目的 建立粗茎秦艽Gentiana crassicaulis透皮吸收液中多种环烯醚萜类化学成分含量测定方法，并对粗茎秦艽体内外经皮渗透特性进行研究，为粗茎秦艽经皮给药制剂的研发、临床用药和传统剂型改革提供科学依据。方法 在课题组前期研究的基础上，采用醇提法制备粗茎秦艽提取液，选用3种常用的透皮促渗剂氮酮、冰片和丙二醇，利用HPLC定量评价单一促渗剂或二元复合促渗剂对粗茎秦艽中马钱苷酸、山栀苷甲酯、獐芽菜苦苷、龙胆苦苷和獐芽菜苷5种主要成分的体外经皮渗透特性的影响；以龙胆苦苷、马钱苷酸和獐芽菜苦苷3种成分为评价指标研究粗茎秦艽醇提物在活体小鼠皮肤模型的渗透特性。结果 与对照组相比，促渗剂的使用可显著增加粗茎秦艽中5种主要成分的体外吸收，A（5%氮酮）、B（5%冰片）、C（5%丙二醇）、A+B（2.5%氮酮+2.5%冰片）、A+C（2.5%氮酮+2.5%丙二醇）、B+C（2.5%冰片+2.5%丙二醇）5组中马钱苷酸、山栀苷甲酯、獐芽菜苦苷、龙胆苦苷和獐芽菜苷的透皮吸收速率（J）分别可达12.306 0、1.248 8、4.187 5、153.030 0、5.012 6 μg/（cm²·h），促渗效果分别是对照组的9.73、2.57、13.94、15.92、8.08倍。其中，A+C组，即2.5%氮酮+2.5%丙二醇组体外促渗效果最为明显。体内经皮渗透实验表明，与空白组对比，2.5%氮酮+2.5%丙二醇组对于活体小鼠皮肤的促渗透效果表现较好。结论 氮酮和丙二醇对粗茎秦艽中马钱苷酸、山栀苷甲酯、獐芽菜苦苷、龙胆苦苷和獐芽菜苷5种主要成分有良好的促渗透效果，为研究粗茎秦艽经皮给药制剂质量控制奠定基础。

Objective To establish a determination method for kinds of chemical components of iridoids in the roots of Gentiana crassicaulis in transdermal absorption liquid, and research its transdermal permeability, so as to provide scientific basis for transdermal delivery system, clinical medication and reform of the traditional forms of G. crassicaulis. Methods Based on the results of the previous investigation, in this paper, using the roots of G. crassicaulis as the research subject, a certain concentration solution of G. crassicaulis extract was prepared by the alcohol extraction method. Three kinds of common penetration enhancers, azone, borneol and propylene glycol were used. The effects of single penetration enhancer and dual compound penetration enhancers on the transdermal penetration of five kinds of chemical components of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside in vitro and the three kinds of chemical components of gentiopicroside, loganic acid and swertimarin in vivo were quantitatively studied by the method of HPLC to investigate the transdermal permeability of G. crassicaulis extract in mice skin model. Results According to the experimental results, compared to the control group, penetration enhancers significantly increased the absorption of five chemical components of G. crassicaulis in vitro. Transdermal absorption rates (J) of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside were 12.306 0, 1.248 8, 4.187 5, 153.030 0 and 5.012 6 μg/(cm²·h), respectively. The transdermal enhancer effects of A (5% azone), B (5% borneol), C (5% propylene glycol), A + B (2.5% azone and 2.5% borneol), A + C (2.5% azone and 2.5% propylene glycol), A + C (2.5% borneol and 2.5% propylene glycol) were 9.73, 2.57, 13.94, 15.92 and 8.08 times faster than the control group, respectively. Among these, the group of A + C had a marked osmotic enhancer effect in vitro. In comparison with the control group, the in vivo percutaneous penetration test indicated that the dual compound penetration enhancers of 2.5% azone and 2.5% propylene glycol had a marked effect for the permeability enhancement. Conclusion This study showed azone and propylene glycol significantly promoted the percutaneous penetration effect of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside of G. crassicaulis, and this study laid a foundation for the quality control of percutaneous drug delivery preparation of G. crassicaulis.

R283.6

国家重点研发计划（2017YFC1700705）；四川省留学人员科技活动项目择优资助经费计划（2018-68）；四川省科技创新苗子工程（2019059）；西南民族大学中央高校基本科研经费重点项目（2018NZD16）