Stable Polypeptide for Oral Diabetes Treatment
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Solution Overview
Problem
Current anti-diabetic agents have limitations such as side effects, inability to cure diabetes completely, and require lifelong medication, while also failing to effectively manage hyperlipidemia, a common complication of diabetes that increases cardiovascular and cerebrovascular risks.
Innovation Solution
A polypeptide with a specific sequence, resistant to enzymatic hydrolysis by pepsin and trypsin, is administered orally or via injection, combining with methionine to provide hypoglycemic and hypolipidemic effects, protecting pancreatic β cells and offering long-term storage stability without toxic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-diabetic agents (metformin, thiazolidinediones, sulfonylureas, etc.) are used to lower blood glucose, then hypoglycemic effect is achieved, but side effects occur (lactic acidemia, hepatotoxicity, hypoglycemia, cough, nausea, etc.)
Solution Approach 1:
The patent changes the chemical structure parameter by designing a novel polypeptide sequence (Formula I) with specific amino acid composition and disulfide bond configuration, which fundamentally alters the pharmacological profile to achieve hypoglycemic effect without the side effects of conventional agents
Solution Approach 2:
The patent creates a composite therapeutic agent combining the polypeptide of Formula I with methionine, where the polypeptide provides hypoglycemic activity and methionine enhances stability and prevents disulfide bond formation, achieving synergistic effect with improved safety profile
2Reliability
If insulin is administered to treat diabetes, then blood glucose control is improved, but convenience and storage requirements worsen (incapable oral administration, inconvenient storage and use)
Solution Approach 1:
The patent changes the molecular parameters by designing a polypeptide with increased stability against enzymatic degradation and oxidation, allowing it to withstand gastrointestinal conditions for oral administration and maintain stability during storage without requiring refrigeration
Solution Approach 2:
The patent uses methionine as an intermediary substance that protects the polypeptide from degradation and enhances its stability, enabling oral administration and convenient storage while maintaining therapeutic efficacy
3Reliability
If long-term diabetes treatment is provided to manage blood glucose, then glycemic control is maintained, but cardiovascular and microvascular complications worsen (atherosclerosis, retinopathy, nephropathy, neuropathy)
Solution Approach 1:
The patent creates a multi-functional therapeutic agent that not only lowers blood glucose but also reduces blood lipid levels (cholesterol, triglycerides, LDL, HDL) and protects against cardiovascular and microvascular complications, providing comprehensive metabolic management in a single agent
4Reliability
If polypeptide is designed to be resistant to enzymatic hydrolysis for oral administration, then bioavailability is improved, but structural complexity increases
Solution Approach 1:
The patent optimizes structural parameters by incorporating specific disulfide bonds (Cys3-Cys20, Cys7-Cys22, Cys15-Cys32) and hydrophobic amino acid clusters that provide enzymatic resistance and structural stability without excessive complexity, achieving oral bioavailability
Data Source
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AI summary
Provided is a polypeptide having hypoglycemic and hypolipidemic activities, and the use thereof in the manufacture of a medicament for lowering the blood glucose and/or blood lipid level in a mammal, or for preventing and/or treating diabetes and/or hyperlipidemia in a mammal. Also provided is a composition comprising the polypeptide.