马钱子总碱贴剂的促渗剂筛选及其镇痛作用研究

Screening of penetration enhancer and analgesic effect of total alkaloids in Semen Strychni Transdermal Patch

目的考察几种挥发油促渗剂对马钱子总碱贴剂的体外经皮促渗作用,并对其中渗透性最好的贴剂进行镇痛作用实验研究。方法利用改良Franz扩散池法,以氮酮为阳性对照、不含促渗剂的马钱子总碱为阴性对照,考察5%荜澄茄油、7%丁香油、10%干姜油、5%氮酮+5%干姜油4种促渗剂对模型药马钱子总碱经裸鼠皮肤的促渗效果,采用HPLC法测定马钱子总碱的含量;以小鼠醋酸扭体法和热板法两种疼痛模型观察马钱子总碱贴剂的镇痛作用。结果上述4种促渗剂对马钱子总碱12 h时的增渗倍数(ER12)分别为:1.69、1.78、2.93、2.45,与阴性对照组比较,其中10%干姜挥发油促渗效果显著(P<0.01),含该促渗剂的马钱子总碱贴剂能显著提高热板法小鼠痛阈值,降低醋酸致小鼠扭体次数(P<0.01)。结论 10%干姜挥发油能明显提高马钱子总碱在贴剂中的渗透量,促渗效果好;并具有显著的镇痛作用,药物效应强度较高,持续时间长。

Objective To investigate in vitro percutaneous penetration enhancemem ettect of several volatile oils on total alkaloids of semen Strychni（TASS） Transdermal Patch,and to explore the analgesic effect of TASS Patch with best drug percutaneous permeability.Methods A modified Franz diffusion cell method was used,with azone as the positive control,TASS Transdermal Patch without penetration enhancers （PEs） as the negative control,enhancing effect of 4 PEs,namely 5 ％ volatile oil of Fructus Litseae （FL）,7 ％ volatile oil of Flos Caryophyllata （FC）,10％ volatile oil of Rhizoma Zingiberis（RZ）,and 5％ azone ＋ 5％ volatile oil of RZ on TASS Transdermal Patch through bared mouse skin in vitro were investigated,the contem of TASS was determined by HPLC; The analgesic effect of TASS Transdermal Patches was observed by hot-plate test and writhing body test in mice.Results Compared with the negative control group,the enhancing rates（ER12） of TASS patch with the 4 PEs in 12 h were 1.69,1.78,2.93,2.45 respectively,and 10％ RZ volatile oil had the highest cumulative permeation volume in 12 h （P ＜ 0.01） ;TASS Transdermal Patch with 10％ RZ volatile oil could obviously improve the mouse＇s pain threshold caused by hot board and reduce the times of body writhing caused by acetic acid（P ＜ 0.01）.Conclusion 10％ RZ volatile oil can enhance permeation volume of TASS Transdermal Patch through bared mouse skin obviously ; the patch shows a marked analgesic effect with high intensity of activity and long endurance time.