CN1791590A - Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins - Google Patents
Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins Download PDFInfo
- Publication number
- CN1791590A CN1791590A CN 200480013498 CN200480013498A CN1791590A CN 1791590 A CN1791590 A CN 1791590A CN 200480013498 CN200480013498 CN 200480013498 CN 200480013498 A CN200480013498 A CN 200480013498A CN 1791590 A CN1791590 A CN 1791590A
- Authority
- CN
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- Prior art keywords
- taxol
- taxols
- mixture
- described method
- extract
- Prior art date
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- 239000011347 resin Substances 0.000 title claims abstract description 106
- 229920005989 resin Polymers 0.000 title claims abstract description 106
- 239000000203 mixture Substances 0.000 title claims description 81
- 229940123237 Taxane Drugs 0.000 title abstract description 13
- 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 title abstract description 5
- 238000000746 purification Methods 0.000 title description 25
- 238000000034 method Methods 0.000 claims abstract description 129
- 239000000463 material Substances 0.000 claims abstract description 61
- -1 taxane compound Chemical class 0.000 claims abstract description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 27
- 229930012538 Paclitaxel Natural products 0.000 claims description 276
- 229960001592 paclitaxel Drugs 0.000 claims description 255
- 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 claims description 246
- 150000004579 taxol derivatives Chemical class 0.000 claims description 74
- 239000000284 extract Substances 0.000 claims description 59
- 241001674343 Taxus x media Species 0.000 claims description 31
- 229920002873 Polyethylenimine Polymers 0.000 claims description 27
- 241001116498 Taxus baccata Species 0.000 claims description 24
- DBXFAPJCZABTDR-WBYYIXQISA-N cephalomannine Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)C(=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@H](O)[C@@H](NC(=O)C(/C)=C/C)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 DBXFAPJCZABTDR-WBYYIXQISA-N 0.000 claims description 18
- 238000011084 recovery Methods 0.000 claims description 18
- 238000006257 total synthesis reaction Methods 0.000 claims description 18
- DBXFAPJCZABTDR-KUEXGRMWSA-N Cephalomannine Natural products O=C(O[C@@H]1C(C)=C2[C@@H](OC(=O)C)C(=O)[C@]3(C)[C@@H](O)C[C@@H]4[C@](OC(=O)C)([C@H]3[C@H](OC(=O)c3ccccc3)[C@@](O)(C2(C)C)C1)CO4)[C@@H](O)[C@H](NC(=O)/C(=C\C)/C)c1ccccc1 DBXFAPJCZABTDR-KUEXGRMWSA-N 0.000 claims description 16
- 239000000088 plastic resin Substances 0.000 claims description 15
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- 241001149649 Taxus wallichiana var. chinensis Species 0.000 claims description 11
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- 239000000126 substance Substances 0.000 claims description 10
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 8
- 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 description 5
- BEHTXUBGUDGCNQ-IEAAAIHOSA-N taxol c Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)C(=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@H](O)[C@@H](NC(=O)CCCCC)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 BEHTXUBGUDGCNQ-IEAAAIHOSA-N 0.000 claims description 5
- 229960003668 docetaxel Drugs 0.000 claims description 4
- SXPIMOCRRJUHJY-MNLIZOKASA-N taxcultine Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)C(=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@H](O)[C@@H](NC(=O)CCC)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 SXPIMOCRRJUHJY-MNLIZOKASA-N 0.000 claims description 4
- 241000015728 Taxus canadensis Species 0.000 claims description 3
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- 125000003277 amino group Chemical group 0.000 claims description 2
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- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 39
- 239000000377 silicon dioxide Substances 0.000 abstract description 18
- 239000007787 solid Substances 0.000 abstract description 12
- 239000011159 matrix material Substances 0.000 abstract description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
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- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
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- 125000003118 aryl group Chemical group 0.000 description 9
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
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- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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Images
Landscapes
- Epoxy Compounds (AREA)
Abstract
Description
Fraction | Beginning | Finish | Total time | Filling area % | Filling quality (mg) |
1 | 6:15 | 15:00 | 8:45 | 10.73 | 12.2 |
2 | 15:00 | 15:15 | 0:15 | 74.95 | 96.4 |
3 | 15:15 | 16:30 | 1:15 | 95.43 | 995.0 |
4 | 16:30 | 29:00 | 12:30 | 99.25 | 4284.6 |
5 | 29:00 | 35:15 | 6:15 | 100.00 | 555.3 |
Summation | 5943.4mg |
Claims (48)
- One kind from the mixture that contains taxol the segregation one or more taxols method, said method comprising the steps of:(a) with the described mixture of PBS plastic resin treatment; Wherein said one or more taxols derive from one or more Chinese yews, and wherein said one or more taxols not only derive from yewtree;(b) with elutriant described one or more taxols of wash-out from the PBS resin; With(c) one or more taxols of recovery institute wash-out.
