to 7,500. According to the present invention, the starting epiK5-N-sulfate-derivatives, preferably 100% N-sulfated (in particular the epiK5-N-sulfate-derivatives consisting of chain mixtures in which at least 90% of said chains have the formula I or I′ or in which the preponderant species has the formula I′a or I′b where X is hydroxymethyl), are subjected to the aforesaid steps (a) and (b), upon termination of which are isolated the corresponding, new epiK5-amine-O-oversulfate-derivatives, in which the amine is not substituted, normally in sodium salt form, which can be transformed into another chemically or pharmaceutically acceptable salt. Particularly advantageous salts are those of alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc and, among these, the salts of sodium, calcium and tetrabutylammonium are preferred. Thus, according to another of its aspects, the present invention refers to new epiK5-amine-O-oversulfate-derivatives and their chemically or pharmaceutically acceptable salts, obtainable by a process characterized in that (a) an epiK5-N-sulfate-derivative, in acidic form, is treated with a tertiary or quaternary organic base, letting the reaction mixture to stand for a time period of 30-60 minutes, maintaining the pH of the solution at a value of 7 by addition of said tertiary or quaternary organic base and its salt is isolated with said organic base; (b) said salt of organic base of said epiK5-N-sulfate-derivative is treated with an O-sulfation reagent in the conditions of O-oversulfation and the epiK5-amine-O-oversulfate-derivative is isolated. Using, as advantageous starting materials of step (a), epiK5-N-sulfate-derivatives consisting of a chain mixture in which at least 90% of said chains has the aforesaid formula I, in which the uronic units are 20-60% consisting of iduronic acid, n is a integer from 3 to 100 and the corresponding cation is chemically or pharmaceutically acceptable, at the end of step (b) an epiK5-amine-O-oversulfate-derivative is obtained consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are 20-60% consisting of iduronic acid, n is a integer from 2 to 100, preferably from 3 to 100, R, R′ and R″ are hydrogen or SO3−, for a sulfation degree of at least 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8 and the corresponding cation is chemically or pharmaceutically acceptable. These epiK5-amine-O-oversulfate-derivatives with a very high degree of sulfation are new products useful as intermediates in the preparation of their N-sulfate or N—(C2-C4)acylated derivatives basically free of activity on the coagulation parameters, but having other interesting pharmacological properties. Advantageous epiK5-amine-O-oversulfate-derivatives with a very high degree of sulfation are consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are 40-60% consisting of iduronic acid, n is a integer from 2 to 100, preferably from 3 to 100, with a mean molecular weight from approximately 2,000 to approximately 40,000, advantageously from approximately 4,500 to approximately 40,000, R is at least 40%, preferably 50-80% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in monosulfate glucuronic acid and 10-15% SO3− in monosulfate iduronic acid, the degree of sulfation is more than 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8, and the corresponding cation is chemically or pharmaceutically acceptable. Preferred epiK5-amine-O-oversulfate-derivatives with a very high degree of sulfation are LMW-epiK5-amine-O-oversulfates consisting of a chain mixture in which at least 90% of said chains have the formula II in which the uronic units are comprised 40-60%, preferably 50-55%, of iduronic acid, R is at least 40%, advantageously 50-80%, preferably approximately 65% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in glucuronic acid and 10-15% SO3− in iduronic acid, n is a integer from 2 to 20, advantageously from 3 to 15, with a mean molecular weight from approximately 4,000 to approximately 8,000 and the corresponding cation is chemically or pharmaceutically acceptable. In practice, said preferred LMW-epiK5-amine-O-oversulfates are consisting of a chain mixture in which at least 90% of said chains have the formula II′ in which the uronic units are 20-60% consisting of iduronic acid, q is a integer from 2 to 20, advantageously from 3 to 15, R, R′ and R″ are hydrogen or SO3−, for a sulfation degree of at least 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8, and the corresponding cation is one chemically or pharmaceutically acceptable ion. Among these LMW-epiK5-amine-O-oversulfates are preferred those consisting of a chain mixture in which the preponderant species has the formula II′a in which the uronic units are 20-60% consisting of iduronic acid, p is a integer from 4 to 8, R, R′ and R″ are as defined above, the degree of sulfation is at least 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8 and the corresponding cation is chemically or pharmaceutically acceptable. The origin of the new LMW-epiK5-amine-O-oversulfates from LMW-epiK5-sulfates obtained by nitrous depolymerization and subsequent reduction with, for example, sodium borohydride, involves, at the reducing end of the majority of the chains in said chain mixture, the presence of a 2,5-anhydromannitol sulfated unit of structure (a′) in which R″ represents hydrogen or SO3−. Thus, the reducing end of the majority of the chains in said chain mixture is represented by the structure (b′) in which the uronic unit can be glucuronic or iduronic. Among the aforesaid new LMW-epiK5-amine-O-oversulfates, are preferred those consisting of mixtures in which the preponderant species is a compound of formula II′b in which the uronic units are 40-60% consisting of iduronic acid, m is 4, 5 or 6, R, R′ and R″ are hydrogen or SO3−, X″ is OH or OSO3−, for a sulfation degree of at least 3.4, advantageously of at least 3.5, more advantageously from 3.55 to 4, preferably from 3.55 to 3.8, the iduronic units being present alternately, starting with a glucuronic or iduronic unit, and the corresponding cation is one chemically or pharmaceutically acceptable ion. All these epiK5-amine-O-oversulfated-derivatives with a very high degree of sulfation are new products which are useful intermediates for the preparation of the new. N-substituted epiK5-amine-O-oversulfated-derivatives and therefore constitute an additional aspect of the present invention. In particular, according to another of its aspects, the invention concerns the use of the aforesaid epiK5-amine-O-oversulfated-derivatives with a very high degree of sulfation for the preparation of new N-substituted epiK5-amine-O-oversulfated-derivatives, in particular N-sulfated or N-acylated. Upon termination of step (c) of the process of the present invention, consisting of an N-sulfation of the epiK5-amine-O-oversulfate-derivatives obtained at the end of step (b) (in particular the epiK5-amine-O-oversulfate-derivatives consisting of chain mixtures in which at least 90% of said chains have the formula II or II′ or in which the preponderant species has the formula II′a or II′b) epiK5-N,O-oversulfate-derivatives are obtained whose iduronic acid content is 20-60% of the total of the uronic acids and whose sulfation degree is at least 4, preferably from 4 to 4.6. Thus, according to another of its aspects, the present invention provides new N-deacetylated derivatives of K5 polysaccharide, O-sulfated and N-sulfated, C5-epimerized to iduronic acid in at least 20% of the total of the uronic units, having a mean molecular weight from approximately 2,000 to approximately 45,000, a sulfation degree of at least 4, said derivatives being basically inactive on the coagulation parameters. Similarly to that stated above, said new derivatives are, as a whole, denoted by the general term “epiK5-N,O-oversulfate-derivatives”, independently of their molecular weight. In particular, the mean molecular weight is between approximately 2,000 to approximately 45,000 since said derivatives originate either from an epi-K5-N-sulfate obtained by N-deacetylation and N-sulfation of K5 by fermentation or by the nitrous depolymerization of the latter. By controlling said nitrous depolymerization it is possible to obtain low molecular weight derivatives in virtually all the aforesaid interval. However, for use of the derivatives of the present invention as pharmaceutical or cosmetic products it is advantageous to prepare low molecular weight derivatives, with a mean molecular weight from approximately 2,000 to approximately 16,000, advantageously from approximately 3,500 to approximately 13,000 with a molecular weight distribution of between approximately 1,000 and approximately 15,000, preferably from approximately 4,500 to approximately 9,000, with a molecular weight distribution from approximately 2,000 to approximately 10,000, or of high molecular weight derivatives, originating from the unfractionated K5, with a mean molecular weight of between approximately 20,000 and approximately 45,000, with a molecular weight distribution from approximately 2,000 to approximately 70,000. In the epiK5-N,O-oversulfate-derivatives of the present invention the degree of sulfation is very high, preferably from 4 to 4.6, the nitrogen of the glucosamine being virtually 100% sulfated. Besides, the epiK5-N,O-oversulfate-derivatives are 100% 6-O-sulfated and 50-80% 3-O-sulfated in their glucosamine units, 5-10% 3-O-monosulfated in glucuronic units, 10-15% O-monosulfated in iduronic units and 2.3-di-O-sulfated in the remaining uronic units, considering that the degree of sulfation is at least 4. Advantageous epiK5-N,O-oversulfate-derivatives according to the present invention are obtained through epiK5-amine-O-oversulfate-derivatives in turn prepared from epiK5-N-sulfate-derivatives consisting of a chain mixture in which at least 90% of said chains has the aforesaid formula I, in which the uronic units are 20-60% consisting of iduronic acid, n is a integer from 2 to 100, advantageously from 3 to 100 and the corresponding cation is chemically or pharmaceutically acceptable. In such case, the new epiK5-N,O-oversulfate-derivatives consisting of chain mixtures in which at least 90% of said chains have the formula III in which the uronic units are 20-60% consisting of iduronic acid, n is a integer from 2 to 100, preferably from 3 to 100, R, R′ and R″ are hydrogen or SO3−, Z is SO3−, the degree of sulfation is at least 4, preferably from 4 to 4.6 and the corresponding cation is chemically or pharmaceutically acceptable. Said cations are advantageously those of alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc and, among these, preferably the salts of sodium, calcium and tetrabutylammonium. Among the aforesaid new epiK5-amine-N,O-oversulfate-derivatives, those consisting of chain mixtures in which at least 90% of said chains has the aforesaid formula III in which R is SO3− in 50%-80%, preferably in approximately 65% of said chains and the degree of sulfation is at least 4, advantageously is from 4 to 4.6, preferably from 4 to 4.3. Advantageous epiK5-N,O-oversulfate-derivatives with a very high degree of sulfation are consisting of a chain mixture in which at least 90% of said chains have the formula II, in which Z is SO3−, the uronic units are 40-60% consisting of iduronic acid, n is a integer from 2 to 100, preferably from 3 to 100, with a mean molecular weight from approximately 2,000 to approximately 45,000, advantageously from approximately 4,500 to approximately 45,000, R is at least 40%, preferably 50-80% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in monosulfate glucuronic acid and 10-15% SO3− in monosulfate iduronic acid, the degree of sulfation is at least 4, from 4 to 4.6 and the corresponding cation is chemically or pharmaceutically acceptable. Preferred N-substituted epiK5-amine-O-oversulfated-derivatives are LMW-epiK5-amine-O-oversulfated consisting of a chain mixture in which at least 90% of said chains have the formula III in which the uronic units are 40-60% comprised, preferably 50-55%, of iduronic acid, R is at least 40%, advantageously 50-80%, preferably approximately 65% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in glucuronic acid and 10-15% SO3− in iduronic acid, Z is 100% SO3− or (C2-C4)acyl, n is a integer from 2 to 20, preferably from 3 to 15, with a mean molecular weight from approximately 4,000 to approximately 8,500 and the corresponding cation is chemically or pharmaceutically acceptable. In practice, said preferred epiK5-N,O-sulfate-derivatives with a very high degree of sulfation are consisting of a chain mixture in which at least 90% of said chains have the formula III′ in which the uronic units are 20-60% consisting of iduronic acid, q is a integer from 2 to 20, advantageously from 3 to 15, R, R′ and R″ represent hydrogen or an SO3− group, Z is SO3−, for a sulfation degree of at least 4, preferably from 4 to 4.6 and the corresponding cation is one chemically or pharmaceutically acceptable ion. Particularly interesting are chain mixtures of formula III′ in which the uronic units are 40-60% comprised, preferably 50-55%, of iduronic acid, R is at least 40%, advantageously 50-80%, preferably approximately 65% SO3−, R′ and R″ are both SO3− or one is hydrogen and the other is 5-10% SO3− in glucuronic acid and 10-15% SO3− in iduronic acid, n is a integer from 2 to 20, advantageously from 3 to 15, with a mean molecular weight from approximately 2,000 to approximately 16,000, advantageously from approximately 3,500 to approximately 13,000, preferably from approximately 4,500 to approximately 9,000 and the corresponding cation is chemically or pharmaceutically acceptable. Among these LMW-epiK5-N,O-oversulfates, are advantageous those consisting of a chain mixture in which the preponderant species has the formula III′a in which the uronic units are 20-60% consisting of iduronic acid, p is a integer from 4 to 8, Z is SO3−, R, R′ and R″ are hydrogen or SO3−, for a sulfation degree of at least 4, preferably from 4 to 4.6 and the corresponding cation is chemically or pharmaceutically acceptable. The origin of the new LMW-epiK5-N,O-oversulfates from LMW-epiK5-sulfates obtained by nitrous depolymerization and subsequent reduction with, for example, sodium borohydride involves, at the reducing end of the majority of the chains in said chain mixture, the presence of a sulfated 2,5-anhydromannitol unit of structure (a′) as shown above, in which R″ represents hydrogen or SO3−. Thus, the reducing end of the majority of the chains in said chain mixture is represented by the structure (b″) in which Z represents SO3− and the uronic unit can be glucuronic or iduronic. Among the aforesaid new LMW-epiK5-N,O-oversulfates, are preferred those consisting of mixtures in which the preponderant species is a compound of formula III′b in which R, R′ and R″ are hydrogen or SO3−, Z is SO3−, X″ is OH or OSO3−, m is 4, 5 or 6, for a sulfation degree of at least 4, preferably from 4 to 4.6, the uronic units are present alternately, starting with a glucuronic or iduronic unit, and the corresponding cation is one chemically or pharmaceutically acceptable ion. Said cations are advantageously those of alkaline metals, alkaline-earth metals, ammonium, (C1-C4)tetraalkylammonium, aluminum and zinc and, among these, preferably the ions of sodium, calcium and tetrabutylammonium. If an epiK5 is used as a starting epiK5-derivative of the process of the present invention, i.e. a K5 polysaccharide, previously N-deacetylated, N-sulfated normally 100%, and 20-60% C5-epimerized and not depolymerized, upon termination of step (c) an epiK5-N,O-oversulfate is isolated which can be subjected to nitrous depolymerization and possible, subsequent reduction with, for example, sodium borohydride to obtain the corresponding LMW-epiK5-N,O-oversulfate having the same degree of sulfation. In particular, LMW-epiK5-N,O-oversulfates are obtained consisting of a chain mixture in which at least 90% of said chains have the formula III′ or III′a, in which the uronic units are 20-60% consisting of iduronic acid, q, R, R′ R″ and Z have the meaning defined above, for a sulfation degree of at least 4, preferably from 4 to 4.6 and the corresponding cation is one chemically or pharmaceutically acceptable ion. In such case, the origin of these LMW-epiK5-N,O-oversulfates from a depolymerization reaction and possible, subsequent reduction with, for example, sodium borohydride involves, at the reducing end of the majority of the chains in said chain mixture, the presence of a 2,5-anhydromanno unit of structure (a″) in which X is formyl or hydroxymethyl and R″ represents hydrogen or SO3−. The new epiK5-N,O-oversulfate-derivatives, especially in their salt form, are highly anionic products able to capture the free radicals and are utilizable in the cosmetics industry as adjuvants against hair loss or to prepare “anti-ageing” creams and, in the pharmaceutical industry, as products for the treatment of dermatitis. Besides, the epiK5-N,O-oversulfate-derivatives of the present invention, in particular the LMW-epiK5-N,O-oversulfates possess antiangiogenetic and antiviral activity and therefore constitute active ingredients for the preparation of medicines. Thus, according to one of its additional aspects, the present invention provides pharmaceutical compositions including, as one of their active ingredients, a pharmacologically active amount of an epiK5-N,O-oversulfate-derivative as shown above or of one of its pharmaceutically acceptable salts, in mixture with a pharmaceutical excipient. In the pharmaceutical compositions of the present invention for oral, subcutaneous, intravenous, transdermal or topical administration, the active ingredients are preferably administered in the form of dosage units, in mixture with the classic pharmaceutical excipients or vehicles. The posology can vary widely depending on the age, weight, and the health condition of the patient. This posology includes the administration of a dose from 1 to 1000 mg, advantageously from 10 to 750 mg, preferably 250 to 500 mg from one to three times a day by intravenous, subcutaneous, oral, transdermal or topical administration. The pharmaceutical compositions of the present invention are formulated with the classic excipients suitable for different ways of administration. Particularly advantageous are the formulations in the form of creams, ointments, liniments, gels, foams, balsams, vaginal pessaries, suppositories, solutions or suspensions suitable for local administration. Advantageously, the compositions of the present invention include, as one of its active ingredients, an epiK5-N,O-oversulfate-derivative obtainable starting with an epiK5-derivative according to steps (a), (b) and (c) of the process described above, or starting with an epiK5 not depolymerized, according to steps (a), (b) and (c) of the process described above, with possible subsequent nitrous depolymerization after step (c), or one of its pharmaceutically acceptable salts, in mixture with a pharmaceutical excipient. Advantageously, said epiK5-N,O-oversulfate-derivative consists of a chain mixture in which at least 90% of said chains have the formula III or III′ or in which the preponderant species is a compound of formula III′a or III′b. Preferred active ingredient is a LMW-epiK5-N,O-oversulfate having a sulfation degree of at least 4, preferably from 4 to 4.6, advantageously having a mean molecular weight from approximately 3,500 to approximately 11,000, more advantageously from approximately 3,500 to approximately 5,200 and basically free of N-acetyl groups. Finally, according to another of its aspects, the present invention provides a cosmetic composition including an effective amount of an epiK5-N,O-oversulfate-derivative or one of its pharmaceutically acceptable salts, in mixture with a cosmetic excipient. A salt selected from the group consisting of salts of sodium, potassium, calcium, magnesium, aluminum and zinc of the epiK5-N,O-oversulfate derivatives, in particular those consisting of chain mixtures in which at least 90% of said chains have the formula III or III′ or in which the preponderant species has the formula III′a or III′b, constitutes an effective active ingredient of the pharmaceutical or cosmetic compositions of the present invention. The following examples illustrate the invention without however limiting it. Preparation I Preparation of K5 Polysaccharide from Escherichia coli At first fermentation is carried out in an Erlenmeyer flask using the following medium: Fat-free soya meal 2 g/l K2HPO4 9.7 g/l KH2PO4 2 g/l MgCl2 0.11 g/l Sodium citrate 0.5 g/l Ammonium sulfate 1 g/l Glucose 2 g/l Spring water 1000 ml pH = 7.3 The medium is sterilized at 120° C. for 20 minutes. The glucose is prepared separately in solution form which is sterilized at 120° C. for 30 minutes and added sterilely to the medium. The Erlenmeyer flask is inoculated with a suspension of E. coli cells Bi 8337/41 (O10:K5:H4) originating from a slant kept in Triptic soy agar, and incubated at 37° C. for 24 hours under controlled agitation (160 rpm, 6 cm stroke). The bacterial growth is measured by counting the cells using a microscope. In a subsequent operation, a 14 l Chemap-Braun fermenter containing the same medium as above, is 0.1% inoculated with the culture of the Erlenmeyer flask as above and fermentation is performed by aeration of 1 vvm, (vvm=volume of air per volume of liquid per minute) 400 rpm agitation and temperature of 37° C. for 18 hours. During fermentation are measured the pH, the oxygen, the glucose residue, K5 polysaccharide produced and bacterial growth. At the end of fermentation the temperature is brought to 80° C. for 10 minutes. The cells are separated from the medium through centrifugation at 10,000 rpm and the supernatant is ultrafiltered using an SS 316 (MST) module fitted with PES membrane with nominal cut-off of 800 and 10,000 D to reduce the volume to ⅕. K5 polysaccharide is then precipitated by addition of 4 volumes of acetone at 4° C. and left to settle overnight at 4° C. Finally it is recovered by centrifugation at 10,000 rpm for 20 minutes or filtration. Deproteinization of the solid obtained is carried out by using a type II protease from Aspergillus orizae in a buffer of 0.1 M NaCl and 0.15 M EDTA at pH 8 containing SDS (0.5% sodium dodecyl sulfate) (10 mg/l of filtrate) at 37° C. for 90 minutes. The solution obtained is ultrafiltered on model SS 316 with membrane at a nominal cut-off of 10,000 D with 2 extractions with 1M NaCl and washed with water until disappearance of absorbance in the ultrafiltrate. K5 polysaccharide is then precipitated with acetone and a yield of 850 mg per litre of fermenter is obtained. The purity of the polysaccharide obtained is measured through the determination of the uronic acids (carbazole method), proton and carbon 13 NMR, UV and protein content. The purity is more than 80%. The polysaccharide obtained is composed of two moieties of different molecular weight, respectively 30,000 and 5,000 D as emerges from the determination by HPLC using a Pharmacia 75 HR column and a single moiety with a retention time of approximately 9 minutes using two seriate columns of Bio-sil SEC 250 (Bio Rad) and Na2SO4 as mobile phase at room temperature and a flow of 0.5 ml/minute. The measurement is performed against a standard curve obtained with moieties of heparin of known molecular weight. The 1H-RMN spectrum of the purified K5 thus obtained shows different signals attributable to methyls of lipophilic substances. Preparation II Purification of K5 In 100 ml of a saturated aqueous solution of sodium chloride and thermostated at 4° C. is dissolved 1 g of K5 obtained at the end of PREPARATION I and to the solution thus obtained are added 3 volumes of cold isopropanol. The saline concentration of the solution is brought to 3 M by addition of the calculated amount of a saturated sodium chloride solution and the solution obtained is left in a cold environment (approximately 4° C.) overnight. The precipitate which forms is separated by centrifugation at 10,000 rpm for 20 minutes and the purity of the product is checked by dialysis overnight and subsequent examination of the 1H-RMN spectrum, from which signals in the region under 1.5 ppm must be absent. Optionally, the operation of dissolution in water saturated with NaCl and precipitation with isopropanol is repeated. The precipitate is dissolved in water and ultrafiltered on a Miniplate Millipore membrane 10,000 D cut off until disappearance of the salts. Thus a K5 having a purity of at least 99% is obtained from whose 1H-RMN spectrum no traces of lipophilic impurities result in the region under 1.5 ppm. Preparation III Preparation of a K5-N-Sulfate (i) N-Deacetylation Ten grams of pure K5 polysaccharide prepared as described in PREPARATION II are dissolved in 1000 ml of 2N sodium hydroxide and the solution thus prepared is left at 60° C. for 24 hours. The solution is brought to room temperature then to neutral pH (pH7) with 6N hydrochloric acid. (ii) N-Sulfation To the solution containing the deacetylated K5, kept at 40° C., are added 16 g of sodium carbonate and afterwards and in 4 hours, 16 g of pyridine.SO3−. At the end of the reaction, after 24 hours, the solution is brought to room temperature, then to pH 6.5-7 with a 5% solution of hydrochloric acid. The product is purified from salts by diafiltration using a 1,000 D helically wound membrane (prepscale cartridge—Millipore). The process is terminated when the conductivity of the permeate is less than 1000 μS, preferably less than 100 μS. The intradialysis is reduced until a 10% concentration of the polysaccharide is obtained using the same in concentration dialysis system. The concentrated solution is dried by lyophilization. Upon 13C-RMN spectrum analysis N-acetyl or NH2 residues do not appear. Preparation IV LMW-K5-N-Sulfate The product obtained as described in Example 1, steps (i) and (ii), of WO 02/068477 is depolymerized by the degradation method with nitrous acid and subsequent reduction of the aldehyde which forms. One continues by dissolving 1 g of K5-N-sulfate in 200 ml of distilled water and adding it with 480 mg of sodium nitrite dissolved in 240 ml of distilled water. The solution is then brought to 4° C. and the pH to 2 with 0.1 N HCl and maintained for 30 minutes. At the end of the reaction the solution is brought to pH 7 with 0.1 M NaOH and then to room temperature. The solution is then added with 450 mg. of NaBH4 and left to react for 4 hours. The excess NaBH4 is eliminated with HCl bringing the pH to 5-6. The product, neutralized with 0.1 M NaOH, is recovered by precipitation with 3 volumes of acetone at 4° C., filtration with filtering funnel and dried at 40° C. in a vacuum oven. 900 mg of LMW-K5-N-sulfate are obtained with a mean molecular weight of approximately 2,000, consisting of a chain mixture in which the preponderant species is a compound of formula I′b in which m is 4 and the uronic units are those of glucuronic acid. EXAMPLE 1 LMW-EpiK5-N-Sulfate. Sequence (i)→(ii) (i) Epimerization to EpiK5-N-Sulfate Ten grams of K5-N-sulfate obtained as described in Example 1, steps (i) and (ii), of WO 02/068477, from whose 1H-RMN spectrum, signals concerning acetyl groups or NH2 do not appear, are dissolved in 600 ml of 25 mM HEPES buffer at pH 7, containing CaCl2 at a concentration of 50 mM and the solution thus obtained is made to recirculate through a 50 ml column filled with Sepharose 4B resin containing 5 g of recombinant C5-epimerase (WO 96/14425) immobilized as described in Example 1 of WO 01/72848. The reaction is carried out at 30° C. at pH 7 with a flow of 200 ml/h for 24 hours. The product obtained is purified by ultrafiltration and precipitation with ethanol. Thus an epiK5-N-sulfate is obtained whose iduronic acid content is 54%. (ii) Depolymerization of EpiK5-N-Sulfate. To a solution of 1 g of the product thus obtained, in 25 ml of distilled water, are added 230 mg of sodium nitrite dissolved in 115 ml of distilled water. The solution is then brought to 4° C. and the pH to 2 with 0.1 N HCl and maintained for 30 minutes. At the end of the reaction the solution is brought to room temperature and the pH to 7 with 0.1 M NaOH. The solution is then added with 450 mg. of NaBH4 and left to react for 4 hours. The product is recovered by precipitation with 3 volumes of acetone at 4° C., filtration with filtering funnel and dried at 40° C. in a vacuum oven. 900 mg of LMW-epiK5-N-sulfate are obtained with an iduronic acid content of 54% and a molecular weight distribution from 1,000 to 4,000, measured with HPLC method. EXAMPLE 2 LMW-EpiK5-N-Sulfate. Sequence (ii)→-(i) (ii) Depolymerization of K5-N-Sulfate 2 g of K5-N-sulfate, obtained as described in Example 1, steps (i) and (ii), of WO 02/068477, is depolymerized as described in PREPARATION I, using 100 mg of sodium nitrite and 300 mg of sodium borohydride. 1.8 g of LMW-K5-N-sulfate are obtained with a mean molecular weight of 5,000. (i) Epimerization of LMW-K5-N-Sulfate 1 g of LMW-K5 N-sulfate obtained in step (ii) herein above is treated as described in step (i) of the Example 1. An epimerized product is obtained with an iduronic acid/glucuronic acid ratio of 44/56 against a ratio of 0/100 of the starting product, with a molecular weight distribution from 2,000 to 10,000 and with a mean molecular weight of 5,000 D. The yield, calculated by measuring the content of uronic acids against a standard with the carbazole method (Bitter and Muir, Anal. Biochem. 1971, 39, 88-92) is 90%. EXAMPLE 3 LMW-EpiK5-N-Sulfate. Sequence (i)→(ii) (i) Epimerization of K5-N-Sulfate A 2 g amount of K5 N-sulfate, obtained as described in Example 1, steps (i) and (ii), of WO 02/068477, is dissolved in 120 ml of 25 mM HEPES buffer, pH 7, containing 50 mM CaCl2. The solution obtained is made to recirculate through a 50 ml column filled with the resin containing the immobilized enzyme obtained as described in WO 96/14425. This operation is carried out at 30° C. with a flow of 200 ml/h for 24 hours. The product obtained is purified through ultrafiltration on a 1000 D membrane and passing over an IR 120H+ ionic exchange column, neutralizing the eluate with 1N NaOH. The sample is recovered by precipitation with ethanol or acetone. An epimerized product is obtained with an iduronic acid/glucuronic acid ratio of 55/45 against a ratio of 0/100 of the starting product. The percentage of epimerization was calculated with 1H-RMN according to the method described in WO 96/14425. The yield, calculated by measuring the content of uronic acids against a standard with the carbazole method (Bitter and Muir Anal. Biochem. 39, 88-92-1971) is 90%. (ii) Depolymerization of Epi-K5-N-Sulfate One gram of product obtained in step (a) is depolymerized by the degradation method with nitrous acid and subsequent reduction of the aldehyde which forms. In particular one continues by dissolving the product in 25 ml of distilled water and adding it with 230 mg of sodium nitrite dissolved in 115 ml of distilled water. The solution is then brought to 4° C. and the pH to 2 with 0.1 N HCl and maintained for 30 minutes. At the end of the reaction the solution is brought to room temperature and the pH to 7 with 0.1 M NaOH. The solution is then added with 450 mg. of NaBH4 and left to react for 4 hours. The product is recovered by precipitation with 3 volumes of acetone at 4° C., filtration with filtering funnel and dried at 40° C. in a vacuum oven. 900 mg of LMW-epiK5-N-sulfate are obtained with a molecular weight distribution measured with HPLC method which ranges from 1,000 to 4,000 and with a glucuronic unit content of 45% and an iduronic unit content of 55%. EXAMPLE 4 EpiK5-N,O-Oversulfate (a) Tetrabutylammonium Salt of EpiK5-N-Sulfate A solution in 40 ml of water of 400 mg of epiK5-N-sulfate, as obtained at the end of step (i) of the Example 1, is thermostated at 4° C., then passed over IR 120+ ionic exchange resin preconditioned with water at 4° C. The eluate obtained, consisting of 100 ml of a solution at pH 1.94, is neutralized with a 15% solution of tetrabutylammonium hydroxide and left at room temperature for one hour, maintaining the pH at 7 by addition of 15% tetrabutylammonium hydroxide and finally is lyophilized. Thus 805 mg of tetrabutylammonium salt of epiK5-N-sulfate are obtained. (b) Epi-K5-Amine-O-Oversulfate A solution containing 805 mg of the salt thus obtained in 30 ml of dimethylformamide is set at 55° C. and treated with 30 ml of dimethylformamide containing 2.26 g of pyridine.SO3 adduct. The reaction at 55° C. is continued overnight then 60 ml of water are added to the mixture. After neutralization with 1 N NaOH, the product is precipitated with 3 volumes of acetone saturated with NaCl and set at 4° C. overnight. The precipitate is recovered by filtration on guch G4 and then ultrafiltered with 1000 D TFF Millipore system and dried at reduced pressure. 550 mg of epi-K5-amine-O-oversulfated are obtained having a content of iduronic acid of 54%, of glucosamine-6-O-sulfate of 100%, of glucosamine 3-O-sulfate of 60%, of monosulfate glucuronic acid of 10%, of monosulfate iduronic acid of 15%, the rest of the uronic units being disulfated, with a sulfation degree of 3.55 measured with the conductometric method according to Casu et al. 1975. (c) EpiK5-Amine-O-Oversulfated-N-Sulfate To a solution of 250 mg of the epi-K5-amine-O-oversulfated obtained in step (b) in 15 ml of water are added 400 mg of sodium carbonate, then to the mixture thus obtained are added 400 mg of pyridine.SO3 adduct in solid form a little at a time in 4 hours. The reaction mixture is kept at 55° C. overnight, then is stopped bringing the pH to 7 with 0.1N HCl. After ultrafiltration on a 1000 D membrane are added 3 volumes of acetone saturated with sodium chloride and the precipitate is recovered by centrifugation at 5000 rpm for 5′. Thus 244 mg of epiK5-N,O-oversulfate are obtained whose sulfation degree, measured with conductometric method according to Casu et al. 1975, is 4.25. By the analysis of the 1H-RMN spectrum it results that the epiK5-N,O-oversulfate thus obtained has an iduronic acid content of 54%, 6-O-sulfate of 100%, N-sulfate of 100%, glucosamine 3-O-sulfate of 60%, monosulfate glucuronic acid of 10%, monosulfate iduronic acid of 15%, the rest of the uronic units being disulfated. From the 1H-RMN spectrum is therefore calculated a sulfation degree of 4.35 which, considering the margins of error of the methods, corresponds to the sulfation degree of epiK5-amine-O-oversulfated obtained upon termination of step (b), 100% N-sulfated. It is therefore assumed that, beyond a certain percentage of sulfate groups, the strong anionic nature of the product can lead to an underestimation of the degree of sulfation determined with the conductometric method.
<SOH> BACKGROUND OF THE INVENTION <EOH>The glycosaminoglycans such as heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate and hyaluronic acid are biopolymers that are industrially extracted from various animal organs. In particular, heparin, mainly obtained by extraction from the intestinal mucous membrane of pigs or bovine lung, is a polydispersed copolymer with a molecular weight distribution from approximately 3,000 to approximately 30,000 D consisting of a chain mixture basically consisting of a uronic acid (glucuronic acid or iduronic acid) and of an amino sugar (glucosamine) linked by α-1→4 or β-1→4 bonds. In heparin, the uronic unit can be O-sulfated in position 2 and the glucosamine unit is N-acetylated or N-sulfated, 6-O-sulfated, and 3-O-sulfated in approximately 0.5% of the glucosamine units present. The properties and natural biosynthesis of heparin in mammals have been described by Lindahl et al., 1986 in Lane, D. and Lindahl, U. (Editors) “Heparin. Chemical and Biological Properties; Clinical Applications”, Edward Arnold, London, Pages 159-190, by Lindahl, U, Feingold D. S. and Roden L, 1986 TIBS, 11, 221-225 and by Conrad H. E. “Heparin Binding Proteins”, Chapter 2: Structure of Heparinoids. Academic Press, 1998. The biosynthesis of heparin occurs starting with its precursor N-acetyl-heparosan consisting of a chain mixture consisting of the repetitive disaccharide unit glucuronyl-β1-4-N-acetylglucosamine. Said precursor undergoes enzymatic modifications which partially hydrolyse the N-acetyl group, substituting it with an SO 3 − group, epimerize the carboxyl in position 5 of a part of the glucuronic units converting them into iduronic units and introducing O-sulfate groups to get a product which, once extracted industrially, has approximately double the number of sulfate groups as regards carboxyl ones per disaccharide unit. These enzymatic modifications lead to, besides, the formation of the pentasaccharide region of a bond to antithrombin III (ATIII), called active pentasaccharide, which is the structure necessary for the high affinity bond of heparin to the ATIII and fundamental for anticoagulant and antithrombotic activity of the heparin itself. This pentasaccharide, present inside only some of the chains which form heparin, contains a sulfated glucosamine unit in position 3 and a glucuronic acid spaced out between disaccharides containing iduronic acids. In nature, the formation of the active pentasaccharide is made possible by the epimerization reaction of the carboxyl of a part of the glucuronic units into iduronic units carried out by the glucuronyl-C5-epimerase (C5-epimerization) and by suitable sulfation which also leads to the introduction of a sulfate group onto the hydroxyl in position 3 of the glucosamine. More particularly, in nature the formation of the active pentasaccharide is made possible by the fact that the C5-epimerization occurs in clusters, i.e. on portions of chains, and extensively, which results in a product that contains more iduronic units than glucuronic ones. Commercial heparin, in fact, contains approximately 70% of iduronic units and 30% of glucuronic units. Alongside the main anticoagulant and antithrombotic activities, heparin also exercises antilipaemic, antiproliferative, antiviral, antitumorous and antimetastatic activities, but its use as a drug is hindered by the side effects due to the anticoagulant action which can cause bleeding.
