Application of α-amylase and Research
α-amylase to be widely distributed throughout microorganisms to higher plants. The International Enzyme classification number is EC. 3.2.1.1, acting on the starch from the starch molecules within the random cut α a 1,4 glycosidic bond to produce dextrin and reducing sugar, because the end product of carbon residues as Α configuration configuration, it is called α-amylase. Now refers to α-amylase were cut from the starch molecules within the α-1,4 glycosidic bond from the liquefaction of a class of enzymes.
α-amylase is an important enzyme, a large number of used food processing, food industry, brewing, fermentation, textile industry and pharmaceutical industries, which account for the enzyme about 25% market share. Currently, both industrial production to large-scale production by fermentation α-amylase. α-amylase in industrial applications
1.1 The bread baking industry, as a preservative enzymes used in baking industry, production of high quality products have been hundreds of years old. In recent decades, malt and microbial α-amylase, α-amylase is widely used in baking industry. The enzymes used for making bread, so that these products are much larger, better colors, more soft particles.
Even today, baking industry have been α-amylase from barley malt and bacterial, fungal leaf extract. Since 1955 and after 1963 in the UK GRAS level validation, fungal amylase, has served as a bread additive. Now, they are used in different areas. Modern continuous baking process, add in f lour α-amylase can not only increase the fermentation rate and reduce dough viscosity (improving product volume and texture) to increase the sugar content in the dough, improved bread texture, skin color and baking quality, but also to extend the preservation time for baked goods. In the storage process, the bread particles become dry, hard, not crisp skin, resulting in deterioration of the taste of bread. These changes collectively referred to as degenerate. Each year simply because the losses caused by deterioration of bread more than 100 million U.S. dollars. A variety of traditional food additives are used to prevent deterioration and improve the texture and taste of baked goods. Recently, people started to pay attention enzyme as a preservative, preservative agent in improving the role of the dough, as amylopectin, amylase enzyme and a match can be effectively used as a preservative. However, excessive amylase causes a sticky bread too. Therefore, the recent trend is the use of temperature stability (ITS) α a amylase activity are high in starch liquefaction, but the baking process is completed before the inactivation. Despite the large number of microbes have been found to produce α-amylase, but with the temperature stability of the nature of the α-amylase only been found in several microorganisms.
1.2 starch liquefaction and saccharification of the main α-amylase starch hydrolysis product market, such as glucose and fructose. Starch is converted into high fructose corn syrup (HFCS). Because of their high sweetness, are used in the soft drink beverage industry sweeteners. The liquefaction process is used in thermal stability at high temperature α-amylase. α-amylase in starch liquefaction of
the application process is already quite mature, and many relevant reports.
1.3 fiber desizing modern fiber manufacturing process in knitting yarn in the process will produce large amounts of bacteria, to prevent these yarn faults, often increase in the surface layer of the yarn can remove the protective layer. The surface layer of the material there are many, starch is a very good choice because it is cheap and easy to obtain, and can be easily removed. Starch desizing α-amylase can be used, it can selectively remove the starch without harming the yarn fibers, but also random degradation of starch dextrin soluble in water, and are easily washed off. 1.4 Paper Industry amylase used in the paper industry mainly to improve the paper coating starch. Paste on the paper is primarily to protect the paper in the process from mechanical damage, it also improved the quality of finished paper. Paste to improve the hardness and strength of paper, enhanced erasable paper, and is a good paper coating. When the paper through two rolls, the starch slurry is added the paper. The process temperature was controlled at 45 ~ 6O ℃, need a stable viscosity of starch. Grinding can also be controlled according to different grades of paper starch viscosity. Nature of the starch concentration is too high for the sizing of paper, you can use part of α-amylase degradation of starch to adjust.
1.5 Application of detergents in the enzyme is a component of modern high-efficiency detergents. Enzymes in detergents in the most important function is to make detergents more modest sound. Automatic dishwasher detergents early is very rough, easy to eat when the body hurts, and on ceramics, wood tableware can also cause damage. α-amylase was used from 1975 to washing powder. Now, 90% of the liquid detergents contain an amylase, and automatic dishwasher detergents α-amylase on demand is also growing. α 1 amylase ca2 + is too sensitive to low ca2 + in the stability of poor environment, which limits an amylase in the remover in. And, most of the wild-type strains produced an amylase on raw materials as one of the oxidants detergents are too sensitive. Keep household detergents, this limitation by increasing the number of process steps can be improved. Recently, two major manufacturers of detergents NovozymesandGcncncoreInternational enzyme protein technology has been used to improve the stability of amylase bleaching. They leucine substitution of Bacillus licheniformis α-amylase protein in the first 197 on the methionine, resulting in enzymes of the oxidant component of resistance increased greatly enhanced the oxidation stability of the enzyme stability during storage better. The two companies have been pushing in the market these new products.
1.6 Pharmaceutical and clinical chemical analysis with the continuous development of biological engineering, the application of amylase involved in many other areas, such as clinical, pharmaceutical and analytical chemistry. Have been reported, based on the liquid α-amylase stability of reagents have been applied to automatic biochemical analyzer (CibaComingExpress) clinical chemistry system. Amylase has been established by means of a method of detecting a higher content of oligosaccharides, is said this method is more than the effective detection method of silver nitrate.
