H.sub.2 -Receptor antagonist and antacid composition

• US 6,090,412 A
• Filed: 05/26/1998
• Issued: 07/18/2000
• Est. Priority Date: 11/27/1995
• Status: Expired due to Fees

• Current Assignee: Astellas Pharma Incorporated
• Original Assignee: Yamanouchi Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Hashimoto, Yoshimi, Kishimoto, Hideyuki, Shiozawa, Hiroyoshi, Setoguchi, Yoichi
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): WARE, TODD
• Application Number:
  US09/077,186
• Time in Patent Office: 784 Days
• Field of Search: 424/479, 424/480, 424/482, 424/474, 424/475, 424/497, 424/494, 424/495, 424/490, 424/400
• US Class Current: 424/490
• 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 31/34 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 33/08 Oxides; Hydroxides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50

Abstract

A solid pharmaceutical composition for oral administration comprising a histamine H₂ -receptor antagonist, a low neutralizing capacity antacid, and a high neutralizing capacity antacid coated with a pH-independent and water-insoluble polymer base, which composition improves the condition of a patient promptly after administration and sustains the effects for an extended period of time in the treatment of digestive disorders on which suppression of gastric acid secretion is effective.

Claims

1. A solid pharmaceutical composition for oral administration which comprises

(1) a histamine H₂ -receptor antagonist,

(2) a low neutralizing capacity antacid, and

(3) a high neutralizing capacity antacid, said high neutralization capacity antacid being coated with a pH-independent and water-insoluble polymer base.

2. A solid pharmaceutical composition according to claim 1, wherein said histamine H₂ -receptor antagonist is selected from the group consisting of cimetidine, ranitidine, nizatidine and famotidine or a pharmaceutically acceptable salt thereof.

3. A solid pharmaceutical composition according to claim 2, wherein said histamine H₂ -receptor antagonist is famotidine.

4. A solid pharmaceutical composition according to claim 1, wherein said antacid having a low neutralizing capacity and said antacid having a high neutralizing capacity give an initial pH of lower than 6 and an initial pH of 6 or higher, respectively, in a test using 30 ml of 0.05N hydrochloric acid and a single dose in accordance with a modified Fuchs method.

5. A solid pharmaceutical composition according to claim 1, wherein said antacid having a low neutralizing capacity and said antacid having a high neutralizing capacity give an initial pH of lower than 6 and an initial pH of 6 or higher, respectively, in a test using 30 ml of 0.05N hydrochloric acid and a single dose in accordance with a modified Fuchs method, said antacid having a low neutralizing capacity and said antacid having a high neutralizing capacity as uncoated are present at a weight ratio of 0.2:

1 to 2;

1, and the coating weight of said pH-independent and water-insoluble polymer base on said antacid having a high neutralizing capacity is 5 to 100% by weight based on said antacid.

6. A solid pharmaceutical composition according to claim 1, wherein said pH-independent and water-insoluble polymer base is at least one member selected from the group consisting of ethyl cellulose, an aqueous dispersion of ethyl cellulose, an ethyl acrylate-methyl methacrylate copolymer emulsion, and a polyethylacrylate methylmethacrylate trimethylammonioethylmethacrylate chloride.

7. A solid pharmaceutical composition according to claim 1, wherein said antacid having a high neutralizing capacity is at least one member selected from the group consisting of sodium hydrogencarbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium silicate, and calcium carbonate.

8. A solid pharmaceutical composition according to claim 1, wherein said antacid having a low neutralizing capacity is at least one member selected from the group consisting of magnesium aluminate, dimagnesium silicate aluminate, magnesium metasilicate aluminate, magnesium bismuth silicate aluminate, synthetic hydrotalcite, dried aluminum hydroxide gel, and aluminum silicate.

9. A solid pharmaceutical composition according to claim 1, which comprises dried aluminum hydroxide gel, magnesium hydroxide, and famotidine.