粉末直接压片法制备甲磺酸多沙唑嗪片

目的:优选甲磺酸多沙唑嗪片粉末直接压片法最佳制备工艺。方法:采用粉末直接压片法,以粉末休止角、片子脆碎度及溶出度为评价指标,制备样品并进行质量考察。结果:所选处方粉末流动性良好,有效成分溶出速率高,各项指标均符合规定。经6个月加速及室温留样考察,样品的外观、含量、有关物质及溶出度均未发生明显变化。结论:优选的处方工艺操作简便、经济、生产周期短,制备的产品质量稳定,适合产业化生产。     

多沙唑嗪对兔膀胱出口部分梗阻致膀胱顺应性减低的影响

目的 探讨多沙唑嗪对兔膀胱出口部分梗阻后膀胱顺应性改变的影响.方法 成年雄性新西兰兔40只随机分为4组,每组10只,A组为假手术对照组,B组为膀胱出口部分梗阻组,C组为膀胱出口部分梗阻后口服多沙唑嗪组,D组为假手术后给予多沙唑嗪组.各组于14周行尿动力学检测,检测完成后处死并留取膀胱标本,行膀胱称重.结果 4组膀胱标本质量分别为(3.2±0.9)、(14.1±2.3)、(5.0±2.0)、(2.9±0.5)g;B、C组均高于A、D组,B组高于C组,差异均有统计学意义(P＜0.01);A、D组间比较差异无统计学意义(P＞0.05).4组逼尿肌漏尿点压分别为(10.2±2.5)、(18.8±6.1)、(13.5±4.7)、(11.6±3.6)cm H2O(1 cm H2O=0.098 kPa),B组高于A、D组,差异有统计学意义(P＜0.01),且高于C组,差异有统计学意义(P＜0.05);A、C、D组间差异无统计学意义(P＞0.05).膀胱顺应性分别为(2.86±0.56)、(1.22±0.39)、(4.25±2.19)、(2.90±0.53)ml/cm H2O,B组与A、D组相比明显下降,差异有统计学意义(P＜0.01);C组高于A、D组,差异有统计学意义(P＜0.05);A、D组间差异无统计学意义(P＞0.05).结论膀胱出口部分梗阻后早期应用多沙唑嗪治疗能够延迟梗阻对膀胱顺应性的损害,保护膀胱储尿功能.

Abstract：

Objective To explore the effect of doxazosin on rabbit bladder compliance after partial bladder outlet obstruction. Methods A total of 40 male New Zealand white rabbits were randomized into 4 groups, with 10 rabbits in each group. Partial bladder outlet obstruction was established in groups B and C, while groups A and D underwent the same operation but without partial bladder outlet obstruction. On the day after the operation, groups C and D received oral administration of doxazosin. After 14 weeks, urodynamic examinations were carried out in all groups, and the bladder was weighted after cystectomy. Results Bladder weight was (3.2±0.9) g in group A, (14.1±2.3) g in group B, (5.0±2.0) in group C,and (2.9±0.5) g in group D. The bladder weight in groups B and C increased significantly compared to groups A and D (P＜0.01), group B increased significantly over group C (P＜0.01), and there was no significant difference between groups A and D (P＞0.05).The detrusor leak point pressure was (10.2±2.5) cm H2O in group A, (18.8±6.1) cm H2O in group B, (13.5±4.7) cm H2O in group C,and (11.6±3.6) cm H2O in group D. The detrusor leak point pressure in group B was significantly higher than group A, group D (P＜0.01) and group C (P＜0.05). There was no significant difference between group A, group C and group D (P＞0.05). The bladder compliance was (2.86±0.56) ml/cm H2O in group A, (1.22±0.39) ml/cm H2O in group B, (4.25±2.19) ml/cm H2O in group C,and (2.90±0.53) ml/cm H2O in group D. The bladder compliance was significantly decreased in group B compared to groups A and D (P＜0.01). Bladder compliance in group C was significantly higher than in groups A and D (P＜0.05), and there was no significant difference between group A and group D (P＞0.05). Conclusion Early use of doxazosin can delay the occurrence of lower bladder compliance after partial bladder outlet obstruction, thus protecting the storage function of bladder.     

The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin

Summary In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n=6) or doxazosin 2 mg (Group 2, n=6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated.BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy.The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml · min^–1 during monotherapy with doxazosin.There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng · ml^–1 · h for the 4 study days (Group 2).     

