Biodegradable computed tomography contrast agents

Patent metadata

Field	Value
Publication number	US-9512072-B2
Application number	US-201414529631-A
Country	US
Kind code	B2
Filing date	Oct 31, 2014
Priority date	Oct 31, 2013
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

Biodegradable computed tomography (CT) contrast agents comprising a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide are described herein. The contrast agents can be used to image a tissue region by administering an effective amount of the biodegradable CT contrast agent to a subject, allowing a sufficient amount of time for the biodegradable CT contrast agent to enter the tissue region, and performing x-ray computed tomography imaging of the tissue region of the subject.

First claim

What is claimed is:

1. A biodegradable macromolecular computed tomography (CT) contrast agent comprising a polyiodinated aryl contrast agent having a structure according to formula I:

wherein P is an organic disulfide, R 1 is a carboxyl or carboxamide group, and R 2 is a an amine, a lower alkyl group, or an amine-bound water soluble polymer or oligomer, and n is from 2 to 10,000 or a structure according to formula II:

wherein P is an organic disulfide, R 1 is a carboxyl or carboxamide group, and R 2 is a an amine, a lower alkyl group, or an amine-bound water soluble polymer or oligomer, R 3 is a lower alkylene or alkylene ether group, and n is from 2 to 10,000.

2. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the polyiodinated aryl contrast agent is PEGylated.

3. The biodegradable macromolecular CT contrast agent of claim 1 , wherein R 2 is an amine.

4. The biodegradable macromolecular CT contrast agent of claim 1 , wherein R 1 is a carboxamide group.

5. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the contrast agent has a structure according to formula III:

wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.

6. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the contrast agent has a structure according to formula IV:

wherein R is a water soluble polymer or oligomer and n is from 2 to 10,000.

7. A method for imaging a tissue region of a subject comprising:
(a) administering an effective amount of a biodegradable macromolecular computed tomography (CT) contrast agent according to claim 1 to the subject;
(b) allowing a sufficient amount of time for the macromolecular biodegradable CT contrast agent to enter the tissue region; and
(c) performing x-ray computed tomography imaging of the tissue region of the subject.

8. The method of claim 7 , wherein
R 2 is a an amine.

9. The method of claim 7 , wherein R 1 is a carboxamide group.

10. The method of claim 7 wherein the biodegradable macromolecular CT contrast agent has a structure according to formula III:

wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.

11. The method of claim 7 , wherein the biodegradable macromolecular CT contrast agent has a structure according to formula IV:

wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.

12. The method of claim 7 wherein the tissue region is a blood vessel.

13. The method of claim 7 , wherein the tissue region is a tumor.

14. A method of making a biodegradable computed tomography (CT) contrast agent, comprising the steps of:
(a) reacting pegylated or non-pegylated 5-amino-2,4,6-triiodoisophthalic acid (ATIPA) with thionyl chloride to provide an diacyl chloride polyiodinated aryl group; and
(b) polymerizing the diacyl chloride iodinated aryl group with an organic disulfide to provide a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide.

15. The method of claim 14 , wherein the dicarboxyl polyiodinated aryl group is 5-amino-2,4,6-triiodoisophthalic acid (ATIPA).

16. The method of claim 14 , wherein the dicarboxyl polyiodinated aryl group is PEGylated 5-amino-2,4,6-triiodoisophthalic acid (ATIPA).

Assignees

• Univ Case Western Reserve

Inventors

• Lu Zheng-Rong
• Jin Erlei
• Wu Xiaohui

Classifications

• A61K49/0438

  Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol · CPC title

• A61K49/0442

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

• C07C319/12

  by reactions not involving the formation of mercapto groups · CPC title

• C07C323/25 Primary

  the carbon skeleton being acyclic and saturated · CPC title

• C07D207/46

  with hetero atoms directly attached to the ring nitrogen atom · CPC title