WO2004099167A1 - Procede de preparation de docetaxel trihydrate - Google Patents
Procede de preparation de docetaxel trihydrate Download PDFInfo
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- WO2004099167A1 WO2004099167A1 PCT/CN2004/000343 CN2004000343W WO2004099167A1 WO 2004099167 A1 WO2004099167 A1 WO 2004099167A1 CN 2004000343 W CN2004000343 W CN 2004000343W WO 2004099167 A1 WO2004099167 A1 WO 2004099167A1
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- WIPO (PCT)
- Prior art keywords
- acetone
- docetaxel
- trihydrate
- water
- certain amount
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- 229950010692 docetaxel trihydrate Drugs 0.000 title claims abstract description 7
- XCDIRYDKECHIPE-QHEQPUDQSA-N docetaxel trihydrate Chemical compound O.O.O.O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 XCDIRYDKECHIPE-QHEQPUDQSA-N 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims abstract description 17
- 150000004684 trihydrates Chemical class 0.000 claims description 10
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 230000001133 acceleration Effects 0.000 claims description 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229960005295 docetaxel anhydrous Drugs 0.000 claims description 3
- 238000005054 agglomeration Methods 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 239000012141 concentrate Substances 0.000 claims 1
- 229960003668 docetaxel Drugs 0.000 abstract description 14
- 239000000203 mixture Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229940123237 Taxane Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000031852 maintenance of location in cell Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the invention belongs to the technical field of pharmaceutical synthesis. Specifically, it relates to a method for preparing docetaxel trihydrate. Background technique:
- Docetaxel is a new anti-cancer drug developed abroad in recent years.
- docetaxel As a representative of the second generation of taxane antitumor drugs, docetaxel (Docetaxel) with its increased water solubility and excellent anticancer broad spectrum Increasingly people's attention.
- Docetaxel has anticancer activity against a variety of tumors, including breast cancer, non-small cell lung cancer, and other malignancies (prostate cancer, esophageal cancer, and head and neck malignancies). It is one of the most effective single drugs for treating metastatic breast cancer.
- Docetaxel can promote tubulin assembly into microtubules and inhibit their disaggregation. It also has better bioavailability, higher intracellular concentration, and longer intracellular retention time.
- Docetaxel is the first semi-synthetic taxane and has been marketed in Europe and the United States. According to Chinese patent 95193984.X, docetaxel trihydrate is more stable than its anhydrous substance. Therefore, one step of crystallization reaction is added in the production of the drug substance.
- the reaction solvents are ethanol and water.
- the inventors found that when ethanol is used, not only the concentration time is long, the temperature of the water bath is high, but also the particles generated by crystallization are very small, and it takes a long time to collect the product by suction filtration. Summary of the invention:
- the technical problem to be solved by the present invention is to overcome the shortcomings of the above method and design an improved preparation method.
- the invention provides a method for preparing docetaxel trihydrate.
- the method is to place docetaxel anhydrous (HPLC purity> 99.5%) at a temperature of 10 ⁇ 39 ° C and put 8 ⁇ 12 parts by weight. It is fully dissolved in several acetone, and then concentrated under reduced pressure to an oily substance under the same temperature condition, and then a certain amount of acetone is added to fully dissolve the oily substance, and then concentrated again to an oily substance, and then a certain amount of acetone (fully dissolved Then, add a certain amount of pure water, which lasts about 10 ⁇ 60min.
- docetaxel anhydrous HPLC purity> 99.5%
- the present invention uses a mixture of acetone and water to prepare a trihydrate, and has the following advantages:
- the operating cycle is short, because the larger particles are formed during crystallization of acetone and water, which greatly reduces the suction filtration time; the smaller particles are formed during crystallization of ethanol and water, and the filtration time is 3 hours; the particles formed during crystallization of acetone and water Larger, the filtration time is 1 hour.
- the operating temperature is low (below 40 ° C). Due to the poor stability of docetaxel at higher temperature, the purity of docetaxel can be avoided during the refining process.
- reaction temperature when using ethanol is 40 ⁇ 60 ° C, but if acetone is used, the reaction can be carried out at 39 ° C, so that the operating temperature of the reaction is lowered and the operation is easier.
