CN1043530C - 10-脱乙酰基浆果赤霉素ⅲ制造方法 - Google Patents
10-脱乙酰基浆果赤霉素ⅲ制造方法 Download PDFInfo
- Publication number
- CN1043530C CN1043530C CN93104616A CN93104616A CN1043530C CN 1043530 C CN1043530 C CN 1043530C CN 93104616 A CN93104616 A CN 93104616A CN 93104616 A CN93104616 A CN 93104616A CN 1043530 C CN1043530 C CN 1043530C
- Authority
- CN
- China
- Prior art keywords
- alcohol
- baccatin iii
- methyl
- ether
- butyl
- 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.)
- Expired - Lifetime
Links
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Peptides Or Proteins (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Fats And Perfumes (AREA)
- Pyrane Compounds (AREA)
- Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Compounds Of Unknown Constitution (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明为用紫杉(Taxus sp.)各部分制备10-脱乙酰基浆果赤霉素Ⅲ的方法,其中用该植物的甲醇提取物进行萃取和选择性结晶。
Description
本发明涉及用含Taxotere或其类似物的植物的各部分制造用于经半合成法制备紫杉醇或红豆杉醇(Taxol)的中间产物的方法。
本发明特别是涉及用各种紫杉或红豆杉(yew)的树皮,树杆,根或叶选择性制取10-脱乙酰基浆果赤霉素Ⅲ的方法。
式(Ⅰ)中Ar尤其指必要时取代的苯基,R可为氧或乙酰基或N-取代氨基甲酰基,R1指氢或N-取代氨基甲酰基且R1可为苯基或R2-O-基,而R2指烷基,烯基,炔基,环烷基,环烯基,双环烷基,苯基或杂环基。
紫杉醇对应于式(Ⅰ)中Ar和R1为苯基且R为乙酰基和R′为氢的产品,而Taxotere对应于式(Ⅰ)中Ar为苯基,R和R′为为氢且R1为叔丁氧基的产品。
自然界中各种紫杉中存在的少量紫杉醇难于在不完全损坏植物的情况下分离出来,如其分离法已见于C.H.O.Huang et alJ.Natl.Prod.49,665(1986),其中用甲醇处理研磨的短叶紫杉树皮,将提取液浓缩,用二氯甲烷莘取浓缩物,再浓缩后将剩余物分散在己烷-丙酮混合物(1-1体积比)用Florisil柱色谱法将可溶部分提纯而得紫杉醇粗产品,用甲醇-水和己烷-丙酮混合物顺序重结晶后再经色谱提纯并再次结晶这样提取的紫杉醇量可为所用植物部分的0.005-0.017%。
紫杉醇也可用另外的方法制成,其中用10-脱乙酰基浆果赤霉素Ⅲ或在US485753所述条件下用Taxotere中间产物或在EP400971或428376所述条件下酯化浆果赤霉素Ⅲ或在US4924011所述条件下酯化10-脱乙酰浆果赤霉素Ⅲ后乙酰化。
各种紫杉(浆果紫杉,短叶紫杉,加拿大紫杉,东北紫杉,佛罗里达紫杉,Taxus media,喜马拉雅紫杉)含taxane衍生物,其中主要为紫杉醇和10-脱乙酰基浆果赤霉素Ⅲ,其它衍生物尤其为Cephalomannin,10-脱乙酰Cephalomannin或浆果赤霉素Ⅲ,必要时与糖相连。
而紫杉醇主要存在于树杆和皮中,10-脱乙酰基浆果赤霉素Ⅲ主要存在于树叶中,而叶中10-脱乙酰基浆果赤霉素Ⅲ量一般大大高于紫杉醇量,而且无论是就树皮,还是树杆或叶而言均如此。
因此尤为重要的是能获得10-脱乙酰基浆果赤霉素Ⅲ,这是比直接从紫杉中提取的办法制取更多紫杉醇并且是制备Taxotere所必须的。
从紫杉叶中提取10-脱乙酰基浆果赤霉素Ⅲ不会完全破坏该植物,其叶在每一生长循环后又可再用。
提取紫杉各部分(皮,杆,根,叶等)存在的taxane衍生物的已知方法一般要求使用时间长且耗费高的色谱技术,其中不能完全和定量分离先存在于植物中的taxane衍生物。
按US4814470所述方法在乙醇中湿法研磨针叶,用有机溶剂如二氯甲烷萃取和后续的色谱分离可分出约40%叶中存在的10-脱乙酰基浆果赤霉素Ⅲ。
紫杉各部分中所含taxane衍生的各种成分也可按尤其见于PCT WO92/07842的反液相色谱法分离,其中主要是在已固定了taxane衍生物的吸附剂上进行反液相色谱处理紫杉粗提取物,洗出taxane衍生物后将其分离,按该法可从1kg研细干叶中分出约25%存在于叶中的10-脱乙酰基浆果赤霉素Ⅲ。
作为本发明主题,现已发现可采用不经色谱技术的简单方法从紫杉各部分,尤其是从叶中选择性提取10-脱乙酰基浆果赤霉素Ⅲ,如可提取约75%存在于叶中的10-脱乙酰基浆果赤霉素Ⅲ。
更具体地讲,本发明方法包括:
1)用脂肪醇处理研细的紫杉部分(Taxus sp)而得含10-脱乙酰基浆果赤霉素Ⅲ的醇提取物,
2)用水稀释任意地浓缩的醇提取物,
3)过滤,沉降或离心分离所得醇/水溶液中存在的不溶物,
4)从醇/水溶液中去除基本上所有醇,
5)用适当有机溶剂从所得水相中萃取10-脱乙酰基浆果赤霉素Ⅲ,
6)从所得含10-脱乙酰基浆果赤霉素Ⅲ的有机萃取物中去除溶剂,
7)在有机溶剂中使10-脱乙酰基浆果赤霉素Ⅲ从所得剩余物中选择性结晶出来,和
8)分离提纯的10-脱乙酰基浆果赤霉素Ⅲ。
可用紫杉的任何适宜部分,如皮,杆,根或叶进行本发明方法,用于进行本发明方法的紫杉优选属于浆果紫杉,短叶紫杉,加拿大紫杉,东北紫杉,佛罗里达紫杉,Taxus media或喜马拉雅紫杉种,特别是用一般来说更富含10-脱乙酰基浆果赤霉素Ⅲ的紫杉叶(浆果紫杉,短叶紫杉),为更好地应用本发明方法,优选用研细并任意地干燥的紫杉各部分,而且所用片段尺寸可为0.5至几毫米,为了方便可有利地用平均尺寸小于1mm的片段。研细且必要时干燥的紫杉部分可经研磨和任意地干燥而得,这任意地在该植物新鲜部分冻融前或后进行或安排在冻融操作之间进行。
研细并任意地干燥的紫杉部分与醇的混合物任意地加热后搅拌而得醇提取物,醇一般选自甲醇,乙醇,丙醇,异丙醇和叔丁醇,特别是甲醇。
