离子导入和超声导入增强白芥子涂方巴布剂治疗哮喘作用

Enhanced anti-asthma effect of white mustard seed varnish cataplasm by iontophoresis and sonophoresis

传统中药外用制剂的透皮速率和剂量小,影响药效发挥。本文制备白芥子涂方巴布剂,考察离子导入(iontophoresis)和超声导入(sonophoresis)作为物理促渗透技术,增强其治疗哮喘的作用。用醇提法获得白芥子、延胡索和甘遂活性成分,用挥发油提取器提取获得细辛挥发油,将其制备成载药量为17%的白芥子涂方巴布剂。用Franz扩散池法和豚鼠皮肤进行白芥子涂方巴布剂的经皮渗透实验,以芥子碱硫氰酸盐累积透过量和稳态透皮吸收速度作为指标,考察离子导入和超声导入方法的促渗透效果。结果发现超声导入促渗透效果优于离子导入;建立豚鼠哮喘模型,在豚鼠背部涂敷白芥子涂方巴布剂,发现施加离子导入和超声导入可明显促进白芥子涂方有效成分的吸收,并增强药效;病理检查发现超声导入和离子导入方法明显改善炎症;与模型组相比,无论是否施加物理促渗手段,各给药组白介素4(interleukin4,IL-4)和免疫球蛋白(immunoglobulinE,Ig E)水平均明显降低,而干扰素γ(interferonγ, IFN-γ)水平明显升高,以巴布剂/超声导入组最明显,已接近健康动物。综上,离子导入和超声导入技术可作为促进白芥子涂方巴布剂透皮吸收和药效的有效手段,其中超声导入方法更为优良。物理促渗透技术为中药透皮制剂的使用提供了新方法。

Topically applied traditional Chinese medicines（TCM） generally show low transdermal rates and doses, leading to weak therapeutic efficacy. Here, cataplasm of white mustard seed varnish was prepared. The effects of iontophoresis and sonophoresis on the transdermal delivery of this TCM and its anti-asthma effect were evaluated. Active components of white mustard seed, rhizoma corydalis and Radix Kansui were obtained after alcohol extraction, respectively. The volatile oil in Asarum Heterotropoides were obtained with volatile oil extraction equipment. The drug loading ratio of cataplasms was 17%（w/w）. Franz cell diffusion method was used to evaluate the accumulated permeation amount and the steady-state transdermal absorption rate of sodium thiocyanate. The improvement of sonophoresis on transdermal absorption was higher than that of iontophoresis. Asthma model of guinea pigs were established. Cataplasms of white mustard seed varnish were applied on the back of guinea pigs. Iontophoresis and sonophoresis obviously promoted the transdermal absorption and enhanced anti-asthma efficacy of white mustard seed varnish cataplasms. Pathological analysis showed that iontophoresis and sonophoresis significantly alleviated inflammation. Compared with the model group, IL-4 and Ig E levels in the cataplasm group, cataplasm/iontophoresis group, cataplasm/sonophoresis group decreased obviously, although the IFN-γ levels markedly increased. Moreover, the therapeutic efficacy of cataplasm/sonophoresis group was the best in all the groups, even leading to levels similar to that of healthy animals. Iontophoresis and sonophoresis are effective methods to promote transdermal absorption of cataplasms. Moreover, the effect of sonophoresis is higher than that of iontophoresis. Physical penetration improvement techniques provide a novel insight for the wide application of transdermal TCM.