青藤碱的制剂与药代动力学研究进展

20104410SH.J.TCMOct.,2010;Vo.l44No.10综述1,212121.(830054)2.(201203),;,;;;R285.5A10071334(2010)10008406StudyprogressonsinomeninepreparationanditspharmacokineticsWANGHuayang1,2LIYan1WEIHai2MOJu1XINGShuning21.CollegeofPharmacy,XinjiangMedicalUniversity2.ShanghaiUniversityofTraditionalChineseMedicineAbstract:Thisarticlereviewsthesinomeninepreparationanditspharmaceutics,includingsustainedreleasepreparations,controlledreleasepreparationsandtransdermaldrugdeliverysystems,andsoon.Also,thisarticleexpoundsthepharmacokineticsofsinomeninefromtheperspectivesofmethodology,physiologicaldispositionanddosageformsetc,aswellastheexistingproblemsandthedevelopmentaldirection.Keywords:Sinomenine;preparation;pharmacokinetics;review[](06DZ19713)[],,,[],,Emai:[e-mail](Thunb.)Rehd.EtWils.,,[12]1,,,;,[3],1.1缓控释制剂1.1.1缓控释片,(HPMC),[4],HPMC[5][6](PolycarbophilCrosslinkedwithChitosan,PCC)HPMC,,,[78][9],[10],[11],,16h,,[12]!84!20104410SH.J.TCMOct.,2010;Vo.l44No.10,[13],,,1.1.2缓释微球注射剂[14],,1∀82∀1,,,,,,[15],,7.06m,10.4%73.3%Higuchi,R=0.9707,t50=9.58h;t50=2.1h,t50(P0.01),,#7.06m(0.002510m)∃,,,,[16]1.1.3缓释微丸()[17][18],,5%,,(0.1mol/L)(pH=6.8pH=7.4),pH1.1.4多囊脂质体,,[19],[20],80%,,,2030m,Higuchi(Q=7.18t1/22.14,r=0.992),t1/252.7h1.2透皮吸收制剂1.2.1凝胶剂[21],NaHSO3,,,;NaHSO3EDTA;;,,pH=6.06.5,,(pH),pH[22],pH;[23]1.2.2贴片PVA1788,70%,,,,,[24]1.2.3贴剂[25],,2h,,,20min,80%10min,,,(0.20&0.02)mm1.2.4微乳,80,,,,[26][27],1.2.5青藤碱喷雾剂[28],,,,,,1.2.6巴布剂[29][30],K30,,,,,,(P0.05)!85!20104410SH.J.TCMOct.,2010;Vo.l44No.10[31],40%,,,,;,2,,,2.1方法学研究,AUC,[32],,,[33],,,[34],#∃[35],[36],2.1.1提取方法,(),,,:(proteinprecipitation,PPT)(solidphaseextration,SPE)(liquidliquidphaseextraction,LLE)[37](microdialysis,MD)2.1.2分析检测方法,,,,,:[38][39][40]2.2青藤碱的药代动力学研究2.2.1体内过程研究(1)不同给药途径的药动学研究,,∋:[41],,[42],,[43]80mg(20mg/),:=(1.559&1.695)h1,=(0.073&0.023)h1,Ka=(2.442&0.636)h1t1/2=(0.791&0.491)h,t1/2=(9.397&2.425)h,Tmax=(1.040&0.274)h,Cmax=(246.604&71.165)ng/m,lAUC=(2651.158&1039.050)g!ml1!h1[44](RPHPLC)3%,0.3ml/100g:t1/2=2.24h,tmax=0.75h;Ke=0.31h1,Cmax=6.26g/m,lAUC=18.07g!ml1!h1[45]5%15g/ml,45mg/kg,,,:TLag=(0.024&0.015)h,Ka=(3.26&1.60)h1,Ke=(0.23&0.054)h1,T1/2(Ka)=(0.31&0.26)h,T1/2(Ke)=(3.15&0.82)h,tmax=(1.05&0.53)h,Cmax=(15.09&4.15)g/m,lAUC0()=(84.27&13.02)g!ml1!h1[46]Beagle10mg/kg,:T1/2(Ka)=(31.52&12.52)min,T1/2(Ke)=(87.62&28.26)min,Tmax=(82.50&13.89)min,Cmax=(0.15&0.027)mg/L,AUC0~T=(28.43&3.48)mg!L1!min1,10mg/kg,:=(0.67&0.36)min1,=(0.028&0.035)min1,t1/2=(1.45&1.02)min,t1/2=(106.68&120.23)min,AUC0~T=(93.32&82.08)mg!L1!min1,:AUC0T,(30.46&4.24)%!86!20104410SH.J.TCMOct.,2010;Vo.l44No.10∗:[47](RPHPLC)3%,0.3ml/100g:t1/2=0.75h,tmax=1.0h;Ke=0.92h1,Cmax=1.17g/m,lAUC=3.24g!ml1!h1,3%,0.3ml/100g[48],,,,,12h[49](),,:AUC0()43.396g!ml1!h1,1.32,20.025h,86%,Cmax1.825g/m,l1.31,Tmax,4h,!;,,(2)分布,[50]SD,150mg!kg1!d1,,,1,Liu[51]:40min,90min,(3)消除,,,[52](40mg/kg),,,,4+,,[53],80mg(20mg/),48h21.5mg,27%,,:=(0.073&0.023)h1,t1/2=(9.397&2.425)h,K10=(0.272&0.293)h1,CL/F=(0.033&0.010)(mg!h1/ng!ml1)(4)其他因素对药动学研究的影响,,,,,[5455],(100mg/kg)(77)Wistar,,[56]2.2.2不同剂型青藤碱的药代动力学及生物等效性研究(1)肠溶片[57](10mg/kg),,:t1/2=(1.45&1.01)min,t1/2=(106.67&12.22)min,AUC0~T=(93.32&8.07)[(mg/L)!min](10mg/kg),,:TLag=(16.84&6.94)min,T1/2(Ka)=(36.0&7.97)min,T1/2(Ke)=(84.77&19.33)min,tmax=(79.27&15.62)min,Cmax=(0.18&0.049)g/m,lAUC0~T=(38.51&13.23)[(g/ml)!h],41.26%,,[58],,(102.77&15.63)%,(2)缓释胶囊[59]120mg,:t1/2=(20.48&6.55)h,tmax=(5.7&1.51)h,∀max=(1031.66&546.15)g!L1,AUC030=(15507.17&6263.07)g!h1!L1120mg,,t1/2!87!20104410SH.J.TCMOct.,2010;Vo.l44No.10=(25.19&10.94)h,tmax=(8.67&1.63)h,Cmax=(1012.23&510.82)g!L1,AUC030=(13797.04&4915.68)g!h!L188.97%,,tmax,t1/2,,,,,(3)控释微丸[60],(60mg,)(60mg,):t1/2:(19.9&4.3)h,(17.8&2.1)h;Cmax:(638&128)ng!ml1,(1738&396)ng!ml1;Tmax:(6.2&1.1)h,(7.0&1.0)h;AUC0t:(20.2&3.3)h!g!ml1,(22.8&5.0)h!g!ml1,(90.1&10.4)%,Beagle,,(4)脂质体缓释片[61](60mg,),(60mg,),AUC024hAUC0),(112.61&8.22)%,CmaxCmaxTmax,Tmax(P0.05),,CSSAUCssCmaxTmax,(DF)(1.76&0.21)(2.41&0.25),(105.75&7.35)%,,,,,,,,3,,,,,,,,,,,,Caco2Caco2,,,,,,/(PK/PD),,,:[1]−..[M].:,1999:19661968.[2].[M].:,1995:427431.[3],,.[J].,2006,17(4):310313.[4],,,.[J].,2004,35(5):390393.[5].[P].,CN101016345A,20070815.[6].[D].:,2008.[7].[M].:,1994:259268.[8],.[J].,2005,30(20):15731576.[9],,,.[J].,2009,34(5):554559.[10],,.[J].,2010,32(2):209213.[11],,.[J].,2003,20(3):165170.[12],,,.[J].,2008,6(2):151153.[13],,,.[J].,2008,19(5):11951196.[14],,,.[P].,CN200710037075.7,20070202.[15].[D].:,2008.[16],,.[J].,2006,41(17):13201324.!88!20104410SH.J.TCMOct.,2010;Vo.l44No.10[17].[M].:,2003:125126.[18],,,.[J].,2008,28(5):360362.[19]ZhongHJ,DengYJ,WangXM,etal.Multivesicularliposomeformulationforthesustaineddeliveryofbreviscapine[J].IntJPharm,2005,301(12):1524.[20],,,.[J].,2008,39(8):11581161.[21],,,.[J].,2003,14(5):275276.[22],,.[J].,2003,23(8):463465.[23],,.[J].,2006,21(3):204205.[24],,.[J].,2000,17(3):200202.[25],,.[J].,2009,26(1):1122.[26],,,.[J].,2006,26(10):12281231.[27],,,.[J].,2008,30(8):11191121.[28],,,.[P].,CN1478475A,20040303.[29],,,.[J].,2003,28(1):711.[30],,.[J].,2007,38(8):564566.[31],.[P].,CN1