Abstract: This invention provides a claycy and sticky substance as a new biomaterial that cannot be found in the current medical field, which is bioresorbable, shows tackiness, plasticity and shape holding ability at a temperature of approximately from 30 to 40° C. and can give unrestricted shapes at body temperature or more by increasing its fluidity. This clayey and sticky substance comprises a copolymer of two or more bioresorbable monomers, preferably any one of copolymers of p-dioxanone with D-lactic acid, L-lactic acid, D,L-lactic acid, trimethylene carbonate and &egr;-caprolactone, or a mixture of two or more of these copolymers. This clayey and sticky or clayey substance is suited for a hemostatic material, an adhesive material for tissues, a prosthetic material for tissue reconstruction use, a carrier of drug delivery system, a plugging material, an accretion-preventing material and a scaffold material for tissue engineering use.

Abstract: The instant invention demonstrates that the 7S domain of type IV collagen disrupts cell aggregation and tissue development. Structural changes in mesoglea, inhibition of cell proliferation, and changes in cell differentiation patterns accompanies the blockage of cell aggregates which indicate that blockage may be due to alterations in mesoglea (extracellular matrix) structure with accompanying effects on cell behavior. Type IV collagen has a critical role in the initial formation of mesoglea and that perturbation of mesoglea formation affects cell division, cell differentiation, and morphogenesis.

Abstract: The invention relates to a process for the preparation of mineralized collagen fibrils, where the fibril formation and mineralization take place in one process step, and to the use thereof as bone substitute material. The collagen is natural collagen.

Abstract: The invention relates to a process for the preparation of mineralized collagen fibrils, where the fibril formation and mineralization take place in one process step, and to the use thereof as bone substitute material. The collagen is recombinant collagen.

Abstract: A method for alleviating arthritis in mammals by the oral administration of a pharmaceutical composition compound of native Type II collagen in helical form and sulfated polysaccharides found in mammalian cartilage, the Type II collagen and sulfated polysaccharides being ionically bound.

Abstract: The present invention is to provide a novel medicine, drink, food or feed having an action of strengthening bone. More specifically, the present invention is to provide a medicine, drink, food or feed combined with collagen, fraction containing collagen or degradation product thereof. Fraction containing collagen was prepared by mincing skin corium layer into pieces, defatting it and lyophylization or by pulverizing bone, decalcifying it and lyophylization. Oral administration of these can stimulate proliferation of osteoblast, inhibit bone resorption and strengthen bone. They can be useful for improvement of osteoporosis, bone fracture, bone pain, etc.

Abstract: The present invention relates to a collagen gel, its production process, a medical material in which it is used or a kit for its production, wherein said collagen gel is obtained by crosslinking collagen with polyanion and carbodiimide.

Abstract: A composition for treating arthroses in animals includes exogenous glucosamine, hydrolyzed collagen and a bioflavanol. Preferred glucosamines are glucosamine hydrochloride (HCI) and glucosamine sulfate. Preferred bioflavanols are those extracted from grape seeds, pine bark or turmeric root. Proanthocyanidin (also referred to as leucocyanidin or pcynogenol) is the most preferred bioflavanol. With horses and larger animals, a preferred treated method involves application of the composition of the present invention as a top dressing twice a day to the animal's feed. A preferred treatment for humans, dogs and cats involves the ingestion of 1 to 4 tablets or capsules per day of the composition of the present invention.

Abstract: The present invention discloses compositions containing natural human extracellular matrices and methods for the use thereof. More particularly, the present invention provides compositions and methods for the repair of skin defects using natural human extracellular matrix by injection.

Abstract: A method of smoothing irregular corneal surfaces and removing protuberances from corneal surfaces by photoablative eximer laser keratectomy is provided. Collagen compositions for use in making collagen modulators useful in photoablative procedures are described. These compositions are applied to irregular corneal surfaces in sufficient amounts to at least fill in depressions or other irregularities on a corneal surface and are converted into a modulator, as a gel or polymerized film, prior to photoablation. The collagen modulators facilitate the photoablative smoothing of irregular corneal surfaces and protect adjacent corneal tissue from undesired photoablation.

