Cyclodextrin Complexes for Anethole Trithione Solubility

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Solution Overview

Problem

Anethole trithione and its derivatives have limited intrinsic aqueous solubility, which hinders their therapeutic potential as site-selective reactive oxygen species (ROS) inhibitors, and existing formulations, such as lipid-based ones, are either ineffective or unstable.

Innovation Solution

A composition comprising sulfobutyl ether-beta-cyclodextrin and anethole trithione or its derivatives, with a molar ratio ranging from 10 to 400, enhances the aqueous solubility and chemical stability of the compounds, maintaining syringeability and allowing for injectable formulations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If lipid-based formulations are used to enhance solubility, then aqueous solubility is improved, but chemical stability deteriorates due to rapid decomposition

Engineering Contradiction:

Improveaqueous solubilityVSAvoidchemical stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent uses cyclodextrins as intermediary molecules that form inclusion complexes with anethole trithione. The cyclodextrin cavity accommodates the lipophilic ATT molecule, while the hydrophilic exterior of the cyclodextrin complex enables aqueous solubility without requiring lipid-based systems that cause decomposition.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical-chemical parameters of the formulation by using cyclodextrin inclusion complexes instead of direct lipid-based formulations. This parameter change from direct lipid solubilization to cyclodextrin-mediated solubilization resolves the stability issue while maintaining solubility enhancement.

Inventive Principle:

Principle #35Parameter changes

2Stability of the object's composition

If intrinsic aqueous solubility is less than 0.3 mg/L, then chemical stability is maintained, but therapeutic potential deteriorates due to inability to formulate injectable medications

Engineering Contradiction:

Improvechemical stabilityVSAvoidtherapeutic potential

Core Design Contradiction:

Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

Cyclodextrins serve as mediators that enable the formulation of injectable medications containing anethole trithione. The inclusion complex formation allows the compound to be delivered in aqueous media suitable for intravenous injection, expanding therapeutic applications while maintaining stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite formulation system consisting of cyclodextrin inclusion complexes. This composite approach combines the lipophilic drug molecule with the amphiphilic cyclodextrin carrier, enabling both solubility enhancement and injectable formulation capability.

Inventive Principle:

Principle #40Composite materials

3Quantity of substance

If hydroxypropyl and sulfobutyl ether beta cyclodextrins are used, then aqueous solubility is enhanced, but syringeability deteriorates due to formation of suspensions

Engineering Contradiction:

Improveaqueous solubilityVSAvoidsyringeability

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The patent optimizes formulation parameters including cyclodextrin concentration, drug-to-cyclodextrin molar ratio, and pH to achieve clear solutions rather than suspensions. By controlling these parameters, the formulation maintains both enhanced solubility and syringeability suitable for intravenous administration.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent selects specific cyclodextrin derivatives (hydroxypropyl-beta-cyclodextrin and sulfobutyl ether-beta-cyclodextrin) with particular properties that balance solubility enhancement with solution clarity. The local quality of these specific cyclodextrin structures enables both solubility improvement and maintainance of syringeability.

Inventive Principle:

Principle #3Local quality

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 formulation significantly improves the bioavailability of anethole trithione derivatives, enabling the preparation of stable and soluble injectable medicaments that can effectively inhibit ROS production.

Implementation Method 1

Methodology Applied

Scientific EffectInclusion complex formation: Absorption (physical)

Data Source

PatentUS12295969B2Pharmaceutical composition comprising cyclodextrin complexes of anethole trithione or derivatives thereof

Publication Date: 2025.05.13 MARIN FREDERIC

AI summary

A composition including anethole trithione or a derivative thereof of formula (I), sulfobutyl ether-beta-cyclodextrin and optionally a co-solvent, wherein the ratio of the sulfobutyl ether-beta-cyclodextrin to the compound of formula (I) ranges from 10 to 400, preferably from 57 to 200. Also, the use of the composition as a drug, namely for the treatment and/or the prevention of free oxygen radical-related diseases. Further, a kit-of-parts and/or a medical device including the composition. Lastly, a method for solubilizing a compound of formula (I) in an aqueous medium.