手性促进剂芳樟醇对萘普生经皮渗透的促透效果  

Enhancing Effect of Chiral Enhancer Linalool on Skin Permeation of Naproxen

作　　者：郭霞[1] 荣毅[1] 张亮[1] 叶金翠[1] 

机构地区：[1]浙江省医学科学院药物研究所制剂室,杭州310013

出　　处：《中国医学科学院学报》2016年第1期55-61,共7页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(30901871);浙江省科技厅项目(2014F10034);省部共建项目(201231507);浙江省卫生高层次创新人才培养工程项目~~

摘　　要：目的研究dl-芳樟醇、d-芳樟醇、l-芳樟醇对模型药物经离体大鼠皮肤渗透促透效果的差异及芳樟醇对角质层类脂神经酰胺的作用。方法采用Valia-Chien双室渗透池进行离体皮肤渗透实验,手性固定相HPLC法测定皮肤渗透液中药物含量,红外光谱法考察芳樟醇对角质层类脂特征吸收峰峰位的影响。结果加入1%dl-芳樟醇、1%d-芳樟醇、1%l-芳樟醇时的稳态渗透速率分别为(2.47±0.63)、(1.53±0.54)、(1.73±0.48)μg·cm-2·h-1,分别是对照组[(0.99±0.42)μg·cm-2·h-1]的2.49、1.55、1.75倍,与对照组相比差异均有统计学意义(P均<0.05)。dl-芳樟醇对萘普生的促透作用显著大于d-芳樟醇和l-芳樟醇(P均<0.05)。与未经芳樟醇处理的角质层相比,经dl-芳樟醇处理过的角质层在亚甲基不对称振动吸收峰位上向高波数移动2.09 cm-1,而经d-芳樟醇和l-芳樟醇处理的角质层在波数上无变化。结论不同构型的芳樟醇对同一药物促透效果的差异与其对角质层脂质神经酰胺的扰乱程度有关。Objective To investigate the permeation-enhancing effect of dl-linalool,d-linalool, and l-linalool on model drugs across excised rat skin and the effect of linalool on the ceramides in stratum corneum lipids. Methods In vitro skin permeation studies were performed with Valia-Chien diffusion cells,and the permeation samples were analyzed by high performance liquid chromatography with chiral stationary phase. Infrared spectroscopy was used to investigate the effect of linalool on stratum corneum lipids. Results When the donor vehicles added with 1% dl-linalool,1% d-linalool,or 1% l-linalool,the steady-state skin permeation rate of naproxen was（ 2. 47 ± 0. 63）,（ 1. 53 ± 0. 54）,（ 1. 73 ± 0. 48） μg·cm^-2·h^-1,respectively,which is 2. 49,1. 55,and1. 75 times（ all P〈0. 05） compared with control group [（ 0. 99 ± 0. 42） μg·cm^-2·h^-1],and the differences were statistically significant（ all P〈0. 05）. The permeation-enhancing effect of dl-linalool on naproxen was found significantly greater than that of d-linalool and l-linalool（ both P〈0. 05）. Compared with the controlgroup,the stratum corneum treated with dl-linalool shifted to higher wave number on 2. 09 cm^-1 of asymmetric CH2 stretching vibrations in attenuated total reflection-fourier transform infrared spectroscopy analysis. However,stratum corneum treated with d-linalool and l-linalool did not display this phenomenon. Conclusion The disturbing degree of dl-linalool on stratum corneum lipids（ ceramides） is different from that of linalool enantiomers,suggesting their different enhancing effect on the same drug.

关 键 词：芳樟醇 萘普生 手性促进剂 经皮给药 

分 类 号：R94[医药卫生—药剂学]