Abstract: The present invention relates to protein matrix materials and devices and the methods of making and using protein matrix materials and devices. More specifically the present invention relates to protein matrix materials and devices that may be utilized for various medical applications including, but not limited to, drug delivery devices for the controlled release of pharmacologically active agents, encapsulated or coated stent devices, vessels, tubular grafts, vascular grafts, wound healing devices including protein matrix suture material and meshes, skin/bone/tissue grafts, biocompatible electricity conducting matrices, clear protein matrices, protein matrix adhesion prevention barriers, cell scaffolding and other biocompatible protein matrix devices. Furthermore, the present invention relates to protein matrix materials and devices made by forming a film comprising one or more biodegradable protein materials, one or more biocompatible solvents and optionally one or more pharmacologically active agents.

Abstract: A microscopic protein device and the method of manufacture and the use of such a device for hemostasis. The device, made with biologic material such as serum albumin from a human or animal source, is less than five micron in any one dimension and typically less than one micron in diameter. It does not have any other biological or drug molecules attached to it in vitro. However, the device has properties that allow it to capture, concentrate, carry or bind biomodifying molecules, such as coagulation factor(s), or potentially other drugs, after exposure to plasma in vitro; and possibly in vivo as well. After infusion of said device intravenously inside the body, hemostatic effects can be demonstrated.

Abstract: Modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.

Abstract: A method for reducing the friability of soft substrates by applying an effective amount of a water soluble, polymeric dispersion to at least a portion of a treatment surface of the substrate, such that less than about 90% of the exterior surface has the dispersion applied thereto.

Abstract: A preparation for the diagnosis of pancreatic exocrine function by determining the amount in which a substance administered to a subject or a degradation product or metabolite thereof migrates into the blood and/or is excreted out of the body, wherein the substance is carried by a carrier and released from the carrier when exposed to the action of a pancreatic exocrine function-related factor.

Abstract: Nanoparticles, the particle matrix of which is based on at least one protein and has at least one active agent embedded therein and methods of producing the nanoparticles with at least one active agent embedded in the protein matrix are disclosed. The use of the nanoparticles for the treatment of tumours, in particular for the treatment of tumours which are resistant to chemical medicaments is also disclosed.

Abstract: A preparation for the diagnosis of pancreatic exocrine function by determining the amount in which a substance administered to a subject or a degradation product or metabolite thereof migrates into the blood and/or is excreted out of the body, wherein the substance is carried by a carrier and released from the carrier when exposed to the action of a pancreatic exocrine function-related factor.

Abstract: It is an object of the present invention to provide a nanoparticle containing a microbicide and a biodegradable polymer, which is safe and excellent in terms of dispersion stability and has high transparency and good absorbability due to its small particle size. The present invention provides a water-dispersible nanoparticle, which comprises a microbicide and a biodegradable polymer.

Abstract: It is an object of the present invention to provide a nanoparticle which comprises a blood circulation promoter and a biodegradable polymer, which is safe and excellent in terms of dispersion stability and has high transparency and good absorbability due to its small particle size. The present invention provides a water-dispersible nanoparticle which comprises a blood circulation promoter and a biodegradable polymer.

Abstract: The invention is related to water-soluble products and pharmaceutical formulations in solid or liquid form mainly for parenteral use. They consist of or comprise a therapeutically active substance (having low aqueous solubility and a substantial binding affinity to plasma proteins) and a plasma protein fraction in controlled aggregation state, whereby the said active substance and the said protein fraction are bound to each other by way of non-covalent bonds. It also covers processes for the preparation of the product and pharmaceutical formulation by dissolving the water-insoluble active substance in a water-miscible, pharmaceutically acceptable solvent, combining said solution with the aqueous solution of a plasma protein fraction in controlled aggregation state whereby a true solution is obtained containing the said active substance and the said protein fraction bound together by way of non-covalent bonds.

Abstract: It is an object of the present invention to provide a skin anti-aging agent for external use which comprises highly safe protein nanoparticles having high transparency due to the small particle size and high permeability into skin. The present invention provides a skin anti-aging agent for external use, which comprises protein nanoparticles containing an active ingredient.

Abstract: An object of the present invention is to provide an external dermatologic preparation which comprises nanoparticles consisting of proteins that can exhibit desirable effects via regulation of particle diameters. The present invention provides an external dermatologic preparation which comprises protein nanoparticles containing an active ingredient and having an average particle size of 200 to 500 nm.

