Protein matrix materials, devices and methods of making and using thereof

• US 8,871,267 B2
• Filed: 02/05/2010
• Issued: 10/28/2014
• Est. Priority Date: 09/25/1998
• Status: Expired due to Term

• Current Assignee: PetVivo Holdings, Inc.
• Original Assignee: Gel-Del Technologies, Inc. (PetVivo Holdings, Inc.)
• Inventors: Masters, David B.
• Primary Examiner(s): PAK, JOHN D
• Application Number:
  US12/700,896
• Publication Number:
  US 20100196478A1
• Time in Patent Office: 1,726 Days
• Field of Search: 424/484, 424/400, 424/409, 424/422, 424/423, 424/439, 424/443, 424/93.7, 514/773, 514/774, 514/775, 514/776, 514/950, 514/953, 623/23.72, 623/23.75, 623/23.76, 623/915
• US Class Current: 424/484
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• 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
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 623/915 Method or apparatus for preparing biological material

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. The film is then partially dried, rolled or otherwise shaped, and then compressed to form the desired protein matrix device.

Claims

1. A tissue graft comprising one or more biocompatible protein materials, combined with one or more biocompatible solvents, wherein the protein material(s) and biocompatible solvent(s) are formed into a cohesive solid body having a solvent content of about 20% to 80% prior to compression and not having the characteristics of cracking, shattering, breaking or being crosslinked so as to inhibit the cohesive solid body from remaining cohesive unto itself when being formed and the cohesive solid body is compressed at a pressure of about 100 psi to 100,000 psi to remove bulk biocompatible solvent and generate additional intermolecular and intramolecular forces between one or more of the protein material(s) and solvent(s) to form the tissue graft having a solvent content of about 10% to 60%, and wherein the tissue graft provides a scaffold for enhancing cellular remodeling by host tissue.

2. The tissue graft of claim 1 wherein the biocompatible proteins may be natural, synthetic or genetically engineered.

3. The tissue graft of claim 2 wherein the biocompatible proteins are natural proteins selected from the group consisting of elastin, collagen, albumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin and antithrombin III.

4. The tissue graft of claim 2 wherein the biocompatible proteins are genetically engineered proteins including blocks of peptide sequences comprising groups of amino acids, collagen-heparin and collagen-chondroiten.

5. The tissue graft 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.

6. The tissue graft of claim 1 further comprising one or more pharmacologically active agents, cells or a combination thereof.

7. The tissue graft of claim 6 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, 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 agents, smoking cessation agents, obstetric agents and antiasmatic agents.

8. The tissue graft of claim 1 further comprising one or more biocompatible polymeric materials.

9. The tissue graft of claim 8 wherein the one or more biocompatible polymeric materials 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(alkylene)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), polycynoacrylates, 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.

10. The tissue graft of claim 1 wherein the tissue graft is crosslinked with one or more crosslinking agents.

11. The tissue graft of claim 10 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.

12. The tissue graft of claim 1 wherein the biocompatible protein materials are collagen and elastin.

13. The tissue graft of claim 1, wherein one or more additives in an amount up to 300% based upon the weight of the biocompatible protein material is included.

14. The tissue graft of claim 6 wherein the one or more pharmacologically active agents are included in the amount of 0.001% to 200% based upon the weight of the biocompatible protein material.

15. A method of replacing damaged, diseased or missing tissue comprising:

providing a tissue graft comprising one or more biocompatible protein materials, combined with one or more biocompatible solvents and one or more pharmacologically active agents, cells or combinations thereof, wherein the protein material(s), biocompatible solvent(s) and pharmacologically active agent(s), cells or combinations thereof are formed into a cohesive solid body having a solvent content of about 20% to 80% prior to compression and not having the characteristics of cracking, shattering, breaking or being crosslinked so as to inhibit the cohesive solid body from remaining cohesive unto itself when being formed and the cohesive solid body is compressed at a pressure of about 100 psi to 100,000 psi to remove bulk biocompatible solvent and generate additional intermolecular and intramolecular forces between one or more of the protein material(s), solvent(s) and/or active agent(s) to form the tissue graft having a solvent content of about 10% to 60%; and

administering the tissue graft to a part of a patient'"'"'s body that is damaged, diseased or missing, wherein the tissue graft provides a scaffold for enhancing cellular remodeling by host tissue.

16. The method of replacing damaged, diseased or missing tissue of claim 15 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

17. The method of replacing damaged, diseased or missing tissue of claim 15 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, 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, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity agents, smoking cessation agents, obstetric agents, antimicrobial agents, glycosaminoglycans, and antiasmatic agents.

