Intravascular delivery of mycophenolic acid

• US 20030017190A1
• Filed: 09/11/2002
• Published: 01/23/2003
• Est. Priority Date: 12/22/2000
• Status: Active Grant

• Current Assignee: Avantec Vascular Corporation
• Original Assignee: Avantec Vascular Corporation
• Inventors: Yan, John, Sirhan, Motasim
• Granted Patent: US 6,858,221 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• 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 in the blood vessel; and

releasing mycophenolic acid at a rate selected to inhibit smooth muscle cell proliferation.

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

g/day to 200 μ

g/day.

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

g/day to 60 μ

g/day.

4. 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.

5. 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.

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

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

8. A method as in claim 6 or 7, 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.

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 release 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 release 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 release 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 release 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.

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.

16. 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 and at least one other substance in addition to mycophenolic acid from the prosthesis when implanted in the blood vessel.