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(1)重组人尿激酶原 (prouk)单剂量分别经静脉和腹腔注射给药均未测出小鼠的LD50 ,因此改作其最大给药量 .结果表明 ,prouk单剂量经静脉及腹腔注射给药小鼠的最大给药量不低于 9,0 0 0万IU /kg .(2 ) prouk 36 .0万IU/kg、6 7.5万IU/kg、135 .0万IU/kg和 2 70 .0万IU/kg四个剂量组连续给食蟹猴静脉滴注 14d ,每组 4只猴 ,雌雄各半 .实验过程中未见动物死亡 .prouk 36 .0万IU/kg剂量组的食蟹猴给药期及恢复期 ,精神状态良好 ,一般行为活动正常 ,体重、分泌物、食欲及摄食量、心电图、血常规、血液生化、体表观察、尿常规和粪便隐血试验等基本正常 ,无明显变化 .给药第 14天和恢复期的脏器系数与病理组织学检查表明 ,动物的脏器、组织均未见由药物引起的异常病理改变 ,与生理盐水组或赋形剂组之间比较均无明显差异 .而prouk 6 7.5万IU/kg、135 .0万IU/kg、2 70 .0万IU /kg剂量组的食蟹猴出现皮下出血、充血、紫癜、尿、粪便隐血反应阳性、贫血以及心率加快等症状 .给药期及恢复期 ,血清中检测出少量prouk抗体 .结果表明 ,prouk的无毒安全剂量不低于 36 .0万IU/kg .
(1) The single dose of recombinant human prouk was administered intravenously and intraperitoneally, respectively, and the LD50 of the mice was not measured, so the maximum dose of prouk was changed to the maximum dose.The results showed that single dose of prouk was given by intravenous and intraperitoneal injection The maximum dose of the drug for mice is not less than 90,000 IU / kg. (2) prouk 360,000 IU / kg, 675,000 IU / kg, 1,350,000 IU / kg and 2,70 .0 million IU / kg four dose groups were given continuous intravenous drip cynomolgus monkey 14d, each group of 4 monkeys, male and female in half .In the course of the experiment no animal death.prouk36 .0 IU / kg dose group of food The cynomolgus monkeys given the period and convalescence, good mental state, the normal behavior and activities of normal weight, secretions, appetite and food intake, electrocardiogram, blood, blood biochemistry, body surface observation, urine routine and fecal occult blood test and other basic normal, No significant changes in the administration of the 14th day and recovery of organ coefficients and histopathological examination showed that no abnormal pathological changes caused by the drug were found in the organs and tissues of the animals and those in the saline group or the vehicle group There was no significant difference between the prouk 675000 IU / kg, 1350000 IU / kg, 2700000 IU / kg dose group of cynomolgus monkeys out Subcutaneous hemorrhage, congestion, purpura, urine, fecal occult blood test positive, anemia and heart rate and other symptoms.Drugs and convalescence, serum detected a small amount of prouk antibody.The results showed that prouk non-toxic safe dose of not less than 36. 0 million IU / kg.