The invention relates to a controlled release tablet which in part or as a whole contains water-insoluble linear polysaccharides, preferably the polysaccharide poly(1,4-xcex1-D-glucan), in the form of microparticles, as retardation material. The tablet is also capable of controllably releasing an active agent.

This is the U.S. national phase of International Application No. PCT/EP99/02386 filed Apr. 8, 1999, the entire disclosure of which is incorporated herein by reference.
1. Field of the Invention
The present invention relates to slow-release tablets comprising linear water-insoluble polysaccharides, a process for preparation, and use thereof, in particular for the controlled release of active compounds.
2. Description of Related Technology
In modern pharmaceutical technology, formulations of excipients whose administration form specifically brings an influence to bear on the biodistribution, bioavailability, biocompatibility and absorption are of importance. Moreover, excipients must have good mechanical properties, such as adequate hardness and resistance to tension and stress. Although a few compounds can already be pressed themselves to give compact stable masses (e.g. sucrose or lactose), ingredientsxe2x80x94tablet auxiliariesxe2x80x94are also necessary, such as binders, fillers, lubricants and additives. Typical dry binders for increasing stability which are used here are:
calcium phosphates, microcrystalline cellulose (e.g. Avicel(copyright), PH 102(copyright), especially Celsphere), polyvinylpyrrolidones (e.g. Kollidon(copyright), Luviskol VA 64(copyright), Plasdone(copyright)), corn, wheat or potato starch, derivatized polysaccharides, so-called gums, (e.g. xanthan gum), cellulose derivatives (e.g. hydroxypropylmethylcellulose: Klucel(copyright)) or ethylcellulose (Aqualon(copyright)). Moreover, the excipients must disintegrate in the body in an optimum and controlled manner in contact with body fluids. Therefore, so-called disintegrants are often added for disintegration control. Typical compounds for this purpose are corn starch, gelatinized starch and starch modifications. Substances which can also be employed are those which develop a disintegrating power due to water absorption and accompanying swelling. These include crosslinked polyvinylpyrrolidones (Kollidon CL(copyright)), carboxymethylcellulose and their calcium salts or galactomannans. With some compounds (e.g. Avicel(copyright) and PH 102(copyright)), it is possible to achieve both the necessary mechanical stability and to control tablet disintegration.
Specific starches, including amylose, are described as advantageous excipients for tablet formulation (Journal of Pharmaceutical Sciences 55 (1966), 340). However, the Nepol amylose used (A. E. Stanley Manufacturing Co., USA) proves disadvantageous, since the active compounds are not exhaustively released and the excipient has a high water content (10-12%), which is why hydrolytically labile active compounds cannot be formulated. In particular, crosslinked amylose (degree of crosslinkage 15%) is as a superior binding agent described (S.T.P. Pharma Sciences 4 (1994), 329-335 and Journal of Controlled Release 15, (1991) 39-46, Journal of Controlled Release 15, (1991) 3946), which on account of its water absorption capacity acts as a disintegration accelerator. In WO 94/21236, crosslinked amylose (degree of crosslinkage 25%) is used as a binder and disintegrant. A high degree of crosslinkage, however, has a disadvantageous effect on the biological compatibility. The crosslinking agent used is up to 30% by weight of the intolerable epichlorohydrin. Even low crosslinkages in the range of a few percent lead to a rapidly growing slowness to react, so residues of unreacted crosslinker which remain have to be expected.
All starch- and amylose-containing excipients on the market until now use plant sources of origin.
It is disadvantageous here that these biopolymers, like all naturally occurring substances, have considerable variations in composition and structure and therefore the necessary reproducibility and thus constant product quality is not guaranteed, even with respect to controlled release of active compound.
In the case of native starch, the content of amylose and amylopectin varies considerably depending on the origin. For example, starch from potatoes contains about 20% by weight of amylose and about 80% by weight of amylopectin, whereas starch from corn contains about 50% by weight of amylose and about 50% by weight of amylopectin. Additional variance within a plant community results due to soil condition, fertilizer absorption, seasonal climatic differences etc.
Moreover, amylose, a 1,4-linked polyglucan, having a molecular weight of approximately 50,000 to 150,000 daltons, and amylopectin, a highly branched 1,4- and 1,6-linked polyglucan, having a molecular weight of approximately 300,000 to 2,000,000 daltons, have wide molecular weight distributions.
The transitions from highly branched to linear are fluid and vary in the original plant material, so that a sharp delimitation is almost impossible. In particular, excipients which still contain amylopectin cause irregular swelling on account of the branchings, whereby the carrier stability is adversely affected. Amylopectin is therefore usually laboriously removed by means of enzymatic debranching (Journal of Controlled Release 45, (1997) 25-33 and EP 0499 648 B1=U.S. Pat. No. 5,468,286).
Beside these marked disadvantages, the wide molecular weight distribution or mixtures of polymers of different spatial arrangements, native polymers contain further constituents such as low molecular weight compounds, e.g. fats and oils, which can only be separated with difficulty and have a disadvantageous effect in further processing and application (e.g. U.S. Pat. No. 3,490,742). In particular, yield-decreasing working steps have to be carried out, in some cases it not being possible to eliminate impurities completely.
Experiments are also known to optimize biopolymers, i.e. even starch, by genetically modifying the plant of origin. WO 94/03049 describes the preparation and use of high amylose-containing starch from genetically modified corn. Regardless thereof, the disadvantages of nonuniformity and contamination remain.
The reproducibility and quality is substantially dependent on the uniformity and purity. To guarantee products of high quality, these starting substances must be clearly definable and characterizable.
The present invention has the object, while avoiding the above disadvantages, of making available a slow-release material which can be used as a slow-release tablet in a pharmaceutical composition for the controlled release of active compounds, preferably for oral administration.
The object is achieved by using as the slow-release material water-insoluble linear polysaccharides which are biocompatible, chemically inert, pressure-stable starting materials which make possible the controlled release of active compound without further additives. Preferably, the starting material used is linear water-insoluble poly(1,4-alpha-D-glucan) as such or in the form of spherical microparticles.
xe2x80x9cSlow-release tabletsxe2x80x9d in the sense of the present invention are, in particular, tablets, coated tablets, pills, pellets, pressings, small plates, disks and the like, whose formulation requires compression. Likewise to be included are capsules which are filled with the slow-release material.
Slow-release materials are to be regarded in the following as linear water-insoluble polysaccharides.
Linear water-insoluble polysaccharides in the sense of the present invention are polysaccharides, preferably polyglucans, in particular poly(1,4-alpha-D-glucan), which consist of monosaccharides, disaccharides, further oligomers thereof or derivatives.
These are always linked to one another in the same way. Each base unit defined in this way has exactly two linkages, each one to another monomer. Excluded therefrom are the two base units, which form the beginning and end of the polysaccharide. These base units have only one linkage to a further monomer. In the case of three or four linkages (covalent bonds) of a monomer to another group, preferably a further saccharide unit, branching is referred to. At least three glycosidic bonds then leave from each saccharide unit in the polymer backbone.
According to the invention, branchings do not occur or only occur to such an insignificant extent that, in the very small branching proportions present, in general they are no longer accessible to the conventional analytical methods. This is the case, for example, when based on the totality of all hydroxyl groups present to one hundred hydroxyl groups which are not needed for the synthesis of the linear polysaccharide, at most five hydroxyl groups are taken by linkages to other saccharide units.
The degree of branching here is maximal (100%) if, on each saccharide unit, the free hydroxyl groups (or other functional groups occurring) have further glycosidic (or other) bonds to further saccharides. The degree of branching is minimal (0%) if, in the saccharides, apart from the hydroxyl groups which determine the linearity of the polymer, no further hydroxyl groups are modified by chemical reaction.
Examples of preferred water-insoluble linear polysaccharides are linear poly-D-glucans, where the type of linkage is insignificant as long as linearity in the sense of the invention is present. Examples are poly(1,4-alpha-D-glucan) and poly(1,3-beta-D-glucan), poly(1,4-alpha-D-glucan) being particularly preferred.
If the base unit has three or more linkages, this is referred to as branching. The so-called degree of branching results here from the number of hydroxyl groups per 100 base units which are not involved in the synthesis of the linear polymer backbone and which form branchings.
According to the invention, the linear water-insoluble polysaccharides have a degree of branching of less than 8%, i.e. they have less than 8 branchings to 100 base units. Preferably, the degree of branching is less than 4% and in particular at most 1.5%.
If the water-insoluble linear polysaccharide is a polyglucan, e.g. poly(1,4-alpha-D-glucan), the degree of branching in the 6-position is less than 4%, preferably at most 2% and in particular at most 0.5%, and the degree of branching in the other positions not involved in the linear linkage, e.g. the 2- or 3-position in the case of the preferred poly(1,4-alpha-D-glucan), is preferably in each case at most 2% and in particular at most 1%. Particularly preferred are polysaccharides, in particular poly-alpha-D-glucans, which have no branchings, or whose degree of branching is so minimal that it is no longer detectable using conventional methods.
According to the invention, the prefixes xe2x80x9calphaxe2x80x9d, xe2x80x9cbetaxe2x80x9d or xe2x80x9cDxe2x80x9d on their own relate to the linkages which form the polymer backbone and not to the branchings.
xe2x80x9cwater insolubilityxe2x80x9d in the sense of the present invention means that no detectable solubility of the compound exists under normal conditions (room temperature of 25xc2x0 C. and an air pressure of 101325 pascals or based on values differing at most 20% therefrom).
In the case of the polysaccharides used according to the invention, in particular of the polyglucans such as poly(1,4-alpha-D-glucan), this means that at least 98% of the amount employed, preferably an amount of greater than 99.5%, is insoluble in water. The term insolubility here can also be explained with the aid of the following observation. If 1 g of the linear polysaccharide to be investigated is heated to 130xc2x0 C. in 1 I of deionized water under a pressure of 1 bar, the resulting solution only remains stable briefly, for a few minutes. On cooling under normal conditions, the substance reprecipitates. After a further cooling and separation using the centrifuge with inclusion of experimental losses, at least 66% of the amount employed can be recovered in this way.
In the context of this invention, linear, water-insoluble polysaccharides are preferably used which can be obtained with the aid of generally defined biotechnological or genetic engineering methods. A particularly advantageous embodiment of the invention described here is the preparation in a biotechnological process, in particular in a biocatalytic process.
Linear polysaccharides prepared by biocatalysis (also: biotransformation) in the context of this invention means that the linear polysaccharide is prepared by catalytic reaction of monomeric base units such as oligomeric saccharides, e.g. of mono- and/or disaccharides, by using a so-called biocatalyst, customarily an enzyme, under suitable conditions. Preferably, poly(1,4-alpha-D-glucan) in particular is prepared by means of polysaccharide syntheses and/or starch synthases and/or glycosyl transferases and/or alpha-1,4-glucan transferases and/or glycogen synthases and/or amylosucrases and/or phosphorylases.
Likewise conceivable are linear polysaccharides from fermentation. In the context of this invention, these are linear polysaccharides which can be obtained by enzymatic processes using naturally occurring organisms, such as fungi, algae or microorganisms or using organisms not occurring naturally, which can be obtained by modification of natural organisms, such as fungi, algae or microorganisms, by means of generally defined genetic engineering methods.
Moreover, linear polysaccharides can be obtained for the preparation of the slow-release tablet described in the present invention from nonlinear polysaccharides which contain branchings by treating them with an enzyme and linear polymers thereof can be obtained with cleavage (e.g. by means of enzymes, such as amylase, isoamylase, gluconohydrolase, pullulanase, inter alia) and removal of the branchings.
The molecular weights Mw of the linear polysaccharides used according to the invention can vary in a wide range from 103 g/mol to 107 g/mol, the molecular weights Mw preferably lie in the range from 2xc3x97103 g/mol to 5xc3x97104 g/mol, in particular 3xc3x97103 g/mol to 2xc3x97104 g/mol. For the linear polysaccharide poly(1,4-alpha-D-glucan) preferably used, corresponding ranges are used.
The molecular weight distribution or polydispersity Mw/Mn can vary within wide ranges depending on the method of preparation of the polysaccharide. A polydispersity of 1.01 to 50 is preferably employed, particularly preferably from 1.5 to 15. In this case, the polydispersity increases with a bimodal distribution of the molecular weights, this not adversely affecting the properties of the tablet formulation.
Mixtures of linear polysaccharides according to the invention and in the form of microparticles with nonlinear polysaccharides are not excluded. xe2x80x9cControlled release of active compoundxe2x80x9d is understood as meaning that the active compound is released after a certain time and/or period of time in a dose advantageous for the biological organism with acceptance of a statistical deviation corresponding to the circumstances.
This definition also includes extremes. On the one hand, the spontaneous release of all active compounds present in the formulation within a period of time approximating to the value zero, on the other hand, the minimal necessary amount dose for the attainment of a therapeutic effect over a long, even infinite period of time, at least a period of time which is necessary to release all active compounds present in the formulation.
For the slow-release formulation present here, therefore, reference is synonymously made to a depot formulation or formulation having delayed release. An xe2x80x9cactive compoundxe2x80x9d is regarded as any biologically active substance and substance combination in the widest sense (specifically in the human and veterinary area), in particular for medicinal indication. In particular: analgesics, anginal preparations, antiallergics, antihistamines, antiinflammatories, bronchodilators, bronchospasmolytics, diuretics, anticholinergics, antiadhesion molecules, cytokine modulators, biologically active endonucleases, recombinant human DNases, neurotransmitters, leukotriene inhibitors, vasoactive intestinal peptides, endothelin antagonists, analeptics, local anesthetics, anesthetics, antiepileptics, anticonvulsants, antiparkinson agents, antiemetics, compounds regulating or stimulating the hormone system, compounds regulating or stimulating the cardiovascular system, compounds regulating or stimulating the respiratory tract system, vitamins, trace elements, antioxidants, cytostatics, antimetabolites, antiinfectives, immunomodulators, immunosuppressants, antibiotics, proteins, peptides, hormones, growth hormones, growth factors, xanthines, vaccines, steroids and beta2-mimetics.
xe2x80x9cTherapeutic effectxe2x80x9d in the sense of this invention means that a therapeutically effective amount of an active compound reaches the desired target site, displays its action there, and causes a physiological reaction. The palliative and/or curative effect is included.
xe2x80x9cBiocompatiblexe2x80x9d in the sense of this invention means that the polysaccharides employed are subjected to complete biodegradation and no concentration in the body takes place. Biodegradation here is understood as meaning any process taking place in vivo which leads to a degradation or destruction of the polymer. In particular, hydrolytic or enzymatic processes are likewise included in this area. For the biocompatibility of the polysaccharides and of its degradation products (metabolites), not least is the naturally identical character of the polysaccharides employed of high importance. Therefore, the polysaccharides used according to the invention are suitable for therapeutic, diagnostic or prophylactic use. The term xe2x80x9cpharmaceutically acceptablexe2x80x9d in the sense of this invention means that a vehicle for an active compound, an auxiliary or alternatively so-called excipient, can be absorbed by a living being without significant side effects arising for the organism.
The tablets are prepared by mixing the starting components, the linear polysaccharide being mixed or homogenized together with the active compound according to known methods, e.g. with the aid of a ball mill. The active compound can have a concentration of up to 50%, a concentration between 1 and 20%, particularly preferably between 5 and 15%, preferably being used. Further customary auxiliaries and additives can be employed. The sum of active compound and polysaccharide according to the invention in the total composition (including possible auxiliaries and additives) should be at least 50%, however 70 to 100% is preferred and 85 to 98% is particularly preferred. The composition of the auxiliaries can vary within wide ranges, the ratios of the composition depending on the interactions with the active compound and the linear water-insoluble polysaccharide.
Auxiliaries which can be employed in tablet production and in the preinserted mixing process are solvents, readily volatile solvents being preferred.
The parent structure of the polysaccharide according to the invention for tablet production can be an amorphous or crystalline structure or grain, such as is obtained directly in synthesis, or alternatively a microparticle, such as is described by the patent application (German Patent Office, ref.: 197 37 481.6). The simple mixing process is preferably used for the preparation of the raw material or raw mixture of the tablet. This preparation procedure of the tablets can affect the properties of the tablet. For example, it is possible to couple the active compound directly on or to the parent structure of the polysaccharide by spraying techniques, for example in the fluidized bed process or by coating in a suspension of the polysaccharide used according to the invention. Absorption processes can be employed here, in which the porous structure of the microparticles is utilized in order to absorb the active compound in a solution (sponge character), or spray-drying techniques. Here, a solution, suspension or emulsion of a linear polysaccharide and of the active compound is dried by means of known spray technologies. In the case of solutions, corresponding organic solvents are employed. Higher temperatures or pressures, and supercritical processes can help to produce the necessary solubilities for short periods of time.
The pressures used during tablet production can vary within wide ranges. Pressure variations can be specifically employed with the polysaccharides described according to the invention to achieve an additionally positively acting slow-release effect. The pressures can vary within wide ranges from 1 MPa to 103 MPa. (105 Pa=1 bar). Pressures in the range from 10 MPa to 300 MPa are preferably to be employed, particularly advantageously pressures in the range from 100 MPa to 250 MPa.

