Coating for implantable devices and a method of forming the same

• US 6,908,624 B2
• Filed: 12/16/2002
• Issued: 06/21/2005
• Est. Priority Date: 12/23/1999
• Status: Expired due to Term

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Wu, Steven Z., Gada, Manish, Hossainy, Syed F. A., Andreacchi, Anthony
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/320,935
• Publication Number:
  US 20040086542A1
• Time in Patent Office: 918 Days
• Field of Search: 424/400, 424/422, 424/424, 623/1.15, 623/1.42, 623/1.43, 623/1.44, 623/1.46, 623/1.49, 623/1.2, 514/822
• US Class Current: 424/424
• 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 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/085 Macromolecular materials
• 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: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters

Abstract

Coatings for implantable devices or endoluminal prosthesis, such as stents, are provided, including a method of forming the coatings. The coatings can be used for the delivery of an active ingredient or a combination of active ingredients.

Claims

1. A method of forming a coating for an implantable device, comprising:

forming a primer layer comprising a polymer on at least a portion of a surface of an implantable device, wherein the primer layer has a weight measurement of X;

forming a reservoir layer comprising a polymer and an active ingredient on at least a selected portion of the primer layer, wherein the reservoir layer has a weight measurement of Y; and

wherein X/Y is equal to or greater than 0.25 and equal to or less than 20.

2. The method of claim 1, wherein the coating has a drug loading equal to or greater than 30% by weight based on the total weight of the reservoir layer.

3. The method of claim 1, wherein X/Y is equal to or greater than 0.33.

4. The method of claim 1, further comprising forming a barrier layer on at least a selected portion of the reservoir layer to reduce the rate at which the active ingredient is released from the reservoir layer after insertion of the device into a body of a patient.

5. The method of claim 1, wherein the primer layer comprises an ethylene vinyl alcohol copolymer or poly(butyl methacrylate).

6. The method of claim 1, further comprising forming asperities on the surface of the primer layer preceding the formation of the reservoir layer.

7. The method of claim 1, wherein the primer layer includes at least a region having a degree of porosity.

30. The method of claim 1 wherein the reservoir layer comprises an ethylene vinyl alcohol copolymer or poly(butyl methacrylate).

31. The method of claim 1 wherein the active ingredient comprises rapamycin or analogs and derivatives thereof.

8. A method of forming a coating for an implantable device, comprising:

forming a primer layer comprising a polymer on at least a portion of a surface of an implantable device, wherein the primer layer has a thickness X;

forming a reservoir layer comprising a polymer and an active ingredient on at least a selected portion of the primer layer, wherein the reservoir layer has a thickness Y; and

wherein X/Y is equal to or greater than 0.25 and equal to or less than 20.

9. The method of claim 8, wherein the thickness X is about 0.5 microns to about 3 microns and the thickness Y is about 1 micron to about 10 microns.

17. The method of claim 8 wherein the coating has a drug loading equal to or greater than 30% by weight based on the total weight of the reservoir layer.

18. The method of claim 8 wherein X/Y is equal to or greater than 0.33.

19. The method of claim 8 further comprising forming a barrier layer on at least a selected portion of the reservoir layer to reduce the rate at which the active ingredient is released from the reservoir layer after insertion of the device into a body of a patient.

20. The method of claim 8 wherein the device is a stent.

21. The method of claim 8 wherein the active ingredient comprises rapamycin or analogs and derivatives thereof.

22. The method of claim 8 wherein the primer region or the reservoir region comprises poly(butyl methacrylate) or an ethylene vinyl alcohol compolymer.

10. An implantable device comprising a coating for delivery of an active ingredient, wherein the coating includes:

a primer region comprising a polymer on at least a portion of a surface of an implantable device, wherein the primer region has a thickness X;

a reservoir region comprising a polymer and an active ingredient on at least a selected portion of the primer region, wherein the reservoir region has a thickness Y; and

wherein the thickness X is measured from the outer surface of the primer region to the surface of the implantable device prior to the migration of the active ingredient from the reservoir region to the primer region, and wherein X/Y is equal to or greater than 0.25 and equal to or less than 20.

11. The implantable device of claim 10, wherein the implantable device is selected from a group of balloon-expandable stents and self-expandable stents.

12. The implantable device of claim 10, wherein the primer region or the reservoir region comprises an ethylene vinyl alcohol copolymer or poly(butyl methacrylate).

13. The implantable device of claim 10, wherein the active ingredient is selected from a group of heparin, heparin sulfate, heparin having a hydrophobic counterion, mannose-6-phosphate, superoxide dismutase, clobetasol, retinoic acid, rapamycin, rapamycin analogs and derivatives, suramin, asiaticoside, hyaluronan and combinations thereof.

14. The implantable device of claim 10, further including a barrier region located on at least a selected portion of the reservoir region for reducing the rate at which the active ingredient is released from the coating after insertion of the device into a body of a patient.

15. The implantable device of claim 10, wherein the primer region includes a porous matrix extending from the interface of the primer region and the reservoir region into the primer.

23. The implantable device of claim 10 wherein the coating has a drug loading equal to or greater than 30% by weight based on the total weight of the reservoir layer.

24. The implantable device of claim 10 wherein X/Y is equal to or greater than 0.33.

25. The implantable device of claim 10 wherein the active ingredient comprises rapamycin or analogs and derivatives thereof.

16. A stent comprising a coating for delivery of an active ingredient, wherein the coating includes a primer region comprising a polymer and a reservoir region comprising a polymer and an active ingredient, and wherein the thickness or the weight of the primer region is sufficiently high so as to allow drug loading of 30% in the reservoir region without causing the coating to significantly crack when the stent is expanded.

26. The stent of claim 16 wherein the primer region or the reservoir region comprises an ethylene vinyl alcohol copolymer or poly(butyl methacrylate).

27. The stent of claim 16 wherein the active ingredient comprises rapamycin or analogs and derivatives thereof.

28. The stent of claim 16 further including a barrier region located on at least a selected portion of the reservoir region for reducing the rate at which the active ingredient is released from the coating after insertion of the device into a body of a patient.

29. The stent of claim 16 wherein the primer region includes at least a region having a degree of porosity.

32. The method of claim wherein the device is a stent.