<SOH> SUMMARY OF THE INVENTION <EOH>It has now surprisingly been found that, unlike that which occurs with the processes described in IT 1230785, WO 92/17507, WO 96/14425, WO 97/43317, WO 01/72848 and U.S. 2002/0062019, starting with an epiK5-N-sulfate it is possible to obtain an epiK5-amine-O-oversulfate with a greater degree of sulfation than every other epiK5-amine-O-sulfate described in literature, for example in WO 01/72848, by preparing the salt with tertiary or quaternary organic base of said epiK5-N-sulfate taking care to let the reaction mixture to stand for a time period of 30-60 minutes maintaining the pH at approximately 7 with the same organic base and then treating the salt obtained with an O-sulfation reagent in the conditions of O-oversulfation. Subjecting the epiK5-amine-O-oversulfates thus obtained to N-sulfation, new epiK5-N,O-oversulfates are obtained which, unlike the products described in IT 1230785, WO 92/17507, WO 96/14425, WO 97/43317, WO 01/72848 and U.S. 2002/0062019, are free of activity on coagulation and useful for the preparation of medicines, particularly pharmaceutical compositions of antiangiogenetic and antiviral activity or of cosmetic compositions. By depolymerization with nitrous acid of said epiK5-N,O-oversulfates new LMW-epiK5-N,O-oversulfates are obtained, free of activity on coagulation, and with antiangiogenetic and antiviral activity. In preparing N,O-sulfate N-deacetylated derivatives of K5 polysaccharide, at least 40% epimerized of iduronic acid as regards the total of the uronic acids and having low molecular weight according to the method described in WO 01/72848, it was ascertained that the depolymerization of the product of high molecular weight obtained at the end of the final N-sulfation step of the process can give varying results since it generally produces some depolymerized products showing much lower activity, than that of high molecular weight products from which they arise, on all the coagulation parameters. It is assumed this takes place because degradation with nitrous acid is influenced by the presence of the sulfate groups. In particular the sulfates in position 3 of the glucosamine result in heterogenous products, as described by Nagasawa et al. in Thrombosis Research, 1992, 65, 463-467 (Nagasawa 1992). It has now been found that subjecting an epiK5-N-sulfate to nitrous depolymerization in which the iduronic acid content as regards the total of uronic acids is 20-60%, advantageously of 40-60%, preferably around 50%, LMW-epiK5-N-sulfates are obtained which constitute new effective intermediates for the preparation of LMW-epiK5-N,O-oversulfates having a high degree of activity on different biological parameters, with or without activity on coagulation parameters. In particular, it was found that it is possible to depolymerize an epiK5-N-sulfate so as to obtain new LMW-epiK5-N-sulfates of mean molecular weight from approximately 2,000 to approximately 4,000, more particularly specific LMW-epiK5-N-sulfates consisting of mixtures in which the predominant compound is a decasaccharide or a dodecasaccharide or a tetradecasaccharide. Also these LMW-epiK5-N-sulfates, otherwise unobtainable, have interesting biological properties and are useful intermediates for the preparation of LMW-epiK5-N,O-oversulfated of antiviral and/or antiangiogenetic activity and surprisingly free of activity on coagulation. By subjecting a LMW-epiK5-N-sulfate to the aforesaid method of salification with a tertiary or quaternary organic base, taking care to let the reaction mixture to stand for a time period of 30-60 minutes maintaining the pH at approximately 7 with the same organic base and then treating the salt obtained with an O-sulfation reagent in the conditions of O-oversulfation, new LMW-epiK5-amine-O-oversulfates are obtained. By subjecting the LMW-epiK5-amine-O-oversulfate to N-sulfation, new N-sulfated and O-oversulfated derivatives (LMW-epiK5-N,O-oversulfates) are obtained, surprisingly free of activity on coagulation and of antiviral and/or antiangiogenetic activity, useful for the preparation of pharmaceutical or cosmetic compositions. These LMW-epiK5-N-sulfates are obtained starting with a K5-N-sulfate with an epimerization reaction with an isolated and purified recombinant C5-epimerase, immobilized on a solid support, at a temperature of approximately 30° C. and at a pH of approximately 7 for 12-24 hours in the presence of a bivalent cation selected among calcium, magnesium, barium and manganese and a subsequent nitrous depolymerization reaction of the epimerized product thus obtained, or vice versa. Surprisingly, from observations made on the course of the epimerization reaction in the aforesaid conditions, it is possible to assume that, contrary to that occurring in nature in the biosynthesis of heparin, ordinary and not “cluster” type C5-epimerization of the substrate occurs every 2 glucuronic acid units which leads to epi-K5-N-sulfate-derivatives characterized by a repetitive tetrasaccharide unit consisting of two glucosamine units separated by a glucuronic unit and followed by an iduronic unit or vice versa. detailed-description description="Detailed Description" end="lead"?
20050531
20101123
20060119
96712.0
A61K31737
0
BERRY, LAYLA D
EPIMERIZED DERIVATIVES OF K5 POLYSACCHARIDE WITH A VERY HIGH DEGREE OF SULFATION
SMALL
0
ACCEPTED
A61K
2,005
10,518,395
ACCEPTED
Method and arrangement for a termination of an electrical cable
A method of building a cable termination is provided. The termination has an outer insulator body, a substantially longitudinally extended interior member having the electrical cable to be terminated, having a conductor for carrying load, an insulating material filled in a cavity between the outer insulator body and the interior member and means for accommodating volume expansions of the insulating material filled within the cavity. The cavity is created by introducing the interior member into the insulator body, filling the insulating material into the cavity and sealing the termination. A volume change compensation member having a predetermined volume to accommodate volume expansions of the insulating material within the cavity is placed into the cavity. Respective terminations are also provided.
1-29. (canceled) 30. A method of building a termination of an electrical cable wherein said termination comprises an outer insulator body; a substantially longitudinally extended interior member comprising said electrical cable to be terminated, said cable comprising a conductor for carrying load; an insulating material filled in a cavity between said outer insulator body and said interior member; and means for accommodating the volume expansions of said insulating material within said cavity, the method comprising the steps of: creating said cavity by introducing said interior member into said outer insulator body; filling said insulating material into said cavity; sealing said termination; and placing a volume change compensation member into said cavity, said volume change compensation member having a predetermined volume to accommodate volume expansions of said insulating material within said cavity. 31. The method according to claim 30, wherein the step of placing the volume change compensation member into the cavity is performed before the step of filling in the insulating material. 32. The method according to claim 30, wherein the step of filling said insulating material into said cavity comprises the steps of filling an insulating filler and an insulating compound. 33. The method according to claim 32, wherein the step of placing said volume change compensation member is carried out after the step of filling said insulating filler. 34. The method according to claim 30, wherein said volume change compensation member is a solid body. 35. The method according to claim 30, wherein said volume change compensation member is a foam body. 36. The method according to claim 30, wherein said volume change compensation member is a hollow body. 37. The method according to claim 30, wherein said volume change compensation member is a compressible body. 38. The method according to claim 30, wherein said volume change compensation member is an inflatable body. 39. The method according to claim 30, further comprising the step of selecting the predetermined volume of the volume change compensation member depending on the temperature of the insulating material. 40. The method according to claim 30, further comprising the step of selecting the predetermined volume of the volume change compensation member depending on the ambient temperature range of the area where said termination has to be installed. 41. The method according to claim 30, further comprising the step of removing the volume change compensation member after the step of filling said insulating material into said cavity. 42. A termination of an electrical cable comprising: an outer insulator body member; a substantially longitudinally extended interior member comprising said electrical cable to be terminated, said cable comprising a conductor for carrying load; an insulating material filled in a cavity between said outer insulator body and said interior member; and means for accommodating the volume expansions of said insulating material within said cavity; said means for accommodating the volume expansions of said insulating material comprising: a volume change compensation member having a predetermined volume to ensure the accommodation of said volume expansions. 43. The termination according to claim 42, wherein said volume change compensation member compensates the volume expansions of said insulating material by changing its own volume. 44. The termination according to claim 42, wherein said volume change compensation member is compressible. 45. The termination according to claim 42, wherein said volume change compensation member is a foam body. 46. The termination according to claim 42, wherein said volume change compensation member is a hollow body. 47. The termination according to claim 42, wherein said volume change compensation member is an inflatable body. 48. The termination according to claim 42, wherein said volume change compensation member is a solid body. 49. The termination according to claim 42, wherein said volume change compensation member is placed in the upper part of said termination. 50. The termination according to claim 45, wherein said foam body contains material that is electrically insulating or semi-conducting. 51. The termination according to claim 45, wherein said foam body contains closed cell material. 52. The termination according to claim 45, wherein said foam body contains encapsulated chemicals. 53. The termination according to claim 45, wherein said foam body contains water absorbing materials. 54. The termination according to claim 46, wherein said hollow body comprises a plurality of compressible elements each having an outer skin and a compressible interior space. 55. The termination according to claim 54, wherein said compressible interior space is filled with gas. 56. The termination according to claim 47, wherein said inflatable body comprises a flexible skin which is blown up with gas. 57. The termination according to claim 56, wherein the material of said skin is made of electrically insulating or semi-conducting material. 58. The termination according to claim 42, further comprising means for controlling electrical stress concentrations.
FIELD OF THE INVENTION The present invention relates to a method of building a termination of an electrical cable. In particular, the present invention relates to a method of building a termination of an electrical cable said termination comprising an outer insulator body, a substantially longitudinally extended interior member comprising the electrical cable to be terminated, the cable comprising a conductor for carrying load, an insulating material, filled in a cavity between the outer insulator body and the interior member, and means for accommodating volume expansions of the insulating material filled within the cavity, wherein the method comprising the steps of creating the cavity by introducing the interior member into the insulator body; filling in the insulating material into the cavity and sealing the termination. Additionally the present invention relates to a respective termination. BACKGROUND OF THE INVENTION Typically, terminations of an electrical cable, particularly high voltage outdoor terminations comprises an outer insulator body containing a cable to be terminated. The space between said cable and the interior wall of said outer insulator body being filled with an insulating material which comprises an insulating compound. Said insulating compound can be a liquid or a cross-linking insulating compound which will be described more in detail later. The liquid or cross-linking insulating compound can be filled with an insulating filler, like polyethylene pellets. Said insulating material has a thermally caused expansion, which is receptable since the termination may be exposed to temperatures ranging about 60 to 70 degree between cold winter nights and hot summer days. The increase of volume inside the insulator body requires a free space at the top of the termination. During thermally caused changes of the volume of the insulation compound the excess volume will reduce the free space at the top of the termination and thus compress the trapped air and cause an increase of pressure. Ensuring that said space on top of the termination is maintained free during the installation is rather complicated and requires a special training of the jointers. The problem of proper installation in this particular step is increased in case of conical insulators, which are used to save insulating material in electrical low stress areas close to the top of the termination. In case said free space (i.e. the space not filled by the insulating material) is too small, a mechanical damage will occur to the insulator body at high temperatures caused by high pressures; in case the space is too large there is a risk of electrical break down because of weaker electrical strength in air than in a liquid or solid material. The general problem to be solved is to increase the quality of the termination and allow for reduction of skill of the jointer, thus leading to a more economical and safer solution. The invention particularly addresses this problem in order to efficiently simplify the method of building a reliably insulated termination. DESCRIPTION OF THE PRIOR ART FIG. 1 shows a typical construction of an outdoor termination OT the building method of which is for example disclosed in EP 1 170 846 A1 as well as in “Fitting instructions for outdoor sealing end FE2XKVI 220 for 220-275 kV XLPE cables with lead sheath (Um=245-300 kV)”, Siemens AG, document number (4)J10000-X0932-N014-E, which is available to customers of the respective outdoor termination. This outdoor termination comprises an insulator body 2 having an upper plate 10 and a lower plate 11, preferably made of metal. At the upper plate 10 a conductor stalk 9 is provided with which the conductor 5.1 of a cable CA is connected. The lower plate 11 is connected to the insulator body 2 at a bottom portion thereof, for example by means of nuts and bolts 11.1. The cable CA extends within the interior of the insulator body 2 and the cable conductor 5.1 is surrounded by an insulation 5. At the lower portion of the insulator body 2 the cable CA is surrounded by an antikinking protection 7 to avoid a breakage of the cable. Also provided at the lower plate 11 (the base plate) there is an entrance bell 8 having a connector 20.1. Furthermore, an electric field control means in the form of a stress cone 4 is provided at a lower portion of the insulator body 2 around the cable insulation 5 in order to appropriately set the electric field conditions inside the insulator body 2. Typically, the insulator body 2 is made of porcelain or is a composite insulator of reinforced epoxy resin and silicone sheds. Through the entrance bell 8 by means of the connector 20.1 an insulating material 3 is injected into the interior of the insulator body 2 such that said insulating material 3 fills at least a portion of the cavity provided by the space among the interior walls 2.1 of the insulator body 2, the cable insulation 5 and the stress cone 4. Typically the outdoor termination is mounted in a substantially upright position such that an unfilled space 1 (i.e. the free space) is formed at an upper portion of the insulator body 2. It should be noted that, depending on the range of application, the stress cone 4 may not be needed. For example, the electric field control means, i.e. the stress cone 4, may in particular be disposed if the high voltage cable CA is a DC cable and the stress control means is made of silicone carbide having an appropriate design. The critical components of the outdoor termination OT shown in FIG. 1 are the upper and lower plates 10, 11 and in particular the insulating material 3, with respect to the liquid/gas-tightness and with respect to possible temperature fluctuations and pressure variations. Firstly, the insulating material 3, e.g. conventionally an insulating fluid or a cross linking material, needs to possess the required dielectric properties and to be chemically neutral with respect to the material of the insulator body 2, the cable insulation 5 and the material of the stress cone 4. Secondly, it must be considered that the outdoor termination OT is arranged in open space and is thus exposed to all kinds of environmental influences, in particular large changes in temperature and/or large stresses due to snow or wind. Temperature changes cause changes in the volumes of the insulating material 3 accompanied by pressure changes. Even when large temperature changes occur, it must be avoided under all circumstances that a leakage occurs at the bottom part of the insulator body 2. On the other hand, when there is a large drop in temperature, particularly in case an insulating fluid is used, it must be avoided that air is sucked into the cavity 1 at the top of the insulator body 2. EP 1 170 846 A1 discloses an outdoor termination for a high voltage cable as mentioned above, comprising an insulator body for receiving the high voltage cable and for containing an insulating material consisting of a mixture of particles (i.e. a filler) and an insulating compound, wherein said particles are solid particles without cavities. A method for making such outdoor termination for a high voltage cable comprises the steps of preparing an insulator body for receiving the high voltage cable, inserting an insulating material into the insulator body to fill at least a portion of the space between the insulator body interior walls and the cable insulation, wherein said insulating material is prepared as a mixture of an insulating compound and solid particles. According to said method in a first step said solid particles are inserted into said insulator body and in a second step said insulating compound is inserted into the insulator body, thus said solid particles and said insulating compound being mixed together. The insulating compound may be an insulating fluid or a cross-linking capable insulating material which forms a gel-like material during the cross-linking when being filled into the insulator body. The particles may for example have a grain-, pellet- or ball-like shape and the material of said particles may be polyethylene, polyvinyl chloride, rubber, glass or porcelain, for example. The filling of the insulating material can be made by filling the solid particles into the insulator body from the top of the insulator body, for example to a certain level, e.g. filling about 90% of the interior of the insulator body such that only a predetermined space is left free at an upper portion of the insulator body. In a second step the insulating compound is inserted into the insulator body, wherein the solid particles and the insulating compound are mixed. The insulating compound is fed to the insulator body interior via a tube controlled by suitable valves. One method to achieve said result consists in evacuating the interior of the insulator body to reach a predetermined pressure. After the vacuum has been obtained within the insulator body the insulating fluid is introduced and mixed with the solid particles already provided therein. During this process the insulating fluid is partially sucked into the insulator body, by the vacuum made inside the insulator body, and is partially pressurized by applying a pressure to the insulating fluid. According to a further method it is not necessary to use a vacuum within the insulator body and it is only necessary to pressurize the insulating fluid. According to a further method, it is also possible to use the vacuum sucking of the material and not to apply a pushing pressure to the insulating fluid, i.e. the insulating fluid is sucked into the insulator body interior merely by the vacuum pressure. In any case it must be guaranteed that there is a good wetting of the solid particles by the insulating compound, in particular if a cross-linking insulating compound is used and that there is an appropriate displacement of air from the places between the filler particles. The insulating compound of a so called dry-type termination is a cross-linkable polymeric material. Prior to the cross-linking, such insulating compound needs to be liquid enough to allow for easy filling into the insulator body. Accordingly, its viscosity in the non-cross-linked state should preferably not exceed 2000 mpas (Brookfield) at 23° C., preferably its viscosity is below 1500 mpas, and most preferably its viscosity is in the range of 700 to 1000 mpas. The density of such insulating compound is not subject to any particular limitation. However, usually the density is in the range of 0.95 to 1.1 g/cm3 in the non-cross-linked state. To build a termination of a cable the insulating compound may be filled into the insulator body together with a particulate material (i.e. a filler). Once such insulating compound is filled into the insulator body, it undergoes a cross-linking reaction, so as to form a soft matrix surrounding the particulate material and the cable. Accordingly, such insulating compound is a cross-linkable compound, which upon cross-linking should exhibit the necessary electric properties and be of a soft, gel-like consistency. The softness of such cross-linked insulating compound is desirable, as it allows for the compensation of mechanical stress on the insulating filling. Typically, the insulating compound upon cross-linking and in the absence of the particulate material may have a hardness according to DIN ISO 2137 of 200 to 500 mm/10, preferably 250 to 400, and most preferably 290 to 350 mm/10. Very good results have been obtained with insulating compounds which exhibit a hardness upon cross-linking of 310 to 350 mm/10. After the cross linking the viscosity of the insulating compound under all operating conditions, e.g. from −40° to 100° C., is preferably such that it can be permanently contained in the insulator body without necessitating gas- or liquid-tight seals. In other words, the cross linked insulating compound forms a soft but solid body. In order to further reduce mechanical stress, it is also desirable that the thermal conductivity of the insulating compound at 20 to 150° C. according to DIN 52612 is in the range of 0.15 W/mK to 0.3 W/mK, particulary preferred are thermal conductivities around 0.2 W/mK. For the same reason it is also preferred that the coefficient of linear expansion of such insulating compound in the cross-linked state is small, i.e. in the range of 200×10-6 m/mK to 400×10-6 m/mK, preferably between 300×10-6 m/mK and 350 m/mK. In terms of the electrical properties, the dielectric strength of such insulating compound (1 mm sheet, IEC 243-2) is in the range of 18 to 30 kV/mm. Values between 20 and 25 KV/mm and in particular values around 23±10% KV/mm are preferred. The volume resistivity measured at 23° C. according to DIN IEC 93 is preferably-in the range of 5×1015 to 5×10-16 Qcm. Very good results have been obtained with insulating compounds having a volume resistivity of 1016±10% Q. It is also preferably that the relative permittivity of such type of insulating compound upon cross linking (VDE 030 T4, 50 Hz) is between 2.5 to 3, preferably between 2.7 and 2.9. Insulating compounds of the above type can be of diverse chemical structure. The common denominator is that they are capable of being cured in the insulator body and satisfy the above requirements particularly in regard to the softness. The curing may thereby be effected according to various methods known in the art. However, addition curing processes that proceed at ambient temperature are preferred. Preferred insulating compounds for dry-type cable terminations are modified hydrocarbons, such as polybutadiene, modified polyolefins and silicone polymers. Under such conditions, i.e. by using such known methods of building a termination of a cable end, the applicant perceived that it is quite complicated to ensure that a free space is maintained on top of the termination during the installation, said space being necessary for accommodating volume changes of the insulating material inside the termination. In case the filling of the insulating material into the termination is carried out by taking into account a filling mark possessed by the insulator body, an appropriate displacement of the air between the solid particles can not be guaranteed above all if the viscosity of the insulating compound is high, therefore an incorrect filling of the insulator body can occur. Additionally, said filling step is time consuming (it may take about an hour) and is a source of unwanted errors. The above-mentioned document “Fitting instructions for outdoor sealing end FE2XKVI 220 for 220-275 kV XLPE cables with lead sheath (Um=245-300 kV)”, Siemens AG, document number (4)J10000-X0932-N014-E on sheets 8 and 9 discloses that in order to fill the termination with an insulating material the amount of said material has to be fixed before filling and to be selected depending on the material temperature and an average ambient temperature, i.e. the average ambient temperature of the place of use of that termination. Such method is also quite complicated. The applicant has found that, during installation, a free space inside the termination can be advantageously maintained by introducing a member whose predetermined volume corresponds to the desired volume of free space to be maintained. SUMMARY OF THE INVENTION As explained above, it is an object of the present invention to increase the reliability of a termination allowing for reduction of skill of the jointer, thus leading to a more economical and safer solution. According to one aspect of the present invention this object is solved by a method of building a termination of an electrical cable said termination comprising an outer insulator body, a substantially longitudinally extended interior member comprising the electrical cable to be terminated, said cable comprising a conductor for carrying load, an insulating material, filled in a cavity between the outer insulator body and the interior member, and means for accommodating volume expansions of the insulating material filled within the cavity. The method comprises the steps of: creating the cavity by introducing the interior member into the insulator body; filling in the insulating material into the cavity and sealing the termination. According to the present invention a volume change compensation member having a predetermined volume to accommodate volume expansions of the insulating material within the cavity is placed into the cavity. Thus, the jointer fills the cavity between the outer member and the interior member of the termination with the insulating compound, possibly after introducing thereinto an insulating filler (like solid particles). It is not necessary to ensure any free space on top of the termination during the process step of introducing the insulating compound since the volume change compensation member accommodates volume expansions of the insulating material within the cavity. The insulating material, to be introduced into said cavity, can comprise a liquid insulating material (like silicone oil or transformer oil), or an insulating cross-linking compound (like a silicone based insulating compound) and a pourable solid insulating material (e.g. an insulating filler like for example solid granules made of a polymeric material as polyethylene, polypropylene, ethylene-propylene rubber or silicone rubber or beads of glass, ceramic, porcelain or epoxy resin, which may be for example approximately spherical, approximately cylindrical or irregular in shape). Preferably, according to the present invention, the step of placing the volume change compensation member into the cavity is performed before the step of filling in the insulating material. Preferably said volume change compensation member comprises at least two parts which may enable an easier installation thereof and, if foreseen, an easier removal of such volume change compensation member. According to one particular embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of selecting the predetermined volume of the volume change compensation member depending on the temperature of the insulating material. With such additional step the predetermined volume of the volume change compensation member can be more exactly selected to accommodate volume expansions of the insulating material filled in the cavity and thus the reliability of the termination can be increased. According to one particular embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of selecting the predetermined volume of the volume change compensation member depending on the ambient temperature range of the area where such termination will be installed. Therefore, the selection criterion may be an average value of the expected ambient temperature of the termination, for example. With such additional step the predetermined volume of the volume change compensation member can be more exactly selected to accommodate volume expansions of the insulating material filled into the cavity and thus the reliability of the termination can be increased. According to a further embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of removing the volume change compensation member after the step of filling said insulating material into the cavity. According to a second aspect, the present invention concerns a termination of an electrical cable comprising an outer insulator body member, a substantially longitudinally extended interior member comprising said electrical cable to be terminated, said cable comprising a conductor for carrying load; an insulating material, filled in a cavity between said outer member and said interior member, and means for accommodating volume expansions of said insulating material filled in said cavity. According to the present invention said means for accommodating the volume expansions of said insulating material comprises a volume change compensation member having a predetermined volume to ensure the accommodation of said volume expansions of said insulating material within said cavity. Said volume change compensation member according to the present invention is shaped to fit in the cavity of said termination. Preferably the volume change compensation member is a compressible member which compensates the volume expansions of the insulating material by changing its own volume. According to one preferred embodiment of the present invention said volume change compensation member is a solid body. Such a solid body may be a cylinder made of any material, preferably of plastic. Its outer diameter may preferably be a little bit smaller than the inner diameter of the outer insulator body. Preferably the gap between said outer diameter and said inner diameter of the outer insulator body ranges from 2 to 10 mm. Such cylinder has a bore, with a diameter a little bit larger than the outer diameter of the cable core, preferable 2 to 10 mm, in the upper part of the termination. The design of such solid body can be modified if a sealing member is present which seals the conductor stalk at the upper end of the termination when fit for use. The solid body will be installed in the interior at the top of the termination during filling of the fluid and removed after the filling process will be completed. To facilitate this, the solid body can consist of two parts. The solid body can be covered with a transparent plate to watch the rising fluid level visually from the top. In one preferred embodiment, such solid body is fixed at a plate which covers the termination during the fitting process. Also such plate for closing the top end of the termination during the filling process, which plate has a member extending into the cavity between the outer member and the interior member of the termination, preferably is at least partly transparent to allow a jointing person watching the filling status of the termination. A solid body as a volume change compensation member can be used for all types of cylindrical terminations, with a fluid or cross linking compound to be filled, with or without any insulating filler. A solid body as a volume change compensation member can be reused therewith saving mounting costs. According to a further preferred embodiment of the present invention, the volume change compensation member is a foam body. Such a foam body may be a cylinder, a cone or even a plate, which will be able to fill the space in the upper part of the termination. The shape of such volume change compensation member depends on the shape of the gap between the outer insulator body and the interior member. In case of a cylindrical outer insulator body, the foam body design itself may be a cylinder with an outer diameter similar to the inner diameter of the insulator body. The foam body may have an opening like a bore with an inner diameter similar to the outer diameter of the cable core. In case of a conical outer insulator body, the foam body may be a cone with a bore. A plate with a special shape, which will form a cone and which will be able to fill the respective space at the top of the interior of the termination with a conical insulator body, can be used as volume change compensation member as well. The material of the foam body may preferably be a closed cell foam material. The preferable hardness depends on the installation method. If the foam body has to be pulled off after installation, the foam body can be harder; if the foam body remains in the termination, the foam body can be softer. The foam material may be either electrically insulating or semi-conductive. In one particular embodiment of the present invention the foam material of the volume change compensation member can contain encapsulated chemicals, which encapsulation breaks at mechanical stress and which chemicals will destroy the foam skeleton. People skilled in the art of foam materials will appreciate which type of chemicals are useable for that purpose and how to encapsulate them inside the foam material. Since that part of this particular embodiment is not in the main focus of the present invention, a detailed description will be omitted herein. Furthermore the foam material may contain water absorbing materials in order to absorb humidity, trapped during installation in respective environmental climate or in case of a broken gasket. Such a volume change compensation member comprising a foam body will be installed in the interior at the top of the termination during filling of the insulating material and removed or be remained after completed filling process. During the step of filling the insulating material into the termination, also such foam body can be covered with a transparent plate to watch the rising fluid level visually from the top of the termination. Such a foam body can be used as a volume change compensation member for all types of cylindrical and conical terminations, with fluid or cross linking compound to be filled, with or without any additional insulating filler, respectively. According to a further preferred embodiment, the volume change compensation member comprises a hollow body. Such a hollow body as a volume change compensation member preferably may consist of a multiplicity of small compressible elements, like balls, each element consisting of a solid skin and a compressible interior space, which is tightened by the skin. This interior space can be filled with air or gas. The material and design of the skin depends on the insulating compound which surrounds said compressible elements. Diffusion of trapped gas from the interior of said elements into the surrounding insulating compound should be avoided or limited to a minimum extend. Thus elements made of metal, plastic or rubber covered with metal or special plastics will preferably be used for insulating fluid and plastic and rubber will preferably be used for insulating cross linking compound. The plastic material can be either insulating or semi-conducting. In order to avoid diffusion of interior gas of said elements into the surrounding insulation compound, in one preferred embodiment of the invention said gas is sulphur hexafluoride or a so called “security tire gas” or “long live gas” as used to inflate tires. The diameter of the compressible elements may be for example in a range between 5 to 20 mm. Preferably the wall thickness can be in the range from 0.01 mm to 1 mm. Preferably the shape of said compressible elements may be ball-like or flattened, like a discus. To allow for a more flexible motion of the skin, the shape of said elements may be wavy so that the skin works like a diaphragm. A multiplicity of said compressible elements can be placed either on top or bottom of the termination, depending on the material of said elements and on the design of the termination and will remain after filling up with the insulating compound. The reason for that is primarily that the electrical field strength distribution will be less negative effected by such compressible elements on top or bottom of the termination than in the area between top and bottom, i.e. in the area around the stress cone. The total volume of said compressible elements has to be adequate to the required volume of the free space. Such compressible elements can be used as a volume change compensation member according to the invention for all types of insulator bodies, cylindrical or conical. According to still a further preferred embodiment the volume change compensation member is an inflatable body. Such an inflatable body may be cylindrical or frusto-conical in shape, it is hollow and presents a bore for receiving the interior member of the termination. The outer skin of such inflatable body can be made of flexible plastic or rubber which can be blown up with air or gas. Preferably, its outer diameter is smaller and the inner diameter is larger than the respective diameters of the outer insulating body and the interior member. Thus the inflatable body can be placed in the space between the insulator body and the cable core. In case, such inflatable body will remain inside the termination after filling, i.e. under conditions of normal usage, the size of such inflatable body will be depending on the ability of such body to increase its volume. Preferably the inflatable body is filled with air or gas up to a pressure between 0.1 bar and 0.5 bar, thus the volume of the inflated body is equal to the required space. For example, the filling process for inflating such body may be performed by means of a valve in the body. After pre-installation of such inflatable body as a volume change compensation member the termination can either be closed