香芹醇硬脂酸酯和油酸酯的合成及其经皮促透活性  

Synthesis and skin permeation enhancement of 5-isopropenyl-2-methylcyclohex-2-en-1-yl stearate and 5-isopropenyl-2-methylcyclohex-2-en-1-yl oleate

作　　者：王曼力[1,2] 陈阳[1] 蒋娟[1] 方亮[1] 

机构地区：[1]沈阳药科大学药学院药剂学系,沈阳110016 [2]北华大学药学院,吉林省吉林市132013

出　　处：《中国科技论文》2013年第6期538-541,共4页China Sciencepaper

基　　金：高等学校博士学科点专项科研基金资助项目(20092134110002)

摘　　要：以香芹醇为先导化合物首次合成香芹醇硬脂酸酯和油酸酯,并对其经皮促透活性进行评价。采用对甲基苯磺酸为催化剂,环己烷为带水剂,利用直接酯化法制备香芹醇硬脂酸酯和油酸酯。应用体外透皮实验评价合成的两种酯对不同脂溶性药物经离体鼠皮吸收的促透活性。结果表明对甲苯磺酸对合成香芹醇硬脂酸酯和油酸酯具有良好的催化活性。合成的优化条件为:醇酸物质的量比为1∶1.2,催化剂用量占原料总质量的3%,环己烷20mL,回流反应1h,产率60%。体外透过实验表明:香芹醇油酸酯具有明显的经皮吸收促透活性,它能使硝酸异山梨酯和5-氟尿嘧啶的经皮渗透系数分别提高到原来的2.40和2.48倍;而香芹醇硬脂酸酯对3种模型药物均无显著促透作用。以对甲苯磺酸为催化剂,环己烷为带水剂,采用直接酯化法可将香芹醇与长链的硬脂酸和油酸成酯。所得的油酸酯具有良好的经皮吸收促透活性,可能成为一种有前途的经皮吸收促透剂。Isopropenyb2-methyleyclohex-2-en-l-yl stearate （CSTE） and 5-isopropenyl-2-methylcyclohex-2-en-l-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 ex- periment 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. CSTE and COLE could be synthesized using p-tolue- nesulfonic 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.

关 键 词：经皮吸收促透活性 香芹醇 硬脂酸 油酸 酯化 对甲苯磺酸 环己烷 

分 类 号：TQ460.1[化学工程—制药化工]