Sustained release compositions, process for producing the same and use thereof

Abstract

Sustained release compositions containing a physiologically active substance or its salt, hydroxynaphthoic acid or its salt and a lactic acid-glycolic polymer or its salt, wherein the product of the weight-average molecular weight of the lactic acid-glycolic acid polymer by the amount (μmol) of the terminal carboxyl group per unit mass (g) of the lactic acid-glycolic acid polymer is from 1,200,000 to 3,000,000 (inclusive); and their production; medicaments containing these sustained release compositions, etc.

1 . A sustained release composition comprising a pharmacologically active substance or its salt, a hydroxynaphthoic acid or its salt and a lactic acid-glycolic acid polymer or its salt, wherein the product of the weight average molecular weight of said lactic acid-glycolic acid polymer by the amount (μmol) of the terminal carboxyl group per unit mass (g) of said lactic acid-glycolic acid polymer is 1,200,000 to 3,000,000 (inclusive).  
   
   
       2 . The sustained release composition according to  claim 1 , wherein the pharmacologically active substance is a physiologically active peptide.  
   
   
       3 . The sustained release composition according to  claim 1 , wherein the pharmacologically active substance is an LH-RH derivative.  
   
   
       4 . The sustained release composition according to  claim 1 , wherein the hydroxynaphthoic acid is 1-hydroxy-2-naphthoic acid.  
   
   
       5 . The sustained release composition according to  claim 1 , wherein the % molar ratio between lactic acid and glycolic acid is 100/0 to 40/60.  
   
   
       6 . The sustained release composition according to  claim 1 , wherein the % molar ratio between lactic acid and glycolic acid is 100/0.  
   
   
       7 . The sustained release composition according to  claim 1 , wherein the weight average molecular weight of the polymer is about 3,000 to about 100,000.  
   
   
       8 . The sustained release composition according to  claim 7 , wherein the weight average molecular weight is about 20,000 to about 50,000.  
   
   
       9 . The sustained release composition according to  claim 3 , wherein the LH-RH derivative is a peptide represented by Formula:  
       5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z  
     wherein Y denotes DLeu, DAla, DTrp, DSer(tBu), D2NaI or DHis(ImBzl), and Z denotes NH—C 2 H 5  or Gly-NH 2 .  
   
   
       10 . The sustained release composition according to  claim 1 , wherein the amount (μmol) of the terminal carboxyl group of the polymer is 50 to 90 μmol per unit mass (g) of the polymer.  
   
   
       11 . The sustained release composition according to  claim 3 , wherein the molar ratio between the hydroxynaphthoic acid or its salt and the LH-RH derivative or its salt is 3:4 to 4:3.  
   
   
       12 . The sustained release composition according to  claim 3  which contains the LH-RH derivative or its salt in an amount of 12% by weight to 24% by weight based on the sustained release composition.  
   
   
       13 . The sustained release composition according to  claim 1 , wherein the physiologically active substance or its salt is a slightly water-soluble or water-soluble substance.  
   
   
       14 . The sustained release composition according to  claim 1  which is a formulation for injection.  
   
   
       15 . A medicament comprising a sustained release composition according to  claim 1 .  
   
   
       16 . A prophylactic or therapeutic agent against prostate cancer, prostate hyperplasia, endometriosis, hysteromyoma, metrofibroma, precocious puberty, dysmenorrhea or mammary cancer or an contraceptive containing a sustained release composition according to  claim 3 .  
   
   
       17 . The sustained release composition according to  claim 1 , wherein the pharmacologically active substance or its salt is released over a period of at least 6 months or longer.  
   
   
       18 . A sustained release composition comprising a pharmacologically active substance or its salt, 1-hydroxy-2-naphthoic acid or its salt and a biodegradable polymer or its salt.