Use of glycyrrhizin and its derivatives as MCP-1 production inhibitors

Abstract

The object of the present invention is to provide the use of glycyrrhizin and its derivatives for inhibition of MCP-1 production. The present invention discloses an MCP-1 production inhibition method and pharmaceutical composition for the same comprising administration of glycyrrhizin and its derivatives in an amount effective for said inhibition to mammals in which migration of monocytes or T lymphocytes is increased, or production of IL-10 is increased, and inhibition of said increase is desired, thereby treating or preventing decreases in infection resistance.

1 . A method of treating or preventing decreases in infection resistance, comprising: administration of a compound represented by the following general formula (I) for inhibiting MCP-production:  
     
       
         
         
             
             
         
       
       wherein R 1  represents a hydrogen atom or a group of the following formula (II) or (III):  
       
         
           
           
               
               
           
         
       
       wherein the groups of formula (II) and formula (III) may also be their pharmaceutically acceptable salts;  
       R 2  represents COOH or a group of the following formula (IV):  
       
         
           
           
               
               
           
         
       
       or their pharmaceutically acceptable salts;  
       X represents C=0 or CH; and,  
       dotted lines suitably represent a double bond,  
       provided that said compound represented by the formula (I) is not MUN-014.  
     
   
   
       2 . The method according to  claim 1 , wherein the pharmaceutically acceptable salts in the above formulas (II), (III) and (IV) are sodium salts, potassium salts, ammonium salts or combinations thereof.  
   
   
       3 . The method according to  claim 1 , wherein the pharmaceutically acceptable salts in the above formulas (II), (III) and (IV) are sodium salts, or ammonium salts.  
   
   
       4 . The method according to  claim 1 , wherein a compound of the above general formula (I) is one of either: 
 olean-11,13(18)-diene-30-carboxy-3β-yl-(disodium 2-O-β-glucopyranuronosyl-β-D-glucopyranuronate);    sodium olean-3β-hydroxy-11-oxo-12-ene-30-ate;    disodium olean-9(11),12-diene-3β,30-diol-3β,30-O-dihemiphthalate;    disodium olean-3β-hydroxy-11,13(18)-diene-30-ate-3β-O-hemiphthalate;    disodium olean-3β-hydroxy-11-oxo-12-ene-30-ate-3β-O-hemiphthalate; or    monoammonium 20β-carboxy-11-oxo-30-norolean-12-en-3β-yl-2-O-β-D-glucopyranuronosyl-β-D-glucopyranosidouronate.    
   
   
       5 . The method according to any one of  claims 1  to  4 , wherein the decreases in infection resistance are decreases in infection resistance to opportunistic infections occurring in burn patients, AIDS patients, cancer patients, encephalitis patients, individuals who have suffered serious injuries or undergone major surgery, or individuals subject to stress or other individuals in which production of MCP-1 has been induced.  
   
   
       6 . A pharmaceutical composition for treatment or prevention of decreases in infection resistance to opportunistic infections occurring in burn patients, AIDS patients, cancer patients, encephalitis patients, individuals who have suffered serious injuries or undergone major surgery, individuals subject to stress or other individuals in which production of MCP-1 has been induced, comprising: 
 a compound according to any one of  claims 1  to  4 , along with an arbitrary pharmaceutically acceptable carrier, in an amount effective for treating or preventing decreases in infection resistance to opportunistic infections occurring in said individuals.