Compositions and methods for acutely raising nitic oxide levels

Abstract

Disclosed herein are compositions and methods for acutely raising nitric oxide levels in a subject. In one example, the composition can include, an effective amount of a NOS dependent source of nitric oxide; an effective amount of a NOS independent source of nitric oxide; and an effective amount of a myeloperoxidase inhibitor; wherein the composition acutely raises nitric oxide levels in a subject above a level provided by the available sources of nitric oxide in the subject prior to administration of the composition. Further presented is a method of treating a subject for a condition or disorder that is response to nitric oxide therapy, including: acutely raising nitric oxide levels in a subject by simultaneously increasing biosynthesis of nitric oxide, increasing nitrate/nitrite levels, and inhibiting meyloperoxidase activity.

What is claimed is: 
     
         1 . A method of treating a subject for a condition or disorder that is responsive to nitric oxide therapy, comprising: acutely raising nitric oxide levels in a subject by simultaneously increasing biosynthesis of nitric oxide, increasing nitrate/nitrite levels, and inhibiting meyloperoxidase activity. 
     
     
         2 . The method of  claim 1 , wherein the condition or disorder is a nitric oxide related pathology. 
     
     
         3 . The method of  claim 2 , wherein the nitric oxide related pathology comprises a member selected from the group consisting of Alzheimer's disease, angina, asthma, congestive disorders, Crohn's disease, deep vein thrombosis, dementia, diabetes (types, 1, 2 and 3), diabetic foot disorders, diminished exercise capacity, endothelial dysfunction, endotoxemia, erectile dysfunction, fibromyalgia, heart attack, heart failure, hypertension, inflammatory bowel disease, leaky gut, macular degeneration, monocyte-mediated arterial plaque formation, motor dysfunction, multiple sclerosis, obesity, oxidation of LDL, peridontal disease, peripheral arterial disease, platelet stickiness, portal hypertension, pregnancy/pre-eclampsia, premature ejaculation, pulmonary hypertension, Raynaud's disease, renal failure, sleep apnea, smooth muscle cell proliferation, stroke, and vasculitis. 
     
     
         4 . The method of  claim 1 , wherein the condition or disorder is a cardio-metabolic disorder. 
     
     
         5 . The method of  claim 4 , wherein the cardio-metabolic disorder comprises a member selected from the group consisting of: Alzheimer's disease, angina, asthma, congestive disorders, Crohn's disease, deep vein thrombosis, dementia, diabetes (types, 1, 2 and 3), diabetic foot disorders, diminished exercise capacity, endothelial dysfunction, endotoxemia, erectile dysfunction, fibromyalgia, heart attack, heart failure, hypertension, inflammatory bowel disease, leaky gut, macular degeneration, monocyte-mediated arterial plaque formation, motor dysfunction, multiple sclerosis, obesity, oxidation of LDL, peridontal disease, peripheral arterial disease, platelet stickiness, portal hypertension, pregnancy/pre-eclampsia, premature ejaculation, pulmonary hypertension, Raynaud's disease, renal failure, sleep apnea, smooth muscle cell proliferation, stroke, and vasculitis. 
     
     
         6 . The method of  claim 4 , wherein the cardio-metabolic disorder comprises a member selected from the group consisting of hypertension, cardiovascular dysfunction, neurodegeneration, arthritis, asthma, and septic shock. 
     
     
         7 . The method of  claim 4 , wherein the cardio-metabolic disorder comprises preventing the formation of arterial plaque. 
     
     
         8 . The method of  claim 4 , wherein the treating of the subject is prophylactic. 
     
     
         9 . The method of  claim 1 , wherein the condition or disorder is a myeloperoxidase related pathology. 
     
     
         10 . The method of  claim 9 , wherein the myeloperoxidase-related pathology is Alzheimer's disease, angina, asthma, general congestive disorders, Crohn's disease, deep vein thrombosis, dementia, diabetes (types, 1, 2 and 3), diabetic foot disorders, diminished exercise capacity, endothelial dysfunction, endotoxemia, erectile dysfunction, fibromyalgia glomerulonephritis, heart attack, heart failure, hypertension, immune deficiency, inflammatory bowel disease, leaky gut, macular degeneration, monocyte-mediated arterial plaque formation, motor dysfunction, multiple sclerosis, obesity, oxidation of LDL, peridontal disease, peripheral arterial disease, platelet stickiness, portal hypertension, pregnancy/pre-eclampsia, premature ejaculation, pulmonary hypertension, Raynaud's disease, renal failure, sleep apnea, smooth muscle cell proliferation, stroke, vasculitis and diseases associated with skin such as slow wound healing, wrinkles, and premature signs of aging. 
     
     
         11 . The method of  claim 9 , wherein the myeloperoxidase related pathology comprises increased oxidized LDL cholesterol. 
     
     
         12 . The method of  claim 9 , wherein the myeloperoxidase related pathology comprises metabolic syndrome, type 1 diabetes, type 2 diabetes, type 3 diabetes, or a combination thereof. 
     
     
         13 . The method of  claim 9 , wherein the myeloperoxidase related pathology comprises leaky gut, endotoxemia, inflammatory bowel disease or a combination thereof. 
     
     
         14 . The method of  claim 9 , wherein the myeloperoxidase related pathology comprises a dermatopic pathology including slow wound healing, wrinkles, sun spots, and premature signs of aging. 
     
     
         15 . The method of  claim 9 , wherein the treating of the subject is prophylactic. 
     
     
         16 . The method of  claim 1 , wherein the condition or disorder is penile dysfunction. 
     
     
         17 . The method of  claim 1 , wherein acutely raising of nitric oxide levels in the subject enhances endothelial functioning, decreases monocyte-mediated arterial plaque formation, decreases the development of peripheral arterial disease, or a combination thereof, wherein an increase or decreases refers to a level in the subject prior to the administering of the therapeutically effective combination. 
     
     
         18 . The method of  claim 1 , wherein the subject is a human. 
     
     
         19 . The method of  claim 1 , wherein the treating of the subject is prophylactic. 
     
     
         20 . The method of  claim 1 , wherein acutely raising nitric oxide levels in the subject comprises raising salivary nitrite levels in the subject beyond a level of the salivary nitrite in the subject as compared to a level prior to administering the therapeutically effective combination. 
     
     
         21 . A system for acutely raising nitric oxide levels in a subject, comprising:
 an effective amount of a NOS dependent source of nitric oxide;   an effective amount of a NOS independent source of nitric oxide; and   an effective amount of a myeloperoxidase inhibitor.   
     
     
         22 . The system of  claim 21 , wherein at least one of the NOS dependent source of nitric oxide, the NOS independent source of nitric oxide, and the myeloperoxidase inhibitor are separate from one another. 
     
     
         23 . The system of  claim 21 , wherein at least one of the NOS dependent source of nitric oxide, the NOS independent source of nitric oxide, and the myeloperoxidase inhibitor are in separate formulations. 
     
     
         24 . The system of  claim 21 , wherein a level of nitric oxide in the subject following administration of the composition is greater than an amount provided by an equivalent amount of any one of the NOS dependent source of nitric oxide, the NOS independent source of nitric oxide, or the myeloperoxidase inhibitor. 
     
     
         25 . The system of  claim 24 , wherein the level of nitric oxide is greater than an additive amount of an equivalent amount of any one of the NOS dependent source of nitric oxide, the NOS independent source of nitric oxide, or the myeloperoxidase inhibitor. 
     
     
         26 . The system of  claim 21 , wherein the system is formulated as a kit.