Abstract: A process for producing a small-sized, lipid-based cochleate is described. Cochleates are derived from liposomes which are suspended in an aqueous two-phase polymer solution, enabling the differential partitioning of polar molecule based-structure by phase separation. The liposome-containing two-phase polymer solution, treated with positively charged molecules such as Ca.sup.2+ or Zn.sup.2+, forms a cochleate precipitate of a particle size less than one micron. The process may be used to produce cochleates containing pharmaceutical agents or biologically relevant molecules. Small-sized cochleates may be administered orally or through the mucosa to obtain an effective method of treatment.

Abstract: Described are compositions, methods, and articles of manufacture for the closure of retinal breaks with a non-toxic polymer. Transformation to a gel-like coat is achieved by photochemical reactivity, chemical reactivity, and by physicochemical response.

Abstract: Methods for treating injured corneal tissue are described. The methods include contacting injured corneal tissue with a contact lens which includes an amniotic composition such that scarring of the injured corneal tissue is reduced. Methods for conditioning a contact lens for treatment of injured corneal tissue are also described. The methods include contacting the contact lens with an amniotic composition whereby the amniotic composition is deposited in or on the surface of said contact lens. Additionally, contact lens packages for treatment of injured corneal tissue are described. The contact lens package includes a container holding a contact lens which includes an amniotic composition and instructions for using the contact lens for treatment of injured corneal tissue.

Abstract: Balanced pH, hyperosmotic, hypoosmotic, or isoosmotic gels are ideal vehicles for drug delivery. They are especially suited for topical body cavity or injection application of drugs or diagnostic agents; for drug or diagnostic agent delivery to the eye of a mammal; as protective corneal shields; or as ablatable corneal masks useful in laser reprofiling of the cornea. The compositions without the addition of a drug or diagnostic agent are useful as medical devices, for instance, in separating surgically or otherwise injured tissue as a means of preventing adhesions.

Abstract: A method of treating a disease or condition comprising administering topically to the skin or exposed tissue of a human, a dosage amount of a pharmaceutical composition, said dosage comprising a therapeutically effective amount of a drug to treat said disease or condition and a form of hyaluronic acid characterized in that the composition is immediately available to transport the drug percutaneously into the epidermis of the skin or exposed tissue to the site of trauma or pathology of the disease or condition to be treated.

Abstract: An O/W emulsion composition for eye drops comprises a drug selected from the group consisting of fluorometholone, clobetasone butyrate and clobetasol propionate; a phospholipid; liquid paraffine; and water. The O/W emulsion composition is excellent in solubility of fluorometholone, clobetasone butyrate and clobetasol propionate in the tear fluid. Therefore, the composition would exhibit an anti-inflammatory activity identical to or superior to those achieved by the conventional pharmaceutical preparations, by the administration thereof at a dose lower than those for these known drugs. The composition would also be excellent from the economical standpoint and permit reduction of systemic side effects which would be encountered when the conventional drugs are instilled in the eyes.

Abstract: The invention refers to a transcorneal system for the actively controlled transcorneal delivery of a medicament into a subject comprising an active substance reservoir and a device provided with a plurality of micro-pins or micro-blades adapted in use to penetrate the stratum corneum of the subject and connected with reservoir via a liquid conveying connection and thereby allow active substance to pass from the reservoir through capillary openings of the micro-pins or along the micro-blades into the subject.

Abstract: The present invention relates, in general, to methods of treating disorders of the eye, and, in particular, to methods of preventing or treating elevated eye pressure and glaucoma. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: An external preparation for topical administration which aims at inhibiting rejection reactions at organ or bone marrow transplantation or treating autoimmune diseases or allergic diseases and contains as the active ingredient 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol or a pharmaceutically acceptable acid addition salt thereof.

Abstract: The present invention is directed to an otological implant for delivery of medicament and a method of using the implant. The implant includes a wick inserted through an aperture in a membrane. One end of the wick is in contact with the treatment site and the other end is readily accessible. The wick is made of a material that will convey medication from one end of the wick to the other end of the wick by capillary action so that the medication is delivered to the treatment site. The implant may also include a tube member for supporting the wick. In use, the tube member is inserted in the membrane aperture and the wick is inserted in the lumen of the tube.

Abstract: Methods of treating or preventing fibrosis and sclerosis by the administration of compositions containing A.sub.1 adenosine receptor antagonists and/or P.sub.2X purinoceptor antagonists, or combinations thereof.

