Rate-reducing membrane for release of an agent

• US 7,014,913 B2
• Filed: 01/15/2004
• Issued: 03/21/2006
• Est. Priority Date: 09/27/2001
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D.
• Primary Examiner(s): Chen, Vivian
• Application Number:
  US10/760,132
• Publication Number:
  US 20040234737A1
• Time in Patent Office: 796 Days
• Field of Search: 428/212, 428/35.8, 428/36.9, 428/36.91, 428/421, 428/422, 428/500, 428/522, 428/521, 428/523, 428/423.1, 428/446, 428/447, 428/457, 623/1.11, 623/1.13, 623/1.15, 623/1.42, 623/1.43, 623/1.44, 623/1.46, 623/1.49, 427/2.1, 427/2.24, 427/2.25, 427/2.3, 427/384, 427/402, 427/407.1
• US Class Current: 428/212
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B05D 7/586 each layer being cured, at least partially, separately
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 53/02 of vinyl-aromatic monomers and conjugated dienes
• CPC Class Codes: C08L 53/025 modified
• CPC Class Codes: C09D 129/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C09D 153/02 Vinyl aromatic monomers and conjugated dienes
• CPC Class Codes: C09D 153/025 modified
• CPC Class Codes: Y10T 428/1355 Elemental metal containing [e.g., substrate, foil, film, coating, etc.]
• CPC Class Codes: Y10T 428/139 Open-ended, self-supporting conduit, cylinder, or tube-type article
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]
• CPC Class Codes: Y10T 428/24942 : including components having same physical characteristic in differing degree
• CPC Class Codes: Y10T 428/31504 : Composite [nonstructural laminate]
• CPC Class Codes: Y10T 428/3154 : Of fluorinated addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31544 : Addition polymer is perhalogenated
• CPC Class Codes: Y10T 428/31551 : Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31663 : As siloxane, silicone or silane
• CPC Class Codes: Y10T 428/31678 : Of metal
• CPC Class Codes: Y10T 428/31855 : Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31931 : Polyene monomer-containing
• CPC Class Codes: Y10T 428/31935 : Ester, halide or nitrile of addition polymer
• CPC Class Codes: Y10T 428/31938 : Polymer of monoethylenically unsaturated hydrocarbon

Abstract

A membrane that reduces the rate at which a therapeutic substance is released from an implantable medical device, such as a stent, is disclosed.

Claims

1. A stent having a therapeutic agent, comprising:

(a) a first coating or layer over a surface of a stent;

(b) a second coating or layer comprising a polymer and an agent over the first coating or layer; and

(c) a third coating or layer comprising a polymer over the second coating or layer, the polymer having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2 ,

wherein the third coating or layer reduces the rate of release of the agent.

2. The stent of claim 1, wherein the agent comprises rapamycin.

3. The stent of claim 1, wherein the agent comprises docetaxel or paclitaxel.

4. The stent of claim 1, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

5. The stent of claim 4, wherein the agent comprises rapamycin.

6. The stent of claim 4, wherein the agent comprises docetaxel or paclitaxel.

7. The stent of claim 1, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

8. The stent of claim 7, wherein the agent comprises rapamycin.

9. The stent of claim 7, wherein the agent comprises docetaxel or paclitaxel.

10. The stent of claim 1, wherein the polymer of the third coating or layer has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

11. The stent of claim 10, wherein the agent comprises rapamycin.

12. The stent of claim 10, wherein the agent comprises docetaxel or paclitaxel.

13. A stent having a therapeutic agent, comprising:

(a) a first coating or layer comprising a polymer and an agent for a stent; and

(b) a second coating or layer comprising a polymer over the first coating or layer, the polymer having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2, wherein the second coating or layer reduces the rate of release of the agent.

