WO2013149571A1 - 人参皂苷c-k的两种晶型及其制备方法 - Google Patents
人参皂苷c-k的两种晶型及其制备方法 Download PDFInfo
- Publication number
- WO2013149571A1 WO2013149571A1 PCT/CN2013/073562 CN2013073562W WO2013149571A1 WO 2013149571 A1 WO2013149571 A1 WO 2013149571A1 CN 2013073562 W CN2013073562 W CN 2013073562W WO 2013149571 A1 WO2013149571 A1 WO 2013149571A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ginsenoside
- crystal form
- crystal
- organic solvent
- solvent
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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 present invention relates to the field of pharmacy, and more particularly to two novel crystal forms of the pharmaceutical ginsenoside c- ⁇ and a process for the preparation thereof.
- Ginsenoside is the main active ingredient of ginseng.
- Ginsenoside CK is a glycol-type ginsenoside. It is not found in natural ginseng. It is the main degradation product of other glycol-type ginsenosides in the human intestine. It is true. An entity that is absorbed and functions. Ginsenoside C-K not only has good activity in anti-tumor, anti-inflammatory, anti-allergic, and liver-protecting, but also has a good regulatory effect on the nervous system and immune system.
- the stability of the crystalline form D and the crystalline form H of the ginsenoside CK proposed by the present invention is better than that of the existing crystalline form G.
- the present invention provides two novel crystal forms of ginsenoside CK, respectively, Form D and Form H, and also provides a preparation method of the two crystal forms, wherein the crystal form D is ginsenoside CK monohydrate. Crystal.
- a crystalline form D of ginsenoside CK is provided, characterized in that the XRPD pattern is about 6.39, 12.71, 13.30, 15.79, 16. 14, 16. 44, 20. 03, 20. 74, 24.
- the crystalline form D of ginsenoside CK is at a value of 2 ⁇ (° ) of about 10.66, 11. 21, 16. 85, 17. 27, 19. 05, 21. 33, 21. 65 22. 52, 23. 48, 24. 93, 25. 46, 26. 76, 27. 99, 29. 15, 30. 39, 34.
- diffraction peaks at 14 There are also diffraction peaks at 14 and it is further preferred that these peaks are secondary diffraction Peak, where 2 ⁇ value error range is ⁇ 0.2.
- the crystalline form D of ginsenoside C-K has an XRPD pattern substantially as shown in Figure 1.
- the crystalline form D of the ginsenoside C-K has an endothermic peak near 154 ⁇ 5 °C in the DSC pattern.
- a method for preparing ginsenoside CK Form D comprising: (1) dissolving ginsenoside CK in an organic solvent or a mixed solvent of an organic solvent and water, preferably an organic solvent.
- the volume ratio to water is 3:1; (2) water is added dropwise thereto, preferably the volume of water is 1-4 times the volume of the organic solvent in step (1) or the mixed solvent volume of organic solvent and water, (3) stirring Then, it was filtered, and the filter cake was vacuum dried to obtain a ginsenoside CK of the D crystal form.
- the organic solvent is selected from the group consisting of n-propanol and tetrahydrofuran.
- a method of preparing ginsenoside CK Form D comprising: (1) dissolving ginsenoside CK in acetonitrile with water, or dimethyl sulfoxide and nitromethane. In the mixed solvent, (2) slowly evaporating to remove the solvent, or slowly evaporating to remove part of the solvent, followed by filtration; (3) vacuum drying the obtained solid to obtain D Crystalline ginsenoside CK.
- the ginsenoside C-K starting material used may be any form of ginsenoside C-K, including G ginsenoside C-K.
- a crystalline form H of ginsenoside C-K characterized by an XRPD pattern of about 5.53, 6.71, 11.11, 13.36, 14.64 at a 2 ⁇ value (°).
- ⁇ "shot peaks there are ⁇ "shot peaks at 26.60 and 28.22.
- these peaks are the main diffraction peaks, and the 2 ⁇ value error range is ⁇ 0.2.