temporarily or sealed with the upper plate, depending on the further installation sequence, i.e. to remove or to keep the inflatable body in the termination for final electrical operation. In one preferred embodiment of the present invention, in case the inflated body remains in the termination, it may consist of semi-conductive material and improve the distribution of electrical field. The electrical contact to high voltage potential may be simply made by compression to the bare conductor stalk in order to ensure the electrical potential of the conductor stalk also at the surface of the inflatable body. In case of a conducting or semi-conducting volume change compensation member shall not be formed comprising any protrusions or other portions of high field strength concentrations. Further advantageous embodiments and improvements of the invention are listed in the dependent claims appending to the description. Furthermore, it should be noted that the disclosure presented herein only lists the preferred mode of the invention and should not be understood as limiting in any way. That is, a skilled person can carry out modifications and variations of the invention on the basis of the teaching of the present specification. In particular, the invention can comprise embodiments which result from an individual combination of features which have been described separately in the description and the claims. BRIEF DESCRIPTION OF THE DRAWINGS In the drawings the same reference numbers indicate the same parts throughout the specification. FIG. 1 shows a typical construction of an outdoor termination according to the prior art; FIG. 2 schematically shows a first exemplary embodiment of a termination of an electrical cable in accordance with the present invention, using a solid body as a volume change compensation member; FIG. 3 schematically shows a second exemplary embodiment of a termination of an electrical cable in accordance with the present invention, using a foam body as a volume change compensation member; FIG. 4 schematically shows a third exemplary embodiment of a termination of an electrical cable in accordance with the present invention, using a plurality of compressible elements as a volume change compensation member; FIG. 5 to 7 schematically show cross sectional views of the shape of possible embodiments of different compressible elements, which can be used in the third embodiment of a termination of an electrical cable, as shown in FIG. 4; FIG. 8 schematically shows a fourth exemplary embodiment of a termination of an electrical cable in accordance with the present invention, using an inflatable body as a volume change compensation member; FIG. 9 shows a schematic flow chart of a first exemplary embodiment of a method of building a termination of an electrical cable in accordance with the present invention; FIG. 10 shows a schematic flow chart of a second exemplary embodiment of a method of building a termination of an electrical cable in accordance with the present invention; and FIG. 11 shows a schematic flow chart of a third exemplary embodiment of a method of building a termination of an electrical cable in accordance with the present invention. Hereinafter, preferred modes of the invention will be described. However, it should be understood that other modifications and variations of the invention are possible on the basis of the teachings herein. First Embodiment of a Termination FIG. 2 shows a first embodiment of a termination according to the present invention. In particular FIG. 2 shows an outdoor termination OT which comprises, as described above, an insulator body 2, an upper plate 10, a lower plate 11, a conductor stalk 9 and an electric field control means 4 in the form of a stress cone 4. The insulator body 2 is tubular in shape and reference sign 2.1 indicates the interior wall of said body 2. At the upper end of the insulator body 2 a volume change compensation member 13 in the form of a pre-manufactured solid body is provided, in the status as shown almost filling a space mentioned as an unfilled space 1 in FIG. 1 above. After removal of the volume change compensation member 13, a cavity will be left. It should be noted that in embodiments of the invention the stress cone 4 is needed, if the high voltage cable CA is an AC cable but may be omitted in some other cases. For example, the electric field control means, i.e. the stress cone 4, may in particular not be needed if the high voltage cable CA is a DC cable. Preferably a stress control means other than a stress cone is made of silicone carbide. Furthermore, the outdoor termination OT in FIG. 2 comprises a sealing element 6 and upper fixing means 12, e.g. a nut. The upper plate 10 at the top of the termination preferably is a transparent plate for controlling the step of filling the insulator body 2. Preferably, said upper plate 10 is not tightly associated to the insulator body 2 in order to allow for removing of air during the filling process. The insulator body 2 receives the high voltage cable CA as well as an insulating material 3, which fills at least a portion of the space between the insulator body interior wall 2.1 and the cable insulation 5 such that a cavity 1 is formed at the upper portion of the insulator body 2 where the connection between the cable conductor 5.1 and the conductor stalk 9 is made. As schematically shown in FIG. 2, the insulating material 3 consists of a mixture of solid insulating particles 3.1 and an insulating compound 3.2. The insulator body 2 is made of an electrically insulating material, for example porcelain. Preferred materials for the solid insulating particles 3.1 are, for example polyethylene, polyvinylchloride (PVC), rubber, glass or porcelain. Generally the solid insulating particles 3.1 are not hollow. Preferably the solid insulating particles 3.1 are free of inclusions of any foreign matter. Preferably, the solid insulating particles are grain-like, pellet-like or ball-like shaped particles having a diameter preferably between 1 to 5 mm. Preferably, the insulating compound 3.2 is an insulating cross linking compound or an insulating fluid. Said insulating fluid can be an organic or synthetic fluid and is to be filled into the termination via an connector 20.1, shown at the lower part of the termination of FIG. 2. Preferably, the specific gravity of the particles 3.1 is substantially equal or greater than the specific gravity of the insulating fluid 3.2. In a particular embodiment of the invention shown in FIG. 2, the insulating compound 3.2 is a cross-linkable insulating fluid which is in a liquid-state when it is inserted into the insulator body 2 and cross-links after the insertion into the insulator body, which has already been filled with the solid particles. Said cross-linkable insulating fluid forms a resin of a gel-like consistency after the cross-linking. The cross-linking is such that the material forms a matrix which is cross-linked and spreads (wets) the solid particles 3.1 and preferably also the insulator body interior walls 2.1 and the cable insulation 5. That is, the cross-linking capable material, after being filled in the insulator body interior as a liquid, undergoes a cross-linking reaction. Preferably, the material also performs a spreading (e.g. wetting) of the interior walls 2.1, of the cable insulation 5 and, if provided, of the stress cone surface 4. Thus, due to the spreading, the cross-linked material somewhat adheres to the interior surface 2.1, the cable insulation 5 and possibly the stress cone surface 4. However, when temperature changes occur, which cause the cross-linked material to more, the cross-linked material should be released from the respective surface so as to relieve the mechanical stress. It is also possible that the material in the course of the cross-linking reaction also forms chemical bonds with the particles 3.1 and preferably also with the interior walls 2.1, the cable insulation 5 and the stress cone surface 4 (if provided). After the cross linking, the viscosity of the cross-linked insulating fluid is so large that permanent seals in particular in the lower portion of the insulator body 2 can be disposed with or the sealing construction can at least be made simpler by contrast to the conventional outdoor terminations. There is no necessity for an absolute sealing at the lower portion. For example, the seals must only provide a temporary sealing function as long as the insulating fluid has not been fully cross-linked with the particles or preferably also with the interior walls and the cable insulation. The volume change compensation member 13 keeps the particles 3.1 in place even if they try to swim up because of their smaller density with respect to the liquid insulating compound 3.2 The upper plate 10 and the volume change compensation member 13 can be designed in one part. After the filling step is completed, the volume change compensation member 13 is removed and the termination is sealed with the upper plate 10. Second Embodiment of a Termination Now a second embodiment of a termination according to the present invention will be described referring to FIG. 3 to 5. FIG. 3 shows a second embodiment of a termination according to the present invention. In particular FIG. 3 shows a termination OT of a cable CA, said termination being provided with a volume change compensation member 13 in the form of a pre-manufactured foam body. The termination is filled with the insulating material 3 mentioned above, for example via a connector, not shown in FIG. 3. Except for the type of volume change compensation member 13, the main difference between the termination according to FIG. 2 and that according to FIG. 3 is the shape of the insulator body. According to said second embodiment a conical insulator body 2 is shown, an upper plate 10, a lower plate 11 coupled with the insulator body 2 via a gasket 14, a conductor stalk 9 and an electric field control means 4 in the form of a stress cone 4. The free space inside the insulator body 2 is filled with an insulating compound 3. The volume change compensation member 13 in the form of a foam body is positioned at the top of the termination, in correspondence of the upper plate 10. The volume change compensation member 13 remains in the termination during operation so that, in case of thermally caused expansion of the insulating material, the foam body is compressed. According to a further embodiment, the volume change compensation member 13 is taken out from the termination after the step of filling the insulating material into the insulator body 2 is completed. Third Embodiment of a Termination FIG. 4 shows a third embodiment of a termination according to the present invention. In particular FIG. 4 shows an outdoor termination OT comprising a lower plate 11 in the form of a tubular body which receives the high voltage cable CA at its lower end and has an opening at its upper end in correspondence with the insulator body 2. A volume change compensation member 13 in the form of compressible bodies is provided in the bottom of the termination inside of the tubular lower plate 11. Said compressible bodies are covered with a cover member 15 in order to prevent swimming-up of said compressible bodies when the insulating fluid 3.2 is filled into the termination. The lower plate 11 is coupled to the insulator body 2 and sealed by a gasket 14. Preferably, said compressible bodies are hollow. In case polyethylene pellets are used as insulating solid particles 3.1 of the insulating material 3 the cover member 15 is not necessary and can be omitted as far as this polyethylene pellets prevent said compressible bodies from movement out of the area of non-critical electrical field. It is necessary to fill in the compressible bodies before filling in the solid insulating particles 3.1 to ensure that the compressible bodies are kept in the area of non-critical electrical field at the bottom of the termination. In case of thermally caused expansion of the insulating compound the compressible bodies in the bottom area of the termination will be compressed, herewith compensating excess volume of the expanded insulating material 3. According to a further embodiment (not shown), compressible bodies are provided at the top of the solid insulating particles 3.1 in the upper part of the termination. In such particular case, however, it is necessary to fill in the compressible bodies after the solid insulating particles 3.1 to ensure that the compressible bodies are in the area of non-critical electrical field at the upper part of the termination. FIGS. 5, 6 and 7 show different compressible hollow bodies according to particular designs. FIG. 5 shows a cross sectional view of a ball shaped hollow body made of rubber and filled with a gas. Preferably the pressure inside said hollow body is the atmospheric pressure. The diameter of this ball shaped body is for example 15 mm and the wall thickness is for example 1 mm. Said ball shaped body can be deformed to any shape by the outer pressure, when the latter increases, and relax as well. FIG. 6 shows a cross sectional view of a shell shaped hollow body made of metal. Two plates with waved structure are welded together and air is trapped inside thereof. The diameter of said body is preferably 20 mm; the wall thickness is preferably 0.05 mm. FIG. 7 shows a cross sectional view of an embodiment similar to that shown in FIG. 6, each of the two plates being provided with two waved portions welded together at their respective ends. Fourth Embodiment of a Termination FIG. 8 shows a forth embodiment of a termination according to the present invention. In particular FIG. 8 shows a volume change compensation member 13 on top of a termination provided with a conical insulator body 2. Said volume change compensation member is in the form of an inflatable body, shown already inflated in FIG. 8 According to FIG. 8, the volume change compensation member 13 is shown positioned at the top of the termination, while the insulator body 2 is already filled with the insulating material 3 and the upper plate 10 is installed. The height of the inflatable body is chosen to occupy the necessary volume at the atmospheric pressure. The pressure within the inflated body, generated for example by a suitable pump is for example of about 0.5 bar and the body increases its volume. In this particular embodiment the material of the inflatable body is a semi-conductive rubber and the inflatable body improves the electrical strength of the termination. In the inflated condition the body can prevent the solid particles of the insulating material from swimming up during the filling process. The insulating compounds, e.g. silicone gel, is filled in at a pressure adequate to the pressure in the body and the body is then compressed to its size at atmospheric pressure by means of the pressure balance in the termination. In case of a temperature rise of the termination the insulating compound 3 will expand and the inflated body will be compressed. In case the temperature drops below installation temperature the insulation compound will shrink. In this case the inflated body will expand and compress the insulating compound until the pressure in the inflated body is in balance with the pressure inside the termination. This property of the inflatable body will allow a close contact of the insulating compound 3 to the inner surface of the insulator body 2 under all conditions. First Embodiment of a Method to Build a Termination FIG. 9 shows a first embodiment of the method of building a termination of an electrical cable in accordance with the invention. Particularly FIG. 9 shows a first embodiment of the method of building a first embodiment of the termination as described above with reference to FIG. 2. However, this first embodiment of the method of building a termination is also applicable to the modification of the second embodiment of a termination as described above with reference to FIG. 3, in which the volume change compensation member 13 in the form of a foam body is taken out from the termination when the step of filling the insulating compound is completed. The procedure starts at step S1, in which an insulator body 2, with the parts as shown in FIG. 1 and FIG. 2 necessary for the electrical functioning of the outdoor termination, is prepared and a high voltage cable CA is provided inside said insulator body 2. In a second step S2, solid particles 3.1 are filled into the insulator body 2 from the upper portion of the termination. For example a filling of about 90% of the interior of the insulator body 2 is carried out and a predetermined space is left free at the upper portion of the insulator body 2. In case the insulating material does not foresee a solid filler, i.e. the solid particles, this step is omitted. In a third step S3, a volume change compensation member 13 is introduced into the insulator body 2 from above, occupying a certain volume of the upper portion of the insulator body 2, and the termination is closed at its upper end, for example by an upper plate 10. In a fourth step S4, the insulating compound 3.2 is filled into the insulator body 2 via the connector 20.1 until the inner space of the termination is approximately totally filled. In a fifth step S5, the volume change compensation member is removed from the upper portion of the termination leaving a certain volume of air at the upper portion of the insulator body 2. Then the termination is closed at its upper end by the upper plate 10. Said procedure may also be applied with a volume change compensation member 13 in the form of an inflatable body instead of a solid body. Second Embodiment of a Method to Build a Termination FIG. 10 shows a second embodiment of the method of building a termination of an electrical cable in accordance with the invention. Particularly FIG. 10 shows a second embodiment of the method of building a termination as described with reference to FIG. 3 and 8. The particular features of said embodiments are that the volume change compensation member 13 is located in the upper area of the termination near the connector stalk and that the volume change compensation member 13 remains in the termination for normal use. The procedure starts at step S11, which is identical to step S1 of the procedure shown in FIG. 9. In a second step S21, solid particles 3.1 are filled into the insulator body 2 from the upper portion of the termination. For example a filling of about 90% of the interior of the insulator body 2 is carried out and a predetermined space is left free at the upper portion of the insulator body 2. In case the insulating material does not foresee a solid filler, i.e. the solid particles, this step is omitted. In a third step S31, a volume change compensation member 13 (for example a foam body, an inflatable body or a compressible body) is introduced into the insulator body 2 from above, occupying a certain volume of the upper portion of the insulator body 2, and the termination is closed at its upper end, for example by an upper plate 10. In a fourth step S41, the insulating compound 3.2 is filled into the insulator body 2 via the connector 20.1 until the inner space of the termination is approximately totally filled. After this, the termination is closed at its upper end by the upper metal work 10 and the procedure ends. Third Embodiment of a Method to Build a Termination FIG. 11 shows a third embodiment of a method of building a termination of an electrical cable in accordance with the invention. Particularly FIG. 11 shows a third embodiment of the method of building a termination as described with reference to FIG. 4. The procedure starts at step S12, in which the lower plate 11 and the high voltage cable CA are fitted together so that the lower plate 11 receives the high voltage cable CA at its lower end. A volume change compensation member 13 in the form of compressible bodies is provided inside of the lower plate 11 and successively covered with a cover member 15. In a second step S22 an insulator body 2, with the parts as shown in FIG. 4 necessary for the electrical functioning of the outdoor termination, is prepared so that the high voltage cable CA is provided inside the insulator body 2, wherein the compressible bodies are provided in the bottom area of the termination. In case the insulating material comprises a solid filler, depending on the nature of such filler said cover member 15 can be omitted as the filler keeps the compressible bodies in place while the termination will be filled with insulating compound. The lower plate 11 is coupled to the insulator body 2 and sealed by a gasket 14. In a third step S32, solid particles 3.1 are filled into the insulator body 2 from the top of the termination, the latter being successively closed at its upper end, for example by means of the upper plate 10. In case the insulating material does not foresee a solid filler, the step of filling in the solid particles can be omitted. In a fourth step S42, the insulating compound 3.2 is filled into the insulator body 2 via the connector 20.1 until the inner space of the termination is approximately totally filled. Finally the termination is closed at its upper end by the upper plate 10. It may be noted that although in this third method embodiment the volume change compensation member 13 is fitted before the insulator body has been prepared, the invention is not restricted to said steps sequence. If the prepared insulator body 2 allows fitting a cover member 15 or if such cover member 15 is not necessary because of using solid insulator particles above the compressible bodies which prevent the latters from leaving the bottom area of the termination during the filling process of the insulating compound, the first step of that method may be similar to the steps Si and S12 of the first and second embodiment of said method. In such case, before the insertion of the solid insulating particles, the compressible bodies are filled into the insulator body 2. Furthermore, it should be noted that the invention is not restricted to the above description of the best modes of the invention as presently conceived by the inventors. That is, various variations and modifications of the invention may be carried out on the basis of the above teachings. In particular, the invention may comprise embodiments, which result from the combination of features which have been individually and separately described and claimed in the description, the figures and the claims.
<SOH> BACKGROUND OF THE INVENTION <EOH>Typically, terminations of an electrical cable, particularly high voltage outdoor terminations comprises an outer insulator body containing a cable to be terminated. The space between said cable and the interior wall of said outer insulator body being filled with an insulating material which comprises an insulating compound. Said insulating compound can be a liquid or a cross-linking insulating compound which will be described more in detail later. The liquid or cross-linking insulating compound can be filled with an insulating filler, like polyethylene pellets. Said insulating material has a thermally caused expansion, which is receptable since the termination may be exposed to temperatures ranging about 60 to 70 degree between cold winter nights and hot summer days. The increase of volume inside the insulator body requires a free space at the top of the termination. During thermally caused changes of the volume of the insulation compound the excess volume will reduce the free space at the top of the termination and thus compress the trapped air and cause an increase of pressure. Ensuring that said space on top of the termination is maintained free during the installation is rather complicated and requires a special training of the jointers. The problem of proper installation in this particular step is increased in case of conical insulators, which are used to save insulating material in electrical low stress areas close to the top of the termination. In case said free space (i.e. the space not filled by the insulating material) is too small, a mechanical damage will occur to the insulator body at high temperatures caused by high pressures; in case the space is too large there is a risk of electrical break down because of weaker electrical strength in air than in a liquid or solid material. The general problem to be solved is to increase the quality of the termination and allow for reduction of skill of the jointer, thus leading to a more economical and safer solution. The invention particularly addresses this problem in order to efficiently simplify the method of building a reliably insulated termination.
<SOH> SUMMARY OF THE INVENTION <EOH>As explained above, it is an object of the present invention to increase the reliability of a termination allowing for reduction of skill of the jointer, thus leading to a more economical and safer solution. According to one aspect of the present invention this object is solved by a method of building a termination of an electrical cable said termination comprising an outer insulator body, a substantially longitudinally extended interior member comprising the electrical cable to be terminated, said cable comprising a conductor for carrying load, an insulating material, filled in a cavity between the outer insulator body and the interior member, and means for accommodating volume expansions of the insulating material filled within the cavity. The method comprises the steps of: creating the cavity by introducing the interior member into the insulator body; filling in the insulating material into the cavity and sealing the termination. According to the present invention a volume change compensation member having a predetermined volume to accommodate volume expansions of the insulating material within the cavity is placed into the cavity. Thus, the jointer fills the cavity between the outer member and the interior member of the termination with the insulating compound, possibly after introducing thereinto an insulating filler (like solid particles). It is not necessary to ensure any free space on top of the termination during the process step of introducing the insulating compound since the volume change compensation member accommodates volume expansions of the insulating material within the cavity. The insulating material, to be introduced into said cavity, can comprise a liquid insulating material (like silicone oil or transformer oil), or an insulating cross-linking compound (like a silicone based insulating compound) and a pourable solid insulating material (e.g. an insulating filler like for example solid granules made of a polymeric material as polyethylene, polypropylene, ethylene-propylene rubber or silicone rubber or beads of glass, ceramic, porcelain or epoxy resin, which may be for example approximately spherical, approximately cylindrical or irregular in shape). Preferably, according to the present invention, the step of placing the volume change compensation member into the cavity is performed before the step of filling in the insulating material. Preferably said volume change compensation member comprises at least two parts which may enable an easier installation thereof and, if foreseen, an easier removal of such volume change compensation member. According to one particular embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of selecting the predetermined volume of the volume change compensation member depending on the temperature of the insulating material. With such additional step the predetermined volume of the volume change compensation member can be more exactly selected to accommodate volume expansions of the insulating material filled in the cavity and thus the reliability of the termination can be increased. According to one particular embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of selecting the predetermined volume of the volume change compensation member depending on the ambient temperature range of the area where such termination will be installed. Therefore, the selection criterion may be an average value of the expected ambient temperature of the termination, for example. With such additional step the predetermined volume of the volume change compensation member can be more exactly selected to accommodate volume expansions of the insulating material filled into the cavity and thus the reliability of the termination can be increased. According to a further embodiment of the present invention, the method of building a termination of an electrical cable further comprises the step of removing the volume change compensation member after the step of filling said insulating material into the cavity. According to a second aspect, the present invention concerns a termination of an electrical cable comprising an outer insulator body member, a substantially longitudinally extended interior member comprising said electrical cable to be terminated, said cable comprising a conductor for carrying load; an insulating material, filled in a cavity between said outer member and said interior member, and means for accommodating volume expansions of said insulating material filled in said cavity. According to the present invention said means for accommodating the volume expansions of said insulating material comprises a volume change compensation member having a predetermined volume to ensure the accommodation of said volume expansions of said insulating material within said cavity. Said volume change compensation member according to the present invention is shaped to fit in the cavity of said termination. Preferably the volume change compensation member is a compressible member which compensates the volume expansions of the insulating material by changing its own volume. According to one preferred embodiment of the present invention said volume change compensation member is a solid body. Such a solid body may be a cylinder made of any material, preferably of plastic. Its outer diameter may preferably be a little bit smaller than the inner diameter of the outer insulator body. Preferably the gap between said outer diameter and said inner diameter of the outer insulator body ranges from 2 to 10 mm. Such cylinder has a bore, with a diameter a little bit larger than the outer diameter of the cable core, preferable 2 to 10 mm, in the upper part of the termination. The design of such solid body can be modified if a sealing member is present which seals the conductor stalk at the upper end of the termination when fit for use. The solid body will be installed in the interior at the top of the termination during filling of the fluid and removed after the filling process will be completed. To facilitate this, the solid body can consist of two parts. The solid body can be covered with a transparent plate to watch the rising fluid level visually from the top. In one preferred embodiment, such solid body is fixed at a plate which covers the termination during the fitting process. Also such plate for closing the top end of the termination during the filling process, which plate has a member extending into the cavity between the outer member and the interior member of the termination, preferably is at least partly transparent to allow a jointing person watching the filling status of the termination. A solid body as a volume change compensation member can be used for all types of cylindrical terminations, with a fluid or cross linking compound to be filled, with or without any insulating filler. A solid body as a volume change compensation member can be reused therewith saving mounting costs. According to a further preferred embodiment of the present invention, the volume change compensation member is a foam body. Such a foam body may be a cylinder, a cone or even a plate, which will be able to fill the space in the upper part of the termination. The shape of such volume change compensation member depends on the shape of the gap between the outer insulator body and the interior member. In case of a cylindrical outer insulator body, the foam body design itself may be a cylinder with an outer diameter similar to the inner diameter of the insulator body. The foam body may have an opening like a bore with an inner diameter similar to the outer diameter of the cable core. In case of a conical outer insulator body, the foam body may be a cone with a bore. A plate with a special shape, which will form a cone and which will be able to fill the respective space at the top of the interior of the termination with a conical insulator body, can be used as volume change compensation member as well. The material of the foam body may preferably be a closed cell foam material. The preferable hardness depends on the installation method. If the foam body has to be pulled off after installation, the foam body can be harder; if the foam body remains in the termination, the foam body can be softer. The foam material may be either electrically insulating or semi-conductive. In one particular embodiment of the present invention the foam material of the volume change compensation member can contain encapsulated chemicals, which encapsulation breaks at mechanical stress and which chemicals will destroy the foam skeleton. People skilled in the art of foam materials will appreciate which type of chemicals are useable for that purpose and how to encapsulate them inside the foam material. Since that part of this particular embodiment is not in the main focus of the present invention, a detailed description will be omitted herein. Furthermore the foam material may contain water absorbing materials in order to absorb humidity, trapped during installation in respective environmental climate or in case of a broken gasket. Such a volume change compensation member comprising a foam body will be installed in the interior at the top of the termination during filling of the insulating material and removed or be remained after completed filling process. During the step of filling the insulating material into the termination, also such foam body can be covered with a transparent plate to watch the rising fluid level visually from the top of the termination. Such a foam body can be used as a volume change compensation member for all types of cylindrical and conical terminations, with fluid or cross linking compound to be filled, with or without any additional insulating filler, respectively. According to a further preferred embodiment, the volume change compensation member comprises a hollow body. Such a hollow body as a volume change compensation member preferably may consist of a multiplicity of small compressible elements, like balls, each element consisting of a solid skin and a compressible interior space, which is tightened by the skin. This interior space can be filled with air or gas. The material and design of the skin depends on the insulating compound which surrounds said compressible elements. Diffusion of trapped gas from the interior of said elements into the surrounding insulating compound should be avoided or limited to a minimum extend. Thus elements made of metal, plastic or rubber covered with metal or special plastics will preferably be used for insulating fluid and plastic and rubber will preferably be used for insulating cross linking compound. The plastic material can be either insulating or semi-conducting. In order to avoid diffusion of interior gas of said elements into the surrounding insulation compound, in one preferred embodiment of the invention said gas is sulphur hexafluoride or a so called “security tire gas” or “long live gas” as used to inflate tires. The diameter of the compressible elements may be for example in a range between 5 to 20 mm. Preferably the wall thickness can be in the range from 0.01 mm to 1 mm. Preferably the shape of said compressible elements may be ball-like or flattened, like a discus. To allow for a more flexible motion of the skin, the shape of said elements may be wavy so that the skin works like a diaphragm. A multiplicity of said compressible elements can be placed either on top or bottom of the termination, depending on the material of said elements and on the design of the termination and will remain after filling up with the insulating compound. The reason for that is primarily that the electrical field strength distribution will be less negative effected by such compressible elements on top or bottom of the termination than in the area between top and bottom, i.e. in the area around the stress cone. The total volume of said compressible elements has to be adequate to the required volume of the free space. Such compressible elements can be used as a volume change compensation member according to the invention for all types of insulator bodies, cylindrical or conical. According to still a further preferred embodiment the volume change compensation member is an inflatable body. Such an inflatable body may be cylindrical or frusto-conical in shape, it is hollow and presents a bore for receiving the interior member of the termination. The outer skin of such inflatable body can be made of flexible plastic or rubber which can be blown up with air or gas. Preferably, its outer diameter is smaller and the inner diameter is larger than the respective diameters of the outer insulating body and the interior member. Thus the inflatable body can be placed in the space between the insulator body and the cable core. In case, such inflatable body will remain inside the termination after filling, i.e. under conditions of normal usage, the size of such inflatable body will be depending on the ability of such body to increase its volume. Preferably the inflatable body is filled with air or gas up to a pressure between 0.1 bar and 0.5 bar, thus the volume of the inflated body is equal to the required space. For example, the filling process for inflating such body may be performed by means of a valve in the body. After pre-installation of such inflatable body as a volume change compensation member the termination can either be closed temporarily or sealed with the upper plate, depending on the further installation sequence, i.e. to remove or to keep the inflatable body in the termination for final electrical operation. In one preferred embodiment of the present invention, in case the inflated body remains in the termination, it may consist of semi-conductive material and improve the distribution of electrical field. The electrical contact to high voltage potential may be simply made by compression to the bare conductor stalk in order to ensure the electrical potential of the conductor stalk also at the surface of the inflatable body. In case of a conducting or semi-conducting volume change compensation member shall not be formed comprising any protrusions or other portions of high field strength concentrations. Further advantageous embodiments and improvements of the invention are listed in the dependent claims appending to the description. Furthermore, it should be noted that the disclosure presented herein only lists the preferred mode of the invention and should not be understood as limiting in any way. That is, a skilled person can carry out modifications and variations of the invention on the basis of the teaching of the present specification. In particular, the invention can comprise embodiments which result from an individual combination of features which have been described separately in the description and the claims.
20060109
20080422
20060615
69490.0
H01R905
0
MAYO III, WILLIAM H
METHOD AND ARRANGEMENT FOR A TERMINATION OF AN ELECTRICAL CABLE
UNDISCOUNTED
0
ACCEPTED
H01R
2,006
10,518,421
ACCEPTED
Actuation indicator for a dispensing device
An actuation indicator that includes a drum sub-assembly, which includes a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, is described. The slipping clutch arrangement includes a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl.
