Dosing regimens and methods of treatment using carbon monoxide

Abstract

The present invention is directed to dosing regimens for the administration of carbon monoxide in the treatment of various indications as well as methods for enhancing organ function following transplant thereof.

1 . A method for treating a patient in need thereof with carbon monoxide, comprising administering to the patient an effective amount of carbon monoxide that results in a carboxyhemoglobin concentration of at least 3%. 
     
     
         2 . The method of  claim 1 , wherein the carboxyhemoglobin concentration is between about 3% and about 15%. 
     
     
         3 . The method of  claim 2 , wherein the carboxyhemoglobin concentration is between about 7% and about 15%. 
     
     
         4 . The method of  claim 1 , wherein the patient is administered carbon monoxide at a dose ranging between about 2 mg/kg to about 3 mg/kg for a sufficient time period that results in an effective carboxyhemoglobin concentration. 
     
     
         5 . The method of  claim 1 , wherein the patient is administered carbon monoxide at a dose of 3 mg/kg for a sufficient time period that results in an effective carboxyhemoglobin concentration. 
     
     
         6 . The method of  claim 1 , wherein carbon monoxide is administered to the patient in a gaseous form, a liquid form, or a combination thereof. 
     
     
         7 . The method of  claim 1 , further comprising administering an additional agent that has a therapeutic effect. 
     
     
         8 . A method for enhancing organ function following transplant thereof, comprising administering to a patient in need thereof an effective amount of carbon monoxide that results in a carboxyhemoglobin concentration of at least 3%, wherein carbon monoxide is administered intra-operatively during transplant of an organ. 
     
     
         9 . The method of  claim 8 , wherein the patient is administered carbon monoxide at the time of reperfusion. 
     
     
         10 . The method of  claim 8 , wherein the carboxyhemoglobin concentration is between about 7% and about 15%. 
     
     
         11 . The method of  claim 8 , wherein the organ is selected from kidney, liver, heart, skin, large or small intestine and pancreas. 
     
     
         12 . The method of  claim 8 , wherein the organ is kidney. 
     
     
         13 . The method of  claim 12 , wherein kidney function is improved as indicated by an improvement in at least one of: serum creatinine level or glomerular filtration rate. 
     
     
         14 . The method of  claim 8 , wherein said patient does not show any neurocognitive impairment when compared to placebo in the 24 hour period following treatment with carbon monoxide. 
     
     
         15 . The method of  claim 8 , wherein said patient does not show any neurocognitive impairment when compared to placebo in the time period up to 24 weeks following treatment with carbon monoxide. 
     
     
         16 . The method of  claim 8 , wherein said patient does not show any cardiovascular effects when compared to placebo during treatment with carbon monoxide. 
     
     
         17 . The method of  claim 8 , wherein said patient does not show any cardiovascular effects when compared to placebo in the 8 hour period following treatment with carbon monoxide.