CN110256517A - A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces - Google Patents
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces Download PDFInfo
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- CN110256517A CN110256517A CN201910657030.2A CN201910657030A CN110256517A CN 110256517 A CN110256517 A CN 110256517A CN 201910657030 A CN201910657030 A CN 201910657030A CN 110256517 A CN110256517 A CN 110256517A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
The invention belongs to fine chemistry industries and pharmaceutical technology field, and in particular to a method of high-purity chenodeoxy cholic acid is produced from pig's bile or leftover bits and pieces.Its process is saponification, crystallization removal of impurities, crystalline mother solution at production technologies such as salt, extraction, crystallizations, entire technique have it is environmental-friendly, safe and non-toxic, it is low in cost, be easy to industrial scale production chenodeoxycholic acid, content is more than or equal to 99%.
Description
Technical field
The invention belongs to fine chemistry industries and pharmaceutical technology field, and in particular to one kind produces high from pig's bile or leftover bits and pieces
The method of purity chenodeoxycholic acid.
Background technique
Chenodeoxycholic acid (Chenodeoxycholic acid, CDCA), i.e. 3 α, 7-5 β of alpha-dihydroxy-cholanic acid.Goose goes
Oxycholic acid is natural primary bile acid, is by the cyclopentanoperhydro-phenanthrene and 1 aliphatic side chains steroidal that totally 24 carbon atoms are constituted of 1 rigidity
Compound, the A ring of steroid nucleus and B ring respectively have a α hydroxyl on 3 and 7 in molecule with one cavity of cis- condensed formation
The hydrophilic face α is collectively formed in the carboxyl being directed toward on concave surface, with side chain, and 3 methyl are then directed toward another side, form the face β of hydrophobic,
With rouge/water parents characteristic.
Chenodeoxycholic acid is one of animal body bile biochemical substances, is natural primary bile acid.In people, animal, fowl
It is widely present in bile.Clinically not only be used as dissolution gall stone and correct saturation bile drug, also have significantly relieving asthma,
Anti-inflammatory, antibechic, reducing blood lipid and the effect of eliminating the phlegm.Its choleretic effect is especially pronounced, it is the absorption by reducing cholesterol, closes
At declining bile inner cholesterol, formed to hinder quasi- cholesterol stone and promote its dissolution, and it is full that cholesterol can be effectively reduced
And degree.
For chenodeoxycholic acid also as the intermediate for producing ursodesoxycholic acid, ursodesoxycholic acid is contained by rare Chinese medicine bear gall
Main component is used clinically for treating various gallbladder diseases and disease of digestive tract.Currently, the rare medicinal animal bile of tradition obtain it is comprehensive
Close development and utilization.Therefore, it prepares chenodeoxycholic acid and also has having very important significance for further preparing ursodesoxycholic acid.
Chenodeoxycholic acid, which mainly has in the bile or animal bile of poultry, to be extracted, due to the Amount of Bile of poultry, especially goose
It is not easy to collect less, people have gone to the leftover bits and pieces after pig's bile, especially extraction bilirubin or hyodesoxycholic acid
Middle extraction, traditional extraction and preparation technique process is complicated, yield is low, and especially purity does not increase, and is less than 98% (HPLC),
His substance (hyodesoxycholic acid, hyocholic acid, pig ketone deoxycholic aicd are higher), and use a large amount of unsafe organic reagents.
At present production hyodesoxycholic acid technology mainly include the following types:
1, silica gel column chromatography although available high-purity chenodeoxy cholic acid (98% or more), but product yield compared with
Low, production capacity is low, and solvent consumption is big, is unsuitable for industrialized production；
2, synthetic method, usually to use high-purity cholic acid is raw material, and domestic cholic acid price is higher than chenodeoxycholic acid at present,
And synthetic route is cumbersome, and industrial value is not high；
3, esterification, acetylation derivatization method preparation chenodeoxycholic acid, though the CDCA of high-content can be obtained, yield compared with
It is low, the toxic reagents such as aceticanhydride, hexane are used, are not especially friendly to environment though being able to achieve industrialization.
