Micellar preparation containing sparingly water-soluble anticancer agent and novel block copolymer

Abstract

A novel micellar preparation in which the solubility of a sparingly water-soluble anticancer agent has been heightened and which after intravenous administration, enables a high blood concentration to be maintained. The preparation has high medicinal activity and/or is reduced in side effects. The micellar preparation is formed from a block copolymer represented by the following general formula (1): [wherein R1 represents hydrogen or C 1-5 alkyl; R2 represents C 1-5 alkylene; R3 represents methylene or ethylene; R4 represents hydrogen or C 1-4 acyl; R5 represents hydroxyl, optionally substituted aryl C 2-8 alkoxyl, substituted C 1-4 alkylamino, or amino having a residue of either an amino acid or a peptide derivative; n is an integer of 5 to 1,000; m is an integer of 2 to 300; and x is an integer of 1 to 300; provided that the proportion of hydroxy in the R5's is 0 to 99% and x is not larger than m] and a sparingly water-soluble anticancer agent.

1 . A micellar preparation formed from a block copolymer represented by general formula (1) below  
     
       
         
         
             
             
         
       
     
     (wherein R1 represents a hydrogen atom or C 1-5  alkyl group; R2 represents a C 1-5  alkylene group; R3 represents a methylene or ethylene group; R4 represents a hydrogen atom or a C 1-4  acyl group; R5 represents a hydroxyl group, an optionally substituted aryl C 2-8  alkoxyl group, a substituted C 1-4  alkylamino group, or an amino group having a residue of a derivative of an amino acid or a peptide; n is an integer of 5 to 1,000, m is an integer of 2 to 300, and x is an integer of 1 to 300; provided that the proportion of a hydroxyl group in the R5 is 0 to 99% and x is not larger than m) and a sparingly water-soluble anticancer agent.  
   
   
       2 . The micellar preparation according to  claim 1  wherein the proportion of hydroxyl group in the R5s of general formula (1) is 0% to 90%.  
   
   
       3 . The micellar preparation according to  claim 1 , wherein, in general formula (1), R1 represents a methyl group, R2 represents a trimethylene group, R3 represents a methylene group, R4 represents an acetyl group, and R5 represents an unsubstituted phenyl C 3-6  alkoxyl group; n is an integer of 20 to 500, m is an integer of 10 to 100, and x is an integer of 1 to 100; provided that x is not larger than m.  
   
   
       4 . The micellar preparation according to any one of  claims 1  to  3 , wherein the sparingly water-soluble anticancer agent is a taxane anticancer agent.  
   
   
       5 . The micellar preparation according to  claim 4 , wherein the taxane anticancer agent is paclitaxel.  
   
   
       6 . An anticancer agent containing, as active ingredient, the micellar preparation according to any one of  claims 1  to  5 .  
   
   
       7 . A block copolymer represented by general formula (1) below  
     
       
         
         
             
             
         
       
     
     (wherein R1 represents a hydrogen atom or C 1-5  alkyl group; R2 represents a C 1-5  alkylene group; R3 represents a methylene or ethylene group; R4 represents a hydrogen atom or a C 1-4  acyl group; R5 represents a hydroxyl group, an optionally substituted aryl C 2-8  alkoxyl group, a substituted C 1-4  alkylamino group, or an amino group having a residue of a derivative of an amino acid or a peptide; n is an integer of 5 to 1,000, m is an integer of 2 to 300, and x is an integer of 1 to 300; provided that the proportion of a hydroxyl group in the R5 is 0 to 99% and x is not larger than m).  
   
   
       8 . The block copolymer according to  claim 7 , wherein, in general formula (1), R1 represents a methyl group, R2 represents a trimethylene group, R3 represents a methylene group, R4 represents an acetyl group, and R5 represents an unsubstituted phenyl C 3-6  alkoxyl group; n is an integer of 20 to 500, m is an integer of 10 to 100, and x is an integer of 1 to 100; provided that x is not larger than m.