High-Purity Non-Animal-Derived UDCA via Enzymatic Reduction
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Solution Overview
Problem
Current methods for synthesizing cholic acid derivatives, particularly ursodeoxycholic acid (UDCA), are inefficient and result in products contaminated with harmful impurities and isomers, and commercially available UDCA is derived from animal sources posing risks of pathogen contamination.
Innovation Solution
Development of non-animal derived UDCA with reduced impurities through stereo-selective enzymatic reduction processes and hydrogenation methods, using intermediates like DKCA, to produce UDCA with specific δ13C signatures and minimal 3β-, 5α-, and 7α-hydroxysteroids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If animal-derived sources are used for UDCA production, then the process is simple and direct, but the product is contaminated by pathogens such as prions and other toxins
Solution Approach 1:
The patent extracts the harmful animal-derived component from the UDCA production process and replaces it with plant-derived precursors. This eliminates the pathogen contamination risk while maintaining the ability to produce UDCA through chemical synthesis, thereby resolving the contradiction between manufacturing simplicity and safety.
Solution Approach 2:
The patent introduces plant-derived sterols and steroids as intermediary substances in the synthesis pathway. These intermediaries serve as safe alternatives to animal bile acids, allowing UDCA production without direct contact with animal-derived materials, thus eliminating pathogen risks while preserving production efficiency.
2Ease of manufacture
If conventional synthesis methods are used for UDCA, then the process is established and straightforward, but the product contains harmful impurities including 3β-hydroxysteroids, 5α-steroids, and 7α-hydroxysteroids
Solution Approach 1:
The patent modifies the synthesis parameters by changing the starting materials from animal-derived bile acids to plant-derived sterols. This parameter change fundamentally alters the impurity profile of the product, eliminating the formation of harmful 3β-hydroxysteroids, 5α-steroids, and 7α-hydroxysteroids while maintaining UDCA production.
Solution Approach 2:
The patent achieves local quality improvement by specifically targeting and eliminating certain impurity types (3β-hydroxysteroids, 5α-steroids, 7α-hydroxysteroids) while preserving the desired UDCA product. The synthesis method is designed to produce high purity UDCA with minimal specific impurities through selective chemical transformations.
3Adaptability or versatility
If multiple reaction steps are used to produce UDCA from cholic acid or bisnoralcohol, then various UDCA can be produced, but the process is cumbersome and inefficient with chromatographic purification required
Solution Approach 1:
The patent performs preliminary action by selecting plant-derived sterols as starting materials that already possess the desired carbon skeleton and stereochemistry. This preliminary selection simplifies the subsequent synthesis steps, reducing the number of reactions required and eliminating the need for chromatographic purification, thereby improving productivity while maintaining versatility.
4Ease of manufacture
If conventional purification methods are used for animal-derived UDCA, then the process is standard, but the product still contains chiral impurities and closely related analogs
Solution Approach 1:
The patent takes out the fundamental problem by eliminating animal-derived materials from the synthesis pathway. Since the starting materials are plant-derived, the harmful chiral impurities and closely related analogs that plague animal-derived UDCA are not formed in the first place, making extensive purification unnecessary and achieving high purity through synthesis design rather than post-processing.
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
Produces high-purity UDCA with minimal impurities, eliminating the need for animal-derived sources and reducing the risk of pathogen contamination, while ensuring efficient and controlled production processes.
Implementation Method 1
contacting the DKCA with a 3α-hydroxysteroid dehydrogenase to stereo-selectively reduce the DKCA to a 3α hydroxy intermediate
Implementation Method 2
contacting the 3α hydroxy intermediate with a 7β-hydroxysteroid dehydrogenase to stereo-selectively reduce the 3α hydroxy intermediate to UDCA
Implementation Method 3
contacting a 4,5 unsaturated 3,7-diketo DKCA precursor with a Pd catalyst in the presence of pyridine or a pyridine derivative, thereby hydrogenating the 4,5 double bond to produce DKCA
Data Source
AI summary
Methods of making cholic acid derivatives, particularly UDCA, from non-animal sources, having exceptional purity and therapeutic utility.