论文部分内容阅读
为了考查L 门冬酰胺酶 (L Asparaginase ,L ASNase)前体脂质体 (Proliposomes) (L ASNasePL)与L ASNase的急性毒性及对外周血中白细胞总数及血小板数的作用。脂质体组小鼠静脉注射给药 (L ASNasePL) ,给药剂量为给以最大药物浓度 (4 0 0 0KU/m1) ,最大静脉注射体积 (0 5m1/ 2 0 g) ;L ASNase组给药体积为 0 4ml/ 2 0 g ,给药一次 ,给药后每天观察记录小鼠活动、死亡情况 ,共观察 14d。结果L ASNasePL的毒性与L AS Nase相比明显降低 ,其小鼠iv的L ASNasePL的最大耐受量为 10 0× 10 5KU/kg ,相当于每日人临床拟用剂量的5 0 0 0倍。对正常小鼠体重、外周血中白细胞总数及血小板数的影响 :L ASNase高剂量组 (10 0 0KU/kg)有显著降低小鼠外周血中白细胞总数及血小板数的作用 (P <0 0 5 ) ,而L ASNasePL对小鼠外周血中白细胞总数及血小板数无明显影响。L ASNasePL组及L ASNase组对小鼠体重增长均无明显影响。说明L 门冬酰胺酶前体脂质体急性毒性明显小于L 门冬酰胺酶 ,L ASNasePL对小鼠外周血中白细胞总数及血小板数无明显影响
In order to investigate the acute toxicity of L ASNase prodiposomes (L ASNasePL) and L ASNase and the effect on peripheral blood leukocytes and platelets. The mice in the liposomal group were injected with L ASNasePL at the maximum drug concentration (4000 KU / ml) and the maximum intravenous injection volume (0.5 ml / 200 g). The L ASNase group The drug volume was 0 4ml / 2 0 g, administered once daily after administration recorded the activity and death of mice and observed a total of 14 days. Results The toxicity of L ASNasePL was significantly lower than that of L AS Nase. The maximum tolerated dose of L ASNasePL in mouse iv was 100 × 10 5 KU / kg, which was equivalent to 500 times of the daily human clinical dose . The effects of L ASNase high dose group (100KU / kg) on the body weight, white blood cell count and platelet count in peripheral blood were significantly decreased (P <0.05) ), While L ASNasePL had no significant effect on the total number of white blood cells and platelets in mice peripheral blood. L ASNasePL group and L ASNase group had no significant effect on body weight gain in mice. L asparaginase precursor liposomes acute toxicity was significantly less than L asparaginase, L ASNasePL had no effect on the total number of white blood cells and platelets in mice peripheral blood