Abstract: Self-dissolving needle-like or filamentous shape percutaneously absorbable preparations, by which inherently poorly absorbable drugs into the body through the skin is efficiently administered. The preparations are made of at least one material selected from the group consisting of proteins, polysaccharides, polyvinyl alcohols, carboxyvinyl polymers and sodium polyacrylic acids. An active substance contained therein is released in a sustained-release fashion (1) by forming a water-insoluble layer on its surface, (2) by holding the active substance in porous materials, or (3) by imparting a long-acting characteristic to the active substance. The present invention also provides a sheet-like carrier for holding the preparations on at least one of the sides thereof, and a piece of equipment for holding the preparations so as to facilitate the administration of them.

Abstract: The present invention provides immunogenic oligosaccharide compositions and methods of making and using them. In particular, the compositions comprise native O-linked and S-linked oligosaccharides coupled to a protein carrier via a linker, wherein the resultant conjugate elicits a protectively immunogenic response, particularly in vaccines against pathogenic Candida species and more particularly against Candida albicans. Preferably the pathogenic Candida species are those that possess cell wall oligosaccharide compositions similar to the ?-mannan component of Candida albicans cell walls.

Abstract: The present invention relates generally to methods and compositions for targeting and delivering solid-phase platelet-dependent vascular occlusion agents. In particular, particles or coils or stents coated with platelet binding agents are directed to target vasculature, such as the vasculature of solid tumor masses or AV-malformations or aneurysms or endoleaks; the solid-phase agent then binds and activates platelets, which in turn bind and activate other platelets. This process results in the rapid formation of a platelet-mediated thrombus about the solid-phase agent causing vessel occlusion.

Abstract: The present invention concerns gyrase inhibitor-protein conjugates and in particular gyrase inhibitor-albumin conjugates, pharmaceutical preparations comprising gyrase inhibitor-protein conjugates in particular for the treatment and/or prophylaxis of inflammatory processes and/or tumours as well as methods for their production.

Abstract: A compound includes a carrier molecule wherein the carrier molecule is linked to a further molecule, wherein the further molecule is at least one cyclic peptide in which the cyclic peptide portion thereof contains at least one sequence encoding a cell receptor recognizing peptide (RRP) and with the proviso that the compound is not a naturally occurring receptor agonist or antagonist. Preferably, the RRP is a receptor specific for Hepatic Stellate Cells (HSC) or a receptor that is up-regulated on HSC during disease. The RFP may be chosen from among a PDGF receptor, a collagen type VI receptor, cytokine receptor(s) such as TGB?, INF? and interleukin?. The cyclic portion of the peptide can contain at least one amino acid sequence RGD or KPT.

Abstract: The invention is related to water-soluble products and pharmaceutical formulations in solid or liquid form mainly for parenteral use. They consist of or comprise a therapeutically active substance (having low aqueous solubility and a substantial binding affinity to plasma proteins) and a plasma protein fraction in controlled aggregation state, whereby the said active substance and the said protein fraction are bound to each other by way of non-covalent bonds. It also covers processes for the preparation of the product and pharmaceutical formulation by dissolving the water-insoluble active substance in a water-miscible, pharmaceutically acceptable solvent, combining said solution with the aqueous solution of a plasma protein fraction in controlled aggregation state whereby a true solution is obtained containing the said active substance and the said protein fraction bound together by way of non-covalent bonds.

Abstract: A substantially solid biomolecular solder for joining tissue comprising a partially denatured biomolecule. The solder can be formed into shapes to suit the needs of a user. The invention also relates to methods for joining tissue and methods for preparing the solder.

Abstract: Multiple myeloma and other hematologic tumors and/or malignancies can be treated by administration of a G1 and/or S phase drug, which is preferably ?-lapachone, or a derivative or analog thereof, combined with a G2/M phase drug such as a taxane derivative, which is advantageously paclitaxel. This combination of the G1 and/or S phase drug with the G2/M phase drug results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in multiple myeloma cells. The invention includes methods of treating multiple myeloma by administering the combination of the G1 and/or S phase drug and the G2/M phase drug, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.