- the above-mentioned crystalline form H of ginsenoside CK of the present invention has diffraction peaks at 2 ⁇ (.) of 11.82, 12.77, 14.23, 19.12, 20.47, 32.29, 42.29, preferably these peaks are To diffract peaks, the 2 ⁇ value error range is ⁇ 0.2.
- Form H of ginsenoside C-K has an XRPD pattern as shown in Figure 3 .
- the crystalline form H of ginsenoside CK has an endothermic peak at 1 ⁇ 5 °C in the DSC pattern.
- the method of H comprises the following steps: (1) dissolving ginsenoside C-K in a mixed solvent of 1-methyl-2-pyrrolidone and butyl acetate; (2) slowly evaporating a part of the solvent at room temperature to obtain a suspension;
- a method for preparing ginsenoside CK Form H comprising: (1) placing ginsenoside CK in acetone, heating and stirring the resulting suspension, most preferably Heating to about 50 ° C; (2) Filtration, vacuum drying of the obtained filter cake to obtain H crystal type ginsenoside CK.
- a method for preparing ginsenoside C-K Form H comprising: (1) dissolving ginsenoside C-K in an organic solvent;
- H-form ginsenoside C-K wherein the organic solvent is selected from the group consisting of acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, and a mixture thereof.
- the ginsenoside C-K used may be any form of ginsenoside C-K, including G ginsenoside C-K.
- the present invention also provides thermal stability data for Form D, Form H and Form G, indicating that the two new forms are more stable than Form G.
- Example 1 is an X-ray powder diffraction pattern of D-form ginsenoside C-K obtained in Example 1;
- FIG. 2 is a DSC chart of the D crystalline ginsenoside CK obtained in Example 1.
- FIG. 3 is a simulated X-ray of the D crystalline ginsenoside CK single crystal obtained in Example 1. Powder diffraction pattern;
- FIG. 4 is an X-ray powder diffraction pattern of the D crystalline product obtained in Example 2;
- FIG. 5 is an X-ray powder diffraction pattern of the H crystalline ginsenoside CK obtained in Example 4;
- the X-ray powder diffraction pattern is the same as that of Figure 5;
- Figure 6 is a DSC spectrum of the H-form ginsenoside C-K obtained in Example 4; the DSC pattern of the H crystal form of Example 5 is identical to Figure 6;
- Figure 7 is an X-ray powder diffraction pattern of the H crystal form obtained in Example 6;
- the crystal form of the raw materials used in the examples are all G crystal forms (obtained according to the method described in the above Document 1).
- ginsenoside CK Take 6g of ginsenoside CK in a container, add 10ml of water and 30ml of positive The alcohol was stirred and dissolved, and 80 ml of water was added dropwise thereto, and the mixture was filtered. The filter cake was washed twice with 40 ml of water and dried under vacuum at room temperature to obtain D-form ginsenoside CK, and its XRPD pattern is shown in Fig. 4.
- ginsenoside CK 3 g was placed in a container, 90 ml of nitromethane and 10 ml of dimethyl sulfoxide were added thereto, and the solvent was stirred, and some of the solvent was slowly evaporated, filtered, and the filter cake was washed twice with 40 ml of water, and dried under vacuum at room temperature to obtain D. Crystal ginsenoside CK.
- ginsenoside C-K 2 g was placed in a container, and 20 ml of acetone was added thereto to raise the temperature to 50 ° C to form a suspension, which was stirred for 72 hours, filtered, and the filter cake was vacuum dried to obtain H crystal type ginsenoside C-K.
