CN107149688A - 透明质酸类产品的无菌生产方法 - Google Patents

透明质酸类产品的无菌生产方法 Download PDF

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CN107149688A
CN107149688A CN201710289385.1A CN201710289385A CN107149688A CN 107149688 A CN107149688 A CN 107149688A CN 201710289385 A CN201710289385 A CN 201710289385A CN 107149688 A CN107149688 A CN 107149688A
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hyalomitome acids
hyaluronic acid
acids product
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CN107149688B (zh
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李秀华
吴兆华
沈荣军
宫慧玲
杨友仁
吴克鹏
刘玲
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Nanjing Hua Kai Biotechnology Co Ltd
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Abstract

本发明公开了一种透明质酸类产品的无菌生产方法，其特征在于：在透明质酸类产品中加入0.01％‑0.5％wt的防腐剂后进行辐照，辐照剂量为6‑10kGy。本发明通过控制生产原辅料、水、环境、包材，在产品中加入适量防腐剂，使用较低剂量的钴60辐照即可达到无菌标准，可防止大分子量透明质酸降解，保持透明质酸的分子量在合理配比范围内，提高产品质量水平。

Description

透明质酸类产品的无菌生产方法
技术领域
本发明涉及一种透明质酸类产品的无菌生产方法，属于医疗器械生产领域。
背景技术
国家食品药品监督管理总局国产器械数据库中共有137项关于透明质酸类产品，其中敷料类有15项。其中透明质酸敷料类无菌产品均采用钴60辐照灭菌。根据ISO11137标准，透明质酸敷料类无菌产品无菌程度应达到10-6，为达到该标准，需使用大于20kGy的辐照剂量。因分子量不同，透明质酸作用于皮肤的作用是不同的，大分子量的透明质酸具有良好的保湿作用和抗炎作用，但因透明质酸由D-葡萄糖醛酸和N-乙酰氨基葡萄糖以β-1,3和β1,4糖苷键反复交替而成的链状高分子粘多糖，在大剂量辐照产生的γ射线作用下会产生分子量降低，粘度下降等现象，大分子量透明质酸会被降解为小分子，进而影响透明质酸对浅表创面的作用，使产品的效果下降。
发明内容
本发明的目的在于提供一种可防止大分子量透明质酸降解的透明质酸类产品的无菌生产方法。
本发明的目的通过以下技术方案实现：
一种透明质酸类产品的无菌生产方法，在透明质酸类产品中加入0.01％-0.5％wt的防腐剂后进行辐照，辐照剂量为6-10kGy。
优选的，所述防腐剂为山梨酸钾、苯甲酸钠或尼泊金酯类。
优选的，所述透明质酸类产品为透明质酸敷料、透明质酸凝胶或透明质酸营养液。
优选的，其步骤包括：
A、对原辅料的pH值、干物质含量、微生物限度进行检测，选择达标的原辅料；
B、包材在使用前先进行辐照灭菌；
C、原辅料及包材的外包装在进入洁净车间前用湿布进行擦拭，然后用75％酒精擦拭，最后紫外灯照射后脱包；
D、生产透明质酸类产品，生产过程中加入山梨酸钾和苯甲酸钠，使用的生产用水先用两层滤膜除菌，生产车间为万级洁净车间，在灌装区使用百级层流罩，车间定期进行臭氧熏蒸和甲醛熏蒸；
E、用6-10kGy的剂量对产品进行辐照消毒。
优选的，紫外灯照射时长不少于30min。
优选的，两层滤膜分别为0.45μm和0.22μm。
本发明通过控制生产原辅料、水、环境、包材，在产品中加入适量防腐剂，使用较低剂量的钴60辐照即可达到无菌标准，可防止大分子量透明质酸降解，保持透明质酸的分子量在合理配比范围内，提高产品质量水平。
具体实施方式
实施例1
一种质量比为0.15％的透明质酸钠敷料的无菌生产方法，其步骤包括：
A、对原辅料的pH值、干物质含量、微生物限度进行检测，选择达标的原辅料，细菌总数应低于1000cfu/g，霉菌应低于100cfu/g；
B、包材在使用前先进行辐照灭菌，包材灭菌剂量根据初始微生物判定，标准依据iso11137.也就是先检查包材初始微生物有多少，然后查标准，订剂量；
C、原辅料及包材的外包装在进入洁净车间前用湿布进行擦拭，然后用75％酒精擦拭，最后紫外灯照射30min后脱包；
D、在生产过程中加入0.5％wt的山梨酸钾，使用的生产用水为无菌水，通过在制水系统加入两层滤膜，其中一层为0.45μm，一层为0.22微米，来对纯净水进行过滤除菌，生产车间为万级洁净车间，在灌装区使用百级层流罩，车间定期进行臭氧熏蒸和甲醛熏蒸；
E、用6kGy的剂量对产品进行辐照消毒，经检测，生产的透明质酸钠敷料粘度为200mpa.s。抽取产品进行无菌试验，产品符合ISO11137标准的无菌要求。
实施例2
一种透明质酸凝胶的无菌生产方法，透明质酸的添加量为0.01％-5％，辅料为卡波姆，添加量为0.1％-10％，其步骤包括：
A、对原辅料的pH值、干物质含量、微生物限度进行检测，选择达标的原辅料，细菌总数应低于1000cfu/g，霉菌应低于100cfu/g；
B、包材在使用前先进行辐照灭菌，包材灭菌剂量根据初始微生物判定，标准依据iso11137，也就是先检查包材初始微生物有多少，然后查标准，订剂量；
C、原辅料及包材的外包装在进入洁净车间前用湿布进行擦拭，然后用75％酒精擦拭，最后紫外灯照射40min后脱包；
D、在生产过程中加入0.01％wt的苯甲酸钠，使用的生产用水为无菌水，通过在制水系统加入两层滤膜，其中一层为0.45μm，一层为0.22微米，来对纯净水进行过滤除菌，生产车间为万级洁净车间，在灌装区使用百级层流罩，车间定期进行臭氧熏蒸和甲醛熏蒸；
E、用10kGy的剂量对产品进行辐照消毒。抽取产品进行无菌试验，产品符合ISO11137标准的无菌要求。
实施例3
一种透明质酸营养液的无菌生产方法，透明质酸添加比例为0.01％-5％，辅料可添加胶原蛋白等其他营养成分配合，其步骤包括：
A、对原辅料的pH值、干物质含量、微生物限度进行检测，选择达标的原辅料，细菌总数应低于1000cfu/g，霉菌应低于100cfu/g；
B、包材在使用前先进行辐照灭菌，包材灭菌剂量根据初始微生物判定，标准依据iso11137，也就是先检查包材初始微生物有多少，然后查标准，订剂量；
C、原辅料及包材的外包装在进入洁净车间前用湿布进行擦拭，然后用75％酒精擦拭，最后紫外灯照射40min后脱包；
D、在生产过程中加入0.06％wt的尼泊金乙酯钠，使用的生产用水为无菌水，通过在制水系统加入两层滤膜，其中一层为0.45μm，一层为0.22微米，来对纯净水进行过滤除菌，生产车间为万级洁净车间，在灌装区使用百级层流罩，车间定期进行臭氧熏蒸和甲醛熏蒸；
E、用8kGy的剂量对产品进行辐照消毒，经检测，生产的透明质酸凝胶粘度为100-200mpa.s。抽取产品进行无菌试验，产品符合ISO11137标准的无菌要求。

