Lactam Compounds for Corneal Epithelium Disorders

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Solution Overview

Problem

Conventional treatments for corneal epithelium disorders, such as dry eye, primarily focus on lacrimal fluid replacement and do not directly act on corneal epithelial cells, resulting in insufficient therapeutic effects, especially for conditions like diabetes mellitus and long-term eye drop use.

Innovation Solution

Development of lactam compounds that enhance sugar transport and have hypoglycemic action, which suppress apoptosis in corneal epithelial cells under hyperosmotic stress, thereby preventing cell injury and increasing lacrimal fluid and mucin production, serving as a direct treatment for corneal epithelium disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional lacrimal fluid replacement therapy is used, then the lacrimal fluid is replaced or drying is prevented, but the therapeutic effect is insufficient because the treatment does not act directly on corneal epithelial cells

Engineering Contradiction:
Improvetherapeutic effectVSAvoiddirect action on corneal epithelial cells
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses lactam compounds as an intermediary substance that bridges the gap between conventional lacrimal fluid replacement and direct cellular treatment. These compounds are administered through eye drops (conventional route) but exert their therapeutic effect by directly acting on corneal epithelial cells to suppress apoptosis, thus resolving the contradiction between ease of administration and direct cellular action.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If conventional treatments focusing on lacrimal fluid replacement are used, then the treatment approach is simple, but sufficient treatment is not achieved for corneal epithelium disorders caused by diabetes mellitus or long-term eye drop use

Engineering Contradiction:
Improvetreatment simplicityVSAvoidtreatment efficacy for specific conditions
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the biochemical parameter of the treatment by introducing lactam compounds that specifically target cellular apoptosis pathways. This parameter change allows the treatment to remain simple in terms of administration (eye drops) while significantly improving efficacy for specific conditions like diabetes mellitus and long-term eye drop use-related corneal epithelium disorders.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The lactam compounds effectively suppress apoptosis and enhance lacrimal fluid and mucin production, improving symptoms and achieving a radical cure for dry eye and other corneal epithelium disorders.

Implementation Method 1

strongly suppress a decrease in the survival rate of corneal epithelial cells caused by hyperosmotic stress, and this action is based on the action of corneal epithelial cells for suppressing apoptosis under hyperosmotic stress

Methodology Applied
Scientific EffectApoptosis suppression:

Implementation Method 2

some lactam compounds that are known to have sugar transport enhancement action

Methodology Applied
Scientific EffectSugar transport enhancement:

Implementation Method 3

the lactam compounds prevent corneal epithelial cell injury and also increase the amount of lacrimal fluid or mucin

Methodology Applied
Scientific EffectLacrimal fluid secretion enhancement:

Implementation Method 4

the lactam compounds prevent corneal epithelial cell injury and also increase the amount of lacrimal fluid or mucin

Methodology Applied
Scientific EffectMucin production enhancement:

Data Source

PatentEP3238723B1Drug for treating disorders of corneal epithelium
Publication Date: 2020.02.05 EA PHARMA CO LTD
  • EP3238723B1 patent drawingFigure 1~2
  • EP3238723B1 patent drawingFigure 3~4
  • EP3238723B1 patent drawingFigure 5~6

AI summary

A new agent for the treatment of a corneal epithelium disorder, which acts directly on corneal epithelial cells, is provided. Disclosed is an agent for the treatment of a corneal epithelium disorder, the agent comprising a compound of Formula (1) or a salt thereof as an active ingredient: wherein A is an aromatic ring, a heterocyclic ring, or an aliphatic ring; R2, R3, and R4, which may be identical or different, each independently are, for example, a hydrogen atom, a halogen atom; B is an aromatic ring which may have a substituent, a heterocyclic ring which may have a substituent, or an aliphatic ring which may have a substituent; -X-, -Y-, and -Z-, which may be identical or different, each independently are O-, -NH-, -NR5-, -S-, -SO-, -SO2-, -CH2-, -CR6R7-, or -CO-; and -W- is -NR1-, -O-, or -CR8R9-.