葫芦素E溶解度、正辛醇-水及脂质体-水分配系数测定

目的测定葫芦素E溶解度、正辛醇-水分配系数及脂质体-水分配系数。方法分别采用平衡法、经典摇瓶法及平衡透析法测定葫芦素E溶解度、正辛醇-水分配系数及脂质体-水分配系数。结果葫芦素E在水中溶解度为0.155 mg.L-1,在乙醇、叔丁醇中有潜溶现象;正辛醇-水分配系数为(2.088±0.054);脂质体-水分配系数为0.003~1.819。结论葫芦素E为水不溶性药物;正辛醇-水分配系数及脂质体-水分配系数均中等偏低。     

蛋白多肽类药物的水凝胶给药系统

蛋白药物由于药效强、特异性高的特点近年来受到广泛的关注.而将蛋白药物引入水凝胶中,利用环境刺激敏感性水凝胶,能够对体内环境微小变化做出响应,从而控制蛋白药物在体内的释放;本文综述了基于蛋白药物合成材料的交联聚合物水凝胶,详述了温度敏感性水凝胶的研究概况以及水凝胶目前存在的问题和未来展望.     

有机介质中的酶促氨解反应

酶促氨解反应是20世纪90年代中期发现的一种新型反应,在脂肪酸酰胺的合成、手性药物（手性酸及手性醇等）的拆分中显示出巨大的应用潜力,是除立体选择性水解、酯化、转酯反应及外的另一具有较大开发应用前景的酶促新型反应。     

麦白霉素含水量的费歇尔测定法

抗生素中水分测定,一般有干燥失重法、费歇尔法等,前法测定供试品中所含水分包括一些挥发性物质,且费时并不适合于低熔点易分解的物质,后法可真实测出供试品中的水分,包括游离水和结晶水,操作简单、特异性高,当然与费歇尔液发生反应的物质除     

吡硫醇丙酯前体药物的合成及其降解动力学

目的:合成吡硫醇前体药物,并研究其在不同pH缓冲溶液中及血浆中的水解动力学。方法:以吡硫醇和丙酸酐为原料,经过简单的酯化反应合成吡硫醇丙酯,利用RP-HPLC法测定前体药物的油水分配系数、溶解度、在不同pH值缓冲溶液中及血浆中的降解动力学。结果:经UV,IR,MS和NMR确证目标化合物的结构。前体药物的水解曲线呈V-型分布,pH值在5~6最稳定,血浆中前药可迅速转化成吡硫醇。结论:吡硫醇丙酯是具有良好前景的前体药物。     

多肽和蛋白微乳制剂及其进展

参阅国内外最新研究文献,分析了蛋白在微乳内的分布、稳定性及蛋白对微乳性质的影响,并介绍了微乳作为蛋白给药系统及在非水酶反应中的应用。表明微乳能够提高蛋白的稳定性并提高其生物利用度和疗效,在非水酶反应中也具有独特的优点,是一种具有发展前景的药物载体。     

《中国药典》2000年版一部含水分的中药材部分含量测定计算的探讨

<中国药典>2000年版一部(以下简称2000年版)收载了156种药材,有含量测定项目的中药材一般均含有一定量的水分,药材含水量各有差异.药材含量测定时对样品中水分的处理大体分为三种情况:①样品在一定的温度下干燥后测定含量;②样品直接测定含量,另测水分,含量折除水分按干燥品计算;③样品直接进行含量测定,未考虑水分因素.对于第三种情况,作者认为有必要做进一步的探讨.     

含D-氨基酸残基多肽的酶促合成

本文介绍了含D-氨基酸残基多肽的酶促合成方法:动力学控制酶反应和非水介质中进行的酶反应.在非水介质中,不仅可以改变蛋白酶的立体选择性,而且使酯酶成为含D-氨基酸残基多肽的合成酶.本文阐述了这两种方法的机理,并列举了一些含D-氨基酸残基多肽酶促合成的例子.     

小分子脂水分配系数最优值的计算机模拟

首先建立了药物小分子进入体内到达细胞内受体表面的数学模型,然后通过计算机模拟,计算药物小分子达到受体表面的浓度,最后比较了不同脂水分配系数下的情况。结果表明,拥有最优脂水分配系数的药物小分子,才能更多的到达受体表面。     

《有机药物合成原理》简介

《有机药物合成原理》一书,由华西医科大学李正化教授主编。人民卫生出版社出版。该书结合有机化学结构理论,反应历程,热力学、动力学和立体化学等基本原理探讨不同类型反应的化学结构与活性规律,研究化学结构因素与反应条件对活性及收率的影响。全书除绪论外,分上、下两篇。上篇中讨     

Pro-inflammatory properties of the kallikrein-kinin system: Potential for new drug therapy

Components of the kallikrein-kinin system are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B₂ receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI₂ and PAF) in the inflamed joint. B₂-receptor antagonists may provide valuable agents as new analgesic drugs. Furthermore, it is suggested that substances to reduce activation of the kallikrein-kinin system (KKS) may provide a pharmacological basis for the synthesis of novel antirheumatic or anti-inflammatory drugs.     

