Fibrin Glue Visualization Agent Concentration Optimization

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Solution Overview

Problem

Current fibrin glue formulations are colorless, making it difficult to control and visualize the application during surgery, especially in laparoscopic procedures, and high concentrations of visualization agents can affect thrombin activity and clot formation.

Innovation Solution

A fibrin glue kit with a visualization agent added at an enzymatically-permissive concentration that allows for clear staining without significantly impacting thrombin activity or clotting, using methylene blue or indigo carmine at specific concentrations to enhance visibility while maintaining clot stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If high concentration of visualization agent is added to improve visibility, then visibility is improved, but thrombin activity is affected and clot formation is compromised

Engineering Contradiction:
ImprovevisibilityVSAvoidthrombin activity
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the concentration of visualization agents (methylene blue or indigo carmine) to fall within a specific range (0.001-0.1% w/v) that simultaneously achieves adequate visibility and maintains thrombin activity. This quantitative parameter optimization resolves the contradiction between visibility enhancement and clot formation reliability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If colorless fibrin glue is used to maintain enzymatic activity, then thrombin activity is preserved, but application control and visibility during surgery are difficult

Engineering Contradiction:
Improveclot formationVSAvoidapplication control
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies color changes by incorporating visualization agents (methylene blue or indigo carmine) into the fibrin glue formulation at optimized concentrations. This allows the fibrin glue to exhibit visible coloration for improved application control and surgical visibility while maintaining sufficient thrombin activity through careful concentration selection.

Inventive Principle:
Principle #32Color changes

3Ease of operation

If visualization agent is added to enable assessment of applied material thickness, then application control is improved, but the concentration must be precisely controlled to avoid affecting coagulation

Engineering Contradiction:
Improveapplication controlVSAvoidconcentration control
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by establishing a specific concentration range (0.001-0.1% w/v) for visualization agents that balances application control benefits with coagulation functionality. This defined parameter range simplifies the complexity of concentration control by providing clear formulation guidelines.

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 kit enables improved visibility and control of fibrin glue application during surgery without compromising thrombin activity or the mechanical properties of the formed clot, effectively reducing post-surgical adhesions and promoting blood coagulation.

Implementation Method 1

The thrombin converts the fibrinogen to fibrin by enzymatic action

Methodology Applied
Scientific EffectEnzymatic reaction: Enzyme

Implementation Method 2

Factor XIII, is typically present in the fibrinogen component of the glue and is an enzyme of the blood coagulation system that cross-links and stabilizes the fibrin clot

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 3

it would be advantageous to use dyed fibrin glue which will enable the user to asses the thickness of the applied material and improve its visibility during surgery

Methodology Applied
Scientific EffectStaining: Absorption (EM radiation)

Data Source

PatentEP2170414B1Kits, formulations and solutions having enzymatically-permissive amounts of visualization agents and uses thereof
Publication Date: 2012.08.29 OMRIX BIOPHARMACEUTICALS LTD
  • EP2170414B1 patent drawingFigure 1A~1B
  • EP2170414B1 patent drawingFigure 2A
  • EP2170414B1 patent drawingFigure 2B

AI summary

The invention relates to a proteolytic enzyme which is capable of forming fibrin when it reacts with fibrinogen, a fibrin-glue kit and a fibrin-glue formulation comprising an enzymatically-permissive concentration of a visualization agent and to their use in methods for prevention and/or reduction of adhesions and/or methods for promotion of blood coagulation sealing or filling body surfaces.