CN115093454A - Co-production preparation method of cholic acid and deoxycholic acid compounds - Google Patents
Co-production preparation method of cholic acid and deoxycholic acid compounds Download PDFInfo
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Abstract
The invention discloses a co-production preparation method of cholic acid and deoxycholic acid compounds, which comprises the following specific steps: heating and reacting ox bile and sodium hydroxide to prepare a mixture of cholic acid A and deoxycholic acid A; reacting the mixture of cholic acid A and deoxycholic acid A with petroleum ether to prepare a mixture of cholic acid B and deoxycholic acid B; reacting the mixture of cholic acid B and deoxycholic acid B with methanol and triethylamine to obtain cholic acid amine A + deoxycholic acid amine A; dissolving cholic acid in water to obtain cholic acid C; refluxing and crystallizing cholic acid C and ethyl acetate to obtain a cholic acid finished product; heating and refluxing deoxycholic acid amine A to prepare deoxycholic acid triethylamine salt B; adding water to dissolve the deoxycholic acid triethylamine salt B to obtain deoxycholic acid C; and reacting the deoxycholic acid C with glacial acetic acid, water and methanol to obtain the deoxycholic acid. The method of the invention solves the problems of low yield, complex operation, poor feasibility, high impurity content and the like existing in the single extraction, and saves resources. The purity of the cholic acid and the deoxycholic acid prepared by the method is over 99 percent.
Description
Technical Field
The invention relates to the technical field of natural product preparation, in particular to a co-production preparation method of cholic acid and deoxycholic acid compounds.
Background
Cholic acid consists of a rigid steroid ring and an aliphatic side chain, and is a generic name of a large group of cholanic acids in bile, which is found and structurally determined by a german scientist heimeri-otto-viland a chemi book.
Deoxycholic acid is a bile acid with a hydroxyl group on C-7, is a free bile acid obtained by derivation of cholic acid with one oxygen atom lost, and exists in bile mainly in a combined form of taurine and glycine. It is mainly used for biochemical research, bacteriology and enzymology research; a lipase accelerator; anion removal agents and protein solubilization.
The existing preparation method of cholic acid mainly comprises the following steps: preparation of crude cholic acid from cattle or sheep, adding 100g/L sodium hydroxide, heating and boiling for 12-18 hr to obtain saponified solution; cooling, adding acid to adjust pH to 1.0,separating out cholic acid, taking out cholic acid, decocting in water, rinsing, drying at 75 deg.C, and grinding to obtain crude cholic acid; bovine and sheep cholic acid [ NaOH ]]→[100℃,12-18h]Saponified liquid [ H ] 2 SO 4 ]→[pH1,75℃]Crude bovine and sheep cholic acid; taking crude cholic acid, adding 0.5-1 times of 95% ethanol, heating and refluxing until the solid is dissolved, and cooling; taking out the crystal, mashing, filtering, and washing with 95% ethanol until the filtrate is colorless; adding 4 times of ethanol into the crystals, adding 100-fold 150g/L of activated carbon, heating and refluxing until the crystals are dissolved, filtering while the crystals are hot, concentrating the filtrate to 1/4 of the original volume, cooling, crystallizing, filtering, adding ethanol to wash the crystals, and drying to obtain the finished product of the taurine.
The preparation method of the deoxycholic acid mainly comprises the following steps: adding sodium hydroxide and 40% water solution into the ox bile hydrolysate, stirring at 80-90 deg.C for 2 hr, cooling to 20 deg.C, filtering, adjusting pH of the filtrate to 1.5 with 50% sulfuric acid at 10 deg.C, filtering, collecting precipitate, and washing with water to neutrality. Stirring the wet filter cake at 40 ℃ with a mixed solution of ethyl acetate and benzene (1:1), filtering insoluble substances while the wet filter cake is hot, cooling, and separating out crystals from the solution to obtain the finished product.
Therefore, cholic acid and deoxycholic acid are both important natural compounds, the extraction method of cholic acid and deoxycholic acid in the prior art is basically independent extraction, a co-production extraction process is not available, and the problems of low yield, complex operation and poor feasibility exist in independent extraction, and the problems of resource waste, high product impurity content and the like also exist.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a co-production preparation method of cholic acid and deoxycholic acid compounds.
