注射用头孢曲松钠溶血性、局部刺激性和过敏反应一致性评价

目的 采用溶血性、血管刺激性试验、肌肉刺激性试验和全身主动过敏试验（ASA）检测受试物注射用头孢曲松钠与市售对照品（罗氏芬）局部毒性和过敏性，进行一致性评价。方法 分别采用肉眼观察法和分光光度法进行体外溶血性试验；以受试物或市售对照品临床iv最高浓度（93 mg·mL^-1）连续4 d耳缘静脉推注给药进行新西兰兔血管刺激性试验；以临床im最高浓度（238 mg·mL^-1，给药体积1 mL）连续4 d右后肢股四头肌im给药进行新西兰兔肌肉刺激性试验；采用传统豚鼠ASA进行过敏性试验，致敏剂量分别0.5、1.5 mg·kg^-1，激发剂量分别为1.0、3.0 mg·kg^-1。结果 肉眼观察法和分光光度法均显示受试物及市售对照品无体外溶血和红细胞凝聚作用；临床等效剂量的受试物及市售对照品均无血管刺激性；最大给药浓度的受试物及市售对照品在末次给药后72 h均有重度肌肉刺激性，恢复期结束时受试物组与市售对照品组动物注射部位肌肉均见纤维化等正常修复现象；受试物及市售对照品均可见弱阳性全身致敏作用，结果具有一致性。结论 受试物注射用头孢曲松钠与市售对照品局部毒性反应和过敏反应情况基本一致，可用于临床。

Consistency evaluation of hemolytic, local irritant and allergic reactions of Ceftriaxone Sodium for Injection

Objective Hemolysis test, vascular irritation test, muscle irritation test and active systemic anaphylaxis test (ASA) were used to observe the local toxicity and anaphylaxis of Ceftriaxone Sodium for Injection and Rochefen, the commercial reference substance, and to evaluate the consistency. Methods The hemolysis tests were performed by naked eye observation and spectrophotometer method. The vascular irritation test of New Zealand rabbits was performed by auricular vein administration with maximum concentration (93 mg·mL^-1) for clinical intravenous administration of test substance or commercially available control substance for four days. The muscle irritation test of New Zealand rabbits was performed by im injection of quadriceps femoris of right hindlimb for four days with highest clinical concentration of intramuscular injection (238 mg·mL^-1, administration volume 1 mL). The active systemic anaphylaxis test was performed by traditional ASA test of guinea pigs. The sensitization doses were 0.5 and 1.5 mg·kg^-1, and the excitation doses were 1.0 and 3.0 mg·kg^-1, respectively. Results Both naked eye observation and spectrophotometer method showed that the test substance and Rochefen had no hemolysis and erythrocyte aggregation in vitro. The clinical equivalent dose of the test substance group and the Rochefen group had no vascular irritation. The maximum administration concentration of the test substance and Rochefen had severe muscle irritation 72 h after the last administration and at the end of the recovery period, normal repair phenomena such as fibrosis were observed in the muscles at the injection site of the animals in the test substance group and the commercial reference substance group. The ASA test showed the weak positive systemic sensitization consistently between the test substance groups and the Rochefen groups. Conclusion The local toxicity and anaphylaxis of ceftriaxone sodium for injection is basically the same as Rochefen which can be used in clinic.