CN108299538B - Method for removing isoursodesoxycholic acid in duck bile - Google Patents
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Abstract
The invention discloses a method for removing isoursodeoxycholic acid from duck bile, which comprises the process steps of preparing a chenodeoxycholic acid crude product, preparing a crystalline liquid, crystallizing to obtain a chenodeoxycholic acid crystalline liquid, preparing a chenodeoxycholic acid pure product and the like. The method can purify chenodeoxycholic acid in the duck bile, separate out the isoursodesoxycholic acid with pharmaceutical value and improve the utilization rate of bile acid resources to the maximum extent. The method of the invention produces less leftovers, and can be recycled by extraction, thereby greatly reducing the loss of bile acid resources.
Description
Technical Field
The invention relates to the technical field of bioengineering, in particular to a method for removing isoursodeoxycholic acid in duck bile.
Background
People have a long history on the research of the cholic acid compound, and the research on the cholic acid compound is also in depth continuously under the promotion of the rapid biochemical development. Chenodeoxycholic acid is one of the most used medicaments for treating gallstones in the world at present, is also a main raw material for synthesizing ursodeoxycholic acid, and under the condition that the market demand of the chenodeoxycholic acid and the ursodeoxycholic acid is rapidly increased continuously, in order to widen the source of the raw material, people begin to extract the chenodeoxycholic acid from duck bile which is low in cost and easy to obtain the raw material, so that more raw materials for preparing the ursodeoxycholic acid are obtained.
In the processing process, in order to improve the extraction purity of the chenodeoxycholic acid, various methods are adopted to remove the allopholic acid impurities in the duck bile, but the effect is not obvious. Years of research show that the duck bile also contains an impurity called isoursodeoxycholic acid, the content of the impurity is generally between 7 and 8 percent, the impurity is second to the content of other cholic acid impurities in the duck bile and is the impurity which is not easy to remove when the chenodeoxycholic acid is purified, and the conversion rate of the chenodeoxycholic acid to prepare the ursodeoxycholic acid is influenced.
In addition, the isoursodeoxycholic acid is an epimer of the ursodeoxycholic acid, and when biochemical analysis is carried out to detect the cholesterol metabolism index of a human body, the high-purity isoursodeoxycholic acid is required to be used as a standard substance, so the isoursodeoxycholic acid has important biological utilization value. Therefore, the removal of the isoursodeoxycholic acid from the chenodeoxycholic acid derived from the duck bile raw material is not only another important step for purifying the chenodeoxycholic acid, but also the isoursodeoxycholic acid obtained by the removal can be used for producing downstream products of the bile acid.
Disclosure of Invention
In order to separate the impurities of the ursodesoxycholic acid when extracting the chenodeoxycholic acid from the duck bile, the method utilizes the solubility difference of the chenodeoxycholic acid and the isoursodesoxycholic acid in a mixed solvent of esters, polyhydric alcohols and aliphatic hydrocarbon compounds with a specific ratio to crystallize and separate the isoursodesoxycholic acid, thereby realizing the refining extraction of the chenodeoxycholic acid.
The technical scheme of the invention is as follows: a method for removing isoursodeoxycholic acid from duck bile is characterized by comprising the following process steps:
(1) preparing a chenodeoxycholic acid crude product: utilizing a duck bile raw material, and preparing a chenodeoxycholic acid crude product by a butyl acetate magnesium salt method, wherein the wet weight of the crude product is less than 0.6%, the content of allocholic acid is less than 1.0%, and the content of isoursodeoxycholic acid is more than 7%.
(2) Preparation of a crystalline liquid: adding ethyl acetate with 6 times of the crude product and less than 1% of water and glycol with 0.5 times of the crude product and 99.5% of purity into the chenodeoxycholic acid crude product prepared in the step (1), stirring and heating to boil, and keeping boiling for dissolving for 1 hour until the crude product is completely dissolved. Standing for 1 hour to separate out a lower-layer water phase, and adjusting the moisture of an upper-layer organic phase through a reaction kettle backflow water separator to enable the moisture content of the upper-layer organic phase to be less than 1.0%; concentrating the upper organic phase at normal pressure, and quantitatively recovering the added mixed solvent of ethyl acetate and ethylene glycol from the concentrated organic phase, wherein the recovery amount is half of the addition amount of the mixed solvent; after recovery, measuring and adjusting the water content of the organic phase to be below 1.0 percent again, and cooling to 29-30 ℃ for later use.
