苯并咪唑类质子泵抑制剂的合成研究进展

消化性溃疡病是临床上的多发病,胃酸是引起溃疡的重要因素之一,迅速有效地抑制胃酸分泌是目前治疗消化性溃疡的重要手段.质子泵抑制剂(proton pump inhibitors,PPI)是已发现的作用最强的一类胃酸抑制剂,主要用于治疗胃溃疡、十二指肠溃疡、反流性食管炎和卓-艾综合症等与胃酸分泌失调有关的疾病.这类药物较其他抑制胃酸分泌的药物具有明显的优越性,如抑酸作用强、选择性高、疗效好、治愈率高、与抗生素配伍的复方制剂可消除幽门螺杆菌等[1-4].已成为治疗胃酸有关疾病的首选药物和研究的热点.     

新一代抗溃疡药—质子泵抑制剂

介绍了奥美拉唑、兰索拉唑、潘多拉唑的合成路线，并介绍了２，３，５－三甲吡啶，２，３－二基吡啶的合成方法。     

质子泵抑制剂的合成研究

胃酸被认为是消化性溃疡的最主要致病因素之一,无论手术治疗还是药物治疗,减少胃酸分泌都是促进溃疡愈合的最常用手段。质子泵抑制剂是一类新型的抑制胃酸分泌的药物。该文叙述了质子泵抑制剂及关键中间体2-巯基苯并咪唑化合物、2-巯基咪唑并[4,5-b]吡啶化合物、2-氯甲基吡啶化合物的合成研究概况,探讨了质子泵抑制剂的较佳合成方案和结构设计思路。     

质子泵抑制剂雷贝拉唑钠的合成

以2,3 -二甲基-4-氯吡啶-N-氧化物为起始原料,经取代、酰化、水解、氯代、缩合、氧化、成盐等反应制得雷贝拉唑钠.所得产物经氢谱、质谱确证结构.此工艺路线方法简便,原料易得,便于工业化生产.     

质子泵抑制剂预防使用指引的制定及思考

目的：提高我院质子泵抑制剂用药合理性,减少用药强度及药占比。方法：制定院内质子泵抑制剂合理应用管理规范,采取处方点评,科室宣教,行政奖惩等措施。对我院质子泵抑制剂的使用情况进行分析。结果：制定规范后最初两个月,用药合理性由30.23%上升至56%,用药强度有减少,但不明显。结论：提高用药合理性并不是仅仅发布了管理规范即可,需要一系列措施以及长期持续跟进的行动,才能形成用药合理,医患满意,持续改进的良性循环。     

消化性溃疡质子泵与中医辨证联合治疗效果分析

目的探讨质子泵与中医辨证联合治疗消化性溃疡临床效果及价值。方法选取我院106例消化性溃疡患者,随机分为西医组和中西结合组,各53例,西医组采用质子泵治疗,中西结合组在西医组的基础上给予中医辨证治疗。结果中西结合组总有效率为94.34%,西医组总有效率为77.36%,2组比较有统计学差异(P<0.05),随访2年中,中西结合者复发7例,复发率为13.21%,西医组复发22例,复发率为41.51%,2组比较有统计学差异(P<0.05)。结论质子泵与中医辨证联合治疗消化性溃疡疗效确切,能够达到对症治疗、标本兼治的效果,而且复发率低,治疗临床推广使用。     

抗消化性溃疡药简析

1、市场 按相应零售价格计算国内市场销售总规模，抗消化性溃疡药（包括抗酸药）通过对全国重点城市抽样医院统计数据研究表明，2005年前三季度，进入抗消化性溃疡药销售前10位的品种中，有5个为质子泵抑制剂，在市场份额上较2003年和2004年全面上升，显示出强大的竞争优势。除奥美拉唑继续保持绝对领先优势外，泮托拉唑取代法莫替丁，占据了第2位，雷贝拉唑、艾美拉唑和兰索拉唑的市场份额进一步扩大。     

