Process for the preparation of pharmaceutically acceptable salts of (SS,RS) -s-adenosyl-l-methionine

Abstract

The present invention relates to a process for the preparation of pharmaceutically acceptable salts of (SS,RS)-S-adenosyl-L-methionine and allows to obtain the salified (RS)-(+)-S-adenosyl-L-methionine diastereoisomer in amounts lower than or equal to 3% with respect to the salified (SS)-(+)-S-adenosyl-L-methionine diastereoisomer; the salts that can be obtained by the process of the invention keep their configuration stable in time.

1 . A process for the preparation of pharmaceutically acceptable salts of (SS,RS)-SAMe, wherein the salified (RS)-(+)-SAMe diastereoisomer is present in amounts lower than or equal to 3% with respect to the salified (SS)-(+)-SAMe diastereoisomer, which, at a temperature of 0-12° C., comprises: 
 the purification of (SS,RS)-S-adenosyl-L-methionine from enriched yeast, which shall contain at least 6 g/l thereof, which comprises: 
 (a) the adjustment of the pH value to 1.2-3.5;  
 (b) the preparation of an aqueous lysate of (SS,RS)-SAMe from the enriched yeast;  
 (c) the microfiltration of the resulting lysate;  
 (d) the absorption of the resulting microfiltrate on a weak acid resin, by eluting with a 0.1-2 N inorganic acid solution;  
 (e) the decolouration of the resulting eluate;  
 
 the concentration of the decolourised eluate by reverse osmosis, from 30 to 70% by volume;  
 the addition of stoichiometric amounts of at least a pharmaceutically acceptable acid to the concentrated eluate, so as to obtain the corresponding pharmaceutically acceptable salt of (SS,RS)-SAMe.  
 
     
     
         2 . Process according to  claim 1 , wherein the pharmaceutically acceptable salt of (SS,RS)-SAMe is subjected to lyophilization.  
     
     
         3 . Process according to  claim 1  or  2 , wherein the pH value in step (a) is 1-2.  
     
     
         4 . Process according to any of the preceding claims, wherein the preparation of the lysate in step (b) takes place by passing the yeast through a cell-breaking equipment.  
     
     
         5 . Process according to any of the preceding claims, wherein the temperature is 2-5° C.  
     
     
         6 . Process according to any of the preceding claims, wherein the enriched yeast contains at least 8-10 g/l of (SS,RS)-S-adenosyl-L-methionine.  
     
     
         7 . Process according to any of the preceding claims, wherein the pharmaceutically acceptable acid is selected from sulphuric acid and paratoluensulphonic acid.  
     
     
         8 . A pharmaceutically acceptable salt of (SS,RS)-S-adenosyl-L-methionine obtainable by the process according to any of the preceding claims.