Methods of treating dry eye disorders

• US 20040058875A1
• Filed: 08/26/2003
• Published: 03/25/2004
• Est. Priority Date: 09/20/2002
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Alcon Incorporated
• Inventors: Gamache, Daniel A.
• Granted Patent: US 7,026,296 B2
• Time in Patent Office: Days
• US Class Current: 514/15
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Inhibitors of cytokine synthesis in nonimmune, resident ocular surface cells are useful for treating dry eye disorders and other disorders requiring the wetting of the eye.

Claims

1. A method for the treatment of dry eye and other disorders requiring the wetting of the eye which comprises administering to a mammal a composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a cytokine synthesis inhibitor selected from the group consisting of mtiogen-activated kinase inhibitors;

c-jun N-terminal kinase inhibitors;

I-kappa kinase inhibitors;

IL-1β

synthesis inhibitors;

TNFα

synthesis inhibitors;

Janus family tyrosine kinase inhibitors;

signal transducers and activators of transcription inhibitors; and

retinoid X receptor ligands.

2. The method of claim 1 wherein the cytokine synthesis inhibitor is selected from the group consisting of MAP kinase inhibitors and p38 kinase inhibitors.

3. The method of claim 1 wherein the cytokine synthesis inhibitor is selected from the group consisting of (5-(2-amino-4-pyrimidinyl)-4-(4-fluorophenyl)-1 -(4-piperidinyl)imidazole);

anthra[1,9-cd]pyrazol-6(2H)-one;

pralnacasan;

(D)Arginyl-(D)Norleucyl-(D)Norleucyl-(D)Arginyl-(D)Norleucyl-(D)Norleucyl-(D)Norleucyl-Glycine-(D)Tyrosine-amide,acetate salt;

2-chloro-N-[3,5-di(trifluoromethyl)phenyl]4-(trifluoromethyl)pyrimidine-5-carboxamide;

triflusal; and

bexarotene.

4. The method of claim 1 wherein the cytokine synthesis inhibitor is selected from the group consisting of c-jun N-terminal kinase inhibitors and activator protein-1 inhibitors.

5. The method of claim 1 wherein the pharmaceutically effective amount of the cytokine synthesis inhibitor is 0.001-1.0% (w/w).

6. The method of claim 1 wherein the composition is topically administered to the eye.

7. The method of claim 1 wherein the dry eye and other disorders requiring the wetting of the eye is symptoms of dry eye associated with refractive surgery.