CN112426359A - 双室袋含糖林格液及其制备方法 - Google Patents
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Abstract
本发明属于医药制造技术领域,具体涉及一种双室袋含糖林格液及其制备方法。所述的双室袋含糖林格液,包含由无水葡萄糖、pH调节剂、注射用水组成的左室液和由氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠、pH调节剂、注射用水组成的右室液,左室液用pH调节剂调节pH值至3.0~4.0,右室液用pH调节剂调节pH值至5.9~7.0。本发明含糖林格液采用双室袋包装,既能够将葡萄糖与无机盐分开,又能让葡萄糖处于一个更合适的酸碱环境中,具有杂质少、稳定性好的特点,能够更好的应用于临床;其制备方法,科学合理、简单易行。
Description
技术领域
本发明属于医药制造技术领域,具体涉及一种双室袋含糖林格液及其制备方法。
背景技术
含糖林格液主要用于循环血量及组织间液减少时的细胞外液的补充及纠正代谢性酸中毒。
葡萄糖高温易降解,在灭菌过程中,葡萄糖降解产生大量的葡萄糖降解产物,包含5-羟甲基糠醛、果糖及大量的二级降解产物(3-脱氧葡糖醛酮、葡萄糖醛酮、3-脱氧半乳糖醛酮、3,4二脱氧葡萄糖、3,4-双脱氧葡萄糖酮-3-烯等细胞毒性物质)。不合适的pH环境及无机盐的存在,均会催化葡萄糖在灭菌过程中的降解,产生的大量葡萄糖降解产物,严重影响产品质量及患者的用药安全。因此,制备含糖林格液时怎样避免葡萄糖过度降解是关键。
相关文献表明,葡萄糖在强酸性水溶液中脱水形成5-羟甲基糠醛,在弱碱性条件下可产生大量的果糖,在灭菌过程中可进一步转化、降解成大量的葡萄糖降解产物。
发明内容
本发明的目的是提供一种双室袋含糖林格液,采用双室袋包装,既能够将葡萄糖与无机盐分开,又能让葡萄糖处于一个更合适的酸碱环境中,具有杂质少、稳定性好的特点,能够更好的应用于临床;本发明同时提供其制备方法,科学合理、简单易行。
本发明的目的通过以下技术方案实现:
所述的双室袋含糖林格液,包含由无水葡萄糖、pH调节剂、注射用水组成的左室液和由氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠、pH调节剂、注射用水组成的右室液,左室液用pH调节剂调节pH值至3.0~4.0,右室液用pH调节剂调节pH值至5.9~7.0。
所述的含糖林格液的包装形式为双室袋。
所述的左室液中,pH调节剂为盐酸、冰醋酸或枸橼酸中的一种或几种,优选盐酸。
所述的右室液中,pH调节剂为氢氧化钠或氢氧化钾中的一种或两种,优选氢氧化钠。
本发明所述的双室袋含糖林格液的制备方法,包括如下步骤:左室液与右室液分别于配制罐1、配制罐2中配制,调节pH值合格后,分别灌装至双室袋左室与右室,然后灭菌、灯检,包装即得。
优选地,所述的双室袋含糖林格液的制备方法,具体包括如下步骤:
1)配制罐1中加入左室液80%处方量的注射用水,配制罐2中加入右室液80%处方量的注射用水;
2)配制罐1中注射用水冷却至50~70℃时,加入按处方量称取的无水葡萄糖,完全溶解后加注射用水至全量,用pH调节剂调节pH值至3.0~4.0;
3)配制罐2加入按处方量称取的氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠,完全溶解后加注射用水至全量,用pH调节剂调节pH值至5.9~7.0;
4)左室液、右室液分别经两级过滤过滤后,灌装至双室袋的左室与右室中,灭菌,检漏、灯检,包装即得。
其中:
