| 初天哲,王贺平,赵利刚.化学通报,2020,83(10):929-934. |
| d-4-萜品醇丁酸酯的合成及其经皮促透活性评价 |
| Construction and Penetration Evaluation of d-4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl Butanoate as Novel Percutaneous Absorption Enhancer |
| 投稿时间：2020-04-04 修订日期：2020-07-03 |
| DOI： |
| 中文关键词: d-4-萜品醇丁酸酯 酯化反应 促透剂 渗透机制 |
| 英文关键词:d-4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl butanoate Esterification Penetration enhancer Penetration mechanism |
| 基金项目:国家自然科学基金项目（81603039）和华北理工大学杰出青年基金项目（JQ201713）资助 |
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| 中文摘要: |
| 本文以d-4-萜品醇（d-4-TER）、丁酸为原料，采用酰氯酯化法合成标题化合物d-4-T-C4，并通过MS和1H NMR进行结构表征。通过体外渗透实验考察了d-4-T-C4对SR-FP的体外促透活性，并利用红外光谱法和分子对接技术研究其促透机制。加入d-4-T-C4时SR-FP的24h累计透过量（Q24h）为383.5±48.75μg·cm-2，分别为对照组和d-4-TER组的3.12、1.34倍，均有显著差异（P<0.05）。同时通过对药物进行手性拆分可以发现，d-4-T-C4对S-FP和R-FP的透过没有显著性差异（P>0.05）。促透机制为d-4-T-C4插入角质层脂质结构域，破坏药物与神经酰胺之间的氢键相互作用，增加脂质迁移率和药物的自由能，从而促进药物的渗透。d-4-T-C4对SR-FP具有显著的促透效果，有望作为新型促透剂在经皮给药系统中广泛应用。 |
| 英文摘要: |
| In this paper, d-4-terpineol (d-4-TER) and butyric acid were used as raw materials to synthesize d-4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl butanoate (d-4-T-C4) by esterification method, and the structure of the product was characterized by MS and 1H NMR. The penetration promoting activity of d-4-T-C4 on SR-FP was investigated, and its penetration mechanism was studied using infrared spectroscopy and molecular docking technology. When d-4-T-C4 was added, the accumulative 24h premeation amount (Q24h) of SR-FP was 383.5±48.75 μg·cm-2, which was 3.12 and 1.34 times of the control group and d-4-TER group, respectively. However, the promoting ability of d-4-T-C4 on S-FP and R-FP were almost identical. Mechanism research showed that d-4-T-C4 insertes into the stratum corneum lipid domain, disrupting the hydrogen bonding interaction between the drug and ceramide, increasing lipid mobility and the free energy of the drug, thereby promoting drug penetration. d-4-T-C4 had a significant enhancing effect on the permeation of SR-FP through the skin and is expected to be widely used as a new type of penetration enhancer in transdermal drug delivery system. |
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