Claims for Patent: 8,153,591

Summary for Patent: 8,153,591

Title:	Protein biomaterials and biocoacervates and methods of making and using thereof
Abstract:	The present invention relates to protein biocoacervates and biomaterials and the methods of making and using protein biocoacervates and biomaterials. More specifically the present invention relates to protein biocoacervates and biomaterials that may be utilized for various medical applications including, but not limited to, drug delivery devices for the controlled release of pharmacologically active agents, coated medical devices (e.g. stents, valves . . . ), vessels, tubular grafts, vascular grafts, wound healing devices including protein suture biomaterials and biomeshes, dental plugs and implants, skin/bone/tissue grafts, tissue fillers, protein biomaterial adhesion prevention barriers, cell scaffolding and other biocompatible biocoacervate or biomaterial devices.
Inventor(s):	Masters; David B. (Minneapolis, MN), Berg; Eric P. (Plymouth, MN)
Assignee:	Gel-Del Technologies, Inc. (St. Paul, MN)
Application Number:	10/929,117
Patent Claims:	1. A biomaterial comprising one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans and one or more biocompatible solvents, the biomaterial is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s); the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into an amorphous thermoplastic biocoacervate; and the biocoacervate is crosslinked to produce the biomaterial. 2. The biomaterial of claim 1 wherein the biomaterial includes collagen and one or more additional primary proteins in addition to collagen selected from the group consisting of laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III. 3. The biomaterial of claim 1 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof. 4. The biomaterial of claim 1 further comprising one or more secondary proteins. 5. The biomaterial of claim 4 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III. 6. The biomaterial of claim 1 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols. 7. The biomaterial of claim 1 further comprising one or more pharmacologically active agents. 8. The biomaterial of claim 7 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity, smoking cessation agents, obstetric agents and antiasmatic agents. 9. The biomaterial of claim 8 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, desmopressin, dexamethazone, bone morphogenic protein, vitamin D, vitamin E, vitamin A, vitamin C, vitamin B, superoxide dismutase, VEGF, FGF, EGF, sufentinal, fentinal, capsaicin, lidocaine bupivacaine, benzocaine, testosterone and cortizone. 10. The biomaterial of claim 1 further comprising one or more biocompatible additives. 11. The biomaterial of claim 10 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 12. The biomaterial of claim 11 wherein the one or more additives are selected from the group consisting of glycine, glutamine, calcium carbonate, calcium sulfate, magnesium sulfate, glucose, ribose, alginate, insoluble collagen, elastin, laminin, hydroxyapatite, polyethylene glycol, glycerol, sodium hydroxide and potassium hydroxide. 13. The biomaterial of claim 10 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 14. The biomaterial of claim 13 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 15. The biomaterial of claim 1 wherein the biomaterial is processed by crosslinking the biomaterial with one or more crosslinking techniques, one or more crosslinking agents or combinations thereof to form a crosslinked biomaterial. 16. The biomaterial of claim 15 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, 1,4-butandiol diglycidylether, formaldehyde, glyoxal, sebacic acid bis (N-succinimidyl) ester (DSS), p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4'azido-2'nitro-phenylamino]hexanoate and 4-[p-Azidosalicylamido]butylamine. 17. The biomaterial of claim 1 wherein the biomaterial is processed in a form selected from the group consisting of a coating, cylinder, wafer, bar, sphere, capsule, vessel, tubular graft, particles, biomesh, plug, sheet and valve. 18. An amorphous thermoplastic biocoacervate comprising one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans and one or more biocompatible solvents, the biocoacervate is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s); the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into the amorphous thermoplastic biocoacervate. 19. The biocoacervate of claim 18 wherein the biocoacervate includes collagen and one or more additional primary proteins in addition to collagen selected from the group consisting of laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III. 20. The biomaterial of claim 18 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof. 21. The biocoacervate of claim 18 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols. 22. The biocoacervate of claim 18 further comprising one or more pharmacologically active agents. 23. The biocoacervate of claim 22 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity, smoking cessation agents, obstetric agents and antiasmatic agents. 24. The biocoacervate of claim 23 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, desmopressin, dexamethazone, bone morphogenic protein, vitamin D, vitamin E, vitamin A, vitamin C, vitamin B, superoxide dismutase, VEGF, FGF, EGF, sufentinal, fentinal, capsaicin, lidocaine bupivacaine, benzocaine, testosterone and cortizone. 25. The biocoacervate of claim 18 further comprising one or more biocompatible additives. 26. The biocoacervate of claim 25 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 27. The biocoacervate of claim 26 wherein the one or more additives are selected from the group consisting of glycine, glutamine, calcium carbonate, calcium sulfate, magnesium sulfate, glucose, ribose, alginate, insoluble collagen, elastin, laminin, hydroxyapatite, polyethylene glycol, glycerol, sodium hydroxide and potassium hydroxide. 28. The biocoacervate of claim 25 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 29. The biocoacervate of claim 28 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 30. The biocoacervate of claim 18 wherein the biocoacervate is processed in a form selected from the group consisting of a coating, cylinder, wafer, bar, sphere, capsule, vessel, tubular graft, particles, biomesh, plug, sheet and valve. 31. The amorphous thermoplastic biocoacervate of claim 18 further comprising one or more secondary proteins. 