Implantable tissue compositions and method

• US 7,919,112 B2
• Filed: 08/24/2005
• Issued: 04/05/2011
• Est. Priority Date: 08/26/2004
• Status: Expired due to Fees

• Current Assignee: Pathak Holdings, LLC
• Original Assignee: Pathak Holdings, LLC
• Inventors: Thigle, Sanjay M., Pathak, Chandraskekhar P.
• Primary Examiner(s): Saucier; Sandra
• Assistant Examiner(s): HANLEY, SUSAN MARIE
• Application Number:
  US11/661,062
• Publication Number:
  US 20070254005A1
• Time in Patent Office: 2,050 Days
• Field of Search: 424/426, 424/423, 514/2
• US Class Current: 424/426
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• 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 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3612 Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3633 : Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3641 : characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3683 : subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3687 : characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/38 : containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Novel implantable tissue fixation methods and compositions are disclosed. Methods and compositions of tissue, fixed using polymeric and/or variable length crosslinks, and di- or polymercapto compounds are described. Also described are the methods and compositions wherein the tissue is fixed using biodegradable crosslinkers. Methods and compositions for making radio-opaque tissue are also described. Methods and compositions to obtain a degradable implantable tissue-synthetic biodegradable polymer composite are also described. Compositions and methods of incorporating substantially water-insoluble bioactive compounds in the implantable tissue are also disclosed. The use of membrane-like implantable tissue to make an implantable drug delivery patch are also disclosed. Also described are the compositions and methods to obtain a coated implantable tissue. Medical applications implantable tissue such as heart valve bioprosthesis, vascular grafts, meniscus implant, drug delivery patch are also disclosed.

Claims

1. A method for forming a composite material of a tissue and synthetic biodegradable polymer, the method comprising:

selecting a tissue suitable for implantation into a patient;

infusing the tissue in vitro with a fluid that comprises an organic solvent and the synthetic biodegradable polymer dissolved in the fluid; and

evaporating the fluid that comprises the solvent;

wherein the polymer comprises a plurality of polymer functional groups that form covalent bonds with tissue functional groups in the tissue.

2. The method of claim 1 wherein the biodegradable polymer has a molecular weight from about 2000 to about 500000 Daltons and comprises a polyhydroxy acid, a polylactone, a polyhydroxyalkanoate, a polyanhydride, a polyglycolide, a poly(orthocarbonate), a poly(carbonate), or a poly(phosphonate).

3. The method of claim 1 wherein the organic solvent comprises alcohol, acetone, tetrahydrofuran, benzene, toluene, xylene, chloroform, methylene chloride, dimethyl sulfoxide, n-vinyl pyrrolidinone, or dimethylacetamide.

4. The method of claim 1 wherein the tissue is crosslinked.

5. The method of claim 1 wherein the biodegradable polymer further comprises an unsaturated group at the time of the infusion.

6. The method of claim 5 wherein the unsaturated groups are activated by free radicals, with some of the unsaturated groups reacting with the tissue and some of the unsaturated groups reacting with each other to form links within the tissue.

7. The method of claim 5 wherein unsaturated groups are cross-linked with organic di-mercapto or poly-mercapto compounds that are present in the fluid that is infused with the tissue.

8. The method of claim 5 wherein the unsaturated groups comprise acrylamide, methacrylamide, acrylate or methacrylate.

9. The method of claim 1 wherein the biodegradable polymer comprises polyethylene glycol.

10. The method of claim 1 wherein the fluid further comprises a bioactive substance.

11. The method of claim 1 wherein the tissue functional groups are amines, carboxylic acids, hydroxyls, or thiols that react with the biodegradable polymer functional groups.

12. The method of claim 1 wherein the polymer functional groups are activatable to react, at pH 7.2 at room temperature, with amine groups or thiol groups.

13. The method of claim 12 wherein the polymer functional groups comprise succinimidyl moieties.

14. The method of claim 1 wherein the tissue is chosen from the group consisting of ureter, artery, pericardial, intestinal, submucosa, cornea, and meniscus.