蛋白质内含子研究进展

介绍了蛋白质内含子的结构、功能和其介导的蛋白质剪接机理及应用研究进展。蛋白质内含子目前已广泛应用于蛋白质纯化、蛋白质连接、以及环肽和毒素蛋白的制备,且对蛋白质结构和功能关系的研究具有重要价值。     

聚合物控释蛋白质系统制备贮存和释放对稳定性的影响

很多新蛋白质和肽类药物不能成功地用于治疗病人由于它们的稳定性较差，难以找到合适的传送系统。但随着低分子量药物传送系统研究不断地取得进展，还促进了活性蛋白质和肽类药控释传送系统的开发。本文主要阐述控释蛋白质系统在制备、贮存和蛋白质从中释放时所遇到的稳定性问题，并讨论制备过程中各步对蛋白质稳定性的影响以及预防蛋白质变性的一些措施。     

脂质体包裹蛋白质药物的制备及影响因素的控制

介绍近年来包裹蛋白质药物的脂质体研究现状。针对脂质体的各种制备方法的特点，探讨提高药物包封率的制备方法和最适的检测手段，以适应蛋白质药物脂质体工业化生产的需要。     

蛋白质的化学合成

蛋白质是生物体中功能最重要的一类生物大分子,目前蛋白质的制备方法主要有3种:生化提取法、基因工程法和化学合成法[1].各种方法利弊并存[2～3],没有一种方法能够完全适用于所有蛋白质的制备.生化提取法来源少,基因工程法翻译后难以修饰,易形成包合体等不恰当的折叠构型;相比之下,化学合成法提供了一条快速、高效的蛋白质制备途径,同时它能方便地引入非天然氨基酸,改变碳链骨架以及其他化学修饰来提高蛋白质活性,构建新蛋白.     

蛋白质芯片在药学中的应用蛋白质芯片在药学中的应用

随着生物芯片技术的发展，蛋白质芯片的制备和应用技术已获得突破性进展，不仅在蛋白质芯片制作方面引入机器人制作和商品化玻片载体，而且较成功的解决了蛋白质固相表面的固定问题，为蛋白质芯片的进一步发展奠定了基础。UetZ等使用酵母双杂交系统构建蛋白质芯片，首次把蛋白质     

吸入用肽类和蛋白质粉末的制备

蛋白质和肽类利用气雾剂给药有许多优点。制备大小合适的吸入性粉末常用的技术是喷射碾磨和喷雾干燥方法，其制已在实验动物和临床进行了研究。另外，简介了粉末的其他制备方法。     

蛋白质、多肽类药物制剂的研究现状

目的：综述蛋白质、多肽类药物制剂的研究现状。方法：依据国内外文献进行综述,包括蛋白质、多肽类药物性能特点、已开发剂型及其制备方法,临床应用效果和发展前景内容。结果：蛋白质、多肽类药物制剂的研究是目前蛋白质、多肽类药物发展的迫切要求,但目前研究工作较少,理论基础研究则更少。结论：蛋白质、多肽类药物将成为21世纪的重要药品,我们应该加强蛋白质、多肽类药物制剂的的研究,使其更适合于临床应用的要求。     

多肽、蛋白质药物缓释微球研究进展

目的介绍多肽、蛋白质缓释微球的研究情况。方法通过查阅国内外文献，综述多肽、蛋白质微球的制备技术，影响微球质量和体外释药的因素以及药物的稳定性问题。结果与结论多肽、蛋白质药物缓释微球在药学领域有着广阔的发展前景。     

蛋白质药品的真空冷冻干燥技术及研究进展

目的介绍真空冷冻干燥技术制备蛋白质药品的方法。方法查阅国内外近年来有关文献，综述了真空冷冻干燥原理、蛋白质药品的冻干工艺及药品贮存期间影响其活性的各个因素。结果真空冷冻干燥过程中可引起蛋白质药品不同程度的变性，加入保护剂可增加其稳定性。结论冷冻干燥时，不同的蛋白质药品需加入不同的保护剂。     

蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球研究进展

缓释微粒给药系统是蛋白质/多肽药物传输系统的一个重要研究方向，聚乳酸和乳酸-羟基乙酸共聚物是制备缓释微球最常用的载体材料。蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球常用的制备方法包括溶剂萃取/挥发法(复乳法)、相分离法和喷雾干燥法。本文总结了微球制备中面临的难点如蛋白质/多肽药物稳定性、包封率、药物突释和药物吸附等问题，并综述了保持药物结构稳定性和生物活性、提高包封率、改善药物释放曲线等微球制备方法和进展。     

Design and synthesis of a focused library of novel aryl- and heteroaryl-ketopiperazides

