CN105873586B - 一种包含缬沙坦和ahu377的三钠盐超分子复合物的晶型及其制备方法 - Google Patents
一种包含缬沙坦和ahu377的三钠盐超分子复合物的晶型及其制备方法 Download PDFInfo
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Abstract
Description
化合物 | 超分子复合物 |
AHU-377浓度(mmol/L) | 1.89 |
缬沙坦浓度(mmol/L) | 1.94 |
Na<sup>+</sup>浓度(mmol/L) | 5.73 |
摩尔比(AHU-377:缬沙坦:Na<sup>+</sup>) | 1:1:3 |
化合物 | 超分子复合物 |
AHU-377浓度(mmol/L) | 2.00 |
缬沙坦浓度(mmol/L) | 2.08 |
Na<sup>+</sup>浓度(mmol/L) | 6.10 |
摩尔比(AHU-377:缬沙坦:Na<sup>+</sup>) | 1:1:3 |
相对湿度 | 11% | 32% | 50% |
保存时间 | 1个月 | 1个月 | 1个月 |
晶型 | II | II | II |
温度 | 30℃ | 40℃ | 50℃ | 60℃ |
保存时间 | 1个月 | 1个月 | 2周 | 2周 |
晶型 | II | II | II | II |
Claims (6)
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CN201910761979.7A CN110922366B (zh) | 2014-12-08 | 2015-12-08 | 一种包含缬沙坦和ahu377的三钠盐超分子复合物的新晶型及其制备方法 |
CN201910761992.2A CN110938042B (zh) | 2014-12-08 | 2015-12-08 | 一种包含缬沙坦和ahu377的三钠盐超分子复合物的新晶型及其制备方法 |
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US201462089225P | 2014-12-08 | 2014-12-08 | |
US62/089,225 | 2014-12-08 | ||
PCT/US2015/064432 WO2016049663A1 (en) | 2014-12-08 | 2015-12-08 | Crystalline forms of trisodium supramolecular complex comprising valsartan and ahu-377 and methods thereof |
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CN201910761992.2A Division CN110938042B (zh) | 2014-12-08 | 2015-12-08 | 一种包含缬沙坦和ahu377的三钠盐超分子复合物的新晶型及其制备方法 |
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CN105873586B true CN105873586B (zh) | 2019-09-13 |
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CN201580002782.5A Active CN105873586B (zh) | 2014-12-08 | 2015-12-08 | 一种包含缬沙坦和ahu377的三钠盐超分子复合物的晶型及其制备方法 |
CN201910761992.2A Active CN110938042B (zh) | 2014-12-08 | 2015-12-08 | 一种包含缬沙坦和ahu377的三钠盐超分子复合物的新晶型及其制备方法 |
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US (2) | US9957240B2 (zh) |
EP (2) | EP3443960A1 (zh) |
JP (3) | JP2017537120A (zh) |
CN (3) | CN110922366B (zh) |
AU (1) | AU2015319831B2 (zh) |
CA (1) | CA2970192C (zh) |
DK (1) | DK3229799T3 (zh) |
ES (1) | ES2706948T3 (zh) |
HU (1) | HUE043014T2 (zh) |
IL (2) | IL252740A0 (zh) |
MX (1) | MX2017007426A (zh) |
PL (1) | PL3229799T3 (zh) |
PT (1) | PT3229799T (zh) |
SI (1) | SI3229799T1 (zh) |
TR (1) | TR201900360T4 (zh) |
WO (1) | WO2016049663A1 (zh) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR057882A1 (es) | 2005-11-09 | 2007-12-26 | Novartis Ag | Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra |
WO2016037552A1 (zh) * | 2014-09-09 | 2016-03-17 | 上海翰森生物医药科技有限公司 | 结晶型ARB-NEPi复合物及其制备方法和应用 |
