奥瑞克010临床前安全性评价  

Preclinical Safety Evaluation of OrienX010

作　　者：王三龙[1] 姜华[1] 沈连忠[1] 李保文[1] 王秀文[1] 李波[1] 李秉坤[1] 

机构地区：[1]中国药品生物制品检定所国家药物安全评价监测中心,北京100176

出　　处：《食品与药品》2010年第7期244-247,共4页Food and Drug

摘　　要：目的奥瑞克010(OrienX010)以人单纯疱疹病毒(HSV-1)为载体,携带人源性或鼠源性的GM-CSF基因。在符合GLP的条件下,应用BALB/c小鼠和豚鼠进行临床前安全性评价研究。方法小鼠急性毒性试验中,采用最大耐受剂量法对BALB/c小鼠尾静脉和肌内注射人源OrienX010和鼠源OrienX010M;全身过敏实验中,豚鼠隔日3次肌内注射OrienX010或牛血清白蛋白V,于末次给药后第10日静脉注射OrienX010,观察3 h内动物的变化;体外溶血试验中,观察本品在3 h内有无溶血和聚集现象。结果 BALB/c小鼠尾静脉注射人源OrienX010和鼠源OrienX010M的最大耐受量分别为4×107 pfu和2×107 pfu,肌内注射人源OrienX010和鼠源OrienX010M的最大耐受量均为6×107 pfu,对豚鼠未见过敏反应,家兔无溶血现象。结论动物实验结果表明,奥瑞克010制剂安全可靠,毒性较低,且无溶血和过敏反应。Objective To evaluate the preclinical safety of OrienX010,a herpes simplex virus type 1（HSV-1） vector expressing immunostimulatory genes（human or animal GM-CSF）,in BALB/c mice and guinea pigs in accordance with the principles of GLP.Methods In the acute toxicity test,human OrienX010 or mouse OrienX010M was intravenously and intramuscularly administered to BALB/c mice at the maximum tolerance dose;in the systematic allergy test,guinea pigs were intramuscularly administered with OrienX010 or bovine serum albumin V three times at an interval of two days and further intravenously administered with OrienX010 on Day 10 after the last administration,and then were observed for three hours;in the in vitro hemolysis test,the occurrence of any hemolysis and aggregation induced by OrienX010 within 3 hours was observed.Results The maximum tolerance doses of human OrienX010 and mouse OrienX010M in mice were 4×10^7pfu and 2×10^7pfu for intravenous injection,respectively,and were both 6×10^7pfu for intramuscular injection.The guinea pigs showed no allergic responses.No hemolysis was observed in rabbits.Conclusion The results from animal tests show that OrienX010 dose not induce high toxicity,hemolysis and allergy and thus is safe for animals.

关 键 词：HSV-1 OrienX010 急性毒性试验 过敏试验 溶血试验 

分 类 号：R979.1[医药卫生—药品]