Cross-linked fatty acid-based biomaterials

• US 9,012,506 B2
• Filed: 12/01/2008
• Issued: 04/21/2015
• Est. Priority Date: 09/28/2004
• Status: Expired due to Fees

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Faucher, Keith M., Tang, Hui, Ferraro, Joseph, Martakos, Paul, Herweck, Steve A., Karwoski, Theodore, Corbeil, Scott E.
• Primary Examiner(s): Basquill, Sean
• Assistant Examiner(s): Rosenthal, Andrew S
• Application Number:
  US12/325,546
• Publication Number:
  US 20090181937A1
• Time in Patent Office: 2,332 Days
• Field of Search: 514/558
• US Class Current: 514/558
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution

Abstract

Fatty acid-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.

Claims

1. A coating for a medical device, comprising fatty acids cross-linked directly to each other by ester or lactone bonds;

wherein the fatty acids comprise approximately 5-50% C₁₆ fatty acids; and

wherein the coating hydrolyzes in vivo.

2. The coating of claim 1, wherein the fatty acids comprise 5-25% C₁₄ fatty acids.

3. The coating of claim 1, wherein the fatty acids comprise 5-30% C₁₆ fatty acids.

14. The coating of any one of claim 1 or 5, wherein the coating comprises lactone cross-links and ester cross-links.

15. The coating of any one of claim 1, 5, 8-9 or 13, wherein the coating contains disordered hydrocarbon chains as determined by infrared absorption and X-ray diffraction.

16. The coating of any one of claim 1, 8-9 or 13, wherein the coating breaks down in vivo into fatty acids, glycerols, and glycerides.

17. The coating of any one of claim 1, 5, 8-9 or 13, wherein the coating comprises approximately 30-90% saturated fatty acids.

18. The coating of any one of claim 1, 5, 8-9 or 13, wherein the coating comprises approximately 30-80% unsaturated fatty acids.

19. The coating of any one of claim 1, 5, or 8-9, wherein the coating further comprises a glyceride.

20. The coating of any one of claim 1, 5, or 8-9, wherein the coating further comprises one or more of the groups consisting of a glyceride, a glycerol, and a fatty alcohol, any of which can be partially cross-linked.

21. The coating of any one of claim 1, 5, 8-9 or 13, wherein the coating does not contain an external cross-linking agent.

22. The coating of any one of claim 1, 5, 9 or 13, wherein the source of the fatty acids and glycerides is an oil.

23. The coating of claim 22, wherein the oil is a fish oil, olive oil, grape oil, palm oil, or flaxseed oil.

24. The coating of claim 22, wherein the oil is a fish oil.

25. The coating of any one of claim 1, 5, 8-9 or 13, further comprising vitamin E.

26. The coating of any one of claim 1, 5, 8-9 or 13, 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 any one of claim 1, 5, 8-9 or 13, further comprising a therapeutic agent.

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

29. The coating of claim 27, wherein the therapeutic agent is Compound A, Compound B, Compound C, Compound n, Compound E, a cyclosporine derivative or rapamycin derivative.

4. A coating for a medical device comprising fatty acids cross-linked directly to each other by ester or lactone bonds;

wherein the coating hydrolyzes in vivo into free fatty acids, glycerides and glycerol; and

wherein the coating is formed from one or more of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), or alpha-linolenic acid (ALA).

5. A coating for a medical device, comprising fatty acids cross-linked directly to each other by ester or lactone bonds;

wherein the fatty acids comprise approximately 5-25% C₁₄ fatty acids and 5-50% C₁₆ fatty acids; and

wherein the coating hydrolyzes in vivo substantially into one or more of free fatty acids, glycerides, or glycerol.

6. A coating for a medical device comprising fatty acids and glycerides;

wherein the fatty acids are cross-linked directly 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.

7. A 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 directly to each other by one or more of ester bonds, or lactone bonds; and

wherein the coating hydrolyzes in vivo.

8. The coating of claim 7, wherein the coating has a peak from approximately 1740-1830 cm⁻

1, as indicated by an infrared absorption spectrum.

9. The coating of claim 7, wherein the biomaterial comprises approximately 60-90% fatty acids with molecular weights below 500.