Adding glacial acetic acid 0.003 times and gasoline 120# 0.15 times of the crude product in step (1) into the organic phase, stirring at 28-30 deg.C to clarify, measuring and adjusting pH of the organic phase to 3.5-4 and water content to 1.2-1.5%. Glacial acetic acid is added to increase the solubility of bile acid, and aliphatic hydrocarbon compound 120# gasoline is added to absorb water and reduce the solubility of isoursodeoxycholic acid.
(3) And (3) crystallization: and (3) carrying out variable-frequency stirring on the crystalline liquid prepared in the step (2) through 12-15HZ, cooling to 23-25 ℃, continuously stirring for reacting for 10-12 hours, gradually changing the crystalline liquid from clear to turbid, and carrying out filter pressing through an embedded plate-and-frame filter press to obtain filter residue of the isoursodeoxycholic acid and chenodeoxycholic acid crystalline liquid. Wherein the filter residue of the isoursodeoxycholic acid is light grey floccule, the wet weight of the filter residue is 29-31% and the purity of the filter residue is 89-91%.
(4) Adding a sodium carbonate solution with the weight of 0.5% of the crystal liquid into the chenodeoxycholic acid crystal liquid prepared in the step (3), adding purified water with the weight of 25% of the crystal liquid, concentrating under normal pressure, controlling the temperature of solvent steam in a kettle to be 65-68 ℃, recovering a mixed solvent of ethyl acetate and No. 120 gasoline in the crystal liquid, stirring and cooling the solution to 30 ℃ after complete recovery, continuously adding purified water with the weight of 50% of the crystal liquid, neutralizing the solution to a pH value of 3.5 by using 10% dilute hydrochloric acid, centrifuging to obtain a chenodeoxycholic acid pure product, and drying by using an airflow boiling bed to obtain a white granular chenodeoxycholic acid dried pure product with the wet weight of less than 1.2% and the content of 96-98%. Through detection, the content of the isoursodeoxycholic acid in the pure chenodeoxycholic acid product is less than 0.1%, and the content of the allopholic acid is less than or equal to 0.5%.
The invention has the advantages that:
1. at present, the theoretical research on how to remove the isoursodeoxycholic acid in a laboratory adopts a conventional resin column-loading method, and the method has the disadvantages of large solvent requirement dosage, long production period, frequent resin replacement, low production efficiency and unsuitability for industrial large-scale production. The extraction and separation method adopted by the invention replaces the resin column-loading method adopted in the theoretical research in the laboratory at present, so that the rapid transition from the laboratory research to the industrial large-scale production is realized for the new topic of extracting the isoursodeoxycholic acid from the duck bile.
2. The method can purify chenodeoxycholic acid in the duck bile, separate out the isoursodesoxycholic acid with pharmaceutical value and improve the utilization rate of bile acid resources to the maximum extent.
3. The isoursodeoxycholic acid separated by the method can be used for producing downstream products of bile acid, such as food additives and the like. Because the isoursodeoxycholic acid and the ursodeoxycholic acid are epimers, the isoursodeoxycholic acid can be directly converted into the ursodeoxycholic acid, and the raw material sources for processing and producing the ursodeoxycholic acid are effectively widened.
4. The sewage generated in the whole process is controllable, and the chemical oxygen demand can reach the discharge standard of the local environmental protection department.
5. The method of the invention has less leftovers, and can be recycled by extraction, thereby greatly reducing the loss of bile acid resources. Auxiliary materials used in the step of separating the isoursodeoxycholic acid, especially solvents are conventional chemical solvents, do not belong to the easily prepared toxic substances, and basically have no environmental hazard and safety risk.
6. The method has low requirements on related process conditions, but the pH value and the moisture standard are fine, and the method has controllability under the condition of complete functions of supporting facilities although the adjusting space is not large.
