TWI870441B - 經口醫藥組合物 - Google Patents
經口醫藥組合物 Download PDFInfo
- Publication number
- TWI870441B TWI870441B TW109127608A TW109127608A TWI870441B TW I870441 B TWI870441 B TW I870441B TW 109127608 A TW109127608 A TW 109127608A TW 109127608 A TW109127608 A TW 109127608A TW I870441 B TWI870441 B TW I870441B
- Authority
- TW
- Taiwan
- Prior art keywords
- salt
- composition
- benzo
- sodium
- thiophen
- Prior art date
Links
- 239000008203 oral pharmaceutical composition Substances 0.000 title description 70
- 239000004480 active ingredient Substances 0.000 claims abstract description 27
- 235000002639 sodium chloride Nutrition 0.000 claims description 181
- 239000000203 mixture Substances 0.000 claims description 164
- 150000003839 salts Chemical class 0.000 claims description 157
- 239000003814 drug Substances 0.000 claims description 127
- 229940079593 drug Drugs 0.000 claims description 126
- 230000003204 osmotic effect Effects 0.000 claims description 109
- -1 7-[4-(4-benzo[b]thiophen-4-yl-piperidin -1-yl)butoxy]-1H-quinolin-2-one salt hydrate Chemical group 0.000 claims description 82
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 77
- 229920003169 water-soluble polymer Polymers 0.000 claims description 58
- 239000000654 additive Substances 0.000 claims description 53
- 229920002678 cellulose Polymers 0.000 claims description 47
- 239000001913 cellulose Substances 0.000 claims description 46
- 229920000642 polymer Polymers 0.000 claims description 44
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 41
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 39
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 39
- 150000002500 ions Chemical class 0.000 claims description 39
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 38
- ARZTVCATAJBVOU-UHFFFAOYSA-N 7-[4-[4-(1-benzothiophen-4-yl)piperidin-1-yl]butoxy]-1H-quinolin-2-one Chemical group S1C2=C(C=C1)C(=CC=C2)C2CCN(CC2)CCCCOC2=CC=C1C=CC(NC1=C2)=O ARZTVCATAJBVOU-UHFFFAOYSA-N 0.000 claims description 31
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 29
- 239000000017 hydrogel Substances 0.000 claims description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 25
- 201000000980 schizophrenia Diseases 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 24
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 24
- 229910019142 PO4 Inorganic materials 0.000 claims description 21
- 230000000996 additive effect Effects 0.000 claims description 20
- 239000010452 phosphate Substances 0.000 claims description 19
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 19
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- MSJMDZAOKORVFC-SEPHDYHBSA-L disodium fumarate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C\C([O-])=O MSJMDZAOKORVFC-SEPHDYHBSA-L 0.000 claims description 16
- 235000019294 sodium fumarate Nutrition 0.000 claims description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 13
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 13
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 13
- 239000002702 enteric coating Substances 0.000 claims description 13
- 238000009505 enteric coating Methods 0.000 claims description 13
- 239000001530 fumaric acid Substances 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 13
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 12
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 12
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 12
- 235000011009 potassium phosphates Nutrition 0.000 claims description 12
- 210000004369 blood Anatomy 0.000 claims description 11
- 239000008280 blood Substances 0.000 claims description 11
- 238000013270 controlled release Methods 0.000 claims description 11
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 9
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 9
- 235000019800 disodium phosphate Nutrition 0.000 claims description 9
- 239000001103 potassium chloride Substances 0.000 claims description 9
- 235000011164 potassium chloride Nutrition 0.000 claims description 9
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 8
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 8
- 229920000609 methyl cellulose Polymers 0.000 claims description 8
- 239000001923 methylcellulose Substances 0.000 claims description 8
- 235000010981 methylcellulose Nutrition 0.000 claims description 8
- 239000001509 sodium citrate Substances 0.000 claims description 8
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 8
- 239000001488 sodium phosphate Substances 0.000 claims description 8
- 235000011008 sodium phosphates Nutrition 0.000 claims description 8
- 235000011006 sodium potassium tartrate Nutrition 0.000 claims description 8
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 7
- 239000003405 delayed action preparation Substances 0.000 claims description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 7
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 7
- 235000011152 sodium sulphate Nutrition 0.000 claims description 7
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 claims description 6
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 6
- 235000011147 magnesium chloride Nutrition 0.000 claims description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 6
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 6
- 235000016337 monopotassium tartrate Nutrition 0.000 claims description 6
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 claims description 6
- 229940086065 potassium hydrogentartrate Drugs 0.000 claims description 6
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 claims description 6
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims description 6
- 229910052939 potassium sulfate Inorganic materials 0.000 claims description 6
- 235000011151 potassium sulphates Nutrition 0.000 claims description 6
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 claims description 6
- 239000001433 sodium tartrate Substances 0.000 claims description 6
- NKAAEMMYHLFEFN-ZVGUSBNCSA-M sodium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O NKAAEMMYHLFEFN-ZVGUSBNCSA-M 0.000 claims description 6
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 claims description 6
