Protein Stabilization Using Polymer Detergent Composite
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Solution Overview
Problem
Existing protein formulations for large-scale industrial production lack stability, particularly those without stabilizing proteins, which limits their shelf life and effectiveness.
Innovation Solution
A formulation comprising a pharmaceutically active protein, a mixture of a hydrophilic polymer and a non-ionic detergent with a specific weight ratio, and a polyalcohol and sugar, all without stabilizing proteins like animal or human serum albumin, to enhance stability and maintain activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If protein formulations are made free of stabilizing proteins for large-scale industrial production, then manufacturing complexity and cost are reduced, but stability and shelf life deteriorate
Solution Approach 1:
The patent changes the chemical composition parameters by replacing protein-based stabilizers with a specific combination of non-ionic detergents (e.g., polysorbate 80 at 0.01-0.5% w/v), hydrophilic polymers (e.g., PVP K30 at 0.1-5% w/v), and reducing agents (e.g., L-cysteine at 0.01-1% w/v). This parameter substitution maintains stability while simplifying manufacturing and reducing immunogenicity risks.
Solution Approach 2:
The invention creates a composite formulation system combining multiple excipients (detergent + polymer + reducing agent + buffer) that work synergistically to stabilize proteins. This composite approach replaces single-protein stabilizers with a multi-component system that provides comparable or superior stability without immunogenicity, resolving the contradiction between manufacturing simplicity and formulation stability.
2Object-affected harmful factors
If stabilizing proteins are removed from formulations, then immunogenicity risk is reduced, but protein activity retention worsens over time
Solution Approach 1:
The patent modifies the formulation composition by eliminating protein-based stabilizers (HSA, BSA, gelatin) that cause immunogenicity, and replacing them with non-protein excipients. The specific parameter changes include adding non-ionic detergents (0.01-0.5% w/v), hydrophilic polymers (0.1-5% w/v), and reducing agents (0.01-1% w/v), which collectively maintain protein activity retention without immunogenicity over extended storage periods.
3Quantity of substance
If conventional formulations without stabilizing proteins are used, then production cost is reduced, but shelf life and effectiveness deteriorate
Solution Approach 1:
The invention develops a cost-effective composite formulation system using commercially available non-protein excipients (polysorbate 80, PVP K30, L-cysteine, phosphate buffer) that extends shelf life to at least 6 months at 2-8°C and maintains effectiveness. This composite approach achieves longer shelf life than conventional protein-free formulations while keeping production costs low by avoiding expensive stabilizing proteins.
Data Source
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AI summary
A formulation free of protein which stabilizes pharmaceutical active proteins, peptides, or mixtures thereof in large scale production processes comprising a mixture of a hydrophilic polymer and a non-ionic detergent, and a mixture of a polyalcohol and a sugar. In some embodiments the polyalcohol is absent.