目的 基于偏头痛药效研究优化青花椒超临界提取部位热熔压敏胶贴剂成形工艺，并对贴剂安全性进行评价。方法 以均匀性、涂展性、渗布程度、皮肤追随性、剥离性、反复揭贴性、残留量等感官评价及初黏力、持黏力、剥离强度为指标，采用单因素试验与Box-Behnken设计-响应面法对热熔压敏胶基质配比进行筛选；采用在体动物评价法，以硝酸甘油型偏头痛大鼠挠头次数为指标筛选贴剂载药量；另外采用小鼠急性毒性试验、家兔皮肤刺激性试验及豚鼠皮肤过敏性试验评价青花椒超临界提取部位热熔压敏胶贴剂的安全性。结果 热熔压敏胶贴剂的最佳基质处方为苯乙烯-异戊二烯-苯乙烯（SIS）弹性体-氢化石油树脂-液体石蜡4∶2∶5；青花椒超临界提取部位贴剂可明显减少硝酸甘油型偏头痛大鼠的挠头次数，70 mg/贴载药量组在30～60 min可将大鼠挠头次数降低81.75%，优选为最佳载药量；该贴剂对小鼠无急性毒性，对新西兰兔完整皮肤和破损皮肤有轻微刺激性，6 h内自行消除，对豚鼠无过敏性。结论 该工艺制备的青花椒超临界提取部位热熔压敏胶贴剂感官性能好，黏附力强，且安全有效。

Objective To optimize the forming process of hot-melt pressure-sensitive adhesive patch from the supercritical extraction part of Zanthoxylum schinifolium, and evaluate the safety of the patch. Methods Based on the sensory evaluation of uniformity, spreadability, degree of infiltration, skin followability, peelability, repeated peelability, and residual amount, as well as initial adhesion, holding adhesion and peeling strength as evaluation indexes, the matrix ratio of hot melt pressure sensitive adhesive was screened by single factor test and Box-Behnken design-response surface method. The in vivo animal evaluation method was used to screen the drug loading of the patch according to the number of head scratching in rats with nitroglycerin migraine. In addition, the safety of hot melt pressure sensitive adhesive was evaluated by mouse acute toxicity test, rabbit skin irritation test and guinea pig skin hypersensitivity test. Results The best matrix prescription of hot melt pressure sensitive adhesive was SIS (styrene-isoprene- styrene) elastomer: hydrogenated petroleum resin: liquid paraffin = 4:2:5. Z. schinifolium supercritical extract patch could significantly reduce the number of head scratching of migraine rats induced by nitroglycerin, 70 mg drug dosage of each gel patch could reduce the number of head scratching in rats by 81.75% within 30—60 min, which was preferably the best drug loading. The patch had no acute toxicity to mice, slightly irritated to the intact and damaged skin of New Zealand rabbits, eliminated itself within 6 h, and had no allergy to guinea pigs. Conclusion The hot melt pressure sensitive adhesive for supercritical extraction of Z. schinifolium prepared by this process has good sensory properties, strong adhesion, safe and effective.

R283.6

四川省中医药管理局花椒专项项目（2018HJZX023）；成都中医药大学中药学学科特色创新科研团队项目（CXTD2018006）；成都中医药大学“杏林学者”学科人才科研提升计划项目（BSH2018007）