Compositions comprising a polymeric reagent and a pharmacologically active agent

摘要

Pharmaceutical compositions of conjugates are provided. The conjugates can be prepared by (among other ways) conjugating a pharmacologically active agent with a polymeric reagent that has a particular arrangement of atoms. Related methods, preparations, and so forth are also provided.

主权项

1. A composition comprising
(i) a polymeric reagent of the following structure,wherein:
POLY1 is a poly(alkylene glycol); POLY2 is a poly(alkylene glycol); (a) is 0, 1, 2 or 3; (b) is 0, 1, 2 or 3; (e) is 0, 1, 2 or 3; (f′) is 0, 1, 2 or 3; (g′) is 0, 1, 2 or 3; (h) is 0, 1, 2 or 3; (j) is 0 to 20; each R1 is independently H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl; X1, when present, is a first spacer moiety; X2, when present, is a second spacer moiety; X5, when present, is a fifth spacer moiety; X6, when present, is a sixth spacer moiety; X7, when present, is a seventh spacer moiety; X8, when present, is an eighth spacer moiety; R5 is a branching moiety selected from the group consisting of  wherein (p) is 1-10 and (q) is 1-10; and Z is a reactive group suitable for reaction with an electrophile or nucleophile of a biologically active agent; and (ii) a pharmacologically active agent,wherein there is an excess of the polymeric reagent relative to the pharmacologically active agent in the composition.