Barium salt of benzimidazole derivative

Abstract

A barium salt of the S-enantiomer of omeprazole which is (S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1H-benzimidazole is provided. Further, processes for preparing the barium salt, pharmaceutical compositions comprising the salt and a method of treatment or prevention of gastrointestinal ulcers comprising administration of the salt are provided.

1 . The barium salt of (S)-omeprazole.  
   
   
       2 . The salt according to  claim 1  in a crystalline form.  
   
   
       3 . The salt according to  claim 1  in an amorphous form.  
   
   
       4 . A process for preparing (S)-omeprazole barium, comprising contacting (S)-omeprazole freebase, or its sodium or potassium salt, with the barium salt of an acid to form (S)-omeprazole barium, wherein the process is carried out in the presence of a base whenever (S)-omeprazole freebase is used.  
   
   
       5 . The process according to  claim 4 , wherein the barium salt of an inorganic acid is used.  
   
   
       6 . The process according to  claim 5 , wherein the barium salt is selected from the group consisting of barium chloride, barium nitrate, barium phosphate, barium carbonate, and barium sulphate.  
   
   
       7 . The process according to  claim 4 , wherein the barium salt of an organic acid is used.  
   
   
       8 . The process according to  claim 7 , wherein the barium salt is selected from the group consisting of barium oxalate, barium acetate, barium lactate, barium succinate, barium citrate, and barium tartrate.  
   
   
       9 . The process according to  claim 4 , wherein the base is selected from the group consisting of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates and ammonium hydroxide.  
   
   
       10 . The process according to  claim 9 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate.  
   
   
       11 . A process for preparing (S)-omeprazole barium, which comprises contacting (S)-omeprazole freebase with barium hydroxide in a suitable solvent.  
   
   
       12 . The process according to claims  4  or  11 , wherein the solvent is selected from the group consisting of water, ketone, alcohols, esters, cyclic ethers, chlorinated hydrocarbons, nitrile, dipolar aprotic solvent, and mixtures thereof.  
   
   
       13 . The process according to  claim 12 , wherein the solvent is selected from the group consisting of water, acetone, methanol and mixtures thereof.  
   
   
       14 . The process according to  claim 4  or  11 , wherein (S)-omeprazole barium precipitates spontaneously from the solvent.  
   
   
       15 . The process according to  claim 4  or  11 , wherein crystalline form of (S)-omeprazole barium is obtained.  
   
   
       16 . The process according to  claim 4  or  11 , wherein amorphous form of (S)-omeprazole barium is obtained.  
   
   
       17 . A process for preparing (S)-omeprazole barium in amorphous form, which comprises concentrating a solution containing (S)-omeprazole barium to dryness, or spray drying the solution.  
   
   
       18 . The process according to  claim 17 , wherein the solution is obtained by dissolving crystalline (S)-omeprazole barium.  
   
   
       19 . A method for treating or preventing gastrointestinal inflammatory diseases, which comprises administering an effective amount of (S)-omeprazole barium.  
   
   
       20 . A method of inhibiting gastric acid secretion comprising administering (S)-omeprazole barium.  
   
   
       21 . The method according to  claim 19  or  20 , wherein (S)-omeprazole barium is used for treatment or prophylaxis of gastric acid-related diseases and gastrointestinal inflammatory diseases selected from the group consisting of erosive or ulcerative gastroesophageal reflux disease (GERD), gastric ulcer, duodenal ulcer, reflux esophagitis, and gastritis.  
   
   
       22 . The method according to  claim 19  to  21 , wherein crystalline form of the (S)-omeprazole barium is used.  
   
   
       23 . The method according to  claim 19  to  21 , wherein amorphous form of the (S)-omeprazole barium is used.  
   
   
       24 . A pharmaceutical composition comprising (S)-omeprazole barium and pharmaceutically acceptable carriers, diluents or excipients.  
   
   
       25 . The pharmaceutical composition according to  claim 24 , wherein a crystalline form of (S)-omeprazole barium is used.  
   
   
       26 . The pharmaceutical composition according to  claim 24 , wherein an amorphous form of (S)-omeprazole barium is used.