5,9-二甲基-1-癸醇(DIMDOL)的合成及对5-氟脲嘧啶和盐酸曲马多穿透离体小鼠皮肤的促进作用

5,9-二甲基-1-癸醇(DIMDOL)的合成及对5-氟脲嘧啶和盐酸曲马多穿透离体小鼠皮肤的促进作用

哈尼夫, 平其能^*, 莫芬珠, 刘国杰

中国药科大学药剂教研室, 南京 210009

收稿日期:1997-12-25 修回日期:1998-05-24 出版日期:1999-03-15 发布日期:1999-03-15
通讯作者: 平其能*

Synthesis and Enhancing Effect of 5,9-Dimethyl-1-decanol on the Transport of 5-Fluorouracil and Tramadol Hydrochloride Across the Excised Rat Skin

Hanif Raja, Ping Qineng^*, Mo Fenzhu, Liu Guojie

Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009

Received:1997-12-25 Revised:1998-05-24 Online:1999-03-15 Published:1999-03-15
Contact: Ping Qineng*

摘要/Abstract

摘要： 四氢香叶醇(THG)是一种开环单萜,通过格林那达试剂,使四氢香叶醇和环氧乙烷反应,合成出一种新的醇类衍生物: 5,9-二甲基-1-癸醇(DIMDOL)。使用双室扩散池装置, 应用体外渗透技术,研究了DIMDOL对5-氟脲嘧啶和盐酸曲马多穿透离体小鼠皮肤的促进作用, 以阿佐恩(Azone)和THG作为对照促进剂进行比较。DIMDOL对5-氟脲嘧啶和盐酸曲马多的渗透率分别增加18.60和73.19倍, 滞后时间分别为3.35和1.20小时, 分配系数和扩散系数也同时增加、结果表明DIMDOL主要影响角质层, 干扰了其中的类脂层和角蛋白层。

关键词: 5-氟脲嘧啶, 盐酸曲马多, 5,9-二甲基-1-癸醇, 阿佐恩, 四氢香叶醇, 透皮吸收

Abstract: New alcohol derivative of tetrahydrogeraniol (THG), an acyclic monoterpene,has been synthesized by reacting THG with Grignard reagent and ethylene oxide. The enhancingeffect of the synthesized derivative, 5,9-dimethyl-1-decanol (DIMDOL) on the penetration of 5-fluorouracil (5-FU) and tramadol hydrochloridc across the excised rat skin was studied by an in vitropermeation technique using two chamber diffusion cells. Azone and THG were used as standardenhancers for comparison. DIMDOL enhanced the permeability of 5-FU and tramadol hydrochloride18.60 fold and 73.19 fold across full-thickness skin with a lag time of 3. 35 h and 1.20 h respectively.Increased partition coefficient and diffusion coefficient values were obtained by this enhancer. Theseresults suggest that DIMDOL mainly affects the stratum corneum and interacts with both lipid-richlayers and keratin-rich layers.

Key words: 5-Fluorouracil, Tramadol hydlochloride, 5,9-Dimethyl-1-dccanol, Azone, Tetrahydrogeraniol, Percutaneous absorption

Supporting:

Supported by the State Natural and Science Foundation

哈尼夫, 平其能^*, 莫芬珠, 刘国杰. 5,9-二甲基-1-癸醇(DIMDOL)的合成及对5-氟脲嘧啶和盐酸曲马多穿透离体小鼠皮肤的促进作用[J]. .

Hanif Raja, Ping Qineng^*, Mo Fenzhu, Liu Guojie. Synthesis and Enhancing Effect of 5,9-Dimethyl-1-decanol on the Transport of 5-Fluorouracil and Tramadol Hydrochloride Across the Excised Rat Skin[J]. .

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