Chinese patent application CN1775798A discloses a kind of Amberlyst process and produces high-purity goose from poultry and livestock bile
The method of oxycholic acid, Chinese patent application CN1830996A disclose a kind of preparation side that chenodeoxycholic acid is prepared with barium salt process
The combination of method, either Amberlyst process or barium salt process or the two, though the higher product of content can be obtained, product is raw
The production period is longer, and the production capacity that macroreticular resin can seriously affect.
Summary of the invention
In order to solve the above technical problems, the present invention provides one kind and produces high-purity chenodeoxycholic from pig's bile or leftover bits and pieces
The method of acid.This method simple process, pollution is small, and product yield is high, purity is big.
To realize above goal of the invention, the present invention the following technical schemes are provided:
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces or pig's bile, alkali and water is added, saponification is cooling, quiet
Layering is set, supernatant is siphoned off and discards, lower layer's paste is taken out, is dissolved in water, Congored test paper is acidified to and becomes blue, acetic acid is added
Ethyl ester stirring extraction, stratification；Ethyl acetate phase is taken, being washed to aqueous pH values is 6-7, and ethyl acetate is added to anhydrous slufuric acid
Sodium dehydration, decolourizes, and filters, and concentration has Precipitation, cools down, refilters or squeeze, and is dried in vacuo, obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, solvent is added, is slowly added to organic alkali agents, stirs
It mixes, cools down, there is a large amount of Precipitations, filter, it is dry, obtain chenodeoxycholic amine acid salt crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate is added, and stirs lower drop
Add hydrochloric acid, stirs, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo, methylene chloride is added, cooled down, stirred, crystallized, filtered, it is dry, it obtains goose and goes
Oxycholic acid final product.
Preferably, in step (1), the alkali is sodium hydroxide or potassium hydroxide；
Preferably, in step (1), the dosage of the alkali is the 3%-50% of bilirubin leftover bits and pieces or pig's bile dosage；
Preferably, in step (1), the saponification adds the dosage of water to be bilirubin leftover bits and pieces or pig's bile dosage
0.2-3 times；
Preferably, in step (1), the temperature of the saponification is 95-100 DEG C；
Preferably, in step (1), the time of the saponification is 16-24h；
Preferably, in step (1), the dosage of water when being dissolved in water is identical as saponification amount of water；
Preferably, in step (1), the acidification agents useful for same is concentrated hydrochloric acid or the sulfuric acid of 30-60%；
Preferably, the sulfuric acid that the sulfuric acid is 50%.
Preferably, in step (1), the ethyl acetate dosage is water is added in lower layer's paste 3-5 times；
Preferably, in step (1), the time of the extraction is 20min-1h；
Preferably, in step (1), the volume after the concentration is the 1/10-1/3 that volume is added in ethyl acetate；
Preferably, described to be cooled to 0-5 DEG C in step (1)；
Preferably, in step (2), the solvent is alkanes or alcohols；
Preferably, in step (2), the solvent is methylene chloride, dichloroethanes, methanol, the tert-butyl alcohol, ethyl alcohol, sec-butyl alcohol
At least one of；
Preferably, in step (2), hyodesoxycholic acid crude product is completely dissolved by the used in amounts of the solvent；
Preferably, in step (2), the time of the stirring is 1-3h；
Preferably, described to be cooled to 0-5 DEG C in step (2)；
Preferably, in step (2), the organic alkali agents are triethylamine, methylamine, diethylamine, propylamine, tert-butylamine or Zhong Ding
At least one of amine, aniline；
Preferably, in step (2), the dosage of the organic alkali agents is 1.1-1.5 times of hyodesoxycholic acid crude product weight.
Preferably, in step (4), the ethyl acetate phase is concentrated into its 1/4-3/4 that volume is added；
Preferably, in step (4), the volume of the methylene chloride and the volume ratio of ethyl acetate phase are 1:1-3, preferably
1:1.