2.1 Research amylase α-amylase enzymes in domestic production and application in 1965, China began to apply for a 7658 BF Bacillus amyloliquefaciens amylase production of one, when only exclusive manufacturing plant in Wuxi Enzyme. 1967 Hangzhou Yi sugar to achieve the application of α-amylase production of caramel new technology can save 7% ~ 10% malt, sugar, increase the rate of 10%.1964, China began a process of enzymatic hydrolysis of starch production of glucose. In September l979 injection of glucose by the enzyme and identification of new technology and worked in North China Pharmaceutical Factory, Hebei Dongfeng Pharmaceutical Factory, Zhengzhou Songshan applied pharmaceutical units and achieved good economic benefits. Compared with the traditional acid to improve the yield of 10% Oh, cost more than 15%. In addition to enzyme for citric acid production in China, glutamic acid fermentation system for beer saccharification, fermentation, rice wine, soy sauce manufacture, vinegar production also has been studied and put into production successfully.
2.2 Overseas Researc h α-amylase, present, and in addition a large number of T for conventional mutation breeding, the overseas production has been initially figure out the regulation of α-amylase gene, the transduction of the transformation and gene cloning techniques such as breeding. The Bacillus subtilis recombinant gene into the production strain to increase α-amylase yield of 7 to 10 times and has been used in food and the wine industry, for breeding high-yield strains of α-amylase to create a new way.
2.3 domestic and foreign research institutions and major research direction as α-amylase is an important value of industrial enzymes, weekly discussion group and outside it was a lot of research. Representative of the domestic units: Sichuan University, major research produc tion of α-amylase strains and culture conditions; Jiangnan University, the main research structure of α-amylase and application performance, such as heat resistance, acid resistance; Northwest universities, major research denatured α-amylase and the environment on the mechanism of α-amylase; South China University of Technology, the main α-amylase of immobilization and dynamic nature; there Huazhong Agricultural University, Chinese Academy of Sciences Institute of Applied Ecology in Shenyang, Tianjin University, Nankai University, College of Life Sciences, Chinese Academy of Agricultural Sciences, Chinese Academy of Sciences Institute of Microbiology and a number of research institutions on a variety of bacterial α-amylase production of a amylase gene cloning and expression. Representative of foreign research units are: Canada UniversityofBritishColumbia, they were a pancreatic amylase structure and mechanism of in-depth research; Denmark's Carlsberg Research Laboratory of the main structure of barley α-amylase domain and binding sites; U.S. WesternRegionalResearchCenter major study α-amylase in barley and the role of antibiotics and the barley α-amylase active site.
3, α-amylase conclusion has become the industrial application of one of the most important enzymes, and a large number of micro-organisms can be used for efficient production of amylase, but large-scale commercial production of the enzyme is still limited to some specific fungi and bacteria. For the effective demand
