Implantable medical device coated with a bioactive agent

• US 20070207184A1
• Filed: 01/19/2007
• Published: 09/06/2007
• Est. Priority Date: 01/27/2006
• Status: Active Grant

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: MED Institute, Inc. (Cook Group Incorporated)
• Inventors: Isch, Andrew, Ruane, Patrick, Little, Jeff
• Granted Patent: US 8,092,819 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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, wherein a bioactive agent and a poly(alkyl cyanoacrylate) polymer are present on the at least one surface and wherein the bioactive agent is water-soluble.

2. The implantable medical device of claim 1, further comprising a second polymer, wherein the second polymer is a biodegradable polymer and is coated on at least a portion of the bioactive agent and the poly(alkyl cyanoacrylate) polymer.

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

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

5. The implantable medical device of claim 1, wherein the release of the bioactive agent 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 bioactive agent 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 bioactive agent is selected from a group consisting of an immunosuppressive, rapamycin, heparin and an antisense compound.

8. The implantable medical device of claim 7, wherein the bioactive agent is an antisense compound.

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 2, 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 bioactive agent 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 bioactive agent and wherein the second polymer is coated on at least a portion of the poly(alkyl cyanoacrylate) polymer.

17. The implantable medical device of claim 2, wherein a mixture comprising the bioactive agent and the poly(alkyl cyanoacrylate) polymer is coated on the at least one surface.

18. The implantable medical device of claim 17, wherein the second polymer is coated on at least a portion of the mixture comprising the bioactive agent the poly(alkyl cyanoacrylate) polymer.

19. An implantable medical device having at least one surface and having a layer comprising a water-soluble bioactive agent and a poly(alkyl cyanoacrylate) polymer coated on the at least one surface, wherein a second polymer is coated onto at least a portion of the layer comprising a water-soluble bioactive agent and a poly(alkyl cyanoacrylate) polymer,

wherein the second polymer is a biodegradable polymer,

wherein the bioactive agent is an antisense agent,

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.

20. A method of delivering a water-soluble bioactive agent to a subject, the method comprising:

inserting an implantable medical device into the subject'"'"'s body, wherein a layer comprising the water-soluble bioactive agent is present on a surface of the implantable medical device and wherein a layer comprising a poly(alkyl cyanoacrylate) polymer overcoats at least a portion of the water-soluble bioactive agent; and

leaving the implantable medical device within the subject'"'"'s body for a time sufficient to allow at least a portion of the water-soluble bioactive agent to be released from the implantable medical device.

21. A method of manufacturing an implantable medical device, the method comprising:

coating at least one surface of the implantable medical device with a water-soluble bioactive agent, and

coating a alkyl cyanoacrylate monomer onto at least a portion of the water-soluble bioactive agent.