Use of nitrite salts in treating tissue damage

Abstract

Methods of treating a subject who has an tissue damage or who is at risk for tissue necrosis are disclosed. Also disclosed are methods of treating a subject who has an inflammatory disorder. The methods can include administering to the subject a pharmaceutical composition comprising inorganic nitrite or a pharmaceutically acceptable salt thereof, for a time and in an amount sufficient to reduce the tissue damage. The subject can be diagnosed as having a medical condition that results tissue damage, for example, diabetes, peripheral artery disease, cardiovascular disease, defective wound healing, arthritis, inflammatory bowel disease, ischemia, or a bacterial infection, e.g., Group A staphylococcal infection. The methods can include the step of monitoring the course of treatment.

1 . A method of treating tissue damage in a subject, the method comprising:
 a) identifying a subject who has tissue damage; and   b) administering to the subject a pharmaceutical composition comprising inorganic nitrite or a pharmaceutically acceptable salt thereof, wherein the nitrite is administered for a time and in an amount sufficient to reduce said tissue damage.   
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the pharmaceutically acceptable salt of inorganic nitrite is sodium nitrite, potassium nitrite, or calcium nitrite. 
     
     
         6 .- 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the nitrite is administered until a symptom of tissue damage in the subject improves. 
     
     
         10 . The method of  claim 9 , wherein the symptom of tissue damage comprises pain, skin pallor, numbness, swelling, ulceration, neuropathy, erythema, decreased plantar sensation, or defective tissue wound healing. 
     
     
         11 . The method of  claim 1 , wherein the amount of nitrite is a dose of about 1 μg/kg to about 5000 μg/kg. 
     
     
         12 . The method of  claim 11 , wherein the dose is about 0.5 μg/kg to about 1000 μg/kg. 
     
     
         13 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the subject has peripheral artery disease, diabetes, atherosclerotic cardiovascular disease, intermittent claudication, critical limb ischemic disease, defective wound healing, stroke, myocardial infarction, inflammatory bowel disease, a bone fracture, a bone infection, or peripheral neuropathy, avascular necrosis, rheumatoid arthritis, lupus, a bacterial infection, a fungal infection, fasciitis, or cellulitis. 
     
     
         20 . The method of  claim 19 , wherein the diabetes is type 1 or type 2 diabetes. 
     
     
         21 .- 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the tissue damage comprises a wound. 
     
     
         24 .- 26 . (canceled) 
     
     
         27 . A method of treating tissue necrosis in a subject, the method comprising:
 a) identifying a subject who has or who is at risk for tissue necrosis; and   b) administering to the subject a pharmaceutical composition comprising inorganic nitrite or a pharmaceutically acceptable salt thereof, wherein the nitrite is administered for a time and in an amount sufficient to reduce said necrosis.   
     
     
         28 .- 30 . (canceled) 
     
     
         31 . The method of  claim 27 , wherein the pharmaceutically acceptable salt of inorganic nitrite is sodium nitrite, potassium nitrite, or calcium nitrite. 
     
     
         32 .- 35 . (canceled) 
     
     
         36 . The method of  claim 27 , wherein the symptom of necrosis comprises pain, skin pallor, numbness, ulceration, neuropathy, erythema, decreased plantar sensation, gangrene or defective tissue wound healing. 
     
     
         37 . The method of  claim 27 , wherein the amount of nitrate is a dose of about 1 μg/kg to about 5000 μg/kg. 
     
     
         38 . The method of  claim 37 , wherein the dose is about 0.5 μg/kg to about 1000 μg/kg. 
     
     
         39 .- 44 . (canceled) 
     
     
         45 . The method of  claim 27 , wherein the subject has peripheral artery disease, diabetes, atherosclerotic cardiovascular disease, intermittent claudication, critical limb ischemic disease, defective wound healing, stroke, myocardial infarction, inflammatory bowel disease, a bone fracture, a bone infection, or peripheral neuropathy, avascular necrosis, an autoimmune disease, a bacterial infection, a fungal infection, fasiculitis, or cellulitis. 
     
     
         46 . The method of  claim 45 , wherein the diabetes is type 1 or type 2 diabetes. 
     
     
         47 .- 48 . (canceled) 
     
     
         49 . The method of  claim 27 , wherein the tissue necrosis comprises a wound. 
     
     
         50 .- 54 . (canceled) 
     
     
         55 . A method of treating an inflammatory disease in a subject, the method comprising:
 a) identifying a subject who has an inflammatory disease; and   b) administering to the subject a pharmaceutical composition comprising inorganic nitrite or a pharmaceutically acceptable salt thereof, wherein the nitrite is administered for a time and in an amount sufficient to treat said inflammatory disease.