Hydrolytically degradable carbamate derivatives of poly(ethylene glycol)
AssigneeShearwater Corporation
InventorsMichael David Bentley, Xuan Zhao
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Abstract
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.
Claims35
A compound having the formula:
- 27
- wherein:
- POLY is a water soluble, non-peptidic polymer;
- L is a hydrolytically stable linking group;
- Ar is an aromatic group;
- and
- X is activating group capable of reacting with a moiety of a biologically active agent to form a carbamate linkage.
A compound having the formula:
- 29
- wherein:
- L is —O— or —NHCO—;
- POLY is poly(ethylene glycol) having a capping group selected from the group consisting of —OH, alkoxy, and 30
- wherein L is as described.
A compound having the formula:
- 31
- wherein:
- POLY is a water soluble and non-peptidic polymer;
- L is a hydrolytically stable linkage;
- Ar is an aromatic group;
- and
- Y is a biologically active agent.
A compound having the formula:
- 33
- wherein:
- L is —O— or —NHCO—;
- Y is a biologically active agent;
- POLY is poly(ethylene glycol) having a capping group selected from the group consisting of —OH, C1-4 alkoxy, and 34
- wherein Y and L are as described.
A compound having the formula:
- Y—Ar—O2C—NH-POLY
- where Y is a biologically active agent having an aromatic group, Ar is the aromatic group of the biologically active agent Y, and POLY is a water soluble, non-petidic polymer.
A hydrolytically degradable hydrogel comprising a backbone bonded to a crosslinking agent through a hydrolyzable carbamate linkage, wherein said backbone comprises at least two amino groups, and wherein said crosslinking agent is selected from the group consisting of:
- 35
- wherein
- POLY is a water soluble, non-peptidic polymer;
- L and L′ are hydrolytically stable linkages;
- Ar and Ar′ are aromatic groups;
- Z is a central branch core moiety;
- n is from 2 to about 100;
- and
- X and X′ are activating groups capable of reacting with said amino groups to form said hydrolyzable carbamate linkages.
A delivery system for delivering a biologically active agent comprising the biologically active agent carried within a hydrolytically degradable hydrogel, wherein said hydrogel comprises a backbone bonded to a crosslinking agent through a hydrolyzable carbamate linkage, said backbone having at least two amino groups, said crosslinking agent being selected from the group consisting of:
- 36
- wherein
- POLY is a water soluble, non-peptidic polymer;
- L and L′ are hydrolytically stable linkages;
- Ar and Ar′ are aromatic groups;
- Z is a central branch core moiety;
- n is from 2 to about 100;
- and
- X and X′ are activating groups capable of reacting with said amino groups to form said hydrolyzable carbamate linkages.
Dependencies are inferred from the claim text.