Oral GLP-1 Solid Composition for Stable Plasma Concentration

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Solution Overview

Problem

The oral administration of GLP-1 peptides is limited due to enzymatic degradation, insufficient absorption, and first-pass metabolism, leading to variability in plasma concentration and increased side effects.

Innovation Solution

A solid composition comprising a GLP-1 peptide with a plasma half-life of at least 60 hours, administered at least three times, with a dosing interval that is every second day or more often, or a ratio of plasma half-life to dosing interval greater than 2:1, to reduce variability in plasma concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If GLP-1 peptides are administered orally, then the ease of operation is improved, but the reliability deteriorates due to enzymatic degradation and insufficient absorption

Engineering Contradiction:

Improveease of administrationVSAvoidplasma concentration consistency

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent employs absorption enhancers as intermediary substances that facilitate the oral absorption of GLP-1 peptides. These enhancers temporarily modify the intestinal mucosa to increase permeability, allowing the peptide to pass through while maintaining its integrity. This mediator approach resolves the contradiction by enabling oral administration without sacrificing plasma concentration reliability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes pH-modifying agents to change the local environment in the gastrointestinal tract. By adjusting the pH parameter, the peptide's stability is improved and absorption is enhanced, thereby maintaining reliability while achieving ease of oral administration.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If GLP-1 peptides are administered orally, then the ease of operation is improved, but the object-affected harmful factors increase due to first-pass metabolism

Engineering Contradiction:

Improveease of administrationVSAvoidfirst-pass metabolism effects

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

Absorption enhancers serve as intermediaries that protect the GLP-1 peptide from first-pass metabolism by facilitating rapid absorption into the bloodstream, bypassing extensive hepatic metabolism. This mediator approach allows oral administration while reducing harmful first-pass effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If the dosing interval is extended, then the productivity is improved, but the stability of the object's composition deteriorates due to plasma concentration variability

Engineering Contradiction:

Improvedosing frequencyVSAvoidplasma concentration variability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent maintains continuous therapeutic action by optimizing the dosing interval to ensure that plasma concentrations remain within the effective range throughout the dosing period. This continuity approach allows for less frequent dosing while maintaining stable plasma concentrations, resolving the contradiction between productivity and stability.

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS12514822B2Oral dosing of GLP-1 compounds

Publication Date: 2026.01.06 NOVO NORDISK AS

AI summary

The present invention relates to improved uses of glucagon-like peptide 1 (GLP-1) peptides in oral therapy.