Factor VIII zwitterionic polymer conjugates
The present invention provides multi-armed high MW polymers containing hydrophilic groups conjugated to Factor VIII, and methods of preparing such polymers.
1. A compound having the following formula:
wherein X is an integer from 1 to 50 and Y is an integer from 1 to 50; and wherein Z is polymer, the polymer is synthesized with a monomer selected from the group consisting of:
wherein R7 is H or C 1-6 alkyl, ZW is a zwitterion, and t is 1 to 6.
2. The compound of claim 1 , wherein the zwitterion is phosphorylcholine.
3. The compound of claim 1 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC) or 2-(acryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate.
4. The compound of claim 2 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC).
5. The compound according to claim 1 , wherein the total molecular weight of the compound is about 500,000 to about 1,000,000 daltons.
6. The compound according to claim 2 , wherein the total molecular weight of the compound is about 650,000 to about 850,000 daltons.
7. The compound according to claim 3 , wherein the total molecular weight of the compound is about 750,000 daltons.
8. A compound selected from the group consisting of:
and
wherein Z is polymer, the polymer is synthesized with a monomer selected from the group consisting of:
wherein R7 is H or C 1-6 alkyl, ZW is a zwitterion, and t is 1 to 6.
9. A method of synthesizing a polymer-functional agent conjugate comprising coupling a functional agent to an unreacted reactive group of the compound of claim 1 to provide the polymer-functional agent conjugate.
10. The compound of claim 8 , wherein the zwitterion is phosphorylcholine.
11. The compound of claim 10 , wherein the monomer is 2-(methacryloyloxyethyl)-2 ‘-(trimethylammoniumethyl) phosphate (MPC) or 2-(acryloyloxyethyl)-2’-(trimethylammoniumethyl) phosphate.
12. The compound of claim 10 , wherein the monomer is 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (MPC).
13. The compound according to claim 8 , wherein the total molecular weight of the compound is about 500,000 to about 1,000,000 daltons.
14. The compound according to claim 11 , wherein the total molecular weight of the compound is about 650,000 to about 850,000 daltons.
15. The compound according to claim 12 , wherein the total molecular weight of the compound is about 750,000 daltons.