CN116459222A - 一种匹维溴铵组合物、制剂及其用途 - Google Patents
一种匹维溴铵组合物、制剂及其用途 Download PDFInfo
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Abstract
本发明属于药物制剂技术领域，具体涉及一种匹维溴铵组合物、制剂及其用途。本发明匹维溴铵组合物由匹维溴铵、十六醇酯蜡组成，解决了匹维溴铵见光、遇热不稳定、易分解的问题。进一步提供了由匹维溴铵组合物和药学上可接受的辅料制备而成的匹维溴铵制剂，在光、热稳定性方面优于市售制剂。
Description
技术领域
本发明属于药物制剂技术领域，具体涉及一种匹维溴铵组合物、制剂及其用途。
背景技术
匹维溴铵由法国苏威制药公司研发，于1975年首次上市，是一种对胃肠道具有高度选择性解痉作用的钙拮抗药，对平滑肌的作用机制和其它钙拮抗剂一样，但对结肠平滑肌具有高度选择作用。匹维溴铵通过阻断钙离子流入肠壁平滑肌细胞，防止肌肉过度收缩而达到解痉作用，能消除肠平滑肌的高反应性，并增加肠道蠕动能力。
匹维溴铵的适应症有：对症治疗与肠道功能紊乱有关的疼痛、排便异常和胃肠不适；对症治疗与胆道功能紊乱有关的疼痛；为钡灌肠做准备。
公开号为CN101467975A的中国专利公开了一种匹维溴铵缓释片，匹维溴铵与填充剂、缓释剂、增塑剂、抗粘剂的重量比为150:(10～500):(10～300):(0～100):(0～100)，达到缓慢释放，能够维持较为平稳的血药浓度和更长的作用时间。公开号为CN101468015A的中国专利公开了一种匹维溴铵干混悬剂，其填充剂为蔗糖、甘露醇等，述矫味剂为氯化钠、阿司帕坦、草莓香精等，助悬剂为卡波姆、羧甲基纤维素钠、羧甲基淀粉钠等。用于治疗与肠易激综合征有关的股痛、排便紊乱、肠道不适，钡灌肠前准备。公开号为CN105315230A的中国专利公开了一种匹维溴铵制剂，将无定型形态匹维溴铵和稀释剂混合过筛得混粉，向混粉中加入润滑剂，混合均匀，压片，包衣，所述辅料均为药学上常用的辅料。公开号为CN101531642A的中国专利公开了一种含匹维溴铵的药物组合物，说明书实施例5-10公开了匹维溴铵片剂、胶囊的处方。
众所周知的是，匹维溴铵不稳定，见光、遇热易分解，因此匹维溴铵制剂的包装及储存条件较为苛刻，要求避光、低温。上述现有技术中均为对所述匹维溴铵制剂进行质量评价，没有解决该问题。
发明内容
克服现有技术的不足，本发明提供了一种稳定的匹维溴铵组合物以及匹维溴铵制剂，解决了匹维溴铵不稳定，见光、遇热易分解的问题。
具体而言，本发明的技术方案如下：
本发明提供了一种匹维溴铵组合物，由匹维溴铵、十六醇酯蜡组成。
在多个实施例中，所述匹维溴铵、十六醇酯蜡的重量份比为10：0.5～2。
在一个较优的实施例中，所述匹维溴铵、十六醇酯蜡的重量份比为10：1。
所述匹维溴铵组合物是由匹维溴铵、十六醇酯蜡按上述比例混合粉碎而成。
本发明的第二个目的在于提供一种匹维溴铵制剂，由上述匹维溴铵组合物和药学上可接受的辅料组成。
进一步的，所述制剂包括但不限于片剂、胶囊剂、颗粒剂。
一种匹维溴铵片，在多个实施例中，所述片剂的组方为：
在一个较优的实施例中，所述片剂的组方为：
进一步的，还可以对上述片剂进行包衣。
一种匹维溴铵胶囊，在多个实施例中，所述胶囊剂的组方为：
在一个较优的实施例中，所述胶囊剂的组方为：
一种匹维溴铵颗粒，在多个实施例中，所述颗粒剂的组方为：
在一个较优的实施例中，所述颗粒剂的组方为：
进一步的，所述制剂按常规制剂的制备方法制得即可。
本发明的第三个目的在于提供上述匹维溴铵组合物在制备治疗肠易激综合征疾病的药物中的用途。
与现有技术相比，本发明的有益效果在于：
