CN104311620A - Method for purifying chenodeoxycholic acid - Google Patents
Method for purifying chenodeoxycholic acid Download PDFInfo
- Publication number
- CN104311620A CN104311620A CN201410500441.8A CN201410500441A CN104311620A CN 104311620 A CN104311620 A CN 104311620A CN 201410500441 A CN201410500441 A CN 201410500441A CN 104311620 A CN104311620 A CN 104311620A
- Authority
- CN
- China
- Prior art keywords
- thick
- courage
- cream
- organic solvent
- powder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for purifying chenodeoxycholic acid. The method comprises the following steps: pretreatments such as degreasing, decoloration and impurity removal are carried out on commercially available crude bile paste or crude bile powder, so as to obtain a component to undergo chromatographic separation; the component to undergo chromatographic separation undergoes purification and separation by the use of a chromatographic column with a hydrophilic resin filler as a stationary phase; and separation products undergo concentration, acidification, washing and drying, so as to obtain chenodeoxycholic acid. In comparison with the prior art, the invention has the following beneficial effects: 1, content of the main component is high; 2, reappearance is high and operability is good; 3, short cycle: it only takes two days to prepare the high-purity chenodeoxycholic acid product from processing of the bile paste raw material; and 4, low content of organic residues: as processes such as solvent extraction, column chromatography on silica gel and the like in the traditional techniques are abandoned, an industrial chromatographic process with low dosage of an organic solvent is adopted and the final product undergoes drying process, the content of the residual organic solvent in the final product is especially low.
Description
technical field
The present invention relates to a kind of method of purifying chenodeoxycholic acid, belong to biological medicine separating and purifying technology field.
background technology
Chenodiol (chenodeoxycholic acid is called for short CDCA), chemistry 3 α, 7 α by name-dihydroxyl-5 β-ursodeoxycholic acid, molecular formula C
24h
40O
4, molecular weight 392.58 is one for the treatment of gallbladdergallstonecholetithiasis medicines that consumption is maximum in the world at present, and be again the raw material of synthesis ursodesoxycholic acid (UDCA) and other steroidal compounds, industrial, Chenodiol extracts primarily of animal bile.
Current document about being separated the report of the method for Chenodiol from animal bile, concentrate on solvent extration, the precipitator method, silica gel column chromatography, ion-exchange-resin process, the methods such as Amberlyst process, as: what Chinese patent CN1775798 adopted is ion exchange method, Chinese patent CN101143886, what CN103113447A and Chinese patent CN101948496A adopted is the precipitator method, what Chinese patent CN 102703556A adopted is Amberlyst process etc., it is numerous and diverse to there is separating technology in these methods, yield is low, product purity is low, poor reproducibility, length consuming time, organic residue is serious, cannot the shortcoming such as scale operation.
summary of the invention
The object of this invention is to provide a kind of technique simple, favorable reproducibility, can the preparation technology of the highly purified Chenodiol of scale operation, utilize the Chenodiol that the inventive method obtains, by efficient liquid phase chromatographic analysis, purity reaches 99%.
The object of the invention is to be achieved through the following technical solutions:
A method for purifying chenodeoxycholic acid, it comprises the steps:
Commercially available thick courage cream or thick courage powder are carried out the pre-treatment of degreasing, decolouring and removal of impurities, obtain the component treating chromatographic separation;
Treat that the component of chromatographic separation carries out purifies and separates in order to the chromatographic column that hydrophilic resin filler is stationary phase by described, separated product carried out concentrate, acidifying, washing and drying, obtain Chenodiol.
Preferably, the method for described pre-treatment specifically comprises following operation:
Use the first organic solvent, at 40 ~ 90 DEG C, at least twice backflow is carried out to thick courage powder or thick courage cream, obtain eliminating the thick courage powder of grease or thick courage cream;
By the described thick courage cream eliminating grease with after the second organic solvent dissolution, add gac, reflux at 40 ~ 90 DEG C, obtain the thick courage powder of degreasing decoloring or thick courage cream;
Be dissolved in aqueous sodium hydroxide solution by the thick courage cream of described degreasing decoloring or thick courage powder, the pH of regulation system is 8 ~ 9, uses the microfiltration membrane in 0.45 μm of aperture and the ultra-filtration membrane elimination impurity in 0.01 μm of aperture successively, obtains the component treating chromatographic separation.
