Endotoxin Extraction via Aliphatic Acid and Amine Solvents

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Solution Overview

Problem

Existing methods for extracting endotoxins from bacteria, particularly Gram-negative bacteria, rely on toxic solvents like phenol and chloroform, leading to health risks and contamination issues, making them unsuitable for human or animal administration and scientific use.

Innovation Solution

A method involving suspending bacterial cells or culture supernatants in a mixture of linear or branched aliphatic acids and basic aqueous solutions of aliphatic amines, followed by separation and solvent elimination, which is faster, safer, and more selective, achieving higher yields without the need for toxic solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If toxic solvents like phenol and chloroform are used for endotoxin extraction, then extraction effectiveness is improved, but health risks and contamination increase

Engineering Contradiction:
Improveextraction effectivenessVSAvoidhealth risks and contamination
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the extraction system by replacing toxic solvents (phenol, chloroform) with a non-toxic alternative system consisting of aliphatic acid and aliphatic amine. This parameter change maintains extraction effectiveness while eliminating health risks and contamination associated with traditional toxic solvents.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful property of requiring toxic solvents for effective extraction into a benefit by discovering that non-toxic aliphatic acid and amine combinations can achieve equal or superior extraction effectiveness, thereby turning the previously harmful extraction process into a safe one.

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

2Quantity of substance

If toxic solvents are used for endotoxin extraction, then extraction yield is improved, but residues make the extract unfit for human or animal administration

Engineering Contradiction:
Improveextraction yieldVSAvoidsuitability for human or animal administration
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical composition parameters by using non-toxic aliphatic acid and amine systems instead of toxic solvents, achieving high extraction yields while producing extracts free of harmful residues, thereby ensuring suitability for human or animal administration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs readily available, non-toxic aliphatic acids and amines that can be easily removed or degraded, replacing expensive and problematic toxic solvents that require complex elimination steps. The simple, non-toxic nature of these reagents ensures no harmful residues remain in the final extract.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Productivity

If toxic solvents are used for endotoxin extraction, then extraction capability is improved, but elimination of residues becomes difficult and expensive

Engineering Contradiction:
Improveextraction capabilityVSAvoidcomplexity of residue elimination
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the chemical parameters by selecting aliphatic acid and amine reagents with favorable properties for easy removal or degradation, eliminating the need for complex residue elimination steps while maintaining effective extraction capability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts endotoxins using a simplified system where the non-toxic aliphatic acid and amine can be easily separated or decomposed, taking out the endotoxins without leaving behind complex residues that would require elaborate elimination procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If conventional extraction methods are used, then endotoxins can be isolated, but the process is time-consuming and complex

Engineering Contradiction:
Improveendotoxin isolation capabilityVSAvoidextraction time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the kinetic and chemical parameters by using aliphatic acid and amine systems that facilitate faster extraction kinetics, reducing the time required for endotoxin isolation while maintaining reliable extraction capability.

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

This method enables rapid extraction of endotoxins within 12-24 hours, with higher yields and reduced contamination, making it suitable for industrial scale and safe for handling, and allows for the preparation of compositions for human or animal administration.

Implementation Method 1

the starting product is a group of bacterial cells or, optionally, a culture supernatant; in a first step, the bacterial cells, or the culture supernatant, are (is) suspended in a mixture of solvents consisting of: 10 to 90%, preferably 30 to 70%, of a solvent chosen from: linear or branched aliphatic acids containing from 3 to 6 carbon atoms; 90 to 10%, preferably 70 to 30%, of a basic aqueous solution of an aliphatic amine

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

in a second step, the particles in suspension are separated from the solution: either by filtration of the composition, or by centrifugation and recovery of the supernatant

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Data Source

PatentUS8137935B2Method for isolating endotoxins
Publication Date: 2012.03.20 UNIVERSITE PARIS SUD 11
  • US8137935B2 patent drawing
  • US8137935B2 patent drawing

AI summary

The invention concerns a novel method for extracting endotoxins from bacteria, and the use of said method for preparing compositions comprising endotoxins or derivatives thereof designed for human or animal use (scientific, medical usage).