Abstract: The use of collagen as a biomedical implant raises safety issues towards viruses and prions. The physicochemical changes and the in vitro and in vivo biocompatibility of collagen treated with heat, and by formic acid (FA), trifluoroacetic acid (TFA), tetrafluoroethanol (TFE) and hexafluoroiso-propanol (HFIP) were investigated. FA and TFA resulted in extensive depurination of nucleic acids while HFIP and TFE did so to a lesser degree. The molecules of FA, and most importantly of TFA, remained within collagen. Although these two acids induced modification in the secondary structure of collagen, resistance to collagenase was not affected and, in vitro, cell growth was not impaired. Severe dehydrothermal treatment, for example 110° C. for 1-3 days under high vacuum, also succeeded in removing completely nucleic acids. Since this treatment also leads to slight cross-linking, it could be advantageously used to eliminate prion and to stabilize gelatin products.

Abstract: Disclosed herein are collagen films which rapidly dissolve at 35° C. Also disclosed are methods for the preparation of the collagen films and their use as a vehicle for delivering a dose of therapeutic compound to a specific tissue site.

Abstract: The present invention provides improved osteogenic compositions having enhanced by the sorption of growth factors, of nutrient factors, or drugs onto or into the compositions. Compositions may consist of collagen and demineralized bone materials onto and into which growth factors, antimicrobial agent,s nutrient factors, or other soluble factors may be sorbed to enhance the osteogenic factor. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: Osteogenic compositions, and methods for preparing same, which compositions comprise a porous or semi-porous matrix, an osteogenic factor and an agent such as growth factors, nutrient factors, drugs, calcium-containing compounds, blood products, large molecular weight proteins, or combinations thereof. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: An auxiliary agent for ophthalmic surgery is based on collagen and, after the completion of surgery, undergoes a lowering in viscosity, and thus can be easily removed. This agent is a neutral solution of collagen which is transparent at a neutral pH and has a denaturation temperature below the intraocular temperature, or a derivative thereof. The agent has a visual light transmission at 400 nm of at least 90% of that before the denaturation, when solution is heated to cause denaturation.

Abstract: The present invention provides a regenerated collagen fiber exhibiting a draping, luster and feel close to those of a natural protein fiber such as a human hair and capable of application of a permanent wave treatment, and a method of manufacturing the regenerated collagen fiber. The amino group and/or carboxyl group of the regenerated collagen is chemically modified to introduce a mercapto group and/or a disulfide linkage to the regenerated collagen. When subjected to a permanent wave treatment, the regenerated collagen fiber retains the waved shape.

Abstract: Novel, stable, cold water dispersible preparations of fat-soluble substances contain a microbially produced oil rich in arachidonic acid. These preparations are manufactured by preparing an aqueous emulsion of the microbially produced oil which has been stabilized with an antioxidant and fish gelatin and if desired converting this emulsion into a dry powder. The preparations in accordance with the invention can be used for human nutrition.

Abstract: A trans-epithelial appliance or shaped article coated with laminin 5. Laminin 5 stimulates cell attachment and may be comprise an insoluble or soluble cell matrix. The appliance will be useful for reducing inflammation and/or infection at the site of entry of the appliance. The appliance may also be used to stimulate gum junctional epithelium adhesion in the treatment of, for example, gingivitis and periodontitis.

Abstract: A body fat percentage-lowering, body composition-improving food composition comprising 10-65 weight % of protein, 5-25 weight % of fat, and 15-70 weight % of carbohydrate, all on a dry weight basis, which composition is to be taken before, during, and/or after exercise, particularly after exercise preceding a resting period, and a method for lowering body fat percentage and improving body composition through utilization of the above food composition.