The invention provides a co-production preparation method of cholic acid and deoxycholic acid compounds, which specifically comprises the following steps:
step 1, adding oxgall into a reaction kettle, stirring, adding sodium hydroxide, heating to a certain temperature, continuing to react at the same temperature for 16 hours, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L sulfuric acid or hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and petroleum ether into a reaction kettle, sealing and intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding the cholic acid B and deoxycholic acid B mixture obtained in the step 2 into a methanol and triethylamine mixed solution, heating and refluxing for 5 hours, cooling and centrifuging, and collecting a filter cake and filtrate to obtain a cholic acid amine A and deoxycholic acid triethylamine salt A solution for later use;
step 4, adding the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L sulfuric acid or hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain cholic acid C for later use;
step 5, adding the cholic acid C and ethyl acetate obtained in the step 4 into a reaction kettle, performing reflux crystallization, centrifuging and drying to obtain a cholic acid finished product;
step 6, heating and refluxing the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain deoxycholic acid triethylamine salt B for later use;
step 7, adding the deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L sulfuric acid or hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain deoxycholic acid C for later use;
and 8, adding the deoxycholic acid C obtained in the step 7 into a mixed solution of glacial acetic acid, water and methanol, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain a finished product of deoxycholic acid.
Further, in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 0.5-2: 0.05-1, and the certain temperature is 100-110 ℃.
Preferably, in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 1: 0.09, and the certain temperature is preferably 110 ℃.
Further, in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 0.5-2: 1-2.
Preferably, in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 1: 1.5.
further, in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 0.5-1.5: 1.5-3: 0.3-0.8.
Preferably, in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 1: 2: 0.65.
further, in the step 5, the feeding ratio of the cholic acid C to the ethyl acetate in the reaction kettle is 0.5-2: 1 to 1.8; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 0.5-2: 1-3: 0.2-0.8: 0.5-2.
Preferably, in the step 5, the feeding ratio of the cholic acid C to the ethyl acetate in the reaction kettle is 1: 1.65; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 1: 1.2: 0.4: 1.
compared with the prior art, the invention has the following beneficial effects:
the method is a co-production extraction process of cholic acid and deoxycholic acid, overcomes the problems of low yield, complex operation, poor feasibility, high impurity content and the like in the single extraction process, and saves resources. The purity of the cholic acid and the deoxycholic acid prepared by the method is over 99 percent.
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FIG. 1 is a flow chart of the preparation method of the present invention.
Detailed Description
The technical solutions of the present invention will be described below clearly and completely in conjunction with the embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A co-production preparation method of cholic acid and deoxycholic acid compounds comprises the following steps:
step 1, adding 1000g of oxgall into a reaction kettle, stirring, adding 90g of sodium hydroxide, heating to 110 ℃, continuing to react for 16h at the same temperature, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 65g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 65g of the mixture of cholic acid A and deoxycholic acid A obtained in the step 1 and 97.5g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 55g of a mixture of cholic acid B and deoxycholic acid B for later use;
step 3, adding 55g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into 110g of mixed solution of methanol and 140.75g of triethylamine, heating and refluxing for 5 hours, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 60g of cholic acid amine A and 140.75g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 60g of the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 40g of cholic acid C for later use;
step 5, adding 40g of cholic acid C obtained in the step 4 and 66g of ethyl acetate into a reaction kettle, performing reflux crystallization, centrifuging and drying to obtain 36.5g of cholic acid finished products, wherein the purity can reach 99.57 percent and meets the medicinal standard;
step 6, heating and refluxing 140.75g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 15g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 15g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 10g of deoxycholic acid C for later use;
and 8, adding a mixed solution of 12g of glacial acetic acid, 4g of water and 10g of methanol into 10g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 6.1g of a deoxycholic acid finished product with the purity of 99.36%.