- the product prepared by the method of the present invention is confirmed by thermogravimetric analysis and differential thermal analysis to confirm that the product obtained by the new process is trihydrate.
- the mass loss at 55 ⁇ 115 ° C is 6.8%, which is consistent with the reaction containing three crystal waters.
- the product obtained by the method of the invention has good stability, and has been confirmed to be consistent with the patent literature.
- the stability test reaction conditions are: 40 ° C, relative humidity 75%, 12 months, during which no change in trihydrate detailed description:
- a mixture of acetone and water is used to prepare a trihydrate.
- the operation cycle is short, the time of light exposure is reduced, and the purity is avoided. At the same time, its operating temperature is low, which avoids the decrease in the purity of docetaxel during the refining process.
Description
多烯紫杉醇三水化合物的制备方法 技术领域：
本发明属于药物合成技术领域。具体涉及多烯紫杉醇三水合物的 制备方法。 背景技术：
多烯紫杉醇化学名： 5β,20-环氧 -1β,2α,4α,7β， 10β，13α-六羟基-紫 杉 -11-烯 -9-酮 -4-乙酸酯 -2_苯甲酸酯- 13-[ (2，R，3，S)-N-叔丁氧羰基 -3，- 苯 基 异 丝 氨 酸 酯 ： | · 三 水 合 物 (2'R,3'S)-N-carboxy-3-phenylisoserine, N-ieri-butyl ester, 13 -ester with 5P,20-epoxy- 1，2α，4，7β, 10β， 13 -hexahydrox tax- 11 -en-9-one 4-acetate 2-benzoate, trihydrate
多烯紫杉醇是近年来由国外开发的一种抗癌新药，作为第二代紫 杉垸类抗肿瘤药物的代表， 多烯紫杉醇（Docetaxel) 以其增加的水溶 性及优异的抗癌广谱性日益受到人们的关注。多烯紫杉醇对于多种肿 瘤都具有抗癌活性， 其中包括乳腺癌、非小细胞肺癌和其它恶性肿瘤 (前列腺癌、 食管癌以及头颈部恶性肿瘤等）。 是治疗转移性乳腺癌 最有效的单药之一。 尤其显著的是， 在 II临床研究中， 于接受过化 疗的患者 （其中包括蒽环类原发耐药者）， 多烯紫杉醇单药化疗 （通 常 100mg/m2， 静滴， 每 3周一次） 的总有效率为 47%。 几组研究报 告表明有效率为 32%— 58%， 其中一组报告 CR (完全有效） 为 4°/。。 对于晚期非小细胞肺癌， 无论是初治者， 还是经过顺铂化疗后的进展 者， 同样显示出独特的抗癌活性。
多烯紫杉醇可促进微管蛋白装配成微管并抑制其解聚， 还具有较 好的生物利用度， 更高的细胞内浓度， 更长的细胞内潴留时间。
多烯紫杉醇是第一个半合成的紫杉类药物， 己在欧美国家上市。 据中国专利 95193984.X报道， 多烯紫杉醇三水物比其无水物稳 定，故在生产原料药时增加一步结晶反应，反应溶剂选择为乙醇和水。 但在实验过程中本发明人发现，使用乙醇时不但浓縮时间长水浴温度 高， 而且结晶生成的颗粒很小， 抽滤收集产品需很长时间。
发明内容：
本发明所要解决的技术问题在于克服上述方法的不足之处，设计 一种改进的制备方法。
本发明提供了一种多烯紫杉醇三水合物的制备方法， 该方法是 将多烯紫杉醇无水物（HPLC纯度〉 99.5%)在 10~39°C的温度下， 放入 8〜12重量份数的丙酮中充分溶解， 然后在相同温度条件下减压 浓缩至油状物， 再加入一定数量的丙酮将油状物充分溶解， 并再一次 浓缩至油状物， 之后再加入一定数量的丙酮（充分溶解， 然后再加一 定数量的纯净水， 历时约 10~60min， 在滴加的过程中注意控制滴加 速度， 以免形成结块， 并再 0Ό以下冷却 2~5小时， 然后抽滤， 之后 滤饼用丙酮： 水 （1 : 1~1 : 5 ) 的混合溶液洗涤。 然后用五氧化二磷 真空干燥， 至恒重， 得到三水合物。
本发明采用丙酮和水的混合物制备三水合物， 具有下列优点：
1、 操作周期短， 因为丙酮和水结晶时形成颗粒较大， 使抽滤时间大 大缩短； 乙醇和水结晶时形成的颗粒较小， 抽滤时间为 3小时； 丙酮 和水结晶时形成的颗粒较大， 抽滤时间为 1小时。
在实验中发现， 多烯紫杉醇曝光 10小时， 纯度下降 0.2%， 它对 光有一定的敏感性。 抽滤时间的缩短， 减少了光暴露的时间， 避免纯 度下降。
