COATINGS FOR IMPLANTABLE MEDICAL DEVICES

Abstract

A composition comprising at least one polymer covalently bonded to heparin, and at least one pharmaceutically active agent other than heparin dispersed within the at least one polymer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the invention will be understood from the following description, the appended claims and the accompanying drawings, in which:

FIG. 1 is a visual schematic of an embodiment of a biological mechanism by which heparin acts;

FIG. 2 is a schematic of the action of sirolimus on cell division; and

FIG. 3 is an experimental set-up for a heparinization process for poly(l-lactide).

Claims

1. A composition comprising at least one polymer covalently bonded to heparin, and at least one pharmaceutically active agent other than heparin dispersed within the at least one polymer.

2. The composition of claim 1, wherein the at least one polymer is biodegradable.

3. The composition of claim 1, wherein the at least one polymer is chosen from poly(l-lactide), racemic polylactide, poly(l-lactide-co-glycolide), racemic poly(l-lactide-co-glycolide), poly(l-lactide-co-caprolactone poly(d,l-lactide-co-caprolactone), poly(l-lactide-co-trimethylene carbonate) and poly(d,l-lactide-co-trimethylene carbonate).

4. The composition of claim 1, wherein the at least one polymer is chosen from polylactides.

5. An implantable medical device, comprising: a coating on at least a portion of the medical device, the coating comprising at least one polymer covalently bonded to heparin; andat least one pharmaceutically active agent other than heparin dispersed within the at least one polymer.

6. The device of claim 5, wherein the at least one polymer is biodegradable.

7. The device of claim 5, wherein the at least one polymer is chosen from poly(l-lactide), racemic polylactide, poly(l-lactide-co-glycolide), racemic poly(l-lactide-co-glycolide), poly(l-lactide-co-caprolactone poly(d,l-lactide-co-caprolactone), poly(l-lactide-co-trimethylene carbonate) and poly(d,l-lactide-co-trimethylene carbonate).

8. The device of claim 5, wherein the at least one polymer is chosen from polylactides.

9. The device of claim 6, wherein the coating comprises at least two biodegradable polymers.

10. The device of claim 5, wherein the device is selected from sutures, staples, anastomosis devices, vertebral disks, bone pins, suture anchors, hemostatic barriers, clamps, screws, plates, clips, vascular implants, tissue scaffolds, bone substitutes, intraluminal devices, and vascular supports.

11. The device of claim 5, wherein the device is implantable into a mammalian lumen.

12. The device of claim 5, wherein the device is a stent.

13. The device of claim 12, wherein the concentration of the at least one pharmaceutically active agent based on the surface area of the stent ranges from 0.1 to about 5 μm/mm2.

14. The device of claim 12, wherein the concentration of the at least one pharmaceutically active agent based on the surface area of the stent ranges from about 0.7 μm/mm2 to about 3.0 μm/mm2.

15. The device of claim 12, wherein the concentration of the at least one pharmaceutically active agent based on the surface area of the stent ranges from about 1.0 to about 1.8 μm/mm2

16. The device of claim 12, wherein the concentration of the at least one pharmaceutically active agent based on the surface area of the stent ranges from about 1.0 to about 1.4 μm/mm2.

17. The device of claim 5, wherein the coating contacts the medical device.

18. The device of claim 5, wherein the coating contacts at least one inner coating that contacts the medical device.

19. The device of claim 18, wherein the at least one inner coating is chosen from ceramics, nonbiodegradable polymers, metals, and carbon.

20. The device of claim 5, wherein the device further comprises a protective coating over the coating, wherein the protective coating is free of a pharmaceutically active agent.

21. The device of claim 20, wherein the protective coating comprises at least one biodegradable polymer.

22. The device of claim 5, wherein the at least one biodegradable polymer is covalently bonded to heparin.

23. The device of claim 5, wherein the device further comprises at least one additional coating comprising a polymer covalently bonded to heparin, the at least one additional coating comprising at least one pharmaceutically active agent.

24. The device of claim 23, wherein at least one of the polymers in the at least one additional coating is biodegradable.