10. The coating of claim 7, wherein the fatty acid is stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, or gamma-linolenic acid.

11. The coating of claim 7, wherein the source of the fatty acid is an oil.

12. The coating of claim 11, wherein the oil is a fish oil, olive oil, grape oil, palm oil, or flaxseed oil.

48. The coating of claim 7, wherein the fatty acid-derived biomaterial comprises delta lactones.

13. A 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 directly to each other by one or more of ester bonds, or lactone bonds;

wherein the coating hydrolyzes in vivo; and

wherein the coating has a contact angle of approximately 90-110 degrees when initially exposed to 0.1 M PBS solution, and, after approximately one hour of exposure, has a contact angle of 50-70 degrees.

30. A method of preparing a coating for a medical device, comprising heating a fatty acid-containing oil in the presence of oxygen, such that:

the double bonds of the oil are oxidized;

fatty acids and glycerides are formed; and

fatty acids cross-linked directly to each other by one or more of ester bonds or lactone bonds are formed;

such that the coating formed hydrolyzes in vivo substantially into one or more of free fatty acids, glycerides, or glycerol.

31. The method of claim 30, wherein the oil is continually heated, without interruption.

34. The method of claim 30 or 32, wherein the oil is heated at approximately 140°

F. to approximately 300°

F.

35. The method of claim 30 or 32, wherein the oil is fish oil.

36. The method of claim 30 or 32, further including adding a therapeutic agent.

37. A non-polymeric, medical device coating produced by the method of claim 30 or 32.

38. The coating of claim 37, further associated with a medical device.

39. The coating of claim 38, wherein the coating is combined with an organic solvent, and sprayed on a medical device.

32. A method of preparing a coating for a medical device comprising heating a fatty acid-containing oil in the presence of oxygen, such that:

the double bonds of the oil are oxidized;

water, hydrocarbons and aldehydes are volatilized; and

fatty acids cross-linked directly to each other by one or more of ester bonds or lactone bonds are formed;

such that the coating formed hydrolyzes in vivo substantially into one or more of free fatty acids, glycerides, or glycerol.

33. The method of claim 32, wherein the oil is continually heated, without interruption.

40. A method of forming a fatty acid-derived biomaterial, comprising:

continued heating of a fatty acid, followed by the cleavage of C═

C double bonds, which convert the fatty acids into oxidation byproducts, and fatty acids cross-linked directly to each other by one or more of ester bonds or lactone bonds are formed;

wherein the fatty acid-derived biomaterial formed hydrolyzes in vivo.

41. The method of claim 40, wherein the oxidation byproducts are one or more of aldehydes, ketones, alcohols, fatty acids, esters, lactones, ethers, or hydrocarbons.

42. The method of claim 40, wherein the byproducts remain within the coating and/or are volatilized during the heating process.

43. The method of claim 40, wherein the cross-links are ester cross-links and lactone cross-links, wherein the ester cross-links and lactone cross-links occur via esterification, alcoholysis, acidolysis, or interesterfication.

44. A method of forming a fatty acid-derived biomaterial, comprising:

continued heating of a fatty acid, thereby oxidizing the double bonds of the unsaturated fatty acid chains while predominantly preserving triglyceride ester functional groups;

thereby increasing the viscosity of the biomaterial;

wherein the fatty acid-derived biomaterial comprises fatty acids cross-linked directly to each other by one or more of ester bonds or lactone bonds; and

wherein the fatty acid-derived biomaterial formed hydrolyzes in vivo.

45. A stand-alone film, comprising:

a non-polymeric, cross-linked fatty acid, comprising approximately 5-50% C₁₆ fatty acids.

46. A method of treating soft tissue damage in a subject in need thereof, comprising administering to the damaged tissue of the subject the stand-alone film of claim 45.

47. A coating for a medical device, comprising fatty acids cross-linked directly to each other by ester or lactone bonds;

wherein the fatty acids comprise approximately 5-50% C₁₆ fatty acids;

wherein the coating hydrolyzes in vivo; and

wherein the coating is formed from an oil comprising at least 40% polyunsaturated fatty acids.