中国中药杂志

2019, v.44(16) 3569-3575

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基于微透析技术的雷公藤白芍微乳凝胶皮肤和血液药物动力学研究
Pharmacokinetics of skin and blood of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel based on micro-dialysis technology

杜清;罗晶;管咏梅;肖芳;臧振中;金晨;陈丽华;
DU Qing;LUO Jing;GUAN Yong-mei;XIAO Fang;ZANG Zhen-zhong;JIN Chen;CHEN Li-hua;Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine;the Fourth Affiliated Hospital of Nanchang University;

摘要(Abstract):

为进一步探究雷公藤白芍微乳凝胶在体内的代谢情况,该研究建立了雷公藤白芍凝胶中雷公藤甲素和芍药苷的LCMS/MS含量测定方法;采用浓度差法(增量法和减量法)测定了血液探针体外回收率。同时建立了雷公藤甲素和芍药苷皮肤和血液微透析方法,并通过微透析技术联合LC-MS/MS定量分析技术对雷公藤白芍微乳凝胶的在体皮肤和血液的药物动力学进行了研究。研究结果显示,雷公藤白芍凝胶中雷公藤甲素和芍药苷成分分析方法在要求范围内线性良好,色谱的专属性、回收率、精密度等均符合微透析样品的研究要求;且冻融稳定性,残留效应均符合生物样品方法学考察标准。在体外回收率试验中,增量法和减量法测得的探针回收率基本一致;芍药苷皮肤和血液微透析回收率分别为(30. 60±1. 09)%,(28. 01±1. 75)%,雷公藤甲素皮肤和血液微透析回收率分别为(26. 79±2. 78)%,(25. 39±1. 86)%,且探针日内回收率在11 h内稳定。药代动力学研究中雷公藤甲素皮肤和血液的Cmax分别为(148. 03±41. 51),(76. 77±15. 27)μg·L-1,Tmax分别为(2. 33±0. 29),(3. 00±0) h,AUC0-11 h分别为(2 814. 05±1 070. 37),(1 580. 63±208. 27)μg·h·L-1,MRT0-11 h分别为(4. 20±0. 33),(4. 54±0. 34)h,T1/2分别为(4. 61±4. 11),(1. 07±0. 13) h。芍药苷皮肤和血液的Cmax分别为(991. 88±152. 22),(407. 02±120. 06)μg·L-1,Tmax分别为(2. 00±0),(2. 83±0. 29) h,AUC0-11 h分别为(18 430. 27±3 289. 35),(6 338. 59±1 659. 32)μg·h·L-1,MRT0-11 h分别为(4. 29±0. 16),(4. 00±0. 05) h,T1/2分别为(2. 16±0. 43),(1. 78±0. 48) h。药代动力学研究结果提示微乳凝胶经皮渗透有形成皮肤储库的作用,在提高药物透皮效率的同时能够使药物持续缓慢、控制释放,形成长效作用。
To further investigate the metabolism of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel in vivo,an LCMS/MS method was established for the determination of triptolide and paeoniflorin in T. wilfordii and P. lactiflora micro-emulsion gel.The extracorporeal recovery rate of blood probe was measured by concentration difference methods( incremental method and decremental method). Meanwhile,the skin and blood micro-dialysis methods of tripterine and paeoniflorin were established,and the pharmacokinetics of T. wilfordii microemulsion gel in skin and blood was studied by micro-dialysis combined with LC-MS/MS quantitative analysis. The results showed that the established method for the determination of triptolide and paeoniflorin in T. wilfordii microemulsion gel was well linear within the required range,and the specificity,recovery rate and degree of precision of the chromatography all conformed to the research requirements of micro-dialysis samples. The stability of freeze-thawing and the residual effect all conformed to the criteria of biological sample methodology. The probe recovery rates measured by incremental method and decremental method were almost consistent with the extracorporeal recovery rate test. The recovery rates of paeoniflorin in skin and blood micro-dialysis were( 30. 60±1. 09) % and( 28. 01± 1. 75) %,respectively. And the recovery rates of skin and blood micro-dialysis were( 26. 79 ± 2. 78) % and( 25. 39±1. 86) %,respectively. The intraday recovery rate of probes was stable within 11 h. The results of pharmacokinetic study showed that the Cmaxvalues of triptolide in skin and blood were( 148. 03±41. 51) and( 76. 77±15. 27) μg·L-1,respectively. And the Tmaxvalues were( 2. 33±0. 29) and( 3. 00± 0) h,respectively. The AUC0-11 hvalues were( 2 814. 05± 1 070. 37) and( 1 580. 63±208. 27) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 20± 0. 33) and( 4. 54± 0. 34) h,respectively. The T1/2 values were( 4. 61±4. 11) and( 1. 07± 0. 13) h,respectively. The Cmaxvalues of paeoniflorin in skin and blood were( 991. 88 ± 152. 22) and( 407. 02±120. 06) μg·L-1,respectively. The Tmaxvalues were( 2. 00±0) h and( 2. 83±0. 29) h,respectively. The AUC0-11 hvalues were( 18 430. 27±3 289. 35) and( 6 338. 59 ± 1 659. 32) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 29 ± 0. 16) and( 4. 00±0. 05) h,respectively. The T1/2 values were( 2. 16±0. 43) and( 1. 78±0. 48) h,respectively. The results suggested that micro-emulsion gel played a role in forming skin reservoir through percutaneous penetration. It not only could improve drug transdermal efficiency,but also control the sustained release of drug and form a long-term effect.

关键词(KeyWords): 雷公藤甲素;芍药苷;皮肤和血液微透析;回收率
triptolide;paeoniflorin;skin and blood microdialysis;recovery

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81460607)

作者(Authors): 杜清;罗晶;管咏梅;肖芳;臧振中;金晨;陈丽华;
DU Qing;LUO Jing;GUAN Yong-mei;XIAO Fang;ZANG Zhen-zhong;JIN Chen;CHEN Li-hua;Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine;the Fourth Affiliated Hospital of Nanchang University;

DOI: 10.19540/j.cnki.cjcmm.20190318.503

参考文献(References):

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