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Spin Lapel Study on the Enhancement Mechanism of Transdermal Absorption Enhancers

透皮吸收促进剂增强机制的旋转翻领研究

基本信息

批准号：
10672030
负责人：
KITAGAWA Shuji
金额：
$ 2.11万
依托单位：
Niigata College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

We examined characteristics of enhancement effects of various compounds on transdermal drug absorption. Among various compounds n-alkyltrimethylammoniums showed marked enhancement effects on relatively hydrophilic drugs. From the analysis of the free energy of transfer of the methylene group of the 4-alkyl substituents of benzoic acid from the aqueous phase to skin on their permeability data, it was suggested that the cationic surfactants made the skin relatively more hydrophilic. To obtain the information on the localization of alkyl compounds in the skin, the electron spin resonance spectra of alkyl spin labels were observed in the excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. According to the analysis fatty acid spin label seemed to be present in the stratum corneum rigid lipid lamella, fatty acid ester spin label in the relatively fluid environment. On the other hand, long-chain cationic spin label seemed to be present in the protein region of the stratum corneum. The latter finding suggested that the interaction of the cationic surfactants with the proteins was the reason for their significant enhancement effects. These findings indicated that the different interaction and different localization of the alkyl compounds depended on their electronic charge as well as their alkyl chain lengths. We furthermore studied the molecular assemblies of double-chained cationic surfactants by spin label study and revealed their enhancement mechanism on transdermal drug absorption.

我们考察了各种化合物对药物经皮吸收促进作用的特点。在各种化合物中，正构烷基三甲胺对相对亲水的药物有显着的增强作用。通过对4-烷基取代苯甲酸的亚甲基从水相到皮肤渗透性数据的自由转移能的分析，认为阳离子表面活性剂使皮肤相对更亲水。为了获得烷基化合物在皮肤中定位的信息，观察了豚鼠背部皮肤、角质层、脱脂皮肤和角质层模型脂质体的烷基自旋标记的电子自旋共振光谱。据分析，脂肪酸自旋标记似乎存在于角质层的硬脂层，而脂肪酸酯自旋标记则在相对流动的环境中。另一方面，长链阳离子自旋标记似乎存在于角质层的蛋白质区域。后者的发现表明，阳离子表面活性剂与蛋白质的相互作用是其显著增强作用的原因。这些结果表明，烷基化合物的不同相互作用和不同的局域化取决于它们的电荷和烷基链长。我们进一步利用自旋标记技术研究了双链阳离子表面活性剂的分子组装，揭示了它们促进药物透皮吸收的机理。