Abstract: A method for preventing, ameliorating, and/or treating memory and other cognitive disorders associated with aging, such as Age-Associated Memory Impairment (also known as Age-Related Cognitive Decline), and other age-related impairments of, and/or changes in, cognitive function. The method comprises administering to a subject a therapeutically effective amount of a lipid-soluble thiamine or a prodrug thereof in an amount averaging from about 0.02 to about 0.5 grams per day per 70 kg body weight over a period of three months or longer.

Abstract: Improved medical devices and instruments prepared by an improved method of producing hydrophilic, gamma-irradiation induced polymerized and chemically grafted coatings on plastic surfaces of articles adapted for contacting living tissue, the improvement comprising carrying out the graft polymerization in an aqueous solution under specific combinations of the following conditions:(a) monomer concentration in the range of from about 0.1% to about 50%, by weight;(b) total gamma dose in the range of from about 0.001 to less than about 0.50 Mrad; and(c) gamma dose rate in the range of from above about 2,500 to about 10.sup.8 rads/minute.

Abstract: A method of forming an implantable and retrievable immunoisolatory vehicles is disclosed, the method comprising the steps of first forming a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of providing a biologically active product or metabolic or immunologic function, said cells being dispersed in a biocompatible hydrogel or extracellular matrix, and then forming around the core a surrounding external biocompatible thermoplastic or hydrogel jacket free of said cells projecting externally thereof, said jacket having molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.

Abstract: Sodium hyaluronate viscous aqueous solutions of molecular weight from 1,200,000 to 2,200,000 Daltons at concentrations from 0.10% to 0.40% by weight are proposed for use as masking fluid in therapeutic photokeratectomy by means of excimer laser (PTK), which realizes the ablation of superficial layers of corneal tissue for the elimination of unevenness and macula derived from different traumatic or pathological conditions. Preferably, the proposed solutions also contain one or more cationic species selected from the group consisting of sodium, potassium, calcium and magnesium ion and one or more anionic species selected from the group consisting of chloride, phosphate and citrate ion and, preferably, glucose. The solutions according to the invention wet the cornea and protect its areas which remain distressed after surgery, enabling the obtainment of uniform and smooth ablated surfaces. Further, they enable the execution of intraoperative corneal topographic tests.

Abstract: A method for treatment of a neurodegenerative condition in a patient comprising implanting in the patient at least one immunoisolatory vehicle comprising a corc comprising a volume of at least 1 .mu.l and at least 10.sup.4 living cells which secrete at least one biologically active product, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and an external jacket surrounding the core, the jacket comprising a biocompatible hydrogel or thermoplastic, the jacket being free of cells projecting externally thereof, said jacket having a molecular weight cutoff permitting the passage of the biologically active product from the core through the jacket.

Abstract: This invention relates to fluid-imbibing delivery devices for delivering a beneficial agent to a biological environment of use. In particular, the devices include a rigid housing defining an internal compartment comprising a substantially impermeable first wall section and a second wall section permeable to fluid in the environment of use. The first wall section may be shape-retaining, with exit means and an open end, and extend for at least 85% of the entire length of the device to define the internal compartment.

Abstract: A polymeric material incorporating a polyvalent cation chelating agent in an amount effective to inhibit the growth of an ocular pathogen, particularly a protozoan, can be used to produce eye care products such as contact lens cases and containers for containing eye care solutions and contact lenses.

Abstract: Balanced pH, thermo-irreversible gels comprising a polyoxyalkylene compound and an ionic polysaccharide are ideal materials for the formation of a protective contact lens over the cornea of the eye of a mammal.

Abstract: Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Abstract: A method for oxidatively consuming volatile sulfur compounds selected from the group consisting of dimethylsulfide, hydrogen sulfide, and methylmercaptan at the epithelial barrier of the rectal, vaginal, urethral, oral, nasal, ocular, and auditory canal orifices to maintain the epithelial barrier and reduce penetration of any of Candida, Actinobacillus actinomycetumcomitans, Pseudomonades, and Porphyromonas gingivalis, said method comprising the step of applying to the orifices a composition comprising a topical preparation selected from the group consisting of liquid solutions, suspensions, semi-solids, salves, creams, and suppositories, wherein the topical preparation contains chlorine dioxide in a concentration in the range of about 0.005% to about 2.0% and a phosphate compound selected from the group consisting of disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodiuit phosphate, or sodium monofluorophosphate in a concentration in the range of about 0.02% to about 3.

