Oligomer-corticosteroid conjugates
View Patent ↗The invention provides corticosteroids that are chemically modified by covalent attachment of a water soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the corticosteroid not attached to the water soluble oligomer.
1. A compound comprising a corticosteroid residue covalently attached via a releasable linkage to a water-soluble, non-peptidic oligomer, wherein the compound is selected from a compound of the formula:
wherein POLY is a water-soluble, non peptidic oligomer having a number of repeating monomers in the range of from 2 to 30.
2. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
3. The compound of claim 2 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
4. The compound of claim 2 , wherein the water-soluble, non-peptidic oligomer has a number of repeating monomers in the range of from 2 to 10.
5. The compound of claim 2 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
6. A composition comprising a compound of claim 1 , and (ii) optionally, a pharmaceutically acceptable excipient.
7. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.
8. A method comprising administering to a subject compound of claim 1 comprising a corticosteroid residue covalently attached via a linkage to a water-soluble, non-peptidic oligomer.
9. The compound of claim 1 , wherein the compound is selected from a compound of the formula
wherein n is an integer from 2 to 10.
10. The compound of claim 9 , wherein n is selected from 3, 7, or 8.