Buffer-Free Protein Liquid Composition for Aggregation Control
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Solution Overview
Problem
Fusion protein drugs face physiochemical instability due to high molecular weights and complex structures, leading to aggregation, fragmentation, and isomerization, which are exacerbated by the use of buffers that increase ionic strength and destabilize the protein.
Innovation Solution
A protein-stabilized liquid composition comprising a stabilizer and surfactant without a buffer, maintaining a pH range of 4 to 8, which enhances stability by using polyols like trehalose and non-ionic surfactants like polysorbate 80, while avoiding buffers that cause aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a buffer is added to maintain pH for protein stability, then pH control is improved, but ionic strength increases causing protein aggregation
Solution Approach 1:
The invention removes the buffer component from the formulation entirely, extracting the harmful element (buffer) that causes ionic strength increase and protein aggregation, while maintaining pH control through alternative means (surfactant and stabilizer system)
Solution Approach 2:
The invention changes the formulation parameters by eliminating buffers and instead using a surfactant-stabilizer system to maintain pH control, thereby changing the chemical composition parameters to reduce ionic strength while preserving pH stability
2Reliability
If buffer concentration is increased to improve pH stability, then pH control is improved, but protein aggregation increases
Solution Approach 1:
The invention extracts and removes the buffer component entirely from the formulation, eliminating the need to balance buffer concentration against aggregation risk
3Quantity of substance
If fusion protein concentration is increased to improve drug efficacy, then therapeutic effect is improved, but physiochemical instability increases
Solution Approach 1:
The invention introduces surfactants and stabilizers as intermediary substances that mediate between the fusion protein and the aqueous environment, preventing direct protein-protein interactions that lead to aggregation while allowing high protein concentrations
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 composition maintains protein stability under severe conditions, reducing aggregation and maintaining biological activity, suitable for intravitreal administration, and is effective in preventing ophthalmic diseases.
Implementation Method 1
a stabilizer; and a surfactant
Implementation Method 2
using polyols like trehalose
Implementation Method 3
non-ionic surfactants like polysorbate 80
Implementation Method 4
a surfactant
Data Source
AI summary
The present invention relates to a protein-stabilized liquid formulation and provides: a composition for protein stabilization, the composition including a stabilizer and a surfactant and not including a buffer; a protein liquid composition including the composition for stabilization and a protein; and a method of producing a protein-stabilized liquid composition which uses the composition for stabilization.