经皮给药论文：经皮给药原理与数学模型分析.doc

经皮给药论文：经皮给药原理与数学模型分析【中文摘要】随着科技的发展和生活水平的提高,人们对健康的关注逐渐加强,对生物医药技术和医疗产品也提出了更高的要求。特别是在治疗疾病的过程中,不但要求有良好的治疗效果,还要求最大限度的减少副作用和降低治疗过程中病人的不适感。另一方面,现代生物技术的发展促进了新型药物药剂的出现,如基于蛋白质、DNA的新型药物或者其他一些生物合成药剂,用口服或注射等常见方式给药,已不能充分发挥其治疗疾病的功效。为了满足新的需求,经皮给药这一古老的给药方法以其独特的优势得到了医药工作者的关注。经皮给药可以使药物避免肝脏的首过效应和肠胃灭活,能够维持血液中药物浓度的稳定,提高药物利用率。此外,经皮给药系统体积小巧、操作简单,具有良好的应用前景。因此,国内外对经皮给药的研究越来越广泛和深入。本文首先对经皮给药研究中所涉及的相关理论进行综述。包括经皮给药的发展历史及研究现状,药物经皮扩散过程原理和影响因素,经皮给药系统的分类与设计方法等。为使内容完整,文章还将现有的促渗方法进行分类和总结,系统介绍了各种方法的原理和应用现状。经皮给药研究中的数学模型可分为基于物理学原理的机械模型和基于数据集的经验模型。本文的第三章对药物在皮肤内扩散的过程进行简化与抽象,根据Fick扩散定律建立药物经皮扩散的机械模型,并结合设定的初始条件和边界条件进行求解,根据所得结果分析扩散系数、表面药物浓度等因素对药物扩散、吸收的影响。第四章则主要是根据定量构效关系的思想,选取药物的分子重量、正辛醇水分配系数、氢键供体数和氢键受体数四个结构参数作为BP神经网络的输入,同时将药物经皮渗透系数作为输出,建立基于数据集的数学经验模型,预测药物经皮渗透系数。我们将预测结果与实测值相比较,证明了模型的可靠性。本文对经皮给药的研究和讨论仅限于理论层面,但对各类模型建立过程的介绍有助于更好的理解经皮给药过程的机理。同时,对求解结果进行分析可以为临床实验提供必要的数据参考。特别是在经皮药物制剂开发前期,可以提高实验效率,降低实验药品和器材的消耗。模型分析结果还可以为促渗方法的研究和优化提供有效的参考和对比。【英文摘要】With the development of technology and the improvement of peoples living standards, health is paid more and more attention now. And people have much higher requirements on biomedical technology and medical products than before. In the therapeutic process of diseases, people not only require a good therapeutic effect, but also to minimize the negative effects and discomfort. Meanwhile, the development of biomedical engineering technology promotes the emergence of new medicinal preparation, such as protein-based and DNA-based drug or other biological synthesis preparation. Common ways, such as oral agents or intravenous injection can not play a good therapeutic effect on diseases. To meet these requirements, medical researchers begin to focus on transdermal drug delivery methods that have its unique advantages over other methods. Drugs in the transdermal drug delivery systems can avoid the metabolism because the liver is initially bypassed. Also, the risk of overdosage when drug enters the plasma is avoided. It helps to maintain a stable plasma drug concentration. Besides, transdermal drug delivery systems have smart shapes and it is easy to use by the patients themselves. Therefore, extensive researches on transdermal drug delivery are under way both at home and abroad.At the beginning, this paper summarizes the development history and hot research areas of transdermal drug delivery. Then introduces the principles of transdermal drug delivery process, and briefly describes the existing enhancing osmosis methods, including their principles and applications.There are two kinds of models in the field of transdermal drug delivery, they are mechanical models and empirical models. In this paper, we first simplify and abstract the diffusion process of drugs in the skin according to establish a mechanical model on the basis of the Ficks Law of Diffusion. And then solve the equation with restrictive initial conditions and boundary conditions. At last we analyze the influence of diffusion coefficient and surface drug concentration on the diffusion process and.absorption of drugs. The fourth chapter mainly discusses QSAR. We choose four structural parameters of drug, including molecular weight, octanol-water partition coefficient, the number of hydrogen bond donor and the number of hydrogen bond acceptor, as the input BP artificial neural network, while the percutaneous permeability coefficient as output. The established empirical model is used to predict the percutaneous permeability coefficient of a given drug. Compare with the measured values, it shows that the model is reliable.Discuss on transdermal drug delivery in this paper is limited to theoretical level, but the results of the models and analysis can provide necessary data reference for clinical trials. Especially at the beginning of development of transdermal drug formulations, it can help to reduce the number of tests, improve test efficiency and reduce consumption of experimental drugs and devices. At the same time, the results of the models can also promote and optimize the research of enhancing osmosis methods.【关键词】经皮给药 扩散 数学模型 定量构效关系 人工神经网络【英文关键词】Transdermal Drug Delivery Diffusion Mathematical Model QSAR Artificial Neural Network【目录】经皮给药原理与数学模型分析目录4-6OCNTENTS6-8摘要8-10ABSTRACT10-11第一章 绪论12-201.1 课题研究背景12-131.2 经皮给药发展历史及研究现状13-181.2.1 经皮给药发展历史13-161.2.2 经皮给药研究现状16-181.3 课题的研究目的和意义181.4 本文的主要工作18-20第二章 经皮给药系统基本原理20-342.1 皮肤基本结构及特性20-242.1.1 皮肤的主要功能21-222.1.2 皮肤结构及渗透特性22-242.2 药物经皮转运机理24-272.2.1 药物经皮肤渗透、吸收的途径24-252.2.2 药物经皮扩散原理25-262.2.3 TDDS系统的基本类型26-272.3 药物经皮渗透的影响因素27-292.3.1 生理因素27-282.3.2 药物性质28-292.4 促渗技术29-332.4.1 物理方法30-312.4.2 化学方法31-322.4.3 其它方法32-332.5 本章小结33-34第三章 药物经皮渗透的数学模型与特性分析34-423.1 药物分子经皮扩散模型34-363.1.1 理论34-353.1.2 计算推导35-363.2 药物经皮扩散特性分析36-413.2.1 药物经皮扩散过程36-383.2.2 皮下组织对药物的吸收38-413.3 本章小结41-42第四章 定量构效关系在药物渗透性预测中的应用42-534.1