Compositions and methods for treating diseases

Abstract

This invention relates to compositions and methods for treatment of vascular conditions. The invention provides arginine polymers and arginine homopolymers for the treatment and/or prevention of glaucoma, pulmonary hypertension, asthma, chronic obstructive pulmonary disease, erectile dysfunction, Raynaud's syndrome, heparin overdose, vulvodynia, and wound healing. The invention also provides arginine polymers and arginine homopolymers for use in organ perfusate and preservation solutions.

1 . A method for treating or preventing a vascular condition in a patient comprising administering locally to said patient a therapeutically effective amount of a composition that increases the metabolic production of NO.  
     
     
         2 . The method of  claim 1  wherein said metabolic production is by NOS.  
     
     
         3 . The method of  claim 2  wherein said NOS is inducible NOS.  
     
     
         4 . The method of  claim 1  wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.  
     
     
         5 . The method of  claim 1  wherein said composition is an arginine homopolymer  
     
     
         6 . The method of  claim 5  wherein said arginine homopolymer comprises essentially of L-arginine residues.  
     
     
         7 . The method of  claim 1  wherein said composition is administered subcutaneously, topically, via inhalation, vaginally, rectally, ocularly, or parenterally.  
     
     
         8 . The method of  claim 1  wherein said condition is selected from the group consisting of aneurysm, anastomatic intimal hyperplasia, atherosclerosis, Behcet's Syndrome, carotid artery disease, chronic obstructive pulmonary disease, chronic rejection, coronary artery disease, degos, dementia, headaches, hemorrhoids, heparin overdose, hereditary angioedema, pulmonary arterial hypertension, ischemia, lymphedema, myoamoya, peripheral arterial disease, pseudoxanthoma elasticum, thoracic outlet syndrome, thromboangiitis obliterans, thrombosis, varicose veins, and Wegener's granulomatosis, atelectasis, acidosis, acute bronchitis, acute mountain sickness, acute pulmonary edema, acute pulmonary thrombolism, adult respiratory distress syndrome, bronchial asthma, early embolic stroke, emphysema, fat embolism in the lung, hypertension, hypoxia, hyaline membrane disease, inflammation of the lung, Kartaagener's syndrome, Legionnaire's disease, myocardial infraction, panacinar emphysema, persistent pulmonary hypertension of newborn, post cardiac surgery acute pulmonary pneumonia, prenatal aspiration syndrome, erectile dysfunction, Peyronie's syndrome, priapism, premature ejaculation, female sexual dysfunctions, vaginal lubrication, vaginal engorgement, pain during intercourse (e.g., dyspareunia or vulvadynia), urologenital infections, estrogen depletion conditions, menopause and post-menopause, hot flashes, preeclampsia, vulvodynia, cataract, intraocular pressure, dry eye, and diabetic retinopathy, aging, necrotizing fascitis, decubitus ulcers, anal fissures, scleroderma, Raynaud's phenomenon, sclerosis, malignant nephroangioscelerosis, infraction from occlusion of major renal vessels, atheromatoous embolization, renal cortical necrosis, and renal vein thrombosis.  
     
     
         9 . A method for treating or preventing glaucoma in a patient comprising administering to said patient a therapeutically effective amount of a composition that increases the metabolic production of NO.  
     
     
         10 . The method of  claim 9  wherein said metabolic production is by NOS.  
     
     
         11 . The method of  claim 10  wherein said NOS is inducible NOS.  
     
     
         12 . The method of  claim 9  wherein said composition is administered topically, parenterally, subcutaneously, or ocularly.  
     
     
         13 . The method of  claim 9  wherein said composition is administered locally to a trabecular meshwork or a Schlemm's canal.  
     
     
         14 . The method of  claim 9  wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.  
     
     
         15 . The method of  claim 9  wherein said composition is an arginine homopolymer.  
     
     
         16 . The method of  claim 15  wherein said arginine homopolymer comprises essentially of L-arginine residues.  
     
     
         17 . The method of  claim 9  further comprising administering to said patient an agent selected from the group consisting of pilocarpine, timolol maleate, betataxolol HCl, epinephrine, dipivefrin, demecarium bromide, echothiophate iodide, A3 subtype adenosine receptor antagonist, antiestrogen, and calmodulin antagonist.  
     
     
         18 . A composition for the preservation and reperfusion having an osmolality level of about 150-350 mOsm/liter comprising an agent that increases the metabolic production of NO.  
     
     
         19 . The method of  claim 18  wherein said metabolic production is by NOS.  
     
     
         20 . The method of  claim 19  wherein said NOS is inducible NOS.  
     
     
         21 . The composition of  claim 18  further comprising hydroxyethyl starch, lactobionate salt, or raffinose.  
     
     
         22 . The composition of  claim 18  wherein said agent is an arginine polymer comprising of at least 9 consecutive arginine residues.  
     
     
         23 . The composition of  claim 18  wherein said agent is an arginine homopolymer.  
     
     
         24 . The composition of  claim 23  wherein said arginine homopolymer comprises essentially of L-arginine residues.  
     
     
         25 . The composition of  claim 18  further comprising one or more agents selects from the group consisting of: insulin, dexamethasone, phenol red, penicillin, sodium gluconate, calcium chloride, magnesium gluconate, HEPES buffer, glucose, adenosine, glutathione, and potassium phosphate.  
     
     
         26 . A drug eluting stent comprising a composition that increases the metabolic production of NO in a cell, tissue, or organ.  
     
     
         27 . A method for treating peripheral arterial disease comprising administering to a patient suffering from said disease a drug eluting stent of  claim 2 .  
     
     
         28 . The stent of  claim 2  wherein said metabolic production NO is by NOS  
     
     
         29 . The method of  claim 2  wherein said NOS is inducible NOS  
     
     
         30 . The method of  claim 3  wherein said composition is an arginine polymer comprising of at least 8 consecutive arginine residues.  
     
     
         31 . The method of  claim 3  wherein said composition is an arginine homopolymer.  
     
     
         32 . The method of  claim 3  wherein said arginine homopolymer comprises essentially of L-arginine residues.