复方I类新药依那普利叶酸片的创新思路

©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(17)159020091817[](02013056)[],,,,:[phone],E2mail:[e-mail][],,,,:[phone],E2mail:[e-mail]1,2,2,3,1,4(1,230032;2,100034;3,100037;4,518060)[],H(),(),,FDAEMEA,,,,[];H;;[]R972.4[]A[]1003-3734(2009)17-05Innovationstrategyforrationaleandclinicalsignificanceofanewcombinationofdrugs:enalaprilmaleateandfolicacidtabletsCHENGuang2liang1,HUOYong2,LIJiang2ping2,LIULi2sheng3,XUXi2ping1,4(1AnhuiMedicalUniversityBiomedicalInstitute,Hefei230032,China;2PekingUniversityFirstHospital,DepartmentofCardiology,Beijing100034,China;3FuwaiCardiologyHospital,Beijing100037;4ShenzhenUniversityBiomedicalInstitute,Shenzhen518060,China)[Abstract]BasedonthethirdNationalSurvey,strokehassurpassedcancertobecometheleadingcauseofdeathinChina.H2typehypertension(definedaswithelevatedplasmahomocysteineandhypertension)consti2tutesabout75%ofallhypertensivepatientsinChina,andisassociatedwithremarkablyhighriskofstrokeinci2denceandstrokedeathinChina.Basedontheconceptofmultipleriskfactorcontrolincardiovasculardiseasepre2vention,anewcombinationofdrugs,enalaprilmaleateandfolicacidtablets,isspecificallydesignedforeffectivecontrolofH2typehypertension,i.e.tocontrolhypertension,lowerplasmahomocysteine,andimproveplasmafo2latelevel.ThisarticlepresentedthetheoreticalframeworkandrationaleforsimultaneouscontrolofhypertensionandelevatedHcyasthebeststrategyforprimarystrokeprevention,includingtheconceptofH2typehypertension,H2typehypertensionasamajorriskfactorforstroke,andtheneedtocontrolformultipleriskfactorsinstrokepre2vention,FDAandEMEAspoliciesoncompounddrugs,andefficacyofstrokepreventionbyloweringplasmaho2mocysteineusingfolicacidsupplementation.Thisarticlealsohighlightedthescientificinnovationsandclinicalad2vantageofenalaprilmaleateandfolicacidtabletsfortreatinghypertension,especially,H2typehypertension,anditsgreatpotentialtocontroltheupwardtrendofstrokemorbidityandmortalityinChina.[Keywords]enalaprilmaleateandfolicacidtablets;H2typehypertensives;strokeprevention;innovationstrategy©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(17)159120091817,,,(homocysteine,Hcy)2,H(Hcy),,Hcy[1-3](Hcy),,(H20080059,H20080060,H20080061),:,1WHO200,Hcy,(Framingham)(MRFTT)(PROCAM),;22,WHO[4]2002;2005JNC7ESH/ESC2007[5]2FDAEMEAFDA[6]EMEA[7],2:,,,,:,,Hcy3,,3HcyGraham[8](1),Hcy2,H5,25304,6,H12.1HHcy1[8]©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(17)1592200918174Hcy2,(128/10)(56/10)2,,121,7131[9]1,Hcy,()[9-13],Hcy,Hcy156/10128/10:(1-2)1(7-13)1()/%193118.8/%363/%104Hcy/mol.L-110-1215/nmol.L-123135HcyRCTMeta(),Wang[14]Meta,18%,25%;3629%;Hcy20%23%;25%,26HcyHOPE22,65%ACEI,,Hcy3.2molL-1,25%[10]Zoungas[15],90.5%,55%Hcy,,,HcyH75%,Hcy[3]2Meta[14]/95%P373/8949405/78920.820.68-1.000.04536224/4078193/30151.000.83-1.210.9536149/4871212/48770.710.57-0.870.001Hcy20%179/2325174/21800.890.55-1.420.6220%172/4967196/40510.770.63-0.940.012179/2325174/21800.890.55-1.420.62194/6624231/57120.750.62-0.910.003152/1827148/18531.040.84-1.290.71221/7122257/60390.750.62-0.900.0027(ACEI),ACEI,MTHFR677TT,Hcy,ACEI,ACEIHcy,ACEIH,HcyHcy,2©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(17)15932009181728;Hcy;Hcy:Hcy:(2005)(TIA)(2006)Hcy[16-17]HcyICD210(2006)[18]:hyperhomocysteinemia(E72.1)ACEI+2008:(JA2MA)WAFACS[19]:54427.3,,ACEI,19%ACEI:WHO(15,2007)ACEI2009ACEI9,;Hcy,,,Hcy,,[][1],.H[J].,2008,47(12):976-977.[2],,,.[J].,2008,88(42):2957-2961.[3],,,.:[J].,2008,88(47):3316-3318.[4]WHO.CVD2RiskManagementPackageforlow2andmedium2re2sourcesettings[S].2002.[5]MANCIAG,DEBACKERG,DOMINICZAKA,etal.2007Guidelinesforthemanagementofarterialhypertension:thetaskforceforthemanagementofarterialhypertensionoftheEuropeanSocietyofHypertension(ESH)andtheEuropeanSocietyofCar2diology(ESC)[J].Hypertension,2007,25(6):1105-1187.[6]FDA.21CFR300.50SubpartB-combinationdrugs.Fixed2com2binationprescriptiondrugsforhumans[S].[7]EMEA.Noteforguidanceonfixedcombinationmedicinalprod2ucts[S].London,1996.[8]GRAHAMIM,DALYLE,REFSUMHM,etal.Plasmahomocys2teineasariskfactorforvasculardisease.TheEuropeanConcert2edActionProject[J].JAMA,1997,277(22):1775-1781.[9]KJELDSENSE,JULIUSS,HEDNERT,etal.Strokeismorecommonthanmyocardialinfarctioninhypertension:analysisbasedon11majorrandomizedinterventiontrials[J].BloodPres2sure,2001,10(4):190-192.[10]WOLF2MAIERK,COOPERRS,BANEGASJR,etal.Hyperten2sionprevalenceandbloodpressurelevelsin6Europeancoun2tries,Canada,andtheUnitedStates[J].JAMA.2003,289(18):2363-2369.[11]LONNE,YUSUFS,ARNOLDMJ,etal.HomocysteineloweringwithfolicacidandBvitaminsinvasculardisease[J].NEnglJMed,2006,354(15):1567-1577.[12],,,.[J].(),2007,39(6):614-618.[13]ROSAMONDW,FLEGALK,FURIEK,etal.Heartdiseaseandstrokestatistics-2008update:areportfromtheAmericanHeartAssociationStatisticsCommit