本发明匹维溴铵组合物利用匹维溴铵与十六醇酯蜡混合，克服了匹维溴铵见光、遇热不稳定、易分解的问题。进一步提供了由匹维溴铵组合物制备的制剂，在光、热稳定性方面，优于市售制剂。
附图说明
图1-2：实施例4-13匹维溴铵制剂、市售匹维溴铵片光稳定性实验结果
图3-4：实施例4-13匹维溴铵制剂、市售匹维溴铵片热稳定性实验结果
具体实施方式
为了使本发明的目的、技术方案更加清楚明白，以下结合实施例，对本发明做进一步的说明，但是本发明的保护范围并不限于这些实施例，实施例仅用于解释本发明。本领域技术人员应该理解的是，凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。
一、匹维溴铵组合物及其稳定性研究
1.匹维溴铵组合物
实施例1匹维溴铵组合物
匹维溴铵 10g
十六醇酯蜡 1g
将上述匹维溴铵、十六醇酯蜡混合粉碎，即得匹维溴铵组合物。
实施例2匹维溴铵组合物
匹维溴铵 10g
十六醇酯蜡 0.5g
将上述匹维溴铵、十六醇酯蜡混合粉碎，即得匹维溴铵组合物。
实施例3匹维溴铵组合物
匹维溴铵 10g
十六醇酯蜡 2g
将上述匹维溴铵、十六醇酯蜡混合粉碎，即得匹维溴铵组合物。
对比实施例1
匹维溴铵 10g
鲸蜡 1g
将上述匹维溴铵、鲸蜡混合粉碎，即得。
对比实施例2
匹维溴铵 10g
棕榈醇 1g
将上述匹维溴铵、棕榈醇混合粉碎，即得。
2.匹维溴铵组合物稳定性验证
2.1匹维溴铵组合物的光稳定性实验
将实施例1-3匹维溴铵组合物、对比实施例1-2、粉碎后的匹维溴铵分别作为供试品，开口放在装有日光灯的光照箱中，于照度为4500lx±500lx的条件下放置30天，分别于第0天、第10天和第30天取样，高效液相法检测匹维溴铵的含量。
表1匹维溴铵组合物的光稳定性实验
2.2匹维溴铵组合物的热稳定性实验
将实施例1-3匹维溴铵组合物、对比实施例1-2、粉碎后的匹维溴铵分别作为供试品，开口置于温度为35±2℃条件下放置30天，分别于第0天、第10天和第30天取样，高效液相法测定匹维溴铵的含量。
表2匹维溴铵组合物的热稳定性实验
3.匹维溴铵组合物稳定性实验结果
表1-2可得，本发明匹维溴铵组合物按照一定比例将匹维溴铵与十六醇酯蜡共同混合粉碎后，能够显著提升匹维溴铵的光、热稳定性，利用同样的粉碎方式对匹维溴铵进行处理，并置于相同的实验条件下，匹维溴铵遇光或热都表现出不同程度的分解。说明本发明匹维溴铵组合物解决了匹维溴铵光、热不稳定的问题。
二、匹维溴铵制剂及其稳定性研究
1.匹维溴铵片
实施例4匹维溴铵片(200片，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、乳糖、羧甲淀粉钠、硬脂酸镁，共混，过筛，直接压片，即得匹维溴铵片。
实施例5匹维溴铵片(200片，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、乳糖、羧甲淀粉钠、硬脂酸镁，共混，过筛，直接压片，即得匹维溴铵片。
实施例6匹维溴铵片(200片，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、乳糖、羧甲淀粉钠、硬脂酸镁，共混，过筛，直接压片，即得匹维溴铵片。
实施例7匹维溴铵片(200片，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、乳糖、羧甲淀粉钠、硬脂酸镁，共混，过筛，直接压片得到素片，素片置包衣锅中利用尤特奇、欧巴代等常规包衣液进行包衣，即得匹维溴铵片。
2.匹维溴铵颗粒
实施例8匹维溴铵颗粒(200袋，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的低取代羟丙纤维素、微晶纤维素、乳糖、滑石粉、30％聚乙二醇-4000水溶液(W/V)，制成软材、制粒、干燥、整粒，分装即得匹维溴铵颗粒。
