Subcutaneous delivery of poly(oxazoline) polymer conjugates
The present disclosure provides polymer conjugates comprising a polymer and an agent, the agent linked to the polymer via a linking group containing a hydrolyzable moiety.
1. A poly(oxazoline) polymer conjugate, the poly(oxazoline) polymer conjugate having the structure
wherein
L is
R 3 forms a linkage with the poly(oxazoline) polymer chain;
R 4 is —CH 2 —C(O)—O—, —CH(CH 3 )—C(O)—O—, —CH 2 —CH 2 —C(O)—O—, —CH 2 —CH 2 —CH 2 —C(O)—O—, —CH 2 —O—C(O)—, —CH(CH 3 )—O—C(O), —CH 2 —CH 2 —O—C(O)— or —CH 2 —CH 2 —CH 2 —O—C(O)—;
R is an initiating group;
R 1 is a non-reactive group;
A is rotigotine;
a is ran which indicates a random copolymer or block which indicates a block copolymer;
o is from 1-50;
m is from 1-1000;
T is a terminating group; and
the conjugate provides a release profile for rotigotine that is dependent on the selection of R 4 .
2. The polymer conjugate of claim 1 , wherein the poly(oxazoline) polymer has a molecular weight range of 300 Da to 200,000 Da.
3. The polymer conjugate of claim 1 , wherein R 3 is —C(O)—(CH 2 ) 3 and R 4 is —CH 2 —C(O)—O—, —CH 2 —CH 2 —C(O)—O—, —CH(CH 3 )—C(O)—O— or —CH 2 —CH 2 —CH 2 —C(O)—O—.
4. The polymer conjugate of claim 1 , wherein L has the structure
5. The polymer conjugate of claim 1 , wherein T is —Z—B-Q
wherein
Z is S, O, or N;
B is an optional linking group; and
Q is a terminal portion of a terminating nucleophile.
6. The polymer conjugate of claim 1 , wherein R is hydrogen, alkyl or substituted alkyl.
7. The polymer conjugate of claim 1 , wherein R 1 is an alkyl or substituted alkyl.
8. The polymer conjugate of claim 1 , wherein the rotigotine is (−)rotigotine.
9. The polymer conjugate of claim 1 , wherein the release profile provides a controllable delivery of the rotigotine over a period of days to weeks.
10. The polymer conjugate of claim 1 , wherein the release profile provides a controllable delivery of the rotigotine over a period of weeks.
11. The polymer conjugate of claim 1 , wherein R 3 is —C(O)—(CH 2 ) 3 — and R 4 is —CH 2 —CH 2 —C(O)—O—.
12. The polymer conjugate of claim 1 , wherein R 3 is —C(O)—(CH 2 ) 3 — and R 4 is —CH(CH 3 )—C(O)—O—.
13. The polymer conjugate of claim 1 , wherein R 3 is —C(O)—(CH 2 ) 3 — and R 4 is —CH 2 —C(O)—O—.
14. The polymer conjugate of claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 .
15. The polymer conjugate of claim 1 , wherein T is —SCH 2 CH 2 —COOH.
16. The polymer conjugate of claim 1 , wherein R 1 is alkyl or substituted alkyl, T is —SCH 2 CH 2 —COOH and R is H, alkyl, or substituted alkyl.
17. The polymer conjugate of claim 4 , wherein R 1 is alkyl or substituted alkyl, T is —SCH 2 CH 2 —COOH and R is H, alkyl, or substituted alkyl.
18. The polymer conjugate of claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 , T is —SCH 2 CH 2 —COOH and R is H or —CH 3 .
19. The polymer conjugate of claim 4 , wherein R 1 is —CH 3 or —CH 2 CH 3 , T is —SCH 2 CH 2 —COOH and R is H or —CH 3 .