膜分离技术在制药工业中的应用

:1007-8924(2003)04-0180-07膜分离技术在制药工业中的应用谢全灵1何旭敏1*夏海平1蓝伟光1,2*(1.,361005;2.(),361009):膜分离技术在制药工业中的应用包括生物发酵制药中药生产和现代生物技术等.膜分离技术在抗生素半合成抗生素维生素和氨基酸生产中尤其常见.随着膜材料膜组件和膜设备的不断改进,膜分离技术在制药工业中将扮演越来越重要角色.:膜分离;抗生素;维生素;氨基酸;中药;生物技术:TQ028.8:A,.,,.,/.,.(1).3.表1制药生产中的膜分离过程(MF)\0.1Lm~0.1MPa(UF)10~100nm0.1~1MPa;,(NF)1~10nm0.5~1.5MPaDonna(RO)[1nm1~10MPa;1在生物发酵制药工业中的应用1.1.(0.1%~5%,),,.,,,.,pH,.,,.1.2,:2003-06-02::(1964-),,,,,,.*,:0592-2184520.234Vo1.23No.420038MEMBRANESCIENCEANDTECHNOLOGYAug.2003,,()100%.,,.(diafltration).,[1].,,,,.,[2].,.1.3.,,,..(),,;,[3].1.4..1.4.1.,.Adikane[4]G,98%.2.9,1.8,41%,.Ruiz[5]200002000,2,20g/L,6-APA.[6]30000Ultra-floC,2%~3%0.2%~013%,,85%90%.,Ultra-flo,,.B-,B-.Alves[7],,1500020000,,.6-APA(6-),7-ACA(7-)C,7-ADCA(7--3-).C,.,,.Schroen[8]7-ADCA-7-ADCA7-ADCA,,-7-ADCA7-ADCA..Danzig[9]6-APA,,,6-APA98.5%.[10]6-APA,6-APA99.6%,98%..[11]6-APA,6-APAmol85%90%,6-APA,4:#181#,6-APA,(2).表2采用纳滤膜浓缩前后结晶收率比较/(L#kg-1)/(Lg#mL-1)/%/%0.850003.593.11.040004.592,().Davies[12]()0.2LmDurapore.,,35.9L/m2#h,,,12.8L/m2#h,.Zhang[13]NP-1,,80000U/mL340000U/mL.NP-1,.[14].,,,.CA-NF-60,4000Lm/mL40000Lm/mL,10Lm/mL.Hooper[15]0.45LmDurapore.,,.(DMCT),7,,,.MorÃo[16]100000PVDF(DMCT),,,DMCT,DMCT,.1.4.2,BC.,VB12()VB12.))),,VB12.,,.VB12.Crespo[17]VB12,,,,.,(CSTR)17.Bainotti[18])))(UAFR)VB12.,.,VB125.1mg/g,UAFR0.20g/L#h,(0.035g/L#h)6.Vc[19].Vc,.[20]Ultra-floVc,,,.,99%,.Ultra-floVc.1.4.35:,..#182#23[21]Ultra-flo.,,97%.:1),;2);3).L-,,80%~90%[22],AgarwalHuang[23],L-.,pHL-.pH,L--10%~90%.L-,.McGregor[24].,,pH10?0.550e,L-100g/L.Lin[25]NAD(Ñ),NAD,.,22,100~1000.,.,[26].[26~29].Grib[28]C-,.Wang[29]L-L-.pH4~9,1000ESNA2()L-L-0%90%,ESNA2L-L-;100ES20()pH100%L-L-.,ES20L-L-.2在中药生产中的应用2.1,,,[30].,,,,,,.,,,[31].2.25000~500000,1000,50000.,,,.[32~34],:1);2);3);4);5)[35].,,().,,,,,,.,.4:#183#3在现代生物技术中的应用.[36].,.,,.,[37].21,,DNA,.:,..[36].,.,(),[38].(HPTFF).10()..,,,.,,,.,,.,(IgG)[39].4结束语,21.,.,.[1]LipnizkiF,BoelsmandJ,MadsenRF.Conceptsofindustrial-scalediafiltrationsystems[J].Desalination.2002,144:179~184.[2]DarnonE,LafitteL,BellevilleMP,etal.Aglobalap-proachofultrafiltraionofcomplexbiologicalsolutions[J].SepPurTechnol,2002,26:283~293.[3],.[J]..2000,31(2):130~133.[4]AdikaneHV,SinghRK,NeneSN.RecoveryofpenicillinGfromfermentationbrothybymicrofiltration[J].JMem-brSci,1999,162:199~123.[5]RuizO,Manuel,YecoraF.etal.Processforproducing6-amino-penicillanicacidandphenylaceticacid[P].USPat:6110699,2000-08-29.[6],,,.C[J].,2001,32(11):497~499.[7]BritesAlvesAM,MorÃoA,CardosoJP.Isolationofan-tibioticsfromindustrialfermentationbrothsusingmem-branetechnology[J].Desalination,2002,148:181~186.