肉毒抗毒素的现状和发展趋势概述

张华捷 杨英超 马霄

张华捷, 杨英超, 马霄. 肉毒抗毒素的现状和发展趋势概述[J]. 疾病监测. doi: 10.3784/jbjc.202012300448
引用本文: 张华捷, 杨英超, 马霄. 肉毒抗毒素的现状和发展趋势概述[J]. 疾病监测. doi: 10.3784/jbjc.202012300448
Zhang Huajie, Yang Yingchao, Ma Xiao. Current status and development trend of botulinum antitoxin[J]. Disease Surveillance. doi: 10.3784/jbjc.202012300448
Citation: Zhang Huajie, Yang Yingchao, Ma Xiao. Current status and development trend of botulinum antitoxin[J]. Disease Surveillance. doi: 10.3784/jbjc.202012300448

肉毒抗毒素的现状和发展趋势概述

doi: 10.3784/jbjc.202012300448
基金项目: 国家重大新药创制(No. 2018ZX09738–005)
详细信息
    作者简介:

    张华捷,男,副研究员,博士,主要从事生物毒素、抗毒素类生物制品的质量控制工作,Email:zhanghj@nifdc.org.cn

    杨英超,男,副研究员,博士,主要生物毒素、疟疾等生物制品的质量控制工作,Email:yangyc@nifdc.org.cn

    通讯作者:

    马霄,Tel: 010–53851695,Email:maxiao412@sina.cn

  • 中图分类号: R211; R378.8+3

Current status and development trend of botulinum antitoxin

Funds: This study was supported by the State Project For Essential Drug Research and Development (No. 2018ZX09738–005)
More Information
  • 摘要: 肉毒毒素是已知毒性最强的生物毒素,其引起的肉毒中毒时有发生,甚至会致死。 肉毒抗毒素是目前唯一的肉毒中毒特异性治疗手段,尽早使用肉毒抗毒素对提高肉毒中毒的治疗效果具有重要意义。 目前国内外批准上市的肉毒抗毒素基本都是马源性制剂,存在引起过敏反应等不良反应的风险。 本文对肉毒抗毒素的国内外现状、生产工艺、质量控制和临床应用等现状进行了阐述,并对其应用前景进行了展望。
  • 表  1  当前全球肉毒抗毒素种类

    Table  1.   Category of botulinum antitoxins used in the world

      产 品毒素型别生产厂家效价(1∶)参考剂量
    7价肉毒抗毒素
    (HBAT,马源)
     A、B、C、D、E、F、G Cangene(加拿大)  A型∶4500
      B型∶3300
      C型∶3000
      D型∶600
      E型∶5100
      F型∶3000
      G型∶600
     1瓶(17岁以上)20%~ 100%成人剂量(1~17岁) 10%成人剂量(1岁以下)
    3价肉毒抗毒素(马源) A、B、E Behring(德国)  A型∶187500
      B型∶125000
      E型∶12500
     2瓶
    3价肉毒抗毒素(马源) A、B、E Biomed(波兰)  A型∶5000
      B型∶5000
      E型∶1000
     1~5瓶
    3价肉毒抗毒素(马源) A、B、E Instituto Butantan(巴西)  A型∶7500
      B型∶5500
      E型∶5000
     1瓶
    2价肉毒抗毒素(马源) A、B 阿根廷公共卫生部  A型∶7500
      B型∶5500
     1瓶
    4价肉毒抗毒素(马源) A、B、E、F 千叶血清(日本)  A型∶10000
      B型∶10000
      E型∶10000
      F型∶4000
     1~3瓶
    肉毒人免疫球蛋白
    (Baby-BIG,人源)
     A、B 加利福尼亚公共卫生部(美国)  A型∶15
      B型∶4 IU/mL
     1 mL/kg体重(1岁以下)
    下载: 导出CSV

    表  2  中国药典与欧洲药典肉毒抗毒素成品质量标准的比较

    Table  2.   Product quality standards of botulinum antitoxins in “Chinese Pharmacopoeia” and “European Pharmacopoeia”

      检测项目《中国药典》2020年版三部欧洲药典9.0
    鉴别试验(动物中和试验或免疫双扩散) 应能中和肉毒毒素  同前
    鉴别试验(免疫双扩散或ELISA) 应与马IgG抗体反应呈阳性  同前
    外观 应为无色或淡黄色的澄明液体,无异物  基本相同
    渗透压摩尔浓度(mOsmol/Kg) 应符合规定  ≥240
    装量(mL/瓶) 应不低于标示量  同前
    pH值 6.0~7.0  应符合规定a
    蛋白质含量(g/L) ≤170  标示量的90%~110%,且≤100
    氯化钠含量(g/L) 7.5~9.5  未作规定
    硫酸铵含量(g/L) ≤1.0  未作规定
    间甲酚含量(g/L) ≤2.5  同前
    甲苯残留量 ≤0.089%(如添加)  未作规定
    分子大小分布 完整IgG与聚合物的含量之和应不高于10%  应符合规定a
    白蛋白检查 应不含或仅含痕量白蛋白迁移率的蛋白质成分  不得高于规定限量,且≤3%
    F(ab′)2含量 ≥60%  与参比品对比,待检产品应无多余的电泳条带
    IgG含量 ≤5%  未作规定
    抗体效价(IU/mL) A型≥2000;B型≥2000;C型≥500;D型≥2000; E型≥1000;F型≥500  A型≥500;B型≥500;E型≥50;
    比活性(IU/g蛋白) A型≥20000;B型≥20000;C型≥5000;D型≥20000; E型≥10000;F型≥5000  未作规定
    无菌检查 应无菌生长  同前
    热原检查 每只家兔每kg体重注射3.0 mL,应符合规定  每只家兔每kg体重注射1.0 mL/kg,应符合规定
    异常毒性检查
    (小鼠、豚鼠)
     观察期内,动物应全部健存,且无异常反应,到期  时体重应增加  未作规定
      注:a. 指该项目只需符合生产厂家自己制定的企业标准即可,欧洲药典对此不作统一要求
    下载: 导出CSV
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出版历程
  • 收稿日期:  2020-12-30
  • 网络出版日期:  2021-04-29

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