薄荷脑对雪上一枝蒿甲素经皮促渗的药动学及体内外相关性研究
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摘要
目的:考察不同浓度的薄荷脑对雪上一枝蒿甲素经皮促渗的药动学及体内外相关性。方法:分别制备含1%、3%、5%薄荷脑的雪上一枝蒿总碱凝胶,采用改良的Franz扩散池法进行体外释放及透皮研究;结合UPLC-MS/MS联用技术检测雪上一枝蒿甲素在小鼠血液中的药物浓度随时间的变化过程,并对其进行体内药动学研究;以体外24h溶出率为横坐标,AUC为纵坐标,对体外透皮结果与体内药动学结果进行回归分析。结果:与未加薄荷脑的雪上一枝蒿总碱凝胶相比,1%、3%、5%三种不同浓度薄荷脑的增渗倍数(ER)分别为2. 62、3. 26、4. 48,促渗雪上一枝蒿甲素的相对生物利用度分别为163. 39%、189. 16%、310. 69%,体内外相关系数为0. 9591。结论:体内外促渗效果一致,此方法可用于评价透皮给药系统体内外的相关性。
Objective: The study was carried out to investigate the pharmacokinetics and in vitro/in vivo correlation of Bullatine A with Different concentrations of menthol aspenetration enhancers(PE) following transdermal administration. Methods: ordinary gel of bullatine A total alkaloids containing 1%,3%,5% concentrations of menthol as PE were prepared. Single-chamber diffusion cell was used in vitro,In vivo tests,the changes of bullatine A in plasma of mice with time in ordinary gel of bullatine A total alkaloids were compared through UPLC-MS/MS,and their pharmacokinetic parameters were also compared andanalyzed. And the linear regression equation was figured through the concentration of cumulative in vitro and the concentration of cumulative absorption in vivo. Results: In comparison with negative control(no PE was added),the ER with 1%,3%,5% concentrations of menthol as PE were determined to be 2. 62,3. 26,and 4. 48,the relative bioavailability values were determined to be 163. 39%,189. 16%,and 310. 69%,The correlation coefficients were measured to be 0. 9591. Conclusion: Promoting effect is the same in vivo and in vitro,and this method can be used to evaluate the correlation between in vitro and in vivo transdermal delivery.
Objective: The study was carried out to investigate the pharmacokinetics and in vitro/in vivo correlation of Bullatine A with Different concentrations of menthol aspenetration enhancers(PE) following transdermal administration. Methods: ordinary gel of bullatine A total alkaloids containing 1%,3%,5% concentrations of menthol as PE were prepared. Single-chamber diffusion cell was used in vitro,In vivo tests,the changes of bullatine A in plasma of mice with time in ordinary gel of bullatine A total alkaloids were compared through UPLC-MS/MS,and their pharmacokinetic parameters were also compared andanalyzed. And the linear regression equation was figured through the concentration of cumulative in vitro and the concentration of cumulative absorption in vivo. Results: In comparison with negative control(no PE was added),the ER with 1%,3%,5% concentrations of menthol as PE were determined to be 2. 62,3. 26,and 4. 48,the relative bioavailability values were determined to be 163. 39%,189. 16%,and 310. 69%,The correlation coefficients were measured to be 0. 9591. Conclusion: Promoting effect is the same in vivo and in vitro,and this method can be used to evaluate the correlation between in vitro and in vivo transdermal delivery.
引文
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2 唐希灿,王祖武,胥彬.雪上一枝蒿甲碱、紫草乌碱和异乌头碱的镇痛作用.药学学报,1966;(3)∶227~228
3 魏文珍,陈晓兰,吴玉梅,等.雪上一枝蒿微乳体外透皮及影响因素研究.时珍国医国药,2015;(9)∶2132~2134
4 吴玉梅,陈晓兰,魏文珍,等.透皮促进剂对雪上一枝蒿甲素经皮渗透的影响.贵阳中医学院学报,2015; 5(37)∶23~26
5 祖强,赵晓莉,狄留庆,等.不同种类离体皮肤及人工合成膜对川芎贴膏体外透皮试验的影响.江苏药学与临床研究,2006; 14(6)∶358~360
6 祖强,狄留庆,赵晓莉,等.穴贴定喘膏体外透皮试验用皮肤的比较研究.中草药,2007; 38(4)∶519~521
7 陈晓兰,陆洋,杜守颖,等. HPLC测定丹皮中丹皮酚在大鼠体内血药浓度及药动学研究.中国中药杂志,2010; 35(21)∶2826
8 王毅,刘子秋,王炯,等. UPLC-MS/MS法测定人血中雪上一枝蒿甲素.中国司法鉴定,2013;(6)∶50
9 吴玉梅,陈晓兰,刘文,等.雪上一枝蒿总碱凝胶中雪甲素经皮药动学研究.中国中药杂志,2016; 41(8)∶1530~1534
10 汉会勋,马云淑,崔利利,等. 3种中药挥发油对磷酸川芎嗪的经皮渗透作用.中国实验方剂学杂志,2012; 18(8)∶1~4
11 罗红梅,马云淑,黄金娥,等.丁香挥发油对磷酸川芎嗪贴剂的经皮促渗作用.中国实验方剂学杂志,2012; 18(11)∶40~43