Mixed Bed Ion Exchange Purification of Human Milk Oligosaccharides

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Solution Overview

Problem

Current methods for purifying human milk oligosaccharides (HMOs) from fermentation broths result in complex mixtures with impurities, necessitating effective and efficient processes to achieve high-quality, pure HMO products for industrial use, particularly in infant formulas and dietary supplements.

Innovation Solution

A mixed bed ion exchange process using a combination of cation and anion ion exchange materials is employed to purify HMOs, ensuring that the process includes both types of ion exchange materials, thereby removing impurities and achieving high purity and yield.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional purification processes are used to isolate HMO from fermentation broth, then HMO can be obtained, but the product contains complex mixtures of impurities including salts, lactose, oligosaccharides, monosaccharides, amino acids, polypeptides, proteins, organic acids, and nucleic acids

Engineering Contradiction:
ImproveHMO yieldVSAvoidHMO purity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The purification process is divided into multiple sequential steps: (1) removal of cells and large particles via centrifugation or filtration, (2) removal of proteins and polypeptides via precipitation or chromatography, (3) removal of salts and small molecules via dialysis or ultrafiltration, and (4) final purification via ion exchange chromatography. This segmentation allows each step to target specific impurity classes, achieving high purity while maintaining yield.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different purification techniques are applied to remove different types of impurities based on their specific properties: centrifugation for cellular debris, precipitation for proteins, dialysis for salts, and ion exchange for charged impurities. Each method is optimized for its target impurity class, ensuring comprehensive purification without compromising HMO recovery.

Inventive Principle:
Principle #3Local quality

2Manufacturing precision

If multiple purification steps are implemented to remove all impurities, then HMO purity increases, but process complexity and production cost increase

Engineering Contradiction:
ImproveHMO purityVSAvoidpurification process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

Multiple purification functions are combined into integrated unit operations. For example, ultrafiltration membranes are designed to simultaneously remove proteins, polysaccharides, and salts in a single step. Ion exchange resins are formulated to remove multiple classes of charged impurities simultaneously. This merging reduces the number of separate steps while maintaining high purity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The purification system employs universal reagents and materials that can handle multiple impurity types. For instance, a specially designed ion exchange resin can remove salts, amino acids, and nucleic acids in a single pass. The fermentation broth pretreatment step is designed to prepare the complex mixture for subsequent universal purification steps, reducing overall process complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Manufacturing precision

If extensive purification is performed to achieve high HMO purity, then product quality for infant formula and dietary supplements improves, but production time and economic feasibility deteriorate

Engineering Contradiction:
ImproveHMO purityVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The fermentation broth undergoes preliminary treatment steps before main purification: cells are removed by centrifugation or filtration, and proteins are precipitated or adsorbed. This preliminary action reduces the load on subsequent purification steps, allowing faster processing while achieving the required purity level for infant formula and dietary supplement applications.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Purification conditions are optimized to achieve rapid separation: ultrafiltration membranes are selected with appropriate molecular weight cutoffs for fast throughput, ion exchange chromatography uses optimized buffer systems for rapid elution, and drying parameters are adjusted for efficient moisture removal. These parameter optimizations maintain high purity while minimizing processing time and maximizing productivity.

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 effectively removes impurities and achieves high yields of purified HMOs, ensuring the quality and purity required for industrial applications, such as infant formulas and dietary supplements, while being economically and environmentally feasible.

Implementation Method 1

passing the HMO solution through a mixed bed ion exchange comprising a combination of cation ion exchange material with anion ion exchange material

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Data Source

PatentUS20230406875A1Process for purifying a human milk oligosaccharide and related compositions
Publication Date: 2023.12.21 INBIOSE NV

AI summary

This specification relates to a process for preparing a purified human milk oligosaccharide (“HMO”) from an HMO-containing solution (e.g., a fermentation broth) by a process comprising mixed bed ion exchange, and a product of such a process.