2、操作温度较低（40°C以下）， 由于多烯紫杉醇在温度较高的下稳定 性差， 避免多烯紫杉醇在精制过程中纯度下降。
专利文献提到用乙醇时的反应温度为 40〜60°C， 但如果用丙酮， 则可以在 39°C进行反应， 使反应的操作温度降低， 更易操作。
采用本发明方法制得的产品采用热解重量分析和差热分析证实 按新工艺得到产品证实是三水物。 55〜115°C下的质量损失为 6.8%， 这与反应物含有三个结晶水相一致。
本发明方法得的产品稳定性好， 经证实与专利文献一致， 稳定性 试验反应条件： 40°C下， 相对湿度 75%， 12个月， 在此期间三水物 没有任何改变
具体实施方式：
实例 1
将 87克多烯紫杉醇无水物 （HPLC纯度〉 99.5%) 在 20°C的温度 下， 放入 1044ml丙酮中充分溶解， 然后在 40°C条件下减压浓缩至油 状物，再加入 348ml丙酮将油状物充分溶解，并再一次浓縮至油状物， 之后再加入 1740ml丙酮充分溶解， 然后在保温 15°C的条件下缓慢滴 加纯净水 2610ml，历时约 15min，在滴加的过程中注意控制滴加速度， 以免形成结块， 并再 0°C冷却 2小时， 然后抽滤， 之后滤饼用丙酮： 水 =1 : 1.5的混合溶液 200ml洗涤三次。 然后用五氧化二磷真空干燥 5个小时， 至恒重， 得到三水物 85克， 水分 6.43% 实例 2
将 200克多烯紫杉醇无水物（HPLC纯度〉 99.5%)在 40°C的温度 下， 放入 2850ml丙酮中充分溶解， 然后在 40°C条件下减压浓缩至油 状物，再加入 950ml丙酮将油状物充分溶解，并再一次浓縮至油状物， 之后再加入 4750ml丙酮充分溶解， 然后在保温 15°C的条件下缓慢滴 加纯净水 9975ml，历时约 50min，在滴加的过程中注意控制滴加速度， 以免形成结块， 并再 0°C冷却 4小时， 然后抽滤， 之后滤饼用丙酮： 水 =1 : 3.5的混合溶液 580ml洗涤三次。 然后用五氧化二磷真空干燥 6.5个小时， 至恒重， 得到三水物 196.5克， 水分 6.2%。 工业实用性：
本发明采用丙酮和水的混合物制备三水合物， 其操作周期短， 减 少了光暴露的时间， 避免纯度下降。 同时其操作温度较低， 避免了多 烯紫杉醇在精制过程中纯度的下降。
Claims
1、 一种多烯紫杉醇三水合物的制备方法， 其特征在于该方法是 将多烯紫杉醇无水物 HPLC 纯度〉 99.5%在 10~39°C的温度下， 放入 8-12 重量份数的丙酮中充分溶解， 然后在相同温度条件下减压浓缩 至油状物， 再加入一定数量的丙酮将油状物充分溶解， 并再一次浓缩 至油状物， 之后再加入一定数量的丙酮， 充分溶解， 然后再加一定数 量的纯净水， 历时约 10~60min， 在滴加的过程中注意控制滴加速度， 以免形成结块， 并再 0°C以下冷却 2〜5小时， 然后抽滤， 之后滤饼用 丙酮： 水， 1-1： 5的混合溶液洗涤， 然后用五氧化二磷真空干燥， 至恒重， 得到三水合物。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/555,889 US7332617B2 (en) | 2003-05-08 | 2004-04-13 | Process for the preparation of docetaxel trihydrate |
| EP04726952A EP1623982B8 (en) | 2003-05-08 | 2004-04-13 | The process for the preparation of docetaxel trihydrate |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031168159A CN1268619C (zh) | 2003-05-08 | 2003-05-08 | 多烯紫杉醇三水化合物的制备方法 |
| CN03116815.9 | 2003-05-08 |
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| Publication Number | Publication Date |
|---|---|
| WO2004099167A1 true WO2004099167A1 (fr) | 2004-11-18 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2004/000343 WO2004099167A1 (fr) | 2003-05-08 | 2004-04-13 | Procede de preparation de docetaxel trihydrate |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7332617B2 (zh) |
| EP (1) | EP1623982B8 (zh) |
| CN (1) | CN1268619C (zh) |
| AR (1) | AR041363A1 (zh) |
| WO (1) | WO2004099167A1 (zh) |
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| WO2007078050A2 (en) | 2006-01-02 | 2007-07-12 | Samyang Genex Corporation | Method for preparation of amorphous, anhydrous crystalline, or hydrated crystalline docetaxel |
