Preload or afterload reduction: Which is more beneficial for patients with ischemic heart disease?

Summary We studied the acute hemodynamic effects of molsidomine, a selective preload reducing agent, and nifedipine, a selective afterload reducing agent. Thirty-two patients with stable angina pectoris and angiographically significant coronary artery disease were randomized into two groups: group A patients received 4 mg of molsidomine, and group B patients received 20 mg of nifedipine orally. Molsidomine was associated with a significant reduction of the left ventricular end-diastolic pressure and an increase in Vcf. Nifedipine caused a significant reduction of the mean arterial pressure and an increase of the heart rate. Hemodynamic parameters associated with chronic exertional angina pectoris in patients with angiographically significant coronary artery disease improved more with a preload reducing agent, like molsidomine.     

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目的评价牙周基础治疗及维护期治疗对使用硝苯地平导致牙龈增生的治疗效果。方法选择2010年9月至2011年12月在佳木斯大学附属口腔医院牙周黏膜病科就诊的因高血压服用硝苯地平导致牙龈增生20例,随机分为试验组（10例）和对照组（10例）,在均不更换药或未停药的情况下,试验组进行牙周基础治疗和维护期治疗,而对照组仅进行牙周基础治疗。在治疗前和治疗后1、12个月时记录各组患者牙龈增生指数（GHI）、茵斑指数（PLI）、龈沟出血指数（SBI）和探诊深度（PD）。结果试验组在观察期间,各项指标（GHI、PLI、SBI、PD）持续改善（P〈0．01）,牙龈炎症减轻,牙龈增生状况明显改善且未复发;对照组在基础治疗后1个月牙龈各项指标改善（P〈0．01）,但12个月后复诊时牙龈出血等复发,且各指标与治疗前比较差异无统计学意义（P〉0．05）。结论牙周基础治疗可改善硝苯地平引起的牙龈增生,定期维护治疗对于预防硝苯地平导致的牙龈增生复发疗效明显。     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

红酒多酚对细胞色素P4503A4介导的硝苯地平代谢的影响

目的体外研究红酒多酚成分对细胞色素P4503A4(CYP3A4)介导的硝苯地平代谢的影响。方法将红酒多酚、人肝微粒体及探针底物睾酮孵育后,用高效液相色谱法测定代谢产物6β-羟基睾酮的生成量,用来考察红酒多酚对CYP3A4抑制的浓度依赖性。将不同浓度红酒多酚、人肝微粒体与硝苯地平孵育,测定硝苯地平的减少率并计算IC₅₀值。在不同浓度硝苯地平存在下,绘制米氏曲线,得到红酒多酚存在时硝苯地平的代谢清除率CL_红酒(K_m-红酒/V_max-红酒),对比空白组,考察红酒多酚对硝苯地平代谢的影响。结果红酒多酚对CYP3A4存在明显的浓度依赖抑制效应(IC₅₀=18.29%)。在以硝苯地平为底物时,IC₅₀为25.04%。红酒多酚对硝苯地平的代谢清除率CL_红酒为14μL·min^-1·mg^-1,显著低于空白组(640μL·min^-1·mg^-1)。结论红酒多酚可通过抑制CYP3A4的活性,减少其对硝苯地平的代谢,具有诱导食物-药物不良反应的风险。     

心脑宁片对大鼠心肌缺血模型ATP酶、LDH及CK活性的影响

目的 研究心脑宁片对大鼠心肌缺血模型ATP酶、LDH及CK活性的影响。方法 选取体质量为230~250 g大鼠70只,♀♂各半,分为7组,其中第1组为空白对照组,其余6组造心肌缺血模型。6组造模大鼠分别灌服高、中、低剂量的心脑宁片混悬液、硝苯地平混悬液、脑心通胶囊混悬液和同体积的0.5%羧甲基纤维素钠。观察心电组织中ATP酶活力,检测血清中LDH、CK活性,并测定心电图变化。结果 与模型组比较,高、中、低剂量心脑宁片组、脑心通胶囊组和硝苯地平片组均可升高心肌组织匀浆中Na⁺-K⁺-ATPase活力(P<0.01);中、低剂量心脑宁片组可升高心肌组织匀浆中Mg²⁺-ATPase活力(P<0.01或P<0.05);低剂量心脑宁片组可升高心肌组织匀浆中Ca²⁺-ATPase活力(P<0.01)。与模型组比较,高、中、低剂量心脑宁片组、脑心通胶囊组和硝苯地平片组均可不同程度地降低血清中LDH活力(P<0.01);高、中、低剂量心脑宁片组、脑心通胶囊组和硝苯地平片组均可降低血清中CK活力(P<0.01或P<0.05),高、中、低剂量心脑宁片组可显著减少心电图ST段的升高。结论 心脑宁片组能有效升高ATP酶活力,降低LDH、CK活力,减少心电图ST段的升高。     

硝苯地平膜控型控释微丸的制备及体外评价

目的研究硝苯地平(NF)膜控型24 h控释微丸的处方与工艺,并考察其体外释放特性。方法采用液相层积、丸芯上药法制备载药速释微丸,以Eudragit RL100、RS100为包衣材料,流化床悬浮包衣法制备膜控型控释微丸,并对影响微丸释放的处方因素进行了考察。通过与市售渗透泵片拜新同的体外释放度的对比研究,探讨硝苯地平膜控型控释微丸的体外释药特征。结果调整Eudragit RL100、RS100的比例、衣层厚度、致孔剂的用量,可以改变药物的释放速率。当Eudragit RL100、RS100的比例为3∶7,包衣增重为6%时,制备的控释微丸体外释药与市售渗透泵片相似(f2=62.8),具有良好的零级释放特性。结论以丸芯上药法,Eudragit RL100、RS100为控释材料制备的NF膜控型控释微丸,具有良好的零级释放特性,结果可为硝苯地平多单元控释制剂的研究开发提供参考。     

International nifedipine trial on antiatherosclerotic therapy (intact)

Summary A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system.This report presents the design of this still-ongoing study as well as inclusion and exclusion criteria. The quantitative evaluation of the coronary angiograms and the mode of compliance test are described in detail. A number of baseline data as well as the preliminary results of the quantitative evaluation of the first coronary angiograms are presented.Beside the results on the effect of the calcium-antagonist nifedipine on the progression of CAD, INTACT might also supply information on the antiatherosclerotic potency of other drugs administered additionally (beta-blockers and nitrates) and of HDL-cholesterol.