Inherently radiopaque polymeric products for embolotherapy

1. An embolotherapy product, comprising a particulate formulation comprising a biocompatible, bioresorbable polymer comprising one or more units of Formula (I):

and optionally including stereoisomers thereof,

wherein X═I or Br; Y1 and Y2 independently=0, 1, 2, 3 or 4; provided that at least one iodine atom is present, or, in the absence of at least one iodine atom, at least two bromine atoms are present;

wherein f is between 0 and less than 1; g is between 0 and 1, inclusive; and f+g is between 0 and 1, inclusive;

wherein A is selected from the group consisting of:

wherein R 1 is independently H or an alkyl group having 1 to about 18 carbon atoms and containing 0 to 5 heteroatoms selected from O and N; and R 3 is a saturated or unsaturated, substituted or unsubstituted alkyl, aryl, or alkylaryl group containing up to about 18 carbon atoms and 0 to 8 heteroatoms selected from O and N;

wherein B is an aliphatic linear or branched diol or a poly(alkylene glycol) unit; and

wherein R and R 2 are independently selected from:

wherein R 7 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)a; wherein R 8 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)n; wherein a and n are independently between 0 and 8 inclusive; J 1 and J 2 are independently Br or I; and wherein Q for R 2 comprises a free carboxylic acid group and Q for each R is independently selected from the group consisting of hydrogen, carboxylic acid esters and carboxylic acid amides, wherein said esters and amides are selected from the group consisting of esters and amides of alkyl and alkylaryl groups containing up to 18 carbon atoms, and esters and amides of biologically active compounds;

wherein the embolotherapy product is inherently radiopaque.

2. The embolotherapy product of claim 1 , wherein said polymer further comprises a homopolymer, a heteropolymer, or a blend thereof.

3. The embolotherapy product of claim 1 , wherein R and R 2 are selected from the groups:

wherein for each R, R 1 is independently an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N and for each R 2 , R 1 is H;

wherein j and m are independently integers from 1 to 8 inclusive; and

wherein Z is independently either 0 or S.

4. The embolotherapy product of claim 1 , wherein said polymer is copolymerized with a poly(C 1 -C 4 alkylene glycol).

5. The embolotherapy product of claim 4 , wherein said poly(C 1 -C 4 alkylene glycol) is present in a weight fraction of less than about 75 wt %.

6. The embolotherapy product of claim 5 , wherein said poly(alkylene glycol) is poly(ethylene glycol).

7. The embolotherapy product of claim 4 , wherein between about 0.01 and about 0.99 percent of said polymer units comprise a pendant —COOH group.

8. The embolotherapy product of claim 1 , wherein said polymer comprises one or more units of Formula (IV):

wherein each X is independently I or Br, Y1 and Y2 for each diphenol unit are independently between 0 and 4, inclusive, and Y1+Y2 for each diphenol unit is between 1 and 8, inclusive;

each R and R 2 are independently an alkyl, aryl or alkylaryl group containing up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N, wherein R 2 further comprises a pendant carboxylic acid group;

wherein A is either:

wherein R 3 is a saturated or unsaturated, substituted or unsubstituted alkyl, aryl, or alkylaryl group containing up to about 18 carbon atoms and 0 to 8 heteroatoms selected from O and N; and

wherein P is a poly(C 1 -C 4 alkylene glycol) unit having a weight fraction of about 75% or less; f is between 0 and less than 1; g is between 0 and 1, inclusive; and f+g is between 0 and 1, inclusive.

9. The embolotherapy product of claim 8 , wherein P is a poly(ethylene glycol) that is present in a weight fraction of about 50% or less.

10. The embolotherapy product of claim 8 , wherein both R and R 2 comprise a pendant COOR 1 group;

wherein for R, the subgroup R 1 is independently an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N; and

wherein for R 2 , the subgroup R 1 is a hydrogen atom.

11. The embolotherapy product of claim 8 , wherein each R and R 2 independently has the structure:

wherein R 7 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)a, wherein R 8 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)n, wherein a and n are independently between 0 and 8 inclusive; and J 1 and J 2 are independently Br or I; and wherein, for each R 2 , Q comprises a free carboxylic acid group, and, for each R, Q is independently selected from the group consisting of hydrogen and carboxylic acid esters and amides, wherein said esters and amides are selected from the group consisting of esters and amides of alkyl and alkylaryl groups containing up to 18 carbon atoms and esters and amides of biologically active compounds.

12. The embolotherapy product of claim 8 , wherein each R 2 independently has the structure:

wherein R 5a is an alkyl group containing up to 18 carbon atoms and from 0 to 5 heteroatoms selected from O and N; wherein m is an integer from 1 to 8 inclusive; and wherein, for each R 2 , R 1 is hydrogen, and, for each R, R 1 is independently an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

13. The embolotherapy product of claim 8 , wherein each R 2 independently has the structure:

wherein j and m are independently an integer from 1 to 8, inclusive, and wherein, for each R 2 , R 1 is hydrogen, and, for each R, R 1 is independently an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

14. The embolotherapy product of claim 8 , wherein R 3 of said polymer is a moiety selected from the group consisting of —CH 2 —C(═O)—, —CH 2 —CH 2 —C(═O)—, —CH═CH— and (—CH 2 -)z, wherein z is an integer from 1 to 8, inclusive.

15. The embolotherapy product of claim 8 , wherein all X groups are ortho-directed.

16. The embolotherapy product of claim 8 , wherein Y1 and Y2 are independently 2 or less, and Y1+Y2=1, 2, 3 or 4.

17. The embolotherapy product of claim 16 , wherein all X groups are iodine.

18. The embolotherapy product of claim 8 , wherein f is greater than 0.1 to about 0.3.

19. The embolotherapy product of claim 8 , wherein said poly(C 1 -C 4 alkylene glycol) weight fraction is less than about 25 wt %.

20. The embolotherapy product of claim 8 , wherein g is greater than about 0.1 to about 0.35.

21. The embolotherapy product of claim 1 , wherein said formulation comprises polymer particles selected from the group consisting of spherical particles, geometrically non-uniform particles, porous particles, hollow particles, solid particles, and particles having an excluded diameter of from about 10 microns to about 5,000 microns, and combinations thereof.

22. The embolotherapy product of claim 1 , wherein the formulation comprises a polymer hydrogel composition.

23. The embolotherapy product of claim 1 , wherein said polymer further comprises an effective amount of at least one therapeutic agent.