达托霉素分离纯化工艺-研究

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1、摘要在0．5mLAbstractDaptomycinisanovellipopeptideantibioticwhichhasin-vitroactivityagainstgram-positivemicroorganisms，especiallytheantibiotic—resistantbacteriasuchasStaphvlococcusaureus(MRSA)，andvancomycin-resistantenterococci(VRE)．Asthedrug—resistanceofbacteriaisincreasinglyserious，theadvan

2、tagesofclinicalapplicationofdaptomycinaremoreremarkable．Atpresent，thedomesticproductionofdaptomycinisgreatlyrestrictedbythehighproductioncost，wheredownstreampurificationoccupiesaconsiderableproportion．Thusithasimportantsignificancetoseparatedaptomycinfromthefermentationbroth．Inthisstudy，

3、theadsorptionbehaviorsofHZ816resintowardsdaptomycinintheaqueoussolutionwereinvestigated．TheequilibriumdatawerefittedbyLangumuirmodelandFreundlichmodelunderdifferenttemperatures，respectively,andthevaluesofadsorptionthermodynamicparameterswerealsoobtained．TheresultsshowedthatFreundlichisot

4、hermswerefoundtobethebestmodeltofitthemeasuredadsorptiondata．Fromthepositivevaluesofboth△日andASobtained．itissuggestedallendothermicreactionandanincreaseinrandomnessatthesolid-liquidinterfaceduringtheadsorptionofdaptomycinontotheresin．Besides，the△Gvalueswereallnegativeindicatingitwasaspon

5、taneousadsorptionprocess．Thepseudofirst-orderandpseudosecond-orderkineticmodelswereappliedtodescribethekineticsofadsorptionprocess，andthehomogeneousparticlediffusionmodelandtheshellprogressivemodelwereusedtodefinethecontrollingmechanismoftheoveralladsorptionprocess．Theresultsshowthatthek

6、ineticdataarewelldescribedbythepseudosecond-orderkineticmodelandparticlediffusionwastherate-limitingstepinthedaptomycinadsorptionprocess．Finally,thepurificationandisolationprocessofdaptomycinwasdetermined．Thefermentationbrothwerepurifiedusingcentrifugationfollowedbyorganicsolventextracti

7、on，macroporousresinabsorptionandionexchangechromatography．Abs仃actFinally,thepurityofdaptomycinwasincreasedfrom3％to87．89％．The目录第一章绪论⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯l1．1达托霉素概述⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯．11．1．1达托霉素结构和性质⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯．31．1．2达托霉素作用机理⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯41．1．