2007年全球上市的新药

参考2008年Scrip 3338期提供的信息与相关资料，2007年全球上市新药23个，其中新化学实体（New Chemical Entities，NCEs）20个，新生物药（New Biologics）3个，包括采用生物技术研发的抗癌基因、抗溶血的单克隆抗体及补血的红细胞生成素产品（药名前加＊表示）。按疗效分类，这些新药中抗肿瘤药物7个（占30．4％），抗感染药物4个（占17．4％），神经与精神疾病用药3个（占13．0％），心血管系统与消化系统用药各2个（各占8．7％），其他药物5个（占21．8％）。具体如下：     

2005年世界上市的新药

根据2006年Scrip（3136期21页）提供的信息及2005年Pharma Projects的相关资料，2005年全世界上市新活性物质（New Active Substance，NAS）28个，其中有20个为新化学物体（New Chemical Entities，NCEs），8个是疫苗或采用生物技术研发的新药。另有玻璃酸酶（Hyaluromidase）及其注射制剂为已上市并被我国及美国药典收载。     

2010年美国FDA批准上市的新药

根据相关信息资料,2010年美国食品药品监督管理局（FDA）共批准21个新药,其中新分子实体（New Molecular Entities,NMEs）13个,复方制剂1个,生物技术类药物7个。具体见表1。     

2014年美国批准新药情况分析

目的：研究2014年美国新药批准情况,供我国药品监管及新药研发人员参考。方法：通过查询美国食品和药物管理局（FDA）官网发布的2014年批准新药数据,结合历年美国新药批准情况,对2014年美国新药批准情况进行简要分析。结果和结论： 2014年美国食品和药物药品管理局（FDA）共批准41种新分子实体药物（New Molecular Entities,NMEs）,批准新药上市申请（New drug applications,NDAs）30种、新生物制剂上市申请（Biologics license applications, BLAs）11种。新药批准数量较2013年27种有显著提升,增长50%,与近5年的平均值31.6种相比,高出30%;共受理新药上市申请41种,与往年相比,总体保持相对稳定;新药创新程度较高,17种新药获批首创一类新药;孤儿药热度依然不减,17种孤儿药获得批准;有9种新药通过创新通过突破性疗法通道获得批准;新药研发重点领域集中在抗肿瘤药、抗感染药、代谢及内分泌系统药物及神经系统药物。2014年美国制药研发企业已更加注重新药开发效率,新药研发依然体现强者恒强的局面。     

2004年世界上市的新药

参考国外的信息与相关资料,2004年全世界上市的新活性物质(New Active Substance,NAS)22个,这些新原料药中有17个为新化学物体(New Chemical Entities,NCEs),5个是采用生物技术研发的生物制品.上市最多的国家是美国(8个),其他依次为日本(3个),中国、德国、英国以及欧洲多个国家(各2个),韩国、瑞士、新西兰(各1个).按疗效分类,上市最多的是治疗肿瘤药物7个(占31.9%),消化系统药物与骨骼病用药各3个(各占13.6%),神经系统药物与皮肤病用药各2个(各占9.1%),其他药物5个(占22.7%).具体内容详见表1.     

2000年世界上市的新药（二）

2001年2月出版的Scrip Magazine在回顾2000年世界上市新药的资料中,介绍了一批对疾病有疗效的新活性物质（New Active Substances,NASs）,除本刊已介绍过的新药外（参阅本刊2001年第3期）,现将其余20个新化学实体（NCEs）与疫苗等分述如下：按疗效分类,最多的是神经与精神系统用药,共5个（25%）,其他依次为抗感染药和消化系统用药各3个（15%）,抗肿瘤药和心血管系统药物各2个（10%）,其他药物共5个（25%）。     

2006年批准上市新药一览

2006年．全球批准上市的新化合物实体（New Molecular Entity，NME）18个（见表1）和新生物药品（New Biologic）6个（见表2），共24个。其中，抗肿瘤药7个，抗感染药4个，中枢神经系统药物3个，降血糖药及其辅助治疗药2个，消化系统药物2个，遗传疾病治疗药2个，心血管药1个，呼吸系统药物1个，眼科药物1个，外用植物药1个。美国FDA已对多个新药发出可批准函．可望不久即可被正式批准上市。     

2006年全球上市的新药

参考2006年Pharma Project提供的信息与相关资料,2006年全世界上市新药35个。其中,首次上市的新化学物体(Newchemical Entities,NCEs)有21个,这些新化学原料药均被制成合适的制剂后销售,以满足人们的用药需求;其余14个除各种疫苗外,还有单克隆抗体(单抗)、重组蛋白、重组酶等采     

2007年世界上市的新药

参考国外期刊[Scrip,2008,(3338):20]提供的信息及相关资料,2007年全世界上市的新药23个,其中首次上市的新化学物体(New chemical entities, NCEs)20个,其余3个是采用生物技术研发的新活性物质(在其药名前均用*表示).     

新药及新适应症审批动态：2007年11月至2008年10月欧洲批准的新产品

2007年11月至2008年10月欧盟通过集中审批制度批准了28个新化学实体（NCE）、复方和疫苗,适应症从癌到心血管病到糖尿病和大流行流感。除了新物质外,欧盟委员会（EC）还批准了众多通用名药、4个生物相似药物和一个沙利度胺（thalidomide）的新适应症（与美法仑和泼尼松联用治疗多发性骨髓瘤）。在这12个月期间批准的通用名药包括：用于精神分裂症的奥氮平（olanzapine）;     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.