Preferably, the method for described purifies and separates specifically comprises following operation:
Getting with hydrophilic resin is the chromatographic column of filler, balances with pure water;
To treat that chromatographic separation component is splined in described chromatographic column, concentrated after carrying out wash-out with pure water, obtain concentrated solution;
Described concentrated solution being acidified to pH is 2 ~ 3, filters, and collects filter residue, and washing described filter residue to the pH of washing lotion is after 6 ~ 7, carries out drying obtain CDCA acid product to filter residue.
Preferably, described thick courage cream or thick courage powder derive from pig courage or duck courage.
Preferably, the addition of described first organic solvent is 3 ~ 6 times of thick courage powder or thick courage cream weight; The addition of described second organic solvent is 4 ~ 8 times of the thick courage cream weight eliminating grease.
Preferably, described first organic solvent is sherwood oil, hexane, hexanaphthene, octane-iso, trimethylpentane, pentamethylene, heptane, toluene, the single-component of dimethylbenzene low polar solvent or any mixed solvent; Described second organic solvent is ethyl acetate, mibk, tetrahydrofuran (THF), methylene dichloride, chloroform, ethanol, the single-component of acetone equal solvent or any mixed solvent.
Preferably, the particle diameter of described hydrophilic resin is 10 ~ 50 μm, and mean pore size is 15nm.
Preferably, described hydrophilic resin is hydrophilic polyamide resin.
Compared with prior art, the present invention has following beneficial effect:
1. the content of main component is high: Chenodiol prepared by the present invention eliminates the impurity that additive method is difficult to remove, and improves the content of composition.Owing to present invention employs state-of-the art industrial hydrophilic chromatographic separation and preparation technology, chromatograph packing material is the polyamide hydrophilic resin isolation material of high separating power, utilizes the high separating power of industrial chromatography, can ensure that the purity of main component reaches more than 99%;
2. circulation ratio is high and operability is good: the present invention utilizes industrial chromatography system and the stable performance of polymeric amide, can ensure to be separated the circulation ratio and stability prepared;
3. the cycle is short: the present invention, from the process of courage cream raw material to the product preparing high-purity Chenodiol, only needs the time of 2 days;
4. organic residue is low: because the present invention has abandoned the technique such as solvent extraction, silica gel column chromatography in traditional technology, have employed the industrial chromatography method that organic solvent usage quantity is less, and the finished product adopt drying treatment, so the organic solvent residual of the finished product is little especially;
5. can realize large-scale commercial production: technique that the present invention adopts is very easy to realize stdn, automatization, be suitable for carrying out industrialization scale operation.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.Following examples will contribute to those skilled in the art and understand the present invention further, but not limit the present invention in any form.It should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, some distortion and improvement can also be made.These all belong to protection scope of the present invention.
embodiment 1
Quantitatively take commercially available pig thick courage cream 1kg, be placed in 10 liters of extractors, add 5 liters of sherwood oils, be heated to 60 DEG C of backflows 3 hours, removing sherwood oil, repeat 1 this operation again, the thick courage cream 850g of grease must be sloughed, thick for this 850g courage cream is added 5L ethyl acetate backflow to dissolve, add again after CL 85g gac decolour at 80 DEG C backflow after 2 hours cross filter gac, remove ethyl acetate again, must be decoloured the Fel Sus domestica unguentum 841g of degreasing, the massfraction thick for this 841g courage cream being dissolved in 4.2kg is in the aqueous sodium hydroxide solution of 1%, the pH adjusting solution is 8, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 250ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and the hcl acidifying of concentrated solution 3mol/L is 3 to pH, filter, collect filter residue, and be 6 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 17.8 g, and through efficient liquid phase chromatographic analysis, its purity is 99.2%.
embodiment 2
Quantitatively take commercially available pig thick courage cream 1kg, be placed in 10 liters of extractors, add 3.8 liters of hexanaphthenes and be heated to 80 DEG C of backflows 3 hours, removing hexanaphthene, repeat 2 these operations again, the thick courage cream 855g of grease must be sloughed, thick for this 855g courage cream is added 5L alcohol reflux to dissolve, add 85g gac after CL again and take off backflow 2 hours, cross and filter gac, remove ethanol again, must be decoloured the thick courage cream 842g of degreasing, the massfraction thick for this 842g courage cream being dissolved in 4.2kg is in the aqueous sodium hydroxide solution of 1%, the pH adjusting solution is 9, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 300ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and it is 3 that the nitric acid of concentrated solution 3mol/L is acidified to pH, filter, collect filter residue, and be 7 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 19. 8g, and through efficient liquid phase chromatographic analysis, its purity is 99.2%.
