Use of nitric oxide adducts

Abstract

The invention provides a method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; coated per se on a surface of the medical device; directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

1 . A method for preventing or inhibiting platelet deposition or for alleviating restenosis in a patient in need thereof comprising administering at least one nitric oxide adduct to a damaged vascular surface, wherein the damaged vascular surface is the interior surface of a blood vessel in which damage to the endothelium or subendothelium, narrowing or stenosis of the vessel has occurred, and wherein the nitric oxide adduct is a sodium nitroprusside, a nitrosothiol, a nitrate, a nitrite, a nitrosated amino acid, a iron-nitrosyl compound, a sydnonimine, or a furoxan.  
   
   
       2 . The method of  claim 1 , wherein the nitric oxide adduct is administered via a medical device.  
   
   
       3 . The method of  claim 2 , wherein the medical device comprises a catheter, a prosthetic heart valve, a synthetic heart valve, a stent, an intubation tube, an arteriovenous shunt or an artificial valve.  
   
   
       4 . The method of  claim 1 , wherein the nitric oxide adduct is administered to the damaged vascular surface by local administration.  
   
   
       5 . The method of  claim 1 , wherein the nitric oxide adduct is administered to the damaged vascular surface through the lumen of an intraarterial or intravenous catheter.  
   
   
       6 . The method of  claim 2 , wherein the nitric oxide adduct is coated on all or a portion of the medical device.  
   
   
       7 . The method of  claim 6 , wherein the medical device comprises a polymer matrix and the nitric oxide adduct is bound to or admixed with the polymer matrix, wherein the polymer is nylon, polyethylene perthalate or polytetrafluoroethylene.  
   
   
       8 . The method of  claim 7 , wherein the polymer matrix provides for sustained release of the nitric oxide adduct.  
   
   
       9 . The method of  claim 1 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
   
   
       10 . The method of  claim 9 , wherein the anti-thrombogenic compound is heparin, hirudin, an analog of hirudin, warfarin, aspirin, indomethacin, dipyridamole, prostacyclin, prostaglandin-E, a sulfinpyrazone, a phenothiazine, a RGD peptide, a RDG peptide mimetic, an agent that blocks platelet glycoprotein IIb-IIIa receptors, ticlopidine or clopidogrel.  
   
   
       11 . The method of  claim 9 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
   
   
       12 . The method of  claim 1 , wherein the nitric oxide adduct delivers at least one of a nitrosonium ion or a nitroxyl ion under physiological conditions.  
   
   
       13 . The method of  claim 1 , wherein the nitrosothiol is a nitrosodithiol or a long carbon chain lipophilic nitrosothiol.  
   
   
       14 . The method of  claim 1 , wherein the nitrate is a thionitrate.  
   
   
       15 . The method of  claim 1 , wherein the nitrite is a thionitrite.  
   
   
       16 . The method of  claim 1 , wherein the nitrate is an organic nitrate.  
   
   
       17 . The method of  claim 16 , wherein the organic nitrate is nitroglycerin.  
   
   
       18 . The method of  claim 1 , wherein the nitrosated amino acid is a nitroso-protein.  
   
   
       19 . The method of  claim 18 , wherein the nitroso-protein comprises at least one thiol group.  
   
   
       20 . The method of  claim 18 , wherein the nitroso-protein is a nitroso-enzyme, a nitroso-transport protein, a nitroso-heme protein or a biologically protective nitroso-protein.  
   
   
       21 . The method of  claim 18 , wherein the nitroso-protein is a S-nitroso-tissue-type plasminogen activator, a S-nitroso-cathepsin, a S-nitroso-lipoprotein, a S-nitroso-hemoglobin, a S-nitroso-albumin, a S-nitroso-immunoglobulin or a S-nitroso-cytokine.  
   
   
       22 . The method of  claim 18 , wherein the nitroso-protein is polynitrosated.  
   
   
       23 . The method of  claim 18 , wherein the nitroso-protein is mononitrosated.  
   
   
       24 . The method of  claim 21 , wherein the nitroso-protein is S-nitroso-albumin.  
   
   
       25 . The method of  claim 24 , wherein the S-nitroso-albumin is polynitrosated.  
   
   
       26 . The method of  claim 24 , wherein the S-nitroso-albumin is mononitrosated.  
   
   
       27 . The method of  claim 24 , wherein the S-nitroso-albumin is S-nitroso-bovine serum albumin.  
   
   
       28 . The method of  claim 24 , wherein the S-nitroso-albumin is S-nitroso-human serum albumin.  
   
