Insulin Polymer Conjugate Burstless Release
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Solution Overview
Problem
Current long-acting insulin formulations fail to provide continuous, structurally intact insulin release over an extended period, leading to variability in plasma concentrations and increased injection frequency, which complicates glucose control and patient adherence to therapy.
Innovation Solution
A pharmaceutical composition with an insulin compound concentration of at least 10 mg/mL, covalently linked within a well-hydrated polymer matrix, ensuring a burstless pharmacokinetic profile and continuous release of structurally intact insulin over the full dosing interval, reducing injection frequency and maintaining predictable plasma levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If current long-acting insulin formulations are used, then injection frequency is reduced to once or twice daily, but plasma concentration variability increases and continuous release is not achieved
Solution Approach 1:
The patent applies preliminary action by pre-formulating insulin as a prodrug conjugated to a polymer carrier with controlled release properties. The insulin-polymer conjugate is prepared in advance with the polymer structure designed to release insulin gradually over extended periods, ensuring continuous plasma concentrations without requiring frequent injections while maintaining stable glucose control.
Solution Approach 2:
The patent uses a polymer carrier as an intermediary substance that temporarily holds the insulin and releases it gradually. This polymer intermediary mediates between the rapid clearance of free insulin and the need for sustained insulin action, providing continuous release over 24-72 hours while maintaining plasma concentration stability and reducing injection frequency.
2Reliability
If insulin is released continuously, then plasma concentration stability improves, but burst release effects may cause harmful hyperinsulinemia
Solution Approach 1:
The patent applies local quality by creating a heterogeneous polymer-insulin conjugate structure where different regions of the polymer matrix have different release characteristics. The polymer structure is designed with specific hydrophilic and hydrophobic regions that control insulin release locally, ensuring continuous low-level release without sudden bursts, thereby maintaining plasma stability while avoiding harmful hyperinsulinemia.
Solution Approach 2:
The patent uses parameter changes by modifying the polymer carrier properties such as molecular weight, hydrophilicity, and crosslinking density to control the release rate. By adjusting these parameters, the formulation achieves continuous insulin release without burst effects, maintaining plasma concentration stability while preventing harmful hyperinsulinemic spikes.
3Reliability
If structurally intact insulin is released continuously, then glucose control improves, but formulation complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the insulin molecule into a prodrug form conjugated to a polymer carrier, which then segments the release into controlled gradual portions over time. This segmentation allows continuous structurally intact insulin release for improved glucose control while managing formulation complexity through modular design of the polymer-insulin conjugate system.
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
The composition achieves a peak to trough ratio of less than 2, ensuring stable insulin levels and reducing the risk of hypoglycemia and hyperglycemia, thereby improving glucose control and patient compliance with less frequent injections.
Implementation Method 1
Structural integrity of the released insulin compound is provided by a well-hydrated polymer matrix minimizing intermolecular contact of insulin molecules
Data Source
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AI summary
The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.