Hydrolytically degradable carbamate derivatives of poly(ethylene glycol)
View Patent ↗Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.
1. A compound having the formula:
wherein:
POLY is a water soluble, non-peptidic polymer;
L is a linking group; and
Ar is an aromatic group.
2. The compound of claim 1 , wherein said POLY is a poly(ethylene glycol) having a molecular weight of from about 200 to about 100,000 Daltons.
3. The compound of claim 1 , wherein said POLY further comprises a capping group selected from the group consisting of OH, alkoxy, and
wherein L′ is a hydrolytically stable linkage, and Ar′ is an aromatic group.
4. The compound of claim 1 , wherein L is a hydrolytically stable linking group.
5. The compound of claim 1 , wherein L comprises a linking group selected from the group consisting of ethers, amines, imides, esters, amides, carbamides, imides and thioethers.
6. The compound of claim 1 , wherein L is —O— or —HN—CO—.
7. The compound of claim 1 , wherein Ar is selected from phenyl, substituted phenyl, biphenyl, substituted biphenyl, polycyclic aryls, substituted polycyclic aryls, heterocyclic aryls, and substituted heterocylic aryls.