Fibrinogen Dissolution Under Sub-Atmospheric Pressure

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Solution Overview

Problem

Fibrinogen is difficult to dissolve in aqueous solvents to achieve high concentrations, leading to prolonged dissolution times and potential foam formation, which can affect the mechanical properties of fibrin sealants.

Innovation Solution

Dissolving solid fibrinogen compositions in an aqueous solvent under sub-atmospheric pressure, followed by equilibration to atmospheric pressure without introducing air, to minimize foam formation and achieve high fibrinogen concentrations within a short time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If solid fibrinogen composition is dissolved in aqueous solvent at atmospheric pressure, then dissolution occurs, but foam forms and dissolution time is prolonged

Engineering Contradiction:
Improvedissolution speedVSAvoidfoam formation
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies vacuum (sub-atmospheric pressure) environment during the dissolution process to prevent foam formation. By maintaining negative pressure in the headspace of the container, air is prevented from entering and mixing with the fibrinogen solution, thereby eliminating foam generation while maintaining rapid dissolution rates.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent creates a vacuum environment in the container before adding the aqueous solvent to the solid fibrinogen composition. This preliminary action of establishing sub-atmospheric pressure prevents foam formation from the outset during the dissolution process, rather than attempting to remove foam after it forms.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If solid fibrinogen composition is dissolved in aqueous solvent, then high concentration solution is achieved, but dissolution time is prolonged

Engineering Contradiction:
Improvefibrinogen concentrationVSAvoiddissolution time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The vacuum environment facilitates faster dissolution by preventing foam formation that would otherwise trap undissolved particles and slow down the process. The sub-atmospheric pressure also enhances solvent penetration into the solid matrix, accelerating dissolution while achieving high concentrations.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent changes the pressure parameter from atmospheric to sub-atmospheric during dissolution. This parameter change fundamentally alters the dissolution dynamics, enabling both high concentration achievement and rapid dissolution time without the trade-off normally present.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If foam is present during dissolution, then dissolution time is further prolonged, but mechanical properties of fibrin sealant are negatively affected

Engineering Contradiction:
Improvedissolution speedVSAvoidmechanical properties of fibrin sealant
Core Design Contradiction:
ProductivityVSStrength

Solution Approach 1:

By maintaining vacuum conditions throughout the dissolution process, the patent prevents foam formation that would compromise both dissolution speed and final product quality. The inert vacuum environment ensures that no air bubbles are incorporated into the solution, preserving both rapid dissolution and optimal mechanical properties.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent converts the potentially harmful effect of pressure changes into a beneficial outcome by using vacuum pressure not only to accelerate dissolution but also to inherently prevent foam formation, thereby protecting mechanical properties without requiring additional anti-foaming measures.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

This method enables rapid dissolution of solid fibrinogen to achieve high concentrations (at least 40 mg/ml) in under 90 seconds with minimal foam presence, maintaining the stability and functionality of the fibrin sealant.

Implementation Method 1

dissolving a solid fibrinogen composition in an aqueous solvent

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

maintaining the internal pressure in the headspace at sub-atmosphere pressure

Methodology Applied
Scientific EffectPressure control: Pressure Increase

Data Source

PatentUS11634473B2Method and device for fast dissolution of solid protein composition
Publication Date: 2023.04.25 OMRIX BIOPHARMACEUTICALS LTD
  • US11634473B2 patent drawing
  • US11634473B2 patent drawing
  • US11634473B2 patent drawing

AI summary

Provided are methods and devices for dissolving solid protein compositions, such as solid compositions comprising fibrinogen, in an aqueous solvent. The methods comprise use of a closed container containing a volume of solid fibrinogen composition and a head space wherein the pressure within the headspace is sub-atmospheric. Aqueous solvent is introduced into the container while maintain the sub-atmospheric pressure, and subsequent to addition of the solvent, the size of the headspace is decreased to bring the pressure to atmospheric pressure. The devices are suitable for use in the disclosed method.