Example 2
A co-production preparation method of cholic acid and deoxycholic acid compounds comprises the following steps:
step 1, adding 800g of oxgall into a reaction kettle, stirring, adding 72g of sodium hydroxide, heating to 100 ℃, continuing to react at the same temperature for 16h, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L sulfuric acid to adjust the pH value to 2.5, centrifuging at the speed of 800 revolutions per minute, and collecting a filter cake to obtain 44g of a mixture of cholic acid A and deoxycholic acid A for later use;
step 2, adding 44g of the mixture of cholic acid A and deoxycholic acid A obtained in the step 1 and 78g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 44g of a mixture of cholic acid B and deoxycholic acid B for later use;
step 3, adding 44g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into a mixed solution of 88g of methanol and 28.6g of triethylamine, heating and refluxing for 5 hours, cooling and centrifuging, and collecting a filter cake and filtrate to obtain 48g of cholic acid amine A and 112.6g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 48g of the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L sulfuric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 32g of cholic acid C for later use;
step 5, adding 32g of cholic acid C obtained in the step 4 and 52.8g of ethyl acetate into a reaction kettle, refluxing, crystallizing, centrifuging and drying to obtain 29.2g of cholic acid finished product, wherein the purity can reach 99.32% and the cholic acid finished product meets the medicinal standard;
step 6, heating and refluxing 112.6g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 12g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 12g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L sulfuric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 8g of deoxycholic acid C for later use;
and 8, adding a mixed solution of 9.6g of glacial acetic acid, 3.2g of water and 8g of methanol into 8g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 4.9g of a finished product of deoxycholic acid, wherein the purity can reach 99.25%.
Example 3
A co-production preparation method of cholic acid and deoxycholic acid compounds comprises the following steps:
step 1, adding 1200g of oxgall into a reaction kettle, stirring, adding 108g of sodium hydroxide, heating to 110 ℃, continuing to react for 16h at the same temperature, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 78g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 78g and 117g of the mixture of cholic acid A and deoxycholic acid A obtained in the step 1 and petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 66g of a mixture of cholic acid B and deoxycholic acid B for later use;
step 3, adding 66g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into a mixed solution of 132g of methanol and 42.9g of triethylamine, heating and refluxing for 5 hours, cooling and centrifuging, and collecting a filter cake and filtrate to obtain 72g of cholic acid amine A and 153.5g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 72g of the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 48g of cholic acid C for later use;
step 5, adding 48g of cholic acid C obtained in the step 4 and 79.2g of ethyl acetate into a reaction kettle, refluxing, crystallizing, centrifuging and drying to obtain 43.8g of cholic acid finished product, wherein the purity can reach 99.45 percent and the cholic acid finished product meets the pharmaceutical standard;
step 6, heating and refluxing 153.5g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 16.4g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 16.4g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 11g of deoxycholic acid C for later use;
and 8, adding 13.2g of glacial acetic acid, 4.4g of water and 11g of methanol into 11g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 6.7g of a deoxycholic acid finished product, wherein the purity can reach 99.30%.
Example 4
A co-production preparation method of cholic acid and deoxycholic acid compounds comprises the following steps:
step 1, adding 500g of oxgall into a reaction kettle, stirring, adding 50g of sodium hydroxide, heating to 100 ℃, continuing to react for 14h at the same temperature, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L sulfuric acid to adjust the pH value to 2, centrifuging, and collecting a filter cake to obtain 32.5g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 32.5g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 65g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 6 hours, centrifuging, and collecting a filter cake to obtain 27.5g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 27.5g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into a mixed solution of 82.5g of methanol and 16.5g of triethylamine, heating and refluxing for 3 hours, cooling and centrifuging, and collecting a filter cake and filtrate to obtain 30g of cholic acid amine A and 70.4g of deoxycholic acid triethylamine salt A solution for later use;
step 4, placing 30g of the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L sulfuric acid for adjusting the pH value to 2, centrifuging, and collecting a filter cake to obtain 20g of cholic acid C for later use;
step 5, adding 20g of cholic acid C obtained in the step 4 and 40g of ethyl acetate into a reaction kettle, performing reflux crystallization, centrifuging and drying to obtain 18.25g of cholic acid finished product, wherein the purity can reach 99.40 percent and the cholic acid finished product meets the medicinal standard;
step 6, heating and refluxing 70.4g of the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 7.5g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 7.5g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L sulfuric acid to adjust the pH value to 2, centrifuging, and collecting a filter cake to obtain 5g of deoxycholic acid C for later use;
and 8, adding 5g of deoxycholic acid C obtained in the step 7 into a mixed solution of 10g of glacial acetic acid, 2g of water and 5g of methanol, heating and refluxing for 3h, cooling, centrifuging, collecting a filter cake, and drying to obtain 3.1g of a deoxycholic acid finished product, wherein the purity can reach 99.16%.