14. The stent of claim 13, wherein the agent comprises rapamycin.

15. The stent of claim 13, wherein the agent comprises docetaxel or paclitaxel.

16. The stent of claim 13, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

17. The stent of claim 16, wherein the agent comprises rapamycin.

18. The stent of claim 16, wherein the agent comprises docetaxel or paclitaxel.

19. The stent of claim 13, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

20. The stent of claim 19, wherein the agent comprises rapamycin.

21. The stent of claim 19, wherein the agent comprises docetaxel or paclitaxel.

22. The stent of claim 13, wherein the polymer of the second coating or layer has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

23. The stent of claim 22, wherein the agent comprises rapamycin.

24. The stent of claim 22, wherein the agent comprises docetaxel or paclitaxel.

25. The stent of claim 13, wherein the stent is a balloon expandable or self-expandable metallic stent.

26. The stent of claim 13, additionally comprising a primer beneath the first coating or layer.

27. A stent having a therapeutic agent, comprising:

(a) a first coating comprising a polymer and an agent for the stent; and

(b) a second coating comprising a polymer over the first coating, the second coating having a solubility parameter not greater than a parameter selected from the group consisting of about 11.5 (cal/cm³)^1/2, about 10 (cal/cm³)^1/2, and about 8.5 (cal/cm³)^1/2.

28. The stent of claim 27, wherein the agent is rapamycin.

29. The stent of claim 27, wherein the agent is docetaxel or paclitaxel.

30. The stent of claim 27, wherein the second coating has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

31. The stent of claim 30, wherein the agent is rapamycin.

32. The stent of claim 30, wherein the agent is docetaxel or paclitaxel.

33. A stent comprising a coating having a first region including rapamycin and a second region above the first region, the second region including a polymer having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2.

34. The stent of claim 33, wherein the polymer has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

35. The stent of claim 33, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

36. The stent of claim 33, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

37. A stent comprising a coating having a first region including docetaxel or paclitaxel and a second region above the first region, the second region including a polymer having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2 .

38. The stent of claim 37, wherein the polymer has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

39. The stent of claim 37, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

40. The stent of claim 37, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

41. A stent comprising a radially expandable metallic body and a coating on the body, the coating having a first region including rapamycin and a second region above the first region, the second region having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2.

42. The stent of claim 41, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

43. The stent of claim 41, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

44. The stent of claim 41, wherein the second region has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

45. A stent comprising a radially expandable metallic body and a coating on the body, the coating having a first region including docetaxel or paclitaxel and a second region above the first region, the second region having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2.

46. The stent of claim 45, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

47. The stent of claim 45, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

48. The stent of claim 45, wherein the second region has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

49. A method of forming a coating for a stent, comprising:

(a) forming a first coating or layer including an agent on the stent;

(b) forming a second coating or layer including a polymer over the first coating or layer, the polymer of the second coating or layer having a solubility parameter not greater than approximately 11.5 (cal/cm³)^1/2, wherein the second coating reduces the rate of release of the agent.

50. The method of claim 49, additionally including forming a primer on the surface of the stent, beneath the first coating or layer.

51. The method of claim 49, wherein the agent comprises rapamycin.

52. The method of claim 49, wherein the agent comprises docetaxel or paclitaxel.

53. The method of claim 49, wherein the solubility parameter is not greater than approximately 10 (cal/cm³)^1/2.

54. The method of claim 53, wherein the agent comprises rapamycin.

55. The method of claim 53, wherein the agent comprises docetaxel or paclitaxel.

56. The method of claim 49, wherein the solubility parameter is not greater than approximately 8.5 (cal/cm³)^1/2.

57. The method of claim 56, wherein the agent comprises rapamycin.

58. The method of claim 56, wherein the agent comprises docetaxel or paclitaxel.

59. The method of claim 49, wherein the polymer of the second coating has an equilibrium water absorption factor of less than about 5% by weight under physiologic conditions.

60. The method of claim 59, wherein the agent comprises rapamycin.

61. The method of claim 59, wherein the agent comprises docetaxel or paclitaxel.

62. The method of claim 49, wherein the forming the second coating or layer comprises applying a composition including the polymer and a non-polar solvent on the first coating or layer.

63. The method of claim 62, wherein the agent is polar.

64. The method of claim 49, wherein the forming the second coating or layer comprises applying a composition including the polymer and a solvent over the first coating or layer, wherein the agent doesn'"'"'t dissolve in the solvent.

65. The method of claim 49, wherein the forming the second coating or layer comprises applying a composition including the polymer and a solvent over the first coating or layer, wherein the composition does not cause a leaching out of the agent out from the first coating or layer.