Intravascular delivery of mycophenolic acid

• US 6,858,221 B2
• Filed: 09/11/2002
• Issued: 02/22/2005
• Est. Priority Date: 12/22/2000
• Status: Expired due to Fees

• Current Assignee: Avantec Vascular Corporation
• Original Assignee: Avantec Vascular Corporation
• Inventors: Yan, John, Sirhan, Motasim
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US10/242,334
• Publication Number:
  US 20030017190A1
• Time in Patent Office: 895 Days
• Field of Search: 424/423, 424/424, 424/425, 424/426, 623/1.1, 623/1.42
• US Class Current: 424/423
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• 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 2/95 Instruments specially adapted for placement or removal of stents or stent-grafts
• CPC Class Codes: A61F 2002/91533 characterised by the phase between adjacent bands
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention provides improved devices and methods for minimizing and/or inhibiting restenosis and hyperplasia after intravascular intervention. In particular, the present invention provides luminal prostheses which allow for programmed and controlled mycophenolic acid delivery with increased efficacy to selected locations within a patient'"'"'s vasculature to inhibit restenosis. An intraluminal delivery prosthesis may comprise an expansible structure and means on or within the structure for releasing mycophenolic acid at a rate selected to inhibit smooth muscle cell proliferation.

Claims

1. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having means thereon or therein for releasing mycophenolic acid in the blood vessel; and

releasing mycophenolic acid from the prosthesis into the blood vessel so as to inhibit smooth muscle cell proliferation.

3. A method as in claim 1, wherein mycoohenolic acid is released at a rate between 5 μ

g/day to 200 μ

g/day.

4. A method as in claim 1, wherein mycophenolic acid is released at a rate between 10 μ

g/day to 60 μ

g/day.

5. A method as in claim 1, wherein mycophenolic acid is released within a time period of 1 day to 45 days in a vascular environment.

6. A method as in claim 1, wherein mycophenolic acid is released within a time period of 7 days to 21 days in a vascular environment.

7. A method as in claim 1, further comprising releasing at least one other substance in addition to mycophenolic acid simultaneously with mycophenolic acid release.

8. A method as in claim 1, further comprising releasing at least one other substance in addition to mycophenolic acid sequentially with mycophenolic acid release.

9. A method as in claim 1, wherein the releasing comprises delaying substantial release of mycophenolic acid for at least one hour following implantation of the prosthesis.

10. A method as in claim 9, wherein delaying release comprises slowing releasing mycophenolic acid from a reservoir with a material that at least partially degrades in a vascular environment over said one hour.

11. A method as in claim 9, wherein delaying release comprises slowing releasing mycophenolic acid with a matrix that at least partially degrades in a vascular environment over said one hour.

12. A method as in claim 9, wherein delaying release comprises slowing releasing mycophenolic acid with a nondegradable matrix that allows diffusion of mycophenolic acid through the nondegradable matrix after said one hour.

13. A method as in claim 9, wherein delaying release comprises slowing releasing mycophenolic acid with a rate limiting barrier that allows diffusion of mycophenolic acid through the barrier after said one hour.

14. A method as in any one of claims 11-13, wherein the prosthesis is coated with the matrix or barrier by spraying, dipping, deposition, or painting.

15. A method as in claim 1, wherein the prosthesis incorporates mycophenolic acid by coating, spraying, dipping, deposition, chemical bonding, or painting mycophenolic acid on the prosthesis.

24. A method as in claim 7 or 8, wherein the at least one additional substance is an immunosuppresive substance selected from the group consisting of rapamycin, mizoribine, riboflavin, tiazofurin, methylprednisolone, FK 506, zafurin, and methotrexate.

2. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis in the blood vessel; and

releasing mycophenolic acid at a rate between 5 μ

g/day to 200 μ

g/day to inhibit smooth muscle cell proliferation.

16. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having means thereon or therein for releasing mycophenolic acid in the blood vessel; and

releasing mycophenolic acid and at least one other substance in addition to mycophenolic acid from the prosthesis when implanted in the blood vessel so as to inhibit smooth muscle cell proliferation.

