Nitric Oxide Coatings for Medical Devices
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.
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.