[8]SchroenCGPH,NierstraszVA,BosmaR,etal.Processde-signforenzymaticadipyl-7-ADCAhydrolysis[J].BiotechnolProcess,2002,18(4):745~751.[9]DanzigJ,TischerW,WandreyC.Continuousenzyme-catalyzedproductionof6-aminopenicillanicacidandprod-uctconcentrationbyreverseosmosis[J].ChemEngTech-nol,1995,18:256~259.[10],,,.6-APA[J].,1998,14(4):468~471.[11],,,.[J].,2001,40(2):495~502.[12]DaviesJL,BaganzF,IsonAP,LyeGJ.Studiesonthein-teractionoffermentationandmicrofiltrationoperations:ErythromycinrecoveryfromSaccharopolysporaerythraeafermentationbroths[J].BiotechnolBioeng2000,69(4):429~439.#184#23[13]ZhangWei,HeGaoHong,GaoPing,etal.Developmentandcharacterizationofcompositenanofiltrationmem-branesandtheirapplicationinconcentrationofantibioties[J].SepPurTechnol,2003,30:27~35.[14],.[J].,2000,26(3):169~171.[15]HooperLA,HolleinHC,SlaterCS.MicrofiltrationofStreptomycesrimosus:Cellharvestingprocessstudies[J].SepSciTechnol,1998,33(12):1747~1765.[16]MorÃoA,AlvesAMB,CardosoJP.Ultrafiltrationofdemethylchlortetracyclineindustrialfermentationbroths[J].SepPurifTechnol,2001,22~23:459~466.[17]CrespoJPSG,MouraMJ,AlmeidaJS,etal.Ultrafi-ltrationmembranecellrecycleforcontinuouscultureofPropionibacterium[J].JMembrSci,1991,61,303~314.[18]AlbertoEB,BelenE,HisashiN,etal.ProductionofV-itaminB12inanupflowanaerobicfiltercontinuousreactorusingacetobacteriumSp[J].BiotechnolLett,2000,22:503~508.[19],,,.Vc[J].,2000,20(3):57~58.[20],,.C[J].,2001,31(1):38~41.[21],,,.[J].,2002,4:1~25.[22]ThienMP,HattonTA,WangDIC.Liquidemulsionmembranesandtheirapplicationsinbiochemicalsepara-tions[A].AsenjoJA,HongJ.Separation,Recovery,andPurificationinBiotechnology(ACSSymposiumSeries314[C].AmericanChemicalSociety,1986.67~77.[23]AgarwalAK,HuangRYM.StudiesonanovelapproachfortheseparationofL-phenylalanineaminoacidfromfermentationbrothusinganewlydevelopedchargedultra-filtrationmembrane.I.singlesolutesystem[J].SepSciTechnol,1994,29(2):171~192.[24]McGregorWC.ConcentrationofL-phenylalaninewithareverseosmosismembrane[J].JBiotechnol,1989,10:277~284.[25]LinShu-Su,HaradaT,HataC,etal.Nanofiltrationmembranebioreactorforcontinuousasymmetricreductionof2-ketoulutaratetoproduceL-glutamatewithNADHregeneration[J].JFermBioeng,1997,83(1):54~58.[26]Martin-OrueC,BouhallabS,GaremA.Nanofiltrationofaminoacidandpeptidesolution:mechanismsofseparation[J].JMembrSci,1998,142:225~233.[27]TimmerJMK,SpeelmansMPJ,VanderHorstHC.Separationofaminoacidsbynanofiltrationandultrafiltra-tionmembranes[J].SepPurTechn