Novel therapeutic uses of glucan

Abstract

A process for the production of β-(1,3)(1,6) glucan from a glucan containing cellular source is described, together with compositions and uses/methods of treatment involving glucan. The process of the invention comprises the steps of: (a) extracting glucan containing cells with alkali and heat, in order to remove alkali soluble components; (b) acid extracting the cells of step (a) with an acid and heat to form a suspension; (c) extracting the suspension obtained of step (b) or recovered hydrolyzed cells with an organic solvent which is non-miscible with water and which has a density greater than that of water separating the resultant aqueous phase, solvent containing phase and interface so that substantially only the aqueous phase comprising β-(1,3)(1,6) glucan particulate material remains; wherein the extraction with said organic solvent provides separation of glucan subgroups comprising branched β-(1,3)(1,6)-glucan, and essentially unbranched β-(1,3) glucan which is associated with residual non-glucan contaminents; and (d) drying the glucan material from step (c) to give microparticulate glucan.

1 . A process for production of β-(1,3)(1,6)-glucan from a glucan containing cellular source which comprises the steps of: 
 (a) extracting glucan containing cells with alkali and heat, in order to remove alkali soluble components;  
 (b) acid extracting the cells of step (a) with an acid and heat to form a suspension;  
 (c) extracting the suspension obtained of step (b) or recovered hydrolyzed cells with an organic solvent which is non-miscible with water and which has a density greater than that of water separating the resultant aqueous phase, solvent containing phase and interface so that substantially only the aqueous phase comprising β-(1,3)(1,6)-glucan particulate material remains; wherein the extraction with said organic solvent provides separation of glucan subgroups comprising branched β-(1,3)(1,6) glucan, and essentially unbranched β-(1,3) glucan which is associated with residual non-glucan contaminents; and  
 (d) drying the glucan material from step (c) to give microparticulate glucan.  
 
     
     
         2 . A process according to  claim 1 , which is a process for producing soluble glucan, wherein step (d) is omitted and the pH of the glucan material is raised so as to effect solubilization of the glucan, and wherein the temperature of reaction is less than about 60° C.  
     
     
         3 . A process according to  claim 1 , which is a process for producing soluble glucan, wherein the particulate glucan of step (d) is suspended in an aqueous alkali solution so as to effect solubilization of the glucan, and wherein the temperature of reaction is less than about 60° C.  
     
     
         4 . A process according to  claim 2  or  3 , wherein the temperature of reaction is between about 2° C. and about 8° C. and wherein the soluble glucan has a polydispersity index suitable for use as a pharmaceutical product.  
     
     
         5 . A process according to  claim 1  wherein the acid used at step (b) is selected from acetic acid, formic acid, phosphoric acid and hydrochloric acid.  
     
     
         6 . A process according to  claim 1  wherein the pH of the acid of step (b) is from about 2 to about 6.  
     
     
         7 . A process according to  claim 1  wherein the organic solvent of step (c) is selected from chloroform, methylchloroform, dichloromethane, tetrachloroethane and carbon tetrachloride.  
     
     
         8 . A process according to  claim 7  wherein said solvent is chloroform.  
     
     
         9 . A process according to  claim 2  or  3  wherein the solution pH after glucan solubilisation is adjusted to the range of about pH 9 to about pH 10, and the resultant soluble glucan is admixed with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         10 . A process according to  claim 2  or  3  wherein the solution pH after glucan solubilisaion is adjusted from about 7 to about 8 so as to form a gel which optionally is admixed with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         11 . Particulate glucan when produced according to the process of  claim 1 , optionally in association with a pharmaceutically acceptable carrier or excipient.  
     
     
         12 . Soluble glucan when produced according the process of any one of  claims 2  to  4 , optionally in association with a pharmaceutically acceptable carrier or excipient.  
     
     
         13 . A glucan gel when produced according to the process of  claim 10 , optionally in association with a pharmaceutically acceptable carrier or excipient.  
     
     
         14 . A composition which consists essentially of branched β(1,3)(1,6)-glucan and which is essentially free or unbranched β(1,3) glucan, optionally in association with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         15 . A glucan composition according to  claim 1 , wherein said glucan is microparticulate, soluble in aqueous solution, or is the form of a gel.  
     
     
         16 . Use of glucan for the manufacture of a medicament for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopaedic devices, or for the prevention/treatment of ultraviolet light induced skin damage.  
     
     
         17 . Use of glucan for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopaedic devices, or for the prevention/treatment of ultraviolet light induced skin damage.  
     
     
         18 . A method for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopaedic devices, or for the prevention/treatment of ultraviolet light induced skin damage which comprises administering glucan to a subject, optionally in association with one or more pharmaceutically, veterinarily or agriculturally acceptable carrier or excipient.  
     
     
         19 . An agent for the treatment of skin ulceration or bone fracture or the enhancement of fixation of implanted orthopaedic devices, or for the prevention/treatment of ultraviolet light induced skin damage which comprises glucan optionally in association with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         20 . Use of glucan according to  claim 16  or  17  wherein said glucan is produced according to any one of  claims 1  to  10 .  
     
     
         21 . A method according to claims  18  wherein said glucan is produced according to any one of  claims 1  to  10 .