COATED MEDICAL DEVICES INCLUDING A WATER-INSOLUBLE THERAPEUTIC AGENT

• US 20130303983A1
• Filed: 03/15/2013
• Published: 11/14/2013
• Est. Priority Date: 05/09/2012
• Status: Active Application

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Inventors: Shirley, Gary B., Barnett, Angela R., Barbick, Julia E., Sarasam, Aparna R., Grable, Charity
• Application Number:
  US13/834,339
• Publication Number:
  US 20130303983A1
• Time in Patent Office: Days
• US Class Current: 604/103.02
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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: A61M 2025/1004 Balloons with folds, e.g. folded or multifolded
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 2025/109 having balloons for removing solid matters, e.g. by grasping or scraping plaque, thrombus or other matters that obstruct the flow
• CPC Class Codes: A61M 25/1002 characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof
• CPC Class Codes: C08L 5/10 : Heparin; Derivatives thereof

Abstract

A medical device includes an implantable structure and a coating layer including a water-insoluble therapeutic agent and one or more additives selected from heparin, heparan sulfate, dextran and dextran sulfate, and physiologically-acceptable salts thereof. The one or more additives can be present in an amount effective to increase the rate of release of the water-insoluble therapeutic agent from the coating layer. The implantable medical device structure can be an expandable structure such as a balloon or stent. Also described are methods of making and using such implantable medical devices and coating layers.

Claims

1. A medical device, comprising:

an implantable medical device structure having a surface; and

a coating layer carried by the surface and including;

(i) a water-insoluble therapeutic agent; and

(ii) one or more additives selected from heparin, heparan sulfate, dextran, and dextran sulfate; and

physiologically-acceptable salts thereof.

2. The medical device of claim 1, wherein the implantable medical device structure is an expandable structure.

3. The medical device of claim 2, wherein the expandable structure is a balloon.

4. The medical device of claim 3, wherein the balloon is an angioplasty balloon.

5. The medical device of claim 3, wherein the balloon has a balloon wall in a folded condition.

6. The medical device of claim 2, wherein the expandable structure is a stent.

7. The medical device of claim 1, wherein the water-insoluble therapeutic agent is an immunosuppressive agent, an antiproliferative agent, a microtubule stabilizing agent, a restenosis-inhibiting agent, or an inhibitor of the mammalian target of rapamycin.

8. The medical device of claim 1, wherein the water-insoluble therapeutic agent is a taxane compound.

9. The medical device of claim 8, wherein the taxane compound is paclitaxel.

10. The medical device of claim 1, wherein the therapeutic agent is a macrolide immunosuppressive agent.

11. The medical device of claim 10, wherein the macrolide immunosuppressive agent is sirolimus, pimecrolimus, tacrolimus, everolimus, zotarolimus, novolimus, myolimus, temsirolimus, deforolimus, or biolimus.

12. The medical device of claim 1, wherein the coating layer is adhered directly to the surface of the implantable medical device structure.

13. The medical device of claim 1, wherein the water-insoluble therapeutic agent is included in the coating layer in a weight ratio in the range of about 20:

1 to about 1;

1 relative to said one or more additives.

14. The medical device of claim 1, wherein the water-insoluble therapeutic agent is included in the coating layer in a weight ratio in the range of about 20:

1 to about 2;

1 relative to said one or more additives.

15. The medical device of claim 1, wherein the one or more additives includes heparin.

16. The medical device of claim 1, wherein the one or more additives is present in an amount effective to increase the rate of release of the water-insoluble therapeutic agent from the coating layer.

17. The medical device of claim 1, wherein the one or more additives is present in an amount effective to increase the rate of release of the water-insoluble therapeutic agent from the coating layer when immersed in a 0.2% aqueous solution of Heptakis (2,6-di-O-methyl)-beta-cyclodextrin under static conditions at 37°

C.

18. The medical device of claim 1, wherein the water-insoluble therapeutic agent is a restenosis-inhibiting agent.

19. The medical device of claim 1, wherein the one or more additives includes heparin or a physiologically-acceptable salt thereof, having a weight average molecular weight in the range of about 2000 to about 40000 Daltons.

20. The medical device of claim 1, wherein the one or more additives includes heparin sodium.

58. A method for treating a patient, comprising:

implanting in the patient an implantable medical device structure of a medical device according to claim 1.

21. A medical device, comprising:

a catheter shaft;

an inflatable balloon mounted on the catheter shaft; and

a coating layer carried by the inflatable balloon and including;

(i) a water-insoluble therapeutic agent; and

(ii) one or more additives selected from heparin, heparan sulfate, dextran and dextran sulfate; and

physiologically-acceptable salts thereof.

22. The medical device of claim 21, wherein the coating layer is adhered directly to a balloon wall of the inflatable balloon.

23. The medical device of claim 22, wherein:

the water-insoluble therapeutic agent is a restenosis-inhibiting agent; and

the restenosis-inhibiting agent is included in the coating layer in a weight ratio in the range of about 20;

1 to about 1;

1 relative to said one or more additives.

24. The medical device of claim 21, wherein:

the water-insoluble therapeutic agent is paclitaxel;

the coating layer comprises the paclitaxel at a level of about 1 micrograms/mm² to about 10 micrograms/mm²; and

the coating layer comprises heparin sodium at a level less than the paclitaxel and in the range of about 0.05 to about 2 micrograms/mm².

