Xanthine Oxidase Inhibitor Formulations for Improved Solubility

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Solution Overview

Problem

Existing xanthine oxidase inhibitors, such as allopurinol and oxypurinol, are poorly soluble and poorly bioavailable, leading to issues like nausea, gastrointestinal discomfort, and poor absorption, making them ineffective in treating conditions associated with hyperuricemia.

Innovation Solution

Formulations incorporating organic bases, particularly basic amino acids and dipeptides, enhance the solubility and bioavailability of xanthine oxidase inhibitors, forming liquid compositions that improve dissolution and absorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If xanthine oxidase inhibitors are formulated in traditional tablet form, then they are easy to manufacture and administer, but they exhibit poor solubility and poor bioavailability

Engineering Contradiction:
Improvetablet formulationVSAvoidbioavailability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the chemical form of the xanthine oxidase inhibitor by converting it into a salt form (e.g., oxypurinol sodium salt) or complex form, which fundamentally alters its solubility parameters while maintaining its pharmacological activity. This parameter change enables the drug to achieve both manufacturability and improved bioavailability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite formulations by combining the xanthine oxidase inhibitor with specific carriers, excipients, or solubilizing agents. These composite materials enhance the solubility and bioavailability of the active ingredient while maintaining the ease of manufacture through standardized formulation processes.

Inventive Principle:
Principle #40Composite materials

2Reliability

If xanthine oxidase inhibitors are used to treat hyperuricemia, then they reduce uric acid levels, but they cause gastrointestinal discomfort and nausea

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidgastrointestinal side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces intermediaries such as solubilizing agents, protective carriers, or pH-modifying excipients that mediate between the drug and the gastrointestinal tract. These intermediaries reduce direct irritation to the GI lining while ensuring the drug remains soluble and absorbable, thereby maintaining therapeutic efficacy while reducing side effects.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts potentially harmful properties of the xanthine oxidase inhibitor (such as its acidity or solubility characteristics that cause GI irritation) into beneficial features by forming salts or complexes that have reduced irritancy while maintaining or enhancing therapeutic effectiveness.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If organic bases are added to enhance solubility, then bioavailability increases, but formulation complexity increases

Engineering Contradiction:
ImprovebioavailabilityVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent systematically evaluates and optimizes parameters such as pH, ionic strength, and solvent composition to achieve enhanced solubility without requiring complex formulation strategies. By carefully controlling these parameters, the patent achieves improved bioavailability through relatively simple formulation approaches.

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 formulations increase solubility and bioavailability of xanthine oxidase inhibitors, reducing side effects and enhancing therapeutic efficacy by increasing nitric oxide availability and decreasing oxygen radical production, thus effectively treating conditions like gout and hypertension.

Implementation Method 1

organic base that enhances or effects solubilisation of the xanthine oxidase inhibitor

Methodology Applied
Scientific EffectSolubilisation: Solvation

Implementation Method 2

increased dissolution rate and solubility of XOI

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentEP3915565B1Xanthine oxidase inhibitor formulations
Publication Date: 2025.09.10 XORTX THERAPEUTICS INC
  • EP3915565B1 patent drawingFigure 1~2
  • EP3915565B1 patent drawingFigure 3~4

AI summary

Disclosed herein are methods and compositions for involving a xanthine oxidase inhibitor that has enhanced solubility. The compositions described herein include a xanthine oxidase inhibitor combined with an organic base. The compositions can be used to treat a disease or medical condition that involves elevated uric acid levels.