Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

5-单硝异山梨酯缓释剂治疗老年单纯收缩期高血压疗效观察

目的 观察5-单硝异山梨酯缓释剂（ISMN）对老年单纯收缩期高血压（ISH）患者降压治疗的疗效。方法 80例ISH患者随机分为对照组39例和治疗组41例，对照组给予氨氯地平5mg，吲达帕安2．5mg每日1次口服，治疗组在上述治疗的基础上给予5-单硝异山梨酯缓释剂40mg每日1次口服，疗程4周。结果 （1）治疗组从第一周开始收缩压（SBP）下降幅度即大于对照组，先于对照组于第二周降至正常，差异有显著性（P〈0．05）；（2）从第一周开始治疗组舒张压（DBP）下降幅度即小于对照组（P〈0．05），第三周开始差距加大，差异有非常显著性（P〈0．01），整个观察期内治疗组DBP下降幅度始终小于对照组，且从第二周开始处于相对稳定状态；（3）第一周开始治疗组脉压（PP）下降幅度即大于对照组（P〈0．05），第二周开始差距进一步加大，差异有非常显著性（P〈0．01）。结论 硝酸酯类药物能降低ISH患者的SBP,而对DBP影响不大，使PP减小，对ISH患者降压治疗有益。     

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 μg/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414±25 vs 290±26 dyn.s/cm⁵ per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98±6 vs 79±7 mmHg), systemic vascular resistance (318±30 vs 207±10 dyn.s/cm⁵ per 100 g), portal pressure (14.0±1.0 vs 11.3±0.9 mmHg) and portal territory vascular resistance (1362±163 vs 1031±182 dyn.s/cm⁵ per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.     

Blood volume and right heart haemodynamics in abrupt hypotension following sublingual isosorbide dinitrate in acute myocardial infarction

Arterial blood pressure and heart rate were measured in 43 patientswith acute myocardial infarction and a systolic blood pressure120 mmHg during sublingual administration of 5 mg of isosorbidedinitrate. In 25 of them right heart haemodynamics were alsomeasured. Severe (25%) hypotension developed in 12 patients(Group 1, systolic blood pressure 158 ± 28 to 78 ±17 mmHg, mean ± SD) but not in the remaining 31 (Group2) and was accompanied by a fall in heart rate (82 ±20 to 70 ± 22beats min^-1, P<0.05), in cardiac output(4.3 ± 0.3 to 3.2 ± 0.4l mm^-1, P<0.02, n =5) and in systemic vascular resistances (2326 ± 463 to1532 ± 442 dynes sec^-1 cm^-5, P<0.02) not present inGroup 2. The reduction in right (Group 1,8 ± 3 to 3 ±1, vs. Group 2,10 ± 3 to 6± 3 mmHg, V <0.005)and in left ventricular filling pressures (Group 1,15 ±4 to 8 ± 2, vs. Group 2,18 ± 6 to 13 ±5 mmHg, P<0.001) was more remarkable in Group 1. In thisgroup there was also a high incidence of anterior infarction(9/12, 75%). Blood volume measured in 30 patients was lowerin Group 1 but differences were not significant. A second doseof 5 mg of isosorbide dinitrate 36–48 h later producedneither symptomatic hypotension (Group 1, 147 ± 29 to129 ± 24 mmHg) nor a fall in cardiac output in any patient,whereas changes infilling pressures were comparable to thoseof the first dose. Thus, severe isosorbide dinitrate-induced hypotension in myocardialinfarction is limited to the acute phase and seems more prevalentin anterior infarction but can not be clearly predicted fromresting haemodynamic or blood volume measurements, at leastin non-hypotensive patients. Moreover, it appears to be causedby an excessive ventricular emptying due to a striking venousand arterial vasodilation, probably during a stage of a particularlydepressed ventricular compliance.     

复方单硝酸异山梨醇酯缓释片人体生物等效性研究

目的 :评价试验制剂复方单硝酸异山梨醇酯缓释片 (T)与参比制剂单硝酸异山梨醇酯缓释片和阿司匹林肠溶片 (R)的生物等效性 ,以及缓释制剂释放特点、稳态血浓度和波动度。方法 :采用高效液相色谱法分别测定单剂和多剂交叉给药单硝酸异山梨醇酯和阿司匹林代谢物水杨酸经时血浓度 ,计算药物动力学参数 ,并进行方差分析和双单侧t检验。结果 :单剂给药试验制剂和参比制剂单硝酸异山梨醇酯半衰期 (t1 2 )分别为 8.3± 0 .6、8.2± 0 .6h ,血浓度峰值 (Cmax)分别为 0 .5 1± 0 .0 9、 0 .5 3±0 .0 9mg·L-1,达峰时间 (tmax)分别为 4 .8± 0 .4、4 .6± 0 .3h ,药时曲线下面积 (AUC0 -t)分别为 4 .90±0 .6 1、5 .2± 0 .8mg·h-1·L-1,相对生物利用度 (F)为(96 .1± 10 .8) % ;试验制剂和参比制剂阿司匹林代谢物水杨酸t1 2 分别为 2 .4± 0 .3、2 .5± 0 .3h ,Cmax分别为 3.4± 0 .5、3.0± 0 .4mg·L-1,tmax分别为 1.7±0 .2h和 4 .9± 0 .3h ,AUC0 -t分别为 13.4± 2 .5和13.0± 2 .5mg·h-1·L-1,以水杨酸计阿司匹林F为(10 3.6± 9.6 ) %。多剂给药试验制剂和参比制剂单硝酸异山梨醇酯Cmax 分别为 0 .6 8± 0 .14、0 .6 7±0 .13mg·L-1,Cmin 分别为 0 .17± 0 .0 3、 0 .17±0 .0 4mg·L-1,波动系数 (DF)     

