CN110179990A - 一种头孢布烯组合物及其颗粒剂和该颗粒剂的制备方法 - Google Patents
一种头孢布烯组合物及其颗粒剂和该颗粒剂的制备方法 Download PDFInfo
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Abstract
本发明涉及药物技术领域，具体公开一种头孢布烯组合物及其颗粒剂和该颗粒剂的制备方法。所述头孢布烯组合物包括质量比为3‑10:1的头孢布烯和脂肪族生物胺。本发明得到的头孢布烯组合物还可以增加头孢布烯对菌体的抗菌性并降低菌体的抗药性，是一种用量少、药效强、抗菌种类多、副作用小的优良抗菌药。
Description
技术领域
本发明涉及药物技术领域，尤其涉及一种头孢布烯组合物及其颗粒剂和该颗粒剂的制备方法
背景技术
头孢布烯为第三代口服头孢菌素类抗生素，其抗菌作用机制与其他β-内酰胺抗生素相同，可与一个或多个青霉素结合蛋白(PBPs)结合而抑制细菌细胞壁的合成。头孢布烯主要通过抑制细菌细胞壁中肽聚糖合成的最后步骤即转肽步骤，从而抑制细胞壁的生物合成，当细胞壁的合成停止时，细菌最终因胞壁自溶性酶的活性而溶解。头孢布烯对产气肠杆菌、大肠埃希杆菌、化脓性链球菌、肺炎链球菌、流感嗜血杆菌、副流感杆菌、卡他莫拉菌、克雷白杆菌、吲哚阳性变形杆菌及其他变形杆菌均有较强的抗菌活性。
头孢布烯口服给药后吸收迅速，在2～3h后可达血药浓度峰值。药物吸收后分布广泛，可在各组织、体腔液、体液中达到有效抗菌浓度。头孢布烯主要经肾以原形随尿液排出，清除半衰期约为2h，在接受血液透析的患者中，经3h的血液透析后，约39％的给药量可被清除，清除率约为每分钟76.9mg。
头孢布烯对革兰阳性菌除化脓性链球菌外作用均较弱，对其它链球菌(草绿色链球菌、肺炎链球菌、无乳链球菌)以及铜绿假单胞菌达不到较好的抗菌效果，其组合物的制备和治疗成本也相应的较高。
发明内容
针对现有头孢布烯的药物治疗成本高、药物机体内作用时间短、对部分菌体抗性较弱以及易产生抗药菌等问题，本发明提供一种头孢布烯组合物及其颗粒剂和该颗粒剂的制备方法。
为达到上述发明目的，本发明实施例采用了如下的技术方案：
一种头孢布烯组合物，包括质量比为3-10:1的头孢布烯和脂肪族生物胺。
相对于现有技术，本发明提供的头孢布烯组合物在生物胺存在时，可出乎意料的提高头孢布烯的抗菌性，增加头孢布烯的疗效，同时可以使细菌对头孢菌素的药性变得极其敏感，加速抑菌的效果，大大减少抗药菌的产生。
优选的，所述生物胺为精胺或亚精胺。
精胺和亚精胺与头孢布烯结合可最大限度的增加菌体对头孢布烯的敏感性，尤其是增加化脓性链球菌和肺炎链球菌对药物的敏感性，可短时间快速达到抑菌效果。
本发明还提供了包含上述头孢布烯组合物的颗粒剂，该颗粒剂，包括如下质量百分比的组分：
头孢布烯4.5-8％、脂肪族生物胺0.8-1.5％、碳酸氢钠0.2-0.5％、抗氧化剂8-10％、崩解剂20-25％、润滑剂0.2-0.5％、调味剂10-12％和余量的填充剂。
相对于现有技术，本发明提供的头孢布烯组合物颗粒剂中，碳酸氢钠的存在，可以延长头孢布烯在机体内的作用时间，使药物在血液内长时间保持较高的浓度，减少药物的用量，进而降低药物的副作用；抗氧化剂的加入，可以增加头孢布烯的稳定性，防止其降解，同时还可以避免头孢布烯发生聚合反应产生大量的聚合物杂质，而失去作用效果；本发明颗粒剂中各成分和含量的配合，还增加了头孢布烯对铜绿假单胞菌和链球菌的抗性，是一种用量少、药效强、抗菌种类多、副作用小的优良抗菌药。
