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1、InternationalJournalofPharmaceutics329(2007)111HistoricalPerspectivesCyclodextrinsandtheirpharmaceuticalapplicationsThorsteinnLoftssona,∗,DominiqueDuchenebaFacultyofPharmacy,UniversityofIceland,Hofsvallagata53,IS-107Reykjavik,IcelandbUMRCNRS8612,Physico-Chimie-Pharmac
2、otechnie-Biopharmacie,Facult´edePharmacie,Universit´eParis-Sud,5,RueJeanBaptisteCl´ement,92290ChˆatenayMalabry,FranceReceived6October2006;receivedinrevisedform25October2006;accepted28October2006Availableonline9November2006AbstractCyclodextrinswerefirstdescribedbyVillie
3、rsin1891.Schardingerlaidthefoundationofthecyclodextrinchemistryin19031911andidentifiedboth-and-cyclodextrin.Inthe1930s,Freudenbergidentified-cyclodextrinandsuggestedthatlargercyclodextrinscouldexist.Freudenbergandco-workersshowedthatcyclodextrinswerecyclicoligosaccha
4、ridesformedbyglucoseunitsandsomewhatlaterCramerandco-workersdescribedtheirabilitytoforminclusioncomplexes.Bytheearly1950sthebasicphysicochemicalcharacteristicsofcyclodextrinshadbeendiscovered,includingtheirabilitytosolubilizeandstabilizedrugs.Thefirstcyclodextrin-relat
5、edpatentwasissuedin1953toFreudenberg,CramerandPlieninger.However,purecyclodextrinsthatweresuitableforpharmaceuticalapplicationsdidnotcomeavailableuntilabout25yearslaterandatthesametimethefirstcyclodextrin-containingpharmaceuticalproductwasmarketedinJapan.Latercyclodext
6、rin-containingproductsappearedontheEuropeanmarketandin1997alsointheUS.Newcyclodextrin-basedtechnologiesareconstantlybeingdevelopedand,thus,100yearsaftertheirdiscoverycyclodextrinsarestillregardedasnovelexcipientsofunexploredpotential.©2006ElsevierB.V.Allrightsreserved
7、.Keywords:Complexation;Cyclodextrin;Drugdelivery;Formulation;History;Regulatory;ToxicologyContents1.Introduction...............................................................................................................22.Theemergingofcyclodextrins................
8、..............................................................................22.1.Thediscoveryperiod,1891tothemid1930s.....