17. A method as in claim 16, wherein the at least one additional substance is an immunosuppressive substance selected from the group consisting of rapamycin, mizoribine, riboflavin, tiazofurin, methylprednisolone, FK 506, zafurin, and methotrexate.

18. A method as in claim 17, wherein the immunosuppressive substance is mizoribine.

19. A method as in claim 17, wherein the immunosuppressive substance is methylprednisolone.

20. A method as in claim 19, wherein mycophenolic acid is released within a time period of 1 day to 45 days and methylprednisolone is released within a time period of 2 days to 3 months.

21. A method as in claim 16, wherein the at least one additional substance comprises at least one agent selected from the group consisting of anti-platelet agent, anti-thrombotic agent, and IIb/IIIa agent.

22. A method as in claim 16, wherein mycophenolic acid and the at least one additional substance are released simultaneously.

23. A method as in claim 16, wherein mycophenolic acid and the at least one additional substance are released sequentially.

25. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having a barrier thereon for releasing mycophenolic acid in the blood vessel; and

releasing mycophenolic acid from the prosthesis barrier into the blood vessel so as to inhibit smooth muscle cell proliferation.

26. A method as in claim 25, wherein the barrier comprises parylene.

27. A method as in claim 25, wherein the barrier has a thickness in the range from 50 nm to 100 microns.

28. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having a matrix thereon for releasing mycophenolic acid in the blood vessel; and

releasing mycophenoli acid from the prosthesis matrix into the blood vessel so as to inhibit smooth muscle cell proliferation.

29. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having a reservoir and a cover thereon for releasing mycophenolic acid in the blood vessel; and

releasing mycophenolic acid from the prosthesis reservoir into the blood vessel so as to inhibit smooth muscle cell proliferation.

30. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis having a reservoir and a cover thereon in the blood vessel; and

releasing mycophenolic acid from the prosthesis reservoir into the blood vessel so as to inhibit smooth muscle cell proliferation by directing energy from an external energy source at the prosthesis reservoir.

31. A method as in claim 30, wherein the external energy source comprises ultrasound, magnetic resonance imaging, magnetic field, radio frequency, temperature change, electromagnetism, x-ray, radiation, heat, gamma, or microwave.

32. A method for inhibiting restenosis in a blood vessel following recanalization of the blood vessel, said method comprising:

implanting a vascular prosthesis in the blood vessel; and

releasing mycophenolic acid from the prosthesis into the blood vessel so as to inhibit smooth muscle cell proliferation by directing a magnetic field from an external magnetic source at the prosthesis, wherein the mycophenolic acid is coupled to magnetic particles.

33. A vascular prosthesis comprising:

an expansible structure which is implantable within a body lumen; and

barrier on or within the structure for releasing mycophenolic acid so as to inhibit smooth muscle cell proliferation.

34. A prosthesis as in claim 33, wherein the barrier comprises parylene.

35. A prosthesis as in claim 33, wherein the barrier has a thickness in the range from 50 nm to 100 microns.

36. A vascular prosthesis comprising:

an expansible structure which is implantable within a body lumen; and

a matrix on or within the structure for releasing mycophenolic acid so as to inhibit smooth muscle cell proliferation.

37. A vascular prosthesis comprising:

an expansible structure which is implantable within a body lumen; and

a reservoir on or within the structure and a cover thereon for releasing mycophenolic acid so as to inhibit smooth muscle cell proliferation.

38. A system prosthesis comprising:

a vascular prothesis comprising an expansible structure which is implantable within a body lumen;

a reservoir on or within the prothesis and a cover thereon; and

an external energy source for releasing mycophenolic acid from the prothesis reservoir so as to inhibit smooth muscle cell proliferation.

39. A system as in claim 38, wherein the external energy source comprises ultrsound, magnetic resonance imaging, magnetic field, radio frequency, temperature change, electromagnetism, x-ray, radiation, heat, gamma, or microwave.

40. A system comprising:

a vascular prosthesis comprising an expansible structure which is implantable within a body lumen; and

an external magnetic source for releasing mycophenolic acid from the prosthesis so as to inhibit smooth muscle cell proliferation, wherein the mycophenolic acid is coupled to magnetic particles.