含10-脱乙酰基浆果赤霉素Ⅲ的醇提取物加水而得醇/水溶液。
为应用该方法,可在水相中采用特殊稀释和醇含量条件,从而避免10浆果赤霉素Ⅲ损失并去除尽可能大量的不溶产物。在这些条件下必须在用水稀释前将含10-浆果赤霉素Ⅲ的醇提取物浓缩。
更具体地讲,向任意地经蒸馏(优选在减压下进行)浓缩的醇提取物中加水稀释必须使稀释剂混合物与醇提取物中存在的干物质之重量比达到4-8,水/醇稀释剂混合物含10-30wt%醇。
不溶于所得醇/水溶液的产品可用常规技术,优选用过滤,沉降或离心法去除,其中过滤时优选在过滤介质,如硅藻土(Celite)和絮凝剂存在下操作。
从所得醇水溶液中去除水的操作优选蒸馏进行,且优选减压下操作,任意地还存在防泡剂,从而避免或限制混合物中各成分热降触。
一般来说,所得水溶液中醇含量一般少于1%,其中的10-脱乙酰基浆果赤霉素Ⅲ用有机溶剂萃取一或多次,有机溶剂选自醚如甲基叔丁基醚,乙基叔丁基醚,甲基正丁基醚,甲基正戊基醚,乙基叔戊基醚,叔丁基异丙基醚,乙基异丁基醚,叔丁基正丙基醚或乙基正己基醚以及脂族酯如乙酸乙酯,乙酸丙酯,乙酸异丙酯,乙酸正丁酯,乙酸叔丁酯,叔丁基乙酸甲酯,丙酸叔丁酯或乙酸叔戊酯,特别是甲基叔丁基醚,乙基叔丁基醚,乙酸乙酯和乙酸正丁酯,更优选乙酸乙酯和乙酸正丁酯。
该有机提取物任意地用弱碱水溶液(如碳酸钠水溶液)和/或水洗涤。干燥后提取物的有机溶剂用常规方法去除,特别是蒸馏去除,任意地减压进行,得到可从中分出10-脱乙酰基浆果赤霉素Ⅲ的常为固态的残余物。
选择性结晶分离10-脱乙酰基浆果赤霉素Ⅲ可用所得残余物的有机溶剂溶液或有机溶剂混合物溶液进行,可有效用于使10-脱乙酰基浆果赤霉素Ⅲ选择性结晶的溶剂为腈如乙腈或丙腈,任意地混入脂肪醇如甲醇,乙醇,丙醇,异丙醇或正丁醇,或脂肪酯如乙酸乙酯,乙酸正丁酯或乙酸叔丁酯或酮如丙酮,甲·乙酮,甲基·丙基酮,甲基·正丁基酮或甲基·异丁基酮,尤其是用乙腈进行选择性结晶,必要时存在乙醇和/或丙酮和/或乙酸乙酯和/或正丁酯。
沉淀的10-脱乙酰基浆果赤霉素Ⅲ可过滤,沉降或离心分离出来。
本发明提取方法得到的10-脱乙酰基浆果赤霉素Ⅲ可用来制备紫杉醇或Taxotere或其衍生物,其条件见于尤其是专利EP0253738,EP0253739,EP0336841,EP0336840,WO92/09589,EP0400971和EP0428376。
以下实施例详述本发明。
实施例1
2001甲醇,1.4kg玻璃棉和250kg平均粒径近于0.8mm的研细紫杉叶(浆果紫杉)放入渗滤器,并加入400l纯甲醇,从顶部以870l/h的速度向渗透器中加入新鲜溶剂并在渗滤器底部收集甲醇提取物,从而在20℃进行5小时渗滤。收集的甲醇液在蒸发器中40℃减压(70-80kpa)蒸发而得固体含量40-80wt%的浓缩物。
应用甲醇提取物(在上述条件下制备),其中含353g干提取物,420g甲醇和40g水,存在的10-脱乙酰基浆果赤霉素Ⅲ为1130mg。
将甲醇提取物引入21反应器中,并搅拌加入1590Cm3水混合物再搅拌1小时后加35g硅藻土(Celite)和25cm3的“Zetag87”絮凝剂。所得最终悬浮液用直径130mm的No.4玻璃多孔体过滤,然后用100g水/甲醇混合物(8/2重量比)洗涤不溶产品和硅藻土。
滤液放在21反应器中,加入2cm3 Silicone 426R,混合物35-42℃下减压(7.3-11kpa)蒸馏,外浴温度45-50℃,得到馏出物(909g)和含0.5%甲醇的浓缩物(1432g)。
浓缩物用700cm3乙酸乙酯萃取一次后用350cm3一份的乙酸乙酯萃取两次,组合有机相2次用700cm3的0.1M碳酸钠溶液洗涤后再用350cm3水洗涤一次,PH达8,有机相(1049g)40℃减压(1.33-21.3kpa)浓缩至干而得16.2g干提取物。
实施例2
向500cm3园底烧瓶中加入45.5g实施例1中所得含9.3%10-脱乙酰基浆果赤霉素Ⅲ的干提取物后加18cm3乙酸乙酯。均匀混合物搅拌并加热到50℃后50℃下15分钟加136cm3乙腈。悬浮液再搅拌约1小时后约3小时内冷至近于20℃的温度。沉淀用No.3玻璃多孔体(直径35mm)过滤分离后用20cm3乙腈洗涤,之后两次用20cm3二异丙醚洗涤,产品40℃减压(1.33kpa)干燥20小时而得5.2g白色产品,含75.8%10-脱乙酰基浆果赤霉素Ⅲ。
结晶收率93.6%。
实施例3
向11园底烧瓶中加入275.2g含3.48g10-脱乙酰基浆果赤霉素Ⅲ的39.6g干物质的乙酸乙酯溶液后减压(6.0kpa)浓缩,收集到164g乙酸乙酯。将36cm3乙醇加入浓缩物,混合物冷至10℃,然后搅拌条件下(30rpm)缓慢加入60cm3乙腈(约1/2小时),悬浮液10℃搅拌1小时后迅速加入84cm3乙腈。沉淀用No.3玻璃多孔体(直径35mm)过滤分离后按顺序2次用20cm3乙腈并2次用20cm3二异丙醚洗涤。产品40℃减压(0.27kpa)干燥12小时而得2.85g白色晶体粉,含93.8%10-脱乙酰基浆果赤霉素Ⅲ。第二次加84cm3乙腈后10℃搅拌15小时。
结晶母液和洗涤液(247g)40℃减压(2.7kpa)浓缩而得36g干物质并用18cm3乙醇萃取,然后缓慢加入72cm3乙腈,混合物近于20℃搅拌15小时。沉淀过滤分离后2次用5cm3乙腈洗涤后2次用5cm3二异丙醚洗涤,再干燥而得0.662g细粉,含62.7%10-脱乙酰基浆果赤霉素Ⅲ。
Claims (22)
1.用紫杉各部分制备10-脱乙酰基浆果赤霉素Ⅲ的方法,其特征是:
1)用脂肪醇处理研细的紫杉部分而得到含10-脱乙酰基浆果赤霉素Ⅲ的醇提取物,
2)用水稀释任意地浓缩的醇提取物,
3)过滤、沉降或离心分离所得醇/水溶液中存在的不溶物,
4)从醇/水溶液中去除基本上所有醇,
5)用适当有机溶剂从所得水相中萃取10-脱乙酰基浆果赤霉素Ⅲ,
6)从所得含10-脱乙酰基浆果赤霉素Ⅲ的有机萃取物中去除溶剂,
7)在有机溶剂中使10-脱乙酰基浆果赤霉素Ⅲ从所得剩余物中选择性结晶出来,和
8)分离提纯的10-脱乙酰基浆果赤霉素Ⅲ。
2.权利要求1的方法,其特征是在选自甲醇、乙醇、丙醇和叔丁醇的脂肪醇中将紫杉部分研细且任意干燥而得到醇提取物。
3.权利要求2的方法,其特征是所述脂肪醇为甲醇。
4.权利要求2的方法,其特征是研细且任意干燥的紫杉部分经研磨和任意干燥的操作而得,所述操作在该植物的新鲜部分冻融操作前或后进行,或安排在该植物新鲜部分冻融操作之间进行。
5.权利要求1-4中任一项的方法,其特征是任意浓缩的甲醇提取物用水稀释而使稀释剂混合物与醇提取物中存在的干物质之重量比达到4-8,并且水/醇稀释剂混合物含10-30wt%醇。
6.权利要求1的方法,其特征是不溶物通过过滤、沉降或离心分离法与醇/水溶液分离。
