Radiopaque polymers for medical devices
Radiopaque polymer compositions and methods for making the compositions are provided. These radiopaque polymer compositions include polymer compositions comprising a crosslinked polymer network, the network comprising a first repeating unit derived from a monofunctional monomer and a second repeating unit derived from a multifunctional non-iodinated monomer wherein neither of the two monomers is fluorinated. Devices formed from radiopaque polymer compositions are also provided.
1. A polymer composition comprising a crosslinked network, the network comprising:
a) a first repeating unit represented by one of Formula 1, 1-A, 1-B or 1-C:
wherein X is Br or I;
m is an integer from 3-5;
R 1 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, or C 5 -C 36 heteroarylene;
L 1 is a single bond, —(CH 2 ) n , —(HCCH) n —, —O—, —S—, —SO—, —SO 2 —, —SO 3 —, —OSO 2 —, —NR 2 —, —CO—, —COO—, —OCO—, —OCOO—, —CONR 3 —, —NR 4 CO—, —OCONR 5 —, —NR 6 COO—, or —NR 7 CONR 8 —;
Ar 1 is a C 5 -C 30 aryl or C 5 -C 30 heteroaryl that is substituted with three or more I, Br or Bi atoms;
each of R 2 -R 8 is independently hydrogen or C 1 -C 10 alkyl; and
n is an integer selected from the range of 1 to 16; and
b) a second repeating unit represented by Formula 2:
wherein R 9 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups, and
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50.
2. The polymer composition of claim 1 , wherein the first repeating unit is represented by Formula 1-D,
wherein n is an integer from 1 to 16, each of X 1 -X 5 is iodine or hydrogen and at least three of X 1 -X 5 are iodine.
3. The polymer composition of claim 1 , wherein the second repeating unit is represented by Formula 2-B, where R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50.
4. The polymer composition of claim 1 , wherein the network further comprises a third repeating unit represented by Formula 7:
wherein R 14 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is an aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups,
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50, and
R 14 is other than R 9 .
5. A polymer composition comprising a crosslinked network formed by polymerization of a monomer mixture comprising:
a) a first monomer having structure of one of Formula 8, 8-A, 8-B or 8-C;
wherein X is Br or I;
m is an integer from 3-5;
wherein R 1 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, or C 5 -C 36 heteroarylene;
L 1 is a single bond, —(CH 2 ) n —, —(HCCH) n —, —O—, —S—, —SO—, —SO 2 —, —SO 3 —, —OSO 2 —, —NR 2 —, —CO—, —COO—, —OCO—, —OCOO—, —CONR 3 —, —NR 4 CO—, —OCONR 5 —, —NR 6 COO—, or —NR 7 CONR 8 —;
Ar 1 is a C 5 -C 30 aryl or C 5 -C 30 heteroaryl that is substituted with three or more I, Br or Bi atoms; and
each of R 2 -R 8 is independently hydrogen or C 1 -C 10 alkyl;
n is an integer selected from the range of 1 to 16; and
b) a second monomer having structure of Formula 9:
wherein R 9 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups, and
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50.
6. The polymer composition of claim 5 , wherein the structure of the first monomer is given by Formula 13-A,
and at least three of X 1 -X 5 are iodine and n is an integer from 1 to 16.
7. The polymer composition of claim 5 , wherein the second monomer has the structure of Formula 9-A where R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50.
8. The polymer composition of claim 5 , wherein the mixture further comprises a monomer having the general structure of Formula 12
wherein R 14 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is an aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups,
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50, and
R 14 is other than R 9 .
9. A method for making a polymer composition comprising a crosslinked network, the method comprising the steps of:
a) forming a monomer mixture comprising
i) a first monomer having structure of one of Formula 8, 8-A, 8-B or 8-C:
wherein X is Br or I;
m is an integer from 3 to 5;
wherein R 1 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, or C 5 -C 36 heteroarylene;
L 1 is a single bond, —(CH 2 ) n —, —(HCCH) n —, —O—, —S—, —SO—, —SO 2 —, —SO 3 —, —OSO 2 —, —NR 2 —, —CO—, —COO—, —OCO—, —OCOO—, —CONR 3 —, —NR 4 CO—, —OCONR 5 —, —NR 6 COO—, or —NR 7 CONR 8 —;
Ar 1 is a C 5 -C 30 aryl or C 5 -C 30 heteroaryl that is substituted with three or more I, Br or Bi atoms; and
each of R 2 -R 8 is independently hydrogen or C 1 -C 10 alkyl;
n is an integer selected from the range of 1 to 16;
ii) a second monomer having structure of Formula 9:
wherein R 9 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups, and
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50; and
iii) a free radical initiator; and
b) polymerizing the monomer mixture.
10. The method of claim 9 , wherein the structure of the first monomer is given by Formula 13-A,
at least three of X 1 -X 5 are iodine and n is an integer from 1 to 16.
11. The method of claim 9 , wherein the second monomer has the structure of Formula 9-A where R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50.
12. The method of claim 9 , wherein the mixture further comprises a monomer having the general structure of Formula 12
wherein R 14 is substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, an oligomeric polyester, an oligomeric polycarbonate, an oligomeric polyurethane,
wherein
R 10 is C 4 -C 20 alkylene and n 3 is an integer from 1 to 50,
wherein R 11 is C 3 -C 20 alkylene and n 4 is an integer from 1 to 50,
R 15 is an aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, aromatic group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group or a combination of linear or branched aliphatic groups and aromatic groups,
R 16 is ether group, silicon-containing group, polyalkyl siloxane group, polyether group, polyester group, polycarbonate group, C 3 -C 20 alkylene, aliphatic group, substituted or unsubstituted C 2 -C 36 alkylene, C 3 -C 36 cycloalkylene, C 2 -C 36 alkenylene, C 3 -C 36 cycloalkenylene, C 2 -C 36 alkynylene, C 5 -C 36 arylene, C 5 -C 36 heteroarylene, or aromatic group, or a combination of aliphatic groups and aromatic groups and n 5 is an integer from 1 to 50, and
R 14 is other than R 9 .
13. The polymer composition of claim 1 , wherein the amount of the first repeating unit in the polymer composition is at least 50 wt %.
14. The polymer composition of claim 13 , wherein the amount of the second repeating unit in the polymer composition is at most 40 wt %.
15. The polymer composition of claim 4 , wherein the network further comprises a fourth repeating unit represented by Formula 5:
wherein R 12 is C 2 to C 36 alkyl.
16. The polymer composition of claim 5 , wherein the amount of the first monomer is at least 50 wt % of the monomer mixture.
17. The polymer composition of claim 16 , wherein the amount of the second monomer is at most 40 wt % of the monomer mixture.
18. The polymer composition of claim 8 , wherein the monomer mixture further comprises a fourth monomer having structure of Formula 10:
wherein R 12 is C 2 to C 36 alkyl.
19. The method of claim 9 , wherein the amount of the first monomer is at least 50 wt % of the monomer mixture.
20. The method of claim 19 , wherein the amount of the second monomer is at most 40 wt % of the monomer mixture.
21. The method of claim 12 , wherein the monomer mixture further comprises a fourth monomer having structure of Formula 10:
wherein R 12 is C 2 to C 36 alkyl.