Fluid treatment of a polymeric coating on an implantable medical device

• US 7,285,304 B1
• Filed: 06/25/2003
• Issued: 10/23/2007
• Est. Priority Date: 06/25/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D., Hossainy, Syed F. A., Ding, Ni
• Primary Examiner(s): CHEN, BRET P
• Application Number:
  US10/603,889
• Time in Patent Office: 1,581 Days
• Field of Search: 427/2.24, 427/2.25, 427/2.27
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

A method of manufacturing an implantable medical device including applying a composition to an implantable medical device, the composition including a polymer, an active agent and a solvent; allowing the solvent to evaporate to form a dry coating, the dry coating comprising less than about 2% residual fluid content (w/w); applying a fluid to the dry coating, the fluid being substantially free from any polymer; and allowing the fluid to evaporate from the coating.

Claims

1. A method of manufacturing a drug delivery implantable medical device, comprising:

applying a composition to an implantable medical device, the composition including a polymer, an active agent and a solvent;

allowing the solvent to evaporate to form a dry coating, the dry coating comprising less than about 2% residual fluid content (w/w);

applying a fluid to the dry coating, the fluid being substantially or completely free from any polymer; and

removing the fluid from the coating.

2. The method of claim 1, wherein fluid is substantially or completely free from any active agents.

3. The method of claim 1, wherein the active agent is at least partially soluble in the fluid.

4. The method of claim 1, additionally comprising prior to applying the composition, forming a primer layer on a surface of the implantable medical device.

5. The method of claim 1, additionally comprising forming a barrier layer on the dry coating wherein the application of the fluid is performed prior to forming the barrier layer.

6. The method of claim 1, wherein the device is a stent.

7. The method of claim 1, wherein the polymer comprises an ethylene vinyl alcohol copolymer, an ethylene-vinyl acetate copolymer, poly(vinylidene fluoride-co-hexafluoropropene), poly(butylmethacrylate), or a combination of the same.

8. The method of claim 1, wherein the dry coating comprises less than about 1% residual fluid content (w/w).

9. The method of claim 1, wherein the active agent is rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin, paclitaxel, docetaxel, or a functional analog or structural derivative thereof.

10. The method of claim 1, wherein subsequent to the act of applying the fluid the total content of the active agent in the coating is at least 80% of the total content of the active agent in the coating prior to application of the fluid.

11. The method of claim 1, wherein the duration of exposure of the fluid is sufficient to decrease the release rate of the active agent from the coating after the coating has been implanted into a biological lumen.

12. The method of claim 1, wherein applying the fluid includes spraying the fluid onto the coating or immersing the device into a bath of fluid.

13. The method of claim 12, wherein the device is immersed for about 30 minutes to about twelve hours.

14. The method of claim 1, wherein the fluid is selected from the group consisting of chloroform, acetone, water, dimethylsulfoxide, propylene glycol methyl ether, iso-propylalcohol, n-propylalcohol, methanol, ethanol, tetrahydrofuran, dimethylformamide, dimethylacetamide, benzene, toluene, xylene, hexane, cyclohexane, pentane, heptane, octane, nonane, decane, decalin, ethyl acetate, butyl acetate, isobutyl acetate, isopropyl acetate, butanol, diacetone alcohol, benzyl alcohol, 2-butanone, cyclohexanone, dioxane, methylene chloride, carbon tetrachloride, tetrachloroethylene, tetrachloroethane, chlorobenzene, 1,1,1-trichloroethane, formamide, hexafluoroisopropanol, 1,1,1-trifluoroethanol, acetonitrile, hexamethyl phosphoramide and a combination thereof.

15. The method of claim 1, wherein the fluid is only applied to a portion of the device along the length of the device.

16. The method of claim 1, wherein the solvent and the fluid are different.

17. The method of claim 1, wherein subsequent to the removal of the fluid, the release rate of the active agent is less than about 30% in 24 hours.

18. The method of claim 1, wherein the temperature of the fluid is greater than room temperature.

19. The method of claim 1, wherein the temperature of the fluid is equal to or greater than the glass transition temperature of the polymer.

20. The method of claim 1, wherein the application of the fluid to the dry coating causes the percent crystallinity of the polymer in the coating to increase.

21. The method of claim 1, wherein the polymer is a blend of two or more polymers.

22. The method of claim 1, wherein the polymer is a semicrystalline polymer having about 10 to 75 percent crystallinity prior to the application of the fluid.

23. The method of claim 1, wherein the polymer is a block copolymer or a graft copolymer.

24. The method of claim 1, wherein the polymer exhibits two or more glass transition temperatures, and wherein the temperature of the fluid is equal to or greater than the lowest exhibited glass transition temperature of the polymer.

25. The method of claim 1, wherein the polymer exhibits two or more glass transition temperatures, and wherein the temperature of the fluid is equal to or greater than the highest exhibited glass transition temperature of the polymer.

32. The method of claim 1, wherein the polymer comprises a polyvinyl aromatic polymer.

35. The method of claim 1, wherein the fluid is completely free from any polymer.

36. The method of claim 1, wherein the fluid is completely free from any polymer and is substantially or completely free from the active agent.

37. The method of claim 1, wherein the fluid is completely free from any polymer and is completely free from the active agent.

38. The method of claim 1, wherein the fluid is completely free from the active agent.

39. The method of claim 1, wherein the fluid is substantially free from the active agent.

43. The method of claim 1, wherein the composition forms a reservoir layer and wherein the dry coating includes a barrier layer formed over the reservoir layer prior to application of the fluid.

44. The method of claim 1, wherein the fluid is removed by evaporation.

26. A method of manufacturing a stent coating, comprising:

applying a composition to a stent, the composition including a semicrystalline polymer and a solvent;

allowing the solvent to evaporate to form a dry coating, the dry coating comprising less than about 2% residual fluid content (w/w); and

exposing the coating to a fluid for a sufficient duration to increase the crystallinity of the polymer in at least a portion of the coating, the fluid being substantially or completely free from any polymer; and

removing the fluid from the coating.

27. The method of claim 26, wherein the polymer has about 10 to 75 percent crystallinity prior to the act of exposing.

28. The method of claim 26, wherein the polymer comprises an ethylene vinyl alcohol copolymer or poly(vinylidene fluoride-co-hexafluoropropene).

29. The method of claim 26, wherein the dry coating comprises less than about 1% residual fluid content (w/w).

30. The method of claim 26, wherein exposing the coating to a fluid includes immersing the stent into a bath of fluid.

31. The method of claim 30, wherein the stent is immersed for about 30 minutes to about twelve hours.

33. The method of claim 26, wherein the polymer comprises a polyvinyl aromatic polymer.

34. The method of claim 26 wherein the composition further comprises an active agent.

40. The method of claim 26, wherein the fluid is completely free from any polymer.

41. The method of claim 26, wherein the fluid is substantially free from an active agent.

42. The method of claim 26, wherein the fluid is completely free from an active agent.

45. The method of claim 26, wherein the fluid is removed by evaporation.

46. The method of claim 26, wherein the fluid is completely free of any polymer and is completely free from an active agent.