APTT Reagent Composition Using Pyrogallol for Precipitation Control

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Solution Overview

Problem

Existing APTT measurement reagents using ellagic acid face issues with precipitation, necessitating the use of environmentally hazardous phenol to suppress this, and there is a need for a safer alternative that effectively prevents ellagic acid precipitation.

Innovation Solution

Incorporating pyrogallol and/or gallic acid into the APTT reagents, along with a phospholipid and calcium ions, to form a complex that suppresses ellagic acid precipitation, thereby stabilizing the reagent composition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If phenol is added to suppress ellagic acid precipitation, then reagent stability is improved, but environmental safety deteriorates

Engineering Contradiction:
Improvereagent stabilityVSAvoidenvironmental safety
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces polyvinyl alcohol as an intermediary substance that mediates between ellagic acid and the aqueous environment. Polyvinyl alcohol forms a protective complex with ellagic acid, preventing its precipitation while avoiding the use of harmful phenol. This intermediary approach resolves the contradiction by providing a safe alternative that maintains reagent stability without environmental hazards.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical composition parameters of the reagent system by replacing phenol with polyvinyl alcohol. This parameter change transforms the system from one relying on hazardous substances to one using environmentally safe materials, while maintaining or improving the precipitation suppression function through different chemical mechanisms.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If ellagic acid is used as coagulation activator, then coagulation reaction efficiency is improved, but precipitation occurs in aqueous solvents

Engineering Contradiction:
Improvecoagulation reaction efficiencyVSAvoidreagent stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent creates a composite system where polyvinyl alcohol and ellagic acid form a stable complex in aqueous solution. This composite material approach allows ellagic acid to maintain its coagulation activator function while the polyvinyl alcohol component prevents precipitation, thereby simultaneously achieving reaction efficiency and reagent stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Polyvinyl alcohol acts as an intermediary that enables ellagic acid to function effectively in aqueous solutions without precipitating. The intermediary substance facilitates the compatibility between ellagic acid and the aqueous environment, allowing the coagulation activator to work at full efficiency while remaining stable in solution.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If amino acids or polyvinyl alcohol are used to suppress precipitation, then environmental safety is improved, but reagent composition complexity increases

Engineering Contradiction:
Improveenvironmental safetyVSAvoidreagent composition complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent optimizes the concentration parameters of polyvinyl alcohol in the reagent formulation. By carefully controlling the amount of polyvinyl alcohol added, the patent achieves effective precipitation suppression with minimal impact on reagent composition simplicity. This parameter optimization balances environmental safety requirements with maintaining reagent formulation simplicity.

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 solution effectively prevents ellagic acid precipitation, ensuring accurate coagulation time measurement and reducing environmental hazards, while maintaining reagent stability and preventing abnormal initial reactions.

Implementation Method 1

Incorporating pyrogallol and/or gallic acid into the APTT reagents, along with a phospholipid and calcium ions, to form a complex that suppresses ellagic acid precipitation

Methodology Applied
Scientific EffectComplex formation: Chemical Bonding

Implementation Method 2

a first reagent comprising an ellagic acid compound, a phospholipid and a compound represented by Formula (I)... and a second reagent comprising a calcium ion; and measuring activated partial thromboplastin time using the mixture

Methodology Applied
Scientific EffectCoagulation: Coagulation

Data Source

PatentEP3798635B1Method for measuring activated partial thromboplastin time and reagent kit for activated partial thromboplastin time measurement
Publication Date: 2025.09.10 SYSMEX CORP
  • EP3798635B1 patent drawingFigure 1~2
  • EP3798635B1 patent drawingFigure 3
  • EP3798635B1 patent drawingFigure 4A

AI summary

Disclosed is a method for measuring activated partial thromboplastin time, the method comprising: mixing: a blood sample; a first reagent comprising an ellagic acid compound and a compound represented by Formula (I); and a second reagent comprising a calcium ion; and measuring activated partial thromboplastin time using the mixture prepared in the mixing step, wherein the compound represented by Formula (I) is shown below wherein X is a hydrogen atom, -(C=O)-Y, or -(C=O)-OZ, Y is a hydroxyl group, a hydrogen atom, a linear or branched alkyl group having a carbon number of 1 or more and 6 or less, or a phenyl group, and Z is an alkali metal.