Compared with the prior art, the present invention has following technical advantage:
(1) present invention using amine salt method remove chenodeoxycholic acid in hyocholic acid, pig ketone deoxycholic aicd, hyodesoxycholic acid with
And non-Cholic acids impurity etc. obtains the chenodeoxycholic amine acid salt of high-purity, the chenodeoxycholic acid product yield of preparation is higher than 85%,
Purity is higher than 99%；With preferable product quality；
(2) solvent that uses of the present invention is mainly alkane or alcohols solvent, compared to the prior art for, can effectively mention
The yield and purity of high chenodeoxycholic acid product；
(3) simple in production process operation of the invention, is easy to industrialized production.
Specific embodiment
Embodiment 1
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces 200g, sodium hydroxide 60g, 400ml water, soap at 95 DEG C is added
Change reaction 16h, it is cooling, it stands, is siphoned off supernatant and discards, water 400ml is added in lower layer's paste, and dense salt is added in stirring and dissolving
Acid is acidified to Congored test paper and becomes blue, and ethyl acetate 1600ml stirring extraction 30min, stratification is added；Ethyl acetate phase is taken,
Being washed to aqueous pH values is 6, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, 10g decoloration 30min, and filtering is concentrated into
320ml (1/5 volume), there is Precipitation, is cooled to 0 DEG C, filters, and vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, methylene chloride 320ml is added, slowly stream plus 1.3
The triethylamine of times weight (in terms of hyodesoxycholic acid crude product), stirring, is cooled to 0 DEG C, there is a large amount of Precipitations, filters, dry, obtains
Chenodeoxycholic amine acid salt crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 200ml (1/2 volume), isometric methylene chloride is added, cooled down, stir
It mixes, crystallizes, filter, it is dry, obtain chenodeoxycholic acid final product, yield 86.7%, purity 99.5%.
Embodiment 2
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking pig's bile 1000ml, potassium hydroxide 30g, 200ml water is added, is saponified at 97 DEG C anti-
20h is answered, it is cooling, it stands, is siphoned off supernatant and discards, water 200ml is added in lower layer's paste, and 50% sulfuric acid is added in stirring and dissolving
It is acidified to Congored test paper and becomes blue, ethyl acetate 600ml stirring extraction 1h, stratification is added；Ethyl acetate phase is taken, is washed to
Aqueous pH values are 6.5, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, 10g decoloration 30min, and filtering is concentrated into 200ml
(1/3 volume), there is Precipitation, is cooled to 5 DEG C, filters, and vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, tert-butyl alcohol 300ml is added, slowly stream adds 1.1 times
The propylamine of weight, stirring, is cooled to 5 DEG C, there is a large amount of Precipitations, filters, dry, obtains chenodeoxycholic amine acid salt crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 300ml (3/4 volume), the methylene chloride of 1/2 volume is added, cooling is stirred
It mixes, crystallizes, filter, it is dry, obtain chenodeoxycholic acid final product, yield 86.3%, purity 99.2%.
Embodiment 3
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces 200g, is added potassium hydroxide 100g, 600ml water, at 100 DEG C
Pressure saponification reacts for 24 hours, cooling, stands, is siphoned off supernatant and discards, and water 600ml is added in lower layer's paste, and stirring and dissolving adds
Enter 50% sulfuric acid and be acidified to Congored test paper change indigo plant, ethyl acetate 3000ml stirring extraction 20min, stratification is added；Take second
Acetoacetic ester phase, being washed to aqueous pH values is 7, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, and 10g decoloration 30min is filtered,
It is concentrated into 300ml (1/10), there is Precipitation, is cooled to 3 DEG C, is filtered, vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, ethyl alcohol 400ml is added, slowly stream plus 1.5 times of weights
The tert-butylamine of amount, stirring, is cooled to 2 DEG C, there is a large amount of Precipitations, filters, dry, obtains chenodeoxycholic amine acid salt crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 100ml (1/4 volume), the methylene chloride of 1/3 volume is added, cooling is stirred
It mixes, crystallizes, filter, it is dry, obtain chenodeoxycholic acid final product, yield 85.6%, purity 99.4%.