Slow release tablet prepared from linear water-insoluble polysacchrides


Novel polymers comprising polyolefin-substituted amines grafted with aromatic N-containing monomers such as aniline, have been found to provide oil soluble polymers having dispersant and antioxidant properties in oleaginous compositions, including fuel and lubricating oils. The polymers of this invention are further useful in electrical applications. These materials are formed by a process which comprises: (a) contacting an amine compound having at least two reactive nitrogen moieties with at least one long chain hydrocarbon-substituted reactant in an amount and under conditions sufficient to form a N-containing polymer adduct containing reactive amine groups, and (b) contacting the N-containing polymer adduct with at least one aromatic N-containing monomer under polymerization conditions to graft said N-containing polymer adduct with aromatic N-containing polymer segments. The long chain hydrocarbon-substituted reactant can comprise materials such as (i) long chain hydrocarbons substituted with mono- or dicarboxylic acid, anhydride or ester groups; (ii) halogenated long chain hydrocarbons; (iii) mixtures of formaldehyde and a long chain hydrocarbyl substituted phenol; and (iv) mixtures of formaldehyde and a reaction product formed by reaction of long chain hydrocarbons substituted with mono- or dicarboxylic acid, anhydride or ester groups and an amino-substituted, optionally hydrocarbyl-substituted phenol.

