Radical scavenger and active oxygen eliminating agent

Abstract

It is an object to provide a radical scavenger, an active oxygen-scavenging agent and the like, which are highly efficacious clinically and novel, and so as to attain the object, 3,4-dihydroxyphenylalanine derivatives such as N-β-alanyl-5-S-glutathionyl-1-3,4-dihydroxyphenylalanine (5-S-GAD) or pharmaceutically acceptable salts thereof are contained as an active ingredient.

1 . A radical scavenger containing a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 1  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 3  represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       2 . A radical scavenger according to  claim 1 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine. 
   
   
       3 . An active oxygen-scavenging agent containing a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 1  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 3  represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       4 . An active oxygen-scavenging agent according to  claim 3 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine. 
   
   
       5 . An antioxidant agent containing a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 1  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 3  represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       6 . An antioxidant agent according to  claim 5 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine. 
   
   
       7 . An agent for preventing and therapeutically treating diseases or symptoms due to free radicals or active oxygen, which contains a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 1  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       8 . An agent for preventing and therapeutically treating diseases or symptoms due to free radicals or active oxygen according to  claim 7 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine. 
   
   
       9 . An ophthalmologic pharmaceutical composition containing a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 4  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 3  represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       10 . An ophthalmologic pharmaceutical composition according to  claim 9 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine. 
   
   
       11 . A composition for organ storage or organ perfusion containing a 3,4-dihydroxyphenylalanine derivative represented by the following formula (I): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 1  represents hydrogen atom or an appropriate amino acid residue; R 2  represents hydrogen atom or a group represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     [in the formula, R 3  represents hydrogen atom or an appropriate amino acid residue; R 4  represents hydroxyl group or an appropriate amino acid residue; and n represents 1 or 2]; when either one of R 1  and R 2  is hydrogen atom, herein, the remaining one is never hydrogen atom], 
     or a pharmaceutically acceptable salt thereof as an active ingredient. 
   
   
       12 . A composition for organ storage or perfusion according to  claim 11 , where the 3,4-dihydroxyphenylalanine derivative is N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine.