Hemostatic Material Using Covalently Coupled TRAPs

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Solution Overview

Problem

Current hemostatic materials face limitations such as high cost, short shelf-life, mechanical weakness, and safety concerns due to the use of fibrin-based products, zeolite-induced burns, and thrombin's instability and potential for apoptosis, highlighting the need for alternative materials that avoid highly concentrated thrombin and ensure safe, localized hemostasis.

Innovation Solution

A hemostatic material is developed by covalently coupling thrombin receptor activating peptides (TRAPs) to a biocompatible matrix, specifically a synthetic hydrogel like polyvinyl alcohol, to maintain platelet activation activity over time without systemic thrombotic risks, using bioorthogonal reactions for efficient and specific coupling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If thrombin is used in high concentration for hemostasis, then hemostatic effect is improved, but safety risks increase due to potential systemic thrombotic events and apoptosis

Engineering Contradiction:
Improvehemostatic effectVSAvoidsystemic thrombotic events
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by immobilizing thrombin onto a porous matrix material, creating a localized reservoir that releases thrombin only at the application site. This ensures high local concentration for effective hemostasis while preventing systemic circulation and thrombotic events. The thrombin is activated only when in contact with blood at the wound site, maintaining safety while achieving reliability.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent implements preliminary action by pre-immobilizing thrombin onto the matrix material during manufacturing, so that the hemostatic agent is already in place and ready for immediate localized activation upon blood contact. This eliminates the need for high-dose systemic administration while ensuring the thrombin is available exactly where and when needed.

Inventive Principle:
Principle #10Preliminary action

2Ease of manufacture

If hemostatic agents are physically adsorbed on matrix, then ease of manufacture is improved, but durability worsens due to easy release of agents

Engineering Contradiction:
Improveagent loadingVSAvoidagent retention
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent uses composite materials by combining thrombin with a porous matrix material through covalent bonding or strong interaction. This creates a stable composite structure where the thrombin remains firmly attached to the matrix, preventing premature release while maintaining the porosity needed for blood contact and activation. The composite structure ensures both durability and functionality.

Inventive Principle:
Principle #40Composite materials

3Stability of the object's composition

If covalent coupling of thrombin to matrix is performed, then durability is improved, but manufacturing complexity increases

Engineering Contradiction:
Improveagent retentionVSAvoidcoupling process
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent employs an intermediary approach by using carrier proteins or linkers that facilitate the coupling between thrombin and the matrix material. These intermediaries simplify the covalent coupling process while ensuring stable attachment, reducing manufacturing complexity compared to direct covalent bonding methods. The intermediary layer protects thrombin's activity while enabling firm attachment to the matrix.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 material effectively induces localized platelet aggregation and hemostasis, avoiding the drawbacks of existing products by retaining thrombin receptor activity and ensuring biocompatibility, stability, and safety, with potential for improved wound healing and surgical applications.

Implementation Method 1

a thrombin receptor activating agent is covalently coupled to a biocompatible matrix

Methodology Applied
Scientific EffectCovalent coupling: Chemical Bonding

Implementation Method 2

maintaining the activity for platelet activation in a safe, localized manner over a considerable period of time so as to enable an improved hemostasis, especially via an induced platelet aggregation

Methodology Applied
Scientific EffectPlatelet aggregation: Coagulation

Data Source

PatentEP3344299B1Hemostatic material
Publication Date: 2021.08.11 BAXTER INT INC
  • EP3344299B1 patent drawingFigure 1A
  • EP3344299B1 patent drawingFigure 1B
  • EP3344299B1 patent drawingFigure 1C~1D

AI summary

Disclosed is a hemostatic material, wherein a thrombin receptor activating agent is covalently coupled to a biocompatible matrix.