7. The crystallization process has obvious effect of removing the isoursodeoxycholic acid and has a certain effect of removing the allocholic acid with the content interval of less than 1.0 percent. The invention verifies that the allocholic acid and the chenodeoxycholic acid have certain solubility difference in a mixed solvent of esters, polyhydric alcohols and aliphatic hydrocarbon compounds in a specific ratio, and the allocholic acid can be removed in a certain ratio although the solubility difference is not as good as that of the isoursodeoxycholic acid. Therefore, when the isoursodeoxycholic acid is removed, impurities such as allocholic acid and the like can be removed to different degrees.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the method of the present invention is further described in detail below with reference to specific examples.
Example one
A method for removing isoursodesoxycholic acid in duck bile comprises the following process steps:
(1) preparing a chenodeoxycholic acid crude product: 500 kg of bile acid raw material of the duck gall is taken, and a butyl acetate magnesium salt method is adopted to prepare a chenodeoxycholic acid crude product, wherein the wet weight of the crude product is 0.48%, the weight of the crude product is 75.6 kg, the content of allocholic acid in the crude product is 0.8%, and the content of isoursodeoxycholic acid is 7.2%.
(2) Preparing a crystalline liquid: putting 75.6 kg of the chenodeoxycholic acid crude product prepared in the step (1) into a 2000L stainless steel kettle, adding 453.6 kg of ethyl acetate with the water content of 0.2 percent, adding 37.8 kg of glycol with the purity of 99.5 percent, stirring and heating to boil, and keeping boiling for dissolving for 1 hour until the crude product is completely dissolved. Standing for 1 hour to separate out a lower-layer water phase, and adjusting the moisture of an upper-layer organic phase through a reaction kettle reflux water separator to ensure that the moisture content of the upper-layer organic phase is 0.95 percent. And concentrating the upper organic phase at normal pressure, metering and recovering 245.7 kg of mixed solvent of ethyl acetate and ethylene glycol, re-measuring the water content of the organic phase to be 0.65 percent after recovery, and cooling to 29 ℃ for later use.
0.23 kg of glacial acetic acid and 11.3 kg of gasoline 120# were added to the organic phase, stirred at 29 ℃ until clear, and the pH of the organic phase was determined and adjusted to 3.8 and the moisture content was 1.2%.
(3) And (3) crystallization: and (3) carrying out variable frequency stirring on the crystalline liquid prepared in the step (2) through 12HZ, cooling to 25 ℃, then continuously stirring for reacting for 10 hours, gradually changing the crystalline liquid from clear to turbid, and carrying out pressure filtration through a 10-square meter embedded plate-and-frame filter press to obtain 8.5 kg of filter residue of the isoursodeoxycholic acid and 324 kg of chenodeoxycholic acid crystalline liquid. Wherein the filter residue of the isoursodeoxycholic acid is light grey floccule, the wet weight of the filter residue is 29.5 percent and the purity of the filter residue is 90.3 percent.
(4) And (3) adding 1.62 kg of sodium carbonate solution into 324 kg of chenodeoxycholic acid crystalline liquid prepared in the step (3), adding 81 kg of purified water, concentrating under normal pressure, controlling the temperature of solvent steam in the kettle to be 65 ℃, and recovering 224 kg of mixed solvent of ethyl acetate and 120# gasoline in the crystalline liquid. And after complete recovery, cooling the solution in the kettle to 30 ℃, continuously adding 162 kg of purified water, stirring uniformly, neutralizing with 10% dilute hydrochloric acid until the pH value is 3.5, centrifuging by using a 1000-type stainless steel centrifuge, treating the centrifuged acid water by a sewage station, centrifuging to obtain 91 kg of wet chenodeoxycholic acid product, and drying by using an airflow fluidized bed to obtain 55 kg of pure chenodeoxycholic acid product in the form of white particles. Quality control, dry wet weight is 1.0%, isoursodeoxycholic acid content is 0.098%, allocholic acid content is 0.45%, and chenodeoxycholic acid content is 96.9%.
Example two
A method for removing isoursodesoxycholic acid in duck bile comprises the following process steps:
(1) preparing a chenodeoxycholic acid crude product: 550 kg of bile acid raw material of the duck gall is taken, and a butyl acetate magnesium salt method is adopted to prepare a chenodeoxycholic acid crude product, wherein the wet weight of the crude product is 0.5 percent, the weight of the crude product is 85.2 kg, the content of allopholic acid in the crude product is 0.83 percent, and the content of isoursodeoxycholic acid is 7.5 percent.
