雷公藤微乳凝胶剂体外透皮和药效学初步研究

华中科技大学硕士学位论文雷公藤微乳凝胶剂体外透皮和药效学初步研究姓名：翁婷申请学位级别：硕士专业：无机化学指导教师：杨祥良20040510I2.55IIAbstractTodecreasethetoxicityofTripterygiumwilfordiiHook.f.,microemulsionwasloadedwiththeethylacetateextractofTripterygiumwilfordiiHook.f.(TWEE).Itstransdermalpermeationthroughmouseskininvitro,viscidityandappearancewerestudied.TheresultsshowthattheNO.5isthebestformulationTWEE0.5g,oleicacid8g,tween8030g,propyleneglycol15g,water40.48g,vitaminE0.02g,menthol1.5g.TheantiinflammationoftheNO.5formulationwasstudied.Theresultshowedthattheformulationcouldrestraintheswelloftherat’stoes.Particularly,thehighdosageandthemiddlingdosagehadthemarkedcurativeeffecttotheacuteinflammation.TheantiimmunityoftheNO.5formulationwasstudied.Theresultshowedthattheformulationcouldrestrainthepathologicalchangesoftheratthatthecompletefreundsadjuvantinduced.Particularly,thehighdosagehadthemarkedcurativeeffecttothepathologicalchangesaftertendays.ThemiddlingdosagehadthesimilarcurativeeffectwiththetrocheofTWEE.Thelowdosagehadnocurativeeffect.TheanalgesiceffectoftheNO.5formulationwasstudied.Theresultshowedthattheformulationhadtheanalgesiceffectanddecreasedthetwistdegreeofthemice.Particularly,thehighdosagehadthemarkedanalgesiceffect.TheirritationoftheNO.5formulationwasstudied.Theresultshowedthatthe2.5%and5%formulationhadthegentleirritation,butitcouldbeaccepted.KEYWORDS:TripterygiumwilfordiiHook.f,microemulsion,transdermal,antiinflammation,antiimmunity,analgesiceffect,irritationIII1123456789101112131415516LichrospherC185µ4.6mmID0.05mol/L6040v/v1.00ml/minµµ2.12.1n=5171819ggggggg3LichrospherC185µ4.6mmID0.05mol/L6040v/v1.00ml/min20µµ2.321222324Wistar4815020g251%1h2h4h6h8h24h26.537.4948.126.5859.1213.7960.2110.0260.149.3045.3716.601mg/kg5.859.4113.838.4912.2310.4521.8112.5119.729.4413.376.6240mg/kg3.826.2415.2612.9949.8610.3861.5114.6960.8410.5740.1211.5080mg/kg4.747.818.398.7440.7913.6740.847.8149.485.3633.7712.7160mg/kg6.417.2315.584.7527.926.4553.6112.0255.697.7033.247.8640mg/kg15.819.8139.153.1960.793.8161.7610.8963.108.4243.9312.26100%=26CelsusP27()()PVC2452282930PearsonWood1959351112Perperetal1971perventivetherapeutic’31~401234100%=324.10101010101235104.620.749.131.894.380.746.880.994.130.648.251.7540mg/kg4.830.759.001.673.830.416.001.094.000.007.330.8280mg/kg4.670.828.832.044.000.635.832.044.170.418.170.98160mg/kg4.500.8410.21.473.670.526.501.054.000.63*6.170.83*1mg/kg4.800.4510.00.714.200.455.200.453.000.71*5.201.64*80mg/kg4.670.528.671.214.670.827.331.034.330.527.330.5233*p0.05510d1.6g/kg40mg/kg80mg/kg160mg/kg1mgkg8omg/kgp0.054.4160mg/kg80mg/kg0mg/kg343536--CRHCRHACTHACTH3760mg38HAFFNERs550mg/20030212202g606120m24039m0.60.2ml20205.15.1min22.513.56.105.17200mg/kg4.86.7**13.207.22*60mg/kg19.514.57.205.4713.33120mg/kg19.812.06.103.1112.0240mg/kg10.312.5*9.705.8554.2260mg/kg9.613.1*11.105.24*57.33P0.01P0.055.1240mg/kg60mg/kg60mg/kg100%=40120mg/kgPGPGPGPGPGE1E2F2PG5.15.1415.1--CRHCRHACTHACTH5.1Triptolide,T10--4243446.16.26.10.0~0.40.5~1.92.0~5.96.0~8.0456.2012340121cm31cm482.556.33416.16.26.36.4466.30.555±0.3850.555±0.3851.313±0.8441.704±0.6122.5%0.000±0.000.222±0.3850.472±0.2650.889±0.5885%0.000±0.000.111±0.1920.556±0.1111.185±0.231P0.001P0.01P0.0547HLADRTTTT4T2448-1interlenkin1IL-1epidermalthymocyteactivalingfactorETAFrmainhistocomtibilitycompIexMHCHLA-DRTIL-1ETAF-2interleukineIL-2THT48ADCBCBDA49AADCBBCD50ABBCDADC51ABADCBCD52BADC532.55341BACD542.55552002/4/2056[1]..,1990,214251256[2]..,1985,202101106[3],,.A2,,1998,2429596[4],,,.T74-1.,1982,443032[5],..,1989,248568572[6],.T4I.T4NK.,1990,122115120[7],..,1990,163216218[8],..,1993,138507509[9],.T.B.,1986,243235[10],,,.T74-1.,1982,443033[11],..,1990,1252425[12],.SLEIgGDNA.,1994,1411214[13],.T4.,571990,233942[14],.IL-2.,1993,153193196[15],.IL-2.,1993,93189192[16],..,1995,264252256[17],..,1989,922024[18],.T4,T7,T15.,1994,1612023[19],..,1993,138507509[20]KupchanS.M.,WillianA.C.,RichardG.D.,etal.Triptoideandtripdiolide,novelantileukemicditerpenoidtriepoxidesfromtripterygiumwilfordii.J.AmChem.Soc.1972,942071947199[21]..,1989,93111113[22],..,1991,125406410[23],,.HeLa.,1989,106550553[24]..,1992,123161164[25],..,1985,167324327[26].HIV.-,1993.81283058[27],.100.,1989,1243032[28]..,1988,715153[29]LawrenceM.J.,ReesG.D.,Microemulsion-basedmediaasnoveldrugdeliverysystems.Advanceddrugdeliveryreviews,2000,45(1):89121[30]TenjarlaS..Microemulsion:anoverviewandpharmaceuticalapplications.Crit.Rev.Ther.DrugCarrierSyst.,1999,16(5):461521[31],,..,1999,204253256[32],..,2001,323139142[33]RheeY.S.,JungG.,ParkE.S.,etal.Transdermaldeliveryofketoprofenusingmicroemulsions.Int.J.Pharm.,2001,228:161170[34]KanikkannanN.,KandimallaK.,Lamba.S.,etal.Structure-activityrelationshipofchemicalpenetrationenhancersintransdermaldrugdelivery.Curr.Med.Chem.,2000,7:593608[35]GascoM.R.,GallarateM.,TrottaM.,etal.Microemulsionsastopicaldeliveryvehicles:ocularadministrationoftimolol.J.Pharm.Biochem.Anal,1989,7:433439[36]KemkenJ.,ZieeglerA.,MullerB.W..Investigationsintothepharmacodynamiceffectsofdermallyadministeredmicroemulsionscontainingbeta-blockers.J.Pharm.Pharmacol.,19