Stable n-3 Diglyceride Emulsions for Ischemic Stroke Therapy

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Solution Overview

Problem

Current treatments for acute ischemic stroke, such as tissue plasminogen activator (t-PA), have limited effectiveness due to a narrow time window and do not effectively deliver neuroprotective agents like omega-3 fatty acids (n-3 FAs) to damaged brain tissue in a timely manner.

Innovation Solution

The development of stable n-3 diglyceride (DG) oil-in-water emulsions for acute therapy, which can be administered intravenously or intra-arterially, providing rapid delivery of n-3 FAs to injured tissues, including the brain, with a broader therapeutic window.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If stable n-3 diglyceride emulsions are developed for acute therapy, then the therapeutic window is expanded and neuroprotection is improved, but the emulsion stability and storage requirements become more complex

Engineering Contradiction:
Improvetherapeutic windowVSAvoidemulsion stability
Core Design Contradiction:
Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by optimizing emulsion composition parameters including using n-3 diglycerides with specific fatty acid profiles (DHA and/or EPA), controlling particle size distribution (mean diameter 10-500 nm), adjusting zeta potential (-30 to -60 mV), and selecting specific emulsifiers (phospholipids, proteins, or small molecules) to achieve both extended therapeutic window and storage stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by formulating complex emulsion systems combining n-3 diglyceride oil phase, aqueous phase, and multiple emulsifying agents (phospholipids like lecithin, proteins, or small molecule surfactants) to create a stable delivery system that maintains both therapeutic efficacy and storage stability

Inventive Principle:
Principle #40Composite materials

2Speed

If n-3 fatty acids are rapidly delivered to injured tissues, then neuroprotection effectiveness is improved, but the delivery system complexity increases

Engineering Contradiction:
Improvedelivery speedVSAvoiddelivery system complexity
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The patent uses emulsions as intermediary carriers that facilitate rapid delivery of n-3 fatty acids to injured tissues. The emulsion system acts as a mediator between the hydrophobic n-3 diglycerides and the aqueous bloodstream, enabling rapid transport and cellular uptake without requiring complex delivery devices or procedures

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent leverages the hydraulic properties of intravenous infusion to achieve rapid delivery. The emulsion formulation is designed for IV administration, utilizing the body's existing fluid circulation system to rapidly distribute n-3 fatty acids to injured tissues throughout the body, including the brain

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 emulsions effectively protect against cellular death, providing neuroprotection and organ protection in conditions such as ischemic stroke, myocardial infarction, and traumatic brain injury, even when administered outside the traditional time window for existing treatments.

Implementation Method 1

stable n-3 diglyceride (DG) oil-in-water emulsions for acute therapy

Methodology Applied
Scientific EffectEmulsion: Emulsion

Data Source

PatentEP4135684B1Stable diglyceride emulsions and methods for treating organ injury
Publication Date: 2025.06.18 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • EP4135684B1 patent drawingFigure 1
  • EP4135684B1 patent drawingFigure 2A~2B
  • EP4135684B1 patent drawingFigure 3

AI summary

The present invention provides compositions and methods involving stable omega-3 diglyceride oil-in-water emulsions for acute therapy to treat and/or prevent tissue or organ injury. The compositions provide protection from cellular death, and find use in patients in need of neuroprotection. For example, the compositions find use in treating ischemia reperfusion injuries, such as ischemic stroke. The compositions further find use for treatment of traumatic injuries, such as traumatic brain injury or spinal cord injury, among others. The compositions have a large time window by which they are effective after onset of traumatic or ischemic injury (e.g., after onset of stroke), and may be administered in conjunction with other therapies.