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介入性内照射抗肿瘤新药^(90)Y-P204-Lipiodol的制备及急性毒性试验研究

Study of Extraction Approach and Acute Toxicity Test of ^(90)Y-P204:a New Internal Irradiation Pharmaceutical for Interventional Therapy of Cancer in Mice
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摘要 目的:通过对瘤内注射用介入性内照射抗肿瘤新药90Y-P204-Lipiodol的制备方法及急性毒性试验的研究,为肿瘤的介入性治疗提供新的内照射药物并进行初步的毒理学评价。方法:选择萃取剂P204作为络合剂对90Y进行酸性络合式萃取,制备90Y-P204-Lipiodol并测定其萃取率。然后将60只KM小鼠随机分成6组,每组10只,一组为对照组,其余5组均腹腔注射90Y-P204-Lipiodol,药物萃取浓度依次为0.01、0.02、0.04、0.08和0.16 mol/l,经验注射量为0.1 ml,分别观察小鼠对受试物90Y-P204-Lipiodol的急性毒性反应、安全剂量、中毒剂量或半数致死量(LD50)。结果:0.01 mol/l的P204碘化油溶液萃取率高达99.9%,符合放射性药物制备的要求。在急性毒性试验中,药物注射浓度为0.16 mol/l(注射量为0.1 ml)时,产生急性毒性反应,中毒剂量或半数致死量(LD50)为256.9 g/kg;药物注射浓度为0.01~0.08 mol/l时,对应剂量为16.1~128.8 g/kg,未出现任何急性毒性反应。结论:酸性络合式萃取法制备介入性内照射抗肿瘤新药90Y-P204-Lipiodol萃取效果满意,急性毒性试验初步显示其较好的药物安全性,90Y-P204-Lipiodol在肿瘤临床治疗中具有潜在的应用价值。 Objective: In order to provide a new internal irradiation pharmaceutical for interventional therapy of cancer, the authors reported a new method of chemical extraction for ^90Y-P204_Lipiodol. Acute toxicity test by intra-peritoneal cavity injection of ^90Y-P204-Lipiodol in mice was also performed. Methods: Complexes of Di-(2 ethylhexyl)-orthophosphoric acid (P204), 2-ethylhexyl phosphoric acid mono ( 2 ethylhexyl) ester ( Ps07 ), Cyanex 272, nonanoic acid, naphthenic acid,oleic acid and oxine were selected as extractants in this study and the extraction efficiency was evaluated. Taking 60 KM mice which were equally divided into 6 groups randomly. 0. lml of ^90Y-P204 were injected into ,the peritoneal cavity with the dosage of 0. 01,0. 02,0. 04,0. 08 and 0.16mol/1 for each group respectively,and one group was taken as control. Of these different groups, acute toxicity reaction, tolerable dose, and intoxicating dose were observed. Results:The extraction efficiency with P204 reached 99.9 %,which was higher than the other extractants, and in accord with the demands of irradiation pharmaceuticals preparation. As the injection dosage 0. l ml with the concentration 0.16tool/1 was used, acute toxicity was created. The intoxicating dose,median lethal dose (LD50) was 256g/kg. There was no any acute toxic reaction when the concentration were 0.01 - 0.08mol/1, with the correspondent dosage as 16.1-128.8g/kg. Conclusion: ^90 Y-P204-Lipiodol is a new, safe and satisfying pharmaceutical for internal irradiation in the interventional therapy of canter.
出处 《放射学实践》 2006年第5期529-532,共4页 Radiologic Practice
关键词 放射肿瘤学 放射学 介入性 药物毒性 Radiation oncology, Radiology,interventional Drug toxicity
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参考文献12

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