Abstract: Methods for preparing products containing moisture-sensitive materials, including biological materials such as proteins, peptides or live cells, comprising at least the steps: (i) providing a coating liquid comprising at least one active, a sugar polymer and a water soluble/miscible solvent; (ii) providing a quantity of microparticles comprising at least water soluble gel forming solid particles; (iii) fluidizing said quantity of microparticles within a processing chamber of a of a suitable apparatus to form a fluidized bed of said microparticles; (iv) spraying said coating liquid onto said fluidized bed from beneath the fluidized bed to coat said microparticles therewith under saturated moisture conditions; and (vi) allowing coated microparticles to dry, are described. Also described are compositions and uses.

Abstract: The invention is related to water-soluble products and pharmaceutical formulations in solid or liquid form mainly for parenteral use. They consist of or comprise a therapeutically active substance (having low aqueous solubility and a substantial binding affinity to plasma proteins) and a plasma protein fraction in controlled aggregation state, whereby the said active substance and the said protein fraction are bound to each other by way of non-covalent bonds. It also covers processes for the preparation of the product and pharmaceutical formulation by dissolving the water-insoluble active substance in a water-miscible; pharmaceutically acceptable solvent, combining said solution with the aqueous solution of a plasma protein fraction in controlled aggregation state whereby a true solution is obtained containing the said active substance and the said protein fraction bound together by way of non-covalent bonds.

Abstract: Methods of and compositions for pulmonary delivery of therapeutic agents which are capable of forming covalent bonds with a site of interest or which have formed a covalent bond with a pulmonary solution protein are disclosed. Therapeutic agents useful in the invention include wound healing agents, antibiotics, anti-inflammatories, anti-oxidants, anti-proliferatives, immunosupressants, anti-infective and anti-cancer agents.

Abstract: Methods and compositions for induction or stimulation of hair growth and retardation of hair loss are provided. Preferably, these compounds will include a perhalogenated alkyl radical having 1 to 4 carbon atoms.

Abstract: The present invention relates to a means for creating a mass having structural integrity, including a rapidly disintegratable tablet for administration with or without the use of water. The present invention has a wide variety of different uses and applications. One embodiment is a tablet intended for oral administration. The tablet comprises at least one active ingredient and a mixture of excipients. The excipients provide desired characteristics and physical properties and when the tablet is sintered or heated, excellent tablet binding characteristics are obtained. The tablet is intended primarily for oral administration and dissolves in the presence of water. Also disclosed is a process for the preparation of a rapidly disintegratable tablet for administration with or without the use of water.

Abstract: Topical skin rejuvenation cream and lotion compositions for dry, damaged or aging skin comprising deionized water, mink oil, vitamin E, retinol acetate (vitamin A), ginseng, aloe vera, glycerin, lanolin (hydrous), gotu kola, soybean oil, fish liver oil, hydrolyzed animal protein, dl-alpha tocopherol acetate, stearic acid, cetyl alcohol, citric acid, silicon, isopropylmyristate, propylene glycol, stearyl alcohol, glycerol stearate, dimethicone, lactic acid, quaternium-15, propylparaben, carbomer 934 and 940, triethanolamine, methylparaben, tetrasodium ethylenediaminetetraacetic acid (EDTA), DMDM hydantoin, diazolidinyl urea and fragrance.

Abstract: A method for preparing solid rapidly disintegrating dosage forms shaped as biconvex tablets having symmetrical top and bottom surfaces and dosage forms obtainable thereby.

Abstract: A method for joining tissue comprising aligning and abutting edges of the tissue to be joined applying biodegradable, biological solder or an analogue thereof, across the edges and exposing the solder to an energy source under conditions which provide transfer of energy from the source to the solder to cause the solder to bond to the tissue surface adjacent the edges to provide a weld holding the edges together.

Abstract: The invention relates to accurately meterable shaped articles, for example granules or pellets, containing hydrophilic macromolecules, active compounds and optionally further pharmaceutically acceptable structure-forming substances and auxiliaries, the active compound being present in a matrix in dissolved, suspended or emulsified form, and a novel process for the production of these shaped articles, the process being particularly economically and ecologically acceptable, and use of the shaped articles as medicaments, in which the bioavailability, shelf life and tolerability is increased. Using the shaped articles or mixtures according to the invention, intermediates or final products for pharmacy, cosmetics, diagnosis, analysis or dietetics (healthcare) can additionally be advantageously prepared.

Abstract: Platelet substitutes, comprising fibrinogen, or analogous products useful in therapy, which further comprise an insoluble carrier to which is bound an essentially non-degraded active protein including the sequence Arg-Gly-Asp. Such conjugates can be made by a conjugation process comprising 0.01 to 2.5% by weight active fibrinogen, and no more that 50% inactive fibrinogen.