for α-amylase more and more, this enzyme by chemical modification of existing or improved technology through the white matter are. Benefit from the development of modern biotechnology, α an amylase in the pharmaceutical aspects of growing importance. Of course, the food and starch indust ries is still the main market, α amylase in these areas, a demand is still the largest.
Journal of Southeast University(English Edition)2008 24（4）
Application of α-amylase and Research α-amylase to be widely distributed throughout microorganisms to higher plants. The International Enzyme classification number is EC. 3.2.1.1, acting on the starch from the starch molecules within the random cut α a 1,4 glycosidic bond to produce dextrin and reducing sugar, because the end product of carbon residues as Α configuration configuration, it is called α-amylase. Now refers to α-amylase were cut from the starch molecules within the α-1,4 glycosidic bond from the liquefaction of a class of enzymes. α-amylase is an important enzyme, a large number of used food processing, food industry, brewing, fermentation, textile industry and pharmaceutical industries, which account for the enzyme about 25% market share. Currently, both industrial production to large-scale production by fermentation α-amylase. α-amylase in industrial applications 1.1 The bread baking industry, as a preservative enzymes used in baking industry, production of high quality products have been hundreds of years old. In recent decades, malt and microbial α-amylase, α-amylase is widely used in baking industry. The enzymes used for making bread, so that these products are much larger, better colors, more soft particles. Even today, baking industry have been α-amylase from barley malt and bacterial, fungal leaf extract. Since 1955 and after 1963 in the UK GRAS level validation, fungal amylase, has served as a bread additive. Now, they are used in different areas. Modern continuous baking process, add in f lour α-amylase can not only increase the fermentation rate and reduce dough viscosity (improving product volume and texture) to increase the sugar content in the dough, improved bread texture, skin color and baking quality, but also to extend the preservation time for baked goods. In the storage process, the bread particles become dry, hard, not crisp skin, resulting in deterioration of the taste of bread. These changes collectively referred to as degenerate. Each year simply because the losses caused by deterioration of bread more than 100 million U.S. dollars. A variety of traditional food additives are used to prevent deterioration and improve the texture and taste of baked goods. Recently, people started to pay attention enzyme as a preservative, preservative agent in improving the role of the dough, as amylopectin, amylase enzyme and a match can be effectively used as a preservative. However, excessive amylase causes a sticky bread too. Therefore, the recent trend is the use of temperature stability (ITS) α a amylase activity are high in starch liquefaction, but the baking process is completed before the inactivation. Despite the large number of microbes have been found to produce α-amylase, but with the temperature stability of the nature of the α-amylase only been found in several microorganisms. 1.2 starch liquefaction and saccharification of the main α-amylase starch hydrolysis product market, such as glucose and fructose. Starch is converted into high fructose corn syrup (HFCS). Because of their high sweetness, are used in the soft drink beverage industry sweeteners. The liquefaction process is used in thermal stability at high temperature α-amylase. α-amylase in starch liquefaction of
