WO2019144889A1 - 中乌宁晶型及其制备方法 - Google Patents
中乌宁晶型及其制备方法 Download PDFInfo
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- WO2019144889A1 WO2019144889A1 PCT/CN2019/072874 CN2019072874W WO2019144889A1 WO 2019144889 A1 WO2019144889 A1 WO 2019144889A1 CN 2019072874 W CN2019072874 W CN 2019072874W WO 2019144889 A1 WO2019144889 A1 WO 2019144889A1
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- crystal form
- zhongwuing
- medium
- crystal
- sample
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Definitions
- the X-ray powder diffraction pattern of the Zhongwuing crystal form A of the present invention is still 2theta values of 11.6° ⁇ 0.2°, 19.8° ⁇ 0.2°, 24.2° ⁇ 0.2°, 26.9°. There is a characteristic peak at ⁇ 0.2°.
- the X-ray powder diffraction pattern of the Zhongwuing crystal form C of the present invention is still 2theta values of 19.9° ⁇ 0.2°, 21.0° ⁇ 0.2°, 23.8° ⁇ 0.2°, 26.6°. There is a characteristic peak at ⁇ 0.2°.
- High-humidity test The sample was placed in an open flat weighing bottle and sampled at a relative humidity of 90% for 10 days, and then sampled according to the stability test, and X-ray powder diffraction analysis was performed.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Alternative & Traditional Medicine (AREA)
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Abstract
Description
批号 | 熔点(℃) |
中乌宁晶型A样品 | 206.6~208.4℃ |
溶剂 | 溶解性 | 说明 |
水 | 易溶 | 1g溶质能在1~10ml溶剂中溶解 |
Claims (14)
- 一种中乌宁晶型A,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱在2theta值为8.3°±0.2°、10.6°±0.2°、13.3°±0.2°、13.7°±0.2°、19.0°±0.2°处具有特征峰。
- 根据权利要求1所述的中乌宁晶型A,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱还在2theta值为11.6°±0.2°、19.8°±0.2°、24.2°±0.2°、26.9°±0.2°处具有特征峰。
- 一种制备权利要求1或2所述的中乌宁晶型A的方法,其特征在于,所述方法包括以下步骤:(1)将中乌宁加入溶剂中,升温至50-90℃溶解,得到中乌宁的溶液;(2)将所述中乌宁的溶液降温至-10-30℃并搅拌析晶,过滤;(3)将步骤(2)过滤得到的固体真空干燥,得到中乌宁晶型A。
- 根据权利要求3所述的方法,其特征在于,所述溶剂选自水、甲醇、乙醇、异丙醇、丙酮、乙腈中的一种或多种。
- 一种中乌宁晶型B,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱在2theta值为6.6°±0.2°、9.2°±0.2°、13.4°±0.2°、14.3°±0.2°、15.5°±0.2°处具有特征峰。
- 根据权利要求5所述的中乌宁晶型B,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱还在2theta值为18.3°±0.2°、20.2°±0.2°、23.6°±0.2°、24.2°±0.2°处具有特征峰。
- 一种制备权利要求5或6所述的中乌宁晶型B的方法,其特征在于,所述方法包括以下步骤:(1)取根据权利要求1所述的中乌宁晶型A在40-60℃下在有机溶剂中悬浮搅拌,得到悬浮液;(2)将所述悬浮液降温至-10-30℃并搅拌析晶,过滤;(3)将步骤(2)过滤得到的固体真空干燥,得到中乌宁晶型B。
- 根据权利要求7所述的方法,其特征在于,所述有机溶剂为N-甲基吡咯烷酮。
- 一种中乌宁晶型C,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱在2theta值为7.90°±0.2°、10.1°±0.2°、13.0°±0.2°、17.4°±0.2°、19.4°±0.2°处具有特征峰。
- 根据权利要求9所述的中乌宁晶型C,其特征在于,使用Cu-Kα辐射,其X-射线粉末衍射图谱还在2theta值为19.9°±0.2°、21.0°±0.2°、23.8°±0.2°、26.6°±0.2°处具有特征峰。
- 一种制备权利要求9或10所述的中乌宁晶型C的方法,其特征在于,所述方法包括以下步骤:将根据权利要求5所述的中乌宁晶型B真空加热,得到中乌宁晶型C。
- 根据权利要求11所述的方法,其特征在于,真空加热的温度为140℃-230℃,优选170℃-200℃。
- 一种药物组合物,其包含权利要求1或2所述的中乌宁晶型A,权利要求5或6所述的中乌宁晶型B或权利要求9或10所述的中乌宁晶型C,及药学上可接受的赋形剂。
