Guanidine Reagent for Accurate Blood Coagulation Time Measurement

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Solution Overview

Problem

Conventional blood coagulation time prolonging agents increase reagent viscosity, reducing sampling accuracy and failing to enhance optical changes sufficiently, making it difficult to measure coagulation time accurately and correctly.

Innovation Solution

A reagent containing a guanidine compound, such as aminoguanidine or its acid addition salt, is used to prolong blood coagulation time and enhance optical changes, allowing for more accurate and sensitive blood coagulability measurements through optical detection methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional blood coagulation time prolonging agents (halide salts, sodium propionate) are added to the reagent, then the coagulation time is prolonged, but the optical change (ΔH) is reduced in a dose-dependent manner

Engineering Contradiction:
Improvecoagulation timeVSAvoidoptical change detection accuracy
Core Design Contradiction:
Duration of action of moving objectVSMeasurement precision

Solution Approach 1:

The patent changes the chemical composition parameter by replacing conventional prolonging agents (halide salts, sodium propionate) with a specifically formulated reagent system containing fibrin, thrombin, and buffer at optimized concentrations. This parameter change achieves both coagulation time prolongation and maintenance of optical change magnitude, resolving the contradiction between extended measurement time and detection accuracy.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite reagent system comprising multiple components (fibrin, thrombin, buffer, and other additives) working synergistically. This composite approach allows simultaneous achievement of coagulation time prolongation and optical change enhancement, overcoming the limitations of single-substance prolonging agents that reduced ΔH.

Inventive Principle:
Principle #40Composite materials

2Productivity

If the coagulation reaction proceeds rapidly, then the measurement process is efficient, but the coagulation time cannot be measured with good accuracy

Engineering Contradiction:
Improvemeasurement efficiencyVSAvoidcoagulation time measurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent creates a dynamically optimized reaction environment where the coagulation rate is modulated through the specific reagent composition. The system maintains sufficient reaction speed for efficiency while extending the measurable phase of coagulation through the sustained optical changes enabled by the fibrin-thrombin-buffer system, allowing accurate time measurement without sacrificing productivity.

Inventive Principle:
Principle #15Dynamics

3Duration of action of moving object

If high molecular materials (polyethylene glycol, polyvinyl alcohol) are added to prolong coagulation time, then the coagulation time is extended, but the viscosity of the reagent is increased reducing sampling accuracy

Engineering Contradiction:
Improvecoagulation timeVSAvoidsampling accuracy
Core Design Contradiction:
Duration of action of moving objectVSManufacturing precision

Solution Approach 1:

The patent extracts and eliminates the harmful high molecular materials (polyethylene glycol, polyvinyl alcohol) from the reagent composition while retaining the beneficial coagulation time prolongation effect through alternative components (fibrin, thrombin, buffer system). This extraction removes the viscosity-increasing side effect that compromised sampling accuracy, while maintaining extended coagulation measurement capability.

Inventive Principle:
Principle #2Taking out (Extraction)

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 use of guanidine compounds effectively prolongs coagulation time and enhances turbidity changes, enabling correct and sensitive measurement of fibrinogen levels, PT, and APTT, improving the accuracy of blood coagulability tests.

Implementation Method 1

A blood coagulation mechanism is broadly divided into two pathways in general. One is an intrinsic pathway, which is initiated by contact activation of blood coagulation factor XII with a foreign substance, and finally produces thrombin through multistep reactions

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 2

The optical detection method refers to a method including detecting white turbidity of a reaction solution due to coagulation as a change in transmitted light or scattered light

Methodology Applied
Scientific EffectScattered light: Scattering

Implementation Method 3

coagulation eventually occurs by conversion of fibrinogen to fibrin through an action of produced thrombin

Methodology Applied
Scientific EffectCoagulation: Coagulation

Data Source

PatentEP3018481B1Blood coagulation time prolonging agent
Publication Date: 2018.02.21 SEKISUI MEDICAL CO LTD
  • EP3018481B1 patent drawingFigure 1
  • EP3018481B1 patent drawingFigure 2
  • EP3018481B1 patent drawingFigure 3

AI summary

A method of measuring blood coagulability, comprising the following steps of: preparing a reaction solution containing a plasma specimen, a blood coagulation activator, the guanidine compound represented by the following formula (1) or an acid addition salt thereof: where R1 represents a hydrogen atom, an amino group, or an alkyl group which may have a substituent; and measuring a coagulation time of the reaction solution by detecting a turbidity change.