Resorbable phenolic polymers
View Patent ↗The invention provides biocompatible resorbable polymers, comprising monomer units having formula (I), formula (II), formula (III) or formula (IV). The polymers degrade over time when implanted in the body, and are useful as components of implantable medical devices.
1. A diphenol having structure
wherein m is 0, 1, or 2; n is 0 to 4, Y is —NHCH 2 CO 2 R′;
and R′ is selected from the group consisting of H, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 8 -C 14 alkylaryl, benzyl, and substituted benzyl.
2. A polymer consisting essentially of monomer units having the formula
wherein m is 0, 1, or 2; n is 0 to 4, and Y is selected from the group consisting of C 1 -C 18 alkylamino, —NHCH 2 CO 2 R′, —NH(CH 2 ) q OR′, —NH(CH 2 CH 2 O) p R′, —NH(CH 2 CH 2 CH 2 O) p R′,
where q is 0 to 4, p is 1 to 5000, and R′ is selected from the group consisting of H, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 8 -C 14 alkylaryl, benzyl, and substituted benzyl; and A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000.
3. A polymer consisting essentially of monomer units having the formula
wherein m is 0, 1, or 2; R′ is selected from the group consisting of H, C 1 -C 18 alkyl, C 2 -C 18 alkenyl, C 8 -C 18 alkylaryl, benzyl, and substituted benzyl; and A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000.
4. A polymer according to claim 2 , wherein A is —CO—X—CO—.
5. A polymer according to claim 2 , wherein between 0.1% and 99.9% of the X moieties are (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r or (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r .
6. A polymer comprising monomer units having formula
wherein Y is OMe or OEt, A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, and X is selected from the group consisting of CH 2 CH 2 , CH 2 CH 2 CH 2 , and CH 2 —O—(CH 2 CH 2 O) s CH 2 , and s is 0 to 200.
7. A polymer according to claim 6 , further comprising monomer units independently having formula
wherein Y is OH or O-benzyl and A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, and X is selected from the group consisting of CH 2 CH 2 , CH 2 CH 2 CH 2 , and CH 2 —O—(CH 2 CH 2 O) s CH 2 , and s is 0 to 200.
8. A polymer comprising monomer units having the formula
wherein m is 0, 1, or 2; n is 0 to 4, Y is —NHCH 2 CO 2 R′;
and R′ is selected from the group consisting of H, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 8 -C 14 alkylaryl, benzyl, and substituted benzyl; and A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O)CO s (CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000.
9. A polymer comprising monomer units having the formula
wherein m is 0, 1, or 2; n is 0 to 4, and Y is selected from the group consisting of C 1 -C 18 alkylamino, —NHCH 2 CO 2 R′, —NH(CH 2 ) q OR′, —NH(CH 2 CH 2 O) p R′, —NH(CH 2 CH 2 CH 2 O) p R′,
where q is 0 to 4, p is 1 to 5000, and R′ is selected from the group consisting of H, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 8 -C 14 alkylaryl, benzyl, and substituted benzyl; and A is —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000.
10. A polymer comprising monomer units having the formula
wherein m is 0, 1, or 2; n is 0 to 4, and Y is selected from the group consisting of C 1 -C 18 alkylamino, —NHCH 2 CO 2 R′, —NH(CH 2 ) q OR′, —NH(CH 2 CH 2 O) p R′, —NH(CH 2 CH 2 CH 2 O) p R′,
where q is 0 to 4, p is 1 to 5000, and R′ is selected from the group consisting of H, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 8 -C 14 alkylaryl, benzyl, and substituted benzyl; and A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000, wherein between 0.1% and 99.9% of the X moieties are (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r or (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r .
11. A polymer according to claim 9 , wherein between 0.1% and 99.9% of the X moieties are (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r or (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r .
12. The polymer according to claim 10 , wherein A is —CO—X—CO—.
13. A polymer according to any one of claims 8 , 9 , or 10 further comprising monomer units independently having the formula
wherein m is 0, 1, or 2; n is 0 to 4; A is selected from the group consisting of —CO—, —C(═NH)—, and —CO—X—CO—, where X is selected from the group consisting of C 1 -C 18 alkylene, C 1 -C 18 alkenylene, divalent C 6 -C 10 arylene, divalent C 7 -C 18 alkylaryl, CH 2 OCH 2 , CH 2 —O—(CH 2 CH 2 O) s CH 2 , (CH 2 ) r CO 2 (CH 2 CH 2 CH 2 O) s CO(CH 2 ) r , and (CH 2 ) r CO 2 (CH 2 CH 2 O) s CO(CH 2 ) r , where r is 2 to 4 and s is 1 to 5000; and Y is OH or O-benzyl.
14. A polymer according to claim 13 , wherein between 1% and 50% of the monomer units have formula
wherein Y is OH or O-benzyl.