目的 檢測重組人干擾素β-1a注射液的制劑安全性并探討可能的影響因素。方法 分別以重組人干擾素β-1a注射液進行家兔肌肉和皮下刺激性試驗、豚鼠主動全身過敏性試驗、大鼠被動皮膚過敏性試驗和體外溶血性試驗,檢測藥物的局部刺激性、Ⅰ型過敏反應性和溶血作用。結果 pH 3.6的11、22 μg/kg重組人干擾素及其空白溶媒對家兔肌肉和皮膚黏膜具有輕度刺激作用,相應劑量下pH為4.3的重組干擾素及其空白溶媒對家兔組織無明顯刺激作用;pH 3.5的5.5、22 μg/kg劑量下重組人干擾素及其空白溶媒對大鼠無被動致敏作用,對豚鼠主動致敏作用呈強陽性,輔料中不含人血清白蛋白的樣品則對豚鼠無致敏作用;pH 3.5的重組人干擾素對家兔紅細胞具有極輕度體外溶血作用,pH 4.5樣品則無體外溶血和致紅細胞凝聚作用。結論 pH值對重組人干擾素β-1a注射液刺激性和體外溶血性具有一定影響,應注意對其pH值的控制;干擾素對豚鼠致敏作用為輔料中人血清白蛋白所致,臨床使用中對人產生致敏的可能性很小。重組人干擾素β-1a注射液制劑安全性較好。

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.