1. An axle of a rotatable element of an actuation indicator, wherein the axle is provided by a spring that is adapted in use to bias the rotatable element towards another element of the actuation indicator with which the rotatable element is engaged. 2. The axle of claim 1, wherein the rotatable element is a pinion. 3. The axle of claim 2, wherein the other element with which the pinion engages is a rack. 4. The axle of claim 1, wherein the rotatable element is an indicator wheel for indicating actuation of a device with which the indicator is associated. 5. The axle of claim 4, wherein there are at least two rotatable elements on the same axle. 6. The axle of claim 4, wherein the other element is a rotatable element mounted on a second axle, the second axle optionally being provided by the spring. 7. An assembly comprising the axle of claim 1, the or each rotatable element on the axle and the other element. 8. The axle of claim 6, wherein the spring comprises the second axle and a biasing section connecting the two axles to bias them together. 9. An actuation indicator comprising a drums sub-assembly comprising a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, wherein the slipping clutch arrangement comprises a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl. 10. The actuation indicator of claim 9, wherein the slipping clutch spring has a generally U-shaped configuration. 11. The actuation indicator of claim 10, wherein the open end of the spring engages a boss of the pinion and the closed end of the spring defines a track for slidingly engaging a boss provided on the pawl. 12. The actuation indicator of claim 9, wherein the ratchet pawl engages a ratchet wheel that is fixed to the indicator wheel. 13. The actuation indicator of claim 12, wherein a resilient, non-return leg engages a tooth of the ratchet wheel to prevent rotation of the ratchet wheel in a direction other than the set direction, and the non-return leg rides up and over the teeth to allow rotation in the set direction. 14. The actuation indicator of claim 9 wherein there are at least two indicator wheels arranged to sequentially count down from a set figure to zero, wherein the indicator wheels lock from further rotation in the set direction when they have counted down to zero, the slipping clutch spring then slipping on further attempts to rotate the mechanism. 15. A casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part having a generally cylindrically shaped section having a generally cylindrical inner surface extending from a top of the sleeve part towards a base wall, and a collar affixable around a neck of the canister, and sized, when around the neck of the canister, to fit through the top of the sleeve part, into the sleeve part, whereat it will contact at least a portion of the generally cylindrical inner surface, wherein the generally cylindrical inner surface has a shoulder for supporting the collar to prevent the collar from being inserted further into the sleeve part, the shoulder being spaced from the top and the base wall of the sleeve part. 16. The casing of claim 15, wherein the top of the sleeve part comprises a chamfered surface to assist with the insertion of the collar into the sleeve part. 17. The casing of claim 15, wherein the shoulder is formed by an annular step in the generally cylindrical inner surface. 18. The casing of claim 15, wherein the shoulder is formed by a ledge attached to the generally cylindrical inner surface. 19. The casing of claim 15, wherein the collar is a split ring collar. 20. The casing of claim 15, wherein the collar, in an assembled canister unit, is welded to the sleeve part. 21. A casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part for receiving a canister and a cap part for receiving a counter assembly of a dose counter for the canister unit, wherein the cap part and counter assembly can be assembled together separate from the sleeve part and canister, the sleeve part and cap part then being joinable together to form the casing. 22. The casing of claim 21, further comprising a counter assembly, the counter assembly comprising a drums sub-assembly. 23. (canceled) 24. The casing of claim 21, wherein the sleeve part is adapted to receive more than one form of valve stem end. 25. The casing of claim 24, wherein the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support adapted to support a different form of valve stem end, whereby more than one valve stem end is supportable in the sleeve part. 26. The casing of claim 25, wherein the supports are annular ledges. 27. The casing of claim 26, wherein the ledges are concentric. 28. The casing of claim 25, wherein a first support is of a first height above the base wall and the second support is of a lesser height above the base wall. 29. (canceled) 30. A sleeve part for receiving a valve stem end of a canister, the sleeve part being adapted to receive more than one form of valve stem end. 31. The sleeve part of claim 30, wherein the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support being for supporting a different form of valve stem end, whereby more than one form of valve stem end is able to be supported in the sleeve part. 32. The sleeve part of claim 31, wherein the supports are annular ledges. 33. The sleeve part of claim 32, wherein the ledges are concentric. 34. The sleeve part of claim 31, wherein a first said support is of a first height above the base wall and a second said support is of a lesser height above the base wall. 35. A drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and, an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a drive wheel adapted to engage the post and to frictionally engage a slipping clutch; a ratchet pawl adapted to engage the slipping clutch; a star wheel adapted to engage the ratchet pawl; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. 36. The drug product of claim 35, comprising three drums adapted to display a count of 000 to 999, and further comprising an arm affixed to a hundred's drum adapted to contact a stop, wherein the slipping clutch is adapted to frictionally slip when the count reaches 000. 37. The drug product of claim 35, comprising a hundred's drum having numerals 0, 1 and 2, a ten's drum having numerals 0 through 9 and a one's drum having numerals 0 through 9. 38. The drug product according to claim 35, wherein the actuation indicating assembly includes one or more grip members adapted to fixedly engage a neck portion of the container. 39. The drug product according to claim 35, wherein the housing includes a mouthpiece. 40. The drug product according to claim 39, wherein the housing includes a passage adapted to pass doses from the container to the mouthpiece. 41. The drug product according to claim 35, wherein the container includes a metering valve adapted to dispense metered doses. 42. The drug product according to claim 35, further including a window adapted to display numerals on one or more drums engaging the star wheel. 43. The drug product according to claim 35, wherein the actuation indicating assembly is fixed to the container by an adhesive, a welded shrink sleeve, a heat form, a crimp, an ultrasonic weld, an o-ring elastomer, or a split-ring collar. 44. The drug product of claim 35, wherein the actuation indicating assembly is permanently fixed to the container. 45. The drug product of claim 35, wherein the medicament is selected from the group consisting of beclomethasone, fluticasone, flunisolide, budesonide, rofleponide, mometasone, triamcinolone, noscapine, albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, terbutaline, tiotropium, ipratropium, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine, tulobuterol, (-)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl }methyl}benzenemethanol, esters, solvates and salts thereof, and combinations thereof. 46. The drug product of claim 45, wherein the medicament is albuterol sulphate. 47. The drug product of claim 45, wherein the medicament is salmeterol xinafoate. 48. The drug product of claim 45, wherein the medicament is fluticasone propionate. 49. The drug product of claim 45, wherein the medicament is beclomethasone dipropionate. 50. The drug product of claim 45, wherein the medicament is the combination of salmeterol xinafoate and fluticasone propionate. 51. The drug product of claim 45, wherein the medicament is salmeterol xinafoate and a salt, ester or solvate of ipratropium. 52. The drug product of claim 35, wherein the housing is constructed from polypropylene. 53. The drug product of claim 35, wherein one or more components of the actuation indicating assembly are constructed from polypropylene. 54. The drug product of claim 35, further comprising one or more knock gears adapted to engage the one or more drums. 55. The drug product of claim 54, comprising first, second and third drums and first and second knock gears. 56. A method of patient compliance comprising the acts of: providing the drug product of claim 35, administering the drug formulation to a patient, counting down a number of available doses remaining in the container on the actuation indicating assembly, and indicating the number of available doses remaining in the container to the patient. 57. The method of claim 56, wherein the container is over-filled with up to 40 actuations. 58. The method of claim 56, wherein the actuation indicating assembly locks out when the count reaches 000 and the drug product remains actuable for up to 40 subsequent actuations. 59. A drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a means for driving a slipping clutch means adapted to engage the post and to frictionally engage the slipping clutch means for grasping a ratcheting means; a pawl means for ratcheting a star wheel adapted to engage the slipping clutch means; a star wheel adapted to engage the pawl ratcheting means; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. 60. The drug product of claim 59, comprising first, second and third drums, and further comprising a means for stopping the first drum. 61. The drug product of claim 59, further comprising a first means for knock locking the first and second drums, and a second means for knock locking the second and third drums. 62. The drug product of claim 59, further adapted to indicate a count of 000 to 999, and further adapted to lock the drums when the count indicates 000. 63-69. (canceled)
RELATED APPLICATION The present application claims priority from UK patent application No. 0214360.0 filed 21 Jun. 2002 and UK patent application No. 0311191.1 filed 15 May 2003, the entire contents of which are hereby incorporated herein by reference. FIELD OF THE INVENTION The present invention relates to an actuation indicator for a dispensing device, e.g. a fluid dispensing device or pressurised fluid dispensing device, such as a pressurised metered dose inhaler (hereinafter referred to as a “pMDI”), and components of such an actuation indicator. BACKGROUND OF THE INVENTION “pMDIs” are well known in the art of inhalation devices. It is therefore not necessary to describe the construction and operation of a PMDI other than in bare essentials. A PMDI comprises an aerosol canister and a tubular actuator. The aerosol canister comprises a pressurised can, typically made from a metal, such as aluminium. Inside the can there is contained the pressurised medicinal aerosol formulation. The can is sealingly capped by a metering valve assembly at what will hereinafter be referred to as the “outlet end” of the aerosol canister. The valve assembly includes a hollow dispensing member or valve stem which projects from the outlet end of the aerosol canister. The dispensing member is mounted for sliding movement relative to the aerosol canister between an extended position, to which the dispensing member is biased by a biasing mechanism in the valve assembly, and a depressed position. Movement of the dispensing member from the extended position to the depressed position results in a metered dose of the aerosol formulation being dispensed from the canister through the dispensing member. The tubular actuator comprises an internal passageway having an open end. The aerosol canister is slidable into the internal passageway through the open end with the outlet end being inserted first into the internal passageway. The actuator has a stand or stem block which receives the dispensing member of the aerosol canister when the aerosol canister is received in the actuator in a “rest position”. The stand has a passageway with an inlet end for receiving the dispensing member and an outlet end which faces a mouthpiece of the actuator. The stand holds the dispensing member stationary in the actuator whereby depression of the aerosol canister from its rest position farther into the actuator to an “actuated position” causes the dispensing member to be displaced from the extended position to the depressed position relative to the canister. A metered dose of the aerosol formulation will thereby be dispensed out of the mouthpiece of the actuator via the internal passageway of the stand. In use, a patient in need of a metered dose of the medicinal aerosol formulation places their lips on the mouthpiece of the actuator and then concurrently inhales and depresses the aerosol canister from the rest position to the actuated position. The inspiratory airflow produced by the patient entrains the medicinal, component of the aerosol into the patient's respiratory tract. Instead of a mouthpiece, there could be provided a nozzle for nasal use. Developments to these pMDIs have included the provision of actuation indicators therefor, for instance dose counters which are either incremented on each actuation of the pMDI to display a running total of the number of doses dispensed from the PMDI or decremented on each actuation to display the number of doses left in the dispenser. See, for example, W096/16686, US-A-4817822 and U.S. Pat. No. 5,482,030. A recently developed dose counter is described in PCT Patent Application No. W098/56444, to Glaxo Group Limited, the entire contents of which are incorporated herein by way of reference. The dose counter is fixably secured on the outlet end of the aerosol canister and includes a display which denotes the number of metered doses of the medicament formulation left in the aerosol canister. The display of the dose counter is visible to the patient through a window provided in the actuator. The display is presented by a plurality of indicator wheels rotatably mounted on a common axle, each wheel having numerals from ‘0’ to ‘9’ displayed in series around the circumference. Before the dose counter is mounted on the aerosol canister, the display wheels are arranged so that the display shows the claimed total number of doses available in the aerosol canister, the so-called “label claim”. Upon each actuation, an indexing mechanism in the dose counter comprising a star wheel, a driver yoke and a rack operates to decrement the number displayed by the display by rotation of one or more of the indicator wheels. When the aerosol canister with attached dose counter is in a rest position in the actuator, the rack, which is formed in the actuator, protrudes into the dose counter. When the aerosol canister is moved from the rest position to the actuated position, this results in relative movement between the dose counter and the rack. During this relative movement, the rack engages the yoke of the indexing mechanism to cause it to operate to decrement the number displayed by the display by turning the star wheel. The index mechanism of the mechanical dose counter known from W098/56444 includes a lost motion coupling to compensate for overtravel of the dose counter relative to the rack as the aerosol canister reciprocates between the rest position and the actuated position in the actuator. A device and method for attaching a dose counter to an aerosol canister is disclosed in PCT application publication WO01/28887, also to Glaxo Group Limited, the entire contents of which are incorporated herein by way of reference. The dose counter is fixedly secured to the outlet end of the aerosol canister through a split-ring collar. More particularly, a skirt portion of the dose counter housing surrounds a neck on the can of the aerosol canister, and the split-ring collar is wedged in-between the skirt and a re-entrant surface of the neck and then ultrasonically welded to the skirt. This effectively provides a permanent connection between the dose counter and the aerosol canister to prevent the dose counter from being tampered with. All these prior art devices, however, require the components thereof to be manufactured to tight tolerances so that they correctly function, or they are difficult to assemble. Accordingly, they are relatively expensive to manufacture. Further, they are unsuitable for attachment to canisters or actuators that are made with wide manufacturing tolerances, as may occur when attempting to reduce the manufacturing cost of actuators or aerosol canisters. It would be desirable to provide an actuator and/or dose counter that is inexpensive to manufacture due to the lack of the need for tight manufacturing tolerances. It would also be desirable to provide an actuator and/or dose counter that is simple and therefore inexpensive to assemble. It would also be desirable to provide an actuator and/or dose counter that can be used with more than one size of aerosol canister. It would also be desirable to provide components of such devices that allow for wide manufacturing tolerances. SUMMARY OF THE INVENTION According to a first aspect of the present invention there is provided an axle of a rotatable element of an actuation indicator (e.g. a dose counter), wherein the axle is provided by a spring that is adapted in use to bias the rotatable element towards another element of the actuation indicator with which the rotatable element is engaged. The other element may be for causing rotation of the rotatable element, or caused to be rotated by the rotatable element. This biasing allows the two elements to be made with wide tolerances while still being able to operate correctly together. Preferably the rotatable element is a pinion. Preferably the other element with which the pinion engages is a rack, for instance extending through the dose counter. Preferably the rotatable element is an indicator wheel for indicating actuation of a device with which the indicator is associated, e.g. for indicating at least a part of a count of the number of doses of a substance left in, or dispensed from, a dispensing device. Preferably there are at least two rotatable elements on the axle, for instance three rotatable elements as in the exemplary embodiment hereinafter to be described. The rotatable elements may respectively be a units wheel and a tens wheel, and hundreds wheel where there is a third rotatable element, for indicating a dose count. Preferably the other element is a rotatable element mounted on a second, preferably parallel, axle. More preferably, the second axle is also provided by the spring. The present invention further provides an axle assembly comprising the axle, the rotatable element(s) on the spring axle and the other element. Preferably the spring also comprises a biasing section which connects the axles and biases the axles towards one another. The section may (i) be U-shaped, (ii) have substantially parallel sides and (iii) be substantially perpendicular to the two axles. The present invention further provides an actuation indicator comprising a drums sub-assembly comprising a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, wherein the slipping clutch arrangement comprises a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl. Preferably the slipping clutch spring has a generally U-shaped configuration. Preferably the open end of the spring engages a boss of the pinion and the closed end of the spring defines a track for slidingly engaging a boss provided on the pawl. Preferably the ratchet pawl engages a ratchet wheel that is fixed to the indicator wheel. Preferably a resilient, non-return leg engages a tooth of the ratchet wheel to prevent rotation of the ratchet wheel in a direction other than the set direction, and the non-return leg rides up and over the teeth to allow rotation in the set direction. Preferably there are at least two indicator wheels arranged to sequentially count down from a set figure to zero, there being at least a tens wheel and a units wheel, wherein the indicator wheels lock from further rotation in the set direction when they have counted down to zero, the slipping clutch spring then slipping upon further attempts to rotate the mechanism. The present invention also provides a casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part having a generally cylindrically shaped section having a generally cylindrical inner surface extending from a top of the sleeve part towards a base wall, and a collar affixable around a neck of the canister, and sized, when around the neck of the canister, to fit through the top of the sleeve part, into the sleeve part, whereat it will contact at least a portion of the generally cylindrical inner surface, wherein the generally cylindrical inner surface has a shoulder for supporting the collar to prevent the collar from being inserted further into the sleeve part, the shoulder being spaced from the top and the base wall of the sleeve part. In accordance with the invention in all its aspects, the canister unit may be a pressurised canister unit, such as an aerosol canister unit, e.g. for use in a pressurised metered dose inhaler. Preferably the top of the sleeve part comprises a chamfered surface to assist with the insertion of the collar into the sleeve part. Preferably the shoulder is formed by an annular step in the generally cylindrical inner surface. Preferably the shoulder is formed by a ledge attached to the generally cylindrical inner surface. Preferably the collar is a split ring collar. Preferably the collar, in an assembled canister unit, is welded to the sleeve part. The present invention also provides a casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part for receiving a canister and a cap part for receiving a counter assembly of a dose counter for the canister unit, wherein the cap part and counter assembly can be assembled together separate from the sleeve part and canister, the sleeve part and cap part then being joinable together to form the casing. Preferably, the casing further comprises a counter assembly, the counter assembly comprising a drums sub-assembly. Preferably the sleeve part is adapted to receive more than one form or type of valve stem end, e.g. pressurised fluid canisters fitted with different valves. Preferably the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support being for supporting a different form of valve stem end, whereby more than one different valve stem end can be supported in the sleeve part. Preferably the supports are annular ledges. Preferably the ledges are concentric. Preferably a first said support is of a first height above the base wall and a second said support is of a lesser height above the base wall. The present invention also provides components for the above casing comprising a cap part and at least two sleeve parts, the two sleeve parts being for different valve stem ends, wherein the cap part is joinable to any one of the sleeve parts to form a casing for a chosen valve stem end. The present invention also provides a sleeve part for receiving a valve stem end of a canister, the sleeve part being adapted to receive more than one form of valve stem end. Preferably the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support adapted for supporting a different form of valve stem end, whereby more than one different form of valve stem end is able to be supported in the sleeve part. Preferably the supports are annular ledges. Preferably the ledges are concentric. Preferably a first support is of a first height above the base wall and the second support is of a lesser height above the base wall. The present invention further provides a drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and, an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a drive wheel adapted to engage the post and to frictionally engage a slipping clutch; a ratchet pawl adapted to engage the slipping clutch; a star wheel adapted to engage the ratchet pawl; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. Preferably there are three drums adapted to display a count of 000 to 999. Preferably, the product further comprises an arm affixed to a hundred's drum adapted to contact a stop, wherein the slipping clutch is adapted to frictionally slip when the count reaches 000. Preferably the drug product comprises a hundred's drum having numerals 0, 1 and 2, a ten's drum having numerals 0 through 9 and a one's drum having numerals 0 through 9. Preferably the actuation indicating assembly includes one or more grip members adapted to fixedly engage a neck portion of the container. Preferably the housing includes a mouthpiece. Preferably the housing includes a passage adapted to pass doses from the container to the mouthpiece. Preferably the container includes a metering valve adapted to dispense metered doses. Preferably a window is provided, adapted to display numerals on one or more drums engaging the star wheel. Preferably the actuation indicating assembly is fixed to the container by an adhesive, a welded shrink sleeve, a heat form, a crimp, an ultrasonic weld, an o-ring elastomer, or a split-ring collar. Preferably the actuation indicating assembly is permanently fixed to the container. Preferably the medicament is selected from the group consisting of beclomethasone, fluticasone, flunisolide, budesonide, rofleponide, mometasone, triamcinolone, noscapine, albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, terbutaline, tiotropium, ipratropium, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine, tulobuterol, (-)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl}methyl}benzenemethanol, esters, solvates and salts thereof, and combinations thereof. Preferably the medicament is albuterol sulphate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate or the combination of salmeterol xinafoate and fluticasone propionate. The medicament may also be salmeterol xinafoate and a salt, ester or solvate of ipratropium. Preferably the housing is constructed from polypropylene. Preferably one or more components of the actuation indicating assembly is constructed from polypropylene. Preferably the drug product further comprises one or more knock gears adapted to engage the one or more drums. Preferably the drug product comprises first, second and third drums and first and second knock gears. The present invention also provides a method of patient compliance comprising the acts of: providing a drug product as described above, administering the drug formulation to a patient, counting down a number of available doses remaining in the container on the actuation indicating assembly, and, indicating the number of available doses remaining in the container to the patient. Preferably the container is over-filled with up to 40 actuations. Preferably the actuation indicating assembly locks out when the count reaches 000, and wherein the drug product remains actuable for up to 40 subsequent actuations. The present invention further provides a drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and, an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a means for driving a slipping clutch means adapted to engage the post and to frictionally engage the slipping clutch means for grasping a ratcheting means; a pawl means for ratcheting a star wheel adapted to engage the slipping clutch means; a star wheel adapted to engage the pawl ratcheting means; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. Preferably the drug product comprises first, second and third drums. Preferably the drug product further comprises a means for stopping the first drum. Preferably the drug product further comprises a first means for knock locking the first and second drums and a second means for knock locking the second and third drums. Preferably the drug product is further adapted to indicate a count of 000 to 999 and further adapted to lock the drums when the count indicates 000. The present invention further provides a dispensing device, e.g. for dispensing a fluid, on which is mounted an actuation indicator either according to the invention or having one or more of the different aspects of the invention as a component thereof. The actuation indicator will be adapted to be operated upon each actuation of the dispensing device to indicate said actuation of the device. Preferably, the actuation indicator will be in the form of a dose counter which displays a numerical count of the number of doses of the content of the device left to be dispensed, or the number of doses dispensed. On actuation of the device, the numerical count is either incremented or decremented, depending on whether the count is of doses left or of doses dispensed. Preferably, the dispensing device has a dispensing or outlet end and the actuation indicator is mounted on this end. Preferably, the dispensing device is an aerosol canister having a can and a valve assembly at the outlet end. The valve assembly may be a metering valve assembly, as for example where for use in a pressurised metered dose inhaler. These and other aspects of the present invention will now be described by way of example with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic perspective view of a pressurised metered dose inhaler (PMDI) having a dose counter module mounted on the outlet end of an aerosol canister unit containing a pressurised medicinal aerosol formulation. FIG. 2 is an exploded perspective view of the dose counter module. FIG. 3 is a further exploded perspective view of the dose counter module, but with a drums sub-assembly and drive wheel sub-assembly of the dose counter in assembled form. FIG. 4 is a first perspective view of a cap part of the dose counter module with the drums sub-assembly and drive wheel sub-assembly mounted therein. FIG. 5 is a second perspective view of the cap part from an opposite direction to that of FIG. 4, with a clutch spring fitted thereto. FIG. 6 is a yet further perspective view of the cap part. FIG. 7 is a perspective front view of the drums sub-assembly. FIG. 8 is a schematic perspective view of the dose counter module inside an actuator of the pMDI, showing the drums and drive wheel sub-assemblies and a rack formed inside the actuator through which the drive wheel sub-assembly is driven. FIG. 9 is a schematic rear perspective view of the drive wheel sub-assembly showing a toggle link-type lost motion coupling through which drive from the drive wheel sub-assembly is transmitted to the drums sub-assembly. FIGS. 10 to 13 are schematic views showing the sequence of steps by which the drive wheel sub-assembly drives the drums sub-assembly. FIGS. 14A-F are a series of views illustrating how the knock gears of the drums sub-assembly transmit rotation from one drum to another to decrement the number displayed by the drums sub-assembly. FIGS. 15A-B are schematic views illustrating the operation of the knock gears. FIGS. 16A-F are a series of views illustrating how the drums sub-assembly reaches a “lockout” state in which the number displayed by the counter is not able to be advanced, while allowing continued actuation of the aerosol canister. FIGS. 17A-B are schematic views illustrating the lockout operation. FIG. 18 is a perspective view of a sleeve part in accordance with the invention for a casing of a canister unit having a diameter of approximately 22 mm. FIG. 19 is an end view of the sleeve part of FIG. 18 viewed in the direction of arrow A. FIG. 20 is an end view of the sleeve part of FIG. 18 viewed in the direction of arrow B. FIG. 21 is a section of the sleeve part through line B of FIG. 19. FIGS. 22 and 23 are sections through a pMDI having a canister unit inserted in an actuator, the canister in FIG. 22 having a valve of a first configuration and the canister in FIG. 23 having a valve of a second, different configuration. DETAILED DESCRIPTION OF THE DRAWINGS FIG. 1 shows a pressurised metered dose inhaler, or PMDI, 1. The PMDI 1 comprises a tubular actuator 3 of a generally L-shape. The actuator 3 is provided with an open-ended through passage or internal passageway 5 which extends from an upper opening or open end 7 to a lower opening (not shown) in a mouthpiece 9. The actuator further comprises a viewing window 11. The pMDI 1 further comprises an aerosol canister unit 15, which comprises an aerosol canister 17, shown in ghost and having a standard construction as described in the ‘Background of the Invention’ section above, and a dose counter module 19 mounted on the outlet end of the canister 17. The aerosol canister 17 contains a pressurised medicinal aerosol formulation, for example a therapeutic agent suspended or dissolved in a liquified gas propellant, typically a hydrofluoroalkane (HFA) propellant, such as HFA-134a or HFA-227. As will be understood from the ‘Background of the Invention’ section above, the aerosol canister unit 15 is adapted to be slid into the passageway 5 of the actuator 3 through the upper opening 7 when the aerosol canister unit 15 is inverted, i.e. with the dose counter module 19 at the leading end, so that it is inserted first into the actuator 3. The aerosol canister unit 15 is slid along the passageway 5 to a rest position in which a dispensing member (not shown) of the aerosol canister 17, which projects into the dose counter module 19, engages a stand (not shown) in the passageway 5 so that the dispensing member is held stationary in the actuator 3. Further depression of the aerosol canister unit 15 into the passageway 5 causes the dispensing member to be depressed into the aerosol canister 17 and a metered dose of the medicinal aerosol formulation will then be dispensed from the aerosol canister 17. The dose will thereby be exhausted from the actuator 3 through the mouthpiece 9. For correct angular orientation of the aerosol canister unit 15 in the actuator 3, the passageway 5 defines a longitudinal inner track portion 21 to receive a complementary protrusion 23 on the outer circumferential surface of the dose counter module 19. The protrusion coincides with a display window 25 of the dose counter module. The window 11 of the actuator 3 is located in the wall of the longitudinal track portion 21 to ensure that the display window 25 on the protrusion 23 registers with the window 11 of the actuator 3. A patient can thereby view the display in the dose counter window 25 when the aerosol canister unit 15 is mounted in the actuator 3. Referring to FIGS. 1 and 2, the dose counter module 19 has a hollow outer casing 30 made from a plastics material, for example polypropylene (PP). As shown in FIG. 2, the outer casing 30 is formed from a cap part 31 and a sleeve part 33. The cap part 31 has a plurality of posts 35 which project upwardly (in inverted orientation) from the periphery of the cap part 31. They are provided to extend through alignment holes (not shown) in the sleeve part 33. The posts 35 are subsequently joined or adhered to an inner surface of the sleeve part 33, for example by welding, such as ultrasonic welding. This ensures a permanent connection of the cap part 31 to the sleeve part 33. The cap and sleeve parts 31,33 both comprise elements of the protrusion 23 of the dose counter module 19. The window 25 is retained in a track 39 formed in those elements of the protrusion 23 when the cap and sleeve parts 31, 33 are mated together. The window may be made of a transparent plastics material, for instance polymethyl methacrylate (PMMA), such as PERSPEX (RTM). As shown in FIGS. 2 to 6, the cap part 31 has a generally U-shape cross section. When the dose counter module 19 is mounted to the outlet end of the aerosol canister 17, the dispensing member (not shown) of the aerosol canister 17 is received in the concave cut-out 41 of the U-shaped cap part 31. Moreover, when the aerosol canister unit 15 is slid into the actuator 3 to its rest position, the stand is received in the cut-out 41 for engagement with the dispensing member. In other words, the cap part 31 of the dose counter module 19 is arranged about the stand. See W098/56444, and in particular FIG. 1 thereof, for a fuller disclosure of the dispensing member and the stand therefor. Turning to FIG. 2, when the dose counter module 19 is assembled, it is mounted to the outlet end of the aerosol canister 17 through a split-ring collar 43, for example made of PP, which is mounted to the neck on the can of the aerosol canister 17 and then wedged between the neck and an inner circumferential surface 45 of the sleeve part 33 of the outer casing 30 prior to welding it thereto by ultrasonic welding, as further detailed in WO-A-0128887, supra. The outer casing 30 of the dose counter module 19 houses a mechanical dose counting mechanism, details of which now follow. As shown in FIG. 4, the cap part 31 of the outer casing 30 retains a drums sub-assembly 50 of the counting mechanism. Referring also to FIG. 2, the drums sub-assembly 50 comprises an axle spring 51 having an upper axle 53, a lower axle 55, which extends parallel to the upper axle 53, and a U-shaped connector section 57 oriented perpendicularly to the upper and lower axles 53,55. The axle spring 51 is made from a metal, such as a stainless spring steel. The connector section 57 operates to bias the upper and lower axles 53, 55 to a closed position, i.e. towards one another. The drums sub-assembly 50 further comprises a set of three indicator wheels 59, 61, 63 which are adapted to be co-axially mounted on the upper axle 53 for rotation thereon. The indicator wheels 59, 61, 63 are formed from a plastics material, e.g. acetal, ideally by injection moulding. Each indicator wheel 59, 61, 63 is provided with a central aperture 60, 62,6 4 to enable them to be slid onto the upper axle 53 of the axle spring 51. Each indicator wheel 59, 61, 63 has numbers arranged circumferentially in order on the rims 65, 67, 69 of the wheels 59, 61, 63, applied for example in the manner disclosed in International patent application publication WO-A-0108733, also to Glaxo Group Limited. The rotational position of each indicator wheel 59, 61, 63 on the upper axle 53 determines which number on its rim 65, 67, 69 is displayed through the window 25 of the dose counter module 19. The indicator wheels 59,6 1, 63 collectively display a three digit number in the window 25, which number identifies the number of metered doses of the medicinal aerosol formulation left in the aerosol canister 17. Thus, at the outset, i.e. before use, the indicator wheels 59, 61, 63 are arranged on the upper axle 53 so that the three digit number displayed in the window 25 corresponds to the label claim of metered doses available in the aerosol canister 17. It is convenient to refer to the right-hand indicator wheel 59 (as viewed in e.g. FIG. 7) as the “units wheel”, the central indicator wheel 61 as the “tens wheel” and the left-hand indicator wheel 63 as the “hundreds wheel” because the numbers displayed thereon correspond to the units, tens and hundreds of the dose count displayed in the window 25. It will be appreciated that the use of three indicator wheels 59, 61, 63 enables the dose counter module 19 to be used with an aerosol canister which is filled with over one hundred metered doses of a medicinal aerosol formulation. As will be understood, the number of indicator wheels could be increased or decreased depending on the number of metered doses in the aerosol canister 17. For instance, if the “label claim” was less than a hundred metered doses, it may be convenient to use only two indicator wheels. Of course, three indicator wheels could still be used. In this embodiment, the units and tens wheels 59, 61 each have the numbers ‘0’ to ‘9’ inclusive equi-angularly arranged thereon in series, while the hundreds wheel 63 only has the numbers ‘0’ to ‘2’ inclusive arranged thereon in series, although with the same inter-number angular spacing (36°) as for the numbers on the units and tens wheels 59, 61. Of course, the series of numbers on the hundreds wheel 63 can be increased or decreased, depending on the “start count” desired. As shown in FIGS. 2 and 5, the units wheel 59 has a ratchet wheel 71 on its right-hand side which is provided with teeth 74 on its circumference 73. The ratchet wheel 71 is supported on the end of a shaft 72 (see FIGS. 7 and 14B). Referring now to FIGS. 7, 14F and 15A, the left-hand side of the units wheel 59 is provided with a boss 75 provided with just two teeth (a “bunny” tooth 77). As shown in FIG. 2, the tens wheel 61 and the hundreds wheel 63 each have a boss 79, 81 on the right-hand side with a toothed circumference 83, 85. FIG. 7 shows that the toothed circumferences 83, 85 have teeth 87,89 whose tips are flush with the rims 67, 69 of the associated indicator wheel 61,63. As shown in FIGS. 7 and 14F, the tens wheel 61 is further provided with a boss 91 on its left-hand side which is also provided with a bunny tooth 93 on its outer circumference 95. As further shown in FIGS. 7 and 14F, as well as FIG. 4, the hundreds wheel 63 has a boss 97 having an outer circumference 99 provided with a radially protruding segment 101 which lies flush with the rim 69 of the hundreds wheel 63. Referring to FIG. 2, the drums sub-assembly 50 further comprises a set of two knock gears 103,105 having axial apertures 107,109 which enable the knock gears 103, 105 to be co-axially mounted on the lower axle 55 of the axle spring 51 for rotation thereon. As shown in FIG. 7, for example, each knock gear 103,105 has a toothed wheel portion 111, 113, a disc portion 115,117 arranged parallel to the associated toothed wheeled portion 111, 113, but axially offset therefrom, and an axially-arranged hollow shaft portion 119, 121 which connects the associated toothed wheel and disc portions 111, 113:115, 117. The knock gears are made of a plastics material, e.g. acetal, and are ideally made by injection moulding. The disc portions 115, 117 of the knock gears 103, 105 function to locate the knock gears and indicator wheels correctly in the cap part 31. In particular, the disc portions 115, 117 inhibit axial play of the indicator wheels and knock gears on the axle spring 51 by overlapping the outer surfaces of the units and hundreds wheels 59, 63, on the one hand, and being overlapped by surface features in the cap part 31 (not shown), on the other hand. So, neither the indicator wheels 59, 61, 63 nor the knock gears 103, 105 can be outwardly axially displaced on the spring axle 51 once located in the outer casing 30. As further shown in FIG. 7, the toothed wheeled portions 111, 113 of the knock gears 103, 105 are divided into two axial sections, a right-hand side section 123, 125 and a left-hand side section 127, 129. The number of teeth presented by the right-hand side sections 123, 125 (4 teeth) is less than the number of teeth presented by the left-hand side sections 127, 129. As will be understood from FIG. 7, when the indicator wheels 59, 61, 63 and knock gears 103, 105 are mounted on the upper and lower axles 53, 55, respectively, the rims 65, 67 of the units and tens wheels 59, 61 are rotatably supported between adjacent teeth in the right-hand side sections 123, 125 of the toothed wheeled portions 111, 113 of the knock gears 103, 105. Moreover, the teeth 87, 89 on the tens wheel 61 and the hundreds wheel 63 mesh with the teeth of the left-hand side sections 127, 129 of the toothed wheel portions 111, 113 of the knock gears 103, 105. As will be further understood from FIG. 7, for example, the inherent biasing force in the axle spring 51 ensures that the indicator wheels 59, 61, 63 and knock gears 103, 105 are biased towards one another so that the interengagable circumferential surfaces thereof interengage one another. In other words, the upper and lower axles 53, 55 need to be parted against the action of the biasing force to accommodate the indicator wheels 59, 61, 63 and knock gears 103, 105. Thus, in the assembled state of the drums sub-assembly 50, the upper and lower axles 53, 55 are spaced apart by a distance which is greater than their spacing in the rest or return state of the axle spring 51. Accordingly, the upper and lower axles 53, 55 push the indicator wheels 59, 61, 63 and knock gears 103, 105, respectively, towards one another. A good connection between the indicator wheels 59, 61, 63 and knock gears 103, 105 therefore results. Also mountable in the cap part 31 of the outer casing 30 of the dose counter module 19 is a drive wheel sub-assembly 150 of the counting mechanism. Referring to FIG. 2 to 6, the drive wheel sub-assembly 150 comprises a drive wheel 151 having a pinion 153 having an outer circumference 155 defined by a series of teeth 157. The drive wheel 151 further comprises a boss 159 extending axially from the left-hand side of the pinion 153 (as viewed in e.g. FIG. 2). An axial passage or passageway 161 extends through the pinion 153 and the boss 159. The drive wheel 151 is a plastics component of the dose counter module 19, e.g. of acetal, for instance made by injection moulding. The drive wheel sub-assembly 150 further comprises a drive wheel support spring 163 made from a metal, such as stainless steel. The drive wheel support spring 163 defines an axle section 165 which is insertable into the axial passageway 161 of the drive wheel 151 for rotatable support of the drive wheel 151. The drive wheel sub-assembly 150 yet further comprises a slipping clutch spring 167, preferably formed from a metal, such as stainless spring steel. The clutch spring 167 is of a generally U-shaped configuration having a pair of generally parallel arm sections 169, 171 connected by a U-bend connector section 173. The connector section 173 biases the arm sections 169, 171 to be closed together thereby enabling the arm sections 169, 171 to be clamped onto the boss 159 of the drive wheel 151, as shown in FIG. 9, for example. More particularly, one of the arm sections 169 of the clutch spring 167 is formed with a curved portion 175 adjacent its free end which is of complementary size and shape to the outer circumferential surface 177 of the boss 159. Thus, when the drive wheel 151 rotates on the axle section 165 of the drive wheel support spring 163, the clutch spring rotates therewith. However, if a sufficient force is applied to the clutch spring 167 which opposes its rotation with the drive wheel 151, the clutch spring 167 slips on the boss 159. Therefore, the rotation of the drive wheel 151 will not be transmitted to the slipping clutch spring 167. FIG. 2 shows that the dose counting mechanism further comprises a rotatable plastics pawl 200 (e.g. acetal) having a pawl arm 201 with a pawl tooth 203 at its tip, a C-shaped hub 205 shaped to be rotatably mounted on the shaft 72 of the units wheel 59, and a boss 207 extending axially from the right-hand side of the rotatable pawl 200 which is adapted to be slidingly received in the track 174 defined between the arm sections 169, 171 of the clutch spring 167. The pawl may be injection moulded. The assembled state of the counting mechanism is shown in FIG. 7, and its arrangement in the cap part 31 of the outer casing 30 of the dose counter module 19 is shown in