CN100429207C - 二甲氧基多西他赛丙酮化物及其制备方法 - Google Patents
二甲氧基多西他赛丙酮化物及其制备方法 Download PDFInfo
- Publication number
- CN100429207C CN100429207C CNB200480026128XA CN200480026128A CN100429207C CN 100429207 C CN100429207 C CN 100429207C CN B200480026128X A CNB200480026128X A CN B200480026128XA CN 200480026128 A CN200480026128 A CN 200480026128A CN 100429207 C CN100429207 C CN 100429207C
- Authority
- CN
- China
- Prior art keywords
- hydroxyl
- acetone
- dimethoxy
- benzoyloxy
- tert
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 title claims abstract description 74
- 239000012453 solvate Substances 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- -1 dimethoxy docetaxel Chemical compound 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 15
- 229960003668 docetaxel Drugs 0.000 title abstract description 4
- 238000002425 crystallisation Methods 0.000 claims abstract description 9
- 229960003328 benzoyl peroxide Drugs 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- GUHWAFYHWQUCJZ-UHFFFAOYSA-N CC(C)(C)OC(=O)C(C(N)(O)C(O)=O)C1=CC=CC=C1 Chemical compound CC(C)(C)OC(=O)C(C(N)(O)C(O)=O)C1=CC=CC=C1 GUHWAFYHWQUCJZ-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 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 abstract description 2
- ZVAFCKLQJCZGAP-WDEREUQCSA-N (2r,3s)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H]([C@@H](O)C(O)=O)C1=CC=CC=C1 ZVAFCKLQJCZGAP-WDEREUQCSA-N 0.000 abstract 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 239000000047 product Substances 0.000 description 6
- 206010013786 Dry skin Diseases 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 230000006837 decompression Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- GUHWAFYHWQUCJZ-QMTHXVAHSA-N (2r,3s)-2-amino-2-hydroxy-4-[(2-methylpropan-2-yl)oxy]-4-oxo-3-phenylbutanoic acid Chemical compound CC(C)(C)OC(=O)[C@H]([C@@](N)(O)C(O)=O)C1=CC=CC=C1 GUHWAFYHWQUCJZ-QMTHXVAHSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
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
- 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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及二甲氧基多西他赛丙酮化物,即4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯,本发明还涉及通过在水-丙酮中结晶制备该化合物的方法。
Description
本发明涉及二甲氧基多西他赛,即4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的丙酮化物,本发明还涉及其制备方法。
4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯具有显著的抗癌和抗白血病的活性。
根据文献中公开的方法,特别是国际专利申请PCT WO 96/30355或国际专利申请PCT WO 99/25704中公开的方法,可以制备4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯,但是根据这些专利文献中公开的方法制备的化合物不是结晶的,而且对这些化合物也没有进行表征。
申请人发现,从化学观点来看,完全可以对4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的丙酮化物进行表征。
根据本发明,可以通过使4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯从水和丙酮的混合物中结晶、然后减压干燥分离的产物可以获得4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的丙酮化物。
实施本发明的方法,具有显著的优点:
-将4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯溶于丙酮中,
