Solvent-Detergent Platelet Lysis for Growth Factor Recovery

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Solution Overview

Problem

Current platelet-derived preparations lack standardization, leading to variability in growth factor content and clinical efficacy due to factors like platelet concentration, activation methods, and storage conditions, and pose risks of immune responses and infectious transmission.

Innovation Solution

A method to prepare a clottable, virally inactivated concentrate of platelet growth factors using a solvent and detergent treatment followed by oil extraction and chromatography, which increases recovery of key growth factors like PDGF, TGF-β, and EGF, and inactivates viruses and intact platelets, ensuring standardized and safe products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If platelet concentrates are activated using conventional methods (thrombin or calcium chloride), then growth factors are released, but the preparations lack standardization and show variability in growth factor content and clinical efficacy

Engineering Contradiction:
Improvegrowth factor contentVSAvoidstandardization
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by modifying the activation conditions of platelets - using a specific pH range (6.0-9.0) and temperature range (2°C-50°C) during solvent/detergent treatment to optimize growth factor release while maintaining standardization. This controlled parameter approach ensures consistent manufacturing outcomes across different batches.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces solvent and detergent as intermediary substances that facilitate the release of growth factors from platelets without requiring traditional activation methods. These intermediaries enable controlled extraction of growth factors while maintaining product standardization and reducing variability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If platelet concentrates are used for therapeutic preparations, then growth factors are available for tissue regeneration, but there is risk of immune responses and infectious transmission

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidimmune response and infection risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful presence of intact platelets and potential viral contaminants into a benefit by using solvent/detergent treatment that inactivates viruses and removes intact platelets while preserving and releasing growth factors. The treatment transforms a risky starting material into a safe therapeutic product.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent extracts and removes harmful components (intact platelets and viruses) from the platelet concentrate through solvent/detergent treatment and oil extraction, while retaining the beneficial growth factors. This selective removal eliminates immune response risks and infectious transmission while maintaining therapeutic efficacy.

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If solvent and detergent treatment is applied to platelet concentrates, then viral inactivation and platelet lysis occur, but recovery of growth factors needs optimization

Engineering Contradiction:
Improveviral load and intact plateletsVSAvoidgrowth factor recovery
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent optimizes growth factor recovery by carefully controlling parameters during solvent/detergent treatment - using specific concentrations (0.2-5% v/v), pH ranges (6.0-9.0), and temperature ranges (2°C-50°C). These parameter optimizations ensure maximum growth factor release while maintaining viral inactivation and platelet lysis effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses oil as an intermediary substance to facilitate the extraction and removal of solvent/detergent from the platelet concentrate after treatment. This intermediary step helps recover growth factors while ensuring complete removal of potentially harmful solvent and detergent residues.

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 significantly enhances the recovery of platelet growth factors, reduces the risk of immune reactions and infectious transmission, and allows for the use of expired platelet stocks, providing a standardized and safe therapeutic product with enhanced efficacy.

Implementation Method 1

contacting a non-activated starting platelet concentrate with a solvent and/or a detergent

Methodology Applied
Scientific EffectSolvent-Detergent Lysis:

Implementation Method 2

inactivating viruses and intact platelets

Methodology Applied
Scientific EffectViral Inactivation:

Implementation Method 3

removing the solvent and/or the detergent by oil extraction

Methodology Applied
Scientific EffectLiquid-Liquid Extraction: Liquid-Liquid Extraction

Implementation Method 4

chromatographic means

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 5

trigger the coagulation cascade and the release of endogenous thrombin. The endogenous and exogenous thrombin also induce polymerisation of fibrinogen and formation of a fibrin-based biomaterial (a clot)

Methodology Applied
Scientific EffectCoagulation: Coagulation

Data Source

PatentEP2249862B1Method for producing a clottable concentrate of platelet growth factors
Publication Date: 2014.07.09 ZHENG YANG BIOMEDICAL TECH
  • EP2249862B1 patent drawingFigure 1
  • EP2249862B1 patent drawingFigure 2A~2D
  • EP2249862B1 patent drawingFigure 3A~3C

AI summary

The present invention relates to a clottable concentrate of platelet growth factors for therapeutic and/or cosmetic use, preferably comprising the growth factors PDGF, TGF-ß, IGF, EGF, CTGF, bFGF and VEGF. In preferred embodiment said clottable concentrate of platelet growth factors does not induce blood cell-related transfusion reactions. The present invention also relates to a method for preparing a clottable concentrate of platelet growth factors according to the invention and comprising the steps of contacting a platelet concentrate with a solvent and/or a detergent, incubating said platelet concentrate with the solvent and/or detergent for a period of at least 5 minutes to 6 hours, at a pH maintained in a range from about 6.0 to about 9.0, and at a temperature within the range of from 2°C to 5O0C, preferably within the range of from 25°C to 45°C, and removing the solvent and/or the detergent by oil extraction and/or chromatographic means.