18. The method of replacing damaged, diseased or missing tissue of claim 15, wherein the pharmacologically active agent comprises a second, migration-vulnerable drug delivery device.

19. The method of replacing damaged, diseased or missing tissue of claim 15, wherein the tissue graft further comprises one or more biocompatible polymeric materials.

20. The method of replacing damaged, diseased or missing tissue of claim 18 wherein the one or more biocompatible polymeric materials 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(alkylene)glycol, polyoxyethylene, sebacic acid polymers, polyvinyl alcohol, 2 hydroxyethyl methacrylate polymers, polymethyl methacrylate, 1,3 bis(carboxyphenoxy)propane polymers, 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 polymers, isopropyl styrene polymers, vinyl pyrrolidone polymers, cellulose acetate dibutyrate polymers, silicone rubber, and copolymers and combinations of these.

21. The method of replacing damaged, diseased or missing tissue of claim 15 wherein all or a portion of the tissue graft is crosslinked with one or more crosslinking agents.

22. The method of replacing damaged, diseased or missing tissue of claim 21 wherein the one or more crosslinking reagents 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.

23. The method of replacing damaged, diseased or missing tissue of claim 15 wherein the biocompatible protein materials are collagen and elastin.

24. The method of replacing damaged, diseased or missing tissue of claim 15 wherein the tissue graft includes one or more additives in an amount up to 300% based upon the weight of the biocompatible protein material.

25. The method of replacing damaged, diseased or missing tissue of claim 15 wherein the one or more pharmacologically active agents are included in the amount of 0.001% to 200% based upon the weight of the biocompatible protein material.

26. A method of making a tissue graft, comprising the steps of:

(a) preparing a coatable composition comprising one or more biocompatible protein materials and one or more biocompatible solvents;

(b) forming the coatable composition into a cohesive solid body having a solvent content of about 20% to 80% prior to compression and not having the characteristics of cracking, shattering, breaking or being crosslinked so as to inhibit the cohesive solid body from remaining cohesive unto itself when being formed;

(c) compressing the cohesive solid body at a pressure of about 100 psi to 100,000 psi to remove bulk biocompatible solvent; and

(d) forming a tissue graft having a solvent content of about 10% to 60% from a compressed cohesive solid body, wherein the tissue graft provides a scaffold for enhancing cellular remodeling by host tissue.

27. The method of making a tissue graft device of claim 26 wherein the biocompatible proteins are selected from the group consisting of elastin, collagen, albumin, keratin, fibronectin, silk, silk fibroin, actin, myosin, fibrinogen, thrombin, aprotinin, antithrombin III, collagen-heparin, collagen-chondroiten and genetically engineered proteins including blocks of peptide sequences comprising groups of amino acids, collagen-heparin and collagen-chondroiten.

28. The method of making a tissue graft of claim 26 wherein the biocompatible solvent is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

29. The method of making a tissue graft of claim 26, wherein the tissue graft further includes one or more pharmacologically active agents, cells or a combination thereof.

30. The method of making a tissue graft of claim 29 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, 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, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity agents, smoking cessation agents, obstetric agents, antimicrobial agents, glycosaminoglycans, and antiasmatic agents.

31. The method of making a tissue graft of claim 29, wherein the pharmacologically active agent comprises a second, migration-vulnerable drug delivery device.

32. The method of making a tissue graft of claim 26, wherein the tissue graft further comprises one or more biocompatible polymeric materials.

33. The method of making a tissue graft of claim 32 wherein the one or more biocompatible polymeric materials 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(alkylene)glycol, polyoxyethylene, sebacic acid polymers, polyvinyl alcohol, 2 hydroxyethyl methacrylate polymers, polymethyl methacrylate, 1,3 bis(carboxyphenoxy)propane polymers, 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 polymers, isopropyl styrene polymers, vinyl pyrrolidone polymers, cellulose acetate dibutyrate polymers, silicone rubber, and copolymers and combinations of these.

34. The method of making a tissue graft of claim 26 further comprising the step of crosslinking all or a portion of the tissue graft with one or more suitable crosslinking agents.

35. The method of making a tissue graft of claim 34 wherein the one or more crosslinking reagents 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.

36. The method of making a tissue graft of claim 26 wherein the biocompatible protein materials are collagen and elastin.

37. The method of making a tissue graft of claim 26 wherein the tissue graft includes one or more additives in an amount up to 300% based upon the weight of the biocompatible protein material.

38. The method of making a tissue graft of claim 29 wherein the one or more pharmacologically active agents are included in the amount of 0.001% to 200% based upon the weight of the biocompatible protein material.