Extractive purification of lipopeptide antibiotics 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
EP1355920 A1 2003-10-29 [EP1355920]EP1355920 A4 2005-04-20 [EP1355920]EP1355920 B1 2008-07-30 [EP1355920]EP1355920 B9 2008-12-10 [EP1355920]EP1355920 B9 2008-12-10 [EP1355920] / 2003-10-292005-04-202008-07-302008-12-102008-12-10
申请号/申请日
2002EP-0705750 / 2002-01-10
发明人
BORDERS DONALD B;FRANCIS NOREEN D;FANTINI AMEDEO A;
申请人
MIGENIX;
主分类号
IPC分类号
A01N-037/46A61K-038/00B01D-011/04C07K-001/14C07K-007/08C07K-007/56C07K-009/00C07K-011/02C12P-001/04
摘要
(EP1355920) The present invention provides a rapid and inexpensive method for extractively isolating acidic lipopeptide antibiotics in high yield and purity.  The lipopeptide antibiotics, which can be cyclic depsipeptides or cyclic peptides, are extracted by contacting an aqueous solution of the lipopeptide antibiotic and a divalent metal ion with an organic solvent, and then contacting the organic solvent extract of the lipopeptide antibiotic with acid.  Alternatively, an acidic lipopeptide antibiotic is partitioned from an aqueous solution into an organic solvent and is then recovered from the organic solvent.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2001US-09760328 2001-01-12 2001US-09948374 2001-09-06 2001US-60286254 2001-04-24 2002WO-US00796 2002-01-10
主权利要求
(EP1355920)  1. A method for purifying an acidic lipopeptide antibiotic, said method comprising the steps of: (a) contacting an aqueous solution of an acidic lipopeptide antibiotic, at a pH above the isoelectric point of the lipopeptide antibiotic, and a divalent metal cation with an organic solvent, thereby extracting the acidic lipopeptide antibiotic into the organic solvent: and (b) contacting the organic solvent extract of the acidic lipopeptide antibiotic with acid, wherein the acidic lipopeptide antibiotic is not laspartomycin. 2. The method of Claim 1 in which the aqueous solution is a fermentation broth or a culture. 3. The method of Claim 1 wherein the lipopeptide antibiotic is a cyclic depsipeptide or a cyclic peptide. 4. The method of Claim 1 wherein the lipopeptide antibiotic is selected from zaomycin, crystallomycin, glumamycin, antibiotic A1437, and antibiotic A-54145. 5. The method of Claim 1 wherein the lipopeptide antibiotic is amphomycin 6.  The method of Claim 1 wherein the lipopetide antibiotic is tsushimycin. 7. The method of Claim 1 wherein the lipopeptide antibiotic is aspartocin. 8. The method of Claim 1 wherein the lipopeptide antibiotic is antibiotic A-21978C or daptomycin. 9. The method of Claim 1 wherein the pH of the aqueous solution of the lipopeptide antibiotic is adjusted to a basic pH. 10. The method of Claim 9 wherein the molar concentration of divalent cation relative to carboxylate groups in the lipopeptide antibiotic is between 4:1 and 10:1. 11. The method of Claim 1 further comprising an initial acidic precipitation step, wherein the pH of the aqueous solution is adjusted to an acidic pH and the aqueous solution is cooled to 4 deg.C. 12. The method of Claim 11 wherein the aqueous solution is and the centrifugate suspended in a second aqueous solution, wherein the second aqueous solution comprises a divalent cation and has a pH above the isoelectric point of said lipopeptide antibiotic. 13. The method of Claim 11 wherein the pH is adjusted to 2.0. 14. The method of Claim 12 wherein the molar concentration of divalent cation relative to carboxylate groups in the lipopeptide antibiotic in the second aqueous solution is between 4:1 and 10:1. 15. The method of Claim 14 wherein the pH of the second aqueous solution is adjusted to a basic pH. 16. The method of any one of Claims 9 or 15 wherein the adjusted pH is in the range of pH 8.0 to pH 9.0. 17. The method of any one of Claims 10 or 15 wherein the divalent cation is selected from Ca **2+,Mg **2+ and Zn **2+. 18. The method of Claim 1 further comprising: extracting the lipopeptide antiobiotic into a third aqueous solution;  extracting the lipopeptide antibiotic into a second organic solvent.;  extracting the lipopeptide antibiotic into a fourth aqueous solution;  and concentrating the fourth aqueous solution to provide a salt of the lipopeptide antibiotic. 19. The method of Claim 18, wherein the organic extract of the lipopeptide antibiotic is extracted into the third aqueous solution by washing with an aqueous base solution. 20. The method of Claim 18, wherein the third aqueous solution of the lipopetide antibiotic is extracted into the second organic solvent by acidifying the third aqueous solution of the lipopeptide antibiotic and contacting with the second organic solvent. 21. The method of Claim 18, wherein the salt of lipopeptide antibiotic is acidified to provide a free acid of lipopeptide antibiotic. 22. The method of Claim 21 in which the organic solvent and the second organic solvent is 1-butanol. 23. A method of isolating an acidic lipopeptide antibiotic according to claim 1, further comprising the step of: (c) contacting the acidified organic phase of step (b) with an aqueous solvent. 24. The method of Claim 23 wherein steps (a) through (c) are repeated. 25. The method of Claim 1 or 2 wherein the organic extract of the lipopeptide antibiotic is extracted with an aqueous base solution. 26. The method of Claim 25 wherein the aqueous solution is a fermentation broth and the lipopeptide antibiotic is amphomycin. 27. The method of any one of Claims 11 to 15 wherein the aqueous solution is fermentation broth.
法律状态
(EP1355920) LEGAL DETAILS FOR EP1355920  Actual or expected expiration date=2013-01-31    Legal state=DEAD    Status=LAPSED     Event publication date=2002-01-10  Event code=EP/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=EP EP02705750  Application date=2002-01-10  Standardized application number=2002EP-0705750     Event publication date=2003-10-29  Event code=EP/A1  Event type=Examination events  Application published with search report  Publication country=EP  Publication number=EP1355920  Publication stage Code=A1  Publication date=2003-10-29  Standardized publication number=EP1355920     Event publication date=2003-10-29  Event code=EP/17P  Event indicator=Pos  Event type=Examination events  Request for examination filed Pruefungsantrag gestellt  Effective date of the event=2003-07-31     Event publication date=2003-10-29  Event code=EP/AK  Event indicator=Pos  Event type=Designated states  Designated contracting states: Benannte vertragsstaaten AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR    Event publication date=2003-10-29  Event code=EP/AX  Event indicator=Pos  Event type=Designated states  Extension of the European patent to Request for extension of the european patent to AL LT LV MK RO SI    Event publication date=2005-01-26  Event code=EP/RIC1  Event type=Classification modifications  Event type=Corrections  Classification (correction) IPC: 7C 07K   7/08   A    Event publication date=2005-01-26  Event code=EP/RIC1  Event type=Classification modifications  Event type=Corrections  Classification (correction) IPC: 7C 07K   7/56   B    Event publication date=2005-01-26  Event code=EP/RIC1  Event type=Classification modifications  Event type=Corrections  Classification (correction) IPC: 7C 07K  11/02   B    Event publication date=2005-04-20  Event code=EP/A4  Event indicator=Pos  Event type=Examination events  Supplementary search report Ergaenzender recherchenbericht  Publication country=EP  Publication number=EP1355920  Publication stage Code=A4  Publication date=2005-04-20  Standardized publication number=EP1355920     Event publication date=2005-04-20  Event code=EP/A4  Event indicator=Pos  Event type=Administrative notifications  Supplementary search report Despatch of supplementary search report  Effective date of the event=2005-03-04     Event publication date=2005-11-23  Event code=EP/RAP1  Event type=Change of name or address  Event type=Reassignment  Transfer of rights of an application Anmelder uebertragung (korr.)    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