Abstract: Sparingly water-soluble active compounds, for example medicinal substances, are converted into the dissolved (molecularly disperse) state by dissolving them in a hydrophilic peptide having a molecular weight above 100 D, for example gelatin. The solubility both during storage and during use of the formulation by the user or patient is thereby ensured, without organic solvents or solubilizing agents which cause undesirable side effects being required.

Abstract: A multipurpose ointment (MPOc) in a semisolid-semiliquid form and a multipurpose particle (MPPc) in a solid soft particulate form are prepared by combining a matrix base in a aqueous solution with a liquid oil base and added modifiers and medications to form either an ointment or suspension of particles for endovascular disposition for embolizing abnormal microvascular beds or nidi. The ointment or particles are formed from a albumin (human serum or chicken egg) matrix or equivalent material or combination of the same in an aqueous solution, typically contrast-medium solution, which has been emulsified with a radiopaque oil base such as ETHIODOL, and then heated to modify the mobility, viscosity, deformability, elasticity, surface tension and friction along with the inclusion of medications and modifiers for the desired physical characteristics and biological end effects.

Abstract: The invention relates to accurately meterable shaped articles, for example granules or pellets, containing hydrophilic macromolecules, active compounds and optionally further pharmaceutically acceptable structure-forming substances and auxiliaries, the active compound being present in a matrix in dissolved, suspended or emulsified form, and a novel process for the production of these shaped articles, the process being particularly economically and ecologically acceptable, and use of the shaped articles as medicaments, in which the bioavailability, shelf life and tolerability is increased. Using the shaped articles or mixtures according to the invention, intermediates or final products for pharmacy, cosmetics, diagnosis, analysis or dietetics (healthcare) can additionally be advantageously prepared.

Abstract: This invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic or bioactive agents. The methods and composition of the invention can be used with several therapeutic or bioactive agents and can achieve site-specific delivery of a therapeutic or biologically-active substance. This can allow for lower doses and for improved efficacy with drugs, particularly agents such as oligonucleotides which are plagued with problems in achieving therapeutic levels at targeted sites.

Abstract: An injectable ivermectin composition having a programmable release rate and providing multiple concentration peaks of active ivermectin to produce a sequence of ivermectin release pulses into the blood of cattle and horses. The composition comprises a solution of 0.2%-10% w/w of ivermectin in a solvent selected from propyleneglycol and a mixture of glycerile caprylate, caproate and caprate, such as glycerides of caproic, caprilic and capric acids in equal parts. The solution is used as a vehicle for suspending microspheres 100 nm-200 .mu.m in diameter of a degradable polymer containing between 0.5% and 50% of ivermectin. The microspheres may be formed from polylactic acid, polyglycolic acid or a copolymer of polylactic-polyglycolic acid. The programmable multi-pulse release system may also be obtained with a biodegradable matrix selected from hardenable natural polymers, such as gelatin or albumin, apart from the copolymers of lactic and gycolic acids.

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: Compositions and processes to alleviate oxygen toxicity are disclosed based on the use of nitroxides in association with physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. Formulations are described herein that interact with free radicals, acting as antioxidant enzyme-mimics, which preserve nitroxides in their active form in vivo. Applications are described including blood substitutes, radioprotective agents, imaging agents, agents to protect against ischemia and reperfusion injury, and in vivo enzyme mimics.

Abstract: Albumin particles in the nanometer and micrometer size range in an aqueous suspension are rendered stable against resolubilization without the aid of a crosslinking agent and without denaturation, by the incorporation of a stabilizing agent in the particle composition. Particles which are primarily albumin in the nanometer and micrometer size range in an aqueous suspension are rendered stable against resolublization by the incorporation of a reducing agent, oxidizing agent, hydrogen-accepting molecule, high molecular weight polymer, sulfur-containing ring compound or combinations thereof.

Abstract: Compositions and methods are provided for increasing the serum half-life of a pharmacologically active agent. The novel compositions are covalent conjugates of the selected pharmacologically active agent and a transthyretin-binding ligand such as tetraiiodothyroacetic acid, 2,4,6-triiodophenol, flufenamic acid, or the like.

Abstract: The present invention provides a method for providing nutrition to elderly patients. Pursuant to the present invention, the enteral composition includes a protein source, a lipid source, and a carbohydrate source. Preferably, the protein source includes at least 18% of the total calories. In an embodiment, the carbohydrate source includes a source of dietary fiber including a balance of soluble to insoluble fiber ratio of approximately 1:3. Still further, the composition of the present invention also includes increased levels of certain vitamins and minerals.

