Macrocyclic Lactone Stability via Meglumine Mediator

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Solution Overview

Problem

Existing antiparasitic compositions face challenges in stability, particularly when combining macrocyclic lactones with levamisole, due to hydrolytic degradation, leading to reduced efficacy and increased resistance in parasitic infections.

Innovation Solution

Incorporating meglumine as a stability enhancer across a wide range of antiparasitic agent concentrations to create stable liquid compositions suitable for oral, topical, and injectable forms, enhancing solubility and stability of macrocyclic lactones and levamisole.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If macrocyclic lactones are combined with levamisole in liquid compositions, then broader parasitic control is achieved, but hydrolytic degradation occurs reducing stability

Engineering Contradiction:
Improveparasitic control rangeVSAvoidcomposition stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

Meglumine acts as an intermediary substance that mediates between the incompatible macrocyclic lactone and levamisole components. It forms a stable complex with the macrocyclic lactone, preventing direct interaction that would cause hydrolytic degradation, while still allowing the combination to provide broad-spectrum parasitic control

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the chemical environment parameters by introducing meglumine, which alters the pH and chemical reactivity conditions. This parameter change prevents the hydrolytic degradation pathway while maintaining the therapeutic effectiveness of both antiparasitic agents

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If stability enhancers are added to prevent degradation, then composition stability improves, but formulation complexity increases

Engineering Contradiction:
Improvecomposition stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

Meglumine serves as a dual-function intermediary that provides stability enhancement while maintaining formulation simplicity. Unlike complex stability enhancers requiring multiple components, meglumine achieves stabilization through its unique ability to form stable complexes with macrocyclic lactones in a single additive approach

Inventive Principle:
Principle #24Intermediary (Mediator)

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 use of meglumine significantly reduces hydrolytic degradation of macrocyclic lactones, maintaining efficacy and extending shelf life, while allowing for increased antiparasitic efficacy and reduced resistance.

Implementation Method 1

The combination of a macrocyclic lactone with levamisole, particularly acidic salts of levamisole, presents a number of challenges from a formulation solubility and stability perspective, as levamisole is known to be acid-stable, while the macrocyclic lactones are acid labile and are subject to hydrolytic degradation.

Methodology Applied
Scientific EffectHydrolytic degradation prevention: Hydrolysis

Data Source

PatentEP2983712B1Composition of macrocyclic lactones, levamisole, an amino sugar and an additional antiparasitic agent
Publication Date: 2020.11.25 ZOETIS SERVICES LLC

AI summary

The present invention is directed to stabilized compositions comprising at least one macrocyclic lactone, or derivative thereof, in combination with levamisole, and an amino sugar stabilizing agent, optionally an additional antiparasitic agent, and a method for treating or controlling a parasitic infection or infestation in an animal by administering said composition.