Thromboplastin Reagent Composition for MNPT Control and Stability

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Solution Overview

Problem

Existing blood coagulation time measuring reagents containing tissue thromboplastin suffer from variability in performance and poor storage stability, with no effective methods to control the average normal prothrombin time (MNPT) or improve stability.

Innovation Solution

Incorporating specific metal ions such as cobalt, manganese, or lithium ions into the reagent composition, either with tissue thromboplastin or phospholipid and calcium, to adjust coagulation time within a preset range and enhance storage stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If tissue thromboplastin is used in a blood coagulation time measuring reagent, then the reagent can perform coagulation testing, but the reagent exhibits poor storage stability and variable performance

Engineering Contradiction:
Improvestorage stabilityVSAvoidperformance consistency
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the chemical parameters of the reagent by adding specific metal ions (nickel ions at 0.01-10 mmol/L, cobalt ions at 0.01-10 mmol/L, or manganese ions at 0.01-10 mmol/L) to modify the coagulation reaction characteristics. This parameter change stabilizes the reagent performance and controls MNPT within the desired range of 11-13 seconds, resolving both the storage stability and performance consistency issues

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite reagent system by combining tissue thromboplastin with specific metal ions (nickel, cobalt, or manganese) and calcium ions. This composite formulation enhances the stability and reliability of the reagent while maintaining its coagulation testing function, addressing the poor storage stability problem

Inventive Principle:
Principle #40Composite materials

2Manufacturing precision

If conventional reagents are used without specific metal ion additives, then the reagent formulation is simple, but the average normal prothrombin time cannot be controlled within the desired range

Engineering Contradiction:
ImproveMNPT controlVSAvoidreagent composition
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent precisely controls the concentration parameters of metal ions (nickel, cobalt, or manganese) within specific ranges (0.01-10 mmol/L) to achieve MNPT control within 11-13 seconds. This parameter optimization enables accurate MNPT control while keeping the reagent composition relatively simple and manageable

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If nickel compound is added to adjust ISI to 1.5 or less, then the international sensitivity index is improved, but the average normal prothrombin time control and storage stability are not adequately addressed

Engineering Contradiction:
ImproveISIVSAvoidstorage stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent employs metal ions (nickel, cobalt, or manganese) that perform multiple functions simultaneously: they adjust ISI to 1.5 or less, control MNPT within 11-13 seconds, and improve storage stability. This multi-functional approach resolves the limitation of previous single-purpose additives

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent optimizes the concentration parameters of metal ions to achieve multiple performance targets simultaneously, including ISI ≤1.5, MNPT control within 11-13 seconds, and enhanced storage stability, thereby addressing all limitations of conventional reagents

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 method allows for controlled MNPT within 11-13 seconds and improved storage stability of the reagent, maintaining performance over time.

Implementation Method 1

measuring blood coagulation time by use of a reagent containing tissue thromboplastin and calcium

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 2

improving the storage stability of a blood coagulation time measuring reagent containing tissue thromboplastin and calcium

Methodology Applied
Scientific EffectStabilization:

Data Source

PatentUS12504434B2Method for measuring blood coagulation time
Publication Date: 2025.12.23 SEKISUI MEDICAL CO LTD

AI summary

A method for controlling MNPT is required.Coexistence of a specific metal ion with tissue thromboplastin enables MNPT to be controlled/adjusted to a desired time. Coexistence of the specific metal ion with tissue thromboplastin also enables improvement of stability when a thromboplastin reagent is stored in a solution form.