(2) Preparing a crystalline liquid: putting 85.2 kg of the chenodeoxycholic acid crude product prepared in the step (1) into a 2000L stainless steel kettle, adding 511.2 kg of ethyl acetate with the water content of 0.15%, adding 42.6 kg of glycol with the purity of 99.5%, stirring and heating to boil, and keeping boiling for dissolving for 1 hour until the crude product is completely dissolved. Standing for 1 hour to separate out a lower-layer water phase, and adjusting the moisture of an upper-layer organic phase through a reaction kettle backflow water separator to enable the moisture content of the upper-layer organic phase to be 0.9%. And concentrating the upper organic phase at normal pressure, quantitatively recovering 276.9 kg of mixed solvent of ethyl acetate and ethylene glycol, re-measuring the water content of the organic phase to be 0.58% after the recovery is finished, and cooling to 29.5 ℃ for later use.
0.26 kg of glacial acetic acid and 12.78 kg of 120# gasoline were added to the organic phase, stirred at 28 ℃ until clear, and the pH of the organic phase was determined and adjusted to 3.6 and the moisture content was 1.25%.
(3) And (3) crystallization: and (3) carrying out variable frequency stirring on the crystalline liquid prepared in the step (2) by 15HZ, cooling to 24.5 ℃, continuously stirring for reacting for 10 hours, gradually changing the crystalline liquid from clear to turbid, and carrying out pressure filtration by a 10-square meter embedded plate-and-frame filter press to obtain 9.4 kg of filter residue of the isoursodeoxycholic acid and 365 kg of chenodeoxycholic acid crystalline liquid. Wherein the filter residue of the isoursodeoxycholic acid is light grey floccule, the wet weight of the filter residue is 30 percent and the purity of the filter residue is 90 percent.
(4) And (3) adding 1.83 kg of sodium carbonate solution into 365 kg of chenodeoxycholic acid crystalline liquid prepared in the step (3), adding 91.3 kg of purified water, concentrating under normal pressure, controlling the temperature of solvent steam in the kettle to be 65 ℃, and recovering 265 kg of mixed solvent of ethyl acetate and 120# gasoline in the crystalline liquid. And after complete recovery, cooling the solution in the kettle to 30 ℃, continuously adding 182.5 kg of purified water, stirring uniformly, neutralizing with 10% dilute hydrochloric acid until the pH value is 3.5, centrifuging by using a 1000-type stainless steel centrifuge, treating the centrifuged acid water by using a sewage station, centrifuging to obtain 100.5 kg of a wet chenodeoxycholic acid product, and drying by using an airflow fluidized bed to obtain 63.3 kg of a pure chenodeoxycholic acid product in a white-like particle shape. Quality control, dry wet weight is 1.1%, isoursodeoxycholic acid content is 0.099%, allocholic acid content is 0.5%, and chenodeoxycholic acid content is 96.4%.
EXAMPLE III
A method for removing isoursodesoxycholic acid in duck bile comprises the following process steps:
(1) preparing a chenodeoxycholic acid crude product: 480 kg of bile acid raw material of the duck bile is taken, and a butyl acetate magnesium salt method is adopted to prepare a chenodeoxycholic acid crude product, wherein the wet weight of the crude product is 0.58%, the weight of the crude product is 73.2 kg, the content of allocholic acid in the crude product is 0.85%, and the content of isoursodeoxycholic acid is 7.3%.
(2) Preparing a crystalline liquid: putting 73.2 kg of the chenodeoxycholic acid crude product prepared in the step (1) into a 2000L stainless steel kettle, adding 439.2 kg of ethyl acetate with the water content of 0.15%, adding 36.6 kg of ethylene glycol with the purity of 99.5%, stirring and heating to boil, and keeping boiling for dissolving for 1 hour until the crude product is completely dissolved. Standing for 1 hour to separate out a lower-layer water phase, and adjusting the moisture of an upper-layer organic phase through a reaction kettle reflux water separator to ensure that the moisture content of the upper-layer organic phase is 0.87%. Then concentrating the upper organic phase under normal pressure, measuring and recovering 237.9 kg of mixed solvent of ethyl acetate and ethylene glycol, measuring the water content of the organic phase to be 0.61% after the recovery is finished, and cooling to 29.5 ℃.
