14-Hydroxy-DHA Analogues Resolve Inflammation

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Solution Overview

Problem

Current understanding of inflammation resolution mechanisms is limited, and there is a need for new biological mediators that can effectively address acute inflammation and its consequences, such as inflammation-related diseases.

Innovation Solution

Identification and development of novel dihydroxy and trihydroxy analogues of docosahexaenoic acid (DHA) with specific hydroxyl group configurations, which are biogenically derived and act as potent anti-inflammatory and pro-resolving mediators by converting DHA into 14S-series compounds that interact with neutrophils and macrophages to enhance inflammation resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If classic lipid mediators such as prostaglandins and leukotrienes are used, then pro-inflammatory roles are achieved, but inflammation resolution is not effectively controlled

Engineering Contradiction:
ImproveinflammationVSAvoidinflammation resolution control
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent converts the harmful pro-inflammatory action of classic lipid mediators into beneficial anti-inflammatory and pro-resolving actions by identifying and utilizing novel endogenous lipid mediators (maresins, protectins, resolvins) that reverse the harmful effects of traditional mediators

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the chemical structure and configuration of lipid mediators by identifying specific hydroxyl group positions (C-4, C-7, C-13, C-14) and stereochemistries in DHA analogues to transform their biological activity from pro-inflammatory to anti-inflammatory and pro-resolving

Inventive Principle:
Principle #35Parameter changes

2Reliability

If omega-3 fatty acids are used as dietary supplements, then general health benefits are achieved, but specific anti-inflammatory and pro-resolving mechanisms are not fully understood

Engineering Contradiction:
Improvehealth benefitVSAvoidmechanism understanding
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent segments the complex omega-3 fatty acid DHA into specific structural components with identified hydroxyl groups at particular positions, allowing systematic analysis of which structural elements are responsible for specific anti-inflammatory and pro-resolving activities

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent identifies novel endogenous lipid mediators (maresins, protectins, resolvins) as intermediary substances that bridge the gap between omega-3 fatty acid intake and the desired anti-inflammatory and pro-resolving effects, revealing the missing mechanistic link

Inventive Principle:
Principle #24Intermediary (Mediator)

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

These DHA analogues demonstrate potent dual anti-inflammatory and pro-resolving actions, potentially linking the beneficial effects of DHA to inflammation reduction and cancer treatment, offering new therapeutic options for inflammation-related conditions.

Implementation Method 1

The main biosynthetic route with DHA for resolvins and protectins proceeds during resolution via a 17S-hydroperoxydocosahexaenoic intermediate produced by a lipoxygenase mechanism

Methodology Applied
Scientific EffectLipoxygenase mechanism: Oxidation

Data Source

PatentEP3037401B114-hydroxy-docosahexaenoic acid compounds
Publication Date: 2020.05.06 THE BRIGHAM & WOMEN S HOSPITAL INC
  • EP3037401B1 patent drawingFigure 1A
  • EP3037401B1 patent drawingFigure 1B
  • EP3037401B1 patent drawingFigure 1C

AI summary

The invention describes novel 14-hydroxy docosahexaenoic acid (DHA) analogues, their preparation, isolation, identification, purification and uses thereof.