ժҪͨĽףصҩﴫϵͳµĽչʽҩϵͳ᳦λҩϵͳͰƼݡ
ؼʣҩﴫϵͳʽҩϵͳ᳦λҩϵͳͰƼ
ҩﴫϵͳ(Drug Delivery Systems,DDS)ϵָڷμĹõĸҩIJͬҩʽ60ǰҩѧгΪ͡עƬҼƬȡſѧĽ͵ķչԶԶԽԭеںҪҩﴫϵͳҩ(Device)Աԭҩ븨Ƴɵĸּ㲻ٴƵҪеĽҩƳעϵͳãеѺϽƳɸҩֲӦãʹٴҩ뻯Ϊ˷ͨƼЧѪŨάʱ̵ȱݣ˳ЧעڷЧҩϵͳ/ƼƤҩϵͳһϵµƼڻ/Ƽص㣬гǰáƼָͨڷҩڻڻͷҩʹЧѪŨά൱ʱƼƼϵָҩٶȽܸҩϵͳĿƣpHøӡθ䶯صӰ1ݣǰƺõijҩƼ㼶ҩãҩ裬᳦λҩƬԼԶҩȵظҩȵȡЩԻ͡Ƽϸ֣ͳΪ/Ƽ
йͬĻ/ƼƷϣƬҡ˨áƤƬҩֲճĤճעȶʽԿڷ/Ƽչ졣轺Ҽ뻺Ƭȣаȫϵߵص㣬һϰɣиСθѸٱҩӰСģƬб䵥μͨƼDzԶˣһ轺ҲθĻ߷ͷŵԼθҺpHֵ仯ĸӰ졣ˣ轺ұȻƬзչǰ
ҹ1977йҩ˷Ѫ没ûʳƻƬⷽоֱ80ű㷺ӡ1995ҹĻ/Ƽ7֬塢ɢҩϵͳԼ᳦λҩϵͳڷҩƼоҲܻԾ(Ŀǰ֬Ʒ)¼и
1ͻ/Ƽоſ
1.1θͿҩϵͳ23ݡɲйס
1.2ʽҩϵͳʱҩѧоҩáӦڹ̾ʱɣѳΪƶʱҩƼҪݡҩʽҹɱ仯Ĺɣǽҩѧоһҩģʽжҩҵоʽҩϵͳѿʼо
ҩϵͳ(pulsatile release system)ڷʱʱصķʽθضλͷҩҩϵͳرҹѺҪһѪŨֵļ(ʧߡؽסֲȱѪಡ)Ҳڳ²λҩյЩ(᳦Խ᳦סڷ)ĿǰͶоҪƽҩѪҩH2ϼȵصȡעĿALZA˾Searle˾ͬάҹҩϵͳƷΪCalan- OROSʵ֤ѪѹѸҩʱΪ峿3ңʱڶӰˮƽߣࡢѪǿܳ⣬øҩϵͳ˯ǰã峿ͷҩʮַϸòɱ仯ҪԤƸüͺܿ켴С
1.2.1ҩƬʱر(time-controlled disintegration mechanism)ƵһָѹƬɴҩ֮ĿġƬоҩɣˮСĸϲɡǺˮԼɿҩʱ䡣磺?NFDA1?ͪΪģҩ(ڽϿθڿɱ)ѡȼάظ(ECG-505)Ӳ֬þΪѹƳƬо⻯(HCO)ϩ(PVC);Ҷ(PEG6000)ɣ9094ڷȡ20ĿԸѹ·ƬPEGǺȼɿˮʡϵͳƽʱΪ(7±1)hʱҩ15 minͷϡ
1.2.2ҩ4ݡʱرϵͳ(time-controlled explosion systemTES)Ľṹɷ4㣬ﵽоҩ㡢ͼ㼰ˮԾۺĤͼ1ˮͨĤϵͳӴͼһˮͼĤĿǿʱĤʼѣҩͷšͨıĤĺͷҩʱ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 μmʱ2hĤʼѣ6hȫƣҩͷͬСTESڸʲͬҩҩϵͳѿʼо
1.3᳦λҩϵͳ511ݡ᳦λԽ᳦ס᳦Ҫڽ᳦λҩ⣬﹤̵ķչࡢҩ࣬ҩͨҪעҩθ϶ȶԼòʲ˿ڷڽ᳦ν⵰ø٣ýϺãƳɽ᳦λҩϵͳࡢҩڷҩϣƿҩϵͳҩϵͳͨмֲƳɡ
1.3.1pHеijܲϡ˫Ĥҩڽ᳦λͷš磺ʹ(25%W/W)(62%W/W)(10%W /W)ȣ10%(W/V)PVPˮҺʪ551%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
1.3.2ʱͲϡͨʳθСֱԼ3hңʳ᳦Լ57hܿ57hҩɴ᳦ҩ֮Чǰʱҩϵͳ࣬ҩϵͳθſʲͬԸϴ
