【作者】 黄英；

【导师】 章竹君；

【作者基本信息】 西南师范大学 ， 分析化学， 2005， 硕士

【摘要】 当药物进入生物体内后,通常要经历吸收、分布、代谢的过程。大部分的药物经代谢反应后会产生一种或者多种新的化合物——代谢物。药物分子及其代谢物分子也能不同程度的与生物大分子如受体、组织、血浆蛋白相结合。在转运和转化的过程中,药物会与组织蛋白(包括受体)及体液蛋白相结合。因此除了未结合的药物及其代谢分子,在组织和体液中还含有与蛋白相结合的药物及其代谢物分子。药物通过血液循环分布于各个组织和器官,血浆中游离的药物可以自由的通过毛细血管壁进入到靶器官而产生药效,而结合型的药物由于分子量较大很难跨膜转运到达作用部位。因此研究药物血浆蛋白的结合在药效学和药代动力学研究中都是非常重要的,只有游离的部分才是药物的起效形式。一些重要的药代动力学性质如肝脏代谢率、肾清除率、生物膜渗析率以及稳态分布量都取决于药物的游离部分。显然药物与蛋白相互作用的研究及相关参数的确定具有非常重要的理论和现实意义。 本论文主要介绍了基于荧光检测的在线药物蛋白反应研究,全文由两部分组成。第一部分是综述,这部分评述了近十年来国内外荧光分析法在药物分析中的应用情况。 第二部分是研究报告,包括两章。第一章是基于荧光检测的在线药物蛋白反应研究,由三小节组成。第一节简要评述了药物蛋白反应的研究进展。 第二节采用在线微透析-流动注射-荧光联用技术,详细研究了甲磺酸酚妥拉明与牛血清白蛋白的相互作用。酚妥拉明可将Cerium(Ⅳ)还原为Cerium(Ⅲ),在硫酸介质中呈现Cerium(Ⅲ)的特征荧光光谱,基于此,建立了一种间接测定酚妥拉明的荧光分析法,并将其与在线微透析取样技术联用,成功应用于药物-蛋白相互作用研究当中。该法简单、快速、易于操作。更多还原

【Abstract】 When a drug enters into the interior of the body, it often undergoes the processes of absortion, distribution and excretion. A large number of drugs would generate a kind or several kinds of new compounds—metabolite, passing through the reaction of metabolism. The drug and the metabolite can also bond with biomacromolecule, such as receptor, tissue and plasma protein, in different degree. In the process of transportation and translation, drug would bond with tissue protein, including receptor, and body fluid protein. Therefore, beside the unbound drug and metabolite, there are still bound drug and metabolite in tissue and body fluid. Passing through body fluid, drug was transferred to each organ and tissue. Free drug in the plasma transfers freely to the target organ, whereas bound drug hardly passes through the blood capillary walls to reach the action site. In this respect, plasma protein binding is an important factor in establishing pharmacokinitic and pharmacodynamic properties of a drug, as only the tree fraction of the drug is pharmacologically active. Some important pharmacokinitic properties such as hepatic metabolism rate, renal excretion rate, biomembrane permeation rate, and the steady state distribution volume, also depend on the unbound drug fraction. Thus, the study of drug-protein binding in body fluid is of great importance.The thesis consists of two parts. The first is a review dealing with the application of fluorescence in pharmaceutical. Emphasis is placed on the development in recent ten years.The other is reseach reports which is composed of 2 chapters.Chapter 1 describes the study of drug-protein interaction in vitro based on fluorescence detection, and three sections are contained in this chapter. The first更多还原