Abstract: An improved process for preparing controlled release pharmaceutical forms comprises exposing a mixture comprising one or more excipients and one or more active ingredients compatible with each other and with said excipients to mechanical or electromechanical actions for a well established time and within a wide range of frequencies to give tablets, matrices or mono or multilayered films. Said forms can be optionally crushed to give a granulate or powder. Depending on the employed excipient, a delayed or rapid but always controllable release of the active ingredient can be attained.

Abstract: The present invention provides a method for providing nutrition to elderly patients. Pursuant to the present invention, the enteral composition includes a protein source, a lipid source, and a carbohydrate source. Preferably, the protein source includes at least 18% of the total calories. In an embodiment, the carbohydrate source includes a source of dietary fiber including a balance of soluble to insoluble fiber ratio of approximately 1:3. Still further, the composition of the present invention also includes increased levels of certain vitamins and minerals.

Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a pre-administration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.

Abstract: The present invention provides an effective method for controlling foliage and root fungus infection in cultivated crops. A fungicide composition in the form of an aqueous formulation which is applied to pre-harvest crops contains ingredients such as pentachloronitrobenzene, sodium bicarbonate, sodium carbonate, potassium oleate, potassium octanoate and xanthan gum. The combination of potassium oleate, potassium octanoate and xanthan gum functions as an effective spreader-sticker medium for forming an adherent coating on plant foliage surfaces, and for saturating ground soil. The coating exhibits both immediate and long duration fungicidal activities.

Abstract: The present invention provides an effective method for controlling foliage and root fungus infection in cultivated crops. A fungicide composition in the form of an aqueous formulation which is applied to pre-harvest crops contains ingredients such as etridiazole, potassium bicarbonate, sodium carbonate, potassium oleate, potassium caprylate and xanthan gum. The combination of potassium oleate, potassium caprylate and xanthan gum functions as an effective spreader-sticker medium for forming an adherent coating on plant foliage surfaces, and for saturating ground soil. The coating exhibits both immediate and long duration fungicidal activities.

Abstract: A method for forming a controlled release polymeric substrate is provided by contacting a polymeric substrate with a liquid mixture containing a cross-linking agent at least partially soluble therein comprising water and an organic liquid, for a period of time and at a temperature and concentration of the agent sufficient for the agent to penetrate the substrate to form cross-linking bridges in the substrate in a decreasing concentration gradient beneath the surface.

Abstract: The present invention provides a fungicidal fertilizer composition which contains ingredients which are biocompatible for purposes of agricultural applications, and which are harmless to animals and humans. An invention fungicide composition in the form of a dry blend formulation remains non-caking and free-flowing under storage conditions. Illustrative of an invention fungicide composition is a formulation which has a content of sodium bicarbonate, potassium bicarbonate, potassium oleate, xanthan gum and a fertilizer-effective content of nitrogen, phosphorus and potassium elements. The combination of potassium oleate and xanthan gum functions as an effective spreader-sticker and film-forming medium when the composition is diluted with water for agricultural applications. When the aqueous medium is hard water, calcium oleate is formed which enhances the sticker properties of the aqueous fungicide composition in agricultural applications.

Abstract: Disclosed is a composition for bonding separated tissues together or for coating tissues or prosthetic materials including at least one natural or synthetic peptide and at least one support material which may be activated by energy and to methods of making and using the same.

Abstract: The present invention provides a method for providing nutrition to elderly patients. Pursuant to the present invention, the enteral composition includes a protein source, a lipid source, and a carbohydrate source. Preferably, the protein source includes at least 18% of the total calories. In an embodiment, the carbohydrate source includes a source of dietary fiber including a balance of soluble to insoluble fiber ratio of approximately 1:3. Still further, the composition of the present invention also includes increased levels of certain vitamins and minerals.

Abstract: The present invention provides a method for providing nutrition to elderly patients. Pursuant to the present invention, the enteral composition includes a protein source, a lipid source, and a carbohydrate source. Preferably, the protein source includes at least 18% of the total calories. In an embodiment, the carbohydrate source includes a source of dietary fiber including a balance of soluble to insoluble fiber ratio of approximately 1:3. Still further, the composition of the present invention also includes increased levels of certain vitamins and minerals.