Abstract: A method of forming an implantable and retrievable immunoisolatory vehicle is disclosed, the method comprising the steps of first forming a jacket of biocompatible thermoplastic or hydrogel, and then loading the jacket with a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of secreting a biocompatible matrix comprising a hydrogel or extracellular matrix, said jacket having a molecular weight cutoff permitting passage of molecules thereacross to provide said biologically active product or said function.

Abstract: Implants comprising active agents are employed for introduction into a suprachoroidal space or an avascular region of an eye for therapeutic purposes. The administration of drugs is controlled and maintained for long periods of time, while ensuring the substantial absence of significant levels outside the site of administration.

Abstract: A stable solution, cream, salve, or spray composition containing chlorine dioxide and phosphates, such as disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, and sodium monofluorophosphate, is disclosed for the prevention and treatment of abnormal conditions of the epithelium of bodily orifices. Examples of such abnormal conditions of the epithelium of the rectal, vaginal, urethral, oral, nasal, ocular, and auditory canal orifices include bacterial infections, such as Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, and fungal infections, such as Candida, and leukoplakia. The preferred concentration ranges are in the range of about 0.005% to about 2.0% chlorine dioxide, and in the range of about 0.02% to about 3.0% phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of about 6.0 to about 7.

Abstract: A method of making an immunoisolatory vehicle comprised of a core comprising living cells dispersed in a biocompatible matrix is disclosed, the cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to an individual, and an external jacket surrounding said core which is a biocompatible, permselective thermoplastic or hydrogel, said jacket being free of said cells, comprising coextruding a suspension comprising said cells dispersed in a precursor matrix material comprising extracellular matrix components or a biocompatible hydrogel precursor, and a solution of a biocompatible jacket precursor from a nested dual-bore extrusion nozzle, wherein the suspension of (a) is coextruded from the inner bore and the solution of (b) is coextruded from the outer bore of the nozzle, to form said jacket as the solution of (b) and the suspension of (a) arc coextruded; and exposing the vehicle to a treatment that forms a core comprising a volume of at least 1 .mu.

Abstract: Immunoisolatory vehicles having a core and a surrounding jacket are disclosed, the core having a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells capable of secreting a biologically active product or of providing a biological function to a patient, the cells dispersed in a biocompatible matrix formed of a hydrogel or an extracellular matrix component, and the external jacket being permselective, biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biological product or function.

Abstract: A method of providing a biologically active molecule or metabolic or immunologic function to a patient, comprising implanting into the body of the patient at least one immunoisolatory vehicle comprising a core comprising a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells dispersed in a biocompatible matrix formed of a hydrogel or extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to the patient; and an external jacket surrounding said core, said jacket being formed from a thermoplastic or hydrogel, said jacket being free of said cells projecting externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biologically active product of function.

Abstract: An improved viscosurgical method involving the administration of a viscoelastic and a corresponding degradative agent, such that the post-operative intraocular pressure spike often observed following the use of viscoelastics in ophthalmic surgery is minimized, and an apparatus and clinical kit useful in the method are provided.

Abstract: A method and apparatus for correcting refractive errors of the eye are disclosed. Accelerated reshaping of the corneal tissue is accomplished by administering one or more enzymes and/or other agents to the eye which temporarily soften the cornea. The cornea is thereafter fitted with a rigid contact lens or a series of lenses which have a concave curvature that will correct a refractive error. The softened cornea then rapidly reshapes its convex curvature to the concave curvature of the contact lens or series of lenses, thereby rendering the eye emmetropic. The enzymes and/or other agents then dissipate from the cornea, and the cornea "hardens" to retain the new emmetropic shape. After "hardening" has occurred, the lens rendering the eye emmetropic is removed.