AU2015319831B2 (en) | 2014-12-08 | 2019-02-14 | Crystal Pharmatech Co., Ltd. | Crystalline forms of trisodium supramolecular complex comprising valsartan and AHU-377 and methods thereof |
US10689352B2 (en) | 2015-06-12 | 2020-06-23 | Teva Pharmaceuticals International Gmbh | Solid state forms of trisodium valsartan: sacubitril |
CN105037289B (zh) * | 2015-07-17 | 2017-08-22 | 华东理工大学 | 血管紧张素受体拮抗剂和中性内肽酶抑制剂超分子复合体的新晶型 |
WO2017012600A1 (en) * | 2015-07-20 | 2017-01-26 | Zentiva, K.S. | A pharmaceutical composition containing valsartan and sacubitril and methods for preparation and stabilization thereof |
CN106854187B (zh) * | 2015-12-08 | 2020-04-14 | 苏州晶云药物科技股份有限公司 | 一种ahu-377和缬沙坦三钠盐共晶水合物晶型ii的制备方法 |
CN106905253B (zh) * | 2015-12-23 | 2020-01-03 | 正大天晴药业集团股份有限公司 | 一种超分子复合物的结晶 |
CN105753733B (zh) * | 2016-04-15 | 2019-06-18 | 苏州晶云药物科技股份有限公司 | Ahu377的晶型及其制备方法与用途 |
EP3511317A4 (en) * | 2016-09-07 | 2020-04-15 | Noratech Pharmaceuticals, Inc. | NEW CRYSTALLINE SODIUM SALT FORM OF SACUBITRIL |
EP3522886A4 (en) | 2016-10-10 | 2020-02-19 | Laurus Labs Limited | STABLE AMORPHE FORM OF THE SACUBITRIL VALSARTAN TRINATRIUM COMPLEX AND METHOD FOR THE PRODUCTION THEREOF |
CN107674038A (zh) * | 2017-01-03 | 2018-02-09 | 上海博志研新药物技术有限公司 | ARB‑NEPi复合物、晶型、制备方法及应用 |
CN108299323A (zh) * | 2017-01-11 | 2018-07-20 | 上海迪赛诺药业股份有限公司 | 一种抗心衰共晶化合物的新晶型 |
WO2018178295A1 (en) | 2017-03-31 | 2018-10-04 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Stable hot-melt extrudate containing valsartan and sacubitril |
WO2019073062A1 (en) | 2017-10-13 | 2019-04-18 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | TABLET CONTAINING VALSARTAN AND SACUBITRIL |
WO2019239432A1 (en) | 2018-06-14 | 2019-12-19 | Cipla Limited | Trisodium sacubitril valsartan complex and hot-melt extruded pharmaceutical composition comprising thereof |
JP2021525791A (ja) | 2018-08-23 | 2021-09-27 | ノバルティス アーゲー | 新たな心不全治療用医薬の使用 |
WO2020039394A1 (en) | 2018-08-24 | 2020-02-27 | Novartis Ag | New drug combinations |
CN111253330B (zh) * | 2020-02-29 | 2023-01-24 | 广州白云山天心制药股份有限公司 | 沙坦类药物的新晶型及其制备方法和用途 |
CN115745904A (zh) * | 2022-09-29 | 2023-03-07 | 浙江美诺华药物化学有限公司 | 一种沙库巴曲缬沙坦钠共晶物的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003059345A1 (en) * | 2002-01-17 | 2003-07-24 | Novartis Ag | Pharmaceutical compositions comprising valsartan and nep inhibitors |
CN102702119A (zh) * | 2005-11-09 | 2012-10-03 | 诺瓦提斯公司 | 血管紧张素受体拮抗剂和nep抑制剂的药物组合产品 |
CN103079554A (zh) * | 2010-08-24 | 2013-05-01 | 诺华有限公司 | 在接受抗凝血剂疗法的哺乳动物中治疗高血压和/或预防或治疗心力衰竭 |
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JP3796763B2 (ja) * | 1994-04-01 | 2006-07-12 | 東ソー株式会社 | 結晶形2,2−ビス(3,5−ジブロモ−4−ジブロモプロポキシフェニル)プロパン及びその製造方法 |
