Localized use of nitric oxide-adducts to prevent internal tissue damage

Abstract

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; can be coated per se on a surface of the medical device; can be 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 introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

What is claimed is:  
     
         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 1 , 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 18 , 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.  
     
     
         45 . The method of  claim 29 , wherein the nitrate is an organic nitrate.  
     
     
         45 . The method of  claim 45 , 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.