High Purity mPEG Purification via Aqueous Solvent Crystallization
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Solution Overview
Problem
Current methods for preparing methoxypolyethyleneglycol (mPEG) with high purity face challenges such as the need for large amounts of organic solvents, sensitivity to water, and difficulties in commercialization due to requirements for specific molecular weight distributions and re-treatment processes.
Innovation Solution
A method involving the reaction and purification of conventional mPEG using intermediates like mPEG-acetic acid and mPEG-phthalate, employing column chromatography and solvent crystallization to achieve high purity mPEG with molecular weight distribution up to 1.05, utilizing aqueous solutions and reducing agents to enhance purity to at least 99%.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods are used to prepare high purity mPEG, then purity can be improved, but a huge amount of organic solvent is required and re-treatment is impossible when byproducts increase
Solution Approach 1:
The patent introduces mPEG-succinate as an intermediary compound with a water-soluble carboxylic acid group that enables aqueous-phase separation. This intermediary allows the reaction mixture to be processed in water rather than requiring large amounts of organic solvents for purification, directly resolving the contradiction between achieving high purity and minimizing organic solvent usage
Solution Approach 2:
The patent changes the solvent system from organic-based to aqueous-based by incorporating a carboxylic acid group in the side chain. This parameter change in solubility characteristics allows the use of water as the primary solvent, dramatically reducing the quantity of organic solvent required while maintaining the ability to achieve high purity through aqueous separation techniques
2Manufacturing precision
If mPEG-succinate is synthesized and separated using methylenechloride, then mPEG with high purity can be obtained, but ester bond sensitivity to water causes disintegration and huge amounts of organic solvent are required
Solution Approach 1:
The patent changes the chemical structure parameter by replacing the water-sensitive ester bond with a water-stable carboxylic acid group. This parameter change in chemical stability allows the molecule to maintain its integrity in aqueous environments during separation processes, eliminating the disintegration problem while enabling high purity through water-based methods
Solution Approach 2:
The patent replaces expensive and problematic organic solvents like methylenechloride with water as the separation medium. This substitution eliminates the stability issues associated with ester bonds in organic solvents while reducing environmental and health concerns, achieving high purity through a safer, more reliable aqueous process
3Manufacturing precision
If gel permeation chromatography is used to separate mPEG, then high purity can be achieved, but this method is only available when molecular weight distribution is significantly different, making commercialization difficult
Solution Approach 1:
The patent changes the separation mechanism from size-based (gel permeation chromatography) to solubility-based (aqueous phase separation). This parameter change in the separation principle allows the method to work effectively regardless of molecular weight distribution, making the process universally applicable and commercially viable while maintaining high purity standards
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 produces mPEG with high purity and stability in aqueous solutions, reducing the need for excessive organic solvents and enabling commercial viability by achieving high purity without the limitations of previous methods.
Implementation Method 1
employing column chromatography and solvent crystallization to achieve high purity mPEG
Implementation Method 2
employing column chromatography and solvent crystallization to achieve high purity mPEG
Data Source
AI summary
The present invention relates to a preparing method of methoxypolyethyleneglycol (mPEG) with high purity and derivatives thereof. More precisely, the method of the present invention to prepare high purity mPEG with at least 99% of purity, up to 1.05 of molecular weight distribution and 350˜100,000 of molecular weight includes the process of reacting commercial mPEG having low purity to give highly purified intermediates, mPEG-acetic acid of formula 1 and mPEG-phthalate of formula 2.