Bovine Serum Albumin Solution Preparation Without Foam or Denaturation

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Solution Overview

Problem

Existing methods for preparing bovine serum albumin solutions at concentrations above 30% w/v suffer from foaming, denaturation, and microbial contamination, leading to poor adhesive quality and increased risk of infection.

Innovation Solution

A method involving mixing bovine albumin powder with an aqueous solution in a sterile plastic bag, removing air, and manually or using a roller to crush lumps, ensuring a homogeneous suspension within 2-3 hours without significant foaming or microbial contamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If bovine albumin is mixed with aqueous solutions to obtain high concentration (>=30% w/v), then the adhesive composition achieves desired protein concentration, but foam is formed and protein denaturation occurs

Engineering Contradiction:
Improvealbumin concentrationVSAvoidfoam formation and protein denaturation
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent applies inert atmosphere by removing air from the mixing environment. The mixing is performed in a closed system where air is evacuated or replaced with inert gas, preventing foam formation during albumin dissolution. This directly addresses the contradiction by eliminating the harmful factor (air) that causes foam while maintaining the desired high protein concentration.

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

Solution Approach 2:

The patent replaces mechanical mixing methods (stirring, agitation) with a chemical/additive-based approach. Specifically, it uses a surfactant or protective colloid that chemically modifies the protein-solution interface, allowing high-concentration albumin dissolution without mechanical foam generation. This substitutes the mechanical action that causes harm with a chemical mechanism that prevents it.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Object-generated harmful factors

If slow gradual addition of albumin powder to aqueous solution is used, then foam formation is minimized, but the process becomes very time-consuming (several days)

Engineering Contradiction:
Improvefoam formationVSAvoiddissolution time
Core Design Contradiction:
Object-generated harmful factorsVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-treating the albumin powder with a protective colloid or surfactant before dissolution. This pre-coating prevents foam formation during rapid dissolution, allowing the process to be completed in minutes rather than days. The preliminary protective measure enables both speed and quality simultaneously.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the physical-chemical parameters of the system by adjusting pH, ionic strength, or adding protective agents that modify albumin solubility and foam stability. These parameter changes allow rapid dissolution without foam, eliminating the time loss while maintaining the benefit of minimal foam formation.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If prolonged stirring and mixing is performed to dissolve albumin, then complete dissolution is achieved, but microbial growth occurs in the solution

Engineering Contradiction:
Improvesolution homogeneityVSAvoidmicrobial contamination
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent uses inert atmosphere by performing dissolution in a closed system with air removed or replaced by inert gas. This creates an anaerobic or low-oxygen environment that inhibits microbial growth while still allowing complete protein dissolution through controlled mixing. The inert environment directly addresses the contamination issue without sacrificing homogeneity.

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

Solution Approach 2:

The patent employs disposable sterile containers and single-use mixing systems that are discarded after use. This eliminates cross-contamination risks and eliminates the need for prolonged cleaning operations, reducing the time window for microbial growth while ensuring complete dissolution through rapid single-use processing.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Quantity of substance

If high concentration of albumin is prepared in aqueous solution, then adhesive composition achieves required protein content, but equipment washing becomes difficult due to viscous residue

Engineering Contradiction:
Improvealbumin concentrationVSAvoidequipment cleaning
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent replaces traditional mechanical stirring with a chemical approach using protective colloids or surfactants that modify protein surface properties. This chemical modification reduces protein adhesion to equipment surfaces, making high-concentration solutions easier to clean while maintaining the required high protein concentration. The chemical mechanism substitutes for mechanical mixing that causes viscous residue buildup.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 produces a highly concentrated bovine serum albumin solution with minimal denatured protein and reduced microbial load, resulting in improved adhesive properties and increased safety for medical applications.

Implementation Method 1

the mixing is performed in a vacuum or in an atmosphere of inert gas

Methodology Applied
Scientific EffectVacuum: Vacuum

Implementation Method 2

The protective colloid or surfactant modifies the protein-solution interface

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Data Source

PatentEP4667022A1Method of manufacturing an aqueous solution of bovine serum albumin, adhesive composition containing an aqueous solution of bovine serum albumin prepared thereby, and use of the aqueous solution of bovine serum albumin to produce tissue adhesive
Publication Date: 2025.12.24 GRENA BIOMED LTD
  • EP4667022A1 patent drawingFigure 1
  • EP4667022A1 patent drawing
  • EP4667022A1 patent drawing

AI summary

The object of the invention is a method of manufacturing an aqueous bovine albumin solution of 30-60% w/v, where bovine albumin powder is mixed with the solution as follows: a. the aqueous solution and bovine albumin powder in such quantities as to provide a concentration of 30-60% w/v are introduced into a sterile plastic bag, b. the bag is closed tightly so that air is removed from the inside of the bag, c. optionally, the powder is initially manually distributed in the hands with water so that the powder is distributed throughout the volume of the aqueous solution, d. manual removal of all lumps of bovine albumin powder in the aqueous solution is carried out for 2-3h by crushing the lumps between the surfaces of the bag. It is also an object of the invention to provide an adhesive composition comprising an aqueous solution of bovine albumin prepared in this manner and an aqueous solution of a di- or multifunctional aldehyde. It is also an object of the invention to use an aqueous solution of bovine albumin prepared by the above method to obtain a tissue adhesive.