复方尼群地平片的溶出度考察

目的　建立复方尼群地平片剂中尼群地平的溶出度测定方法。方法　 30 %乙醇的 0 .1mol·L-1盐酸溶液 2 5 0ml为溶剂 ,转速 75r/min ,4 5min取样 ,紫外分光光度法于波长 35 6nm处 ,测其吸收度计算容出量。结果　在 12～ 2 8μg·ml-1范围内 ,吸收度与浓度呈良好线性关系 ,A =0 .0 1915 C- 0 .0 2 2 8,r=0 .9999,平均回收率 10 0 .5 % ,RSD为 0 .77% ,3批样品溶出均一性试验结果满意 ,4 5min溶出度均 70 %以上。结论　本法操作简便 ,试剂用量少 ,结果正确。     

模式识别法评价尼群地平片的质量

用模糊聚类分析和模式识别方法，对两年多来全国抽验的《中国药典》品种“尼群地平片”的质量进行进一步评价。     

血浆中尼莫地平的反相高效液相色谱测定法

为准确测定血浆中尼莫地平浓度，本文建立了离子抑制性反相高效液相色谱法。血浆样品碱后以乙醚－氯仿混合溶剂提取，提取液挥干，甲醇溶解后进样分析。采用μ－Ｂｏｕｄａｐａｋ Ｃ１８径向加压柱系统，甲醇－磷酸盐缓冲液为流动相，紫外检测波长２３６ｎｍ。选择尼群地平为内标峰面积定量。     

Novel halogenated dihydropyridine derivatives with high vascular selectivity

Summary Calcium channel antagonists of the dihydropyridine type exhibit preferential vasodilator properties. To study whether this vascular selectivity is due to distinct steric modifications or may be influenced by the physicochemical nature of these drugs, contractility in guinea pig heart isolated papillary muscles, vasodilator properties in isolated rabbit femoral arteries and the lipophilicity of some novel halogenated dihydropyridines have been examined. All newly synthesized derivatives exhibited dose-dependent negative inotropic and vasodilator effects. The negative inotropic potency of all the halogenated derivatives was weaker than that of the parent compound nitrendipine. In contrast, compared to nitrendipine the vasodilator potency of the ester substituted derivatives was slightly increased, while halogen substitution in position 2 and 6 of the dihydropyridine nucleus decreased the vasodilator potency. As a result of the different influence on cardiac and vascular smooth muscle an improved vascular selectivity of the drugs was attained. The ester-substituted dihydropyridine derivatives showed a 9 times (3-bromoethyl-nitrendipine) or 11 times (3-chloroethyl-nitrendipine) higher vascular selectivity with respect to nitrendipine. Correlation of the lipophilicity with the physiological properties showed an increase in biological activity with decreasing lipophilicity. Within the ester-halogenated dihydropyridine derivatives an inverse trend was observed (increasing vasodilation with increasing lipophilicity), indicating a different influence of lipophilicity with the ester-substituted compounds on the different tissues examined. The improved vascular selectivity of the novel halogenated dihydropyridines may be at least in part a consequence of the different lipophilicity of the drugs. In addition, differences in the binding affinities of the dihydropyridines subordinate to distinct voltage dependent conformation states of the calcium channel may contribute.Send offprint requests to U. Fricke     

尼群地平片剂生物利用度的研究

为提高国产尼群地平片剂的生物利用度,采用球磨混合粉碎法工艺进行处方设计,试制出新处方片剂,与西德Bayer公司片剂进行了体外溶出、体内生物利用度的比较。体内血浆药浓用GC-MS法测定,体内数据按零级溶出、一级吸收口服单室模型,经计算机用Gauss-Newton-Damping法处理求得药动学参数。本文研制的尼群地平新处方片剂生物利用度已超过西德Bayer公司片剂。     

尼群地平对糖尿病大鼠心肌钙分布和肌膜通透性的影响

观察钙拮抗剂尼群地平对链脲佐菌素引起的糖尿病大鼠心肌钙分布、肌膜通透性和心肌舒缩功能的影响。结果提示尼群地平对糖尿病心肌有一定保护作用。     

Comparison of casual,ambulatory and self-measured blood pressure in a study of nitrendipine vs bisoprolol

