Composition or method including (t)ew-7197 for treating or preventing corneal endothelial diseases

A technology of EW-7197 and corneal endothelium, which is applied in the field of corneal endothelial cell preservation technology, can solve the problems of corneal endothelial malnutrition and insufficient supply of cornea

Pending Publication Date: 2020-09-25
DOSHISHA CO LTD +1
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Fuchs corneal endothelial dystrophy is considered to have no other effective treatment except corneal transplantation, but the supply of corneas in Japan is insufficient, and there are about 2,600 patients waiting for corneal transplantation, but only about 1,700 cases of corneal transplantation are performed in China in a year

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Composition or method including (t)ew-7197 for treating or preventing corneal endothelial diseases
  • Composition or method including (t)ew-7197 for treating or preventing corneal endothelial diseases
  • Composition or method including (t)ew-7197 for treating or preventing corneal endothelial diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0164] (Example 1: Inhibition effect of EW-7197 on corneal endothelial cell disorder)

[0165] In this example, using immortalized human corneal endothelial cells (iFECD) from patients with Fuchs endothelial corneal dystrophy, the inhibitory effect of EW-7197 on corneal endothelial cell disorders was observed. The observation method of cells was performed based on the above-mentioned observation examples. As a subject, SB431542 (refer to International Publication No. 2015 / 064768 ), which is known to suppress corneal endothelial cell disorders, was used.

[0166] (Materials and methods)

[0167] Seed iFECD on 12-well plate, after culturing for 24 hours, remove the medium, add SB431542 (WAKO, 192-16541) and EW-7197 (Selleck Chemicals, S7530) to the final concentrations of 0.1, 0.3, 1, 3, 10 μM, respectively, Incubate for 24 hours. As a medium, DMEM+2%FBS+1%P / S was used.

[0168] After 24 hours, remove the medium, add SB431542 and EW-7197 to the final concentrations of 0.1, 0...

Embodiment 2

[0172] (Example 2: Discussion on the concentration of EW-7197)

[0173] In this example, the concentration of EW-7197 at which the effect of effectively suppressing corneal endothelial cell disturbance was observed was examined. The inhibitory effect of the corneal endothelial cell disorder was observed by the same method as in Example 1.

[0174] (Materials and methods)

[0175] at 7.0×10 4 Sow iFECD in a 12-well plate at a ratio of 12, culture for 24 hours, remove the medium, add EW-7197 (Selleck Chemicals, S7530) to 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30 μM Final concentration, cultured for 24 hours. As a medium, DMEM+2%FBS+1%P / S was used.

[0176] After 24 hours, remove the medium and add 10 ng / ml recombinant human transforming growth factor β2 (WAKO, 200-19911) and EW-7197 to 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30 μM The final concentration was incubated for 24 hours. As a medium, DMEM+2%FBS+1%P / S was used.

[0177] After 24 hours, cell morpholo...

Embodiment 3

[0180] (Example 3: cell viability and Caspase3 / 7 activity)

[0181] In this example, analysis of cell viability and Caspase 3 / 7 activity in the presence of EW-7197 was performed. SB431542 was used as a comparative control.

[0182] (Materials and methods)

[0183] (Analysis of cell viability)

[0184] Take 3 x 10 per hole 3 Seed iFECD in a 96-well plate at a ratio of 37 °C (5% CO 2 ) to confluence. As a medium, DMEM+10%FBS+1%P / S was used.

[0185] After 24 hours, the medium was removed, and SB431542 (WAKO, 192-16541) and EW-7197 (Selleck Chemicals, S7530) were added to final concentrations of 0.01, 0.1, 1, and 10 μM, respectively, and cultured for 48 hours. As a medium, DMEM+2%FBS+1%P / S was used.

[0186] After 24 hours, the cell morphology was observed under a phase-contrast microscope.

[0187] After the observation, the cell viability was analyzed by the Cell Titer-Glo luminescent cell viability assay (Luminescent Cell Viability Assay) in the following procedure. T...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present disclosure provides a composition for treating or preventing symptoms, disorders, or diseases of the corneal endothelium. The present invention specifically provides a composition which isfor treating or preventing symptoms, disorders, or diseases of the corneal endothelium, and includes (T)EW-7197 (N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline), a derivative thereof, a pharmaceutically acceptable salt thereof, or a solvate of any of the foregoing.

Description

technical field [0001] The present invention relates to a new application of (T)EW-7197. Specifically, it relates to a compound containing (T)EW-7197 (N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6 -methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline) or derivatives thereof, or pharmaceutically acceptable salts thereof, or solvates thereof, for the treatment or prevention of corneal Techniques and methods for symptoms, disorders, or diseases of endothelium, and agents used therefor, and techniques for preserving corneal endothelial cells using the technique. Background technique [0002] Visual information reaches the retina through the light input from the cornea, the most transparent tissue at the front of the eye, which excites the nerve cells of the retina, and the electrical signals generated are transmitted to the visual cortex of the brain through the optic nerve to be recognized. For good vision, the cornea needs to be transparent. The transparency of th...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K31/444A61P27/02A61P43/00
CPCA61K31/444A61P27/02A61P43/00A61K31/4439A61K9/0048A61K9/08A61K47/02
Inventor小泉範子奥村直毅山本真弓
OwnerDOSHISHA CO LTD