Protein Formulations Using Hydroxytryptophan to Limit Oxidation
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Solution Overview
Problem
Oxidation of amino acid residues in proteins, particularly methionine, cysteine, histidine, tryptophan, and tyrosine, is a common issue during protein pharmaceutical processing, leading to potential loss of biological function and stability, and standard excipients like L-tryptophan can enhance this oxidation.
Innovation Solution
Formulations containing specific compounds such as 5-hydroxy-tryptophan, 5-hydroxy indole, or serotonin, which prevent oxidation of proteins by reactive oxygen species, are developed, along with methods to screen and test these compounds for their efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If L-tryptophan is used as an excipient in protein formulations, then protein stability is improved, but protein oxidation is enhanced
Solution Approach 1:
The patent changes the chemical structure parameter of the excipient by using hydroxytryptophan derivatives (with hydroxyl groups at positions 5, 6, or 7 on the indole ring) instead of L-tryptophan. This structural modification reduces the oxidation potential and photosensitivity of the excipient, thereby preventing protein oxidation while maintaining formulation stability.
Solution Approach 2:
The patent employs readily available hydroxytryptophan derivatives as alternative excipients that can be easily incorporated into formulations. These compounds serve as effective antioxidants with lower oxidation potential compared to L-tryptophan, providing a practical solution to prevent protein oxidation during storage and processing.
2Object-generated harmful factors
If compounds with higher oxidation potential are used to prevent protein oxidation, then protein oxidation is reduced, but the compounds themselves become more photosensitive
Solution Approach 1:
The patent optimizes the oxidation potential parameter by selecting hydroxytryptophan derivatives with hydroxyl groups at specific positions (5, 6, or 7) on the indole ring. This parameter optimization achieves the right balance: sufficient oxidation potential to protect proteins while reduced photosensitivity compared to L-tryptophan, as evidenced by lower hydrogen peroxide generation upon light exposure.
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
These formulations effectively reduce protein oxidation, maintaining protein stability and biological activity by using compounds with lower oxidation potential and reduced photosensitivity compared to L-tryptophan.
Implementation Method 1
Oxidation of amino acid residues has the potential to impact the biological activity of the protein. These formulations effectively reduce protein oxidation, maintaining protein stability and biological activity
Implementation Method 2
a compound which prevents oxidation of the protein in the formulation
Data Source
AI summary
The invention provides formulations comprising a protein in combination with a compound that prevents oxidation of the protein. The invention also provides methods for making such formulations and methods of using such formulations. The invention further provides methods of screening for compounds that prevent oxidation of a protein in a protein composition and methods of preventing oxidation of a protein in a formulation.