FR2897060B1 (fr) * | 2006-02-08 | 2008-07-25 | Sanofi Aventis Sa | Le monohydrate de rimonabant, son procede de preparation et les compositions pharmaceutiques en contenant |
US7994238B2 (en) * | 2007-09-04 | 2011-08-09 | General Electric Company | Article and associated method |
EP4186491A1 (en) | 2007-11-06 | 2023-05-31 | Novartis AG | Pharmaceutical compositions |
WO2014175303A1 (ja) * | 2013-04-24 | 2014-10-30 | あすか製薬株式会社 | レボノルゲストレルの結晶多形α及びその製造方法 |
AU2015319831B2 (en) * | 2014-12-08 | 2019-02-14 | Crystal Pharmatech Co., Ltd. | Crystalline forms of trisodium supramolecular complex comprising valsartan and AHU-377 and methods thereof |
CN104860894B (zh) * | 2015-06-10 | 2017-05-17 | 北京博全健医药科技有限公司 | 一种抗心衰药lcz696的制备方法 |
US10689352B2 (en) | 2015-06-12 | 2020-06-23 | Teva Pharmaceuticals International Gmbh | Solid state forms of trisodium valsartan: sacubitril |
CN105037289B (zh) | 2015-07-17 | 2017-08-22 | 华东理工大学 | 血管紧张素受体拮抗剂和中性内肽酶抑制剂超分子复合体的新晶型 |
CN106854187B (zh) * | 2015-12-08 | 2020-04-14 | 苏州晶云药物科技股份有限公司 | 一种ahu-377和缬沙坦三钠盐共晶水合物晶型ii的制备方法 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003059345A1 (en) * | 2002-01-17 | 2003-07-24 | Novartis Ag | Pharmaceutical compositions comprising valsartan and nep inhibitors |
CN102702119A (zh) * | 2005-11-09 | 2012-10-03 | 诺瓦提斯公司 | 血管紧张素受体拮抗剂和nep抑制剂的药物组合产品 |
CN103079554A (zh) * | 2010-08-24 | 2013-05-01 | 诺华有限公司 | 在接受抗凝血剂疗法的哺乳动物中治疗高血压和/或预防或治疗心力衰竭 |
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CN110922366B (zh) | 2023-02-03 |
TR201900360T4 (tr) | 2019-02-21 |
EP3229799A1 (en) | 2017-10-18 |
DK3229799T3 (en) | 2019-02-11 |
US20170362189A1 (en) | 2017-12-21 |
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AU2015319831A1 (en) | 2017-07-20 |
US20180201589A1 (en) | 2018-07-19 |
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HUE043014T2 (hu) | 2019-07-29 |
JP2018168180A (ja) | 2018-11-01 |
JP2020203936A (ja) | 2020-12-24 |
CN105873586A (zh) | 2016-08-17 |
CN110938042A (zh) | 2020-03-31 |
ES2706948T3 (es) | 2019-04-01 |
EP3443960A1 (en) | 2019-02-20 |
IL276233B1 (en) | 2023-03-01 |
MX2017007426A (es) | 2018-04-20 |
IL276233A (en) | 2020-09-30 |
CA2970192C (en) | 2020-08-04 |
IL276233B2 (en) | 2023-07-01 |
EP3229799B1 (en) | 2018-10-17 |
PT3229799T (pt) | 2019-01-29 |
CN110922366A (zh) | 2020-03-27 |
US9957240B2 (en) | 2018-05-01 |
SI3229799T1 (sl) | 2019-03-29 |
AU2015319831B2 (en) | 2019-02-14 |
JP2017537120A (ja) | 2017-12-14 |
CA2970192A1 (en) | 2016-03-31 |
PL3229799T3 (pl) | 2019-05-31 |
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