| 摘要 |
FIELD: medicine, pharmacy. ^ SUBSTANCE: invention relates to conjugate of glycoprotein erythropoietin that has at least one free amino-group and elicits biological activity in vivo providing elevating production of reticulocytes and erythrocytes by bone marrow cells. Conjugate is taken among the group involving human erythropoietin and its analogues that have sequence of human erythropoietin modified by addition of 1 to 6 sites of glycosylation or rearrangement of at least one site of glycosylation. This glycoprotein is bound covalently with 1-3 (lower)-alkoxypoly-(ethylene glycol) groups and each poly-(ethylene glycol) group is bound covalently with glycoprotein through linker of the formula -C(O)-X-S-Y. The C(O)-group of linker forms amide bond with one of these amino-groups wherein X means -(CH2)k- or -CH2(O-CH2-CH2)k- wherein k means 1-10; Y means ^ ^ ^ ^ ^ An average molecular mass of each poly-(ethylene glycol) fragment is from about 20 to about 40 kDa and molecular mass of conjugate is from about 51 to about 175 kDa. Also, invention relates to pharmaceutical compositions, composition, method for prophylaxis and/or therapeutic treatment and method for preparing conjugate. Invention provides preparing conjugates exhibiting the longer half-time life value in blood stream and plasma retention time, reduced clearance and higher activity in vivo. ^ EFFECT: improved preparing and treatment methods, valuable properties of conjugates. ^ 39 cl, 3 dwg, 1 tbl, 4 ex |