实施例9匹维溴铵颗粒(200袋，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的低取代羟丙纤维素、微晶纤维素、乳糖、滑石粉、10％聚乙二醇-6000水溶液(W/V)，制成软材、制粒、干燥、整粒，分装即得匹维溴铵颗粒。
实施例10匹维溴铵颗粒(200袋，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的低取代羟丙纤维素、微晶纤维素、乳糖、滑石粉、50％聚乙二醇-4000水溶液(W/V)，制成软材、制粒、干燥、整粒，分装即得匹维溴铵颗粒。
3.匹维溴铵胶囊
实施例11匹维溴铵胶囊(200粒，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、淀粉、微粉硅胶，共混，过筛，分装，装入4号空心胶囊，即得匹维溴铵胶囊。
实施例12匹维溴铵胶囊(200粒，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、淀粉、微粉硅胶，共混，过筛，分装，装入4号空心胶囊，即得匹维溴铵胶囊。
实施例13匹维溴铵胶囊(200粒，规格：50mg)
配方：
制备方法：将配方量的匹维溴铵、十六醇酯蜡混合粉碎，加入粉碎后的微晶纤维素、淀粉、微粉硅胶，共混，过筛，分装，装入4号空心胶囊，即得匹维溴铵胶囊。
4.匹维溴铵制剂的稳定性研究
4.1匹维溴铵制剂的光稳定性
将实施例4-13匹维溴铵制剂、市售匹维溴铵片(国药准字H20133036)分别作为供试品，开口放在装有日光灯的光照箱中，于照度为4500lx±500lx的条件下放置90天，分别于第0天、第10天、第30天、第60天、第90天取样，高效液相法检测匹维溴铵制剂中匹维溴铵的含量。
4.2匹维溴铵制剂的热稳定性
将实施例4-13匹维溴铵制剂、市售匹维溴铵片(国药准字H20133036)分别作为供试品，开口置于温度为35±2℃条件下放置90天，分别于第0天、第10天、第30天、第60天、第90天取样，高效液相法测定匹维溴铵制剂中匹维溴铵的含量。
4.3匹维溴铵制剂的稳定性研究结果
图1-2为实施例4-13匹维溴铵制剂、市售匹维溴铵片光稳定性实验结果，显示本发明匹维溴铵制剂光照稳定性更高，优于市售制剂。图3-4为实施例4-13匹维溴铵制剂、市售匹维溴铵片光稳定性实验结果，显示本发明匹维溴铵制剂热稳定性更高。
Claims (10)
1.一种匹维溴铵组合物，其特征在于，所述匹维溴铵组合物由匹维溴铵、十六醇酯蜡组成。
2.根据权利要求1所述的匹维溴铵组合物，其特征在于，所述匹维溴铵、十六醇酯蜡的重量份比为10：0.5～2；优选的，所述匹维溴铵、十六醇酯蜡的重量份比为10：1。
3.一种匹维溴铵制剂，其特征在于，所述匹维溴铵制剂由权利要求1或2所述的匹维溴铵组合物和药学上可接受的辅料组成。
4.根据权利要求3所述的匹维溴铵制剂，其特征在于，所述制剂包括但不限于片剂、胶囊剂、颗粒剂。
5.根据权利要求4所述的匹维溴铵制剂，其特征在于，所述片剂的组方为：
优选的，所述片剂的组方为：
6.根据权利要求5所述的匹维溴铵制剂，其特征在于，所述片剂还可进行包衣。
7.根据权利要求4所述的匹维溴铵制剂，其特征在于，所述胶囊剂的组方为：
优选的，
8.根据权利要求4所述的匹维溴铵制剂，其特征在于，所述颗粒剂的组方为：
优选的，
9.根据权利要求4所述的匹维溴铵制剂，其特征在于，所述制剂按常规制备方法制得。
10.权利要求1或2所述的匹维溴铵组合物在制备治疗肠易激综合征疾病的药物中的用途。
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