帕立骨化醇亚微乳注射剂的溶血性和血管刺激性实验

Hemolysis and Vascular Irritation of Paricalcitol Submicroemulsion Injection

目的:评价帕立骨化醇亚微乳注射剂的溶血性和血管刺激性。方法:以家兔红细胞为受试物,设帕立骨化醇亚微乳注射剂(样品)组和市售帕立骨化醇注射液(市售品)组各5个剂量,加药量(5μg/ml)分别为每管0.5、0.4、0.3、0.2、0.1 ml,观察3 h内的溶血和红细胞凝聚情况,同时设阴性对照(0.9%氯化钠注射液)组和阳性对照(纯化水)组进行比较。取家兔随机分为5μg/ml样品和市售品的单次给药组和多次给药组,采用同体左右侧自身对比法,耳缘静脉左侧注射供试品0.5 ml,右侧注射0.9%氯化钠注射液0.5 ml,多次给药试验隔天给药1次,共给药5次,观察注射部位血管刺激性症状,并进行病理组织学检查。结果:阴性对照组细胞未见出现溶血和红细胞凝聚;阳性对照组细胞发生全溶血,未见红细胞凝聚;各剂量样品组和市售品组细胞3 h内均未出现溶血或红细胞凝聚。样品的单次给药组和多次给药组家兔耳缘静脉均未见血管刺激性;市售品的单次给药组和多次给药组家兔耳缘静脉均有血栓形成,对血管有轻度刺激性。结论:5μg/ml的帕立骨化醇亚微乳注射剂对家兔未见溶血性和血管刺激性。

OBJECTIVE： To evaluate the hemolysis and vascular irritation of Paricalcitol submicroemulsion injection. METHODS： The red blood cells of rabbit was taken as the subject and divided into Paricalcitol submicroemulsion injection groups （sample group） and marketed Paricalcitol injection groups （marketed product groups） at 5 different dose levels including 0.5, 0.4, 0.3, 0.2 and 0.1 ml/tube with adding amount of 5μg/ml. The hemolysis and red cell condensation were observed within 3 h. They were compared with negative control group （0.9% Sodium chloride injection） and positive control group （purified water）. Rabbits were randomly divided into single administration group and multiple administration group of 5 μg/ml sample and marketed product. Using the self comparison of left and right side, rabbits of each test group were injected 0.5 ml test samples into the left ear vein while 0.5 ml 0.9% Sodium chloride injection into the right ear vein. Multiple administration group was injected once every other day for 5 times altogether. Vascular irritation symptoms were observed by naked eyes. Histopathological examination was carried out at the same time. RESULTS： Hemolytic trial showed that no hemolysis and condensation reaction were found in negative control group; significant hemolysis was found in positive control group without condensation reaction; no hemolysis and condensation reaction were found in both sample group and marketed product group within 3 h. Vascular irritation trial showed that no vascular irritation was observed in rabbits＇ ear vein after single and multiple intravenous administration of sample. However, mild vascular irritation and thrornbus were observed in single and multiple administration group of marketed product group. CONCLUSIONS： Paricalcitol submicroemulsion injection 5 μg/ml dosen＇t show the property of hemolysis and vascular irritation to rabbits.