BIOCOMPATIBLE PROTEIN-BASED PARTICLES AND METHODS THEREOF

• US 20100143487A1
• Filed: 12/26/2008
• Published: 06/10/2010
• Est. Priority Date: 12/26/2007
• Status: Active Grant

• Current Assignee: PetVivo Holdings, Inc.
• Original Assignee: Gel-Del Technologies, Inc. (PetVivo Holdings, Inc.)
• Inventors: Masters, David B.
• Granted Patent: US 11,890,371 B2
• Time in Patent Office: Days
• US Class Current: 424/499
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease

Abstract

The present invention relates to biocompatible protein-based particles and their methods of preparation and use. More specifically the present invention relates protein-based particles including protein matrix, spread matrix and/or biocoacervate materials derived from one or more biocompatible purified proteins combined with one or more biocompatible solvents that are used to replace or repair tissue and/or bone in treatments for spinal disc(s), joint(s) (e.g. knee, hip, finger, ankle, elbow, shoulder . . . ) and organ(s) (e.g. bladder, lips, vagina, penis, urethra . . . ). In various embodiments of the present invention the protein-based particles may also include one or more pharmacologically active agents and/or one or more additives.

Claims

1. A method of treating or enhancing the function of a spinal disc comprising:

administering a plurality of particles to the spinal disc or the surrounding fluid, space, tissue or bone of the spinal disc, said particles comprising one or more protein-based biomaterials at least partially produced from one or more biocoacervate material(s), the biocoacervate material(s) precipitated from a solution including one or more biocompatible protein(s), one or more glycosaminioglycans and one or more biocompatible solvents.

2. The method of claim 1 wherein the particles have a size of approximately 500 nm to 1000 μ

m.

3. The method of claim 1 wherein the one or more biocompatible protein(s) that are selected from the group consisting of elastin, collagen, albumin, keratin, laminin, 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-heparin and collagen-chondroiten.

4. The method of claim 1 wherein the one or more biocompatible solvent(s) is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

5. The method of claim 1 wherein the particles further includes one or more pharmacologically active agents 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, permeation enhancers, 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.

6. The method of claim 5 wherein the pharmacologically active agent is selected from anesthetics, analgesics, anti-coagulant agents or neurotoxins.

7. The method of claim 1 wherein the particles further include one or more biocompatible additives.

8. The method 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, humectants, 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 or combinations of these.

9. The method of claim 1 wherein all or a portion of the particles are crosslinked with one or more crosslinking agents.

10. The method of claim 9 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, formaldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, 1,4-butandiol diglycidylether, N-Succinimidyl 6-[4′

azido-2′

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

11. A method of treating or enhancing the function of a joint comprising:

administering a plurality of particles to the joint or the surrounding fluid, space, tissue or bone of the joint, said particles comprising one or more protein-based biomaterials at least partially produced from one or more biocoacervate material(s), the biocoacervate material(s) precipitated from a solution including one or more biocompatible protein(s), one or more glycosaminioglycans and one or more biocompatible solvents.

12. The method of claim 11 wherein the particles have a size of approximately 500 nm to 1000 μ

m.

13. The method of claim 11 wherein the one or more biocompatible protein(s) that are selected from the group consisting of elastin, collagen, albumin, keratin, laminin, 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-heparin and collagen-chondroiten.

14. The method of claim 11 wherein the one or more biocompatible solvent(s) is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

15. The method of claim 11 wherein the particles further includes one or more pharmacologically active agents 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, permeation enhancers, 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 method of claim 15 wherein the pharmacologically active agent is selected from anesthetics, analgesics, anti-coagulant agents or neurotoxins.

17. The method of claim 11 wherein the particles further include one or more biocompatible additives.

18. The method 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, humectants, 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 or combinations of these.

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

20. The method of claim 19 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, formaldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, 1,4-butandiol diglycidylether, N-Succinimidyl 6-[4′

azido-2′

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

21. A method of treating or enhancing the function of an organ comprising:

administering a plurality of particles to the organ or the surrounding fluid, space, tissue or bone of the organ, said particles comprising one or more protein-based biomaterials at least partially produced from one or more biocoacervate material(s), the biocoacervate material(s) precipitated from a solution including one or more biocompatible protein(s), one or more glycosaminioglycans and one or more biocompatible solvents.

22. The method of claim 21 wherein the particles have a size of approximately 500 nm to 1000 μ

m.

23. The method of claim 21 wherein the one or more biocompatible protein(s) that are selected from the group consisting of elastin, collagen, albumin, keratin, laminin, 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-heparin and collagen-chondroiten.

24. The method of claim 21 wherein the one or more biocompatible solvent(s) is selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.

25. The method of claim 21 wherein the particles further includes one or more pharmacologically active agents 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, permeation enhancers, 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.

26. The method of claim 25 wherein the pharmacologically active agent is selected from anesthetics, analgesics, anti-coagulant agents or neurotoxins.

27. The method of claim 21 wherein the particles further include one or more biocompatible additives.

28. The method 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, humectants, 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 or combinations of these.

29. The method of claim 21 wherein all or a portion of the particles are crosslinked with one or more crosslinking agents.

30. The method of claim 29 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, formaldehyde, p-Azidobenzolyl Hydazide, N-5-Azido 2-nitrobenzoyloxysuccinimide, 1,4-butandiol diglycidylether, N-Succinimidyl 6-[4′

azido-2′

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