7.权利要求1-4中任一项的方法,其特征是醇通过任意减压进行的蒸馏法从醇/水溶液中去除。
8.权利要求1-4中任一项的方法,其特征是去除醇后的水相用有机溶剂提取10-脱乙酰基浆果赤霉素Ⅲ。
9.权利要求8的方法,其特征是所述有机溶剂选自醚和脂族酯。
10.权利要求9的方法,其特征是所述醚选自甲基叔丁基醚、乙基叔丁基醚、甲基正丁基醚、甲基正戊基醚、乙基叔戊基醚、叔丁基异丙基醚、乙基异丙基醚、叔丁基正丙基醚、乙基正己基醚和叔丁基异丙基醚。
11.权利要求9的方法,其特征是所述脂族酯选自乙酸乙酯、乙酸丙酯、乙酸异丙酯、乙酸正丁酯、乙酸叔丁酯、叔丁基乙酸甲酯、丙酸叔丁酯和乙酸叔戊酯。
12.权利要求8的方法,其特征是所述有机溶剂为乙酸乙酯或乙酸正丁酯。
13.权利要求1-4中任一项的方法,其特征是用选自脂族腈并任意地混入脂族醇或脂族酯或脂族酮的有机溶剂选择性结晶分出10-脱乙酰基浆果赤霉素Ⅲ。
14.权利要求13的方法,其特征是所述腈选自乙腈或丙腈。
15.权利要求13的方法,其特征是所述脂肪醇选自甲醇、乙醇、丙醇、异丙醇和正丁醇。
16.权利要求13的方法,其特征是所述脂肪酯选自乙酸甲酯、乙酸异丙酯、乙酸正丁酯和乙酸叔丁酯。
17.权利要求13的方法,其特征是所述脂肪酮选自丙酮、甲基·乙基酮、甲基·丙基酮、甲基·正丁基酮和甲基·异丁基酮。
18.权利要求13的方法,其特征是选择性结晶用乙腈并任意地混入乙醇和/或乙酸乙酯或正丁酯和/或丙酮进行。
19.权利要求1-4中任一项的方法,其特征是10-脱乙酰基浆果赤霉素Ⅲ过滤、沉降或离心分离出来。
20.权利要求1-4中任一项的方法,其特征是从紫杉叶中提取10-脱乙酰基浆果赤霉素Ⅲ。
21.权利要求20的方法,其特征是所述紫杉属于浆果紫杉、短叶紫杉、加拿大紫杉、东北紫杉、佛罗里达紫杉、Taxus media或喜马拉雅紫杉品种。
22.用权利要求1-21中任一项的方法所得10-脱乙酰基浆果赤霉素Ⅲ制备紫杉醇、Taxotere或其衍生物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9211746A FR2696463B1 (fr) | 1992-10-05 | 1992-10-05 | Procédé d'obtention de la désacétyl-10 baccatine III. |
FR9211746 | 1992-10-05 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1085551A CN1085551A (zh) | 1994-04-20 |
CN1043530C true CN1043530C (zh) | 1999-06-02 |
Family
ID=9434124
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN93104616A Expired - Lifetime CN1043530C (zh) | 1992-10-05 | 1993-04-21 | 10-脱乙酰基浆果赤霉素ⅲ制造方法 |
Country Status (30)
Country | Link |
---|---|
US (1) | US5393895A (zh) |
EP (1) | EP0663910B1 (zh) |
JP (1) | JP3299754B2 (zh) |
KR (1) | KR100301236B1 (zh) |
CN (1) | CN1043530C (zh) |
AT (1) | ATE148883T1 (zh) |
AU (1) | AU680629B2 (zh) |
CA (1) | CA2146373C (zh) |
CZ (2) | CZ284615B6 (zh) |
DE (1) | DE69308155T2 (zh) |
DK (1) | DK0663910T3 (zh) |
EE (1) | EE03126B1 (zh) |
ES (1) | ES2098061T3 (zh) |
FI (1) | FI109794B (zh) |
FR (1) | FR2696463B1 (zh) |
GE (1) | GEP20001937B (zh) |
GR (1) | GR3022617T3 (zh) |
HU (1) | HU226862B1 (zh) |
LT (1) | LT3398B (zh) |
LV (1) | LV10621B (zh) |
MX (1) | MX9305771A (zh) |
NO (1) | NO310413B1 (zh) |
NZ (1) | NZ256450A (zh) |
PL (1) | PL177316B1 (zh) |
RU (1) | RU2107065C1 (zh) |
SK (1) | SK280949B6 (zh) |
TW (1) | TW255890B (zh) |
UA (1) | UA44227C2 (zh) |
WO (1) | WO1994007882A1 (zh) |
ZA (1) | ZA937313B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108904137A (zh) * | 2018-05-27 | 2018-11-30 | 肖军威 | 一种卫生巾芯片的制备方法及卫生巾芯片的加工设备 |
Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2696462B1 (fr) * | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Procédé d'obtention de la désacétyl-10 baccatine III. |
ATE339975T1 (de) | 1993-07-19 | 2006-10-15 | Angiotech Pharm Inc | Anti-angiogener stent und verfahren zu dessen herstellung |
DK0726801T3 (da) * | 1993-11-02 | 2000-05-01 | Rhone Poulenc Rorer Gmbh | Fremgangsmåde til adskillelse af en blanding |
FR2714053B1 (fr) * | 1993-12-22 | 1996-03-08 | Pf Medicament | Procédé d'extraction et d'isolement de la 10-désacétylbaccatine III. |
