Deoxycholic Acid Purification via Two-Step Recrystallization
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Solution Overview
Problem
There is a need for a method to purify deoxycholic acid that is free from animal-derived contaminants and pathogenic moieties, as mammalian sourced deoxycholic acid is often contaminated with cholic acid, which can form gall stones, and existing purification methods are not effective in achieving high purity levels.
Innovation Solution
A two-step recrystallization process involving the use of methylene chloride and deionized water to purify crude deoxycholic acid, along with hydrogenation and oxidation steps to achieve a purity of at least 99%, ensuring the removal of contaminants and achieving high purity deoxycholic acid or its salts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If mammalian sourced deoxycholic acid is used, then the production cost is reduced and availability is improved, but the product is contaminated with cholic acid and pathogenic moieties
Solution Approach 1:
The patent applies extraction by using selective crystallization to separate deoxycholic acid from cholic acid and other contaminants. The process extracts pure deoxycholic acid from mammalian bile through controlled crystallization conditions, removing harmful moieties while retaining the beneficial compound.
Solution Approach 2:
The patent uses a composite purification approach combining multiple purification steps including crystallization, filtration, and characterization. This composite method ensures complete removal of pathogenic contaminants while maintaining product purity and efficacy.
2Device complexity
If conventional purification methods are used, then the process is simple, but the purity of deoxycholic acid cannot reach 99%
Solution Approach 1:
The patent applies segmentation by dividing the purification process into distinct sequential steps: initial crystallization, filtration, second crystallization, and characterization. Each step targets specific impurities and progressively increases purity to achieve the required 99% purity level.
Solution Approach 2:
The patent uses parameter changes by controlling crystallization conditions including temperature, solvent composition, and pH levels. These parameter adjustments optimize the crystallization process to achieve high purity while maintaining process simplicity.
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 method effectively purifies deoxycholic acid to a high degree (at least 99% purity), ensuring it is free from animal-derived contaminants and other bile acids, thereby providing a safe and effective medicament for human use.
Implementation Method 1
i) a first recrystallization of the crude deoxycholic acid or a salt thereof from a C1-3 alcohol in methylene chloride to provide a product; and ii) a second recrystallization of the product of step i) from a mixture of deionized water and a C1-3 alcohol to provide pure deoxycholic acid or a salt thereof
Implementation Method 2
contacting compound 1 with hydrogen and Pd/C under hydrogenation conditions comprising hydrogen and Pd on carbon in an autoclave maintained at elevated pressure
Implementation Method 3
oxidizing any of the 12-hydroxyl groups formed during hydrogenation with pyridiniumchlorochromate under oxidizing conditions to provide compound 2
Implementation Method 4
reacting compound 2 with lithium tri-t-alkoxyaluminum hydride under reducing conditions to provide compound 3
Implementation Method 5
exposing compound 3 to deprotection and hydrolysis conditions to form crude deoxycholic acid or a salt thereof
Data Source
AI summary
Comppositions directed to the purification of deoxycholic acid and its salts are provided. A first composition consists of deoxycholic acid or a salt thereof and a mixture of one or more C1-3-alcohols and methylene chloride. A second composition consists of deoxycholic acid or a salt thereof and a mixture of one or more C1-3-alcohols and deionized water.