TWI586378B - 新穎醫藥調配物 - Google Patents
新穎醫藥調配物 Download PDFInfo
- Publication number
- TWI586378B TWI586378B TW102108766A TW102108766A TWI586378B TW I586378 B TWI586378 B TW I586378B TW 102108766 A TW102108766 A TW 102108766A TW 102108766 A TW102108766 A TW 102108766A TW I586378 B TWI586378 B TW I586378B
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- Taiwan
- Prior art keywords
- compound
- formula
- lactose
- magnesium stearate
- weight
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 124
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 116
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 66
- 229960001375 lactose Drugs 0.000 claims description 66
- 239000008101 lactose Substances 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 65
- 229910052751 metal Inorganic materials 0.000 claims description 60
- 239000002184 metal Substances 0.000 claims description 60
- 235000019359 magnesium stearate Nutrition 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 50
- 239000007787 solid Substances 0.000 claims description 33
- 239000004480 active ingredient Substances 0.000 claims description 31
- 239000000126 substance Substances 0.000 claims description 31
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 30
- 238000009472 formulation Methods 0.000 claims description 28
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- 235000021355 Stearic acid Nutrition 0.000 claims description 21
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 21
- 239000008117 stearic acid Substances 0.000 claims description 21
- 239000003381 stabilizer Substances 0.000 claims description 17
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical group O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 8
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- 238000002144 chemical decomposition reaction Methods 0.000 claims description 7
- 239000011859 microparticle Substances 0.000 claims description 6
- AORIRZIYEBBHJD-UHFFFAOYSA-N COCCN(CCCCC#CC1=C2C(=CC=C1)N=C(N(C2=O)CC3=CC=CC=C3Cl)CN4C5=NC=NC(=C5C(=N4)C6=CC(=CC=C6)O)N)CCOC Chemical group COCCN(CCCCC#CC1=C2C(=CC=C1)N=C(N(C2=O)CC3=CC=CC=C3Cl)CN4C5=NC=NC(=C5C(=N4)C6=CC(=CC=C6)O)N)CCOC AORIRZIYEBBHJD-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 59
- 239000000843 powder Substances 0.000 description 35
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 18
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 16
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- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 12
- QANDQRKVQCIBES-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CCCCCCCCCCCCCCCCCC(O)=O Chemical compound OC(=O)\C=C\C(O)=O.CCCCCCCCCCCCCCCCCC(O)=O QANDQRKVQCIBES-WLHGVMLRSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 11
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- 238000004566 IR spectroscopy Methods 0.000 description 8
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- 229910052757 nitrogen Inorganic materials 0.000 description 8
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 7
- 108010044467 Isoenzymes Proteins 0.000 description 7
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- 239000012453 solvate Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
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- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
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- -1 magnesium stearate Chemical class 0.000 description 5
- 229910021645 metal ion Inorganic materials 0.000 description 5
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000002355 alkine group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000008116 calcium stearate Substances 0.000 description 4
- 235000013539 calcium stearate Nutrition 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229960000289 fluticasone propionate Drugs 0.000 description 4
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 4
- ONUHRYKLJYSRMY-UHFFFAOYSA-N hex-5-yn-1-amine Chemical compound NCCCCC#C ONUHRYKLJYSRMY-UHFFFAOYSA-N 0.000 description 4
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 4
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- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 3
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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| TW102108767A TWI617561B (zh) | 2012-03-13 | 2013-03-13 | 呈晶體型式之新穎化合物，包含其之醫藥組成物，製備該化合物之方法及包括該組成物之吸入裝置 |
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| AU2013234081B2 (en) | 2012-03-13 | 2017-02-02 | Respivert Limited | Crystalline PI3 kinase inhibitors |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| JP6434416B2 (ja) | 2012-11-08 | 2018-12-05 | ライゼン・ファーマシューティカルズ・エスアー | ＰＤＥ４阻害剤とＰＩ３δ阻害剤または二重ＰＩ３δ−γキナーゼ阻害剤とを含有する薬学的組成物 |
| TW201522341A (zh) | 2013-03-15 | 2015-06-16 | Respivert Ltd | 化合物 |
| AR095353A1 (es) | 2013-03-15 | 2015-10-07 | Respivert Ltd | Compuesto |
| PE20160685A1 (es) | 2013-10-04 | 2016-07-23 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN113620958A (zh) | 2014-03-19 | 2021-11-09 | 无限药品股份有限公司 | 用于治疗PI3K-γ介导的障碍的杂环化合物 |
| KR20170082490A (ko) | 2014-07-04 | 2017-07-14 | 루핀 리미티드 | Pi3k 억제제로서 퀴놀리지논 유도체 |
| WO2016005443A1 (en) * | 2014-07-09 | 2016-01-14 | Arven Ilac Sanayi Ve Ticaret A.S. | A process for the preparation of formulations for inhalation |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| PH12018500554B1 (en) | 2015-09-14 | 2024-01-24 | Infinity Pharmaceuticals Inc | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| SG10202010192YA (en) | 2016-04-15 | 2020-11-27 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | Inhaled preparation of isoglycyrrhizic acid or salt thereof, and use in preparing drugs for treating respiratory system diseases |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
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