血管紧张素转换酶抑制剂对血清钾水平的影响

[目的]观察肾功能不全的病人应用血管紧张素转换酶抑制剂(ACEI)时血清钾的水平。[方法]将病人分成肾功能正常组和肾功能不全组,二组病人都口服依那普利5mg/d。有11例因水肿同时口服安体舒通40~60mg/d。在口服前和口服后1.5个月分别作血清钾测定。在肾功能不全组的病人出现血清钾升高后改服氨氯地平5mg/d。[结果]在口服依那普利5mg/d后,肾功能不全组的血清钾水平高于肾功能正常组,改服氨氯地平5mg/d后血清钾恢复正常。Logistic回归分析显示,同时口服安体舒通和肌酐水平是引起血清钾升高的危险因素。[结论]肾功能不全组病人在口服依那普利5mg/d后血清钾高于肾功能正常组。在服用ACEI时必须监测血清钾浓度。     

Separation and determination of nimesulide related substances for quality control purposes by micellar electrokinetic chromatography

A micellar electrokinetic chromatography (MEKC) method has been developed and validated for the determination of nimesulide related compounds in pharmaceutical formulations. Electrophoretic separation of six European Pharmacopoeia (EP) impurities (A–F) was performed using a fused silica capillary (L_eff. = 50 cm, L_tot. = 57 cm, 50 μm i.d.) with a background electrolyte (BGE) containing 25 mM borate buffer (pH 9.5), 30 mM sodium dodecyl sulphate and φ = 3% (v/v) acetonitrile. The influence of several factors (surfactant and buffer concentration, pH, organic modifier, applied voltage, capillary temperature and injection time) was studied. The method was suitably validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. The calibration curves obtained for the six compounds were linear over the range 5–12 μg ml⁻¹ (0.05–0.12%). The relative standard deviations (s_r) of intra- and inter-day experiments were less than 5.0%. The detection limits ranged between 0.7 and 1.6 μg ml⁻¹ depending on the impurity. The proposed method was applied successfully to the quantification of nimesulide impurities in its pharmaceutical formulation.     

依那普利联合硝苯地平控释片治疗原发性高血压疗效观察

目的探讨依那普利联合硝苯地平控释片治疗原发性高血压的疗效。方法将106例原发性高血压患者随机分为治疗组和对照组各53例。治疗组予依那普利胶囊5mg口服,每天2次;硝苯地平10mg口服,每天3次。对照组单用依那普利,用法同治疗组。2组均连续服用21d为1个疗程。观察2组临床疗效和血压变化情况。结果治疗组总有效率为94.3%高于对照组的83.0%,差异有统计学意义(P<0.05)。2组治疗后收缩压和舒张压均低于治疗前,差异均有统计学意义(P<0.05);治疗组治疗后血压低于对照组,差异有统计学意义(P<0.05)。结论依那普利联合硝苯地平控释片治疗原发性高血压具有良好的协同作用,可有效控制患者血压水平。     

醋柳黄酮治疗中、重度高血压的随机对照研究

目的　探讨醋柳黄酮治疗中、重度高血压的疗效、特点和不良反应。方法　采用同期随机对照的方法。 78例合格的中、重度高血压病患者 (BP≥ 16 0 / 10 0mmHg)随机分为醋柳黄酮治疗组和依那普利对照组 (各 39例 ) ,治疗 6周 ,观察血压变化及其规律。结果　醋柳黄酮治疗 6周后血压下降 18.1± 8.2 / 12 .4± 10 .1mmHg ,与依那普利的降压水平相似。但醋柳黄酮对中、重度高血压病患者的降压速度稍慢 ,2～ 4周后与依那普利的降压水平基本一致。不良反应总发生率低 ,主要为头昏头晕 ,短期内可自行改善。结论　醋柳黄酮能降低中、重度高血压病的血压水平 ,安全性好。     

依那普利联合吲达帕胺治疗糖尿病合并高血压的临床分析

目的 观察依那普利与吲达帕胺联合治疗老年2型糖尿病合并高血压的临床疗效.方法 将99例确诊糖尿病合并高血压的患者随机分为治疗组和对照组,治疗组（50例）用依那普利加吲达帕胺治疗,对照组（49例）单用依那普利治疗.治疗12周比较治疗前后的降压效果、血浆内皮素-1及血清钾、降糖疗效.结果 治疗组的降压效果（82.0%）和降低血浆内皮素-1[（75.42±12.16）pg/ml]方面要优于对照组[65.3%,（99.09±13.31）pg/ml],但两组在血清钾和降糖方面无显著性差异（P＞0.05）.结论 依那普利与吲达帕胺联用可作为治疗糖尿病合并高血压的一种较好的治疗方案.     