CDK抑制剂的研究进展

周期蛋白依赖性激酶是一类丝/苏氨酸激酶,是一种细胞内重要的信号转导分子。目前以细胞周期蛋白依赖性激酶为靶点的药物可以阻断细胞的周期,控制细胞的增殖,从而达到抗肿瘤的目的。文章简单的对几种与肿瘤相关的CDK抑制剂进行综述,对新的CDK抑制剂研发提供背景分析。     

天然气水合物抑制剂研究进展

介绍了天然气水合物热力学抑制剂、动力学抑制剂、防聚剂的研究现状、作用基理、种类、应用范围以及存在的缺陷;针对现有的抑制剂的不足,提出了今后研究工作的发展方向。     

磷矿浮选抑制剂研究进展

为了绿色高效地开发利用磷矿资源,综述了近年来国内外部分磷矿浮选药剂的文献资料。详细介绍了磷矿浮选中抑制剂的研究进展,并提出了今后的发展趋势。     

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.     

Proton Pump Inhibitors and Bone Health: An Update Narrative Review

Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.     

Megalin,Proton Pump Inhibitors and the Renin–Angiotensin System in Healthy and Pre-Eclamptic Placentas

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is increased in pre-eclampsia. The proton pump inhibitor (PPI) lowers sFlt-1, while angiotensin increases it. To investigate whether PPIs lower sFlt-1 by suppressing placental renin–angiotensin system (RAS) activity, we studied gene expression and protein abundance of RAS components, including megalin, a novel endocytic receptor for prorenin and renin, in placental tissue obtained from healthy pregnant women and women with early-onset pre-eclampsia. Renin, ACE, ACE2, and the angiotensin receptors were expressed at identical levels in healthy and pre-eclamptic placentas, while both the (pro)renin receptor and megalin were increased in the latter. Placental prorenin levels were upregulated in pre-eclamptic pregnancies. Angiotensinogen protein, but not mRNA, was detectable in placental tissue, implying that it originates from maternal blood. Ex vivo placental perfusion revealed a complete washout of angiotensinogen, while prorenin release remained constant. The PPI esomeprazole dose-dependently reduced megalin/(pro)renin receptor-mediated renin uptake in Brown Norway yolk sac epithelial cells and decreased sFlt-1 secretion from placental villous explants. Megalin inhibition blocked angiotensinogen uptake in epithelial cells. In conclusion, our data suggest that placental RAS activity depends on angiotensinogen taken up from the maternal systemic circulation. PPIs might interfere with placental (pro)renin-AGT uptake/transport, thereby reducing angiotensin formation as well as angiotensin-induced sFlt-1 synthesis.     

酪氨酸酶抑制剂的研究进展

介绍了酪氨酸酶的主要功能、活性中心结构及酪氨酸酶抑制荆的抑制机理,重点综述了4种酪氨酸酶抑制剂的研究进展,为新型酪氨酸酶抑制剂的开发提供了参考。     

Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver

Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.     

质子交换膜燃料电池研究进展

介绍了燃料电池的工作原理及目前世界上主要燃料电池的主要特性;综述了质子交换膜燃料电池(PEMFC)的主要基础研究进展;简单介绍了PEMFC关键部件的研究方向。     

蛋白酶体抑制剂的研究进展

随着近期美国食品和药物管理局(FDA)批准将Carfilzomib用于难治性多发性骨髓瘤患者的治疗,20 S蛋白酶体已经成为一种越来越引人关注的肿瘤治疗靶标。目前,已经开发出了一系列低纳摩尔浓度的合成和天然20 S蛋白酶体抑制剂,作为抗癌和抗炎的药物进入各期临床实验。此外,蛋白酶抑制剂继续作为有价值的研究工具,通过阐明蛋白质在泛素-蛋白酶体降解途径这一重要的生物学过程,在细胞生物学中发挥作用。