Polyol Stabilizer Combination for Protein Formulations
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Solution Overview
Problem
Therapeutic proteins face challenges due to their high molecular weight, low bioavailability, sensitivity to digestive proteases, instability, and denaturation during industrial processes, limiting their administration methods and requiring strict control of environmental conditions, with existing stabilizers like trehalose being rare, expensive, and unsuitable for diabetic patients.
Innovation Solution
A combination of a polyol with 12 carbon atoms, such as maltitol, and a polyol with 4 to 6 carbon atoms, like sorbitol or xylitol, is used as a protein stabilizer, providing a biobased alternative that is easier to access and more effective than trehalose, with a synergistic effect that enhances protein stability during processing and storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If trehalose is used as a protein stabilizer, then protein stability is improved, but the cost increases and accessibility decreases
Solution Approach 1:
The patent changes the chemical parameters of the stabilizer by replacing trehalose (a disaccharide) with polyols having different carbon atom counts (C4-C6 and C12). This parameter change maintains the stabilizing function while improving accessibility and reducing cost, as polyols are more readily available and easier to manufacture than trehalose.
Solution Approach 2:
The patent creates a functional copy of trehalose's stabilizing effect using polyols. The polyol combination replicates the protein stabilization mechanism of trehalose through similar molecular interactions (hydrogen bonding, steric protection), achieving equivalent stability without the manufacturing and accessibility limitations of the original substance.
2Reliability
If trehalose is used as a protein stabilizer, then protein stability is improved, but it becomes unsuitable for diabetic patients
Solution Approach 1:
The patent replaces trehalose with polyols that have different metabolic characteristics. Polyols are not metabolized in the same way as carbohydrates and do not significantly impact blood glucose levels, making them suitable for diabetic patients while maintaining the protein stabilization function.
Solution Approach 2:
The patent changes the chemical nature of the stabilizer from a carbohydrate (trehalose) to polyols, fundamentally altering the metabolic parameter. This change eliminates the glycemic impact while preserving the physical-chemical stabilization mechanism through hydrogen bonding and steric protection.
3Reliability
If proteins are subjected to industrial treatments for purification or viral inactivation, then therapeutic effectiveness is improved, but protein denaturation increases
Solution Approach 1:
The patent applies polyol stabilizers to proteins before they undergo industrial treatments such as cryogenization, lyophilization, or heat treatments. The polyols form protective complexes with the proteins in advance, creating a cushioning effect that prevents denaturation during subsequent harsh processing while allowing the therapeutic treatments to proceed effectively.
4Ease of operation
If lyophilized products are replaced with products in solution for injectable proteins, then patient convenience is improved, but protein stability during storage deteriorates
Solution Approach 1:
The patent changes the formulation parameters by introducing polyol stabilizers into solution-based protein products. The polyols modify the solution chemistry to prevent protein aggregation and denaturation, enabling stable liquid formulations that can be stored and administered conveniently without requiring lyophilization.
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
The combination of polyols offers improved protein stability, chemical stability, and a good match between solubility and viscosity, outperforming trehalose and other carbohydrate combinations, making it suitable for injectable solutions and reducing the risk of immune reactions.
Implementation Method 1
The Applicant has shown that a synergy operates between the polyol (i) consisting of 12 carbon atoms, in particular maltitol, and the polyol (ii) consisting of 4 to 6 carbon atoms
Implementation Method 2
The combination of polyols offers improved protein stability, chemical stability, and a good match between solubility and viscosity
Data Source
AI summary
One subject of the present invention is the use of a combination of a polyol (i) consisting of 12 carbon atoms and of a polyol (ii) consisting of 4 to 6 carbon atoms, as protein stabilizer. Another subject of the present invention is protein compositions comprising such a combination. A final subject of the present invention is a process for preparing protein compositions using such a combination.