Abstract: This application relates to a pharmaceutical composition for the prevention and treatment of skin conditions in a patient having a sugar compound that is converted to a glycosaminoglycan in the patient in an amount sufficient to thicken the skin, a primary antioxidant component in an amount sufficient to substantially inhibit the formation of collagenase and elastase, at least one amino acid component in an amount sufficient to assist in the thickening of the skin, and at least one transition metal component in an amount effective to bind collagen and elastic fibers and rebuild skin. In one preferred form, the composition further includes a catechin-based preparation, a glucosamine or a pharmaceutically acceptable salt or ester thereof, and a chondroitin or a pharmaceutically acceptable salt or ester thereof. In a more preferred form, the invention further includes a vitamin E source, a cysteine source, a vitamin B.sub.3 source, quercetin dihydrate, pyridoxal 5 phosphate-Co B.sub.

Abstract: This process for preparing a collagen-based composition, comprises grinding collagen fibers to a particle size of between 10 and 100 microns and mixing them with water in a sufficient quantity to give a gel.

Abstract: This invention relates to a pharmaceutical composition for the treatment of acne having an acne reduction component in an amount sufficient to reduce the redness and blemishes associated with acne. The invention also relates to pharmaceutical compositions having, in addition to the acne reduction component, a skin cell conditioning component in an amount sufficient to properly regulate the keratin and sebum production of the skin cells, thereby inhibiting the appearance of acne. In a preferred form, the skin cell conditioning component is a chromium component. In another preferred form, the composition further includes at least one of a vitamin C source, burdock root, yellow dock root, horsetail extract, a catechin-based composition, a vitamin B.sub.1 source, a vitamin B.sub.2 source, a vitamin B.sub.3 source, a vitamin B.sub.5 source, and a vitamin E source. In a more preferred form, the invention also includes at least one amino acid component, a magnesium component, a selenium component, and biotin.

Abstract: The present invention is directed to a method and pharmaceutical formulations for the treatment of systemic sclerosis in mammals, by oral administration of collagen, including type I collagen, or biologically active peptide fragments thereof.

Abstract: Tasteless, hydrolyzed collagen from gelatin, gelatin or animal collagenic connective tissue having an average molecular weight of from 1 to 40 kD for the preparation of agents for the treatment of osteoporosis. It may be combined with conventional agents for combatting osteoporosis, such as calcitonin, calcium salts, and/or progesterone.

Abstract: Methods are provided for preparing compositions suitable for protecting irritated or damaged skin from further oxidative and biochemical damage and thus permitting natural healing processes to progress, for accelerating the rate of healing of burns and surgical wounds, for stimulating melanogenesis, and for increasing the size of hair follicles and the rate of hair growth. The compositions generally comprise complexation of peptone digests of various proteins with copper(II) salts, indium (III) salts, tin(II) salts and tin(IV) salts.

Abstract: Methods are provided for the treatment of a host suffering from a cellular proliferative disease through administration of a chemotherapeutic agent in conjunction with a cell membrane permeant. Optionally, the cell membrane permeant and/or chemotherapeutic agent will be present in a pharmaceutically acceptable vehicle capable of acting as a depot. In the subject methods, the chemotherapeutic agent and membrane permeant are administered at least proximal to a target site of the host. Administration of chemotherapeutic agents in accordance with the subject methods results in improved efficacy of, and/or decreased host toxicity to, the intralesionally administered chemotherapeutic agent.

Abstract: Recognizing substances, including epidermal growth factor, gelatin, collagen and hyaluronic acid, have been covalently bound to liposomal surfaces and utilized to attach liposomes onto a cellular or an extracellular matrix (ECM) target site. These "bioadhesive" liposomes offer several advantages including the mutual protection of both the drug and biological environment; an increase in drug bioavailability and retention at the target site; and improved adherence or adhesion to the designated target site.

Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

Abstract: This application relates to a pharmaceutical composition for the prevention and treatment of skin conditions in a patient having a sugar compound that is converted to a glycosaminoglycan in the patient in an amount sufficient to thicken the skin, a primary antioxidant component in an amount sufficient to substantially inhibit the formation of collagenase and elastase, at least one amino acid component in an amount sufficient to assist in the thickening of the skin, and at least one transition metal component in an amount effective to bind collagen and elastic fibers and rebuild skin. In one preferred form, the composition further includes a catechin-based preparation, a glucosamine or a pharmaceutically acceptable salt or ester thereof, and a chondroitin or a pharmaceutically acceptable salt or ester thereof. In a more preferred form, the invention further includes a vitamin E source, a cysteine source, a vitamin B.sub.3 source, quercetin dihydrate, pyridoxal 5 phosphate-Co B.sub.