Abstract: An implantable device is provided which incorporates a retinoid for improving the biocompatability of the device in tissue. The device may be bioerodible for the purpose of systemically or locally releasing a therapeutic agent in tissue or it may be a permanent implant which includes a surface treated with a retinoid for increasing the biocompatibility thereof.

Abstract: An implantable device is provided which incorporates a retinoid for improving the biocompatability of the device in eye tissue. The device may be bioerodible for the purpose of systemically or locally releasing a therapeutic agent in tissue or it may be a permanent implant which includes a surface treated with a retinoid for increasing the biocompatibility thereof.

Abstract: This invention relates to formulations comprising film-forming components capable of forming per se a physical barrier to pathogens. Thermoreversible gels such as poloxamers are particularly preferred for that use. The film-forming formulations may further comprise microbicides, spermicides or any other drug, which choice is guided by the pathogen, organism or the disease to be inactivated or treated. The formulations are therefore efficient as a physical, and optionally, as a chemical or pharmacological barrier as well as usable as a sustained drug-release system at the locus of administration. A part of the drug may also be entrapped in liposomes or other drug carriers. These formulations are intended for use in the prevention of sexually transmitted diseases, as well as in the treatment of infections, cancer, inflammation or any disease or state which requires a pharmacological treatment. Formulations are applicable to mucosae, skin and eye, for example.

Abstract: Implants which are capable of sustained release of a cell proliferation modulating agent, together with methods for their preparation and use, are provided. The proliferation modulating agent is associated either covalently or non-covalently with the material from which the implant is prepared, generally a biologically inert polymer which is physiologically compatible. The implants are implanted in the tissue, and the drug is released such that the drug is substantially retained within the implant region. The device can be used to inhibit cellular proliferation around the implant. The device can be provided as a sterile kit, preferably in a form suitable for immediate use.

Abstract: The present invention involves the discovery that synthetic thyroid hormones can be used as compositions to reduce intraocular pressure in vivo. Methods of screening synthetic thyroid hormones for effect on intraocular pressure, aqueous pressure, hydraulic conductivity, hyaluronic acid secretion, and extracellular matrix assembly are provided. Methods of treating glaucoma and treating excess intraocular pressure with synthetic thyroid hormones and compositions therefore are also provided.

Abstract: A process for producing a controlled drug-release contact lens, containing a first member which forms a front fact of the lens and a second member which forms a rear face of the lens, the first and second members defining a space in the contact lens, which entails a) preparing the first and second members from a non-crosslinked polymer; b) bonding the prepared first and second members by melt pressing; and c) crosslinking the bonded members by hydration treatment, wherein the non-crosslinked polymer is obtained from a polymerizable methoxy silicone compound and another monomer copolymerizable therewith.

Abstract: A galactolipid material from wheat, produced by extraction of crushed wheat grains and subsequent chromatography of the extracted material, and having a content of DGDG of 51.5%, was mixed with the polar solvents, water and glycerol in order to test the swellability. The samples, prepared in glass tubes, were alternately mixed with a rod and centrifugated at room temperature until homogeneous. The samples were inspected as to physical appearance after storing for at least a week at room temperature.Results:20% (w/w) of galactolipid material in water gave a slightly yellow, highly viscous dispersion. Small liposomes could be observed in a polarizing microscope. At higher galactolipid concentrations a stiff gel was formed.10% (w/w) of the same lipid material in anhydrous glycerol resulted in the formation of an opaque, highly viscous gel.

Abstract: A stable solution cream, salve, or spray composition containing activated stabilized 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 Porphyromonoas gingivalis, and fungal infections, such as Candida, and leukoplakia. The preferred concentration ranges are between about 0.005%-2.0% chlorine dioxide, and between about 0.02%-3.0% phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of 6.0 to 7.

Abstract: A pharmaceutical composition comprising a plurality of effective non-toxic dosage amounts of a composition for topical administration to the site of pathology or trauma of skin or exposed tissue of a human patient in need of treatment suffering from a disease or condition, each such dosage amount comprising a therapeutically effective non-toxic dosage amount of a drug for the treatment of the disease or condition of the skin or exposed tissue at the site of the pathology or trauma and an effective non-toxic dosage amount of hyaluronic acid or salts thereof or homologues, analogues, derivatives, complexes, esters, fragments, or sub-units of hyaluronic acid to transport the drug to the site of the pathology or trauma of the disease or condition.

Abstract: (Meth)acrylic acid/maleic acid copolymers for improving mucosal permeability and pharmaceutical compositions containing them are described.

