HYDROXYALKYLSTRACH (HAS)-POLYPEPTIDE-CONJUGATE(HAS-POLYPEPTIDE), A METHOD FOR ITS PRODUCTION AND USE THEREOF IN THE MANUFACTURE OF MEDICAMENTS FOR THERATING ANEMIC DISORDERS

摘要

Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.