Implantable medical device coated with a bioactive agent

• US 8,092,819 B2
• Filed: 01/19/2007
• Issued: 01/10/2012
• Est. Priority Date: 01/27/2006
• Status: Active Grant

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Inventors: Ruane, Patrick H., Little, Jeff P., Isch, Andrew P.
• Primary Examiner(s): VIVLEMORE, TRACY ANN
• Application Number:
  US11/655,300
• Publication Number:
  US 20070207184A1
• Time in Patent Office: 1,817 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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: C08L 35/04 Homopolymers or copolymers of nitriles C08L35/06, C08L35/08 take precedence

Abstract

The present invention provides an implantable medical device comprising a bioactive agent and poly(alkyl cyanoacrylate) polymer. In one embodiment of the invention, the bioactive agent is a water-soluble material, such as an antisense agent.

Claims

1. An implantable medical device having at least one surface,

a first mixture comprising an antisense compound and a poly(alkyl cyanoacrylate) polymer coated directly on the at least one surface to form a first polymer layer, and

a second mixture comprising a solvent and a biodegradable polymer coated directly on at least a portion of the first layer to form a second polymer layer that is the outermost layer of the device, wherein the second mixture is free of the antisense compound.

2. The implantable medical device of claim 1, wherein the second polymer is polylactic acid and the poly(alkyl cyanoacrylate) polymer is poly(n-butyl cyanoacrylate).

3. The implantable medical device of claim 1, wherein the antisense compound has a solubility in water of greater than 2.5 g/L.

4. The implantable medical device of claim 3, wherein the antisense compound has a solubility in water of greater than 25 g/L.

5. The implantable medical device of claim 1, wherein the poly(alkyl cyanoacrylate) polymer is selected from a group consisting of poly(n-butyl cyanoacrylate), poly(isohexyl cyanoacrylate), poly(n-hexyl cyanoacrylate) and poly(n-octyl cyanoacrylate) and wherein the release of the antisense compound into an environment in which the implantable medical device is placed is controlled by the poly(alkyl cyanoacrylate) polymer.

6. The implantable medical device of claim 1, wherein the antisense compound is selected from a group consisting of an anti-thrombocytic agent, an anti-inflammatory agent and an anti-proliferative agent.

7. The implantable medical device of claim 1, wherein the antisense compound is selected from a group consisting of a natural nucleic acid oligonucleotide and a nucleic acid oligonucleotide having a modified backbone.

8. The implantable medical device of claim 7, wherein the antisense compound is a nucleic acid oligonucleotide having a modified backbone.

9. The implantable medical device of claim 8, wherein the antisense compound inhibits cellular proliferation.

10. The implantable medical device of claim 1, wherein the poly(alkyl cyanoacrylate) polymer comprises an alkyl group comprising between 3 and 12 carbon atoms.

11. The implantable medical device of claim 10, wherein the poly(alkyl cyanoacrylate) polymer is selected from a group consisting of poly(n-butyl cyanoacrylate), poly(isohexyl cyanoacrylate), poly(n-hexyl cyanoacrylate) and poly(n-octyl cyanoacrylate).

12. The implantable medical device of claim 11, wherein the poly(alkyl cyanoacrylate) polymer is poly(n-butyl cyanoacrylate).

13. The implantable medical device of claim 1, wherein the second polymer is selected from a group consisting of polylactic acid, poly-L-lactic acid, poly(D,L-lactide), poly(lactide-co-glycolide), poly(ethylene glycol), polyglycolide and block copolymers of these compounds.

14. The implantable medical device of claim 13, wherein the second polymer is polylactic acid.

15. The implantable medical device of claim 1, wherein the implantable medical device comprises a vascular stent.

16. The implantable medical device of claim 2, wherein the antisense compound is coated on the least one surface of the implantable medical device, wherein the poly(alkyl cyanoacrylate) polymer is coated on at least a portion of the antisense compound and wherein the second polymer is coated on at least a portion of the poly(alkyl cyanoacrylate) polymer.

18. The implantable medical device of claim 1, wherein the second polymer is applied by a spray coating method.

19. The implantable medical device of claim 18, wherein the second polymer is applied by an ultrasonic spray coating method.

20. The implantable device of claim 1, wherein first polymer layer consists of an antisense compound and a poly(alkyl cyanoacrylate) polymer.

17. An implantable medical device having at least one surface and having a first layer consisting essentially of an antisense compound and a poly(alkyl cyanoacrylate) polymer coated directly on the at least one surface, and a second polymer coated directly onto at least a portion of the first layer, wherein the second polymer is a biodegradable polymer forming an outermost surface of the device,

wherein the poly(alkyl cyanoacrylate) polymer comprises an alkyl group comprising between 3 and 12 carbon atoms,

wherein the second polymer is selected from a group consisting of polylactic acid, poly-L-lactic acid, poly(D,L-lactide), poly(lactide-co-glycolide), poly(ethylene glycol), polyglycolide and block copolymers of these compounds and

wherein the poly(alkyl cyanoacrylate) polymer and the second polymer are present at a weight ratio of between 400:

1 and 1;

400.