Comparative example 1 (compares, methylene chloride is not contained in step (4)) with embodiment 1
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces 200g, sodium hydroxide 60g, 400ml water, soap at 95 DEG C is added
Change reaction 16h, it is cooling, it stands, is siphoned off supernatant and discards, water 400ml is added in lower layer's paste, and dense salt is added in stirring and dissolving
Acid is acidified to Congored test paper and becomes blue, and ethyl acetate 1600ml stirring extraction 30min, stratification is added；Ethyl acetate phase is taken,
Being washed to aqueous pH values is 6, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, 10g decoloration 30min, and filtering is concentrated into
320ml has Precipitation, is cooled to 0 DEG C, filters, and vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, methylene chloride 320ml is added, slowly stream plus 1.3
The triethylamine 21.5g of times weight, stirring, is cooled to 0 DEG C, there is a large amount of Precipitations, filters, dry, obtains chenodeoxycholic amine acid salt
Crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 200ml, cooled down, stirred, crystallized, filtered, it is dry, obtain chenodeoxycholic acid
Final product, yield 80.3%, purity 93.2%.
Comparative example 2 (compares, cooling temperature is different) with embodiment 1
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces 200g, sodium hydroxide 60g, 400ml water, soap at 95 DEG C is added
Change reaction 16h, it is cooling, it stands, is siphoned off supernatant and discards, water 400ml is added in lower layer's paste, and dense salt is added in stirring and dissolving
Acid is acidified to Congored test paper and becomes blue, and ethyl acetate 1600ml stirring extraction 30min, stratification is added；Ethyl acetate phase is taken,
Being washed to aqueous pH values is 6, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, 10g decoloration 30min, and filtering is concentrated into
320ml has Precipitation, is cooled to 10 DEG C, filters, and vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: taking hyodesoxycholic acid crude product, methylene chloride 320ml is added, slowly stream plus 1.3
The triethylamine 21.5g of times weight, stirring, is cooled to 10 DEG C, there is a large amount of Precipitations, filters, dry, obtains chenodeoxycholic amine acid salt
Crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 200ml, isometric methylene chloride is added, cooled down, stirred, crystallization, mistake
Filter, it is dry, obtain chenodeoxycholic acid final product, yield 77.9%, purity 94.4%.
Comparative example 3 (compares, organic base changes barium chloride into) with embodiment 1
A method of producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces 200g, sodium hydroxide 60g, 400ml water, soap at 95 DEG C is added
Change reaction 16h, it is cooling, it stands, is siphoned off supernatant and discards, water 400ml is added in lower layer's paste, and dense salt is added in stirring and dissolving
Acid is acidified to Congored test paper and becomes blue, and ethyl acetate 1600ml stirring extraction 30min, stratification is added；Ethyl acetate phase is taken,
Being washed to aqueous pH values is 6, and ethyl acetate is added to the dehydration of 20g anhydrous sodium sulfate, 10g decoloration 30min, and filtering is concentrated into
320ml (1/5 volume), there is Precipitation, is cooled to 0 DEG C, filters, and vacuum drying obtains hyodesoxycholic acid crude product；
(2) prepared by goose deoxycholate: taking hyodesoxycholic acid crude product, methylene chloride 320ml is added, slowly stream adds 1.3 times
The barium chloride solution of weight, stirring, is cooled to 0 DEG C, there is a large amount of Precipitations, filters, dry, and it is thick to obtain chenodeoxycholic acid barium salt
Product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate 400ml, stirring is added
Lower dropwise addition hydrochloric acid (1:1) 24ml, stirring, stratification；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo to 200ml (1/2 volume), isometric methylene chloride is added, cooled down, stir
It mixes, crystallizes, filter, it is dry, obtain chenodeoxycholic acid final product, yield 86.7%, purity 99.5%.
It follows that the method provided by the invention for producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, tool
There are preferable yield and purification effect, is a kind of production method of simple, efficient chenodeoxycholic acid.
