Gartlan M G, Hoffman H T
Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City 52242.
Otolaryngol Head Neck Surg. 1993 Feb;108(2):135-40. doi: 10.1177/019459989310800205.
Laryngeal injection of botulinum toxin type A is currently the most effective method of treating spasmodic dysphonia. Botox, a crystalline preparation of botulinum toxin type A, is the only toxin approved for clinical use in the United States and is packaged in vials of 100 mouse units (MU). One MU corresponds to the calculated median lethal intraperitoneal dose (LD50) injected in mice. The logistic problems arising from the need for repeated injections of small amounts of Botox have been addressed by several investigators by refreezing unused Botox for use at a later time. Although FDA labeling recommends that Botox not used within 4 hours of reconstitution be discarded, data regarding degradation in potency after reconstitution and refreezing are not currently available. Using the LD50 Swiss-Webster mouse bioassay and statistical analysis by the Probit procedure, a 69.8% loss in potency was found when Botox was reconstituted, immediately frozen, and then assayed 2 weeks later (p < 0.0001). Statistically significant degradation in potency was seen after refrigerator storage for 12 hours (p = 0.007), but not for 6 hours (p = 0.16). Clinical implications regarding the dilution, use, and storage of Botox are discussed.
目前，喉内注射A型肉毒杆菌毒素是治疗痉挛性发音障碍最有效的方法。保妥适（Botox）是A型肉毒杆菌毒素的结晶制剂，是美国唯一获批用于临床的毒素，每瓶包装为100鼠单位（MU）。1个MU相当于给小鼠腹腔注射计算得出的半数致死剂量（LD50）。一些研究人员通过将未使用的保妥适重新冷冻以便日后使用，解决了因需要反复注射少量保妥适而产生的后勤问题。尽管美国食品药品监督管理局（FDA）的标签建议丢弃复溶后4小时内未使用的保妥适，但目前尚无关于复溶和重新冷冻后效力下降的数据。采用LD50瑞士韦伯斯特小鼠生物测定法并通过概率单位法进行统计分析，发现保妥适复溶后立即冷冻、2周后进行测定时效力损失了69.8%（p < 0.0001）。冷藏保存12小时后效力出现了具有统计学意义的下降（p = 0.007），但6小时时未出现（p = 0.16）。文中讨论了有关保妥适稀释、使用和保存的临床意义。
