Compositions and methods for delivering carbon monoxide (CO) and nitric oxide (NO) to tissue using heme proteins as carriers

Abstract

The present invention relates to compositions and methods for delivering nitric oxide (NO) or carbon monoxide (CO) to cells using heme proteins as carriers. In one embodiment, the present invention relates to the use of modified hemoglobin to deliver NO or CO to cells

1 . A method of delivering XO to tissue, wherein X is N or C, comprising: 
 a) preparing an XO-hemoglobin (Hb) complex; and    b) contacting the cells with the XO-Hb complex.    
   
   
       2 . The method of  claim 1 , wherein the Hb is modified.  
   
   
       3 . The method of  claim 2 , wherein the modified Hb is surface modified Hb.  
   
   
       4 . The method of  claim 3 , wherein the surface modified Hb is Hb to which maleimidyl-activated polyethylene glycol (MalPEG) has been attached.  
   
   
       5 . The method of  claim 1 , wherein X is C.  
   
   
       6 . The method of  claim 1 , wherein X is N.  
   
   
       7 . The method of  claim 1 , wherein the tissue is red blood cells.  
   
   
       8 . A method of making an XO-Hb complex, wherein X is N or C, comprising the steps of: 
 a) preparing an aqueous solution of Hb; and    b) introducing gasous NO or CO into the solution.    
   
   
       9 . The method of  claim 7 , wherein the Hb does not contain free sulfhydryl groups.  
   
   
       10 . The method of  claim 7 , further comprising the step of blocking the Hb sulfhydryl groups.  
   
   
       11 . The method of  claim 9 , wherein blocking the Hb sulfhydryl groups further comprises mixing the Hb with an excess amount of MalPEG.  
   
   
       12 . A pharmaceutical composition for delivering XO to tissue, wherein X is N or C, comprising: 
 a) an XO-Hb complex; and    b) a pharmaceutically acceptable carrier.    
   
   
       13 . The composition of  claim 11 , wherein the pharmaceutical composition is adapted for administration to a mammal.  
   
   
       14 . The composition of  claim 11 , wherein X is CO.  
   
   
       15 . The composition of  claim 11 , wherein X is NO.  
   
   
       16 . The composition of  claim 13 , wherein the hemoglobin is MalPEG-Hb