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dz̸ҩﴫϵͳоļȵ

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ժҪͨĽףصҩﴫϵͳµĽչʽҩϵͳ᳦λҩϵͳͰƼݡ

ؼʣҩﴫϵͳʽҩϵͳ᳦λҩϵͳͰƼ

ҩﴫϵͳ(Drug Delivery Systems,DDS)ϵָڷμĹõĸҩIJͬҩʽ60ǰҩѧгΪ͡עƬҼƬȡſѧĽ͵ķչԶԶԽԭеںҪҩﴫϵͳҩ(Device)Աԭҩ븨Ƴɵĸּ㲻ٴƵҪеĽҩƳעϵͳãеѺϽƳɸҩֲӦãʹٴҩ뻯Ϊ˷ͨƼЧѪŨάʱ̵ȱݣ˳ЧעڷЧҩϵͳ/ƼƤҩϵͳһϵµƼڻ/Ƽص㣬гǰáƼָͨڷҩڻڻͷҩʹЧѪŨά൱ʱƼƼϵָҩٶȽܸҩϵͳĿƣpHøӡθ䶯صӰ1ݣǰƺõijҩƼ㼶ҩ͸ãҩ΢裬᳦λҩƬԼԶҩȵظҩȵȡЩ׶Ի͡Ƽϸ֣ͳΪ/Ƽ

йͬĻ/ƼƷϣƬҡ˨͸á͸ƤƬҩֲճĤճעȶʽԿڷ/Ƽչ졣΢轺Ҽ뻺Ƭȣаȫϵߵص㣬һϰ΢ɣиСθѸٱҩӰ΢СģƬб䵥μͨƼDzԶˣһ΢轺Ҳ׶θĻ߷ͷŵԼθҺpHֵ仯ĸӰ졣ˣ΢轺ұȻƬзչǰ

ҹ1977йҩ˷Ѫ没ûʳƻƬⷽоֱ80ű㷺ӡ1995ҹ׼Ļ/Ƽ7֬塢΢򡢺΢΢ɢҩϵͳԼ᳦λҩϵͳڷҩƼоҲܻԾ(Ŀǰ֬׼Ʒ)¼и

1ͻ/Ƽоſ

1.1θͿ͸ҩϵͳ23ݡɲйס

1.2ʽҩϵͳʱҩѧоҩáӦڹ̾ʱɣѳΪƶʱҩƼҪݡҩʽҹɱ仯Ĺɣǽҩѧоһҩģʽжҩҵоʽҩϵͳѿʼо

ҩϵͳ(pulsatile release system)ڷʱʱصķʽθضλͷҩҩϵͳرҹѺҪһѪŨֵļ(ʧߡؽסֲȱѪಡ)Ҳڳ²λҩյЩ(᳦Խ᳦סڷ)ĿǰͶоҪƽҩѪҩH2ϼȵصȡעĿALZA˾Searle˾ͬάҹҩϵͳƷΪCalan- OROSʵ֤ѪѹѸҩʱΪ峿3ңʱڶӰˮƽߣࡢѪǿܳ⣬øҩϵͳ˯ǰã峿ͷҩʮַϸòɱ仯ҪԤƸüͺܿ켴С

1.2.1ҩƬʱر(time-controlled disintegration mechanism)ƵһָѹƬɴҩ֮ĿġƬоҩɣˮ͸СĸϲɡǺˮ͸Լɿҩʱ䡣磺?NFDA1?ͪΪģҩ(ڽϿθڿɱ)ѡȼ׻άظ(ECG-505)Ӳ֬þΪ󻬼ѹƳƬо⻯(HCO)ϩ(PVC);Ҷ(PEG6000)ɣ9094ڷȡ20ĿԸѹ·ƬPEGǺȼɿˮ͸ʡϵͳƽʱΪ(7±1)hʱҩ15 minͷϡ

1.2.2ҩ΢4ݡʱرϵͳ(time-controlled explosion systemTES)΢Ľṹɷ4㣬ﵽоҩ㡢ͼ㼰ˮԾۺĤͼ1ˮͨĤϵͳ͸ӴͼһˮͼĤĿǿʱĤʼѣҩͷšͨıĤĺͷҩʱ䡣磬о(nonpareil)ΰҩ㡢Ͳ(L-HPC)ECĤͲ(180 μm)̶ʱECĤĺȿӰҩʱ(tL)θTESECĤΪ20 μmʱtLΪ1 hECĤΪ25 μmʱtLΪ2 hECĤΪ30 μmʱtLΪ3hECĤ(25 μm)̶L-HPCĺɵҩʱ䣬tiap ride hydrochloride TES,L-HPCΪ120 μmʱ1hʱͺҩĤ6hҲδƣL-HPCΪ180 μmʱ2hĤʼѣ6hȫƣҩͷͬСTESڸʲͬҩҩϵͳѿʼо

1.3᳦λҩϵͳ511ݡ᳦λԽ᳦ס᳦Ҫڽ᳦λҩ⣬﹤̵ķչࡢҩ࣬ҩͨҪעҩθ϶ȶԼòʲ˿ڷڽ᳦ν⵰׵ø٣ýϺãƳɽ᳦λҩϵͳࡢҩڷҩϣƿ͸ҩϵͳҩϵͳͨмֲƳɡ

1.3.1pHеijܲϡ˫Ĥҩڽ᳦λͷš磺ʹ(25%W/W)(62%W/W)(10%W /W)ȣ10%(W/V)PVPˮҺʪ551%M.SΦ 4.5 mmѹƬHPMC²(35.7%䷽ΪMethocel K15 5.0,PEG400 1.0,Talc 2.0,PVP 2.5Ҵ84.0ˮ5.5)ٰ²(5%䷽Ϊ8%(W/V)Eudragitl,2%DEP)ܳpHֵ仯Ӱ졣