- 239000001476 sodium potassium tartrate Substances 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- 229940074439 potassium sodium tartrate Drugs 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 7
- 229940095064 tartrate Drugs 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 61
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- 238000002360 preparation method Methods 0.000 description 106
- 239000003826 tablet Substances 0.000 description 89
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- 238000004090 dissolution Methods 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 44
- 238000007922 dissolution test Methods 0.000 description 38
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 36
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- 238000000576 coating method Methods 0.000 description 30
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- 239000002585 base Substances 0.000 description 24
- 238000000634 powder X-ray diffraction Methods 0.000 description 24
- 238000011156 evaluation Methods 0.000 description 23
- 235000019359 magnesium stearate Nutrition 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 229920001477 hydrophilic polymer Polymers 0.000 description 21
- 239000000314 lubricant Substances 0.000 description 20
- 235000021317 phosphate Nutrition 0.000 description 20
- 239000002904 solvent Chemical class 0.000 description 20
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- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 18
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 229940050411 fumarate Drugs 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 229940001468 citrate Drugs 0.000 description 13
- 238000000862 absorption spectrum Methods 0.000 description 12
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 8
- MSJMDZAOKORVFC-UAIGNFCESA-L disodium maleate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C/C([O-])=O MSJMDZAOKORVFC-UAIGNFCESA-L 0.000 description 8
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- VRVKOZSIJXBAJG-TYYBGVCCSA-M monosodium fumarate Chemical compound [Na+].OC(=O)\C=C\C([O-])=O VRVKOZSIJXBAJG-TYYBGVCCSA-M 0.000 description 8
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- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 8
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Landscapes
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- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOPCT/JP2019/031895 | 2019-08-13 | ||
| PCT/JP2019/031895 WO2021029020A1 (ja) | 2019-08-13 | 2019-08-13 | 経口医薬組成物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
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| TW109127609A TWI870442B (zh) | 2019-08-13 | 2020-08-13 | 含有雜環化合物之經口醫藥組合物 |
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| WO2021029020A1 (ja) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | 経口医薬組成物 |
| CN118742293A (zh) * | 2022-01-31 | 2024-10-01 | 住友精化株式会社 | 药物控释制剂用组合物和药物控释制剂 |
| JP2023173950A (ja) * | 2022-05-27 | 2023-12-07 | 同仁医薬化工株式会社 | 経口液剤 |
| AU2024247059A1 (en) * | 2023-03-29 | 2025-10-30 | Merck Sharp & Dohme (Uk) Limited | Controlled release pde10a formulations |
Citations (2)
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| US20140120185A1 (en) * | 2011-04-05 | 2014-05-01 | Tsuyoshi Hirose | Combinations comprising brexpiprazole or a salt thereof and a second drug for use in the treatment of a cns disorder |
| US20140234417A1 (en) * | 2011-10-14 | 2014-08-21 | Otsuka Pharmaceutical Co., Ltd. | Tablet comprising 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1h-quinolin-2-one or a salt thereof |
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| US2799241A (en) | 1949-01-21 | 1957-07-16 | Wisconsin Alumni Res Found | Means for applying coatings to tablets or the like |
| US3173876A (en) | 1960-05-27 | 1965-03-16 | John C Zobrist | Cleaning methods and compositions |
| NL271831A (https=) | 1960-11-29 | |||
| US3276586A (en) | 1963-08-30 | 1966-10-04 | Rosaen Filter Co | Indicating means for fluid filters |
| US3546142A (en) | 1967-01-19 | 1970-12-08 | Amicon Corp | Polyelectrolyte structures |
| US3541006A (en) | 1968-07-03 | 1970-11-17 | Amicon Corp | Ultrafiltration process |
| US3541005A (en) | 1969-02-05 | 1970-11-17 | Amicon Corp | Continuous ultrafiltration of macromolecular solutions |
| US3865108A (en) | 1971-05-17 | 1975-02-11 | Ortho Pharma Corp | Expandable drug delivery device |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US4002173A (en) | 1974-07-23 | 1977-01-11 | International Paper Company | Diester crosslinked polyglucan hydrogels and reticulated sponges thereof |
| GB1478759A (en) | 1974-11-18 | 1977-07-06 | Alza Corp | Process for forming outlet passageways in pills using a laser |
| US4207893A (en) | 1977-08-29 | 1980-06-17 | Alza Corporation | Device using hydrophilic polymer for delivering drug to biological environment |
| TWI320783B (en) * | 2005-04-14 | 2010-02-21 | Otsuka Pharma Co Ltd | Heterocyclic compound |
| JP4315393B2 (ja) | 2005-04-14 | 2009-08-19 | 大塚製薬株式会社 | 複素環化合物 |
| JP4540700B2 (ja) * | 2006-10-13 | 2010-09-08 | 大塚製薬株式会社 | 医薬 |
| TWI632921B (zh) * | 2011-10-19 | 2018-08-21 | 大塚製藥股份有限公司 | 口服溶液 |
| AR090775A1 (es) * | 2012-04-23 | 2014-12-03 | Otsuka Pharma Co Ltd | Preparado inyectable |
| EP2911670A1 (en) * | 2012-10-25 | 2015-09-02 | Otsuka Pharmaceutical Co., Ltd. | Prophylactic and/or therapeutic agent for behavioral and psychological symptoms associated with neurodegenerative disease or impulsive symptoms associated with mental disease containing brexpiprazole or salt thereof |
| CN106667969A (zh) * | 2017-02-23 | 2017-05-17 | 佛山市弘泰药物研发有限公司 | 一种依匹哌唑缓释胶囊及其制备方法 |
| JP6886654B2 (ja) | 2017-04-11 | 2021-06-16 | 学校法人帝京大学 | 抗カンジダ活性組成物 |
| WO2021029020A1 (ja) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | 経口医薬組成物 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140120185A1 (en) * | 2011-04-05 | 2014-05-01 | Tsuyoshi Hirose | Combinations comprising brexpiprazole or a salt thereof and a second drug for use in the treatment of a cns disorder |
| US20140234417A1 (en) * | 2011-10-14 | 2014-08-21 | Otsuka Pharmaceutical Co., Ltd. | Tablet comprising 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1h-quinolin-2-one or a salt thereof |
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