0.22 kg of glacial acetic acid and 10.98 kg of 120# gasoline were added to the organic phase, stirred at 30 ℃ until clear, and the pH of the organic phase was determined and adjusted to 3.75 and the moisture content was 1.28%.
(3) And (3) crystallization: and (3) carrying out variable frequency stirring on the crystalline liquid prepared in the step (2) by 15HZ, cooling to 25 ℃, then continuously stirring for reaction for 10 hours, gradually changing the crystalline liquid from clear to turbid, and carrying out pressure filtration by a 10-square meter embedded plate-and-frame filter press to obtain 8.2 kg of filter residue of the isoursodeoxycholic acid and 312 kg of chenodeoxycholic acid crystalline liquid. Wherein the filter residue of the isoursodeoxycholic acid is light grey floccule, the wet weight of the filter residue is 30.3 percent and the purity of the filter residue is 89.7 percent.
(4) And (3) adding 1.56 kg of sodium carbonate solution into 312 kg of chenodeoxycholic acid crystalline liquid prepared in the step (3), adding 78 kg of purified water, concentrating under normal pressure, controlling the temperature of solvent steam in the kettle to be 68 ℃, and recovering 212 kg of mixed solvent of ethyl acetate and 120# gasoline in the crystalline liquid. And after complete recovery, cooling the solution in the kettle to 30 ℃, continuously adding 156 kg of purified water, stirring uniformly, neutralizing with 10% dilute hydrochloric acid until the pH value is 3.5, centrifuging by using a 1000-type stainless steel centrifuge, treating the centrifuged acid water by a sewage station, centrifuging to obtain 88.1 kg of wet chenodeoxycholic acid product, and drying by using an airflow fluidized bed to obtain 51.8 kg of pure chenodeoxycholic acid product in the form of white granules. Quality control, dry wet weight 0.9%, isoursodeoxycholic acid content 0.089%, allocholic acid content 0.38%, and chenodeoxycholic acid content 97.58%.
The results of the examination of the chenodeoxycholic acid crude product in the three examples are as follows:
the inspection results of the chenodeoxycholic acid finished product in the three examples are as follows:
the following can be obtained from the test data in the above two tables: when the method is used for extracting the chenodeoxycholic acid from the duck bile raw material, the high-content chenodeoxycholic acid can be obtained, the stubborn impurity isoursodesoxycholic acid can be separated to the maximum extent, and other related impurities such as allocholic acid and the like can be removed to different degrees.
Claims (5)
1. A method for removing isoursodeoxycholic acid from duck bile is characterized by comprising the following process steps:
(1) preparing a chenodeoxycholic acid crude product: preparing a chenodeoxycholic acid crude product from a duck bile raw material by a butyl acetate magnesium salt method;
(2) preparation of a crystalline liquid: adding ethyl acetate in an amount which is 6 times that of the chenodeoxycholic acid crude product in the step (1) and glycol in an amount which is 0.5 times that of the chenodeoxycholic acid crude product in the step (1) into the chenodeoxycholic acid crude product prepared in the step (1), stirring and heating to boil, and keeping boiling for dissolving for 1 hour until the crude product is completely dissolved; standing for 1 hour to separate out a lower-layer water phase, and adjusting the moisture of an upper-layer organic phase through a reaction kettle backflow water separator to enable the moisture content of the upper-layer organic phase to be less than 1.0%; concentrating the upper organic phase at normal pressure, and quantitatively recovering the added mixed solvent of ethyl acetate and glycol from the concentrated organic phase; after the recovery, measuring and adjusting the water content of the organic phase to be below 1.0 percent again, and cooling to 29-30 ℃ for later use;
adding glacial acetic acid in an amount which is 0.003 times that of the chenodeoxycholic acid crude product in the step (1) and 120# gasoline in an amount which is 0.15 times that of the chenodeoxycholic acid crude product in the step (1) into the organic phase, stirring the mixture at the temperature of between 28 and 30 ℃ until the mixture is clear, measuring and adjusting the pH value of the organic phase to be between 3.5 and 4 and the water content to be between 1.2 and 1.5 percent;
