内毒素的去除策略

28220036GuangzhouChemistryVol.28No.2June20031009-220X(2003)02-0038-081116012TQ464A1EndotoxinAGNB[1]400,000~1,000,000lipopolysaccharideLPSLPSGNBLPSLPSALipidA1.1PSO-O-AntigenCoreoligosaccharide2002-07-081n=4~40O-(A)239O-O-4~40[2]1.2ALPSA3.1pHpH3.1ALipidA210~18O-AA22.1[3]2ng/kg199521mL4000XID1kg2mL2EU/mL10EU/mL2.2AA12A40281A.1ng0.2~0.5nglShwartzmanlbonemarrowreactionlIEUcopenialthrombocytopenialnonspecificresistanceltolerantladjuvantlBlTNFIL-1.IL-6lllClHagemanl3.13.2123DNA3.33.3.1RabbitPyrogenicTestRTRT2413.3.2LimulusTestLTLTLimulusAmoebocytelysateLALRT10~1000.01~1ng/mLpg/mLRT1.5ng/kg0.5~10g/kgLTLTLT3.3.3ASPD50CELD50LTLT44.12501hpHCa2Mg2NaK4.24.2.15000100004228[4][5,6][7]pH4.2.2[8][9]4.2.3[10]4.2.4Liu[11]TritonX-11499%90%4.2.5DEAE[13]Chibata[14]CelluloseR-A-XRAXH4.2.680SatoshiMinobe[9,15,16]I=0.02pH3~8[17~19]BSALegeklallails[20]PEVAIgG2434.334(1)(2)2.4106EU/gEU1EU120pg344428(3)10~20(4)100mL/min0.2MPapH3~11pHpH100mL2%pH3.915mL/min90%80%pHpH6pH5[1],.[M].:,1999.9~10.[2].[][D].:,1996.[3].[M].:1999.120~123.245[4],,,.[J].,1999,19(3):8~12.[5],,.[J].,1994,29(4):214~217.[6],,.[J].,1995,19(4):289~292.[7]KennethCH,RichardZaniewski.Depyrogenationbyendotoxinremovalwithpositivelychargeddepthfiltercartridge[J],JournalofParenteralScience&Technology,1990,44(4):204~209.[8]HowardF,SpoonerECR.Removaloftaintsfromwater,ChemInd,1946,186~189.[9]SatoshiMinobe,TaizoWatanabe,TadashiSato,etal.Characteristicsandapplicationsofadsorbentsforpyrogenremoval[J],BiotechnologyandAppliedBiochemistry,1988,10:143~153.[10]CampbellDH,CherkinA.Thedestructionofpyrogenbyhydrogenperoxides[J].Science,1945,102:535~538.[11]LiuShi-gui,RowelTobias,ShannonMcclure,etal.Removalofendotoxinfromrecombinantproteinpreparations[J].ClinicalBiochemistry,1997,30(6):455~463.[12]AnspachFB,HilbeckO.Removalofendotoxinbyaffinitysorbents[J].JChromatogr,A,1995,711:81~92.[13]IchiroChibata.Methodforreducingthepyrogencontentorremovingpyrogensfromsubstancescontaminatedtherewith[P].USPatent4,381,239.[14]SatoshiMinobe,TadashiSatoTetsuyaIchiroChibata.Characteristicsofimmobilizedhistamineforpyrogenadsorbent[J].JChromatography,1983,262:193~198.[15]HiroakiMatsumae.Satoshi.Minobe,KumikoKindan,etal.Specificremovalofendotoxinfromproteinsolutionbyimmobilizedhistidine[J].BiotechnologyandAppliedBiochemistry,1990,12:129~140.[16]WeiGuo,ZhenhuaShang,YinianYu,etal.Removalofendotoxinfromaqueoussolutionsbyaffinitymembrane[J].BiomedicalChromatography,1995,11:164~166.[17].[J].199725(9):1010~1015.[18],,,.[J].,1998,17(2):8~12.[19]LegallaisC,AnspachFB,BuenoSMA,etal.StrategiesforthedepyrogenationofcontaminatedimmunoglobulinGsolutionsbyhistidine-immobilizedhollowfibermembrane[J].JChromatographyB,1997,691:33~41.MethodsforEndotoxinRemovalSHAOYing-guangLIJing-huaWEIGui-linWANGJun-deDalianInstituteofChemicalPhysicsChineseAcademyofSciencesDalian116012ChinaAbstractTheessentialityandharmofendotoxinareintroducedinthisarticleandonthebasisofourexperienceinthisfieldsomemethodsofendotoxinremovalarereported.Keywordsendotoxinaffinitymembraneremoval