Methods of treating an inflammatory-related disease

• US 8,394,847 B2
• Filed: 08/26/2009
• Issued: 03/12/2013
• Est. Priority Date: 12/13/2001
• Status: Expired due to Term

• Current Assignee: Natrogen Therapeutics International, Inc.
• Original Assignee: Natrogen Therapeutics International, Inc.
• Inventors: Wang, Longgui, Liu, Xiao Mei, Mo, Lian, Mencher, Simon K., McCarron, James P. Jr.
• Primary Examiner(s): Anderson, James D
• Assistant Examiner(s): SPRINGER, STEPHANIE K
• Application Number:
  US12/548,083
• Publication Number:
  US 20090325895A1
• Time in Patent Office: 1,294 Days
• Field of Search: None
• US Class Current: 514/414
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to pharmaceutical compositions and methods of treating inflammatory-related diseases associated with pro-inflammatory cytokine expression and/or reduced expression of anti-inflammatory cytokines. The method typically comprises administration of one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, such as, Meisoindigo and NATURA. Preferably the pharmaceutical composition comprises one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, an anti-inflammatory agent, and a pharmaceutically acceptable carrier.

Claims

1. A method of treating an inflammatory bowel disease, the method comprising administering meisoindigo to an animal in need of such treatment, wherein meisoindigo is administered in an amount sufficient to treat the inflammatory bowel disease.

2. The method according to claim 1, wherein the animal is a human being.

3. The method according to claim 1, wherein the inflammatory bowel disease is selected from the group consisting of:

Crohn'"'"'s disease and ulcerative colitis.

4. The method according to claim 1, wherein the compound is administered at a concentration sufficient to inhibit a cytokine selected from the group consisting of:

IL-1α

, β

, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, TNF-α

, LT, LIF, Oncostatin, and IFNc1α

, β

, γ

;

but the amount is less than sufficient to substantially inhibit cyclin dependent kinases.

5. The method according to claim 1, where the compound is administered at a concentration sufficient to stimulate expression of a cytokine selected from the group consisting of:

IL-4, IL-10, IL-11, W-13 and TGFβ

;

but the amount is less than sufficient to substantially inhibit cyclin dependent kinases.

6. The method according to claim 3, wherein the inflammatory bowel disease is Crohn'"'"'s disease.

7. The method according to claim 1, wherein the amount is less than sufficient to inhibit 50% of cyclin dependent kinases (CDKs) selected from the group consisting of:

CDK2, CDK4, and CDK6.

8. The method according to claim 7, wherein the amount is less than sufficient to inhibit 40% of cyclin dependent kinases selected from the group consisting of:

CDK2, CDK4, and CDK6.

9. The method according to claim 8, wherein the amount is less than sufficient to inhibit 30% of cyclin dependent kinases selected from the group consisting of:

CDK2, CDK4, and CDK6.

10. The method according to claim 7, wherein the cyclin dependent kinase is CDK2.

11. The method according to claim 7, wherein the cyclin dependent kinase is CDK4.

12. The method according to claim 7, wherein the cyclin dependent kinase is CDK6.

13. The method according to claim 1, further comprising an anti-inflammatory agent.

14. The method according to claim 13, wherein the anti-inflammatory agent is selected from the group consisting of:

an analgesic;

an antirheumatic agent;

an gastrointestinal agent;

a gout preparation;

glucocorticoids;

opthalmic preparation;

respiratory agent;

a nasal preparation; and

a mucous membrane agent, wherein the analgesic is selected, from the group consisting of;

naproxen, indomethacin, ibuprofen, ketorolac tromethamine, choline magnesium trisalicylate and rofecoxib;

the antirheumatic agent is selected from the group consisting of;

cyclosporine, sulfasalazine, valdecoxib, penicillamine and dexamethasone;

the gastrointestinal agent is selected from the group consisting of mesalamine, balsalazide disodium and olsalazine sodium;

the gout preparation is sulindac;

the glucocorticoid is selected from the group consisting of;

dexamethasone, dexamethasone phosphate, methylprednisolone acetate, hydrocortisone and hydrocortisone sodium phosphate;

the nasal preparation is selected from the group consisting of beclomethasone dipropionate monohydrate, fluticasone propionate, triamcinolone acetonide, flunisolide, mometasone furoate monohydrate and budesonide;

the opthalmic preparation is ketorolac tromethamine;

the respiratory agent is nedocromil sodium; and

the mucous membrane agent is selected from the group consisting of;

alclometasone dipropionate, hydrocortisone butyrate, flurandrenolide, betamethasone valerate and clobetasol propionate.