1.3.2ʱͲϡͨʳθСֱԼ3hңʳ᳦Լ57hܿ57hҩ߼ɴ᳦ҩ֮Чǰʱҩϵͳ࣬ҩϵͳθſʲͬԸϴ

1.3.3øͲϡý᳦λе΢øԽ߷Ӳ϶ҩ磬żۺȿɱ᳦е΢øҩϽ᳦λרԽǰǿ

1.3.4øƵңڽװһ΢ȦڸƵųȦѶҩ

1.4Զڸҩϵͳ1213ݡɲйס

2ҩϵͳо״

ٴƼĹҪҩİԣ޶ȵǿҩЧͬʱʹҩIJӦͣ˰ҩϵͳ(TDDS)ѳΪִҩѧҪݡͨɽƼֳࣺһרоοƼҩͷŵٶȣ㼶һʽҩֻԵʽҩȵ(ǰ)һרоοƼҩͷŵȥһҪߡѶȸƼڰƼеۡ

2.1ҩƼķ

2.1.1ҩ;֡ȫðҩƼͨڷעȷʽҩʹҩﵼ跢õIJλȫõİҩƼֲҩҩڸòλá

2.1.2÷ʽ֡(active targeting)ҩƼʶ֯ϸĴӣΪ(passive targeting)ҩƼ֬塢΢򡢺΢΢Ƽ԰ϸʶɾѪѭDzͨëϸѪܴڸòλҩ

2.1.3ҩˮƽ֡һ΢Ƽֻܽҩض٣ϵָܽҩijٵضλϵָܽҩضλIJϸڡܽҩƳƼʹҩϸˮƽϷãҩרŹϸϸûл򼸺ûвӰ죬ʹҩЧﵽij̶ȡ

2.1.4̬֡ˮƼָ֬塢΢򡢺΢ˮ΢ƼһˮԵԴƼϳɴȻ(۶ǡ塢ǡ)ƼҩİҪƾϵͳʵֿ֣ɳΪҩϵͳ (drug-carrier systems)

Ͼ뱻ҩƼķ෨

оУҩо϶࣬֬΢Ƽ󣬿ɰСֲڲͬע712 μm΢ɱβеԽ˶ȡע12 μm΢ëϸѪܴΡУǻע0.10.2 μm΢ܿ챻״Ƥϵͳ(RES)ľϸյݷϸøС

2.2ҩϵͳչơΪһҩİԣ1415ݣѧֽʶϸĴҩı(ҩֱ)磺¡ںҩ֬(΢)ı棬ҩϸİԣʵѪڲЧǶϿϸ˵¡(chTNT)֬壬ʹʵڵЧȵ֬Ϊߣ֬ΪҩﴫϵͳоΪ࣬Ŀǰܹѧߵձע

оϸϵҶ壬ͻϾϸö࣬ƱҶ֬壬ҶΪ鵼֬ϸİԡ

Ҷ֬׵“”ϸĤΪҩϵͳchTNT-֬״͸“”ϸĤϸˣΪҩϵͳֲͬİ֬ƲͬڵĹ

1966Morellȷֲ鶯ĸʵϸĤȥҺǵ(Asialoglycoprotein receptor,ASGPr)רһԵʶ԰Ϊ˻ǵףǵΪ壬ɽҩﵼʵϸ(ηʵϸ(ݷϸƤϸ)ıи¶)ϸøתˣ屾»صϸĤ

ĿǰͰƼо϶ֽ࣬ͨ鵼ʽҩİԣʹҩЧӵãӦС

ɽҩƳɴƼҩİԣ纬΢ᰢùص΢򣬶עڰų£ҩŨȱȾעͬ밢ùظ߳100ٴƼеĴԳ΢ӿԶڰȫرų⡣дڴųǿȡݶ“۽”⣬ųǷıϸĻܺ͸ıѪķʽ⣬дһо

ܶ֬(LDL)16Ǵڲ鶯Ѫе֬סѪLDLЯѪ̴2/3ϸԴԵ̴ҪԴLDLڴлҪϸĤLDLʶ𣬴ӶϸڱãϸڵԴԵ̴ҪʱͨϸĤLDLĿͻԣӶLDLնӶԴԵ̴áLDLҪضLDLϸԴԵ̴ϳϰֳƣϸĤԵ̴ĴϸLDLĻԼijЩϸи߳ϸ20ϣˣLDLؿҩɴ߶ijЩϸİԡLDLԴ֬ףΪҩ壬ɱ֬塢¡ѭб״ƤϵͳѸ⣬ֲֿһڵİԲIJ㣬ԽǰҩﻯдڵİԲӦҪ塣

ϸСҩ΢ѭʱױRESľϸɣӶӰҩﵽƵİʴˣرRESѳΪҩԵص֮һ1718ݡհRESͣȻٸҩ壬ֱ˾ٻʹ߹𣬲鷢ʴ˷ȡԻԴLDLΪ壬ɻرRESɡо϶ǻرRES֬(RES-avoiding immunoliposomes)ںҩ֬ıIgG߿壬ֹPEGͼ2Ȼر˾ϸɣֿɽҩﵼϸPEGɻرRESɵĻδȫ壬PEGӾ߶ؽṹйأǿˮԺһйأƲPGEģ°ϸϸڵĶǻĹܡرRESķӱԼ(nonionic surfactant vesicles,NsVsNiosomes)PEG2000-̴(PEG-ch)ƳɵijѭùطӱԼ(long circulation adriamycin NsVs,L-ADM-NsVs)ϵPEGǿ˸ݵˮԣӶRESɣӳѪѭʱ䣬߰Ժԡ

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