Glu-plasminogen Isolation via pH-Selective Dissolution
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Solution Overview
Problem
Current methods for isolating plasminogen, particularly Glu-plasminogen, from blood plasma fractions yield low concentrations and purity, posing challenges in treating and preventing thrombotic events due to side effects and health risks associated with anticoagulant drugs.
Innovation Solution
A method involving dispersing a precipitate of blood plasma fraction in a basic aqueous buffer, separating solid parts, and extracting plasminogen with an acidic aqueous buffer containing lysine or other specific compounds to achieve high yields and purity of Glu-plasminogen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional blood fractionation processes (Cohn or Kistler-Nitschmann) are used to obtain plasminogen, then established industrial processes are utilized, but plasminogen is obtained at low concentrations and yields
Solution Approach 1:
The patent applies parameter changes by adjusting the pH to basic conditions (pH 8-10) during the dispersion step, which alters the solubility characteristics of plasminogen and associated proteins. This pH modification enables selective dissolution of plasminogen in the basic aqueous buffer, separating it from the precipitate matrix and achieving high concentrations and yields without requiring process redevelopment
Solution Approach 2:
The patent employs preliminary action by first precipitating plasma proteins under acidic conditions to form a cake, then selectively dissolving plasminogen in a basic buffer before other proteins. This preliminary selective dissolution step concentrates plasminogen in the supernatant, enabling high-yield recovery in subsequent processing steps
2Reliability
If anticoagulant drugs are used to prevent thrombotic events, then thrombus formation is inhibited, but severe side effects and health risks occur
Solution Approach 1:
The patent extracts and purifies Glu-plasminogen from blood plasma fractions through a multi-step process involving pH-based selective dissolution and chromatography. This isolation of the specific fibrinolytic agent enables targeted therapy that activates endogenous fibrinolytic pathways without the systemic anticoagulant effects and bleeding risks associated with conventional anticoagulant drugs
3Reliability
If Lys-plasminogen is used for treatment, then thrombotic events can be addressed, but undesired side effects such as bleeding occur and half-life is short
Solution Approach 1:
The patent inverts the conventional approach by specifically isolating and purifying Glu-plasminogen rather than using Lys-plasminogen. This inversion is achieved through pH-based selective dissolution where Glu-plasminogen dissolves in basic buffer at pH 8-10 while Lys-plasminogen remains in the precipitate. The inverted approach yields a product with longer half-life and fewer side effects
4Manufacturing precision
If purification processes are applied to obtain Glu-plasminogen, then purity is improved, but work effort and process complexity increase
Solution Approach 1:
The patent uses parameter changes (pH adjustment to basic conditions) to achieve selective dissolution of Glu-plasminogen, which simplifies the purification process. This single parameter change enables separation of Glu-plasminogen from other plasma proteins without requiring multiple complex chromatography steps, reducing both process complexity and work effort while maintaining high purity
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 provides high yields and purity of Glu-plasminogen with low work efforts, reducing side effects and improving treatment outcomes for thrombotic events.
Implementation Method 1
dispersing a precipitate of blood plasma fraction comprising plasminogen in a basic aqueous buffer of pH 7 to 10
Implementation Method 2
extracting the plasminogen with an acidic aqueous buffer
Data Source
AI summary
The present invention relates to a method for isolating plasminogen from a blood plasma fraction comprising dispersing a precipitate of a blood plasma fraction containing plasminogen in a basic aqueous buffer, separating solid parts thereof and removing at least parts of other proteins, and extracting the plasminogen with an acidic aqueous buffer.