High-Sugar Glucagon Formulation for Pump Stability
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Solution Overview
Problem
Current glucagon formulations for treating hypoglycemia are chemically and physically unstable, leading to rapid degradation and gel formation, making them unsuitable for use in bi-hormonal pumps, which require a stable and pump-able solution for extended periods at body temperature.
Innovation Solution
A stable glucagon formulation is achieved by incorporating high concentrations of sugar (20% or more) to inhibit fibril formation and chemical degradation, creating a hypertonic solution that remains non-gelling and chemically stable for 3.5 to 7 days, suitable for use in insulin or bi-hormonal pumps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If glucagon is formulated as a reconstituted solution with lactose monohydrate and sterile water, then it provides a dry environment for chemical stability, but the reconstituted solution becomes chemically and physically unstable and must be used immediately
Solution Approach 1:
The patent changes the concentration parameter of sugar from conventional low levels to high concentrations (20% or more, preferably 40-70%). This parameter change fundamentally alters the solution properties, creating a hypertonic environment that prevents glucagon degradation and gel formation, thereby extending stability duration from immediate use to 3.5-7 days at body temperature
Solution Approach 2:
The patent creates a composite formulation combining glucagon with high concentrations of sugar (dextrose, sucrose, or other acceptable sugars). This composite system leverages the sugar's ability to form a protective matrix that stabilizes glucagon, preventing both chemical degradation and physical gelation while maintaining pumpability
2Ease of operation
If glucagon is delivered in small volumes through narrow-bore infusion tubing, then it enables pump delivery, but the solution must remain non-gelling and pump-able for extended periods
Solution Approach 1:
The patent adjusts the viscosity and tonicity parameters by incorporating high sugar concentrations. This creates a hypertonic solution that maintains appropriate flow characteristics for pump delivery through narrow-bore tubing while preventing gel formation during extended storage at body temperature for 3.5-7 days
Solution Approach 2:
The patent enables the use of disposable pump reservoirs containing pre-formulated stable glucagon solution. The formulation's stability allows these disposable components to be prepared in advance and used over extended periods, replacing the need for frequent manual preparation of unstable solutions
3Stability of the object's composition
If high concentrations of sugar (20% or more) are incorporated to inhibit fibril formation, then glucagon stability is maintained for 3.5 to 7 days, but the solution becomes hypertonic
Solution Approach 1:
The patent converts the potentially harmful effect of hypertonicity into a beneficial stabilizing mechanism. The high sugar concentration creates a hypertonic environment that draws water into the solution, preventing glucagon from interacting with water molecules that would otherwise promote degradation and gel formation. The hypertonicity itself becomes the protective factor
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 high-sugar glucagon solution effectively prevents gelation and chemical degradation, maintaining glucagon stability and allowing for safe, prolonged use in pumps, enhancing the management of hypoglycemia by maintaining blood glucose levels.
Implementation Method 1
incorporating high concentrations of sugar (20% or more) to inhibit fibril formation and chemical degradation
Implementation Method 2
high concentrations of sugar (20% or more) to inhibit fibril formation and chemical degradation, creating a hypertonic solution that remains non-gelling
Data Source
AI summary
This invention relates to compositions of glucagon suitable for administration by manual injection or by an insulin pump or other injection device to treat hypoglycemia. Said compositions comprise glucagon and a sugar, have a final pH between about 1.5 and 3, and are gel-free, chemically-stable at body temperature and pump-able.