METHODS OF TREATING AN INFLAMMATORY-RELATED DISEASE

• US 20090325895A1
• Filed: 08/26/2009
• Published: 12/31/2009
• Est. Priority Date: 12/13/2001
• Status: Active Grant

• Current Assignee: Natrogen Therapeutics International, Inc.
• Original Assignee: Natrogen Therapeutics International, Inc.
• Inventors: Mo, Lian, Liu, Xiao Mei, McCarron, James P. JR., Mencher, Simon K., Wang, Longgui
• Granted Patent: US 8,394,847 B2
• Time in Patent Office: Days
• US Class Current: 514/43
• 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 pharmaceutical composition for treating an inflammatory-related disease comprising at least one compound of formula (I), (II), or (III)

2. The composition according to claim 1, wherein at least R₁ or R₂ is a monosaccharide, a disaccharide unsubstituted or substituted with one or more hydroxy moieties or carboxy moieties;

a halogen;

a hydrocarbyl group, or a functional hydrocarbyl group unsubstituted or substituted with one or more hydroxy moieties, carboxy moieties, nitroxy moieties, monosaccharides, disaccharides, amines, amides, thiols, sulfates, sulfonates, sulfonamides or halogens, wherein the hydrocarbyl has 1 to 8 carbon atoms.

3. The composition according to claim 2, wherein at least R₁ or R₂ is an acetylated monosaccharide.

4. The composition according to claim 2, wherein at least R₁ or R₂ is a methyl group.

5. The pharmaceutical composition according to claim 1, wherein the compound is Meisoindigo, tri-acetylated glyco-Meisoindigo (pro-drug) or NATURA, shown as Formulas (IV), (V), and (VI) respectively:

6. A method of treating an inflammatory-related disease associated with cytokine expression levels, which comprises administering to an animal in need of such treatment at least one compound of formula (I), (II) or (III)

7. The method according to claim 6, wherein at least R₁ or R₂ is a monosaccharide, a disaccharide unsubstituted or substituted with one or more hydroxy moieties or carboxy moieties;

a halogen;

a hydrocarbyl group, or a functional hydrocarbyl group unsubstituted or substituted with one or more hydroxy moieties, carboxy moieties, nitroxy moieties, monosaccharides, disaccharides, amines, amides, thiols, sulfates, sulfonates, sulfonamides or halogens, wherein the hydrocarbyl has 1 to 8 carbon atoms.

8. The method according to claim 7, wherein at least R₁ or R₂ is a tri-acetylated monosaccharide.

9. The method according to claim 6, wherein at least R₁ or R₂ is a methyl group.

10. The method according to claim 6, wherein the animal is a human being.

11. The method according to claim 6, wherein at least two of the compounds are administered concurrently or sequentially.

12. The method according to claim 7, wherein the disease is selected from the group consisting of arthritis, rheumatoid arthritis, arthritis, rheumatoid arthritis, an inflammatory bowel disease;

psoriasis;

multiple sclerosis;

a neurodegenerative disorder;

congestive heart failure;

stroke;

aortic valve stenosis;

kidney failure;

lupus;

pancreatitis;

allergy;

fibrosis;

anemia;

atherosclerosis;

a metabolic disease;

a bone disease;

a cardiovascular disease, a chemotherapy/radiation related complication;

diabetes type I;

diabetes type II;

a liver disease;

a gastrointestinal disorder;

an ophthamological disease;

allergic conjunctivitis;

diabetic retinopathy;

Sjogren'"'"'s syndrome;

uvetitis;

a pulmonary disorder, a renal disease;

dermatitis;

HIV-related cachexia;

cerebral malaria;

ankylosing spondolytis;

leprosy;

anemia; and

fibromyalgia.

13. The method according to claim 12, wherein the neurodegenerative disorder is selected from the group consisting of:

Alzheimer'"'"'s disease and Parkinson disease;

the inflammatory bowel disease is selected from the group consisting of;

Crohn'"'"'s disease or uncerative colitis;

the gastrointestinal complication is diarrhea;

the liver disease is selected from the group consisting of;

an autoimmune hepatitis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, or fulminant liver failure;

the gastrointestinal disorder is selected from the group consisting of;

celiac disease and non-specific colitis;

the pulmonary disorder is selected from the group consisting of;

allergic rihinitis, asthma, chronic obstructive pulmonary disease, chronic granulomatous inflammation, cystic fibrosis, and sarcoidosis;

the cardiovascular disease is selected from the group consisting of;

atheroscleotic cardiac disease, congestive heart failure and restenosis; and

the renal disease is selected from the group consisting of;

glomerulpnephritis and vasculitis.

14. The method according to claim 6, wherein the compound is administered at a concentration sufficient to inhibit cytokine IL-1α

, β

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

, LT, LIF, Oncostatin, or IFNc1α

, β

, γ

.

15. The method according to claim 6, where the compound is administered at a concentration sufficient to stimulate expression of cytokine IL-4, IL-10, IL-11, W-13 or TGFβ

.