WO2022166369A1 - 一种化合物晶型及其制备方法和应用 - Google Patents
一种化合物晶型及其制备方法和应用 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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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
Abstract
Description
2θ角 | 相对强度 |
12.21±0.2° | 100 |
13.381±0.2° | 2.5±0.5 |
15.181±0.2° | 4.48±0.5 |
16.171±0.2° | 7.05±0.5 |
17.101±0.2° | 17.79±0.5 |
19.801±0.2° | 14.02±0.5 |
21.511±0.2° | 6.47±0.5 |
24.391±0.2° | 6.56±0.5 |
25.321±0.2° | 5.44±0.5 |
2θ角 | 相对强度 |
12.21±0.2° | 100 |
13.381±0.2° | 2.5±0.5 |
15.181±0.2° | 4.48±0.5 |
16.171±0.2° | 7.05±0.5 |
17.101±0.2° | 17.79±0.5 |
19.801±0.2° | 14.02±0.5 |
21.511±0.2° | 6.47±0.5 |
24.391±0.2° | 6.56±0.5 |
25.321±0.2° | 5.44±0.5 |
2θ角 | 面间距 | 强度 | 相对强度 |
12.21 | 7.24273 | 881 | 100 |
13.381 | 6.61191 | 37 | 2.5 |
15.181 | 5.8317 | 44.3 | 4.48 |
16.171 | 5.47682 | 81.3 | 7.05 |
17.101 | 5.18099 | 75.4 | 17.79 |
19.801 | 4.48017 | 103 | 14.02 |
21.511 | 4.12771 | 53.2 | 6.47 |
24.391 | 3.64643 | 48.8 | 6.56 |
25.321 | 3.51457 | 37 | 5.44 |
起始样品 | 加热温度(℃) | 加热时间(min) | 产物晶型 |
Form A | 120 | 40 | Form A |
Form B | 120 | 40 | Form A |
Form C | 120 | 40 | Form A |
Form D | 120 | 40 | Form A |
起始样品混合物 | 混悬溶剂组成 | 混悬时间(天) | 产物晶型 |
Form A+Form B | 异丙醇 | 2 | Form A |
Form A+Form C | 异丙醇 | 2 | Form A |
Form A+Form D | 异丙醇 | 2 | Form A |
Form B+Form C | 异丙醇 | 2 | Form A |
Form B+Form D | 异丙醇 | 2 | Form A |
Form C+Form D | 异丙醇 | 2 | Form A |
成分 | 用量 |
原料药(晶型A/B/C/D) | 1份 |
蔗糖 | 24份 |
乳糖 | 24份 |
交联聚维酮(CL-M) | 0.3份 |
聚维酮K30 | 0.3份 |
Claims (10)
- 如权利要求1所述的晶型A,其特征在于,所述晶型A的X-射线粉末衍射图谱包括选自下组的2θ值:12.21±0.2°、13.381±0.2°、15.181±0.2°、16.171±0.2°、17.101±0.2°、19.801±0.2°、21.511±0.2°、24.391±0.2°、25.321±0.2°。
- 如权利要求1所述的晶型A,其特征在于,所述2θ值位置峰对应的相对强度为:
2θ角 相对强度 12.21±0.2° 100 13.381±0.2° 2.5±0.5 15.181±0.2° 4.48±0.5 16.171±0.2° 7.05±0.5 17.101±0.2° 17.79±0.5 19.801±0.2° 14.02±0.5 21.511±0.2° 6.47±0.5 24.391±0.2° 6.56±0.5 25.321±0.2° 5.44±0.5 - 如权利要求1所述的晶型A,其特征在于,所述晶型A具有基本如图2所示的XRPD图。
- 如权利要求1所述的晶型A,其特征在于,所述晶型A具有一个或多个选自下组的特征:1)所述晶型A的TGA图在式I化合物分解前无失重;2)所述晶型A的DSC图在峰值为172±5℃处具有特征吸收峰;3)所述晶型A在0-95%相对湿度下吸湿增重≤1%,较佳地,0.4%±0.3%。
- 如权利要求1所述的晶型A,其特征在于,所述晶型A具有一个或多个选自下组的特征:1)所述晶型A具有基本如图3所示的TGA图;2)所述晶型A具有基本如图4所示的DSC图;3)所述晶型A具有基本如图5所示的DVS图;4)所述晶型A具有基本如图6所示的IR图。
- 一种晶体组合物,所述晶体组合物包含如权利要求1-7任一所述的晶型A。
- 一种如权利要求1-7任一所述的晶型A的制备方法,其特征在于,所述方法包括:将式I化合物混悬于惰性溶剂中,搅拌,过滤,得所述晶型A;其中,所述惰性溶剂选自异丙醇或正己烷。
- 一种权利要求1-7任一所述晶型A或权利要求8所述晶型组合物的用途,其特征在于,用于制备用于预防和/或治疗前列腺增生疾病的药物。
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US20150099772A1 (en) * | 2013-10-04 | 2015-04-09 | Mallinckrodt Llc | Substituted berbines and their synthesis |
WO2018041112A1 (zh) | 2016-08-31 | 2018-03-08 | 中国医药工业研究总院 | 一种四氢异喹啉的盐衍生物及其晶体的制备方法和应用 |
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US20150099772A1 (en) * | 2013-10-04 | 2015-04-09 | Mallinckrodt Llc | Substituted berbines and their synthesis |
WO2018041112A1 (zh) | 2016-08-31 | 2018-03-08 | 中国医药工业研究总院 | 一种四氢异喹啉的盐衍生物及其晶体的制备方法和应用 |
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