Abstract: A composite surgical material comprising a collagen matrix reinforced by a layer of a synthetic bioabsorbable material such as polylactide/polyglycolide or oxidized regenerated cellulose, and wherein oil droplets are dispersed in the collagen matrix. The oil droplets comprise 1% to 75% of the weight of the composite and result in improved leak-proofing of the composite. The composite, in the form of a sheet or a tube, is especially useful as a temporary, fully bioabsorbable prosthesis, for membranes or blood vessels where a highly leak-proof prosthesis is required. The invention also provides a method of making a composite surgical material comprising the steps of: providing a layer of a synthetic bioabsorbable material; providing a dispersion of collagen in an oil-in-water emulsion; coating at least one face of the layer of synthetic bioabsorbable material with the said dispersion; and drying the composite material thus obtained.

Abstract: A method is provided for inhibiting or reducing the risk of macular degeneration with phytoestrogenic isoflavones. A further method is provided for inhibiting or reducing the risk of macular degeneration with a soy protein material containing phytoestrogenic isoflavones.

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: A flexible ocular insert device adapted for the controlled sustained release of an ophthalmic drug into the eye. In one embodiment, the device includes an elongated body of a polymeric material in the form of a rod or tube containing a pharmaceutically active ingredient and with at least two anchoring protrusions extending radially outwardly from the body. The device has a length of at least 8 mm and the diameter of its body portion including the protrusions does not exceed 1.9 mm. The sustained release mechanism may, for example, be by diffusion or by osmosis or bioerosion. The insert device is advantageously inserted into the upper or lower fornix of the eye so as to be independent of movement of the eye by virtue of the fornix anatomy. The protrusions may be of various shapes such as, for example, ribs, screw threads, dimples or bumps, truncated cone-shaped segments or winding braid segments.

Abstract: The invention relates to a pharmaceutical composition containing an association of active principles, wherein the active principles are clopidogrel and aspirin, each constituent being present in a free form or in the form of a pharmaceutically acceptable salt.

Abstract: Compositions and methods for delivering agents across cell membranes are disclosed. The compositions include an agent to be delivered, a viscous material, such as a hydrogel, lipogel or viscous sol, and, optionally, a carrier that includes a ligand that binds to or interacts with cell surface receptors. The agent to be delivered binds to or otherwise interacts with cell surface receptors, is attached, either covalently or ionically to a molecule that binds to or interacts with a cell surface receptor, or is associated with the carrier. Agents to be delivered include bioactive compounds and diagnostic agents. The compositions have an apparent viscosity roughly equal to the viscosity of the cytosol in the cell to which the agent is to be delivered. The rate of cellular internalization is higher when the viscosity of the viscous material and that of the cytosol in the cell are approximately the same, relative to when they are not the same.

Abstract: Disclosed are preservative systems useful in aqueous pharmaceutical compositions containing an active agent and a cyclodextrin. The preservative systems comprise boric acid and one or more compounds selected from the group consisting of C.sub.16 benzalkonium halide compounds, polymeric quatemary ammonium compounds, and quatemary ammonium alkylene glycol phospholipid derivatives of the following structure ##STR1## where a+b=3; R.sup.1 is C.sub.8 -C.sub.22 alkyl or alkene; X is NH, O, or CH.sub.2 ; R.sup.2 is C.sub.2 -C.sub.6 alkyl; each R.sup.3 is independently C.sub.1 -C.sub.12 alkyl or alkene; and Y is nothing or C.sub.1 -C.sub.6 alkyl or alkene; and pharmaceutically acceptable salts thereof.

Abstract: The present invention is directed to methods for the prophylactic and therapeutic treatment of retinal ischemia and retinal inflammation. The methods involve the administration of an inhibitor of the protein tyrosine kinase pathway to an animal, such as a mammal, in particular a human, in an amount sufficient to treat the retina for ischemia or inflammation prophylactically or therapeutically. The inhibitor of the protein tyrosine kinase pathway is preferably genistein or an analogue or prodrug thereof or a pharmaceutically acceptable salt of any of the foregoing.

Abstract: A method to reduce the likelihood of conjunctivitis in farm animals, especially cattle, includes the step of injecting an implant containing an antibiotic effective against the microbes associated with conjunctivitis subcutaneously into the animal in close proximity to the eye. Preferably the implant includes a matrix to allow time release of the antibiotic and the implant is placed in the animal near the first part of July. Also preferably the antibiotic is tetracycline.

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: The present invention relates to compositions which maintain the structural integrity of the anterior chamber of the eye during ophthalmologic surgery, thereby protecting the tissues that form and line the anterior segment from potential damage and simultaneously providing sustained delivery of pharmaceuticals, including miotic, mydriatic, or anesthetic agents.

