IαIp Purification via pH-Dependent Chromatography

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Solution Overview

Problem

Current methods for treating sepsis and septic shock are ineffective, with high mortality rates and limited treatment options, and there is a need for efficient purification methods for inter-alpha inhibitor proteins (IαIp) to modulate severe systemic inflammation.

Innovation Solution

A method for purifying IαIp by exposing the protein to conditions of pH 4.0 or lower, using chromatography and buffer solutions, to increase binding and biological activity, resulting in a pharmaceutical composition for treating sepsis, septic shock, and other inflammatory diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional purification methods are used for IαIp, then the purification process is simple, but the binding affinity and biological activity are insufficient

Engineering Contradiction:

Improvebinding affinityVSAvoidpurification process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by utilizing pH as a critical parameter to control the binding affinity of IαIp to its target. By adjusting the pH to specific ranges (e.g., pH 4.0-6.0 for binding, pH 7.0-9.0 for elution), the invention optimizes the interaction between the protein and chromatography medium, thereby enhancing binding affinity and biological activity while maintaining a relatively simple purification process.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If IαIp is purified using standard chromatography, then the purification is efficient, but the protein may lose biological activity

Engineering Contradiction:

Improvebiological activityVSAvoidpurification efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The invention employs parameter changes by carefully controlling pH levels throughout the purification process. The chromatography medium is activated at specific pH ranges to ensure optimal binding conditions, while elution is performed at higher pH to maintain protein stability and biological activity. This approach preserves the functional properties of IαIp while achieving efficient purification.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses pH-adjusted buffer solutions as intermediaries to facilitate the purification process. These buffers serve as mediators between the chromatography medium and the IαIp protein, enabling selective binding and elution while maintaining protein stability and biological activity throughout the process.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If the purification method is simplified, then the process is easier to perform, but the purity and concentration of IαIp are reduced

Engineering Contradiction:

Improveprotein concentrationVSAvoidpurification steps

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention achieves high protein concentration and purity through parameter changes in pH during a simplified chromatography process. By optimizing the pH for binding (4.0-6.0) and elution (7.0-9.0), the method concentrates IαIp effectively while maintaining a relatively simple purification protocol with fewer steps.

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 method effectively purifies IαIp, increasing its binding and biological activity, providing a therapeutic option for sepsis, septic shock, and other inflammatory conditions, with potential for reduced mortality and improved treatment outcomes.

Implementation Method 1

The method involves placing blood, a blood plasma fraction, or an intermediate plasma fraction on a chromatography column, subjecting the column to a wash buffer with a pH of about 4.0 or lower

Methodology Applied

Scientific EffectChromatography: Chromatography