WO2009049439A1 - Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers - Google Patents
Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers Download PDFInfo
- Publication number
- WO2009049439A1 WO2009049439A1 PCT/CN2007/002874 CN2007002874W WO2009049439A1 WO 2009049439 A1 WO2009049439 A1 WO 2009049439A1 CN 2007002874 W CN2007002874 W CN 2007002874W WO 2009049439 A1 WO2009049439 A1 WO 2009049439A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- snow
- cholestyramine
- preparation
- medicament
- extract
- Prior art date
Links
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Definitions
- the present invention relates to a process for the preparation of a medicinal ingredient, gentiocin, and a novel use in the preparation of a medicament for the treatment of cancer.
- Snow bilirubin is a mixture of snow bilirubin and cedar. It was first isolated from the roots of Hemsleya amalils Diels by Chen Weixin et al. (Acta Chem., 1975, 33 (1), 5), and the gentian was identified as a 19-carbon-93-methyl group. -10 ⁇ -3 ⁇ -hydrogen-2 ⁇ , 3 ⁇ , 16 ⁇ , 20, 25-pentahydroxy ⁇ 5 lanosterene-11, 20-dione-25-acetate (Il a) ie cucurbitacin F ( Ic ) 23.
- Chinese patent application CN01102620.0 discloses a "nano Xuedansu preparation medicine and a preparation method thereof", which is prepared by using nano-snow cholestyr as a raw material, and is prepared into a new pharmaceutical preparation, and the particle fineness reaches 1200- 1500 mesh, particle size of 0.1-200 nm, most of which are less than 100 nm, and have new physical properties. It is made by steps of microwave extraction, concentration under reduced pressure, and supersonic jet technique spray drying.
- CN03159197.3 discloses a "snow cholestidine dropping pill and a preparation method thereof", characterized in that 1 part by weight of ultrafinely pulverized gentian fine powder is added to 1 to 10 parts by weight of a molten substrate. In the middle, fully mix, the dropping method is condensed into a pellet in a coolant, and the coolant is removed, which is obtained.
- Chinese patent application confirmation CN02134164.8 discloses a "snow cholenoid derivative and its preparation method and application as an antibacterial agent", and provides a snow cholestyr derivative different from the prior art, and a preparation method thereof, An antibacterial agent for active ingredients.
- Another object of the present invention is to provide a use of snow cholestyramine for the preparation of a medicament for treating cancer.
- the preparation method of the snow cholestyramine according to the present invention comprises the following steps: 1. taking the roots of the genus Snowy genus, pulverizing, using 18-26 weight times of acetone as a solvent, extracting by using a percolation method, and extracting the solution at 60- Recovered in a 75 ° C water bath, that is, an extract;
- the crude product is heated and dissolved in a water bath with methanol or ethanol, filtered, placed at room temperature, and recrystallized to obtain a columnar crystal, that is, a snow bilirubin having a purity of 98% or more.
- the snow genus plant described in the first step is a Luopan bottom, a long fruit snow urchin, an Emei snow stalk, and the like.
- the impurities are eluted with pure chloroform, and then eluted with a gradient of chloroform:methanol; the purity of the snow bilirubin obtained in the third step is more than 98% by high performance liquid chromatography (HPLC), and the melting point is 226-228 ° C.
- HPLC high performance liquid chromatography
- Ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry were identified as snow biliary. Its structural formula is:
- the invention relates to the application of snow cholestyramine in the preparation of a medicament for treating liver cancer.
- the invention relates to the application of snow cholestyramine in the preparation of a medicament for treating lung cancer.
- the invention relates to the application of snow cholestyramine in the preparation of a medicament for treating gastric cancer.
- the invention relates to the application of snow cholestyramine in the preparation of a medicament for treating laryngeal cancer.
- the invention relates to the use of snow cholestyramine in the preparation of a medicament for treating leukemia.
- the invention relates to the use of snow cholestyramine in the preparation of a medicament for treating prostate cancer.
- the monomeric component of the snow cholestyramine has been tested for anti-cancer activity in vitro and in vivo, confirming that the product has an inhibitory or killing effect on human solid cancer cells in vitro, and the Ic50 (ug ml) for growth of human lung cancer cell A549 is 1.50, and cisplatin Ic50 1.60 is basically the same.
- the anti-cancer test in mice is related to the type of preparation and the route of administration. In contrast, oral administration is slightly worse than injection, and the inhibition rate of the emulsion by intravenous injection is up to 59%.
