Injection Pen Insulin Formulation Balancing Stability and Rapid Onset

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Solution Overview

Problem

Existing insulin formulations, including rapid and ultra-rapid acting analogues, face stability issues due to hexamer dissociation, leading to physical and chemical instability, particularly when high concentrations are used, which impairs their onset of action.

Innovation Solution

An injection pen system comprising an aqueous liquid pharmaceutical composition containing insulin, ionic zinc, and an alkyl glycoside as a non-ionic surfactant, which stabilizes the insulin and maintains rapid or ultra-rapid action, even at high concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If hexameric insulin is used to improve stability, then physical stability is improved, but onset of action becomes slower

Engineering Contradiction:

Improvephysical stabilityVSAvoidonset of action

Core Design Contradiction:

Stability of the object's compositionVSSpeed

Solution Approach 1:

The patent changes the chemical parameters of insulin by introducing specific amino acid modifications (insulin analogues with modified B-chain residues) that alter zinc binding affinity. This allows the insulin to maintain hexameric stability during storage but dissociate more rapidly at the injection site, achieving both stability and fast onset of action.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses zinc ions as an intermediary that mediates between stability and rapid action. Zinc binds to insulin to form stable hexamers during storage, but the modified insulin analogues are engineered to dissociate from zinc rapidly after injection, enabling fast onset while maintaining storage stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If high concentration of insulin is used to improve efficacy, then therapeutic effect is improved, but physical and chemical instability increases

Engineering Contradiction:

Improveinsulin concentrationVSAvoidphysical and chemical stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent modifies the chemical structure of insulin through specific amino acid substitutions that change zinc binding characteristics. This allows high concentrations of insulin to be formulated while maintaining stability, as the modified residues prevent aggregation and degradation that would normally occur at high concentrations.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite formulation combining modified insulin analogues with specific excipients and zinc ions. This composite approach allows high insulin concentrations to be maintained while the excipients and zinc ions work together to preserve physical and chemical stability throughout the formulation.

Inventive Principle:

Principle #40Composite materials

3Speed

If rapid acting insulin analogues are used to improve onset of action, then speed of action is improved, but stability deteriorates

Engineering Contradiction:

Improveonset of actionVSAvoidphysical and chemical stability

Core Design Contradiction:

SpeedVSStability of the object's composition

Solution Approach 1:

The patent systematically modifies specific amino acid residues at critical positions in the insulin B-chain (such as positions 28-30) to optimize zinc binding. These parameter changes enable the insulin to dissociate rapidly from zinc for fast onset of action while the modified structure simultaneously enhances resistance to aggregation and degradation, improving overall stability.

Inventive Principle:

Principle #35Parameter changes

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 significant stability and rapid onset of action, outperforming prior art formulations, especially under stress conditions, while maintaining high insulin concentrations.

Implementation Method 1

an alkyl glycoside as a non-ionic surfactant, which stabilizes the insulin and maintains rapid or ultra-rapid action

Methodology Applied

Scientific EffectSurfactant: Surfactant

Implementation Method 2

the hexameric form is absorbed from the injection site considerably more slowly than the monomeric and dimeric forms. Therefore, a faster onset of insulin action can be achieved if the hexameric form is destabilised allowing a more rapid dissociation of the zinc-bound hexamer into dimers and monomers

Methodology Applied

Scientific EffectMetal ion binding:

Data Source

PatentUS20250302735A1Injection pen system for the delivery of an insulin compound

Publication Date: 2025.10.02 ARECOR LTD

AI summary

There is provided inter alia an injection pen system comprising an injector mechanism and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said injector mechanism to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (ii) an alkyl glycoside as a non-ionic surfactant.