Opioid Antagonist Particles for Controlled Release

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Solution Overview

Problem

Current opioid receptor antagonists, such as methylnaltrexone, have a narrow therapeutic window and can cause undesirable side effects like orthostatic hypotension due to high plasma levels, and existing delivery methods, like subcutaneous injection, are invasive and not suitable for all patients.

Innovation Solution

Development of particles comprising opioid receptor antagonists with enhanced absorption properties, including enteric coatings and time-release agents, to improve bioavailability and reduce required doses, allowing for targeted and controlled release, thereby minimizing side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If opioid receptor antagonists like methylnaltrexone are administered to treat opioid-induced side effects, then the side effects are reversed, but high plasma levels cause undesirable side effects such as orthostatic hypotension

Engineering Contradiction:

Improveefficacy in reversing opioid side effectsVSAvoidorthostatic hypotension and other side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The particles are designed to release the opioid receptor antagonist in a controlled manner over time, preventing the sudden spike in plasma levels that causes orthostatic hypotension while still achieving the therapeutic effect of reversing opioid-induced side effects

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention changes the delivery parameters of the antagonist by using particles with specific size ranges (30-1000 nm) and incorporating time-release agents, which transforms the pharmacokinetic profile from rapid absorption to controlled, sustained release, thereby maintaining efficacy while reducing peak-level side effects

Inventive Principle:

Principle #35Parameter changes

2Reliability

If subcutaneous injection is used to deliver methylnaltrexone, then the drug is delivered effectively, but the method is invasive and not suitable for all patients

Engineering Contradiction:

Improvedrug delivery efficacyVSAvoidinvasiveness and patient suitability

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The invention replaces the mechanical injection system with an oral or rectal particle delivery system. The particles are designed to be absorbed through the gastrointestinal tract, substituting the invasive subcutaneous injection mechanism with a non-invasive route that is more suitable for chronic opioid users and all patient populations

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If high doses of opioid receptor antagonists are administered, then therapeutic effects are achieved, but the therapeutic window is narrow and side effects increase

Engineering Contradiction:

Improvetherapeutic effectVSAvoiddose required and therapeutic window

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The particles incorporate time-release agents that enable continuous, sustained release of the opioid receptor antagonist over an extended period. This continuous delivery maintains therapeutic plasma levels within the narrow therapeutic window without requiring high doses, thereby achieving reliable therapeutic effects while avoiding the dose-related side effects

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS10507188B2Particles containing an opioid receptor antagonist and methods of use

Publication Date: 2019.12.17 UNIVERSITY OF CHICAGO

AI summary

Particles comprising an opioid receptor antagonist as well as methods of their use and methods of their preparation are provided herein. Such particles may be used for treating and preventing opioid-induced side effects in patients, and may be provided to chronic opioid users as well.