Stabilized pharmaceutical composition

• US 5,433,959 A
• Filed: 09/10/1993
• Issued: 07/18/1995
• Est. Priority Date: 02/13/1986
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Hirai, Shin-ichiro, Tabata, Tetsuro, Makino, Tadashi
• Primary Examiner(s): Cintins, Marianne M.
• Assistant Examiner(s): WEDDINGTON, KEVIN E
• Application Number:
  US08/120,867
• Time in Patent Office: 676 Days
• Field of Search: 424/475, 424/495, 424/683, 424/686, 424/692, 514/394, 514/395, 514/925, 514/927
• US Class Current: 424/475
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R¹ is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R² is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R³ and R⁵ are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R⁴ is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

Claims

1. A stabilized pharmaceutical composition for the inhibition of gastric acid secretion, comprising:

an effective amount of a 2-[(2-pyridyl)methylsulphinyl]benzimidazole compound of a pharmaceutically acceptable salt thereof having a gastric acid secretion inhibitory property;

a basic inorganic salt stabilizing agent which is present in an amount effective to stabilize the composition, the benzimidazole compound or its salt being in contact with the basic inorganic salt evenly; and

an enteric coating for the composition.

2. The composition of claim 1, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of magnesium which is effective to stabilize the composition.

3. The composition of claim 1, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of calcium which is effective to stabilize the composition.

4. The composition of claim 1, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of potassium which is effective to stabilize the composition.

5. The composition of claim 1, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of sodium which is effective to stabilize the composition.

6. The composition of claim 1, wherein the composition comprises a plurality of enteric coated granules, each of the granules containing therein said benzimidazole compound or its salt and the stabilizing agent.

7. A method of providing a gastric acid secretion inhibitory effect to a subject in need thereof, comprising:

orally administering to the subject a stabilized pharmaceutical composition comprising;

an effective amount of a 2-[(2-pyridyl)methylsulphinyl]benzimidazole compound or a pharmaceutically acceptable salt thereof having a gastric acid secretion inhibitory property;

a basic inorganic salt stabilizing agent which is present in an amount effective to stabilize the composition, the benzimidazole compound or its salt being in contact with the basic inorganic salt evenly; and

an enteric coating for the composition.

8. The composition of claim 7, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of magnesium which is effective to stabilize the composition.

9. The composition of claim 7, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of calcium which is effective to stabilize the composition.

10. The composition of claim 7, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of potassium which is effective to stabilize the composition.

11. The composition of claim 7, wherein the basic inorganic salt stabilizing agent is a basic inorganic salt of sodium which is effective to stabilize the composition.

12. A stabilized pharmaceutical composition for the inhibition of gastric acid secretion, comprising:

an effective amount of a 2-[(2-pyridyl)methylsulphinyl]benzimidazole compound or a pharmaceutically acceptable salt thereof having a gastric acid secretion inhibitory property;

a basic inorganic magnesium or calcium stabilizing agent which is present in an amount effective to stabilize the composition, the benzimidazole compound or its salt being in contact with the basic inorganic salt evenly; and

an enteric coating for the composition.

13. The composition of claim 12, wherein the stabilizing agent is selected from the group consisting of heavy magnesium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium metasilicate aluminate, magnesium silicate, magnesium aluminate, synthetic hydrotalcite, aluminum magnesium hydroxide, precipitated calcium carbonate and calcium hydroxide.

14. A method of providing a gastric acid secretion inhibitory effect to a subject in need thereof, comprising:

orally administering to the subject a stabilized pharmaceutical composition comprising;

an effective amount of a 2-[(2-pyridyl)methylsulphinyl]benzimidazole compound or a pharmaceutically acceptable salt thereof having a gastric acid secretion inhibitory property;

a basic inorganic magnesium or calcium stabilizing agent which is present in an amount effective to stabilize the composition, the benzimidazole compound or its salt being in contact with the basic inorganic salt evenly; and

an enteric coating for the composition.

15. The method of claim 14, wherein the stabilizing agent is selected from the group consisting of heavy magnesium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium metasilicate aluminate, magnesium silicate, magnesium aluminate, synthetic hydrotalcite, aluminum magnesium hydroxide, precipitated calcium carbonate and calcium hydroxide.