Proteoglycan Endotoxin Reduction While Preserving Molecular Weight

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Solution Overview

Problem

Existing methods for producing proteoglycan for medical use face challenges in reducing endotoxin while maintaining a predetermined molecular weight, which is crucial for effective use in regenerative medicine.

Innovation Solution

A method involving a nonionic surfactant is used to reduce endotoxin in proteoglycan derived from animal tissues, followed by a chromatography carrier treatment to further minimize endotoxin levels, while maintaining the desired molecular weight.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If a basic organic solvent method is used to remove endotoxin from proteoglycan, then endotoxin removal is effective, but the molecular weight of proteoglycan cannot be maintained

Engineering Contradiction:
Improveendotoxin contentVSAvoidmolecular weight of proteoglycan
Core Design Contradiction:
Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

A nonionic surfactant is introduced as an intermediary substance to facilitate endotoxin removal. The surfactant forms micelles that selectively bind and solubilize endotoxin from the proteoglycan solution, allowing endotoxin extraction without directly exposing proteoglycan to harsh basic organic solvents that would cause molecular weight degradation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The method changes the chemical environment parameters by using nonionic surfactants at controlled concentrations and pH levels. This creates a mild extraction condition where endotoxin can be removed through micelle formation and phase separation, avoiding the extreme pH and solvent conditions that would otherwise degrade proteoglycan molecular weight.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If endotoxin is reduced in proteoglycan for medical use, then safety for animal use is improved, but production complexity increases

Engineering Contradiction:
Improvesafety for medical useVSAvoidproduction process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The production process is segmented into distinct stages: (1) proteoglycan extraction from animal tissue, (2) nonionic surfactant addition and micelle formation, (3) phase separation to remove endotoxin-surfactant complexes, and (4) surfactant removal. This segmentation allows each step to be optimized independently and simplifies process control while achieving reliable endotoxin reduction.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The nonionic surfactant serves as a temporary intermediary that facilitates endotoxin removal through reversible binding. After endotoxin extraction, the surfactant can be easily removed by dialysis or ultrafiltration, leaving the proteoglycan in its native state. This intermediary approach avoids the need for complex multi-step purification protocols.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 reduces endotoxin to 4 EU/mg or less in the proteoglycan, ensuring its suitability for medical applications and compliance with biological standards.

Implementation Method 1

a nonionic surfactant is used to reduce endotoxin in proteoglycan derived from a tissue of an animal

Methodology Applied
Scientific EffectSurfactant micelle formation: Surfactant

Implementation Method 2

a second reduction step of treating the proteoglycan with a chromatography carrier, thereby reducing endotoxin in the proteoglycan

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS20250382338A1Agent for reducing endotoxin in proteoglycans derived from animal tissues, and method for producing proteoglycan
Publication Date: 2025.12.18 ICHIMARU PHARCOS CO LTD
  • US20250382338A1 patent drawing
  • US20250382338A1 patent drawing

AI summary

The present disclosure provides an agent capable of reducing endotoxin and used for reducing endotoxin in animal tissue-derived proteoglycan, and a method for producing proteoglycan and capable of reducing endotoxin. The agent of the present disclosure for reducing endotoxin in the animal tissue-derived proteoglycan comprises a nonionic surfactant.