Claims (6)

1.一种透明质酸类产品的无菌生产方法，其特征在于：在透明质酸类产品中加入0.01％-0.5％wt的防腐剂后进行辐照，辐照剂量为6-10kGy。
2.根据权利要求1所述的透明质酸类产品的无菌生产方法，其特征在于：所述防腐剂为山梨酸钾、苯甲酸钠或尼泊金酯类。
3.根据权利要求2所述的透明质酸类产品的无菌生产方法，其特征在于：所述透明质酸类产品为透明质酸敷料、透明质酸凝胶或透明质酸营养液。
4.根据权利要求1-3中任一项所述的透明质酸类产品的无菌生产方法，其步骤包括：
A、对原辅料的pH值、干物质含量、微生物限度进行检测，选择达标的原辅料；
B、包材在使用前先进行辐照灭菌；
C、原辅料及包材的外包装在进入洁净车间前用湿布进行擦拭，然后用75％酒精擦拭，最后紫外灯照射后脱包；
D、生产透明质酸类产品，生产过程中加入山梨酸钾和苯甲酸钠，使用的生产用水先用两层滤膜除菌，生产车间为万级洁净车间，在灌装区使用百级层流罩，车间定期进行臭氧熏蒸和甲醛熏蒸；
E、用6-10kGy的剂量对产品进行辐照消毒。
5.根据权利要求4所述的透明质酸类产品的无菌生产方法，其特征在于：紫外灯照射时长不少于30min。
6.根据权利要求4所述的透明质酸类产品的无菌生产方法，其特征在于：两层滤膜分别为0.45μm和0.22μm。
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