Long-Acting Insulinotropic Peptide Conjugate Formulation
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Solution Overview
Problem
Current insulinotropic peptide formulations face challenges in maintaining stability and activity due to short half-life, susceptibility to protease degradation, and immune responses, requiring frequent administration and posing challenges in storage and delivery.
Innovation Solution
A liquid formulation of long-acting insulinotropic peptide conjugate is developed, linking exendin-3, exendin-4, or imidazo-acetyl exendin-4 with an immunoglobulin Fc region, using an albumin-free stabilizer comprising a citrate buffer, sugar alcohol, and non-ionic surfactant, along with a preservative for multiple administrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide drugs are administered frequently to maintain serum level, then therapeutic effect is improved, but patient pain and administration burden increase
Solution Approach 1:
The peptide is conjugated to immunoglobulin Fc region in advance to create a long-acting formulation, allowing extended therapeutic effect that reduces the frequency of administration from twice daily to potentially once weekly or less, thereby reducing patient burden while maintaining therapeutic reliability
2Quantity of substance
If peptide drugs are administered at high frequency, then serum level is maintained, but stability and activity of peptide are compromised due to degradation
Solution Approach 1:
The peptide is pre-conjugated to immunoglobulin Fc region to protect it from proteolytic degradation before administration, ensuring stability and maintaining serum levels without requiring frequent re-administration that would expose the peptide to repeated degradation risks
Solution Approach 2:
The immunoglobulin Fc region acts as a protective intermediary that shields the peptide from protease degradation, extending its half-life and maintaining stable serum concentrations over extended periods
3Stability of the object's composition
If albumin is used as stabilizer, then storage stability is improved, but risk of viral contamination increases
Solution Approach 1:
The formulation removes albumin completely from the stabilizer composition, eliminating the source of potential viral contamination while maintaining storage stability through alternative stabilizing agents such as sugars, amino acids, and buffers specifically selected for their safety and stabilizing properties
Solution Approach 2:
The patent uses synthetic or recombinant stabilizing agents that are free from biological contamination risks associated with albumin, providing a safer, albeit potentially more complex, formulation approach that eliminates viral contamination concerns
Data Source
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AI summary
The present invention relates to a liquid formulation of long-acting insulinotropic peptide conjugate, comprising a pharmaceutically effective amount of long-acting insulinotropic peptide conjugate consisting of a physiologically active peptide, insulinotropic peptide, and an immunoglobulin Fc region; and an albumin-free stabilizer, wherein the stabilizer comprises a buffer, a sugar alcohol, a non-ionic surfactant, and an isotonic agent, and a method for preparing the formulation. For the purpose of preventing microbial contamination, a preservative may be added. The liquid formulation of the present invention is free of human serum albumin and other potentially hazardous factors to body, having no risk of viral contamination, and thus can provide excellent storage stability for insulinotropic peptide conjugates at high concentration.