Cross-linked fatty acid-based biomaterials

Patent metadata

Field	Value
Publication number	US-9000040-B2
Application number	US-36476309-A
Country	US
Kind code	B2
Filing date	Feb 3, 2009
Priority date	Sep 28, 2004
Publication date	Apr 7, 2015
Grant date	Apr 7, 2015

Abstract

Fatty acid-based, pre-cure-derived biomaterials, methods of making the biomaterials, and methods of using them as drug delivery carriers are described. The fatty acid-derived biomaterials can be utilized alone or in combination with a medical device for the release and local delivery of one or more therapeutic agents. Methods of forming and tailoring the properties of said biomaterials and methods of using said biomaterials for treating injury in a mammal are also provided.

First claim

What is claimed is:

1. A coating for a medical device, comprising: fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, and a therapeutic agent, wherein the fatty acids are partially cross-linked to each other by one or more of ester bonds or lactone bonds before association with the therapeutic agent, and wherein the coating hydrolyzes in vivo.

2. The coating of claim 1 , wherein the therapeutic agent is contained within the coating in such a manner that the therapeutic agent has an enhanced release profile.

3. The coating of claim 1 , further comprising pre-cured glyceride.

4. A fatty-acid based, pre-cure-derived coating for a medical device, comprising: one or more therapeutic agents and fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, wherein the fatty acids are partially cross-linked to each other by one or more of ester bonds or lactone bonds before association with the therapeutic agent, wherein the fatty acids comprise approximately 5-50% C 16 fatty acids, and wherein the coating hydrolyzes in vivo.

5. The coating of claim 1 , wherein the oil comprises 5-25% C 14 fatty acids.

6. The coating of claim 1 , wherein the oil comprises 5-30% C 16 fatty acids.

7. A fatty-acid based, pre-cure-derived coating for a medical device comprising a therapeutic agent and fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, wherein the fatty acids comprise approximately 5-25% C 14 fatty acids and 5-50% C 16 fatty acids, and wherein the coating hydrolyzes in vivo.

8. A fatty-acid based, pre-cure-derived coating for a medical device comprising fatty acids and glycerides, wherein the fatty acids are cross-linked to each other by one or more of ester bonds or lactone bonds, wherein the fatty acids and glycerides have disordered alkyl groups, which cause the coating to be flexible and hydratable, and wherein the coating hydrolyzes in vivo into one or more of free fatty acids, glycerols, or glycerides.

9. A fatty-acid based, pre-cure-derived coating for a medical device comprising a fatty acid-derived biomaterial, wherein the fatty acid-derived biomaterial comprises fatty acids and glycerides, wherein the fatty acids are cross-linked to each other by one or more of ester bonds or lactone bonds, and wherein the coating hydrolyzes in vivo into one or more of free fatty acids, glycerols, or glycerides.

10. A fatty-acid based, pre-cure-derived coating for a medical device, wherein the coating comprises fatty acids and glycerides, wherein the fatty acids are cross-linked to each other by one or more of lactone bonds or ester bonds, as indicated by an infrared absorption spectrum having a peak from approximately 1740-1850cm −1 , and wherein the coating hydrolyzes in vivo into one or more of free fatty acids, glycerols, or glycerides.

11. A fatty-acid based, pre-cure-derived coating for a medical device, comprising a cross-linked, fatty acid-derived biomaterial, wherein approximately 60-90% of the biomaterial is constituted by fatty acids with molecular weights below 500, wherein the coating comprises fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, and wherein the coating hydrolyzes in vivo into one or more of free fatty acids, glycerols, or glycerides.

12. A fatty-acid based, pre-cure-derived biomaterial suitable for achieving modulated healing in a tissue region in need thereof, wherein the biomaterial is administered in an amount sufficient to achieve the modulated healing, wherein the modulated healing comprises a modulation of platelet or fibrin deposition in or near the tissue region, wherein the biomaterial comprises one or more fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, and wherein the biomaterial hydrolyzes in vivo into one or more of free fatty acids, glycerols, or glycerides.

13. The biomaterial of claim 12 , wherein the tissue region is the vasculature of a subject.

14. A fatty-acid based, pre-cure-derived biomaterial suitable for achieving modulated healing at a site of vascular injury in need thereof, wherein the biomaterial is formed from one or more of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA) or alpha-linolenic acid (ALA), wherein the biomaterial comprises fatty acids cross-linked to each other by one or more of ester bonds or lactone bonds, wherein the biomaterial is administered in an amount sufficient to achieve the modulated healing, wherein the modulated healing comprises a modulation of at least one metric of organized tissue repair and wherein the biomaterial hydrolyzes in vivo into one or more of fatty acids, glycerols, or glycerides.

15. The fatty-acid based, pre-cure-derived biomaterial of claim 14 , wherein the vascular healing is the inflammatory stage of vascular healing.

16. The fatty-acid based, pre-cure-derived biomaterial of claim 14 , wherein the organized tissue repair comprises platelet or fibrin deposition at the site of vascular injury.

17. The fatty-acid based, pre-cure-derived biomaterial of claim 14 , wherein the modulation of at least one metric of organized tissue repair is a delay in the healing process at a site of vascular injury.

18. The fatty-acid based, pre-cure-derived biomaterial of claim 12 or 14 , wherein the biomaterial is administered to the region in need thereof via a catheter, balloon, stent, surgical mesh, surgical dressing, or graft.

19. The coating of claim 4 , wherein the coating hydrolyzes in vivo substantially into one or more of free fatty acids, glycerides, or glycerols.

20. The coating of claim 1 , wherein the coating comprises approximately 30-90% saturated fatty acids.

21. The coating of claim 1 , wherein the coating comprises approximately 30-80% unsaturated fatty acids.

22. The coating of claim 1 , wherein the coating further comprises a glyceride.

23. The coating of claim 1 , wherein the coating further comprises one or more of the group consisting of a glyceride, a glycerol, and a fatty alcohol, any of which can be partially cross-linked.

24. The coating of claim 1 , further comprising vitamin E.

25. The coating of claim 1 , wherein the coating is associated with an implantable device.

26. The coating of claim 1 , wherein the coating is associated with a medical device, and the medical device is a stent, a catheter, a surgical mesh, or a balloon.

27. The coating of claim 1 , wherein the therapeutic agent is an anti-proliferative drug, an anti-inflammatory agent, an antimicrobial agent or antibiotic agent.

28. The coating of claim 1 , wherein the therapeutic agent is Compound A, Compound B, Compound C, Compound D, Compound E, a cyclosporine derivative or rapamycin derivative.

29. The coating of claim 1 , wherein the coating has a release profile of the therapeutic agent in 0.01 M phosphate buffered saline (PBS) out to about 5-20 days.

30. The coating of claim 1 , wherein the coating releases the therapeutic agent at a desired release rate in vivo.

31. The coating of claim 1 , wherein the coating has a release profile of the therapeutic agent in 0.01 M phosphate buffered saline (PBS) out to more than 20 days.

32. The coating of claim 1 , wherein the coating comprises approximately 10-20% C 14 saturated fatty acids and approximately 25-50% C 16 satur

Assignees

• Faucher Keith M
• Tang Hui
• Martakos Paul
• Herweck Steve A
• Karwoski Theodore
• Sullivan Allison
• Melville Greg
• Corbeil Scott E
• Atrium Medical Corp

Inventors

• Faucher Keith M
• Tang Hui
• Martakos Paul
• Herweck Steve A
• Karwoski Theodore
• Sullivan Allison
• Melville Greg
• Corbeil Scott E

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title