CN105412896B - 一种避免安神补脑液中维生素b1含量下降的方法 - Google Patents

一种避免安神补脑液中维生素b1含量下降的方法 Download PDF

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CN105412896B
CN105412896B CN201610006578.7A CN201610006578A CN105412896B CN 105412896 B CN105412896 B CN 105412896B CN 201610006578 A CN201610006578 A CN 201610006578A CN 105412896 B CN105412896 B CN 105412896B
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张贵民
赵震震
于龙环
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Abstract

本发明提供一种防止安神补脑液中维生素B1含量下降的方法。安神补脑液中含有的维生素B1在灭菌过程中及长期放置过程中含量逐渐下降，使该药物疗效逐渐下降。本发明优化了安神补脑液的pH值，并采用稳定剂甲硫氨基酸、L‑半胱氨酸、精氨酸等增加了药物的稳定性，避免了维生素B1含量的下降。经过本方法制备的安神补脑液，维生素B1含量在三年有效期内可以维持在90％以上，远远优于药典标准的80％。

Description

一种避免安神补脑液中维生素B1含量下降的方法
技术领域
本发明涉及一种避免安神补脑液中维生素B1含量下降的方法，属于药物制剂领域。
背景领域
安神补脑液处方中含有鹿茸、制何首乌、淫羊藿、干姜、甘草、大枣及维生素B1，其中维生素B1可以增进食欲，维持正常的神经功能活动，对安神补脑液的药效其重要的作用。由于安神补脑液中糖粉含量大，容易滋生细菌，影响药物安全性，因此制备工艺中包含高温灭菌过程。在灭菌过程中，维生素B1含量下降明显，另外安神补脑液长期放置期间维生素B1含量也有所下降，影响药物的质量与疗效。在安神补脑液制备与放置过程中，维生素B1含量下降情况见下表：
批次 灭菌前 灭菌后 6个月 12个月 24个月 36个月
1 105.3％ 101.2％ 98.2％ 93.6％ 82.5％ 75.1％
2 105.4％ 101.8％ 97.9％ 92.5％ 83.2％ 74.6％
3 106.2％ 102.1％ 98.4％ 94.5％ 85.2％ 75.4％
2015版中国药典规定，安神补脑液中维生素B1含量范围是80％-120％，上表中维生素B1含量灭菌前后变化较大，且长期放置24个月含量接近下限，36月后维生素B1含量低于下限80％，药品不合格。
关于如何避免安神补脑液中维生素B1含量下降，目前未见专利报道。
发明内容
经过多次试验，本发明提供一种避免安神补脑液中维生素B1含量下降的方法，具体如下：一种避免安神补脑液中维生素B1含量下降的方法，具体为调节药液pH及添加稳定剂。药液的pH调节为2.0-3.5，优化为2.5-3.2。添加的稳定剂为甲硫氨基酸、L-半胱氨酸、L-精氨酸中的至少一种，其用量按照质量体积比为0.05％-0.25％，优选为0.1％-0.2％。
本发明所用稳定剂甲硫氨基酸、L-半胱氨酸、L-精氨酸均为人体中含有的氨基酸，日常食品中也大量存在，可以为人体吸收利用，在本品用量范围内无明显毒副作用。按照本方法改良后的安神补脑液维生素B1含量稳定性明显增加，药液放置36个月药品仍合格，提高了药品质量和疗效。
维生素B1注射液已被中国药典收载，市售产品pH在4.0左右，在该pH范围下维生素B1比较稳定，注射液可高温灭菌。但是安神补脑液中成分众多，对维生素B1稳定性产生影响的因素也比较难以分析，实验证明，pH为4.0不能保证维生素B1在安神补脑液中的稳定性。经过多次试验，我们发现，pH下调至2.0-3.5可以显著增加安神补脑液中维生素B1的稳定性，使其100℃高温灭菌30分钟含量下降范围在可接受范围内。但是仅仅调节pH无法保证安神补脑液长期放置过程中维生素B1含量的稳定性。
