高效液相色谱法同时测定六种二氢吡啶类钙拮抗剂血药浓度

This paper presents the use of an HPLC method to assay nifedipine,nitrendipine,nimoldipine,nisoldip-ine,felodipine, m-nisoldipine concentration in human plasma simultaneously。 Separation was obtained using ODS column and mobile phase of acetonitrile-water(60:40,V/V)with flow rateof 1 mL/min。They were monitored with UV detector at 238 nm,The retention times for 6 drugs mentionedabove were 5.08,7.50,8.57,10.0,11. 91 and 12. 95 min,respectively。The recoveries were all 97%。     

流动注射化学发光抑制法测定尼群地平

基于尼群地平在碱性条件下对铁氰化钾鲁米诺化学发光体系有较强的抑制作用,联用流动注射技术建立了测定尼群地平的新方法.本法的线形范围为0.1～100.0 μg/mL,检出限0.02 μg/mL ,此法用于尼群地平片剂含量测量和药典法对照结果满意.     

不同降压药物组合疗效观察及对机体代谢的影响

目的：观察小剂量双氢克尿噻、小剂量双氢克尿噻与卡托普利、尼群地平合用治疗新疆农牧区高血压病患者的有效性、安全性、依从性。方法：在新疆农牧区高血压患者中筛选出的234名患者根据血压下降分为双氢克尿噻（67例）、双氢克尿噻＋卡托普利（99例）、双氢克尿噻＋尼群地平（68例）三组,分别观察用药前后血压、心率变化及血糖、血脂、离子等生化指标的变化,随访3月。结果：三组治疗方案基线资料均无统计学差异（P〉0．05）;三组治疗后血压均明显下降,治疗效果显著（P=0．000）。三组治疗后心率均有下降（P〈0．05）。双氢克尿噻＋卡托普利组用药后甘油三酯下降（P=0．048）,低密度脂蛋白明显上升（P=0．006）。双氢克尿噻＋尼群地平组用药后总胆固醇明显下降（P=0．005）。乏组病人用药后血钠均明显降低（P〈0．05）。各组用药后血钾、血钙,总胆固醇、高密度脂蛋白、血糖无显著变化（P〉0．05）。结论：三组用药方案治疗新疆农牧区高血压病效果显著,对患者血糖、血脂、离子无明显不利影响。     

尼群地平透皮吸收的研究

利用自制Franz扩散池,测定了含不同透皮吸收促进剂的尼群地平乙醇混悬液离体鼠皮透皮作用,提出了尼群地平的可逆透皮机理,求得了透皮速率常数.实验发现,使用丙三醇、丙二醇作透皮促进剂,使尼群地平的透皮速率常数分别提高了3.73和2.62倍.     

Acrylate-based pressure sensitive adhesive in fabrication of transdermal therapeutic system

An acrylate-based pressure sensitive adhesive (PSA) was synthesized to incorporate in a design of a drug-in-adhesive (DIA) type transdermal therapeutic system (TTS) for nitrendipine and nicorandil in treatment of hypertension and angina pectoris, respectively. Solutions of 2-ethylhexyl acrylate (EHA; 85% w/w), methyl methacrylate (MMA; 10% w/w), acrylic acid (AA; 3% w/w) and vinyl acetate (VA; 2% w/w) in either ethyl acetate, acetone or methanol were polymerized under free radical conditions to synthesize the PSA. The effects of solvent, reaction time, initiator concentration and reaction temperature on polymerization were studied. The resultant copolymers were characterized by ¹H-NMR, IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and the intrinsic viscosities, refractive index, peel strength, moisture uptake and skin irritation potential were determined. The PSA was used to develop DIA type patches for delivery of nitrendipine and nicorandil. The TTS were evaluated for thickness, weight, peel strength, moisture uptake, in vitro release and in vitro skin permeation through guinea-pig skin. The copolymer found to effectively control the rate of drug release and the corresponding TTSs could be successfully employed in transdermal delivery of nitrendipine and nicorandil. Copyright © 2003 John Wiley & Sons, Ltd.     

胶束电动毛细管色谱双通道电化学检测尼群地平

创建了尼群地平的胶束电动毛细管色谱双通道电化学检测的分析新方法。采用 两台安培检测器并联构成双通道检测系统，采用单一碳糊工作电极，两台安培检测 器的检测电位分别设为+0.7V和-0.8V(vs.SCE)同，同时对尼群地平进行氧化和还原 测定，并实时对数据进行采集、处理，以图形方式显示。采用NH3－NH4Cl为背景电 解质，并加入十二烷基硫酸钠（SDS）和甲醇组成运行电泳介质，应用氧化、还原 双通道检测系统对尼群地平及其片剂进行了胶束电动毛细管色谱分离检测；对工作 电极的选择、电极电位的选择、SDS的浓度、甲醇浓度、运行缓冲溶液种类以及工 作电压和进样时间对分离检测的影响进行了研讨，取得满意结果。     

不同剂量尼群地平治疗轻型高血压病疗效观察

本文采用随机氨酰心安对照试验,观察不同剂量尼群地平4周疗法治疗轻型高血压病61例。结果表明,20mg/d组总有效率为85％。收缩压下降3.03±1.16KPα。舒张压下降1.61±0.68KPα,P均小于0.001。长期疗效(3m0)达88.2％,无明显副反应。     

Development and validation of a reversed-phase HPLC method for determination of nitrendipine in rat plasma: application to pharmacokinetic studies

A simple and sensitive method for the determination of nitrendipine in rat plasma was developed using high-performance liquid chromatography (HPLC). The procedure involves extraction of nitrendipine in dichloromethane/sodium hydroxide, followed by reversed phase HPLC using a Waters, Spherisorb ODS2 (250 x 4.6 mm, 5 microm) column and UV detection at 238 nm. The retention times of nitrendipine and internal standard (felodipine) were 5.0 min and 7.5 min, respectively. The calibration curves were linear over the range of 5 ng/mL (lower limit of quantification, LOQ) to 200 ng/mL for nitrendipine. The intra- and inter-day coefficients of variation for all criteria of validation were less than 15% over the linearity range. The sensitivity and precision of the method were within the accepted limits (< 15%) throughout the validation period. The present method was also successfully applied for the study of plasma pharmacokinetics of nitrendipine loaded solid lipid nanoparticles (SLN) in rats.     

尼群地平-β-环糊精包合物的制备与分析

尼群地平是治疗高血压的常用药物,但其难溶性限制了药物的剂型开发运用.采用研磨法、饱和水溶液法、超声波法进行制备,并通过正交实验设计确定最佳制备方法及工艺.利用显微观察、X-衍射法、紫外分光光度法来鉴定及研究包合物性质.结果表明超声波法制备的包合收率最优,其最佳包合工艺为超声功率为40 W;β-CD:尼群地平为2:1(摩尔比);超声温度为40 ℃;超声时间为70min.包合后的药物比原料药的溶解性增强了10.5倍,光稳定性增强3.7倍,其性质的改善,有助于其制剂生物利用度的提高.     

两步法合成尼群地平的工艺改进

3 -硝基苯甲醛在酸催化剂作用下 ,与乙酰乙酸乙酯用生成纯 3-硝基苄叉基乙酰乙酸乙酯。该物质再与 β -氨基巴豆酸甲酯作用 ,在苄胺类复合催化剂作用下生成高纯度的尼群地平。杂质总含量小于 0 .5 % ;其中二甲酯对称物含量小于 0 .2 %。二乙酯对称物含量小于 0 .1%。