Aramchol Salts for Enhanced Solubility

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Solution Overview

Problem

There is an unmet need for new forms of Aramchol with desirable physicochemical properties, particularly increased solubility and bioavailability, to effectively treat fatty liver disease and Non-Alcoholic SteatoHepatitis (NASH).

Innovation Solution

The development of salts of Aramchol with amino alcohols, amino sugars, or amino acids, such as N-methylglucamine, lysine, and tromethamine salts, which exhibit improved solubility, absorption, and bioavailability, allowing for lower dosing and easier processing into pharmaceutical formulations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Aramchol free acid is used, then the compound has the required therapeutic activity, but the solubility and bioavailability are insufficient

Engineering Contradiction:
Improvetherapeutic activityVSAvoidsolubility
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by converting Aramchol free acid into different salt forms (sodium salt, potassium salt, magnesium salt, calcium salt, aluminum salt, zinc salt, manganese salt, iron salt, copper salt, cobalt salt, nickel salt, lithium salt, ammonium salt, and organic amine salts). This chemical parameter change transforms the compound's physicochemical properties, specifically improving solubility and bioavailability while preserving the core therapeutic activity of the aramchol molecule.

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If Aramchol free acid is used, then the compound structure is simple, but the absorption and exposure are limited

Engineering Contradiction:
Improvecompound structureVSAvoidabsorption and exposure
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent changes the chemical parameter of the Aramchol compound by forming salts with various cations. This transformation maintains the relatively simple molecular structure while dramatically improving absorption and exposure characteristics, as evidenced by the increased solubility and bioavailability observed in the salt forms compared to the free acid.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If Aramchol free acid is used, then the formulation processing is straightforward, but the flow properties are inadequate

Engineering Contradiction:
Improveformulation processingVSAvoidflow properties
Core Design Contradiction:
Ease of manufactureVSEase of operation

Solution Approach 1:

The patent applies parameter changes by converting Aramchol into salt forms, which fundamentally alters the physical properties of the compound. The salt forms exhibit improved flow properties compared to the free acid, making them more suitable for formulation processing into solid dosage forms while maintaining ease of manufacture.

Inventive Principle:
Principle #35Parameter changes

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 new salts of Aramchol demonstrate enhanced solubility and bioavailability, leading to higher therapeutic efficacy and easier formulation into solid dosage forms, effectively reducing liver fat and improving metabolic parameters associated with fatty liver disease.

Implementation Method 1

Aramchol is an amide conjugate of arachidic acid and 3-aminocholic acid, effective in reducing liver fat content as well as improving metabolic parameters associated with fatty liver disease

Methodology Applied
Scientific EffectMetabolic modulation:

Data Source

PatentEP3077047B1Aramchol salts
Publication Date: 2019.04.24 GALMED RESEARCH & DEVELOPMENT LTD
  • EP3077047B1 patent drawingFigure 1
  • EP3077047B1 patent drawingFigure 2
  • EP3077047B1 patent drawingFigure 3

AI summary

The present invention relates to salts of arachidyl amido cholanoic acid (Aramchol), pharmaceutical compositions comprising Aramchol salts, methods for their preparation, and methods of use thereof in medical treatment.