POE Sorbitans and PEGs Stabilize Protein Formulations

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Solution Overview

Problem

Polysorbates, commonly used as protein stabilizers, undergo degradation, producing byproducts that increase turbidity and protein aggregation in formulations, necessitating the need for alternative compositions to prevent protein aggregation.

Innovation Solution

The use of polyoxyethylene (POE) sorbitans and polyethylene glycols (PEGs) at specific concentrations in protein-containing formulations to stabilize proteins and prevent aggregation, either alone or in combination with other stabilizers, in both aqueous and solid forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polysorbates are used as protein stabilizers, then protein stability is improved, but degradation byproducts increase turbidity and cause protein aggregation

Engineering Contradiction:
Improveprotein stabilityVSAvoiddegradation byproducts causing turbidity and aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes the harmful degradation byproducts (fatty acids, POE sorbitan, PEG esters, alkyl acids) from the system by replacing polysorbates with alternative stabilizers. This eliminates the source of turbidity and aggregation while maintaining the beneficial protein stabilization function.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs alternative stabilizers (polyols, amino acids, peptides, proteins, surfactants) that do not undergo degradation to produce harmful byproducts. These replacement compounds serve the stabilization function without the long-term degradation issues of polysorbates, effectively creating a disposable-free system.

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

2Object-affected harmful factors

If polysorbates are used to prevent surface adsorption, then protein protection is improved, but fatty acid degradation increases protein aggregation

Engineering Contradiction:
Improvesurface adsorption protectionVSAvoidfatty acid-induced aggregation
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent introduces intermediary substances (polyols, amino acids, peptides, proteins, and alternative surfactants) that mediate between the protein and the aqueous environment. These intermediaries provide surface adsorption protection without degrading into aggregation-causing byproducts, replacing the dual-function but problematic polysorbate system.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If alternative stabilizers are used to replace polysorbates, then protein stability is maintained, but formulation complexity increases

Engineering Contradiction:
Improveprotein stabilityVSAvoidformulation composition complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs stabilizers with multiple functions: polyols (glycerol, sorbitol, mannitol) provide both osmotic balance and protein stabilization; amino acids and peptides offer both buffering capacity and stabilization; surfactants provide both surface protection and aggregation prevention. This multi-functionality reduces the need for multiple separate additives, simplifying the overall formulation despite the variety of options available.

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

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

POE sorbitans and PEGs effectively prevent protein aggregation and enhance stability by reducing turbidity and maintaining protein solubility, even under agitation, thereby improving the physical stability of protein formulations.

Implementation Method 1

POE sorbitans and PEGs effectively prevent protein aggregation and enhance stability by reducing turbidity and maintaining protein solubility

Methodology Applied
Scientific EffectSolubility enhancement: Solvation

Data Source

PatentEP3513810A1Compositions and methods useful for stabilizing protein- containing formulations
Publication Date: 2019.07.24 F HOFFMANN LA ROCHE & CO AG
  • EP3513810A1 patent drawingFigure 1
  • EP3513810A1 patent drawingFigure 2
  • EP3513810A1 patent drawingFigure 3

AI summary

The invention relates to use of non-surfactant compounds including, for example, polyoxyethylene (POE) sorbitans and polyethylene glycols (PEGs), for stabilizing protein-containing formulations and for the prevention of aggregation of proteins in such formulations.