Polyaniline is one of the oldest polymers known, and has been prepared in the form of emeraldine hydrochloride by oxidizing an aqueous hydrochloric acid solution of aniline with ammonium peroxy disulfate at ambient temperature. Polyaniline is a cheap, highly electrically conducted polymer, but is processable with difficulty in its powder form. Conventionally, making such conjugated conducting polymers oil-soluble and processible has been a very difficult problem.
S. Li et al., Synth. Met. 20 (2), 141-9 (1987) discloses the graft polymerization of polyaniline with polyaminostyrene to form polyaniline soluble in common organic solvents (DMF and DMSO, and slightly soluble in methanol and trichloromethane). This procedure involved the nitration of polystyrene (of 120,000 molecular weight) with either fuming nitric acid or a chloroform solution of 100% nitric acid and acetic anhydride. The resulting polynitrostyrene was hydrogenated with phenylhydrazine under nitrogen to form the polyaminostyrene.
S. Li, "Synthesis and Characterization of Soluble Polyaniline," Syn. Met. 29 (E329-E336) (1989) reports three general synthetic routes for the solubilization of polyaniline in DMF and DMSO. The experimental synthesis employed either formation of block polyaniline (employing either Para-aminobenzenesulfonylchloride/poly(ethylene glycol) reaction products or para-aminobenzoyl chloride/poly(ethylene glycol) reaction products, and the preparation of graft polyanilines by polymerization of aniline on polyaminostyrene, polyacrylamides or polyepichlorohydrin.
S. P. Armes et al., "The Synthesis of Polymeric Surfactants for the Preparation of Sterically-Stabilized Polyaniline Colloids," Polym. Mater. Sci. Eng., 60, 751-753 (1989) discloses copolymerization of 2- or 4-vinyl pyridine with para-aminostyrene.
T. Kobayashi et al., "Polyaniline Film-Coated Electrodes as Electrochromic Display Devices," J. Electroanal. Chem. 161, 419-423 (1984) discloses evaluations of the electrochromic properties of polyaniline films.
A. G. MacDiarmid et al., "`Polyaniline`: Interconversion of Metallic and Insulating Forms," Mol. Cryst. Lig. Cryst., 121, 173-180 (1985) describes the synthesis of polyaniline powder and the conversion of this material to various insulating and metallic forms by acid/base and oxidation/reduction mechanisms.
Y. Cao et al., "Spectroscopic and Electrical Characterization of Some Aniline Oligomers and Polyaniline," Syn. Met. 16, 305-315 (1986) describes the preparation of aniline oligomers and polyaniline, and proton-doped derivatives.
W. Huang et al., "Polyaniline, a Novel Conducting Polymer," J. Chem. Soc., Faraday Trans. 1, 82, 2385-2400 (1986) discloses the chemical synthesis of polyaniline and electrochemical synthesis of polyaniline from aniline.
F. L. Lu et al., "Phenyl-Capped Octaaniline (COA): An Excellent Model for Polyaniline," JACS 108, 8311-8313 (1986) discloses the preparation of a mono-dispersed polyaniline of molecular weight of 806 and its conversion to a partially oxidized form.
F. Wudl et al., "Poly(p-phenyleneamine): Synthesis and Comparison to Polyaniline," JACS 109, 3677-3684 (1987) discloses the preparation of small polyaniline oligomers by a double condensation of para-phenyl amino-substituted anilines with diethyl succinoyl succinate and the preparation of poly(p-phenaline amine) by the reaction of succino succinic acid (2,5-dioxo-1,4-cyclohexane dicarboxylic acid) and p-phenyline diamine.
A. G. MacDiarmid et al., "The Polyanilines: Processing, Molecular Weight, Oxidation State and Derivatives," Polymer Pre-prints 30, 147-48 (1989); M. Angelopoulos et al. "Polyaniline: Solutions, Films and Oxidation State," Mol. Cryst. Lig. Cryst. 160, 151-163 (1988); A. Andreatta et al., "Electrically-Conducted Fibers of Polyaniline Spun From Solutions in Concentrated Sulfuric Acid," Syn. Met. 26, 383-389 (1988); A. Ray et al., "Polyaniline: Doping, Structure and Derivatives," Synth. Met. 29, 141-150 (1989); S. P. Armes et al., "Novel Colloidal Dispersions of Polyaniline," J. Chem. Soc., Chem. Commun. 88-89 (1989) also relate to preparation of polyaniline.
Y. Wei et al., "Synthesis and Electrochemistry of Alkyl Ring-Substituted Polyanilines," J. Phys. Chem.. 93, 495-499 (1989) discloses the synthesis of poly(o-toluidine), poly(m-toluidine) and poly(o-ethylaniline), by chemical and electrochemical syntheses.
S. K. Manohar et al., "N-Substituted Derivatives of Polyaniline," Syn. Met. 29, 349-56 (1989) discloses the preparation of N-methylated polyaniline.
U.S. Pat. No. 4,604,427 relates to forming electrically conducting polymer blends by impregnating a pre-formed host polymer with a cyclic monomer such as aniline and then exposing the mixture with a chemical oxidant to form the conductive polymer reaction product within the surface layer of the host polymer.
Canadian Patent 806,736 relates to an antioxidant for hydrocarbon-type rubber which is in the form of an aromatic polymer having repeating units which consist of an NH-group attached to a difunctional aromatic group prepared by reacting either hydroquinone or para-benzoquinone with various aromatic diamines, such as para-phenylene diamine and 2,7-diamino naphthylene (page 4). The antioxidant activity of exemplary polymers were demonstrated in ethylene-propylene copolymer rubber vulcanisate (pages 7-8).
European Patent Publication 314,311 relates to the preparation of conducting articles by (a) forming a gel of a carrier polymer in a compatible solvent, (b) polymerizing, within the gel, a selected monomer, and (c) doping the article so provided. Disclosed carrier polymers include high molecular weight (M.W.>100,000) flexible chain polymers, such as polyethylene, isostatic polypropylene, poly(ethylene oxide) and polystyrene, and lower molecular weight polymers (10,000-100,000) having "rigid-rod" molecules, such as aramid polymers, aromatic polyesters, PBT and PBI. The polymerization step (b) can include oxidative-coupling polymerization employing aniline. The polymeriztion step results in the formation, within the carrier polymer, of a normally intractable polymeric material derived from the selected monomer.
European Patent Publication 314,845 discloses graft copolymers characterized by oil-soluble substantially linear, carbon-carbon backbone polymer having graft polymerized thereon units derived from RNH.sub.2 monomer, wherein R is a hydrocarbon containing a polymerizable ethylenically unsaturated double bond. Illustrated amine monomers include p-aminostyrene and p-(aminomethyl) styrene.
U.S. Pat. No. 3,219,666 discloses lubricating oil dispersants comprising oil-soluble, acylated nitrogen compositions, having within its structure (A) a substantially hydrocarbon-substituted polar group wherein the substantially hydrocarbon substituent contains at least about 50 carbon atoms, and (B) a nitrogen-containing group characterized by a nitrogen atom attached directly to the polar group and which are prepared, e.g., by reacting a polyalkenyl-substituted succinic anhydride with an amine. Aniline and N-cyclohexyl-aniline are disclosed as amine reactants.

Polyolefin-substituted amines grafted with poly(aromatic-N-monomers) for oleaginous compositions


A tire chain assembly is provided with a quick connecting male and female fastener for easily securing together the inner circumferential chain on the inner side of the tire without the need for elevating the tire. The outer circumferential chain on the outer side of the tire is provided with a toggle type fastener for securing together the ends of the outer circumferential chain and tightening the outer circumferential chain abut the tire.

This invention relates to anti-skid tire chain assemblies of the type that may be installed upon a tire without the need for elevating the tire from the surface upon which the tire rests when attached to a vehicle. One such tire chain assembly is shown in U.S. Pat. No. 3,616,830.
It is an object of this invention to provide a fastener attached to the opposite ends of the inner circumferential chain on the inner side of the tire which can be easily connected together and easily disconnected while the tire rests on its supporting surface or roadway.
It is a further object of this invention to provide an economical and convenient anti-skid tire chain assembly.
The foregoing and other objects of this invention, the principles of this invention, and the best modes in which I have contemplated applying such principles will more fully appear from the following description and accompanying drawings in illustration thereof.


A delay locked loop is used in a semiconductor memory device. The delay locked loop includes a controllable delay chain block for controlling a delay time of a clock signal coupled thereto, a comparison block for detecting the increase and decrease in the delay time by comparing a reference clock signal with a delayed clock signal generated from the controllable delay chain block, and an instant locking delay control block for controlling the increase and decrease in the delay time of the delay chain block in response to an output signal of the comparison block, the delayed clock signal and the reference clock signal.