| WO2009006590A3 (en) * | 2007-07-04 | 2009-03-12 | Reddys Lab Ltd Dr | Docetaxel process and polymorphs |
| KR100965867B1 (ko) * | 2009-06-23 | 2010-06-24 | 주식회사 삼양제넥스 | 수화결정형 도세탁셀의 제조방법 |
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| US8703982B2 (en) | 2003-03-17 | 2014-04-22 | Phyton Holdings Llc | Purification of taxanes |
| CN101291659A (zh) | 2005-08-31 | 2008-10-22 | 阿布拉科斯生物科学有限公司 | 包含水难溶性药剂和抗微生物剂的组合物 |
| NZ592132A (en) * | 2005-08-31 | 2012-12-21 | Abraxis Bioscience Llc | Composition comprising nanoparticles of docitaxel and a citrate |
| JP2009533330A (ja) * | 2006-03-21 | 2009-09-17 | ドクター レディズ ラボラトリーズ リミテッド | ドセタキセルの多形体およびプロセス |
| KR101266549B1 (ko) * | 2006-10-20 | 2013-05-24 | 시노팜 싱가포르 피티이 리미티드 | 결정형 무수 도세탁셀을 제조하는 방법 |
| PL388144A1 (pl) | 2009-05-29 | 2010-12-06 | Przedsiębiorstwo Produkcyjno-Wdrożeniowe Ifotam Spółka Z Ograniczoną Odpowiedzialnością | Solwaty (2R,3S)-3-tert-butoksykarbonylamino-2-hydroksy-3-fenylopropionianu 4-acetoksy-2α-benzoiloksy -5β,20-epoksy-1,7β,10β-trihydroksy-9-okso-taks-11-en-13α-ylu, sposób ich otrzymywania i zastosowanie |
| US8686165B2 (en) * | 2009-11-04 | 2014-04-01 | Emcure Pharmaceuticals Limited | Process for preparation of taxane derivatives |
| US8633240B2 (en) | 2012-06-01 | 2014-01-21 | The University Of Utah Research Foundation | Paclitaxel trihydrates and methods of making thereof |
| CN106674156A (zh) * | 2015-11-09 | 2017-05-17 | 上海贝美医药科技有限公司 | 多西他赛新晶型及其制备方法 |
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| EP0253738A1 (fr) * | 1986-07-17 | 1988-01-20 | Rhone-Poulenc Sante | Dérivés du taxol, leur préparation et les compositions pharmaceutiques qui les contiennent |
| CN1151741A (zh) * | 1994-07-08 | 1997-06-11 | 罗纳-布朗克罗莱尔股份有限公司 | 新型丙酸紫杉烯酯三水合物的制备方法 |
| US5688977A (en) * | 1996-02-29 | 1997-11-18 | Napro Biotherapeutics, Inc. | Method for docetaxel synthesis |
| US6107497A (en) * | 1996-02-29 | 2000-08-22 | Napro Biotherapeutics, Inc. | Intermediate for use in docetaxel synthesis and production method therefor |
| CN1372466A (zh) | 1999-08-31 | 2002-10-02 | 阿文蒂斯药物股份有限公司 | 多西他奇在治疗肝细胞癌中的应用 |
-
2003
- 2003-05-08 CN CNB031168159A patent/CN1268619C/zh not_active Expired - Fee Related
- 2003-09-23 AR ARP030103461A patent/AR041363A1/es unknown
-
2004
- 2004-04-13 EP EP04726952A patent/EP1623982B8/en not_active Expired - Fee Related
- 2004-04-13 WO PCT/CN2004/000343 patent/WO2004099167A1/zh active Application Filing