25. A medical device, comprising:

an implantable medical device structure having a surface; and

a coating layer carried by the surface and including;

(i) paclitaxel or a macrolide immunosuppressive agent; and

(ii) at least one additive selected from heparin, heparan sulfate, dextran, and dextran sulfate; and

physiologically-acceptable salts thereof.

26. The medical device of claim 25, wherein the implantable medical device structure is an expandable structure.

27. The medical device of claim 26, wherein the expandable structure is a balloon.

28. The medical device of claim 26, wherein the balloon is a vascular angioplasty balloon.

29. The medical device of claim 27, wherein the balloon has a balloon wall in a folded condition.

30. The medical device of claim 26, wherein the expandable structure is a stent.

31. The medical device of claim 25, wherein the at least one additive includes heparin or a physiologically-acceptable salt thereof, having a weight average molecular weight in the range of about 2000 to about 40000 Daltons.

32. The medical device of claim 25, wherein the coating layer is adhered directly to the surface of the implantable medical device structure.

33. The medical device of claim 25, wherein the paclitaxel or macrolide immunosuppressive agent is included in the coating layer in a weight ratio in the range of about 20:

1 to about 1;

1 relative to said one or more additives.

34. The medical device of claim 25, wherein the paclitaxel is included in the coating layer in a weight ratio in the range of about 20:

1 to about 2;

1 relative to said one or more additives.

35. The medical device of claim 25, wherein the coating layer includes paclitaxel and heparin sodium, and wherein the paclitaxel is included in the coating layer in a weight ratio in the range of about 12:

1 to about 7;

1 relative to the heparin sodium.

36. The medical device of claim 35, wherein the paclitaxel is included in the coating layer in a weight ratio in the range of about 12:

1 to about 9;

1 relative to the heparin sodium.

37. The medical device of claim 25, wherein the coating layer includes the paclitaxel or macrolide immunosuppressive agent at a level of about 0.1 to about 10 micrograms/mm², and wherein the coating layer includes the one or more additives at a level of about 0.05 to 2 micrograms/mm².

38. A method for manufacturing a medical device, comprising:

applying a flowable medium comprising liquid, a water-insoluble therapeutic agent and one or more additives selected from heparin, heparan sulfate, dextran and dextran sulfate, and physiologically-acceptable salts thereof, to a surface of an implantable medical device structure or to a surface of a coating layer carried by the implantable medical device structure; and

removing liquid from the medium to form a coating layer comprising the water-insoluble therapeutic agent and the one or more additives.

39. The method of claim 38, wherein the liquid comprises water.

40. The method of claim 38, wherein the liquid comprises an organic solvent.

41. The method of claim 40, wherein the organic solvent is water-miscible.

42. The method of claim 38, wherein the liquid comprises less than about 20% by volume water.

43. The method of claim 38, wherein said removing comprises evaporating.

44. The method of claim 38, wherein the implantable medical device structure is an expandable structure.

45. The method of claim 38, wherein the implantable medical device structure is a balloon.

46. The method of claim 45, wherein the balloon is a vascular angioplasty balloon.

47. The method of claim 45, wherein the balloon has a balloon wall in a folded condition.

48. The method of claim 38, wherein the implantable medical device structure is a stent.

49. The method of claim 38, wherein the water-insoluble therapeutic agent is a taxane.

50. The method of claim 49, wherein the taxane is paclitaxel.

51. The method of claim 38, wherein the water-insoluble therapeutic agent is an inhibitor of the mammalian target of rapamycin.

52. The method of claim 51, wherein the inhibitor is a macrolide immunosuppressive agent.

53. The method of claim 38, wherein the at least one additive includes heparin or a physiologically-acceptable heparin salt, having a weight average molecular weight in the range of about 2000 to about 40000 Daltons.

54. The method of claim 38, wherein the water-insoluble therapeutic agent is present in the flowable medium in a weight ratio in the range of about 20:

1 to about 1;

1 with respect to the one or more additives.

55. The method of claim 38, wherein the one or more additives is present in an amount effective to increase the rate of release of the water-insoluble therapeutic agent from the coating layer.

56. The method of claim 38, wherein the water-insoluble therapeutic agent is a restenosis-inhibiting agent.

57. The method of claim 38, wherein the one or more additives includes heparin sodium.

59. A coating layer including (i) a water-insoluble therapeutic agent and (ii) one or more additives selected from heparin, heparan sulfate, dextran and dextran sulfate, and physiologically acceptable salts thereof, for delivery of the water-insoluble therapeutic agent from an implantable medical device structure.

60. The coating layer of claim 59, wherein the implantable medical device structure is configured for temporary or permanent implantation in a vascular vessel of a patient, and wherein the water-insoluble therapeutic agent is a restenosis-inhibiting agent.

61. The coating layer of claim 59, wherein the water-insoluble therapeutic agent is paclitaxel.

62. The coating layer of claim 59, wherein the implantable medical device structure is an expandable structure.

63. The coating layer of claim 59, wherein the at least one additive includes heparin or a physiologically-acceptable salt thereof.

64. The coating layer of claim 59, wherein the heparin or physiologically-acceptable salt thereof is present in the coating layer at a level of about 0.05 to about 2 micrograms/mm².

65. The coating layer of claim 59, wherein:

the water-insoluble therapeutic agent is present in the coating layer in a weight ratio in the range of about 20;

1 to about 1;

1 with respect to said one or more additives.

66. The coating layer of claim 59, wherein:

said at least one additive is present in the coating layer in an effective amount to increase the rate of release of the water-insoluble therapeutic agent from the coating layer.