1.3.3øͲϡý᳦λеøԽ߷Ӳ϶ҩ磬żۺȿɱ᳦еøҩϽ᳦λרԽǰǿ
1.3.4øƵңڽװһȦڸƵųȦѶҩ
1.4Զڸҩϵͳ1213ݡɲйס
2ҩϵͳо״
ٴƼĹҪҩİԣȵǿҩЧͬʱʹҩIJӦͣ˰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ƼϸʶɾѪѭDzͨëϸѪܴڸòλҩ
2.1.3ҩˮƽ֡һƼֻܽҩض٣ϵָܽҩijٵضλϵָܽҩضλIJϸڡܽҩƳƼʹҩϸˮƽϷãҩרŹϸϸûлûвӰ죬ʹҩЧﵽij̶ȡ
2.1.4̬֡ˮƼָ֬塢ˮƼһˮԵԴƼϳɴȻ(۶ǡ塢ǡ)ƼҩİҪƾϵͳʵֿ֣ɳΪҩϵͳ (drug-carrier systems)
Ͼ뱻ҩƼķ෨
оУҩо϶࣬֬ƼɰСֲڲͬע712 μmɱβеԽ˶ȡע12 μmëϸѪܴΡУǻע0.10.2 μmܿ챻״Ƥϵͳ(RES)ľϸյݷϸøС
2.2ҩϵͳչơΪһҩİԣ1415ݣѧֽʶϸĴҩı(ҩֱ)磺¡ںҩ֬()ı棬ҩϸİԣʵѪڲЧǶϿϸ˵¡(chTNT)֬壬ʹʵڵЧȵ֬Ϊߣ֬ΪҩﴫϵͳоΪ࣬Ŀǰܹѧߵձע
оϸϵҶ壬ͻϾϸö࣬ƱҶ֬壬ҶΪ鵼֬ϸİԡ
Ҷ֬“”ϸĤΪҩϵͳchTNT-֬״“”ϸĤϸˣΪҩϵͳֲͬİ֬ƲͬڵĹ
1966Morellȷֲ鶯ĸʵϸĤȥҺǵ(Asialoglycoprotein receptor,ASGPr)רһԵʶΪ˻ǵףǵΪ壬ɽҩﵼʵϸ(ηʵϸ(ݷϸƤϸ)ıи¶)ϸøתˣ屾»صϸĤ
ĿǰͰƼо϶ֽ࣬ͨ鵼ʽҩİԣʹҩЧӵãӦС
ɽҩƳɴƼҩİԣ纬ᰢùصעڰų£ҩŨȱȾעͬ밢ùظ߳100ٴƼеĴԳӿԶڰȫرų⡣дڴųǿȡݶ“۽”⣬ųǷıϸĻܺıѪķʽ⣬дһо
ܶ֬(LDL)16Ǵڲ鶯Ѫе֬סѪLDLЯѪ̴2/3ϸԴԵ̴ҪԴLDLڴлҪϸĤLDLʶ𣬴ӶϸڱãϸڵԴԵ̴ҪʱͨϸĤLDLĿͻԣӶLDLնӶԴԵ̴áLDLҪضLDLϸԴԵ̴ϳϰֳƣϸĤԵ̴ĴϸLDLĻԼijЩϸи߳ϸ20ϣˣLDLؿҩɴ߶ijЩϸİԡLDLԴ֬ףΪҩ壬ɱ֬塢¡ѭб״ƤϵͳѸ⣬ֲֿһڵİԲIJ㣬ԽǰҩﻯдڵİԲӦҪ塣
ϸСҩѭʱױRESľϸɣӶӰҩﵽƵİʴˣرRESѳΪҩԵص֮һ1718ݡհRESͣȻٸҩ壬ֱ˾ٻʹ߹𣬲鷢ʴ˷ȡԻԴLDLΪ壬ɻرRESɡо϶ǻرRES֬(RES-avoiding immunoliposomes)ںҩ֬ıIgG߿壬ֹPEGͼ2Ȼر˾ϸɣֿɽҩﵼϸPEGɻرRESɵĻδȫ壬PEGӾ߶ؽṹйأǿˮԺһйأƲPGEģ°ϸϸڵĶǻĹܡرRESķӱԼ(nonionic surfactant vesicles,NsVsNiosomes)PEG2000-̴(PEG-ch)ƳɵijѭùطӱԼ(long circulation adriamycin NsVs,L-ADM-NsVs)ϵPEGǿ˸ݵˮԣӶRESɣӳѪѭʱ䣬߰Ժԡ
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