Stent coating

• US 6,569,195 B2
• Filed: 06/18/2001
• Issued: 05/27/2003
• Est. Priority Date: 07/02/1999
• Status: Expired due to Fees

• Current Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Stanslaski, Joel L., Wang, Lixiao, Smith, Scott R., Yang, Dachuan
• Primary Examiner(s): Willse, David H.
• Assistant Examiner(s): GHERBI, SUZETTE JAIME J
• Application Number:
  US09/883,870
• Publication Number:
  US 20010032014A1
• Time in Patent Office: 708 Days
• Field of Search: 623/1-6-, 623/1-2-, 427/2.25, 427/2.21
• US Class Current: 623/1.46
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• 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 2300/608 having two or more layers
• 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 35/00 Antineoplastic agents
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A stent having a polymeric coating for controllably releasing an included active agent. The polymeric coating includes a blend of a first polymeric material, which if alone, would release the agent at a first, higher rate, and a second polymeric material, which if alone would release the agent at a second, lower rate over a longer time period. One stent coating utilizes a faster releasing hydrophilic polymeric material and a slower releasing hydrophobic material. One stent coating includes a blend of a faster releasing PLA-PEO copolymer and a slower releasing PLA-PCL copolymer. One active agent is Taxol. One use of the Taxol delivering stent is to inhibit restenosis following angioplasty.

Claims

1. An implantable stent prosthesis for delivering a biologically active material to a patient comprising:

(a) a stent body having a surface adapted for exposure to body tissue of the patient;

(b) a coating disposed over at least a portion of the surface of the stent body;

wherein the coating comprises;

(i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and

(ii) a mixture of a first co-polymer and a second co-polymer, wherein said first co-polymer releases the biologically active material at a first rate and said second co-polymer releases the biologically active material at a second rate, wherein said second rate is slower than said first rate.

2. The stent of claim 1, wherein said first co-polymer is hydrophilic.

3. The stent of claim 1, wherein said second co-polymer is hydrophobic.

4. The stent of claim 1, wherein said first co-polymer is hydrophilic and said second co-polymer is hydrophobic.

5. The stent of claim 1, wherein said first co-polymer comprises polylactic acid/polyethylene oxide.

6. The stent of claim 1, wherein said second co-polymer comprises polylactic acid/polycaprolactone.

7. The stent of claim 1, wherein said first co-polymer includes polylactic acid/polyethylene oxide and said second co-polymer includes polylactic acid/polycaprolactone.

8. The stent of claim 7, wherein said coating comprises about 20% by weight polylactic acid/polyethylene oxide and about 80% by weight polylactic acid/polycaprolactone.

9. The stent of claim 7, wherein said coating comprises about 50% by weight polylactic acid/polyethylene oxide and about 50% by weight polylactic acid/polycaprolactone.

10. The stent of claim 1, wherein said anti-thrombogenic agent is heparin or ticlopidine.

11. The stent of claim 1, wherein said anti-angiogenesis agent is trapidil.

12. The stent of claim 1, wherein said anti-proliferative agent is selected from the group consisting of angiopeptin, colchicine, hirudin, paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof.

13. The stent of claim 1, wherein said growth factors are selected from the group consisting of VEGF, TGF-beta, IGF, PDGF, and FGF.

14. A method of making an implantable stent prosthesis for delivering a biologically active material to a patient, wherein said method comprises:

(a) providing a stent body having a surface adapted for exposure to body tissue of the patient;

(b) applying a coating over at least a portion of said surface;

wherein said coating comprises;

(i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and

(ii) a mixture of a first co-polymer and a second co-polymer, wherein said first co-polymer releases said biologically active material at a first rate and said second co-polymer releases said biologically active material at a second rate, and wherein said second rate is slower than said first rate.

15. The method of claim 14, wherein said anti-thrombogenic agent is heparin or ticlopidine.

16. The method of claim 14, wherein said anti-angiogenesis agent is trapidil.

17. The method of claim 14, wherein said anti-proliferative agent is selected from the group consisting of angiopeptin, colchicine, hirudin, paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof.

18. The method of claim 14, wherein said growth factors are selected from the group consisting of VEGF, TGF-beta, IGF, PDGF, and FGF.

19. The method of claim 14, wherein said first co-polymer is hydrophilic.

20. The method of claim 14, wherein said second co-polymer is hydrophobic.

21. The method of claim 14, wherein said first co-polymer comprises polylactic acid/polyethylene oxide.

22. The method of claim 14, wherein said second co-polymer comprises polylactic acid/polycaprolactone.

23. The method of claim 14, wherein said first co-polymer includes polylactic acid/polyethylene oxide and said second co-polymer includes polylactic acid/polycaprolactone.

24. The method of claim 14, wherein said coating comprises about 20% by weight polylactic acid/polyethylene oxide and about 80% by weight polylactic acid/polycaprolactone.

25. The method of claim 14, wherein said coating comprises about 50% by weight polylactic acid/polyethylene oxide and about 50% by weight polylactic acid/polycaprolactone.

26. An implantable stent prosthesis for delivering a restinosis inhibiting agent to a patient comprising:

(a) a stent body having a surface adapted for exposure to body tissue of the patient;

(b) a coating disposed over at least a portion of the surface of the stent body, wherein the coating comprises;

(i) the restinosis inhibiting agent selected from the group consisting of paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof; and

(ii) a mixture of about 50% by weight of a copolymer of polylactic acid/polyethylene oxide and about 50% by weight of a copolymer of polylactic acid/polycaprolactone.

27. The implantable stent of claim 26, wherein said paclitaxel derivatives are selected from the group consisting of 2-succinyl-taxol, 2′

-succinyl-taxol triethanolamine, 2′

-glutaryl-taxol, 2-glutaryl-taxol triethanolamine salt, 2-O-ester with N-(dimethylaminoethyl) glutamine, and 2′

-O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt.

28. An implantable stent prosthesis for delivering a biologically active material to a patient comprising:

(a) a stent body having a surface adapted for exposure to body tissue of the patient;

(b) a coating disposed over at least a portion of the surface of the stent body;

wherein the coating comprises;

(i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and

(ii) a mixture of a first polymer and a second polymer, wherein said first polymer releases the biologically active material at a first rate and said second polymer releases the biologically active material at a second rate, wherein said second rate is slower than said first rate.

29. The stent of claim 28, wherein said first polymer is hydrophilic.

30. The stent of claim 28, wherein said second polymer is hydrophobic.

31. The stent of claim 28, wherein said first polymer is hydrophilic and said second polymer is hydrophobic.

32. A method of making an implantable stent prosthesis for delivering a biologically active material to a patient, wherein said method comprises:

(a) providing a stent body having a surface adapted for exposure to body tissue of the patient;

(b) applying a coating over at least a portion of said surface;

wherein said coating comprises;

(i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and

(ii) a mixture of a first polymer and a second polymer, wherein said first polymer releases said biologically active material at a first rate and said second polymer releases said biologically active material at a second rate, and wherein said second rate is slower than said first rate.

33. The method of claim 32, wherein said first polymer is hydrophilic.

34. The method of claim 33, wherein said second polymer is hydrophobic.