- 2004-04-13 US US10/555,889 patent/US7332617B2/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0253738A1 (fr) * | 1986-07-17 | 1988-01-20 | Rhone-Poulenc Sante | Dérivés du taxol, leur préparation et les compositions pharmaceutiques qui les contiennent |
| CN1151741A (zh) * | 1994-07-08 | 1997-06-11 | 罗纳-布朗克罗莱尔股份有限公司 | 新型丙酸紫杉烯酯三水合物的制备方法 |
| US5688977A (en) * | 1996-02-29 | 1997-11-18 | Napro Biotherapeutics, Inc. | Method for docetaxel synthesis |
| US6107497A (en) * | 1996-02-29 | 2000-08-22 | Napro Biotherapeutics, Inc. | Intermediate for use in docetaxel synthesis and production method therefor |
| CN1372466A (zh) | 1999-08-31 | 2002-10-02 | 阿文蒂斯药物股份有限公司 | 多西他奇在治疗肝细胞癌中的应用 |
Non-Patent Citations (3)
| Title |
|---|
| MILANESIO, MARCO ET AL.: "Ab Initio Conformational Study of the Phenylisoserine Side Chain of Paclitaxel", J.MED.CHEM., vol. 42, no. 2, 1999, pages 291 - 299, XP003016358 * |
| See also references of EP1623982A4 |
| ZASKE, L. ET AL.: "Docetaxel. Solid state cheracterization by x-ray powder diffraction and thermogravimetry", JOURNAL DE PHYSIQUE IV, vol. 90, 2001, pages 221 - 226, XP008077819 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007078050A2 (en) | 2006-01-02 | 2007-07-12 | Samyang Genex Corporation | Method for preparation of amorphous, anhydrous crystalline, or hydrated crystalline docetaxel |
| WO2007078050A3 (en) * | 2006-01-02 | 2008-01-03 | Samyang Genex Corp | Method for preparation of amorphous, anhydrous crystalline, or hydrated crystalline docetaxel |
| KR100995390B1 (ko) | 2006-01-02 | 2010-11-19 | 주식회사 삼양제넥스 | 무정형, 무수결정형 또는 수화 결정형 도세탁셀의 제조방법 |
| US8163940B2 (en) | 2006-01-02 | 2012-04-24 | Samyang Genex Corporation | Method for preparation of amorphous, anhydrous crystalline or hydrated crystalline docetaxel |
| CN101415697B (zh) * | 2006-01-02 | 2012-10-17 | 株式会社三养吉尼克斯Bio | 制备非晶的多西紫杉醇的方法 |
| WO2009006590A3 (en) * | 2007-07-04 | 2009-03-12 | Reddys Lab Ltd Dr | Docetaxel process and polymorphs |
| KR100965867B1 (ko) * | 2009-06-23 | 2010-06-24 | 주식회사 삼양제넥스 | 수화결정형 도세탁셀의 제조방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1548426A (zh) | 2004-11-24 |
| EP1623982A1 (en) | 2006-02-08 |
| US7332617B2 (en) | 2008-02-19 |
| US20060217436A1 (en) | 2006-09-28 |
| EP1623982B1 (en) | 2012-01-04 |
| EP1623982A4 (en) | 2007-09-05 |
| AR041363A1 (es) | 2005-05-11 |
| CN1268619C (zh) | 2006-08-09 |
| EP1623982B8 (en) | 2012-03-14 |
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