Hydrogel Prodrugs

摘要

The present invention relates to a process for the preparation of a hydrogel and to a hydrogel obtainable by said process. The present invention further relates to a process for the preparation of a hydrogel-spacer conjugate, to a hydrogel-spacer conjugate obtainable by said process, to a process for the preparation of a carrier-linked prodrug and to carrier-linked prodrugs obtainable by said process, in particular to carrier-linked prodrugs that provide for a controlled or sustained release of a drug from a carrier. In addition, the invention relates to the use of the hydrogel for the preparation of a carrier-linked prodrug.

主权项

1: A process for the preparation of a hydrogel comprising the steps of:
(a) providing a mixture comprising;
(a-i) at least one backbone reagent, wherein the at least one backbone reagent has a molecular weight ranging from 1 to 100 kDa, and comprises at least three amines (—NH2 and/or —NH—);(a-ii) at least one crosslinker reagent, wherein the at least one crosslinker reagent has a molecular weight ranging from 6 to 40 kDa, the at least one crosslinker reagent comprising:
(i) at least two carbonyloxy groups (—(C═O)—O— or —O—(C═O)—), and additionally; and(ii) at least two activated functional end groups selected from the group consisting of activated ester groups, activated carbamate groups, activated carbonate groups and activated thiocarbonate groups;wherein the at least one crosslinker reagent is PEG-based comprising at least 70% PEG; and(a-iii) a first solvent and at least a second solvent, which second solvent is immiscible in the first solvent;wherein a weight ratio of the at least one backbone reagent to the at least one crosslinker reagent is in a range of from 1:99 to 99:1; and (b) polymerizing the mixture of step (a) in a suspension polymerization to a hydrogel.