High-Concentration Insulin Pump with Surfactant Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current insulin formulations, especially at higher concentrations, face challenges with stability and rapid onset of action, leading to occlusions in infusion pumps due to insulin aggregation, and existing solutions like EDTA-based formulations compromise stability for speed.
Innovation Solution
A medical infusion pump system with a reservoir containing an aqueous liquid pharmaceutical composition of insulin at 400 U/mL or more, combined with ionic zinc and a non-ionic surfactant, delivering the composition in pulses of 0.5 μL or less, which enhances stability and rapid action while minimizing occlusions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If insulin concentration is increased to 400 U/mL or more, then the volume of insulin reservoir is reduced, but insulin aggregation occurs leading to occlusions in infusion pumps
Solution Approach 1:
A non-ionic surfactant is introduced as an intermediary substance to prevent insulin aggregation. The surfactant molecules interact with insulin molecules, creating a protective interface that prevents insulin from forming aggregates that would cause occlusions, thereby enabling high-concentration insulin storage without compromising pump reliability
Solution Approach 2:
The chemical composition parameters of the insulin formulation are changed by adding specific non-ionic surfactants and adjusting auxiliary ingredients. This modifies the physical-chemical properties of the insulin solution, reducing its tendency to aggregate at high concentrations while maintaining stability during infusion pump operation
2Speed
If zinc cations are removed to achieve faster onset of action, then insulin action speed is improved, but insulin stability is impaired
Solution Approach 1:
The formulation creates different local environments for zinc cations: in the stored insulin reservoir, zinc is present in controlled amounts to maintain stability, but during infusion, the local concentration changes to promote rapid dissociation and fast action. This spatial and temporal variation in zinc availability resolves the contradiction between stability and speed
3Reliability
If insulin is delivered in small pulses of 0.5 μL or less, then occlusion risks are reduced, but delivery frequency must be increased
Solution Approach 1:
The insulin delivery system employs periodic pulsing rather than continuous flow. By delivering insulin in small, regularly spaced pulses of 0.5 μL or less, the system prevents aggregate formation that would cause occlusions while maintaining effective insulin delivery through the cumulative effect of repeated doses
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 system provides stable, rapid-acting insulin delivery with high concentrations, maintaining a fast onset of action and reducing occlusion risks, as demonstrated by improved pharmacokinetic and pharmacodynamic profiles in diabetic models.
Implementation Method 1
the composition comprises (i) an insulin compound at a concentration of 400 U/mL or more, (ii) ionic zinc and (iii) a non-ionic surfactant
Implementation Method 2
the composition comprises (i) an insulin compound at a concentration of 400 U/mL or more, (ii) ionic zinc
Implementation Method 3
the said pump delivers the composition in pulses wherein the volume of the pulse is 0.5 μL or less
Data Source
AI summary
There is provided inter alia medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said pump to a mammal wherein the composition comprises (i) an insulin compound at a concentration of 400 U/mL or more, (ii) ionic zinc and (iii) a non-ionic surfactant and wherein the said pump delivers the composition in pulses wherein the volume of the pulse is 0.5 μL or less.