embodiment 3
Quantitatively take commercially available pig thick courage powder 1kg, be placed in 10 liters of extractors, add 4.2 liters of normal hexanes and be heated to 65 DEG C of backflows 3 hours, removing normal hexane, repeat 1 this operation again, the thick courage powder 845g of grease must be sloughed, thick for this 845g courage powder is added the backflow of 7.6L chloroform to dissolve, add 85g gac after CL again and take off backflow 2 hours, cross and filter gac, remove chloroform again, must be decoloured the thick courage powder 831g of degreasing, it is in the aqueous sodium hydroxide solution of 1% that thick for this 831g courage powder is dissolved in 4.2kg massfraction, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 200ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and it is 3 that the nitric acid of concentrated solution 3mol/L is acidified to pH, filter, collect filter residue, and be 7 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 13.9 g, and through efficient liquid phase chromatographic analysis, its purity is 99.5%.
embodiment 4
Quantitatively take commercially available duck thick courage cream 1kg, be placed in 10 liters of extractors, add 5 liters of normal heptanes and be heated to 90 DEG C of backflows 3 hours, removing normal heptane, repeat 1 this operation again, the thick courage cream 945g of grease must be sloughed, thick for this 945g courage cream is added 5L methylene chloride reflux to dissolve, add 95g gac after CL again and take off backflow 2 hours, cross and filter gac, remove normal heptane again, must be decoloured the thick courage cream 921g of degreasing, the massfraction thick for this 921g courage cream being dissolved in 4.2kg is in the aqueous sodium hydroxide solution of 1%, the pH adjusting solution is 8, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 200ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and it is 3 that the nitric acid of concentrated solution 3mol/L is acidified to pH, filter, collect filter residue, and be 7 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 14.9 g, and through efficient liquid phase chromatographic analysis, its purity is 99.3%.
embodiment 5
Quantitatively take commercially available duck thick courage powder 1kg, be placed in 10 liters of extractors, add 5 liters of toluene and be heated to 80 DEG C of backflows 3 hours, removing toluene, repeat 1 this operation again, the thick courage powder 935g of grease must be sloughed, thick for this 935g courage powder is added the backflow of 5L tetrahydrofuran (THF) to dissolve, add 93g gac after CL again and take off backflow 2 hours, cross and filter gac, remove tetrahydrofuran (THF) again, must be decoloured the thick courage powder 911g of degreasing, the massfraction thick for this 911g courage powder being dissolved in 4.2kg is in the aqueous sodium hydroxide solution of 1%, the pH adjusting solution is 8, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 240ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and it is 3 that the nitric acid of concentrated solution 3mol/L is acidified to pH, filter, collect filter residue, and be 7 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 19. 4g, and through efficient liquid phase chromatographic analysis, its purity is 99.2%.
embodiment 6
Take commercially available duck thick courage cream 1kg, be placed in 10 liters of extractors, add 5 liters of toluene and be heated to 90 DEG C of backflows 3 hours, removing toluene, repeat 1 this operation again, the thick courage cream 933g of grease must be sloughed, thick for this 933g courage cream is added the backflow of 5L mibk to dissolve, add 93g gac after CL again and take off backflow 2 hours, cross and filter gac, remove mibk again, must be decoloured the thick courage cream 912g of degreasing, the massfraction thick for this 912g courage cream being dissolved in 4.2kg is in the aqueous sodium hydroxide solution of 1%, the pH adjusting solution is 8.5, use the microfiltration membrane in 0.45 μm of aperture successively, the colloidal particle impurity that the ultrafiltration membrance filter removing in 0.01 μm of aperture suspends obtains the limpid component treating chromatographic separation,
Get the industrial chromatography post that column length is 600 millimeters, internal diameter is 130 millimeters, using particle diameter be 10 ~ 20 microns, mean pore size is that the polyamide hydrophilic resin extender of 15nm is as stationary phase, arranging flow velocity is 200 ml/min, first use pure water equilibrium chromatographic column 20 minutes, get the component sample 270ml to be separated that pre-treatment obtains, sample introduction, uses pure water wash-out, Fraction collection elution fraction; Wash-out terminates, and again balances pillar, waits for next sample introduction; Merge collecting the target elution fraction obtained, nanofiltration membrane concentrates, and the hcl acidifying of concentrated solution 3mol/L is 3 to pH, filter, collect filter residue, and be 7 with pure water filter residue to washing lotion pH, drying obtains CDCA acid product 19. 4g, and through efficient liquid phase chromatographic analysis, its purity is 99.1%.
