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

目的 考察盐酸氨酮戊酸溶液剂及水凝胶两种制剂的透皮及皮内转化效果的差异,为药物的临床应用提供参考。方法 通过体外透皮实验考察了盐酸氨酮戊酸的参比制剂和待测制剂的透皮效果,并测定两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,综合比较两种制剂的潜在治疗效果的差异。结果 体外透皮实验中,凝胶制剂的在新生猪皮肤中的滞留量、单位面积累积透过量（Q）、透皮速率（Flux）、透皮时滞（TL）分别为59.90 ±28.68 mg·cm2、2135.8 ±223.5 ng/mg、12.27± 5.99 mg·cm-2·h-1和0.70±0.35 h；溶液剂分别为52.68 ± 9.95 mg·cm2、 2173.5 ± 480.8 ng/mg、13.22 ± 5.82 mg·cm-2·h-1和0.80 · 0.32 h； 体内实验中,用药4h时裸鼠单位质量皮肤中的PpIX含量分别为41.91 ± mg/cm2（溶液剂）和38.83 ± 15.70 g/cm2（水凝胶）。 结论 体外实验结果表明,两种制剂在的透皮效果及皮肤内滞留量无显著差异,在体实验中两种制剂皮肤中PpIX的含量无显著性差异。

Transdermal effect of Aminolevulinic Acid Hydrochloride for Topical Solution

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.