Cationic Polymer Matrix for Oral Macromolecule Delivery

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Solution Overview

Problem

Current pharmaceutical formulations struggle to achieve high systemic bioavailability of poorly permeable hydrophilic macromolecules, such as heparins and proteins, due to their limited absorption through the mucosal barrier, primarily due to their negative charge and hydrophilic nature, which leads to low and erratic absorption when administered orally.

Innovation Solution

A pharmaceutical form comprising a polymeric matrix with a cationic polymer that prevents the selective distribution of the active compound on the surface, ensuring it remains in contact with the polymeric matrix, thereby enhancing absorption by forming a stable complex that facilitates release at the mucosal site.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If hydrophilic macromolecules with negative charge are administered orally, then they can be given by a convenient non-invasive route, but their absorption through the gastrointestinal mucosa is very low due to repulsion from the negatively charged mucosal surface

Engineering Contradiction:
Improveconvenience of administrationVSAvoidabsorption efficiency
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent introduces a cationic polymer as an intermediary substance that forms a complex with the negatively charged hydrophilic macromolecule. This complex has reduced negative charge or reversed surface charge, allowing it to overcome the repulsion from the negatively charged mucosal surface and achieve effective absorption. The cationic polymer acts as a mediator that facilitates the interaction between the drug and the mucosal barrier.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the surface charge parameter of the drug formulation by complexing with cationic polymers. This parameter change transforms the negatively charged surface of the original macromolecule into a complex with reduced negative charge or positive charge, enabling it to interact favorably with the negatively charged mucosal surface and achieve effective absorption.

Inventive Principle:
Principle #35Parameter changes

2Speed

If the active compound is distributed on the surface of the pharmaceutical form, then release may be rapid, but absorption is limited due to the negative charge repelling the negatively charged mucosa

Engineering Contradiction:
Improverelease rateVSAvoidmucosal absorption
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The cationic polymer complex acts as an intermediary that modifies the surface properties of the pharmaceutical form. The complexed drug maintains rapid release capability while the cationic polymer layer on the surface facilitates mucosal absorption by reducing charge repulsion and enhancing interaction with the negatively charged mucosal surface.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If parenteral administration is used to ensure reliable delivery, then absorption is guaranteed, but the treatment requires frequent injections which is inconvenient and burdensome

Engineering Contradiction:
Improvedelivery assuranceVSAvoidadministration convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The cationic polymer complex enables oral administration of macromolecules that would otherwise require parenteral delivery. This intermediary approach transforms the delivery route from invasive injection to convenient oral administration while maintaining reliable absorption through the gastrointestinal mucosa.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of manufacture

If the pharmaceutical form uses large particle size for easy manufacturing, then production is simplified, but absorption through the mucosal barrier decreases

Engineering Contradiction:
Improveproduction simplicityVSAvoidabsorption efficiency
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The cationic polymer complex serves as an intermediary that enhances mucosal absorption capability regardless of particle size. The charge-modified surface of the complex facilitates interaction with the negatively charged mucosal surface, allowing larger particles to maintain good absorption efficiency while preserving manufacturing advantages.

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

This approach significantly increases the absorption and bioavailability of molecules like heparins and insulin, achieving yields of at least 80% incorporation and rapid release within 60 minutes, overcoming the limitations of traditional formulations.

Implementation Method 1

a pharmaceutical form comprising at least one active compound and a polymeric matrix, wherein: a) the active compound is a poorly permeable hydrophilic molecule containing groups with negative charges at pH greater than or equal to 4, and b) the polymeric matrix comprises at least one polymer of cationic nature

Methodology Applied
Scientific EffectElectrostatic attraction: Coulomb's Law

Data Source

PatentEP2219611B1Pharmaceutical forms for the release of active compounds
Publication Date: 2013.01.09 LAB FARM ROVI SA
  • EP2219611B1 patent drawingFigure 1
  • EP2219611B1 patent drawingFigure 2
  • EP2219611B1 patent drawingFigure 3A~3D

AI summary

Pharmaceutical form containing at least an active compound and a polymeric matrix, wherein said polymeric matrix comprises at least one polymer of cationic nature, process of preparation of said pharmaceutical form, pharmaceutical formulation comprising said pharmaceutical form, their uses for preparing a medicament and a method of therapeutic treatment using the pharmaceutical forms and formulations.