-用水处理得到的溶液,
-向上述溶液中加入产物在丙酮/水混合物中的悬浮液进行种晶,然后再次用水处理,
-分离产生的结晶,然后
-减压干燥。
通常而言,将4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯溶于丙酮中。优选相对于4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的重量(以克表示),丙酮的量为5-20体积份(ml)(最好为10)。
优选种晶的浓度为每升混合物采用60-80g(最好为68g),所述混合物为体积比65/35-75/25、优选约68/32的丙酮/水混合物。沉淀结束时,丙酮/水混合物的体积比为70/30-30/70(最好为45/55)。根据本发明优选的实施方案,整个结晶过程于20±5℃(最好为20℃)进行。
分离4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯丙酮化物结晶,优选通过过滤或离心。干燥在减压下进行,通常为0.5-30kPa,优选0.7kPa,温度为30-60℃,优选40℃。
对产物的干燥进行分析。为此,将4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的丙酮化物样品于70℃以上(70-100℃)进行小心处理,表明随着温度的升高丙酮含量逐渐减少。因此,干燥时,优选的温度为30-60℃,更优选40℃。丙酮含量的均值为7%,这表示接近于丙酮的化学计算量,对于含有一个丙酮分子的溶剂化物而言,该量为6.5%。
用下面的实施例对本发明进行更详细地描述,但是本发明的范围不受其限制。
实施例1
于20±5℃环境温度下,将940ml纯净水加至207g约92%重量的4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基的约2升丙酮溶液中,然后加入2g 4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯在20ml水和20ml丙酮的混合物中的悬浮液进行种晶。将混合物搅拌约10-22小时,用4-5小时加入1.5升纯净水,然后将混合物搅拌60-90分钟,减压过滤悬浮液,用450ml丙酮和550ml纯净水的混合液洗涤滤器上的滤饼,在烘箱中于55℃减压下(0.7kPa)干燥4小时。得到197g 4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯丙酮化物,其中含有0.1%水和7.2%丙酮(溶剂化物化学计算的理论量为6.5%)。
干燥研究
将产物置于烘箱中,随后分别于0.7kPa减压下于60℃干燥18小时,于约80%相对湿度下(160mmHg压力)于60℃干燥3小时和于约80%相对湿度下(200mmHg压力)于70℃干燥18小时。此时,含水量为0.2%,丙酮含量为4.7%(194g)。同时,取1g/份于5mmHg减压下于80℃干燥18小时(丙酮残留量为0.5%),然后于100℃干燥21小时(丙酮残留量为0.02%)。于5mmHg减压下于80℃将其余部分干燥31小时(丙酮含量为1.7%,水含量为0.3%,相对于96.5%,纯度高于99%).
获得图(图1)所用的操作条件
该分析在配有Anton Paar TTK温度控制室的Bruker D5000衍射仪上进行。反射设置具有Bragg-Brentano型聚焦几何形状(θ-θ)。将粉末置于一个空的铝样品支架上。钴对阴极管(40kV/30mA)提供铁过滤的(iron-filtered)入射的辐射线。辐射在两个波长处发出:和铁过滤并不能完全去除Kβ辐射(对钴, ),因此仍然可以以Kα双线强度的1%(生产商提供的数据)参加入射的辐射。
Soller狭缝可以提高光束的平行度。可变的前狭缝(variable front slits)使得样品的光照区保持恒定。在所述管和测定室之间的1mm的平行光管限制了散射。采用Braun 50M多室线性检测器。检测视窗的2θ角的宽度为10°。记录该图的条件如下:2θ扫描为1.5-50°,于室温、环境压力和相对湿度下2θ每度计数30秒。
图1代表实施例1的产物的丙酮化物(A型)的参照PXRD图。
实施例1的产物的NMR数据:
1H NMR数据(400MHz,CDCl3,δ以ppm表示):1.20(s,3H),1.22(s,3H),1.37(s,9H),1.67(s,1H),1.72(s,3H),1.80(mt,1H),1.88(s,3H),2.17(s,6H),2.20-2.40(mt,2H),2.36(s,3H),2.70(mt,1H),3.30(s,3H),3.46(s,3H),3.47(mt,1H),3.82(d,J=7.5Hz,1H),3.86(dd,J=11,6.5Hz,1H),4.17(d,J=8.5Hz,1H),4.30(d,J=8,5Hz,1H),4.63(mt,1H),4.80(s,1H),4.97(宽峰d,J=10Hz,1H),5.27(宽峰d,J=10Hz,1H),5.44(d,J=10Hz,1H),5.64(d,J=7.5Hz,1H),6.21(t,J=9Hz,1H),7.25-7.45(mt,5H),7.49(t,J=7.5Hz,2H),7.60(宽峰t,J=7.5Hz,1H),8.09(d,J=7.5Hz,2H)。
Claims (10)
1.4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯的丙酮化物,其中含有6.5%重量的丙酮。
2.制备4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯丙酮化物的方法,其特征在于使4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯从水和丙酮的混合物中结晶,用上述产物在丙酮/水混合物中的悬浮液种晶,然后用水处理,减压干燥得到的产物。
3.根据权利要求2的方法,其特征在于种晶以每升混合物采用60-80g的浓度进行,所述混合物含有丙酮与水的体积比为65/35-75/25。
4.根据权利要求3的方法,其特征在于种晶在丙酮与水的体积比为68/32的混合物中进行。
5.根据权利要求2的方法,其特征在于结晶结束时丙酮与水的体积比为70/30-30/70。
6.根据权利要求5的方法,其特征在于结晶结束时丙酮与水的体积比为45/55。
7.根据权利要求3-7中任一项的方法,其中所述结晶于20±5℃进行。
8.根据权利要求2的方法,其中干燥于30-60℃进行。
9.根据权利要求2的方法,其中干燥于0.7kPa压力下于40℃进行。