阿司匹林对抗血栓的分析研究方法 姓名：陈曦 班级：制药132 学号：2013013085
阿司匹林对抗血栓的分析研究方法 【摘要】心血管疾病是危害人类健康的严重疾病，而抗血栓治疗是此类疾病抢救措施及预防策略的核心。抗血栓药按作用机制主要分为抗血小板药、抗凝血药和溶栓药三类。 【关键词】心血管疾病；抗血栓治疗；抗血小板药；抗凝血药。 心血管疾病是危害人类健康的严重疾病，是造成死亡的主要原因之一。心血管疾病是指由于心脏及血管病变而引起的一系列疾病，包括心脏病、高血压、高脂血症等。抗血栓治疗一直是心血管疾病抢救措施及预防策略的核心。抗血栓药按作用机制主要分为抗血小板药、抗凝血药和溶栓药三类。前两类主要用于预防血栓形成，是抗血栓治疗的重要方法，后一类主要用于急性心肌梗死、脑梗死后，溶解已形成的血栓。 1.抗凝血药 抗凝血药是通过影响凝血过程中的某些凝血因子阻止凝血过程的药物。正常人由于有完整的血液凝固系统和抗凝及纤溶系统，所以血液在血管内既不凝固也不出血，始终自由流动完成其功能，但当机体处于高凝状态或抗凝及纤溶减弱时，则发生血栓栓塞性疾病。目前常用的抗凝血药根据化学结构主要有以下两类： 1.1肝素类 肝素是一种由D-葡糖醛酸和N-乙酰-D葡糖胺残基交替排列，并经脱乙酰和硫酸化，D-葡糖醛酸转化为L-艾杜糖醛酸等一系列修饰而成的直链粘多糖。肝素是最早使用的抗凝药，在体内外均有很强的抗凝
作用，这是通过抗凝血酶Ⅲ来实现的，可有效地防止深静脉血栓和肺栓塞的形成，临床上常用于治疗急性心肌梗死和不稳定型心绞痛。该制剂只能静脉给药，当用量过多引起出血时，可用等量鱼精蛋白中和，长期使用肝素有引起出血的危险，副作用较大。与普通肝素相比，低分子量肝素类物质具有较强的抗Xa因子活性和促纤溶作用，其抑制凝血酶及血小板的作用较弱，且不增加血管通透性，故血小板减少及出血发生率明显减少。低分子量肝素类物质血浆蛋白非特异性结合力低，其生物利用度可达98%，量效关系明确，预期浓度和疗效准确，加之其本身对APTT影响不明显．故无需药物监测。低分子量肝素类物质血浆半衰期长，达200~300分钟，为未分馏肝素类物质的2~4倍。因此用药简单，一般经皮下注射给药，每日注射1次即可。 在1993年以前，深度静脉血栓和肺栓塞的治疗几乎完全依赖于肝素（heparin）。然而时至今日，由于低分子量肝素类产品更易给药且副反应发生率低，尤其是出血风险大为降低及用药后不需密集监测，故它们已经成为用来预防和治疗深度静脉血栓的主要临床选择。 1.2香豆素类 香豆素是一类含有4-羟基香豆素基本结构的物质，口服参与体内代谢才能发挥抗凝作用，称为口服抗凝药，这是唯一在临床广泛应用的口服抗凝血药，如双香豆素、华法林(苄丙酮香豆素)和醋硝香豆素，它们的化学结构与维生素K类似，故亦称为维生素K拮抗剂，它们的药理作用相同。 华法林与维生素K竞争羧化酶，使凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ合成
A/O法活性污泥中氨氧化菌群落的动态与分布 摘要: 我们研究了在厌氧—好氧序批式反应器（SBR)中氨氧化菌群落(AOB)和亚硝酸盐氧化菌群落(NOB)的结构活性和分布。在研究过程中,分子生物技术和微型技术被用于识别和鉴定这些微生物。污泥微粒中的氨氧化菌群落结构大体上与初始的接种污泥中的结构不同。与颗粒形成一起，由于过程条件中生物选择的压力,AOＢ的多样性下降了。DGGE测序表明，亚硝化菌依然存在,这是因为它们能迅速的适应固定以对抗洗涤行为。DGGE更进一步的分析揭露了较大的微粒对更多的AOB种类在反应器中的生存有好处。在SＢR反应器中有很多大小不一的微粒共存，颗粒的直径影响这AＯB和NOB的分布。中小微粒（直径<0．6ｍm）不能限制氧在所有污泥空间的传输。大颗粒(直径>０．9mm）可以使含氧量降低从而限制NＯB的生长。所有这些研究提供了未来对ＡOB微粒系统机制可能性研究的支持。 关键词:氨氧化菌(AＯB），污泥微粒,菌落发展，微粒大小,硝化菌分布，发育多样性 ?简介 在浓度足够高的条件下，氨在水环境中对水生生物有毒，并且对富营养化有贡献。因此,废水中氨的生物降解和去除是废水处理工程的基本功能。硝化反应,将氨通过硝化转化为硝酸盐,是去除氨的一个重要途径。这是分两步组成的，由氨氧化和亚硝酸盐氧化细菌完成。好氧氨氧化一般是第一步,硝化反应的限制步骤:然而,这是废水中氨去除的本质。对16S ｒRNA的对比分析显示，大多数活性污泥里的氨氧化菌系统的跟?-变形菌有关联。然而，一系列的研究表明,在氨氧化菌的不同代和不同系有生理和生态区别,而且环境因素例如处理常量,溶解氧，盐度,pH，自由氨例子浓度会影响氨氧化菌的种类。因此,废水处理中氨氧化菌的生理活动和平衡对废水处理系统的设计和运行是至关重要的。由于这个原因,对氨氧化菌生态和微生物学更深一层的了解对加强处理效果是必须的。当今,有几个进阶技术在废水生物处理系统中被用作鉴别、刻画微生物种类的有价值的工具。目前,分子生物技术的应用能提供氨氧化菌群落的详细分类说明。
药物化学论文 题目：苯佐卡因的合成 作者陈媛学号 系别化学化工系专业11师范班完成时间二0一四年六月十日
摘要：本文主要介绍了苯左卡因以硝基苯甲酸为原料的制备方法，以及苯左卡因的实验制备过程。通过对本文的学习，我们能够了解苯左卡因的化学 性质和发展状况以及他在医药方面的相关用途。 关键词：苯左卡因；硝基甲酸；合成 Abstract: This article mainly introduced benzene left Kain take the nitryl benzoic acid as raw material preparation method, as well as the benzene left Kain's experiment prepares the process.Through to this article study, we can understand the benzene left Kain's chemical property and the development condition as well as he in the medicine aspect related use. Key word: Benzene left Kain; Nitryl formic acid; Synthesis
