CA2516811C - Improved process for isolation and purification of paclitaxel from natural sources - Google Patents
Improved process for isolation and purification of paclitaxel from natural sources Download PDFInfo
- Publication number
- CA2516811C CA2516811C CA002516811A CA2516811A CA2516811C CA 2516811 C CA2516811 C CA 2516811C CA 002516811 A CA002516811 A CA 002516811A CA 2516811 A CA2516811 A CA 2516811A CA 2516811 C CA2516811 C CA 2516811C
- Authority
- CA
- Canada
- Prior art keywords
- paclitaxel
- solution
- acetone
- process according
- mixture
- 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 - Fee Related
Links
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 175
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 175
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 175
- 238000000034 method Methods 0.000 title claims abstract description 64
- 238000000746 purification Methods 0.000 title claims abstract description 24
- 238000002955 isolation Methods 0.000 title claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 185
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 239000002028 Biomass Substances 0.000 claims abstract description 48
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 38
- 238000002425 crystallisation Methods 0.000 claims abstract description 35
- 239000002904 solvent Substances 0.000 claims abstract description 34
- 230000008025 crystallization Effects 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000002994 raw material Substances 0.000 claims abstract description 30
- 229940123237 Taxane Drugs 0.000 claims abstract description 16
- 238000000605 extraction Methods 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 238000001556 precipitation Methods 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 11
- 239000000049 pigment Substances 0.000 claims abstract description 11
- 239000011347 resin Substances 0.000 claims abstract description 11
- 229920005989 resin Polymers 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000012535 impurity Substances 0.000 claims abstract description 8
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002798 polar solvent Substances 0.000 claims abstract description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 159
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 60
- 239000013078 crystal Substances 0.000 claims description 54
- 239000000741 silica gel Substances 0.000 claims description 54
- 229910002027 silica gel Inorganic materials 0.000 claims description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 24
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 24
- 238000010828 elution Methods 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 238000005119 centrifugation Methods 0.000 claims description 17
- 238000001914 filtration Methods 0.000 claims description 17
- 235000002639 sodium chloride Nutrition 0.000 claims description 16
- 238000009423 ventilation Methods 0.000 claims description 14
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 241001116500 Taxus Species 0.000 claims description 11
- 238000001704 evaporation Methods 0.000 claims description 9
- 239000012454 non-polar solvent Substances 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- WPPPFZJNKLMYBW-FAEUQDRCSA-N 13-acetyl-9-dihydrobaccatin iii Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)[C@H](O)[C@]3(C)[C@@H](O)C[C@H]4OC[C@]4([C@H]31)OC(C)=O)C2(C)C)C)OC(=O)C)C(=O)C1=CC=CC=C1 WPPPFZJNKLMYBW-FAEUQDRCSA-N 0.000 claims description 7
- FFCWRLFQIKDRNO-UHFFFAOYSA-N 9-dihydro-13-acetyl baccatin III Natural products CC(=O)OC1C2C(O)CC(OC(=O)C)C3(CO3)C2C(OC(=O)C)C4(O)CC(OC(=O)C)C(=C(C1OC(=O)C)C4(C)C)C FFCWRLFQIKDRNO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003570 air Substances 0.000 claims description 7
- 230000003381 solubilizing effect Effects 0.000 claims description 7