The present invention relates to a semiconductor memory device; particularly to a time delay locked loop having a short locking time.
In general, a delay locked loop represents a circuit that is used to synchronize an internal clock of a synchronous memory device with an external clock without errors. That is, since a timing delay occurs when the external clock is inputted into the inside of the memory device, the delay locked loop is used to control the timing delay to thereby synchronize the internal clock with the external clock.
Referring to FIG. 1, there is illustrated a block diagram of a conventional delay locked loop.
If a clock signal Clock_1 is coupled thereto, a controllable delay chain block 100 delays the clock signal Clock_1 by a predetermined delay time to thereby produce a delayed clock signal Delayed_clock.
The delayed clock signal Delayed_clock is fed to a pre-delay/post-delay comparison block 110 that compares the delayed clock signal Delayed_clock with a reference clock signal Reference_clock to thereby determine whether increasing or decreasing the predetermined delay time is required. Through the comparison process, the pre-delay/post-delay/comparison block 110 generates output signals Add_delay and Subtract_delay that are, in turn, fed back to the controllable delay chain block 100 so as to adjust the delay time.
The above delay and comparison processes are repeated until a delayed time of the delayed clock signal Delayed_clock is identical to that of the reference clock signal Reference_clock.
Referring to FIG. 2, there is shown a block diagram of a conventional time delay locked loop employing a careful delay controller.
Once a clock signal Clock_1 is coupled thereto, a controllable delay chain block 200 generates a delayed clock signal Delayed_clock by delaying the clock signal Clock_1 and the delayed clock signal Delayed_clock is provided to a predelay/post-delay comparison block 210.
The pre-delay/post-delay comparison block 210 compares the delayed clock signal Delayed_clock with a reference clock signal Reference_clock so as to determine whether increasing or decreasing the delay time of the delayed clock signal Delayed_clock is necessary. As a result of the comparison process, the pre-delay/post-delay comparison block 210 produces output signals Add_delay_i and Sub_delay_i to a careful delay controller 220.
The careful delay controller 220 is employed to preclude an incorrect determination for the delay time, wherein the incorrect determination may occur by a noise introduced by the power supply or an irregular noise at a system. That is, the delay controller 220 controls the controllable delay chain block 200 to change the delay time only when the delay time determination satisfies a predetermined standard by collecting the results of more than two continuous determination processes instead of directly applying the result of the pre-delay/post-delay comparison block 210 to change the delay time. The output signals Add_delay and Subtract_delay of the delay controller 220 are fed back to the controllable delay chain block 20 to thereby adjust the delay time.
As described above, the conventional delay locked loop of FIG. 2 is insensitive to noise at the state when the delayed locked loop normally operates and the locking is done. However, there is a disadvantage that it takes a very long time from an initial condition in which the locking is not caused to the locking: That is, since, in order to adjust the time delay, there must be at least two determination processes for the increase or decrease in the delay time generated by the pre-delay/post-delay comparison block 210, the time required for the locking may be much longer compared with that of using only one time of determination, as in the delay locked loop of FIG. 1.
It is, therefore, a primary object of the present invention to provide a time delay locked loop which classifies a locking state of the delay locked loop into a locked state and a unlocked state, and either uses a conventional time delay adjusting method in the unlocked state or reduces or eliminates a incorrect determination of the locking introduced by a noise in the locked state.
In accordance with the present invention, there is provided a delay locked loop for use in a semiconductor memory device, comprising: a controllable delay chain block for controlling a delay time of a clock signal coupled thereto; a comparison block for detecting the increase and decrease in the delay time by comparing a reference clock signal with a delayed clock signal generated from the controllable delay chain block; and an instant locking delay control block for controlling the increase and decrease in the delay time of the delay chain block in response to an output signal of the comparison block, the delayed clock signal and the reference clock signal.

Delay locked loop for use in semiconductor memory device


In some embodiments, the present invention provides for a computer system that may include a camera component configured to acquire a visual content, where the visual content includes a plurality of frames having a visual representation of a person's face; and a processor configured to: train a face detection regressor with a synthetic face model database to obtain a face detection trained regressor; apply, for each frame, the face detection trained regressor to detect or to track the face based on facial features, local features, and a pre-defined hyperparameter; construct an intermediate multi-dimensional face model; apply machine learning to determine features of an intermediate multi-dimensional head model; construct a multi-dimensional avatar; and utilize the multi-dimensional avatar to perform an activity associated with the person.

In computing, an avatar is typically a graphical representation of the user or the user's alter ego or character. An icon or figure representing a particular person in a video game, Internet forum, virtual reality environment, augmented reality environment, etc. It may take either a three-dimensional form or a two-dimensional form.

Dynamic real-time generation of three-dimensional avatar models of users based on live visual input of users' appearance and computer systems and computer-implemented methods directed to thereof


For the preparation of a catalytic composite for purifying exhaust gases, first, at least one perov-skite-type compound oxide of the formula RMO.sub.3, where R is La or a combination of La and Ce, and M is Co, Mn or a combination thereof, is supported together with cerium dioxide and alumina sol on a heat resistant carrier made of an inorganic oxide selected from the group consisting of cordierite and mullite, and then iron and palladium are further supported together thereon. As a result, a catalytic composite having a high degree of oxidation activity at low temperatures and also having excellent heat resistance can be obtained.

1. Field of the Invention:
The present invention relates to a catalytic composite for purifying exhaust gases and a method for preparing the catalytic composite. More particularly, it relates to a catalytic composite capable of completely burning unburnt portions of hydrocarbons and carbon monoxides released from various kinds of combustion equipment so as to decompose them into carbon dioxide and water.
2. Description of the Prior Art:
As an oxidation catalytic composite which converts hydrocarbon and carbon monoxide into carbon dioxide and steam in the coexistence of air, there is, for example, a catalytic composite including a catalyst made of a metal of the platinum group such as platinum, palladium or rhodium and also including a heat resistant material made of alumina, silica, or the like on which the catalyst is supported. It is known that this catalytic composite has a high degree of oxidation activity. Thus, it is widely used as a catalytic composite for purifying exhaust gases.
Base metals such as cobalt, nickel and iron are also used as a catalyst in the catalytic composite for purifying exhaust gases. In recent years, however, research has been conducted to develop catalysts made of compound oxides including a plurality of base metals, rather than catalysts of metal oxides including a single base metal. Among the compound oxides which have been developed as the catalyst, compound oxides having perovskite structures of the formula RMO.sub.3 have attracted attention because they have a high degree of oxidation activity. Among the perovskite-type compound oxides, LaCoO.sub.3 and LaMnO.sub.3 are particularly excellent in oxidation activity. It has been reported that the oxidation activity of these perovskite-type compound oxides are further improved by replacing some of the metals at the R-sites in the compound oxides with divalent alkaline earth metals (e.g., strontium).
In general, a catalytic compound for purifying exhaust gases is used for both high-temperature combustion equipment and low-temperature combustion equipment. The temperature of the exhaust gases released from the former ranges from 700.degree. to 800.degree. C. while the temperature of those released from the latter ranges from 300.degree. to 400.degree. C. Therefore, a catalytic compound for purifying exhaust gases is required to have excellent heat resistance at a high temperature of 700.degree. to 800.degree. C. and excellent oxidation activity at a low temperature of 300.degree. to 400.degree. C. Catalysts made of perovskite-type compound oxides including base metals are generally superior in heat resistance at a temperature of 700.degree. to 800.degree. C., but inferior in oxidation activity at low temperatures, as compared with catalysts made of a metal of the platinum group. In order to improve the low-temperature oxidation activity, there has been proposed the addition of a small amount of metal from the platinum group to the perovskite-type compound oxides. By the addition of a small amount of metal of the platinum group, the low-temperature oxidation activity of the resulting perovskite-type compound oxide can be improved. However, when this compound oxide is heated to a temperature of 700.degree. to 800.degree. C., the metal of platinum group added thereto deteriorates due to the high temperature, thereby reducing the degree of oxidation activity thereof.

Catalytic composite for purifying exhaust gases and a method for preparing the same

Matsushita Electric Industrial Co., Ltd.


A method and apparatus is provided for producing a synthetic multifilament yarn having appearance, bulk and hand characteristics of conventional spun yarns of staple fibers while retaining strength characteristics of continuous filament yarns. The multifilament yarn is air jet textured to form loops, bows, coils and the like in at least the surface filaments thereof and at least some of these loops, bows, coils and the like only in the surface filaments are parted while the interior or core filaments remain substantially intact to form a yarn having free filament or fiber ends projecting from a substantially continuous filament core. The interior or core filaments are shielded or protected from being parted by false twisting the yarn (without heat setting the twist therein) to provide a substantially closed form with the interior or core filaments surrounded by the surface filaments and by parting the surface filaments while the yarn has twist therein. Also, other steps are taken and means are provided for limiting the filament parting action solely to the surface filaments. Finally, the yarn is heat set after the filaments are parted and after the twist is removed to fix the characteristics imparted in the previous processing steps therein.

In the production of yarns for various and sundry textile fabrics and other uses, much attention has been given to finding a method by which certain desirable characteristics of conventional spun yarns, e.g. appearance, bulk and hand, could be imparted to synthetic multifilament yarns. It has previously been proposed, e.g. U.S. Pat. No. 3,946,548, to produce synthetic multifilament yarns having such characteristics by over-feeding the multifilament yarn through a high velocity air jet texturing device whereby the filaments of the yarn are entangled and have loops, bows, coils and the like formed therein. The action of an air jet texturing device on such yarns is well known to persons skilled in the texturing art. The yarn after passing through the air jet texturing device is false twist textured by twisting, heat setting the twist (and the loops, bows, coils and the like formed by the air jet texturing) in the yarn and then untwisting in well-known manner.
In this previously proposed process, the textured yarn is contacted by a friction element, either before the yarn reaches or after it has left the false twist texturing zone, which parts at least some of the filaments of the yarn to produce free filament ends projecting from the yarn. While providing the desired yarn characteristics of appearance, bulk and hand, this process has presented substantial disadvantages. Foremost among these disadvantages is the fact that the strength characteristics of the yarn are materially degraded. This degradation of the strength of the yarn is due to the fact that the friction element may contact and part any of the filaments of the yarn including those filaments which would normally be considered as interior or core filaments. Therefore, the structural integrity of the yarn, normally obtained with continuous filaments, is destroyed and the yarn strength is considerably impaired.

Method and apparatus for producing spun yarn characteristics in synthetic multifilament yarns

Barmag Barmer Maschinenfabrik Aktiengesellschaft


A swimming pool heating system which utilizes a heat pump that is used for heating heat transfer fluid which is circulated through the primary coil of a heat exchanger. The pool water is circulated through the secondary coil of the heat exchanger by means of a standard pool pump. Rather than heating all of the water which is handled by the pump, a system bypass line is connected to the pool outlet line and a diverter valve, which is located in the pool return line, is used to divert a portion of the circulated pool water to the heating system. A three-way regulator valve located in the system bypass line divides the diverted pool water, directing a selected portion of it to the heat exchanger and a selected portion of it to the pool return line in order to automatically control the heating effect the pool heater has on the heat transfer fluid, thereby keeping the discharge pressure of the heat pump relatively constant so that it operates in its most efficient range. A defrost bypass is associated with the regulator valve in order to override the regulator valve when the heat pump operates in a defrost cycle, thereby ensuring that adequate pool water is directed to the heat exchanger to provide a sufficient heating load. A thermostatic control is included to allow heat pump operation to be responsive to the swimming pool heating demand and a pressure control terminates operation of the system upon discontinued or reduced availability of pool water.

