苦豆子生物碱衍生物9002#急性毒性及体内抑癌活性的实验研究

Experimental Study of Alkaloid Derivative 9002# on Acute Toxicity and in vivo Anti-tumor Effects

目的 使用昆明种小白鼠对苦豆子生物碱衍生物 90 0 2 #进行急性毒性实验。使用 IRM-2纯系小鼠进行淋巴瘤和乳腺癌的体内抑癌活性的实验研究。方法 急性毒性实验 :以腹腔给药 ( ip)方式给药 ,测定小鼠 LD50 。抑癌试验 :建立荷瘤小鼠模型 ,IP方式给予 2个不同剂量的药物水溶液 ,观察瘤重和体重 ,测定抑瘤率。结果 经实验测定 90 0 2 #的 LD50 为 43 62± 810 mg· kg- 1 ,毒性较低 ,经重复试验 90 0 2 #确有明显的抑癌作用。对淋巴瘤 ,剂量 5 0 mg· kg- 1 × 10 ,抑瘤率 5 0 .3 %～ 5 3 .5 %( P<0 .0 1) ,15 0 mg· kg- 1 为 3 1.3 %～ 3 5 .7%( P<0 .0 5 ) ;对乳腺癌 ,剂量 5 0 mg· kg- 1× 10 ,抑瘤率为 5 7.1%( P<0 .0 1) ,15 0 mg· kg- 1为 48.6%( P<0 .0 1)。 结论 苦豆子生物碱衍生物 90 0 2 #属低毒而有抑癌活性的化合物 ,对 IRM-2纯系小鼠移植肿瘤有明显的抑制作用 ,以 5 0 mg· kg- 1× 10剂量组对淋巴瘤和乳腺癌抑制效果最显著 。

OBJECTIVE Acute toxicity experiment of Sophora alopecuroides alkaloid derivative 9002 # was performed in Kunming mice ,In vivo anti tumor activity tests of 9002 # were performed in inbred strain IRM 2 mice using lymphoma and mammary adenoma.METHODS Acute toxicity experiment:the drug solution was administered intraperitoneally(ip),and LD 50 was surveyed by conventional method.Anti tumor tests:tumor bearing mice models were set up,2 separate dosages of drug solutions were administrated intraperitoneally(ip),the changes of sarcoma weights and body weights were observed,and inhibitory rates of tumors were surveyed RESULTS LD 50 of 9002 #was determined through the experiment,up to4362±810mg·kg -1 ,a less toxicity compound.It was proved by repeated tests that 9002 #has a certain tumor inhibitory effect.For lymphoma 50mg·kg -1 ×10 dosage,inhibitory rate was 50 3%～53 5%(P<0 01),and 150mg·kg -1 dosage that was 31 3%～35 7%(P<0 05) .For mammary adenoma,50mg·kg -1 ×10 dosage ,inhibitory rate was 57 1%(P<0 01) and 150mg·kg -1 ×10 dosage that was 48 6%(P<0 01).CONCLUSION Alkaloid derivative 9002 #has less toxicity and a certain inhibitory effect to animal transplant sarcomas in inbred strain IRM 2 mice.50mg·kg -1 ×10 dosage group has more obvious inhibitory effect to lymphoma and mammary adenoma,it is worthy to study deeply.