1-Phenyl-4-piperazinyl-carbonyl-substituted nitrogen-containing heterocycles were discovered at Zentaris as a new class of potent, synthetic, small molecule tubulin inhibitors with strong antiproliferative activity. The lead structure of this class, D-24203, proved to be a potent inhibitor of in vivo tumor growth in different xenograft models including mammary and renal cancers. As part of our efforts in the lead optimization process to expand structural diversity as well as to optimize bioavailability parameters such as solubility and metabolic stability for these compounds, we produced and evaluated a focused library containing 320 compounds. Five new heterocyclic compound classes with comparable activity properties in the cytotoxicity and tubulin polymerization assay could be identified. In silico calculated bioavailability parameters for selected library members provides new compound classes with improved solubility properties. Library design, development of adequate solution phase methodology, and synthesis will be presented, as well as results of lead optimization.     

Cannabis and symptoms of PMS and PMDD

Cannabis has been found to alleviate a wide array of medical symptoms, including those that overlap with physical and emotional symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), including insomnia, irritability, depression, and joint pain. Little work has addressed the use of cannabis as a treatment for PMS or PMDD or the role of women’s cannabis treatment expectancies as a predictor of consumption. Women who reported having experienced PMS and PMDD and endorsed lifetime cannabis use (N?=?145), completed an online survey assessing their frequency of cannabis use, PMS/PMDD symptoms, expectancies of cannabis-induced relief from symptoms, as well as cannabis-related problems. Women were found to hold meaningful expectancies that cannabis would treat all PMS/PMDD symptoms, except for overeating/food cravings. Cannabis treatment expectancies were positively associated with PMS/PMDD symptoms and with monthly cannabis use, and were negatively associated with cannabis-related problems. Research should further examine the relationship of cannabis treatment expectancies with individuals’ cannabis use, as findings indicate the potential for these expectancies to serve a punitive or protective role in the development of cannabis-related problems. Increased research on how cannabis might ameliorate symptoms of PMS and PMDD could help establish an alternative treatment plan that offers relief with fewer negative side effects.     

眼用制剂生产质量管理风险分析及控制

随着中国药典2010年版将眼用制剂列入无菌制剂,眼用制剂的生产质量管理被提出了更高的要求。本文对目前眼用制剂生产现状进行分析,探讨眼用制剂生产与质量控制的关键风险点,并提出了一些风险控制策略,为企业提供参考。     

盐酸吗啡、咖啡因的FTIR检验及谱图解释

目的 提高用红外光谱法鉴定盐酸吗啡、咖啡因纯品、二者混合物的水平.方法 用红外光谱法有针对性地选择特征峰,探明盐酸吗啡、咖啡因红外光谱与结构的关系.结果 获得盐酸吗啡、咖啡因的特征峰.结论 该方法 克服了鉴定中的盲目性,重现性好,特异性强.     

药动学和药效学评价生物制品:挑战与局限性

近年来,重组蛋白多肽和蛋白质已发展成为主流药物。多肽和蛋白类药物在临床前和临床研究以及治疗用药中均占有相当大的比重。理解药物动力学和药效动力学,包括剂量-浓度-效应之间的关系,对于包括多肽和蛋白类在内的任何药物都是至关重要的,因为它奠定了优化给药方案和临床合理用药的基础。比起传统的基于小分子的疗法,多肽和蛋白类药物的药物暴露/效应评价往往由于下列因素而变得复杂:(1)与内源性多肽、蛋白及营养物质的相似性;(2)能在分子水平直接参与体内生理过程;(3)具有高分子特性及免疫原性;(4)由于存在着很多相似的分子,目标物的分析和量化具有一定的挑战性。不像传统的小分子药物,多肽和蛋白质口服后往往没有治疗活性。为选择最适当的给药途径,需要全面了解多肽和蛋白质理化性质以外的吸收特性,包括化学和代谢稳定性、吸收部位、免疫反应性、跨膜过程以及主动摄取和外排过程。肽和蛋白质的各种分布特性决定了其在靶器官能否达到适宜浓度从而发挥预期疗效,而结合现象和受体介导的细胞摄取有可能使这个问题更加复杂化。消除过程作为药物全身暴露的一个关键因素,可以是众多通路的综合,包括肾脏及肝脏代谢通路以及广义的蛋白水解作用与受体介导的内吞作用。多肽和蛋白质为基础药物的药代动力学/药效学结合研究常因其与内源性物质密切的相互作用以及生理调节反馈机制而错综复杂。本文重点阐述了与大多数生物制品相关的一些主要动力学特性及过程,为具有药效特性的多肽和蛋白质疗法提供范例。理解了生物疗法和传统小分子药物之间药动学与药效学的差异,将有助于从事药物研发的科学家以及医疗保健人员在药物开发和应用药物治疗过程中用最适宜的方法去处理、评价和用药。     

