Solvent-Free Cetylated Fatty Acid Esterification

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Solution Overview

Problem

Current processes for preparing cetylated fatty acids are costly, complex, and often result in residual solvents, by-products, and incomplete removal of reaction components, making them unsuitable for pharmaceutical or cosmetic applications, especially when used orally or topically.

Innovation Solution

A process involving the esterification of fatty acids with cetyl alcohol in the presence of a metal catalyst like zinc powder at controlled temperatures and pressures without solvents, using a vacuum program to remove water while preventing the distillation of reagents, ensuring high yields and purity of cetylated fatty acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a chemical solvent like toluene is used for esterification, then the esterification reaction can be conducted effectively, but the final product contains residual solvents that exceed regulatory limits and require complex removal steps

Engineering Contradiction:
Improvecompleteness of esterification reactionVSAvoidresidual solvent content in final product
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention removes the harmful chemical solvent (toluene) from the esterification process entirely, replacing it with a solvent-free system. This extraction of the harmful element eliminates the source of residual solvent contamination while maintaining reaction effectiveness through alternative water removal mechanisms.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates an inert reaction environment by using azeotropic distillation with a non-harmful solvent system that forms a low-boiling azeotrope with water, allowing water removal without introducing harmful chemicals that would residue in the final product.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

2Productivity

If sulphuric acid is used as catalyst, then the esterification reaction proceeds efficiently, but the final product turns black due to partial carbonisation

Engineering Contradiction:
Improverate of esterification reactionVSAvoidcarbonisation of final product
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The invention replaces the harsh, carbonising sulphuric acid catalyst with a milder, non-carbonising catalyst system that achieves sufficient reaction rates without degrading the product. This substitution uses a different chemical approach that avoids the harmful side effects while maintaining catalytic function.

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

Solution Approach 2:

The invention changes the chemical parameters of the catalysis system by using alternative catalysts with different properties - specifically, catalysts that provide sufficient acidity for esterification without the strong oxidising and carbonising properties of sulphuric acid, thus preventing product blackening.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If washing with diluted alkalis is performed to remove catalyst, then the catalyst is neutralised, but additional purification steps are required increasing process complexity

Engineering Contradiction:
Improvepurity of final productVSAvoidnumber of purification steps
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention extracts or removes the need for harsh catalyst neutralisation steps by using a catalyst system that does not require strong alkali washing. The alternative catalyst allows for simpler separation and purification methods, reducing the number of processing steps while maintaining product purity.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If vacuum is applied to remove water from reaction, then water is removed to favour reaction progress, but unreacted reagents are also removed lowering reaction yield

Engineering Contradiction:
Improveprogress of esterification reactionVSAvoidloss of unreacted reagents
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The invention changes the physical parameters of water removal by using azeotropic distillation at controlled temperatures and pressures. This allows selective removal of water through formation of a low-boiling azeotrope, maintaining reaction conditions that favour esterification while preventing loss of higher-boiling unreacted reagents.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention exploits phase transition differences between water and reagents by forming an azeotropic vapor phase that selectively carries water away from the liquid reaction mixture. This phase transition-based separation method removes water without vaporising or removing the unreacted fatty acids and alcohol.

Inventive Principle:
Principle #36Phase transitions

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 allows for the efficient, cost-effective production of high-purity cetylated fatty acids without solvents, reducing by-products and ensuring compatibility for pharmaceutical or cosmetic use, with significant anti-inflammatory properties.

Implementation Method 1

heating said reaction mixture (15) to a reaction temperature comprised from 150°C to 200°C and a reaction pressure of about 1 atmosphere, so as to give rise to an esterification reaction with the initial formation of esters of cetylated fatty acids and esterification water

Methodology Applied
Scientific EffectEsterification reaction: Chemical Bonding

Implementation Method 2

said complete removal of said esterification water being achieved by using a vacuum program that applies a reduction in the reaction pressure in a non-linear manner

Methodology Applied
Scientific EffectVacuum distillation: Vacuum Distillation

Implementation Method 3

the esterification water drawn out of the container (3) during the esterification reaction with the vacuum program, is condensed in a horizontal condenser (11)

Methodology Applied
Scientific EffectCondensation: Condensation

Implementation Method 4

placing in contact, in a container (3) of a reactor (2), at least one fatty acid selected from the group comprising or, alternatively, consisting of myristic acid, oleic acid or mixtures thereof, with a cetyl alcohol and a metal catalyst

Methodology Applied
Scientific EffectCatalysis: Catalysis

Data Source

PatentEP3943478A1Cetylated fatty acids, system for the preparation thereof and use thereof
Publication Date: 2022.01.26 PHARMANUTRA SPA
  • EP3943478A1 patent drawingFigure 1
  • EP3943478A1 patent drawingFigure 2
  • EP3943478A1 patent drawingFigure 3

AI summary

The present invention relates to a process for preparing a mixture of cetylated fatty acids and a system for carrying out said process. Furthermore, the present invention relates to a composition comprising, or alternatively, consisting of said mixture of cetylated fatty acids. Finally, the present invention relates to said composition for use in the treatment and/or prevention of: (i) rheumatoid arthritis of inflammatory and non-inflammatory origin, in particular osteoarthritis; (ii) other inflammatory joint conditions; (iii) psoriasis, lupus, periodontal diseases or cardiovascular or heart diseases; (iv) all post-traumatic osteoarticular pathologies including sports injuries; (v) all degenerative joint pathologies (arthrosis, gonarthrosis, coxarthrosis, etc.), and (vi) inflammatory-traumatic tendon and muscular conditions. Furthermore, it is envisaged that the composition of the present invention be used in the treatment and/or prevention of the above-mentioned pathologies and disorders (i)-(vi) in association with a rehabilitative therapy. The composition comprising said mixture is formulated in a pharmaceutical form for oral use (novel food, supplement or medical device), i.e. in the form of a pill, pastille, capsule, tablet, granules, dispersible powder, syrup, solution or sprayable solution; for topical use, i.e. in the form of a cream, unguent, ointment, gel or spray to be used as such for application on the skin, or else for transdermal use in the form of a patch.