- 241000218631 Coniferophyta Species 0.000 claims description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- 239000012156 elution solvent Substances 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 239000012080 ambient air Substances 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 2
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 244000162450 Taxus cuspidata Species 0.000 claims 2
- 235000009065 Taxus cuspidata Nutrition 0.000 claims 2
- 150000002576 ketones Chemical class 0.000 claims 2
- 241001249699 Capitata Species 0.000 claims 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- 241000202349 Taxus brevifolia Species 0.000 claims 1
- 241000015728 Taxus canadensis Species 0.000 claims 1
- 241001330459 Taxus wallichiana var. wallichiana Species 0.000 claims 1
- 238000004108 freeze drying Methods 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 63
- 229960001866 silicon dioxide Drugs 0.000 description 41
- 239000012071 phase Substances 0.000 description 28
- 238000011097 chromatography purification Methods 0.000 description 17
- 239000000499 gel Substances 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 14
- -1 chloromethylene Chemical group 0.000 description 7
- 229960004132 diethyl ether Drugs 0.000 description 7
- 239000011877 solvent mixture Substances 0.000 description 7
- 239000002245 particle Substances 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 229920000742 Cotton Polymers 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)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 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000005185 salting out Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 229930190007 Baccatin Natural products 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 101100467574 Mus musculus Mras gene Proteins 0.000 description 1
- 241001274197 Scatophagus argus Species 0.000 description 1
- WXYIONYJZVWSIJ-UHFFFAOYSA-N acetonitrile;methanol;hydrate Chemical compound O.OC.CC#N WXYIONYJZVWSIJ-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 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 1
- 230000029305 taxis Effects 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/375,474 US6759539B1 (en) | 2003-02-27 | 2003-02-27 | Process for isolation and purification of paclitaxel from natural sources |
| US10/375,474 | 2003-02-27 | ||
| PCT/CA2004/000107 WO2004076435A1 (en) | 2003-02-27 | 2004-01-27 | Improved process for isolation and purification of paclitaxel from natural sources |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2516811A1 CA2516811A1 (en) | 2004-09-10 |
| CA2516811C true CA2516811C (en) | 2009-04-14 |
Family
ID=32594996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002516811A Expired - Fee Related CA2516811C (en) | 2003-02-27 | 2004-01-27 | Improved process for isolation and purification of paclitaxel from natural sources |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6759539B1 (enExample) |
| EP (1) | EP1608636B1 (enExample) |
| JP (1) | JP4563994B2 (enExample) |
| KR (1) | KR101114982B1 (enExample) |
| CN (1) | CN1774431B (enExample) |
| AT (1) | ATE382613T1 (enExample) |
| CA (1) | CA2516811C (enExample) |
| DE (1) | DE602004011034T2 (enExample) |
| WO (1) | WO2004076435A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR054215A1 (es) * | 2006-01-20 | 2007-06-13 | Eriochem Sa | Una formulacion farmaceutica de un taxano, una composicion solida de un taxano liofilizado a partir de una solucion de acido acetico, un procedimiento para la preparacion de dicha composicion solida de un taxano, una composicion solubilizante de un taxano liofilizado, y un conjunto de elementos (kit |
| KR101455694B1 (ko) * | 2012-09-18 | 2014-11-03 | 학교법인 선목학원 | 에틸아세테이트 및 아세토니트릴의 유기용매 혼합액을 이용한 액체-액체 추출법을 포함하는 약물 검출법 |
| KR101381502B1 (ko) * | 2012-09-28 | 2014-04-04 | 공주대학교 산학협력단 | 파클리탁셀의 정제방법 |
| CN103877600B (zh) * | 2014-03-27 | 2017-04-05 | 沈祖鸿 | 含有红豆杉提取物的喷雾剂及其制造方法和制造配方 |
| CN104031008B (zh) * | 2014-06-30 | 2015-12-09 | 牛兆颖 | 一种紫杉醇粗提物的制备方法 |
| CN108101869A (zh) * | 2017-12-20 | 2018-06-01 | 上海金和生物制药有限公司 | 一种天然紫杉醇的提取方法 |