- ginsenoside CK 0. 7g ginsenoside CK was placed in a container, and 15 ml of ethyl acetate was added thereto. 45 ml of acetone, the mixture was heated to 45 ° C, stirred and dissolved, cooled to 4 ° C to obtain a solid, filtered, and the filter cake was vacuum dried to obtain a H crystal type ginsenoside CK.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1941MUN2014 IN2014MN01941A (zh) | 2012-04-01 | 2013-04-01 | |
EP13772541.2A EP2835377B1 (en) | 2012-04-01 | 2013-04-01 | New crystal form h of ginsenoside c-k and method for preparing same |
JP2015502084A JP2015511608A (ja) | 2012-04-01 | 2013-04-01 | ジンセノシドc−kの2つの結晶形およびその製造方法 |
US14/389,345 US9643992B2 (en) | 2012-04-01 | 2013-04-01 | Two crystal forms of ginsenoside C-K and method for preparing same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210093293.3 | 2012-04-01 | ||
CN201210093293.3A CN103360450B (zh) | 2012-04-01 | 2012-04-01 | 人参皂苷c-k的两种晶型及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013149571A1 true WO2013149571A1 (zh) | 2013-10-10 |
Family
ID=49299992
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2013/073562 WO2013149571A1 (zh) | 2012-04-01 | 2013-04-01 | 人参皂苷c-k的两种晶型及其制备方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US9643992B2 (zh) |
EP (1) | EP2835377B1 (zh) |
JP (1) | JP2015511608A (zh) |
CN (2) | CN105949264A (zh) |
IN (1) | IN2014MN01941A (zh) |
WO (1) | WO2013149571A1 (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1417345A (zh) * | 2001-11-06 | 2003-05-14 | 中国科学院大连化学物理研究所 | 用酶水解人参皂甙制备20-β-D-吡喃葡萄糖基原人参二醇 |
CN1465694A (zh) * | 2002-06-20 | 2004-01-07 | 中国科学院大连化学物理研究所 | 一种黑曲霉及用其酵解人参皂甙制备稀有低极性人参皂甙的方法 |
CN101921304A (zh) * | 2009-06-17 | 2010-12-22 | 浙江海正药业股份有限公司 | 一种运用大孔树脂纯化人参皂甙compound-K的方法 |
CN102251009A (zh) * | 2011-06-09 | 2011-11-23 | 华侨大学 | 一种稀有人参皂甙ih-901结晶的简易生产方法 |
CN103087138A (zh) * | 2013-01-10 | 2013-05-08 | 天津大学 | 一种人参皂苷c-k一水合物晶体及制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2396079A1 (en) * | 2000-01-07 | 2001-07-19 | Transform Pharmaceuticals, Inc. | High-throughput formation, identification, and analysis of diverse solid-forms |
CN100487131C (zh) * | 2004-04-27 | 2009-05-13 | 复旦大学 | 一种制备人参皂甙Compound-K的方法 |
CN101139562B (zh) | 2007-07-02 | 2010-06-09 | 昆明诺唯金参生物工程有限责任公司 | 一种链霉菌发酵三七皂苷制备稀有人参皂苷Compound K的方法 |
-
2012
- 2012-04-01 CN CN201610297739.2A patent/CN105949264A/zh active Pending
- 2012-04-01 CN CN201210093293.3A patent/CN103360450B/zh active Active
-
2013
- 2013-04-01 EP EP13772541.2A patent/EP2835377B1/en not_active Not-in-force
- 2013-04-01 WO PCT/CN2013/073562 patent/WO2013149571A1/zh active Application Filing
- 2013-04-01 IN IN1941MUN2014 patent/IN2014MN01941A/en unknown
- 2013-04-01 US US14/389,345 patent/US9643992B2/en active Active
- 2013-04-01 JP JP2015502084A patent/JP2015511608A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1417345A (zh) * | 2001-11-06 | 2003-05-14 | 中国科学院大连化学物理研究所 | 用酶水解人参皂甙制备20-β-D-吡喃葡萄糖基原人参二醇 |