本发明提供的头孢布烯组合物颗粒剂中的各组分原料易得、成本低。
优选的，所述抗氧化剂为维生素C。
维生素C的加入不仅可以提高药物的稳定性，还可以促进机体对药物的吸收，进一步加强药物的作用效果，缩短治疗疗程。
优选的，所述崩解剂为微晶纤维素。
优选的，所述润滑剂为硬脂酸镁。
优选的，所述调味剂为蔗糖。
优选的，所述填充剂为糊精或淀粉。
优选的，所述各组分的粒径≤0.15mm。
本发明还提供所述头孢布烯组合物颗粒剂的制备方法。该制备方法，至少包括以下步骤：
a、按质量比将头孢布烯、生物胺、碳酸氢钠、抗氧化剂、崩解剂、润滑剂、调味剂和填充剂混合均匀，得到混合物；
b、将混合物研磨粉粹过100目筛，得到混合粉末；
c、采用离心造粒技术将混合粉末制备成粒径为0.3-0.4mm的颗粒剂。
相对于现有技术，本发明提供的头孢布烯组合物颗粒剂的制备方法，制备过程简单，不需使用特殊设备，且各组分原料易得、成本低。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
实施例1
一种头孢布烯组合物，包括质量比为3:1的头孢布烯和精胺。
包含该头孢布烯组合物的颗粒剂，包括如下质量的组分：
头孢布烯4.5g、精胺1.5g、碳酸氢钠0.2g、维生素C 8g、微晶纤维素20g、硬脂酸镁0.2g、蔗糖10g、淀粉55.6g。
所述头孢布烯组合物颗粒剂的制备方法，包括以下步骤：
a、按质量比将头孢布烯、精胺、碳酸氢钠、维生素C、微晶纤维素、硬脂酸镁、蔗糖和淀粉混合均匀，得到混合物；
b、将混合物研磨粉粹过100目筛，得到混合粉末；
c、采用离心造粒技术将混合粉末制备成粒径为0.4mm的颗粒剂。
将得到的头孢布烯组合物颗粒剂进行分装，得到100包头孢布烯组合物颗粒剂。
实施例2
一种头孢布烯组合物，包括质量比为5:1的头孢布烯和精胺。
包含该头孢布烯组合物的颗粒剂，包括如下质量的组分：
头孢布烯6g、精胺1.2g、碳酸氢钠0.4g、维生素C 9g、微晶纤维素22g、硬脂酸镁0.4g、蔗糖11g、糊精50g。
所述头孢布烯组合物颗粒剂的制备方法，包括以下步骤：
a、按质量比将头孢布烯、精胺、碳酸氢钠、维生素C、微晶纤维素、硬脂酸镁、蔗糖和糊精混合均匀，得到混合物；
b、将混合物研磨粉粹过100目筛，得到混合粉末；
c、采用离心造粒技术将混合粉末制备成粒径为0.3mm的颗粒剂。
将得到的头孢布烯组合物颗粒剂进行分装，得到100包头孢布烯组合物颗粒剂。
实施例3
一种头孢布烯组合物，包括质量比为10:1的头孢布烯和亚精胺。
包含该头孢布烯组合物的颗粒剂，包括如下质量的组分：
头孢布烯8g、亚精胺0.8g、碳酸氢钠0.5g、维生素C 10g、微晶纤维素25g、硬脂酸镁0.5g、蔗糖12g和糊精43.2g。
所述头孢布烯组合物颗粒剂的制备方法，包括以下步骤：
a、按质量比将头孢布烯、亚精胺、碳酸氢钠、维生素C、微晶纤维素、硬脂酸镁、蔗糖和糊精混合均匀，得到混合物；
b、将混合物研磨粉粹过100目筛，得到混合粉末；
c、采用离心造粒技术将混合粉末制备成粒径为0.3mm的颗粒剂。
