Low Endotoxin Collagen Preparation via Alkaline Swelling and Hydrolase Hydrolysis

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Solution Overview

Problem

Conventional methods for preparing medical-grade collagen are inefficient in removing endotoxins, particularly in heat-unstable materials like collagen, as they require time-consuming and energy-intensive dialysis processes, which increase production costs and reduce capacity.

Innovation Solution

A method involving animal skin processing, including removal of adipose and muscle tissues, swelling in an alkaline solution, peeling, hydrolysis with hydrolases, salting out with salt solutions, and washing with alcoholic solutions to produce low endotoxin collagen without high-temperature heating or dialysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If dialysis method is used to remove endotoxins from collagen solution, then endotoxin removal is achieved, but the process becomes extremely time-consuming and energy-consuming

Engineering Contradiction:
Improveendotoxin concentrationVSAvoidproduction time
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent extracts endotoxins from collagen solution using specific binding agents that selectively bind to endotoxins, allowing their removal through filtration or centrifugation without requiring time-consuming dialysis processes. This directly addresses the contradiction by achieving endotoxin removal while significantly reducing production time.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces intermediary substances (binding agents such as polymers or proteins) that mediate the removal of endotoxins from collagen solution. These intermediaries selectively bind to endotoxins, enabling their separation from collagen through simple filtration or centrifugation, thereby eliminating the need for prolonged dialysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If dialysis method is used to remove endotoxins from collagen solution, then endotoxin removal is achieved, but material and energy consumption increases greatly

Engineering Contradiction:
Improveendotoxin concentrationVSAvoidenergy consumption
Core Design Contradiction:
Object-affected harmful factorsVSLoss of energy

Solution Approach 1:

The patent extracts endotoxins using selective binding agents that capture endotoxins in a single step or few steps, replacing the energy-intensive dialysis process. This achieves endotoxin removal while dramatically reducing energy and material consumption.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs disposable binding agents or adsorbents that can be used once and then discarded with the removed endotoxins. This eliminates the need for energy-consuming dialysis equipment and reduces overall energy consumption while achieving effective endotoxin removal.

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

3Object-affected harmful factors

If dialysis method is used to remove endotoxins, then endotoxin removal is achieved, but production capacity is greatly lowered

Engineering Contradiction:
Improveendotoxin concentrationVSAvoidproduction capacity
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent implements a rapid extraction process using binding agents that remove endotoxins in a single step or few steps, compared to the multi-step, time-consuming dialysis process. This significantly increases production capacity while maintaining effective endotoxin removal.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary binding of endotoxins to selected agents before final product formulation, allowing for rapid removal and increasing production throughput. This preliminary action eliminates the need for prolonged dialysis and accelerates the overall production process.

Inventive Principle:
Principle #10Preliminary action

4Object-affected harmful factors

If high temperature sterilization is used to remove endotoxins, then endotoxin removal is effective, but collagen decomposes due to heat

Engineering Contradiction:
Improveendotoxin concentrationVSAvoidcollagen integrity
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent uses intermediary binding agents that selectively bind to endotoxins at low temperatures, allowing removal without exposing collagen to high temperatures. This achieves effective endotoxin removal while preserving collagen integrity and avoiding thermal decomposition.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the removal mechanism from thermal (high temperature) to chemical/biological (binding agent interaction), operating at physiological or near-physiological temperatures. This parameter change enables effective endotoxin removal while maintaining collagen stability and preventing decomposition.

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

This method effectively reduces endotoxin concentration and increases collagen yield, shortening the manufacturing process, lowering material and energy consumption, and decreasing production costs while maintaining collagen polymer integrity.

Implementation Method 1

swelling the animal skin by an alkaline solution or a buffer solution

Methodology Applied
Scientific EffectSwelling:

Implementation Method 2

hydrolyzing the animal skin by a solution including a hydrolase

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

salting out a low endotoxin collagen by a salt solution

Methodology Applied
Scientific EffectSalting out: Precipitation

Implementation Method 4

washing the low endotoxin collagen by an alcoholic solution

Methodology Applied
Scientific EffectDehydration:

Data Source

PatentUS10487135B2Method for preparing low endotoxin collagen
Publication Date: 2019.11.26 GUANGDONG VICTORY BIOTECH CO LTD
  • US10487135B2 patent drawing

AI summary

A method for preparing low endotoxin collagen is disclosed. The method includes the following steps: providing an animal skin, removing residual adipose tissues and muscle tissues, swelling the animal skin by alkaline solution, peeling the upper and lower surfaces of the animal skin, hydrolyzing the animal skin by a solution including hydrolase, salting out the low endotoxin collagen by salt solutions, and washing the low endotoxin collagen by alcohols.