Chenodeoxycholic Acid Purification via Solvent System Optimization
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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, long processing times, and difficulties in separating the compound from impurities, especially when the bile contains 35-55 wt% chenodeoxycholic acid content.
Innovation Solution
A process involving pre-treatment of swine bile with an organic solvent and salt, followed by esterification, acetylation, crystallization, and deprotection steps, using specific solvents and conditions to enhance yield and purity, including the use of ethyl acetate, hexane, and alkaline conditions to achieve high purity and reduced processing time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional purification process is used on swine bile solid with 35-55 wt% chenodeoxycholic acid content, then purification can be attempted, but stirring and filtering become difficult since the desired compound is precipitated and coagulated along with impurities
Solution Approach 1:
The patent changes the solvent system from conventional water-based or single organic solvent to a specific mixed solvent system (ethyl acetate and n-hexane in 1:1 v/v ratio). This parameter change in solvent composition prevents coagulation and precipitation of chenodeoxycholic acid during purification, maintaining solution clarity and enabling easy stirring and filtering operations while achieving high purification quality.
2Manufacturing precision
If conventional processes are used for purifying chenodeoxycholic acid from swine bile, then purification steps can be completed, but the yield and purity are low making it economically unreasonable
Solution Approach 1:
The patent optimizes multiple parameters including solvent system (ethyl acetate-n-hexane 1:1), crystallization temperature (4°C), and pH control during deprotection. These parameter changes simultaneously achieve high purity (99% or more by HPLC) and high yield (85% or more), making the process economically viable by resolving the trade-off between purity and productivity.
Solution Approach 2:
The patent performs preliminary esterification and acetylation steps that protect the chenodeoxycholic acid molecules from degradation and facilitate selective crystallization. This preliminary action ensures that the compound remains in soluble form during purification and can be recovered in high yield and purity after deprotection.
3Manufacturing precision
If conventional processes are used for purifying chenodeoxycholic acid, then purification can be attempted, but the time required for the entire process is long
Solution Approach 1:
The patent uses a optimized solvent system and controlled crystallization conditions that enable rapid separation and purification. The ethyl acetate-n-hexane system allows for quick phase separation and crystal formation at 4°C, significantly reducing processing time while maintaining purity of 99% or more.
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 achieves high purity (99% or more) and yield of chenodeoxycholic acid with significantly reduced processing time, making it economically viable for industrial manufacturing by optimizing the crystallization and deprotection steps.
Implementation Method 1
dissolving swine bile solid derived from swine bile, containing the mixture of chenodeoxycholic acids of Formulae I-IV, and having 35-55 wt% of chenodeoxycholic acid content, in organic solvent containing salt
Implementation Method 2
acetylation of the mixture of esters of chenodeoxycholic acids of formulae I to IV by adding anhydrous acetic acid and a weak base selected from anhydrous sodium acetate or pyridine
Implementation Method 3
crystallizing and removing the acetylated esters of chenodeoxycholic acids of formulae III to IV, and a part of the acetylated ester of chenodeoxycholic acid of formula II
Implementation Method 4
deprotection of the compound of formula V obtained from step (5) by adding water and base selected from sodium hydroxide or potassium hydroxide
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.