# US 9,040,564 B2 · Stabilized composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,564 B2 - Document ID: US9040564B2 - Status: Granted - Kind: B2 - Application number: 11/937,393 - Filed: 2007-11-08 - Published: 2008-06-19 - Granted: 2015-05-26 - Earliest claimed: 2005-04-28 - Assignees: Eisai R&D Management Co., Ltd. - Applicants: Koji Ukai; Norishige Takami - Inventors: Koji Ukai; Norishige Takami - Web page: https://patentgrep.com/patent/US9040564B2 ## CPC - A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 9/5078: {with drug-free core} - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - 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 It is intended to provide a pharmaceutical composition which contains a proton pump inhibitor and is stable even if it is stored for a long time. It is also intended to provide a pharmaceutical composition which contains a proton pump inhibitor susceptible to acid, and does not dissolve in the stomach but dissolves in the intestine to release a primary drug product promptly. The object could be achieved by the pharmaceutical composition characterized in that a layer containing a proton pump inhibitor and ethyl cellulose, a layer containing an enteric polymer, and if necessary an intermediate layer composed of one or more layers are formed on a pharmacologically inactive core substance. The intermediate layer is composed of a water-insoluble polymer, a water-soluble polymer, a lubricant and the like. ## Claims ### Claim 1 A pharmaceutical composition comprising a core substance coated with a principal ingredient layer, said principal ingredient layer comprising rabeprazole or a pharmaceutically acceptable salt thereof as a proton pump inhibitor and ethyl cellulose; and said principal ingredient layer does not contain a basic substance. ### Claim 2 (depends on 1) The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is further coated with an exterior layer comprising an enteric polymer on an exterior side of the principal ingredient layer. ### Claim 3 (depends on 2) The pharmaceutical composition according to claim 2, wherein the enteric polymer is one or more selected from the group consisting of hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, methacrylic acid methacrylic acid methyl copolymer, methacrylic acid acrylic acid ethyl copolymer, carboxymethylethyl cellulose and cellulose acetate phthalate. ### Claim 4 (depends on 2) The pharmaceutical composition according to claim 2, wherein one or more intermediate layers is coated between the principal ingredient layer and the exterior layer. ### Claim 5 (depends on 4) The pharmaceutical composition according to claim 4, wherein two intermediate layers are coated. ### Claim 6 (depends on 4) The pharmaceutical composition according to claim 4, wherein at least one of the intermediate layers comprises one or more selected from the group consisting of a non-water-soluble polymer, a water-soluble polymer and a lubricant. ### Claim 7 (depends on 4) The pharmaceutical composition according to claim 4, wherein the composition comprises two or more intermediate layers, and wherein at least one of the intermediate layers comprises a non-water-soluble polymer, a water-soluble polymer and a lubricant, and another intermediate layer comprises crospovidone. ### Claim 8 (depends on 1) The pharmaceutical composition according to claim 1, wherein based on the total amount of the layer comprising the rabeprazole or pharmaceutically acceptable salt thereof and ethyl cellulose, the weight of ethyl cellulose in said layer is not more than 25%. ### Claim 9 (depends on 1) The pharmaceutical composition according to claim 1, wherein the core substance is a granule substance having one or more components selected from the group consisting of sugars, sugar alcohols, celluloses and starches. ### Claim 10 (depends on 1) The pharmaceutical composition according to claim 1, which is a granule. ### Claim 11 (depends on 1) The pharmaceutical composition according to claim 1, which is a tablet or an encapsulated formulation. ### Claim 12 (depends on 10) The pharmaceutical composition according to claim 10, which is a drug product formulation used for tube administration further comprising a thickening agent. ### Claim 13 (depends on 2) The pharmaceutical composition according to claim 2, wherein in a dissolution test using a test solution having a pH of 5.5 or higher, 75% or more of the rabeprazole compound is dissolved within 30 minutes.