微针对白脉软膏经皮渗透性及应用安全性研究  

Study on percutaneous permeability and application safety of microneedles targeting Baimai Ointment

作　　者：肖五庆 梁军[1] 竺楹银 刘凯列 钟宛凌 杨天姿 席铖 胡晓红 武慧超[1] 杜守颖[1] XIAO Wu-qing;LIANG Jun;ZHU Ying-yin;LIU Kai-lie;ZHONG Wan-ling;YANG Tian-zi;XI Cheng;HU Xiao-hong;WU Hui-chao;DU Shou-ying(Beijing University of Chinese Medicine,Beijing 102488,China;Tibet Cheezheng Tibetan Medicine Co.,Ltd.,Linzhi 860000,China)

机构地区：[1]北京中医药大学,北京102488 [2]西藏奇正藏药股份有限公司,西藏林芝860000

出　　处：《中草药》2023年第6期1766-1774,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(82104545);国家重点研发计划(2019YFC1712403);中央高校基本科研业务费专项资金资助(2020-JYBZDGG-024)。

摘　　要：目的为改善白脉软膏经皮渗透性,采用微针技术进行促透,考察其对白脉软膏经皮渗透性和应用安全性的影响,以筛选安全、有效的微针应用条件。方法以小鼠腹皮作为实验材料,采用改良的Franz扩散池进行体外渗透性评价,计算不同微针条件下白脉软膏3个主要成分甘草酸铵、甘松新酮、姜黄素的24 h累积经皮渗透量及稳态透皮速率,评估促透性能;采用光学相干断层扫描法(optical coherence tomography,OCT)记录微针处理后0、10、20、30、40、50、60、90、120min时的微孔道深度,进而对皮肤损伤及恢复程度进行量化评分,作为安全性评价依据。综合体外渗透性、皮肤损伤及恢复程度为评分指标(权重分别占40%、30%、30%),运用正交试验设计将微针长度、作用力度和作用时间作为考察因素进行条件优化,筛选适宜的微针条件。结果3个因素对综合评分的影响大小为微针长度>作用时间>作用力度,最终筛选出的微针条件为微针长度250μm、作用力度5 N、作用时间5 min。结论综合考虑了微针对白脉软膏体外渗透性、皮肤损伤及恢复程度的影响,为白脉软膏及微针促透的临床合理安全应用提供理论参考。Objective In order to improve the percutaneous permeability of Baimai Ointment(白脉软膏,BO),microneedle technology was used to promote penetration,and its effects on the percutaneous permeability and application safety of BO were investigated to screen safe and effective microneedle application conditions.Methods The abdominal skin of mice was used as experimental material,and the improved Franz diffusion cell was used to evaluate the permeability in vitro.The 24 h cumulative transdermal penetration amount and steady-state percutaneous penetration rate of ammonium glycyrrhizinate,nardosinone and curcumin,the three main components of BO under different microneedle conditions,were calculated to evaluate the penetration performance.Optical coherence tomography(OCT)was used to record the depth of micropores at 0,10,20,30,40,50,60,90,and 120 min after microneedle treatment,and then the degree of skin damage and recovery was quantified as the basis for safety evaluation.The external permeability,skin damage and recovery degree of the complex were taken as the scoring indexes(the weights were 40%,30%and 30%,respectively).The length,action intensity and action time of the microneedle were used as the investigation factors to optimize the conditions by orthogonal experimental design,and the appropriate microneedle conditions were screened.Results The results showed that the influence of three factors on the comprehensive score was microneedle length>action time>action intensity,and the final microneedle condition was microneedle length 250μm,action force 5 N,action time 5 min.Conclusion In this paper,the effects of microneedle on the permeability,skin damage and recovery of BO in vitro were comprehensively considered to provide theoretical reference for rational and safe clinical application of BO and microneedle penetration promotion.

关 键 词：白脉软膏 微针 经皮渗透 光学相干断层扫描法 综合评价 甘草酸铵 甘松新酮 姜黄素 

分 类 号：R283.6[医药卫生—中药学]