Pharmaco- and toxicokinetics of selected exogenous and endogenous estrogens: A review of the data and identification of knowledge gaps

Chemicals with estrogenic activity are derived from many different natural and synthetic processes and products, including endogenous production (e.g., estradiol, conjugated estrogens), drugs (e.g., ethinyl estradiol, conjugated estrogens), plants used as foods (phytoestrogens such as genistein, daidzein, S-equol), and man-made chemicals (xenoestrogens such as bisphenol A). Human exposure to low doses of endogenous estrogens, estrogenic drugs, phytoestrogens, and xenoestrogens has the potential to improve health or disrupt normal endocrine activity, as well as impact the diverse systems with which estrogens interact, including the cardiovascular system, and lipid and carbohydrate metabolism. Mechanisms of action and diversity of adverse and non-adverse effects following human exposure to low doses of estrogen active chemicals (EACs, defined as chemicals which interact with an estrogen receptor [ER]) are poorly understood. This review summarizes our current understanding of the pharmacological action with a focus on pharmacokinetics (PK) and toxicokinetics (TK) of several representative EACs in both physiological and pathological processes. The goal of this review is to assess the current state-of-the-science on: (i) the potential for EACs to interfere with endocrine activity, (ii) factors which contribute to endocrine-related clinical outcomes, and (iii) existing knowledge gaps. While classical PK approaches (compartmental or non-compartmental) can be used to characterize absorption, distribution, metabolism, and elimination of EACs, many of the detailed pharmacological characteristics necessary to understand benefit-risk balance have not yet been clarified. Pharmacological complexities mirror the complexity of determining whether and under what conditions exposure to estrogens in drugs, foods or to xenoestrogenic chemicals are beneficial or harmful to human health.     

Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids

Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation.     

Applications of polymorphisms and pharmacogenomics in obstetrics and gynecology

The number of reports investigating disease susceptibility based on the carriage of low-penetrance, high-frequency polymorphisms has steadily increased over the last years. Evidence based on meta-analyses of individual case-control studies is accumulating, defining specific individual variations in disease susceptibility. For example, genetic variations of the estradiol metabolism have been described as significant contributors to disease susceptibility with variations depending on ethnic background. In the field of obstetrics and gynecology, the genetic contribution of polymorphic markers to a series of disorders has been characterized. These disorders include recurrent pregnancy loss, pre-eclampsia, endometriosis, breast cancer, and hormone replacement therapy (HRT)-related complications such as thrombosis. Among other genetic markers, thrombophilic genetic variants, such as the Factor V Leiden and prothrombin G20210A polymorphisms, as well as genetic variants of cytochrome P450 (CYP) enzymes, for example, CYP19 and CYP1B1, have been established as genetic risk markers and disease modifiers of recurrent and sporadic pregnancy loss and HRT-independent and -dependent breast cancer, respectively. In addition, meta-analyses of data in the literature established the TGFBR1*6A, GSTP I105V, and TP53 R72P polymorphisms, as well as the GSTM1 gene deletion as low-penetrance genetic risk factors of sporadic breast cancer. With respect to genetic modulation of therapeutic effects, beneficial effects of estrogen replacement therapy and HRT are modulated by the carriage of single nucleotide polymorphisms, for example, osteoprotection and blood lipid changes by the estrogen receptor-alpha (ER-a) PvuII polymorphism. Polymorphisms of the catechol-O-methyltransferase (COMT), ER-alpha, IL-1 receptor antagonist, and Factor V genes have been demonstrated to modulate the timing of natural menopause. Lastly, a strong genetic contribution of polymorphisms to the development and the clinical course of endometriosis has been established with data pointing to polymorphisms of the COMT, GST, NAT-2, and ER-alpha genes as susceptibility markers. In summary, the available evidence points to a number of polymorphisms of a wide variety of genes as strong hereditary determinants of the susceptibility to benign and malignant gynecologic and obstetric conditions.     

Nasal administration of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and of different enhancing agents

Summary The systemic availability of glucagon and human calcitonin given intranasally to healthy volunteers as spray solutions or powders has been examined.Glucagon was absorbed only when surfactants were used, and 9-lauryl ether (as a spray) and sodium glycocholate (as spray or powder) were equally active. Calcitonin was poorly absorbed when given alone but the surfactants dihydrofusinate (as spray or powder) and glycocholate (as a spray) were equally active in promoting absorption. Thus, enhancers are required to obtain significant nasal absorption of glucagon and calcitonin and powders and spray solutions did not differ in terms of systemic availability.     

辅酶Q的生物合成途径以及相关的酶和基因

综述了辅酶Q在生物体中的合成途径以及催化各步反应的酶和编码基因。