- 权利要求1或2所述的中乌宁晶型A,权利要求5或6所述的中乌宁晶型B或权利要求9或10所述的中乌宁晶型C或权利要求13所述的药物组合物在制备强心剂和抗心衰剂中的用途。
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EP19743596.9A EP3744712B1 (en) | 2018-01-24 | 2019-01-23 | Crystalline forms of mesaconine and preparation method therefor |
EA202091779A EA202091779A1 (ru) | 2018-01-24 | 2019-01-23 | Кристаллические формы мезаконина и способы их получения |
JP2020562818A JP7072674B2 (ja) | 2018-01-24 | 2019-01-23 | メサコニンの結晶形およびその調製方法 |
US16/963,026 US10941116B2 (en) | 2018-01-24 | 2019-01-23 | Crystalline forms of mesaconine and preparation methods therefor |
AU2019212668A AU2019212668B2 (en) | 2018-01-24 | 2019-01-23 | Crystalline forms of mesaconine and preparation method therefor |
CA3089268A CA3089268C (en) | 2018-01-24 | 2019-01-23 | Crystalline forms of mesaconine and preparation methods therefor |
KR1020207022252A KR102528854B1 (ko) | 2018-01-24 | 2019-01-23 | 메사코닌의 결정형 및 그의 제조방법 |
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PCT/CN2019/072874 WO2019144889A1 (zh) | 2018-01-24 | 2019-01-23 | 中乌宁晶型及其制备方法 |
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JP (2) | JP7072674B2 (zh) |
KR (2) | KR102528854B1 (zh) |
CN (3) | CN110066248B (zh) |
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KR102528854B1 (ko) * | 2018-01-24 | 2023-05-03 | 굿닥터 파머수티클 그룹 씨오., 엘티디. | 메사코닌의 결정형 및 그의 제조방법 |
CN112250632B (zh) * | 2019-12-19 | 2023-01-24 | 好医生药业集团有限公司 | 一种3,14,15-三乙酰乌头宁碱的制备方法 |
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CN107445893A (zh) * | 2017-08-31 | 2017-12-08 | 珠海润都制药股份有限公司 | 盐酸去甲乌药碱新晶型及其制备方法 |
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KR102528854B1 (ko) * | 2018-01-24 | 2023-05-03 | 굿닥터 파머수티클 그룹 씨오., 엘티디. | 메사코닌의 결정형 및 그의 제조방법 |
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Publication number | Publication date |
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CN110066247A (zh) | 2019-07-30 |
AU2019212668A1 (en) | 2020-08-13 |
EP3744712A1 (en) | 2020-12-02 |
KR20200110368A (ko) | 2020-09-23 |
KR102528854B1 (ko) | 2023-05-03 |
CN112375080A (zh) | 2021-02-19 |
AU2019212668B2 (en) | 2021-04-15 |
WO2019144888A1 (zh) | 2019-08-01 |
US10941116B2 (en) | 2021-03-09 |
CA3089268A1 (en) | 2019-08-01 |
KR20200108004A (ko) | 2020-09-16 |
US20200339514A1 (en) | 2020-10-29 |
JP2021512941A (ja) | 2021-05-20 |
EP3744712A4 (en) | 2021-07-07 |
EP3744711A4 (en) | 2021-07-07 |
JP6952206B2 (ja) | 2021-10-20 |
JP7072674B2 (ja) | 2022-05-20 |
EA202091779A1 (ru) | 2020-10-14 |
US20210040042A1 (en) | 2021-02-11 |
EP3744711B1 (en) | 2022-09-21 |
CN110066247B (zh) | 2021-01-01 |
EP3744712B1 (en) | 2023-04-12 |
KR102518166B1 (ko) | 2023-04-05 |
JP2021511390A (ja) | 2021-05-06 |
CN110066248A (zh) | 2019-07-30 |
US11465971B2 (en) | 2022-10-11 |
EP3744711A1 (en) | 2020-12-02 |
CA3089268C (en) | 2023-03-07 |
CN110066248B (zh) | 2020-10-27 |
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