通过分析维生素B1的结构和可能影响其长期放置稳定性的因素，我们测试了数十种稳定剂，其中包括抗氧剂、螯合剂、增溶剂及成盐、络合等方法改变其特性，其中一些抗氧剂及螯合剂虽能提高其稳定性，但是往往对高温灭菌及某些中药成分过于敏感，会引起溶液析出、混浊等难以预料的质量问题，某些辅料也会存在安全性问题等。最终意外发现甲硫氨基酸、L-半胱氨酸、L-精氨酸三种稳定剂及其用量，这三种稳定剂不仅可以保证安神补脑液长期放置过程中维生素B1含量的稳定性，还会对其耐受高温灭菌产生一定的帮助。
调节pH及加入稳定剂同时使用，可以使安神补脑液中维生素B1可以耐受高温灭菌的同时也可以在长期放置过程中含量保持稳定，不仅提高了产品质量也提高了其安全性。
具体实施方式：
以下通过实施例进一步说明本发明，但这些实施例不以任何方式限制本发明。检测方法和标准执行2010版中国药典。
实施例1
按照普通工艺制备安神补脑液1L，加入甲硫氨基酸0.5g，用0.1M盐酸溶液调节pH至2.0。滤过，100℃灭菌30分钟即得。
实施例2
按照普通工艺制备安神补脑液1L，加入L-半胱氨酸1.0g，甲硫氨基酸0.5g，用0.1M盐酸溶液调节pH至2.8。滤过，100℃灭菌30分钟即得。
实施例3
按照普通工艺制备安神补脑液1L，加入L-精氨酸2.5g，用0.1M盐酸溶液调节pH至3.5。滤过，100℃灭菌30分钟即得。
实施例4
按照普通工艺制备安神补脑液1L，加入甲硫氨基酸2.0g，用0.1M盐酸溶液调节pH至3.0。滤过，100℃灭菌30分钟即得。
对比实施例1
按照普通工艺制备安神补脑液1L，滤过，100℃灭菌30分钟即得。
对比实施例2
按照普通工艺制备安神补脑液1L，用0.1M盐酸溶液调节pH至2.3。滤过，100℃灭菌30分钟即得。
对比实施例3
按照普通工艺制备安神补脑液1L，加入甲硫氨基酸0.5g。滤过，100℃灭菌30分钟即得。
稳定性试验1：灭菌前后维生素B1含量变化情况(100℃蒸汽灭菌30分钟)
Figure BDA0000901652610000031
稳定性试验2：长期放置维生素B1含量情况(室温、避光保存)
0个月 6个月 12个月 24个月 36个月
实施例1 99.8％ 98.5％ 97.6％ 95.2％ 93.1％
实施例2 100.2％ 98.9％ 97.5％ 96.3％ 94.6％
实施例3 99.7％ 98.6％ 97.3％ 95.2％ 93.4％
实施例4 100.1％ 99.6％ 98.6％ 96.8％ 93.9％
对比实施例1 95.2％ 90.5％ 85.7％ 79.9％ 70.8％
对比实施例2 98.6％ 93.5％ 87.8％ 83.4％ 76.7％
对比实施例3 96.7％ 95.6％ 93.4％ 91.7％ 89.1％
由稳定性试验1和稳定性试验2结果可知，经本发明方法改进过后，安神补脑液中维生素B1含量在灭菌前后及长期放置过程中稳定性均有大幅提高。本发明有效避免了安神补脑液高温灭菌及长期放置过程中维生素B1含量的下降，提高了产品质量和疗效。

Claims (7)

1.一种避免安神补脑液中维生素B1含量下降的方法，其特征在于，调节药液pH为2.0-3.5及添加稳定剂；所述稳定剂为甲硫氨基酸、L-半胱氨酸、精氨酸中的至少一种；所述稳定剂用量按照质量体积比为0.05%-0.25%。
2.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，调节药液的pH为2.5-3.2。
3.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，调节药液的pH为3.0。
4.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，所述稳定剂为L-半胱氨酸或/和甲硫氨基酸。
5.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，稳定剂为L-精氨酸。
6.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，添加的稳定剂用量按照质量体积比为0.1%-0.2%。
7.如权利要求1所述的避免安神补脑液中维生素B1含量下降的方法，其特征在于，添加的稳定剂用量按照质量体积比为0.15%。
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