Patent ID: 9345662
Filing Date: 2016-05-24
CPC Classification: A61K,A61P

Claim Text:
1. A pharmaceutical formulation capable of forming a biodegradable hydrogel in situ to provide timed release of an active agent comprising: (1) a therapeutically effective amount of one or more active agents, (2) a hydrophilic agent that is a polyethylene glycol polymer or copolymer comprising a plurality of cross-linking functional groups, and (3) a multifunctional polyethylene glycol cross-linker comprising a plurality of cross-linking functional groups co-reactive with said cross-linking functional groups on said hydrophilic agent, which forms a hydrogel in situ by interaction between said co-reactive functional groups on the cross-linker and said co-reactive functional groups on the hydrophilic agent, wherein: one of said hydrophilic agent and said cross-linker comprise a polyethylene glycol with up to eight degradable cross-linking functional group segments independently comprising the structure: wherein R 1 is H, an amino acid selected from the group consisting of GABA (gamma-amino butyric acid), AHA (6-aminohexanoic acid) and AOA (8-aminooctanoic acid), or an amino acid dimer, each member of which is independently selected from the group consisting of GABA, AHA and AOA; and R 2 is a functional group that reacts with a functional group on the other of said hydrophilic agent and said cross-linker to form said hydrogel; and one of said hydrophilic agent and said cross-linker further comprises a pendant degradable segment comprising a glutamic acid moiety having the structure: wherein R 3 is an active agent comprising a free amino group bonded to the-γ-carboxylic group of said glutamic acid moiety through an amide bond, and the free α-amino group of said glutamic acid moiety provides timed cleavage by reacting with the γ-carboxylic group, resulting in cleavage of the γ-amide bond and formation of a five member cyclic ring, releasing the active agent.