Abstract: A surgical implant or external wound dressing which functions as both a hemostat and a device to safely and effectively deliver any of a number of pharmaceuticals to targeted tissue at a controlled rate is disclosed. The device generally comprises a carrier in the form of fibers, sutures, fabrics, cross-linked solid foams or bandages, a pharmaceutical in solid micoparticulate form releasably bound to the carrier fibers, and a lipid adjuvant which aids the binding of the microparticles to the fibers as well as their function in the body.

Abstract: Agents which modulate pathways of apoptotic induction or repression in which products of opioid peptide precursors genes participate, useful as inducers of apoptosis in cells and in tumor cells in particular, are disclosed. Methods of treatment employing such agents and pharmaceutical compositions containing them are also described.

Abstract: The invention is directed to the use of .omega.-conotoxins for the prevention and treatment of retinal or optic nerve head damage in humans. Compositions and methods are disclosed.

Abstract: The present invention relates to compositions which maintain the structural integrity of the anterior chamber of the eye during ophthalmologic surgery, thereby protecting the tissues that form and line the anterior segment from potential damage and simultaneously providing sustained delivery of a miotic or mydriatic agent. The present invention provides for compositions which comprise a viscoelastic polymer, wherein sustained release of a miotic or mydriatic agent is mediated by ionic interactions, as well as for compositions wherein sustained release of a miotic or mydriatic agent is mediated by microcapsules or copolymer micelles.

Abstract: A transparent cellulose hydrogel having a transmittance of visible light of not less than 70%/mm and a tensile strength of not less than 10 kg/cm.sup.2, wherein the hydroxyl groups of cellulose constituting said hydrogel are not chemically crosslinked; and a process for producing a transparent cellulose hydrogel, comprising coagulation and regeneration of cellulose from a cellulose solution using an aqueous solution containing an organic solvent in a proportion of 20-95 wt %. The cellulose hydrogel of the present invention is useful as a raw material of an ophthalmic material, such as soft contact lens, artificial crystal lens, artificial cornea, artificial vitreous body and the like, a carrier of fragrance, and a base of gel and cream, and the like. In addition, the transparent cellulose hydrogel of the present invention has a densely packed and uniform structure, so that it can provide a material of a separation membrane having a small molecular cutoff and high pressure resistance.

Abstract: Surgical instruments, surgical techniques, grafts, cell and tissue isolation techniques, and a method for transplanting retinal cells, including photoreceptors, retinal pigment epithelium, and choroidea within their normal configuration, or all three tissues in a co-transplantation procedure are provided.

Abstract: Balanced pH, hyperosmotic, hypoosmotic, or isoosmotic gels are ideal vehicles for drug delivery. They are especially suited for topical body cavity or injection application of drugs or diagnostic agents; for drug or diagnostic agent delivery to the eye of a mammal; as protective corneal shields; or as ablatable corneal masks useful in laser reprofiling of the cornea. The compositions without the addition of a drug or diagnostic agent are useful as medical devices, for instance, in separating surgically or otherwise injured tissue as a means of preventing adhesions.

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: Liposome eye drops contain taurine, glucose and inorganic salts having a pH of 5.5-8.0. The osmolarity is between 250 and 450 mOsm and at least a portion of the taurine and inorganic salts is encapsulated in the liposomes. A preferred embodiment also contains aspartate.

Abstract: In the present invention method, the surface of articles made of acrylic polymers and methacrylic polymers are converted into thin biomimetic layers by using the process involving at least the following two steps:(a) The polymer surface is contacted, in the presence of water and for a predetermined reaction time necessary to form a continuous surface layer thinner than about 500 microns, with a solution containing one or more tetraalkylammonium hydroxides of the general formula:R.sub.1 R.sub.2 R.sub.3 R.sub.4 N.sup.+ OH.sup.-where R.sub.1, R.sub.2, R.sub.3, R.sub.4 are the alkyl substituents, in which the sum of the number of carbon atoms is equal to or larger than 8 but smaller than 45; and,(b) The article is removed from the aqueous reaction solution and excess of tetraalkylammonium hydroxide is removed from the polymer surface by washing the polymer with a liquid miscible with the tetraalkylammonium hydroxide.

Abstract: A stable solution, cream, salve, or spray composition containing activated chlorine dioxide and phosphates, such as disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, and sodium monofluorophosphate, is disclosed for the treatment of vaginitis and endometriosis by reducing any of Candida, Actinobacillus actinomycetemcomitans, Pseudomonades, and Porphyromonas gingivalis present in the vagina or the uterus. The preferred concentration ranges are in the range of about 0.005% to about 2.0% of chlorine dioxide, and in the range of about 0.02% to about 3.0% of phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of 6.0 to 7.4, at which pH chlorine dioxide becomes activated and releases sufficient chlorine dioxide to reduce motility and become lethal to the involved micro-organisms.

