ͼƬ dz̸ҩﴫϵͳоļȵ__ֻapp**

_ֻapp**

ǰλãҳ > ҵ > ҽҩѧ > ҩѧ > >

dz̸ҩﴫϵͳоļȵ

Դ::δ֪ | :_ֻapp** | Ӱ

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

ο

1Ansel HC,Popovich NG,Allen LV.Pharmaceutical dosage forms and drug delivery systems.Williams & Wilkins Baltimore.6th ed.New York:Marcel Dekker Inc,1995.218220

2Deshpande AA,Shah NH,Rhodes CT,et al.Development of a novel controlled-release system for gastric retention.Pharm Res,1997,14(6)815

3Shalaby WSW,Blevins WE,Park K.In vitro and in vivo studies of enzyme-digesbible hydrogels for oral drug delivery.J Controlled Release,1992,19(13)131

4Ueda S,Yamagulchi H,Kotani M,et al.Development of a novel drug release system,time-controlled explosion system(TES).Chem Pharm Bull,1994,42(4)246

5Bieck PR.Colonic drug absorption and metabolism.New York:Marcel Dekker Inc,1993.169172

6Gazzanig A,Sangalli ME,Giordano F.Oral chronotopic drug delivery systems:achievement of time and/or sit specifity.Eur J Pharm Biopharm,1994,40(4)246

7Rubinstein A,Radai R,Ezra M,et al.In vitro evaluation of calcium pectinate:a potential colon-specific drug delivery carrier.Pharm Res,1993,10(2)258

8Ashford M,Fell J,Attwood D,et al.Studies on pectin formulations for colonic drug delivery.J Controlled Release,1994,30(3)225

9Leopold CS,Friend DR.A dexamethasone-poly (L-aspartic acid) conjugate as potential prodrug for colon-specific drug delivery.Eur J Pharm Biopharm,1996,42(Suppl 1)S485

10Bieck PR.Colonic drug absorption and metabolism.New York:Marcel Dekker Inc,1993.145148

11Sako K,Nakashima H,Sawada T,et al.Relationship between gelation rate of controlled-release acetaminophen tablets containing ployethylene oxide and colonic drug release in dogs.Pharm Res,1996,13(4)549

12Anderson JM,Kim SW,Kopech J,et al.Advances in drug delivery systems 5.LondonNew York,Tokyo:Elsevier Amsterdam,1992.145159

13Kitano S,Koyamay ,Kataoka K,et al.A novel drug delivery system utilizing a glucose responsive polymer complex between poly(vinyl alcohol)and poly(N-vinl-2-pyrrolidone)with a phenylboronic acid moiety.J Controlled Release,1992,19(13)161

14Gottschalk S,Cristiano RJ,Smith LC,et al.Folate receptor mediated DNA delivery into tumor cells:potosomal disruption results in enhanced gene expression.Gene Ther,1994,1(1)185

15Rojansakuly.Antisense oligonucleotide therapeutics:drug delivery and targeting.Adv Drug Delivery Rev,1996,18(2)115

16Bijsterbosch MK,Berkel TJCV.Native and modified lipoproteins as drug delivery systems.Adv Drug Delivery Rev,1990,5(3)231

17Herron JN,Gentry CA,Davies SS,et al.Antibodies as targeting moiesties:affinity measurements conjugation chemistry and applications in immanoliposomes.J Controlled Release,1994,28(13)155

18Kuke I,Hayashi T,Tabata Y,et al.Synthesis of poly (ethylene glycol)derivatives with different branchings and their use for protein modification.J Controlled Release,1994,30(1)27


_ֻapp**