| CN109384749A (zh) * | 2018-12-26 | 2019-02-26 | 重庆市碚圣医药科技股份有限公司 | 一种紫杉醇的纯化方法 |
| CN110845451A (zh) * | 2019-11-28 | 2020-02-28 | 云南皓瑞逸生物科技有限公司 | 一种从红豆杉中提取紫杉醇的方法 |
| CN112521349B (zh) * | 2020-11-11 | 2023-04-07 | 福建齐衡科技有限公司 | 一种紫杉醇的纯化方法 |
| JP2023552685A (ja) * | 2020-11-16 | 2023-12-19 | ヘモテック アーゲー | 被覆された医療製品 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2601676B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
| FR2629818B1 (fr) | 1988-04-06 | 1990-11-16 | Centre Nat Rech Scient | Procede de preparation du taxol |
| US5019504A (en) | 1989-03-23 | 1991-05-28 | The United States Of America As Represented By The Secretary Of Agriculture | Production of taxol or taxol-like compounds in cell culture |
| US5175315A (en) | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
| MY110249A (en) | 1989-05-31 | 1998-03-31 | Univ Florida State | Method for preparation of taxol using beta lactam |
| US5015744A (en) | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
| US5136060A (en) | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
| US5475120A (en) | 1990-11-02 | 1995-12-12 | University Of Florida | Method for the isolation and purification of taxol and its natural analogues |
| US5380916A (en) | 1990-11-02 | 1995-01-10 | University Of Florida | Method for the isolation and purification of taxane derivatives |
| US5312740A (en) | 1991-02-12 | 1994-05-17 | Nippon Steel Corporation | Process for producing taxol by cell culture of taxus species |
| EP0580759B1 (en) | 1991-04-19 | 1999-05-26 | The University Of Mississippi | Methods and compositions for isolating taxanes |
| CA2072400C (en) | 1991-07-05 | 2003-08-19 | Jayaprakash B. Nair | Supercritical extraction of taxanes |
| IT1258838B (it) | 1992-01-31 | 1996-02-29 | Indena Spa | Processo per l'estrazione di tassolo e derivati da cultivar del genere taxus |
| US5445809A (en) | 1992-03-03 | 1995-08-29 | Research And Development Institute At Montana State University | Production of taxol from the yew tree |
| US5451392A (en) | 1992-03-03 | 1995-09-19 | The Research And Development Institute At Montana State University | Production of taxol |
| US5200534A (en) | 1992-03-13 | 1993-04-06 | University Of Florida | Process for the preparation of taxol and 10-deacetyltaxol |
| CA2092849C (en) | 1992-04-07 | 2003-11-18 | Paul M. Cino | Callus cell induction and the preparation of taxanes |
| US5322779A (en) | 1992-04-16 | 1994-06-21 | The Research And Development Institute, Inc. At Montana State University | Taxol production by taxomyces andreanae |
| DE69325454T2 (de) | 1992-04-17 | 2000-01-20 | Abbott Laboratories, Abbott Park | Taxol-derivate |
| GB9213077D0 (en) | 1992-06-19 | 1992-08-05 | Erba Carlo Spa | Polymerbound taxol derivatives |
| US5470866A (en) | 1992-08-18 | 1995-11-28 | Virginia Polytechnic Institute And State University | Method for the conversion of cephalomannine to taxol and for the preparation of n-acyl analogs of taxol |
| US5684169A (en) | 1992-11-27 | 1997-11-04 | Ensuiko Sugar Refining Co., Ltd. | Cyclodextrin inclusion complex of taxol, and method for its production and its use |
| US5380751A (en) | 1992-12-04 | 1995-01-10 | Bristol-Myers Squibb Company | 6,7-modified paclitaxels |
| US5279949A (en) * | 1992-12-07 | 1994-01-18 | Board Of Trustees Operating Michigan State University | Process for the isolation and purification of taxol and taxanes from Taxus spp |
| CA2126698A1 (en) * | 1992-12-07 | 1994-06-23 | Muraleedharan G. Nair | Process for the isolation and purification of taxol and taxanes from taxus spp. |
| EP1260507A1 (en) | 1993-02-05 | 2002-11-27 | Bryn Mawr College | Synthesis of taxol, analogs and intermediates with variable A-nng side chains |
| US5703247A (en) | 1993-03-11 | 1997-12-30 | Virginia Tech Intellectual Properties, Inc. | 2-Debenzoyl-2-acyl taxol derivatives and methods for making same |
| US5440055A (en) | 1993-03-12 | 1995-08-08 | Aphios Corporation | Method and apparatus for extracting taxol from source materials |
