Use of nitric oxide adducts

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 inhibiting platelet deposition in a patient in need thereof comprising administering a therapeutically effective amount of a nitric oxide adduct to the patient to inhibit platelet deposition; wherein the nitric oxide adduct is a nitrate which has at least one —O—NO 2  group selected from the group consisting of a polypeptide; an amino acid; a sugar; an oligonucleotide; a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         2 . The method of  claim 1 , wherein the nitrate which has at least one —O—NO 2  group is selected from the group consisting of a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         3 . The method of  claim 2 , wherein the nitrate which has at least one —O—NO 2  group is nitroglycerin.  
     
     
         4 . The method of  claim 2 , wherein the nitrate which has at least one —O—NO 2  group is an angiotensin converting enzyme inhibitor.  
     
     
         5 . The method of  claim 1 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
     
     
         6 . The method of  claim 5 , 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.  
     
     
         7 . The method of  claim 5 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
     
     
         8 . A method for alleviating restenosis in a patient in need thereof comprising administering a therapeutically effective amount of a nitric oxide adduct to the patient to alleviate restenosis; wherein the nitric oxide adduct is a nitrate which has at least one —O—NO 2  group selected from the group consisting of a polypeptide; an amino acid; a sugar; an oligonucleotide; a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         9 . The method of  claim 8 , wherein the nitrate which has at least one —O—NO 2  group is selected from the group consisting of a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         10 . The method of  claim 9 , wherein the nitrate which has at least one —O—NO 2  group is nitroglycerin.  
     
     
         11 . The method of  claim 9 , wherein the nitrate which has at least one —O—NO 2  group is an angiotensin converting enzyme inhibitor.  
     
     
         12 . The method of  claim 8 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
     
     
         13 . The method of  claim 12 , 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.  
     
     
         14 . The method of  claim 12 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
     
     
         15 . A method for treating a vascular complication caused by platelet deposition or thrombus formation in a patient in need thereof comprising administering a therapeutically effective amount of a nitric oxide adduct to the patient to treat the vascular complication caused by platelet deposition or thrombus formation; wherein the vascular complication caused by platelet deposition or thrombus formation is myocardial infarction, thrombophlebitis, thrombocytopenia or bleeding disorder; wherein the nitric oxide adduct is a nitrate which has at least one —O—NO 2  group selected from the group consisting of a polypeptide; an amino acid; a sugar; an oligonucleotide; a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         16 . The method of  claim 15 , wherein the nitrate which has at least one —O—NO 2  group is selected from the group consisting of a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         17 . The method of  claim 16 , wherein the nitrate which has at least one —O—NO 2  group is nitroglycerin.  
     
     
         18 . The method of  claim 16 , wherein the nitrate which has at least one —O—NO 2  group is an angiotensin converting enzyme inhibitor.  
     
     
         19 . The method of  claim 15 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
     
     
         20 . The method of  claim 19 , 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.  
     
     
         21 . The method of  claim 20 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
     
     
         22 . A method for inhibiting platelet deposition, platelet adhesion or thrombus formation in a patient in need thereof comprising administering a therapeutically effective amount of a nitric oxide adduct to the patient to treat a myocardial infarction, thrombophlebitis, thrombocytopenia or a bleeding disorder caused by the platelet deposition, platelet adhesion or the thrombus formation; wherein the nitric oxide adduct is a nitrate which has at least one —O—NO 2  group selected from the group consisting of a polypeptide; an amino acid; a sugar; an oligonucleotide; a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         23 . The method of  claim 22 , wherein the nitrate which has at least one —O—NO 2  group is selected from the group consisting of a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         24 . The method of  claim 23 , wherein the nitrate which has at least one —O—NO 2  group is nitroglycerin.  
     
     
         25 . The method of  claim 23 , wherein the nitrate which has at least one —O—NO 2  group is an angiotensin converting enzyme inhibitor.  
     
     
         26 . The method of  claim 22 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
     
     
         27 . The method of  claim 26 , 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.  
     
     
         28 . The method of  claim 26 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.  
     
     
         29 . A method for treating a dysfunction in the endothelium of a patient comprising administering a therapeutically effective amount of a nitric oxide adduct to the patient wherein the nitric oxide adduct is a nitrate which has at least one —O—NO 2  group selected from the group consisting of a polypeptide; an amino acid; a sugar; an oligonucleotide; a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         30 . The method of  claim 29 , wherein the nitrate which has at least one —O—NO 2  group is selected from the group consisting of a branched or unbranched, saturated or unsaturated aliphatic hydrocarbon; an aromatic hydrocarbon; or a heterocyclic compound.  
     
     
         31 . The method of  claim 30 , wherein the nitrate which has at least one —O—NO 2  group is nitroglycerin.  
     
     
         32 . The method of  claim 30 , wherein the nitrate which has at least one —O—NO 2  group is an angiotensin converting enzyme inhibitor.  
     
     
         33 . The method of  claim 29 , further comprising administering at least one anti-thrombogenic compound or a therapeutic agent.  
     
     
         34 . The method of  claim 33 , 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.  
     
     
         35 . The method of  claim 33 , wherein the therapeutic agent is a monoclonal antibody, a fragment of recombinant human protein, a viral vector or an anti-sense molecule.