Raman光谱法与经典方法验证尼群地平固体分散体

目的:用Raman光谱法和经典方法(红外光谱法和X-射线衍射法)研究尼群地平固体分散体的分散性,以期获得1种新的、简单易行的检查固体分散体分散性的方法.方法:采用溶剂法制备尼群地平固体分散体,用显微共焦拉曼光谱仪、傅里叶变换红外光谱仪和X-射线衍射仪分别采集尼群地平、PVP K30,尼群地平:PVP K30(1:6)的...     

Glutamate increases the [Ca]i but stimulates Ca-independent release of [H]GABA in cultured chick retina cells

The effect of glutamate of [Ca²⁺]_i and on [³H]γ-aminobutyric acid (GABA) release was studied on cultured chick embryonic retina cells. It was observed that glutamate (100 μM) increases the [Ca²⁺]_i by Ca²⁺ influx through Ca²⁺ channels sensitive to nitrendipine, but not to ω-conotoxin GVIA (ω-Cg Tx) (50%), and by other channels insensitive to either Ca²⁺ channel blocker. Mobilization of Ca²⁺ by glutamate required the presence of external Na⁺, suggesting that Na⁺ mobilization through the ionotropic glutamate receptors is necessary for the Ca²⁺ channels to open. The increase in [Ca²⁺]_i was not related to the release of [³H]GABA induced by glutamate, suggesting that the pathway for the entry of Ca²⁺ triggered by glutamate does not lead to exocytosis. In fact, the glutamate-induced release of [³H]GABA was significantly depressed by Ca_o²⁺, but it was dependent on Na_o⁺, just as was observed for the [³H]GABA release induced by veratridine (50 μM). The veratridine-induced release could be fully inhibited by TTX, but this toxin had no effect on the glutamate-induced [³H]GABA release. Both veratridine- and glutamate-induced [³H]GABA release were inhibited by 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid (NNC-711), a blocker of the GABA carrier. Blockade of the NMDA and non-NMDA glutamate receptors with MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively, almost completely blocked the release of [³H]GABA evoked by glutamate. Continuous depolarization with 50 mM K⁺ induced maximal release of [³H]GABA of about 1.5%, which is much smaller than the release evoked by glutamate under the same conditions (6.0–6.5%). Glycine (3 μM) stimulated [³H]GABA release induced by 50 mM K⁺, and this effect was blocked by MK-801, suggesting that the effect of K⁺ on [³H]GABA release was partially mediated through the NMDA receptor which probably was stimulated by glutamate released by K⁺ depolarization. We conclude that glutamate induces Ca²⁺-independent release of [³H]GABA through reversal of the GABA carrier due to Na⁺ entry through the NMDA and non-NMDA, TTX-insensitive, channels. Furthermore the GABA carrier seems to be inhibited by Ca²⁺ entering by the pathways open by glutamate. This Ca²⁺ does not lead to exocytosis, probably because the Ca²⁺ channels used are located at sites far from the active zones.     

Transdermal absorption of nitrendipine from adhesive patches

The possibility of transdermal administration of nitrendipine was examined on healthy human subjects. Patches containing nitrendipine and Azone ® were prepared, in vitro release and permeation of nitrendipine from patches were investigated, transdermal absorption of nitrendipine from patches was studied in vivo, and clinical trials of nitrendipine patches were conducted in 150 hypertensive patients. Skin irritation was observed neither in rabbits nor in human subjects.     

血管紧张素转化酶抑制剂用于阿尔茨海默病合并高血压的探讨

目的探讨血管紧张素转化酶抑制剂治疗阿尔茨海默病合并高血压的临床疗效。方法选取本院80例阿尔茨海默病合并高血压的患者,将其分为治疗组和对照组,每组各40例。对照组给予尼群地平治疗,治疗组给予尼群地平联合依那普利治疗。观察两组患者血压变化及简易智能精神状态检查量表（MMSE）的评定结果 ,并比较两组疗效。结果经过治疗后,治疗组收缩压与舒张压均低于对照组（P〈0.05）;治疗组治疗后MMSE各项指标评分均高于对照组,治疗组MMSE总分高于与对照组比较（P〈0.05）。结论血管紧张素转化酶抑制剂治疗阿尔茨海默病合并高血压具有较好的疗效,值得临床推广应用。     

