目的 以剂型改造为出发点优选复方蜘蛛香凝胶贴膏（ Compound Zhizhuxiang Gel Plaster，CZGP）处方，考察单一促渗剂与二元复合促渗剂的促渗作用，并初步考察CZGP与原处方香果健消片（ Xiangguo Jianxiao Tablets，XJT）的镇痛作用。方法 以初黏力、持黏力、剥离强度和感官评分为评价指标，采用D-最优混料设计优化凝胶贴膏处方；选择3种常用透皮促渗剂氮酮、丙二醇、薄荷醇，以木香烃内酯、去氢木香内酯、橙皮苷为指标，通过干加热透皮系统评价单一促渗剂和二元复合促渗剂的促渗作用，筛选最优促渗剂；通过小鼠（幼鼠）醋酸扭体实验初步评价CZGP与XJT的镇痛作用。结果 CZGP的最佳处方为酒石酸1.000 g、PVP K90 6.000 g、NP700 11.000 g、甘羟铝0.800 g、甘油35.000 g、水21.200 g；不同的一元促渗剂及二元促渗剂中，以3%丙二醇促渗作用最好，木香烃内酯、去氢木香内酯、橙皮苷的渗透速率分别为45.744、49.903、14.898 μg/(cm²·h)，增渗倍数分别为1.523、1.602、2.636； CZGP对小鼠（幼鼠）醋酸扭体具有镇痛作用，且镇痛率高于XJT。结论 CZGP具有良好的体外经皮渗透性及镇痛作用，为中药复方口服制剂改造为经皮给药制剂提供思路。关键词： D-最优混料设计；复方蜘蛛香；凝胶贴膏；体外透皮；醋酸扭体实验；香果健消片；药效学；镇痛；初黏力；持黏力；剥离强度；氮酮；丙二醇；薄荷醇；木香烃内酯；去氢木香内酯；橙皮苷；干加热透皮系统

Objective To optimize of the best prescription of Compound Zhizhuxiang Gel Plaster (复方蜘蛛香凝胶贴膏, CZGP) based on dosage form transformation, and investigated the penetration promotion effects of single and binary compound penetration enhancers, and the analgesic effects of gel plaster and Xiangguo Jianxiao Tablets (香果健消片, XJT). Methods Using initial adhesion, adhesion holiding, peeling strength and sensory score as evaluation indexes, the optimal prescription was optimized by D-optimal mixture design. Three commonly used transdermal enhancers, azone, propylene glycol and menthol, were selected. With costunolide, dehydrocostus lactone and hesperidin as indicators, the permeation promotion effects of single and binary compound enhancers were evaluated by dry heating transdermal system and screened the best penetration enhancers. The analgesic effect of CZGP and XJT was preliminarily evaluated by acetic acid writhing experiment in mice (young mice). Results The best prescription of CZGP was tartaric acid 1.000 g, PVPK90 6.000 g, NP700 11.000 g, aluminum glycolate 0.800 g, glycerin 35.000 g and water 21.200 g; 3% propylene glycol is the best one for different monobasic and binary penetration enhancers, and the penetration rates of costunolide, dehydrocostus lactone and hesperidin were 45.744, 49.903 and 14.898 μg/(cm²·h), and the enhancement ratios were 1.523, 1.602 and 2.636, respectively. CZGP had analgesic effect on acetic acid writhing in mice (young mice), and the analgesic rate was better than XJT. Conclusion CZGP has good transdermal permeability and analgesic effect in vitro, which provides ideas for transforming compound oral preparations of traditional Chinese medicine into transdermal preparations.

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国家自然科学基金资助项目(82174065);国家自然科学基金资助项目(82060723);云南省科技厅-云南中医学院应用基础研究联合专项项目(2018FF001);云南省科学技术院重大科技专项项目(202002AA100007)