白藜芦醇三甲醚乳胶体外经皮渗透研究

Preparation of 3,5,4′-trimethoxy-trans-stilbene and its transdermal absorption ex vivo

目的制备白藜芦醇三甲醚(BTM)乳胶,考察载药量、促渗剂及其组合对BTM经皮渗透性的影响,评价药物透皮给药的可行性。方法以卡波姆940为凝胶基质制备BTM乳胶,选用改良Franz扩散池,以离体乳猪腹部皮肤为屏障进行体外经皮渗透实验,用HPLC-UV法测定各时间点接收室中药物浓度,计算经皮渗透动力学参数。结果载药量由1%增加到2%时,BTM 24 h单位面积渗透量增加1倍,2%与4%乳胶渗透量没有统计学差异(P>0.1)。促渗剂均可显著促进BTM透皮吸收,其透皮速率为:2%香叶醇>2%肉豆蔻酸异丙酯>2%油酸>2%氮酮>2%橙花叔醇>无促渗剂;香叶醇的浓度大小对BTM的透皮吸收无明显影响(P>0.05);与单用2%香叶醇相比,促渗剂联用(2%香叶醇+2%丙二醇、2%香叶醇+2%肉豆蔻酸异丙酯)未显示出显著协同促渗作用(P>0.05),而2%香叶醇+2%异丙醇则显示弱拮抗促渗作用(P<0.05)。结论常用促渗剂均能不同程度促进BTM经皮渗透,载药量为2%、促渗剂为2%香叶醇时,BTM体外透皮可达最大吸收。但BTM体外透皮吸收具有饱和性,该结果为BTM经皮给药研究提供了基础。

Objective To prepare 3,5,4′-trimethoxy-trans-stilbene（BTM） emulsion-gel and investigate the effect of dosage,different penetration enhancers and their combinations on percutaneous absorption of BTM and discuss the feasibility of transdermal administration of BTM.Methods BTM emulsion-gel was prepared with carbopol 940 as the base material.The percutaneous permeation experiment was carried out with modified Franz-type diffusion cell with isolated piglets skin as the barrier and the concentration of each sample in the reception room was determined by HPLC-UV to calculate the parameters.Results The cumulative permeation quantity of BTM at 24 h doubled as the dosage increased from 1% to 2%,but showed no significant difference（P〉0.1） between 2% and 4%.Enhancers obviously promoted the percutaneous absorption of BTM with the effect of enhancers as follows： 2% geraniol〉2% isopropyl myristate〉2% oliec acid〉2% azone〉2% nerolidol〉control,but no difference in permeation quantity（P〉0.05） was observed when the concentration of geraniol in BTM emulsion-gel increased,as well as enhancers combined（2% geraniol＋2% isopropyl myristate,2% geraniol＋2% propylene glycol）.There was a weak antagonistic effect of penetration when 2% geraniol combining 2% isopropanol.Conclusion The percutaneous absorption of BTM significantly increases with the enhancers and reaches its biggest absorption when 2% dosage and 2% geraniol are used.The transdermal penetration of BTM can be saturated,which provides a basis for futher transdermal delivery study.