CN1112433A (zh) * | 1994-05-24 | 1995-11-29 | 郭明 | 红豆杉属植物提取物及其应用 |
AU716005B2 (en) | 1995-06-07 | 2000-02-17 | Cook Medical Technologies Llc | Implantable medical device |
FR2736355B1 (fr) * | 1995-07-07 | 1997-11-07 | Pf Medicament | Procede d'extraction et d'isolement de la 10-desacetylbaccatine iii |
US5750736A (en) * | 1996-07-11 | 1998-05-12 | Napro Biotherapeutics, Inc. | Method for acylating 10-deacetylbaccatin III selectively at the c-10 position |
US5965752A (en) * | 1996-08-23 | 1999-10-12 | Institut National De La Recherche Scientifique | Preparative scale isolation and purification of taxanes |
EP1019347B1 (en) | 1997-08-21 | 2003-03-19 | Florida State University | Method for the synthesis of taxanes |
US6002024A (en) * | 1998-07-27 | 1999-12-14 | Dabur Research Foundation | Process for the isolation of 14β-hydroxy-10-deacetyl baccatin-III |
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 |
US6495705B2 (en) | 2000-03-16 | 2002-12-17 | Napro Biotherapeutics, Inc. | Efficient process for the production of 10-DAB III by selective hydrazinolysis of various taxanes |
US6281368B1 (en) | 2000-03-16 | 2001-08-28 | Napro Biotherapeutics, Inc. | Simple and efficient hydrazinolysis of C-10 and C-13 ester functionalities of taxanes to obtain 10-DAB III |
CA2307393A1 (en) | 2000-05-01 | 2001-11-01 | The University Of British Columbia | Ginsenoside chemotherapy |
US20030157170A1 (en) * | 2001-03-13 | 2003-08-21 | Richard Liggins | Micellar drug delivery vehicles and precursors thereto and uses thereof |
CA2440935A1 (en) | 2001-03-13 | 2002-09-19 | Richard Liggins | Micellar drug delivery vehicles and precursors thereto and uses thereof |
ES2286244T3 (es) * | 2001-04-20 | 2007-12-01 | The University Of British Columbia | Sistemas de suministro de farmaco micelar para farmacos hirofobicos. |
US7351542B2 (en) | 2002-05-20 | 2008-04-01 | The Regents Of The University Of California | Methods of modulating tubulin deacetylase activity |
EP1594459B1 (en) | 2002-12-30 | 2010-02-17 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
JP2007525188A (ja) | 2003-05-16 | 2007-09-06 | インターミューン インコーポレイテッド | 合成ケモカイン受容体リガンドおよびその使用方法 |
US7846940B2 (en) | 2004-03-31 | 2010-12-07 | Cordis Corporation | Solution formulations of sirolimus and its analogs for CAD treatment |
US7989490B2 (en) | 2004-06-02 | 2011-08-02 | Cordis Corporation | Injectable formulations of taxanes for cad treatment |
US8003122B2 (en) | 2004-03-31 | 2011-08-23 | Cordis Corporation | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
KR20070045219A (ko) * | 2004-07-02 | 2007-05-02 | 아이박스 파마슈티컬스 에스.알.오. | 파클리탁셀과 세팔로마닌의 분리 방법 |
US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
US8691780B2 (en) | 2005-02-17 | 2014-04-08 | The Board Of Trustees Of The Leland Stanford Junior University | Txr1 and enhanced taxane sensitivity based on the modulation of a pathway mediated thereby |