HPLC用于复方单硝酸异山梨酯-阿司匹林缓释片的质量分析

 目的建立用HPLC分析复方单硝酸异山梨酯-阿司匹林缓释片质量的方法。方法用高效液相色谱法检测复方单硝酸异山梨酯缓释片中药物的含量和释放度。色谱条件为：Hypersil C₁₈柱；甲醇-水(30∶70)加1‰磷酸调节pH值至3.0为流动相；流速为1 mL·min^-1；UV检测波长为235 nm。以乙腈为溶剂配制对照品溶液及样品溶液。结果复方中两种成分及阿司匹林水解产物水杨酸在20 min内达到良好分离。单硝酸异山梨酯、阿司匹林的线性范围分别为16.0～112.0 μg·mL^-1(r=0.999 9)，20.0～140.0 μg·mL^-1(r=0.999 9)。平均回收率分别为100.4%(RSD=0.66%)和100.7%(RSD=0.69%)。结论本法简便、快速，结果准确，可用于同类药品的质量标准研究和质量检验。     

星点设计-效应面法优化单硝酸异山梨酯微孔渗透泵片处方

目的:应用星点设计-效应面法优化单硝酸异山梨酯微孔渗透泵片处方.方法:以渗透压活性物质用量、致孔剂用量、包衣增重量为影响片剂释放的主要因素,2、4、7、9、12 h的药物累积释药量为效应值,应用Design Expert进行处方优化,并对优化处方进行验证.结果:成功找到了最优释药区域;优化处方呈零级释放特性.结论:通过星点设计-效应面法成功建立了处方优化模型,实现了单硝酸异山梨酯微孔渗透泵片的处方筛选.     

单硝酸异山梨酯、缬沙坦、螺内酯复方对大鼠的长期毒性研究

目的 观察SD大鼠连续6个月口服单硝酸异山梨酯、缬沙坦、螺内酯复方所产生的毒性反应,比较3种药物联合应用后,毒性是否增加或产生新的毒性。方法 健康SD大鼠200只,雌雄各半,分为5组：空白对照组、复方73、244、733 mg·kg-1及缬沙坦600mg·kg-1对照组,每组40只。给药体积为10mL·kg-1,每日ig给药1次,每周给药6d,连续给药6个月,停药观察4周。实验期间,每日进行一般状态观察,每周测定1次体质量及摄食量,于给药3、6个月及停药4周后,各组动物分别进行血压、血液学、血液生化学指标检测,动物剖检并进行病理组织学检查。结果 复方73、244、733 mg·kg-1及缬沙坦600 mg·kg-1对照组血压出现明显降低,为复方药物药理作用结果。244、733 mg·kg-1及缬沙坦600 mg·kg-1对照组RBC、HCT、HGB及Ret均出现明显降低,肾功能指标CREA、UREA及电解质K＋明显升高,组织病理学检查肾脏出现明显病理学改变,当停药恢复期结束后,上述各指标恢复正常。结论 本试验条件下,单硝酸异山梨酯、缬沙坦、螺内酯复方口服6个月无不良反应剂量（NOAEL）为73 mg·kg-1,当大鼠6个月给药剂量达到244 mg·kg-1时,血液学、血钾及肾功出现明显毒性反应,停药后可恢复正常。复方中3种药物联合应用,同缬沙坦单独使用相比未见毒性增加或产生新的毒性。     

联用心通口服液与硝酸异山梨醇酯治疗冠状动脉粥样硬化性心脏病心绞痛疗效观察

目的：探讨联用中药心通口服液与西药硝酸异山梨醇酯治疗冠状动脉粥样硬化性心脏病（冠心病）心绞痛的疗效。方法：将６８ 例冠心病心绞痛患者随机分为２ 组。治疗组（３６ 例）用中药心通口服液与西药硝酸异山梨醇酯治疗,对照组（３２ 例）单用硝酸异山梨醇酯治疗;药物剂量：心通口服液１０ ｍ ｌ,硝酸异山梨醇酯１０ ｍ ｇ,均为每日３ 次口服,３ 周为１ 个疗程。结果：治疗组及对照组临床症状改善总有效率分别为８８９％ 及６１８％ ,有显著性差异（ Ｐ＜ ００５）;心电图改善总有效率分别为８０６％ 及５３１％ ,亦有显著性差异（ Ｐ＜ ００５）。结论：心通口服液与硝酸异山梨醇酯合用治疗冠心病心绞痛对心绞痛症状及心电图的心肌缺血改善均优于单用硝酸异山梨醇酯。     

益气活血通脉汤联合单硝酸异山梨酯、阿司匹林治疗陈旧性心肌梗死临床评价

目的 探讨益气活血通脉汤联合单硝酸异山梨酯、阿司匹林治疗陈旧性心肌梗死的临床疗效,以及对患者N末端脑利钠肽原(NT-proBNP)、肌酸激酶-同工酶(CK-MB)、乳酸脱氢酶(LDH)水平的影响.方法 选取医院2018年1月至2020年1月收治的陈旧性心肌梗死患者84例,按随机数字表法分为观察组和对照组,各42例.两组...