Radiopaque polymers

Patent metadata

Field	Value
Publication number	US-2019142946-A1
Application number	US-201916243672-A
Country	US
Kind code	A1
Filing date	Jan 9, 2019
Priority date	Sep 6, 2013
Publication date	May 16, 2019
Grant date	—

Abstract

Radiopaque hydrogels, in particular radiopaque hydrogel microspheres comprising a polymer having 1,2-diol or 1,3-diol groups acetalised with radiopaque species.

First claim

1 .- 35 . (canceled)

36 . A polyvinyl alcohol (PVA) polymer comprising 1,3-diol groups of the PVA acetalised with a radiopaque species, such that the PVA backbone comprises 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 2-6 alkenylene, C 2-6 alkynylene, 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.

37 . The polymer according to claim 36 , wherein Q is a phenyl group substituted by one or more iodines.

38 . The polymer according to claim 36 , wherein Q is a phenyl substituted by 3 or 4 iodines.

39 . The polymer according to claim 36 , 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.

40 . The polymer according to claim 36 , 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—.

41 . The polymer according to claim 36 , 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.

42 . The polymer according to claim 36 , further comprising greater than 10% iodine by dry weight.

43 . The polymer according to claim 36 , comprising greater than 30% iodine by dry weight.

44 . The polymer according to claim 36 , wherein the polymer is cross linked.

45 . The polymer according to claim 37 , wherein the polymer is cross linked.

46 . The polymer according to claim 38 , wherein the polymer is cross linked.

47 . The polymer according to claim 39 , wherein the polymer is cross linked.

48 . The polymer according to claim 40 , wherein the polymer is cross linked.

49 . The polymer according to claim 41 , wherein the polymer is cross linked.

50 . The polymer according to claim 42 , wherein the polymer is cross linked.

51 . The polymer according to claim 43 , wherein the polymer is cross linked.

52 . A method of making a radiopaque polyvinyl alcohol (PVA) polymer or co-polymer 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 2-6 alkenylene, C 2-6 alkynylene, 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.

53 . The method according to claim 52 , wherein Q is a phenyl group substituted by one or more iodines.

54 . The method according to claim 52 , wherein Q is a phenyl substituted by 3 or 4 iodines.

55 . The method according to claim 52 , 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.

56 . The method according to claim 52 , 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—.

57 . The method according to claim 52 , 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.

58 . The method according to claim 52 , wherein Q is a phenyl group substituted by 2, 3 or 4 iodines.

59 . The method according to claim 52 , wherein Q is a 2,3,5 triiodophenyl group or a 2,4,6 triiodophenyl group or a 2,3,4,6 tetraiodophenyl group.

60 . The method according to claim 52 , wherein the radiopaque species is an iodinated benzyl aldehyde, iodinated phenyl aldehyde or an iodinated phenoxyaldehyde.

61 . The method according to claim 52 , wherein the reaction is conducted in polar organic solvent and at a temperature of greater than 25° C.

62 . The method according to claim 52 , wherein A is an aldehyde, acetal, hemiacetal, thioacetal or dithioacetal group.

63 . The method according to claim 52 , wherein A is selected from the group consisting of —CHO, —CHOR 1 OR 2 —CHOR 1 OH, —CHSR 1 OH and —CHSRSR 2 wherein R 1 and R 2 are independently selected from C 1-4 alkyl.

64 . The method according to claim 52 , 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.

65 . A polyvinyl alcohol (PVA) polymer or co-polymer comprising 1,3-diol groups of the PVA acetalised with a radiopaque species, wherein the PVA backbone comprises a structure according to the general formula I

wherein X is an iodinated phenyl group.

66 . A PVA polymer or co-polymer comprising 1,3-diol groups of the PVA acetalised with a radiopaque species, wherein the PVA backbone comprises a structure according to any of the general formulas a to e

Assignees

• Biocompatibles Uk Ltd

Inventors

• Hohn Stephane
• Lewis Andrew Lennard
• Willis Sean Leo
• Dreher Matthew R
• Ashrafi Koorosh
• Tang Yiqing

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/41

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title