摘要
目的:考察萜烯类手性促进剂芳樟醇和薄荷醇对氟比洛芬(flurbiprofen,FP)经皮渗透的对映体选择性作用。方法:采用Valia-Chien双室渗透扩散池,以大鼠离体皮肤为渗透屏障,以稳态经皮渗透速率为评价指标,用对映体选择性高效液相色谱法对FP对映体进行浓度测定,考察手性促进剂芳樟醇或薄荷醇对FP对映体选择性的影响。结果:无论供给液是否含单个对映体或消旋体,若供给液中不含促透剂,FP经大鼠离体皮肤渗透未见对映体选择性。当供给液中含有dl-薄荷醇时,RSFP的稳态渗透速率分别为R-FP、S-FP的1.34,1.27倍,差异有显著性(P<0.05);而供给液中含有l-薄荷醇时,FP对映体及消旋体间的皮肤渗透速率无显著差异(P>0.05)。l-薄荷醇和dl-薄荷醇对同一药物构型R-FP或S-FP的促透效果相当;然而,dl-薄荷醇对RS-FP的促透作用是l-薄荷醇的1.44倍。l-芳樟醇或dl-芳樟醇作为手性促透剂时,未发现对映体选择性渗透现象。结论:dl-薄荷醇对FP的促透作用出现了对映体选择性,而l-薄荷醇、l-芳樟醇和dl-芳樟醇未引起FP的对映体选择性渗透,且所有渗透实验均未发现对映体转化。
OBJECTIVE To study the influences of chiral enhancers of terpenes,linalool and menthol,on the enantioselective permeation of Flurbiprofen（FP）.METHODS The enantioselective permeation of FP across excised rat skin was investigated using Valia-Chien chambers.Steady state skin permeation rate was used as the evaluation parameter,The concentrations of enantiomer and racemic of FP were determined by enantioselective HPLC method.RESULTS In the absence of enhancers,the permeation profiles of R-and S-FP from donor solutions containing either RS-FP or pure enantiomers were comparable.In the presence of dl-menthol,the ratio of RS-FP to R-FP and S-FP were 1.34-to 1.27-fold in permeation rates,respectively.While in the presence of l-menthol,the permeation rates of enantiomer and racemic of FP showed no significant differences.Furthermore,the enhancing effects of dl-menthol and l-menthol on permeation of R-FP or S-FP were comparable.However,the permeation of RS-FP in the presence of dl-menthol was about 1.44-fold higher compared to l-menthol.No such effect was seen with dl-linalool or l-linalool.CONCLUSION dl-menthol can produce difference in percutaneous permeation of enantiomer and racemic of FP,while no enantioselectivity was seen when using donor solution containing l-menthol,dl-linalool or l-linalool.Through the study,no enantiomeric inversion was observed during the permeation process.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2015年第6期481-484,共4页
Chinese Journal of Hospital Pharmacy
基金
浙江省科技计划项目(编号:2014F10034)
关键词
手性促透剂
氟比洛芬
经皮渗透
对映体选择性
chiral permeation enhancer flurbiprofen percutaneous permeation enantioselective
