基于计算机模拟的冰片经皮吸收促进机理多尺度研究

It is of great significant to investigate the percutaneous penetration enhancement mechanism of volatile oil components from traditional Chinese medicine (TCM) for different types of drug as well as summarize its promotion law, which could make contribution to the reasonable application of volatile oil penetration enhancer (PE) and the development of transdermal drug delivery preparation in TCM. In order to deeply research the internal mechanism of the interaction between PE with biological membrane and drugs as well as to summarize the penetration enhancement law, computer simulation and experimental method are used comprehensively. This combined method would effectively help to improve research efficiency and promote the scientific research and developments of transdermal drug delivery preparation. In this project, corneum lipid layer models in both microscopic and mesoscopic scales are constructed by computer simulation methods on the basis of the preliminary studies, which are the main barrier of drug percutaneous absorption. This study tries to explain the influence of volatile oil for corneum lipid layer and the penetration enhancement performance of drugs with different constructions, using borneol and menthol as carriers to elucidate the penetration kinetics of volatile oil visually and dynamically. Combined with other experimental methods (such as spectroscopy, electron microscopy, transdermal performance testing and other classic experiment), the percutaneous penetration enhancement mechanism of volatile oil is exposited in different levels. The study also summarizes the promotion law of volatile oil PE for drugs with different constructions, which will provide guidance for the further research and application of volatile oil. In addition, a multiscale study method, computer simulation combined with experimental method, for pharmaceutic adjuvant is developed in this project, which will provide an approach for screening PE in the development process of transdermal drug delivery preparation.

研究中药挥发油类成分对不同类型药物的经皮促透机理，总结其促透规律，对于科学应用中药挥发油类经皮促进剂，促进中药经皮给药制剂的开发具有重要意义。采用计算机模拟与经典实验相结合的方法，可从微介观层面深入探讨经皮促进剂与药物及生物膜相互作用的内在机理，总结促透规律，从而提高研究效率，推进我国中药经皮给药制剂的研发。 本项目在前期研究的基础上，采用计算机模拟工具搭建微观与介观尺度的药物经皮吸收主要屏障- - 角质层脂质层模型，以冰片为研究载体，考察冰片对角质层脂质膜的影响及对不同结构药物的促透性能，直观、动态地研究挥发油促透的动力学过程，同时与光谱、电镜、透皮性能测试等经典实验相结合，从不同层面阐释冰片促透的作用机理，总结其对不同类型药物的促透规律，为其进一步研究应用提供指导。在此基础上，建立一种计算机模拟与实验相结合的多尺度药用辅料研究模式，为经皮制剂开发过程中透皮促进剂的筛选提供方法。

研究中药挥发油类成分对不同类型药物的经皮促透机理，总结其促透规律，对于科学应用中药挥发油类经皮促进剂，促进中药经皮给药制剂的开发具有重要意义。本项目在前期研究的基础上，采用计算机模拟方法构建了基于角质层脂质模型的药物经皮透过研究方法，考察了浓度、温度等因素对模型形态、结构的影响，为研究促透剂与生物膜的相互作用提供方法学指导。采用该方法系统研究了冰片对不同性质待促透药物的促透作用，阐明了冰片对不同药物促透性能的差异性及其分子机制。采用电镜、透皮性能测试等经典实验方法考察冰片对不同性质药物的促透特性及其对角质层形态的影响，进一步阐释了冰片的促透机理，并对计算机模拟结果进行了验证。基于促透实验研究结果，总结了冰片的促透规律，为其在经皮给药系统中的应用提供了指导。在此基础上，考察了常用挥发油类促透剂薄荷醇对不同极性药物的促透作用，比较其与冰片促透作用及机制的差异，验证了本项目所建方法的适用性。本项目建立的计算机模拟与经典实验相结合的多尺度研究方法，从宏观、介观、微观多层次对天然冰片的经皮促透机理进行了阐释，为天然冰片作为经皮吸收促进剂的合理应用提供指导，为推动基于挥发油促透作用的中药经皮给药制剂发展具提供了有效方法。