Powdered Hemostatic Composition with Aldehyde-Functionalized Polymer

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Solution Overview

Problem

Current hemostatic materials face challenges in achieving rapid and effective hemostasis, particularly due to the instability of acid-sensitive proteins like thrombin and fibrinogen when used with carboxylic-oxidized cellulose, which can denature these biologics, and the need for improved ease of application and rapid onset of hemostasis in various surgical and wound scenarios.

Innovation Solution

A method of forming powdered hemostatic materials comprising aggregates of fibrinogen, thrombin, and oxidized regenerated cellulose (ORC) fibers, with additives like Lysine or Tris, using a non-aqueous solvent suspension that is agitated and dried to create a powdered composition with integrated ORC fibers, fibrinogen, and thrombin, facilitating rapid gelling and strong adhesion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If carboxylic-oxidized cellulose is used as a hemostatic material, then hemostatic performance is improved, but acid-sensitive proteins like thrombin and fibrinogen denature and lose effectiveness

Engineering Contradiction:
Improvehemostatic performanceVSAvoidprotein stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces an intermediary substance (aldehyde-functionalized polymer) that mediates between the oxidized cellulose and acid-sensitive proteins. This intermediary provides a neutral or buffered interface that prevents direct harmful interaction between the acidic oxidized cellulose and the proteins, while still enabling the desired hemostatic function.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the cellulose derivative by introducing aldehyde functional groups through controlled oxidation. This parameter change (from carboxylic acid groups to aldehyde groups) fundamentally alters the chemical behavior, eliminating the denaturing effect on proteins while maintaining hemostatic performance.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If traditional hemostatic materials are used, then ease of application is maintained, but rapid onset of hemostasis is not achieved

Engineering Contradiction:
Improveease of applicationVSAvoidonset of hemostasis
Core Design Contradiction:
Ease of operationVSSpeed

Solution Approach 1:

The patent creates a composite material combining oxidized regenerated cellulose fibers with aldehyde-functionalized polymer and acid-sensitive proteins. This composite structure integrates the rapid hemostatic action of oxidized cellulose with the stability and efficacy of protected proteins, achieving both rapid onset and ease of application.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent performs preliminary action by pre-complexing the acid-sensitive proteins with the aldehyde-functionalized polymer in a stable formulation. This pre-prepared complex ensures that when applied, the proteins are immediately available and protected, eliminating delays associated with on-site preparation or activation.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If fibrinogen and thrombin are combined with oxidized cellulose, then hemostatic efficacy is improved, but the biologics denature due to acid sensitivity

Engineering Contradiction:
Improvehemostatic efficacyVSAvoidacid denaturation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The aldehyde-functionalized polymer serves as a protective intermediary that binds to acid-sensitive proteins through Schiff base formation or other non-denaturing interactions. This intermediary layer shields the proteins from direct exposure to acidic environments while maintaining their biological activity and hemostatic function.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the pH sensitivity parameter by using aldehyde groups instead of carboxylic acid groups. This chemical parameter change eliminates the low pH environment that causes denaturation, allowing fibrinogen and thrombin to maintain their native structure and function while still providing enhanced hemostatic efficacy.

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 resulting hemostatic composition exhibits rapid gelling, strong adhesion, and effective clotting, even in challenging conditions such as lung air leaks, with improved solubility and uniformity, addressing the limitations of existing materials by ensuring rapid and reliable hemostasis.

Implementation Method 1

forming a suspension of a mixture comprising particles of fibrinogen, thrombin, and ORC fibers in a non-aqueous solvent

Methodology Applied
Scientific EffectSuspension: Suspension

Implementation Method 2

adding water to allow particles to agglomerate

Methodology Applied
Scientific EffectAgglomeration: Flocculation

Implementation Method 3

allowing the non-aqueous solvent to evaporate

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3752212B1Method of making hemostatic compositions
Publication Date: 2023.08.09 ETHICON INC
  • EP3752212B1 patent drawingFigure 1
  • EP3752212B1 patent drawingFigure 2
  • EP3752212B1 patent drawingFigure 3~4

AI summary

The present invention is directed to hemostatic compositions comprising at least partially integrated agglomerated ORC fibers, fibrinogen, and thrombin and methods of forming a powdered hemostatic composition, comprising the steps of: forming a suspension of a mixture comprising particles of fibrinogen, thrombin, ORC fibers in a non-aqueous low boiling solvent, agitating and shearing said suspension in a high shear mixing reactor, adding water to allow particles to agglomerate, allowing the non-aqueous solvent to evaporate, drying and sieving the composition; and thus forming the powdered hemostatic composition.