目的 考察不同浓度和不同种类促渗剂作用下,少腹逐瘀方贴剂(SZTP)中9种效应成分的体外经皮渗透特性并优选适宜的促渗剂,为SZTP的研发、临床用药和传统剂型改革提供科学依据。方法 采用改良的Franz扩散池,以大鼠离体腹部皮肤为透皮屏障,以UPLC-TQ/MS/MS测定不同时间点接收室中药物浓度,运用主成分分析方法建立一种中药多组分经皮渗透研究的评价方法以求算累积渗透量及稳态透皮速率。结果 与无促渗剂组相比,不同浓度促渗剂混合组稳态透皮速率(J_S)均明显增加,说明促渗剂效果显著,其中以2.5%氮酮+2.5%丙二醇促渗效果最为明显,为无促渗剂组的2.7倍。结论 氮酮和丙二醇能显著促进SZTP中9种主要效应成分的经皮渗透效果,为SZTP开发成经皮给药制剂提供了一定的依据和参考。

Objective To study the effect of different penetration enhancers on the percutaneous absorption of nine active components in Shaofu Zhuyu Transdermal Patches (SZTP) across skin of mice and optimize the proper penetration enhancers in order to provide the scientific basis for SZTP research, clinical medication, and reform of the traditional forms. Methods Using improved Franz diffusion cells and taking isolated rat abdomen skins as transdermal barrier, the concentration of these components was determined by UPLC-MS/MS, then the total factor scores of the concentrations at different time were calculated using PCA and employed instead of the concentration to compute the cumulative amounts and steady fluxes. Results The results showed that compared to the control group, the steady fluxes of the other groups increased significantly, and furthermore, 2.5% azone with 2.5% propylene glycol manifested the best effect. The nine components could penetrate through skin well under the action of penetration enhancers. Conclusion Azone and propylene glycol could significantly promote the percutaneous penetration effect of the nine active components in SZTP, and it could provide a scientific basis for the preparation research of SZTP.

国家自然科学基金资助项目(30973885,81373889);江苏省高校自然基金重大基础研究项目(11KJA360002,06KJA36022);江苏省方剂高技术研究重点实验室建设项目(BM2010576);江苏省理血方剂创新药物工程中心建设项目;江苏省中药资源产业化过程协同创新中心建设平台