Method of manufacturing a medicated porous metal prosthesis

• US 6,240,616 B1
• Filed: 04/15/1997
• Issued: 06/05/2001
• Est. Priority Date: 04/15/1997
• Status: Expired due to Term

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Yan, John Y.
• Primary Examiner(s): Hughes, S. Thomas
• Assistant Examiner(s): JIMENEZ, MARC QUEMUEL
• Application Number:
  US08/837,993
• Time in Patent Office: 1,512 Days
• Field of Search: 295/272, 294/28, 623/1.42, 623/1.46, 623/1.47, 623/1.48, 623/1.44, 623/1.39, 623/1.4, 623/1.49, 623/1.54, 419/2
• US Class Current: 29/527.2
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• 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 2/92 Stents in the form of a rolled-up sheet expanding after insertion into the vessel , e.g. with a spiral shape in cross-section
• 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 2300/45 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 31/022 Metals or alloys
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• 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: Y10T 29/49982 Coating
• CPC Class Codes: Y10T 428/12153 Interconnected void structure [e.g., permeable, etc.]
• CPC Class Codes: Y10T 428/12479 Porous [e.g., foamed, spongy, cracked, etc.]

Abstract

A method of manufacturing a medicated prosthesis such as a stent. The method includes forming a stent out of porous metal and loading a therapeutic agent into the pores of the metal. In one embodiment the stent is formed from a sintered metal wire, sheet, or tube and can include adding a coating to the stent. When the stent is implanted into the vasculature of a patient, the therapeutic agent in the stent dissipates into the tissue of the vasculature proximate the stent.

Claims

1. A method of manufacturing a stent for providing local delivery of a therapeutic agent at an implantation site, comprising:

sintering metallic fibers into a sintered stent material having a plurality of porous holding cavities open to one side;

forming the sintered stent material into a stent; and

loading a therapeutic agent into the cavities of the stent prior to implanting the stent at the implantation site.

2. The method of claim 1, wherein said plurality of porous holding cavities extend throughout the sintered stent material.

3. The method of claim 1, futher comprising the step of weaving said metallic fibers prior to sintering the metallic fibers to form said sintered stent material.

4. The method of claim 1, wherein:

the sintered stent material comprises a sheet; and

the forming step includes chemical etching the sheet into the form of an expandable stent.

5. The method of claim 2, wherein the metallic fibers are woven into a sheet prior to said sintering step.

6. The method of claim 1, wherein:

the sintered stent material comprises a sheet; and

the forming step includes cutting the sheet with a laser into the form of a stent.

7. The method of claim 5, wherein the metallic fibers are woven into a sheet prior to said sintering step.

8. The method of claim 1, wherein said sintered stent material comprises a porous metal wire.

9. The method of claim 1, further comprising the step of weaving the metallic fibers into a sheet.

10. The method of claim 2, wherein the stent is emersed for a period of time sufficient to permit a therapeutic agent to be absorbed into the porous cavities of the stent.

11. The method of claim 2, wherein the stent is emersed for a period of time sufficient to permit a therapeutic agent to be absorbed into the porous cavities of the stent.

12. The method of claim 2, wherein the therapeutic agent is an anti-fibrin agent.

13. The method of claim 2, wherein the therapeutic agent is an antithrombin agent.

14. The method of claim 2, wherein the therapeutic agent is an anti-proliferative agent.

15. The method of claim 2, wherein the therapeutic agent is an anti-coagulant.

16. The method of claim 2, wherein the therapeutic agent is a GPII₆III_a blocker.

17. The method of claim 2, wherein the therapeutic agent is selected from the group consisting of forskolin, aspirin, dipyridamole, coumadin, ticlopodine, and heparin.

18. The method of claim 2, wherein the therapeutic agent is a vaso-active drug.

19. The method of claim 2, wherein the therapeutic agent is an anti-inflammatory agent.

20. The method of claim 2, wherein the therapeutic agent promotes endothelialization.

21. The method of claim 2, further comprising coating the stent with a polymer.

22. The method of claim 21, wherein the coating step occurs after the loading step.

23. The method of claim 21, wherein the polymer is configured to release the therapeutic agent at a substantially constant rate.

24. The method of claim 21, wherein the polymer is a biopolymer.

25. The method of claim 21, wherein the polymer is a poly lactic acid or fibrin.

26. The method of claim 25, wherein the polymer is selected from the group consisting of polyurethane, polyethylene teraphthalate tetrafluoride, polyethylene, polyethylene oxide (PEO) and silicone.

27. The method of claim 21, wherein the polymer is a synthetic polymer.

28. The method of claim 27, wherein the polymer is a hydrogel.

29. The method of claim 21, wherein the polymer is a heparin coating.

30. The method of claim 21, wherein the polymer is mixed with the therapeutic agent.

31. The method of claim 21, wherein the polymer is degradable.

32. The method of claim 1, wherein the cavities are open on their respective one ends and the sintered stent material forms closure walls on the respective opposite ends.

33. The method of claim 1, wherein said sintered stent material forms respective cavity side walls to define the respective holding cavities, and such side walls cause such cavities to cooperate with the loaded therapeutic agent in providing surface tension for holding the therapeutic agent in the respective cavities.

34. The method of claim 1, wherein said sintered stent material comprises a plurality of layers with at least one layer configured with the cavities opening outwardly to the one side and second layer forming a closure wall closing the respective cavities from opening to the opposite side.

35. The method of claim 1, wherein said sintered stent material comprises a pair of coextensive outer layers formed with the cavities facing outwardly in opposite directions and an intermediate layer sandwiched between the outer layers.

36. The method of claim 1, wherein the cavities are of substantially uniform size.

37. The method of claim 1, wherein the cavities are of substantially irregular size.

38. The method of claim 1, wherein said sintered stent material comprises a single layer.