Compositions and methods to evaluate hepatobiliary/gastrointestinal health, enterohepatic circulation, and drug interactions

Patent metadata

Field	Value
Publication number	US-9597417-B2
Application number	US-201414535397-A
Country	US
Kind code	B2
Filing date	Nov 7, 2014
Priority date	Nov 8, 2013
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

The present invention relates to the synthesis and use of a novel trifluorinated bile acid analog, that being, CA-sar-TFMA which is useful as an imaging probe, diagnostic agent or contrast agent and is resistant to bacterial deconjugation, wherein the trifluorinated bile acid analog can be used as a 19 F MRI tracer exhibiting an increased half-life due to its resistance to choloylglycine hydrolase.

First claim

That which is claimed is:

1. A trifluorinated bile acid analogue compound having the following structure:

wherein the trifluorinated bile acid analogue compound is a 19 F magnetic resonance imaging probe.

2. The trifluorinated bile acid analogue compound of claim 1 , formulated for administration forms selected from tablets, capsules, powders, solutions, suspensions, dispersions or syrups.

3. The trifluorinated bile acid analogue compound of claim 2 , further comprising a physiologically acceptable carrier.

4. The trifluorinated bile acid analogue compound of claim 1 , wherein the compound is not susceptible to bacterial deconjugation by choloylglycine hydrolase.

5. The trifluorinated bile acid analogue compound of claim 1 , wherein the compound is used to determine the mechanism underlying bile acid malabsorption.

6. A method to image gallbladder and/or gastrointestinal regions of a subject, the method comprising:
administering to a patient a CA-sar-TFMA compound having the following structure:

wherein the Ca-sar-TFMA compound is a 19 F magnetic resonance imaging probe,
and subjecting the patient to magnetic resonance imaging to provide magnetic resonance images of the gallbladder and/or gastrointestinal region.

7. The method of claim 6 , wherein the magnetic resonance images are interpreted in comparison to baseline MRI studies to determine the mechanisms underlying bile acid malabsorption.

8. The method of claim 6 , where in the administration is by oral route.

9. The method of claim 8 , wherein the oral route comprising oral administration of a form selected from tablets, capsules, powders, solutions, suspensions, dispersions or syrups.

10. The method of claim 6 , wherein the CA-sar-TFMA compound is combined with a physiologically acceptable carrier.

11. The method of claim 6 , wherein the magnetic resonance images are used to evaluate the reabsorption of bile acids into enteroheptic system.

12. The method of claim 6 , wherein the magnetic resonance images are used to monitor the progression of the disease state in a patient and/or pharmacological activity of anti-bile acid malabsorption (BAM) agents over the course of time.

13. The method of claim 6 , wherein the CA-sar-TFMA compound is administered in an amount from about 5 mg/kg to 200 mg/kg.

14. A method for diagnosis of bile acid diarrhea caused by at least the failure of enterohepatic recycling of the bile acids and excess amounts of bile acid entering the colon of a subject, the method comprising:
administering to a patient CA-sar-TFMA having the following structure

wherein the Ca-sar-TFMA compound is a 19 F magnetic resonance imaging probe,
and subjecting the patient to magnetic resonance imaging to provide magnetic resonance images.

15. The method of claim 14 , wherein the magnetic resonance images are interpreted in comparison to baseline MRI studies to determine the least the failure of enterohepatic recycling of the bile acids and excess amounts of bile acid entering the colon.

16. The method of claim 14 , where in the administration is by oral route.

17. The method of claim 16 , wherein the oral route comprising oral administration of a form selected from tablets, capsules, powders, solutions, suspensions, dispersions or syrups.

18. The method of claim 14 , wherein the CA-sar-TFMA compound is combined with a physiologically acceptable carrier.

19. The method of claim 14 , wherein the magnetic resonance images are used to evaluate the reabsorption of bile acids into enteroheptic system.

20. The method of claim 14 , wherein the CA-sar-TFMA compound is administered in an amount from about 5 mg/kg to 200 mg/kg.

21. The method of claim 14 , wherein the magnetic resonance images are used to evaluate the activity of an anti-BAM drug.

22. A kit comprising an effective amount of the compound of claim 1 for administration into different body tissues, ducts or cavities of a subject to monitor movement of bile acids.

Assignees

• The Us Dept Of Veteran Affairs
• Univ Maryland
• The Us Departmetn Of Veterans Affairs

Inventors

• Polli James E
• Raufman Jean-Pierre
• Vivian Diana

Classifications

• A61K49/085 Primary

  conjugated systems · CPC title

• A61K49/10

  Organic compounds · CPC title