盐酸氨酮戊酸溶液剂与水凝胶的透皮及体内转化效果评价  

Transdermal and Biotramsformation Differences between Amindevulinic Acid Hydrochloride Solution and Gel Formula

作　　者：郭倩倩[1,2] 刘金华[1,2] 刘二刚[2] 赵永星[1] 华海婴[2] 薛逸君 黄永焯[2] 蒋剑平 苏勇 

机构地区：[1]郑州大学药学院,郑州450001 [2]中科院上海药物研究所,上海201203 [3]上海复旦张江生物医药有限公司,上海201203

出　　处：《中国现代应用药学》2014年第1期57-60,共4页Chinese Journal of Modern Applied Pharmacy

基　　金："重大新药创制"国家科技重大专项(2009ZX09401-001;2012ZX09401001);上海市科研计划项目(13431901900;11PJ1411800)

摘　　要：目的考察盐酸氨酮戊酸溶液剂及水凝胶2种制剂的透皮性能及皮内转化效果,为药物的临床应用提供参考。方法通过体外透皮实验考察盐酸氨酮戊酸的水凝胶和溶液剂的透皮效果,并对2种制剂在活体动物皮肤中的转化产物原卟啉IX(PpIX)进行定量分析,综合考察2种制剂的潜在治疗效果。结果体外透皮实验中,溶液剂在乳猪单位面积皮肤中的滞留量为(52.68-9.95)-g·cm-2,4 h累积透过量(Q)为(38.83-15.70)-g·cm-2,透皮速率为(12.27-5.99)μg·cm-2·h-1,透皮时滞(TL)为(0.70-0.35)h;凝胶剂分别为(59.90-28.68)-g·cm-2,(41.91-18.80)-g·cm-2,(13.22-5.82)μg·cm-2·h-1和(0.80-0.32)h;体内实验中,用药4 h时裸鼠单位质量皮肤中的PpIX含量分别为(2.14-0.22)μg·mg-1(水凝胶)和(2.17-0.48)μg·mg-1(溶液剂)。结论体内外实验结果表明,2种制剂的透皮效果及动物皮肤内转化生成PpIX的能力无显著差异,可根据临床需要选择合适的剂型和给药方案。OBJECTIVE To assess the transdermal and in vivo biotransformation differences between two kinds of formulations of topical applied aminolevulinic acid hydrochloride （ALA） in the form of solution and gel. METHODS Transdermal behevier of the two formulations were performed in Franz diffusion cell; ALA converted protoporphyrin（PpIX） in mice skin was also quantified as an index to assess transformation efficiency of the two formula. RESULTS Cumulative retained and permeated（Q） amount of ALA in pig skin, transdermal flux and lag time（TL） of ALA gel was 59.90 ± 28.68 μg·cm-2, 2135.8 ± 223.5 ng·mg-1, 12.27 ± 5.99 mg·cm-2·h-1, and 0.70 ± 0.35 h; The same results got from ALA solution was 52.68 ± 9.95 ±g·cm2, 2173.5 ± 480.8 ng·mg-1, 13.22 ± 5.82 mg·cm-2·h-1and 0.80 ± 0.32 h; Biotransformed PpIX from ALA was 41.91 ± 18.80 μg·cm-2 （for gel） and 38.83 ± 15.70 g·cm-2（for solution）, respectively. CONCLUSION There are no statistically differences between ALA gel and solution both in transdermal behevier and PpIX transformation efficiency, based on in vitro and vivo experiments.

关 键 词：盐酸氨酮戊酸 透皮吸收 原卟啉IX 

分 类 号：R943[医药卫生—药剂学]