目的 探究滚轮微针联合电致孔对青藤碱（SIN）透皮贴剂的促渗作用。方法 制备SIN透皮贴剂，采用桨碟法考察其释药行为；通过Franz扩散池评估体外透皮性能；以SIN 24 h累积渗透量(Q₂₄)为评价指标，结合单因素与正交实验优化电致孔参数；通过体内药动学研究验证其促渗效果。结果 所制备的SIN透皮贴剂符合一级释药特征；最优电致孔参数为：脉冲电压80 V、脉冲时间40 ms、脉冲个数300个、脉冲频率40 pulses.min^-1，此时Q₂₄达（1 504.28±18.50）μg·cm^-2，为对照组（无微针及电致孔预处理）的5.36倍。体内药动学结果显示，滚轮微针联合电致孔贴剂组的半衰期(t_1/2)为（16.38±4.84）h，较ig组提高1.54倍；药时曲线下面积(AUC_0～t)为（47.32±9.06）μg.h.m L^-1，较ig组和单纯贴剂组（无联合促渗处理）分别提高2.39倍和1.54倍，且该联合组相对ig组的生物利用度达（238.99±20.05）%。结论 滚轮微针联合电致孔促渗技术可延长SIN透皮贴剂的体内滞留时间，维持更稳定的血药浓度，为SIN透皮贴剂的高效促渗提供可行的策略。

Objective To investigate the penetration promoting effect of roller microneedle combined with electroporation on sinomenine（SIN） transdermal patch. Methods The SIN transdermal patch was prepared and its drug release behavior was investigated using the paddle over disk method. In vitro transdermal performance was evaluated via the Franz diffusion cell. Using the 24-hour cumulative permeation amount of SIN(Q₂₄) as the evaluation index, the electroporation parameters were optimized by combining single-factor and orthogonal experiments. Its penetration enhancing effect was validated through in vivo pharmacokinetic studies. Results The formulated SIN transdermal patch exhibited a first-order drug release profile. The optimized electroporation parameters were as follows: Pulse voltage 80 V, pulse time 40 ms, pulse number 300, and pulse frequency 40 pulses·min^-1. Under these conditions, the Q₂₄ reached（1 504.28 ±18.50） μg·cm^-2, which was 5.36 times that of the control group（without microneedle or electroporation pretreatment）. In vivo pharmacokinetic results demonstrated that the roller microneedle combined with electroporation patch group achieved the half-life(t_1/2) of（16.38 ±4.84） h, which was 1.54 times than that of the ig group. The area under the plasma concentrationtime curve(AUC_0～t) was（47.32 ±9.06） μg.h.m L^-1, representing 2.39 times and 1.54 times increases compared to the ig group and the simple patch group（without combined penetration enhancement treatment）, respectively. Moreover, the relative bioavailability of this combined group reached（238.99 ±20.05）% compared to the ig group. Conclusion The combination of roller microneedles and electroporation technology prolonged the in vivo residence time of the SIN transdermal patch and maintained a more stable plasma concentration, which provides a viable strategy for enhancing the permeation efficiency of SIN transdermal patches.

R943.4

黑龙江省自然科学基金资助项目(PL2024H195)