- One kind from the mixture that contains taxol the segregation one or more taxols method, said method comprising the steps of:(a) with the described mixture of PBS plastic resin treatment; Wherein said mixture comprises and is lower than 25 weight % or greater than the elementary taxol of 40 weight %;(b) with elutriant described one or more taxols of wash-out from the PBS resin; With(c) one or more taxols of recovery institute wash-out.
- One kind the segregation one or more taxols method, this method may further comprise the steps:(a) contain the mixture of taxol with the PBS plastic resin treatment; Wherein said mixture comprises the elementary taxol of about 25 weight %~40 weight %; Wherein said one or more taxols not only derive from yewtree;(b) described one or more taxols of wash-out from the PBS resin; With(c) one or more taxols of recovery institute wash-out.
- 4. one kind from the method by one or more taxols of segregation semi-synthetic or the material that comprises taxol compound that total synthesis method obtains, and described isolation process may further comprise the steps:(a) with the described material of PBS plastic resin treatment; The molecule that wherein is used as reactant in semi-synthetic or total synthesis method not only derives from yewtree;(b) described one or more taxols of wash-out from the PBS resin; With(c) one or more taxols of recovery institute wash-out.
- 5. one kind from the method by one or more taxols of segregation semi-synthetic or the material that comprises taxol compound that total synthesis method obtains, and described isolation process may further comprise the steps:(a) with the described material of PBS plastic resin treatment; Wherein said material comprises the C-2 ' benzoic ether that total content is lower than taxol A, B, C, D, E, F or the G of about 8 weight %;(b) described one or more taxols of wash-out; With(c) one or more taxols of recovery institute wash-out.
- 6. one kind from the method by one or more taxols of segregation semi-synthetic or the material that comprises taxol compound that total synthesis method obtains, said method comprising the steps of:(a) with the described material of PBS plastic resin treatment; Wherein said material comprises the C-2 ' benzoic ether that total content is lower than taxol B, C, D, E, F or the G of 1.0 weight %;(b) described one or more taxols of wash-out; With(c) one or more taxols of recovery institute wash-out.
- 7. the method for a segregation taxol A from the mixture that contains natural deutero-taxol said method comprising the steps of:(a) with the described taxol mixture of PBS plastic resin treatment;(b) wash-out taxol A from the PBS resin; With(c) the taxol A of recovery institute wash-out.
- 8. method of one or more taxols of purifying from bio-extract said method comprising the steps of:(a) prepare bio-extract with the method except that chromatography;(b) with the described bio-extract of PBS plastic resin treatment;(c) described one or more taxols of wash-out from the PBS resin; With(d) one or more taxols of recovery institute wash-out.
- 9. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from Taxus x media cultivation mutation.
- 10. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from this Taxus x media of west.
- 11. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from general dark green Taxus x media.
- 12. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from European yew.
- 13. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from taxus chinensis in northeast.
- 14. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from the Florida Ramulus et folium taxi cuspidatae.
- 15. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from T. canadensis.
- 16. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from Xizang Taxus chinensis.
- 17. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from taxusyunnanensis.
- 18. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from Chinese Ramulus et folium taxi cuspidatae.
- 19. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from the Deng Sifumi Taxus x media.
- 20. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from the Brownie Taxus x media.
- 21. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from this Taxus x media of west.
- 22. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from blue handsome Taxus x media.
- 23. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from the Sarasvati Taxus x media.
- 24. as each described method of claim 1~3, wherein, the described mixture that contains taxol comprises the bio-extract that derives from the Dao Tuoni Taxus x media.
- 25., wherein, be taxol A by isolating described taxol as each described method of claim 4~6.
- 26., wherein, be taxol B by isolating described taxol as each described method of claim 4~6.
- 27., wherein, be taxol C by isolating described taxol as each described method of claim 4~6.
- 28., wherein, be taxol D by isolating described taxol as each described method of claim 4~6.