comparative example 1 the method of Chenodiol in macroporous resin Isolation of duck bile disclosed in reference Chinese patent CN102703556A:
Get the thick courage cream of duck, add 5 ~ 20 times of water by sequestered bile acide weight in wet base and be diluted to diluent, and adjust diluent pH value to 9 with sodium carbonate or sodium hydroxide; Add water saturated magnesium sulfate by 0.15 times of diluent weight, and mix abundant reaction, obtain bile acide magnesium salts, then in bile acide magnesium salts, add hydrochloric acid tune pH value to 4.5 ~ 6.5, filter and obtain sequestered bile acide magnesium salts; Or add water saturated calcium chloride by 0.15 times of diluent weight, and mix abundant reaction, obtain bile acide calcium salt, then in bile acide calcium salt, add hydrochloric acid tune pH value to 5.5, filter and obtain sequestered bile acide calcium salt; In the ratio of sequestered bile acide magnesium salts or sequestered bile acide weight of calcium salt 7 times add concentration be 75% methanol eddy dissolve sequestered bile acide magnesium salts or sequestered bile acide calcium salt obtains lysate; Lysate is placed in the chromatography column that macroporous resin is housed, the macroporous resin Intake Quantity in chromatography column is that often liter of chromatography column volume loads 0.5 ~ 0.8kg macroporous resin; Then:
The first step: be the hydrophilic impurities that 35 ~ 55% methyl alcohol or ethanol elution fall in lysate by the concentration of chromatography column volume 10 times amount;
Second step: be that 60 ~ 80% methyl alcohol or ethanol elution chromatography column obtain CDCA acid solution by the concentration of chromatography column volume 10 times amount again; CDCA acid solution adds 3g sodium carbonate or sodium hydroxide by often liter, methyl alcohol in heating recovery CDCA acid solution or ethanol, to the methyl alcohol in CDCA acid solution or alcohol concn below 10%, filter after being cooled to normal temperature, filtrate adds industrial hydrogen peroxide for decoloration after 18 hours, with hydrochloric acid adjust pH to 3.5 by the amount of 3.5g/L, refilter, filter cake washes with water to pH value to neutral, and oven drying at low temperature filter cake, just obtains Chenodiol.Through efficient liquid phase chromatographic analysis, its purity is 86.2%.
To sum up, compared with prior art, the present invention has following beneficial effect:
1. the content of main component is high: Chenodiol prepared by the present invention eliminates the impurity that additive method is difficult to remove, and improves the content of composition.Owing to present invention employs state-of-the art industrial hydrophilic chromatographic separation and preparation technology, chromatograph packing material is the polyamide hydrophilic resin isolation material of high separating power, utilizes the high separating power of industrial chromatography, can ensure that the purity of main component reaches more than 99%;
2. circulation ratio is high and operability is good: the present invention utilizes industrial chromatography system and the stable performance of polymeric amide, can ensure to be separated the circulation ratio and stability prepared;
3. the cycle is short: the present invention, from the process of courage cream raw material to the product preparing high-purity Chenodiol, only needs the time of 2 days;
4. organic residue is low: because the present invention has abandoned the technique such as solvent extraction, silica gel column chromatography in traditional technology, have employed the industrial chromatography method that organic solvent usage quantity is less, and the finished product adopt drying treatment, so the organic solvent residual of the finished product is little especially;
5. can realize large-scale commercial production: technique that the present invention adopts is very easy to realize stdn, automatization, be suitable for carrying out industrialization scale operation.
Above specific embodiments of the invention are described.It is to be appreciated that the present invention is not limited to above-mentioned particular implementation, those skilled in the art can make various distortion or amendment within the scope of the claims, and this does not affect flesh and blood of the present invention.
Claims (8)
1. a method for purifying chenodeoxycholic acid, is characterized in that, comprises the steps:
Commercially available thick courage cream or thick courage powder are carried out the pre-treatment of degreasing, decolouring and removal of impurities, obtain the component treating chromatographic separation; Treat that the component of chromatographic separation carries out purifies and separates in order to the chromatographic column that hydrophilic resin filler is stationary phase by described, separated product carried out concentrate, acidifying, washing and drying, obtain Chenodiol.
