Methods and compositions for optimization of oxygen transport by cell-free systems

Abstract

Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

1 - 44 . (canceled)  
   
   
       45 . An aqueous cell-free composition for administration to a subject, comprising polyalkylene oxide modified hemoglobin in an aqueous solution, wherein said modified hemoglobin has a molecular radius larger than native hemoglobin, wherein said composition has a viscosity at least half that of blood, and an oncotic pressure higher than that of plasma, and wherein said polyalkylene oxide is covalently attached to cysteine residues on the hemoglobin.  
   
   
       46 . The composition according to  claim 45 , wherein P50 of said composition is equal to or lower than that of blood.  
   
   
       47 . The composition according to  claim 45 , wherein the modified hemoglobin is human hemoglobin.  
   
   
       48 . The composition according to  claim 45 , wherein the viscosity is from 2 to 4.5 cPs.  
   
   
       49 . The composition according to  claim 48 , wherein the viscosity is at least 2 cPs.  
   
   
       50 . The composition according to  claim 49 , wherein the viscosity is 2.5 cPs.  
   
   
       51 . The composition according to  claim 45 , wherein the modified hemoglobin concentration is greater than 4.0 g/dl.  
   
   
       52 . The composition according to  claim 45 , wherein P50 of said composition is less than 28 mm Hg.  
   
   
       53 . The composition according to  claim 45 , wherein the polyalkylene oxide is polyethylene glycol.  
   
   
       54 . The composition according to  claim 45 , wherein the oncotic pressure is greater than 25 mm Hg.  
   
   
       55 . The composition according to  claim 45 , wherein the oncotic pressure is from 20 to 60 mm Hg.  
   
   
       56 . The composition according to  claim 45 , wherein said polyalkylene oxide is covalently attached to sulfhydryl groups of said cysteine residues.  
   
   
       57 . An aqueous cell-free composition for administration to a subject, comprising polyethylene glycol conjugated to sulfhydryl groups on human hemoglobin to form a modified hemoglobin in an aqueous solution, wherein said modified hemoglobin has a molecular radius larger than native hemoglobin, wherein said composition has a viscosity from 2 to 4.5 cPs, an oncotic pressure from 20 to 60 mm Hg, and a modified hemoglobin concentration greater than 4.0 g/dl.  
   
   
       58 . The composition according to  claim 57 , wherein said sulfhydryl groups are on cysteine residues.