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MULTIOBJECTIVEOPTIMIZATIONRESEARCHFOREFFECTIVECONSTITUENTSOFQILIQIANGXINCAPSULEOFCHINESEFORMULAHONGTAOWANG,JIMINGJIA,SIWENTANG,DENGFENGXU,YAJIEZHENG,HUIXINZHANG,YILINGWU#PHARMACOLOGYLABORATORYTHEINTEGRATIONOFTRADITIONALANDWESTERNMEDICALRESEARCHACADEMYOFHEBEIPROVINCESHIJIAZHUANG,CHINA#CORRESPONDINGAUTHORRENQUANLIUBEIJINGUNIVERSITYOFCHINESEMEDICINEBEIJING,CHINAAABSTRACTTHESYSTEMATICEFFECTSFROMMANYACTIVEINGREDIENTSINCHINESEMEDICINEPREPARATIONARETHEHIGHLIGHTTOEVALUATECURATIVEEFFECTSANDOPTIMIZETHEFORMULATHECOMMONDESIGNCOULDGETTHEIDEALOPTIMIZATIONQILIQIANGXINQLQXCAPSULEEXERTSITSEFFECTSONCHRONICHEARTFAILURETHROUGHCARDIACANDDIURESISANDDILATINGVESSELINOURPREVIOUSRESEARCH12SAMPLESWEREOBTAINEDBYWATERANDALCOHOLEXTRACTINGANDMACROPOROUSRESINPURIFYINGTHEACTIVESITESWERESCREENEDWITHTHEEXPERIMENTSOFISOLATEDFROGHEARTANDAORTAPERFUSIONANDDIURESISTHERESULTSSUGGESTEDTHATW3,W4,E2,E3,E4WEREMAJORACTIVESITESHERETHELARSWASADOPTEDTODESIGNTHEEXPERIMENTOFHEARTFAILUREINRATSANDOPTIMIZEDIFFERENTINDEXINTHERESULTSTHESTUDYWASTOEXPLOREANOVELMETHODTOOPTIMIZECHINESEMEDICINEFORMULAKEYWORDSEFFECTIVECONSTITUENTS;MULTIOBJECTIVEOPTIMIZATION;DATAMINING;CHINESEMEDICINEINTRODUCTIONFORMULAINTRADITIONALCHINESEMEDICINEHAVEHELPEDCHINESEANCIENTSTOFIGHTWITHDISEASESDURINGPASTTHOUSANDSYEARSANDVALIDATEDBYMOREANDMORECLINICALEXPERIENCEQILIQIANGXINCAPSULEQLQXISANEFFECTIVEFORMULATOTREATCHRONICHEARTFAILURECHFINCLINICS1MANYCLINICALEVIDENCESHAVEDEMONSTRATEDTHEEFFICIENCYOFITHOWEVER,THEMATERIALBASISOFTHEFORMULAFORTREATINGTHEDISEASEREMAINSUNCLEARRELATIONSHIPBETWEENCHEMICALINGREDIENTSOFQLQXANDBIOLOGICALPARAMETERSTHATSIGNIFICANTLYASSOCIATEDWITHTHECHFISABETTERAVENUETOUNCOVERTHEMATERIALBASISOFTHEFORMULABASEDONTHERELATIONSHIPBUILT,THEOPTIMALPROPORTIONOFHERBALSTHATCONSTITUTETHEFORMULACANBECALCULATEDFROMTHEPROPERPROPORTIONOFHERBALSMEANSTHATEACHHERBALHASITSDIFFERENTROLETOPLAYINCONSTITUTINGAFORMULA,WHICHISANIMPORTANTTHEORYANDVIEWPOINTINTCMTHEFIVEHERBALSINTHEQLQXCANBESEENASA“TEAM’TOFIGHTWITHCHFSINCETHEREARESEVERALBIOLOGICALPARAMETERSTOEVALUATECHF,THEREFORE,THEOPTIMALPROPORTIONOFHERBALSSHOULDBECOMPUTEDBYMULTIOBJECTIVEOPTIMIZATIONALGORITHMINTHISPAPER,WEPRESENTEDANOVELMETHODTOESTABLISHRELATIONSHIPBETWEENCHEMICALINGREDIENTSOFQLQXANDBIOLOGICALPARAMETERSOFCHFANDPREDICTTHEOPTIMALPROPORTIONOFHERBALSWEFIRSTLYCARRIEDOUTAUNIFORMDESIGNTOCOMBINETHEDIFFERENTCONCENTRATIONOFFIVEINGREDIENTSTHENANIMALSMODELWITHCHFWEREBUILTTOEVALUATETHECOMBINATIONTHENTHELEASTANGLEALGORITHMWASUSEDTOESTABLISHRELATIONSHIPBETWEENFIVEHERBALSANDBIOLOGICALPARAMETERSFINALLY,