32. The biocoacervate of claim 31 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III. 33. A method of delivering one or more pharmacologically active agents to a patient comprising administering to the patient a biomaterial comprising one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans, one or more pharmacologically active agents, and one or more biocompatible solvents, the biomaterial is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s); the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into an amorphous thermoplastic biocoacervate; and the biocoacervate is crosslinked to produce the biomaterial, wherein one or more pharmacologically active agents are added to the solution prior to precipitation of the biocoacervate and/or added to the biocoacervate after precipitation. 34. The method of delivering one or more pharmacologically active agents of claim 33 wherein the amorphous thermoplastic material is administered by one or more administration techniques selected from the group consisting of oral, nasal, mucosal, intraocular, pulmonary, subcutaneous, intradermal, intrathecal, sublingual, epidural, subdural, tissue implantable and parenteral. 35. The method of delivering one or more pharmacologically active agents of claim 33 wherein the biomaterial includes collagen and one or more additional primary proteins selected from the group consisting of laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III. 36. The method of delivering one or more pharmacologically active agents of claim 33 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof. 37. The method of delivering one or more pharmacologically active agents to a patient of claim 33 further comprising one or more secondary proteins. 38. The method of delivering one or more pharmacologically active agents of claim 37 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III. 39. The method of delivering one or more pharmacologically active agents of claim 33 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols. 40. The method of delivering one or more pharmacologically active agents of claim 33 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity, smoking cessation agents, obstetric agents and antiasmatic agents. 41. The method of delivering one or more pharmacologically active agents of claim 40 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, desmopressin, dexamethazone, bone morphogenic protein, vitamin D, vitamin E, vitamin A, vitamin C, vitamin B, stem cells, superoxide dismutase, VEGF, FGF, EGF, sufentinal, fentinal, capsaicin, lidocaine bupivacaine, benzocaine, testosterone and cortizone. 42. The method of delivering one or more pharmacologically active agents of claim 33 wherein the thermoplastic material includes one or more biocompatible additives. 43. The method of delivering the one or more pharmacologically active agents of claim 42 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 44. The method of delivering one or more pharmacologically active agents of claim 43 wherein the one or more additives are selected from the group consisting of hydroxyapatite, polyethylene glycol, glycerol, sodium hydroxide and potassium hydroxide. 45. The method of delivering one or more pharmacologically active agents of claim 42 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 46. The method of delivering one or more pharmacologically active agents of claim 45 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 47. The method of delivering one or more pharmacologically active agents of claim 33 wherein the thermoplastic biocoacervate is crosslinked with one or more crosslinking agents to form a biomaterial. 48. The method of delivering one or more pharmacologically active agents of claim 47 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, 1,4-butandiol diglycidylether, formaldehyde, glyoxal, sebacic acid bis (N-succinimidyl) ester (DSS), p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4'azido-2'nitro-phenylamino]hexanoate and 4[p-Azidosalicylamido]butylamine. 49. The method of delivering one or more pharmacologically active agents of claim 33 wherein the biomaterial is processed in a form selected from the group consisting of a coating, cylinder, wafer, bar, sphere, capsule, vessel, tubular graft, particles, biomesh, plug, sheet and valve. 50. A method of treating a tissue void or wrinkle of a patient comprising administering to the void or wrinkle an amount of a biomaterial to substantially fill or slightly overfill the void or wrinkle, the biomaterial including one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans and one or more biocompatible solvents, the biomaterial is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s); the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into an amorphous thermoplastic biocoacervate; and the biocoacervate is crosslinked to produce the biomaterial. 51. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the biomaterial includes collagen and one or more additional primary proteins in addition to collagen selected from the group consisting of laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III. 52. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof. 53. The method of treating a tissue void or wrinkle of a patient of claim 50 further comprising one or more secondary proteins. 54. The method of treating a tissue void or wrinkle of a patient of claim 53 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III. 55. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols. 56. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the thermoplastic material includes one or more pharmacologically active agents. 57. The method of treating a tissue void or wrinkle of a patient of claim 56 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents, chemoattractants, obstetric agents and antiasmatic agents. 58. The method of treating a tissue void or wrinkle of a patient of claim 57 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, desmopressin, dexamethazone, bone morphogenic protein, vitamin D, vitamin E, vitamin A, vitamin C, vitamin B, superoxide dismutase, VEGF, FGF, EGF, sufentinal, fentinal, capsaicin, lidocaine bupivacaine, benzocaine, testosterone and cortizone. 59. The method of treating a tissue void or wrinkle of a patient of claim 50 further comprising one or more biocompatible additives. 