Albumin Purification via Sodium Caprylate Stabilization

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Solution Overview

Problem

Existing methods for albumin purification from plasma, such as ethanol precipitation, suffer from protein denaturation, reduced yield, and contamination issues, and do not effectively utilize the relationship between total protein concentration and sodium caprylate ratio during pasteurization.

Innovation Solution

A method involving contacting plasma with sodium caprylate at specific concentrations, pasteurizing at near-neutral pH, and separating albumin from non-albumin phases, optimizing the total protein concentration and sodium caprylate to total protein ratio for high yield and purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If ethanol precipitation method is used for plasma fractionation, then proteins can be isolated and concentrated, but protein denaturation occurs resulting in decreased yield and contamination with aggregates

Engineering Contradiction:
Improveprotein concentrationVSAvoidprotein integrity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the precipitation process by using sodium caprylate instead of ethanol, and by controlling pH in the near-neutral range (6.5-7.5) during pasteurization, thereby achieving protein precipitation without denaturation and maintaining protein integrity while still achieving concentration

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces sodium caprylate as an intermediary substance that mediates the precipitation process. The caprylate ion acts as a stabilizer that binds to albumin and prevents aggregation during precipitation, enabling high-purity isolation without the harmful effects of traditional ethanol precipitation

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If caprylate and tryptophan are added as stabilizers during pasteurization, then HSA integrity is maintained, but the process requires precise control of multiple parameters including pH, temperature, and reagent ratios

Engineering Contradiction:
ImproveHSA integrityVSAvoidprocess control complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the need for tryptophan from the stabilization regimen, using only sodium caprylate as the stabilizing agent. This simplification reduces the number of parameters that need to be controlled while maintaining HSA integrity during pasteurization

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the pH parameter from the traditional acidic range to near-neutral (6.5-7.5), which simplifies the stabilization requirements and allows effective use of sodium caprylate alone, reducing process complexity while maintaining protein integrity

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If ethanol precipitation is used to obtain protein fractions, then separation can be achieved, but insoluble protein and lipid material hinder further purification reducing yield

Engineering Contradiction:
Improveprotein fraction separationVSAvoidpurification efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent changes the chemical environment by using near-neutral pH and sodium caprylate instead of ethanol, which prevents the formation of insoluble aggregates and lipid-protein complexes that hinder filtration, thereby maintaining high purification efficiency throughout the process

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potential harm of precipitation into a benefit by using controlled precipitation with sodium caprylate that selectively precipitates impurities while keeping albumin in solution, thereby achieving separation without the formation of harmful insoluble material

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 achieves high yield and purity of albumin, stabilizing the protein and selectively precipitating impurities, resulting in a high-quality albumin solution with improved recovery and purity.

Implementation Method 1

The caprylate ion is believed to decrease the rate of reversible partial unfolding by binding to HSA

Methodology Applied
Scientific EffectProtein binding: Absorption (physical)

Implementation Method 2

heating the plasma at a near neutral pH range... separating the albumin from non-albumin-phase

Methodology Applied
Scientific EffectDifferential precipitation: Precipitation

Data Source

PatentUS11427613B2Method for purification of albumin
Publication Date: 2022.08.30 EVOLVE BIOLOGICS INC
  • US11427613B2 patent drawing
  • US11427613B2 patent drawing
  • US11427613B2 patent drawing

AI summary

A method for the purification of albumin from plasma is described. The method comprises (a) contacting the plasma with sodium caprylate (NaCP) at an amount dependent on total protein concentration and the ratio of NaCP to total protein in the plasma, (b) heating the plasma at a near neutral pH range, and (c) separating the albumin from non-albumin-phase. The said method provides for a high yield and purity albumin solution.