Summary In a double-blind, placebo-controlled study the antihypertensive efficacy and tolerability of a single morning dose of either 10 mg bisoprolol (n=26) or 20 mg nitrendipine (n=27) were investigated. Blood pressure was measured by three techniques: (1) Casual blood pressure 24 h after the dose; (2) ambulatory 24-h whole-day monitoring; and (3) self-recorded blood pressure in the morning 24 h after the dose (6–8 a.m.) and in the evening (6–8 p.m.). After 4 weeks of therapy bisoprolol had produced a highly significant reduction in blood pressure as assessed by casual, ambulatory day- and night-time monitoring, and self-measured morning and evening readings. Bisoprolol was significantly more effective than nitrendipine, which did not induce a significant reduction in the ambulatory night-time recordings. Whole-day ambulatory blood pressure profiles showed an antihypertensive effect of bisoprolol throughout the entire 24-h period. 24-h blood pressure curves after nitrendipine demonstrated a markedly shorter duration of action, with no reduction in early morning blood pressure. Adverse effects and tolerability of the two drugs were comparable. The average changes in systolic and diastolic blood pressure after bisoprolol and nitrendipine in 2-h periods of ambulatory monitoring (6–8 a.m. and 6–8 p.m.) and self-measured blood pressure (6–8 a.m. and 6–8 p.m.) showed a good agreement between ambulatory and self-measured blood pressure determinations with no significant difference between the methods.The results show that 24 h antihypertensive efficacy was more pronounced for bisoprolol than for nitrendipine at the doses studied. Further, self-measured blood pressures at home were suitable for accurate estimation of the 12-h and 24-h antihypertensive efficacy of the two drugs. The methodological findings of this study have important implications for further pharmacological trials investigating the duration of action of antihypertensive drugs.     

Treatment of Isolated Systolic Hypertension in the Elderly: The Syst-Eur Trial

The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Patients ≥ 60 years) were randomly assigned to active treatment (n = 2398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or matching placebos (n = 2297). In the intention-to-treat analysis, the beween-group difference in blood pressure amounted to 10.1/4.5 mm Hg (P < 0.001). Active treatment reduced the total incidence of stroke (primary endpoint) by 42% (P = 0.003), of all cardiac endpoints by 26% (P = 0.03), and of all cardiovascular endpoints combined by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%; P = 0.07), but all-cause mortality was not influenced (-14%; P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with higher systolic blood pressure at entry (P = 0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. It can be concluded that stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.     

小剂量氢氯噻嗪联合尼群地平治疗农村地区高血压疗效分析

目的 评价小剂量氢氯噻嗪联合尼群地平治疗农村地区高血压的疗效.方法 2006年6月,按整群随机抽样方法,在辽宁省阜新县选取原发高血压患者5292例,分为健康教育组(对照组)及药物干预组(干预组);干预组以阶梯式加药方式给予氢氯噻嗪、尼群地平及卡托普利,观察药物的降压效果及对脑卒中发病的影响.结果 5292例高血压患者平均随访15个月.至随访结束共有308例失访(失访率为5.8%).进入队列的4984例完成各种指标检测,其中干预组2530例,对照组2454例.经过健康教育及药物干预后,干预组平均血压下降16.1/9.4 mm Hg(1 mm Hg=0.133kPa),对照组平均血压下降6.7/3.5 mmHg.干预组的血压控制率高于对照组(33.1%比15.1%,P＜0.001).药物干预后,干预组比对照组非致死性脑卒中发病风险减少57.3%,总脑卒中发病风险减少59.4%.差异有统计学意义(P＜0.05).至随访结束,两组人群的严重低血钾发生率及新发糖尿病发生率差异无统计学意义.结论 以噻嗪利尿剂为基础的低成本降压方案,降压效果好,安全性高,显示良好的价效比,适合在中国农村地区推广.     

尼群的平、间硝苯吡啶及其油剂降压特点的研究

用肾动脉狭窄观察大鼠形成高血压过程,血压稳步上升,到40～47天达稳定状态。尼群的平降压峰值为4～6h,高血压动物长期给药(一个月)后24h仍使血压降低原水平16％。尼群的平降压作用较间硝苯吡啶弱,前者降低原水平33.4％,后者39.1％,二者比较F值为9.79,P<0.01。二者用油剂20mg/kg im,隔天或三天给药一次,降压作用显著持久,均可持续48～72h之久。