香芹醇硬脂酸酯和油酸酯的合成及其经皮促透活性

Isopropenyl-2-methylcyclohex-2-en-1-yl stearate (C-STE) and 5-isopropenyl-2-methylcyclohex -2-en-1-yl Oleate (C-OLE) have been synthesized from carveol and fatty acids using p-toluenesulfonic acid as the catalyst and cyclohexane as the water-carrying agent. The skin permeation enhancement of the two synthesized esters has also been evaluated by in vitro permeation experiment using rat skin. The optimum conditions for esterification reaction were as follows: the amount of substance ratio of carveol to fatty acids was 1:1.2, the amounts of p-toluenesulphonic acid and cyclohexane were 3% and 10 mL respectively, the reaction time was 1 h, and the yield of carvyl ester was 60%. The results of in vitro permeation experiment showed that C-OLE improved the skin permeability coefficient of 5-fluorouracil and isosorbide dinitrate to 2.40- and 2.48-fold compared with control, while C-STE exhibited no permeation enhancement for three model drugs. C-STE and C-OLE could be synthesized using p-toluenesulfonic acid as the catalyst and cyclohexane as the water-carrying agent. C-OLE, which has excellent potential to enhance skin permeation, might be a promising skin penetration enhancer.