Process for coating stents

• US 6,153,252 A
• Filed: 04/19/1999
• Issued: 11/28/2000
• Est. Priority Date: 06/30/1998
• Status: Expired due to Term

• Current Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Hossainy, Syed F. A., Kopia, Gregory A., Llanos, Gerard H., Roller, Mark B.
• Primary Examiner(s): Beck, Shrive
• Assistant Examiner(s): MICHENER, JENNIFER KOLB
• Application Number:
  US09/294,164
• Time in Patent Office: 589 Days
• Field of Search: 427/421, 427/435, 427/355, 427/409, 427/235, 427/2.25, 427/2.28, 427/232, 427/2.3
• US Class Current: 427/2.3
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• 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: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0047 Enzymes, e.g. urokinase, streptokinase
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 73/02 Polyanhydrides
• CPC Class Codes: C08L 77/00 Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08L79/06; of polyamideimides or polyamide acids C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 77/12 Polyester-amides
• CPC Class Codes: C08L 85/02 containing phosphorus

Abstract

A process is provided for coating stents having a first and second surface with passages there between to avoid blockage and bridging of the passages. The process comprises contacting the stent with a liquid coating solution containing a film forming biocompatible polymer under conditions suitable to allow the film forming biocompatible polymer to coat at least one surface of the stent while maintaining a fluid flow through said passages sufficient prevent the film forming biocompatible polymer from substantially blocking said passages. Also described are stents coated by this process.

Claims

1. A method for coating a stent having an outer surface and inner surface with passages between the outer surface and inner surfaces comprising:

(a) contacting the stent with a liquid coating solution containing a film forming biocompatible polymer under conditions suitable to allow the film forming biocompatible polymer to coat at least one surface of the stent;

(b) before the coating solution dries creating fluid movement out of the passages of the stent sufficient to prevent the film forming biocompatible polymers from substantially blocking said passages thereafter;

(c) drying the stent to provide at least a partially coated stent with a first coating

wherein said fluid movement is created by contacting a mandrel with the inner surface of the stent and moving the mandrel relative to the stent to prevent bridges from forming in said passages.

2. The method of claim 1 wherein the stent is contacted with the coating solution by dipping the stent into the coating solution.

3. The method of claim 1 wherein the stent is contacted with the coating solution by spraying the coating solution on to the stent.

4. The method of claim 2 wherein fluid movement is created by contacting the outer surface of the stent with the inner surface of a tube and moving the tube relative to the stent to prevent bridges from forming in said passages.

5. The method of claim 3 wherein fluid movement is created by contacting the outer surface of the stent with the inner surface of a tube and moving the tube relative to the stent to prevent bridges from forming in said passages.

6. The method of claim 1 wherein the film forming biocompatible polymer is selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amido groups, poly(anhydrides), polyphosphazenes, biomolecules and blends thereof.

7. The method of claim 1 wherein the film forming polymer is a biocompatible aliphatic polyester.

8. The method of claim 7 wherein the film forming polymer is an elastomeric, biocompatible aliphatic polyester.

9. The method of claim 8 wherein the elastomeric, bicompatible aliphatic polyester is selected from the group consisting of elastomeric copolymers of ε

-caprolactone and glycolide, elastomeric copolymers of ε

-caprolactone and lactide, elastomeric copolymers of p-dioxanone and lactide, elastomeric copolymers of ε

-caprolactone and p-dioxanone, elastomeric copolymers of p-dioxanone and trimethylene carbonate, elastomeric copolymers of trimethylene carbonate and glycolide, elastomeric copolymer of trimethylene carbonate and lactide and blends thereof.

10. The method of claim 1 wherein additionally contained in the coating solution is a pharmaceutically active compound.

11. The method of claim 10 wherein the pharmaceutically active compound is selected from the group consisting of antiproliferative/antimitotic agents, antibiotics, enzymes, antiproliferative/antimitotic alkylating agents, antiproliferative/antimitotic antimetabolites;

hormones;

anticoaglants;

fibrinolytic agents;

antiplatelet agents;

antimigratory agents;

antisecretory agents;

antiinflammatory agents;

immunosuppressive agents;

angiogenic agents;

nitric oxide donors;

anti-sense olgio nucleotides and combinations thereof.