1 苯佐卡因概况 1.1苯佐卡因的基本性质 苯佐卡因，英文名BenLzocaine，化学名为对氨基苯甲酸乙酷(Ethylp一aminobenzoate)或4一氨基苯甲酸乙酷(p~Aminobenzoieacidethylester)，化学分子式为CgHllNOZ，相对分子量为165.19。苯佐卡因为白色针状晶体，无臭，味苦。熔点91~92e，沸点183~184e(1.87kPa)。微溶于水，溶于乙醇!氯仿，乙醚。它是重要的医药中间体，可作为奥索仿!奥索卡因!普鲁卡因等前体原料。 1.2国内外制剂开发现状 国外使用苯佐卡因的制剂很多，美国药物索引1984年收载苯佐卡因制剂即达一百多种，其中片剂27种，软膏17种，霜剂6种，胶囊剂3种，还有凝胶剂!栓剂!洗剂!气雾剂等。苯佐卡因作用的特点适用于口腔科，如美国Beutllch生产的/Hurrieaine0是以水溶性聚乙二醇为基质，含20%苯佐卡因的软膏，主要用于口腔科注射前局部麻醉和牙结石!牙酿手术前的麻醉止痛;Armour生产的/AAA0气雾剂，含苯佐卡因1.5%，氯化节基十六烷基二甲基胺0.0413%，用于治疗由寒冷!滴鼻后和其他刺激所引起的咽喉痛，口腔溃疡及口腔咽喉的轻度感染;英国ICI的/复方洗必泰片0(HibitaneantisePtie)含盐酸洗必泰smg，苯佐卡因Zmg，治疗口腔和咽喉感染，缓解咽喉痛和喉炎，防止扁桃体切除术和牙科手术后的继发性感染。 美国药典(第24版)!英国药典(1998年版)!中国药典(2000年版)等对苯佐卡因制剂均有收载l6]。国内有制成散剂!5%软膏!栓剂，国外制剂品种较多，用于口腔杀菌!溃疡!咽喉止疼止痒，并且含片!喷雾剂!以及耳用制剂品种较多。与国外相比，苯佐卡因在我国的使用范围是非常狭窄的，仅仅在一些外用软膏中作为止痒成份，因此它的作用特点没有得到充分的发挥。美国药典(24版)还收载有单复方凝胶!软膏!霜剂!表面溶液剂等，我国这方面品种还没有。仅见盐酸丁卡因片(1997年新药品种汇编)适用于消化道内镜检查前麻醉咽喉粘膜。苯佐卡因疗效确切，安全有效，5中国药品6把它列为我国第一批非处方药(OTC)。其制剂的开发需要进一步加强。 2苯佐卡因合成研究现状 苯佐卡因的制备，有从甲基苯胺出发，有从对硝基苯甲酸出发，亦有从甲苯出发。当前国内厂家生产的苯佐卡因大部分都以对硝基苯甲酸和乙醇为原料，经酷
(文档含英文原文和中文翻译) 中英文对照外文翻译文献 Biological effects of the Magnetic Stimulation on the T oad Heart Abstract-W e stimulated the exposed toad heart by a low frequency and high energy magnetic. By analyze the data of this experiment, it shows that the pulsating of the weak toad heart would make change after stimulated by magnetic. W eak heartbeat strengthened, the single peak curve would become the two peaks curve with atria wave and ventricle wave after the magnetic stimulation. But the cycling of rhythmic pulsatile curve of toad doesn't change. I. INTRODUTION All life forms have magnetism. All kinds of magnetic field would have some effects on the configuration and activities of life forms that whichever environmental magnetic, additional magnetic or inside magnetic of organism. The biologic effects are related to the characteristics and
药物分析新技术的研究进展 【摘要】本文介绍近年来药物分析领域中发展起来的几种新技术，包括高效毛细管电泳技术、高效液相色谱-质谱联用技术、高速逆流色谱技术、时间分辨荧光分析法、手性药物的液相色谱分析法，以及它们的最新 应用进展。 药物分析目的是保证药物的质量和用药的安全有效。它研究药物的化学检验、药物稳定性、生物利用度、药物临床监测和中草药有效成分的定性和定量等。传统的药物分析,大多是应用化学方法分析药物分子,控制药品质量。然而,现代药物分析在计算机技术以及分析技术的飞速发展下已经发生了翻天覆地的的变化。本文主要介绍一些基于现代色谱、现代波谱、色谱连用技术上的用于药物分析的现代化技术方法。 1、高效毛细管电泳技术 高效毛细管电泳（high performance capillary electrophore-sis，HPCE）又称毛细管电泳（CE）。毛细管电泳 ( CE)是 80年代后期在世界范围内迅速发展起来的一种分离分析技术，是经典电泳技术和现代微柱分离相结合的产物。其分析应用的范围极广 ,小至无机离子 ,大至生物大分子 ,都可以用 CE来测定。HPCE 在DNA、氨基酸及蛋白质的分析中应用非常广泛，已在生命科学和生物工程等领域中显示出极其重要的应用前景，被用于DNA分析，如实现微量DNA的检测、DNA片段的分离、DNA的测序、DNA突变的检测、DNA损伤判断、临床诊断等[1]。 HPCE 技术因其特别适宜快速大量地分析复杂的中药成分而被广泛用于中药材鉴别和质量控制、中药有效成分的分离与测定、中成药和中药制剂的分析。韩乐等[2]建立了HPCE 同时测定玄参中梓醇、桃叶珊瑚苷、哈巴苷、哈巴俄苷、毛蕊花糖苷及肉桂酸含量的方法，用于玄参药材内在质量的评价和控制。Yu 等[3]等采用中心组合设计法和多变量分析法，以黄芩苷、黄芩素和汉黄芩素作为控制标准建立黄芩毛细管指纹图谱，对34个不同产地的黄芩进行质量分析控制，方法快速、精密、可靠，对所有来源的药材进行了质量评价。 2、高效液相色谱-质谱联用技术 高效液相色谱-质谱（High performance liquid chro-matography-mass spectrometry，HPLC-MS）联用技术是近几年来发展起来的一项新的分离分析技术。它将高效液相色谱（HPLC）对复杂样品的高分离能力，与MS具有高选择性、高灵敏度及能够提供相对分子质量与结构信息的优点结合起来，在生物、药物、临床医学、化工和环境等领域得到了广泛的应用，是分析和鉴定复杂混合物的强有力的工具,尤其适用于生物样品中痕量药物的测定。Zhu等[4]采用液相色谱-串联质谱联用(LC-MS/MS)法测定人血浆中奥普力农. 3 高速逆流色谱技术 高速逆流色谱（high-speed countercurrent chromatogra-phy，HSCCC）技术是20 世 纪80 年代发展起来的一种连续高效的新型液-液分配色谱分离技术，最初由美国国立健 康研究院（NIH）的Ito教授研制开发。HSCCC最大的优点是无需固相载体作固定相，并 具有操作简单快捷、分离纯度高、样品回收率高、适用范围广、可一步制备纯品的优点。既 适用于小量分析，也可用于规模纯化，在中药、生化、食品、天然产物化学、环境分析等领域 有着广泛的应用。 HSCCC 在天然植物活性成分的分离中得到了相当广泛的应用，在有机酸、黄酮、生物碱、植物多酚、醌类、萜类、木脂素、香豆素、皂苷等几乎所有的天然植物化学成分的分离中 都有应用。HSCCC可以用来对天然产物的粗提物进行有效成分的提纯以及对天然产物进 行除杂处理。 王晓丽等[5]通过紫外-可见分光光度计法对高速逆流色谱仪分离芦荟多糖的溶剂系统进 行研究，探索出分离芦荟多糖的溶剂系统为PEG600-KH2PO4-K2HPO4-H2O （5∶15∶15∶65，w/w）体系。钱俊青等[6]采用高速逆流色谱法分离纯化大豆异黄酮，并选 用HPLC法测定样品的质量分数，成功分离得到大豆苷91.65%，染料木苷92.97%。高 赛男等[7]采用正己烷-乙酸乙酯-甲醇-水（3.0∶5.0∶3.5∶5.0，v/v）溶剂体系，采用高速逆流 色谱法从丁公藤中成功分离纯化得到东莨菪内酯，纯度可达98.04%。 4 时间分辨荧光分析法 时间分辨荧光分析（timeresolved fluorescence assay，TR-FA）是近年来发展起来的非同