2. purification process as claimed in claim 1, it is characterized in that, the method for described pre-treatment specifically comprises following operation:
Use the first organic solvent, at 40 ~ 90 DEG C, at least twice backflow is carried out to thick courage powder or thick courage cream, obtain eliminating the thick courage cream of grease or thick courage powder;
The thick courage cream eliminating grease by described or thick courage powder, with after the second organic solvent dissolution, add gac, reflux at 40 ~ 90 DEG C, obtain thick courage cream or the slightly courage powder of degreasing decoloring;
Be dissolved in aqueous sodium hydroxide solution by the thick courage powder of described degreasing decoloring or thick courage cream, the pH of regulation system is 8 ~ 9, uses the microfiltration membrane in 0.45 μm of aperture and the ultra-filtration membrane elimination impurity in 0.01 μm of aperture successively, obtains the component treating chromatographic separation.
3. purification process as claimed in claim 1, it is characterized in that, the method for described purifies and separates specifically comprises following operation:
Getting with hydrophilic resin is the chromatographic column of filler, balances with pure water;
To treat that chromatographic separation component is splined in described chromatographic column, concentrated after carrying out wash-out with pure water, obtain concentrated solution;
Described concentrated solution being acidified to pH is 2 ~ 3, filters, and collects filter residue, and washing described filter residue to the pH of washing lotion is after 6 ~ 7, carries out drying obtain CDCA acid product to filter residue.
4. purification process as claimed in claim 1 or 2, is characterized in that, described thick courage cream or thick courage powder derive from pig courage or duck courage.
5. purification process as claimed in claim 2, is characterized in that, the addition of described first organic solvent is 3 ~ 6 times of thick courage powder or thick courage cream weight; The addition of described second organic solvent is 4 ~ 8 times of the thick courage cream weight eliminating grease.
6. the purification process as described in claim 2 or 5, is characterized in that, described first organic solvent is sherwood oil
,at least one in normal hexane, hexanaphthene, octane-iso, trimethylpentane, pentamethylene, heptane, toluene, dimethylbenzene; Described second organic solvent is at least one in ethyl acetate, mibk, tetrahydrofuran (THF), methylene dichloride, chloroform, ethanol, acetone.
7. the purification process as described in claim 1 or 3, is characterized in that, the particle diameter of described hydrophilic resin is 10 ~ 50 μm, and mean pore size is 15nm.
8. purification process as claimed in claim 7, it is characterized in that, described hydrophilic resin is hydrophilic polyamide resin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410500441.8A CN104311620A (en) | 2014-09-26 | 2014-09-26 | Method for purifying chenodeoxycholic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410500441.8A CN104311620A (en) | 2014-09-26 | 2014-09-26 | Method for purifying chenodeoxycholic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104311620A true CN104311620A (en) | 2015-01-28 |
Family
ID=52366956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410500441.8A Pending CN104311620A (en) | 2014-09-26 | 2014-09-26 | Method for purifying chenodeoxycholic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104311620A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294801A (en) * | 2015-07-02 | 2016-02-03 | 扬子江药业集团南京海陵药业有限公司 | Method for synthesizing, separating and determining obeticholic acid (OCA) isomer |
| CN105936641A (en) * | 2016-05-20 | 2016-09-14 | 临沂希波科生物工程有限公司 | New method for producing ursodesoxycholic acid from duck bile powder |
| CN107573396A (en) * | 2017-08-08 | 2018-01-12 | 湖北中医药大学 | A kind of method for preparing high-purity chenodeoxy cholic acid using chromatogram 3 and dynamic axial compression column chromatography purifying |
| CN109929896A (en) * | 2019-04-23 | 2019-06-25 | 南京久安源环保科技有限公司 | A kind of production technology of ursodesoxycholic acid |
| CN109988211A (en) * | 2018-06-27 | 2019-07-09 | 药璞(上海)医药科技有限公司 | A kind of purification process of glycochenodeoxycholate sodium |
| CN110627857A (en) * | 2019-10-18 | 2019-12-31 | 河南利伟生物药业股份有限公司 | Environment-friendly method for removing oil in animal bile |
| CN112679572A (en) * | 2020-12-24 | 2021-04-20 | 高陵蓝晓科技新材料有限公司 | Novel process for preparing high-purity chenodeoxycholic acid |
