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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 p H 3.6的11、22μg/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p H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;p H 3.5的5.5、22μg/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;p H 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,p H 4.5样品则无体外溶血和致红细胞凝聚作用。结论 p H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p H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 detect the safety of the preparation of recombinant human interferon β-1a injection and explore the possible influencing factors. Methods Rabbit muscle and subcutaneous irritation test, active systemic anaphylaxis test in guinea pigs, passive skin allergy test in rats and hemolysis test in vitro were respectively carried out with recombinant human interferon β-1a injection to test the local irritation of drug Ⅰ Allergic reactions and hemolysis. Results 11, 22μg / kg recombinant human interferon and its blank vehicle at p H 3.6 had mild stimulation on muscle and mucocutaneous in rabbits. The recombinant interferon with p H of 4.3 and blank control No significant stimulation; p H 3.5 5.5,22μg / kg dose recombinant human interferon and its blank vehicle no passive sensitized rats active sensitization was strongly positive for guinea pigs, excipients contained no human serum Protein samples did not sensitize guinea pigs; p H 3.5 recombinant human interferon had very mild in vitro hemolysis on rabbit erythrocytes, while p H 4.5 samples had no hemolysis and no erythrocyte aggregation in vitro. Conclusion The p H value has some influence on the irritation and in vitro hemolytic activity of recombinant human interferon β-1a injection, and its p H value should be paid attention to. The sensitization of interferon to guinea pig is caused by human serum albumin , The clinical use of human sensitization is unlikely. Recombinant human interferon β-1a injection preparation is safe.