FIGS. 4-6. The operation of the counting mechanism to show the number of metered doses of the medicinal aerosol formulation left will now be described. When the aerosol canister unit 15 is in its rest position in the actuator 3, the counting mechanism of the dose counter module 19 is in the state shown in FIGS. 8, 9 and 10A-B. More particularly, a rack 13 projecting upwardly from a base surface of the actuator 3 extends through an aperture 20 in the cap part 31 of the outer casing 30 of the dose counter module 19 so that a set of teeth 14 on the rack 13 mesh with the teeth 157 of the pinion 153 of the drive wheel 151. In this regard, the drive wheel support spring 163 biases the drive wheel 151 towards the window 25. The interaction of the rack 13 with the pinion 153 causes the drive wheel 151 to be displaced against the biasing force of the drive wheel support spring 163. This results in the pinion teeth 157 being biased against the rack teeth 14 thereby ensuring a good engagement therebetween. In the rest position of the aerosol canister unit 15 in the actuator 3, the rotatable pawl 200 has an angular orientation relative to the ratchet wheel 71 which results in the pawl tooth 203 engaging behind one of the ratchet teeth 74. If the aerosol canister unit 15 has been previously unused, the indicator wheels 59,61,63 are arranged on the upper axle 53 of the axle spring 51 so that the numerical indicia thereon are lined up to show in the window 25 of the actuator 3 the starting number of metered doses available in the aerosol canister 17 for dispensing. This starting number corresponds to the number of metered doses stated on the label of the aerosol canister 17, e.g. the “label claim”. As an example, the starting number of metered doses may be ‘160’, as indicated in FIG. 15A. The label claim need not, however, match the actual number of available doses since an aerosol canister will usually be overfilled slightly to allow for losses during storage, for example. This also provides a reserve of doses for a user once the counter has reached zero in case of emergencies. When a patient wishes to dispense a metered dose of the aerosol formulation, the patient places their lips on the mouthpiece 9 of the actuator 3 then simultaneously inhales and depresses the aerosol canister unit 15 into the actuator 3. The start of this downstroke of the aerosol canister unit 15 into the actuator 3 is shown in FIGS. 11A-B. In comparison FIGS. 10A-B shows the counting mechanism at rest. The downstroke causes the dose counter module 19 to move downwardly in the direction of arrow A relative to the rack 13 of the actuator 3. This relative movement causes the teeth 14 of the rack 13 to rotate the drive wheel 151 in the direction of arrow B through its interaction with the pinion 153. The rotation of the drive wheel 151 causes the clutch spring 167 mounted on the boss 159 to rotate therewith. This in turn causes the rotatable pawl 200 to rotate on the shaft 72 of the units wheel 59 in the direction of arrow C, which direction is opposite to the direction of rotation B of the drive wheel 151. As will be appreciated from FIG. 11A, the rotation of the pawl 200 in the direction of arrow C is caused through the location of the boss 207 of the pawl 200 in the guide track 174 defined in the clutch spring 167. As will be further appreciated from FIG. 11A, the rotation of the pawl 200 in the direction of arrow C on the units wheel 59 causes the pawl arm 201 to disengage from behind the trailing surface of the ratchet tooth 74 it was engaged with in the rest position, and to slide up the leading flank surface of the next adjacent ratchet tooth 74. Continued depression of the aerosol canister unit 15 into the actuator 3 causes the valve thereof to open, and for a metered dose of the medicinal aerosol formulation to be discharged from the mouthpiece 9, generally, in use, into the respiratory tract of the patient. As shown in FIG. 12A, the rotation of the pawl 200 on the units wheel 59 is continued until the pawl tooth 203 drops behind the trailing flank surface of the next adjacent ratchet tooth 74. From this it will be appreciated that the pawl arm 201 is a resilient arm whereby the pawl tooth 203 at the free end thereof falls from the tip of one ratchet tooth 74 to the leading flank surface of the next adjacent ratchet tooth during the downstroke. The rotation of the pawl 200 on the units drum 59 is not transmitted thereto due to a fixed pawl or resilient non-return leg 18 in the cap part 31 of the outer casing 30 of the dose counter module 19 engaging behind the trailing flank surface of one of the ratchet teeth 74 of the ratchet wheel 71 of the units wheel 59. Comparison of FIG. 12A to FIG. 11A shows that the rotation of the pinion 153 of the drive wheel 151 is able to be translated into counter-rotation of the pawl 200 on the units wheel 59 through the ability of the boss 207 of the pawl 200 to slide in the guide track 174 defined in the clutch spring 167. In other words, there is a “toggle link”-type coupling between the drive wheel 151 and the pawl 200. As further shown in FIG. 12A, when the rack 13 causes the pinion 153 to rotate the drive wheel 151 a predetermined angle, the pawl 200 abuts with an end stop 221 which extends downwardly from the sleeve part 33 of the outer casing 30 of the dose counter module 19. This prevents the pawl 200 over-rotating on the units wheel 59 and the pawl tooth 203 being indexed over more than one ratchet tooth 74 on the downstroke of the aerosol canister unit 15. Once the pawl 200 bears against the end stop 221, continued depression of the aerosol canister unit 15 into the actuator 3 (e.g. to open the valve) is accommodated by the clutch spring 167 slipping on the boss 159 of the drive wheel 151 (as a result of the clutch spring 167 only being retained thereon by friction forces). That is to say, the drive wheel 151 is free to continue rotating once the pawl 200 abuts with the end stop 221 without this rotation being transmitted to the pawl 200 due to the drive wheel 151 rotating relative to the clutch spring 167, i.e. there is a lost motion coupling. Once the aerosol canister unit 15 has been depressed to the bottom of its downstroke, and a metered dose of the medicinal aerosol formulation released, the patient releases, or reduces, the downward pressure on the aerosol canister unit 15 whereupon the biasing mechanism in the valve assembly of the aerosol canister 17 biases the aerosol canister unit 15 back towards its rest position. The return stroke of the aerosol canister unit 15 in the actuator 3 is shown schematically in FIGS. 13A-B. As shown, as the aerosol canister unit 15 is translated upwardly in the direction of arrow D, the engagement of the rack 13 with the pinion 153 causes the drive wheel 151 to rotate in an opposite direction (arrow E). The toggle-link coupling between the drive wheel 151 and pawl 200 causes the pawl 200 to rotate in an opposite direction (arrow F). The rotation of the pawl 200 in the direction of arrow F causes the pawl arm 201 to pull the units wheel 59 in the same direction through the engagement of the pawl tooth 203 with the trailing flank surface of the ratchet tooth 74 which it dropped over on the downstroke of the aerosol canister unit 15 in the actuator 3. In this regard, the fixed pawl 18 is resiliently formed so that it is able to be flexed out of the way by one of the ratchet teeth 74 and then drop behind that tooth 74 to prevent counter-rotation of the units wheel 59 at the end of the return stroke of the aerosol canister unit 15 in the actuator 3. As shown in FIG. 9, once the rack 13 has caused the drive wheel 151 to rotate a predetermined angular extent, the pawl 200 abuts with another end stop 66, this time presented by the cap part 31 of the outer casing 30. This prevents the pawl 200 causing more than one ratchet tooth 74 to pass the fixed pawl 18 on the return stroke of the aerosol canister unit 15. If at this stage the return stroke of the aerosol canister unit is incomplete, i.e. the rest position has not been reached, the drive wheel 151 is free to continue rotating relative to the slipping clutch spring 167 in the direction of arrow E (through the engagement of the rack 13 with the pinion 153). The result of the rotation of the units wheel 59 in the direction of arrow F is to cause the numerical indicia it displays in the window 25 to be decreased by one, thereby indicating to the patient that there is now one less metered dose left in the aerosol canister 17. Thus, upon each actuation cycle of the aerosol canister unit 15, the units wheel 59 is caused to be rotatably indexed by an angular amount sufficient to cause the previous units figure displayed in the window 25 to be advanced and replaced by the next unit figure in the series, which is one less than the previous figure. Bearing in mind that the numerical indicia on the units wheel 59 are equi-angularly spaced about the circumference thereof, the units wheel 59 is rotatively indexed by 36° upon each actuation cycle of the aerosol canister unit 15. It will thus be appreciated that the number of ratchet teeth 74 on the ratchet wheel 71 corresponds to the number of numerical indicia on the units wheel 59, i.e. 10. It will further be appreciated that after each complete revolution of the units wheel 59 the same units figure is displayed in the window 25. As the units wheel 59 is rotatively indexed by the pawl-and-ratchet mechanism, the bunny tooth 77 of the units wheel 59 will engage the left-hand side section 127 of the toothed wheel portion 11l of the right-hand knock gear 103 at the same point in each revolution of the units wheel 59 on the upper axle 53. As indicated in FIG. 15A, the bunny tooth 77 is arranged on the units wheel 59 so that its engagement with the left-hand side section 127 of the toothed wheel portion 111 of the right-hand knock gear 103 coincides with the number ‘0’ being displayed by the units wheel 59 in the window 25. The next actuation cycle of the aerosol canister unit 15 causes the bunny tooth 77 to transmit a rotational force to the right-hand knock gear 103, through its engagement with the left-hand side section 127 of its toothed wheel portion 111. The rotation imparted to the right-hand knock gear 103 by the bunny tooth 77 of the units wheel 59 is transmitted to the tens wheel 61 through the meshing of the left-hand side section 127 of the toothed wheel portion 111 with the teeth 87 of the tens wheel 61. The net result of this is that the numerical indicia displayed by the units wheel 59 and tens wheel 61 are concurrently decremented by one. In the case shown in FIGS. 15A-B, the result is to decrement the number displayed in the window 25 from ‘160’ to ‘159’. This is also illustrated in FIGS. 14A-F. During the transmission of the rotational indexing of the units wheel 59 to the tens wheel 61 through the right-hand knock gear 103, the right-hand side section 123 of the toothed wheel portion ill of the right-hand knock gear 103 is received in a recess 78 (FIG. 15A) formed in the rim 65 of the units wheel 59 which is co-extensive with the gap between the ears of the bunny tooth 77. As the tens wheel 61 is incrementally driven by the units wheel 59 through the right-hand knock gear 103 at every complete rotation of the units wheel 59 (when the ‘0’ decrements to ‘9’), the bunny tooth 93 on the tens wheel 61 is advanced towards engagement with the left-hand knock gear 105, specifically the left-hand side section 129 of the toothed wheel portion 113 thereof. As before, when the tens wheel 61 is angularly positioned so that it displays the FIG. 10 in the window 25 (at which point the units wheel 59 also displays its ‘0’ figure in the window 25), the bunny tooth 93 is disposed adjacent a tooth of the left-hand side section 129 of the toothed wheel portion 113 of the left-hand knock gear 105. The result of the next actuation cycle of the aerosol canister unit 15 is to cause the rotation or motion imparted to the tens wheel 59, by the co-operation of the units wheel 59 and the right-hand knock gear 103, to be transmitted to the hundreds wheel 63 in likewise manner. This results in the numerical indicia displayed by the hundreds wheel 63 in the window 25 being decrement by one, whereby the full number displayed in the window by the drums sub-assembly 50 is decremented by one from a number which is a factor of one hundred, e.g. ‘100’ to ‘099’. As will be understood from FIGS. 8 and 14A-F, when the tens wheel 61 drives the hundreds wheel 63 through the left-hand knock gear 105, the right-hand side section 125 of the toothed wheel portion 113 of the left-hand knock gear 105 is received in a recess 94 in the rim 67 of the tens wheel 61 which is co-extensive with the space between the ears of the bunny tooth 93. In addition to the features of the counting mechanism described above, the counting mechanism further comprises a “lockout” arrangement which locks the drums sub-assembly 50 from being driven when each indicator wheel 59, 61, 63 is angularly positioned on the upper axle 53 of the axle spring 51 so that the display reads ‘000’. However, the lockout arrangement is such as not to prevent the aerosol canister unit 15 still being able to be actuated to dispense doses of medicinal aerosol formulation still remaining in the aerosol canister 17. In this connection, as a matter of routine, medicinal aerosol canisters are overfilled (compared to the label claim) for safety issues. For example, for rescue medicaments, such as bronchodilators, it is imperative that the patient still be able to use the aerosol canister unit 15 after the label claim of metered doses has been used. Referring now to FIGS. 4, 16A and 17A, for example, the hundreds wheel 63 carries a peg 98 which, when the hundreds wheel 63 is angularly oriented so as to display a ‘0’ in the window 25, abuts with a stop 42 provided in the cap part 31 of the outer casing 30 of the dose counter module 19. This abutment of the peg 98 with the stop 42 prevents further rotation of the hundreds wheel 63 by the pawl-and-ratchet drive mechanism. Moreover, the left-hand knock gear 105 is also locked from further rotation due to its interengagement with the locked hundreds wheel 63. So, once the hundreds wheel 63 has been locked by the abutment of the peg 98 with the stop 42, the tens wheel 61 is able to complete one further revolution on the upper axle 53 before it too becomes locked from further rotation through engagement of the bunny tooth 93 with the left-hand knock gear 105. The locking of the tens wheel 61 further results in the right-hand knock gear 103 being locked from further rotation due to its tooth engagement with the tens wheel 61. As will be understood, the tens wheel 61 becomes locked out when it too displays a ‘0’ in the window 25. Once the tens wheel 61 has been locked out, the units wheel 59 is able to complete just one more revolution for it to display a ‘0’ in the window 25. The units wheel 59 then in turn becomes locked out by the interengagement of its bunny tooth 77 with the right-hand knock gear 103. See FIGS. 16A-F. If a patient wishes to use the aerosol canister unit 17 after the drums sub-assembly 50 has been locked out, the actuation cycle is still able to be completed through the clutch spring 167 slipping on the boss 159 of the drive wheel 151. In other words, the drive system is disconnected from the drum sub-assembly 50 by the slipping clutch 167. This is shown schematically in FIG. 17B. Referring now to FIGS. 18 to 21, a preferred sleeve part 33 is shown. This sleeve part 33, like the one shown in FIGS. 1 to 3, is adapted to be attached to a cap part 31 (see FIG. 5) to form a casing for a dose counter module 19. It has four holes 131, 132, 133, 134 for receiving posts 35 on the cap part 31. Two of the holes 131, 132 are cylindrical for receiving cylindrical posts 35. The other two holes are generally cylindrical but with a flattened part (i.e. generally D shaped) for receiving correspondingly shaped posts 35 on the cap part 31. The two non-cylindrical holes 133, 134 are relatively rotated so that the cap part 31 can only be fitted in one orientation even if the posts 35 are symmetrically arranged. Differently shaped holes could be provided, and would need to be provided for differently shaped posts 35 such as those shown in FIG. 4 (only one post 35 is non-cylindrical) or FIG. 3 (the posts 35 have a square section, with hook clips 37 on the ends thereof). Two posts 135 are also provided on the sleeve part 33 extending from the bottom 137 thereof. These posts 135 engage into holes 136 provided in the cap part 31 (see FIG. 5). The posts 135 on the sleeve part 33 are shorter than the posts 35 on the cap part 31. The sleeve part 33 is generally cylindrical. However, in the bottom 137, there is moulded a base moulding having a generally U-shaped configuration to match the U-shaped configuration of the cap part 31 defined by the concave cut-out 41 (see, e.g., FIG. 4). This U-shaped base moulding further defines the position for the canister's valve stem 27 (see FIGS. 22 and 23) and the stand or stem block 13 (described above with reference to the prior art) to fit into. Further it defines part of the protrusion 23 described above (the protrusion 23 receives the window 25). The base moulding extends from the bottom 137 of the sleeve part 33 up to a base wall 139. The outlet end of the canister 17 may, in use, rest against an upper side of this base wall 139 (or on supports provided thereon), as will be described with reference to FIGS. 22 and 23 below. The moulding, on its lower side, however, provides, in combination with the cap part 31, a cavity into which the indexing or counting mechanism, such as the drums sub-assembly 50, can be fitted. See FIGS. 22 and 23. The cylindrical portion 140 of the sleeve part 33 can accept more than one style of canister 17, in this embodiment different styles of valve assembly. As an example, FIG. 22 shows a canister 17 which is fitted with a first type of valve assembly 250. FIG. 23 shows the canister 17 fitted with a second, different type of valve assembly 300 (i.e. the can is the same, but the valve assembly differs). As will be seen, the valves 250,300 have valve stem ends 29 (or ferrules) of different shape. In the first valve assembly 250, there is a small nose 49 adjacent the valve stem 27. The nose 49 of the second valve assembly 300, however, is much longer, axially. Moreover, the valve assemblies 250, 300 protrude from the associated cans by a different distance D1, D2, i.e. the valve assemblies 250, 300 have a different thickness. So, the valve stems 27 are spaced outboard from the can at different distances D1, D2. As a result of these differences, the canisters 17 sit differently in the sleeve part 33. However, it is important that the tip of each valve stem 27 be positioned at a common, or substantially common, position relative to a reference surface of the dose counter module 19, e.g. the base wall 139. In other words, the spatial position of the tip of each valve stem 27 in the dose counter module 19, when assembled to the respective aerosol canister 17, must be the same, or substantially the same. Expressed another way, the valve stems 27 must be spaced at the same, or substantially same, distance from the reference surface of the dose counter module 19. To this end, the upper side of the base wall 139 has two differently sized concentric supports or ledges 141, 142. The first ledge 141 comprises an annulus (see FIG. 20) extending upwards from the base wall 139. It has an appropriate height to support, in use, the first valve assembly 250, as shown by arrow 143 in FIG. 22. The second ledge 142 comprises a smaller annulus extending upwards from the base wall 139. It is concentric with the first ledge 141. However, it extends upwards to a lesser extent. It is adapted to support, in use, the second valve assembly 300, as marked by arrow 144 in FIG. 23. The base wall 139 also comprises an aperture 145 in its centre, concentric with the two annuluses. The aperture 145 allows the valve stem 27 of the canister 17 to extend through the base wall 139 so that it can be inserted into the stand or stem block 333. As shown in FIGS. 22 and 23, the ledges 141, 142 respectively support the first and second valve assemblies 250, 300 in the sleeve part 33 such that the valve stems 27 extend through the aperture 45 by the same distance, or substantially the same distance. In this way, the rest positions in the actuator 3 of the aerosol canister units 15 incorporating the different valve assemblies 250,300 is the same, or substantially the same. This is because the spatial position of the valve stem tips in the respective dose counter module 19 is the same. The sleeve part 33 also comprises a split ring collar 43, as previously described, for assisting in the connection of the sleeve part 33 to the canister 17 via the neck 47, which is annular. The wall 147 of the cylindrical portion 140 of the sleeve part 33 has an internal wall surface having a step or shoulder 146 for resting the collar 43 on. FIG. 3 shows this as a separately made ledge that is attached to the internal wall surface. The shoulder 146 assists in locating the collar 43 correctly for adhering or welding it to the sleeve part 33 for securing the canister 17 in the sleeve part 33 with the correct depth of insertion. The top 138 of the wall 147 is chamfered also to assist in the insertion of the collar 43 and canister 17 into the sleeve part 33. The above described components all can easily be fabricated and can be assembled using automated apparatus. Therefore they provide a more cost effective solution than the prior art. Although the pMDI 1 described above with reference to the FIGURES of drawings is shown for oral inhalation, the mouthpiece 9 may be replaced with a nozzle for insertion into a patient's nostril, i.e. for intra-nasal use. The therapeutic agent contained in the aerosol canister 17 may for the treatment of mild, moderate or severe acute or chronic symptoms or for prophylactic treatment. The therapeutic agent is preferably for treating respiratory diseases, e.g. asthma, chronic obstructive pulmonary disease (COPD), although may be for other therapeutic indications, e.g. treating rhinitis. Appropriate therapeutic agents or medicaments may thus be selected from, for example, analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. as the sodium salt), ketotifen or nedocromil (e.g. as the sodium salt); antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyrilene; anti- inflammatories, e.g., beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. as the propionate ester), flunisolide, budesonide, rofleponide, mometasone (e.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as the acetonide), 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioic acid S-(2-oxo-tetrahydro-furan-3-yl) ester or 6α, 9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester; antitussives, e.g., noscapine; bronchodilators, e.g., albuterol (e.g. as free base or sulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g. as hydrobromide), formoterol (e.g. as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. as acetate), reproterol (e.g. as hydrochloride), rimiterol, terbutaline (e.g. as sulphate), isoetharine, tulobuterol or 4-hydroxy-7-[2-([2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H) benzo-thiazolone; PDE4 inhibitors e.g. cilomilast or roflumilast; leukotriene antagonists e.g. montelukast, pranlukast and zafirlukast; [adenosine 2a agonists, e.g. 2R, 3R, 4S, 5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol (e.g. as maleate)]; [α4 integrin inhibitors e.g. (2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbony}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-ethylphenoxy)acetyl]amino)pentanoyl)amino]propanoic acid (e.g as free acid or potassium salt)), diuretics, e.g., amiloride; anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, e.g., aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, e.g., insulin or glucagons. It will be clear to a person skilled in the art that, where appropriate, the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimise the activity and/or stability of the medicament and/or to minimise the solubility of the medicament in the propellant. Preferably, the medicament is an anti-inflammatory compound for the treatment of inflammatory disorders or diseases such as asthma and rhinitis. Preferably, the medicament is formulated in a hydrofluoroalkane propellant, such as HFA-134a or HFA-227 or a combination thereof. Preferably, the medicament is an anti-inflammatory steroid, such as a corticosteroid, for instance fluticasone, e.g. as the propionate ester, or a long acting beta agonist (LABA), such as salmeterol, e.g. as the xinafoate salt, or a combination thereof. Preferred medicaments are salmeterol, salbutamol, albuterol, fluticasone and beclomethasone and salts, esters or solvates thereof, for instance fluticasone propionate, albuterol sulphate, salmeterol xinafoate and beclomethasone diproprionate. The medicament may also be a glucocorticoid compound, which has anti-inflammatory properties. One suitable glucocorticoid compound has the chemical name: 6α, 9α-Difluoro-17α-(1-oxopropoxy)-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester (fluticasone propionate). Another suitable glucocorticoid compound has the chemical name: 6α, 9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester. A further suitable glucocorticoid compound has the chemical name: 6α, 9α-Difluoro-11β-hydroxy-16α-methyl-17β-[(4-methyl-1,3-thiazole-5-carbonyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester. Other suitable anti-inflammatory compounds include NSAIDs e.g. PDE4 inhibitors, leukotriene antagonists, iNOS inhibitors, tryptase and elastase inhibitors, beta-2 integrin antagonists and adenosine 2a agonists. The medicaments may be delivered in combinations. As an example, there may be provided salbutamol (e.g. as the free base of the sulphate salt) or salmeterol (e.g. as the xinafoate salt) in combination with an anti-inflammatory steroid, such as beclomethasone (e.g. as an ester, preferably dipropionate) or fluticasone (e.g. as an ester, preferably propionate). The actuation indicator of the present invention is not limited for use with an aerosol container, as in the example described with reference to the FIGURES of drawings, but may be used with other types of dispensing device. Moreover, the dispensing device need not necessarily be for dispensing medicament. The present invention has been described above purely by way of example. Modifications, in detail, however, may be made within the scope of the invention, as defined in the claims appended hereto. For the avoidance of doubt, the use of words herein such as “substantially”, “generally”, “about” and the like in relation to parameters or properties etc. is meant to encompass the absolute parameter or property as well as non-consequential deviations therefrom.
<SOH> BACKGROUND OF THE INVENTION <EOH>“pMDIs” are well known in the art of inhalation devices. It is therefore not necessary to describe the construction and operation of a PMDI other than in bare essentials. A PMDI comprises an aerosol canister and a tubular actuator. The aerosol canister comprises a pressurised can, typically made from a metal, such as aluminium. Inside the can there is contained the pressurised medicinal aerosol formulation. The can is sealingly capped by a metering valve assembly at what will hereinafter be referred to as the “outlet end” of the aerosol canister. The valve assembly includes a hollow dispensing member or valve stem which projects from the outlet end of the aerosol canister. The dispensing member is mounted for sliding movement relative to the aerosol canister between an extended position, to which the dispensing member is biased by a biasing mechanism in the valve assembly, and a depressed position. Movement of the dispensing member from the extended position to the depressed position results in a metered dose of the aerosol formulation being dispensed from the canister through the dispensing member. The tubular actuator comprises an internal passageway having an open end. The aerosol canister is slidable into the internal passageway through the open end with the outlet end being inserted first into the internal passageway. The actuator has a stand or stem block which receives the dispensing member of the aerosol canister when the aerosol canister is received in the actuator in a “rest position”. The stand has a passageway with an inlet end for receiving the dispensing member and an outlet end which faces a mouthpiece of the actuator. The stand holds the dispensing member stationary in the actuator whereby depression of the aerosol canister from its rest position farther into the actuator to an “actuated position” causes the dispensing member to be displaced from the extended position to the depressed position relative to the canister. A metered dose of the aerosol formulation will thereby be dispensed out of the mouthpiece of the actuator via the internal passageway of the stand. In use, a patient in need of a metered dose of the medicinal aerosol formulation places their lips on the mouthpiece of the actuator and then concurrently inhales and depresses the aerosol canister from the rest position to the actuated position. The inspiratory airflow produced by the patient entrains the medicinal, component of the aerosol into the patient's respiratory tract. Instead of a mouthpiece, there could be provided a nozzle for nasal use. Developments to these pMDIs have included the provision of actuation indicators therefor, for instance dose counters which are either incremented on each actuation of the pMDI to display a running total of the number of doses dispensed from the PMDI or decremented on each actuation to display the number of doses left in the dispenser. See, for example, W 0 96/16686, US-A-4817822 and U.S. Pat. No. 5,482,030. A recently developed dose counter is described in PCT Patent Application No. W 0 98/56444, to Glaxo Group Limited, the entire contents of which are incorporated herein by way of reference. The dose counter is fixably secured on the outlet end of the aerosol canister and includes a display which denotes the number of metered doses of the medicament formulation left in the aerosol canister. The display of the dose counter is visible to the patient through a window provided in the actuator. The display is presented by a plurality of indicator wheels rotatably mounted on a common axle, each wheel having numerals from ‘0’ to ‘9’ displayed in series around the circumference. Before the dose counter is mounted on the aerosol canister, the display wheels are arranged so that the display shows the claimed total number of doses available in the aerosol canister, the so-called “label claim”. Upon each actuation, an indexing mechanism in the dose counter comprising a star wheel, a driver yoke and a rack operates to decrement the number displayed by the display by rotation of one or more of the indicator wheels. When the aerosol canister with attached dose counter is in a rest position in the actuator, the rack, which is formed in the actuator, protrudes into the dose counter. When the aerosol canister is moved from the rest position to the actuated position, this results in relative movement between the dose counter and the rack. During this relative movement, the rack engages the yoke of the indexing mechanism to cause it to operate to decrement the number displayed by the display by turning the star wheel. The index mechanism of the mechanical dose counter known from W 0 98/56444 includes a lost motion coupling to compensate for overtravel of the dose counter relative to the rack as the aerosol canister reciprocates between the rest position and the actuated position in the actuator. A device and method for attaching a dose counter to an aerosol canister is disclosed in PCT application publication WO01/28887, also to Glaxo Group Limited, the entire contents of which are incorporated herein by way of reference. The dose counter is fixedly secured to the outlet end of the aerosol canister through a split-ring collar. More particularly, a skirt portion of the dose counter housing surrounds a neck on the can of the aerosol canister, and the split-ring collar is wedged in-between the skirt and a re-entrant surface of the neck and then ultrasonically welded to the skirt. This effectively provides a permanent connection between the dose counter and the aerosol canister to prevent the dose counter from being tampered with. All these prior art devices, however, require the components thereof to be manufactured to tight tolerances so that they correctly function, or they are difficult to assemble. Accordingly, they are relatively expensive to manufacture. Further, they are unsuitable for attachment to canisters or actuators that are made with wide manufacturing tolerances, as may occur when attempting to reduce the manufacturing cost of actuators or aerosol canisters. It would be desirable to provide an actuator and/or dose counter that is inexpensive to manufacture due to the lack of the need for tight manufacturing tolerances. It would also be desirable to provide an actuator and/or dose counter that is simple and therefore inexpensive to assemble. It would also be desirable to provide an actuator and/or dose counter that can be used with more than one size of aerosol canister. It would also be desirable to provide components of such devices that allow for wide manufacturing tolerances.
<SOH> SUMMARY OF THE INVENTION <EOH>According to a first aspect of the present invention there is provided an axle of a rotatable element of an actuation indicator (e.g. a dose counter), wherein the axle is provided by a spring that is adapted in use to bias the rotatable element towards another element of the actuation indicator with which the rotatable element is engaged. The other element may be for causing rotation of the rotatable element, or caused to be rotated by the rotatable element. This biasing allows the two elements to be made with wide tolerances while still being able to operate correctly together. Preferably the rotatable element is a pinion. Preferably the other element with which the pinion engages is a rack, for instance extending through the dose counter. Preferably the rotatable element is an indicator wheel for indicating actuation of a device with which the indicator is associated, e.g. for indicating at least a part of a count of the number of doses of a substance left in, or dispensed from, a dispensing device. Preferably there are at least two rotatable elements on the axle, for instance three rotatable elements as in the exemplary embodiment hereinafter to be described. The rotatable elements may respectively be a units wheel and a tens wheel, and hundreds wheel where there is a third rotatable element, for indicating a dose count. Preferably the other element is a rotatable element mounted on a second, preferably parallel, axle. More preferably, the second axle is also provided by the spring. The present invention further provides an axle assembly comprising the axle, the rotatable element(s) on the spring axle and the other element. Preferably the spring also comprises a biasing section which connects the axles and biases the axles towards one another. The section may (i) be U-shaped, (ii) have substantially parallel sides and (iii) be substantially perpendicular to the two axles. The present invention further provides an actuation indicator comprising a drums sub-assembly comprising a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, wherein the slipping clutch arrangement comprises a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl. Preferably the slipping clutch spring has a generally U-shaped configuration. Preferably the open end of the spring engages a boss of the pinion and the closed end of the spring defines a track for slidingly engaging a boss provided on the pawl. Preferably the ratchet pawl engages a ratchet wheel that is fixed to the indicator wheel. Preferably a resilient, non-return leg engages a tooth of the ratchet wheel to prevent rotation of the ratchet wheel in a direction other than the set direction, and the non-return leg rides up and over the teeth to allow rotation in the set direction. Preferably there are at least two indicator wheels arranged to sequentially count down from a set figure to zero, there being at least a tens wheel and a units wheel, wherein the indicator wheels lock from further rotation in the set direction when they have counted down to zero, the slipping clutch spring then slipping upon further attempts to rotate the mechanism. The present invention also provides a casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part having a generally cylindrically shaped section having a generally cylindrical inner surface extending from a top of the sleeve part towards a base wall, and a collar affixable around a neck of the canister, and sized, when around the neck of the canister, to fit through the top of the sleeve part, into the sleeve part, whereat it will contact at least a portion of the generally cylindrical inner surface, wherein the generally cylindrical inner surface has a shoulder for supporting the collar to prevent the collar from being inserted further into the sleeve part, the shoulder being spaced from the top and the base wall of the sleeve part. In accordance with the invention in all its aspects, the canister unit may be a pressurised canister unit, such as an aerosol canister unit, e.g. for use in a pressurised metered dose inhaler. Preferably the top of the sleeve part comprises a chamfered surface to assist with the insertion of the collar into the sleeve part. Preferably the shoulder is formed by an annular step in the generally cylindrical inner surface. Preferably the shoulder is formed by a ledge attached to the generally cylindrical inner surface. Preferably the collar is a split ring collar. Preferably the collar, in an assembled canister unit, is welded to the sleeve part. The present invention also provides a casing adapted to be attached over a valve stem end of a canister to form a canister unit, the casing comprising a sleeve part for receiving a canister and a cap part for receiving a counter assembly of a dose counter for the canister unit, wherein the cap part and counter assembly can be assembled together separate from the sleeve part and canister, the sleeve part and cap part then being joinable together to form the casing. Preferably, the casing further comprises a counter assembly, the counter assembly comprising a drums sub-assembly. Preferably the sleeve part is adapted to receive more than one form or type of valve stem end, e.g. pressurised fluid canisters fitted with different valves. Preferably the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support being for supporting a different form of valve stem end, whereby more than one different valve stem end can be supported in the sleeve part. Preferably the supports are annular ledges. Preferably the ledges are concentric. Preferably a first said support is of a first height above the base wall and a second said support is of a lesser height above the base wall. The present invention also provides components for the above casing comprising a cap part and at least two sleeve parts, the two sleeve parts being for different valve stem ends, wherein the cap part is joinable to any one of the sleeve parts to form a casing for a chosen valve stem end. The present invention also provides a sleeve part for receiving a valve stem end of a canister, the sleeve part being adapted to receive more than one form of valve stem end. Preferably the sleeve part comprises a top through which, in use, a valve stem end of the canister will be inserted and a base wall spaced from the top having more than one support thereon, each support adapted for supporting a different form of valve stem end, whereby more than one different form of valve stem end is able to be supported in the sleeve part. Preferably the supports are annular ledges. Preferably the ledges are concentric. Preferably a first support is of a first height above the base wall and the second support is of a lesser height above the base wall. The present invention further provides a drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and, an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a drive wheel adapted to engage the post and to frictionally engage a slipping clutch; a ratchet pawl adapted to engage the slipping clutch; a star wheel adapted to engage the ratchet pawl; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. Preferably there are three drums adapted to display a count of 000 to 999. Preferably, the product further comprises an arm affixed to a hundred's drum adapted to contact a stop, wherein the slipping clutch is adapted to frictionally slip when the count reaches 000 . Preferably the drug product comprises a hundred's drum having numerals 0, 1 and 2, a ten's drum having numerals 0 through 9 and a one's drum having numerals 0 through 9. Preferably the actuation indicating assembly includes one or more grip members adapted to fixedly engage a neck portion of the container. Preferably the housing includes a mouthpiece. Preferably the housing includes a passage adapted to pass doses from the container to the mouthpiece. Preferably the container includes a metering valve adapted to dispense metered doses. Preferably a window is provided, adapted to display numerals on one or more drums engaging the star wheel. Preferably the actuation indicating assembly is fixed to the container by an adhesive, a welded shrink sleeve, a heat form, a crimp, an ultrasonic weld, an o-ring elastomer, or a split-ring collar. Preferably the actuation indicating assembly is permanently fixed to the container. Preferably the medicament is selected from the group consisting of beclomethasone, fluticasone, flunisolide, budesonide, rofleponide, mometasone, triamcinolone, noscapine, albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, terbutaline, tiotropium, ipratropium, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine, tulobuterol, (-)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl}methyl}benzenemethanol, esters, solvates and salts thereof, and combinations thereof. Preferably the medicament is albuterol sulphate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate or the combination of salmeterol xinafoate and fluticasone propionate. The medicament may also be salmeterol xinafoate and a salt, ester or solvate of ipratropium. Preferably the housing is constructed from polypropylene. Preferably one or more components of the actuation indicating assembly is constructed from polypropylene. Preferably the drug product further comprises one or more knock gears adapted to engage the one or more drums. Preferably the drug product comprises first, second and third drums and first and second knock gears. The present invention also provides a method of patient compliance comprising the acts of: providing a drug product as described above, administering the drug formulation to a patient, counting down a number of available doses remaining in the container on the actuation indicating assembly, and, indicating the number of available doses remaining in the container to the patient. Preferably the container is over-filled with up to 40 actuations. Preferably the actuation indicating assembly locks out when the count reaches 000, and wherein the drug product remains actuable for up to 40 subsequent actuations. The present invention further provides a drug product for dispensing a drug formulation comprising a propellant and a medicament comprising: a housing; a container containing the drug formulation having an outlet member and adapted to be actuable within the housing; and, an actuation indicating assembly, fixedly attached to the container, comprising: a body cradle having a post; a means for driving a slipping clutch means adapted to engage the post and to frictionally engage the slipping clutch means for grasping a ratcheting means; a pawl means for ratcheting a star wheel adapted to engage the slipping clutch means; a star wheel adapted to engage the pawl ratcheting means; and one or more drums adapted to engage the star wheel; wherein the fixedly attached container and actuation indicating assembly are reversibly removable from the housing as a single unit. Preferably the drug product comprises first, second and third drums. Preferably the drug product further comprises a means for stopping the first drum. Preferably the drug product further comprises a first means for knock locking the first and second drums and a second means for knock locking the second and third drums. Preferably the drug product is further adapted to indicate a count of 000 to 999 and further adapted to lock the drums when the count indicates 000. The present invention further provides a dispensing device, e.g. for dispensing a fluid, on which is mounted an actuation indicator either according to the invention or having one or more of the different aspects of the invention as a component thereof. The actuation indicator will be adapted to be operated upon each actuation of the dispensing device to indicate said actuation of the device. Preferably, the actuation indicator will be in the form of a dose counter which displays a numerical count of the number of doses of the content of the device left to be dispensed, or the number of doses dispensed. On actuation of the device, the numerical count is either incremented or decremented, depending on whether the count is of doses left or of doses dispensed. Preferably, the dispensing device has a dispensing or outlet end and the actuation indicator is mounted on this end. Preferably, the dispensing device is an aerosol canister having a can and a valve assembly at the outlet end. The valve assembly may be a metering valve assembly, as for example where for use in a pressurised metered dose inhaler. These and other aspects of the present invention will now be described by way of example with reference to the accompanying drawings.
20041217
20090310
20060511
72377.0
A61M1500
1
SMITH, RICHARD A
ACTUATION INDICATOR FOR A DISPENSING DEVICE
UNDISCOUNTED
0
ACCEPTED
A61M
2,004
10,518,616
ACCEPTED
Scattered light smoke detector
The smoke detector contains an optical measuring chamber, having a sensor arrangement (2) with at least one light source (12, 12′) and one light receiver (11), and a labyrinth system (7) with screens (16) arranged on the periphery of the measuring chamber. The light source (12, 12′) and the light receiver (11) are each arranged in a housing (14, 15: 13). The above-mentioned housings (14, 15; 13) have an elongated shape and a small window opening The at least one light source (12, 12′) and light receiver (12, 12′) are arranged in the rear part of their housings (14, 15; 13), so that between the window openings of the housings (14, 15; 13) and the light-penetrated optical surfaces of the at least one light source (12, 12′) and/or the lens of the light receiver (11) a relatively large gap is formed. This gap is preferably greater than the diameter of the above-mentioned optical surfaces, or of the above-mentioned lens. In the measuring chamber between the light exit and entry side of the housings (14, 15; 13) and the screens (16) opposite them, a compact, open scattering space is formed.