10.根据权利要求2的方法,其中制备直接于通过在酸性介质中使4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,4S,5R)-3-叔丁氧基羰基-2-(4-甲氧基苯基)-4-苯基噁唑烷-5-甲酸酯脱保护获得的4-乙酰氧基-2α-苯甲酰氧基-5β,20-环氧基-1-羟基-7β,10β-二甲氧基-9-氧代紫杉-11-烯-13α-基(2R,3S)-3-叔丁氧基羰基氨基-2-羟基-3-苯基丙酸酯溶液中进行。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0311016A FR2859996B1 (fr) | 2003-09-19 | 2003-09-19 | Solvat acetonique du dimethoxy docetaxel et son procede de preparation |
FR0311016 | 2003-09-19 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1849311A CN1849311A (zh) | 2006-10-18 |
CN100429207C true CN100429207C (zh) | 2008-10-29 |
Family
ID=34224354
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB200480026128XA Active CN100429207C (zh) | 2003-09-19 | 2004-09-16 | 二甲氧基多西他赛丙酮化物及其制备方法 |
Country Status (38)
Country | Link |
---|---|
US (1) | US7241907B2 (zh) |
EP (1) | EP1667986B1 (zh) |
JP (1) | JP5010279B2 (zh) |
KR (1) | KR101123588B1 (zh) |
CN (1) | CN100429207C (zh) |
AR (1) | AR045667A1 (zh) |
AU (1) | AU2004274212B2 (zh) |
BE (1) | BE2013C036I2 (zh) |
BR (1) | BRPI0414492A8 (zh) |
CA (1) | CA2539309A1 (zh) |
CR (1) | CR8292A (zh) |
CY (2) | CY1114575T1 (zh) |
DK (1) | DK1667986T3 (zh) |
ES (1) | ES2403149T4 (zh) |
FR (2) | FR2859996B1 (zh) |
HK (1) | HK1093340A1 (zh) |
HR (1) | HRP20130322T1 (zh) |
HU (1) | HUS1300025I1 (zh) |
IL (1) | IL174240A (zh) |
LU (1) | LU92172I2 (zh) |
MA (1) | MA28045A1 (zh) |
ME (2) | MEP11708A (zh) |
MX (1) | MXPA06002639A (zh) |
MY (1) | MY136668A (zh) |
NO (2) | NO335997B1 (zh) |
NZ (1) | NZ545835A (zh) |
PA (1) | PA8612401A1 (zh) |
PE (1) | PE20050870A1 (zh) |
PL (1) | PL1667986T3 (zh) |
PT (1) | PT1667986E (zh) |
RS (2) | RS54614B1 (zh) |
RU (1) | RU2342373C2 (zh) |
SI (1) | SI1667986T1 (zh) |
TN (1) | TNSN06086A1 (zh) |
TW (1) | TWI382022B (zh) |
UA (1) | UA87115C2 (zh) |
WO (1) | WO2005028462A1 (zh) |
ZA (1) | ZA200602255B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102746258A (zh) * | 2012-07-25 | 2012-10-24 | 重庆泰濠制药有限公司 | 卡巴他赛的结晶形式及其制备方法 |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2007226937A1 (en) * | 2006-03-21 | 2007-09-27 | Dr. Reddy's Laboratories Ltd. | Docetaxel polymorphs and processes |
US7855591B2 (en) * | 2006-06-07 | 2010-12-21 | Atmel Corporation | Method and system for providing a charge pump very low voltage applications |
US7652522B2 (en) * | 2006-09-05 | 2010-01-26 | Atmel Corporation | High efficiency low cost bi-directional charge pump circuit for very low voltage applications |
JP2010516625A (ja) | 2007-01-24 | 2010-05-20 | インサート セラピューティクス, インコーポレイテッド | 制御された薬物送達のためのテザー基を有するポリマー−薬物コンジュゲート |
AU2013205442B2 (en) * | 2008-01-17 | 2016-05-12 | Aventis Pharma S.A. | Crystalline forms of dimethoxy docetaxel and methods for preparing same |
FR2926551A1 (fr) | 2008-01-17 | 2009-07-24 | Aventis Pharma Sa | Formes cristallines du dimethoxy docetaxel et leurs procedes de preparation |
