Alpha-1 Proteinase Inhibitor Purification Yield

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Solution Overview

Problem

Current methods for isolating alpha-1 proteinase inhibitor (a1PI) from human plasma are inefficient and costly, leading to a limited supply and high production costs due to significant a1PI loss during the purification process.

Innovation Solution

Thawing and incubating frozen protein fractions at an ambient temperature of 2-25°C for several hours before a washing step to reduce a1PI loss and increase yield, followed by subsequent purification steps such as polyethylene-glycol precipitation, ZnCl2 precipitation, and anion-exchange chromatography.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If frozen Cohn fraction IV-1 paste is directly subjected to washing and purification steps, then the process time is reduced, but significant a1PI is lost during the washing step

Engineering Contradiction:
Improvea1PI lossVSAvoidprocess time
Core Design Contradiction:
Loss of substanceVSLoss of time

Solution Approach 1:

The patent applies preliminary action by thawing the frozen Cohn fraction IV-1 paste and incubating it at ambient temperature (2-25°C) for at least 4 hours before subjecting it to the washing step. This pre-treatment allows a1PI to become more accessible and less tightly bound to the paste matrix, thereby significantly reducing a1PI loss during subsequent washing while maintaining overall process efficiency

Inventive Principle:
Principle #10Preliminary action

2Productivity

If conventional purification methods are used, then the process is simpler, but the yield of a1PI is low due to significant losses during processing

Engineering Contradiction:
Improvea1PI yieldVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The incubation step at ambient temperature for at least 4 hours serves as a preliminary action that prepares the a1PI-containing paste by allowing a1PI to become more accessible. This simple temperature and time control step significantly reduces a1PI loss during washing without requiring complex equipment or additional chemicals

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes parameter changes by controlling the incubation temperature within the range of 2-25°C and maintaining it for at least 4 hours. This parameter optimization allows a1PI to transition from a tightly bound state in frozen paste to a more accessible state, improving recovery yield without complicating the process

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If the washing step is performed immediately on frozen paste, then the manufacturing cost is lower, but a1PI yield decreases due to loss

Engineering Contradiction:
Improvemanufacturing costVSAvoida1PI yield
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent introduces a preliminary incubation step at ambient temperature for at least 4 hours before washing. This low-cost step requires only temperature control and time, no expensive equipment or reagents, yet it dramatically reduces a1PI loss during washing, thereby improving yield without significantly increasing manufacturing cost

Inventive Principle:
Principle #10Preliminary action

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

Significantly increases the yield of a1PI during the purification process, reducing losses during the washing step and improving the overall efficiency and cost-effectiveness of a1PI production.

Implementation Method 1

thawing it at an ambient temperature of 2-25°C until the protein fraction has reached ambient temperature

Methodology Applied
Scientific EffectThawing: Melting

Implementation Method 2

subjected to a polyethylene-glycol precipitation

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 3

followed by another ZnCl2-precipitation

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 4

applied to a QAE-column

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP1913024B1METHOD FOR THE PURIFICATION OF ALPHA-1 PROTEINASE INHIBITOR (a1PI)
Publication Date: 2009.05.13 BAXTER INT INC

AI summary

The present invention relates to a method for the purification of alpha-1 proteinase inhibitor (a1PI) from protein fractions. More specifically, the invention relates to an improved method for the purification of alpha-1 proteinase inhibitor (a1PI), wherein the yield of a1PI can be increased by thawing the starting material and incubating it for several hours before subjecting it to a washing step.