CN107913286A - 一种复方利血平药物组合物及其制备方法 - Google Patents
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Abstract
本发明涉及了一种治疗高血压的复方利血平药物组合物及其制备方法,具体涉及医药及医药生产技术领域,包含复方利血平、淀粉、三硅酸镁,用利血平和适量淀粉进行预混合,确保利血平的含量均匀度;辅料中使用了三硅酸镁,三硅酸镁水解游离出的酸,可以提高复方制剂中利血平、维生素B1、维生素B6、硫酸双肼屈嗪的稳定性;使该药物组合物起效时间短,药效持续时间长,便于患者长期治疗,提高了用药安全性,同时处方工艺稳健性强,不受环境温湿度的影响,显著降低了制剂批间差异和提高样品的稳定性。
Description
技术领域
本发明涉及制药领域关于药物制剂技术,特别是涉及一种治疗高血压的复方利血平药物组合物及其制备方法。
背景技术
复方血平组合物通常是由利血平、硫酸双肼屈嗪、维生素B1、维生素B6、氢氯噻嗪、氯化钾、盐酸异丙嗪等多种成分组成的复方组合物制剂,该类复方组合物制剂临床上已经应用多年,有效性和安全性已经得到了充分的验证。
其中利血平为肾上腺素能神经阻滞药,可妨碍肾上腺素能神经末梢内介质的贮存,将囊泡中具有升压作用的介质耗竭。硫酸双肼屈嗪为血管扩张药,可松弛小动脉平滑肌,降低外周阻力。氢氯噻嗪则为利尿降压药。三药联合应用有显著的协同作用,促进血压下降,提高了疗效,从而降低了各药的不良反应,同时,氢氯噻嗪能增加利血平和硫酸双肼屈嗪的降压作用;还能降低他们的水钠潴留的副作用。
专利CN2014107362357中,采用肼屈嗪代替硫酸双肼屈嗪。肼屈嗪的作用与硫酸双肼屈嗪的作用类似,降压作用持久,但是肼屈嗪的起效较快,不利于平稳地控制血压。
专利CN201110369547中,采用加入酸性物质磷酸二氢盐来维持复方利血平制剂中有效成分的稳定性,但是经过尝试,该无机酸性物质虽然能够提高维生素B6和维生素B1的稳定性,但却对硫酸双肼屈嗪的稳定性提高无能为力。申请号CN201210455548的中国专利申请采用对维生素B1进行包衣的方式来提高维生素B1稳定性,但确对不稳定性活性成分维生素B6、硫酸双肼屈嗪等未加考虑,同时对维生素B1进行包衣也增加了工艺步骤流程,增加了大量的工作。
在高血压的治疗方面,常规降压药物在高血压病的降压过程中血压波动大,药物治疗效果差,副作用大,起效时间长,药效持续时间短。另外,复方利血平组合物配方中,利血平药物含量极低,与其他较低含量的活性成分差30倍以上,与其他较高含量的活性成分差上千倍,极易造成药物含量均匀度不符合规定,通过适宜的方法,改善活性成分的药物含量均匀度得到各指标均符合要求的复方利血平组合物制剂。
发明内容
本发明的目的是针对复方利血平组合物配方传统制备方法存在的缺陷,提供一种以利血平、硫酸双肼屈嗪、维生素B1、维生素B6、三硅酸镁、氢氯噻嗪、氯化钾、盐酸异丙嗪等多种活性成分的一种治疗高血压的复方利血平药物组合物制剂及其制备方法。
因利血平的规格极小,为确保利血平的含量均匀度符合标准要求,本发明在制粒工艺中先将利血平与适量淀粉进行稀释预混合。预混合均匀后,再与其他物料进行制粒。
由于处方中存在维生素B6、维生素B1、硫酸肼屈嗪等,稳定性较差,易受外界环境影响(如温度,光照,氧气等)而发生变化,药物含量降低。如果采用无机酸的话,又对口腔、食道的环境有影响,故采用三硅酸镁等水解后呈酸性的盐,在保护内环境的同时,提高药物组分的稳定性。
采用利用本发明技术方案制备的复方利血平药物组合物制剂毒副作用少,降压过程中血压波动小,起效时间短,药效持续时间长,便于患者长期治疗,提高了用药安全性,并改善了用药的依从性。本发明同时采用了新处方和新工艺制备治疗高血压的复方利血平药物组合物制剂,显著降低了制剂批间均匀性及溶出差异和提高样品的稳定性。
具体实施方式
下列实施例用于进一步解释或理解本发明的内容,但不能限制本发明的范围。
实施例1:
复方利血平片处方及其制备工艺(以1000片计)
利血平 0.03g
硫酸双肼屈嗪 5g
维生素B1 2.5g
维生素B6 2.5g
氢氯噻嗪 7.5g
盐酸异丙嗪 5.0g
氯化钾 75g