Example 5
A co-production preparation method of cholic acid and deoxycholic acid compounds comprises the following steps:
step 1, adding 1400g of oxgall into a reaction kettle, stirring, adding 700g of sodium hydroxide, heating to 100 ℃, continuing to react at the same temperature for 18h, cooling, adding hydrogen peroxide, stirring intermittently, adding 2mol/L sulfuric acid to adjust the pH value to 4, centrifuging, and collecting a filter cake to obtain 91g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 91g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 91g of petroleum ether into a reaction kettle, sealing and intermittently stirring for 10 hours, centrifuging, and collecting a filter cake to obtain 77g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 77g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into a mixed solution of 154g of methanol and 40.8g of triethylamine, heating and refluxing for 7h, cooling and centrifuging, and collecting a filter cake and filtrate to obtain 84g of cholic acid amine A and 197.05g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 84g of the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L sulfuric acid for adjusting the pH value to 4, centrifuging, and collecting a filter cake to obtain 56g of cholic acid C for later use;
step 5, adding 56g of cholic acid C obtained in the step 4 and 50.4g of ethyl acetate into a reaction kettle, refluxing, crystallizing, centrifuging and drying to obtain 51.1g of cholic acid finished product, wherein the purity can reach 99.24 percent and the cholic acid finished product meets the medicinal standard;
step 6, heating and refluxing 197.05g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 21g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 21g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L sulfuric acid to adjust the pH value to 4, centrifuging, and collecting a filter cake to obtain 14g of deoxycholic acid C for later use;
and step 8, adding a mixed solution of 21g of glacial acetic acid, 5.6g of water and 14g of methanol into 14g of deoxycholic acid C obtained in the step 7, heating and refluxing for 7 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 8.54g of a deoxycholic acid finished product with the purity of 99.20%.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (9)
1. A co-production preparation method of cholic acid and deoxycholic acid compounds is characterized by comprising the following steps:
step 1, adding oxgall into a reaction kettle, stirring, adding sodium hydroxide, heating to a certain temperature, continuously reacting at the same temperature for 16 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L sulfuric acid or hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding the cholic acid B and deoxycholic acid B mixture obtained in the step 2 into a methanol and triethylamine mixed solution, heating and refluxing for 5 hours, cooling and centrifuging, and collecting a filter cake and filtrate to obtain a cholic acid amine A and deoxycholic acid triethylamine salt A solution for later use;
step 4, adding the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolving, filtering, adding 2mol/L sulfuric acid or hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain cholic acid C for later use;
step 5, adding the cholic acid C and ethyl acetate obtained in the step 4 into a reaction kettle, performing reflux crystallization, centrifuging and drying to obtain a cholic acid finished product;
step 6, heating and refluxing the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain deoxycholic acid triethylamine salt B for later use;
step 7, adding the deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolving, adding 2mol/L sulfuric acid or hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain deoxycholic acid C for later use;
and 8, adding the deoxycholic acid C obtained in the step 7 into a mixed solution of glacial acetic acid, water and methanol, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain a finished product of deoxycholic acid.
2. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 1, wherein in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 0.5-2: 0.05-1, and the certain temperature is 100-110 ℃.
3. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 2, wherein in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 1: 0.09, and the certain temperature is preferably 110 ℃.
4. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 1, wherein in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 0.5-2: 1-2.
5. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 4, wherein in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 1: 1.5.
6. the co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 1, wherein in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 0.5-1.5: 1.5-3: 0.3-0.8.
7. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 6, wherein in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 1: 2: 0.65.
8. the co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 1, wherein in the step 5, the feeding ratio of cholic acid C and ethyl acetate in a reaction kettle is 0.5-2: 1 to 1.8; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 0.5-2: 1-3: 0.2-0.8: 0.5-2.
9. The co-production preparation method of cholic acid and deoxycholic acid compounds according to claim 8, wherein in the step 5, the feeding ratio of cholic acid C and ethyl acetate in a reaction kettle is 1: 1.65; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 1: 1.2: 0.4: 1.
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| GB695504A (en) * | 1950-10-18 | 1953-08-12 | Drug Res Inc | Method of isolating and purifying cholic and desoxycholic acids |
| US2661356A (en) * | 1951-06-13 | 1953-12-01 | Armour & Co | Separation of bile acids |
| CN109810159A (en) * | 2019-01-22 | 2019-05-28 | 常德云港生物科技有限公司 | A kind of method that allocholic acid yield can be improved from duck bile |
| CN114369132A (en) * | 2021-11-19 | 2022-04-19 | 四川澄华生物科技有限公司 | Preparation method of deoxycholic acid |
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