Radiopaque polymers
Radiopaque hydrogels, in particular radiopaque hydrogel microspheres, comprising a polymer having 1,2-diol or 1,3-diol groups acetalised with radiopaque species.
1. A polyvinyl alcohol (PVA) polymer comprising a PVA backbone having a structure according to the general formula I
wherein X is a group of the formula
ZQ II
wherein:
Z is a linking group, or is absent, such that Q is directly bonded to the cyclic acetal;
if Z is present, then Z is C 1-6 alkylene C 1-6 alkoxylene; or C 1-6 alkoxyalkylene;
Q is a C 5 to C 12 aryl, or heteroaryl; and
Q is substituted by one or more iodines.
2. The polymer according to claim 1 , wherein Q is a phenyl group substituted by one or more iodines.
3. The polymer according to claim 1 , wherein Q is a phenyl substituted by 3 or 4 iodines.
4. The polymer according to claim 1 , wherein if Z is present, Z is (i) C 1-6 alkylene, C 1-4 alkoxylene or (ii) is a group (CH 2 ) p —O—(CH 2 ) q — wherein q is 0, 1 or 2 and p is 1 or 2.
5. The polymer according to claim 1 , wherein if Z is present, Z is —(CH 2 ) 2 O(CH 2 ) 2 —, —CH 2 OCH 2 —, —(CH 2 ) 2 O—, or —CH 2 O—.
6. The polymer according to claim 1 , wherein Q is a phenyl group substituted by one or more iodines; and if Z is present, Z is a C 1-6 alkylene or a group —(CH 2 ) q —O—(CH 2 ) p — wherein p is 0, 1 or 2 and q is 1 or 2.
7. The polymer according to claim 1 , further comprising greater than 10% iodine by dry weight.
8. The polymer according to claim 1 , comprising greater than 30% iodine by dry weight.
9. The polymer according to claim 1 , wherein the polymer is cross linked.
10. The polymer according to claim 2 , wherein the polymer is cross linked.
11. The polymer according to claim 3 , wherein the polymer is cross linked.
12. The polymer according to claim 4 , wherein the polymer is cross linked.
13. The polymer according to claim 5 , wherein the polymer is cross linked.
14. The polymer according to claim 6 , wherein the polymer is cross linked.
15. The polymer according to claim 7 , wherein the polymer is cross linked.
16. The polymer according to claim 8 , wherein the polymer is cross linked.
17. A method of making a radiopaque polyvinyl alcohol (PVA) polymer or co-polymer comprising the general formula I of claim 1 , comprising reacting a PVA polymer or co-polymer comprising 1,3-diol groups with a radiopaque species capable of forming a cyclic acetal with said 1,3 diols under acidic conditions, wherein the radiopaque species is a compound of the formula
X-A; and I
X is a group of the formula
ZQ II
wherein:
Z is a linking group, or is absent; if Z is present, then Z is C 1-6 alkylene C 1-6 alkoxylene; or C 1-6 alkoxyalkylene;
Q is a C 5 to C 12 aryl, or heteroaryl group; and
Q is substituted by one or more iodines; and
A is a group capable of forming a cyclic acetal with a 1,3 diol under acidic conditions.
18. The method according to claim 17 , wherein Q is a phenyl group substituted by one or more iodines.
19. The method according to claim 17 , wherein Q is a phenyl substituted by 3 or 4 iodines.
20. The method according to claim 17 , wherein if Z is present, Z is (i) C 1-6 alkylene, C 1-4 alkoxylene or (ii) is a group (CH 2 ) p —O—(CH 2 ) q — wherein q is 0, 1 or 2 and p is 1 or 2.
21. The method according to claim 17 , wherein if Z is present, Z is —CH 2 OCH 2 —, —(CH 2 ) 2 O(CH 2 ) 2 —, —(CH 2 ) 2 O—, or —CH 2 O—.
22. The method according to claim 17 , wherein Q is a phenyl group substituted by one or more iodines; and if Z is present, Z is (i) a C 1-6 alkylene or (iii) is a group —(CH 2 ) q —O—(CH 2 ) p — wherein p is 0, 1 or 2 and q is 1 or 2.
23. The method according to claim 17 , wherein Q is a phenyl group substituted by 2, 3 or 4 iodines.
24. The method according to claim 17 , wherein Q is a 2,3,5 triiodophenyl group or a 2,4,6 triiodophenyl group or a 2,3,4,6 tetraiodophenyl group.
25. The method according to claim 17 , wherein the radiopaque species is an iodinated benzyl aldehyde, iodinated phenyl aldehyde or an iodinated phenoxyaldehyde.
26. The method according to claim 17 , wherein the reaction is conducted in polar organic solvent and at a temperature of greater than 25° C.
27. The method according to claim 17 , wherein A is an aldehyde, acetal, hemiacetal, thioacetal or dithioacetal group.
28. The method according to claim 17 , wherein A is selected from the group consisting of —CHO, —CHOR 1 OR 2 —CHOR 1 OH, —CHSR 1 OH and —CHSR 1 SR 2 wherein R 1 and R 2 are independently selected from C 1-4 alkyl.
29. The method according to claim 17 , wherein the radiopaque species is selected from the group consisting of 2,3,5-triiodobenzaldehyde, 2,3,4,6-tetraiodobenzyaldehyde and 2-(2,4,6-triiodophenoxy)acetaldehyde.
30. A polyvinyl alcohol (PVA) polymer or co-polymer comprising a PVA backbone having a structure according to the general formula I
wherein X is an iodinated phenyl group.
31. A PVA polymer or co-polymer comprising a structure according to any of the general formulas a to e