Mimylin Peptide Stability at Neutral pH for GLP-1 Co-formulation
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Solution Overview
Problem
Current amylin and calcitonin receptor agonists are chemically unstable at neutral pH, prone to fibrillogenesis, and have limited solubility profiles, making them inconvenient for medical use, especially when combined with GLP-1 compounds, and they do not effectively enhance weight loss when used with liraglutide.
Innovation Solution
Development of mimylin peptides with an amino acid sequence at least 66% identical to EASELSTAALGRLSAELHELATLPRTETGPESP, which act as agonists to both amylin and calcitonin receptors, showing stability and solubility across a wide pH range, including neutral pH, and can be co-formulated with GLP-1 compounds without affecting their stability or pharmacokinetic profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional amylin and calcitonin receptor agonists are used, then they can treat diabetes and obesity, but they are chemically unstable at neutral pH and prone to fibrillogenesis
Solution Approach 1:
The patent modifies the amino acid sequence of amylin and calcitonin receptor agonists to create mimylin peptides that maintain receptor activity while achieving stability across a broader pH range including neutral pH. This sequence modification resolves the contradiction by changing the chemical parameters of the peptide to prevent fibrillogenesis and instability at physiological pH levels.
Solution Approach 2:
The patent creates composite peptide structures by combining features of both amylin and calcitonin receptor agonists into a single mimylin peptide. This composite approach allows the peptide to maintain stability and avoid fibrillogenesis while retaining activity at both receptor types, resolving the stability issue without sacrificing therapeutic efficacy.
2Reliability
If amylin and calcitonin receptor agonists are provided in acidic solution, then they remain chemically stable, but they have limited solubility profiles and are inconvenient for medical use
Solution Approach 1:
The patent changes the pH stability parameters of the peptide by modifying its amino acid sequence. The mimylin peptides are engineered to maintain chemical stability across a broader pH range (pH 6.0-8.5) compared to traditional agonists that require acidic conditions. This allows flexible formulation options including neutral pH solutions for co-administration with GLP-1 compounds.
3Productivity
If mimylin peptides are co-formulated with GLP-1 compounds, then weight loss benefits are enhanced, but formulation complexity increases
Solution Approach 1:
The patent merges mimylin peptides with GLP-1 compounds into a single co-formulation. The mimylin peptide's stability at neutral pH enables it to be combined with GLP-1 compounds in the same formulation without requiring separate acidic containers. This merging approach achieves synergistic weight loss effects while simplifying the formulation system compared to separate administrations.
4Reliability
If pramlintide is used as a human amylin analogue, then it can treat diabetes, but it is chemically unstable at neutral pH and must be provided in acidic solution
Solution Approach 1:
The patent modifies the amino acid sequence of pramlintide and other human amylin analogues to create mimylin peptides that maintain the desired pharmacological activity but achieve stability at neutral pH. This parameter change in the peptide structure eliminates the need for acidic formulation requirements while preserving therapeutic efficacy for diabetes treatment.
Data Source
Figure 1
AI summary
The present invention relates to peptides comprising an amino acid sequence SEQ ID NO: 1 (EASELSTAALGRLSAELH ELATLPRTETGPESP), analogues and derivatives thereof and pharmaceutical compositions comprising such peptides and derivatives. This invention further regards the use of these peptides according to SEQ ID NO : 1, analogues and derivatives thereof as medicaments.