This invention relates to a heating system for swimming pools and in particular to such a system which utilizes a heat pump.
In the past electricity has been the predominant energy source for heating swimming pools, due to its being a readily available and clean source of energy. In the past when electrical energy has been used for this purpose, it has normally been used in the form of resistance heating, however, resistance heating is inefficient and as the cost of electrical power increases it becomes increasingly desirable to use other, more efficient, types of electrical heating, such as a heat pump. Even though heat pumps are relatively efficient means of utilizing electrical energy for heating they have certain operating characteristics which seriously limit their use for heating swimming pools. In the operation of a heat pump it is imperative that the pressure of the heat transfer fluid as it is discharged from the heat pump remain relatively constant. Otherwise the heat pump will often be operating in a range where its efficiency is significantly reduced. This characteristic of heat pumps is not a serious limitation when they are used for space heating since the heat capacity of the air being heated is much lower than that of the heat transfer fluid. Therefore, even when the space being heated becomes quite cool, the discharge pressure, is not overly effected. In addition, even if the discharge temperature of the heat transfer fluid is reduced below the desirable range, the space is raised to the desired temperature rather quickly and then kept at a relatively constant temperature. Therefore, any effect temperature has on operating efficiency of the heat pump is of short duration and thus of little importance.
On the other hand, the water being heated in a swimming pool has a much larger heat capacity than air. Therefore, when cool water is being heated it is much more likely to cause the discharge temperature of the heat transfer fluid to drop than is the case with air. Furthermore, it typically takes a much longer time to heat a cool swimming pool than a cool house and accordingly the heat pump will be forced to operate in an inefficient mode for a much longer period of time in the former case than in the latter.
What is needed, therefore, is a means for automatically regulating the discharge pressure of the heat transfer fluid in a heat pump when the heat pump is used for heating a swimming pool, so that the heat pump always operates within its desired range.
The heating system of the present invention serves this end by continuously regulating the amount of pool water which is subjected to being heated by the heat pump, thereby causing the heat pump to be operated at a constant discharge pressure.
The heating system of the present invention includes a system bypass line, which is connected to the pool outlet line, to divert a portion of the pool water to the heating system. A manually operable diverter valve located in the pool return line ensures that a controlled amount of water is so diverted. The diverted portion of the pool water is then passed through the secondary coil of a commercially available heat exchanger which has the heated heat transfer fluid from the heat pump being circulated through its primary coil.
The regulating element consists of a three-way regulator valve which is located in the system bypass line upstream of the heat exchanger. The regulator valve is connected so that its inflow port receives pool water from the pool, a first outlet port discharges water into a regulator return line which is connected to the pool return and a second outflow port discharges water back into the pool bypass line for passage to the heat exchanger. The position of the regulator valve is responsive to the discharge pressure of the heat transfer fluid through operation of control means so that if the pool water causes undue cooling of the heat transfer fluid from the heat pump, therefore causing its temperature, and thus its pressure, to drop, the regulator valve will direct a greater portion of the pool water out of its first outflow port thus correcting this effect. On the other hand, when the discharge pressure of the heat transfer fluid increases, a greater portion of the pool water is passed out of the second outflow port to the heat exchanger. As a result, the discharge pressure remains relatively constant and within the range where the heat pump operates more efficiently. While the regulator valve maintains the heat pump within its desired range, a separate thermostatically controlled switch located in the pool outlet line causes the heat pump to initiate and terminate operation responsive to pool demand.
One drawback of using a regulator valve of this type is that it operates to eliminate any heating load from being available when the heat pump is reversed to defrost its evaporator coil. In this event as the heat transfer fluid passing to the heat exchanger becomes cooled, since in this configuration the heat pump is operating as a refrigeration unit, the regulator valve would normally respond by directing an increasingly greater portion of the pool water through the regulator return line rather than through the heat exchanger. Thus there would be increasingly less pool water available to serve as a heat source for the heat pump as it continued in its defrost cycle.
In the present invention this problem is solved by placing a defrost bypass line between the inflow and second outflow ports of the regulator valve and placing a solenoid-operated first bypass control valve in the bypass line. In addition, a solenoid-operated second bypass control valve is located in the regulator return line. Accordingly, the bypass control valves are annunciated by the heat pump controls so that during defrost the first valve is opened and the second valve is closed. As a result, all of the pool water is directed through the heat exchanger to act as the heat source for the heat pump.
Accordingly, it is a principal object of the present invention to provide a system for heating a swimming pool with a heat pump wherein the discharge pressure of the heat transfer fluid in the heat pump automatically remains within a predetermined range at all times.
It is a further object of the present invention to provide such a system wherein the heat pump can also be operated in a defrost cycle.
It is a further object of the present invention to provide such a system which is operated on a demand basis responsive to pool temperature.
It is a still further object of the present invention to provide such a system having an emergency shutdown which terminates operation of the heat pump in the event the flow of pool water is discontinued or severely curtailed.
The foregoing and other objectives, features and advantages of the present invention will be more readily understood upon consideration of the following detailed description of the invention taken in conjunction with the accompanying drawings.


A valve mechanism for supplying liquid to a container until the surface of the liquid reaches a predetermined level includes a valve body disposable in the container and defining a cavity, an inlet port for communication with a liquid source and an cutlet port communicating with the interior of the container. A valve seat is provided in the cavity adjacent to the outlet port, and a valve member in the shape of a ball is disposed within the cavity and moveable between a normal closed condition and an open condition relative to the valve seat for respectively closing and opening the outlet port. A guide tube depends from the valve body in communication with the outlet port and has a float coupled to it. A valve actuator includes a base seated in the container and a rod extending upwardly therefrom into the guide tube. The actuator rod is engageable with the valve member for holding the valve member in its open condition when the surface of the liquid in the container is below the predetermined level. The actuator withdraws from the outlet port to also allow the valve member to move to its normal closed condition when the surface of the liquid in the container is at or above the predetermined level.

1. Field of the Invention
The present invention relates to shut-off valves for controlling the level of fluid in a container, and more particularly, to valves of the type including a float and a valve actuator which cooperate to operate the valve between open and closed conditions in response to a change in the fluid level.
2. Description of the Prior Art
Valve mechanisms of the type provided with a float device that rises with the liquid supply level flowing into a container are well known.
U.S. Pat. No. 1,219,567 to Leitch discloses a valve mechanism with a valve body positioned a fixed distance from a container therebelow. Liquid flows into a valve body chamber via an inlet port coupled to an external supply source and flows out of the chamber through an outlet port. The outlet port is sized to receive a tube which is carried by a float, and which tube moves concentrically through the outlet port, rising and falling relative to the supply level in the container. As the supply level rises, the upper extremity of the tube extending into the valve body cavity is moved toward contact engagement with a partly-conical valve member (button). Once a predetermined liquid level has been reached in the container, the upper extremity of the tube will contact the button sealing the further flow of liquid from the outlet port into the container.
U.S. Pat. No. 1,586,405 to Burge discloses a valve mechanism having a float coupled to a rod which together movably seat and unseat a ball-shaped valve member to close and open a passageway through a fixed position valve body (pipe). Through this passageway flows liquid from an external feed line into a container, the float being buoyantly disposed in the container to mechanically cause pivoting of the rod as the liquid level in the container changes.
U.S. Pat. No. 2,130,876 to Cordts discloses a valve mechanism including a float which rises concentrically up into an orifice defined by the outlet port of a valve body, the float rising as the liquid in a container approaches a predetermined level. A ball adapted to normally rest on the inner, upper end of the outlet port is also provided. The shape of a lower end of the outlet port is conical and adapted to cooperate with a closure valve on the upper side of the float. A tubular extension on the float initially is movable upwardly and engageable to unseat the ball, allowing liquid to flow into the container. As the float rises further in response to the rise in the liquid level, the closure valve and Conically-shaped lower end of the outlet port are brought into Contact, sealing the outlet and restricting further flow into the container.
It is well known in the prior art, therefore, to provide valve mechanisms of the type including a float which rises and falls with the liquid level to operate a valve member to control flow of liquids through a valve body. However, all such valve mechanisms are similar in that the floating activator moves with respect to a fixed or stationary valve body. Consequently, mounting apparatus must be provided for holding the valve body stationary relative to the container.


A method for transmitting a message in a vehicle, in which the message is received according to a source protocol, a communication mechanism which is used by the message and corresponds to the source protocol is converted in such a way that the communication mechanism corresponds to a canonical protocol, the communication mechanism corresponding to the canonical protocol is converted in such a way that the communication mechanism corresponds to a predefined target protocol, and the message is transmitted according to the target protocol.

According to the related art, highly diverse field busses such as CAN or FlexRay, and occasionally tree, ring, or star topologies are used for transmitting messages between control units (electronic control units, ECUs) and field devices such as sensors or final controlling elements. The different communication mechanisms utilized by the messages therefore require the use of different protocol families, some of which are based on the Internet Protocol (IP); examples of such protocol families are mentioned in the standards IEC 61784-1 and IEC 61784-2, for example.
DE 1983 2531 A1 describes a controller for a large number of electrical consumers in a motor vehicle, in the case of which a simple configuration and a flexible applicability and extensibility is achieved by the fact that each one of the electrical consumers is situated together with a local computer in a consumer module and is controlled within the consumer module by the associated local computer, and that the local computers are linked to a central computer via a data bus and exchange control data in accordance with a standard protocol.