25. The device of claim 23, wherein the device comprises at least two additional coatings.

26. The device of claim 23, wherein the device comprises at least one additional coating and a protective coating.

27. The device of claim 5, wherein the at least one pharmaceutically active agent is nonpolar.

28. The device of claim 5, wherein the at least one pharmaceutically active agent is chosen from antithrombotics, anticoagulants, antiplatelet agents, thrombolytics, antiproliferatives, anti-inflammatories, antimitotic, antimicrobial, agents that inhibit restenosis, smooth muscle cell inhibitors, antibiotics, fibrinolytic, immunosuppressive, and anti-antigenic agents.

29. The device of claim 5, wherein the at least one pharmaceutically active agent is chosen from paclitaxel, sirolimus, and flavonoids.

30. The device of claim 29, wherein the flavonoid is selected from chalcones, dihydrochalcones, flavanones, flavonols, dihydroflavonols, flavones, flavanols, isoflavones, neoflavones, aurones, anthocyanidins, proanthocyanidins and isoflavanes.

31. The device of claim 29, wherein the flavonoid is selected from flavanones, flavonols, and isoflavones.

32. The device of claim 29, wherein the flavonoid is selected from narigenin, naringin, eriodictyol, hesperetin, hesperidin (esperidine), kampferol, quercetin, rutin, cyanidol, meciadonol, catechin, epi-gallocatechin-gallate, taxifolin (dihydroquercetin), genistein, genistin, daidzein, biochanin, glycitein, chrysin, diosmin, luetolin, apigenin, tangeritin and nobiletin.

33. The device of claim 5, wherein the at least one pharmaceutically active agent is paclitaxel.

34. The device of claim 5, wherein the at least one pharmaceutically active agent is sirolimus.

35. The device of claim 5, wherein the at least one pharmaceutically active agent is genistein.

36. The device of claim 5, wherein the at least one polymer degrades by hydrolysis in a natural intraluminal human body environment at preselected rates of degradation.

37. A stent comprising a coating comprising a heparinized biodegradable polymer and paclitaxel dispersed within the polymer.

38. A stent comprising a coating comprising a heparinized biodegradable polymer and rapamycin dispersed within the polymer.

39. A stent comprising a coating comprising a heparinized biodegradable polymer and genistein dispersed within the polymer.

40. The stent of claim 39, wherein the coating further comprises rapamycin.

41. A method of treating at least one disease or condition associated with vascular injury or angioplasty comprising, implanting in a subject in need thereof a medical device having a coating for at least a portion thereof comprising a composition comprising at least one polymer covalently bonded to heparin, and at least one pharmaceutically active agent other than heparin dispersed within the at least one polymer.

42. The method of claim 41, wherein the at least one disease or condition is a proliferative disorder.

43. The method of claim 42, wherein the proliferative disorder is restenosis.

44. The method of claim 42, wherein the proliferative disorder is a tumor.

45. The method of claim 42, wherein the proliferative disorder comprises the proliferation of smooth muscle cells.

46. The method of claim 41, wherein the at least one disease or condition is an inflammatory disease.

47. The method of claim 41, wherein the at least one disease or condition is an autoimmune disease.

48. The method of claim 41, wherein the at least one disease or condition is neointima and neointimal hyperplasia.

49. The method of claim 41, wherein the at least one disease or condition is selected from thrombosis, embolism, and platelet accumulation.

50. A composition comprising at least one polymer covalently bonded to heparin, and at least one pharmaceutically active agent other than heparin contained within the at least one polymer either covalently bound or ionically bound or unbound to the polymer.

51. A medical device having a coating comprising the composition of claim 50, on at least a portion of the surface thereof.

52. The device of claim 51, wherein the device comprises one or more additional polymer coatings comprising the same as or a different polymer from the at least one polymer wherein the one or more additional polymer coatings either contain or do not contain one or more pharmaceutically active agents that are the same as or different from the at least one pharmaceutically active agent.

53. The device of claim 51, wherein the device comprises one or more additional polymer coatings containing covalently bound heparin.