Benignprostatichyperplasia (BPH)isanage re lated ,progressivediseasecharacterizedbyabenignen largementoftheprostateglandthataffectsalargepartofmenover 5 0yearsofage .Ithasbeenwellestablishedthatgrowthofthepros tateisstimulatedbyandrogens,anditnowappearsthat5a dihydrotestosterone (DHT)playsaprimaryroleinthetrophicsupportofthisorgan .Thestudieshavedemonstratedselectiveretardat ionofprostategrowthbyinhibitionofhumansteroid.5α reductase (SR)isanenzymeresponsiblefortheconversionoftestosterone (T)intoDHT .Thusse lectiveinhibitionofSRcouldofferanalternativetherapyforBPH .Asaninhibitorof 5a reductasesfortreatmentofBPH ,Finasteride (tradenameProscar)hasbeenavailableinUSAsince 1 992 .AndEpristeride(SK&F1 0 5 65 7)isapotentuncompetitiveinhibitorofDHTthatbelongstoafamilyof 3 androstene 3 car boxylicacidsandisbeingclinicallyevaluatedforthetreatmentofBPH .Wesuccessfullyimprovedthesynthesisofepris teridewithanewlydesignedsix stageprocessandhavepreparedcontrolled releasemicropelletofepristeridewhichhavebeenputintoproduction .Meanwhile ,newbiodegradablemicrospheresmeetingtherequirementoftherapyarealsotried .Microspheretechnologyhasbeenstudiedextensive lyforthesustaineddeliveryoftherapeuticagents .Owingtotheirbiocompatibilityandbiodegradabilitythepoly(d ,l lactide co glycolide)appearstobevaluablema terialsforthepreparationofmicrospheresutilizedforcontrolleddrugrelease .Thepurposeofthisstudywastodevelopthecontrolreleasetechniqueofepristeridemi crospherecontainingpoly (d ,l lactide co glycolide)(PLGA)andtoevaluatethecharacterist icsofepristeridemicrospheresfortwopreparationways.1 MaterialsandMethods1 1 MaterialsEpristeridewasobtainedthroughoursynthesis.Poly (d ,l tactide co glycolide) (PLGA)polymerwithhydrophilicendgroup (MW 2 0 0 0 0 ,copolymerratio 5 0∶5 0 ,ResomerRG5 0 3H)andhydrophobicendgroup(MW 2 0 0 0 0 ,copolymerratio 5 0∶5 0ResomerRG5 0 3)wereobtainedfromBochringerIngelheim (Ingelheim ,Germany) .Allotherchemicalswereobtainedcommer ciallyasanalyticalgradereagents.Aeromatic FielderDryer (Strea 1 ,NiroPharmaSystems,Switzerland) ,LEO 1 45 0ScanningElectronMicroscope (LEOElectronMicroscopyLtd .,Cam bridge ,England) ,BETAnalyzer (SA31 0 0 ,CoulterBeckmanLtd .,USA) ,MoistureAnalyzer (Mettler Toledo,AG ,Schwerzenbach ,Switzerland ) ,Dr.HielscherUltrasonicEmulsifier (Dr.hielscherGmbHCorp .Germany) ,VanderKampDissolutionApparatus(Biochemie ,AG .Switzerland) ,UV/VISSpectropho to meter (Shimadzu ,Model2 0 0 1 ,Japan) .1 2 Methods1 2 1 MicrospherePreparationThefollowingtwowayswereusedtoprepareepris teridemicrospheres:WayA :Themicrosphereswerepreparedbyawa ter in oil in waterdoubleemulsiontechnique .Briefly,adispersedphasewaspreparedbyadding 1 . 5gepris teridein 30mlofC2 H5OHto 2 . 5ml1 . 7mol/LNaClin 1 0 0ml0 . 2 %PVA ;1 0ghydrophobicPLGA (Re somerRG5 0 3)dissolvedin 1 0 0gCH2 Cl2 ( 1 0 %wt/wt) .TheaboveepristeridephasewasaddedintothehydrophobicPLGA CH2 Cl2 phaseandemulsifiedbyvor texvigorousfor 5min .Theemulsionwasthenaddedto6Lof 0 . 2 %PVAbyusingastainlesssteelsyringewithneedlea ndwasfollowedbysonicationwithabathsonicator.WayB:Themicrosphereswerepreparedbytheconventionaloil in wateremulsiontechnique .Briefly ,Adispersedphasewaspreparedbyadding 1 . 5gepris teridein 30mlofC2 H5OHto 1 60mldissolving 2 0ghy drophilicPLGA (ResomerRG5 0 3H)inCH2 Cl2 ( 1 2 .5 % ,wt/wt) .Thedispersedphasewasintroducedto 6Lcontinuousphase ( 77mol/LNaClin 0 . 2 %PVA)byusingastainlesssteelsyringewithneedle .Thecon tinuousphasewasstirredat 70 0 0r/minbyemulsifier.After 1 0min ,thetemperatureofthemixingphaseswasadjustedto 40℃todriveoffCH2 Cl2 .Inaddition ,maintainingtemperaturewas >40℃ ,andthevacuumwasalsoappliedtofurtheraccelerateCH2 Cl2 removal.DryingofMicrospheresintheAeromatic FielderDryer.EpristeridemicrospherewasspraydriedintheAeromatic FielderDryer.Dryingtemperatureusedwas90℃fortheinletand 60℃fortheoutlet.Theemulsi fiedliquidwasintroducedtotheAeromatic FielderDryerbyatopfluidnozzleandthefeedspeedwas 0 . 3ml/min .Thedrypurgedair ( 2m3/min)wasintroducedandheatedpriortop
More abstracts about the 两种乳化技术制备的爱普列特微球的特性研究(英文)