Abstract: A veterinary method for clinically modifying the behavior of a household pet dog exhibiting a recognized type of canine affective aggression behavior is provided. The veterinary behavior modification method administers at least one compound selected from the group consisting of R enantiomers, S enantiomers, or a racemic mixture of selective serotonic reuptake inhibitors or their active metabolites to the dog upon one or multiple occasions; and the administration of these compounds will modify clinically the canine affective aggression behavior of the household dog permanently or for an indefinite period of time. This veterinary behavior modification method can be usefully employed as an adjunct to conditioning approaches presently employed and will avoid the need for euthanasia in extreme behavioral circumstances.

Abstract: Tetrahydroquinoline analogues and compositions containing them for topically treating glaucoma to effectively reduce intraocular eye pressure.

Abstract: The invention relates to an oxidation inhibitor coating for high-melting metals selected from the group of molybdenum, tungsten, tantalum and niobium and/or alloys thereof. The oxidation inhibitor coating comprises 1 to 14% by weight boron, 0.1 to 4% by weight carbon and the balance silicon.

Abstract: A bioadhesive ophthalmic insert is described which is intended more particularly for the prolonged and controlled release of a medicinal substance. The insert comprises a composite polymeric material matrix in which the medicinal substance is incorporated.The composite polymeric material matrix comprises a water-soluble biocompatible polymer and a bioadhesive biocompatible polymer and, where applicable, a water-insoluble biocompatible polymer.

Abstract: A simple and implantable sustained release drug delivery device with an inner core containing an effective amount of a low solubility agent covered by a non-bioerodible polymer coating layer that is permeable to the low solubility agent is disclosed. A method for treating a mammal to obtain a desired local or systemic physiological or pharmacological effect by surgically implanting such a sustained release drug delivery device into a mammal in need of treatment is also disclosed.

Abstract: Ophthalmic preparation for use as artificial tear containing hyaluronate as a viscosity thickener, preferably in the form of sodic salt and having a molecular weight of 500,000 to 4,000,000 daltons, at a concentration of 0.05 to 2% by weight, as well as the following minimum quantities of ionic species: 40 mmol/l sodium ion, 12 mmol/l potassium ion, 0.4 mmol/l calcium ion, 0.4 mmol/l magnesium ion, 50 mmol/l chloride ion, 7 mmol/l phosphate ion and, preferably, 0.7 mmol/l citrate ion. The formulation, which as an osmolarity of 140 to 280 mOsm/l, is useful for the treatment of keratoconjunctivitis sicca and may be administered whenever the use of artifical tears is advisable, e.g. for the treatment of eye irritations caused by environmental conditions or contact lenses.

Abstract: Implants comprising active agents are employed for introduction into a suprachoroidal space or an avascular region of an eye for therapeutic purposes. The administration of drugs is controlled and maintained for long periods of time, while ensuring the substantial absence of significant levels outside the site of administration.

Abstract: An insoluble pharmaceutical dosage form for ocular administration including a matrix including at least one polymer and at least one active ingredient and a first layer of glycerides distributed at least over a surface of the matrix. The dosage form is an insoluble solid tablet.

Abstract: A veterinary method for clinically modifying the behavior of a household pet dog exhibiting a recognized type of canine affective aggression behavior is provided. The veterinary behavior modification method administers at least one preferential serotonin reuptake inhibitor compound to the dog upon one or multiple occasions; and the administration of these compounds will modify clinically the canine affective aggression behavior of the household dog permanently or for an indefinite period of time. This veterinary behavior modification method can be usefully employed as an adjunct to conditioning approaches presently employed and will avoid the need for euthanasia in extreme behavioral circumstances.

Abstract: Bi-aromatic compounds are provided along with methods for their preparation and use.

Abstract: The invention provides novel compositions of matter for delivering water-insoluble steroid drugs suitable for therapeutic use. The invention also provides stable aqueous suspensions of water-insoluble steroid drugs of particle sizes of .ltoreq.30 .mu.m which remain in such a state so as to allow for immediate suspension, when desired, even after extended periods of settling.

Abstract: The present invention relates to a ready-to-use indomethacin eye lotion comprising, in aqueous solution:indomethacin,a .beta.- or .gamma.-cyclodextrin etherified with C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 hydroxyalkyl groups, the cyclodextrin being present in a molar ratio with respect to the indomethacin of at least 10/1, and the pH of the solution being from 4.0 to 6.0.

