Compositions and methods for inhibiting gastric acid secretion using derivatives of small dicarboxylic acids in combination with PPI

摘要

The present invention is related to novel oral compositions comprising an irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI) as a gastric acid secretion inhibitor and one or more aliphatic carboxylic acid derivative molecules which activate parietal cells, wherein the derivatives possess delayed or sustained enhancement effect on the PPI activity compared to the non-derivatized acid molecules. The present invention further relates to a method of using such compositions to reduce gastric acid secretion in a mammal.

主权项

1. A pharmaceutical composition wherein the active ingredients consist of a pharmaceutically effective amount of:
(i) a parietal cell activator comprising one or more aliphatic carboxylic acid derivatives, wherein the one or more derivatives of aliphatic carboxylic acid is monomethyl or dimethyl ester of succinic acid; and (ii) an irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI), wherein the PPI particles are formulated as enteric-coated delayed release granules or as granules coated with non-enteric time-dependent release polymers,wherein the derivatives possess delayed, sustained, or both delayed and sustained parietal cell activation compared to non-derivatized acid molecules,wherein the one or more aliphatic carboxylic acid derivatives in conjunction with the PPI reduces gastric acid secretion in the stomach,wherein a ratio between the one or more derivatives of aliphatic carboxylic acid molecules and the PPI is about 20:1 to about 1:5, andwherein the active ingredients are formulated as:
(a) press-coat or double-layered tablets comprising the enteric-coated PPI in one layer and the aliphatic carboxylic acid derivatives either non-coated or coated with hydroxypropyl methylcellulose in a second layer; (b) a single dosage form comprising hard gelatin capsules comprising a mixed population of beads selected from the PPI particles and beads comprising one or more of the aliphatic carboxylic acid derivatives either non-coated or coated with hydroxypropyl methylcellulose or alginate; or (c) a solid dosage form, wherein the solid dosage form is a capsule or a multi-layered tablet containing the PPI particles and particles of the aliphatic carboxylic acid derivative.