【作者】 徐兵河；

【导师】 孙燕；

【作者基本信息】 中国协和医科大学 ， 肿瘤学， 1999， 博士

【摘要】 一、中文摘要 硒酸酯多糖是一种新型的有机硒制剂，为了确定其临床应用价值，进行了Ⅰ期及Ⅱ期临床试验。 Ⅰ期临床试验中，分别对12例恶性肿瘤患者与15例健康自愿者做了硒酸酯多糖药物耐受性及药代动力学试验。耐受性试验结果表明，此药对心、肝、肺、肾等重要器官无明显毒性作用。当剂量为100mg／日时，个别病例出现头晕及轻微恶心。30～50mg／日时，免疫功能有不同程度的提高，血、尿β₂—微球蛋白降低。推荐Ⅱ期临床试验剂量为：（1）用于恢复期患者提高免疫功能为30～50mg／日口服；（2）化、放疗期间减轻毒副作用为50mg／日口服或100mg／日间断口服。 用极谱法测定硒酸酯多糖胶囊在正常人体内药代动力学。结果显示，药代动力学模型为一室模型。血硒达峰时间为4～5小时，半衰期为21～26小时。各剂量血药峰浓度（Cmax）及曲线下面积（AUC）随剂量的递增而增加，而达峰时间及其它各常数Ke、Ka、t_1／2（Ka）、t_1／2（Ke）等均接近。进食对正常人体药代动力学无明显影响。给药剂量为10mg、30mg、50mg、100mg时，96小时内尿总的排泄率分别为41.10％、37.40％、38.84％和34.78％。 Ⅱ期临床试验采用随机双盲的实验方法。共入组42例，其中，化疗加硒酸酯多糖组26例（治疗组），化疗加安慰剂组16例（对照组）。Ⅱ期试验进一步证实了Ⅰ期试验的部分结果。患者服用硒酸酯多糖后T₄细胞明显增加，巨嗜细胞吞噬率亦明显上升，提示服用硒酸酯多糖能使接受化疗患者的免疫功能增强。同时，治疗组患者血小板计数明显高于对于对照组，治疗组患者血、尿β₂—微球蛋白化疗前、后均保持在正常范围内，而对照组患者化疗前、后血、尿β₂—微球蛋白均有上升，提示硒酸酯多糖对接受顺铂治疗的患者，可能有保护肾功能的作用。另外，合用硒酸酯多糖并不降低化疗疗效。 本研究结果表明，硒酸酯多糖为一安全有效的免疫反应调节剂。更多还原

【Abstract】 To evaluate the clinical usefulness of κ-Selenocarrageenan in immunomodulation, we completed phase I and phase II clinical trials. The aim of the phase I clinical trial was to examine the drug tolerance and pharmacokinetics, the study was conducted in 12 patients with malignances and 15 healthy volunteers, respectively. They were divided to receive oral κ-selenocarrageenan in designed doses and conditions. From this study, it was revealed that κ -selenocarrageenan had no apparent toxicity to vital organs such as heart, liver, lung and kidney except for dizziness and slightly nausea in very few patients when they took 100mg of the drug per day. Immune functions were enhanced and levels of β₂-microglobulins （β₂-MG） in blood and urine were decreased when the patients took 30mg to 50mg per day. Recommended doses for phase II clinical trial were: （1） the doses of κ-selenocarrageenan were 30mg to 50mg per day for the purpose of immunomodunation in convalescents; （2） the doses of κ-selenocarrageenan were 50mg per day during the chemotherapy or radiotherapy or 100mg per day for two weeks during the periods of three weeks in order to decrease side effects of the chemotherapy of radiotherapy.The concentrations of serum selenium were determined by更多还原