Natamycin Salt Purification via Chromatography

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Solution Overview

Problem

The low solubility of natamycin in aqueous environments hinders its purification and formulation, leading to rapid sedimentation in suspensions and limitations in chromatographic purification processes.

Innovation Solution

A process involving the mixing of crude natamycin with a metal salt of a carboxylic acid and water, followed by chromatography, to achieve high concentrations of natamycin and facilitate the isolation of trace compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If natamycin is used in aqueous suspension form, then it can be formulated for administration, but it sediments rapidly making it difficult to dispense evenly

Engineering Contradiction:
Improveease of dispensingVSAvoidsuspension stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the physical-chemical parameters of natamycin by converting it from its conventional neutral form to a salt form (sodium, potassium, or ammonium salt). This parameter change fundamentally alters the molecular properties, enabling the compound to form stable aqueous solutions rather than suspensions, thereby eliminating sedimentation issues while maintaining ease of dispensing.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If chromatographic purification is attempted with conventional natamycin, then purity can be improved, but the low solubility prevents reaching sufficiently high concentrations

Engineering Contradiction:
ImprovepurityVSAvoidconcentration
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by converting natamycin to its salt form, which dramatically increases aqueous solubility. This enables preparative chromatography to be performed at much higher concentrations (up to 100 mg/mL or higher) compared to conventional natamycin, thereby achieving both high purity and high concentration simultaneously.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high concentrations of dissolved natamycin are achieved, then solubility limitations are overcome, but substantial amounts of organic solvents are required

Engineering Contradiction:
ImproveconcentrationVSAvoidorganic solvent usage
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical parameter of natamycin by forming water-soluble salts, which enables high concentrations to be achieved in purely aqueous environments. This eliminates or minimizes the need for organic solvents, removing the associated harmful factors while maintaining high concentration capability.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If natamycin is purified to high purity levels, then unwanted side effects from contaminants are avoided, but the complexity and cost of purification processes increase

Engineering Contradiction:
ImprovepurityVSAvoidpurification process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent simplifies the purification process by changing natamycin to its salt form, which inherently improves solubility and enables more efficient chromatographic separation. This parameter change reduces the number of purification steps required and simplifies the overall process while achieving high purity levels.

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 approach allows for the preparation of high-concentration natamycin solutions, enhancing its stability and enabling efficient preparative chromatography, thereby overcoming the challenges of low solubility and rapid sedimentation.

Implementation Method 1

mixing a composition comprising crude natamycin, a metal salt of a carboxylic acid and water

Methodology Applied
Scientific EffectComplex formation: Chemical Bonding

Implementation Method 2

subjecting the resulting mixture to chromatography whereby fractions are collected

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS12202853B2Epoxide polyene amphoteric macrolide and process for purifying natamycin
Publication Date: 2025.01.21 DSM IP ASSETS BV
  • US12202853B2 patent drawing
  • US12202853B2 patent drawing
  • US12202853B2 patent drawing

AI summary

The present invention is directed to a process for purifying natamycin, to an epoxide polyene amphoteric macrolide, to a composition comprising said polyene amphoteric macrolide and to a process for preparing said polyene amphoteric macrolide.