Treatment of autoimmune diseases with combinations of RXR agonists and thyroid hormones

Patent metadata

Field	Value
Publication number	US-11690832-B2
Application number	US-202217585349-A
Country	US
Kind code	B2
Filing date	Jan 26, 2022
Priority date	Mar 10, 2016
Publication date	Jul 4, 2023
Grant date	Jul 4, 2023

Abstract

The present specification provides methods of treating autoimmune diseases with a combination of a RXR agonist and a thyroid hormone.

First claim

The invention claimed is:

1. A method of treating an autoimmune gastrointestinal disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of a RXR agonist and a thyroid hormone, wherein the RXR agonist has the structure of Formula II

wherein R is H or lower alkyl of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof;
wherein administration of the RXR agonist and the thyroid hormone treats the autoimmune gastrointestinal disorder in the individual more effectively than either the RXR agonist or the thyroid hormone alone.

2. The method according to claim 1 , wherein is the RXR agonist is a selective RXR agonist comprising 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid.

3. The method according to claim 1 , wherein the RXR agonist is 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic ethyl ester.

4. The method according to claim 1 , wherein the thyroid hormone is thyroxine.

5. The method according to claim 1 , wherein the therapeutically effective amount of an ester of the RXR agonist having the structure of Formula II is about 0.001 mg/day to about 1000 mg/day.

6. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 0.001 mg/day to about 1000 mg/day.

7. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 1 mg/day to about 100 mg/day.

8. The method according to claim 4 , wherein the therapeutically effective amount of the thyroxine is about 12.5 μg/day to about 250 μg/day.

9. The method according to claim 1 , wherein the RXR agonist is administered by topical administration.

10. The method according to claim 4 , wherein the RXR agonist and the thyroxine are both administered by topical administration.

11. The method according to claim 1 , wherein the RXR agonist is administered orally.

12. The method according to claim 4 , wherein the RXR agonist and the thyroxine are both administered substantially simultaneously.

13. The method according to claim 4 , wherein the RXR agonist and the thyroxine are administered on different schedules.

14. The method according to claim 4 , wherein the thyroxine is administered orally.

15. The method according to claim 4 , wherein the thyroxine is administered subcutaneously.

16. The method according to claim 1 , wherein the autoimmune gastrointestinal disorder is an inflammatory bowel disease.

17. The method according to claim 16 , wherein the inflammatory bowel disease is an ulcerative colitis.

18. The method according to claim 16 , wherein the inflammatory bowel disease is Crohn's disease.

19. The method according to claim 1 , wherein the autoimmune gastrointestinal disorder is celiac disease.

20. A method of treating an autoimmune gastrointestinal disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid (IRX4204), and thyroxine; and wherein administration of the combination reduces the severity of the autoimmune gastrointestinal disorder in the individual more effectively than either the IRX4204 or the thyroxine alone.

Assignees

• Io Therapeutics Inc
• Io Therapeutics

Inventors

• Chandraratna Roshantha A
• Sanders Martin E

Classifications

• A61P11/06

  Antiasthmatics · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/192 Primary

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title