Microparticle Purification Using Zn2+ Non-Solvent Washing
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Solution Overview
Problem
Existing methods for processing microparticles, such as those containing proteins like hGH and insulin, often result in structural damage due to the use of organic solvents and supercritical fluids, and can lead to agglomeration when using aqueous solutions with divalent cations, which complicates the harvesting and purification of these particles.
Innovation Solution
A method involving the use of a non-solvent containing uncomplexed Zn2+ cations to separate microparticles from reaction media, allowing for the removal of non-volatile materials while avoiding agglomeration and structural damage, by forming a mixture with one or more liquid phases and removing these phases to retain the microparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If organic solvents and supercritical fluids are used to wash microparticles, then microparticles can be harvested, but structural damage occurs to protein-containing microparticles
Solution Approach 1:
The patent changes the chemical parameters of the washing medium by using aqueous solutions with controlled ionic strength and specific ion compositions (divalent cations like Ca2+ or Mg2+ at controlled concentrations) instead of organic solvents. This parameter change enables effective washing while preserving protein structure and preventing agglomeration.
Solution Approach 2:
The patent introduces specific ions (divalent cations such as Ca2+ or Mg2+) as intermediary substances in the aqueous washing solution. These ions act as mediators that prevent direct harmful interactions between the washing medium and protein microparticles, thereby preventing agglomeration and structural damage while still enabling effective harvesting.
2Ease of manufacture
If aqueous solutions containing divalent cations are used to wash microparticles, then washing can be performed, but agglomeration of particles occurs
Solution Approach 1:
The patent carefully controls the concentration parameters of divalent cations in the aqueous solution and maintains specific pH ranges. By optimizing these parameters, the solution achieves effective washing capability while preventing the conditions that lead to particle agglomeration, thus maintaining stable particle dispersion.
Solution Approach 2:
The patent uses aqueous solutions that replicate the beneficial washing properties of organic solvents while avoiding their harmful effects. The controlled aqueous environment with specific ion compositions copies the harvesting effectiveness without causing structural damage or agglomeration.
3Productivity
If phase separation methods are used to form microparticles, then microparticles can be produced, but non-volatile materials remain that require removal
Solution Approach 1:
The patent employs aqueous washing solutions with specific ionic compositions to extract and remove non-volatile materials from the microparticle surface. The controlled aqueous environment enables selective removal of unwanted substances while preserving the microparticle structure and preventing agglomeration during the extraction process.
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 approach enables the efficient separation and purification of microparticles without organic solvent residues, preventing agglomeration and structural damage, thereby enhancing manufacturing efficiency and maintaining the integrity of the particles.
Implementation Method 1
providing a non-solvent comprising an aqueous solution containing at least one free multivalent cation... wherein the non-volatile material is more soluble in the non-solvent than are the microparticles
Data Source
AI summary
A method for processing multi-phasic dispersions is provided. The method comprises providing a multi-phasic dispersion including dispersed and continuous phases, providing one or more non-solvents comprising an aqueous solution containing at least one multivalent cation, exposing the multi-phasic dispersion to the non-solvent to form a suspension containing one or more liquid phases and the solid microparticles, and removing at least a portion of the resulting one or more liquid phases while retaining at least the microparticles, thereby removing at least a portion of the non-volatile material from the microparticles.