将得到的头孢布烯组合物颗粒剂进行分装，得到100包头孢布烯组合物颗粒剂。
对比例1
用等量的酪胺代替实施例1中的精胺，得到头孢布烯组合物和包含该头孢布烯组合物的颗粒剂，颗粒剂的制备方法与实施例1相同，分装得到100包头孢布烯组合物颗粒剂。
将实施例1-3和对比例1得到的头孢布烯组合物进行体外抗菌检测，实施例1-3的头孢布烯组合物对大肠杆菌、化脓性链球菌、肺炎链球菌、无乳链球菌、流感嗜血杆菌、副流感杆菌、卡他莫拉菌、克雷白杆菌、各种变形杆菌以及铜绿假单胞菌都具有非常强的抗菌活性，其对上述菌体的MIC90(90％范围的最小抑菌浓度)值≤0.5mg/L；对比例1的头孢布烯组合物对铜绿假单胞菌的MIC90值≤1mg/L，对上述其它菌体的MIC90值≤0.8mg/L。
在腹腔感染的小鼠模型中，实施例1-3的头孢布烯组合物颗粒剂对大肠杆菌、克雷白杆菌、奇异变形杆菌的ED50(半数有效量)值比先力腾(头孢布烯胶囊)减少1/4-1/5，对比文件1的头孢布烯组合物颗粒剂对大肠杆菌、克雷白杆菌、奇异变形杆菌的ED50(半数有效量)值与先力腾(头孢布烯胶囊)相当。
对实施例1-3和对比例1得到的头孢布烯组合物颗粒剂进行临床试验，每组试验通过对15名健康受试者分别用药500mg后，进行药代动力学参数检测，检测结果如下表：
有上述检测结果可知，本发明实施例1-3的头孢布烯组合物颗粒剂在临床用药过程中，短时间内，血液中药物可达到较高的浓度，加快药物作用时间，达到快速治疗的目的，同时AUC0-t和AUC0-∞的值差别不大，说明本药物极易被人体吸收，较少的药物用量即可达到良好的治疗效果。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换或改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.一种头孢布烯组合物，其特征在于：包括质量比为3-10:1的头孢布烯和脂肪族生物胺。
2.如权利要求1所述的头孢布烯组合物，其特征在于：所述生物胺为精胺或亚精胺。
3.包含权利要求1-2任一项所述的头孢布烯组合物的颗粒剂，其特征在于：包括如下质量百分比的组分：
头孢布烯4.5-8％、脂肪族生物胺0.8-1.5％、碳酸氢钠0.2-0.5％、抗氧化剂8-10％、崩解剂20-25％、润滑剂0.2-0.5％、调味剂10-12％和余量的填充剂。
4.如权利要求3所述的颗粒剂，其特征在于：所述抗氧化剂为维生素C。
5.如权利要求3所述的颗粒剂，其特征在于：所述崩解剂为微晶纤维素。
6.如权利要求3所述的颗粒剂，其特征在于：所述润滑剂为硬脂酸镁。
7.如权利要求3所述的颗粒剂，其特征在于：所述调味剂为蔗糖。
8.如权利要求3所述的颗粒剂，其特征在于：所述填充剂为糊精或淀粉。
9.如权利要求3所述的颗粒剂，其特征在于：所述各组分的粒径≤0.15mm。
10.权利要求3所述的颗粒剂的制备方法，其特征在于：至少包括以下步骤：
a、按质量比将头孢布烯、生物胺、碳酸氢钠、抗氧化剂、崩解剂、润滑剂、调味剂和填充剂混合均匀，得到混合物；
b、将混合物研磨粉粹过100目筛，得到混合粉末；
c、将混合粉末制备成粒径为0.3-0.4mm的颗粒剂。
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