CN1465694A (zh) * | 2002-06-20 | 2004-01-07 | 中国科学院大连化学物理研究所 | 一种黑曲霉及用其酵解人参皂甙制备稀有低极性人参皂甙的方法 |
CN101921304A (zh) * | 2009-06-17 | 2010-12-22 | 浙江海正药业股份有限公司 | 一种运用大孔树脂纯化人参皂甙compound-K的方法 |
CN102251009A (zh) * | 2011-06-09 | 2011-11-23 | 华侨大学 | 一种稀有人参皂甙ih-901结晶的简易生产方法 |
CN103087138A (zh) * | 2013-01-10 | 2013-05-08 | 天津大学 | 一种人参皂苷c-k一水合物晶体及制备方法 |
Non-Patent Citations (1)
Title |
---|
"Studies on the preparation, crystal structure and bioactivity of ginsenoside compound K", JOURNAL OF ASAN NATURAL PRODUCTS RESEARCH, vol. 8, no. 6, 2006, pages 519 - 527 |
Also Published As
Publication number | Publication date |
---|---|
CN105949264A (zh) | 2016-09-21 |
EP2835377A1 (en) | 2015-02-11 |
US20150057440A1 (en) | 2015-02-26 |
US9643992B2 (en) | 2017-05-09 |
JP2015511608A (ja) | 2015-04-20 |
IN2014MN01941A (zh) | 2015-07-10 |
EP2835377B1 (en) | 2018-12-05 |
CN103360450B (zh) | 2016-05-11 |
CN103360450A (zh) | 2013-10-23 |
EP2835377A4 (en) | 2016-03-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2015145415A2 (en) | Ibrutinib solid forms and production process therefor | |
WO2016165677A1 (en) | New forms of ixazomib citrate | |
WO2016131431A1 (en) | Solid forms of empagliflozin | |
KR20170057441A (ko) | Jak 억제제의 바이설페이트의 결정형 및 이의 제조방법 | |
KR102522895B1 (ko) | Jak 키나아제 억제제 바이설페이트의 결정형 및 이의 제조방법 | |
CN106543072A (zh) | 匹莫范色林化合物 | |
WO2010129636A2 (en) | Lenalidomide polymorph | |
CN102311382B (zh) | 罗氟司特的晶态及其制备方法 | |
CN103755723B (zh) | 一种利福平i晶型的制备方法 | |
CN102675395B (zh) | 醋酸乌利司他的多晶型及其制备方法 | |
WO2015081566A1 (zh) | 曲美替尼及其溶剂化物的晶型、其制备方法、含有它们的药物组合物及其用途 | |
CN104861014A (zh) | 一种盐酸表阿霉素结晶的制备方法 | |
CN102558275A (zh) | α型多晶型醋酸阿比特龙结晶、其制备方法、用途和药物组合物 | |
WO2014127686A1 (zh) | 3,3',5,5'-四异丙基-4,4'-二联苯酚的新晶型及其制备方法 | |
WO2014036865A1 (zh) | 芬戈莫德粘酸盐及其晶体的制备方法和用途 | |
CN104418857A (zh) | 无定型利格列汀及其制备方法 | |
WO2014195977A2 (en) | Novel polymorphs of vismodegib | |
WO2013149571A1 (zh) | 人参皂苷c-k的两种晶型及其制备方法 | |
JP2016533361A (ja) | ピラゾロピリジン化合物の固体形態 | |
WO2017177781A1 (zh) | Ahu377的晶型及其制备方法与用途 | |
CN102321141B (zh) | 一种17α-乙酰氧基-11β-(4-N,N-二甲氨基苯基)-19-去甲孕甾-4,9-二烯-3,20-二酮的无定形物及其制备方法 | |
RU2018129465A (ru) | Винорелбина монотартрат и его фармацевтическое применение | |
CN106146498A (zh) | 一种新的利格列汀化合物 | |
EP3004104A1 (en) | Crystalline form of n,n-dicyclopropyl-4-(1,5-dimethyl-1 h-pyrazol-3-ylamino)-6-ethyl-1 -methyl-1,6-dihyrdroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide for the treatment of myeloproliferative disorders | |
CN108727417B (zh) | 多环化合物钠盐及其多晶型、制备方法及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13772541 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2015502084 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14389345 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013772541 Country of ref document: EP |