Corn Phytoglycogen Formulations for Stress-Induced Protein Stability
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Solution Overview
Problem
Aqueous formulations of proteins, particularly therapeutic proteins, are susceptible to degradation due to various stress conditions such as agitation, freeze/thaw cycles, and increased temperature, leading to protein unfolding, aggregation, and loss of biological activity.
Innovation Solution
Formulations incorporating corn phytoglycogen as a stabilizing excipient, along with adjunct stabilizing excipients like polypropylene glycol and polyoxazoline, enhance protein stability by reducing degradation and adverse infusion-related effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein formulations are exposed to stress conditions (agitation, freeze/thaw, temperature increase), then protein degradation and aggregation occur, but adding stabilizing excipients like phytoglycogen can reduce degradation by 10-70%
Solution Approach 1:
The patent introduces phytoglycogen as an intermediary stabilizing excipient that mediates between the protein and stress conditions. The phytoglycogen forms a protective matrix around the protein, reducing direct exposure to harmful stress factors like agitation, freeze/thaw cycles, and temperature increases, thereby reducing protein degradation by 10-70%
Solution Approach 2:
The formulation creates a composite system combining the protein active ingredient with phytoglycogen and other excipients (polypropylene glycol, polyoxazoline). This composite material provides enhanced stability properties that neither component would provide alone, creating a synergistic effect against protein degradation
2Reliability
If conventional surfactants are used to stabilize protein formulations, then protein stability improves, but adverse infusion-related effects in patients increase
Solution Approach 1:
The patent replaces conventional surfactants with phytoglycogen, a biodegradable, naturally-derived excipient from corn. This substitute provides comparable or superior stabilization while being metabolically compatible and free from the adverse infusion reactions associated with conventional surfactants
Solution Approach 2:
The formulation changes the chemical parameters by using phytoglycogen with different properties than conventional surfactants. The phytoglycogen provides stabilization through a different mechanism that does not trigger immune responses, eliminating adverse infusion-related effects while maintaining protein stability
3Quantity of substance
If protein concentration in formulation is increased to improve therapeutic efficacy, then treatment effectiveness improves, but protein aggregation and degradation accelerate
Solution Approach 1:
The phytoglycogen acts as a protective intermediary matrix that allows high protein concentrations to be maintained without accelerated aggregation. The excipient creates a protective environment around each protein molecule, preventing intermolecular interactions that lead to aggregation even at high concentrations
Data Source
AI summary
Provided are formulations that utilize phytoglycogen as a stabilizing excipient. The phytoglycogen may be from maize, or more specifically maize harboring a mutation on the sugary1 (su1) gene. Also provided are methods of stabilizing a protein active ingredient by formulation the protein active ingredient with phytoglycogen.