Corneal endothelium ecm therapeutic medicaments

Patent metadata

Field	Value
Publication number	US-2023310402-A1
Application number	US-202318330510-A
Country	US
Kind code	A1
Filing date	Jun 7, 2023
Priority date	Jul 30, 2013
Publication date	Oct 5, 2023
Grant date	—

Abstract

The present invention provides medicaments for treating or preventing a disease, disorder, or condition associated with extracellular matrix (ECM) abnormality in a corneal endothelium, wherein the medicaments comprise a TGF-beta signal inhibiting agent. More specifically, this disease, disorder, or condition is a disorder associated with Fuchs' endothelial corneal dystrophy. Such a disorder includes photophobia, blurred vision, vision disorder, eye pain, lacrimation, hyperemia, pain, bullous keratopathy, ophthalmic unpleasantness, a decrease in contrast, glare, edema in corneal stroma, bullous keratopathy, corneal opacity, and the like. A preferable TGF-beta signal inhibiting agent includes 4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide.

First claim

1 . A medicament for treating or preventing a disease, disorder, or condition associated with extracellular matrix (ECM) abnormality in a corneal endothelium, wherein the medicament comprises an effective amount of a TGF-beta signal inhibiting agent.

2 . The medicament for treating or preventing according to claim 1 , wherein the disease, disorder, or condition is a disorder related to Fuchs' endothelial corneal dystrophy.

3 . The medicament for treating or preventing according to claim 1 , wherein the disease, disorder, or condition comprises at least one selected from the group consisting of photophobia, blurred vision, vision disorder, eye pain, lacrimation, hyperemia, pain, bullous keratopathy, ophthalmic unpleasantness, a decrease in contrast, glare, edema in corneal stroma, bullous keratopathy, and corneal opacity in Fuchs' endothelial corneal dystrophy.

4 . The medicament for treating or preventing according to claim 1 , wherein the TGF-beta signal inhibiting agent comprises at least one of 4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide, BMP-7, anti-TGF-beta antibody, anti-TGF-beta receptor antibody, siRNA of TGF-beta, siRNA of a TGF-beta receptor, shRNA of TGF-beta, shRNA of a TGF-beta receptor, an aptamer of TGF-beta, an aptamer of a TGF-beta receptor, an antisense oligonucleotide of TGF-beta, 6,7-dimethoxy-2-((2E)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine-3-yl-prop-2-enoyl))-1,2,3,4-tetrahydroisoquinolone, 3-(6-methyl-2-pyridinyl)-N-phenyl-4-(4-quinolinyl)-1H-pyrazole-1-carbothioamide, 2-(3-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine, 6-(4-(piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine, 2-(5-chloro-2-fluorophenyl)-4-[(4-pyridinyl)amino]pteridine, 4-[3-(2-pyridinyl)-1H-pyrazol-4-yl]-quinoline, pharmaceutically acceptable salts or solvates thereof, or solvates of the pharmaceutically acceptable salts.

5 . The medicament for treating or preventing according to claim 1 , wherein the TGF-beta signal inhibiting agent comprises 4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide or a pharmaceutically acceptable salt thereof.

6 . The medicament for treating or preventing according to claim 1 , wherein the corneal endothelium is of a primate.

7 . The medicament for treating or preventing according to claim 1 , wherein the corneal endothelium is of a human.

8 . The medicament for treating or preventing according to claim 1 , comprising an additional medicinal component.

9 . The medicament for treating or preventing according to claim 1 , being eye-drops.

Assignees

• Kyoto Prefectural Public Univ Corp
• The Doshisha
• Senju Pharma Co

Inventors

• Koizumi Noriko
• Okumura Naoki
• Kinoshita Shigeru

Classifications

• A61K31/4439 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title