Solutions for use as plasma expanders and substitutes

Abstract

An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, which is buffered by lactate and has a pre-administration pH of between 4 and 6.5 is disclosed. In one embodiment, the artificial plasma-like solution may have at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplementation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. Methods for the administration of the plasma-like solution are also disclosed.

What is claims is:  
     
         1 . A method for increasing the circulating volume of a hypovolemic subject comprising administering to said subject a plasma-like substance comprising an aqueous solution of at least one water soluble polysaccharide oncotic agent and a small organic acid salt, with the proviso that: 
 (a) when said oncotic agent is a hydroxyethyl starch, said hydroxyethyl starch is selected from the group consisting of high molecular weight and low molecular weight hydroxyethyl starches; and    (b) said solution has at least one of the following characteristics: 
 (i) is terminally heat sterilized;  
 (ii) does not contain a biological buffer; and  
 (iii) has a pH between 4 and 6.5.  
   
     
     
         2 . The method according to  claim 1 , wherein said polysaccharide oncotic agent is a glucan polymer.  
     
     
         3 . The method according to  claim 2 , wherein said glucan polymer is a hydroxyethyl starch.  
     
     
         4 . The method according to  claim 3 , wherein said hydroxyethyl starch has a molar substitution of 0.7.  
     
     
         5 . The method according to  claim 3 , wherein said hydroxyethyl starch has a molar substitution of 0.45.  
     
     
         6 . The method according to  claim 1 , wherein said small organic acid salt is a salt of a small organic acid ion that may be metabolized.  
     
     
         7 . The method according to  claim 6 , wherein said small organic acid ion is selected from the group consisting lactate, acetate, pyruvate, gluconate and succinate.  
     
     
         8 . The method according to  claim 1 , wherein said solution does not comprise a biological buffer.  
     
     
         9 . The method according to  claim 1 , wherein said solution is a terminally heat sterilized solution.  
     
     
         10 . The method according to  claim 1 , wherein said solution has a pH between 4 and 6.5.  
     
     
         11 . A method for increasing the circulating volume of a hypovolemic subject comprising administering to said subject a plasma-like substance comprising an aqueous solution of at least one water soluble hydroxyethyl starch selected from the group consisting of high and low molecular weight hydroxyethyl starches and a small organic acid salt of an ion selected from the group consisting of lactate, acetate, pyruvate, gluconate and succinate, wherein said solution has a pH between 4 and 6.5.  
     
     
         12 . The method according to  claim 11 , wherein said hydroxyethyl starch has a molar substitution of 0.7.  
     
     
         13 . The method according to  claim 12 , wherein said hydroxyethyl starch is hetastarch.  
     
     
         14 . The method according to  claim 11 , wherein said hydroxyethyl starch has a molar substitution of 0.45.  
     
     
         15 . The method according to  claim 14 , wherein said hydroxyethyl starch is pentastarch.  
     
     
         16 . The method according to  claim 11 , wherein said solution does not comprise a biological buffer.  
     
     
         17 . The method according to  claim 11 , wherein said solution is a terminally heat sterilized solution.  
     
     
         18 . A plasma-like substance comprising an aqueous solution of at least one water soluble polysaccharide oncotic agent and a small organic acid salt, with the proviso that: 
 (a) when said oncotic agent is a hydroxyethyl starch, said hydroxyethyl starch is selected from the group consisting of high molecular weight and low molecular weight hydroxyethyl starches; and    (b) said solution has at least one of the following characteristics: 
 (i) is terminally heat sterilized;  
 (ii) does not contain a biological buffer; and  
 (iii) has a pH between 4 and 6.5.  
   
     
     
         19 . The plasma-like substance according to  claim 18 , wherein said polysaccharide oncotic agent is a glucan polymer.  
     
     
         20 . The plasma-like substance according to  claim 19 , wherein said glucan polymer is a hydroxyethyl starch.  
     
     
         21 . The plasma-like substance according to  claim 20 , wherein said hydroxyethyl starch has a molar substitution of 0.7.  
     
     
         22 . The plasma-like substance according to  claim 20 , wherein said hydroxyethyl starch has a molar substitution of 0.45.  
     
     
         23 . The plasma-like substance according to  claim 18 , wherein said small organic acid salt is a salt of a small organic acid ion that may be metabolized.  
     
     
         24 . The plasma-like substance according to  claim 23 , wherein said small organic acid ion is selected from the group consisting lactate, acetate, pyruvate, gluconate and succinate.  
     
     
         25 . The plasma-like substance according to  claim 18 , wherein said solution does not comprise a biological buffer.  
     
     
         26 . The plasma-like substance according to  claim 18 , wherein said solution is a terminally heat sterilized solution.  
     
     
         27 . The plasma-like substance according to  claim 18 , wherein said solution has a pH between 4 and 6.5.  
     
     
         28 . A plasma-like substance comprising an aqueous solution of at least one water soluble hydroxyethyl starch selected from the group consisting of high and low molecular weight hydroxyethyl starches and a small organic acid salt of an ion selected from the group consisting of lactate, acetate, pyruvate, gluconate and succinate, wherein said solution has a pH between 4 and 6.5.  
     
     
         29 . The plasma-like substance according to  claim 28 , wherein said hydroxyethyl starch has a molar substitution of 0.7.  
     
     
         30 . The plasma-like substance according to  claim 29 , wherein said hydroxyethyl starch is hetastarch.  
     
     
         31 . The plasma-like according to  claim 28 , wherein said hydroxyethyl starch has a molar substitution of 0.45.  
     
     
         32 . The plasma-like according to  claim 31 , wherein said hydroxyethyl starch is pentastarch.  
     
     
         33 . The plasma-like according to  claim 28 , wherein said solution does not comprise a biological buffer.  
     
     
         34 . The plasma-like according to  claim 28 , wherein said solution is a terminally heat sterilized solution.