MX2011001583A (es) | 2008-08-11 | 2011-04-04 | Nektar Therapeutics | Conjugados de alcanoato polimericos de multiples brazos. |
FR2945211A1 (fr) * | 2009-05-06 | 2010-11-12 | Sanofi Aventis | Combinaison antitumorale comprenant la cabazitaxel et la capecitabine |
AU2015200149B2 (en) * | 2009-10-29 | 2016-12-01 | Aventis Pharma S.A. | Novel antitumoral use of cabazitaxel |
KR101712231B1 (ko) * | 2009-10-29 | 2017-03-03 | 아벤티스 파마 소시에떼아노님 | 카바지탁셀의 신규한 항종양 용도 |
CA2708489A1 (en) * | 2009-10-29 | 2011-04-29 | Aventis Pharma S.A. | Use of cabazitaxel and a prednisone or a prednisolone in the treatment of prostate cancer |
WO2012088422A1 (en) | 2010-12-22 | 2012-06-28 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of taxane-based compounds |
WO2012088445A1 (en) | 2010-12-22 | 2012-06-28 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of cabazitaxel-based compounds |
EA023950B1 (ru) * | 2011-04-12 | 2016-07-29 | Тева Фармасьютикалз Интернэшнл Гмбх | Твердофазные формы кабазитаксела и способы их получения |
WO2013024495A1 (en) * | 2011-08-18 | 2013-02-21 | Dr. Reddys Laboratories Limited | Pharmaceutical formulations of cabazitaxel |
TWI526437B (zh) * | 2011-09-09 | 2016-03-21 | 台灣神隆股份有限公司 | 卡巴他賽之結晶型 |
US8722900B2 (en) | 2011-10-31 | 2014-05-13 | Scinopharm Taiwan, Ltd. | Process for cabazitaxel, and intermediates thereof |
CN103874692A (zh) | 2011-11-01 | 2014-06-18 | 费森尤斯卡比肿瘤学有限公司 | 卡巴他赛的无定形形式和用于其制备的方法 |
EP2785701B1 (en) | 2011-11-28 | 2019-01-02 | Fresenius Kabi Oncology Limited | Crystalline form of carbazitaxel and process for preparation thereof |
JP6025861B2 (ja) | 2011-12-13 | 2016-11-16 | アベンティス・ファーマ・ソシエテ・アノニム | カバジタキセルの結晶形およびこれを調製するための方法 |
WO2013111157A1 (en) * | 2012-01-03 | 2013-08-01 | Shilpa Medicare Limited | Process for preparing amorphous cabazitaxel |
MX2014009610A (es) * | 2012-02-10 | 2015-09-25 | Aventis Pharma Sa | Nuevos usos pediatricos del cabazitaxel. |
US9394266B2 (en) | 2012-03-08 | 2016-07-19 | IVAX International GmbH | Solid state forms of cabazitaxel and processes for preparation thereof |
CN102675257B (zh) * | 2012-05-10 | 2014-07-02 | 上海金和生物技术有限公司 | 一种卡巴他赛晶体及其制备方法 |
US9012665B2 (en) | 2012-07-31 | 2015-04-21 | Yung Shin Pharm. Ind. Co., Ltd. | Amorphous cabazitaxel |
TWI599373B (zh) | 2012-08-15 | 2017-09-21 | 永信藥品工業股份有限公司 | 卡巴利他索(cabazitaxel)之穩定醫藥調配物 |
CN103664836B (zh) * | 2012-09-20 | 2016-04-20 | 齐鲁制药有限公司 | 7β,10β-二甲氧基多西紫杉醇氘代丙酮合物的晶型A及其制备方法 |
US20140094432A1 (en) | 2012-10-02 | 2014-04-03 | Cerulean Pharma Inc. | Methods and systems for polymer precipitation and generation of particles |
CN103804323A (zh) * | 2012-11-14 | 2014-05-21 | 上海希迈医药科技有限公司 | 一种卡巴他赛溶剂化物及其制备方法和应用 |
CN103058960B (zh) * | 2012-12-12 | 2014-12-10 | 江苏奥赛康药业股份有限公司 | 卡巴他赛多晶型形式及其制备方法 |
EP2743264A1 (en) | 2012-12-13 | 2014-06-18 | INDENA S.p.A. | New crystalline form of cabazitaxel, process for the preparation and pharmaceutical compositions thereof |