1. Scattered light smoke detector with an optical measuring chamber, comprising: a sensor arrangement with at least one light source and one light receiver; a labyrinth system with screens arranged on the periphery of the measuring chamber; a housing having an elongated shape and a small window opening and, wherein the at least one light source and light receiver are arranged in a rear part of the housing, so that between the window opening of the housing and a light-penetrated optical surface of the at least one light source and light receiver a relatively large gap is formed. 2. The smoke detector of claim 1, wherein the gap is greater than the diameter of the optical surface. 3. The smoke detector of claim 1, wherein the measuring chamber is delimited upward by a carrier disc, from which the housing extends downward, and that the labyrinth system forms a lid-like component which can be fixed to the carrier disc and has a floor and a side wall, and which can be plugged onto the carrier disc from below. 4. The smoke detector of claim 1, wherein the window opening of the housing is enclosed by a one-part frame. 5. The smoke detector of claim 3, wherein the housing, apart from the window opening, is open downward, and the floor of the component has lids for the housing. 6. The smoke detector of claim 3, wherein in the measuring chamber between a light exit and an entry side of the housing and screens opposite them, a compact, open scattering space is formed. 7. The smoke detector of claim 6, wherein the housing has grooves for fixing polarisation filters. 8. The smoke detector of claim 7, wherein the surfaces, which face each other, of the carrier disc and the floor of the component which forms the labyrinth system have corrugation. 9. The smoke detector of claim 8, wherein the screens and the corrugated surfaces of the carrier disc and of the floor of the component have a glossy surface. 10. The smoke detector of claim 6, wherein the screens are arranged on the periphery of the measuring chamber and are substantially L-shaped, the shorter leg pointing into the measuring chamber, and the gap between adjacent screens is a multiple of their thickness. 11. The smoke detector of 3, wherein on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug or plug connector. 12. The smoke detector of claim 11, wherein the multiple plug is integrated on the top side of the carrier disc, in so-called insert technology. 13. The smoke detector of claim 7, wherein the screens are arranged on the periphery of the measuring chamber and are substantially L-shaped, the shorter leg pointing into the measuring chamber, and the gap between adjacent screens is a multiple of their thickness. 14. The smoke detector of claim 8, wherein the screens are arranged on the periphery of the measuring chamber and are substantially L-shaped, the shorter leg pointing into the measuring chamber, and the gap between adjacent screens is a multiple of their thickness. 15. The smoke detector of claim 9, wherein the screens are arranged on the periphery of the measuring chamber and are substantially L-shaped, the shorter leg pointing into the measuring chamber, and the gap between adjacent screens is a multiple of their thickness. 16. The smoke detector of claim 5, wherein on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug or plug connector. 17. The smoke detector of claim 7, wherein on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug or plug connector. 18. The smoke detector of claim 9, wherein on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug or plug connector. 19. The smoke detector of claim 10, wherein on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug or plug connector. 20. The smoke detector of claim 19, wherein the multiple plug is integrated on the top side of the carrier disc, in so-called insert technology.
This invention concerns a scattered light smoke detector with an optical measuring chamber, having a sensor arrangement with at least one light source and one light receiver, and a labyrinth system with screens arranged on the periphery of the measuring chamber, the at least one light source and the light receiver each being arranged in a housing. In the case of scattered light smoke detectors, which if required can contain, as well as the optical measuring chamber, a further sensor, for instance a temperature sensor, it is known that the optical measuring chamber is in such a form that interfering external light cannot penetrate it, and smoke can penetrate it very easily. The at least one light source and one light receiver are arranged so that no light beams can reach from the at least one light source to the receiver directly. If smoke particles are present in the path of the beam, the light from the at least one light source is scattered on them, and part of this scattered light falls on the light receiver and causes an electrical signal. It is obvious that the reliability and security against false alarms of such scattered light smoke detectors depend essentially on their constant sensitivity. As well as the ageing of the opto-electronic components, it is in particular pollution of the light-penetrated optical surfaces of the stated components which have a negative effect on sensitivity. The invention is now intended to give a scattered light smoke detector of the type mentioned initially, such that the light-penetrated optical surfaces are as little polluted as possible, so that the detector has constant sensitivity. The stated object is achieved according to the invention by the above-mentioned housings having an elongated shape and a small window opening, and the at least one light source and light receiver being arranged in the rear part of their housings, so that between the window openings of the housings and the light-penetrated optical surfaces of the at least one light source and/or light receiver a relatively large gap is formed. Practical tests have shown that by the small window openings of the housings and by the arrangement of the opto-electronic components in the rear part of their housings, the optical surfaces are so well protected from pollution that the relevant detectors have constant sensitivity. A further advantage of the arrangement according to the invention is that each of the ray beams has a relatively small cross-section, so that the scattered light which reaches the light receiver is derived with high certainty from smoke particles in the centre of the measuring chamber and not, for instance, from smoke particles deposited on its floor. A first, preferred embodiment of the smoke detector according to the invention is characterized in that the stated gap is greater than the diameter of the stated optical A second, preferred embodiment of the smoke detector according to the invention is characterized in that the measuring chamber is delimited upward by a carrier disc, from which the stated housings extend downward, and that the labyrinth system forms a lid-like component which can be fixed to the carrier disc and has a floor and a side wall, and which can be plugged onto the carrier disc from below. A third, preferred embodiment of the smoke detector according to the invention is characterized in that at least one of the window openings of the above-mentioned housings is enclosed by a one-part frame. A fourth, preferred embodiment of the smoke detector according to the invention is characterized in that the above-mentioned housings, apart from the window openings, are open downward, and that the floor of the above-mentioned component has lids for the housings. According to a fifth preferred embodiment, in the measuring chamber between the light exit and entry side of the housings and the screens opposite them, a compact, open scattering space is formed. Another preferred embodiment of the smoke detector according to the invention is characterized in that on the carrier disc, a multiple plug for the electrical connection of the detector to a plug connector which is provided in a detector base is arranged, and that the electrical connection is made by a tangential movement of the multiple plug and/or plug connector The multiple plug is preferably integrated on the top side of the carrier disc, in so-called insert technology. Below, the invention is explained in more detail on the basis of embodiments and the drawings. FIG. 1 shows a perspective representation of an embodiment of a detector according to the invention, seen from in front and below, FIG. 2 shows a perspective representation of a cross-section through the detector of FIG. 1, FIG. 3 shows a perspective representation of an axial cross-section through the detector of FIG. 1, and FIG. 4 shows a perspective representation of a top view of the detector of FIG. 1, without the base. The smoke detector which is shown in FIGS. 1 to 4 consists in known fashion of three main components, a base 1, an optical sensor system 2 and a housing 3. This construction can be seen best in FIG. 3. FIG. 2 shows, in a cross-section through the detector looked at from below, a view of a part of the optical sensor system 2. The base 1 is provided for fitting to the ceiling of the room to be monitored. The fitting is either direct on a flush box or on the surface with or without an additional base. The base 1, which consists substantially of a circular plate and a fin extending downward around the edge, includes, among other things, a plug connector 4 (FIGS. 3, 4) which is provided to receive a multiple plug 5 (FIG. 4) which is connected to the sensor system. The optical sensor system 2 includes a plate-shaped carrier 6 for the optical sensor, a lid-like labyrinth 7 which is fixed to the underside of the carrier 6, a printed circuit board 8 which is arranged on the top side of the carrier 6 facing the base 1, with the analysis electronics, and a cover 9 which covers the printed circuit board 8 on the edge and above, and forms part of the housing 3. The multiple plug 5 is an integrated part of the carrier plate 6, and extends upward from it. The cover 9 is substantially in the form of a plate with a collar running round the edge, and with an opening 10 for the multiple plug 5 to pass through, so that it extends into the plane of the plug connector 4 which is arranged in the base 1. The optical sensor which can be seen in FIG. 2 includes a measuring chamber which is formed by the carrier 6 and labyrinth 7, with a light receiver 11 and two light sources 12, 12′, each of which is arranged in a housing 13, 14, 15. These housings consist of a floor part, in which the appropriate diode (photodiode or IRED) is held, and which has, on its front side which faces the centre of the measuring chamber, a window opening for light entry and exit. As can be seen in the figure, the scattering space which is formed in the measuring chamber, in the area in front of the above-mentioned window-like openings of the housings 13, 14, 15, is compact and open. This arrangement and conformation makes the detector most suitable for use of a transparent body which can be inserted into this scattering space for smoke simulation. Such transparent bodies are used for calibration or for testing the smoke sensitivity when the detector is manufactured (see EP-B-0 658 264). At least in the case of the housings 14 and 15, the frames of the window openings are in one-part form, thus reducing the tolerances for smoke sensitivity. In known scattered light smoke detectors, the window frames consist of two parts, one of which is attached to the roof of the measuring chamber, the other to the floor. When the floor is put on, fitting difficulties constantly occur, and the result is variable window sizes and the formation of a light gap between the two window halves and thus undesired interference with the emitted and received light. With the one-part housing windows, interference of this kind is excluded, and no problems with the positioning precision of window halves can occur. The windows are rectangular or square, and between the window openings and the associated light source 12, 12′ and/or the lens of the associated light receiver 11, there is a relatively large gap, resulting in a relatively small opening angle of the relevant light beams. A small opening angle of the light beams has the advantage that on the one hand light from the light sources 12, 12′ hardly meets the floor, and on the other hand the light receiver 11 does not “see” the floor, so that smoke particles deposited on the floor cannot generate any interfering scattered light. A further advantage of the large gap between the windows and the light source 12, 12′ or the lens of the light receiver 11 is that the optical surfaces which are penetrated by light are relatively deep inside the housing, and therefore well protected from pollution, resulting in constant sensitivity of the opto-electronic elements. The labyrinth 7 consists of a floor and peripherally arranged screens 16, and contains flat lids for the above-mentioned housings 13, 14, 15. The floor and the screens 16 are used to screen the measuring chamber against light from an external source, and to suppress the so-called background light (see also EP-A-0 821 330 and EP-A-1 087 352). The peripherally arranged screens 16 each consist of two legs and are L-shaped. The shape and arrangement of the screens 16, particularly their distance from each other, ensure that the measuring chamber is sufficiently screened against light from an external source and nevertheless its function can be tested with an optical testing device (EP-B-0 636 266). Also, the screens 16 are arranged asymmetrically, so that smoke can penetrate into the measuring chamber similarly well from all directions. The front edges of the screens 16, pointing into the measuring chamber, are in as sharp a form as possible, so that only a little light can fall on such an edge and be reflected. The floor and roof of the measuring chamber, that is the surfaces, which face each other, of the carrier 6 and labyrinth 7, are in corrugated form, and all surfaces in the measuring chamber, particularly the screens 16 and the above-mentioned corrugated surfaces, are glossy and act like black mirrors. This has the advantage that impinging light is not diffusely scattered but reflected directionally. The arrangement of the two light sources 12 and 12′ is chosen so that the optical axis of the light receiver 11 encloses an obtuse angle with the optical axis of the one light source, as shown the light source 12, and an acute angle with the optical axis of the other light source, as shown the light source 12′. The light of the light source 12, 12′ is scattered by smoke which penetrates into the measuring chamber, and a part of this scattered light falls on the light receiver 11. In the case of an obtuse angle between the optical axis of light source and light receiver, this is called forward scattering, and in the case of an acute angle between the optical axes, it is called backward scattering. It is known that the scattered light which is generated by forward scattering is significantly greater than what is generated by backward scattering. The two scattered light parts are characteristically different for different types of fire. This phenomenon is known, for instance, from WO-A-84/01950 (=U.S. Pat. No. 4,642,471) where it is disclosed, among other things, that the ratio, which is different for different types of smoke, of scattering at a small scattering angle to scattering at a larger scattering angle can be exploited to detect the type of smoke. Also that the larger scattering angle can even be chosen to be over 90°, so that the forward and backward scattering are analysed. The analysis of the scattered light parts from the two light sources 12 and 12′ is not the subject of this application, and is therefore not described in more detail here. For better discrimination between different aerosols, active or passive polarisation filters can be provided in the beam path on the transmitter and/or receiver side. The carrier 6 is appropriately prepared, and has grooves (not shown) which are provided in the housings 13, 14 and 15, and in which polarisation filters can be fixed. As a further option, as light sources 12, 12′ diodes which emit radiation in the wavelength range of visible light can be used (see EP-A-0 926 646), or the light sources can emit radiation of different wavelengths, e.g. red light from one light source and blue light from the other. The housing 3 of the smoke detector is essentially constructed in two parts, and consists of the previously mentioned cover 9 and a detector hood 17 which contains the optical sensor system 2. The latter consists of an upper ring-shaped part and a plate which is at a distance from it, forms the cap of the detector, and is connected to the upper, ring-shaped part by arc-shaped or rib-shaped fins 18. The space (marked with reference symbol 19) between the upper and lower parts of the detector hood 17 forms an opening, which runs round the whole circumference of the housing, for the entry of air and thus smoke to the optical sensor system 2. This opening is interrupted only by the relatively narrow fins 18. An even number of fins 18 is provided, four being shown. The detector hood 17 and cover 9 are fixed to the carrier 6 by hook-like spring-loaded latches (not shown), and the whole detector is fixed in the base 1. In the upper part of the detector hood 17, a ring 20, which carries an insect grille 21 of a suitable flexible material, is inserted. When the detector hood 17 is attached, the carrier 6 is pressed against the ring 20, so that the insect grille 21 is fixed in the detector. The detector is fixed in the base 1 by a kind of bayonet catch The detector is pushed from below into the base 1, which is only possible in a single relative position between detector and base, because of mechanical coding which is formed by guide ribs and guide grooves. The detector is then rotated in the base 1 by an angle of about 20° (FIG. 4), whereby the multiple plug 5, which forms part of the carrier 6 and extends upward from it, is pushed tangentially into the plug connector which is fitted in the base 1, and the electrical contact between the plug connector 4 and multiple plug 5, and thus between detector and base, is made. The detector is then fixed mechanically in the base 1 by the above-mentioned bayonet catch. The multiple plug 5 is integrated in the top side of the carrier 6 in so-called insert technology, and manufactured in one piece with the carrier 6. From the plug contacts of the multiple plug 5, the electrical connections are fed to a stamping which is sealed in the carrier 6 with metallic, mutually insulated metal conductors. The free ends of these metal conductors extend out of the carrier 6 next to the multiple plug 5, and form contact points for the production of soldered joints to the analysis electronics on the printed circuit board 8. The electrical connection between detector and base through the two elements, plug connector 4 and multiple plug 5, has a series of advantages: To make the plug-and-socket connection, only simple mechanics is required, and in particular no conversion of a rotary movement into a translatory movement is necessary. The compact plug-and-socket connection allows simple loop contacts and has outstanding properties regarding electromagnetic compatibility (EMC). As can be seen in FIG. 3, a light guide 22, which on the one hand extends upward to the printed circuit board 8 and on the other hand extends out of the detector hood through a hole in the bottom part of the detector hood 17, is fixed to the floor of the component which forms the labyrinth 7. The detector hood has a spherical depression 23, which surrounds the free end of the light guide 22, in the area of the hole. The light guide 22 is used as a so-called alarm indicator for optical indication of alarm states of the detector. For this purpose, a LED (not shown), which is activated in the case of an alarm state and applies light to the light guide 22, is provided on the printed circuit board 8. The alarm indicator requires little current, and because it is in the area of the detector vertex, it is visible from practically all sides Admittedly visibility from all sides is given only from a viewing angle of 20° or more to the horizontal, but since the detector is fitted on the ceiling, this condition is fulfilled in most cases. As can be seen, in particular, in FIG. 2, the light guide 22 is taken through the measuring chamber in the area between the housings 14 and 15. The two housings 14 and 15 are joined to each other at the front, and thus form, with their inner side surfaces and the joining surface between them, a wall which surrounds the light guide 22 and to a large extent screens the scattering space of the measuring chamber against the light guide 22. The smoke detector which has been described until now is a purely optical detector, with smoke detection on the basis of the scattered light which is caused by the smoke particles which penetrate into the measuring chamber. The detector can optionally be in is the form of a two-criteria detector, and additionally include a temperature sensor. According to FIGS. 1 and 2, two temperature sensors 24 in the form of NTC resistors are provided, and are arranged in the area of two fins 18 opposite each other. The fins 18 have an elongated recess 25 in the middle, into which the temperature sensors 24, which are fixed to the printed circuit board 8, extend from above. Opto-thermal detectors are known, so that a description of the signal analysis is omitted here. Obviously, the detector could include further sensors, for instance a combustion gas sensor (CO, NOx). With appropriately small dimensions, these could be arranged within the measuring chamber. Whereas temperature sensors which are arranged in the axis of the detector are completely independent of direction, in the case of a peripherally arranged sensor there is a strong direction dependency, and the response behaviour depends on whether the sensor is on the side of the detector facing the fire or facing away from it. This problem is solved by using two temperature sensors 24 opposite each other. It is essential that the detector, irrespective of the flow direction, has homogeneous, rotationally symmetrical sensitivity. This is achieved by the fins 18 in co-operation with the insect grille 21. On the one hand, the fins 18 protect the temperature sensors 24 from mechanical force effects and guide the air optimally to the sensors, and on the other hand, in co-operation with the insect grille 21, they guide the air along the housing externally. As was mentioned in the introduction to the description, today optical, opto-thermal and thermal fire detectors are in use, and gas detectors may be added to them. Additionally, the optical, thermal and opto-thermal detectors can also have a combustion gas detector The presented detector covers the optical and opto-thermal variants (to which a combustion gas detector may be added). Obviously, in the case of the purely optical detector no temperature sensors 24 are provided. Apart from that, however, the detector construction in the case of the two variants which have been described until now is mechanically exactly the same. By using a double photodiode as the light receiver 11, optimum redundancy (two light emitters, two light receivers, two temperature sensors) can be achieved.
20050901
20080429
20060126
76014.0
G08B1710
0
TON, TRI T
SCATTERED LIGHT SMOKE DETECTOR
UNDISCOUNTED
0
ACCEPTED
G08B
2,005
10,518,654
ACCEPTED
Carvedilol phosphate salts and/or solvates thereof, corresponding compositions and/or methods of treatment
The present invention relates to carvedilol phosphate salts, which include novel crystalline forms of carvedilol dihydrogen phosphate (i.e., dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol) and/or carvedilol hydrogen phosphate, etc.), and/or solvates thereof, compositions containing the aforementioned salts and/or solvates, and methods of using the aforementioned salts and/or solvates to treat hypertension, congestive heart failure and angina, etc.
1. A compound which is carvedilol dihydrogen phosphate hemihydrate. 2. The compound according to claim 1 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta as shown in FIG. 1. 3. The compound according to claim 2 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 7.0±0.2 (2θ), 11.4±0.2 (2θ), 15.9±0.2 (2θ), 18.8±0.2 (2θ), 20.6±0.2 (2θ), 22.8±0.2 (2θ), and 25.4±0.2 (2θ). 4. The compound according to claim 1 having an infrared spectrum which comprises characteristic absorption bands expressed in wave numbers as shown in FIG. 6. 5. The compound according to claim 1 having a Raman spectrum which comprises characteristic peaks as shown in FIG. 3. 6. A compound which is carvedilol dihydrogen phosphate dihydrate. 7. The compound according to claim 6 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta (2θ) as shown in FIG. 9. 8. The compound according to claim 7 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 6.5±0.2 (2θ), 7.1±0.2 (2θ), 13.5±0.2 (2θ), 14.0±0.2 (2θ), 17.8±0.2 (2θ), 18.9±0.2 (2θ), and 21.0±0.2 (2θ). 9. The compound according to claim 6 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta (2θ) as shown in FIG. 25. 10. The compound according to claim 9 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2) at about 6.4±0.2 (2θ), 9.6±0.2 (2θ), 16.0±0.2 (2θ), 18.4±0.2 (2θ), 20.7±0.2 (2θ), and 24.5±0.2 (2θ). 11. A compound which is carvedilol dihydrogen phosphate methanol solvate. 12. The compound according to claim 11 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta (2θ) as shown in FIG. 24. 13. The compound according to claim 12 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 6.9±0.2 (2θ), 7.2±0.2 (2θ), 13.5±0.2 (2θ), 14.1±0.2 (2θ), 17.8±0.2 (2θ), and 34.0±0.2 (2θ). 14. A compound which is carvedilol dihydrogen phosphate. 15. The compound according to claim 14 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta (2θ) as shown in FIG. 28. 16. The compound according to claim 15 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 13.2±0.2 (2θ), 15.8±0.2 (2θ), 16.3±0.2 (2θ), 21.2±0.2 (2θ), 23.7±0.2 (2θ), and 26±0.2 (2θ). 17. A compound which is carvedilol hydrogen phosphate. 18. The compound according to claim 17 having an x-ray diffraction pattern which comprises characteristic peaks in degrees two-theta (2θ) as shown in FIG. 29. 19. The compound according to claim 18 having characteristic peaks from 0° degrees 2-theta (2θ) to 35° degrees 2-theta (2θ) at about 5.5±0.2 (2θ), 12.3±0.2 (2θ), 15.3±0.2 (2θ), 19.5±0.2 (2θ), 21.6±0.2 (2θ), and 24.9±0.2 (2θ). 20. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier. 21. A pharmaceutical composition comprising the compound according to claim 6 and a pharmaceutically acceptable carrier. 22. A pharmaceutical composition comprising the compound according to claim 14 and a pharmaceutically acceptable carrier. 23. A pharmaceutical composition comprising the compound according to claim 17 and a pharmaceutically acceptable carrier. 24. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the compound according to claim 1. 25. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the compound according to claim 6. 26. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the compound according to claim 14. 27. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the compound according to claim 17. 28. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the composition according to claim 20. 29. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the composition according to claim 21. 30. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the composition according to claim 22. 31. A method of treating hypertension, congestive heart failure or angina which comprises administering to a subject in need thereof an effective amount of the composition according to claim 23.
FIELD OF THE INVENTION The present invention relates to a salt of carvedilol and/or corresponding solvates thereof, compositions containing such a salt of carvedilol and/or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain disease states in mammals, in particular man. The present invention further relates to carvedilol phosphate salts, which include novel crystalline forms of carvedilol dihydrogen phosphate (i.e., such as dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), carvedilol hydrogen phosphate,etc.), and/or other corresponding solvates thereof, compositions containing such salts and/or solvates, and methods of using the aformentioned compounds to treat hypertension, congestive heart failure and angina, etc. BACKGROUND OF THE INVENTION The compound, 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]-amino]-2-propanol is known as Carvedilol. Carvedilol is depicted by the following chemical structure: Carvedilol is disclosed in U.S. Pat. No. 4,503,067 to Wiedemann et al. (i.e., assigned to Boehringer Mannheim, GmbH, Mannheim-Waldhof, Fed. Rep. of Germany), which was issued on Mar. 5, 1985. Currently, carvedilol is synthesized as free base for incorporation in medication that is available commercially. The aforementioned free base form of Carvedilol is a racemic mixture of R(+) and S(−) enantiomers, where nonselective β-adrenoreceptor blocking activity is exhibited by the S(−) enantiomer and α-adrenergic blocking activity is exhibited by both R(+) and S(−) enantiomers. Those unique features or characteristics associated with such a racemic Carvedilol mixture contributes to two complementary pharmacologic actions: i.e., mixed venous and arterial vasodilation and non-cardioselective, beta-adrenergic blockade. Carvedilol is used for treatment of hypertension, congestive heart failure and angina. The currently commercially available carvedilol product is a conventional, tablet prescribed as a twice-a-day (BID) medication in the United States. Carvedilol contains an α-hydroxyl secondary amine functional group, which has a pKa of 7.8. Carvedilol exhibits predictable solubility behaviour in neutral or alkaline media, i.e. above a pH of 9.0, the solubility of carvedilol is relatively low (<1 μg/mL). The solubility of carvedilol increases with decreasing pH and reaches a plateau near pH=5, i.e. where saturation solubility is about 23 μg/mL at pH=7 and about 100 μg/mL at pH=5 at room temperature. At lower pH values (i.e., at a pH of 1 to 4 in various buffer systems), solubility of carvedilol is limited by the solubility of its protonated form or its corresponding salt formed in-situ. The hydrochloride salt of carvedilol generated in situ in acidic medium, which simulates gastric fluid, is less soluble in such medium. In light of the foregoing, a salt, and/or novel crystalline form of carvedilol with greater aqueous solubility, chemical stability, etc. would offer many potential benefits for provision of medicinal products containing the drug carvedilol. Such benefits would include products with the ability to achieve desired or prolonged drug levels in a systemic system by sustaining absorption along the gastro-intestinal tract of mammals (i.e., such as humans), particularly in regions of neutral pH, where a drug, such as carvedilol, has minimal solubility. Surprisingly, it has now been shown that a novel crystalline form of carvedilol phosphate salt (i.e., such as carvedilol dihydrogen phosphate and/or carvedilol hydrogen phosphate, etc.) can be isolated as a pure, crystalline solid, which exhibits much higher aqueous solubility than the corresponding free base or other prepared crystalline salts of carvedilol, such as the hydrochloride salt. This novel crystalline form also has potential to improve the stability of carvedilol in formulations due to the fact that the secondary amine functional group attached to the carvedilol core structure, a moiety pivotal to degradation processes, is protonated as a salt. In light of the above, a need exists to develop different carvedilol forms and/or different compositions, respectively, which have greater aqueous solubility, chemical stability, sustained or prolonged drug or absorption levels (i.e., such as in neutral gastrointestinal tract pH regions, etc.). There also exists a need to develop methods of treatment for hypertension, congestive heart failure or angina, etc. which comprises administration of the aforementioned carvedilol phosphate salts and/or solvates thereof or corresponding pharmaceutical compositions, which contain such salts, and/or solvates. The present invention is directed to overcoming these and other problems encountered in the art. SUMMARY OF THE INVENTION The present invention relates to a salt of carvedilol and/or corresponding solvates thereof, compositions containing such carvedilol and/or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain disease states in mammals, in particular man. The present invention further relates to carvedilol phosphate salts, which include novel crystalline forms of carvedilol phosphate (i.e., such as dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), carvedilol hydrogen phosphate,etc.), and/or other-corresponding solvates thereof. The present invention relates to a pharmaceutical composition, which contains carvedilol phosphate salts and/or solvates thereof. The present invention further relates to a method of treating hypertension, congestive heart failure and angina, which comprises administering to a subject in need thereof an effective amount of a carvedilol phosphate salt (which include novel crystalline forms) and/or solvates thereof or a pharmaceutical composition (i.e., which contains such salts and/or solvates of carvedilol phosphate), etc. BRIEF DESCRIPTION OF THE INVENTION FIG. 1 is an x-ray powder diffractogram for carvedilol dihydrogen phosphate hemihydrate (Form I). FIG. 2 shows the thermal analysis results for carvedilol dihydrogen phosphate hemihydrate (Form I). FIG. 3 is an FT-Raman spectrum for carvedilol dihydrogen phosphate hemihydrate (Form I). FIG. 4 is an FT-Raman spectrum for carvedilol dihydrogen phosphate hemihydrate in the 4000-2000 cm−1 region of the spectrum (Form I). FIG. 5 is an FT-Raman spectrum for carvedilol dihydrogen phosphate hemihydrate in the 2000-400 cm−1 region of the spectrum (Form I). FIG. 6 is an FT-IR spectrum for carvedilol dihydrogen phosphate hemihydrate (Form I). FIG. 7 is an FT-IR spectrum for carvedilol dihydrogen phosphate hemihydrate in the 4000-2000 cm−1 region of the spectrum (Form I). FIG. 8 is an FT-IR spectrum for carvedilol dihydrogen phosphate hemihydrate in the 2000-500 cm−1 region of the spectrum (Form I). FIG. 9 is an x-ray powder diffractogram for carvedilol dihydrogen phosphate dihydrate (Form II). FIG. 10 shows the thermal analysis results for carvedilol dihydrogen phosphate dihydrate (Form II). FIG. 11 is an FT-Raman spectrum for carvedilol dihydrogen phosphate dihydrate (Form II). FIG. 12 is an FT-Raman spectrum for carvedilol dihydrogen phosphate dihydrate in the 4000-2000 cm−1 region of the spectrum (Form II). FIG. 13 is an FT-Raman spectrum for carvedilol dihydrogen phosphate dihydrate in the 2000-400 cm−1 region of the spectrum (Form II). FIG. 14 is an FT-IR spectrum for carvedilol dihydrogen phosphate dihydrate (Form II). FIG. 15 is an FT-IR spectrum for carvedilol dihydrogen phosphate dihydrate in the 4000-2000 cm−1 region of the spectrum (Form II). FIG. 16 is an FT-IR spectrum for carvedilol dihydrogen phosphate dihydrate in the 2000-500 cm−1 region of the spectrum (Form II). FIG. 17 shows the thermal analysis results for carvedilol dihydrogen phosphate methanol solvate (Form III). FIG. 18 is an FT-Raman spectrum for carvedilol dihydrogen phosphate methanol solvate (Form II). FIG. 19 is an FT-Raman spectrum for carvedilol dihydrogen phosphate methanol solvate in the 4000-2000 cm−1 region of the spectrum (Form II). FIG. 20 is an FT-Raman spectrum for carvedilol dihydrogen phosphate methanol solvate in the 2000-400 cm−1 region of the spectrum (Form II). FIG. 21 is an FT-IR spectrum for carvedilol dihydrogen phosphate methanol solvate (Form II). FIG. 22 is an FT-IR spectrum for carvedilol dihydrogen phosphate methanol solvate in the 4000-2000 cm−1 region of the spectrum (Form III). FIG. 23 is an FT-IR spectrum for carvedilol dihydrogen phosphate methanol solvate in the 2000-500 cm−1 region of the spectrum (Form II). FIG. 24 is an x-ray powder diffractogram for carvedilol dihydrogen phosphate methanol solvate (Form III). FIG. 25 is an x-ray powder diffractogram for carvedilol dihydrogen phosphate dihydrate (Form IV). FIG. 26 is a solid state 13C NMR for carvedilol dihydrogen phosphate dihydrate (Form I). FIG. 27 is a solid state 31P NMR for carvedilol dihydrogen phosphate dihydrate (Form I). FIG. 28 is an x-ray powder diffractogram for carvedilol dihydrogen phosphate (Form V). FIG. 29 is an x-ray powder diffractogram for carvedilol hydrogen phosphate (Form VI). DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a salt of carvedilol and/or corresponding solvates thereof, compositions containing such carvedilol salts and/or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain disease states in mammals, in particular man. The present invention further relates to carvedilol phosphate salts, which include novel crystalline