Organic compounds

Abstract

A polylactide in a purified state, which meets the requirements of the color strengths of reference solutions B 2 -B 9 of the brown colour test of the European Pharmacopoeia, 2nd Edition (1980) part I, Section V, 6.2 and containing one or more metals in cationic form, the metal ion(s) having a concentration of at most 10 ppm. The polylactide is especially suitable for use as microparticles or implants, and contains preferably a hydrophilic drug, like octreotide or a lipophilic drug like bromocriptine.

What we claim is:  
     
         1 . A polylactide in a purified state, which meets the requirements of 
 the colour strengths of reference solutions B 2 -B 9  of the brown colour test of the European Pharmacopoeia, 2nd Edition (1980) part I, Section V, 6.2 and    containing one or more metals in cationic form, the metal ion(s) having a concentration of at most 10 ppm.    
     
     
         2 . A polylactide according to  claim 1 , having the colour strength of reference solutions B 4 -B 9 .  
     
     
         3 . A polylactide according to  claim 2 , having the colour strength of reference solution B 9 .  
     
     
         4 . A polylactide according to  claim 1 , in which the metal ion is Sn ++ .  
     
     
         5 . A polylactide according to  claim 4 , having a Sn ++  concentration of at most 1.5 ppm.  
     
     
         6 . A polylactide according to claims  4 , in which the Sn ++  accompanying salt anion is ethyl hexanoate.  
     
     
         7 . A polylactide according to  claim 6 , having an ethyl hexanoate concentration of at most 0.5% by weight of the polylactide.  
     
     
         8 . A polylactide according to  claim 1 , having a  
       
         
           
                 
                 
               
                     
                 
                     
                 
                   monomer 
                   content of at most 1% by weight of the polylactide 
                 
                   water 
                   content of at most 1% by weight of the polylactide 
                 
                   organic solvent 
                   content of at most 1% by weight of the polylactide 
                 
                   ash 
                   content of at most 0.1% by weight of the polylactide 
                 
                 
               
                   and having an acid number of at most 10. 
                 
                     
                 
                     
                 
             
                
                
               
               
                
                
                
                
               
            
             
                
                
                
               
            
           
         
       
     
     
         9 . A polylactide according to  claim 1 , containing additionally glycolide units.  
     
     
         10 . A polylactide according to  claim 9 , having lactide/glycolide molar ratio's of 100-25/0-75.  
     
     
         11 . A polylactide according to  claim 10 , having molar rations of 75-25/25-75.  
     
     
         12 . A polylactide according to  claim 11 , having molar ratio's of 60-40/40-60.  
     
     
         13 . A polylactide according to  claim 1 , being an ester of a polyol containing at least 3 hydroxyl groups.  
     
     
         14 . A polylactide according to  claim 13 , being an ester of a sugar or of a sugar alcohol.  
     
     
         15 . A polylactide according to  claim 13 , being a glucose ester.  
     
     
         16 . A polylactide according to claims  1 , being a linear polylactid-glycolide.  
     
     
         17 . A polylactide according to claims  13  having a mean molecular weight M w  of from 10000 to 200000.  
     
     
         18 . A polylactide according to  claim 13 , having a polydispersity Mw/Mn of from 1.7 to 3.0.  
     
     
         19 . A polylactide according to  claim 16 , having a mean molecular weight M w  of from 25,000 to 100,000.  
     
     
         20 . A polylactide according to  claim 16 , having a polydispersity Mw/Mn of from 1.2 to 2.0  
     
     
         21 . A polylactide according to  claim 1 , obtained by contacting a solution of the impure polylactide with a matrix having on its surface acidic groups.  
     
     
         22 . A method for obtaining the polylactide according to  claim 1 , by contacting a solution of the impure polylactide with a matrix having on its surface carboxylic groups and isolating the purified polylactide from the eluate.  
     
     
         23 . A method for obtaining the polylactide according to  claim 1 , by contacting a solution of the impure polylactide with active charcoal and isolating the purified polylactide from the eluate.  
     
     
         24 . A method according to  claim 23 , in which the isolation includes a further purification step, which is ultrafiltration.  
     
     
         25 . A method according to  claim 23  in which the impure polylactide is dissolved in acetone.  
     
     
         26 . A pharmaceutical composition containing a polylactide according to  claim 1  as a matrix for a drug compound.  
     
     
         27 . A pharmaceutical composition according to  claim 26 , comprising bromocriptine as the drug compound.  
     
     
         28 . A pharmaceutical composition according to  claim 26 , comprising a peptide as the drug compound.  
     
     
         29 . A pharmaceutical composition according to  claim 28 , comprising a somatostatin as the drug compound.  
     
     
         30 . A pharmaceutical composition according to  claim 29 , comprising octreotide or an acid addition salt or a derivative therof.  
     
     
         31 . Process for the preparation of the pharmaceutical composition of  claim 26 , which comprises working up the polylactide of  claim 1  with the drug compound to form an implantate or a microparticle.