Biomatrix structural containment and fixation systems and methods of use thereof

• US 8,623,393 B2
• Filed: 04/29/2003
• Issued: 01/07/2014
• Est. Priority Date: 04/29/2002
• Status: Active Grant

• Current Assignee: PetVivo Holdings, Inc.
• Original Assignee: Gel-Del Technologies, Inc. (PetVivo Holdings, Inc.)
• Inventors: Masters, David B., Berg, Eric Peter
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US10/513,071
• Publication Number:
  US 20050163817A1
• Time in Patent Office: 3,906 Days
• Field of Search: None
• US Class Current: 424/422
• 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 biomatrix 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 system comprising

a containment and fixation sleeve including one or more sheet(s) of biomatrix material, the one or more of the sheet(s) having one or more biocompatible proteins combined with one or more biocompatible solvents to form a cohesive body having a solvent content of about 10% to 80% by weight prior to compression, the cohesive body is compressed at a pressure of about 100 psi to about 100,000 psi to form the sheet(s) of biomatrix material having a solvent content of about 5% to 60% by weight, said sleeve having two or more ends adhered together with one or more fastening device(s) to form an enclosure;

and

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

2. The biomatrix containment and fixation system 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, genetically engineered proteins including blocks of peptide sequences comprising groups of amino acids, collagen-heparin, collagen-elastin-albumin-heparin, collagen-albumin, collagen-elastin-heparin and collagen-chondroitin.

3. The biomatrix containment and fixation system 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 system of claim 1 wherein the sleeve includes one or more pharmacologically active agents and the one or more pharmacologically active agents included in the sleeve or in the sleeve and particles are selected from the group consisting of analgesics, anesthetics, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antiglacoma agents, antialcohol agents, anti-coagulants agents, genetic material, antithrombolytic agents, anticancer agents, anti-Parkinson agents, antiepileptic agents, anti-inflammatory agents, anticonception agents, enzymes, 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 system of claim 4 wherein the pharmacologically active agents are hydroxyapatite, bone morphogenic protein VEGF or combinations thereof.

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

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

8. The biomatrix containment and fixation system 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), polyethylene glycol, poly(vinyl chloride), polypropylene oxide, poly(akylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2-hydroxyethyl methacrylate, polymethyl methacrylate, 1,3-bis(carboxyphenoxy)propane, lipids, polyhydroxybutyrate, polyhydroxyvalerate, 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 system of claim 1 wherein all or a portion of the sleeve and particles are crosslinked with one or more crosslinking agents.

10. The biomatrix containment and fixation system 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.

11. The biomatrix containment and fixation system of claim 1 wherein the particles have a size of approximately 10 nm to 5 mm.

12. The biomatrix containment and fixation system of claim 2 wherein the biocompatible proteins include collagen.

13. The biomatrix containment and fixation system of claim 2 wherein the biocompatible proteins include collagen and elastin.

14. The biomatrix containment and fixation system of claim 3 wherein the biocompatible solvent includes water.

15. The biomatrix containment and fixation system of claim 10 wherein the one or more crosslinking agents includes glutaraldehyde.

16. The biomatrix containment and fixation system of claim 1 wherein the sleeve and particles are formed from a cohesive body including the one or more biocompatible proteins, the one or more biocompatible solvents and optionally the one or more pharmacologically active agents.

17. The biomatrix containment and fixation system of claim 1, wherein the fastening device to form an enclosure includes staples, adhesives or sutures.

18. The biomatrix containment and fixation system of claim 1 wherein the fastening device includes one or more bindings.

19. The biomatrix containment and fixation system of claim 1 wherein the particles are formed from one or more cohesive bodies for particle preparation including one or more biocompatible proteins, one or more biocompatible solvents and one or more pharmacologically active agents, wherein the solvent content for each cohesive body for particle preparation is reduced from about 10% to 80% to about 5% to 60% by one or more techniques selected from the group consisting of compression, freeze drying, vacuum and heating, and wherein the solvent reduced cohesive bodies are further processed into the particles that are administered to the enclosure of the sleeve.