Biocompatible iodinated diphenol monomers and polymers

Patent metadata

Field	Value
Publication number	US-10087285-B2
Application number	US-201514983801-A
Country	US
Kind code	B2
Filing date	Dec 30, 2015
Priority date	Dec 23, 2014
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

Disclosed are monomeric compounds which may be polymerized to form novel biodegradable and bioresorbable polymers and co-polymers. These polymers and co-polymers, while not limited thereto, may be adapted for radioopacity and are useful for medical device applications and controlled release therapeutic formulations.

First claim

What is claimed is:

1. A copolymer comprising a first repeating unit having the structure:

and a second repeating unit having the structure:

wherein X 1 , X 2 , X 4 and X 5 , are independently selected from the group consisting of O, S and NR 3 , wherein R 3 is selected from the group consisting of hydrogen and alkyl groups containing from one to six carbon atoms;
Ar 1 is phenylene substituted with at least one iodine atom, optionally further substituted with from one to three substituents independently selected from the group consisting of halogen, halomethyl, halomethoxy, methyl, methoxy, thiomethyl, nitro, sulfoxide and sulfonyl; and
B is selected from the group consisting of optionally substituted alkylene groups of 1 to 18 carbon atoms, optionally substituted heteroalkylene groups of 1 to 18 carbon atoms, optionally substituted alkenylene groups of 2 to 18 carbon atoms and optionally substituted heteroalkenylene groups of 2 to 18 carbon atoms;
wherein said copolymer is a block copolymer or a random copolymer or a graft copolymer.

2. The polymer of claim 1 wherein X 1 , X 2 , X 4 and X 5 are all oxygen atoms.

3. The polymer of claim 1 wherein Ar 1 is phenylene substituted with two iodine atoms in positions ortho to X 1 .

4. The polymer of claim 1 wherein B is an alkylene group comprising the structure (CH 2 ) n wherein n is an integer from 1 to 10.

5. The polymer of claim 4 wherein n is an integer selected from the group consisting of 3, 5 and 6.

6. The polymer of claim 4 wherein B is a methylene group having the formula —CH 2 —.

7. The polymer of claim 1 wherein B is a branched chain ethylene group having the formula —CH(CH 3 )—.

8. A radio-opaque copolymer of lactic acid with 3,5-diiodo-4-hydroxybenzoic acid.

9. A radio-opaque copolymer of glycolic acid with 3,5-diiodo-4-hydroxybenzoic acid.

10. A radio-opaque copolymer of lactic acid and glycolic acid with 3,5-diiodo-4-hydroxybenzoic acid.

11. A compound having the structure:

wherein X 1 , X 2 , X 3 , X 4 , X 5 , and X 6 are independently selected from the group consisting of O, S and NR 3 wherein R 3 is selected from the group consisting of hydrogen and alkyl groups containing from one to six carbon atoms;
Ar 1 and Ar 2 are independently selected from the group consisting of phenylene,

substituted with from one to four iodine atoms and optionally substituted with substituents independently selected from the group consisting of other halogens, halomethyl, halomethoxy, methyl, methoxy, thiomethyl, nitro, sulfoxide, and sulfonyl;
R 2 is a bond or is selected from the group consisting of optionally substituted alkylene containing from 1 to 10 carbon atoms, heteroalkylene containing from 1 to 10 carbon atoms, alkenylene containing from 2 to 10 carbon atoms, and heteroalkenylene containing from 2 to 10 carbon atoms;
R 5 and R 6 are independently selected from the group consisting of hydrogen and alkyl groups containing from one to six carbon atoms; and B is a carbonyl group.

