关于单硝酸异山梨酯片的研制

本文从化学结构,生产工艺、药代动力学、 药效等几方面阐述了单硝酸异山梨酯片的特点。     

HPLC法测定复方单硝酸异山梨酯缓释片中单硝酸异山梨酯和阿司匹林的含量

目的　采用高效液相色谱法测定复方单硝酸异山梨酯缓释片中单硝酸异山梨酯和阿司匹林的含量。方法　色谱柱为LUNAODSC18(4 6mm× 2 5 0mm ,5 μm) ;流动相为 1%醋酸溶液 (含 0 1%三乙胺 ,pH 3 0 ) -甲醇 (5 5∶4 5 ) ;检测波长 :2 3 0nm ;流速 :1 0ml·min-1。结果　单硝酸异山梨酯进样量在 0 3 93 2～ 6 2 912 μg ;阿司匹林在 0 2 4 72～ 3 95 5 2 μg范围内与峰面积呈良好的线性关系 ,相关系数依次为 0 9999、0 9999,平均回收率依次为 99 4 %、10 0 0 % ,RSD依次为 1 1%、0 8%。结论　本法简便 ,灵敏 ,准确     

硝酸异山梨酯片假冒单硝酸异山梨酯片的检测

目的 建立硝酸异山梨酯片假冒单硝酸异山梨酯片的检测方法.方法 采用TLC、HPLC和MS分析方法.结果 所抽查样品被硝酸异山梨酯假冒.结论 所用方法专属性强、灵敏度高、操作简便,可作为药检部门监督打假的参考方法.     

复方单硝酸异山梨酯缓释片中单硝酸异山梨酯的释放度测定

目的建立高效液相色谱法,测定复方单硝酸异山梨酯缓释片中单硝酸异山梨酯的释放度。方法以pH=5．0的磷酸盐缓冲液250mL为溶剂．转速为100r／min。以高效液相色谱法测定含量,色谱柱为LunaODS C18（250mm×4．6mm,5μm）,流动相为1％醋酸溶液（加0．1％三乙胺）-甲醇（55：45）,检测波长230nm,流速1．0mL／min。结果单硝酸异山梨酯质量浓度线性范围为19．66～314．56μg／mL（r=0．9999）,平均回收率为100．27％,RSD=1．78％（n=9）;体外释放符合Higuchi方程,与国外对照样品一致。结论该方法简便、准确,可作为复方单硝酸异山梨酯缓释片的释放度测定方法。     

气相色谱法测定单硝酸异山梨酯片含量

单硝酸异山梨酯（５ＩＳＭＮ）为新一代硝酸异山梨酯类抗心绞痛药，口服吸收迅速，无肝脏首过效应，生物利用度高，有效血药浓度稳定，作用维持时间较长，１９８１年首先在西德上市，国内已批准生产，用于临床。含量测定报道有比色法［１］、气相色谱法［２］、高效液相...     

单硝酸异山梨酯的制备

单硝酸异山梨酯（IsosorbideMononitrate，商品名：异乐定）是抗心肌缺血药硝酸异山梨酯体内主要活性代谢产物[1]，是无首过代谢的长效硝酸盐，口服吸收迅速，生物利用度高，达到100％；有效血药浓度稳定，持续时间长，其半衰期间／2约在5h左右；个体差异小，无药物交互作用，可适用于冠心病的长期治疗，预防心肌梗塞后持续的症状，特别适用于冠心病心绞痛的防治。本文只就实验室合成单硝酸异山梨酯的方法进行探索，选择最佳的合成途径。1·异山梨醇（IS）直接硝化法：[2]合成路线为：这种方法的缺点是反应生成物是四种化合物的混合物，包…     

单硝酸异山梨酯片的HPLC测定

单硝酸异山梨酯（１）为新一代异山梨酯类抗心绞痛药。１９８１年首先在西德上市,国内已有片剂和缓释胶囊剂产品。其含量测定有比色法［卫生部药品标准ＷＳ－１３０（Ｘ－１１０）－９４］、气相色谱法［１］（用于片剂）和ＨＰＬＣ法［２］（用于胶囊剂）。本文采用ＨＰＬＣ外标法测定其片剂含量,与比色法相比,本法简便、快速,结果准确。１　仪器与试药ＴＳＰ高效液相色谱仪（美国理光光学仪器公司）,包括ＵＶ－６０００ＬＰ型检测器。色谱柱：ＰｈｅｎｏｍｅｎｅｘＣ１８柱（２５０×４．６０ｍｍ,５μｍ）;流动相：甲醇－水（４０…     