forms of carvedilol dihydrogen phosphate (i.e., such as dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), carvedilol hydrogen phosphate,etc.) and/or other carvedilol phosphate solvates thereof. The present invention relates to a pharmaceutical composition, which contains carvedilol phosphate salts and/or solvates thereof. The present invention further relates to a method of treating hypertension, congestive heart failure and angina, which comprises administering to a subject in need thereof an effective amount of a carvedilol phosphate salt (which include novel crystalline forms), and/or solvates thereof or a pharmaceutical composition (i.e., which contains such salts and/or solvates of carvedilol phosphate), etc. Carvedilol is disclosed and claimed in U.S. Pat. No. 4,503,067 to Wiedemann et al. (“U.S. '067 Patent”). Reference should be made to U.S. '067 Patent for its full disclosure, which include methods of preparing and/or using the carvedilol compound, etc. The entire disclosure of the U.S. '067 Patent is incorporated hereby by reference in its entirety. The present invention relates to a compound, which is a salt and/or novel crystalline forms of carvedilol phosphate (i.e., which include crystalline forms of carvedilol dihydrogen phosphate, carvedilol hydrogen phosphate, etc.) and/or solvates of carvedilol phosphate (i.e., which include carvedilol dihydrogen phosphate hemihydrate, carvedilol dihydrogen phosphate dihydrate (i.e., such as Forms II and IV, respectively, etc.), and/or carvedilol dihydrogen phosphate methanol solvate, etc.) In accordance with the present invention, it has been unexpectedly found that carvedilol dihydrogen phosphate can be isolated readily as novel crystalline forms, which displays much higher solubility when compared to the free base of carvedilol. An example in the present invention of a novel carvedilol phosphate salt is a novel crystalline form of carvedilol dihydrogen phosphate (i.e., identified as the dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol). In accordance with the present invention, other carvedilol phosphate salts, and/or solvates of the present invention may be isolated as different solid and/or crystalline forms. Moreover, a specific identified species of a carvedilol phosphate salt (or a specific identified corresponding solvate species) also may also be isolated in various different crystalline or solid forms. For example, carvedilol dihydrogen phosphate, may be isolated in two different and distinct crystalline forms, Forms II and IV (see, Examples 2 and 4), respectively represented and substantially shown FIGS. 9 to 6 (for Form II) and FIG. 25 (for Form IV), which are represent spectroscopic and/or other characterizing data. It is recognized that the compounds of the present invention may exist in forms as stereoisomers, regioisomers, or diastereiomers, etc. These compounds may contain one or more asymmetric carbon atoms and may exist in racemic and optically active forms. For example, carvedilol may exist as as racemic mixture of R(+) and S(−) enantiomers, or in separate respectively optically forms, i.e., existing separately as either the R(+) enantiomer form or in the S(+) enantiomer form. All of these individual compounds, isomers, and mixtures thereof are included within the scope of the present invention. Suitable solvates of carvedilol phosphate as defined in the present invention, include, but are not limited to carvedilol dihydrogen phosphate hemihydrate, carvedilol dihydrogen phosphate dihydrate (i.e., which include Forms II and IV, respectively), carvedilol dihydrogen phosphate methanol solvate, and carvedilol hydrogen phosphate, etc. In particular, crystalline carvedilol dihydrogen phosphate hemihydrate of the instant invention can be prepared by crystallization from an acetone-water solvent system containing carvedilol and H3PO4. In accordance with the present invention suitable, solvates of the present invention may be prepared by preparing a slurrying a carvedilol phosphate salt, such as a carvedilol dihydrogen salt, in a solvent, such as methanol. According to the instant invention, the various forms of carvedilol dihydrogen phosphate (i.e. which include salts and/or solvates thereof) are distinguished from each other using different characterization or identification techniques. Such techniques, include solid state 13C Nuclear Magnetic Resonance (NMR), 31P Nuclear Magnetic Resonance (NMR), Infrared (IR), Raman, X-ray powder diffraction, etc. and/or other techniques, such as Differential Scanning Calorimetry (DSC) (i.e., which measures the amount of energy (heat) absorbed or released by a sample as it is heated, cooled or held at constant temperature). In general, the aforementioned solid state NMR techniques are non-destructive techniques to yield spectra, which depict an NMR peak for each magnetically non-equivalent carbon site the solid-state For example, in identification of compounds of the present invention, 13C NMR spectrum of a powdered microcrystalline organic molecules reflect that the number of peaks observed for a given sample will depend on the number of chemically unique carbons per molecule and the number of non-equivalent molecules per unit cell. Peak positions (chemical shifts) of carbon atoms reflect the chemical environment of the carbon in much the same manner as in solution-state 13C NMR. Although peaks can overlap, each peak is in principle assignable to a single type of carbon. Therefore, an approximate count of the number of carbon sites observed yields useful information about the crystalline phase of a small organic molecule. Based upon the foregoing, the same principles apply to phosphorus, which has additional advantages due to high sensitivity of the 31P nucleus. Polymorphism also can be studied by comparison of 13C and 31P spectra. In the case of amorphous material, broadened peak shapes are usually observed, reflecting the range of environments experienced by the 13C or 31P sites in amorphous material types. Specificallly. carvedilol dihydrogen phosphate salts, hydrates, and/or solvates thereof, substantially shown by the data described in FIGS. 1-29. For example, crystalline carvedilol dihydrogen phosphate hemihydrate (see, Example 1: Form I) is identified by an x-ray diffraction pattern as shown substantially in FIG. 1, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 7.0±0.2 (2θ), 11.4±0.2 (2θ), 15.9±0.2 (2θ), 18.8±0.2 (2θ), 20.6±0.2 (2θ), 22.8±0.2 (2θ), and 25.4±0.2 (2θ). Crystalline carvedilol dihydrogen phosphate dihydrate (see, Example 2: Form II) is identified by an x-ray diffraction pattern as shown substantially in FIG. 9, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 6.5±0.2 (2θ), 7.1±0.2 (2θ), 13.5±0.2 (2θ), 14.0±0.2 (2θ), 17.8±0.2 (2θ), 18.9±0.2 (2θ), and 21.0±0.2 (2θ). Crystalline carvedilol dihydrogen phosphate methanol solvate (see, Example 3: Form II) is identified by an x-ray diffraction pattern as shown substantially in FIG. 24, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 6.9±0.2 (2θ), 7.2±0.2 (2θ), 13.5±0.2 (2θ), 14.1±0.2 (2θ), 17.8±0.2 (2θ), and 34.0±0.2 (2θ). Crystalline carvedilol dihydrogen phosphate dihydrate (see, Example 4: Form IV) is identified by an x-ray diffraction pattern as shown substantially in FIG. 25, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 6.4±0.2 (2θ), 9.6±0.2 (2θ), 16.0±0.2 (2θ), 18.4±0.2 (2θ), 20.7±0.2 (2θ), and 24.5±0.2 (2θ). Crystalline carvedilol dihydrogen phosphate (see, Example 5: Form V) is identified by an x-ray diffraction pattern as shown substantially in FIG. 28, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 13.2±0.2 (2θ), 15.8±0.2 (2θ), 16.3±0.2 (2θ), 21.2±0.2 (2θ), 23.7±0.2 (2θ), and 26.0±0.2 (2θ). Crystalline carvedilol hydrogen phosphate (see, Example 6: Form VI) is identified by an x-ray diffraction pattern as shown substantially in FIG. 29, which depicts characteristic peaks in degrees two-theta (2θ): i.e., 5.5±0.2 (2θ), 12.3±0.2 (2θ), 15.3±0.2 (2θ), 19.5±0.2 (2θ), 21.6±0.2 (2θ), and 24.6±0.2 (2θ). The present invention also relates to a pharmaceutical composition, which contains a salt of carvedilol phosphate and/or corresponding solvates thereof. Importantly, the chemical and/or physical properties of carvedilol forms described herein, which include salts of carvedilol dihydrogen phosphates, such as novel crystalline forms, and/or solvates thereof indicate that those forms may be particularly suitable for inclusion in medicinal agents, pharmaceutical compositions, etc. For example, solubility of various carvedilol salts, and/or solvates as those described herein may facilitate provision or development of a dosage form from which the drug substance becomes available for bioabsorption throughout the gastrointestinal tract (i.e., in particular the lower small intestine and colon). In light of the foregoing, it may be possible to develop stable controlled release dosage forms containing such carvedilol phosphate salts and/or solvates of the present invention, etc., for once-per-day dosage, delayed release or pulsatile release to optimize therapy by matching pharmacokinetic performance with pharmacodynamic requirements. Compounds or compositions within the scope of this invention include all compounds or compositions, wherein the compound of the present invention is contained in an amount effective to achieve its intended purpose. While individual needs vary, determination of optimal ranges of effective amounts of each component is within the skill of the art. Thus, this invention also relates to a pharmaceutical composition comprising an effective amount of carvedilol dihydrogen phosphate salts and/or solvates thereof, with any of the characteristics noted herein, in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents thereof, and if desired, other active ingredients. Moreover, the quantity of the compound or composition of the present invention administered will vary depending on the patient and the mode of administration and can be any effective amount. Treatment regimen for the administration of the compounds and/or compositions of the present invention can also be determined readily by those with ordinary skill in art. The quantity of the compound and/or composition of the present invention administered may vary over a wide range to provide in a unit dosage an effective amount based upon the body weight of the patient per day to achieve the desired effect. In particular, a composition of the present invention is presented as a unit dose and taken preferably from 1 to 2 times daily, most preferably once daily to achieve the desired effect. Depending upon the treatment being effected, the compounds, and/or or compositions of the present invention can be administered orally, intravascularly, intraperitoneally, subcutaneously, intramuscularly or topically. Preferably, the composition is adapted for oral administration. In general, pharmaceutical compositions of the present invention are prepared using conventional materials and techniques, such as mixing, blending and the like. In accordance with the present invention, compounds and/or pharmaceutical composition can also include, but are not limited to, suitable adjuvants, carriers, excipients, or stabilizers, etc. and can be in solid or liquid form such as, tablets, capsules, powders, solutions, suspensions, or emulsions, etc. Typically, the composition will contain a compound of the present invention, such as a salt of carvedilol or active compound(s), together with the adjuvants, carriers and/or excipients. In particular, a pharmaceutical composition of the present invention comprises an effective amount of a salt of carvedilol (i.e., such as carvedilol dihydrogen phosphate salts) and/or corresponding solvates (i.e., as identified herein) thereof, with any of the characteristics noted herein, in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents thereof, and if desired, other active ingredients. In accordance with the present invention, solid unit dosage forms can be conventional types known in the art. The solid form can be a capsule and the like, such as an ordinary gelatin type containing the compounds of the present invention and a carrier, for example, lubricants and inert fillers such as, lactose, sucrose, or cornstarch, etc. In another embodiment, these compounds are tableted with conventional tablet bases such as lactose, sucrose, or cornstarch in combination with binders like acacia, cornstarch, or gelatin, disintegrating agents, such as cornstarch, potato starch, or alginic acid, and a lubricant, like stearic acid or magnesium stearate, etc. The tablets, capsules, and the like can also contain a binder, such as gum tragacanth, acacia, corn starch, or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose, or saccharin, etc. When the dosage unit form is a capsule, it can contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. Various other materials may be present as coatings or to modify the physical form of the dosage unit. For instance, tablets can be coated with shellac, sugar, or both, etc. A syrup can contain, in addition to active ingredient, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye, and flavoring such as cherry or orange flavor, etc. For oral therapeutic administration, these active compounds can be incorporated with excipients and used in the form of tablets, capsules, elixirs, suspensions, syrups, and the like. The percentage of the compound in compositions can, of course, be varied as the amount of active compound in such therapeutically useful compositions is such that a suitable dosage will be obtained. Typically in accordance with the present invention, the oral maintenance dose is between about 25 mg and about 50 mg, preferably given once daily. In accordance with the present invention, the preferred unit dosage forms include tablets or capsules. The active compounds of the present invention may be orally administered, for example, with an inert diluent, or with an assimilable edible carrier, or they can be enclosed in hard or soft shell capsules, or they can be compressed into tablets, or they can be incorporated directly with the food of the diet, etc. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form should be sterile and should be fluid to the extent that easy syringability exists. It should be stable under the conditions of manufacture and storage and should be preserved against the contaminating action of microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils, etc. The compounds or pharmaceutical compositions of the present invention may also be administered in injectable dosages by solution or suspension of these materials in a physiologically acceptable diluent with a pharmaceutical adjuvant, carrier or excipients. Such adjuvants, carriers and/or excipients, include, but are not limited to sterile liquids, such as water and oils, with or without the addition of a surfactant and other pharmaceutically and physiologically acceptable carrier, including adjuvants, excipients or stabilizers, etc. Illustrative oils are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, or mineral oil, etc. In general, water, saline, aqueous dextrose and related sugar solution, and glycols, such as propylene glycol or polyethylene glycol, are preferred liquid carriers, particularly for injectable solutions, etc. These active compounds may also be administered parenterally. Solutions or suspensions of these active compounds can be prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Illustrative oils are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, or mineral oil, etc. In general, water, saline, aqueous dextrose and related sugar solution, and glycols such as, propylene glycol or polyethylene glycol, etc., are preferred liquid carriers, particularly for injectable solutions. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The compounds and/or compositions prepared according to the present invention can be used to treat warm blooded animals, such as mammals, which include humans. Conventional administration methods may be suitable for use in the present invention. The present invention further relates to a method of treating hypertension, congestive heart failure and angina, which comprises administering to a subject in need thereof an effective amount of a carvedilol phosphate salt (i.e., which include novel crystalline forms) and/or solvates thereof or a pharmaceutical composition (i.e., which contains such salts and/or solvates of carvedilol phosphate), etc. The Examples set forth below are illustrative of the present invention and are not intended to limit, in any way, the scope of the present invention. EXAMPLES Example 1 Form I Carvedilol Dihydrogen Phosphate Hemihydrate Preparation A suitable reactor is charged with acetone. The acetone solution is sequentially charged with carvedilol and water. Upon addition of the water, the slurry dissolves quicky. To the solution is added aqueous H3PO4. The reaction mixture is stirred at room temperature and carvedilol dihydrogen phosphate seeds are added in one portion. The solid precipitate formed is stirred, then filtered and the collected cake is washed with aqueous acetone. The cake is dried under vacuum to a constant weight. The cake is weighed and stored in a polyethylene container. Example 2 Form II Carvedilol Dihydrogen Phosphate Dihydrate Preparation Form I is slurried in acetone/water mixture between 10 and 30° C. for several days. Example 3 Form III Carvedilol Dihydrogen phosphate Methanol Solvate Preparation Form I is slurried in methanol between 10 and 30° C. for several days. Example 4 Form IV—Carvedilol Dihydrogen Phosphate Dihydrate Preparation Carvedilol dihydrogen dihydrogen phosphate is dissolved in an acetone/water mixture. The acetone is removed by distillation. A solid crystallizes during acetone removal and is filtered and dried. Example 5 Form V—Carvedilol Dihydrogen Phosphate Preparation Carvedilol dihydrogen phosphate hemihydrate (Form I) was suspended in water, and the suspension was placed on a mechanical shaker at room temperature. After 48 hours of shaking, the solid was isolated from suspension by filtration, then dried in a desiccator under vacuum for a few days. Example 6 Form VI—Carvedilol Hydrogen Phosphate Preparation A suitable reactor is charged with acetone. The acetone solution is sequentially charged with SK&F 105517 and water. Upon addition of the water, the slurry dissolves quicky. To the solution is added aqueous H3PO4 (at ½ the molar quantity of Carvedilol). The reaction mixture is stirred and allowed to crystallize. The solid precipitate formed is stirred and cooled, then filtered and the collected cake is washed with aqueous acetone. Example 7 13C and 31P Solid State NMR Data Analysis of Carvedilol Dihydrogen Phosphate Hemihydrate (Form I) A sample of carvedilol dihydrogen phosphate hemihydrate (Form I) was analyzed by solid-state 13C NMR and 31P NMR (i.e., to probe solid compound form structure). Carvedilol dihydrogen phosphate (Parent MW=406.5; Salt MW=504.5) has the following structure and numbering scheme: Experimental Details and 13C and 31P Analysis The solid state 13C NMR methods used to analyze compounds of the present invention produce a qualitative picture of the types of carbon sites within the solid material. Because of variable polarization transfer rates and the need for sideband suppression, the peak intensities are not quantitative (much like the case in solution-state 13C NMR). However, the 31P spectra are inherently quantitative. For the 13C analysis, approximately 100 mg of sample was packed into a 7-mm O.D. magic-angle spinning rotor and spun at 5 kHz. The 13C spectrum of the sample was recorded using a CP-TOSS pulse sequence (cross-polarization with total suppression of sidebands). An edited spectrum containing only quaternary and methyl carbons was then obtained using an CP-TOSS sequence with NQS (non-quaternary suppression). The 13C spectra are referenced externally to tetramethylsilane via a sample of solid hexamethylbenzene. For 31P Solid State NMR, approximately 40 mg of sample was packed into a 4-mm O.D. rotor and spun at 10 kHz. Both CP-MAS and single-pulse MAS 31P pulse sequences were used with 1H decoupling. The 31P data are externally referenced to 85% phosphoric acid by a secondary solid-state reference (triphenylphosphine oxide). The Bruker AMX2-360 spectrometer used for this work operates at 13C, 31P and 1H frequencies of 90.556, 145.782 and 360.097 MHz, respectively. All spectra were obtained at 298 K. Results and Discussion The highly sensitive 13C and 31P Solid State NMR identification methods were used for the analysis and characterization of a polymorphic form of Carvedilol phosphate, which confirms its chemical structure in the solid-state. The form of Carvedilol dihydrogen phosphate is defined by these spectra, where both 13C and 31P spectra show clear and distinct differences. In particular, FIG. 26 shows the 13C CP-TOSS spectrum of carevedilol dihydrogen phosphate. An assignment of the numerous 13C resonances in FIG. 1 can be made by chemical shift assignment, the NQS spectrum and comparisons with solution-state 13C assignments. At least two non-equivalent molecules per unit cell are observed in this form of Carvedilol phosphate. FIG. 27 shows the 31P MAS spectrum of carvedilol dihydrogen phosphate. A single phosphorus signal is observed at 4.7 ppm, which is characteristic of phosphate salts. It is to be understood that the invention is not limited to the embodiments illustrated hereinabove and the right is reserved to the illustrated embodiments and all modifications coming within the scope of the following claims. The various references to journals, patents, and other publications which are cited herein comprise the state of the art and are incorporated herein by reference as though fully set forth.
<SOH> BACKGROUND OF THE INVENTION <EOH>The compound, 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]-amino]-2-propanol is known as Carvedilol. Carvedilol is depicted by the following chemical structure: Carvedilol is disclosed in U.S. Pat. No. 4,503,067 to Wiedemann et al. (i.e., assigned to Boehringer Mannheim, GmbH, Mannheim-Waldhof, Fed. Rep. of Germany), which was issued on Mar. 5, 1985. Currently, carvedilol is synthesized as free base for incorporation in medication that is available commercially. The aforementioned free base form of Carvedilol is a racemic mixture of R(+) and S(−) enantiomers, where nonselective β-adrenoreceptor blocking activity is exhibited by the S(−) enantiomer and α-adrenergic blocking activity is exhibited by both R(+) and S(−) enantiomers. Those unique features or characteristics associated with such a racemic Carvedilol mixture contributes to two complementary pharmacologic actions: i.e., mixed venous and arterial vasodilation and non-cardioselective, beta-adrenergic blockade. Carvedilol is used for treatment of hypertension, congestive heart failure and angina. The currently commercially available carvedilol product is a conventional, tablet prescribed as a twice-a-day (BID) medication in the United States. Carvedilol contains an α-hydroxyl secondary amine functional group, which has a pKa of 7.8. Carvedilol exhibits predictable solubility behaviour in neutral or alkaline media, i.e. above a pH of 9.0, the solubility of carvedilol is relatively low (<1 μg/mL). The solubility of carvedilol increases with decreasing pH and reaches a plateau near pH=5, i.e. where saturation solubility is about 23 μg/mL at pH=7 and about 100 μg/mL at pH=5 at room temperature. At lower pH values (i.e., at a pH of 1 to 4 in various buffer systems), solubility of carvedilol is limited by the solubility of its protonated form or its corresponding salt formed in-situ. The hydrochloride salt of carvedilol generated in situ in acidic medium, which simulates gastric fluid, is less soluble in such medium. In light of the foregoing, a salt, and/or novel crystalline form of carvedilol with greater aqueous solubility, chemical stability, etc. would offer many potential benefits for provision of medicinal products containing the drug carvedilol. Such benefits would include products with the ability to achieve desired or prolonged drug levels in a systemic system by sustaining absorption along the gastro-intestinal tract of mammals (i.e., such as humans), particularly in regions of neutral pH, where a drug, such as carvedilol, has minimal solubility. Surprisingly, it has now been shown that a novel crystalline form of carvedilol phosphate salt (i.e., such as carvedilol dihydrogen phosphate and/or carvedilol hydrogen phosphate, etc.) can be isolated as a pure, crystalline solid, which exhibits much higher aqueous solubility than the corresponding free base or other prepared crystalline salts of carvedilol, such as the hydrochloride salt. This novel crystalline form also has potential to improve the stability of carvedilol in formulations due to the fact that the secondary amine functional group attached to the carvedilol core structure, a moiety pivotal to degradation processes, is protonated as a salt. In light of the above, a need exists to develop different carvedilol forms and/or different compositions, respectively, which have greater aqueous solubility, chemical stability, sustained or prolonged drug or absorption levels (i.e., such as in neutral gastrointestinal tract pH regions, etc.). There also exists a need to develop methods of treatment for hypertension, congestive heart failure or angina, etc. which comprises administration of the aforementioned carvedilol phosphate salts and/or solvates thereof or corresponding pharmaceutical compositions, which contain such salts, and/or solvates. The present invention is directed to overcoming these and other problems encountered in the art.
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a salt of carvedilol and/or corresponding solvates thereof, compositions containing such carvedilol and/or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain disease states in mammals, in particular man. The present invention further relates to carvedilol phosphate salts, which include novel crystalline forms of carvedilol phosphate (i.e., such as dihydrogen phosphate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), carvedilol hydrogen phosphate,etc.), and/or other-corresponding solvates thereof. The present invention relates to a pharmaceutical composition, which contains carvedilol phosphate salts and/or solvates thereof. The present invention further relates to a method of treating hypertension, congestive heart failure and angina, which comprises administering to a subject in need thereof an effective amount of a carvedilol phosphate salt (which include novel crystalline forms) and/or solvates thereof or a pharmaceutical composition (i.e., which contains such salts and/or solvates of carvedilol phosphate), etc.
20041216
20070911
20051027
97224.0
4
BARKER, MICHAEL P
CARVEDILOL PHOSPHATE SALTS AND/OR SOLVATES THEREOF, CORRESPONDING COMPOSITIONS AND/OR METHODS OF TREATMENT
UNDISCOUNTED
0
ACCEPTED
2,004
10,518,812
ACCEPTED
Parametric fitting of a cochlear implant
A method of fitting an auditory stimulation system to a recipient the system having a plurality of channels, and the method including the steps of establishing an initial current level profile representative of a current level setting spanning across at least some of the plurality of channels and adjusting parameters of the initial current level profile in the presence of a stimulation signal. There is further included a programming apparatus adapted to be interfaced with the auditory stimulation system to allow manipulation of threshold (T) and comfort (C) levels of the system. The apparatus includes a graphical display means adapted to display a graphical representation of the current profile of the channel array and means for adjusting a current level setting of the current pmfile of the array.
1. A method of fitting an auditory stimulation system having a plurality of channels to a recipient, the method comprising the steps of: establishing an initial current level profile representative of a current level setting spanning across at least some of the plurality of channels; and adjusting parameters of the initial current level profile in the presence of a stimulation signal. 2. A method of fitting an auditory stimulation system of claim 1 further comprising the step of: determining the desired parameters representative of an optimum current level profile corresponding to a recipient's threshold and/or maximum comfort current level profile. 3. A method of fitting an auditory stimulation system as claimed in claim 1 further comprising the steps of establishing the initial current level profile from measurements of the ECAP thresholds for each or at least some of the channels of the auditory stimulation system, and establishing a current level profile based upon the measurements. 4. A method of fitting an auditory stimulation system in claim 1 further comprising the step of establishing the initial current level profile from measurements of the ECAP thresholds for at least one channel of the auditory stimulation system, with the full profile being interpolated from the measurements. 5. A method of fitting an auditory stimulation system as claimed in claim 1 further comprising the steps of establishing the initial current level profile by performing a statistical analysis of recipient mapping data over a number of recipients and subsequently using this analysis to form an initial current level profile for a particular recipient. 6. A method of fitting an auditory stimulation system as claimed in claim 1 further comprising the steps of establishing the initial current level profile by performing psychophysical measurements of the recipient in combination with statistical analysis of recipient mapping data over a number of recipients, and thereby determine a suitable initial current level profile for a particular recipient. 7. A method of fitting an auditory stimulation system as claimed in claim 1 wherein the parameters of the initial current level profile being adjusted include one or a combination of shift, tilt and curvature. 8. A method of fitting an auditory stimulation system as claimed in claim 7 wherein the shift parameter is adjusted by adding/subtracting a fixed amount of current level from each individual channel in the profile. 9. A method of fitting an auditory stimulation system as claimed in claim 7 wherein the tilt parameter is adjusted by adding/subtracting a derived amount of current level from each individual channel in the profile. 10. A method of fitting an auditory stimulation system as claimed in claim 7 wherein the curvature parameter is adjusted by adding/subtracting a derived amount of current level from each individual channel in the profile in a non-uniform manner. 11. A method of fitting an auditory stimulation system as claimed in claim 9 wherein the amount of current added/subtracted from each individual channel varies dependent upon whether the channel is positioned in a basal region or in an apical region of the cochlea. 12. A method of fitting an auditory stimulation system as claimed in claim 11 wherein the current level for channels positioned in the apical region of the cochlea is increased and the current level for channels positioned in the basal region of the cochlea is decreased a derived amount. 13. A method of fitting an auditory stimulation system as claimed in claim 11 wherein the current level for channels positioned in the apical region of the cochlea is decreased and the current level for channels positioned in the basal region of the cochlea is increased a derived amount. 14. A method of fitting an auditory stimulation system as claimed in claim 1 wherein the stimulation signal is derived from a broadband sound signal. 15. A method of fitting an auditory stimulation system as claimed in claim 14 wherein the broadband sound signal is a live speech signal. 16. A method of fitting an auditory stimulation system as claimed in claim 14 wherein the broadband sound signal is an artificial signal. 17. A method of fitting an auditory stimulation system as claimed in claim 14 wherein the broadband sound signal is a recorded signal. 18. A method of fitting an auditory stimulation system as claimed in claim 1 wherein the step of adjusting parameters of the initial current level profile in the presence of a stimulation signal includes adjusting the shift parameter of the initial current level profile until the stimulation signal can just be detected by the recipient, indicative of the stimulation reaching a threshold level. 19. A method of fitting an auditory stimulation system as claimed in claim 16 wherein following establishing the stimulation has reached a threshold level, the tilt parameter of the current level profile is adjusted until an optimal threshold level is perceived by the recipient. 20. A programming apparatus adapted to be interfaced with an auditory stimulation system having a plurality of channels to allow manipulation of threshold (T) and comfort (C) levels of the system, the programming apparatus comprising: a graphical display means adapted to display a graphical representation of the current profile of the channel array; and means for adjusting a current level setting of the current profile of the channel array. 21. A programming apparatus as claimed in claim 20 wherein an initial current level profile representative of the current level setting spanning across at least some of the plurality of channels is established. 22. A programming apparatus as claimed in claim 21 wherein parameters of the initial current level profile are adjusted in the presence of a stimulation signal. 23. A programming apparatus as claimed in claim 22 wherein the initial current level is established from measurements of the ECAP thresholds for each or at least some of the channels of the auditory stimulation system, and a current level profile is established based upon the measurements. 24. A programming apparatus as claimed in claim 22 wherein the initial current level profile is established from measurements of the ECAP thresholds for at least one channel of the auditory stimulation system, with the full profile being interpolated from the measurements. 25. A programming apparatus as claimed in claim 22 wherein the initial current level profile is established by performing a statistical analysis of recipient mapping data over a number of recipients, the analysis subsequently being used to form the initial current level profile for a particular recipient. 26. A programming apparatus as claimed in claim 22 wherein the initial current level profile is established by performing psychophysical measurements of the recipient in combination with statistical analysis of recipient mapping data over a number of recipients, thereby determining a suitable initial current level profile for a particular recipient. 27. A programming apparatus as claimed in claim 22 wherein the parameters of the initial current level profile being adjusted include one or a combination of shift, tilt and curvature. 28. A programming apparatus as claimed in claim 27 wherein the shift parameter is adjusted by adding/subtracting a fixed amount of current level from each individual channel in the profile. 29. A programming apparatus as claimed in claim 27 wherein the tilt parameter is adjusted by adding/subtracting a derived amount of current level from each individual channel in the profile. 30. A programming apparatus as claimed in claim 27 wherein the curvature parameter is adjusted by adding/subtracting a derived amount of current level from each individual channel in the profile in a non-uniform manner. 31. A programming apparatus as claimed in claim 29 wherein the amount of current added/subtracted from each individual channel varies dependent upon whether the channel is positioned in a basal region or in an apical region of the cochlea. 32. A programming apparatus as claimed in claim 31 wherein the current level for channels positioned in the apical region of the cochlea is increased and the current level for channels positioned in the basal region of the cochlea is decreased a derived amount. 33. A programming apparatus as claimed in claim 31 wherein the current level for channels positioned in the apical region of the cochlea is decreased and the current level for channels positioned in the basal region of the cochlea is increased a derived amount. 34. A programming apparatus as claimed in claim 22 wherein the stimulation signal is derived from a broadband sound signal. 35. A programming apparatus as claimed in claim 34 wherein the broadband sound signal is a live speech signal. 36. A programming apparatus as claimed in claim 34 wherein the broadband sound signal is an artificial signal. 37. A programming apparatus as claimed in claim 34 wherein the broadband sound signal is a recorded signal. 38. A programming apparatus as claimed in claim 22 wherein the adjusted parameters include the shift parameter of the initial current level profile, which shift parameter is adjusted until the stimulation signal can just be detected by the recipient, indicative of the stimulation reaching a threshold level.
