Biomatrix structural containment and fixation systems and methods of use thereof

• US 20050163817A1
• Filed: 04/29/2003
• Published: 07/28/2005
• Est. Priority Date: 04/29/2002
• Status: Active Grant

• Current Assignee: PetVivo Holdings, Inc.
• Original Assignee: Gel-Del Technologies, Inc. (PetVivo Holdings, Inc.)
• Inventors: Berg, Eric Peter, Masters, David B
• Granted Patent: US 8,623,393 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61B 17/68 Internal fixation devices , including fasteners and spinal fixators, even if a part thereof projects from the skin bone staples A61B17/0642
• CPC Class Codes: A61B 2017/561 Implants with special means for releasing a drug
• CPC Class Codes: A61B 2017/564 Methods for bone or joint treatment
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/112 Phosphorus-containing compounds, e.g. phosphates, phosphonates
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/60 characterised by a special physical form
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence

Abstract

The containment and fixation system of the present invention generally includes a biomatix sleeve, biomatrix particles or combinations thereof made of a biomatrix material. The biomatrix material is comprised of one or more biocompatible proteins and one or more biocompatible solvents. The biomatrix material utilized in the sleeve and/or particles may also include one or more pharmacologically active agents like therapeutic biochemicals such as a bone mending biochemical (e.g. hydroxyapatite) or an angiogenic growth factor (e.g. BMP).

Claims

1. A biomatrix containment and fixation sleeve comprising one or more biocompatible proteins combined with one or more biocompatible solvents and one or more pharmacologically active agents, said sleeve having two ends adhered together with a fastening device to form an enclosure.

2. The biomatrix containment and fixation sleeve of claim 1 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, ovalbumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, elastinlike blocks, silklike blocks, collagenlike blocks, lamininlike blocks, fibronectinlike blocks and silklike, elastinlike blocks, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin collagen-elastin-heparin and collagen-chondroiten.

3. The biomatrix containment and fixation sleeve of claim 1 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

4. The biomatrix containment and fixation sleeve of claim 1 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, antithrombyolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflamatory 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.

5. The biomatrix containment and fixation sleeve of claim 4 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein VEGF or combinations thereof.

6. The biomatrix containment and fixation sleeve of claim 1 wherein the fastening device is one or more devices selected from the group consisting of staples, cerclages, screws, plates, adhesives, bindings and sutures.

7. The biomatrix containment and fixation sleeve of claim 1 further comprising one or more biocompatible additives.

8. The biomatrix containment and fixation sleeve of claim 7 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, 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), fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.

9. The biomatrix containment and fixation sleeve of claim 1 wherein all or a portion of the biomatrix containment sleeve is crosslinked with one or more crosslinking agents.

10. The biomatrix containment and fixation sleeve of claim 9 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4′

azido-2′

nitro-phenylamino]hexanoate and 4-[p-Azidosalicylamido]butylamine.

27. The biomatrix containment and fixation system of claim 1, wherein the sleeve, particles or both further comprise one or more biocompatible additives.

28. The biomatrix containment and fixation system of claim 27 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, 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), fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.

35. The method of treating a fracture of claim 1 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

39. The method of treating a fracture of claim 1 further comprising one or more biocompatible additives.

40. The biomatrix containment and fixation sleeve of claim 39 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, 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), fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.

11. A particle fixation device comprising a plurality of protein particles, said protein particles including one or more biocompatible proteins combined with one or more biocompatible solvents and one or more pharmacologically active agents.

12. The particle fixation device of claim 11 wherein the particles have a size of approximately 10 nm to 5 mm.

13. The particle fixation device of claim 11 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, ovalbumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, elastinlike blocks, silklike blocks, collagenlike blocks, lamininlike blocks, fibronectinlike blocks and silklike, elastinlike blocks, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin collagen-elastin-heparin and collagen-chondroiten.

14. The particle fixation device of claim 11 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

15. The particle fixation device of claim 11 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, 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.

