目的研究盐酸青藤碱醇质体的最佳制备工艺,并考察不同促渗剂对其体外经皮渗透的影响和该制剂的皮肤过敏性。方法采用注入法制备盐酸青藤碱醇质体,以包封率为评价指标,通过正交设计优化最佳制备工艺;同时对其形态、Zeta电位、粒径大小进行分析;以氮酮为阳性促渗剂,研究丁香精油等不同促渗剂预处理离体小鼠腹部皮肤24 h后,对盐酸青藤碱24 h累积渗透量的影响。以豚鼠为动物模型,进行皮肤过敏性试验。目的所得青藤碱醇质体平均包封率为(66.18±1.84)%,平均粒径为(102.2±10.4)nm,Zeta电位为(52.4±1.5)mV。2%丁香酚预处理皮肤组,盐酸青藤碱醇质体24 h的累积渗透量为412.493 2μg/cm2,大约是醇质体组(未促渗)的1.6倍、水溶液组(未促渗)的5.8倍。该制剂外用对皮肤无致敏性。结论优选得到的盐酸青藤碱醇质体处方和制备工艺合理,醇质体稳定性良好,经皮给药安全。2%丁香酚可显著提高盐酸青藤碱的体外渗透效果。

Objective To optimize the preparation technology of sinomenine hydrochloride ethosomes (SHEs) and evaluate the effect of different penetration enhancers on transdermal permeation in vitro and its skin allergy reactionMethods SHEs were prepared by ethanol injection method; Orthogonal test was used to optimize the preparation method with entrapment efficiency (EE) as the evaluation index. The forms, Zeta potential, and particle size were analyzed. Azone was used as a positive penetration enhancer to study the effect of different penetration enhancers, such as clove oil after pretreatment of isolated mouse abdominal skin for 24 h being applied on the accumulative permeation quantity of ethosomes in sinomenine hydrochloride in 24 h. The cobaya experimental model was used for allergic study of SHEsResults The average EE, particle size, and Zeta potential of SHEs were (66.18 ± 1.84)%, (102.2 ± 10.4) nm, and (?52.4 ± 1.5) mV, respectively. The accumulative permeation amount of SHEs in 24 h was 412.493 2 μg/cm2 after 2% eugenol pretreatment 24 h, which was about 1.6 times of that in the blank group, 5.8 times of that in sinomenine hydrochloride water solution. No allergic reaction was observed in in vitro experimentConclusion The selected formulation and preparation technology of SHEs are rational. SHEs are stable and safe. Eugenol (2%) could achieve the best transdermal penetration of sinomenine hydrochloride in vitro.

国家重大新药创制科技重大专项(2009ZX09502-019);陕西省教育厅产业培育项目(2010JC20)