CN103910696B (zh) * | 2012-12-30 | 2016-01-20 | 上海医药工业研究院 | 卡巴他赛异丙醚合物及其结晶 |
CN103910698B (zh) * | 2012-12-30 | 2016-01-20 | 上海医药工业研究院 | 卡巴他赛丙酮合物及其结晶 |
EP2777691A1 (en) | 2013-03-14 | 2014-09-17 | Pharmachemie B.V. | Taxoid - Purification of Liquid Excipients |
EP2815749A1 (en) | 2013-06-20 | 2014-12-24 | IP Gesellschaft für Management mbH | Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern |
WO2015000165A1 (zh) * | 2013-07-04 | 2015-01-08 | 北京新天宇科技开发有限公司 | 二甲氧基多西紫杉醇一丙酮化物的稳定转化物及其结晶形式、以及它们的制备方法 |
CN104277014A (zh) * | 2013-07-04 | 2015-01-14 | 北京新天宇科技开发有限公司 | 二甲氧基多西紫杉醇一丙酮化物的稳定转化物及其结晶形式、以及它们的制备方法 |
EP2865675A1 (en) | 2013-10-23 | 2015-04-29 | INDENA S.p.A. | A crystalline anhydrous form of Cabazitaxel, process for the preparation and pharmaceutical compositions thereof |
EP2865674A1 (en) | 2013-10-23 | 2015-04-29 | INDENA S.p.A. | Crystalline solvate forms of Cabazitaxel |
CN103601704B (zh) * | 2013-11-22 | 2015-05-06 | 石家庄智恒医药科技有限公司 | 无定形卡巴他赛的制备 |
EP3247350B1 (en) | 2015-01-12 | 2021-12-22 | Emcure Pharmaceuticals Limited | Liquid formulation of cabazitaxel |
JP6841772B2 (ja) * | 2015-02-17 | 2021-03-10 | エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム | 前立腺癌の処置におけるカバジタキセルの使用 |
EP3093014A1 (en) | 2015-05-13 | 2016-11-16 | Aventis Pharma S.A. | Cabazitaxel and its use for treating cancer |
US10188626B2 (en) | 2015-11-03 | 2019-01-29 | Cipla Limited | Stabilized cabazitaxel formulations |
CA3043499A1 (en) | 2016-11-29 | 2018-06-07 | Censa Pharmaceuticals Inc. | Polymorphic form of sepiapterin |
AU2017366879C1 (en) | 2016-11-29 | 2022-08-11 | Ptc Therapeutics Mp, Inc. | Polymorphs of sepiapterin and salts thereof |
CN111491635A (zh) | 2017-09-01 | 2020-08-04 | 显莎制药公司 | 包含墨蝶呤的药物组合物及其用途 |
JP7502197B2 (ja) | 2018-05-30 | 2024-06-18 | ピーティーシー セラピューティクス エムピー,インコーポレイテッド | セピアプテリン血漿曝露を増加させるための方法 |
WO2020249507A1 (en) | 2019-06-11 | 2020-12-17 | Indena S.P.A. | Anhydrous crystalline form of cabazitaxel, a process for its preparation and pharmaceutical compositions containing it |
EP3797834A1 (en) | 2019-09-25 | 2021-03-31 | Sanofi Mature IP | Cabazitaxel in mcrpc patients previously treated with docetaxel and who failed a prior androgen signaling targeted inhibitor agent |
EP3808345A1 (en) | 2019-10-15 | 2021-04-21 | Sanofi Mature IP | Cabazitaxel in mcrpc patients previously treated with docetaxel and who failed a prior androgen signaling targeted inhibitor agent |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1367691A (zh) * | 1998-08-17 | 2002-09-04 | 阿文蒂斯药物股份有限公司 | 紫杉醇类衍生物的新用途 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5766635A (en) * | 1991-06-28 | 1998-06-16 | Rhone-Poulenc Rorer S.A. | Process for preparing nanoparticles |
MA23823A1 (fr) * | 1995-03-27 | 1996-10-01 | Aventis Pharma Sa | Nouveaux taxoides, leur preparation et les compositions qui les contiennent |
FR2745814B1 (fr) * | 1996-03-06 | 1998-04-03 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
