核酸适配体类抗HIV-1药物的研究进展

核酸适配体是指能特异结合蛋白质或其它小分子物质的寡核苷酸片段,可通过对某些酶或蛋白因子的抑制达到抗病毒的目的。近年来,核酸适配体类药物的研发已经取得了进展,尤其是在抗艾滋病病毒方面,此类药物展现出了广阔的临床应用前景。目前,核酸适配体类抗HIV-1药物按作用机制可分为抑制HIV-1逆转录酶的适配体、抑制HIV-1核糖核酸酶H的适配体和抑制HIV-1 Tat蛋白介导的反式激活的适配体。介绍这3种核酸适配体类抗HIV-I药物的有关研究情况。     

核酸适配体在抗肿瘤药物主动靶向传递中的应用

核酸适配体是通过指数级富集的配体系统进化技术(systematic evolution of ligands by exponential enrichment,SELEX)从合成的大容量单链随机寡核苷酸文库中筛选并富集的对某些靶点具有高特异性和高结合率的小分子DNA或RNA片段.核酸适配体具有直接抑制肿瘤细胞增殖的作用,通过结构修饰可增强在体内的稳定性.此外,它可与载药纳米结构键合,用于肿瘤诊断和治疗.本文综述了核酸适配体的肿瘤靶点、筛选方法及其在肿瘤诊断和治疗中的应用.     

核酸适配体修饰与包载及其在疾病靶向性治疗和检测中的应用

核酸适配体是一类能形成独特三维结构、长度较短的寡聚(脱氧)核苷酸,能与多种靶标分子特异性结合,具有与抗体类似的作用,在疾病的治疗、诊断等方面具有巨大潜力,但同时核酸适配体与其他寡聚核苷酸一样存在血清稳定性差、入胞困难、经肾脏较快排泄等缺陷。以提高稳定性、延长组织驻留时间、提高与靶标亲和力等为目的,大量的研究采取末端共价缀合、糖环修饰、骨架修饰的策略对核酸适配体进行修饰,改善了核酸适配体的药动学性质。本文综述了核酸适配体修饰的新进展,及已获得的修饰物理化性质,特别是已上市及处于临床试验阶段的候选物情况,介绍了其在靶向治疗、生物检测等方面的应用及其新型包载跨膜转运研究方面的进展。     

核酸适配体AS1411肽缀合物发挥药效的结构模式研究

目的研究靶向肿瘤细胞高表达核仁素的核酸适配体AS1411与靶标作用的结合模式。方法利用CD光谱评价了退火及末端修饰对AS1411平行及反平行G-四链体(G-4)结构的影响,同时利用肿瘤细胞生长抑制实验评价了退火及末端修饰对AS1411抗肿瘤活性的影响,并通过流式细胞术对末端荧光基团缀合AS1411的靶向肿瘤细胞摄取进行了考察。结果推测G-4结构的端基参与靶蛋白的结合,3'-末端缀合对细胞靶向摄取有较明显的影响,说明AS1411的肿瘤细胞摄取与其抗肿瘤活性有一定程度的关联。结论利用等当量AS1411与其3'-末端缀合物退火形成不对称的反平行G-4,可以更好地保持其与肿瘤细胞的靶向结合及生长抑制活性,说明AS1411的端基是其发挥药效的重要区域。该结果可进一步应用于肿瘤的靶向检测和治疗研究。     

手性药物代谢研究中的对映体分析方法

生物体是一个复杂的手性系统,其手性特征促使了它们与手性化合物的立体选择性相互作用。手性药物的两个对映体在吸收、分布、代谢、排泄过程中存在着动力学差异,尤其是代谢行为。因此,在手性药物代谢的研究中,同时测定对映体是极为重要的。本文通过综述近年来发表的众多文献,详细论述了在药物代谢中应用广泛的手性分析方法,包括高效液相色谱、高效液相色谱-质谱联用、气相色谱和毛细管电泳等。     

大分子生物药物生物分析方法验证—解读欧洲药品管理局指导原则

本文对生物大分子药物生物分析方法的全面验证、部分验证、交叉验证和真实样品分析等方面进行阐述.     

生物分析方法确认策略

本文介绍了葛兰素威康研究实验室药物代谢研究部门对生物分析方法进行确认的策略。阐述了设计一个恰当生物分析方法的基本原理，以及建立一个适当的方法之前必须对实验数据进行评估，评估参数包括选择性、专属性、定量检出限、线性、准确度、精密度和回收率等。本文还讨论了药物各发展阶段确认设计前必须考虑的一些要点，如生物基质、分析工作标准、样品分批量大小及组成、分析仪器、初始方法确认、临床前方法确认、临床方法确认、方     

生物药物分析方法的认证,质量控制及其标准操作规程

探讨生物样品中药物分析方法学的研究方法，讨论分析方法效能参数的意义和实验方法，并论述了质量控制和标准操作规程。     

Recent advances in bioanalytical sample preparation for LC-MS analysis

Sample preparation has historically been, and continues to be, the most challenging part of the bioanalytical workflow. Several techniques have been developed over the years to deal with the problems of recovery and matrix effects in an effort to increase the reliability and robustness of the bioanalytical method. In recent years certain techniques have come into prominence and gained acceptance in routine sample preparation, and some have shown promise in their use in a discovery environment where speed is critical and method development time is often limited. The aim of this review is to examine several of these techniques and provide examples of their use from the literature, as well as comment on their utility in current workflows.     