5─单硝酸异山梨酯治疗劳力型心绞痛

目的：比较鲁南药厂生产的５－单硝酸异山梨酯（鲁南ＩＳ－５－ＭＮ）与圣多纳药厂生产的５－单硝酸异山梨酯（圣多纳ＩＳ－５－ＭＮ）治疗劳力型心绞痛的疗效。方法：劳力型心绞痛５０例（男性３０例，女性２０例；年龄５８±ｓ６ａ）采用鲁南ＩＳ－５－ＭＮ２０～４０ｍｇ，ｐｏ，ｔｉｄ治疗。另有劳力型心绞痛２０例（男性１２例，女性８例；年龄５９±８ａ）采用圣多纳ＩＳ－５－ＭＮ２０～４０ｍｇ，ｐｏ，ｔｉｄ治疗。２组疗程均为１４ｄ。结果：临床症状与心电图改善的总有效率，鲁南ＩＳ－５－ＭＮ组依次为９８％与８０％，圣多纳ＩＳ－５－ＭＮ组依次为１００％与８５％，组间比较Ｐ值均＞０．０５。２药不良反应均轻微。结论：２个药厂生产的ＩＳ－５－ＭＮ疗效相似。     

尼索地平对单硝酸异山梨酯在大鼠体内药动学的影响

目的：考察尼索地平对单硝酸异山梨酯在大鼠体内药动学的影响。方法：将大鼠随机均分为单用（单硝酸异山梨酯5.4mg·kg-1）组和联用（单硝酸异山梨酯5.4mg·kg-1＋尼索地平5.4mg·kg-1）组,每组6只,灌胃给药。于给药前和给药后8.0h内眼球后静脉丛取血,用高效液相色谱法测定血浆中单硝酸异山梨酯的浓度,以DAS软件处理,并用非房室模型统计矩方法计算和比较药动学参数。结果：单用组与联用组单硝酸异山梨酯的药动学参数为：t1/2分别为（2.309±0.916）、（1.324±0.500）h,cmax分别为（2.292±0.700）、（2.735±0.439）mg·L-1,AUC0～8h分别为（3.339±0.663）、（4.152±0.719）mg·h·L-1,Vd分别为（0.881±0.378）、（0.462±0.202）L,均符合二室模型;其中与单用组比较,联用组t1/2、Vd明显减小（P〈0.05）,其他参数无明显变化。结论：尼索地平可加快单硝酸异山梨酯在大鼠体内的消除。     

尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响

目的考察尼索地平对单硝酸异山梨酯在小鼠体内组织分布的影响。方法 30只健康昆明种小鼠,♂,随机分成2组,分别为单独给药组和联合给药组,HPLC测定组织中单硝酸异山梨酯的浓度。结果小鼠组织中单硝酸异山梨酯浓度在给药后0.083 h为小肠>胃>心>肝>肾,给药后0.5 h为胃>小肠>肾>心>肝。胃中最大浓度出现时间因给药方案不同而异:单独给药组在给药后0.5 h单硝酸异山梨酯浓度最大,联合给药组在给药后0.083 h浓度最大。胃中单硝酸异山梨酯最大浓度,2组具有显著性差异(P<0.05)。结论尼索地平对单硝酸异山梨酯在小鼠组织中的分布具有一定影响。     

单硝酸异山梨酯胶囊溶出度比较

目的 :考察同类产品内在质量 ,为临床用药提供参考。方法 :采用HPLC法 ,按《中国药典》溶出度测定法测定单硝酸异山梨酯胶囊的溶出度。结果与结论 :10min平均累积溶出百分率产品C>D>F>A>E>B。6个厂家供试品45min时的溶出量均大于标示量的85 % ,但其溶出度参数m、T50、Td 的差别均有非常显著意义     

LC-MS法测定人血浆中单硝酸异山梨酯

目的:建立高效液相色谱-质谱法测定人血浆中单硝酸异山梨酯浓度的方法.方法:以茶碱为内标,血浆样品经乙酸乙酯提取后,用Zorbax XDB-C18分析柱(150 mm×2.1 mm,5 μm),流动相为A:0.01%冰乙酸,流速为0.15 ml·min-1;B:甲醇,流速为0.05 ml·min-1.采用四极杆质谱检测器大气压电喷雾离子源,负离子检测,检测离子:单硝酸异山梨酯为m/z 250,内标为m/z 179.结果:血浆中单硝酸异山梨酯浓度在0.0125～1.2 mg·L-1范围内线性关系良好(r=0.999 6),最低检测浓度为0.0125 mg·L-1,平均提取回收率为86.0%,日内RSD＜8.9%,日间RSD＜4.8%.结论:该法简便、快速,灵敏度高,可用于单硝酸异山梨酯制剂的药动学研究.     

兔血浆中5-单硝酸异山梨醇酯及药动学参数的毛细管气相色谱-电子捕获检测法测定

采用毛细管气相色谱－电子捕获检测法测定兔血浆中的5－单硝酸异山梨醇酯及其在兔体内的获物动力学参数。结果显示血浆药物浓度在50－1500ng/ml范围内线性关系良好，通过回收率试验确定了方法的准确度。     

Isosorbide-5-mononitrate in the treatment of acute left ventricular failure following acute myocardial infarction