所述的两级过滤,一级为0.45μm的微孔除菌滤膜、二级为0.22μm的微孔除菌滤膜。
所述的灭菌具体为:121℃水浴灭菌12分钟。
所述的左室液、右室液的体积比为1:1。
与现有技术相比,本发明的有益效果如下:
1、本发明中的双室袋含糖林格液采用双室袋包装,既可以将葡萄糖与无机盐分开,又可以让葡萄糖处于一个更合适的酸碱环境中,大大降低了灭菌过程中葡萄糖的降解,具有杂质少、稳定性好的特点,保证了产品质量和患者的用药安全,可以更好的应用于临床,具有更明显的优势。
2、本发明的制备方法,科学合理、简单易行。
具体实施方式
下面结合具体实施方式对本发明作进一步说明。
实施例1
处方:
左室液 | |
无水葡萄糖 | 10.00kg |
盐酸 | 适量 |
制成500L |
制备方法:
1)配制罐1中加入左室液80%处方量的注射用水,配制罐2中加入右室液80%处方量的注射用水。
2)配制罐1中注射用水冷却至55℃时,加入按处方量称取的无水葡萄糖,完全溶解后加注射用水至全量,用盐酸调节pH值至3.1。
3)配制罐2加入按处方量称取的氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠,完全溶解后加注射用水至全量,用氢氧化钠调节pH值至6.6。左室液、右室液分别经两级过滤(一级为0.45μm的微孔除菌滤膜、二级为0.22μm的微孔除菌滤膜)过滤后灌装至双室袋的左室与右室中,再经121℃水浴灭菌12分钟,检漏、灯检,包装即得。
实施例2
处方:
左室液 | |
无水葡萄糖 | 10.00kg |
盐酸 | 适量 |
制成500L |
右室液 | |
葡萄糖酸钙 | 0.673kg |
氯化钠 | 6.370kg |
氯化钾 | 0.298kg |
氯化镁 | 0.203kg |
醋酸钠 | 3.402kg |
枸橼酸钠 | 0.588kg |
氢氧化钾 | 适量 |
制成500L |
制备方法:
1)配制罐1中加入左室液80%处方量的注射用水,配制罐2中加入右室液80%处方量的注射用水。
2)配制罐1中注射用水冷却至67℃时,加入按处方量称取的无水葡萄糖,完全溶解后加注射用水至全量,用盐酸调节pH值至3.8。
3)配制罐2加入按处方量称取的氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠,完全溶解后加注射用水至全量,用氢氧化钾调节pH值至6.2。左室液、右室液分别经两级过滤(一级为0.45μm的微孔除菌滤膜、二级为0.22μm的微孔除菌滤膜)过滤后灌装至双室袋的左室与右室中。经121℃水浴灭菌12分钟,检漏,灯检,包装即得。
对比例
处方:
无水葡萄糖 | 10.00kg |
葡萄糖酸钙 | 0.673kg |
氯化钠 | 6.370kg |
氯化钾 | 0.298kg |
氯化镁 | 0.203kg |
醋酸钠 | 3.402kg |
枸橼酸钠 | 0.588kg |
氢氧化钠 | 适量 |
制成1000L |
制备方法:
1)配制罐80%处方量的注射用水,加入按处方量称取的无水葡萄糖、氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠,完全溶解后加注射用水至全量,用盐酸调节pH值至6.0,经两级过滤(一级为0.45μm的微孔除菌滤膜、二级为0.22μm的微孔除菌滤膜)过滤后灌装。再经121℃水浴灭菌12分钟,检漏,灯检,包装即得。
对实施例和对比例制备的含糖林格液进行检测,测试结果见表1。采用的测试方法如下:
5-羟甲基糠醛:中国药典2015年版四部通则0401紫外-可见分光光度法在284nm的波长处测定。