   
       29 . A method for treating or preventing a myocardial infarction, thrombophlebitis, thrombocytopenia or a bleeding disorder in a patient in need thereof comprising administering at least one nitric oxide adduct to a damaged vascular surface, wherein the damaged vascular surface is the interior surface of a blood vessel in which damage to the endothelium or subendothelium, narrowing or stenosis of the vessel has occurred, and wherein the nitric oxide adduct is a sodium nitroprusside, a nitrosothiol, a nitrate, a nitrite, a nitrosated amino acid, a iron-nitrosyl compound, a sydnonimine, or a furoxan.  
   
   
       30 . The method of  claim 29 , wherein the nitric oxide adduct is administered via a medical device.  
   
   
       31 . The method of  claim 30 , wherein the medical device comprises a catheter, a prosthetic heart valve, a synthetic heart valve, a stent, an intubation tube, an arteriovenous shunt or an artificial valve.  
   
   
       32 . The method of  claim 29 , wherein the nitric oxide adduct is administered to the damaged vascular surface by local administration.  
   
   
       33 . The method of  claim 29 , wherein the nitric oxide adduct is administered to the damaged vascular surface through the lumen of an intraarterial or intravenous catheter.  
   
   
       34 . The method of  claim 30 , wherein the nitric oxide adduct is coated on all or a portion of the medical device.  
   
   
       35 . The method of  claim 34 , wherein the medical device comprises a polymer matrix and the nitric oxide adduct is bound to or admixed with the polymer matrix, wherein the polymer is nylon, polyethylene perthalate or polytetrafluoroethylene.  
   
   
       36 . The method of  claim 35 , wherein the polymer matrix provides for sustained release of the nitric oxide adduct.  
   
   
       37 . The method of  claim 29 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
   
   
       38 . The method of  claim 37 , wherein the anti-thrombogenic compound is heparin, hirudin, an analog of hirudin, warfarin, aspirin, indomethacin, dipyridamole, prostacyclin, prostaglandin-E, a sulfinpyrazone, a phenothiazine, a RGD peptide, a RDG peptide mimetic, an agent that blocks platelet glycoprotein IIb-IIIa receptors, ticlopidine or clopidogrel.  
   
   
       39 . The method of  claim 37 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
   
   
       40 . The method of  claim 29 , wherein the nitric oxide adduct delivers at least one of a nitrosonium ion or a nitroxyl ion under physiological conditions.  
   
   
       41 . The method of  claim 29 , wherein the nitrosothiol is a nitrosodithiol or a long carbon chain lipophilic nitrosothiol.  
   
   
       42 . The method of  claim 29 , wherein the nitrate is a thionitrate.  
   
   
       43 . The method of  claim 29 , wherein the nitrite is a thionitrite.  
   
   
       44 . The method of  claim 29 , wherein the nitrate is an organic nitrate.  
   
   
       45 . The method of  claim 44 , wherein the organic nitrate is nitroglycerin.  
   
   
       46 . The method of  claim 29 , wherein the nitrosated amino acid is a nitroso-protein.  
   
   
       47 . The method of  claim 46 , wherein the nitroso-protein comprises at least one thiol group.  
   
   
       48 . The method of  claim 46 , wherein the nitroso-protein is a nitroso-enzyme, a nitroso-transport protein, a nitroso-heme protein or a biologically protective nitroso-protein.  
   
   
       49 . The method of  claim 46 , wherein the nitroso-protein is a S-nitroso-tissue-type plasminogen activator, a S-nitroso-cathepsin, a S-nitroso-lipoprotein, a S-nitroso-hemoglobin, a S-nitroso-albumin, a S-nitroso-immunoglobulin or a S-nitroso-cytokine.  
   
   
       50 . The method of  claim 46 , wherein the nitroso-protein is polynitrosated.  
   
   
       51 . The method of  claim 46 , wherein the nitroso-protein is mononitrosated.  
   
   
       52 . The method of  claim 46 , wherein the nitroso-protein is S-nitroso-albumin.  
   
   
       53 . The method of  claim 52 , wherein the S-nitroso-albumin is polynitrosated.  
   
   
       54 . The method of  claim 52 , wherein the S-nitroso-albumin is mononitrosated.  
   
   
       55 . The method of  claim 52 , wherein the S-nitroso-albumin is S-nitroso-bovine serum albumin.  
   
   
       56 . The method of  claim 52 , wherein the S-nitroso-albumin is S-nitroso-human serum albumin