硕士论文-从催吐萝芙木中提取利血平的工艺研究

上海交通大学硕士学位论文从催吐萝芙木中提取利血平的工艺研究姓名：孙蕾申请学位级别：硕士专业：微生物与生化药学指导教师：赵凤生20080128–————————————————————————————————————HZ-81898.4%29.8%660.6%~74.3%–————————————————————————————————————ABSTRACTReserpine,asignificantalkaloid,actssteadilyandlastinglyforhypertensiontherapy.Traditionalmethodofreserpinepurificationtookbenzeneasextractionsolvent,whichledtoalowrecoveryyieldandsevereenvironmentpollution.Thepaperimprovedthepurificationmethodofreserpine.AcidicwatercontainingethanolwasappliedtoextractreserpinefromRauvolfiavomitoria.HZ-818macroporousresinwasusedtoadsorbreserpineforpurification.Theconditionsofadsorptionanddesorptionwereinvestigated.Moreover,variousfactorsaffectingreserpinecrystallizationwerestudiedandthepurificationprocessinlaboratoryscalewasdetermined.ReserpinewasextractedfromRauvolfiavomitoria,thenitwaspurifiedthroughaprocessincludingadsorptionanddesorptionwithresin,precipitationofalkaloids,dissolutionofprecipitation,sedimentationofgum,crystallizationandrecrystallization.Thepurityofobtainedreserpinewas98.4%.Totalrecoveryyieldwas29.8%.AccordingtothepurificationprocessofreserpinefromRauvolfiavomitoriainlaboratoryscale,pilotexperimentofreserpinepurificationwasstudiedtoachieveastableandhigh-recoveringpurificationprocess.Therecoveryyieldsofsuccessive6experimentswere60.6~74.3%.ThequalityofreserpinewascheckedaccordingtoChinesePharmacopoeiaandwasuptostandards.Thepurificationprocessissuperiortothetraditionalpurificationprocesswithbenzene.Itissuitabletoindustrialproductionofreserpine.Keywords:Rauvolfiavomitoria,reserpine,alkaloid,purification2008120___√√20081202008120–————————————————————————————————————111.1[1]19751.1.1RauvolfiaLour.Baill.[2]1359423[3]–————————————————————————————————————2RauvolfiaverticillataLour.Baill.R.serpentinaL.BenthR.yunnanensisTsiangR.vomitoriaAfzelR.verti-cillatavar.hainanensis[4,5]13m34312cm13cm0.51.0cm51018mm510mm5mm2104[6,7]1-11-21-11-2Fig.1-1TherootofRauvolfiaFig.1-2ThefruitsofRauvolfia–————————————————————————————————————3[8]1952Muller[9][10][11][12]19701980GAP[13]19652070[6][1]–————————————————————————————————————41.1.2[14]21301200mm80%85%9001600m45cm070%30cm50%60%[4]1.1.3[3][15~17]reserpineyohimbinequebrachinerescinnaminecanescineraunescineserpentitinerauwolfiaA[18,19]β-β-sitosterolpKa10.411.0–————————————————————————————————————5pKa8.158.30ajmalicinerauwolfinepKa6.07.5[20,21]1%2%2515mm0.570%155mm0.463%51.5mm0.452%[22]1-3[23]1-31-3FDANHNHHOOCH3HOOCH3OCH3OCH3OH3COH3COHHHNNOHHHCH3HHCH3HONHNOHH3COOCHHH1-3Fig.1-3Molecularstructureofreserpine,ajmalineandyohimbine–————————————————————————————————————61.1.410[24]80[4][12][11][24][25][20][26]–————————————————————————————————————71.1.5[27]RauwolfiaserpentineBenth.[28,29]20506080SHRSHRSP2050150.51.0mg/kg210mg/kgα1958——[2]–————————————————————————————————————81.1.62060[30]1-4[31,32]0.1%312h30minpH6pH3pH9102-3401-4Fig.1-4PurificationprocessoftotalalkaloidsinRauwolfia–————————————————————————————————————9[33]pH17.92%1.220——0500kg25002000kg1.2.118-345-[34,35][36]5-[37,38]C33H10N2O9608.681-3pH21202hpH8.511520min30%–————————————————————————————————————10264265αD-118°[39][4042][43]1.2.21.2.2.1[44,45]–————————————————————————————————————111.2.2.25-[46]1.2.2.317-1.2.2.4LD5015.75mg/kg[22]–————————————————————————————————————121.2.3[3]1952Muller2021500kg23t2200t3050t197019802030/kg–————————————————————————————————————131.2.4[47,48]1-55h601g8ml1.5ml6ml1g100ml1-5Fig.1-5Traditionalpurificationprocessofreserpine5h–————————————————————————————————————14[49]1.3[13]1.4–————————————————————————————————————1522.12.1.1Aglient1100SeriesAglientΦ15mm×200mmΦ10mm×150mmΦ11mm×35mmΦ35mm×600mmSHB-RE-2000TGL-16RO-M-150CAT.No.1290Lab-LineHZQ-QAB-204N-YP600SCQ250–————————————————————————————————————16N-3000100µl2.1.22-12Φ160cm×280cm2Φ140cm×103cm3Φ120cm×200cm4Φ100cm×130cm2Φ60cm×100cm2Φ20cm×150cm1Φ15cm×97cm3Φ90cm×70cm1Φ75cm×45cm1R-22010L1BÜCHIRotavapor101A-41LC-2010AHT1Kromasil100-5C184.6mm×250mm5µm–————————————————————————————————————17crushingmachineextractiontankΦ160cm×280cmstoragetankΦ140cm×103cmstoragetankΦ120cm×200cmconcentratorΦ100cm×130cm–————————————————————————————————————18resincolumnconcentratorΦ60cm×100cmΦ20cm×150cmΦ15cm×97cmstirredtankΦ90cm×70cmcentrifugeΦ75cm×45cm–————————————————————————————————————19R-220R-220rotaryevaporator101A-4101A-4dryerLC-2010AHTLC-2010AHTHPLC2-1Fig.2-1Mainequipmentinpilotplant2.22.2.1sigma-aldrich–————————————————————————————————————20XAD-4HP-20H-103CPD-820SIPI-1300SIPI-101HZ-801HZ-8182.2.2caledonHZ-818–————————————————————————————————————212.32.3.12.3.1.1ZORBAXSB-C184.6mm×250mm5µm-H2O-72280.011.0ml/min267nm30sigma-aldrich15.7mg1ml10ml31.4µg/ml62.8µg/ml94.2µg/ml125.6µg/ml157.0µg/ml20µlYX2.3.1.28000r/min5min20µl2.3.22.3.2.1400g400ml4000ml50%0.05mol/LH2SO44h0.142mg/ml2.3.2.231mol/LNaOH50%1mol/LHCl–————————————————————————————————————222.3.2.383ml10mm3.81300ml0.50.6ml/min10ml3ml/min30ml-991pH1.00.50.6ml/min2.3.2.46HZ-8183ml10mm3000ml615pH4.05.06.07.08.00.50.6ml/min10ml3ml/min2.3.2.5HZ-8183ml10mm300ml10ml3ml/minpH1.00.50.6ml/minmg/ml=/%=/×100%2.3.2