Nitric Oxide Coatings for Medical Devices

• US 20090118819A1
• Filed: 06/30/2006
• Published: 05/07/2009
• Est. Priority Date: 06/30/2005
• Status: Abandoned Application

• Current Assignee: Accord Biomaterials, Inc., MC3 Incorporated, Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: ., MC3 Incorporated
• Inventors: Merz, Scott, Nandivada, Himabindu, Lahann, Joerg, Meyerhoff, Mark E., Reynolds, Melissa M., Hwang, Sangyeul
• Application Number:
  US11/994,007
• Publication Number:
  US 20090118819A1
• Time in Patent Office: Days
• US Class Current: 623/1.420
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/082 Inorganic 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

The disclosure provides for devices and coatings that are substantially free of organic solvent sand suitable for insertion into a patient, and that comprise a metal layer and a coating with a thickness of about 20 nm to about 2000 nm wherein the coating comprises a biocompatible polymer comprising at least one residue covalently bonded to a nitric oxide generating compound.

Claims

1. A medical device substantially free of organic solvent capable of generating a pharmaceutically effective amount of nitric oxide and suitable for insertion into a mammal comprising:

a metal layer;

a coating with a thickness of about 10 nm to about 2000 nm on said metal layer;

wherein said coating comprises a biocompatible polymer comprising at least one residue covalently bonded to a nitric oxide generating compound.

2. The medical device of claim 1, wherein said nitric oxide generating compound is a metal ion binding moiety.

3. The medical device of claim 1, wherein said nitric oxide generating compound is a N_x-donor ligand where x is 2, 3, 4, 5, 6, 7, 8 or 9.

4. The medical device of claim 1, wherein said nitric oxide generating compound is a S_y-donor ligand where y is 2, 3, 4, 5, 6, 7, 8 or 9.

5. The medical device of claim 2 wherein said polymer comprises a (N_x-donor ligand-alkyl)-photoactive residue wherein said allyl is a C_1-8 alkyl.

6. The medical device of claim 5, wherein said polymer comprises a (cyclen-alkyl)methylacrylate residue.

7. The medical device of claim 1, wherein said nitric oxide generating compound is dibenzo[e,k]-2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene;

dibenzo[e,k]-2,3,8,9-tetramethyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene;

dibenzo[e,k]-2,3,8,9-tetraethyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene, and/or salts thereof.

8. The medical device of claim 2, further comprising metal ions.

9. The medical device of claim 7, further comprising metal ions.

10. The medical device of claim 9, wherein said metal ions are selected from the ions of one or more of:

Cu, Co, Zn, Ca, Mg, Pt, Sn, Se, or Mn.

11. The medical device of claim 10, wherein said metal ion is Cu(II).

12. The medical device of claim 1, wherein said polymer comprises polymerized [2.2]paracyclophanes.

13. The medical device of claim 1, wherein said metal layer comprises at least one of stainless steel, titanium, copper, gold, nickel, or alloys thereof.

14. The medical device of claim 1 where said medical device is a catheter, a stent, a graft, or a pacemaker lead.

15. The medical device of claim 1, wherein said coating is about 20 nm to about 200 nm thick.

16. The medical device of claim 1, further comprising another pharmaceutically effective agent.

17. A method of preventing an unwanted inflammatory response in a patient comprising:

providing the coating on the medical device of claim 1 with an effective amount of nitric oxide generating compound; and

implanting the medical device into a patient in need thereof.

18. The method of claim 17, wherein said unwanted inflammatory response is sub-acute thrombosis.

19. A medical device suitable for implantation to a patient comprising:

a metal layer;

a nitric oxide generating coating with a thickness of about 20 nm to about 2000 nm on said metal layer;

wherein said coating comprises a polymer comprising at least one residue covalently bonded to a nitric oxide generating compound;

wherein said medical device substantially prevents an inflammatory response as compared to the inflammatory response obtained by implanting a medical device with a coating that does not include a nitric oxide generating compound.

20. The medical device of claim 19, wherein said nitric oxide generating coating is substantially free of organic solvents.

21. A method for substantially preventing or treating unwanted inflammatory response in a patient in need of an implantable medical device, comprising:

implanting a medical device into patient thereby providing a pharmaceutically effective amount of nitric oxide to said patient, wherein said medical device comprises;

a metal layer;

a coating with a thickness of about 20 nm to about 2000 nm on said metal layer;

wherein said coating comprises a polymer and a nitric oxide generating compound.

22. The method of claim 21, wherein said inflammatory response is sub-acute thrombosis.

23. The method of claim 21, wherein said coating is substantially free of organic solvents.