Above-mentioned detailed description is illustrating for one of them possible embodiments of the present invention, the embodiment not to
The scope of the patents of the invention is limited, all equivalence enforcements or change without departing from carried out by the present invention are intended to be limited solely by the technology of the present invention
In the range of scheme.
Claims (10)
1. a kind of method for producing high-purity chenodeoxy cholic acid from pig's bile or leftover bits and pieces, comprising the following steps:
(1) hyodesoxycholic acid cleans: taking bilirubin leftover bits and pieces or pig's bile, alkali and water is added, carry out saponification, stand and divide
Layer takes out lower layer's paste, is dissolved in water, and is acidified, and ethyl acetate extraction, stratification is added；Ethyl acetate phase is taken, is washed to
Aqueous pH values are 6-7, and ethyl acetate phase dehydration decolourizes, is concentrated, and cooling obtains hyodesoxycholic acid crude product；
(2) prepared by chenodeoxycholic amine acid salt: hyodesoxycholic acid crude product is taken, solvent is added, organic alkali agents are added, is stirred, cooling,
Obtain chenodeoxycholic amine acid salt crude product；
(3) preparation of high-purity chenodeoxy cholic acid: taking chenodeoxycholic amine acid salt crude product, and ethyl acetate is added, and hydrochloric acid is added dropwise, and stands
Layering；Ethyl acetate is taken to be added to water washing to neutrality, it is spare；
(4) ethyl acetate phase is concentrated in vacuo, methylene chloride is added, cooled down, crystallization obtains chenodeoxycholic acid final product.
2. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (1), the alkali is
Sodium hydroxide or potassium hydroxide；The dosage of the alkali is the 3%-50% of bilirubin leftover bits and pieces or pig's bile dosage.
3. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (1), the saponification is anti-
The dosage of Ying Jiashui is 0.2-3 times of bilirubin leftover bits and pieces or pig's bile dosage；In step (1), the temperature of the saponification is 95-
100℃；The time of the saponification is 16-24h.
4. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (1), the acidification institute
It is concentrated hydrochloric acid or 30-60% sulfuric acid with reagent.
5. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (1), the extraction
Time is 20min-1h；Volume after the concentration is the 1/10-1/3 that volume is added in ethyl acetate；It is described to be cooled to 0-5 DEG C.
6. the method for high-purity chenodeoxy cholic acid a method as claimed in any one of claims 1 to 5, which is characterized in that described in step (2)
Solvent is alkanes or alcohols.
7. the method for high-purity chenodeoxy cholic acid as claimed in claim 6, which is characterized in that in step (2), the solvent is
At least one of methylene chloride, dichloroethanes, methanol, the tert-butyl alcohol, ethyl alcohol, sec-butyl alcohol.
8. the method for high-purity chenodeoxy cholic acid as claimed in claim 6, which is characterized in that in step (2), the stirring
Time is 1-3h；It is described to be cooled to 0-5 DEG C.
9. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (2), the organic base
Reagent is at least one of triethylamine, methylamine, diethylamine, propylamine, tert-butylamine or sec-butylamine, aniline.
10. the method for high-purity chenodeoxy cholic acid as described in claim 1, which is characterized in that in step (4), the dichloro
The volume of methane and the volume ratio of ethyl acetate phase are 1:1-3, preferably 1:1.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110724085A (en) * | 2019-11-06 | 2020-01-24 | 河南利伟生物药业股份有限公司 | Co-production method for extracting bilirubin, hyodeoxycholic acid and chenodeoxycholic acid from pig bile |
| CN113912660A (en) * | 2021-10-29 | 2022-01-11 | 四川澄华生物科技有限公司 | Chenodeoxycholic acid phenethylamine salt, preparation method and refining method thereof, and chenodeoxycholic acid preparation method |
| CN114085263A (en) * | 2021-12-27 | 2022-02-25 | 安徽科宝生物工程有限公司 | Synthesis process of ursodeoxycholic acid |
| CN115181149A (en) * | 2021-04-01 | 2022-10-14 | 苏州恩泰新材料科技有限公司 | Novel crystal form of chenodeoxycholic acid and preparation method |
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