Method and device for transmitting a message in a vehicle


The present application includes a main rotor assembly for an aircraft. The rotor assembly has a main rotor mast configured for rotation about a mast axis and two yokes pivotally connected to the mast for rotation therewith about the mast axis. Each yoke is independently pivotable relative to the mast about at least one flap axis that is generally perpendicular to the mast axis. In at least one embodiment, a torque splitter connects the yokes and allows for limited rotation of the yokes relative to each other about the mast axis. Each yoke is configured for the attachment of rotor blades extending generally radially relative to the mast axis.

1. Field of the Invention
The present application generally relates to rotors for aircraft and specifically relates to a multiple-yoke main rotor assembly for aircraft.
2. Description of Related Art
Demand is increasing for rotary-wing aircraft, such as helicopters and tiltrotors, to provide more thrust, higher speeds, and carry heavier loads and/or heavier fuselages. For example, there is a demand for more powerful tiltrotor aircraft. Where performance criteria such as these are to be increased, the functional systems of the rotary-wing aircraft must be improved to provide the desired resultant performance enhancements. The rotor system is one of the many functional systems which require improvement in order to meet the demand for improved rotary-wing aircraft performance.
Rotary-wing aircraft have at least one rotor for providing lift and propulsion forces. These rotors have at least two airfoil blades connected to a central hub, and the hub is mounted on a rotatable mast driven in rotation by an engine or motor. These blades may be adjustable for pitch angle, and the pitch angle is typically controlled by a swashplate assembly and linkage for connecting a rotating portion of the swashplate assembly to each blade.
Existing rotor assemblies have many configurations. One example of a prior-art system is a teetering rotor, in which a yoke attaches the blades to a central hub, and the yoke is pivotally attached to the mast, allowing for the yoke to teeter about a central flap axis that intersects the mast axis. FIG. 1 is a schematic view of a teetering system 11 mounted to a mast 13. Yoke 15 has two blades 17 attached at opposite ends of yoke 15, and yoke 15 is pivotally attached to mast 13 for rotation therewith about mast axis 19. To provide for a pivoting connection to mast 13, opposing cylindrical trunnions 21 extend radially from mast 13, defining flap axis 23. This configuration allows the rotor assembly of yoke 15 and blades 17 to freely pivot, or "teeter," about flap axis 23 relative to mast 13, as indicated by directional arrows 25. This type of rotor system has been used, for example, as a main rotor system on the Bell UH-1 Iroquois helicopter.
A twin teetering system 27, as shown in schematic form in FIG. 2, has been used as a tail-rotor system, such as in the Boeing AH-64 Apache helicopter. Two yokes 15 each have two blades 17 attached at opposite ends of yokes 15, and yokes 15 are pivotally attached to mast 13 for rotation therewith about mast axis 19. To provide for a pivoting connection to mast 13, two pairs of opposing cylindrical trunnions 21 extend radially from mast 13, defining flap axes 23. This configuration allows the rotor assemblies of each yoke 15 and the associated blades 17 to freely "teeter" about the corresponding flap axis 23 relative to mast 13 and to each other, as indicated by directional arrows 25.
Although there have been significant developments in rotor systems, significant room for improvement remains.
While the system of the present application is susceptible to various modifications and alternative forms, specific embodiments thereof have been shown by way of example in the drawings and are herein described in detail. It should be understood, however, that the description herein of specific embodiments is not intended to limit the method to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the application as defined by the appended claims.


Disclosed is a communication device wherein, in order to improve operability when sending electronic mail to which image data has been attached, the communication device is provided with an image capture means for capturing image data of a subject; a storage means for storing registered information associating a predetermined action with a destination address; and a control means that, in response to a predetermined action being performed during operation of the image capture means, controls the image capture means so that the storage means records image data that is being captured by the image capture means, and additionally set a destination address recorded in the registered information associated with the predetermined action as a destination, and creates an electronic mail message to which the recorded image data has been attached.

In recent years, such an operation of photographing an object by using a mobile communication terminal equipped with a camera unit and transmitting an e-mail attached with the image data having been acquired through the photography has been generally performed. This operation is usually performed in accordance with the following procedure.
That is, first, the user starts the camera unit included in the mobile communication terminal. The camera unit scans an object to acquire the image data related thereto, and further, displays the acquired image data on a display unit. The user performs an acquisition by pushing a shutter button thereof with watching the display unit. In response to the shutter button being pushed down, the image data being displayed on the display unit is stored into a memory portion. Next, the user performs an operation of terminating an imaging mode, and further, starts an e-mail function. The user creates a new e-mail, and further, designates the stored image data as an attachment file of the e-mail. Further, the user input a destination address and an e-mail body, and then, the user executes a mail transmission operation.
By performing such operations as described above, the user can acquire the image of the object by using a camera unit, and can transmit the e-mail to which the acquired image data is attached. However, in order to transmit an e-mail with which the image data related to an object is attached, the user needs many operations. Therefore, there is a disadvantage in that the operability is insufficient for users.
For example, Japanese Patent Application Laid-Open No. 2004-153453, Japanese Patent Application Laid-Open No. 2004-289879 and Japanese Patent Application Laid-Open No. 2005-100191 disclose solutions of the above described disadvantage. Japanese Patent Application Laid-Open No. 2004-153453 discloses a folding-type mobile termination apparatus which is configured to, when, in a folded condition, made into an unfolded condition under the state where a selected image is displayed on a display area provided on the back thereof, automatically start an e-mail function. The mobile terminal apparatus displays a screen for creating a new e-mail on the display area, and further, automatically attaches the image data related to the selected image to the e-mail.
Japanese Patent Application Laid-Open No. 2004-289879 discloses a mobile communication terminal which is configured to, when an e-mail transmission operation is performed during an imaging mode in which a still image being acquired by a camera is displayed on a display unit, start an e-mail transmission mode. When, under the state where the e-mail transmission mode is started, the user inputs information necessary for an e-mail transmission, and further, creates a e-mail body, the mobile communication terminal attaches the encoded data corresponding to the still image being displayed on the display unit to the e-mail body, and further, transmits the e-mail.
Japanese Patent Application Laid-Open No. 2005-100191 discloses a mobile communication terminal which is configured to, in a transmission process mode for an e-mail with which the image is attached, when an operation of a key, which is allocated in advance, is performed, start a camera function, and further, store the image data. The mobile communication terminal attaches the stored image data to an e-mail, and further, transmits the e-mail to a destination which is associated with the above-described key in advance.

Communication apparatus and electronic mail creation method


A method of developing latent electrostatic images comprising the steps of stirring a developer containing toner particles and carrier granules to triboelectrically charge the toner particles to a polarity suitable for developing a latent electrostatic image on an image bearing surface, causing the latent electrostatic image on the surface to electrostatically attract toner particles in the stirred developer to convert the latent image to a visible image and replenishing the developer used for the development and containing a reduced quantity of toner particles with toner particles different in triboelectric chargeability (capability of being triboelectrically charged by frictional contact with carrier granules) from the toner particles initially contained in the developer before the development.

The present invention relates to a method of developing latent electrostatic images, and more particularly to a latent electrostatic image developing method in which a latent electrostatic image on an image bearing surface is converted to a visible image with a developer containing toner particles and carrier granules, namely with a so-called two-component developer.
Magnetic brush developing devices or cascade developing devices are known as devices for practicing such a latent electrostatic image developing method. With use of these developing devices, the developing method has actually been performed and has found wide application in the field of electrographic copying machines. The latent electrostatic developing method, as performed by the above-mentioned devices, comprises the following steps (1) to (3):
(1) The developer is forcibly stirred as by a rotating roller (generally having a spiral blade on its periphery) to triboelectrically charge the toner particles in the developer to a polarity suitable for development (usually to a polarity opposite to the polarity of latent electrostatic images).
(2) The stirred developer is fed, by magnetic conveying means, bucket conveyor or like means, to the developing station, where toner particles in the developer are electrostatically attracted to a latent electrostatic image on an image bearing surface. The latent image is converted to a visible image by the electrostatic attraction of the toner particles to the latent image.
(3) The developer used for the development and containing a reduced quantity of toner particles is collected in the developing device. The developer is replenished with fresh toner particles by toner supply means.
The latent electrostatic image developing method described above has various advantages and therefore has found wide use as already stated, whereas the method still involves problems in the durability of the developer, in other words, with respect to variations in the properties of the carrier granules. It is desired to overcome these problems.
These problems will be described below.
With repeated development of latent electrostatic images by the above method, toner particles initially contained in the developer are incessantly replaced by fresh toner particles, while the carrier granules initially contained in the developer are repeatedly used. If the development of latent images is repeated over a prolonged period of time, a substance, so-called spent toner, progressively thermally adheres to the surfaces of the carrier granules, consequently varying the inherent properties of the carrier granules per se. I have confirmed that, of the variations of the properties, the variation of the triboelectrifying ability of the carrier granules (the ability of the carrier granules to triboelectrically charge the toner particles by frictional contact therewith) immediately adversely affects the development of the latent electrostatic image and leads to the following objections.
(a) When a certain type of developer is used for the developing method, the quantity of the toner particles electrostatically attracted to the latent image gradually increases with the repetition of development, also markedly fogging the nonimage areas (the background of the latent image). Additionally toner particles are deposited on the image bearing surface in the form of a trail rearward from the latent image with respect to the movement of the surface relative to the developing device. (For convenience sake, the deposition of the toner particles will hereinafter be referred to briefly as "trailing.") My research appears to indicate that these objections are attributable to a reduction in the triboelectrifying ability of the carrier granules and to the resulting decrease in the amount of triboelectric charges on the toner particles.
(b) When another type of developer is used for the developing method, the quantity of the toner particles electrostatically attracted to the latent image gradually decreases with the repetition of development and that markedly in the solid center portions of the latent image. My analysis appears to reveal that this is attributable to an increase in the triboelectrifying ability of the carrier granules and to the resulting increase in the amount of triboelectric charges on the toner particles.
To solve these problems, it has recently been proposed to form a hard coating as of Teflon over the surfaces of the carrier granules, but the proposal involves limitations on the kind of resin usable for preparing the toner particles and another problem that the coated carrier granules have a relatively low triboelectrifying ability. The proposed remedy therefore still remains to be fully improved.
It has also been proposed to replenish the developer used for development with toner particles of larger size than the toner particles contained in the developer before it is used for development. However the use of toner particles up to 8 .mu.m in mean size generally causes fogging to the nonimage area, whereas toner particles larger than 15 .mu.m in mean size, if used, usually produce a rough toner image, so that it is presently impossible to use toner particles of widely varying sizes. Thus the second proposed method similarly involves problems and still remains to be fully improved before actual use. Although the method has proved satisfactory for application to developers of the type referred to in paragraph (b) above, the method fails to achieve any good result with use of developers of the type (a). And what is worse, it has been found that the method, if practiced with a developer of the type (a), aggravates the aforementioned adverse effects on development.
Accordingly the developer used for the developing method and containing contaminated carrier granules must invariably be discarded for replacement by a fresh developer after the developer has been repeatedly used for developing latent electrostatic images over a prolonged period of time (to be more specific, after making 10,000 to 20,000 copies, calculated as A4 size, with an electrophotographic copying machine presently commercially available and incorporating a magnetic brush development unit), in other words, about the time when the contamination of the carrier granules in the developer is likely to produce a serious adverse effect on development. Such developer disposal and replacement is very cumbersome and uneconomical.