- A549 human lung cancer cell line A549 human lung cancer cell line
- Kunming mice were used to inoculate H22 liver cancer and mouse Lewis lung cancer respectively. Three preparations, suspension, emulsion and lyophilized preparation were used, intragastric administration, intraperitoneal injection, intravenous injection, high dose, medium and low dose. The three therapeutic doses were compared with the positive control to calculate the anti-tumor inhibition rate.
- the experimental results are shown in the following tables:
- gentian A is suitable for various cancers, including liver cancer, lung cancer, and gastric cancer.
- Laryngeal cancer, prostate cancer, leukemia and the like have significant inhibitory or killing effects, and the intensity of the action is related to the dosage form, administration route and dosage.
- Figure 1 is a high performance liquid phase analysis map.
- Example 1 Take 5 kg of Luohu bottom in Qiaojia County, Yunnan province, pulverize it into medium powder, and put it into a seepage container. After soaking for 24 hours at 15-25 ° C, add 24 times acetone, according to Chinese Pharmacopoeia.
- Percolation recovery of percolate, extract the same amount of silica gel, dry at 50-70 ° C, onto a silica gel column, gradient elution with chloroform:methanol as eluent, collecting at a concentration of 3-5% methanol After the eluent is recovered, the crude product can be obtained, and the product is recrystallized several times with methanol to obtain a column crystal, melting point 226-228 ° C, and the purity of HPLC analysis is 98.98%. See Figure 1. Confirmed as snow bilirubin by ultraviolet, infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry.
- a suspension, an emulsion, a lyophilized preparation, a nano lyophilizate, a tablet, a pill, a dropping pill, a capsule, a controlled release agent, a microcapsule, Tablets, liposomes and the like for the treatment of liver cancer, lung cancer, stomach cancer, laryngeal cancer, prostate cancer and leukemia.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/601,303 US20100168451A1 (en) | 2007-10-19 | 2007-10-19 | Preparative method of dihydrocucurbitacin f-25-o-acetate and the use thereof in the manufacture of medicaments for treating cancers |
PCT/CN2007/002874 WO2009049439A1 (fr) | 2007-10-19 | 2007-10-19 | Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2007/002874 WO2009049439A1 (fr) | 2007-10-19 | 2007-10-19 | Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009049439A1 true WO2009049439A1 (fr) | 2009-04-23 |
Family
ID=40566965
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2007/002874 WO2009049439A1 (fr) | 2007-10-19 | 2007-10-19 | Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers |
Country Status (2)
Country | Link |
---|---|
US (1) | US20100168451A1 (zh) |
WO (1) | WO2009049439A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109557251A (zh) * | 2018-04-03 | 2019-04-02 | 四川辅正药业股份有限公司 | 峨眉雪胆质量检验方法 |
CN115336532A (zh) * | 2022-07-13 | 2022-11-15 | 云南农业大学 | 一种可抑制雪胆块茎愈伤组织褐变的诱导方法 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111693596A (zh) * | 2020-06-05 | 2020-09-22 | 清华大学 | 一种建筑物中气态污染物的非靶向测试方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1883484A (zh) * | 2006-05-30 | 2006-12-27 | 沈阳药科大学 | 葫芦素药理新用途 |
CN1944453A (zh) * | 2006-07-21 | 2007-04-11 | 云南明镜制药有限公司 | 一种提取雪胆素的方法 |
CN101074255A (zh) * | 2006-05-19 | 2007-11-21 | 樊献俄 | 雪胆甲素的制备方法和在制备治疗癌症的药物中的应用 |
-
2007
