Glucose-Responsive Microgel Composition for Hypoglycemia Prevention

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Solution Overview

Problem

Current hypoglycemia prevention technologies require significant patient intervention, are not glucose-responsive, and are limited in effectiveness due to impaired counter-regulation in type 1 diabetes, making them inadequate for preventing hypoglycemic episodes.

Innovation Solution

A composition and device using glucose-responsive microgels containing crosslinked polymers with glucose-responsive moieties and blood glucose-raising therapeutic agents, such as glucagon, to rapidly release the agent during hypoglycemic conditions, incorporating stabilizing and loading-assisting components to ensure effective delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If emergency glucagon injections are used to treat severe hypoglycemia, then hypoglycemia can be treated, but significant patient intervention is required which is challenging for patients with hypoglycemia-unawareness or nocturnal hypoglycemia

Engineering Contradiction:

Improvehypoglycemia treatment effectivenessVSAvoidpatient intervention requirement

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The microgel system automatically detects hypoglycemic conditions through glucose-responsive moieties and triggers glucagon release without patient intervention. The system serves itself by using the hypoglycemic condition as both the trigger signal and the therapeutic target, eliminating the need for patient awareness or manual administration.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The glucose-responsive moieties in the microgel create a feedback mechanism where the system continuously monitors glucose levels and automatically responds when hypoglycemia is detected. This closed-loop system provides real-time detection and response, ensuring reliable treatment without requiring patient intervention.

Inventive Principle:

Principle #23Feedback

2Reliability

If non-glucose responsive glucagon treatment is used, then glucagon can be delivered, but the risk of hyperglycemia increases due to lack of glucose-responsive control

Engineering Contradiction:

Improveglucagon deliveryVSAvoidhyperglycemia risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The system changes its physical state and drug release parameters in response to glucose concentration changes. At normal glucose levels, the microgel remains stable with controlled release; at hypoglycemic levels, the glucose-responsive moieties trigger structural changes that accelerate glucagon release, providing glucose-dependent control.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The microgel system transitions from a static delivery system to a dynamic one that adapts its release rate based on glucose levels. The glucose-responsive moieties enable the system to change its conformation and release properties in real-time, ensuring safe and effective delivery without hyperglycemia risk.

Inventive Principle:

Principle #15Dynamics

3Reliability

If insulin therapy is used to maintain euglycemia in type 1 diabetes, then blood glucose control is improved, but the risk of acute hypoglycemia increases due to over-estimation of insulin requirements

Engineering Contradiction:

Improveblood glucose controlVSAvoidhypoglycemia risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The glucose-responsive microgel system provides preliminary protective action against hypoglycemia by being pre-loaded with glucagon that is triggered to release only when hypoglycemia occurs. This preemptive approach counteracts the hypoglycemic effect of insulin therapy before severe hypoglycemia can develop, allowing for more aggressive insulin dosing if needed.

Inventive Principle:

Principle #9Preliminary anti-action

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 a glucose-responsive delivery mechanism that rapidly releases therapeutic agents like glucagon during hypoglycemia, effectively preventing and treating low blood glucose levels without requiring patient intervention, mimicking natural counter-regulatory responses.

Implementation Method 1

a polymeric system containing glucose-responsive moieties

Methodology Applied

Scientific EffectGlucose-responsive recognition:

Data Source

PatentUS12447133B2Composition and device for preventing hypoglycemia and use thereof

Publication Date: 2025.10.21 THE GOVERNING COUNCIL OF THE UNIV OF TORONTO

AI summary

A composition for preventing or treating hypoglycemia in a patient in need thereof has a microgel that includes crosslinked polymers containing glucose-responsive moieties; and blood glucose-raising therapeutic agent loaded on or within the microgel. The microgel further includes any one or a combination of a stabilizing component and a loading-assisting component for the blood glucose-raising therapeutic agent. The polymers containing the glucose-responsive moieties form secondary crosslinks in response to low glucose level, thereby causing shrinking of the microgel and rapid release of the blood glucose-raising therapeutic agent. The composition can be used to prepare a composite microneedle patch for preventing or treating hypoglycemia, where the composition is embedded or integrated within an array of the microneedles of the microneedle patch device.