Ripasudil Rho Kinase Inhibitor Corneal Transplant Rejection

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Solution Overview

Problem

Corneal transplantation faces significant challenges with rejection, particularly in high-risk cases, due to insufficient immune tolerance and side effects from current immunosuppressants, and there is a need for improved graft survival rates and long-term tolerance without donor cornea limitations.

Innovation Solution

A Rho kinase inhibitor, specifically ripasudil or its salt/solvate, is used to suppress angiogenesis and promote regulatory T cells, thereby reducing rejection in corneal transplantation by administering it as an ophthalmic preparation for improved graft survival and immune tolerance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immunosuppressants such as steroid and cyclosporine are used to reduce acute rejection, then the incidence of acute rejection is reduced, but side effects (infection, drug toxicity) occur and they are ineffective for chronic rejection

Engineering Contradiction:

Improvegraft survival rateVSAvoidside effects (infection, drug toxicity)

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the mechanism of action from traditional immunosuppression to Rho kinase inhibition. By targeting the Rho kinase pathway, the invention achieves immunomodulation through a different biological mechanism that suppresses rejection and promotes Treg cells without the harmful side effects of conventional immunosuppressants

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces Rho kinase inhibitors as an intermediary substance that mediates between the immune system and the transplanted cornea. This intermediary blocks the Rho kinase enzyme, thereby preventing the harmful immune responses while promoting regulatory T cell function, without directly suppressing the entire immune system like traditional immunosuppressants

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If the number of donor corneas is limited, then transplantation availability is restricted, but establishing long-term immune tolerance is clinically important

Engineering Contradiction:

Improvetransplantation availabilityVSAvoidlong-term immune tolerance

Core Design Contradiction:

ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by administering Rho kinase inhibitors before and during the transplantation process to pre-condition the immune system. This preliminary modulation of the immune response through Treg cell promotion establishes a foundation for long-term tolerance that persists even after discontinuation of the medication

Inventive Principle:

Principle #10Preliminary action

3Reliability

If regulatory T cells are reduced (reduced Foxp3 expression), then the ability to suppress effector T cells is reduced, but this leads to increased rejection

Engineering Contradiction:

Improverejection suppression abilityVSAvoidregulatory T cells (Foxp3 expression)

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent employs dynamics by actively promoting the differentiation and expansion of regulatory T cells through Rho kinase inhibition. Rather than statically maintaining Treg levels, the dynamic modulation of the Rho kinase pathway continuously stimulates Treg cell generation and function, creating an adaptive immune environment that actively suppresses rejection

Inventive Principle:

Principle #15Dynamics

Data Source

PatentUS10537579B2Rejection reaction suppressant

Publication Date: 2020.01.21 KOWA CO LTD

AI summary

To provide a novel method for suppressing rejection after corneal transplantation.The method for suppressing rejection after corneal transplantation includes administering an effective amount of a Rho kinase inhibitor to a patient who needs it.