辣椒碱乳胶剂的体外经皮渗透、镇痛作用及刺激性研究

Study of capsaicin emulgel on in vitro transdermal permeation, analgesic actions,and irritation

目的制备辣椒碱乳胶剂,并对其体外经皮渗透性能、镇痛作用和皮肤刺激性进行考察。方法采用改良Franz扩散池,通过单因素法考察了不同促渗剂对乳胶剂的体外经皮渗透行为的影响,确定最佳处方,并考察辣椒碱乳胶剂透皮吸收行为;采用热板法考察其镇痛作用;选择家兔为动物模型,评价辣椒碱乳胶剂的皮肤刺激性。结果薄荷油、桉叶油和氮酮3种促渗剂均无显著促渗作用,故最终乳胶剂的优化处方不含促渗剂。体外透皮实验显示,市售乳膏、自制凝胶剂和乳胶剂三者的24 h累积渗透率分别为18.98%、37.04%、54.75%。在热板法实验中,市售乳膏和乳胶剂高剂量给药30、60、90 min后对热板致小鼠疼痛的抑制率分别为14.07%、14.49%、16.81%,18.63%、22.50%、25.57%。家兔皮肤刺激性实验结果表明乳胶剂无明显的皮肤刺激性。结论辣椒碱乳胶剂具有良好的透皮性能且无皮肤刺激性,乳胶剂中、高剂量具有良好的镇痛活性,为研发辣椒碱及其新型局部给药制剂提供依据。

Objective To prepare capsaicin emulgel and investigate its transdermal delivery ability in vitro, analgesic effect and skin irritation. Methods The effect of different penetration enhancers on the percutaneous permeation of emulgel in vitro was investigated by using the modified Franz diffusion cell. The optimal prescription was determined and the transdermal absorption of capsaicin emulgel was investigated; Analgesic effect was tested by hot plate method; The rabbit skin irritation test was used to evaluate the safety of capsaicin emulgel. Results Peppermint oil, eucalyptus oil, and azone three kinds of penetration enhancers had no significant effect on enhancing permeation effect, so the final formulation of the emulgel was optimized without penetration enhancers. In vitrotransdermal test showed that the cumulative permeation quantity of commercially available creams, self-made gels and emulgel was 18.98%, 37.04%, and 54.75%, respectively. In the hot plate method, the inhibitory rates of commercially available creams and high dose of emulgel after oral administration of 30, 60, and 90 min were 14.07%, 14.49%, 16.81%, 18.63%, 22.50%, and 25.57%. The skin irritation test results indicated that emulgel has no irritation to the rabbit skin. Conclusion Capsaicin emulgel has good percutaneous permeability without skin irritation, the middle and high dose of emulgel have good analgesic activity, which will supply evidence for the selection for the local transdermal formulations of capsaicin.