- 29., wherein, be taxol E by isolating described taxol as each described method of claim 4~6.
- 30., wherein, be taxol F by isolating described taxol as each described method of claim 4~6.
- 31., wherein, be taxol G by isolating described taxol as each described method of claim 4~6.
- 32., wherein, be Docetaxel by isolating described taxol as each described method of claim 4~6.
- 33. as each described method of claim 1~8, wherein said PBS resin has about 60 mean pore sizes to about 300 scopes.
- 34. as each described method of claim 1~8, wherein said PBS resin has about 100 mean pore sizes to about 200 scopes.
- 35. as each described method of claim 1~8, wherein said PBS resin has the mean pore size of about 120 .
- 36. as each described method of claim 1~8, wherein said PBS resin has about 0.25 median size to about 500 mu m ranges.
- 37. as each described method of claim 1~8, wherein said PBS resin has the median size in 1~100 mu m range.
- 38. as each described method of claim 1~8, wherein said PBS resin has about 10 median sizes to about 120 mu m ranges.
- 39. as each described method of claim 1~8, wherein said PBS resin has about 20 median sizes to about 60 μ m.
- 40. as each described method of claim 1~8, wherein said PBS resin has the median size of about 40 μ m.
- 41. as each described method of claim 1~13, wherein said PBS resin is DEAM.
- 42. as each described method of claim 1~8, wherein said PBS resin is PEI.
- 43. as each described method of claim 1~8, wherein said PBS resin has about 60 mean pore sizes to about 800 scopes.
- 44. as each described method of claim 1~8, wherein said PBS resin has primary amino or secondary amino group on the polyethyleneimine: amine moiety.
- 45. as each described method of claim 1~8, the amino of wherein said PEI polymkeric substance functionalised.
- 46. as each described method of claim 4~6, wherein described one or more taxols of institute's wash-out have the purity at least about 70%.
- 47. as each described method of claim 4~6, wherein described one or more taxols of institute's wash-out have the purity at least about 80%.
- 48. as each described method of claim 4~6, wherein described one or more taxols of institute's wash-out have the purity at least about 90%.
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US45537703P | 2003-03-17 | 2003-03-17 | |
US60/455,377 | 2003-03-17 | ||
US60/456,478 | 2003-03-21 | ||
US10/664,539 | 2003-09-18 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102219764A (en) * | 2011-05-12 | 2011-10-19 | 河南省科学院化学研究所有限公司 | Method for separating and purifying paclitaxel industrially |
CN106943985A (en) * | 2017-04-11 | 2017-07-14 | 南昌大学 | Preparation method for the amino modified mesoporous silicon oxide of separating and purifying taxol |
CN110531000A (en) * | 2019-09-20 | 2019-12-03 | 杭州师范大学 | It is a kind of for distinguishing the metabolic markers and its detection method of pseudotaxus chienii and taxusyunnanensis |
Families Citing this family (1)
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CN108101869A (en) * | 2017-12-20 | 2018-06-01 | 上海金和生物制药有限公司 | A kind of extracting method of natural Japanese yew alcohol |
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US5475120A (en) * | 1990-11-02 | 1995-12-12 | University Of Florida | Method for the isolation and purification of taxol and its natural analogues |
EP1051505B1 (en) * | 1998-01-26 | 2003-05-28 | Man Woo Han | Process of extracting taxol from taxus cuspidata |
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 |
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2004
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102219764A (en) * | 2011-05-12 | 2011-10-19 | 河南省科学院化学研究所有限公司 | Method for separating and purifying paclitaxel industrially |
CN102219764B (en) * | 2011-05-12 | 2013-06-26 | 河南省科学院化学研究所有限公司 | Method for separating and purifying paclitaxel industrially |
CN106943985A (en) * | 2017-04-11 | 2017-07-14 | 南昌大学 | Preparation method for the amino modified mesoporous silicon oxide of separating and purifying taxol |
CN110531000A (en) * | 2019-09-20 | 2019-12-03 | 杭州师范大学 | It is a kind of for distinguishing the metabolic markers and its detection method of pseudotaxus chienii and taxusyunnanensis |
CN110531000B (en) * | 2019-09-20 | 2022-07-12 | 杭州师范大学 | Metabolism marker for distinguishing white bean Chinese yew and taxus yunnanensis and detection method thereof |
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AR103853A2 (en) | 2017-06-07 |
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