LV, AI FENG,吕爱锋,呂愛鋒,SUN, CHANG AN,孙长安,孫長安,WANG, RUI JUN,王瑞军,王瑞軍,CHEN, KE RAN,陈克然,陳克然,LI, YUN BO,李蕴波,李蘊波,WANG, YALI,王亚里,王亞里
申请号：
TW097125013
公开号：
TWI430811B
申请日:
2008.07.03
申请国别(地区):
TW
年份:
2014
代理人:
摘要：
The present invention discloses pegylated erythropoietin conjugates, which are obtained by reacting -CH2- group in formula -CH2-X-S-Y- of methoxy polyethylene glycol group with amino group of erythropoietin to form a bond of -NH2-CH2-. The present invention also discloses the method of preparing above conjugates, i.e. the conjugates are prepared by the reductive amination of reacting erythropoietin with aldehydes containing protected mercaptos to form activated erythropoietin connected by -NH2-CH2-； the activated erythropoietin further were coupled to methoxy polyethylene glycol derivatives to obtain the pegylated erythropoietin conjugates. The method has the advantages of being more specific of the reaction sites and the quality being more controllable. The pegylated erythropoietin conjugates or the pharmaceutical composition containing the same provided by the present invention can be used widely for the treatment of diseases characterized in the deficiency of erythropoietin and the lack or defect of erythrocyte group.本發明公開了一種聚乙二醇化促紅血球生成素偶聯物，所述偶聯物是由甲氧基聚乙二醇基團通過式-CH2-X-S-Y-中的-CH2-基團與促紅血球生成素的氨基形成-NH-CH2-鍵連接而得到。本發明還公開了上述偶聯物的製備方法，即偶聯物是由促紅血球生成素和含有已保護巰基的醛類物質發生還原胺化反應，形成通過-NH-CH2-鍵連接的活化促紅血球生成素；進一步與甲氧基聚乙二醇衍生物偶聯而得到，該方法具有反應位點更單一，品質更可控制的優點。本發明提供的聚乙二醇化促紅血球生成素偶聯物或含有聚乙二醇化促紅血球生成素偶聯物的藥物組合物可在治療以缺乏紅血球生成素或紅血球群缺少或缺陷為特徵的疾病中廣泛應用。