Abstract: A polymeric material incorporating a polyvalent cation chelating agent in an amount effective to inhibit the growth of an ocular pathogen, particularly a protozoan, can be used to produce eye care products such as contact lens cases and containers for containing eye care solutions and contact lenses.

Abstract: Novel bioartificial hydrogels consisting of a three-dimensional crosslinked mixture of: (a) a bifunctionalized polyethylene oxide, activated with an activating agent, dissolved in an aqueous solution; and (b) albumin type protein. The novel hydrogels are based on the crosslinking of albumin type protein of various sources including, for example, bovine serum albumin, lactalbumin or ovalbumin, with a bifunctionalyzed polyethylene oxide, most preferably polyethylene glycol, or a mixture of bifunctionalyzed polyethylene oxides preferably polyethylene glycol, of various molecular masses (Mr 2,000 to 35,000), dissolved in aqueous solution in adequate proportions. Also provided is a method and conditions for preparing the novel hydrogels. Also divulged are a variety of biomedical applications for the novel hydrogels.

Abstract: The present invention provides a sustained-release delivery composition for ophthalmic drugs comprising cross-linked hydrogel microspheres having a binding affinity for the drug.

Abstract: A method of masking the cornea of an eye during surgical application of laser energy by forming an ablatable mask on the eye.

Abstract: A contact lens made of a polymeric hydrogel material having absorbed therein as a leachable additive of desferrioxamine, and a method for making the composition by soaking the polymeric material in a solution of the additive.

Abstract: This invention is concerned with novel 1-?cycloalkylpioeridin-4-yl!-2H benzimidazolones, their compositions and method of use. The novel compounds are selective muscarinic agonists of the m2 subtype with low activity at the m3 subtype. The compounds are effective for the treatment of glaucoma with fewer side effects than the pilocarpine therapy.

Abstract: A collagen-hydrogel for promoting epithelial cell growth and regeneration of the stroma is shown. Also shown is an optical lens for the eye, fabricated from the collagen-hydrogel, which, when affixed to Bowman's membrane, promotes and supports epithelial cell growth, enables corneal epithelium of the cornea of an eye, during the healing process, to attach to and cover the anterior surface of the lens implanting the same and to regenerate the stroma which grows over the edge of and attaches to the optical lens. Laid down in the layers of the regenerated stroma are new keratocytes and collagen fibial produced from keratocytes. The collagen-hydrogel is a hydrogel polymer formed by the free radical polymerization of a hydrophilic monomer solution gelled and crosslinked in the presence of an aqueous stock solution of collagen to form a three dimensional polymeric meshwork for anchoring collagen. The collagen-hydrogel material has a ratio by weight of collagen-to-hydrogel in the range of about 0.

Abstract: In a preferred embodiment, drugs having pharmacological properties which are useful in the medicinal therapy of fibrotic disease for the reparation and prevention of fibrotic lesional tissues, such drugs including as active ingredient(s) one or more N-substituted 2-(1H) pyridone(s) and/or N-substituted 3-(1H) pyridones. The composition of this invention is novel as an anti-fibrotic drug, namely, as an agent for treating fibrosis. Any existing compounds have not been shown to be effective for the reparation and prevention of fibrotic lesions.

Abstract: The invention relates to the use of cucurbitine or extracts of Cucurbitaceae pips for the preparation of a cosmetic or pharmaceutical, in particular dermatological, composition having antiallergic activity, or for the preparation of cosmetic or pharmaceutical compositions having a reduced risk of being allergenic.

Abstract: The present invention relates to a scleral plug made of lactic acid copolymer; a scleral plug containing a drug that is designed to gradually release the drug into a vitreous body; and a scleral plug that is used to treat or prevent diseases of the retina or to promote recovery from damage after vitreous surgery taking advantage of its sustained release action for drug delivery.

Abstract: The invention is directed to an improved system for controlled release of biologically active materials and to a liquid composition for its formation. The liquid composition is composed of a thermoplastic polymer, rate modifying agent, bioactive material and organic solvent. The liquid composition is capable of forming a biodegradable and/or bioerodible microporous, solid polymer matrix. The matrix is useful as an implant in patients (humans and animals) for delivery of biologically active substances to tissues or organs.

