CN102675426B - 一种达托霉素的提取纯化方法 - Google Patents
一种达托霉素的提取纯化方法 Download PDFInfo
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- CN102675426B CN102675426B CN2012101250753A CN201210125075A CN102675426B CN 102675426 B CN102675426 B CN 102675426B CN 2012101250753 A CN2012101250753 A CN 2012101250753A CN 201210125075 A CN201210125075 A CN 201210125075A CN 102675426 B CN102675426 B CN 102675426B
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- daptomycin
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- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 title claims abstract description 126
- 108010013198 Daptomycin Proteins 0.000 title claims abstract description 125
- 229960005484 daptomycin Drugs 0.000 title claims abstract description 125
- 238000000034 method Methods 0.000 title claims abstract description 73
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 40
- 238000010828 elution Methods 0.000 claims description 34
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 34
- 238000004587 chromatography analysis Methods 0.000 claims description 33
- 239000007864 aqueous solution Substances 0.000 claims description 29
- 238000010521 absorption reaction Methods 0.000 claims description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 20
- 239000003480 eluent Substances 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 17
- 235000019253 formic acid Nutrition 0.000 claims description 17
- 238000001728 nano-filtration Methods 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 238000010606 normalization Methods 0.000 claims description 12
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 10
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- 239000000203 mixture Substances 0.000 claims description 6
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
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- HWUYMSFDCDZRHM-UHFFFAOYSA-N C(C)(=O)[O-].Cl[NH3+].[Na] Chemical compound C(C)(=O)[O-].Cl[NH3+].[Na] HWUYMSFDCDZRHM-UHFFFAOYSA-N 0.000 claims description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 10
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
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- 239000006210 lotion Substances 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
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- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- 108010028921 Lipopeptides Proteins 0.000 description 3
- 241000933218 Streptomyces parvus Species 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
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- 150000001450 anions Chemical class 0.000 description 3
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- 150000001413 amino acids Chemical class 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
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- 238000011210 chromatographic step Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
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- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- 239000006035 Tryptophane Substances 0.000 description 1
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- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 1
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- 229960004799 tryptophan Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
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- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106866789A (zh) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | 一种分离纯化达托霉素rs-8杂质的方法 |
CN106866791A (zh) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | 一种高纯度达托霉素内酯水解物的制备方法 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105001305A (zh) * | 2015-04-29 | 2015-10-28 | 利穗科技(苏州)有限公司 | 利用层析技术提取高纯度达托霉素的方法 |
CN106518985A (zh) * | 2015-09-15 | 2017-03-22 | 江苏海阔生物医药有限公司 | 一种万古霉素沉淀方法 |
CN105111285A (zh) * | 2015-10-17 | 2015-12-02 | 霍进铭 | 一种达托霉素的提取方法 |
CN105481950B (zh) * | 2016-01-28 | 2019-01-04 | 丽珠集团福州福兴医药有限公司 | 一种达托霉素提取方法 |
CN112979756B (zh) * | 2019-12-13 | 2023-01-03 | 浙江昌海制药有限公司 | 达托霉素的提纯方法 |
CN114685610A (zh) * | 2020-12-28 | 2022-07-01 | 杭州中美华东制药有限公司 | 一种达托霉素RS-8a杂质的内酯水解物及制备方法 |
CN113563424B (zh) * | 2021-09-15 | 2023-03-28 | 丽珠集团福州福兴医药有限公司 | 一种达托霉素的纯化方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6696412B1 (en) * | 2000-01-20 | 2004-02-24 | Cubist Pharmaceuticals, Inc. | High purity lipopeptides, Lipopeptide micelles and processes for preparing same |
CN101070703B (zh) * | 2007-05-31 | 2010-06-16 | 李来友 | 一种在绿化地上的桩基施工法 |
PT2398817E (pt) * | 2009-02-19 | 2015-08-28 | Xellia Pharmaceuticals Aps | Processo para purificar lipopéptidos |
CN101830970B (zh) * | 2009-03-12 | 2012-06-27 | 成都雅途生物技术有限公司 | 一种高纯度达托霉素(Daptomycin)的纯化制备方法 |
CN101899094B (zh) * | 2009-06-01 | 2012-11-21 | 安徽丰原发酵技术工程研究有限公司 | 一种高纯达托霉素的制备方法 |
CN102276696B (zh) * | 2010-06-09 | 2014-11-05 | 上海来益生物药物研究开发中心有限责任公司 | 达托霉素的纯化方法 |
CN101899410B (zh) * | 2010-07-13 | 2012-05-16 | 杭州华东医药集团生物工程研究所有限公司 | 一种小链霉菌及其在达托霉素制备中的应用 |
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2012
- 2012-04-26 CN CN2012101250753A patent/CN102675426B/zh active Active
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106866789A (zh) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | 一种分离纯化达托霉素rs-8杂质的方法 |
CN106866791A (zh) * | 2015-12-11 | 2017-06-20 | 北大方正集团有限公司 | 一种高纯度达托霉素内酯水解物的制备方法 |
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