翁沥通联合甲磺酸多沙唑嗪治疗前列腺炎相关症状的疗效观察

目的观察翁沥通联合可多华为主的综合治疗对慢性前列腺炎相关症状的改善情况。方法78例慢性前列腺炎患者同时服用翁沥通胶囊和可多华,并辅以相关治疗12周,观察相关临床症状的改善情况、前列腺按摩液镜检情况及慢性前列腺症状指数(NIH-CPSI)评分。结果治疗12周,78例患者症状好转26例,明显改善29例,症状消失23例;53例患者治疗12周后前列腺液中WBC<5个/HP或消失;治疗前、后患者NIH-CPSI评分间差别有显著性意义(P<0.001)。结论翁沥通联合可多华为主的综合治疗可使慢性前列腺炎患者的相关症状好转、改善,甚至消失。     

多沙唑嗪联合非那雄胺治疗良性前列腺增生观察

目的:研究非那雄胺联合多沙唑嗪治疗良性前列腺增生(BPH)的疗效.方法:将前列腺体积＞30 mL、国际前列腺症状评分(IPSS)＞15分的良性前列腺增生80例随机分为A和B2组,2组均给予非那雄胺5 mg/d及多沙唑嗪4 mg/d联合治疗.A组3月后停用多沙唑嗪,B组6月后停用多沙唑嗪.2组在停用多沙唑嗪后均继续服用非...     

多沙唑嗪治疗轻中度高血压疗效和安全性的临床研究

目的 评价新一代α_1受体拮抗剂甲磺酸多沙唑嗪的降压疗效及安全性,并与盐酸特拉唑嗪相比较。方法 采用随机分组平行对照方法,将226例轻、中度高血压患者分成两组:多沙唑嗪组(111例)口服甲磺酸多沙唑嗪2mg/d;盐酸特拉唑嗪组(115例)口服盐酸特拉唑嗪2mg/d。疗程8周。每两周一次上午监测诊室谷值坐位舒张压、心率,立位舒张压,并观察不良反应。用药前及治疗第8周后检测血液生化指标。第2周末谷值坐位舒张压仍大于90mmHg者加量至4mg/d,第4周末谷值坐位舒张压仍大于90mmHg者加量至6mg/d,第6周末谷值坐位舒张压仍大于90mmHg者,终止试验,改服其它药物。结果 治疗8周后甲磺酸多沙唑嗪组与盐酸特拉唑嗪组治疗有效反应率分别为74.77％和76.52％,(P>0.05);治疗后两组平均谷值坐位舒张压均有明显降低(P<0.05)。两组均无严重不良反应发生。结论 甲磺酸多沙唑嗪与盐酸特拉唑嗪降压疗效相似,不良反应发生率均较低,是一种安全、有效的治疗轻、中度原发性高血压的药物。     

多沙唑嗪对前列腺癌裸鼠移植瘤的抑制作用

目的:探讨α1肾上腺素能受体拮抗剂多沙唑嗪对雄激素非依赖性前列腺癌细胞系PC-3在裸鼠体内生长的影响及其作用机制.方法:建立前列腺癌细胞系PC-3的裸鼠体内移植瘤模型,将30只荷瘤裸鼠随机分为5组[A组(对照组),B组(多沙唑嗪3 mg/kg),C组(多沙唑嗪10 mg/kg),D组(多沙唑嗪30 mg/kg),E组(多沙唑嗪100mg/kg)].接种肿瘤细胞1周后每天1次灌胃给药,每周测量肿瘤体积2次,给药2周后处死裸鼠,取肿瘤组织做免疫组织化学Ki67及细胞凋亡DNA原位标记法(TUNEL法)检测,并用免疫印迹法研究蛋白Smad-4及IκBα在各组肿瘤组织中的表达情况.结果:多沙唑嗪给药组肿瘤体积较对照组显著缩小,肿瘤的重量较对照组亦显著减轻,而不同剂量的多沙唑嗪给药组间肿瘤大小差异无统计学意义.免疫组织化学结果显示前列腺癌细胞Ki67的阳性率在A至E组依次为36.5%±8.5%,37.7%±11.3%,40.1%±12.7%,37.2%±12.3%,39.3%±13.1%,各组间差异无统计学意义(P＞0.05);而前列腺癌细胞的TUNEL阳性率在A至E组依次为9.5%±3.5%,24.7%±8.3%,25.7%±9.7%,28.2%±12.1%,27.5%±11.3%,各用药组明显高于对照组(P＜0.01);免疫印迹结果表明用药组蛋白Smad-4及IκBα的表达显著高于对照组.结论:α1肾上腺素能受体拮抗剂多沙唑嗪对雄激素非依赖性前列腺癌细胞PC-3裸鼠体内移植瘤的生长具有明显抑制作用,其作用机制可能是药物诱导了前列腺癌细胞凋亡,对细胞的增殖并没有明显的影响;而TGF-β1信号转导通路的激活可能是多沙唑嗪引起前列腺癌细胞凋亡的重要机制.