三硅酸镁 75g
淀粉 85g
糊精 25g
硬脂酸镁 300g
羧甲基淀粉钠 7.5g
羟丙基纤维素 10g
将利血平和适量淀粉进行稀释预混合,再将硫酸双肼屈嗪、维生素B1、维生素B6、氢氯噻嗪、盐酸异丙嗪、氯化钾、三硅酸镁、淀粉、糊精、硬脂酸镁、羧甲基淀粉钠、羟丙基纤维素分别粉碎、过筛80目筛网,称取处方量的上述原辅料,按等量递增法混合均匀后,加入流化床制粒包衣机中,预热,调节流化温度至40℃、干燥空气流量100m3*h-1,取上述乙醇溶液,用蠕动泵以顶喷方式5ml/min的流速泵入雾化室雾化制粒,雾化压力为1.2bar,逐步提高泵入速率到40ml/min至包衣液用完,提高流化温度到50℃,继续在流化床中流化干燥45分钟后取出,选取小于18目颗粒,检查合格后,加入处方量的硬脂酸镁,混合5min,压片,包装即可。
Claims (4)
1.一种复方利血平组合物,其特征在于,由如下原辅料组成:利血平、硫酸双肼屈嗪、维生素B1、维生素B6、三硅酸镁、氢氯噻嗪、氯化钾、盐酸异丙嗪、淀粉、糊精、硬脂酸酸镁、羧甲基淀粉钠、羟丙基纤维素。
2.根据权利要求1所述的复方利血平组合物,其特征在于,
使用填充剂为甘露醇、乳糖、蔗糖、糊精、淀粉、微晶纤维素、海藻多糖和壳聚糖中的任一种或一种以上;
使用崩解剂为羧甲基淀粉钠、交联聚维酮、交联羧甲基纤维素钠、低取代羟丙基纤维素和羧甲基纤维素钙中的任一种或一种以上;
使用粘合剂为欧巴代、羟丙甲纤维素、羟丙基纤维素、聚维酮、聚乙烯醇和羧甲基纤维素钠中的任一种或一种以上;
使用润滑剂为滑石粉、氢化植物油、微粉硅胶、硬脂酸富马酸钠、硬脂酸钙、十二烷基硫酸钠、硬脂酸镁和硬脂醇中的任一种或一种以上。
3.根据权利要求1所述的复方利血平组合物的制备方法,其特征在于使用淀粉和利血平进行预混合,以确保活性成分利血平的含量均匀度。
4.根据权利要求1所述的复方利血平组合物的制备方法,其特征在于使用酸性物质提高活性成分利血平、维生素B1、维生素B6、硫酸双肼屈嗪的稳定性,酸性物质可以用磷酸二氢盐、富马酸、三硅酸镁等,优选三硅酸镁。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101548985A (zh) * | 2009-05-15 | 2009-10-07 | 赖福平 | 一种复方降压药物及其制备方法 |
CN102499923A (zh) * | 2011-11-18 | 2012-06-20 | 上海理工大学 | 一种药物组合物、其制备方法及用途 |
CN103800367A (zh) * | 2012-11-14 | 2014-05-21 | 上海信谊药厂有限公司 | 治疗高血压的药物组合物及其制备方法 |
CN105902564A (zh) * | 2015-11-03 | 2016-08-31 | 郑州泰丰制药有限公司 | 一种治疗高血压的药物组合物及制备方法 |
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Patent Citations (4)
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CN101548985A (zh) * | 2009-05-15 | 2009-10-07 | 赖福平 | 一种复方降压药物及其制备方法 |
CN102499923A (zh) * | 2011-11-18 | 2012-06-20 | 上海理工大学 | 一种药物组合物、其制备方法及用途 |
CN103800367A (zh) * | 2012-11-14 | 2014-05-21 | 上海信谊药厂有限公司 | 治疗高血压的药物组合物及其制备方法 |
CN105902564A (zh) * | 2015-11-03 | 2016-08-31 | 郑州泰丰制药有限公司 | 一种治疗高血压的药物组合物及制备方法 |
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Title |
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