四、肺部吸入给药系统课件

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1、四、肺部吸入给药系统优点：面积,上皮细胞间隙，肺泡、血管和淋巴管，血流速度，无首过破坏、无促进剂系统限制和要求：沉着部位及重现性、长期毒性Inhalationtherapy(Historicalperspective)1955,Metered-doesinhaler(MDI)developedbyGeorgeMaison1956marketed,FDAapprovalMay,1974,Sugarloafconferencemilestoneintheclinicaluseofaerosolizeddrugtherapy1980s-1990s,deve

2、lopmentanddeliveryofdrugformulationadditionaldevice,↓oropharyngeallossdrypowderinhaler2000Non-CFCpropellantmedicationsotherthanpulmonarydiseaseInhalationtherapy(Historicalperspective)InhalationforairwaydiseaseLungTotalsurface80M2Majorcontactbetweenbody&environmentHostdefensemec

3、hanismhasevolvedtocopewithnoxiousinhaledsubstancesAfewkeyprocessesinasthmapathogenesisaresurfaceprocessesBenefitsofinhalationrouteforairwaydiseaseLunghasmorepotentialsurfaceareaformolecularexchangewithblood&rapidabsorptionActionviaabsorptionthroughtracheobronchialmucosalungpare

4、nchymal(alveolar-capillary)topicallyreactwithreceptorinairwaybothMacromoleculesandAirwayMacromoleculesairwaysurface(3.0M2)nearlyimpermeablelungperiphery(alveoli,80-100M2)dopermeateComparisonoftherapeuticratiousingthreeroutesofadministrationofahypotheticaldrugforequivalentthera

5、peuticbenefitsIVOralInhaledunitsavailable1005010toexerteffectreachingtargettissue211reachingothertissues98499therapeuticratio1/491/491/9(effectivedrug/drugactingatothertissue)InhalabledrugforsystemictherapyEfficientlydelivertothelungperipheryReproducibletherapeuticdrugdoseAccom

6、modateflexibledosingStableformulationatroomTemp.DevicemustbeportableandeasytouseInhalabledrugindustrytodayAtleast5companiesAeroGenAlkermesAradigmcorporationDurapharmaceuticalsInhaleTherapeuticSystemsKnowndevelopinginhalableproteinsAventisBeringα-1proteinaseinhibitorforemphysema

7、BiogenAVONEX(IFNβ-1a)forMSPfizer,AventisPharmainhalableinsulinMedicalconditionsthatcouldbenefitsfrompulmonarydeliveryPainPanicandanxietyAnaphylaxisCardiacarrhythmiaOtherCVconditionsDiarrheaNauseaandvomitingNicotinewithdrawalUrinaryincontinenceSpasmInsomniaMacromoleculecandidate

8、sforpulmonarydeliveryInsulinGrowthhormoneAnti-obesityp