| CN113234115A (en) * | 2021-05-31 | 2021-08-10 | 山东海钰生物技术股份有限公司 | Production process for extracting chenodeoxycholic acid from chicken bile |
-
2014
- 2014-09-26 CN CN201410500441.8A patent/CN104311620A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294801A (en) * | 2015-07-02 | 2016-02-03 | 扬子江药业集团南京海陵药业有限公司 | Method for synthesizing, separating and determining obeticholic acid (OCA) isomer |
| CN105936641A (en) * | 2016-05-20 | 2016-09-14 | 临沂希波科生物工程有限公司 | New method for producing ursodesoxycholic acid from duck bile powder |
| CN107573396A (en) * | 2017-08-08 | 2018-01-12 | 湖北中医药大学 | A kind of method for preparing high-purity chenodeoxy cholic acid using chromatogram 3 and dynamic axial compression column chromatography purifying |
| CN107573396B (en) * | 2017-08-08 | 2020-04-21 | 湖北中医药大学 | Method for purifying and preparing high-purity chenodeoxycholic acid by utilizing chromatography-3 and dynamic axial compression column chromatography |
| CN109988211A (en) * | 2018-06-27 | 2019-07-09 | 药璞(上海)医药科技有限公司 | A kind of purification process of glycochenodeoxycholate sodium |
| CN109988211B (en) * | 2018-06-27 | 2021-09-10 | 药璞(上海)医药科技有限公司 | Purification method of glycochenodeoxycholic acid sodium salt |
| CN109929896A (en) * | 2019-04-23 | 2019-06-25 | 南京久安源环保科技有限公司 | A kind of production technology of ursodesoxycholic acid |
| CN109929896B (en) * | 2019-04-23 | 2022-06-14 | 南京久安源环保科技有限公司 | Production process of ursodeoxycholic acid |
| CN110627857A (en) * | 2019-10-18 | 2019-12-31 | 河南利伟生物药业股份有限公司 | Environment-friendly method for removing oil in animal bile |
| CN112679572A (en) * | 2020-12-24 | 2021-04-20 | 高陵蓝晓科技新材料有限公司 | Novel process for preparing high-purity chenodeoxycholic acid |
| CN113234115A (en) * | 2021-05-31 | 2021-08-10 | 山东海钰生物技术股份有限公司 | Production process for extracting chenodeoxycholic acid from chicken bile |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104311620A (en) | Method for purifying chenodeoxycholic acid | |
| CN101812009B (en) | Novel technique for extracting L-tryptophan from fermentation broth | |
| CN102766185B (en) | Method for respectively recovering ursodesoxycholic acid and chenodeoxycholic acid from ursodesoxycholic acid waste mother liquor | |
| US20150105591A1 (en) | Method for Scale Extraction Quebrachitol from Natural Rubber Industry Waste Water | |
| CN102001947A (en) | Method for preparing honeysuckle chlorogenic acid | |
| CN105111098B (en) | Method for extracting and purifying monomeric macamide compounds from maca | |
| CN101891781A (en) | Method for preparing high-purity gardenoside | |
| CN101721979B (en) | Method for preparing macroporous adsorbent resin special for separating valine | |
| CN105254500A (en) | Method for preparing high-purity chlorogenic acid from eucommia ulmoides leaf crude extract | |
| CN106349324A (en) | Method for extracting and separating maslinic acid from olive leaves | |
| CN101985459B (en) | Process for extracting greater than or equal to 98% of ursolic acid from loquat leaf | |
| CN1563073A (en) | Method for preparing enoxolone | |
| CN102993134B (en) | A kind of method of purification of Lipstatin | |
| CN104311616B (en) | A kind of extraction high purity cortex fraxini and method of fraxin from Cortex Fraxini | |
| CN113527087B (en) | Preparation method of high-purity ferulic acid | |
| CN110818585A (en) | Separation method for simultaneously preparing five dopamine compounds from aspongopus | |
| CN104119229A (en) | Technology for producing pure chlorogenic acid | |
| CN104418740B (en) | The method of high-purity chlorogenic acid is prepared from leaf of canada potato | |
| CN104356105A (en) | Preparation method for high-content EGCG | |
| CN107286071A (en) | It is a kind of that bilirubin and cholic acid co-production cholesterol, the method for lecithin are extracted from bile | |
| CN107929367B (en) | Method for separating and preparing gelsemium elegans alkaloid from gelsemium elegans by ion exchange method | |
| CN103012535B (en) | Method for preparing refined cholesterol by separating cholesterol from egg oil | |
| WO2016161686A1 (en) | Technology for extracting and preparing high-purity raffinose from defatted wheat germ | |
| CN103420838B (en) | Method for separating and purifying chlorogenic acid by utilizing temperature to induce aqueous two-phase system | |
| CN113527402B (en) | Method for simultaneously extracting oleuropein, maslinic acid and oleanolic acid from olive leaves |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150128 |