WO2007062036A2 (en) | 2005-11-21 | 2007-05-31 | Med Institute, Inc. | Implantable medical device coatings with biodegradable elastomer and releasable therapeutic agent |
MX2008011978A (es) | 2006-03-22 | 2009-04-22 | Medigene Ag | Tratamiento del cancer de seno negativo al triple receptor. |
EP2043704B2 (en) | 2006-06-30 | 2017-04-19 | Cook Medical Technologies LLC | Methods of manufacturing and modifying taxane coatings for implantable medical devices |
US8409601B2 (en) | 2008-03-31 | 2013-04-02 | Cordis Corporation | Rapamycin coated expandable devices |
US8420110B2 (en) | 2008-03-31 | 2013-04-16 | Cordis Corporation | Drug coated expandable devices |
US8273404B2 (en) | 2008-05-19 | 2012-09-25 | Cordis Corporation | Extraction of solvents from drug containing polymer reservoirs |
US9198893B2 (en) | 2008-05-22 | 2015-12-01 | Galera Labs, Llc | Combination antitumor therapy |
EP2310507A4 (en) | 2008-07-08 | 2013-03-20 | David Gladstone Inst | METHODS AND COMPOSITIONS FOR MODULATING ANGIOGENESIS |
US8642063B2 (en) | 2008-08-22 | 2014-02-04 | Cook Medical Technologies Llc | Implantable medical device coatings with biodegradable elastomer and releasable taxane agent |
US20120302954A1 (en) | 2011-05-25 | 2012-11-29 | Zhao Jonathon Z | Expandable devices coated with a paclitaxel composition |
US20120303115A1 (en) | 2011-05-25 | 2012-11-29 | Dadino Ronald C | Expandable devices coated with a rapamycin composition |
CN104039771B (zh) | 2011-09-26 | 2017-10-27 | Kabi费森尤斯肿瘤学有限公司 | 包括c(7)‑oh和c(13)‑oh甲硅烷基化或仅c(7)‑oh甲硅烷基化的用于制备卡巴他赛的方法 |
US9956385B2 (en) | 2012-06-28 | 2018-05-01 | The Spectranetics Corporation | Post-processing of a medical device to control morphology and mechanical properties |
US9181343B2 (en) | 2012-07-19 | 2015-11-10 | Redwood Bioscience Inc. | Antibody specific for CD22 and methods of use thereof |
WO2014074218A1 (en) | 2012-11-12 | 2014-05-15 | Redwood Bioscience, Inc. | Compounds and methods for producing a conjugate |
CN103804326A (zh) * | 2012-11-15 | 2014-05-21 | 刘胜远 | 一种从含10-去乙酰基巴卡亭ⅲ的浸膏分离和提纯10-去乙酰基巴卡亭ⅲ的方法 |
DK3300745T3 (da) | 2013-02-15 | 2019-11-04 | Univ California | Kimærisk antigenreceptor og fremgangsmåder til anvendelse deraf |
CN103145652B (zh) * | 2013-03-05 | 2015-09-30 | 无锡尔云科技有限公司 | 一种从红豆杉属植物中提取紫杉醇及其衍生物的方法 |
CN105358531B (zh) | 2013-03-14 | 2017-11-14 | 利兰-斯坦福大学初级学院的董事会 | 线粒体醛脱氢酶‑2调节剂和其使用方法 |
AU2014354643B2 (en) | 2013-11-27 | 2020-03-05 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
WO2015127137A1 (en) | 2014-02-19 | 2015-08-27 | Aldea Pharmaceuticals, Inc. | Mitochondrial aldehyde dehydrogenase 2 (aldh2) binding polycyclic amides and their use for the treatment of cancer |
CN108135917B (zh) | 2015-09-25 | 2021-07-09 | Zy医疗 | 基于包含多糖-维生素缀合物的颗粒的药物制剂 |
