Gastric acid secretion inhibiting composition

Abstract

An oral pharmaceutical dosage form comprises pharmacologically effective amounts of an acid susceptible proton pump inhibitor or a salt thereof, an H2 receptor antagonist or a salt thereof and a pharmaceutically acceptable carrier. The dosage form is capable of raising gastric pH to above 4 within two hours after administration and to keep it at that level for at least 4 hours. Also disclosed is a method of manufacture of the dosage form, its use in treating dyspepsia and infection by Helicobacter pylori , and a method of treating disorders associated with gastric acid secretion.

1 . An oral pharmaceutical dosage form comprising pharmacologically effective amounts of an acid susceptible proton pump inhibitor or a salt thereof and an H2 receptor antagonist or a salt thereof, and a pharmaceutically acceptable carrier, wherein the acid susceptible proton pump inhibitor or a salt thereof is separated from the H2 receptor antagonist by an enteric coating.  
   
   
       2 . The dosage form of  claim 1 , wherein the acid susceptible proton pump inhibitor is selected from lanzoprazole, omeprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole, their pharmaceutically acceptable salts, enantiomers and salts of enantiomers.  
   
   
       3 . The dosage form of  claim 1 , comprising from 1 mg to 100 mg per single dose of an acid susceptible proton pump inhibitor or a salt thereof.  
   
   
       4 . The dosage form of  claim 1 , wherein the H2 receptor antagonist is selected from cimetidine, ranitidine, nizatidine and famotidine, their pharmaceutically acceptable salts, isomers and salts of isomers.  
   
   
       5 . The dosage form of  claim 1 , comprising from 1 mg to 800 mg of H2 receptor antagonist or salt thereof.  
   
   
       6 . The dosage form of  claim 1 , wherein said pharmacologically effective amounts are amounts capable to raise gastric pH to above 4 within two hours after administration and to keep it above 4 for at least 4 hours.  
   
   
       7 . The dosage form of  claim 6 , wherein said amounts are capable to keep gastric pH above 4 for at least 8 hours.  
   
   
       8 . The dosage form of  claim 1 , wherein said pharmacologically effective amounts are amounts capable to raise gastric pH to above 3 within 2 hours from administration and to keep it above 3 for at least 4 hours.  
   
   
       9 . The dosage form of  claim 8 , wherein said amounts are amounts capable to keep gastric pH above 3 for at least 8 hours.  
   
   
       10 . The dosage form of any of claims  1 - 9 , comprising from 100 mg to 1000 mg of antacid agent and/or alginate.  
   
   
       11 . The dosage form of  claim 10 , wherein the antacid agent comprises one or several of aluminum hydroxide, calcium carbonate, magnesium carbonate, basic magnesium carbonate, magnesium hydroxide, magnesium oxide, sodium hydrogen carbonate.  
   
   
       12 . The dosage form of any of claims  1 - 11 , wherein said acid susceptible proton pump inhibitor or a salt thereof is protected by an enteric coating layer and, optionally, a layer separating it from the enteric coating.  
   
   
       13 . The dosage form of any of claims  1 - 12 , comprising two concentric layers optionally separated by one or more separating layer(s), one layer comprising said acid susceptible proton pump inhibitor or salt thereof, the other layer comprising said H2 receptor antagonist or salt thereof.  
   
   
       14 . The dosage form of  claim 13 , wherein the inner layer comprises the acid susceptible proton pump inhibitor or salt thereof and the outer layer comprises the H2 receptor antagonist or salt thereof.  
   
   
       15 . The dosage form of claims  13 , wherein the outer layer comprises the acid susceptible proton pump inhibitor or salt thereof and the inner layer comprises the H2 receptor antagonist or salt thereof.  
   
   
       16 . The dosage form of  claim 15 , wherein the inner layer comprises a disintegrant.  
   
   
       17 . A capsule according to any of claims  1 - 12 .  
   
   
       18 . A divided powder/pellet formulation according to any of claims  1 - 12 .  
   