FIELD OF THE INVENTION The present invention relates to an improved method of clinically fitting a cochlear implant to a recipient to satisfy the recipient's hearing needs. DESCRIPTION OF THE PRIOR ART Cochlear implants have been developed to assist people who are profoundly deaf or severely hearing impaired, by enabling them to experience hearing sensation representative of the natural hearing sensation. In most such cases, these individuals have an absence of or destruction of the hair cells in the cochlea which naturally transduce acoustic signals into nerve impulses which are interpreted by the brain as sound. The cochlear implant therefore bypasses the hair cells to directly deliver electrical stimulation to the auditory nerves with this electrical stimulation being representative of the sound. Cochlear implants have traditionally consisted of two parts, an external speech processor unit and an implanted receiver/stimulator unit. The external speech processor unit has been worn on the body of the user and its main purpose has been to detect the external sound using a microphone and convert the detected sound into a coded signal through an appropriate speech processing strategy. This coded signal is then sent to the receiver/stimulator unit which is implanted in the mastoid bone of the user, via a transcutaneous link. The receiver/stimulator unit then processes this coded signal into a series of stimulation sequences which are then applied directly to the auditory verve via a series of electrodes positioned within the cochlea, proximal to the modiolus of the cochlea. With improvements in technology it is possible that the external speech processor and implanted stimulator unit may be combined to produce a totally implantable cochlear implant unit that is capable for operating, at least for a portion of time, without the need for any external device. In such a device, a microphone would be implanted within the body of the user, for example in the ear canal or within the stimulator unit, and sounds would be detected and directly processed by a speech processor within the stimulator unit, with the subsequent stimulation signals delivered without the need for any transcutaneous transmission of signals. Such a device would, however, still have the capability to communicate with an external device when necessary, particularly for program upgrades and/or implant interrogation, and if the operating parameters of the device required alteration. Typically, following the surgical implantation of a cochlear implant; the recipient must have the implant fitted or customised to conform with the specific demands of that recipient. This procedure is often referred to as programming or “mapping” and is the term given to the process of measuring and controlling the amount of electrical current delivered by the cochlea implant to provide comfortable and usable stimulation to the recipient. This process leads to the creation of a program or map that ensures stimulation from the implant provides a recipient with comfortable and useful auditory perception, and is essential in ensuring that the recipient receives maximum benefit from the cochlear implant. As the implant system is designed to present acoustic information, in particular speech, to a recipient in a useable form, the initial aim of the mapping process is to optimise the information provided for a particular recipient. A fundamental aspect of this procedure is the collection and determination of recipient specific parameters such as threshold levels (known as T levels) and. maximum comfort levels (known as C levels) for each stimulation channel. The T and C levels vary from recipient to recipient and from stimulation channel to stimulation channel and are essential in determining how well the recipient hears and understands detected speech or sounds. Conventionally, the step of determining T and C levels is manually performed by applying stimulation pulses for each electrode channel of the implant and receiving an indication from the implant recipient as to the level and comfort of the resulting sound. The T level is defined as the level at which the recipient first identifies sound sensation, and is the lowest level of stimulation that evokes the sensation of sound for that channel. The T level is often determined by passing the recipient's hearing threshold twice using an ascending method and determining the level at which the recipient experiences sound by observing their response by indicating gestures in the case of adults, or behavioural reactions in the case of children. The C level sets the maximum allowable stimulation level for each electrode channel and is defined as the maximum stimulation level that feels comfortable to the recipient. In setting and establishing the C levels, it is usual to instruct the recipient to indicate a level which is “as loud as would be comfortable for long periods” whilst slowly increasing the stimulation. The C levels affect how speech sounds to the recipient more than T levels as most of the acoustic speech signal will be mapped onto the top 20% of the T and C level range. Establishing and setting T and C levels for each electrode channel in a programming process is an important aspect of a fitting session for a cochlear implant. For implants with a large number of electrode channels for stimulation, this process is quite time consuming and rather subjective as it relies heavily on the recipient's subjective impression of the stimulation rather than any specific measurement. This aspect is further complicated in the case of very young children, children with multiple handicapping conditions and/or are developmentally delayed, and pre-lingually or congenitally deaf recipients who are unable to supply an accurate impression of the resultant hearing sensation. In these cases, the fitting of the implant may be non-optimal. In such cases an incorrectly fitted implant will result in the recipient not receiving optimum benefit from the implant and in the cases of children may directly hamper the speech and hearing development of the child. A number of proposals have been put forward to provide a more objective approach to fitting a cochlear implant to a recipient that reduces the reliance of the process on feedback from the recipient in response to stimulation. However such proposals typically attempt to make an estimate of appropriate T and C levels for each specific electrode channel, and still allow for fine tuning based upon some form of subjective input from the recipient. U.S. Pat. No. 5,626,629 provides one such approach whereby the T and/or C levels are estimated for each stimulation channel by measuring the stapedius reflex and/or EABR in response to stimulation pulses applied on each of the channels. Such a system enables the mapping process to proceed without relying upon subjective feedback from the recipient, but still requires the objective measurements to be obtained for all of the electrode channels which is both a time consuming and complicated process. Further, when the patient is able to provide subjective feedback, each of the T and C levels for each channel still require manual adjustment, which is a common problem of the prior art. U.S. Pat. No. 6,157,861 also provides a system for obtaining objective measurements of the T and/or C levels without relying on subjective feedback from the recipient. In this approach, the stapedius reflex is detected for stimulaiion applied on each channel in accordance with a dedicated stapedius reflex sensor system. As was the case in the above mentioned patent, this approach also requires that the stapedius reflex be measured for each specific electrode channel which is both a time consuming and delicate process. The present invention is directed to a process of programming the operation of a cochlear implant that address the problems described herein. In order to improve the programming process and decrease the time taken to develope a useful map for a recipient, there is a need to obtain and manipulate the T and C levels more effectively than has previously been the case. In the past, T and C levels have been obtained and manipulated on a one-by-one basis and not globally, taking into consideration the interaction between channels. This has resulted in there being a number of degrees of freedom and a great degree of variability and uncertainty in the manipulation of T and C levels. The present invention aims to reduce the variability and uncertainty associated with setting the T and C levels for a recipient and to concentrate on manipulating these levels parametrically, based upon objective measures, statistical analysis of recipient maps and from other such observations or theoretical considerations. The present invention preferably provides a method for fitting a speech processor and implantable cochlear stimulator to a particular recipient in a quicker and more effective manner than has historically been the case. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application. SUMMARY OF THE INVENTION In accordance with one aspect of the invention, there is provided a method of fitting an auditory stimulation system having a plurality of channels to a recipient, the method comprising the steps of: establishing an initial current level profile representative of a current level setting spanning across at least some of the plurality of channels; and adjusting parameters of the initial current level profile in the presence of an stimulation signal. In a further embodiment of this aspect, the method can further comprise a step of: determining the desired parameters representative of an optimum current level profile corresponding to a recipient's threshold and/or maximum comfort current level profile. According to a second aspect of the invention, there is provided a programming apparatus adapted to be interfaced with an auditory stimulation system having a plurality of channels to allow manipulation of the threshold (T) and comfort (C) levels. of the system, the programming apparatus comprising: a graphical display means adapted to display a graphical representation of the current profile of the channel array; and means for adjusting a current level setting of the current profile of the array.. In a preferred embodiment, the auditory stimulation system comprises a cochlear implant system. The cochlear implant system preferably utilises an electrode array to deliver electrical stimulations to the cochlear of a recipient. In one embodiment, the array comprises 22 intracochlear electrodes and at least one extracochlear electrode. By manipulating the parameters of a current level profile spanning preferably all electrode channels of the electrode array, there is no need to adjust threshold and comfort level currents for each individual electrode channel in the array of an implant following implantation in the recipient. Instead, manipulation is preferably applied to the entire channel profile resulting in a greatly reduced amount of psychophysical measurements required and a programming/fitting procedure that is more recipient friendly, more time efficient and more cost effective. Preferably, the step of establishing an initial current level profile includes a step of obtaining measurements of the evoked compound action potential (ECAP) thresholds for each or a number of the electrode channels and establishing a current level profile based upon these measurements. In another embodiment, the initial current level profile is preferably established from measurements of the ECAP thresholds for at least one electrode channel of the auditory stimulation system, with the full profile being interpolated from such measurements. In another embodiment, the step of establishing an initial current level profile. includes the step of performing a statistical analysis of recipient mapping data over a number of recipients and using this analysis to form an initial current level profile for a particular recipient. In yet another embodiment, the step of establishing an initial current level profile includes the step of performing a number of psychophysical and/or electrophysiological measurements of the recipient in combination with statistical analysis of recipient mapping data over a number of recipients to determine a suitable initial current level profile for a particular recipient. The initially determined suitable current level profile is preferably represented on the graphical display means of the programming apparatus to allow ready determination by a clinician of the current profile of the array. The step of adjusting the overall parameters of the initial current level profile preferably includes adding/subtracting a fixed or derived amount of current level from each individual electrode channel in the profile. This parameter adjustment is referred to as a “shift” manipulation, and has the effect of moving the profile up or down in a vertical direction on a graph plotting current level against electrode channel number. By “shifting” the profile “up”, either a fixed amount of current is added to the current level of each individual electrode channel in the profile (linear shift), or an individually derived current level is added to each electrode channel (non-linear shift), thereby increasing the amount of current delivered by the electrode channels when operated with that particular profile. By “shifting” the profile “down”, either a fixed amount of current is subtracted from the current level of each individual electrode channel in the profile (linear shift), or an individually derived current level is subtracted from each electrode channel (non-linear shift), thereby decreasing the amount of current delivered by the electrode channels when operated with that particular profile. The overall parameters of the initial current profile can also be adjusted by adding an electrode channel specific derived amount of current level to a subset of electrode channels in the profile and subtracting an electrode channel specific derived amount of current level from the remaining electrode channels. This parameter adjustment is preferably referred to as a “tilt” manipulation, and has the effect of tilting the profile clockwise or anti-clockwise on a graph plotting current level against electrode channel. In a preferred embodiment, the “tilt” manipulation may be performed by using at least one electrode channel, for example electrode channel 12 of said plurality of electrode channels, as a pivot point and for each electrode channel 1-11 the individual current levels of each electrode channel is decreased by a varying percentage of a fixed amount of current, and for each electrode channel 13-22, the current level for each electrode is increased by a varying percentage of a fixed amount of current, or vice versa. In this regard and where the electrode array is adapted to be positioned within the cochlea, the electrodes positioned in the apical region may have their current levels increased and those within the basal region may have their current levels decreased, or vice versa. The amount of current level to be added/subtracted from the electrode channel can be a function solely depending on the distance of the electrode channel in question to the pivot point (linear tilt) or can have a more complex dependency, e.g. depend from a separate “tilt profile” in addition (non-linear tilt). The overall parameters of the initial current level profile can also be adjusted by adding/subtracting a derived amount of current level from each individual electrode channel in the profile in such a way as to bend the current level profile. This can be interpreted as a profile manipulation using 2 pivot points, which might be allocated but are not limited to the most basal and most apical electrode channel. These pivot points might even be situated outside the actual range of electrode channels available. This parameter adjustment can be referred to as a “curvature” manipulation and has the effect of causing the profile to curve or change shape on a graph plotting current level against electrode channel. The “curvature” can be achieved in a linear and non-linear manner, as described above. The derived values used for the non-linear manipulations can stem from statistical analysis, such as factor analysis of available clinical data. They can be influenced by several factors, such as the actual starting level, whether it is a T or a C level, the implant and electrode type used or the coding strategy applied. Other sources of influence and any combination of factors can be used to calculate the derived data. Other parameter manipulations suitable to adjusting the current level profile are also included within the scope of the present invention. In a preferred embodiment, the step of adjusting the overall parameters of the initial current level profile can include any one or combination of a “shift” manipulation, a “tilt” manipulation and/or a “curvature” manipulation. Adjustment of the profile is preferably performed through a clinician interface that allows the current profile of the electrode array to be adjusted in the manner described herein. In one embodiment, a software package can be run on a computer, with the software package offering input means that allows the clinician to readily adjust the current profile of the array. The input means can comprise one or more of a mouse, joystick, roller ball, keyboard, or keypad, that allows the clinician to adjust the settings within the software package. In a preferred embodiment, the overall parameters of the initial current level profile are adjusted in the presence of a broad band signal, preferably a live speech signal. The broadband signal alternatively may be an artificial signal or a recorded signal. In such a case, the implant delivers stimulation representative of the signal, in accordance with the current level profile. By adjusting the parameters of the current level profile the stimulation delivered by the implant varies, allowing the stimulation signal to be optimised in terms of recipient threshold and maximum current levels. The method and apparatus according to the present invention present a number of potential advantages over existing techniques. In particular, it is envisaged that fewer psychophysical measurements will be needed to prepare a map for a particular recipient and the channels will be manipulated globally rather than individually. The ability to use live sounds is also potentially more interesting for small children than arbitrary stimuli used to date. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which: FIG. 1 is a graphical example of a typical recipient map generated by conventional mapping techniques; FIG. 2 is a graphical representation of a typical ECAP waveform showing negative (N1) and positive (P1) peaks; FIG. 3 is a graphical representation of the changes in ECAP as a function of the stimulus current level; FIG. 4 shows the ECAP growth function; FIG. 5 shows the relationship between the average ECAP thresholds and the behavioural T and C levels for a group of 82 recipients using the Nucleus® 24 implant; FIG. 6 shows the relationship between the ECAP thresholds and the behavioural T and C levels from a recipient implanted with a Nucleus® 24 Contour™ implant; FIG. 7 is a flow chart of the method of the present invention; FIG. 8 shows the step of importing ECAP thresholds according to one embodiment of the present invention; FIG. 9 shows the step of interpolating the CL profile from the imported ECAP thresholds of FIG. 8, according to an embodiment of the present invention; FIG. 10 shows complete ECAP thresholds used as an initial CL profile according to another embodiment of the present invention.; FIG. 11 shows the initial CL profile being shifted below the recipient's hearing threshold according to step 2 of FIG. 7; FIG. 12 shows the CL profile representative of when a recipient can just hear live speech according to steps 3 and 4 of FIG. 7; FIG. 13 shows the CL profile tilted a current level value of +5 according to step 5 of FIG. 7; FIG. 14 shows the CL profile tilted a current level value of +10 according to step 5 of FIG. 7; FIG. 15 shows the CL profile tilted a current level value of +15 according to step 5 of FIG. 7; FIG. 16 shows the CL profile tilted a current level value of −5 according to step 5 of FIG. 7; FIG. 17 shows the CL profile tilted a current level value of −10 according to step 5 of FIG. 7; and FIG. 18 shows an example of an optimum T-level profile generated from the initial CL profile according to step 9 of FIG. 7. PREFERRED MODE OF CARRYING OUT THE INVENTION The following description is directed to a cochlear implant system having an electrode array, in particular an array having twenty-two intracochlear electrodes. It will be appreciated that the invention has potential applicability to any auditory stimulation system utilising an electrode array and in particular to electrode arrays comprising less or more electrodes than that described herein. Throughout the specification a channel is considered to be a pair of electrodes that provide a path for current to flow . One electrode is called the active electrode and the other is called the reference electrode. Pulses of current flow from the reference to the active electrode and back again to stimulate nearby nerves. Our implant provides up to 22 channels. In order to better understand the present invention, it is appropriate to firstly consider one method of programming a cochlear implant and creating a map which enables the speech processor to output data in a form which can be decoded by the receiver/stimulator. As a map is a complete set of instructions for the speech processor which includes the minimum and maximum stimulation levels for each stimulation channel, conventional programming methods have required the clinician creating the map for the recipient of the implant, to measure T and C levels for each channel, for the stimulation mode and speech processing strategy chosen for the recipient. This process requires an experienced clinician/audiologist to present a stimulus, usually a fixed phase biphasic pulse at a fixed rate and duration, to each channel of the recipient's implanted electrode array. The clinician/audiologist then asks the subject to estimate the lowest level at which that stimulus can be detected (T level) and the level judged by the recipient as being the upper limit of comfort (C level). This process is repeated for all of the channels, for example, all 22 electrode channels in a current Nucleus® model device as manufactured by the present applicant, until a map is created which includes T and C levels for each channel that delivers stimulation pulses. It has been found that initial estimates of the T and C levels as determined by the clinician/audiologist working in conjunction with the recipient (where possible) using the conventional method are variable and may take months to stabilise. As such, it is easy to appreciate that the conventional programming method is a laborious task requiring much experience and expertise by the clinician and relying on good feedback from the recipient to create the most optimal map. FIG. 1 shows the T and C levels for a typical recipient map which may be generated by a clinician during such a mapping session. These levels have been generated using a software package developed by the present applicant to assist the clinician by providing an interface that is easy for the clinician to manipulate and visualise. The horizontal sections numbered 1-22 (along the top) indicate the channel number along the intracochlear array of the implant, and the vertical axis represents current level for each electrode channel in the array. This software package is run on a computer that outputs signals set by the software package through an interface. The interface is adapted to connect to the speech processor and allow transmission of signals from the computer to the processing control system of the speech processor which in turn outputs stimulation signals via the transcutaneous radio frequency (RF) link to the implanted receiver/stimulator unit of the system. As is shown in this particular example, the upper vertical limit for each channel is the maximum comfort level (C level) which represents for that particular channel, the maximum amount of current which can be delivered to deliver a sensation to the recipient at a loudness level which is just tolerable to that recipient. The lower vertical limit for each channel is the threshold level (T level) which represents the amount of current which can be delivered by that channel to produce a sensation that is just audible to the recipient. In this particular example, the T and C levels for a number of channels are specifically shown, for example the T and C levels for electrode channel 11 are 128 and 168 respectively, and in use all sounds detected are mapped between these 2 levels to produce the equivalent sound sensation to the recipient. In the software package as shown in FIG. 1, the T and C levels can be altered up or down by the clinician using appropriate controls on the computer so leading to altered signals being sent to the speech processor which in turn adjusts the stimulation signals output by the electrode array. This alteration can be made with feedback from the recipient indicating whether the sensation is either too loud orjust audible. Whilst the conventional mapping techniques are time consuming and arduous for both the clinician and the recipient, there has to date been no reliable alternative implemented on a wide scale. However, with an increased understanding of the response of nerves to electrical stimulation, there has been research into how this increased understanding can assist in understanding the parameters associated with delivering electrical stimulation, and this has suggested possible new ways to improve the conventional mapping process. For a number of years it has been possible to record the electrically evoked auditory brain stem response (EABR) in cochlear implant recipients and a number of studies have been conducted which have attempted to correlate EABR thresholds to mapped threshold and/or comfort levels. Such EABR measurements have required the use of surface recording electrodes and the complications and lengthy nature of this measuring process have hindered this technique from becoming routinely adopted. Still further, the recipient being assessed has often had to be asleep or heavily sedated to avoid contaminated measurements from being recorded by the recording electrodes. It is only more recently that a simple and more direct way to assess auditory nerve function in cochlear implants has been possible, by measuring the electrically evoked compound action potential (ECAP). This potential reflects the synchronised response of peripheral auditory nerves delivered by an intracochlear electrode, and the response typically resembles a waveform having an initial negative peak followed by a positive peak. Initially, such ECAP measurements could only be obtained intraoperatively through the use of a temporary intracochlear electrode array, or with cochlear implant recipients having a device with a percutaneous plug. In such cases, the ability to perform such measurements was only done experimentally, and as special instances had to be set up to allow such measurements to be taken, it was not possible to obtain such results for everyday use. Recent developments undertaken by the present applicant have allowed for a quick and non-invasive method for recording the ECAP of the peripheral auditory nerves in situ, without the need for dedicated devices or plugs. Such a method has been designed into the conventional cochlear implant system to provide an additional feature of the system which can be utilised to take such measurements. The applicant's Nucleus® 24 model cochlear implants were the first implant system with such capabilities, and only now are the benefits of such a feature becoming fully realised. The feature for recording the ECAPs in the Nucleus® 24 model device is known as Neural Response Telemetry (NRT) and whilst this application focuses on the NRT feature, it should be appreciated that this invention will be also applicable to other such methods of recording ECAPs, and hence should not be limited to use with the specific NRT feature. In the mentioned feature, the bi-directional telemetry system that is present in the cochlear implant is used to measure the ECAP of the recipient's auditory nerve. Dedicated ECAP measurement software communicates with the implanted receiver/stimulator unit via the speech processor and RF link and biphasic current pulses are delivered to a single intracochlear electrode of the array. The resulting ECAP is measured from a neighbouring electrode, amplified, encoded and sent back to the speech processor via the RF link. The data is then analysed using the speech processor and the dedicated ECAP measurement software, with the software then presenting the results in a manner easily interpreted by a clinician or implant specialist. As mentioned previously, in such a system the ECAP measurement can be taken without the need of any extra equipment, and therefore has considerable advantages over other evoked potential measures, such as the electrically evoked auditory brainstem response (EABR). U.S. Pat. No. 5,758,651 describes one system and apparatus for recovering ECAP data from a cochlear implant. This system measures the neural response to the electrical stimulation by using the stimulus array to not only apply the stimulation but to also detect and receive the response. In this system the array used to stimulate and collect information is a standard intra-cochlear and/or extra-cochlear electrode array. Following the delivery of a stimulation pulse via chosen stimulus electrodes, all electrodes of the array are open circuited for a period of time prior to measurement of the induced neural response. The purpose of open circuiting all electrodes prior to measurement is to reduce the detected stimulus artefact measured with the ECAP nerve response. Whilst the above system has proven useful in capturing and investigating evoked neural response in the cochlea, there are still a number of limitations intrinsic with this system, in particular in resolving the neural response from the stimulus artefact. This process has presented considerable difficulties, including problems such as the fact that the signals that are to be measured are extremely low level signals (down to the order of 10 μV.). In cochlear implant applications in particular, a stimulus pulse is delivered with an amplitude typically in the range of 1 V. to 10 V., which is orders of magnitude greater than the response that is to be measured resulting from this stimulation. 'Providing for a system that is firstly able to deliver a stimulus of sufficient amplitude and also to detect the elicited response of the nerves to that particular stimulation has therefore been problematic. Due to the nature of the neural response, the sensing system must be ready to record this response within a short delay (preferably less than 50 μs) after the trailing edge of the stimulus. In order to properly resolve the very small neural signal a large amplifier gain is required (typically of about 60 dB to 80 dB), however the neural signal is superimposed on a much larger artefact which distorts the actual measured signal considerably. In order to overcome the above mentioned problems, the system as described in International Patent Application PCT/AU02/00500 was developed which delivers, subsequent to the first stimulus, a compensatory stimulus in order to counteract a residue charge distribution caused by the first stimulus. In this system, the artefacts associated with the stimulus could be addressed at the time of measuring the ECAPs, without the need for post measurement processing, thereby providing a more exact and useable measurement. This application also describes a method of optimising the parameters of the compensatory stimulus to take into account differences in the artefacts present, as may be the case from electrode to electrode or from recipient to recipient. With improved methods of obtaining such measurements, there has been an interest in investigating ways to use this information in a clinical setting, rather than using the information merely to check that the electrodes are delivering stimulation. A number of initial studies have been undertaken to investigate potential clinical applications of such measurements, with a focus of such measurements being on determining whether the ECAP response can be used to aid in the programming of the cochlear implant speech processor. It is considered that such an application would be beneficial to clinicians and audiologists who work with very young children, where programming the speech processor presents significant challenges. One such investigation was reported in Brown CJ, Hughes ML, Luk B, Abbas PJ, Wolaver A, Gervais J (2000) “The Relationship Between EAP and EABR Thresholds and Levels Used to Program the Nucleus 24 Speech Processor: Data from Adults” Ear & Hearing, 21, 151-163. In this investigation, ECAP thresholds were correlated with conventionally mapped T and C levels and it was shown that the correlation was not sufficiently strong to suggest that ECAP measurements could be directly used without some level of behavioural information. This investigation suggested that whilst ECAP thresholds alone may not be strong predictors of either T or C levels, a combination of these results with a small amount of behavioural information may allow clinicians working with individuals with limited attention and/or response capabilities to be fitted with a cochlear implant with reasonable accuracy. This finding was also consistent with a finding reported in Hughes ML, Brown CJ, Abbas PJ, Wolaver AA, Gervais JP (2000) “Comparison of EAP Thresholds with MAP Levels in the Nucleus 24 Cochlear Implant: Data from Children” Ear & Hearing, 21, 164-174. In this investigation, ECAP thresholds were shown to fall between T and C levels for 18 out of 20 subjects tested. However, there existed a level of variability across recipients sufficient to make map threshold or comfort level predictions based solely on the objective ECAP measures to have a significant error in most cases. Therefore, the ECAP thresholds could provide an indication of “safe” levels of stimulation. In order to understand this further, a typical ECAP waveform is shown in FIG. 2, with the ECAP waveform consisting of an initial negative peak (labelled N1) followed by a positive peak (labelled P1). Using a recipient's Nucleus® 24 model implant, the ECAP measurement can be taken without the need for any extra equipment, as a neighbouring electrode to that which delivers the stimulation can be used to measure the ECAP, whereby the implant amplifies, encodes, and transmits the signal back to an external unit which then analyses the data with dedicated software, to enable the data to be easily interpreted by the clinician. The N1 and P1 amplitude of the ECAP waveform vary with stimulating current as can be seen in FIG. 3, with the amplitudes increasing with increases in stimulating current level. It is the amplitude growth function that can be used to estimate the ECAP threshold, and to quantify how the response changes with stimulus intensity. This is obtained via dedicated software that uses the ECAP amplitude, which is the difference (in μV.) between the N1 and P1 amplitudes, which is evident in the graph in FIG. 2. The ECAP threshold may be estimated visually by reviewing the amplitude growth series and selecting the electrical stimulation level which produces the smallest repeatable N1 and P1 peaks in the waveform, or software can be used to extrapolate the ECAP threshold from the amplitude growth function. As is shown in FIG. 4, the amplitude growth function is a plot of the ECAP amplitudes as a function of stimulus current levels and it has been found that a linear regression line can be fitted to the data to extrapolate the ECAP threshold and to define the slope of the function. As mentioned above, the clinical value of the ECAP thresholds has been investigated, and it has been shown that there are some important relationships between the current levels of the ECAP thresholds and the behavioural T and C levels established by a clinician during a mapping procedure. The main relationships are that the ECAP thresholds correlate with the behavioural T and C levels, however the ECAP thresholds are not equal to the T or C levels but typically lie between the T and C levels, with the ECAP thresholds being typically audible to the recipient. This aspect is shown in FIG. 5, where there is shown the average ECAP thresholds (T-NRT) and the behavioural T and C levels for a group of 82 recipients using the Nucleus® 24 model implant. A further finding has been the fact that the profile of the ECAP threshold levels as a function of electrode number resembles the profiles of the T levels and to a lesser extent the C levels. This is shown in FIG. 6, where the ECAP threshold profile (T-NRT) and the behavioural T and C levels are shown from a recipient implanted with a Nucleus® 24 model implant and Contour™ model array, which is manufactured by the present applicant. With this understanding of how objective measurements can be taken which show the response of the peripheral auditory nerves to electrical stimulation delivered by the cochlear implant, there is a need to attempt to utilise these developments to make the fitting/programming session(s) for a cochlear implant more user friendly and clinically efficient. An embodiment of the method according to the present invention is depicted by the flowchart in FIG. 7. This method preferably provides a more efficient method of establishing and setting the T and C levels which are specific to each particular recipient. The method of the present invention consists essentially of 2 steps which are used in the same manner to establish the T and C levels for a recipient. The starting point in all cases is to establish an initial current level profile across all electrode channels that can be manipulated by adjusting a few profile parameters to establish the T and C levels for that recipient. These parameters include, but are not limited to, vertical position shift, profile tilt and profile curvature of the current level profile. The first step essentially moves each initial current level in the profile a series of increments until a target is met. This target would be either the fact that the threshold point has been determined, or that the maximum current level has been determined. Once this has occurred, the next step is to identify optimal values for other parameters describing the profile, to best achieve the target, namely that the threshold point has been achieved or that the maximum comfort point has been achieved. The first step of the present invention is to establish a predefined initial current level (CL) profile (ie. step 1 of the flow chart). This profile gives a current level setting for each electrode channel and is the basis from which the final T and C level profiles are established. It is envisaged that more than one initial profile could be used, for example, one profile for setting T levels, another for setting C levels etc. As mentioned previously, this initial CL profile may be the result of measurements of the ECAP thresholds for each or a few of the electrodes, the result of a statistical analysis of recipient mapping data over a number of subjects, or the result of a number of electrophysiological and/or psychophysics measurements in combination with statistical analysis, such as multiple regression. It is also conceivable that the initial CL profile may be a straight line. Ideally, the initial CL profile is established without the need for subjective feedback from the recipient and without the need for multiple tests to be performed on the recipient for each specific electrode channel. As is shown in FIG. 8, the initial CL profile may be derived from a small number of measured ECAP thresholds for specific electrode channels, with the full profile being predicted for non-measured channels, similar to as is shown in FIG. 9. In this depicted example, ECAP thresholds were measured for 7 electrode channels with the values for the non-measured channels being extrapolated therefrom. However, in a another embodiment, the ECAP thresholds for each channel would be used as the initial CL profile, as is shown in FIG. 10. Once the initial CL profile has been established in step 1, it is then preferably manipulated to establish appropriate T and C levels for the recipient. In step 2 of this process, the initial profile is shifted below the predicted desired target setting. In the case of setting the T-level profile, the initial CL profile would be shifted down to a level that would be below a recipient's threshold of hearing; for example, the maximum current level of the CL profile could be reduced to a current level of 80 with all other levels being relative to this. In the case of setting the C level profile, the initial CL profile could be moved to any level that is below the maximum comfort level of the recipient as a starting point, for example, the previously identified threshold. A graphical example of this in relation to the setting of T levels can be seen in FIG. 11, wherein the initial CL profile is shown as the thin line, and the dotted line represents the initial CL profile being shifted down below an arbitrary threshold level, ie. should the electrodes be stimulated to those current levels, the recipient would not experience sound sensation. It is this “shift” action that provides the first manipulation or adjustment of the CL profile. In step 3, the recipient is presented with a broad band signal, for example a live speech sample, and the stimulation representative of this signal is delivered by the electrode array of the implant to the recipient within the constraints of the CL profile set by step 2. If the recipient does not detect the live speech, the CL profile is then shifted up or increased by a level step size (for example iterations of 5 current levels at a time) until the live speech is detected by the recipient, and what is considered as the “shift target” is met. FIG. 12 is a graphical representation of this, showing the CL profile which has been shifted up a number of level steps from that shown in FIG. 11, with this profile indicative of the point where the recipient indicates that they are detecting live speech. At this stage in the process, the CL profile can be lowered one incremental step, and the profile manipulated by adjusting one parameter of a limited set of parameters, thereby changing the characteristics of the CL profile (ie step 5 in FIG. 7). In one embodiment, this manipulation is performed by applying a “tilt” manipulation to the profile, wherein a derived amount of current level is added/subtracted to each individual current level value for the individual electrode channels of the electrode array. This manipulation literally “tilts” the profile as represented on a graph of current level against electrode channel number. That is, the profile is shifted down for high frequency channels and up for low frequency channels or vice versa. It is envisaged that the “tilt” may be linear or non-linear, e.g. derived from a tilt profile. A software package can automatically apply this “tilt” manipulation, by using, for example, electrode channel 12 as the pivot point. In the case of a linear tilt, for each channel from 22-13, the current level is increased by a varying percentage of fixed current levels, and for each channel from 11-1, the current levels are decreased by a varying percentage of fixed current levels, or vice versa. The use of other electrode channels in the array as “pivot points” for the tilt manipulation can be envisaged. In a preferred embodiment, the fixed current level may be 5. FIG. 13 is a graphical example of such a CL profile manipulation indicative of a current level tilt of 5. In this step of the process, the CL profile is manipulated by using the “tilt” value, until the live speech is no longer detected, ie. the target is not met. Then, step 3 as described above is repeated (shown in FIG. 7 as step 6) until the recipient can again detect the live speech. If no further shift/tilt combination meets the target criteria (i.e. sound detection in this example), then the current value for shift is the target shift value. The target shift value is that, which did not meet the target criterion and includes the highest CL amongst the profiles using the target shift and a tilt meeting the target. This CL profile is then saved in step 7. FIGS. 14-17 illustrate examples of different tilt values which may be used for steps 5 and 6, namely a fixed current level tilt of 10, 15, −5 or −10 may be used for these steps. FIG. 18 represents a graphical example of an optimum threshold CL level achieved using this process, ie the initial CL profile which has been shifted down 10 current levels and tilted 10 current levels. Having met the condition leading to step 7, the optimum CL profile is set as the T-level profile for use in the recipient's map. Alternatively, the process could be continued by manipulating other profile parameters, such as profile curvature. Whilst this process has been shown only in relation to setting the T levels, it can easily be used to set the C levels, with the only change required being the criterion of the “target”. For setting the C levels, the “target” criterion is maximum comfort of sound perceived by the recipient, rather than sound detection, as is the case in setting the T levels. Further, whilst the process described above has combined the shift and tilt functions, the two functions can be applied separately. In this regard, the shift function can be used to move the CL profile to a threshold or maximum comfort position where the tilt or other such functions can be applied to the CL profile to optimise and fine time the CL profile. One example of the present invention being employed to set the T and C levels for an implant recipient that previously had the T and C levels set individually for each channel is described as follows: 1. An initial current level profile was set for the recipient based upon previous statistical threshold level data. 2. The initial current level profile was dropped below the recipient's threshold level. 3. The current level profile was then raised in incremental shifts in the presence of live voice until indication was obtained of the sound becoming audible to the recipient. 4. Upon establishing the point where the live signal became audible, the current level profile was fixed as the T-level profile. 5. The current level profile was then raised in incremental shifts in the presence of live voice until indication was given by the recipient of the loudness of the sound being at its maximum comfortable level. 6. The tilt of the current level profile at maximum comfort level was then increased/decreased and subjective judgement was obtained to determine the optimum current level profile which was then set as the C-level profile. 7. Step 6 was then repeated for the T-level profile. This procedure took less than 5 minutes to complete, and the T and C levels were then programmed into their speech processor map for subsequent use. The recipient reported that sound perception using the map created by the present invention was substantially the same as the sound perception using the map created by the conventional mapping techniques. The present invention therefore requires minimal psychophysics measurements using live voice, compared to many psychophysical measurements (roughly equivalent to twice the number of channels) using artificial stimuli as is the case in conventional mapping procedures. As a result, the present invention provides a programming/mapping procedure that is more recipient friendly, and makes the fitting procedure, especially for small children, simpler, more time efficient and more cost effective then has historically been the case. It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to an improved method of clinically fitting a cochlear implant to a recipient to satisfy the recipient's hearing needs.
<SOH> SUMMARY OF THE INVENTION <EOH>In accordance with one aspect of the invention, there is provided a method of fitting an auditory stimulation system having a plurality of channels to a recipient, the method comprising the steps of: establishing an initial current level profile representative of a current level setting spanning across at least some of the plurality of channels; and adjusting parameters of the initial current level profile in the presence of an stimulation signal. In a further embodiment of this aspect, the method can further comprise a step of: determining the desired parameters representative of an optimum current level profile corresponding to a recipient's threshold and/or maximum comfort current level profile. According to a second aspect of the invention, there is provided a programming apparatus adapted to be interfaced with an auditory stimulation system having a plurality of channels to allow manipulation of the threshold (T) and comfort (C) levels. of the system, the programming apparatus comprising: a graphical display means adapted to display a graphical representation of the current profile of the channel array; and means for adjusting a current level setting of the current profile of the array.. In a preferred embodiment, the auditory stimulation system comprises a cochlear implant system. The cochlear implant system preferably utilises an electrode array to deliver electrical stimulations to the cochlear of a recipient. In one embodiment, the array comprises 22 intracochlear electrodes and at least one extracochlear electrode. By manipulating the parameters of a current level profile spanning preferably all electrode channels of the electrode array, there is no need to adjust threshold and comfort level currents for each individual electrode channel in the array of an implant following implantation in the recipient. Instead, manipulation is preferably applied to the entire channel profile resulting in a greatly reduced amount of psychophysical measurements required and a programming/fitting procedure that is more recipient friendly, more time efficient and more cost effective. Preferably, the step of establishing an initial current level profile includes a step of obtaining measurements of the evoked compound action potential (ECAP) thresholds for each or a number of the electrode channels and establishing a current level profile based upon these measurements. In another embodiment, the initial current level profile is preferably established from measurements of the ECAP thresholds for at least one electrode channel of the auditory stimulation system, with the full profile being interpolated from such measurements. In another embodiment, the step of establishing an initial current level profile. includes the step of performing a statistical analysis of recipient mapping data over a number of recipients and using this analysis to form an initial current level profile for a particular recipient. In yet another embodiment, the step of establishing an initial current level profile includes the step of performing a number of psychophysical and/or electrophysiological measurements of the recipient in combination with statistical analysis of recipient mapping data over a number of recipients to determine a suitable initial current level profile for a particular recipient. The initially determined suitable current level profile is preferably represented on the graphical display means of the programming apparatus to allow ready determination by a clinician of the current profile of the array. The step of adjusting the overall parameters of the initial current level profile preferably includes adding/subtracting a fixed or derived amount of current level from each individual electrode channel in the profile. This parameter adjustment is referred to as a “shift” manipulation, and has the effect of moving the profile up or down in a vertical direction on a graph plotting current level against electrode channel number. By “shifting” the profile “up”, either a fixed amount of current is added to the current level of each individual electrode channel in the profile (linear shift), or an individually derived current level is added to each electrode channel (non-linear shift), thereby increasing the amount of current delivered by the electrode channels when operated with that particular profile. By “shifting” the profile “down”, either a fixed amount of current is subtracted from the current level of each individual electrode channel in the profile (linear shift), or an individually derived current level is subtracted from each electrode channel (non-linear shift), thereby decreasing the amount of current delivered by the electrode channels when operated with that particular profile. The overall parameters of the initial current profile can also be adjusted by adding an electrode channel specific derived amount of current level to a subset of electrode channels in the profile and subtracting an electrode channel specific derived amount of current level from the remaining electrode channels. This parameter adjustment is preferably referred to as a “tilt” manipulation, and has the effect of tilting the profile clockwise or anti-clockwise on a graph plotting current level against electrode channel. In a preferred embodiment, the “tilt” manipulation may be performed by using at least one electrode channel, for example electrode channel 12 of said plurality of electrode channels, as a pivot point and for each electrode channel 1 - 11 the individual current levels of each electrode channel is decreased by a varying percentage of a fixed amount of current, and for each electrode channel 13 - 22 , the current level for each electrode is increased by a varying percentage of a fixed amount of current, or vice versa. In this regard and where the electrode array is adapted to be positioned within the cochlea, the electrodes positioned in the apical region may have their current levels increased and those within the basal region may have their current levels decreased, or vice versa. The amount of current level to be added/subtracted from the electrode channel can be a function solely depending on the distance of the electrode channel in question to the pivot point (linear tilt) or can have a more complex dependency, e.g. depend from a separate “tilt profile” in addition (non-linear tilt). The overall parameters of the initial current level profile can also be adjusted by adding/subtracting a derived amount of current level from each individual electrode channel in the profile in such a way as to bend the current level profile. This can be interpreted as a profile manipulation using 2 pivot points, which might be allocated but are not limited to the most basal and most apical electrode channel. These pivot points might even be situated outside the actual range of electrode channels available. This parameter adjustment can be referred to as a “curvature” manipulation and has the effect of causing the profile to curve or change shape on a graph plotting current level against electrode channel. The “curvature” can be achieved in a linear and non-linear manner, as described above. The derived values used for the non-linear manipulations can stem from statistical analysis, such as factor analysis of available clinical data. They can be influenced by several factors, such as the actual starting level, whether it is a T or a C level, the implant and electrode type used or the coding strategy applied. Other sources of influence and any combination of factors can be used to calculate the derived data. Other parameter manipulations suitable to adjusting the current level profile are also included within the scope of the present invention. In a preferred embodiment, the step of adjusting the overall parameters of the initial current level profile can include any one or combination of a “shift” manipulation, a “tilt” manipulation and/or a “curvature” manipulation. Adjustment of the profile is preferably performed through a clinician interface that allows the current profile of the electrode array to be adjusted in the manner described herein. In one embodiment, a software package can be run on a computer, with the software package offering input means that allows the clinician to readily adjust the current profile of the array. The input means can comprise one or more of a mouse, joystick, roller ball, keyboard, or keypad, that allows the clinician to adjust the settings within the software package. In a preferred embodiment, the overall parameters of the initial current level profile are adjusted in the presence of a broad band signal, preferably a live speech signal. The broadband signal alternatively may be an artificial signal or a recorded signal. In such a case, the implant delivers stimulation representative of the signal, in accordance with the current level profile. By adjusting the parameters of the current level profile the stimulation delivered by the implant varies, allowing the stimulation signal to be optimised in terms of recipient threshold and maximum current levels. The method and apparatus according to the present invention present a number of potential advantages over existing techniques. In particular, it is envisaged that fewer psychophysical measurements will be needed to prepare a map for a particular recipient and the channels will be manipulated globally rather than individually. The ability to use live sounds is also potentially more interesting for small children than arbitrary stimuli used to date.
20051011
20140408
20061019
93251.0
A61B500
0
HOLMES, REX R
Parametric fitting of a cochlear implant
UNDISCOUNTED
0
ACCEPTED
A61B
2,005