共研磨法改善尼群地平体外溶出度的研究

目的:采用共研磨法改善尼群地平的体外溶出度。方法:设计单因素试验考察药物与辅料的共研相数(单相、两相和三相)、共研辅料种类(微晶纤维素(MCC)、聚乙烯吡咯烷酮k30(PVPk30)、羟丙基纤维素(HPC)、羟丙基甲基纤维素(HPMC))、共研时间(0、10、20、30、40、50、60min)及主药与共研辅料MCC比例(1∶1、1∶2、1∶3、1∶4、1∶5、1∶6、1∶7、1∶8、1∶9)对尼群地平粉末及片剂体外溶出度的影响。结果:确定共研磨法条件为共研相数为两相,辅料为HPC或MCC,共研时间40min,主药与MCC比例1∶4。在此条件时,共研粉末的药物10min累积溶出百分率可达80%以上,共研粉末片剂40min可达80%以上。结论:难溶性药物尼群地平在适当条件下采用共研磨法可以显著改善其体外溶出度。     

尼群地平单用与联合依那普利对原发性高血压治疗作用比较

目的观察单用尼群地平和联合依那普利治疗原发性高血压的临床疗效和安全性。方法将120例轻中度高血压患者随机分为对照组（尼群地平）和治疗组（尼群地平＋依那普利）,疗程12周,检测两组治疗前后血压、心率、心电图和血、尿实验室检查的变化及药物的不良反应。结果对照组和治疗组总有效率分别为71.6%和95%（P〈0.05）,联合用药不良反应与单独用药相比较无明显增加。结论尼群地平和依那普利治疗原发性高血压较单独用尼群地平更有效地控制血压,具有良好的安全性。     

Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats

The aim of this study was to compare the roles of dihydropyridine calcium antagonists nifedipine, nitrendipine, amlodipine on doxorubicin (DXR)-induced nephrotoxicity in rats using biochemical, histopathological and immunohistochemical approaches. Male Sprague-Dawley rats were randomly divided into five experimental groups: control; DXR; DXR+nifedipine (15 mg/kg); DXR+nitrendipine (10 mg/kg); DXR+amlodipine (5 mg/kg). Results showed that treatment with DXR alone caused significant changes in the levels of urinary protein, serum creatinine (SCr), and blood urea nitrogen (BUN). Co-administration with amlodipine effectively reversed the effect of DXR on these parameters. In contrast, nifedipine and nitrendipine either had no effect or worsened DXR induced changes in the levels of urinary protein, SCr and BUN. Furthermore, DXR treatment caused significant increases in the levels of malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) and significant decreases in the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), and superoxide dismutase (SOD). These effects were significantly reduced by co-administration with amlodipine but not affected by nifedipine and worsened by nitrendipine. In addition to the biochemical changes, histopathological studies showed that DXR caused significant structural damages in the kidneys. Glomerular cell apoptosis, a decrease in Bcl-2 expression and an increase in Bax expression were observed in all rats treated with DXR. Co-administration with amlodipine effectively reversed the effect of DXR while nifedipine and nitrendipine had no effect. In conclusion, this study clearly indicated that amlodipine protected against DXR-induced nephrotoxicity while nifedipine and nitrendipine had no effect.     

阿替洛尔对人体内尼群地平药动学的影响研究

目的:探讨阿替洛尔在健康人体内对尼群地平药动学的影响。方法:16名健康受试者随机分为A、B组,A组口服尼群地平片20mg,B组口服复方尼群地平片4片(每片含尼群地平5mg,阿替洛尔10mg)。采用气相色谱法测定血浆中尼群地平的浓度,并计算药动学参数。结果:2组尼群地平药动学参数无显著性差异(P>0.05)。结论:单次服药时,阿替洛尔在健康受试者体内对尼群地平的药动学参数未产生显著性影响。     

液相色谱-质谱联用法检测中药中非法添加的硝苯地平、尼群地平和尼莫地平

目的:建立快速、准确、高灵敏度的检测中药中非法添加硝苯地平、尼群地平和尼莫地平的分析方法。方法:采用液相色谱-质谱联用法。通过相对分子质量、二级质谱碎片信息、液相色谱保留时间和紫外光谱4方面信息,对中药降压制剂的提取液进行液相色谱-质谱分析。通过与标准品的光谱、色谱及质谱行为相比较,对中药降压制剂中非法掺入的合成降压药进行定性鉴别。结果:结合4方面信息,发现在3种受试中药降压制剂中分别掺有硝苯地平、尼群地平和尼莫地平。结论:该方法选择性强,灵敏度高,可用于分析检测中药降压制剂中非法掺入的硝苯地平、尼群地平和尼莫地平。     

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.