   
       19 . A tablet according to any of claims  1 - 16 .  
   
   
       20 . The tablet of  claim 19 , divisible.  
   
   
       21 . The tablet of  claim 19 , dispersible in water.  
   
   
       22 . The tablet of  claim 21 , comprising a disintegrant.  
   
   
       23 . A method for the manufacture of an oral tableted dosage form comprising amounts of an acid susceptible proton pump inhibitor or salt thereof and an H2 receptor antagonist or salt thereof pharmacologically effective in treating a condition related to dyspepsia, the method comprising forming a first layer comprising said acid susceptible proton pump inhibitor or salt thereof, an enteric coat surrounding said first layer, and a second layer comprising said H2 receptor antagonist or salt thereof surrounding said first layer and said enteric coat.  
   
   
       24 . A method for the manufacture of an oral dosage form comprising amounts of an acid susceptible proton pump inhibitor or salt thereof and an H2 receptor antagonist or salt thereof pharmacologically effective in treating a condition related to dyspepsia, the method comprising forming pellets comprising said acid susceptible proton pump inhibitor or salt thereof, covering said pellets with enteric coat, and mixing said pellets covered with said enteric coat with a carrier comprising said H2 receptor antagonist or salt thereof.  
   
   
       25 . The method of  claim 24 , wherein said carrier comprises a disintegrant.  
   
   
       26 . The method of  claim 24  or  25 , comprising forming a tablet of said mixture.  
   
   
       27 . The method of  claim 24 , comprising filling a capsule capable of disintegrating in gastrointestinal fluids to release its contents with said mixture.  
   
   
       28 . The method of any of claims  23 - 27 , wherein said acid susceptible proton pump inhibitor is selected from lansoprazole, omeprazole, pantoprazole, rabeprazole, pariprazole, leminoprazole, their pharmaceutically acceptable salts, enantiomers and salts of enantiomers.  
   
   
       29 . The method of any of claims  23 - 27 , wherein said H2 receptor antagonist is selected from are cimetidine, ranitidine, nizatidine and famotidine, their pharmaceutically acceptable salts, isomers and salts of isomers.  
   
   
       30 . Use of the dosage form of any of claims  1 - 22  for the manufacture of a medicament for the treatment of a disorder associated with gastric acid secretion.  
   
   
       31 . Use of the dosage form of any of claims  1 - 22  in association with one or more antibiotic agent(s) for the eradication of  Helicobacter pylori.    
   
   
       32 . A method of treating disorders associated with dyspepsia, comprising the administration of the dosage form of any of claims  1 - 22  or the concomitant administration of two separate oral dosage forms, one comprising a pharmacologically effective amount of an acid susceptible proton pump inhibitor or salt thereof, the other comprising a pharmacologically effective amount of an H2 receptor antagonist or salt thereof.  
   
   
       33 . A method of treating an infection by  Helicobacter pylori , comprising the administration of the dosage form of any of claims  1 - 22  or the concomitant administration of two separate oral dosage forms, one comprising a pharmacologically effective amount of an acid susceptible proton inhibitor or salt thereof, the other comprising a pharmacologically effective amount of an H2 receptor antagonist or salt thereof, in association with the administration of one or more antibiotic agent(s) effective against  H. pylori.    
   
   
       34 . The method of  claim 32  or  33 , comprising a dose regimen capable of maintaining gastric pH above 4 for at least 95% of the time period starting at 2 hours from the administration of the first dose and extending until 6 hours from the administration of the last dose.  
   
   
       35 . The method of  claim 34 , wherein said time period is one week or more.  
   
   
       36 . The method of  claim 34 , wherein said time period is two weeks or more.  
   
   
       37 . The method of  claim 34 , wherein said time period is four weeks or more.  
   
   
       38 . The method of  claim 32  or  33 , comprising a dose regimen capable of maintaining gastric pH above 3 for at least 95% of the time period starting at 2 hours from the administration of the first dose and extending until 6 hours from the administration of the last dose, in particular for four weeks or more.