Amelioration of intestinal fibrosis and treatment of crohn's disease

Patent metadata

Field	Value
Publication number	US-2016166587-A1
Application number	US-201615051850-A
Country	US
Kind code	A1
Filing date	Feb 24, 2016
Priority date	Dec 28, 2012
Publication date	Jun 16, 2016
Grant date	—

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 treating a subject to relieve the symptoms of inflammatory bowel disease, the method comprising administering to the subject a therapeutically effective dose of a compound of Formula (I)

and administering a composition comprising RO 30201195 or SCIO 323,
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 of Formula (I) comprises CARD-024.

3 . The method of claim 1 , comprising administering to the patient a compound selected from RO 30201195 and SCIO 323.

4 . 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.

5 . The method according to claim 4 , wherein the compound has a single bond 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 7 , wherein carbon 24 is in the R configuration.

8 . The method according to claim 4 , wherein the compound has a double bond in the E configuration between carbon 22 and carbon 23.

9 . The method according to claim 8 , wherein carbon 24 is in the S configuration.

10 . The method according to claim 8 , wherein carbon 24 is in the R configuration.

11 . The method according to claim 4 , wherein the subject is diagnosed with inflammatory bowel disease.

12 . The method according to claim 4 , wherein the subject is diagnosed with Crohn's disease.

13 . The method according to claim 4 , wherein the subject is a human subject.

14 . The method according to claim 4 , comprising administering 5 mcg to 500 mcg of the compound.

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

16 . The method according to claim 4 , comprising administering 20 mcg to 1000 mcg of the compound in a delayed release composition.

17 . The method according to claim 16 , comprising administering the delayed release composition once per day.

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

19 . The method of claim 4 , 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, RO 30201195, SCIO 323 and alosetron.

20 . The method of claim 4 , 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, RO 30201195, SCIO 323, and alosetron.

21 . The method of claim 12 , 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, RO 30201195, SCIO 323 and alosetron.

22 . The method of claim 12 , 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, RO 30201195, SCIO 323 and alosetron.

Assignees

• Univ Michigan

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

• A61K45/06

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

• A61K9/0053

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

• A61K31/592 Primary

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