Positively Charged Cyclodextrin Preservation for Ischemia-Reperfusion Injury

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Solution Overview

Problem

Current preservation solutions for organs, tissues, and cells are inadequate in maintaining viability and function during and after transplantation, particularly due to issues with ischemia-reperfusion damage and time constraints, and there is a need for improved solutions to extend preservation time and enhance post-transplant recovery.

Innovation Solution

A composition comprising positively charged modified cyclodextrin, preferably associated with an antioxidant like resveratrol, which is effective in protecting and preserving cells, tissues, or organs by reducing damage from ischemia-reperfusion and improving long-term viability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If conventional preservation solutions (UW, IGL-1, Celsior, Custodiol) are used, then organs can be preserved for a limited period, but tissue damage occurs during cold and hot ischemia and worsens at reperfusion

Engineering Contradiction:
Improvepreservation timeVSAvoidischemia-reperfusion damage
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent introduces positively charged cyclodextrins as intermediary molecules that mediate between the preservation solution and organ tissues. These cyclodextrins form protective complexes with membrane components and antioxidants, acting as a buffer against ischemia-reperfusion injury during the preservation period

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite preservation solution combining positively charged cyclodextrins with antioxidants (such as resveratrol, vitamin C, vitamin E) and other preservation agents. This composite formulation synergistically addresses multiple damage mechanisms simultaneously, improving both preservation duration and tissue protection

Inventive Principle:
Principle #40Composite materials

2Duration of action of stationary object

If preservation time is extended for marginal donors, then more organs become available for transplantation, but tissue quality and long-term viability deteriorate

Engineering Contradiction:
Improvepreservation timeVSAvoidlong-term viability
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent applies prior cushioning by incorporating antioxidants and positively charged cyclodextrins into the preservation solution before the organ is placed. These agents pre-establish protective mechanisms against oxidative stress and membrane damage that will occur during extended preservation, cushioning the organ against future injury

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The invention changes the chemical parameters of the preservation solution by using positively charged cyclodextrins instead of conventional neutral or negatively charged surfactants. This parameter change allows for extended preservation times while maintaining membrane integrity and cellular function through electrostatic interactions with tissue components

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 composition significantly enhances the preservation and functional recovery of organs post-transplantation by improving diuresis, reducing creatinine levels, controlling proteinuria, and minimizing tissue damage, as demonstrated in renal transplantation models.

Implementation Method 1

comprising at least one positively charged modified cyclodextrin

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Implementation Method 2

the positively charged modified cyclodextrin is intimately associated with an antioxidant

Methodology Applied
Scientific EffectAntioxidant activity: Oxidation

Data Source

PatentEP2207556B1Compositions based on positively-charged cyclodextrins for preserving cells, tissues and organs, and uses thereof
Publication Date: 2017.01.04 CENT HOSPITALER UNIV DE POITIERS
  • EP2207556B1 patent drawing
  • EP2207556B1 patent drawing
  • EP2207556B1 patent drawing

AI summary

The invention relates to a composition for protecting and/or preserving cells, tissues and organs, characterised in that it includes at least one modified positively-charged cyclodextrin preferably closely associated with an anti-oxidant. The invention also relates to a method for obtaining this composition and to the uses thereof.