Electrographic magnetic developing method


In an information processing apparatus connectable to a terminal through a network, a terminal type of the terminal is specified based on a first request requesting Web information, said first request sent from the terminal through the network, and reference Web information is generated so as to include reference path created by adding terminal type information showing the specified terminal type to a path indicated in the first request for accessing the Web information and to allow the terminal to automatically accesses to the reference path. Then, the reference Web information is sent to the terminal as a response with respect to the first request, and a second request for requesting the Web information specified by the reference path is received.

1. Field of the Invention
The present invention generally relates to an information processing apparatus capable of connecting to a terminal through the Internet and including a plurality of Web applications and an information processing method in that terminal type information, language information, and profile information of the terminal can be succeeded while a page transition is conducted by a user of the terminal among the plurality of Web applications, and in that information suitable for the terminal can be provided while maintaining user-friendliness.
2. Description of the Related Art
Recently, the Internet has been widely used by not only a client PC (Personal Computer) but also mobile phone and PDA (Personal Digital Assistant) terminal, and information has been provided in various languages and to various level users. A method for providing information has bee diversified.
In order to provide information corresponding to a terminal such as the client PC, the mobile phone, or PDA terminal, Japanese Laid-Open Patent Application No. 11-175515 discloses that display contents corresponding to the terminal type of the terminal is generated for HTML data created beforehand. Or, Japanese Laid-Open Patent Application No. 2002-63108 discloses that a gateway server, that intermediates between a Web server for providing information and a terminal for requesting information, deletes unnecessary data and adjusts color attributes of an image with respect to information provided from the Web server in response to the request of the terminal, based on the terminal type of the terminal.
Moreover, Japanese Laid-Open Patent Application No. 2002-7095 discloses a data processing apparatus including a Web server function capable of providing information concerning a image forming process. In the data processing apparatus, a user of the terminal can obtain information concerning a device for conducting a image forming process and provided with the data processing apparatus, through the Internet.
Furthermore, Japanese Laid-Open Patent Application No. 11-306070 discloses a data succeeding method in that by using information input by the user of the terminal is stored in a predetermined storage area, the information can be succeeded while the user conducts the page transition.
However, the above-mentioned conventional methods have the following problems.
In the Web server having the Web server function capable of providing information concerning the image forming process, in a case in that a state of the image forming process or a device such as a plotter controlled by the Web server for conducting the image forming process is provided, since the information should be provided timely, HTML data cannot be prepared beforehand. Accordingly, the method disclosed by Japanese Laid-Open Patent Application No. 11-175515 cannot be applied in this case. In a case of Japanese Laid-Open Patent Application No. 2002-63108, a cost of installing the gateway server and maintenance of the gateway server are required.
In the data processing apparatus disclosed by Japanese Laid-Open Patent Application No. 2002-7095, it is impossible to provide information suitable for the size of a display screen of the terminal such as the client PC, the mobile phone, and the PDA terminal.
Moreover, in the data succeeding method disclosed by Japanese Laid-Open Patent Application No. 11-306070, a page for allowing the user to input information concerning the user of the terminal is required and the user is required to explicitly input the information into the page. In addition, it is required to manage the information, which is to be succeeded, for each user. Accordingly, it is impossible to automatically provide information suitable for the size of the display screen.

This patent is subject to a terminal disclaimer.

Information processing apparatus and information processing method


A method and apparatus is disclosed in which one or more standard faces are transformed into a target face so as to allow expressions corresponding to the standard face(s) to be used as animation vectors by the target face. In particular, a non-linear morphing transformation function is determined between the standard face(s) and the target face. The target face animation vectors are a function of the morphing transformation function and the animation vectors of the standard face(s).

In computer graphics providing realistic human facial animation is a difficult problem. The human face is one of the most studied and scrutinized parts of the body. In addition, we as humans have the ability to read an expression and to identify individuals and expressions of emotions based on facial communicative signals, and to know when an expression is false from the slightest deviations.
The shape of a computer generated face can be approximated by a set of geometric primitives such as polygons or curvilinear elements such as polynomials, splines, or NURBS (Non-Uniform Rational B-Splines). These geometric primitives can be described in terms their position in a predetermined set of spatial coordinates using the two or three-dimensional coordinates of their vertices or end points. In addition, other data such as derivatives or normals of these surfaces or functions may also be used.
These vertices are typically collected and combined into a matrix A in which the row vectors of the matrix A represent each image of the face, and the column vectors represent the various locations in two or three dimensions of the vertices used to define a face or object. In general if each of the vertices are defined in three dimensions, then for k vertices of a face or object, there will be 3*k column vectors.
In the instance in which the face is moving, e.g., translating or rotating in space, or deforming, e.g., the relative displacement of the vertices changes relative to a body centered coordinate axis, then the vertices in the matrix are a function of time, t, or sample, k.
Each row of vectors comprising the matrix A could be an emotion or facial expression displayed by an actor for a model face. All of the row vectors in a particular matrix A therefore taken together could represent a range of emotions and facial expressions for that model face. A subset of these various row vectors could be selected, weighted appropriately, and combined together to form a composite face having complex facial expressions or dynamics that could be processed and displayed by a computer system.
However obtaining a complete set of expressions and facial dynamics for a particular face is often not possible. The person whose face is desired may not be capable of generating the necessary facial expressions, or may not be available to generate the necessary facial expressions. The process of collecting the data is also time consuming. In addition, the process of collecting data can require specialized equipment such as a 3D digital motion-capture system. Such a system can include a video camera or single two-dimensional (2D) image that has been converted to a 2D or 3D computer graphics model.
Therefore, it would be advantageous if dynamic animation data for a model face could be morphed or deformed to represent a static geometry or an image taken photograph so as to avoid the costs of collecting and analyzing facial data for the static object or photograph.

Non-linear morphing of faces and their dynamics


A processor having multiple distinct instruction sets is disclosed where one set, a default set, is always available for execution while a second set is only available once a valid control code is externally supplied to the processor to effectively “unlock” and enable the second set. Once the second set is so unlocked, then the instructions in both sets are available for subsequent execution by the processor to provide enhanced functionality only available through use of the second set, such as accessing on-line services and content information. Multiple unlockable instruction sets can also be similarly provided, each being separately unlocked and enabled through entry of an corresponding externally supplied control code.

Embedded processors in end-user devices are commonly known. Within this context, an embedded processor is a special-purpose microprocessor embedded in the device it controls. In contrast to a general-purpose processor, such as those for use in a personal computer (PC), an embedded processor performs a limited number of pre-defined tasks, typically with very specific requirements and a specific instruction set. Since the processor is dedicated to specific tasks, design engineers can optimize it, reducing its size and cost. An end-user device within this context is an electronic device whose main functionality is intended for everyday use by the end-user, typically a consumer. Examples of user devices are a mobile telephone, another personal communication device, a navigational aid, an ADSL modem, etc.
Typical examples of such processors are the DSTni-LX/DSTni-EX embedded processors from Lantronix, the NS7520 Microprocessor from Netsilicon, the ADSP-21xx Processor and Blackfin Processors from Analog Devices.
Other examples are the processors with an x86-compatible CPU of the 80286 series. These processors have an operational mode referred to as the "protected mode" that serves to limit access by a software program to certain processor instructions and addressable memory areas, to the discretion of the developer of that program. That is, the conditions for limited access are set during programming. For more background see, e.g., "Overview of the Protected Mode Operation of the Intel Architecture", author Steve Gorman, a white paper published by Intel Corporation.


The present invention is directed to a process for the preparation of modified copolymers as a pigment dispersant for coating compositions comprising the steps of. a) polymerizing PA1 b) reating stepwise or simultaneously said isocyanate groups with. i) an ethylenically unsaturated monomer containing an isocyanate group with PA2 ii) ethylenically unsaturated monomer having no functional group capable of undergoing a reaction with said isocyanate group to form a copolymer with isocyanate and PA2 iii) a polyalkylenglycol monoalkyl ether or amine and PA2 iv) optionally, a compound having one primary or one secondary amino group or another alcohol.

