# US 2010/0247634 A1 · Compositions and Methods for Inhibiting Gastric Acid Secretion > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0247634 A1 - Document ID: US20100247634A1 - Status: Published application - Kind: A1 - Application number: 12/768,375 - Filed: 2010-04-27 - Published: 2010-09-30 - Earliest claimed: 2005-05-11 - Assignees: Vecta, Ltd. - Inventors: Aleksey Kostadinov; Ayelet David; Sabina Glozman - Web page: https://patentgrep.com/patent/US20100247634A1 ## CPC - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50} - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 1/06: Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia - A61P 3/04: Anorexiants; Antiobesity agents - A61P 31/04: Antibacterial agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract 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 small carboxylic acid molecules as parietal cell activators in the gastric lumen. Unexpectedly, the compositions of the present invention are capable of enhancing the anti-acid activity of PPI in the stomach. The present invention further relates to a method of using such compositions to reduce gastric acid secretion in a mammal. ## Claims ### Claim 1 A pharmaceutical composition in a solid dosage form suitable for oral administration, wherein the active ingredients of said composition consist of a pharmaceutically effective amount of: (i) a parietal cell activator, wherein the parietal cell activator is one or more small carboxylic acid molecules or any salts thereof which activate parietal cells, wherein the small carboxylic acid molecules or any salts thereof are saturated or non-saturated monocarboxylic, dicarboxylic or tricarboxylic acid molecules or any salts thereof involved in the mitochondrial respiration circle (krebs cycle) having between three to six carbon atoms selected from the group consisting of maleic acid, citric acid, pyruvate, fumarate, alpha-ketoglutarate, succinyl-CoA and oxaloacetate; and (ii) an irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI), wherein the solid dosage form is suitable for administration to a human patient, wherein the solid dosage form disintegrates in the stomach and the release of the active ingredients is controlled such that the activity of the PPI is synchronized with the parietal cell activity of the carboxylic acid molecules or any salts thereof in the stomach, the PPI is enteric-coated and formulated for absorption in the small intestine and the carboxylic acid molecules or any salts thereof is in a form for release in the stomach in an amount sufficient to activate parietal cells located in the gastric lumen of the human patient so that the parietal cells are active while the PPI is in the patient's blood having been absorbed through the small intestine, the amount of the small carboxylic acid molecules or any salts thereof being between 50 to 2500 mg, wherein the carboxylic acid molecules or any salts thereof in conjunction with the PPI reduces gastric acid secretion in the stomach. ### Claim 2 (depends on 1) The composition of claim 1, wherein the one or more small carboxylic acid molecules or any salts thereof are in a form for extended release in the stomach while the PPI is absorbed in the proximal part of the small intestine. ### Claim 3 (depends on 1) The composition of claim 1, in a form suitable for oral administration, wherein the release of the one or more small carboxylic acid molecules or any salts thereof is delayed in the stomach, the release being delayed sufficiently to synchronize activation of the parietal cells in the gastric lumen with the absorption of the PPI in the small intestine to increase the effectiveness of the PPI. ### Claim 4 (depends on 1) The composition of claim 1, wherein the active ingredients are formulated in a single unit oral dosage form selected from: a multi-layered tablet, a press-coat tablet, a multi-particulate capsule, an effervescent tablet and a suspension tablet. ### Claim 5 (depends on 4) The composition of claim 4, wherein the one or more small carboxylic acid molecules or any salts thereof are granulated into beads which are compressed into mini-tabs and mixed with enteric-coated PPI pellets in hard or soft gelatin capsules or wherein the composition comprises multiple beads of the one or more small carboxylic acid molecules or any salts thereof and the PPI in hard gelatin capsule. ### Claim 6 (depends on 1) The composition of claim 1, wherein the weight ratio between the one or more small carboxylic acid molecules or any salts thereof and the PPI is about 20:1 to about 1:5. ### Claim 7 (depends on 1) The composition of claim 1, wherein the PPI is selected from the group consisting of: rabeprazole, omeprazole, esomeprazole, lansoprazole, pantoprazole, leminoprazole, tenatoprazole, single enantiomers thereof, alkaline salts thereof, pro-drugs thereof, and mixtures thereof. ### Claim 8 A pharmaceutical kit for administration to a human patient wherein the active ingredients consist of a pharmaceutically effective amount of: (i) a parietal cell activator, wherein the parietal cell activator is one or more small carboxylic acid molecules or any salts thereof which activate parietal cells, wherein the small carboxylic acid molecules or any salts thereof are saturated or non-saturated monocarboxylic, dicarboxylic or tricarboxylic acid molecules or any salts thereof involved in the mitochondrial respiration circle (krebs cycle) having between three to six carbon atoms selected from the group consisting of maleic acid, citric acid, pyruvate, fumarate, alpha-ketoglutarate, succinyl-CoA and oxaloacetate; and (ii) an irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI), wherein the kit comprises a solid capsule and/or tablet dosage form suitable for administration to a human patient that disintegrate in the stomach and the release of the active ingredients is controlled such that the activity of the PPI is synchronized with the parietal cell activity of the carboxylic acid molecules or any salts thereof in the stomach, the PPI is enteric-coated and is formulated for absorption in the small intestine and the carboxylic acid molecules or any salts thereof are in a form for release in the stomach in an amount sufficient to activate parietal cells located in the gastric lumen of the human patient so that the parietal cells are active while the PPI is in the patient's blood having been absorbed through the small intestine, the amount of the small carboxylic acid molecules or any salts thereof being between 50 to 2500 mg, wherein the carboxylic acid molecules or any salts thereof in conjunction with the PPI reduces gastric acid secretion