Glucagon Polymer Conjugate for Solubility and Stability

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Solution Overview

Problem

Current treatments for congenital hyperinsulinism, hypoglycemia, and metabolic syndrome face challenges due to the low solubility and short half-life of glucagon, leading to limited efficacy and convenience, particularly in formulations that precipitate at neutral pH, and existing anti-obesity drugs have side effects or weak effects.

Innovation Solution

A glucagon derivative or conjugate with an altered amino acid sequence and linked biocompatible material, such as a polymer, to improve solubility and stability, allowing for a long-acting formulation that can effectively treat congenital hyperinsulinism, hypoglycemia, and metabolic syndrome.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If glucagon is used as a therapeutic agent, then it shows anti-obesity effect and increases blood glucose levels, but it has low solubility and precipitates at neutral pH

Engineering Contradiction:

Improvetherapeutic effectVSAvoidsolubility

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent creates a composite material by conjugating glucagon with hydrophilic polymers (such as polyethylene glycol or polysorbate). This composite structure combines the therapeutic functionality of glucagon with the solubility-enhancing properties of the polymer, allowing the formulation to remain soluble at neutral pH while maintaining biological activity

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The hydrophilic polymer acts as an intermediary between glucagon and the aqueous environment. The polymer chain serves as a mediator that prevents glucagon aggregation and precipitation, facilitating solubility without requiring extreme pH conditions

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If conventional anti-obesity drugs are used, then they show weight loss effects, but they have serious adverse effects or very weak anti-obesity effects

Engineering Contradiction:

Improveweight loss effectVSAvoidadverse effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the delivery parameters of glucagon by using polymer conjugation to extend its half-life and improve solubility. This allows for sustained release and reduced dosing frequency, improving therapeutic productivity while maintaining safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Instead of using expensive drugs with serious side effects, the patent employs a biologically derived peptide (glucagon) that is modified with inexpensive hydrophilic polymers, creating an affordable therapeutic alternative with improved safety profile

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If glucagon is administered frequently due to short half-life, then therapeutic effect is maintained, but treatment convenience is reduced

Engineering Contradiction:

Improvetherapeutic effectVSAvoidtreatment convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The polymer conjugation creates a sustained-release formulation that maintains continuous therapeutic action. The hydrophilic polymer slows down the clearance of glucagon from circulation, extending its half-life and eliminating the need for frequent administrations

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS11142559B2Glucagon derivative, conjugate thereof, composition comprising same, and therapeutic use thereof

Publication Date: 2021.10.12 HANMI PHARM CO LTD

AI summary

The present invention relates to a glucagon derivative, a conjugate thereof, and a composition comprising the same, and a therapeutic use thereof, and in particular, for metabolic syndrome, hypoglycemia, and congenital hyperinsulinism.