Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers

A series of amides and sulfonamides, structurally related to DM235 (sunifiram) and MN19 (sapunifiram), derived by ring expansion or contraction, or by inversion of the exocyclic amide function, have been synthesized and tested for cognition-enhancing activity in the mouse passive-avoidance test. Some of the compounds display good antiamnesic and procognitive activity, with higher potency than piracetam, and with a potency similar to the parent compounds.     

中药透皮吸收促进剂的研究进展

经皮给药系统(transdermal drug delivery system,TDDS)由于具有超越一般给药方式的独特优点,其研究已经成为第3代药物制剂开发研究的中心内容之一。然而在经皮给药的临床应用中,人们发现,药物的经皮吸收存在着各种障碍,使得药物很难达到预期的有效的治疗效果。近年来,透皮吸收促进剂(penetration enhancers,PE)的应用为经皮给药系统的研究与应用带来了契机,而天然的中药PE以其具有起效快、效果好、副作用小等优点,正日益引起人们的重视,显示出广阔的发展前景。     

多肽类药物的研究进展

多肽在包括细胞增殖分化、免疫防御、肿瘤病变等在内的生命活动过程中起着至关重要的作用。自 1953 年首个人工合成的具有生物活性的多肽问世至今,全球上市的多肽药物有 80 多个,有大量多肽药物进入临床研究。多肽类药物具有独特的优势：活性显著、特异性强、毒性较弱,在体内不易产生蓄积,与其他药物的相互作用比较少。综述了目前国内外多肽药物的发展情况,希望对从事多肽类药物研发的同行有所帮助。     

2015 年度中国医药市场发展蓝皮书——公立医院终端市场部分 （ Ⅱ ）

介绍了我国的卫生机构状况、药品市场终端规模,以及我国公立医院终端化学药和中成药各大类药品市场份额状况,并分别对我国公立医院终端化学药和中成药各大类重点品种的销售额 Top10 进行了分析。     

In vitro assessment of alkylglycosides as permeability enhancers

A series of alkylglycosides has been evaluated on human cell lines to determine its ability to open cellular tight junctions. Alkylglycosides were applied to cell monolayers; the resulting change in resistance was determined by transepithelial electrical resistance measurements. Change in resistance across cell monolayers is an indieation of tight junction activation, whereas subsequent increase in resistance signifies monolayer recovery. Of the 13 alkylglycosides tested, 4 caused irreversible solubilization of cell membranes, 5 allowed a partial recovery of the monolayer after a relatively rapid reduction in resistance, and 4 induced a decrease in resistance with more complete cell recovery. Alkylglycosides allowing extensive cell recovery after removal may indieate tight junctions activity dominance over membrane fluidity Repeated application of alkylglycosides for 6 hours lowered resistance across cells, which returned to near-normal values after a recovery period of 48 hours. A model dye was transported across the cell monolayer only in the presence of an alkylglycoside, although recovery of cells was incomplete. Activity of the alkylglycosides was unrelated to either the carbon chain length or to the carbohydrate moiety. A direct correlation was established between the concentration of applied alkylglycoside and reduction in resistance over a constant time period. Dodecylmaltoside and oetylglucoside were found to be optimal in decreasing resistance at low concentrations and allowing significant recovery of cells. Therefore these 2 alkylglycosides may be useful in facilitating drug transport across biological membranes. Published: October 19, 2001.     

New enhancers for the chemiluminescent peroxidase catalysed chemiluminescent oxidation of pyrogallol and purpurogallin

The effects of various boronate compounds, 4-biphenylboronic acid, 4-bromobenzeneboronic acid, trans-4-(3-propionic acid)phenylboronic acid and 4-iodophenylboronic acid, on the horseradish peroxidase (HRP) catalysed chemiluminescent oxidation of pyrogallol and purpurogallin by peroxide were investigated. trans-4-(3-Propionic acid)phenylboronic acid produced a 13.7-fold enhancement in the peak light emission from the chemiluminescent HRP catalysed pyrogallol reaction (detection limit for HRP < 1.25 fmol). At low enhancer concentration a single peak of light emission was observed and as the enhancer concentration increased the time to peak light emission became progressively longer. The chemiluminescence showed two peaks at higher concentrations (> 54.3 μmol/L) and the individual peak times depended upon the concentration of the enhancer. All of the boronates enhanced peak light emission in the chemiluminescent HRP catalysed purpurogallin reaction. 4-Biphenylboronic acid was the most effective and it enhanced peak light emission 314-fold. The practical detection limit for HRP (Type VIA) using this enhancer was 4.18 pmol (peak emission at 20 minutes). This compound also enhanced peak light emission 232-fold from a chemiluminescent HRP-purpurogallin reaction in which molecular oxygen replaced peroxide as the oxidant.     

2015年度中国医药市场发展蓝皮书——产业经济部分 （ Ⅰ ）

从产业经济角度,包括医药工业总产值、医药工业销售收入、医药工业盈利水平、医药流通行业销售规模、医药商业效益水平、     

我国儿童药物发展环境与市场分析

我国儿童药物处于市场需求大、竞争小、政策利好的环境中,面临着前所未有的发展机遇。分析了我国儿童药物的发展环境和市场现状,并对儿童药物的市场开发策略给予了建议。     

Monoclonal antimyogenin antibodies define epitopes outside the bHLH domain where binding interferes with protein-protein and protein-DNA interactions

We have developed a panel of monoclonal antibodies against rat myogenin, a skeletal muscle regulatory protein of the bHLH family. Some of these monoclonals have been widely used by others, and details of their production are presented. Mapping the epitopes by immunoprecipitation of myogenin deletion mutants demonstrates that this panel recognizes epitopes spanning the entire molecule outside the HLH region. Four antibodies against epitopes outside the bHLH region interfere with the binding of myogenin/E-protein heterodimers to DNA sequences containing the myogenin heterodimer consensus recognition site. Three of these epitopes are partially masked in the heterodimers; antibody binding to these epitopes reduces the interactions between myogenin and E12. This suggests that surfaces outside the HLH dimerization domain may contribute to the stability of myogenin/E12 complexes. The binding of one antibody to its epitope did not appear to affect the myogenin/E12 interaction but nonetheless interfered with the binding of the complex to DNA, suggesting that this epitope lies near to a surface occupied by DNA. © 1996 Wiley-Liss, Inc.     

2015年值得关注的药物预测

回顾2014年值得关注的3种药物（Sovaldi、Anoro Ellipta和Zydelig）的上市和销售情况。重点介绍2015年值得关注药物的适应证、上市申请、临床开发情况以及市场前景展望等