MULTIOBJECTIVEOPTIMIZATIONALGORITHMWEREPRESENTEDTOCALCULATETHEOPTIMALPROPORTIONITMATERIAL11ANIMAL280SDRATS,FEMALEANDMALE,WEIGHT140160G,BEIJINGVITALRIVEREXPERIMENTALANIMALTECHNIQUECO12TESTEDARTICLETESTEDARTICLEW3、W4、E2、E3、E4WASSUPPLIEDBYHEBEIYILINGMEDICINALINSTITUTEEVERYSAMPLEWASPREPAREDFOR11DIFFERENTCONCENTRATIONRESPECTIVELYAND11NEWSAMPLESWASOBTAINEDBYEVERY5SAMPLECOMBINATIONFOLLOWINGTABLE11TABLE11THEEXPERIMENTALDESIGNOF11LEVELSWITH5INGREDIENTSNOW3W4E3E4E2112357224610333694104481965510432661789773102588527199751810109864111111111111TABLE12COMPOSITIONWITHACTIVESITES(UNITMG/ML)NOW3CONW4CONE3CONE4CONE2CONQLQX10034804346081962306227200QLQX20069512072238957037806531QLQX30139033533696641844979299QLQX40278093146040165630319040QLQX505560258740117081475904571QLQX61112002608341354504255509QLQX72224007243995201180813328QLQX844480201200573736034032009781424447138/10/25002010IEEEQLQX98896055888167260944638857QLQX1017792155244487652882709329QLQX113558443123314217879731132813REAGENTTRIPHENYLTETRAZOLIUMCHLORIDEPURCHASEDFROMSINOPHARMCOLTDBATCHNUMBERF20040531。14INSTRUMENTSBL420EBIOLOGICALSIGNALACQUISITIONSYSTEM,CHENDOUTAIMENGSCIENCEANDTECHNOLOGYCOLTD2METHODSANDRESULTS21SURGICALPREPARATIONSDRATSWASANESTHETIZEDWITHCHLORALHYDRATE350MG/KGTHELEFTTHORACOTOMYWASPERFORMEDINTHEFOURTHINTERCOSTALSSPACEANDTHEPERICARDIUMWASOPENEDTOEXPOSETHEHEARTA0SILKSUTUREWASPASSEDAROUNDTHELEFTANTERIORDESCENDINGCORONARYARTERYAPPROXIMATELY12MMFROMITSORIGINANDLIGATEDTHEARTERYTOOCCLUDETHEBLOODFLOWTHESHAMGROUPUNDERWENTTHESAMEPROCEDUREWITHOUTLIGATINGTHECORONARYARTERY22MEASUREMENTOFCARDIACFUNCTIONTHELEFTVENTRICULARINTUBATIONWASADOPTEDTODETERMINESYSTOLICBLOODPRESSURESBP,DIASTOLICBLOODPRESSUREDBP,MEANARTERIALPRESSURESMAP,LEFTVENTRICULARPRESSURE(LVP,LEFTVENTRICULARENDDIASTOLICPRESSURE(LVEDP),MAXIMALRISINGANDFALLINGRATEOFLEFTVENTRICULARPRESSURE(LVDP/DTMAXANDHEARTRATEHR23INFARCTSIZEDETERMINATIONPETTYMA,DOWJ,GRISARJM,JONGWDEEFFECTOFACARDIASELECTIVEALFATOCOPHEROLANALOGUEONREPERFUSIONINJURYINRATSINDUCEDBYMYOCARDIALISCHEMIAEURJPHARMACOL1991;192383388HAYASHIN,FUJIMURAY,YAMAMOTOS,KOMETANIM,NAKAOKPHARMACOLOGICALPROFILEOFVALSARTAN,ANONPEPTIDEANGIOTENSINIITYPERECEPTORANTAGONISTARZNEIMITTELFORCHUNG1997;47625629THEFRESHHEARTWASEXCISED,RINSED,FROZENFORABOUT1HOUR,ANDSLICEDINTO5SECTIONSFROMAPEXTOBASETHESLICESWEREINCUBATEDIN1TRIPHENYLTETRAZOLIUMCHLORIDEPHOSPHATEBUFFERSOLUTIONAT37℃FOR15MINTHEINFARCTIONAREAWASSEPARATEDFROMWHOLEHEARTANDWEIGHTEDTHEINFARTIONSIZEWASCACULATEDWITHTHEFORMULATHEINFARTIONSIZEWEIGHTOFINFARCTIONSIZE/WEIGHTOF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