采用定时释药技术制备复方中药舒胸缓释制剂的研究

目的：采用定时释药技术制备复方中药舒胸缓释制剂。方法：以崩解时间、加水后片剂体积膨胀率为指标，筛选片芯处方。采用压制包衣技术，选用聚乙二醇6000、氢化蓖麻油和乙烯-醋酸乙烯共聚物作为包衣材料制备定时控释片并考察处方、工艺、体外溶出条件对药物释放的影响。结果：经过筛选确定片芯处方为原药30％、微晶纤维素50%、羧甲基淀粉钠20%。外包衣层中聚乙二醇6000含量、包衣层用量、片剂硬度对定时控释片的释药时滞具有显著影响，溶出介质黏度和转蓝转速对时滞影响不大，但对时滞期后的释药速率有较大影响。结论：以优化处方压制的片芯，具有较好的膨胀性和崩解能力。通过调整外包衣层处方可获得不同时滞的定时控释片。由片芯、时滞为3 h和6 h的定时控释片组合而成的舒胸缓释制剂在体外可于0，3，6 h依次释药，理化性质不同的各成分在不同时间达到了同步释放。     

Enalapril对实验性糖尿病大鼠肾脏的保护作用机理研究

目的　研究血管紧张素转换酶抑制剂 Enalapril对糖尿病的肾病治疗作用机理。方法　以Enalapril治疗实验性糖尿病大鼠 ,并将正常组、糖尿病对照组及治疗组尿蛋白水平及肾组织转化生长因子 β、糖基化终末产物含量进行比较。结果　 Enalapril治疗组大鼠肾组织转化生长因子 β及糖基化终末产物含量与糖尿病对照组相比无下降。结论　 Enalapril的肾脏保护作用并非通过抑制肾组织转化生长因子 β上调或糖基化终末产物积聚     

卡维地洛与依那普利配伍治疗慢性充血性心力衰竭38例观察

目的 :观察卡维地洛与依那普利治疗慢性充血性心力衰竭 ( CHF)的疗效和安全性。方法 :将 76例缺血性 ( 82 % )或非缺血性 ( 1 8% )心脏病并发轻、中度心力衰竭的患者随机分为两组 ,治疗组 38例应用卡维地洛配伍依那普利 ,对照组 ( 38例 )单用依那普利。在心力衰竭标准用药的基础上 ,卡维地洛、依那普利均由小剂量开始 ,逐渐递增至目标剂量。在1 2个月内检查超声心动图 3次 ,以评价左室功能和容积。结果 :治疗后两组的左室射血分数( L VEF)均有增加 ,左室收缩末期容积 ( L VESV)和左室舒张末期容积 ( LVEDV)均有减少 ,但卡维地洛联合依那普利组与单用依那普利组比较 ,有显著性差异 ( P<0 .0 5 )。卡维地洛联合依那普利组有 2 7例 ( 71 % )耐受目标剂量 ,其常见不良反应为头晕、咳嗽 ,但不良反应与单用依那普利组比较 ,无显著性差异 ( P>0 .0 5 )。两组均未发现肝肾功能损害或电解质、糖代谢变化。结论 :卡维地洛配伍依那普利在心力衰竭标准用药基础上治疗轻中度 CHF患者安全、有效 ,可显著改善左室重塑。     

氯沙坦钾和依那普利联合治疗Ⅳ期糖尿病肾病的临床观察

目的观察氯沙坦钾和依那普利联合治疗Ⅳ期糖尿病肾病（DN）的疗效。方法将74例Ⅳ期DN患者随机分为三组，氯沙坦钾组：151服氯沙坦钾100mg，1次／d；依那普利组；151服依那普利10mg，1次／d；联合治疗组：同时服用以上两种药物，且剂量不变。三组患者治疗均在3年以上。监测治疗前后24h尿蛋白定量及血清肌酐。结果三组患者24h尿蛋白定量较治疗前均下降，差异有统计学意义（P〈0．05），联合治疗组效果更好（P〈0．01）。血清肌酐仅联合治疗组下降，差异有统计学意义（P〈0．05）。结论联合应用氯沙坦钾和依那普利可以有效控制Ⅳ期DN患者蛋白尿，延缓肾脏病进展。     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.