Ellagic Acid Solubilization via Cyclodextrin Complexes

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Solution Overview

Problem

Ellagic acid, a key reagent for activating blood coagulation pathways, is insoluble in water, making it unstable and difficult to use in coagulation assays, particularly in single-use disposable cartridges, due to its aqueous insolubility and instability when stored, leading to inefficiencies and safety concerns with existing solubilization methods.

Innovation Solution

A coagulation test system incorporating ellagic acid stabilized with a cyclodextrin and optionally a polyether compound, such as polyethylene glycol, ensuring at least 80% of the ellagic acid remains active, combined with a thrombin-cleavable peptide and a detectable moiety on a polymer layer for precise analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ellagic acid is used as a reagent for activating blood coagulation pathways, then the coagulation assay can be performed, but the ellagic acid is insoluble in water making it unstable and difficult to use

Engineering Contradiction:
Improvestability of ellagic acidVSAvoidaqueous insolubility of ellagic acid
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses cyclodextrin as an intermediary substance to solubilize ellagic acid in aqueous solutions. The cyclodextrin forms a complex with ellagic acid, allowing it to remain stable and soluble in water-based coagulation assay reagents, thereby resolving the contradiction between maintaining ellagic acid stability and achieving aqueous solubility.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If existing solubilization methods are used for ellagic acid, then solubility is improved, but stability is compromised and preparation time increases

Engineering Contradiction:
Improvesolubility of ellagic acidVSAvoidstability of ellagic acid preparation
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

Cyclodextrin serves as a mediator that simultaneously improves solubility and maintains stability. The cyclodextrin-ellagic acid complex prevents degradation while keeping the reagent ready-to-use, eliminating the need for lengthy preparation protocols associated with traditional solubilization methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If ellagic acid is stored for extended periods, then it can be used in coagulation assays, but it degrades and loses activity

Engineering Contradiction:
Improveavailability of reagentVSAvoidshelf-life of ellagic acid
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The cyclodextrin intermediary protects ellagic acid from degradation during storage by forming a stable complex that prevents hydrolysis and oxidation. This extends the shelf-life of the reagent while maintaining its coagulation-activating activity, allowing for extended storage without significant loss of function.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of operation

If ellagic acid is solubilized using traditional methods, then it becomes more available, but preparation time and safety concerns increase

Engineering Contradiction:
Improveavailability of solubilized reagentVSAvoidpreparation time of reagent
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The cyclodextrin is pre-mixed with ellagic acid during manufacturing to create a stable, ready-to-use reagent formulation. This preliminary solubilization action eliminates the need for time-consuming preparation steps in the laboratory, allowing the reagent to be used directly from storage without additional processing.

Inventive Principle:
Principle #10Preliminary action

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 system provides a stable, highly soluble ellagic acid reagent for coagulation assays, enhancing the precision and reliability of coagulation tests by maintaining the activity of ellagic acid and facilitating efficient detection of thrombin activity, thus improving the accuracy of coagulation assessments in single-use cartridges.

Implementation Method 1

A coagulation test system incorporating ellagic acid stabilized with a cyclodextrin and optionally a polyether compound, such as polyethylene glycol, ensuring at least 80% of the ellagic acid remains active

Methodology Applied
Scientific EffectInclusion complex formation:

Data Source

PatentEP3198281B1Ellagic acid formulations for use in coagulation assays
Publication Date: 2023.01.25 ABBOTT POINT OF CARE INC
  • EP3198281B1 patent drawingFigure 1
  • EP3198281B1 patent drawingFigure 2~4
  • EP3198281B1 patent drawingFigure 5~6

AI summary

The present invention relates to ellagic acid formulations for performing coagulation assays that are highly stable for long term storage and reduce assay time. Particularly, aspects of the present invention are directed to a composition and method of preparing ellagic acid in a highly soluble format for use in a coagulation assay. For example, the ellagic acid may be solubilized in one or more of sodium hydroxide, methanol, a polyether compound, particularly polyethylene glycol, polyethylene oxide, or polyoxyethylene, and a cyclodextrin guest-host complex.