FR2771092B1 (fr) | 1997-11-18 | 1999-12-17 | Rhone Poulenc Rorer Sa | Procede de preparation de derives de la classe des taxoides |
US6346543B1 (en) * | 1998-08-17 | 2002-02-12 | Aventis Pharma S.A. | Use of a taxoid to treat abnormal cell proliferation in the brain |
US6136989A (en) * | 1998-12-30 | 2000-10-24 | Phytogen Life Sciences, Incorporated | Method for high yield and large scale extraction of paclitaxel from paclitaxel-containing material |
US5969165A (en) * | 1999-01-07 | 1999-10-19 | 508037 (Nb) Inc. | Isolation and purification of paclitaxel and other related taxanes by industrial preparative low pressure chromatography on a polymeric resin column |
ATE256117T1 (de) * | 1999-05-17 | 2003-12-15 | Bristol Myers Squibb Co | Neue umsetzungsbedingungen für die spaltung von silylethern bei der herstellung von paclitaxel (taxol(r)) und paclitaxel -analogen |
RU2284328C2 (ru) * | 2001-11-29 | 2006-09-27 | Дайити Фармасьютикал Ко., Лтд. | Кристаллы производных таксана и способ их получения |
-
2003
- 2003-09-19 FR FR0311016A patent/FR2859996B1/fr not_active Expired - Lifetime
-
2004
- 2004-08-19 PE PE2004000799A patent/PE20050870A1/es not_active Application Discontinuation
- 2004-09-16 PL PL04787385T patent/PL1667986T3/pl unknown
- 2004-09-16 RS RS20060189A patent/RS54614B1/en unknown
- 2004-09-16 DK DK04787385.6T patent/DK1667986T3/da active
- 2004-09-16 CA CA002539309A patent/CA2539309A1/fr not_active Abandoned
- 2004-09-16 EP EP04787385A patent/EP1667986B1/fr active Active
- 2004-09-16 AU AU2004274212A patent/AU2004274212B2/en active Active
- 2004-09-16 ES ES04787385T patent/ES2403149T4/es active Active
- 2004-09-16 RS YUP-2006/0189A patent/RS20060189A/sr unknown
- 2004-09-16 WO PCT/FR2004/002344 patent/WO2005028462A1/fr active Application Filing
- 2004-09-16 MX MXPA06002639A patent/MXPA06002639A/es active IP Right Grant
- 2004-09-16 KR KR1020067005396A patent/KR101123588B1/ko active IP Right Grant
- 2004-09-16 ME MEP-117/08A patent/MEP11708A/xx unknown
- 2004-09-16 CN CNB200480026128XA patent/CN100429207C/zh active Active
- 2004-09-16 SI SI200432016T patent/SI1667986T1/sl unknown
- 2004-09-16 NZ NZ545835A patent/NZ545835A/en not_active IP Right Cessation
- 2004-09-16 PA PA20048612401A patent/PA8612401A1/es unknown
- 2004-09-16 UA UAA200604360A patent/UA87115C2/ru unknown
- 2004-09-16 BR BRPI0414492A patent/BRPI0414492A8/pt not_active Application Discontinuation
- 2004-09-16 PT PT4787385T patent/PT1667986E/pt unknown
- 2004-09-16 JP JP2006526663A patent/JP5010279B2/ja active Active
- 2004-09-16 RU RU2006113122/04A patent/RU2342373C2/ru active Protection Beyond IP Right Term
- 2004-09-16 ME MEP-2008-117A patent/ME00054B/me unknown
- 2004-09-16 AR ARP040103329A patent/AR045667A1/es not_active Application Discontinuation
- 2004-09-17 TW TW093128097A patent/TWI382022B/zh active