有关物质:色谱条件与系统适用性试验:用磺化交联的苯乙烯二乙烯基苯共聚物为填充剂的强阳离子钙型交换柱(Waters Sugar-PakTMⅠ,6.5×300mm或分离效能相当的色谱柱);以水为流动相;流速为每分钟0.5ml;柱温为80℃;示差折光检测器,检测温度40℃。麦芽三糖和麦芽糖分离度不得小于1.3,其他相邻峰(除麦芽糖峰与异麦芽糖峰)之间的分离度不得小于1.5。取麦芽糖、异麦芽糖、麦芽三糖、果糖对照品各适量,精密称定,加水溶解并定量稀释制成每1ml中约含麦芽三糖20μg、麦芽糖20μg、异麦芽糖20μg和果糖500μg的混合对照品溶液;称取麦芽糖、异麦芽糖、麦芽三糖、果糖对照品各适量,精密称定,用本品溶解并定量稀释制成每1ml中约含麦芽三糖20μg、麦芽糖20μg、异麦芽糖20μg和果糖500μg的溶液,作为系统适用性溶液;取本品作为供试品溶液;精密量取供试品溶液1ml,置100ml量瓶中,用水稀释至刻度,摇匀,作为对照溶液。分别精密量取混合对照品溶液、供试品溶液、对照溶液各10μl,注入液相色谱仪,记录色谱图。供试品溶液中如有与已知杂质峰保留时间一致的色谱峰,按外标法以峰面积计算杂质含量;其他杂质按主成分自身对照法计算含量。
表1
注:双室袋包装产品需打开隔断,充分混合后检测。
Claims (10)
1.一种双室袋含糖林格液,其特征在于:包含由无水葡萄糖、pH调节剂、注射用水组成的左室液和由氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠、pH调节剂、注射用水组成的右室液,左室液用pH调节剂调节pH值至3.0~4.0,右室液用pH调节剂调节pH值至5.9~7.0。
2.根据权利要求1所述的双室袋含糖林格液,其特征在于:所述的左室液中,pH调节剂为盐酸、冰醋酸或枸橼酸中的一种或几种。
3.根据权利要求2所述的双室袋含糖林格液,其特征在于:所述的左室液中,pH调节剂为盐酸。
4.根据权利要求1所述的双室袋含糖林格液,其特征在于:所述的右室液中,pH调节剂为氢氧化钠或氢氧化钾中的一种或两种。
5.根据权利要求4所述的双室袋含糖林格液,其特征在于:所述的右室液中,pH调节剂为氢氧化钠。
6.一种权利要求1-5任一所述的双室袋含糖林格液的制备方法,其特征在于:包括如下步骤:左室液与右室液分别于配制罐1、配制罐2中配制,调节pH值合格后,分别灌装至双室袋左室与右室,然后灭菌、灯检,包装即得。
7.根据权利要求6所述的双室袋含糖林格液的制备方法,其特征在于:具体包括如下步骤:
1)配制罐1中加入左室液80%处方量的注射用水,配制罐2中加入右室液80%处方量的注射用水;
2)配制罐1中注射用水冷却至50~70℃时,加入按处方量称取的无水葡萄糖,完全溶解后加注射用水至全量,用pH调节剂调节pH值至3.0~4.0;
3)配制罐2加入按处方量称取的氯化钠、氯化钾、氯化镁、葡萄糖酸钙、醋酸钠、枸橼酸钠,完全溶解后加注射用水至全量,用pH调节剂调节pH值至5.9~7.0;
4)左室液、右室液分别经两级过滤过滤后,灌装至双室袋的左室与右室中,灭菌,检漏、灯检,包装即得。
8.根据权利要求7所述的双室袋含糖林格液的制备方法,其特征在于:所述的两级过滤,一级为0.45μm的微孔除菌滤膜、二级为0.22μm的微孔除菌滤膜。
9.根据权利要求7所述的双室袋含糖林格液的制备方法,其特征在于:所述的灭菌具体为:121℃水浴灭菌12分钟。
10.根据权利要求7所述的双室袋含糖林格液的制备方法,其特征在于:所述的左室液、右室液的体积比为1:1。
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