60. The method of treating a tissue void or wrinkle of a patient of claim 59 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 61. The method of treating a tissue void or wrinkle of a patient of claim 60 wherein the one or more additives are selected from the group consisting of hydroxyapatite, polyethylene glycol, glycerol, sodium hydroxide and potassium hydroxide. 62. The method of treating a tissue void or wrinkle of a patient of claim 59 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 63. The method of treating a tissue void or wrinkle of a patient of claim 62 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 64. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the thermoplastic biocoacervate is crosslinked with one or more crosslinking agents to form a biomaterial. 65. The method of treating a tissue void or wrinkle of a patient of claim 64 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, 1,4-butandiol diglycidylether, formaldehyde, glyoxal, sebacic acid bis (N-succinimidyl) ester (DSS), p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4'azido-2'nitro-phenylamino]hexanoate and 4[p-Azidosalicylamido]butylamine. 66. The method of treating a tissue void or wrinkle of a patient of claim 50 wherein the biomaterial is processed into a particulate form. 67. A vessel graft comprising a biomaterial including one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans and one or more biocompatible solvents, the biomaterial is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s); the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into an amorphous thermoplastic biocoacervate; the biocoacervate is formed into a tube configuration and crosslinked to produce the biomaterial vessel graft. 68. The vessel graft of claim 67 further including a structural scaffolding coated or encapsulated with the thermoplastic biomaterial. 69. The vessel graft of claim 67 wherein the biomaterial includes collagen and one or more additional primary proteins in addition to collagen selected from the group consisting of laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III. 70. The vessel graft of claim 67 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof. 71. The vessel graft of claim 67 further comprising one or more secondary proteins. 72. The vessel graft of claim 71 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III. 73. The vessel graft of claim 67 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols. 74. The vessel graft of claim 67 further comprising one or more pharmacologically active agents. 75. The vessel graft of claim 74 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, angiogenic growth factors, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents and chemoattractants. 76. The vessel graft of claim 75 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, dexamethazone, vitamin E, vitamin C, superoxide dismutase, VEGF, FGF, EGF and cortizone. 77. The vessel graft of claim 67 further comprising one or more biocompatible additives. 78. The vessel graft of claim 77 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 79. The vessel graft of claim 77 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 80. The vessel graft of claim 79 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 81. The vessel graft of claim 67 wherein the thermoplastic biomaterial is crosslinked with one or more crosslinking agents to form a crosslinked material. 82. The vessel graft of claim 81 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, 1,4-butandiol diglycidylether, formaldehyde, glyoxal, sebacic acid bis (N-succinimidyl) ester (DSS), p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4'azido-2'nitro-phenylamino]hexanoate and 4-[p-Azidosalicylamido]butylamine. 83. A coated medical device comprising a medical device coated with a biomaterial including one or more soluble or solubilized primary proteins, wherein one of the primary proteins is collagen, one or more glycosaminoglycans and one or more biocompatible solvents, the biomaterial is formed by adding the glycosaminoglycan(s) to one or more of the primary protein(s) that are dissolved in the solvent(s) at a temperature of about 30.degree. C. to about 150.degree. C.; the glycosaminoglycan(s), primary protein(s) and solvent(s) are minimally mixed to form a precipitate that aggregates into an amorphous body that falls out of solution; the amorphous body is extracted and formed into an amorphous thermoplastic biocoacervate; the medical device is coated with the biocoacervate and crosslinked to produce the coated medical device the biomaterial coating. 84. The coated medical device of claim 83 further comprising one or more pharmacologically active agents. 85. The coated medical device of claim 84 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, angiogenic growth factors, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulant agents, antithrombolytic agents, anticancer agents, anti-inflammatory agents, anticonception agents, enzymes agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents and chemoattractants. 86. The coated medical device of claim 85 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, dexamethazone, vitamin E, vitamin C, superoxide dismutase, VEGF, FGF, EGF and cortizone. 87. The coated medical device of claim 83 further comprising one or more biocompatible additives. 88. The coated medical device of claim 87 wherein the one or more biocompatible additives are selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly(amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly(amido amines), bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these. 89. The coated medical of claim 87 wherein the one or more additives includes one or more glycosaminoglycan(s) that are added to the biocoacervate when molten. 90. The coated medical device of claim 29 wherein the one or more glycosaminoglycan(s) are selected from the group consisting of heparin, hyaluronic acid and chondroitin sulfate. 91. The coated medical device of claim 83 further comprising one or more secondary proteins. 92. The coated medical device of claim 83 wherein the thermoplastic biomaterial is crosslinked with one or more crosslinking agents to form a crosslinked material. 93. The coated medical device of claim 83 wherein the medical device is selected from the group consisting of stents, pacemakers, ophthalmic devices, shunts and orthopedic devices.

Details for Patent 8,153,591

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bayer Healthcare Pharmaceuticals Inc.	TRASYLOL	aprotinin	Injection	020304	12/29/1993		2040-03-31