Crosslinked polymers with the crosslinker as therapeutic for sustained release
View Patent ↗Crosslinked polymers, methods for their preparation and use, are described in which the crosslinked polymers are formed from at least two polymer precursors, one of which is designed, upon degradation of the crosslinked polymer, to release the second polymer precursor in its original, unmodified chemical form.
1. A polymer precursor comprising a formula
wherein 1≦n≦500,000, and m≧2;
C=represents a core molecule;
R 1 =—H, or an amino acid side chain;
R 2 =an alkyl group; and
R 3 =an electrophilic functional group selected from the group consisting of —CO 2 N(COCH 2 ) 2 , —CO 2 H, —CHO, —CHOCH 2 , —N═C═O, —SO 2 CH═CH 2 , —N(COCH 2 ) 2 , and —S—S—(C 5 H 4 N), or a nucleophilic functional group selected from the group consisting of —NH 2 , —SH, —OH, —PH 2 , and —CO—NH—NH 2 .
2. The polymer precursor of claim 1 , wherein R 1 comprises an amino acid side chain selected from the group consisting of CH 3 , CH 2 —OH, CH 2 —CH(CH 3 ) 2 , CH 2 —CH 2 —CO 2 H, CH 2 —CH 2 —S—CH 3 , CH 2 —SH, CH 2 —CH 2 —CH 2 —CH 2 —NH 2 , CH 2 —CH 2 —CO—NH 2 , CH 2 —CO 2 H, CH 2 —CO—NH 2 , CH(CH 3 ) 2 , C 8 H 6 N 1 —CH 2 , CH(OH)CH 3 , C 6 H 5 —CH 2 , CH 2 —C 6 H 5 —OH, CH 2 —CH 2 —CH 2 —NH—C(NH)(NH 2 ), CH 2 —C 3 H 3 N 2 , (CH 2 ) 2 —CH—OH—CH 2 —NH 2 , CH 2 —(C 6 H 2 I 2 )—(C 6 H 2 I 2 )—OH, CH 2 —(C 3 H 2 N 2 )—CH 3 , CH 2 —CH 2 —CH 2 —CH 2 —NH—CH 3 , CH 2 —CH 2 —CH 2 —CH 2 —N—(CH 3 ) 3 , CH 2 —CH 2 —CH 2 —CO 2 H, CH—(CH 3 )—O—P—(O)(OH) 2 , CH 2 —C 6 H 4 —O—P—(O)(OH) 2 , CH 2 —CH 2 —CH 2 —NH—C—(NH)(NH—CH 3 ), CH 2 —CH 2 —CH 2 —CH 2 —NH—C—(O)(CH 3 ).
3. The polymer precursor of claim 1 , wherein R 1 comprises a natural amino acid side chain not found in proteins selected from the group consisting of CH 2 —CH 2 —OH, CH 2 —CH 2 —SH, CH 2 —O—CO—CH═N═N, CH 2 —S—CH(NH 2 )(CO 2 H), CH(OH)(C 6 H 5 ), C(SH)(CH 3 ) 2 , CH 2 —CH 2 —CH 2 —NH 2 , CH 2 —CH 2 —CH 2 —NH—C(O)(NH 2 ).
4. The polymer precursor of claim 1 , wherein R 2 comprises a C 1 -C 20 alkyl group.
5. The polymer precursor of claim 1 , wherein the core molecule is selected from the group consisting of glycerol, pentaerythritol and sorbitol.
6. The polymer precursor of claim 1 , wherein the core molecule comprises pentaerythritol.