Aqueous coating compositions are known and described for example in U.S. Pat. Nos. 4,794,147; 4,791,168; 4,518,724; and 4,403,055.
These aqueous coating compositions comprise a principal resin, optionally a crosslinker, pigments dispersed in a grind resin and other additives such as solvents, control agents fillers and the like.
Many pigments, especially organics, used in coating compositions for the automotive industry are hydrophobic. These pigments, when used in aqueous coating systems require the use of specialized grind resins with the additions of dispersing agents and solvents to overcome their incompatibility with water and poor ability to grind.
Pigment pastes are usually prepared by dispersing a pigment in a grinding resin in the presence of plasticizers, wetting agents, surfactants or other ingredients in a ball mill, sand mill, cowles mill or continuous mill until the pigment has been reduced to the desired particle size and is wetted by the resin or dispersed in it.
One disadvantage of pigment pastes is that they contain volatile organic compounds (VOC). Also, they often require a large amount of resin relative to pigment, and the resulting pigment pastes are not very concentrated. In addition, pastes made with conventional resins often do not have optimum color development.
It is therefore an object of the present invention to provide a process for the preparation of a pigment dispersant for an aqueous coating composition which does not need the use of volatile organic compounds and which provides stable aqueous pigment pastes or pigment dispersions. Another object is to increase the amount of pigments in the dispersion and simultaneously reduce the amount of resin. Yet another object of the invention is an aqueous coating composition comprising such pigment pastes or pigment dispersions.

Process for the preparation of a modified copolymer as a pigment dispersant for aqueous coating compositions


An encoder device coupled to a roller or “scroll wheel” includes a mechanism to convert a rotating movement of the roller into a reciprocating movement that causes intermittent electrical conduction between two metal contacts so as to output an intermittent electrical signal indicative of roller movement without continuous power consumption.

Input or output devices having a roller thereon are becoming increasingly popular. The roller is typically arranged to enable a user to scroll a display on a screen. If the roller if depressed, an extra predetermined program or function will be activated, such as logging onto the internet, receiving e-mails, and so forth. Because of the convenience of the roller, manufacturers are rushing to create or to build related structures or methods for practical use.
U.S. Pat. No. 5,912,661, U.S. Pat. No. 6,157,369, and U.S. Pat. No. 6,326,949 show conventional encoder devices that utilize a grating wheel and in which a light transmitter and a light detector are located at each side of the grating wheel. The projected light from the transmitter is intermittently blocked by a plurality of slots on the grating wheel that causes the detector to sense the changes in dark and light as to output an intermittent electrical signal. Disadvantages of this arrangement are that the transmitter and detector must be in precise alignment, and the transmitter must emit light continuously even when the grating wheel blocks transmission, so that further movement of the grating wheel can be detected.
U.S. Pat. No. 6,198,057 shows an alternative arrangement in which a rotary encoder 2 is coupled with an axle 5 of a roller 4, and a plurality of brushes are rotatably-connected with a corresponding number of contacts to generate an intermittent signal. This arrangement is simpler to assemble than optical encoders, and only a generates and electric signal when contact is made, but still requires relatively precise alignment of contacts and encoder wheel.
Finally, U.S. Pat. No. 5,657,051 discloses a switch-like encoder arranged to output intermittent signals following depression of a user's finger. The structure is easy to build, but the way that the user has to move his finger forward and backward tends not only to cause fatigue over the user's hand, but also inconvenience in use in comparison with the roller type.


Phencylidine, PCP, derivatives having a non-oxo carbonyl functionality linked directly or through a linking group to the phenyl ring are provided for conjugation to antigenic compositions, particularly poly(amino acids), and enzymes. The antigenic conjugates are employed for the production of antibodies, which find particular use in immunoassays for the determination of phencyclidine, while the enzyme conjugate finds use in a homogeneous enzyme immunoassay for the determination of phencyclidine.

1. Field of the Invention
1-(1'-phenylcyclohexyl-1')piperidine, otherwise known as phencyclidine, PCP, was originally used as an analgesic anaesthetic drug (pain-killing) for humans. It is now legally used exclusively as an animal tranquilizer due to its strong side effects, such as euphoria and hallucinations. Probably because of these side effects, PCP has become prevalent in the illicit drug market. It is often sold as "peace pill", "angel dust", "dust", "crystal", or "supergrass".
PCP is a dangerous and potent drug with lethal potential and has become a major drug abuse problem. Thus it is desirable that there be a simple accurate rapid technique for detecting the presence of PCP in physiological fluids, such as blood serum, urine and saliva.
2. Description of the Prior Art
There have been difficulties in attempting to identify PCP in physiological fluids. In one investigation (D. C. K. Lin et al., Biochem. Mass Spec. 206 (1975)) of urine from patients intoxicated by PCP, no metabolites were detected in untreated urine. However, two urinary metabolites were freed from conjugates by enzymatic hydrolysis and identified as 4-phenyl-4-piperidinocyclohexanol and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine. An additional metabolite, tentatively identified as 1-phenyl-(4-hydroxycarboxyl)-4-hydroxypiperidine, was found in the urine from rhesus monkeys after administration of PCP.

Phencyclidine conjugates to antigenic proteins and enzymes


An electrical connector comprises a first housing, a mating terminal retained in the first housing, a second housing mated with the first housing, a contact member disposed in the second housing, and an insertion/extraction assist protrusion. The contact member is electrically connected with the mating terminal by pinching the mating terminal with a plurality of spring pieces facing each other. The spring pieces each have a contact portion protruding inward. The insertion/extraction assist protrusion is adapted to expand a gap between the spring pieces when the first housing and the second housing move relative to one another in a mating direction. The insertion/extraction assist protrusion is arranged offset from the contact portions in a plane crossing the mating direction and is arranged nearer to a start point of the mating than the contact portions during the mating in the mating direction.

Electrical connectors are known which are configured to pinch a flat terminal with a clip contact. Japanese Patent Application No. JP 2017-091805A discloses a configuration in which a contact avoiding portion is provided in one housing. The contact avoiding portion is adapted to expand an open width of the clip contact in order to prevent a mating terminal from being damaged from contact with the clip contact.
In JP 2017-091805A, when the mating terminal is inserted, the contact avoiding portion enters the clip contact to expand the open width of the contact. This allows the mating terminal to be inserted into the contact without making contact with the contact. Then, as a moving housing moves in the process of mating of the connector, the contact avoiding portion is extracted from the contact. Thereupon, the open width of the contact having the mating terminal inserted therein is narrowed, and thus the mating terminal makes contact with the contact.
In JP 2017-091805A, the clip contact makes contact with the mating terminal without sliding thereon during mating of the connector. Therefore, if an insulating substance has adhered to the mating terminal, the interposition of the insulating substrate between the clip contact and the mating terminal may cause a contact failure.


A replication-defective recombinant virus, preferably an adenovirus that lacks E1a, E1b and E4 ORF 6, capable of infecting an eye and containing a ORF encoding a protein that when expressed in lens epithelial cells of an eye, suppresses, at the level of the germinative epithelium of the lens of the eye, cellular proliferation which is stimulated by eye surgery and which would otherwise result in secondary cataract formation in the eye is disclosed. The ORF, to be expressed, is under the control of a promoter sequence which is expressly exclusively in human lens epithelial cells. The preferred ORFs, to be expressed, include a non-phosphorylatable retinoblastoma ORF, a dominant negative mutant of a human RAS ORF and a Herpes thymidine kinase ORF. The preferred promoter sequences include: a) a promoter of a human Major Intrinsic Protein gene, particularly from -259 nt to +34 nt, b) a promoter of a human .beta. crystallin gene, particularly from -345 nt to +45 nt, and especially c) the promoter of the Major Intrinsic Protein gene or .beta. crystallin gene or portions thereof, in combination with elements of the promoter of the rat Early Growth Response-1 gene, from -518 nt to -236 nt. Use of the recombinant virus for the treatment of an eye, undergoing eye (e.g. cataract) surgery, in order to reduce the incidence of cellular proliferation in the eye following the surgery, and thereby to prevent the formation of secondary cataracts is disclosed.

This invention relates to materials and methods for the construction of recombinant viral, particularly adenoviral, delivery systems that provide lens epithelial cell type specific regulation of expression of proteins which inhibit cellular proliferation. This invention also relates to the use of these recombinant viral delivery systems for inhibiting or preventing the formation of secondary cataracts following surgical intervention on the eye.
Cataract operations are the second most frequent operation in the western world. The cataract is an affliction characterized by an opacification of the crystalline lens of the eye which reduces the visual acuity of the patient. The surgical technique currently utilized for removing cataracts consists of removing the crystalline with a small aspirator. Access to the interior of the crystalline capsule is achieved by a circular opening at the anterior face of the lens capsule. This permits the surgeon to insert a new lens, which will restore the eye's ability to focus incoming light on the surface of the retina.
Secondary cataracts constitute the most frequent complication following this operation, occurring in up to 50% of adult eyes and even more frequently following surgery of children with congenital cataracts (Nischi et al., 1986). (Surgical interventions on the eyes of rabbits also result in secondary cataract formation (100%) in the weeks following the operation (Blomstedt. et al., 1987)). Human secondary cataracts are characterized by a secondary opacification of the posterior capsule appearing in the months following surgery. They are the consequence of the stimulated proliferation at the level of the germinative epithelium of the lens, which are the only cells with division potential in the mature eye. Laser treatment, which is the accepted means of treating secondary cataracts, unfortunately risks additional complications, the most notable of which is detachment of the retina (Salvenson et al., 1991).

Somatic gene therapy to suppress secondary cataract formation following eye surgery