皮肤脱色剂的研究进展

目的从脱色剂的脱色机制及应用角度对近年来的脱色剂研究新进展进行综述。方法以生物及天然来源的化学脱色剂中常用的脱色剂为例介绍了两大类型脱色剂的脱色机制和应用。结果这些脱色剂都能抑制黑色素合成,均为临床可选药物,但有待进一步临床试验以评价它们的安全性。结论为各种脱色剂或增白剂制定安全的使用标准提供依据。     

Synthesis and biological evaluation of novel phenylcarbazoles as potential anticancer agents

We here report the synthesis and biological evaluation of new phenylcarbazole derivatives designed as potential anticancer agents. Indole and hydroxyindole were used to generate three scaffolds that were successively exploited to introduce various substituents on the maleimide moiety. The synthesis includes a final intramolecular key Heck-type reaction, which was carried out with a triflate derivative or with a bromophenyl derivative. Each step was optimized and the complete chemical strategy is detailed. Several compounds showed a marked cytotoxicity against CEM human leukemia cells with IC(50) values in the 10-100 nM range. Precise structure-activity relationships were delineated. Cell cycle analysis, topoisomerase I inhibition, and interaction with DNA were evaluated, and inhibition of CDK activity was also investigated. Although binding of the drugs to DNA likely contributes to the cytotoxic action, the exact molecular targets of these molecules remain undiscovered. The efficient chemical routes reported here for the design of highly cytotoxic compounds provide novel opportunities to identify antitumor agents in the phenylcarbazole series.     

Detection of chemical threat agents in drinking water by an early warning real-time biomonitor

Having a safe water supply for civilian organizations and military personnel is an important objective to avoid toxic contamination of civilians and soldiers. Chemical warfare (CW) agents, especially organophosphorous nerve compounds, are the most toxic of known chemical agents. The Daphnia Toximeter system is a continuously working test system that uses Daphnia magna as a sensitive organism for monitoring drinking water. Both small doses (allowable for short-term water ingestion) and graduated higher concentrations induced toxic reactions in the Daphnia Toximeter system, leading to alarms sounding. The system is sensitive to a wide range of CW agents and their hydrolysis products. Concentrations below acute human toxicity can be discovered in a very short time, with the actual time depending on the concentrations applied. In every case alarms were triggered within 2 h at concentrations in water low enough for that water to be allowed for use as drinking water in exceptional conditions.     

神经肌肉阻滞药及其拮抗药的临床应用及市场现状

神经肌肉阻滞药是一种作用于外周神经系统、不具有中枢作用的肌肉松弛药,常作为手术麻醉时的辅助用药,但它的使用会导致阻滞残留作用,临床上常用拮抗药拮抗或者逆转其残留阻滞作用。本文总结了近年来神经肌肉阻滞药及其拮抗药的临床应用及市场现状,并阐述了其在国内的发展机遇和挑战。     

Progress in the research of antituberculous drugs(I)

结核病仍为最具破坏性的细菌性疾病之一，发病率和死亡率都很高。结核分枝杆菌能侵入宿主免疫系统，在肺肉芽肿中持留，致使目前的抗结核药物无法杀灭菌体。近年来药物耐受以及伴有HIV感染的结核病发病率急剧增加都给结核的控制带来了很大的困难，迫切需要深入了解目前抗结核药物的作用机制及耐药机制、病菌繁殖的分子机制，以指导开发对持留菌和耐药菌更加有效的新型药物。文中综述了近年来通过天然物筛选、新药设计合成以及对现有抗结核药物的再修饰等途径，发现的一些有抗结核活性的化合物，以及结核杆菌分子生物学和抗结核治疗靶点的研究进展。     

Heterocyclic compounds as inflammation inhibitors

Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with significant toxicity particularly in the gastrointestinal tract and kidney. Various approaches such as formulation co-administration (of agents to protect the stomach), chemical manipulation and synthesis of new safer anti-inflammatory drugs reported in the literature to overcome the toxicity of NSAIDs have been summarized. As far as synthesis of new more effective and safer anti-inflammatory drugs is concerned, we have reported recent findings in the area of synthesis of heterocyclic compounds such as pyrimidines, imidazole, benzimidazole, thiazole, thiazolidine, acridine, thiourea, alkanoic acid derivatives and other related heterocyclic compounds and their role as inflammation inhibitors.     

2009年SFDA批准注册的国产化学药品统计分析

目的了解和分析2009年我国新注册的化学药品分布情况。方法全面检索国家食品药品监督管理局数据库和相关资源,登记2009年注册的国产化学药品的名称、批准文号、药物化学治疗分类、是否属国家基本药物等,然后运用Excel进行分类汇总分析。结果 2009年共注册国产化学药品1 583个,涉及通用名药物489个,药品批准文号数量排序前三位的依次为抗微生物药物、作用于中枢神经系统的药物和作用于消化系统的药物。结论 2009年国产化学药品注册依然存在药品注册与需求不完全一致、个别药品"一药多号"、抗微生物药物生产竞争激烈等问题,同时也出现基本药物注册小高峰等新迹象。     

4'-烷氧基-1,1'-联苯-4-羧酸脂三肽的合成

目的 制备用于全合成新型卡泊芬类环六脂肽抗真菌剂的关键脂三肽中间体4′-烷氧基-1,1′-联苯-4-羧酸脂三肽。方法以L-脯氨酸叔丁酯为原料,依次经与N-（9-芴甲氧羰基）-L-苏氨酸叔丁醚（a）或N-（9-芴甲氧羰基）-L-丝氨酸叔丁醚（b）缩合、脱N-保护基后与N^α-（9-芴甲氧羰基）-N^δ-苄氧羰基-L-鸟氨酸缩合、再脱N“-保护基后与4′-烷氧基-1,1′-联苯-4-羧酸-N-羟基苯并三氮唑“活泼酯”（Ie-If）缩合5步反应制备目标脂三肽1。结果以67．4％～80．0％的总收率合成了8个脂三肽1ae-1ah和1be-1bh,其结构经电喷雾质谱（ESI-MS）和元素分析确证。结论该合成路线具有反应条件温和、操作简便、总收率高的优点。