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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 investigate the enantioselective effect of terpene chiral enhancers linalool and menthol on transdermal permeation of flurbiprofen (FP). Methods: The enantiomer selective high performance liquid chromatography (HPLC) was used to determine the enantiomeric excess of the FP enantiomer using Valia-Chien dual-chamber infiltration diffusion cell. Concentration determination of the chiral enhancer linalool or menthol on the FP enantioselectivity. RESULTS: Irrespective of whether the feed solution contained a single enantiomer or racemate, there was no enantioselectivity for the permeation of FP through isolated rat skin if the permeation enhancer was not included in the feed solution. The steady-state permeation rates of RSFP were 1.34 and 1.27 times higher than that of R-FP and S-FP, respectively (P <0.05) when the dl-menthol was contained in the feed solution. The feed solution contained l-menthol There was no significant difference in the rate of skin permeation between the enantiomers and racemates of FP (P> 0.05). Peptides and dl-menthol have comparable propholactivities to the same drug configuration, R-FP or S-FP; however, dl-menthol is 1.44 times more permeable to RS-FP than l-menthol. l-linalool or dl-linalool as a chromatid stimulant, no enantioselective osmosis was found. CONCLUSION: The enantioselectivity of dl-menthol on the permeation of FP appears enantioselectively, whereas l-menthol, l-linalool and dl-linalool do not cause enantioselective permeation of FP and all penetrations None of the experiments found enantiomeric conversion.