Peritoneal dialysis solution containing modified icodextrins

Abstract

The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrins respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed.

What is claimed is:  
     
         1 . A sterilized peritoneal dialysis solution comprising: 
 a starch comprising a glucose polymer selected from the group consisting of                          wherein R is selected from the group consisting of CH 3 , CH 3 CH 2 , (CH 2 OH) 2 CH, CH 2 (OH)CH(OH)CH 2 , and [CH 2 (OH)CH(OH)CH 2 (OH)]CH, and wherein the polymer is linked by α-1,4 bonds, that comprise at least 85%, by number, of the linkages.    
     
     
         2 . The peritoneal dialysis solution of    claim 1    wherein the solution is substantially free of formaldehyde.  
     
     
         3 . The peritoneal dialysis solution of    claim 1    wherein the solution is substantially free of furfurals.  
     
     
         4 . The peritoneal dialysis solution of    claim 1    wherein the partially hydrolyzed starch is substantially of terminal aldehyde groups.  
     
     
         5 . A method of administering an autoclavable osmotic agent to a subject in need thereof wherein the osmotic agent is prepared by the steps comprising: 
 providing a solution of starch dissolved in water; and    adding NaBH 4  to the starch solution to reduce the starch.    
     
     
         6 . The method of    claim 5    further comprising the step of purifying the reduced starch solution by passing the reduced starch solution through an anionic exchange resin.  
     
     
         7 . The method of    claim 5    wherein the dissolving and adding steps are carried out at room temperature.  
     
     
         8 . The method of    claim 6    further comprising the following step after the adding step and prior to the purifying step: 
 allowing the solution to stand for about 10 hours.  
 
     
     
         9 . The method of    claim 5    wherein the starch is maltodextrin.  
     
     
         10 . The method of    claim 5    wherein the starch is reduced to an icodextrin linked predominately by α-1,4 bonds and having the formula:  
       
         
           
           
               
               
           
         
       
     
     
         11 . A method of administering a sterilizable osmotic agent to a subject in need thereof wherein the osmotic agent is prepared by the steps comprising: 
 providing a solution of starch dissolved in water;    providing a solution of NaOCl; and    adding the NaOCl solution to the starch solution to oxidize the starch.    
     
     
         12 . The method of    claim 11    further comprising the step of 
 purifying the oxidized starch solution by passing the oxidized starch solution through a gel permeation chromatograph.  
 
     
     
         13 . The method of    claim 11    wherein the adding step is carried out at room temperature.  
     
     
         14 . The method of    claim 12    further comprising the following step after the adding step and prior to the purifying step: 
 allowing the solution to stand for about 2 hours.  
 
     
     
         15 . The method of    claim 11    wherein the starch is maltodextrin.  
     
     
         16 . The method of    claim 11    wherein the starch is oxidized to an icodextrin linked predominately by α-1,4 bonds and having the formula:  
       
         
           
           
               
               
           
         
       
     
     
         17 . A method of administering a sterilizable osmotic agent to a subject in need of same wherein the osmotic agent is prepared by the steps comprising: 
 dissolving starch in an acid and an alcohol selected from the group consisting of methanol, butanol and glycerol.    
     
     
         18 . The method of    claim 17    further comprising the step of stirring the starch, alcohol and acid for about 2 hours.  
     
     
         19 . The method of    claim 17    wherein the stirring step is carried out at a temperature of about 100° C.  
     
     
         20 . The method of    claim 17    wherein the starch is maltodextrin.  
     
     
         21 . The method of    claim 17    wherein the acid is HCl.  
     
     
         22 . The method of    claim 17    wherein the starch is glycosylated to an icodextrin linked predominately by α-1,4 bonds and having the formula:  
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of CH 3 , CH 3 CH 2  and (CH 2 OH) 2 CH.