LysB29-Acylated Insulin Compounds for Extended Glucose Control
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Solution Overview
Problem
Current insulin therapies for diabetes fail to adequately mimic the physiological insulin secretion pattern, leading to risks of nocturnal hypoglycemia and variability in dosing times, and there is a need for alternative treatments with extended action profiles and improved stability.
Innovation Solution
Development of acylated insulin compounds, specifically Compounds 12 and 19, with a modified lysine side-chain to enhance stability and duration of action, featuring a slower clearance rate and increased chemical stability, which are administered via parenteral routes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If longer-acting basal insulin is administered to control blood glucose levels for 24 hours or more, then the duration of action is extended, but the risk of nocturnal hypoglycemia increases
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of insulin through acylation at the LysB29 position with specific fatty acid chains (C14, C16, C18). This structural modification alters the pharmacokinetic parameters of insulin, extending its duration of action to 24 hours or more while reducing clearance rate. The acylated insulin compounds maintain stable blood glucose control without significant nocturnal hypoglycemia, resolving the contradiction between extended duration and hypoglycemia risk.
2Stability of the object's composition
If acylated insulin compounds are developed to reduce clearance rate and extend shelf-life stability, then chemical stability is improved, but the device complexity increases
Solution Approach 1:
The patent applies local quality by introducing acyl groups specifically at the LysB29 position of the insulin molecule, while leaving the rest of the insulin structure intact. This localized modification at a specific site (B29 lysine residue) provides enhanced chemical stability and extended shelf-life without requiring complex structural changes throughout the entire molecule. The targeted modification approach maintains simplicity while achieving the desired stability improvement.
Data Source
AI summary
The presently described compounds relate to the treatment of diabetes and/or hyperglycemia. More particularly, the described compounds relate to acylated insulin compounds that lower blood glucose, pharmaceutical compositions containing such compounds, therapeutic uses of such compounds, and an intermediate compound used to make the acylated insulin compounds.