Summary Eleven patients with acute left ventricular failure following acute myocardial infarction (mean pulmonary capillary wedge pressure [PCW]>20 20 mmHg) were entered into an open, haemodynamic study of oral isosorbide-5-mononitrate (ISMN). Left ventricular failure was resistant to intravenous diuretic therapy. No patient received concurrent cardioactive drugs nor further diuretic therapy during the study period. Haemodynamic data were acquired via a flow-directed thermodilution catheter placed in the pulmonary artery. Baseline data were acquired prior to the intravenous administration of an ISMN challenge. Thereafter, oral ISMN (20 mg, 8 hourly) was administered over 48 h.Following intravenous ISMN challenge, mean PCW fell from 26.2 to 17.5 mmHg. Cardiac index fell from 2.4 to 2.3 l/min/m² due to a fall in heart rate (103 to 96.8 beats/min) as stroke volume and blood pressure were unchanged. At 8 h following ISMN, two patients were withdrawn due to hypotension (systolic pressure <85 mmHg). In the remainder, PCW remained acceptable throughout 48 h (13.1 mmHg at 48 h), cardiac output, systemic blood pressure and heart rate showed no further significant change.These data suggest that ISMN is effective in the treatment of acute left ventricular failure following acute myocardial infarction.     

液质联用研究5—单硝酸异山梨醇酯缓释胶囊人体生物等效性

目的评价国产和进口5-单硝酸异山梨醇酯缓释胶囊在人体生物等效性研究.方法18名健康受试者随机交叉给药,分别单次(40mg)及多次口服进行人体生物等效性研究,用液相色谱/质谱联用测定血浆中5-单硝酸异山梨醇酯的浓度.结果经数据处理,单次口服国产和进口5-单硝酸异山梨醇酯缓释胶囊的AU0-36分别为7490±1144μg·h·L和7355±1007μg·h·L-1,tpeak分别为4.92±1,31h和4.67±0.79h,Cmax分别为519.15±60.53μg·L-1和523.67±68.99μg·L-1;多次口服达稳态时AUC0-36分别为8514±1318μg·h·L-1和8586±836μg·h·L-1,tpeak分别为4.83±0.94h和4.75±1.14h,Cmax分别为570.44±78.89μg·L-1和580.43±64.04 μ g·L-1,波动系数FI分别为135.10±15.53%和134.82±9.71%.国产5-单硝酸异山梨醇酯缓释胶囊单次给药及多次给药稳态时的相对生物利用度分别为101.9±7.3%和99.1±11.9%.结论单次及多次给药所得梯形法计算的两者的AUC0-36、Cmax、tpeak进行方差分析和双单侧检验结果表明两者具有生物等效性.     

Isosorbide-5-mononitrate and isosorbide dinitrate retard in the treatment of coronary heart disease: a multi-centre study

A multi-centre study was carried out in 200 coronary patients to compare the efficacy and tolerance of isosorbide dinitrate retard (40 mg) and isosorbide-5-mononitrate (20 mg) with regard to the frequency of anginal attacks and consumption of sub-lingual (short acting) nitrates. After receiving treatment for 2 weeks with isosorbide dinitrate retard at a dosage of 2 or 3 tablets per day, only those patients continued the study who had a weekly average of 4 or more anginal attacks during this basal period. The selected patients were divided in 4 groups of 50 patients and received treatment for a further 4 weeks with either isosorbide dinitrate retard at a dosage of 2 tablets (Group D2) or 3 tablets (D3) per day or isosorbide-5-mononitrate at a dosage of 2 tablets (Group M2) or 3 tablets (Group M3) per day. A progressive improvement in symptoms was seen at the end of 2 and 4 weeks with both drugs. The greater therapeutic benefits were obtained in patients in Group M2; the greater difference was observed between Group M2 and D2 (p less than 0.01) and there were also significant differences (p less than 0.05) between Groups M2 and D3 and between Groups M3 and D3. Analysis of the results showed that the more frequently angina attacks had occurred during the basal period, the greater was therapeutic benefit obtained with isosorbide-5-mononitrate compared to isosorbide dinitrate retard at the end of the study. Heart rate at the end of the study showed a slight tendency to increase over initial levels in all groups. In contrast, systolic blood pressure decreased very significantly in all groups (p less than 0.001). Diastolic blood pressure also decreased in all groups but only to a highly significant degree in patients treated with isosorbide-5-mononitrate (p less than 0.001) and the two sub-groups M2 and M3 (p less than 0.005). In patients treated with isosorbide dinitrate retard, the reduction in diastolic pressure was only statistically significant when the 100 patients in the group were considered as a whole (p less than 0.05), while this was not the case for the two sub-groups D2 and D3. The most frequent side-effect was headache, which improved gradually. During treatment there was a progressive dissociation between reduction in the intensity and frequency of this adverse effect and the increasing anti-anginal action of the nitrates.     

单硝酸异山梨酯缓释片的研制及其释放度和吸收分数的测定

本文报导了单硝酸异山梨酯缓释片(Ⅰ)的制备,以及辅料羟丙甲纤维素(HPMC)、聚维酮(PVP)对该片剂质量的影响;Ⅰ的体外释放属一级动力学过程,释放速率为0.0716h~(-1);6名健康志愿者单剂量(40mg)口服Ⅰ后血药浓度-时间数据经计算机程序处理,求得体内吸收分数。