Recent advances in anticancer drugs

During the last few years, research in anticancer drug development has revealed a number of new approaches. These include new types of prodrugs, small peptides and synthetic molecules affecting signal transduction pathways and cell cycle, topoisomerase inhibitors, antisense compounds, anti-angiogenic and antimetastatic agents, gene therapy and vaccines. The aim of the meeting was to present and discuss the recent results in these areas, with respect to the R and D of new anticancer compounds. This review focuses on the most recent advances in anticancer drugs presented and discussed in the plenary sessions.     

免疫抑制剂研究新进展

免疫抑制剂在器官移植中起着极其重要的作用。由于众多高效、低毒免疫抑制剂的开发应用，使近年来器官移植的成功率大大提高。综述了已在临床使用或处于临床研究的霉酚酸酯、 他克莫司、西罗莫司、咪唑立宾、人源化单克隆抗体、FTY720等新免疫抑制剂的作用机制、临床用途及不良反应等情况，给临床合理用药提供帮助。     

Recent advances in non-steroid anti-inflammatory drugs

Recent advances in NSAID, particularly those developed in Japan, are described. They may be classified into some categories. Firstly, useful new compounds such as propionic acids which have an excellent pharmacological activity with mild side-effects have been developed. Secondly, the progress of drug delivery systems (DDS) has been observed in the treatment with NSAID. Thirdly, a new type of NSAID, whose mechanism of action is different from the inhibition of cyclooxygenase. Lastly, NSAID are widely used against not only inflammatory disease but also the other diseases in which prostaglandins and thrombosis have an important role in pathogenesis.     

Recent advances in computer-aided drug design methods

A number of computational advances have had significant impact on the field of computer-aided drug design over the last several years. These advances can be grouped into three basic areas: conformational modelling (of small molecules, macromolecules and their complexes), property modelling (of physical, biological and chemical properties) and molecular design (to optimise physical, biological or chemical properties). The current state of the art in each of these areas is introduced. Recent patents related to these three topics are critically reviewed and their impact on the field of computer-aided drug design is assessed.     

传统植物药和兰花的最新进展(英文)

The main objective of this paper is to review recent advances in plant drug research and developments in orchid study, in an attempt to provide useful references for plant drug studies. Plants have been used as medicine for millennia. Out of estimated 250 000 to 350 000 plant species identified so far, about 35000 are used worldwide for medicinal purposes. It has been confirmed by WHO that herbal medicines serve the health needs of about 80 percent of the world's population; especially for millions of people in the vast rural areas of developing countries.Meanwhile, consumers in developed countries are becoming disillusioned with modem healthcare and are seeking alternatives. The recent resurgence of plant remedies results from several factors: 1) the effectiveness of plant medicines; 2) the side effect of most modem drugs; and 3) the development of science and technology. It has been estimated that in the mid-1990s over 200 companies and research organizations worldwide are screening plant and animal c     

Recent advances in drugs and prodrugs design of chitosan

The aim of this review is to outline the recent advances in chitosan molecular modeling, especially its usage as a prodrug or drug in a field of antibacterial, anticarcinogenic and antioxidant activity. Polymeric materials like peptides, polysaccharides and other natural products have recently attracted attention as biodegradabile drug carriers. They can optimize clinical drug application, minimize the undesirable drug properties and improve drug efficiency. They are used for the slow release of effective components as depot forms, to improve membrane permeability, solubility and site-specific targeting. Chitosan is such a prospective cationic polysaccharide which has shown number of functions in many fields, including bio medicinal, pharmaceutical, preservative, microbial and others. This article discusses the structure characteristics of chitosan, a number of factors such as degree of polymerization, level of deacetylation, types of quarternisation, installation of various hydrophilic substituents, metal complexation, and combination with other active agents. Biodegradable, non-toxic and non-allergenic nature of chitosan encourages its potential use as a carrier for drug delivery systems in all above mentioned targets. The use of chitosan prodrug conjugates is aimed at the site-specific transport to the target cells use, for example, a spacer tetrapeptide Gly-Phe-Leu-Gly, promotion of drug incorporation into cells via endocytosis, hybridization or synergism of two types of drugs or a drug with a bioactive carrier. The design of chitosan macromolecule prodrugs is also discussed.