Abstract: An ocular drug delivery device includes a reservoir which holds medicine and is locatable outside the eye during drug delivery to a patient, and a conduit having one end coupled to the reservoir and a free end which is positionable within the fornix of the eye of a patient. Through gravity and/or capillary action, the medicine flows from the reservoir through the conduit and into the eye. The rate of delivery of the medicine to the eye may be adjusted according to the size and material of the conduit. According to a first embodiment, the reservoir is preferably made of an absorbent material and is provided with an impermeable backing which acts as a barrier between the medicine and facial skin of the patient. Preferably the backing has an edge to prevent medicine from rolling off the reservoir surface. The backing may also be provided with an adhesive for removably coupling the reservoir to the facial skin of the patient, particularly to an area adjacent the eye.

Abstract: Mixtures of perfluorocarbon liquids having an index of refraction different than water enable their visualization for use in intraocular surgery. These mixtures are used in the surgical repair retinal tears or detachments. Mixtures of perfluoroperhydrophenanthrene and perflurooctane or perfluorooctyl bromide are preferably used.

Abstract: A pharmaceutical composition comprising a plurality of effective non-toxic dosage amounts of a composition for topical administration to the site of pathology and/or trauma of skin and/or exposed tissue of a human patient in need of treatment suffering from a disease or condition, each such dosage amount comprising a therapeautically effective non-toxic (to the patient) dosage amount of a drug for the treatment of the disease and/or condition of the skin and/or exposed tissue at the site of the pathology and/or trauma and an effective non-toxic dosage amount of hyaluronic acid and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments, and/or sub-units of hyaluronic acid to transport (to facilitate or cause the transport of) the drug to the site of the pathology and/or trauma of the disease or condition.

Abstract: Biodegradable polymer networks are provided which are useful in a variety of dental and orthopedic applications. The biodegradable polymer networks can be formed in one embodiment by polymerizing anhydride prepolymers including crosslinkable groups, such as unsaturated moieties. The anhydride prepolymers can be crosslinked, for example in a photopolymerization reaction by irradiation of the prepolymer with light in the presence of a free radical initiator. Suitable anhydride prepolymers include dianhydrides of a dicarboxylic acid and a carboxylic acid molecule comprising a crosslinkable group. For example, methacrylic acid dianhydrides of monomers or oligomers of a diacid such as sebacic acid or 1,3-bis(p-carboxyphenoxy)-hexane can be used. The anhydride prepolymers can be applied in vivo to a site where an orthopedic implant is needed, and then may be crosslinked, for example, by irradiation with U.V. light, to form a biodegradable implant such as a rods, pin or plate.

Abstract: A stable solution, cream, salve, or spray composition containing chlorine dioxide and a phosphate, 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 brought about by any of leukoplakia, hairy leukoplakia, vaginitis, endometriosis, Candida Albicans, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Pseudomonades, Candida species, and leukoplakia vulvae. The preferred concentration ranges are between about 0.005%-2.0% chlorine dioxide, and between about 0.02%-3.0% phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of 6.0 to 7.

Abstract: A method and device for treating a mammalian organism to obtain a desired local or systemic physiological or pharmacological effect is provided. The method includes administering a sustained release drug delivery system to a mammalian organism in need of such treatment at an area wherein release of an effective agent is desired and allowing the effective agent to pass through the device in a controlled manner. The device includes an inner core or reservoir comprising the effective agent; a first coating layer, which is permeable to the passage of the effective agent; a second coating layer, which is essentially impermeable to the passage of the effective agent; and a third coating layer, which is permeable to the passage of the effective agent. The first coating layer covers at least a portion of the inner core.

Abstract: In accordance with the present invention, there are provided prosthetic articles having polyurethane coatings with biologically active compounds incorporated within the interstices of the polymer. Methods for the preparation of such articles are also provided. Thus, a polyurethane coating is applied to a prosthetic article, the coating then swelled (without significantly dissolving the polymer) so that substantial quantities of biologically active compounds can be incorporated within the interstices of the polymer. Upon long term exposure of a prosthetic article of the invention to physiological conditions, the biologically active compound is slowly released by the treated polymer. The biologically active compound is, therefore, released only at the site where it is desired, i.e., where the prosthetic article is positioned.