Expandable medical device for delivery of beneficial agent

• US 7,208,010 B2
• Filed: 09/07/2001
• Issued: 04/24/2007
• Est. Priority Date: 10/16/2000
• Status: Expired due to Term

• Current Assignee: Conor Medsystems Incorporated
• Original Assignee: Conor Medsystems Incorporated
• Inventors: Eigler, Neal L., Park, Kinam, Shanley, John F., Edelman, Elazer R.
• Primary Examiner(s): Stewart; Alvin J.
• Assistant Examiner(s): Blanco; Javier G.
• Application Number:
  US09/948,989
• Publication Number:
  US 20020082680A1
• Time in Patent Office: 2,055 Days
• Field of Search: 623 115- 117, 623/1.39, 623 142- 146, 427/2.24, 427/2.25, 606/194
• US Class Current: 623/1.42
• 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 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2250/003 differing in adsorbability or resorbability, i.e. in adsorption or resorption time
• CPC Class Codes: A61F 2250/0031 made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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

Abstract

An expandable medical device has a plurality of elongated struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter. At least one of the plurality of struts includes at least one opening extending at least partially through a thickness of the strut. A beneficial agent is loaded into the opening within the strut in layers to achieve desired temporal release kinetics of the agent. Alternatively, the beneficial agent is loaded in a shape which is configured to achieve the desired agent delivery profile. A wide variety of delivery profiles can be achieved including zero order, pulsatile, increasing, decrease, sinusoidal, and other delivery profiles.

Claims

1. An expandable medical device comprising:

a plurality of elongated struts, said plurality of elongated struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, said plurality of struts each having a strut width in a circumferential direction and a strut thickness in a radial direction;

at least one strut opening in at least one of the plurality of struts, the strut opening extending through the strut with the strut opening having a substantially constant cross section from a radially outermost surface of the strut to a radially innermost end of the strut opening; and

at least one beneficial agent provided in the at least one strut opening in a plurality of layers, wherein the beneficial agent is provided into the at least one opening without coating the outermost surface.

2. The expandable medical device according to claim 1, wherein said at least one strut opening comprises a plurality of strut openings.

3. The expandable medical device according to claim 1, wherein said plurality of beneficial agent layers include layers of different chemical compositions.

4. The expandable medical device according to claim 3, wherein said different chemical compositions include a barrier composition and an active beneficial agent composition.

5. The expandable medical device according to claim 4, wherein said barrier composition has an opening formed therein.

6. The expandable medical device according to claim 3, wherein said different chemical compositions include different active beneficial agents.

7. The expandable medical device according to claim 6, wherein said different active beneficial agents include anti-thrombotic agents and anti-proliferative agents.

8. The expandable medical device according to claim 1, wherein said plurality of beneficial agent layers include layers of beneficial agent having the same chemical composition in different concentrations.

9. The expandable medical device according to claim 1, wherein said plurality of beneficial agent layers include a baffler layer at a radially innermost location in the at least one opening.

10. The expandable medical device according to claim 1, wherein the plurality of beneficial agent layers include a baffler layer between two active beneficial agent layers.

11. The expandable medical device according to claim 1, wherein said beneficial agent is formulated to be activated by a systemically applied agent.

12. The expandable medical device according to claim 11, wherein said systemically applied agent is ultrasound.

13. The expandable medical device according to claim 11, wherein said systemically applied agent is a chemical agent.

14. The expandable medical device according to claim 1, wherein the beneficial agent is contained in microspheres.

15. The expandable medical device according to claim 14, wherein said plurality of layers include layers with microspheres of different sizes.

16. The expandable medical device according to claim 1, wherein the strut opening has a shape configured to vary the release rate of a beneficial agent over time.

17. The expandable medical device according to claim 1, wherein the beneficial agent is provided in the at least one opening in a biodegradable carrier.

18. The expandable medical device according to claim 1, wherein the beneficial agent is configured to diffuse from a carrier in the opening.

19. The expandable medical device according to claim 1, wherein the beneficial agent layers include a bio-degradable barrier layer configured to terminate a therapy at a predetermined time.

20. The expandable medical device according to claim 1, wherein the beneficial agent is paclitaxel.

21. The expandable medical device according to claim 1, wherein the beneficial agent is rapamycin.

22. The expandable medical device according to claim 1, wherein the plurality of beneficial agent layers are substantially cylindrical.

23. The expandable medical device according to claim 1, further comprising a barrier layer at a first surface of the plurality of struts which substantially prevents an active beneficial agent from being delivered from the at least one strut opening to the first surface of the struts.

24. The expandable medical device according to claim 23, wherein the barrier layer is coated on the device.

25. The expandable medical device according to claim 23, wherein the barrier layer is loaded in the strut openings.

26. The expandable medical device according to claim 1, wherein the beneficial agent is a protein drug.

27. The expandable medical device according to claim 1, wherein the plurality of layers of beneficial agent are arranged on top of one another in the radial direction.

