核磁共振波谱法测定安立生坦对照品的含量

摘 要 目的： 建立测定安立生坦对照品含量的方法。 方法: 采用核磁共振波谱法,使用Bruker AscendTM 400超导核磁共振谱仪,以氘代DMSO为溶剂,在脉冲宽度10.0 μs, 延迟时间5 s和扫描次数16的条件下采集试样氢谱。结果:以化学位移分别为6.16 ppm和6.28 ppm的安立生坦和顺丁烯二酸的氢质子峰作为定量峰,其峰面积比与其质量比的线性回归方程为Y=0.140 7X+0.034 8,相关系数为0.999 4,含量测定重复性试验的RSD为0.2%（n=6）。测得安立生坦对照品的绝对含量为99.9%。结论: 分析结果表明,在没有对照品的情况下,该方法可行,且具有快速、准确、简便的优点。     

Ambrisentan,a Non‐peptide Endothelin Receptor Antagonist

Increasing numbers of experimental investigations and recently also of clinical trials strongly suggest an integral involvement of the endothelin (ET)‐system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system. Ambrisentan (LU 208075), a selective ET_A‐receptor antagonist, is an orally active diphenyl propionic acid derivative. It has been shown to have a very promising efficacy to safety ratio in the initial clinical trials. Phase II and Phase III trials with ambrisentan in pulmonary arterial hypertension have been performed. The pharmacological properties and data from the experimental investigations suggest additional possible uses of ambrisentan in the prevention of reperfusion injury after organ transplantation and in restenosis following coronary artery dilatation. Furthermore, the pharmacological profile of ambrisentan indicates that this drug may also be suitable in the treatment of cerebrovascular disorders. In the present article basic investigations, animal studies and clinical trials with ambrisentan are reviewed. This review may help to define pathophysiological conditions, in which ambrisentan could be indicated and further evaluated in appropriate preclinical and clinical trials.     

Effect of ambrisentan on peripheral circulation in patients with systemic sclerosis

Systemic sclerosis (SSc) is characterized by disturbed blood circulation. The effect of ambrisentan, an endothelin-A receptor-selective antagonist, on impaired peripheral circulation in SSc remains largely elusive. Here we show SSc patients, whose clinical symptoms such as cyanosis and Raynaud's phenomenon, were ameliorated by the treatment with ambrisentan. Additionally, objective evaluations with thermography showed improvement of hand coldness in steady-state and cold challenge tests. Ambrisentan might have a potential to improve peripheral circulation in SSc.     

BMPR2 gene mutation in pulmonary arteriovenous malformation and pulmonary hypertension: A case report

The transforming growth factor-β superfamily signaling pathway is thought to be involved in the pathogenesis of pulmonary arteriovenous malformation (PAVM). However, the association between bone morphogenetic protein receptor type 2 (BMPR2) gene mutations and PAVM remains unclear. We present a case of concurrent PAVM and pulmonary arterial hypertension (PAH), with a deletion mutation in exon 6 and exon 7 of the BMPR2 gene. Drug treatment for PAH improved the patient's hemodynamics and exercise capacity, but worsened oxygenation. This case suggests that BMPR2 gene mutation may be associated with the complex presentation of PAVM combined with PAH.     

安立生坦治疗肺动脉高压42例临床观察

目的观察安立生坦治疗肺动脉高压（pulmonary arterial hypertension,PAH）临床疗效。方法 2011年4月—2013年10月在武汉亚洲心脏病医院住院的PAH 89例,将应用安立生坦治疗的42例作为治疗组,将仅采用基础治疗的47例作为对照组,于治疗前及治疗12周后测量两组6 min步行距离、超声心动图测量指标、WHO肺动脉高压心功能分级（WHO FC）以及血浆B型钠尿肽（BNP）以及血常规和生化指标的变化情况。结果治疗12周后治疗组6 min步行距离较治疗前和对照组增加,BNP和血清总胆红素水平较治疗前和对照组下降（P〈0.01）;超声心动图测量右心室舒张末内径（RVEDD）较治疗前和对照组缩小,左心室舒张末内径（LVEDD）较治疗前和对照组扩大（P〈0.01）。WHO FC心功能分级较治疗前和对照组明显好转（P〈0.01）。对照组治疗前后6 min步行距离、BNP和血清总胆红素水平、RVEDD、LVEDD、WHO FC心功能分级比较差异无统计学意义（P＞0.05）。治疗组无死亡病例,不良反应轻微,其中下肢水肿者给予利尿剂好转,其他均自行缓解。对照组死亡2例,均为猝死。结论安立生坦可显著改善PAH患者心功能及运动耐力,安全性和耐受性良好。     

内皮素受体拮抗剂治疗肺动脉高压的研究进展

近年来肺动脉高压的药物治疗多从调控内源性血管收缩因子（如内皮素-1、血栓素A2）和增殖介质（前列腺素和一氧化氮）的失衡入手。本文综述了基于内皮素-1途径的内皮素受体拮抗剂,如波生坦、安立生坦以及新近上市的macitentan,该类药物具有全身副作用小和口服优势,日益受到关注。     

顶空气相色谱法测定安立生坦原料中的残留溶剂

摘 要 目的： 建立顶空气相色谱法测定安立生坦原料中甲醇、乙醇、叔丁基甲基醚、乙酸乙酯、二氧六环、N, N- 二甲基甲酰胺等残留量的方法。方法: 采用HP 5（30 m×0.53 mm,1.5 μm）石英毛细管柱,载气为高纯氮气,FID检测器,采用程序升温和顶空进样,柱温35 ℃保持5 min,再以20 ℃·min^-1升温至110 ℃,保持5 min。结果: 6种残留溶剂的分离度符合要求,线性关系良好（r≥0.999 0）。回收率均在99.3%～105.2%范围内,3批安立生坦样品检测结果均符合限度要求。结论:该方法检测灵敏、准确, 可用于检测安立生坦原料药的残留溶剂。