Abstract: The intraocular use of combinations of lens epithelial cell growth stimulators (e.g., TGF-.beta.) and antimetabolites (e.g., mitomycin C) is described. The combination is applied to the capsular bag to prevent or retard the formation of secondary cataracts following cataract surgery. The lens epithelial cell stimulators activate DNA synthesis in dormant lens epithelial cells, and thereby make those cells susceptible to the anti-metabolites. This enables the antimetabolites to suppress the proliferation of lens epithelial cells to a much greater extent, relative to the proliferation observed when the metabolites alone are utilized. The increased suppression of the growth of lens epithelial cells results in a significant improvement in the ability to prevent or retard the formation of opacities on the lens capsule (i.e., secondary cataracts).

Abstract: A biocompatible poly(ethylene oxide) gel implant and method for production which can be injected into the human body for tissue replacement and augmentation. The implant is prepared by dissolving a sample of essentially pure poly(ethylene oxide) in a saline solution in a sealed canister, removing all free oxygen from the container and replacing it with an inert gas, such as argon, and irradiating the canister with a gamma ray source to simultaneously crosslink the polyethylene oxide while sterilizing it. The gel can then be placed into a syringe and injected into the body.

Abstract: Methods of facilitating surgical operations that involve the eye or eye area comprise introducing an opthalmologically acceptable composition containing hyaluronic acid into the site of the surgical operation. The hyaluronic acid comprises a chemically unmodified sterilized hyaluronic acid substance having a weight average molecular weight of from 4,500,000 to 12,000,000 daltons, a zero shear viscosity of from 1,000 to 80,000 Pas as measured on a 1.3-1.6% (wv) solution of hyaluronic acid substance in physiological phosphate buffer, and an absorbance at 257 nm of less than 3.5 when measured on a 1% solution of hyaluronic acid substance in sodium chloride buffer in a 10 mm cuvette. Preferred sterilized solutions of hyaluronic acid comprise hyaluronic acid which is chemically unmodified from the naturally occurring hyaluronic acid and has a weight average molecular weight of from 4,500,000 to 8,000,000 daltons, a zero shear viscosity of from 1,000 to 20,000 Pas and an absorbance at 257 nm of less than 3.5.

Abstract: A method of treating an intraocular structural disorder of an eye comprising introducing into the intraocular structure under treatment a liquid silicone/fluorosilicone oil in an amount effective to treat the intraocular structural disorder.

Abstract: A method for preparing a pharmaceutical microdispersion exhibiting enhanced bioavailability, including the steps of providing a thermodynamically stable pharmaceutical composition comprising at least one lipophilic pharmaceutical agent incorporated in a physiologically acceptable liquid carrier, the liquid carrier comprising one or more lipophilic solvents such as fluorochemicals and preferably at least one nonfluorinated co-solvent, and combining the stable pharmaceutical composition with an amount of at least one miscible diluent sufficient to initiate phase separation of the lipophilic pharmaceutical agent from the pharmaceutical composition wherein a microdispersion of the pharmaceutical composition is formed. Also disclosed are microdisperse pharmaceutical compositions and kits for forming such compositions.

Abstract: Methods for preventing and treating corneal haze resulting from exposure of the eye to laser irradiation are disclosed. The methods include administration of compositions of wound healing modulators to the eye. Compositions for use in preventing and treating the corneal haze are also disclosed.

Abstract: Stable formulations of positively charged, hydrolytically unstable drug compounds are obtained by adding a sulfated polyvinyl alcohol copolymer to the formulations.

Abstract: Absorbable ocular inserts fabricated of materials that are biologically inert, biodegradable, non-allergenic, and insoluble in tear liquid, and a method for delivering substances to the eye using the ocular insert, are disclosed. In embodiment A of the invention, the insert and method include the covalent attachment of a carboxylic acid-containing substance to be delivered to a polymer that contains pendent carboxylic acid groups, through anhydride linkages. The drug is released over time by hydrolysis of the anhydride bonds. In embodiment B of the invention, a substance to be delivered (whether or not it contains a carboxylic acid group) is dispersed within an anhydride polymer or copolymer matrix and the mixture is formed into an appropriately shaped article for ocular delivery.

Abstract: Disclosed are storage-stable preserved ophthalmic compositions containing acidic drugs in combination with polymeric quaternary ammonium compounds and boric acid.