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: Type I collagen gel with an H.sub.2 O content not exceeding 20% by weight, in the form of a sheet of thickness between 0.02 and 2 mm, of compact transparent structure, with a capacity for absorbing aqueous biological liquids limited to a maximum of 15 times its weight, being free from native collagen degradation products, and suitable for the therapeutic treatment of wounds and burns.

Abstract: Microcapsules based on crosslinked plant polyphenols are described. These microcapsules are obtained by the interfacial crosslinking of plant polyphenols, particularly flavonoids. When incorporated in a composition such as a cosmetic, pharmaceutical, dietetic or food composition, these microcapsules make it possible to prevent any impairment of this composition, in particular any color modification, while at the same time preserving the activity, especially the anti-free radical and/or antioxidizing activity, of the plant polyphenols, particularly the flavonoids.

Abstract: Disclosed are methods, compositions and devices for use in transferring nucleic acids into bone cells in situ. The transfer of an osteotropic gene into bone progenitor cells is described, which event is shown to stimulate the progenitor cells and to promote bone growth, repair and regeneration in vivo. These gene transfer protocols are suitable for use in transferring various nucleic acid materials into bone, and have many uses, for example, in treating various bone-related diseases and defects, such as, in promoting fracture repair, use in connection with implants, and in treating osteoporosis and osteogenesis imperfecta.

Abstract: It has been discovered that it is possible to treat solutions of connective tissue material for the inactivation of prions in a manner such that connective tissue molecules are not adversely affected by the inactivation treatment. For example, solubilized atelopeptide collagen can be treated with sodium hydroxide for the inactivation of prions and other infectious agents without affecting the ability of the solubilized collagen to form stable fibers.

Abstract: This invention provides a method for alleviating the symptoms of arthritis in mammals which comprises orally administering a composition obtained by separating water-insoluble undenatured Type II collagen containing animal tissue from animal tissue not containing Type II collagen, subdividing and sterilizing said tissue under conditions which do not change the original structure of the Type II collagen, in an amount effective and for time effective to alleviate such symptoms.

Abstract: A composition and method are provided that are effective in revitalizing scar tissue by introducing a bioactive substance having angiogenic activity into the scar tissue. The bioactive substance can be introduced by itself, or it can be introduced into the scar tissue in a timed release form. The present invention is effective in treating stress urinary incontinence or localized muscular dysfunction.

Abstract: Cell culture substrates comprising dried films of native fibrillar collagen produced by a method in which collagen fibers are hydrolyzed in acid, solubilized, and reformed as gels on porous surfaces under non-physiologic salt conditions to produce large fibers with the striations characteristic of collagen fibers found in vivo. The gels are collapsed onto the porous surfaces by drawing the interfibril fluid out of the gel through the underside of the porous surface and then dried to form films. Dried collagen films made in this manner retain native fibrillar collagen structure and excellent diffusion characteristics. Native fibrillar collagen films produced according to the methods of the invention are useful as cell culture substrates. They have particularly advantageous properties for growth and differentiation of epithelial cells. This effect is synergistically enhanced by addition of butyric acid as a differentiation inducing agent.

Abstract: The present invention provides improved osteogenic compositions having enhanced by the sorption of growth factors, of nutrient factors, or drugs onto or into the compositions. Compositions may consist of collagen and demineralized bone materials onto and into which growth factors, antimicrobial agent, a nutrient factors, or other soluble factors may be sorbed to enhance the osteogenic factor. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: Affinity bound collagen matrices for the delivery of biologically active agents, and methods for preparing such matrices, are disclosed. A preferred method for preparing the matrices of the invention comprises mixing a binding ligand and an active agent together, allowing the resulting binding ligand-active agent mixture to form an affinity bound complex, then combining the resulting affinity bound complex with collagen to form a matrix. Particular affinity bound matrices comprising collagen, heparin, and an active agent are also disclosed, as well as methods for using the matrices of the invention for delivery of biologically active agents.

