目的 检测重组人干扰素β-1a注射液的制剂安全性并探讨可能的影响因素。方法 分别以重组人干扰素β-1a注射液进行家兔肌肉和皮下刺激性试验、豚鼠主动全身过敏性试验、大鼠被动皮肤过敏性试验和体外溶血性试验,检测药物的局部刺激性、Ⅰ型过敏反应性和溶血作用。结果 pH 3.6的11、22 μg/kg重组人干扰素及其空白溶媒对家兔肌肉和皮肤黏膜具有轻度刺激作用,相应剂量下pH为4.3的重组干扰素及其空白溶媒对家兔组织无明显刺激作用;pH 3.5的5.5、22 μg/kg剂量下重组人干扰素及其空白溶媒对大鼠无被动致敏作用,对豚鼠主动致敏作用呈强阳性,辅料中不含人血清白蛋白的样品则对豚鼠无致敏作用;pH 3.5的重组人干扰素对家兔红细胞具有极轻度体外溶血作用,pH 4.5样品则无体外溶血和致红细胞凝聚作用。结论 pH值对重组人干扰素β-1a注射液刺激性和体外溶血性具有一定影响,应注意对其pH值的控制;干扰素对豚鼠致敏作用为辅料中人血清白蛋白所致,临床使用中对人产生致敏的可能性很小。重组人干扰素β-1a注射液制剂安全性较好。

Objective To test the preparation safety of recombinant human interferon β-1a injection and investigate probable influencing factors. Methods The study includes rabbit im and sc irritation test, guinea pigs active systemic anaphylaxis test (ASA), rat passive cutaneous anaphylaxis test (PCA), and hemolysis test of recombinant human interferon β-1a injection, and intends to investigate the drug's local irritation, type I allergy, and hemolysis. Results Recombinant human interferon (11 and 22 g/kg), and the blank solvent in pH 3.6 had mild stimulation on rabbit muscle, skin, and surrounding tissue, otherwise the corresponding dose for pH 4.3 recombinant interferon and its blank solvent had no stimulation on rabbit tissue. The passive sensitization was negative in the rats administered with 5.5 and 22 g/kg doses of pH 3.5 recombinant human interferon and blank solvent. Meanwhile the guinea pigs had strong positive initiative sensitization with the same doses of pH 3.5 recombinant human interferon which contained human serum albumin, and the human serum albumin free materials had not induced sensitization at all. Recombinant human interferon (pH 3.5) had very mild hemolysis to rabbit erythrocytes in vitro, but the pH 4.5 sample had no hemolysis and condensation effect in vitro to the rabbit erythrocyte. Conclusion The pH value obviously influenced the stimulation and hemolysis in vitro of recombinant human interferon β-1a injection, attentions should be paid to controlling the pH value of the preparation. The cause of the active sensitization to guinea pigs is the human serum albumin in preparation's accessories, so the sensitization occurring clinically will be rare. The preparation of recombinant human interferon β-1a injection will be safe in clinic.