28. The expandable medical device according to claim 1, wherein the beneficial agent is an anti-thrombotic agent.

29. The expandable medical device according to claim 1, wherein the beneficial agent is an anti-inflammatory agent.

30. The expandable medical device according to claim 1, wherein the beneficial agent is an antimitotic agent.

31. The expandable medical device according to claim 1, wherein the beneficial agent is an anti-platelet agent.

32. An expandable medical device comprising:

a plurality of elongated struts, said plurality of elongated struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, said plurality of elongated struts each having a strut width in a circumferential direction and a strut thickness in a radial direction;

at least one opening in at least one of the plurality of struts; and

at least one beneficial agent provided in the at least one opening in a plurality of layers, wherein the beneficial agent is provided into the at least one opening without coating a radially outermost surface of the strut, wherein the at least one opening comprises a plurality of openings containing the beneficial agent and a plurality of openings extending through the struts and remaining open.

33. A method of forming an expandable medical device, the method comprising:

providing an expandable medical device with a plurality of struts, said plurality of struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter;

forming at least one strut opening in at least one of the plurality of struts, the strut opening extending through the strut with the strut opening having a substantially constant cross section from a radially outermost surface of the strut to a radially innermost end of the strut opening; and

delivering at least one beneficial agent into the at least one strut opening in a plurality of layers without coating the outermost surface.

34. The method according to claim 33, wherein said at least one strut opening comprises a plurality of strut openings.

35. The method according to claim 33, wherein the beneficial agent delivered is paclitaxel.

36. The method according to claim 33, wherein the beneficial agent delivered is rapamycin, or an analogue or derivative thereof.

37. The method according to claim 33, further comprising positioning a barrier layer to substantially prevent an active beneficial agent from being delivered from the strut openings to one side of the medical device while allowing active beneficial agent to be delivered to another side of the medical device.

38. The method according to claim 37, wherein the barrier layer is coated on the device.

39. The method according to claim 37, wherein the barrier layer is loaded in the strut openings.

40. The method according to claim 33, wherein the beneficial agent is a protein drug.

41. An expandable medical device comprising:

a substantially cylindrical, expandable medical device formed of a plurality of struts;

a plurality of openings in the plurality of struts, the openings extending through the struts with the openings having a substantially constant cross section from a radially outermost surface of the strut to a radially innermost surface of the strut;

a beneficial agent provided in the plurality of openings; and

a barrier layer provided in the plurality of openings and configured to substantially prevent delivery of the beneficial agent to a first side of the medical device while allowing delivery of the beneficial agent to a second side of the medical device, wherein the beneficial agent and barrier layer are provided into the at least one opening without coating the outermost surface.

42. The expandable medical device according to claim 41, wherein the barrier layer is positioned adjacent an inner surface of the substantially cylindrical medical device.

43. The expandable medical device according to claim 41, wherein the barrier layer is coated on the device.

44. The expandable medical device according to claim 41, wherein the barrier layer is loaded in the openings.

45. The expandable medical device according to claim 41, wherein the expandable medical device is a stent.

46. The expandable medical device according to claim 41, wherein the beneficial agent is paclitaxel.

47. The expandable medical device according to claim 41, wherein the beneficial agent is rapamycin, or an analogue or derivative thereof.

48. The expandable medical device according to claim 41, wherein the beneficial agent is a protein drug.

49. The expandable medical device according to claim 41, wherein the beneficial agent and barrier layers are arranged on top of one another in the radial direction.

50. The expandable medical device according to claim 41, wherein the beneficial agent is an anti-thrombotic agent.

51. The expandable medical device according to claim 41, wherein the beneficial agent is an anti-inflammatory agent.

52. The expandable medical device according to claim 41, wherein the beneficial agent is an antimitotic agent.

53. The expandable medical device according to claim 41, wherein the beneficial agent is an anti-platelet agent.

54. An exapandable medical device comprising:

an expandable cylindrical device having a plurality of struts;

a plurality of through openings in the plurality of struts, each opening having a radial innermost end and a radial outermost end;

a beneficial agent provided in the plurality of through openings in a plurality of degradable beneficial agent layers; and

a barrier layer provided at the radial innermost send of the plurality of through openings, the barrier layer degrading more slowly than the beneficial agent layers, and the barrier layer substantially preventing fluid passage there through, wherein the beneficial agent layers and barrier layer are provided into the last one opening without a radially outermost surface of the strut.

55. The expandable medical device according to claim 54, wherein the barrier layer is loaded in the plurality of through openings.

56. The expandable medical device according to claim 54, wherein the beneficial agent is paclitaxel.

57. The expandable medical device according to claim 54, wherein the beneficial agent is rapamycin.

58. The expandable medical device according to claim 54, wherein the beneficial agent is a protein drug.

59. The expandable medical device according to claim 54, wherein the plurality of degradable beneficial agent layers are arranged on top of one another in the radial direction.

60. The expandable medical device according to claim 54, wherein the beneficial agent is an anti-thrombotic agent.

61. The expandable medical device according to claim 54, wherein the beneficial agent is an anti-inflammatory agent.

62. The expandable medical device according to claim 54, wherein the beneficial agent is an antimitotic agent.

63. The expandable medical device according to claim 54, wherein the beneficial agent is an anti-platelet agent.