Abstract: A method is provided for the rapid formation of a biocompatible gel, and may be carried out in situ, i.e., at a selected site within a patient's body. The method involves admixing a biocompatible crosslinking component A having m sulfhydryl groups wherein m≧2 and a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein n≧2 and m+n>4, wherein the sulfhydryl-reactive groups are capable of covalent reaction with the sulfhydryl groups upon admixture of the components under effective crosslinking conditions to form a gel in less than one minute. Suitable reaction conditions for carrying out the crosslinking reaction will depend on the particular components and the type of reaction involved; that is, the “effective crosslinking conditions” may involve reaction in bulk or in a solvent, addition of a base, and/or irradiation of the admixture in the presence of a free radical initiator.

Abstract: Crosslinkable compositions are provided that readily crosslink in situ to provide biocompatible, nonimmunogenic crosslinked biomaterials. The compositions contain at least three biocompatible, nonimmunogenic components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. In a preferred embodiment, a first component is polynucleophilic, a second component is polyelectrophilic, and at least one third component contains one or more functional groups reactive with the nucleophilic moieties one the first or second component. At least one of the components is a polyfunctional hydrophilic polymer; the other components may also comprise hydrophilic polymers, or they may be low molecular weight, typically hydrophobic, crosslinkers. Methods for preparing and using the compositions are also provided.

Abstract: New forms of ecarin, a procoagulant protein from Echis carinatus venom, are described, as are polynucleotides encoding the new proteins, methods for production of the new proteins, and methods for activation of prothrombin using the new proteins. The new ecarins comprise a serine at position 396 of the protein. The new proteins may be used for activation of prothrombin, and are particularly useful for the production of recombinant thrombin.

Abstract: Crosslinkable compositions are provided that readily crosslink in situ to provide biocompatible, nonimmunogenic crosslinked biomaterials. The compositions contain at least three biocompatible, nonimmunogenic components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. In a preferred embodiment, a first component is polynucleophilic, a second component is polyelectrophilic, and at least one third component contains one or more functional groups reactive with the nucleophilic moieties one the first or second component. At least one of the components is a polyfunctional hydrophilic polymer; the other components may also comprise hydrophilic polymers, or they may be low molecular weight, typically hydrophobic, crosslinkers. Methods for preparing and using the compositions are also provided.

Abstract: This invention relates generally to two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired. In particular, they are useful as tissue sealants, in promoting hemostasis, for drug delivery, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Abstract: This invention relates generally to two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired. In particular, they are useful as tissue sealants, in promoting hemostasis, for drug delivery, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Abstract: The present invention relates to thrombin-containing hemostatic compositions, their preparation and use. In particular, it relates to hemostatic compositions comprising stabilized thrombin and microfibrillar collagen in an aqueous medium. In a preferred embodiment of the present invention, the compositions are used in a kit comprising two different components, one of which is autologous patient's plasma as the source of fibrinogen, and the other of which is the thrombin-containing composition which also contains microfibrillar collagen.

Abstract: The present invention relates to thrombin-containing hemostatic compositions, their preparation and use. In particular, it relates to hemostatic compositions comprising stabilized thrombin and microfibrillar collagen in an aqueous medium. In a preferred embodiment of the present invention, the compositions are used in a kit comprising two different components, one of which is autologous patient's plasma as the source of fibrinogen, and the other of which is the thrombin-containing composition which also contains microfibrillar collagen having an average diameter of about 3-30 nanometers.

Abstract: Cross-linked hydrogels comprise a variety of biologic and non-biologic polymers, such as proteins, polysaccharides, and synthetic polymers. Such hydrogels preferably have no free aqueous phase and may be applied to target sites in a patient's body by extruding the hydrogel through an orifice at the target site. Alternatively, the hydrogels may be mechanically disrupted and used in implantable articles, such as breast implants. When used in vivo, the compositions are useful for controlled release drug delivery, for inhibiting post-surgical spinal and other tissue adhesions, for filling tissue divots, tissue tracts, body cavities, surgical defects, and the like.

Abstract: Molecular cross-linked gels comprise a variety of biologic and non-biologic polymers, such as proteins, polysaccharides, and synthetic polymers. Such molecular gels may be applied to target sites in a patient's body by extruding the gel through an orifice at the target site. Alternatively, the gels may be mechanically disrupted and used in implantable articles, such as breast implants. When used in vivo, the compositions are useful for inhibiting post-surgical spinal and other tissue adhesions, for filling tissue divots, tissue tracts, body cavities, surgical defects, and the like.

Abstract: Gelatin film compositions are useful for immobilization over tissue, usually by the application of energy to the films. Exemplary films comprise cross-linked and non-cross-linked granular and non-granular gelatin sheets, typically including a plasticizer. The gelatin films are dry, thin, and preferably meet certain pliability, elasticity, melting temperature, and other criteria. Methods are described for producing these films from collagen. Methods are further described for applying these films to tissue.

Abstract: Biological materials are joined, repaired or fused by heating the material in proximity to a mechanical support. Preferably, the mechanical support comprises a patch or bridge structure. In the most preferred embodiment, the patch is formed from collagen having a thickness from between 2 to 30 mils, and most preferably from 2 to 15 mils thick. Preferably, the patch or support structure contains holes or interlock vias which permit the coagulum to form a mechanical bond therewith, whether preformed or generated by an electrical energy source during welding. The preferred method comprises the steps of: first, placing the patch in contact with the materials to be joined, supplying energy to the tissue in an amount sufficient to form a coagulum at the surface of the patch, and finally, permitting the coagulum to form a mechanical bond with the support or patch.

Abstract: Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding atelopeptide collagen to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide collagen/polymer conjugates. The atelopeptide collagen can be type I, type II or type III and may be fibrillar or non-fibrillar. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The collagen-polymer conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object.

Abstract: Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Abstract: Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Abstract: Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding atelopeptide collagen to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide collagen/polymer conjugates. The atelopeptide collagen can be type I, type II or type III and may be fibrillar or non-fibrillar. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The collagen-polymer conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object.

Abstract: Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding atelopeptide collagen to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide collagen/polymer conjugates. The atelopeptide collagen can be type I, type II or type III and may be fibrillar or non-fibrillar. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The collagen-polymer conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object.

Abstract: Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Abstract: Injectable implant compositions comprise a biocompatible ceramic matrix present in a fluid carrier, where the ceramic matrix comprises particles having a size distribution in the range from 50 .mu.m to 250 .mu.m. Optionally, the compositions may further comprise collagen, where the relative amounts of collagen and ceramic matrix at least partly determine the physical properties of implants formed by injecting the compositions. The fluid carrier is an aqueous buffered medium, typically including an organic polymer base material when there is no collagen present in the composition. The compositions are particularly suitable for repair and augmentation of soft and hard tissues by injection.

Abstract: Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding atelopeptide collagen to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide collagen/polymer conjugates. The atelopeptide collagen can be type I, type II or type III and may be fibrillar or non-fibrillar. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The collagen-polymer conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object.