Compositions containing histamine-H2-receptor antagonists at low dosage

• US 5,629,026 A
• Filed: 05/17/1995
• Issued: 05/13/1997
• Est. Priority Date: 12/20/1991
• Status: Expired due to Term

• Current Assignee: Smithkline Beecham PLC
• Original Assignee: Smithkline Beecham PLC
• Inventors: Davis, Adrian F.
• Primary Examiner(s): Geist, Gary
• Assistant Examiner(s): Frazier, Barbara S.
• Application Number:
  US08/443,290
• Time in Patent Office: 727 Days
• Field of Search: 424/605, 424/653, 424/683, 424/684, 424/686, 424/687, 424/690, 424/692, 514/370, 514/400, 514/471, 514/544, 514/547, 514/549
• US Class Current: 424/686
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/08 Oxides; Hydroxides
• CPC Class Codes: A61K 33/10 Carbonates; Bicarbonates
• CPC Class Codes: A61K 33/12 Magnesium silicate
• CPC Class Codes: A61K 33/245 Bismuth; Compounds thereof
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions for oral administration for the treatment of gastric disorders comprising histamine H₂ -receptor antagonist and antacid, optionally buffered to promote local absorption of the H₂ -receptor antagonist, wherein the quantity of H₂ -receptor antagonist per unit dosage form is less than 25 mg.

Claims

1. A pharmaceutical composition for treating gastric disorders, said composition comprising a histamine H₂ -receptor antagonist and an antacid, wherein the composition is optimally buffered to confer a pH substantially equal to that of the pKa of the histamine H₂ -receptor antagonist and promote local absorption of the H₂ -receptor antagonist, characterized in that the dose of histamine H₂ -receptor antagonist per unit dosage form is less than 25 mg, provided that the composition does not contain sodium polyacrylate.

2. The composition as claimed in claim 1 characterised in that the composition is optimally buffered with a buffering component which is an antacid having equilibrium pH, acid neutralising capacity and gastric residence time values which provide a pH profile with time conferring a local pH level substantially equal to that of the pKa of the histamine H₂ -receptor antagonist.

3. The composition as claimed in claim 1 for treating gastric disorders in ulcer patients.

4. The composition as claimed in claim 1 for the single-dose treatment of acute gastric disorders.

5. The composition as claimed in claim 1 wherein the histamine H₂ -receptor antagonist is cimetidine, ranitidine, or famotidine.

6. The composition as claimed in claim 5 wherein the histamine H₂ -receptor antagonist is cimetidine.

7. The composition as claimed in claim 6 wherein the dose level of cimetidine is between 1 and 25 mg per dosage form.

8. The composition as claimed in claim 7 wherein the dose level of cimetidine is between 1 and 10 mg per dosage form.

9. The composition as claimed in claim 1 wherein the composition is buffered with aluminium hydroxide, magnesium hydroxide, aluminium hydroxide-magnesium carbonate co-dried gel, magnesium carbonate, magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate, bismuth carbonate, magnesium aluminium silicate, alkali metal salts of citric, tartaric, benzoic, sorbic or phosphoric acid, or combinations thereof.

10. A method of treating gastric disorders comprising orally administering to a sufferer an effective amount of a pharmaceutical composition, said composition comprising a histamine H₂ -receptor antagonist and an antacid, wherein the composition is optimally buffered such that the equilibrium pH, the acid neutralizing capacity and the gastric residence time values confer a pH level substantially equal to that of the pKa of the histamine H₂ -receptor antagonist, characterized in that the dose of histamine H₂ -receptor antagonist per unit dosage form is less than 25 mg, provided that the composition does not contain sodium polyacrylate.