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目的通过对重组人血管内皮生长因子受体-抗体融合蛋白注射液(KH902)进行家兔玻璃体注射给药,考察局部毒性,对KH902进行初步药品毒性评价。方法 12只日本大耳白兔,随机分为KH902组和溶剂对照组2组(n=6,雌雄各半),右眼玻璃体内分别单次注射KH902(0.5 mg/50μl/眼)或等体积溶剂对照品,左眼做假注射对照或空白对照。给药后每日进行肉眼观察,定期使用间接检眼镜及裂隙灯进行检查。给药后14 d处死动物,取眼球进行组织病理学检查。通过观察结果及组织病理学检查结果,考察供试品的局部毒性。结果日本大耳白兔眼玻璃体内注射给药后,6只给予KH902的眼睛中,有1只肉眼观察见睑结膜轻微充血,1只见少量分泌物。同时,分别在给予溶剂对照侧、假注射侧或空白对照侧眼睛观察到相同现象,且发生率及发生时间与给予KH902侧眼睛基本一致。裂隙灯及检眼镜检查各组动物给药侧及对照侧眼睛均未见明显异常。由此可排除这些现象是由药物引起的刺激反应。组织病理学检查见所有眼球组织结构均正常。结论在本次试验条件下,兔眼单次玻璃体注射给予KH902(0.5 mg/50μl/眼),未引起局部剌激性或组织损伤反应。
Objective To evaluate the toxicity of KH902 by injecting recombinant human vascular endothelial growth factor receptor-antibody fusion protein injection (KH902) into rabbits for vitreous injection to investigate the local toxicity. Methods Twelve Japanese white rabbits were randomly divided into 2 groups: KH902 group and solvent control group (n = 6, male and female respectively), single intravitreal injection of KH902 (0.5 mg / 50μl / eye) or equal volume Solvent control, left eye false injection control or blank control. Daily visual observation after administration, regular use of indirect ophthalmoscope and slit lamp to check. The animals were sacrificed 14 days after the administration and the eyeballs were taken for histopathological examination. By observing the results and histopathological examination results, examine the local toxicity of the test article. Results After Japan rabbits eyes vitreous injection, the eyes of 6 rabbits given KH902 had one macular conjunctiva with macroscopic hyperemia and one with a small amount of secretions. At the same time, the same phenomenon was observed in the eyes of the control side, the pseudo-injection side or the blank control side, respectively, and the incidence and timing were basically the same as that of the eyes on the KH902 side. Slit lamp and ophthalmoscopy Each group of animals on the administration side and the control side of the eyes were no obvious abnormalities. This can be excluded from the phenomenon of these drugs is caused by the stimulus response. Histopathology showed that all ocular structures were normal. Conclusion Under this test condition, single intravitreal injection of KH902 (0.5 mg / 50 μl / eye) in rabbits did not cause local irritation or tissue damage.