| US5516676A (en) | 1993-06-15 | 1996-05-14 | Bristol-Myers Squibb Company | Preparation of C-13 hydroxyl-bearing taxanes using nocardioides or a hydrolase isolated therefrom |
| US5405972A (en) | 1993-07-20 | 1995-04-11 | Florida State University | Synthetic process for the preparation of taxol and other tricyclic and tetracyclic taxanes |
| EP1054065B1 (en) | 1993-11-15 | 2002-07-31 | Mitsui Chemicals, Inc. | A method of producing a taxane-type diterpene and method of obtaining cultured cells which produce the taxane-type diterpene at a high rate |
| US5508447A (en) | 1994-05-24 | 1996-04-16 | Board Of Regents, The University Of Texas System | Short synthetic route to taxol and taxol derivatives |
| US5616330A (en) | 1994-07-19 | 1997-04-01 | Hemagen/Pfc | Stable oil-in-water emulsions incorporating a taxine (taxol) and method of making same |
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| US5780653A (en) | 1995-06-07 | 1998-07-14 | Vivorx Pharmaceuticals, Inc. | Nitrophenyl, 10-deacetylated substituted taxol derivatives as dual functional cytotoxic/radiosensitizers |
| FR2736355B1 (fr) * | 1995-07-07 | 1997-11-07 | Pf Medicament | Procede d'extraction et d'isolement de la 10-desacetylbaccatine iii |
| US5760251A (en) | 1995-08-11 | 1998-06-02 | Sepracor, Inc. | Taxol process and compounds |
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| US5756536A (en) | 1995-11-03 | 1998-05-26 | Purdue Research Foundation | Microbial transformation of taxol and cephalomannine |
| US5767297A (en) | 1997-02-05 | 1998-06-16 | Ensuiko Sugar Refining Co., Ltd. | Taxoid derivative and method of producing thereof |
| US5795909A (en) | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
| US5773629A (en) | 1996-06-14 | 1998-06-30 | Industrial Technology Research Institute | Synthesis of (4S, 5R) -2, 4-diphenyl-5-carboxy-oxazoline derivative as taxol side-chain precursor |
| US5750737A (en) | 1996-09-25 | 1998-05-12 | Sisti; Nicholas J. | Method for paclitaxel synthesis |
| US5739359A (en) | 1997-01-24 | 1998-04-14 | Virginia Tech Intellectual Properties, Inc. | Methods for preparing 1-deoxy paclitaxels |
| 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 |
| CA2299149C (fr) * | 1999-06-22 | 2010-09-21 | Chaichem Pharmaceuticals International | Procede d'isolation et de purification du paclitaxel a partir de sources naturelles |
| US6452024B1 (en) * | 2000-02-22 | 2002-09-17 | Chaichem Pharmaceuticals International | Process for extraction and purification of paclitaxel from natural sources |
-
2003
- 2003-02-27 US US10/375,474 patent/US6759539B1/en not_active Expired - Fee Related
-
2004
- 2004-01-27 CA CA002516811A patent/CA2516811C/en not_active Expired - Fee Related
- 2004-01-27 DE DE602004011034T patent/DE602004011034T2/de not_active Expired - Lifetime
- 2004-01-27 CN CN2004800097904A patent/CN1774431B/zh not_active Expired - Fee Related
- 2004-01-27 EP EP04705360A patent/EP1608636B1/en not_active Expired - Lifetime
- 2004-01-27 KR KR1020057015967A patent/KR101114982B1/ko not_active Expired - Fee Related
- 2004-01-27 JP JP2006501397A patent/JP4563994B2/ja not_active Expired - Fee Related
- 2004-01-27 WO PCT/CA2004/000107 patent/WO2004076435A1/en not_active Ceased
- 2004-01-27 AT AT04705360T patent/ATE382613T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ATE382613T1 (de) | 2008-01-15 |
| DE602004011034T2 (de) | 2009-02-12 |
| KR101114982B1 (ko) | 2012-03-06 |
| CN1774431A (zh) | 2006-05-17 |
| EP1608636A1 (en) | 2005-12-28 |
| KR20050114627A (ko) | 2005-12-06 |
| EP1608636B1 (en) | 2008-01-02 |
| HK1087109A1 (en) | 2006-10-06 |
| JP4563994B2 (ja) | 2010-10-20 |
| WO2004076435A1 (en) | 2004-09-10 |
| CN1774431B (zh) | 2011-03-23 |
| JP2006519184A (ja) | 2006-08-24 |
| US6759539B1 (en) | 2004-07-06 |
| DE602004011034D1 (de) | 2008-02-14 |
| CA2516811A1 (en) | 2004-09-10 |
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| EEER | Examination request | ||
| MKLA | Lapsed |
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