- 2004-09-17 US US10/944,254 patent/US7241907B2/en active Active
- 2004-09-17 MY MYPI20043787A patent/MY136668A/en unknown
-
2006
- 2006-03-09 IL IL174240A patent/IL174240A/en active IP Right Grant
- 2006-03-15 CR CR8292A patent/CR8292A/es unknown
- 2006-03-17 MA MA28881A patent/MA28045A1/fr unknown
- 2006-03-17 ZA ZA200602255A patent/ZA200602255B/en unknown
- 2006-03-17 TN TNP2006000086A patent/TNSN06086A1/en unknown
- 2006-04-19 NO NO20061714A patent/NO335997B1/no active Protection Beyond IP Right Term
- 2006-12-28 HK HK06114182.3A patent/HK1093340A1/xx not_active IP Right Cessation
-
2013
- 2013-03-20 LU LU92172C patent/LU92172I2/fr unknown
- 2013-04-10 HR HRP20130322TT patent/HRP20130322T1/hr unknown
- 2013-04-16 CY CY20131100313T patent/CY1114575T1/el unknown
- 2013-05-13 CY CY2013016C patent/CY2013016I1/el unknown
- 2013-06-07 HU HUS1300025C patent/HUS1300025I1/hu unknown
- 2013-06-13 BE BE2013C036C patent/BE2013C036I2/fr unknown
- 2013-07-04 FR FR13C0037C patent/FR13C0037I2/fr active Active
-
2015
- 2015-04-22 NO NO2015013C patent/NO2015013I1/no not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1367691A (zh) * | 1998-08-17 | 2002-09-04 | 阿文蒂斯药物股份有限公司 | 紫杉醇类衍生物的新用途 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102746258A (zh) * | 2012-07-25 | 2012-10-24 | 重庆泰濠制药有限公司 | 卡巴他赛的结晶形式及其制备方法 |
US9353076B2 (en) | 2012-07-25 | 2016-05-31 | Chongqing Taihao Pharmaceutical Co., Ltd. | Crystal form of cabazitaxel and preparation method thereof |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100429207C (zh) | 二甲氧基多西他赛丙酮化物及其制备方法 | |
CN102558182A (zh) | 一种厄他培南钠晶型及其制备方法 | |
KR20240093977A (ko) | 이소부티레이트 뉴클레오시드 화합물의 결정형 및 그 제조방법 | |
CN101652356A (zh) | 稳定的无水晶体多西他赛及其制备方法 | |
CN1067997C (zh) | 苯基丙酸紫杉烯-13α酯三水合物的制备方法 | |
CN106916147A (zh) | 化合物及其制备方法和用途 | |
CN113307788B (zh) | 一种近红外氧杂蒽荧光探针及其制备方法和应用 | |
CN115073406B (zh) | 一种桉烷型倍半萜内酯类tba衍生物及其用途 | |
PL213614B1 (pl) | Nowy 7-O-p-D-4'"-metoksyglukopiranozyd 8-prenylonaringeniny i sposób jego wytwarzania | |
CN101274923B (zh) | 一种制备紫杉醇,巴卡亭ⅲ及其衍生物的方法 | |
CN104334561B (zh) | 化合物jk12a及其制备 | |
CN1305486A (zh) | 从α-D-木糖衍生的新化合物,制备方法和治疗用途 | |
CN113956266A (zh) | 一种规模化合成河豚毒素的方法 | |
CN1236779A (zh) | 雷尼替丁枸橼酸铋盐的制备方法 | |
CN109320562A (zh) | 一种简便合成薄荷醇葡萄糖苷的方法 | |
CN113712961B (zh) | 一种β硒醚咪唑类化合物在制备抗肿瘤药物中的应用 | |
CA3131792C (en) | Salt of aldose reductase inhibitor, and preparation method and application thereof | |
CN101139329A (zh) | 一种选择性酰化紫杉烷c(10)位羟基的方法 | |
CN115093431A (zh) | 一种合成头孢泊肟酯的方法 | |
WO2008123737A1 (en) | Docetaxel / mono propylene glycol clathrate and method for the preparation thereof | |
CN118307610A (zh) | 一种红景天苷晶型及其制备方法 | |
CN115925777A (zh) | 一种金盏花素e的水合物、其晶型、其制备方法及其应用 | |
CN116947949A (zh) | 一种3-o-甲基鸟苷的制备方法 | |
CN109071584A (zh) | 3’-唾液乳糖钠盐n水合物的晶体及其制造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1093340 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1093340 Country of ref document: HK |