Modified Krill Oil Parenteral Emulsion for Oxidative Stability

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Solution Overview

Problem

Current parenteral lipid emulsions containing omega-3 fatty acids, primarily from fish oil triglycerides, face challenges such as oxidative degradation and adverse effects due to high polyunsaturated fatty acid content, and the high phospholipid content of krill oil makes it unsuitable for use as a major source in injectable emulsions due to potential interference with plasma clearance and adverse reactions.

Innovation Solution

A composition comprising krill oil with a modified fatty acid profile, where omega-3 fatty acids are predominantly attached to the phospholipid backbone, particularly in the second position, and a mixture with fish oil is used to create a stable and effective parenteral formulation, potentially replacing or supplementing egg phospholipids as surfactants, and incorporating astaxanthin for antioxidant properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If krill oil with high phospholipid content is used as a major source in injectable emulsions, then the antioxidant protection and omega-3 fatty acid delivery are improved, but plasma clearance interference and adverse reactions occur

Engineering Contradiction:
Improveantioxidant protectionVSAvoidplasma clearance interference
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes phospholipids from krill oil to create a triglyceride-based formulation. This extraction eliminates the harmful high phospholipid content while retaining the beneficial omega-3 fatty acids (EPA and DHA) and astaxanthin antioxidant, thereby resolving the contradiction between antioxidant protection and plasma clearance interference

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the compositional parameters of krill oil by reducing phospholipid content to less than 10% w/w (preferably less than 5% w/w, more preferably less than 1% w/w) while maintaining or enhancing omega-3 fatty acid content. This parameter modification allows the oil to provide antioxidant protection without causing plasma clearance interference

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If omega-3 fatty acids are positioned at position-2 on the glyceride backbone, then oxidation resistance and bioavailability are improved, but manufacturing complexity increases

Engineering Contradiction:
Improveoxidation resistanceVSAvoidmanufacturing complexity
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent specifies that omega-3 fatty acids should be predominantly at position-2 on the glyceride backbone (at least 70%, preferably at least 80%, more preferably at least 90%). This positional parameter change enhances oxidation resistance and bioavailability while the patent acknowledges this may require specialized manufacturing processes

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If vegetable or marine-based polyunsaturated fatty acids are used in injectable lipid emulsions, then nutritional support is improved, but oxidative degradation occurs

Engineering Contradiction:
Improvenutritional supportVSAvoidoxidative degradation
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful susceptibility to oxidation into a benefit by incorporating astaxanthin, a potent natural antioxidant, at concentrations of at least 0.01 mg/L (preferably at least 0.1 mg/L, more preferably at least 1.0 mg/L). The astaxanthin protects the polyunsaturated fatty acids from oxidative degradation while maintaining their nutritional value

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

Solution Approach 2:

The patent modifies the fatty acid composition parameters by ensuring omega-3 fatty acids comprise at least 20% w/w (preferably at least 30% w/w, more preferably at least 40% w/w) of total fatty acids, with EPA and DHA specifically targeted. This compositional change provides nutritional support while the associated astaxanthin content prevents oxidative degradation

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 modified krill oil composition enhances the stability and bioavailability of omega-3 fatty acids, reduces oxidative degradation, and improves the safety and efficacy of parenteral administration by stabilizing emulsions and mitigating adverse effects, offering a safer treatment for conditions like sepsis and endotoxicosis.

Implementation Method 1

krill oil possesses another unique attribute, in that it contains the naturally occurring antioxidant, astaxanthin, but in amounts 10x to 100x higher than the antioxidants naturally found in commonly used polyunsaturated triglyceride oil-in-water parenteral emulsions

Methodology Applied
Scientific EffectAntioxidant: Oxidation

Implementation Method 2

a parenteral oil-in-water emulsion comprising a phospholipid obtained from a marine crustacean

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 3

replacing or supplementing egg phospholipids as surfactants

Methodology Applied
Scientific EffectSurfactant: Surfactant

Data Source

PatentEP2720701B1Therapeutic application of parenteral krill oil
Publication Date: 2017.08.09 STABLE SOLUTIONS LLC

AI summary

A method of parenterally administering a composition, the method including parenterally administering to a person a composition including krill oil in an oil-in-water emulsion. A parenterally applicable pharmaceutical composition, including an oil-in-water emulsion including a phospholipid obtained from a marine crustacean.