摘要
采用离体皮肤扩散等技术研究了5-Fu在人皮肤各层次中的渗透性质和1,8-CN对药物渗透及皮肤热转变的影响。实验表明5-Fu在皮肤各层次中有相近分配系数,但扩散性质不同。角质层、全皮层、脱脂角质层和去角质层全皮扩散系数依次为1.32×10^(-7),1.01×10^(-7),1.37×10^(-6)和54.09×10^(-6)cm^2/h。用1,8-CN处理上述皮肤样品12h后,5-Fu在各组织的分配均减少,角质层和全皮的通透性显著增加(P<0.05),对去脂角质层和去角质层全皮的通透性无明显影响。结合DSC分析证明,角质层是5-Fu经皮渗透的重要屏障,类脂对5-Fu的扩散和1,8-CN的增效具重要意义。
The role of stratum corneum (SC) and its lipid constituents in skin permeability was assessed in vitro in diffusion system combined with the determination of partition coefficients (PC) and DSC technique. 5-Fu and 1, 8-CN were used as the hydrophilic drug and penetration enhancer, respectively. The results showed that the PCs of 5-Fu were the same in SC, delipid SC, full skin and SC-stripped full skin, but the diffusion coefficients (D) of 5-Fu were different from each other. They were 1.32±0. 37×10^(-7), 13.71±5.12×10^(-7), 1.01±0.31×10^(-7) and 540. 85±50.99±10^(-7) cm^2/h, respectively. When the skin membranes were pretreated with 1,8-CN for 12 h, the PCs were reduced to similar extent. However, the D was increased significantly in SC and in full skin, there was a small increase for delipid SC. No change was found in the D of stripped skin. DSC analysis indicated that 1, 8-CN might change the thermal behaviour of SC lipid and the influence disappeared when SC was extracted with organic solvent. These results suggest that SC was the main barrier for 5-Fu diffusion through human skin, and the intercellar lipids played an important role for the hydrophilic drug penetration regardless of the presence of the enhancer in SC.
出处
《药学学报》
CAS
CSCD
北大核心
1993年第12期924-930,共7页
Acta Pharmaceutica Sinica
基金
国家自然科学基金
关键词
角质层
5-氟脲嘧啶
差热分析
Stratum corneum (SC)
Lipids
5-Fluorouracil (5-Fu)
1,8-Cineole (1,8-CN)
Differencial scanning calorimetry (DSC)