- 2007-10-19 WO PCT/CN2007/002874 patent/WO2009049439A1/zh active Application Filing
- 2007-10-19 US US12/601,303 patent/US20100168451A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101074255A (zh) * | 2006-05-19 | 2007-11-21 | 樊献俄 | 雪胆甲素的制备方法和在制备治疗癌症的药物中的应用 |
CN1883484A (zh) * | 2006-05-30 | 2006-12-27 | 沈阳药科大学 | 葫芦素药理新用途 |
CN1944453A (zh) * | 2006-07-21 | 2007-04-11 | 云南明镜制药有限公司 | 一种提取雪胆素的方法 |
Non-Patent Citations (6)
Title |
---|
ATTARD E. ET AL.: "Cytotoxicity of cucurbitacin E extracted from Ecballium elaterium in vitro", JOURNAL OF NATURAL REMEDIES, vol. 4, no. 2, 2004, XP009097469 * |
CHEN JIANCHAO ET AL.: "Chemical Constituents from the Tubers Hemsleya delavayi.", ACTA CHIMICA SINICA (CHINESE)., vol. 65, no. 16, August 2007 (2007-08-01), pages 1679 - 1684 * |
DATABASE CA [online] 2005, "false", Database accession no. 142:253999 * |
SHI YAQIN ET AL.: "Studies on the Chemical Constituents of Emeixuedan (Hemsleya emeiensis).", ZHONGCAOYAO (CHINESE), vol. 26, no. 12, 1995, pages 619 - 621 * |
WU P. ET AL.: "Cytotoxic and Anti-HIV Principles from the Rhizomes of Begonia nantoensis.", CHEM. PHARM. BULL., vol. 52, no. 3, 2004, pages 345 - 349 * |
YANG QUNFANG ET AL.: "Progression on study of Radix Hemsleyae and preparation thereof.", CHINA PHARMACEUTICALS (CHINESE), vol. 12, no. 9, 2003, pages 76 - 77 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109557251A (zh) * | 2018-04-03 | 2019-04-02 | 四川辅正药业股份有限公司 | 峨眉雪胆质量检验方法 |
CN115336532A (zh) * | 2022-07-13 | 2022-11-15 | 云南农业大学 | 一种可抑制雪胆块茎愈伤组织褐变的诱导方法 |
Also Published As
Publication number | Publication date |
---|---|
US20100168451A1 (en) | 2010-07-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113563172B (zh) | 一种薁类化合物及其制备方法与应用 | |
CN100463916C (zh) | 雪胆甲素的制备方法和在制备治疗癌症的药物中的应用 | |
WO2006063515A1 (fr) | Utilisation de radix sanguisorbae et de son extrait pour la preparation d’un medicament visant a accroitre la numeration erythrocytaire et le taux d’hemoglobine | |
CN1210289C (zh) | 两头尖提取物的制备工艺和用途 | |
CN102078443B (zh) | 一种药物组合物及其用途和制剂 | |
WO2008145064A1 (fr) | Procédé d'obtention d'un extrait contenant du séquoyitol à partir d'une espèce du genre trifolium, de soja et de ginkgo biloba, et utilisation de celui-ci | |
CN102342945B (zh) | 救必应皂苷化合物用于制备抗炎镇痛药物 | |
CN111454317B (zh) | 具有抗炎活性的人参二醇型三萜皂苷、三七叶提取物、药物组合物和化妆品组合物 | |
CN101422466B (zh) | 雪胆甲素在制备治疗癌症的药物中的应用 | |
WO2009049439A1 (fr) | Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers | |
CN101612183B (zh) | 一种乌骨藤皂苷提取物、药物组合物、制备方法及其应用 | |
CN111925404B (zh) | 一种木脂素类化合物的制备方法与应用 | |
CN113018347B (zh) | 一种中药提取物纳米粒及其制备方法和应用 | |
CN112062738B (zh) | 暗绿蒿醇a-b及其药物组合物和其制备方法与应用 | |
CN114573456A (zh) | 一种贝壳杉烷型二萜化合物及其制备方法和应用 | |
CN103027932A (zh) | 一种香加皮抗肿瘤有效组分提取物及其制法和用途 | |
CN104383547B (zh) | 天山雪莲提取物磷脂复合物、口腔崩解片及其制备方法 | |
CN101062045B (zh) | 一类三萜皂苷化合物在制备肿瘤药物中的用途 | |
CN114507265B (zh) | 一种植物药百两金中的新单萜苷化合物及其提取分离方法和应用 | |
CN100546602C (zh) | 抗肿瘤复方虎杖根、藤梨根、水杨梅根制剂及其制备方法和应用 | |
CN115710300B (zh) | 一种从中华雪胆中提取的葫芦烷型五环三萜类化合物的制备方法及其应用 | |
CN113968780B (zh) | 白木香素a和b及其制备方法与其药物组合物和应用 | |
CN109248169B (zh) | 一种三萜皂苷化合物在制备治疗三阴性乳腺癌产品中的应用 | |
CN101428029A (zh) | 雪胆甲素在制备治疗癌症的药物中的应用 | |
CN101766633A (zh) | 雪胆甲素在制备治疗癌症的药物中的应用 |
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: 07816488 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12601303 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 29.07.2010) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 07816488 Country of ref document: EP Kind code of ref document: A1 |