in the stomach. ### Claim 9 A method of reducing gastric acid secretion in a human patient, the method comprising administering to the patient an effective amount of a pharmaceutical composition in a solid dosage form selected from the group consisting of: capsules and tablets suitable for administration to a human patient, wherein the active ingredients of said composition consist of a parietal cell activator, wherein the parietal cell activator is one or more small carboxylic acid molecules or any salts thereof which activate parietal cells, wherein the small carboxylic acid molecules or any salts thereof are saturated or non-saturated monocarboxylic, dicarboxylic or tricarboxylic acid molecules or any salts thereof involved in the mitochondrial respiration circle (krebs cycle) having between three to six carbon atoms selected from the group consisting of maleic acid, citric acid, pyruvate, fumarate, alpha-ketoglutarate, succinyl-CoA and oxaloacetate; and an effective amount of an enteric-coated proton pump inhibitor (PPI), wherein the tablet or capsule solid dosage form disintegrates in the stomach and the release of the active ingredient is controlled such that the activity of the PPI is synchronized with the parietal cell activity of the carboxylic acid molecules or any salts thereof in the stomach, the carboxylic acid molecules or any salts thereof being in a form for release in the stomach in an amount sufficient to activate parietal cells located in the gastric lumen of the human patient so that the parietal cells are active while the PPI is in the patient's blood having been absorbed through the small intestine, the amount of the small carboxylic acid molecules or any salts thereof being between 50 to 2500 mg, wherein the carboxylic acid molecules or any salts thereof in conjunction with the PPI reduces gastric acid secretion in the human patient. ### Claim 10 (depends on 9) The method of claim 9, wherein the human patient has a disorder selected from the group consisting of: reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, pathologies associated with nonsteroidal anti-inflammatory drugs (NSAID), non-ulcer Dyspepsia, gastro-esophageal reflux disease, gastrinomas, acute upper gastrointestinal bleeding, stress ulceration, Helicobacter pylori infections, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis. ### Claim 11 (depends on 9) The method of claim 9, wherein the one or more small carboxylic acid molecules or any salts thereof are administered simultaneously or following the administration of the PPI. ### Claim 12 (depends on 9) The method of claim 9, wherein the release of the one or more small carboxylic acid molecules or any salts thereof in the stomach is delayed by between 10 to 60 minutes to synchronize the release with absorption of the PPI in the blood. ### Claim 13 (depends on 9) The method of claim 9, wherein the weight ratio between the one or more small carboxylic acid molecules or any salts thereof and the PPI is about 20:1 to about 1:5. ### Claim 14 (depends on 9) The method of claim 9, wherein the release of the one or more small carboxylic acid molecules or any salts thereof in the stomach is delayed. ### Claim 15 A pharmaceutical composition in a solid dosage form suitable for oral administration to a human patient, wherein the active ingredients of the capsules and tablets consist of a pharmaceutically effective amount of (i) a parietal cell activator, wherein the parietal cell activator is one or more small carboxylic acid molecules or any salts thereof which activate parietal cells, wherein the small carboxylic acid molecules or any salts thereof are saturated or non-saturated monocarboxylic, dicarboxylic or tricarboxylic acid molecules or any salts thereof involved in the mitochondrial respiration circle (krebs cycle) having between three to six carbon atoms selected from the group consisting of maleic acid, citric acid, pyruvate, fumarate, alpha-ketoglutarate, succinyl-CoA and oxaloacetate; and (ii) an enteric-coated irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI) selected from the group consisting of rabeprazole, omeprazole, isomeprazole, lansoprazole, pantoprazole, leminoprazole, tenatoprazole, single enantiomers thereof, alkaline salts thereof, pro-drugs thereof, and mixtures thereof, wherein the small carboxylic acid molecules or any salts thereof are in a form for release in the stomach in an amount of between 50 to 2500 mg so that the parietal cells located in the gastric lumen of the human patient are active while the PPI is in the patient's blood, wherein the carboxylic acid molecules or any salts thereof enhance the activity of the PPI at inhibiting gastric acid secretion in the stomach. ### Claim 16 (depends on 15) The composition of claim 15, wherein the PPI is released prior to the one or more small carboxylic acid molecules or any salts thereof in the stomach. ### Claim 17 (depends on 15) The composition of claim 15, wherein the capsules or tablets are selected from the group consisting of: multi-layered tablets, press-coat tablets, suspension tablets, effervescent tablets, hard gelatin capsules, and soft gelatin capsules. ### Claim 18 A pharmaceutical composition in a solid dosage form suitable for administration to a human patient, wherein the active ingredients of said composition consist of a pharmaceutically effective amount of: (i) a parietal cell activator, wherein the parietal cell activator is one or more small carboxylic acid molecules or any salts thereof which activate parietal cells, wherein the small carboxylic acid molecules or any salts thereof are saturated or non-saturated monocarboxylic, dicarboxylic or tricarboxylic acid molecules or any salts thereof having between three to six carbon atoms selected from the group consisting of maleic acid, citric acid, pyruvate, fumarate, alpha-ketoglutarate, succinyl-CoA and oxaloacetate; and (ii) an enteric-coated irreversible gastric H+/K+-ATPase proton pump inhibitor (PPI), wherein the weight ratio between the carboxylic acid molecules or any salts thereof and the PPI is about 20:1 to 1:5 and the carboxylic acid molecules or any salts thereof are in a form for release in the stomach so that the parietal cells located in the gastric lumen of the human patient are active while the PPI is in the patient's blood, wherein the carboxylic acid molecules or any salts thereof enhance the activity of the PPI at inhibiting gastric acid secretion in the stomach. ### Claim 19 (depends on 18) The composition of claim 18, wherein the weight ratio between the one or more small carboxylic acid molecules or any salts thereof and the PPI is 20:1 to 5:1.