药物分析——药品质量标准的制订 药品（质量）标准是国家对药品质量、规格及检验方法所作的技术规定，是药品生产、供应、使用、检验和药政管理部门共同遵循的法定依据。我国现行的药品标准分为三级：国家药典（中国药典）、部标准（卫生部药品标准）和地方标准（各省、直辖市、自治区药品标准）。 制订药品质量标准的原则： 1、从人民健康需要出发，坚持质量第一的观点； 2、同一品种新药原则上只能制订一个部级标准，并有二年试行期，期满后修订转为正式标准； 3、后申报的标准必须达到已申报的标准水平；若比已申报的标准先进，则按先进的药品标准修订； 4、同时申报新药的，要统一标准，按其中高的标准制订，若因生产水平及工艺条件不同造成杂质项目检查有不同者，可将杂质检查项目共存； 5、从药品的生理效用和临床应用的方法合理性来制订。总之要体现“安全有效，技术先进，经济合理”的方针。 制订药品质量标准的基础： 一、查阅文献和新药命名：首先要查阅大量的文献，查阅其化学名、俗称、英文名及中文名；其次要介绍药品的研制过程，简略
说明实验室研究与临床试验的时间、机构和试验结论。国外已生产的，要介绍最早上市的国家（或厂家）和时间。 二、新药化学结构或处方的确定：通过各种方法（试验数据、图谱、图谱的解析、有关文献资料）确证化学结构或组份，并注意可能存在的各种异构体。在有些情况下要规定无效异构体的限度。处方要效果更优，不良反应更小。 三、生产工艺和晶型：不同生产工艺会有不同的异构体。还会产生不同的晶型。 四、晶型的性质与药效：晶型不同其生物利用度往往不同，可能会影响疗效、剂量、熔点和红外图谱等。 五、生产或贮存过程中带来的杂质或降解产物：不同生产路线会带来不同的杂质，在贮存过程中要考虑到药物的分解。 六、含量测定方法的制订：一种药物的含量可用多种方法进行测定，但在制订质量标准时往往只选其中一种。对选取这种方法的理由应加以解释，必要时需附不同方法的测定结果进行比较。同时还要说明测定的原理、方法的精度与准确度，还要讨论影响测定结果的因素等。 七、药理及毒理作用的研究：有的药物随着临床药理研究的深入，会发现还有其它方面的药理作用。新药研制时还要做毒理试验、“三致”（致癌、致畸、致突变）试验。 八、药物动力学研究：主要是研究药物的吸收速率、吸收程度、在体内重要器官的分布和维持情况，以及排泄的速率和程度，作
2016-20 17学年第1 学期 文献综述 名称高效液相色谱法手性固定相分手性药物研究进展专业2016级药物化学 学号161320217 姓名李松子 导师柯美荣 指导老师林子俺 时间2016年12月19日
高效液相色谱法手性固定相分手性药物研究进展 摘要 手性（chirality)是指化合物的分子式和结构式相同，因分子空间排列不同导致两个分子互为镜像和实物的现象。手性药物（chiral drug)是指药物分子结构中引人手性中心后得到的一对互为实物与镜像的对映异构体（enantiomer) 这些对映构体的理化性质基本相似，仅旋光性质有所差别。目前在约2000种常用药物中有近500种药物以外消旋体的形式存在。外消旋体药物中可能只有一种对映异构体有药效，其镜像分子却有毒副作用或药效相反或无药效：如左旋巴比妥酸盐抑制神经活动而右旋巴比妥酸盐却兴奋神经；右旋甲状腺素钠可降低血脂而左旋甲状腺素钠对心脏有毒副作用；抗菌药左旋氧氣沙星的药效高于其右旋体数倍对映异构体也对香料化学和农业化学方面有重要作用：如S-型的香芹酮有香菜味,而R-型却具有荷兰薄荷香味；农药溴氰菊酯的8个异构体中，（3R,1R,S）异构体的杀虫活性是（3S, lS，R)的70多倍。手性药物的分离分析在生物和化学领域一直是研究热点。 色谱法利用固定相与外消旋体之间的作用力不同使流动相洗脱时各组分保 留时间不同而实现分离的目的。色谱法以其优良的识别能力成为目前应用最广泛的手性拆分方法，尤其在性药物的分离分析和纯度检测等方面。常用的手性色谱分离技术包括高效液相色谱法（HPLC)、气相色谱法（GC)、毛细管电色谱法（CEC)等根据侍分离化合物的分子结构选择合适的手性色谱非常重要。 在用HPLC法分离手性物质时，可以通过改变色谱柱的流动相和固定相来改变改善HPLC的分离效果。根据手性固定相的不同来源，可分为天然、半合成和全合成三大类。本文介绍国内外近几年手性固定相拆分手性药物的研究进展，包括几种经典类型及一些新型手性固定相。固定相可分为几种经典的固定相：环糊精类手性固定相、多糖类手性固定相、Pirkle 型手性固定相、蛋白质类手性固定相。根据添加剂的性质可将手性流动相添加剂(CMPA)分为4类：配基交换型手性添加剂、手性离子型配合剂、环型葡聚糖添加剂以及基于其他作用的手性流动相添加剂。 1.几种经典手性固定相的手性药物拆分
Journal of Pharmaceutical and Biomedical Analysis 108(2015)97–101 Contents lists available at ScienceDirect Journal of Pharmaceutical and Biomedical Analysis j o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /j p b a Short communication Development of the MAE/UHPLC-MS-TOF method for determination of benzodiazepines in human bio-?uids for toxicological analysis Aneta Wo ′zniakiewicz,Renata Wietecha-Pos?uszny ?,Micha?Wo ′zniakiewicz, Julia Nowak,Pawe?Ko′s cielniak Laboratory for Forensic Chemistry,Department of Analytical Chemistry,Jagiellonian University,3Ingardena Street,30-060Kraków,Poland a r t i c l e i n f o Article history: Received 24October 2014 Received in revised form 3February 2015Accepted 5February 2015 Available online 16February 2015 Keywords: Benzodiazepines Human serum and blood analysis Microwave-assisted extraction Liquid chromatography Mass spectrometry a b s t r a c t A rapid method of microwave-assisted extraction (MAE)followed