Water-soluble chitosan having low endotoxin concentration and methods for making and using the same

Abstract

Water-soluble chitosan having a low concentration of endotoxin is disclosed. Products containing the water-soluble chitosan are also disclosed. Methods of making and using water-soluble chitosan having a low concentration of endotoxin are further disclosed.

1 . A water-soluble chitosan having low endotoxin content, 
 wherein the water-soluble chitosan has an_endotoxin content of less than about 100 equivalent units (e.u.) of endotoxin per gram of dry water-soluble chitosan, and    wherein the water-soluble chitosan is formed by: 
 contacting water-insoluble chitosan with a basic solution for a first period of time;  
 rinsing the water-insoluble chitosan to remove any residual basic solution;  
 partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;  
 dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant;  
 adjusting a pH of the aqueous solution to a pH of at least 7.0;  
 adding a water-miscible solvent into the aqueous solution having a pH of at least 7.0;  
 further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content;  
 separating the water-soluble chitosan having low endotoxin content from the aqueous solution; and  
 washing the water-soluble chitosan having low endotoxin content with the water-miscible solvent.  
   
     
     
         2 . A water-soluble chitosan having low endotoxin content, 
 wherein the water-soluble chitosan has an endotoxin content of less than about 50 equivalent units (e.u.) of endotoxin per gram of dry water-soluble chitosan, and    wherein the water-soluble chitosan is formed by: 
 contacting water-insoluble chitosan with a basic solution for a first period of time;  
 rinsing the water-insoluble chitosan to remove any residual basic solution;  
 partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;  
 dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant;  
 adjusting a pH of the aqueous solution to a pH of at least 7.0;  
 adding a water-miscible solvent into the aqueous solution having a pH of at least 7.0;  
 further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content;  
 separating the water-soluble chitosan having low endotoxin content from the aqueous solution; and  
 washing the water-soluble chitosan having low endotoxin content with the water-miscible solvent.  
   
     
     
         3 . A water-soluble chitosan having low endotoxin content, 
 wherein the water-soluble chitosan has an_endotoxin content of less than about 20 equivalent units (e.u.) of endotoxin per gram of dry water-soluble chitosan, and    wherein the water-soluble chitosan is formed by: 
 contacting water-insoluble chitosan with a basic solution for a first period of time;  
 rinsing the water-insoluble chitosan to remove any residual basic solution;  
 partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;  
 dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant;  
 adjusting a pH of the aqueous solution to a pH of at least 7.0;  
 adding a water-miscible solvent into the aqueous solution having a pH of at least 7.0;  
 further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content;  
 separating the water-soluble chitosan having low endotoxin content from the aqueous solution; and  
 washing the water-soluble chitosan having low endotoxin content with the water-miscible solvent.  
   
     
     
         4 . A water-soluble chitosan having an endotoxin content of less than about 100 equivalent units per gram of dry water soluble chitosan, formed by: 
 contacting water-insoluble chitosan with a NaOH solution for a first period of time of greater than 1 hour;    partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;    dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant and having a pH of from about 7.0 at about 7.4; and    adding a water-miscible solvent into the aqueous solution and further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content from the aqueous solution/water-miscible solvent mixture.    
     
     
         5 . A pharmaceutically acceptable solution comprising the water-soluble chitosan of  claim 4  and at least one buffer material.  
     
     
         6 . The pharmaceutically acceptable solution of  claim 5 , where the pharmaceutically acceptable solution is a contact lens cleaning solution.  
     
     
         7 . A pharmaceutically acceptable solution comprising: 
 at least one buffer material; and    a water-soluble chitosan made by: 
 contacting water-insoluble chitosan with a basic solution for a first period of time;  
 rinsing the water-insoluble chitosan to remove any residual basic solution;  
 partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;  
 dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant;  
 adjusting a pH of the aqueous solution to a pH of at least 7.0;  
 adding a water-miscible solvent into the aqueous solution having a pH of at least 7.0;  
 further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content;  
 separating the water-soluble chitosan having low endotoxin content from the aqueous solution; and  
 washing the water-soluble chitosan having low endotoxin content with the water-miscible solvent.  
   
     
     
         8 . The pharmaceutically acceptable solution of  claim 7 , where the pharmaceutically acceptable solution is a contact lens cleaning solution.  
     
     
         9 . A pharmaceutically acceptable solution comprising: 
 at least one buffer material; and    a water-soluble chitosan made by: 
 contacting water-insoluble chitosan with a NaOH solution for a first period of time of greater than 1 hour;  
 partially acetylating the water-insoluble chitosan in a reaction solution containing a phase transfer agent to form partially acetylated water-soluble chitosan;  
 dissolving the partially acetylated water-soluble chitosan in an aqueous solution containing a surfactant and having a pH of from about 7.0 at about 7.4; and  
 adding a water-miscible solvent into the aqueous solution and further adjusting the pH of the aqueous solution to a pH of at least 8.0 to cause precipitation of water-soluble chitosan having low endotoxin content from the aqueous solution/water-miscible solvent mixture.  
   
     
     
         10 . The pharmaceutically acceptable solution of  claim 9 , where the pharmaceutically acceptable solution is a contact lens cleaning solution.