Mitochondrial Uncoupling Composition for Cold-Stressed Tissue Viability

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Solution Overview

Problem

Current methods for inducing severe therapeutic hypothermia in non-hibernating mammals face complications, and prolonged cold storage of organs and tissues leads to oxidative stress and cellular damage, necessitating improved compositions and methods for preserving cells, tissues, and organs at low temperatures.

Innovation Solution

A composition comprising a mitochondrial uncoupling agent, protease inhibitor, and reducing agent is used to protect cells, tissues, or organs from low temperature environments, targeting mitochondrial and protein degradation machineries to enhance survival and recovery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If severe therapeutic hypothermia is induced in non-hibernating mammals, then brain protection is improved, but complications and irreversible damage increase

Engineering Contradiction:
Improvebrain protectionVSAvoidcomplications and irreversible damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-treating cells, tissues, or organs with a composition containing a mitochondrial uncoupling agent, protease inhibitor, and reducing agent before exposing them to low temperature environments. This pre-treatment prepares the biological material to withstand cold stress by establishing protective mechanisms in advance, thereby enabling severe therapeutic hypothermia to be performed with reduced complications and irreversible damage.

Inventive Principle:
Principle #10Preliminary action

2Duration of action of stationary object

If prolonged cold storage is used for organ preservation, then organ viability is improved, but oxidative stress and cellular damage increase

Engineering Contradiction:
Improveorgan viabilityVSAvoidoxidative stress and cellular damage
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent uses an intermediary composition as a mediator between the cold storage environment and the organ tissue. This composition, containing a mitochondrial uncoupling agent, protease inhibitor, and reducing agent, acts as a protective intermediary that mitigates the harmful effects of prolonged cold storage. The reducing agent specifically counteracts oxidative stress while the protease inhibitor prevents cellular damage, thereby extending organ viability during storage.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If cold storage solution is enriched with antioxidant components, then oxidative injury is reduced, but microtubule disruption and degradation still occur

Engineering Contradiction:
Improveoxidative injuryVSAvoidmicrotubule stability
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent employs a composite protective composition that combines multiple functional components: a mitochondrial uncoupling agent to address oxidative stress, a protease inhibitor to prevent protein degradation, and a reducing agent to maintain cellular redox balance. This composite formulation provides comprehensive protection against cold storage damage, simultaneously preventing both oxidative injury and microtubule disruption, thereby maintaining microtubule stability during prolonged cold storage.

Inventive Principle:
Principle #40Composite materials

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 effectively preserves the viability of cells, tissues, and organs at low temperatures, reducing oxidative stress and maintaining morphological integrity, enabling successful transplantation and therapeutic hypothermia.

Implementation Method 1

The composition includes a mitochondrial uncoupling agent... targeting mitochondrial and protein degradation machineries to enhance survival and recovery

Methodology Applied
Scientific EffectMitochondrial uncoupling:

Implementation Method 2

The composition includes a mitochondrial uncoupling agent, at least one protease inhibitor, and a reducing agent... reducing oxidative stress

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentUS12383554B2Compositions and methods to protect mammalian tissue against cold and other metabolic stresses
Publication Date: 2025.08.12 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • US12383554B2 patent drawing
  • US12383554B2 patent drawing
  • US12383554B2 patent drawing

AI summary

A composition for preserving viability of cells, tissues, or organs at a low temperature is provided. The composition includes a mitochondrial uncoupling agent, at least one protease inhibitor, and a reducing agent. Methods to protect cells, tissues, or organs from exposure to cold and other metabolic stress are also provided.