Abstract: The instant invention demonstrates that the 7S domain of type IV collagen disrupts cell aggregation and tissue development. Structural changes in mesoglea, inhibition of cell proliferation, and changes in cell differentiation patterns accompanies the blockage of cell aggregates which indicate that blockage may be due to alterations in mesoglea (extracellular matrix) structure with accompanying effects on cell behavior. Type IV collagen has a critical role in the initial formation of mesoglea and that perturbation of mesoglea formation affects cell division, cell differentiation, and morphogenesis.

Abstract: A composition and method are provided that are effective in revitalizing scar tissue by introducing a bioactive substance having angiogenic activity into the scar tissue. The bioactive substance can be introduced by itself, or it can be introduced into the scar tissue in a timed release form. The present invention is effective in treating stress urinary incontinence or localized muscular dysfunction.

Abstract: A collagen-based delivery matrix including collagen particles, wherein each of the particles has a diameter between 5 .mu.m and 850 .mu.m and, when suspended in an aqueous solution at a pH of about 7.0, has a net charge density between -20 moles/mole collagen and -500 moles/mole collagen, or between +20 moles/mole collagen and +250 moles/mole collagen. Also disclosed are methods of preparing and using such a delivery matrix.

Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.

Abstract: This invention provides a composition useful as an edible supplement for alleviating the symptoms of arthritis for oral consumption by mammals, said composition comprising animal tissue containing water-insoluble Type II collagen, which has been separated from non-Type II collagen containing tissue and has been sterilized in subdivided form without changing the original structure of the Type II collagen.

Abstract: The present invention is an injectable medical composition useful for replacing natural lubricating fluids in the body of humans or animals. The method and composition can be used for the treatment of joints and other parts of the body wherein natural lubrication between surfaces is deficient or where additional lubrication is required. The composition comprises a hydrophilic polymer suspended in a hydrophobic carrier so that the suspension is easily injectable into the desired body part. After injection, the carrier diffuses away from the polymer and is replaced by aqueous body fluids thereby causing the polymer to absorb or adsorb water forming a viscous, lubricating fluid.

Abstract: This invention provides a method of preparing animal tissue containing water-insoluble undenatured Type II collagen for use in treating autoimmune arthritis, particularly rheumatoid arthritis.

Abstract: The present invention relates to a method of treating a patient with visco-surgery, particularly ocular visco-surgery, utilizing a collagen-based viscoelastic solution having a reversibly high viscosity. The invention also relates to collagen-based viscoelastic solutions which further include mucopolysaccarides or growth factors.

Abstract: Thermally stable collagen gels formed by the addition of small amounts of neutralized slightly cross-linked polyacrylic acid. Thermally stable gels resulting from 0.3 to 4.0 percent by weight of collagen and 0.10 to 0.50 percent by weight of neutralized slightly cross-linked polyacrylic acid. The thermally stable gels are useful in wound care management. Further, synergistic effects are noted by the addition of 0.5 to 3.0 percent by weight of natural gums, particularly those containing glucuronic acid segments. Gelatin, a partially hydrolyzed collagen, behaves in a similar manner to collagen.

Abstract: The invention provides methods for stabilizing amino-substituted steroid therapeutic agents in topical ophthalmic and other pharmaceutical formulations using effective stabilizing amounts of lightly cross-linked carboxy-containing polymers; and methods for stabilizing and solubilizing amino-substituted steroid therapeutic agents in such pharmaceutical formulations using effective stabilizing amounts of lightly cross-linked carboxy-containing polymers and amounts of selected cyclodextrin derivatives sufficient to at least partially solubilize the therapeutic agents. The cyclodextrin derivatives are selected from the group consisting of the hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of .beta.- and .gamma.-cyclodextrin. Stabilized and stabilized/solubilized pharmaceutical compositions adapted for various routes of administration are also described.

Abstract: Treatment of cellular disorders involving abnormal solid cellular growths involves introduction of cytotoxic reagents dispersed in a physiologically acceptable proteinaceous matrix into the solid cellular growth or area of an existing or removed solid cellular growth. Enhanced effectiveness of the drug is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Other drugs may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.