16. The particle fixation device of claim 15 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein or both.

17. The particle fixation device of claim 11 further comprising one or more biocompatible additives.

18. The particle fixation device of claim 17 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, 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), fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.

19. The particle fixation device of claim 11 wherein all or a portion of the particles are crosslinked with one or more crosslinking agents.

20. The particle fixation device of claim 19 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4′

azido-2′

nitro-phenylamino]hexanoate and 4-[p-Azidosalicylamido]butylamine.

21. A biomatrix containment and fixation system comprising

a containment and fixation sleeve including one or more biocompatible proteins combined with one or more biocompatible solvents and optionally one or more pharmacologically active agents, said sleeve having two ends adhered together with a fastening device to form an enclosure;

and

a plurality of protein particles administered within said sleeve, said protein particles including one or more biocompatible proteins combined with one or more biocompatible solvents and one or more pharmacologically active agents.

22. The biomatrix containment and fixation system of claim 21 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, ovalbumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, elastinlike blocks, silklike blocks, collagenlike blocks, lamininlike blocks, fibronectinlike blocks and silklike, elastinlike blocks, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin collagen-elastin-heparin and collagen-chondroiten.

23. The biomatrix containment and fixation system of claim 21 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

24. The biomatrix containment and fixation system of claim 21 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, 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.

25. The biomatrix containment and fixation system of claim 24 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein VEGF or combinations thereof.

26. The biomatrix containment and fixation system of claim 21 wherein the fastening device is one or more devices selected from the group consisting of staples, cerclages, screws, plates, adhesives, bindings and sutures.

29. The biomatrix containment and fixation system of claim 21 wherein all or a portion of the sleeve and particles are crosslinked with one or more crosslinking agents.

30. The biomatrix containment and fixation system of claim 29 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, N-Succinimidyl 6-[4′

azido-2′

nitro-phenylamino]hexanoate and 4-[p-Azidosalicylamido]butylamine.

31. The biomatrix containment and fixation system of claim 21 wherein the particles have a size of approximately 10 nm to 5 mm.

32. A method of treating a fracture comprising:

positioning around a fracture a sleeve including one or more biocompatible materials

securing one end of the sleeve to an opposite end of the sleeve with one or more fastening devices to enclose and contain the fracture.

33. The method of treating a fracture of claim 32 wherein the sleeve comprises one or more biocompatible proteins combined with one or more biocompatible solvents and optionally one or more pharmacologically active agents.

34. The method of treating a fracture of claim 33 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, ovalbumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, elastinlike blocks, silklike blocks, collagenlike blocks, lamininlike blocks, fibronectinlike blocks and silklike, elastinlike blocks, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin collagen-elastin-heparin and collagen-chondroiten.

36. The method of treating a fracture of claim 32 wherein the sleeve includes one or more pharmacologically active agents and the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, 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.

37. The method of treating a fracture of claim 36 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein, VEGF or combinations thereof.

38. The method of treating a fracture of claim 32 wherein the fastening device is one or more devices selected from the group consisting of staples, cerclages, screws, plates, adhesives, bindings and sutures.

41. The method of treating a fracture of claim 32 further comprising administering a plurality of particles into the sleeve, said particles including one or more biocompatible proteins combined with one or more biocompatible solvents and one or more pharmacologically active agents.

42. The method of treating a fracture of claim 41 wherein the particles have a size of approximately 10 nm to 5 mm.

43. The method of treating a fracture of claim 41 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, ovalbumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, elastinlike blocks, silklike blocks, collagenlike blocks, lamininlike blocks, fibronectinlike blocks and silklike, elastinlike blocks, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin collagen-elastin-heparin and collagen-chondroiten.

44. The method of treating a fracture of claim 41 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

45. The method of treating a fracture of claim 41 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, 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.

46. The method of treating a fracture of claim 45 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein VEGF or combinations thereof.

47. The method of treating a fracture of claim 41 further comprising one or more biocompatible additives.

48. The method of treating a fracture of claim 47 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, 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), fibrin, graphite, flexible fluoropolymer, isobutyl-based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.