US10654875B2 (en) | 2015-11-12 | 2020-05-19 | The Board Of Trustees Of The Leland Stanford Junior University | Cell-penetrating, guanidinium-rich oligophosphotriesters for drug and probe delivery |
TWI760319B (zh) | 2015-12-30 | 2022-04-11 | 杏國新藥股份有限公司 | 乳癌治療 |
KR20180135458A (ko) | 2016-04-26 | 2018-12-20 | 알.피.쉐러 테크놀러지즈 엘엘씨 | 항체 컨쥬게이트 및 이의 제조 및 이용 방법 |
PL3463308T3 (pl) | 2016-06-01 | 2022-03-14 | Servier IP UK Limited | Preparaty poli(tlenku alkilenu)-asparaginazy oraz sposoby ich wytwarzania i zastosowania |
TW201825087A (zh) | 2017-01-05 | 2018-07-16 | 杏國新藥股份有限公司 | 胰臟癌治療 |
KR20190130559A (ko) | 2017-01-18 | 2019-11-22 | 에프1 온콜로지, 인코포레이티드 | Axl 또는 ror2에 대한 키메라 항원 수용체 및 이의 사용 방법 |
EP3388082A1 (en) | 2017-04-13 | 2018-10-17 | Galera Labs, LLC | Combination cancer immunotherapy with pentaaza macrocyclic ring complex |
SG11202007317XA (en) | 2018-01-31 | 2020-08-28 | Galera Labs Llc | Combination cancer therapy with pentaaza macrocyclic ring complex and platinum-based anticancer agent |
WO2019200181A1 (en) | 2018-04-11 | 2019-10-17 | Ohio State Innovation Foundation | Methods and compositions for sustained release microparticles for ocular drug delivery |
EP3823674A4 (en) | 2018-07-18 | 2022-12-28 | Manzanita Pharmaceuticals, Inc. | CONJUGATES FOR DELIVERING AN ANTI-CANCER AGENT TO NERVE CELLS, METHODS OF USE AND METHODS OF PRODUCTION THEREOF |
US11529402B2 (en) | 2019-01-14 | 2022-12-20 | Ignite Immunotherapy, Inc. | Recombinant vaccinia virus and methods of use thereof |
CA3129883A1 (en) | 2019-02-14 | 2020-08-20 | Ignite Immunotherapy, Inc. | Recombinant vaccinia virus and methods of use thereof |
BR112021019701A2 (pt) | 2019-04-02 | 2021-12-14 | Kenjockety Biotechnology Inc | Anticorpos multiespecíficos para antígeno de câncer de bomba de efluxo e composições, reagentes, kits e métodos relacionados aos mesmos |
CN110317183B (zh) * | 2019-08-08 | 2021-03-12 | 无锡紫杉药业有限公司 | 一种红豆杉天然提取产物的纯化方法 |
IL293627A (en) | 2019-12-12 | 2022-08-01 | Ignite Immunotherapy Inc | Variant of oncolytic vaccinia virus and methods of using it |
CA3164608A1 (en) | 2020-01-29 | 2021-08-05 | Kenjockety Biotechnology, Inc. | Anti-mdr1 antibodies and uses thereof |
CN116323662A (zh) | 2020-06-04 | 2023-06-23 | 肯乔克蒂生物技术股份有限公司 | 抗abcg2抗体及其用途 |
CN116529267A (zh) | 2020-06-04 | 2023-08-01 | 肯乔克蒂生物技术股份有限公司 | Abcg2外排泵-癌症抗原多特异性抗体及其相关组合物、试剂、试剂盒和方法 |
JP2023533567A (ja) | 2020-07-14 | 2023-08-03 | ファイザー・インク | 組み換えワクシニアウイルス |
CN116490522A (zh) | 2020-09-02 | 2023-07-25 | 肯乔克蒂生物技术股份有限公司 | 抗abcc1抗体及其应用 |
CA3203652A1 (en) | 2020-11-13 | 2022-05-19 | William Robert ARATHOON | Anti-mrp4 (encoded by abcc4 gene) antibodies and uses thereof |
CN112694458A (zh) * | 2020-12-29 | 2021-04-23 | 重庆臻源红豆杉发展有限公司 | 一种10-去乙酰基巴卡亭ⅲ提取纯化方法 |
CA3238353A1 (en) | 2021-12-13 | 2023-06-22 | William Robert ARATHOON | Anti-abcb1 antibodies |
