Nitric oxide generating medical devices

Abstract

Medical devices having a catalyst capable of catalyzing the generation of nitric oxide attached to the medical device and methods of treating a vascular condition using the devices are provided.

1 . A medical device comprising a polymer and a metal complex attached to the polymer wherein the metal complex catalyzes the in vivo generation of nitric oxide  
   
   
       2 . The medical device of  claim 1  wherein in vivo generation of nitric oxide is nitric oxide generation in the blood stream or tissue adjacent to the medical device.  
   
   
       3 . The medical device of  claim 1  further comprising a coating for the medical device wherein the coating comprises the polymer.  
   
   
       4 . The medical device of  claim 1  wherein the medical device is a bioabsorbable stent comprising the polymer.  
   
   
       5 . The medical device of  claim 1  wherein the metal complex comprises copper.  
   
   
       6 . The medical device of  claim 1  wherein the metal complex comprises Cyclen, Cyclam, DTTCT, or a bipyridine ligand.  
   
   
       7 . The medical device of  claim 1  where in the metal complex comprises copper and at least one of Cyclen, Cyclam, DTTCT, or a bipyridine ligand.  
   
   
       8 . The medical device of  claim 1  wherein the metal complex attaches to the polymer via a spacer.  
   
   
       9 . The medical device of  claim 7  wherein the metal complex attaches to the polymer via a spacer.  
   
   
       10 . The medical device of  claim 8 , wherein the spacer is a short chain alkyl group, phenyl group, aryl group, or poly(ethylene glycol).  
   
   
       11 . The medical device of  claim 1  wherein the metal complex comprises a metal selected from the group consisting of Cu, Co, Ni, Zn, Mn, Al, or Fe.  
   
   
       12 . The medical device of  claim 1  wherein the metal complex comprises an ion selected from the group consisting of Cu 2+ , Co 2+ , Ni 2+ , Zn +2+ , Mn 2+ , Al 3+ , or Fe 3+ .  
   
   
       13 . The medical device of  claim 1  further comprising a drug adapted to be released from the device.  
   
   
       14 . The medical device of  claim 1  additionally including a coating having a drug.  
   
   
       15 . The medical device of  claim 14  wherein the coating includes the polymer.  
   
   
       16 . The medical device of  claim 1 , which is a stent.  
   
   
       17 . The medical device of  claim 1  which is a bioabsorbable stent.  
   
   
       18 . The medical device of  claim 1  wherein the nitric oxide is released from a nitrosylated biomolecule present in the blood stream or tissue adjacent to the medical device.  
   
   
       19 . The medical device of  claim 1  wherein the nitric oxide is released from a nitrosylated protein or S-nitrosothiols present in the blood stream or a tissue adjacent to the medical device.  
   
   
       20 . A medical device comprising a metal complex, 
 wherein the metal complex attaches to a surface of the medical device or a coating on the medical device, and    wherein the metal complex catalyzes the generation of nitric oxide in the blood stream or a tissue adjacent to the medical device.    
   
   
       21 . The medical device of  claim 20 , wherein the nitric oxide is released from a nitrosylated biomolecule present in the blood stream or a tissue adjacent to the medical device.  
   
   
       22 . The medical device of  claim 20 , wherein the nitric oxide is released from a nitrosylated protein or S-nitrosothiol present in the blood stream or a tissue adjacent to the medical device.  
   
   
       23 . The medical device of  claim 20 , wherein the metal complex is a copper complex.  
   
   
       24 . The medical device of  claim 20 , wherein the metal complex comprises Cyclen, Cyclam, DTTCT, or a bipyrridine liand.  
   
   
       25 . The medical device of  claim 20 , wherein the metal complex is attached to the surface of the medical device or the coating via a spacer.  
   
   
       26 . The medical device of  claim 25 , wherein the spacer is a short chain alkyl group, phenyl group, aryl group, or poly(ethylene glycol).  
   
   
       27 . The medical device of  claim 20 , wherein the metal complex comprises an ion selected from the group consisting of Cu 2+ , Co 2+ , Ni 2+ , Zn +2+ , Mn 2+ , Al 3+ , or Fe 3+ .  
   
   
       28 . The medical device of  claim 20  which is a bioabsorbable polymer stent.  
   
   
       29 . The medical device of  claim 20  which is a biodurable polymer stent.  
   
   
       30 . A medical device comprising a coating wherein the coating comprises: 
 a polymer, and    a metal complex that catalyzes the in vivo generation of nitric oxide in the blood stream or tissue adjacent to the medical device,    wherein the metal complex comprises an ion selected from the group consisting of Cu 2+ , Co 2+ , Ni 2+ , Zn +2+ , Mn +2 , Al 3+ , or Fe 3+ ; and    a ligand selected from Cyclen, Cyclam, DTTCT, or a bipyridine ligand.    
   
   
       31 . The medical device of  claim 30  wherein the metal complex attaches to the polymer via a spacer that is at least one of a short chain alkyl group, phenyl group, aryl group, or poly(ethylene glycol).  
   
   
       32 . The medical device of  claim 30  further comprising a drug.  
   
   
       33 . The medical device of  claim 30  wherein the coating further comprises a drug.  
   
   
       34 . The medical device of  claim 30  in which the medical device is an endovascular stent.  
   
   
       35 . A medical device comprising: 
 a polymer, and    a metal complex that catalyzes the in vivo generation of nitric oxide in the blood stream or tissue adjacent to the medical device,    wherein the metal complex comprises    an ion selected from the group consisting of Cu 2+ , Co 2+ , Ni 2+ , Zn +2+ , Mn 2+ , Al 3+ , or Fe 3+ ; and    a ligand selected from Cyclen, Cyclam, DTTCT, or a bipyridine ligand.    
   
   
       36 . The medical device of  claim 35  wherein the metal complex attaches to the polymer via a spacer that is at least one of a short chain alkyl group, phenyl group, aryl group, or poly(ethylene glycol).  
   
   
       37 . The medical device of  claim 35  further comprising a coating on the polymer wherein the coating comprises the metal complex.  
   
   
       38 . The medical device of  claim 35  further comprising a drug.  
   
   
       39 . The medical device of  claim 37  wherein the coating further comprises a drug.  
   
   
       40 . The medical device of  claim 35  in which the medical device is a bioabsorbable stent.  
   
   
       41 . A method of treating a disorder in a patient comprising implanting in the patient the medical device of  claim 1  wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.  
   
   
       42 . A method of treating a disorder in a patient comprising implanting in the patient the medical device of  claim 20 , wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.