Chenodeoxycholic Acid Purification via Low-Temperature Crystallization
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Solution Overview
Problem
Current methods for purifying chenodeoxycholic acid from swine bile are economically unreasonable due to low yield and purity, along with lengthy processing times, especially when attempting to isolate chenodeoxycholic acid from swine bile with low concentrations.
Innovation Solution
A process involving pre-treatment of swine bile with an organic solvent and salt, followed by esterification, acetylation, crystallization, and deprotection steps, utilizing specific solvents and conditions to enhance yield and purity, including recrystallization to achieve high purity chenodeoxycholic acid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional purification process is used on low grade chenodeoxycholic acid mixture, then processing can be performed, but yield and purity remain low (80% content even after two recrystallizations)
Solution Approach 1:
The patent changes the solvent system from conventional ethanol to a specific mixture of ethyl acetate and n-hexane, and modifies the crystallization temperature range to -30°C to -70°C. These parameter changes enable simultaneous achievement of high purity (99.5% or more) and high yield (80% or more), resolving the contradiction between manufacturing precision and productivity.
Solution Approach 2:
The patent utilizes controlled phase transition through low-temperature crystallization in a specific solvent system. By maintaining the crystallization temperature between -30°C and -70°C, the process achieves efficient separation of chenodeoxycholic acid from impurities, obtaining both high purity and high yield in a single crystallization step.
2Manufacturing precision
If conventional purification process is used, then standard procedures can be followed, but processing time is lengthy due to multiple recrystallization steps required
Solution Approach 1:
By changing the solvent system to ethyl acetate and n-hexane mixture and adjusting crystallization temperature to -30°C to -70°C, the patent achieves high purity (99.5% or more) in a single crystallization step, eliminating the need for multiple recrystallization cycles and significantly reducing processing time.
Solution Approach 2:
The patent performs preliminary concentration of the crude mixture before crystallization, which prepares the sample in optimal condition for single-step crystallization. This preliminary action ensures that the crystallization step directly produces high purity product without requiring subsequent recrystallization steps.
3Ease of manufacture
If conventional methods are used on low grade mixture (5-35 wt% content), then processing can proceed, but economic viability is poor due to low yield and purity
Solution Approach 1:
The patent modifies the crystallization parameters including solvent system (ethyl acetate and n-hexane mixture) and temperature range (-30°C to -70°C), which enables efficient purification of low grade mixtures (5-35 wt% content) to achieve high purity (99.5% or more) and high yield (80% or more), making the process economically viable.
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 process significantly increases the yield and purity of chenodeoxycholic acid to 99% or more, reducing the overall processing time and making the method more economically viable for industrial applications.
Implementation Method 1
deprotection of the compound of formula V obtained from step (5) by adding water and base selected from sodium hydroxide or potassium hydroxide to the compound of formula V, and crystallization of the compound of formula I in the presence of water by adding acid selected from hydrochloric acid or sulfuric acid
Data Source
AI summary
The present invention relates to a process for purifying chenodeoxycholic acid (3a,7a-dihydroxy-5ß-cholic acid). In particular, the present invention relates to a process for purifying chenodeoxycholic acid from low grade of chenodeoxycholic acid mixture in swine bile solid, with high yield and purity.