WO2023159220A1 (en) | 2022-02-18 | 2023-08-24 | Kenjockety Biotechnology, Inc. | Anti-cd47 antibodies |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4814470A (en) * | 1986-07-17 | 1989-03-21 | Rhone-Poulenc Sante | Taxol derivatives, their preparation and pharmaceutical compositions containing them |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2629819B1 (fr) | 1988-04-06 | 1990-11-16 | Rhone Poulenc Sante | Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii |
FR2629818B1 (fr) | 1988-04-06 | 1990-11-16 | Centre Nat Rech Scient | Procede de preparation du taxol |
US5175315A (en) | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
US5136060A (en) | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
US5380916A (en) | 1990-11-02 | 1995-01-10 | University Of Florida | Method for the isolation and purification of taxane derivatives |
MX9102128A (es) | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
WO1992018492A1 (en) * | 1991-04-19 | 1992-10-29 | The University Of Mississippi | Methods and compositions for isolating taxanes |
IT1258838B (it) | 1992-01-31 | 1996-02-29 | Indena Spa | Processo per l'estrazione di tassolo e derivati da cultivar del genere taxus |
-
1992
- 1992-10-05 FR FR9211746A patent/FR2696463B1/fr not_active Expired - Lifetime
-
1993
- 1993-01-27 US US08/010,083 patent/US5393895A/en not_active Expired - Lifetime
- 1993-04-10 UA UA95038244A patent/UA44227C2/uk unknown
- 1993-04-21 CN CN93104616A patent/CN1043530C/zh not_active Expired - Lifetime
- 1993-09-21 MX MX9305771A patent/MX9305771A/es unknown
- 1993-10-01 ZA ZA937313A patent/ZA937313B/xx unknown
- 1993-10-02 TW TW082108103A patent/TW255890B/zh not_active IP Right Cessation
- 1993-10-04 RU RU95110687/04A patent/RU2107065C1/ru active
- 1993-10-04 NZ NZ256450A patent/NZ256450A/en not_active IP Right Cessation
- 1993-10-04 DE DE69308155T patent/DE69308155T2/de not_active Expired - Lifetime
- 1993-10-04 JP JP50879294A patent/JP3299754B2/ja not_active Expired - Lifetime
- 1993-10-04 HU HU9500973A patent/HU226862B1/hu unknown
- 1993-10-04 WO PCT/FR1993/000972 patent/WO1994007882A1/fr active IP Right Grant
- 1993-10-04 ES ES93921987T patent/ES2098061T3/es not_active Expired - Lifetime
- 1993-10-04 GE GEAP19932511A patent/GEP20001937B/en unknown
- 1993-10-04 AU AU51155/93A patent/AU680629B2/en not_active Expired
- 1993-10-04 PL PL93308244A patent/PL177316B1/pl unknown
- 1993-10-04 EP EP93921987A patent/EP0663910B1/fr not_active Expired - Lifetime
- 1993-10-04 AT AT93921987T patent/ATE148883T1/de active
- 1993-10-04 CA CA002146373A patent/CA2146373C/fr not_active Expired - Lifetime
- 1993-10-04 CZ CZ95845A patent/CZ284615B6/cs not_active IP Right Cessation
- 1993-10-04 KR KR1019950701306A patent/KR100301236B1/ko not_active IP Right Cessation
- 1993-10-04 LV LVP-93-1120A patent/LV10621B/xx unknown
- 1993-10-04 DK DK93921987.9T patent/DK0663910T3/da active
- 1993-10-04 SK SK433-95A patent/SK280949B6/sk not_active IP Right Cessation
