Parenteral Omega-3 Emulsion Stability via Surfactant Optimization

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Solution Overview

Problem

Current parenteral lipid emulsions containing omega-3 fatty acids are often unstable and require high dosages due to low concentrations of omega-3 fatty acids, leading to potential health issues from increased cholesterol and saturated fatty acid intake, and existing formulations may not provide optimal bioavailability and stability.

Innovation Solution

A composition comprising an aqueous phase and 5 to 30% oil phase, with at least 60% omega-3 fatty acid triglycerides, less than 1% medium chain triglycerides, and incorporating amphoteric surfactants, co-surfactants, and co-solvents, specifically lecithin and polyethylene glycol, to create a stable oil-in-water emulsion with reduced sodium oleate content.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If fish oils are used as the lipid source in parenteral emulsions, then omega-3 fatty acid content is improved, but emulsion stability deteriorates

Engineering Contradiction:
Improveomega-3 fatty acid contentVSAvoidemulsion stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by optimizing the surfactant composition (specifically using lecithin at 0.5-5% w/v) and oil phase composition (fish oil at 10-30% w/v) to achieve both high omega-3 content and emulsion stability. The controlled addition of sodium oleate (0.01-0.03% w/v) further fine-tunes the emulsion properties to prevent instability while maintaining high omega-3 levels.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If high dosages of parenteral lipid emulsions are administered to achieve adequate omega-3 fatty acid levels, then omega-3 supply is improved, but intake of cholesterol and saturated fatty acids increases

Engineering Contradiction:
Improveomega-3 fatty acid supplyVSAvoidcholesterol and saturated fatty acid intake
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates the beneficial omega-3 fatty acids from fish oil while minimizing the accompanying cholesterol and saturated fatty acids through careful control of the oil phase composition and purification processes. The emulsion formulation achieves high omega-3 concentration (10-30% w/v fish oil) while limiting unwanted components, allowing effective omega-3 supplementation at lower total lipid doses.

Inventive Principle:
Principle #2Taking out (Extraction)

3Ease of manufacture

If unrefined fish oils are used directly in emulsions, then processing complexity is reduced, but emulsion stability and safety deteriorate due to impurities

Engineering Contradiction:
Improveprocessing simplicityVSAvoidemulsion stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by pre-purifying the fish oil through controlled refinement processes that remove impurities such as sterols, waxes, and phenols before emulsion formulation. This preliminary purification step ensures emulsion stability and safety while maintaining a relatively simple overall manufacturing process. The refined fish oil is then immediately emulsified with controlled surfactant addition to prevent re-contamination.

Inventive Principle:
Principle #10Preliminary action

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 achieves enhanced stability and potentially lower dosages of omega-3 fatty acids, improving bioavailability and reducing the intake of cholesterol and saturated fatty acids, while maintaining the benefits of high omega-3 fatty acid content.

Implementation Method 1

wherein the composition further comprises at least one amphoteric surfactant, at least one co-surfactant and at least one co-solvent

Methodology Applied
Scientific EffectSurfactant: Surfactant

Implementation Method 2

wherein the composition further comprises at least one amphoteric surfactant, at least one co-surfactant and at least one co-solvent

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentEP3099289B1Composition comprising EPA and DHA triglycerides for parenteral administration
Publication Date: 2020.03.25 FRESENIUS KABI DEUTSCHLAND GMBH
  • EP3099289B1 patent drawingFigure 1

AI summary

The present invention relates to a composition for parenteral administration comprising an aqueous phase and 5 to 30 % by weight of an oil phase, based on the total weight of the composition, wherein the oil phase comprises omega-3 fatty acid triglycerides selected from the group consisting of eicosapentaenoic acid triglycerides, docosahexaenoic acid triglycerides and mixtures thereof, and wherein the composition further comprises at least one amphoteric surfactant, at least one co-surfactant and at least one co-solvent, and wherein the composition comprises less than 0.03 % by weight of sodium oleate, based on the total weight of the composition. Further, the present invention relates to a method for preparing such a composition as well as to such a composition for use as a medicament, in particular for use in treating stroke, sepsis, Alzheimer's disease or cancer. Furthermore, the present invention relates to a method for treating stroke, sepsis, Alzheimer's disease or cancer comprising parenterally administering such a composition to a patient in need thereof and to a method of providing parenteral nutrition to a patient suffering from at least one disease selected from stroke, sepsis, Alzheimer's disease or cancer, the method comprising administering such a composition to the patient.