by ultrahigh performance liquid chro-matography with mass spectrometry with time of ?ight detection (UHPLC-MS-TOF)was optimized and validated for the purpose of determination of ?ve benzodiazepines in human serum and blood sam-ples.Extraction parameters and conditions of the UHPLC-MS-TOF method were de?ned.Validation of the developed method was performed at three concentration levels:10,100and 250ng/mL of each drug for both serum and blood samples.For serum and blood the limit of detection was found in the ranges 0.46–2.58ng/mL and 0.43–1.87ng/mL,precision (RSD):0.3–6.7%and 0.9–8.4%,accuracy of the assay (RE):?5.3to +2.4%and ?5.7to +7.6%,recovery:80.5–104.3%and 79.9–106.9%,matrix effects:95.9–110.5%and 97.5–114.2%,respectively.Moreover,the optimized and validated MAE/UHPLC-MS-TOF method was applied to analysis of blood samples. ?2015Elsevier B.V.All rights reserved. 1.Introduction Benzodiazepines (BZDs)are a large group of psychoactive drugs which demonstrate unique properties,depending on the substi-tuted groups attached to the core [1–3].Long-term use of BZDs can induce physical and mental addiction.However,despite these threats,they are the most frequently prescribed medications due to their positive properties and high treatment effectiveness [4].Therefore,it is important to develop new analytical methods for the determination of BZDs in the human body.In recent years,much attention has been directed to the application of microwave radiation to the sample preparation step [5–7].Moreover,liquid chromatography with mass spectrometry has been widely used to screen,identify and quantify BZDs or their metabolites in various materials [4,8,9]. The aim of this research was to exploit microwave-assisted extraction (MAE)in the preparation step of the serum and blood samples in order to determine ?ve BZDs:alprazolam,estazolam,lorazepam,diazepam and tetrazepam.Extracts of the studied compounds were analyzed by means of ultrahigh performance liquid chromatography (UHPLC)coupled to mass spectrometry with a time of ?ight mass analyzer (MS-TOF).The validated ?Corresponding author.Tel.:+48126632084;fax:+48126632084.E-mail address:wietecha@https://www.doczj.com/doc/3316037276.html,.pl (R.Wietecha-Pos?uszny). MAE/UHPLC-MS-TOF method was then applied to analysis of serum reference materials and forensic blood samples. 2.Material and methods 2.1.Standards,reagents and materials Drug standards:alprazolam (Alp),estazolam (Est),lorazepam (Lor),diazepam (Dia),tetrazepam (Tetr)were purchased from LGC Standards (Teddington,UK).The deutered analogues of BZDs:estazolam-d5(Est-d5),lorazepam-d4(Lor-d4)and diazepam-d5(Dia-d5)were obtained from Lipomed AG (Arlesheim,Switzerland).Drug stock solutions (10mg/mL)were prepared in methanol and stored in ?20?C.Spiking solutions were prepared daily by appro-priately diluting stock solutions with water.Standard drug solu-tions were prepared by diluting stock solutions with a mobile phase to concentrations of 75,150ng/mL and 1.88?g/mL –(correspond-ing to 10,20and 250ng/mL,respectively,within 1mL of bio?uid sample).LC–MS grade acetonitrile and methanol,ammonium for-mate,isopropyl alcohol,electrospray calibrant solution and sodium tetraborate decahydrate were purchased from Sigma–Aldrich (St.Louis,MO,USA).Analytical grade formic acid was supplied by Merck (Darmstadt,Germany).Ethyl acetate and 30%NaOH water solution,both of analytical grade,were purchased from POCH (Gli-wice,Poland).Water (18.2M cm,TOC <5ppm)was ultrapuri?ed and ?ltered through a Milli-Q Plus system (Millipore,Bedford,MA, https://www.doczj.com/doc/3316037276.html,/10.1016/j.jpba.2015.02.009 0731-7085/?2015Elsevier B.V.All rights reserved.