- 1993-10-04 LT LTIP1397A patent/LT3398B/lt not_active IP Right Cessation
-
1994
- 1994-11-18 EE EE9400364A patent/EE03126B1/xx unknown
-
1995
- 1995-04-03 NO NO19951282A patent/NO310413B1/no not_active IP Right Cessation
- 1995-04-04 FI FI951596A patent/FI109794B/fi not_active IP Right Cessation
-
1997
- 1997-02-20 GR GR960402767T patent/GR3022617T3/el unknown
-
1998
- 1998-02-06 CZ CZ1998367A patent/CZ287065B6/cs not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4814470A (en) * | 1986-07-17 | 1989-03-21 | Rhone-Poulenc Sante | Taxol derivatives, their preparation and pharmaceutical compositions containing them |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108904137A (zh) * | 2018-05-27 | 2018-11-30 | 肖军威 | 一种卫生巾芯片的制备方法及卫生巾芯片的加工设备 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1043530C (zh) | 10-脱乙酰基浆果赤霉素ⅲ制造方法 | |
CN1041310C (zh) | 10-脱乙酰基浆果赤霉素ⅲ制造方法 | |
US5279949A (en) | Process for the isolation and purification of taxol and taxanes from Taxus spp | |
US5478736A (en) | Process for the isolation and purification of taxol and taxanes from Taxus using methanol or acetone | |
US5969165A (en) | Isolation and purification of paclitaxel and other related taxanes by industrial preparative low pressure chromatography on a polymeric resin column | |
CA2299149C (fr) | Procede d'isolation et de purification du paclitaxel a partir de sources naturelles | |
US5453521A (en) | Process for obtaining 10-deacetylbaccatin III | |
WO1997009443A1 (en) | PROCESS FOR THE ISOLATION AND PURIFICATION OF TAXOL AND TAXANES FROM TAXUS spp | |
CN1150179C (zh) | 一种从红豆杉类植物的可再生部分中分离10-脱乙酰浆果赤霉素iii的方法 | |
JPH10504727A (ja) | イチイ属植物からのタキソールの大量生産方法 | |
US7169307B2 (en) | Process for the extraction of paclitaxel and 9-dihydro-13-acetylbaccatin III from Taxus | |
JP4563994B2 (ja) | 天然資源からのパクリタキセルの改良された単離及び精製方法 | |
KR100259396B1 (ko) | 택서스속 식물체로부터 택솔의 대량 추출 정제방법 | |
KR100259395B1 (ko) | 택서스속 식물체로부터 택솔의 대량 추출 정제방법 | |
RU2373198C2 (ru) | СПОСОБЫ ПОЛУЧЕНИЯ ПАКЛИТАКСЕЛА ИЗ РАСТЕНИЙ РОДА Taxus | |
CA2258066C (en) | Isolation and purification of paclitaxel, and other related taxanes by industrial preparative low pressure chromatography on a polymeric resin column | |
KR0150339B1 (ko) | 분별침천에 의한 텍서스속 식물체로 부터 택솔의 정제방법 | |
CZ200070A3 (cs) | Izolace a čištění paclitaxelu a dalších příbuzných taxanů průmyslovou preparativní nízkotlakou chromatografií na polymerních kolonách |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee |
Owner name: AVENTIS PHARMA S.A. Free format text: FORMER NAME OR ADDRESS: RHONE-POULENC RORER S.A. |
|
CP03 | Change of name, title or address |
Address after: French Anthony Patentee after: Awentis Pharmaceutical S. A. Address before: French Anthony Patentee before: Rhone-Poulenc Rorer S. A. |
|
C17 | Cessation of patent right | ||
CX01 | Expiry of patent term |
Expiration termination date: 20130421 Granted publication date: 19990602 |