12. The method of claim 11 wherein the pharmaceutically active compound is rapamycin.

13. The method of claim 1 wherein after the stent is dried a second coating is applied.

14. The method of claim 13 wherein the second coating is applied by spraying a solution containing a film forming biocompatible polymer onto at least one surface of the stent.

15. The method of claim 13 wherein the second coating contains a film forming biocompatible polymer not present in the first coating.

32. The method of claim 6 wherein additionally present is a biocompatible hydrophilic polymer.

16. A method for coating a tubular stent having a first surface and second surface with passages between the first surface and second surfaces comprising;

(a) placing the tubular stent on a mandrel;

then

(b) contacting the stent and mandrel with a liquid coating solution containing a film forming biocompatible polymer under conditions suitable to allow the film forming biocompatible polymer to coat at least one surface of the stent while moving the stent relative to the mandrel to cause fluid flow through said passages sufficient to prevent the film forming biocompatible polymer from substantially blocking said passages;

thereafter

(c) drying the stent to provide at least a partially coated tubular stent with a first coating.

17. The method of claim 16 wherein the film forming biocompatible polymer is selected from the group consisting of of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amido groups, poly(anhydrides), polyphosphazenes, biomolecules and blends thereof.

18. The method of claim 16 wherein the stent is coated with an elastomeric aliphatic polyester.

19. The method of claim 18 wherein the elastomeric, bicompatible aliphatic polyester is selected from the group consisting of elastomeric copolymers of ε

-caprolactone and glycolide, elastomeric copolymers of ε

-caprolactone and lactide, elastomeric copolymers of p-dioxanone and lactide, elastomeric copolymers of ε

-caprolactone and p-dioxanone, elastomeric copolymers of p-dioxanone and trimethylene carbonate, elastomeric copolymers of trimethylene carbonate and glycolide, elastomeric copolymer of trimethylene carbonate and lactide and blends thereof.

20. The method of claim 19 wherein the elasomertic polyester is ε

-caprolactone-co-glycolide.

21. The method of claim 20 wherein a second coating is applied.

22. The method of claim 21 wherein the first coating is ε

-caprolactone-co-glycolide and the second coating is ε

-caprolactone-co-glycolide.

23. The method of claim 22 wherein the first coating contains a pharmaceutically active compound.

24. The method of claim 19 wherein the elasomertic polyester is ε

-caprolactone-co-lactide.

25. The method of claim 24 wherein a second coating is applied.

26. The method of claim 25 wherein the first coating is ε

-caprolactone-co-lactide and the second coating is ε

-caprolactone-co-lactide.

27. The method of claim 25 wherein the first coating is ε

-caprolactone-co-lactide and the second coating is ε

-caprolactone-co-glycolide.

28. The method of claim 26 wherein the first coating contains a pharmaceutically active compound.

29. The method of claim 27 wherein the first coating contains a pharmaceutically active compound.

30. The method of claim 26 wherein the pharmaceutically active compound is rapamycin.

31. The method of claim 27 wherein the pharmaceutically active compound is rapamycin.

33. The method of claim 31 wherein the biocompatible hydrophilic polymer is selected from the group consisting of polyethylene oxide, polyvinyl pyrrolidone, polyethylene glycol, carboxylmethyl cellulose, hydroxymethyl cellulose and combination thereof.

34. The method of claim 25 wherein the second coating is a coating applied to modulate the release rate of the pharmaceutical agent in the first coating.

35. The method of claim 34 wherein the second coating weights between about 10 micrograms and about 2000 micrograms.

36. The method of claim 34 wherein the second coating weights between about 100 micrograms and about 1700 micrograms.

37. The method of claim 21 wherein additionally present are at least two top coats.

38. The method of claim 21 wherein additionally present are at least three top coats.