Coated medical devices for the treatment of vascular disease

• US 20030060877A1
• Filed: 04/15/2002
• Published: 03/27/2003
• Est. Priority Date: 09/25/2001
• Status: Active Grant

• Current Assignee: Cardinal Health Switzerland 515 GmbH (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Falotico, Robert, Spaltro, John
• Granted Patent: US 7,195,640 B2
• Time in Patent Office: Days
• US Class Current: 623/1.42
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/0469 Suturing instruments for use in minimally invasive surgery, e.g. endoscopic surgery
• CPC Class Codes: A61B 17/0644 penetrating the tissue, deformable to closed position
• CPC Class Codes: A61B 17/11 for performing anastomosis; Buttons for anastomosis
• CPC Class Codes: A61B 17/115 Staplers for performing anastomosis in a single operation
• CPC Class Codes: A61B 2017/06028 by means of a cylindrical longitudinal blind bore machined at the suture-receiving end of the needle, e.g. opposite to needle tip
• CPC Class Codes: A61F 2/064 with special features to facilitate anastomotic coupling anastomosis of natural blood vessels A61B17/11
• 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 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/3008 radio-opaque, e.g. radio-opaque markers
• CPC Class Codes: A61F 2002/91533 characterised by the phase between adjacent bands
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 2250/0098 radio-opaque, e.g. radio-opaque markers
• CPC Class Codes: A61F 2310/0097 Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• CPC Class Codes: A61F 2310/00976 Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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 2300/608 : having two or more layers
• CPC Class Codes: A61L 27/34 : Macromolecular materials
• CPC Class Codes: A61L 29/085 : Macromolecular materials
• CPC Class Codes: A61L 31/022 : Metals or alloys
• 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: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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 27/12 : containing fluorine atoms
• CPC Class Codes: C08L 27/14 : Homopolymers or copolymers of vinyl fluoride
• CPC Class Codes: C08L 27/16 : Homopolymers or copolymers or vinylidene fluoride

Abstract

Medical devices, and in particular implantable medical devices, may be coated to minimize or substantially eliminate a biological organism'"'"'s reaction to the introduction of the medical device to the organism. The medical devices may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. In addition to reducing or substantially eliminating a biological organism'"'"'s reaction to the introduction of the medical device to the organism, the medical device in combination with one or more therapeutic drugs, agents and/or compounds may be utilized to treat various vascular diseases, for example, restenosis and vulnerable plaque. In the case of vulnerable plaque, one or more drugs, agents or compounds may be utilized to treat the various aspects of vulnerable plaque and these drugs, agents and/or compounds may be released with a given release profile for the most effective treatment. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned.

Claims

1. A medical device for the treatment of vascular disease comprising:

a scaffold structure for maintaining luminal patency;

a biocompatible vehicle affixed to at least a portion of the scaffold structure; and

one or more agents in therapeutic dosages incorporated into the biocompatible vehicle, wherein the biocompatible vehicle is configured to release the one or more agents over one or more time periods to treat both an acute phase and a chronic phase of the vascular disease.

2. The medical device for the treatment of vascular disease according to claim 1, wherein the scaffold structure comprises a stent.

3. The medical device for the treatment of vascular disease according to claim 2, wherein the stent is balloon expandable.

4. The medical device for the treatment of vascular disease according to claim 2, wherein the stent is self-expanding.

5. The medical device for the treatment of vascular disease according to claim 1, wherein the biocompatible vehicle comprises a polymeric coating.

6. The medical device for the treatment of vascular disease according to claim 5, wherein the polymeric coating comprises at least one layer configured to release the one or more agents at a first rate and for a first duration to treat the acute phase of the vascular disease and to release the one or more agents at a second rate and for a second duration to treat the chronic phase of the vascular disease, the first rate being faster than the second rate and the first duration being shorter than the second duration.

7. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a lipid lowering agent, the lipid lowering agent being incorporated into the at least one layer.

8. The medical device for the treatment of vascular disease according to claim 7, wherein the lipid lowering agent comprises an HMG co-enzyme reductase inhibitor or statin.

9. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antiinflammatory/inflammation blocking agent.

10. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antiproliferative.

11. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antithrombogenic.

12. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises rapamycin.

13. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises dexamethasone.

14. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises antiinflammatory corticosteroids.

15. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises rapamycin derivatives.

16. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises rapamycin analogs.

17. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a direct inhibitor of the target of rapamycin kinase (mTOR).

18. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a taxane, including paclitaxel and a taxane derivative that inhibits microtubule function.

19. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a cyclin dependent kinase inhibitor that will block the cell cycle.

20. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a retinoid.

21. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a growth factor receptor kinase inhibitor.

22. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a farnesyl transferase inhibitor.

23. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a P38 MAP kinase inhibitor.

24. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antagonist of tumor necrosis factor.

25. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a mast cell stabilizer.

26. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antioxidant.

27. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a protease inhibitor including a matrix metalloprotease inhibitor.

28. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises an antiapoptotic agent.

29. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a TGFbeta agonist.

30. The medical device for the treatment of vascular disease according to claim 6, wherein the one or more agents comprises a vitronectin antagonist.

31. A medical device for the treatment of atherosclerotic vulnerable plaque comprising:

a stent for maintaining vessel patentcy and providing structural support for a fibrous cap of the vulnerable plaque lesion;

a biocompatible vehicle affixed to at least a portion of the stent;

at least one first agent in a therapeutic dosage incorporated into the biocompatible vehicle for treating the fibrous cap of the vulnerable plaque lesion; and

at least one second agent in a therapeutic dosage incorporated into the biocompatible vehicle for treating a lipid core of the vulnerable plaque lesion, the biocompatible vehicle being configured to release the at least one first agent faster than the at least one second agent and to release the at least one first agent for a shorter duration than the at least one second agent.

32. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 31, wherein the stent is balloon expandable.

33. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 31, wherein the stent is self-expanding.

34. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 31, wherein the biocompatible vehicle comprises a polymeric coating.

35. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 34, wherein the polymeric coating comprises at least one layer configured to release the at least one first agent faster than the at least one second agent and to release the at least one first agent for a shorter duration than the at least one second agent.

36. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises an antiinflammatory/inflammation blocking agent.

37. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises an antiproliferative agent.

38. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises an antithrombogenic agent.

39. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises rapamycin.

40. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises dexamethasone.

41. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises antiinflammatory corticosteroids.

42. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one first agent comprises rapamycin derivatives.

43. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises rapamycin analogs.

44. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a direct inhibitor of the target of rapamycin kinase (mTOR).

45. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a taxane, including paclitaxel and a taxane derivative that inhibits microtubule function.

46. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a cyclin dependent kinase inhibitor that will block the cell cycle.

47. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a retinoid.

48. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a growth factor receptor kinase inhibitor.

49. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a farnesyl transferase inhibitor.

50. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a P38 MAP kinase inhibitor.

51. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises an antagonist of tumor necrosis factor.

52. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises a mast cell stabilizer.

53. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35 wherein the at least one first agent comprises an antioxidant.

54. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one second agent comprises a lipid lowering agent.

55. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 54, wherein the lipid lowering agent is an HMG co-enzyme reductase inhibitor or statin.

56. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 54, wherein the lipid lowering agent comprises rapamycin.

57. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one second agent comprises a protease inhibitor including a matrix metalloprotease inhibitor.

58. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one second agent comprises an antiapoptotic agent.

59. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one second agent comprises a TGFbeta agonist.

60. The medical device for the treatment of atherosclerotic vulnerable plaque according to claim 35, wherein the at least one second agent comprises a vitronectin antagonist.

61. A method for treating atherosclerotic vulnerable plaque comprising:

maintaining vessel patentcy and providing structural support for a fibrous cap of the vulnerable plaque lesion through the introduction of a coated stent;

releasing at least one first agent in a therapeutic dosage incorporated into the coated stent at a first rate and for a first duration for treating the fibrous cap of the vulnerable plaque lesion; and

releasing at least one second agent in a therapeutic dosage incorporated into the coated stent at a second rate and for a second duration for treating a lipid core of the vulnerable plaque lesion, the coated stent being configured to release the at least one first agent faster than the at least one second agent and to release the at least one first agent for a shorter duration than the at least one second agent.