12. The compound of claim 11 wherein each X 1 , X 2 , X 3 , X 4 , X 5 and X 6 is an O atom.

13. The compound of claim 12 wherein both Ar 1 and Ar 2 are phenylene groups substituted with two iodine atoms.

14. The compound of claim 11 wherein R 2 is an alkylene group containing from one to ten carbon atoms, or a bond.

15. The compound of claim 11 wherein R 2 is a bond.

16. A polymer comprising at least one repeating unit having the structure:

wherein, X 1 , X 2 , X 3 , X 4 , X 5 , and X 6 are independently selected from the group consisting of O, S and NR 3 wherein R 3 is selected from the group consisting of hydrogen and alkyl groups containing from one to six carbon atoms;
Ar 1 and Ar 2 are independently selected from the group consisting of phenylene,

optionally substituted with from one to four substituents independently selected from the group consisting of halogen, halomethyl, halomethoxy, methyl, methoxy, thiomethyl, nitro, sulfoxide, and sulfonyl;
provided that at least one of Ar 1 and Ar 2 is substituted with at least one iodine atom;
R 2 is independently a bond or is selected from the group consisting of optionally substituted alkylene containing from 1 to 10 carbon atoms, heteroalkylene containing from 1 to 10 carbon atoms, alkenylene containing from 2 to 10 carbon atoms, and heteroalkenylene containing from 2 to 10 carbon atoms; and B 1 is a carbonyl group.

17. The polymer of claim 16 wherein each X 1 , X 2 , X 3 , X 4 , X 5 , and X 6 is an oxygen atom.

18. The polymer of claim 16 wherein each Ar 1 and Ar 2 is independently phenylene substituted with at least one iodine atom.

19. The polymer of claim 18 wherein Ar 1 and Ar 2 are both phenylene groups substituted with two iodine atoms.

20. The polymer of claim 16 wherein R 2 is an alkylene group containing from one to ten carbon atoms, or a bond.

21. The polymer of claim 19 wherein R 2 is a bond.

22. The polymer of claim 16 , characterized in that said polymer is a block copolymer with a hydroxy endcapped macromer, a mercapto endcapped macromer or an amino endcapped macro mer.

23. The polymer of claim 22 , wherein said hydroxy endcapped macromer block comprises at least one macromer block selected from the group consisting of hydroxy endcapped polycaprolactones, hydroxy endcapped polylactic acids, hydroxy endcapped polyglycolic acids, hydroxy endcapped poly(lactic acid-co-glycolic acids), hydroxy endcapped poly(alkylene diols), poly(alkylene oxides) and hydroxy endcapped polydioxanones.

24. The polymer of claim 23 , wherein the alkylene diol of said poly(alkylene diol) is hexane diol.

25. The polymer of claim 22 , wherein the weight ratio of said polymer to said hydroxy-capped macromer is between about 25:75 and about 99:1.

26. The polymer of claim 16 comprising at least one repeating unit having the structure:

wherein the segment —X 6 -D-X 1 — is obtained from an intermediate HX 6 -D-X 1 H which defines an alkylene diol containing up to 24 carbon atoms, an alkylene diamine containing up to 24 carbon atoms, an alkylene dimercaptan containing up to 24 carbon atoms, a hydroxy endcapped macromer, a mercapto endcapped macromer or an amine endcapped macromer.

27. The polymer of claim 26 , wherein said hydroxy endcapped macromer block comprises at least one macromer block selected from the group consisting of hydroxy endcapped poly-caprolactones, hydroxy endcapped polylactic acids, hydroxy endcapped polyglycolic acids, hydroxy endcapped poly(lactic acid-co-glycolic acids), hydroxy endcapped poly(alkylene diols), poly(alkylen

Assignees

• Univ Rutgers

Inventors

• Bolikal Durgadas
• Kohn Joachim B

Classifications

• C07C69/84 Primary

  of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring · CPC title

• A61K49/0442

  Polymeric X-ray contrast-enhancing agent comprising a halogenated group · CPC title

• C08G81/00

  Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42}) · CPC title

• C08G63/64

  Polyesters containing both carboxylic ester groups and carbonate groups · CPC title

• C08G64/10 Primary

  containing halogens · CPC title