Amelioration of intestinal fibrosis and treatment of Crohn's disease

Patent metadata

Field	Value
Publication number	US-9517241-B2
Application number	US-201615051850-A
Country	US
Kind code	B2
Filing date	Feb 24, 2016
Priority date	Dec 28, 2012
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

Methods of treating patients with inflammatory bowel disease, intestinal fibrosis, or Crohn's disease involve administering a therapeutic amount of CARD-024 or related compound.

First claim

We claim:

1. A method of ameliorating intestinal fibrosis in a subject, the method comprising administering to the subject a composition comprising a compound of Formula (I)

wherein Et is ethyl,
wherein the dashed line indicates a single bond or a double bond in the E configuration between carbon 22 and carbon 23, and
wherein the configuration at carbon 24 to which Et is attached is in the R configuration or the S configuration.

2. The method according to claim 1 , wherein the compound has a single bond between carbon 22 and carbon 23.

3. The method according to claim 2 , wherein carbon 24 is in the S configuration.

4. The method according to claim 1 , wherein carbon 24 is in the R configuration.

5. The method according to claim 1 , wherein the compound has a double bond in the E configuration between carbon 22 and carbon 23.

6. The method according to claim 5 , wherein carbon 24 is in the S configuration.

7. The method according to claim 5 , wherein carbon 24 is in the R configuration.

8. The method according to claim 1 , wherein the subject is diagnosed with Crohn's disease.

9. The method according to claim 1 , wherein the subject is a human subject.

10. The method according to claim 1 , comprising administering 5 mcg to 500 mcg of the compound.

11. The method according to claim 1 , comprising administering 1 to 4 doses per day of the composition.

12. The method according to claim 1 , comprising administering 20 mcg to 1000 mcg of the compound in a delayed release composition.

13. The method according to claim 12 , comprising administering the delayed release composition once per day.

14. The method according to claim 2 , comprising administering the effective dose orally.

15. The method of claim 1 , further comprising administering to the patient a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.

16. The method of claim 1 , comprising administering to the patient a composition comprising CARD-024 and a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323, and alosetron.

17. The method of claim 8 , comprising administering to the patient a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4, 6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.

18. The method of claim 8 , comprising administering to the patient a composition comprising CARD-024 and a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-1-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.

Assignees

• Univ Michigan Regents

Inventors

• Simpson Robert U
• Higgins Peter D R
• Johnson Laura A

Classifications

• A61K31/59 Primary

  Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/592

  9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2 · CPC title

• A61K45/06

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