药物分析 题目：抗血栓药的分析研究方法 姓名：黄丹 班级：11级制药工程班 学号：14112701349
抗血栓药的分析研究方法 【摘要】心血管疾病是危害人类健康的严重疾病，而抗血栓治疗是此类疾病抢救措施及预防策略的核心。抗血栓药按作用机制主要分为抗血小板药、抗凝血药和溶栓药三类。 【关键词】心血管疾病；抗血栓治疗；抗血小板药；抗凝血药。 心血管疾病是危害人类健康的严重疾病，是造成死亡的主要原因之一。心血管疾病是指由于心脏及血管病变而引起的一系列疾病，包括心脏病、高血压、高脂血症等。抗血栓治疗一直是心血管疾病抢救措施及预防策略的核心。抗血栓药按作用机制主要分为抗血小板药、抗凝血药和溶栓药三类。前两类主要用于预防血栓形成，是抗血栓治疗的重要方法，后一类主要用于急性心肌梗死、脑梗死后，溶解已形成的血栓。 1.抗凝血药 抗凝血药是通过影响凝血过程中的某些凝血因子阻止凝血过程的药物。正常人由于有完整的血液凝固系统和抗凝及纤溶系统，所以血液在血管内既不凝固也不出血，始终自由流动完成其功能，但当机体处于高凝状态或抗凝及纤溶减弱时，则发生血栓栓塞性疾病。目前常用的抗凝血药根据化学结构主要有以下两类： 1.1肝素类 肝素是一种由D-葡糖醛酸和N-乙酰-D葡糖胺残基交替排列，并经脱乙酰和硫酸化，D-葡糖醛酸转化为L-艾杜糖醛酸等一系列修饰而成的直链粘多糖。肝素是最早使用的抗凝药，在体内外均有很强的抗凝
作用，这是通过抗凝血酶Ⅲ来实现的，可有效地防止深静脉血栓和肺栓塞的形成，临床上常用于治疗急性心肌梗死和不稳定型心绞痛。该制剂只能静脉给药，当用量过多引起出血时，可用等量鱼精蛋白中和，长期使用肝素有引起出血的危险，副作用较大。与普通肝素相比，低分子量肝素类物质具有较强的抗Xa因子活性和促纤溶作用，其抑制凝血酶及血小板的作用较弱，且不增加血管通透性，故血小板减少及出血发生率明显减少。低分子量肝素类物质血浆蛋白非特异性结合力低，其生物利用度可达98%，量效关系明确，预期浓度和疗效准确，加之其本身对APTT影响不明显．故无需药物监测。低分子量肝素类物质血浆半衰期长，达200~300分钟，为未分馏肝素类物质的2~4倍。因此用药简单，一般经皮下注射给药，每日注射1次即可。 在1993年以前，深度静脉血栓和肺栓塞的治疗几乎完全依赖于肝素（heparin）。然而时至今日，由于低分子量肝素类产品更易给药且副反应发生率低，尤其是出血风险大为降低及用药后不需密集监测，故它们已经成为用来预防和治疗深度静脉血栓的主要临床选择。 1.2香豆素类 香豆素是一类含有4-羟基香豆素基本结构的物质，口服参与体内代谢才能发挥抗凝作用，称为口服抗凝药，这是唯一在临床广泛应用的口服抗凝血药，如双香豆素、华法林(苄丙酮香豆素)和醋硝香豆素，它们的化学结构与维生素K类似，故亦称为维生素K拮抗剂，它们的药理作用相同。 华法林与维生素K竞争羧化酶，使凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ合成
微生物技术分子生物技术 中英文资料外文翻译文献 A/O法活性污泥中氨氧化菌群落的动态与分布 摘要： 我们研究了在厌氧—好氧序批式反应器（SBR）中氨氧化菌群落（AOB）和亚硝酸盐氧化菌群落（NOB）的结构活性和分布。在研究过程中，分子生物技术和微型技术被用于识别和鉴定这些微生物。污泥微粒中的氨氧化菌群落结构大体上与初始的接种污泥中的结构不同。与颗粒形成一起，由于过程条件中生物选择的压力，AOB的多样性下降了。DGGE测序表明，亚硝化菌依然存在，这是因为它们能迅速的适应固定以对抗洗涤行为。DGGE更进一步的分析揭露了较大的微粒对更多的AOB种类在反应器中的生存有好处。在SBR反应器中有很多大小不一的微粒共存，颗粒的直径影响这AOB和NOB的分布。中小微粒（直径<0.6mm）不能限制氧在所有污泥空间的传输。大颗粒（直径>0.9mm）可以使含氧量降低从而限制NOB的生长。所有这些研究提供了未来对AOB微粒系统机制可能性研究的支持。 关键词：氨氧化菌（AOB），污泥微粒，菌落发展，微粒大小，硝化菌分布，发育多样性 1.简介 在浓度足够高的条件下，氨在水环境中对水生生物有毒，并且对富营养化有贡献。因此，废水中氨的生物降解和去除是废水处理工程的基本功能。硝化反应，将氨通过硝化转化为硝酸盐，是去除氨的一个重要途径。这是分两步组成的，由氨氧化和亚硝酸盐氧化细菌完成。好氧氨氧化一般是第一步，硝化反应的限制步骤：然而，这是废水中氨去除的本质。对16S rRNA的对比分析显示，大多数活
性污泥里的氨氧化菌系统的跟?-变形菌有关联。然而，一系列的研究表明，在氨氧化菌的不同代和不同系有生理和生态区别，而且环境因素例如处理常量，溶解氧，盐度，pH，自由氨例子浓度会影响氨氧化菌的种类。因此，废水处理中氨氧化菌的生理活动和平衡对废水处理系统的设计和运行是至关重要的。由于这个原因，对氨氧化菌生态和微生物学更深一层的了解对加强处理效果是必须的。当今，有几个进阶技术在废水生物处理系统中被用作鉴别、刻画微生物种类的有价值的工具。目前，分子生物技术的应用能提供氨氧化菌群落的详细分类说明。 如今，主要由于其细胞固定策略，好氧污泥颗粒处理已经成为传统废水处理的替代工艺。颗粒有更加彻底的紧密结构和快速适应速率。因此，颗粒污泥系统比传统活性污泥法有更高的混合悬浮固体浓度浓度(MLSS)和更长的污泥龄(SRT)。更长的污泥龄能提供足够长的时间让时代时间长的微生物生长(例如氨氧化菌)。有些研究表示，硝化颗粒可以在富铵离子废水中培养出来，并且颗粒的直径很小。其他研究报告说，大直径颗粒已经在序批式反应器(SBR)中人工合成的有机废水里培育出来了。污泥颗粒里的大量不同微生物共存，并去除COD和氮磷。然而，对于直径大于0.6mm的大颗粒来说，由于氧传递被限制不能到达颗粒核心，外部好氧壳和内部厌氧地带共存。这些特性表明，大颗粒污泥内部环境不适合氨氧化菌的生长。有些研究表明，颗粒大小和密度导致了氨氧化菌、亚硝酸氧化菌和反硝化菌的分布和优势种群。虽然不少研究力求评估废水处理系统中氨氧化菌的生态生理，但是至今仍然被污泥颗粒化过程的水力学、分布、氨氧化菌群落的数量化限制着。 2.原理和方法 2.1反应器设置和操作 污泥颗粒被接种在有效体积为4L的实验室规模的SBR里。反应器有效直径和高度分别为10cm和51cm。水力停留时间设为8h。来自全尺寸污泥处理设置(中国天津污水处理厂)的活性污泥被作为反应器的种污泥，其MLSS初始浓度为3876mg/L。反应器操作6小时为一循环，由2分钟的进水时间，90分钟厌氧混合，240反正抛弃阶段和5分钟出水阶段组成。在20天80个SBR循环后，污泥沉降时间逐渐从10分钟降到5分钟，并且只有沉降速度大禹4.5m/h的颗粒才能在反应器中停留。入流中的主要化合物包括NaAc(450mg/L)，NH4Cl(100mg/L)，