Collagen Separation via pH and Temperature Control

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Solution Overview

Problem

Current methods are inadequate for efficiently separating pure collagen from various animal tissues, particularly from bone tissues, limiting the availability of collagen for medical and other applications.

Innovation Solution

A method involving treatment of collagen under specific temperature and pH conditions, followed by centrifugation and dissolution in a weakly-acidic solvent, to concentrate and prepare a collagen solution suitable for forming a matrix or highly-concentrated solution, utilizing differences in pH and temperature changes for effective separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional separation methods are used, then collagen can be extracted from tissues, but the separation efficiency and purity are insufficient

Engineering Contradiction:
Improvecollagen separation purityVSAvoidcollagen extraction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies parameter changes by utilizing pH and temperature variations to control collagen solubility and separation. Specifically, the method employs acidic pH conditions (pH 2-4) to dissolve collagen while maintaining it in a soluble state, then adjusts pH to neutral or alkaline conditions to precipitate and separate collagen from tissues. Temperature control at 4-10°C during extraction and 30-37°C during precipitation further optimizes separation efficiency and purity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions of collagen between soluble and insoluble states through pH and temperature changes. Collagen transitions from a soluble state in acidic conditions to an insoluble precipitated state in neutral/alkaline conditions, enabling effective separation from tissue matrices. This phase transition mechanism allows for efficient purification without denaturation.

Inventive Principle:
Principle #36Phase transitions

2Quantity of substance

If large amounts of raw materials are used to secure sufficient collagen quantities, then collagen availability increases, but the complexity and cost of processing increases

Engineering Contradiction:
Improvecollagen quantityVSAvoidprocessing complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent improves processing efficiency by optimizing pH and temperature parameters to maximize collagen yield from smaller amounts of raw materials. The method uses acidic pH (pH 2-4) to efficiently dissolve collagen from tissues, then controlled precipitation at neutral/alkaline pH to concentrate the collagen solution, reducing the need for large material quantities while maintaining high output.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements continuous processing through sequential pH adjustments and temperature controls that maintain collagen in desired states throughout the extraction and purification process. The continuous application of acidic conditions for dissolution followed by controlled neutralization for precipitation creates an uninterrupted flow of collagen from tissue to purified solution, enhancing productivity.

Inventive Principle:
Principle #20Continuity of useful action

3Manufacturing precision

If collagen is treated to achieve high purity, then product quality improves, but the loss of collagen during processing increases

Engineering Contradiction:
Improvecollagen purityVSAvoidcollagen loss
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The patent minimizes collagen loss during purification by carefully controlling pH and temperature parameters to prevent denaturation and degradation. The method uses mild acidic conditions (pH 2-4) for extraction and controlled precipitation at neutral/alkaline pH, avoiding extreme conditions that would cause collagen breakdown. Temperature control at 4-10°C during extraction and 30-37°C during precipitation further prevents thermal degradation while maintaining purity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses pH adjustment as an intermediary mechanism to selectively separate collagen from impurities without direct harsh treatment. By controlling the ionization state of collagen through pH changes, the method achieves purification through selective solubility differences rather than harsh enzymatic or chemical treatments that would cause collagen loss.

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

This method enables efficient separation and concentration of collagen from diverse animal tissues, enhancing the quality and reliability of collagen products, such as hemostatic matrices and skin fillers, while maintaining biocompatibility and physiological activity.

Implementation Method 1

Collagen is not decomposed in water, dilute acids and dilute alkalis, but boiling of collagen results in conversion thereof into a single-stranded structure of gelatin that is soluble

Methodology Applied
Scientific EffectSolubility:

Implementation Method 2

treating a collagen solution having a predetermined concentration under neutral conditions at a low temperature, followed by overnight treatment at a temperature of 30 to 35° C.

Methodology Applied
Scientific EffectTemperature effect:

Implementation Method 3

concentrating collagen by centrifugation

Methodology Applied
Scientific EffectCentrifugation: Centrifuge

Data Source

PatentUS7781158B2Method of separating collagen from the various animal tissues for producing collagen solution and product using the same
Publication Date: 2010.08.24 CELLONTECH
  • US7781158B2 patent drawing
  • US7781158B2 patent drawing
  • US7781158B2 patent drawing

AI summary

A method for separation the collagen from the various animal tissues is disclosed for preparing collagen solution and product using the same. The porcine tissues are processed to have proper form and size for acid-treatment. The acid-treatment is repeated with pepsin to separate type I or II collagens. The separated collagen is salt-treated for fractionation and ethanol-treated for obtaining 5˜10% of collagen from the initial tissue weight. The prepared tissues are processed for separating collagen through the collagen separating process. The separated collagen is processed for preparing product. The method for preparing product is comprised: treating a collagen solution having a predetermined concentration under a neutral condition at a low temperature, followed by overnight treatment at a temperature of 30 to 35° C.; concentrating collagen by centrifugation; and dissolving the thus-concentrated collagen in refrigerated weakly-acidic solvent or phosphate buffered saline (PBS), thereby preparing collagen having a concentration of 1 to 5 mg/mL.