# US 11,077,062 B2 · Pharmaceutical composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,062 B2 - Document ID: US11077062B2 - Status: Granted - Kind: B2 - Application number: 16/485,971 - Filed: 2018-02-14 - Published: 2020-02-27 - Granted: 2021-08-03 - Earliest claimed: 2017-02-15 - Assignees: Taiho Pharmaceutical Co., Ltd. - Applicants: Taiho Pharmaceutical Co., Ltd. - Inventors: Shinji Okada - Web page: https://patentgrep.com/patent/US11077062B2 ## CPC - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/1611: {Inorganic compounds} - A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient} - A61K 31/47: Quinolines; Isoquinolines - A61K 31/04: Nitro compounds - 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) ## Abstract An object of the present invention is to provide a pharmaceutical composition which has excellent stability, disintegratability, and absorbability, is easily prepared, and contains 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and a cyclodextrin derivative. The present invention relates to a pharmaceutical composition containing 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and hydroxypropyl-β-cyclodextrin. ## Claims ### Claim 1 A pharmaceutical composition, comprising: A 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N -methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof; hydroxypropyl-β-cyclodextrin; and the composition includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0)(°) in powder X-ray structure diffraction. ### Claim 2 (depends on 1) The pharmaceutical composition according to claim 1, wherein the composition includes peaks at diffraction angles 2θ (±0.2°) of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction. ### Claim 3 (depends on 1) The pharmaceutical composition according to claim 1, wherein the composition includes peaks at chemical shift values [δ (ppm)] of 162.6, 130.4, 103.1, 82.7, 73.3, 41.9, and 19.9 in solid 13C-NMR. ### Claim 4 (depends on 1) The pharmaceutical composition according to claim 1, wherein the composition includes peaks at 5 or more absorption bands selected from the group consisting of 1663, 1352, 1225, 1156, 1032, 720, and 553 (cm−1) in an infrared absorption spectrum. ### Claim 5 (depends on 1) The pharmaceutical composition according to claim 1, wherein hydroxypropyl-β-cyclodextrin is contained at 0.1 to 5.5 parts by mass with respect to 1 part by mass of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy -N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof. ### Claim 6 (depends on 1) The pharmaceutical composition according to claim 1, further comprising: a silicic acid derivative. ### Claim 7 (depends on 1) The pharmaceutical composition according to claim 1, further comprising: a cellulose derivative. ### Claim 8 A pharmaceutical composition, comprising: 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline -6-carboxamide or a pharmaceutically acceptable salt thereof; hydroxypropyl-β-cyclodextrin; includes peaks at 5 or more diffraction angles 2θ (±0.2°) selected from the group consisting of 6.5. 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction; and wherein the pharmaceutical composition is produced by physical mixing that does not include a step in which 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N -methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof is converted into a solution state when the pharmaceutical composition is produced. ### Claim 9 (depends on 8) The pharmaceutical composition according to claim 8, wherein the physical mixing is mixing or granulation. ### Claim 10 (depends on 8) The pharmaceutical composition according to claim 8, wherein the composition includes peaks at diffraction angles 2θ (±0.2°) of 6.5, 7.8, 9.6, 12.4, 18.8, 21.2, 23.0, 24.5, and 26.0 (°) in powder X-ray structure diffraction. ### Claim 11 (depends on 8) The pharmaceutical composition according to claim 8, wherein the composition includes peaks at chemical shift values [δ (ppm)] of 162.6, 130. 4, 103.1, 82.7, 73.3, 41.9, and 19.9 in solid 13C-NMR. ### Claim 12 (depends on 8) The pharmaceutical composition according to claim 8, wherein the composition includes peaks at 5 or more absorption bands selected from the group consisting of 1663, 1352, 1225, 1156, 1032, 720, and 553 (cm−1) in an infrared absorption spectrum. ### Claim 13 (depends on 8) The pharmaceutical composition according to claim 8, wherein hydroxypropyl-β-cyclodextrin is contained at 0.1 to 5.5 parts by mass with respect to 1 part by mass of a mesylate salt of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide. ### Claim 14 (depends on 8) The pharmaceutical composition according to claim 8, further comprising: a silicic acid derivative. ### Claim 15 (depends on 8) The pharmaceutical composition according to claim 8, further comprising: a cellulose derivative. ### Claim 16 A method for producing a pharmaceutical composition, comprising performing physical mixing of 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and hydroxypropyl-β-cyclodextrin. ### Claim 17 (depends on 16) The production method according to claim 16, wherein the physical mixing is a production method that does not include a step in which 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof is converted into a solution state when the pharmaceutical composition is produced. ### Claim 18 (depends on 16) The production method according to claim 16, wherein the physical mixing is mixing or granulation.