(3) and (3) crystallization: carrying out variable-frequency stirring on the crystalline liquid prepared in the step (2) through 12-15HZ, cooling to 23-25 ℃, continuously stirring for reaction for 10-12 hours, gradually changing the crystalline liquid from clear to turbid, and carrying out filter pressing through an embedded plate-and-frame filter press to obtain filter residue of the isoursodeoxycholic acid and chenodeoxycholic acid crystalline liquid; wherein the filter residue of the isoursodeoxycholic acid is light grey floccule, the wet weight is 29-31% and the purity is 89-91% through detection;
(4) adding a sodium carbonate solution with the weight of 0.5% of the crystal liquid into the chenodeoxycholic acid crystal liquid prepared in the step (3), adding purified water with the weight of 25% of the crystal liquid, concentrating under normal pressure, controlling the temperature of solvent steam in a kettle to be 65-68 ℃, recovering a mixed solvent of ethyl acetate and No. 120 gasoline in the crystal liquid, stirring and cooling the solution to 30 ℃ after complete recovery, continuously adding purified water with the weight of 50% of the crystal liquid, neutralizing the solution with 10% dilute hydrochloric acid until the pH value is 3.5, centrifuging to obtain a chenodeoxycholic acid pure product, and drying by an airflow boiling bed to obtain a white granular chenodeoxycholic acid dried pure product with the wet weight of less than 1.2% and the purity of 96-98%; through detection, the content of the isoursodeoxycholic acid in the pure chenodeoxycholic acid product is less than 0.1%, and the content of the allopholic acid is less than or equal to 0.5%.
2. The method for removing isoursodeoxycholic acid from duck bile according to claim 1, wherein the wet weight of the chenodeoxycholic acid crude product prepared in the step (1) is less than 0.6%, the content of allocholic acid is less than 1.0%, and the content of isoursodeoxycholic acid is greater than 7%.
3. The method for removing ursodeoxycholic acid from duck bile according to claim 1, wherein the water content of the ethyl acetate added in the step (2) is less than 1%.
4. The method for removing ursodeoxycholic acid from duck bile according to claim 1, wherein the purity of the ethylene glycol added in the step (2) is 99.5%.
5. The method for removing ursodeoxycholic acid from duck bile according to claim 1, wherein after the organic phase is concentrated in the step (2), the recovery amount of the mixed solvent of ethyl acetate and glycol is half of the amount of the mixed solvent added in advance.
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Denomination of invention: A method for removing isoursodeoxycholic acid from duck bile Effective date of registration: 20220210 Granted publication date: 20200602 Pledgee: Bank of Changsha Limited by Share Ltd. Changde science and Technology Branch Pledgor: CHANGDE YUNGANG BIOTECHNOLOGY Co.,Ltd. Registration number: Y2022980001452 |
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Address after: 415001 No. 8, Fenglin Road, sujiadu community, Zhangmuqiao street, Changde economic and Technological Development Zone, Hunan Province Patentee after: Changdeyungang Biotechnology Co.,Ltd. Address before: Kongjiarong community, guojiapu street, Dingcheng District, Changde City, Hunan Province (north of Yongfu Road and west of Yongxing Road, Qiaonan Industrial Park) Patentee before: CHANGDE YUNGANG BIOTECHNOLOGY Co.,Ltd. |
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| CP03 | Change of name, title or address | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20200602 Pledgee: Bank of Changsha Limited by Share Ltd. Changde science and Technology Branch Pledgor: CHANGDE YUNGANG BIOTECHNOLOGY Co.,Ltd. Registration number: Y2022980001452 |
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| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A Method for Clearing Isoursodeoxycholic Acid from Duck Bile Granted publication date: 20200602 Pledgee: Changsha Bank Co.,Ltd. Changde Economic Development Zone Branch Pledgor: Changdeyungang Biotechnology Co.,Ltd. Registration number: Y2024980005358 |
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| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20200602 Pledgee: Changsha Bank Co.,Ltd. Changde Economic Development Zone Branch Pledgor: Changdeyungang Biotechnology Co.,Ltd. Registration number: Y2024980005358 |
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| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for clearing isoursodeoxycholic acid from duck bile Granted publication date: 20200602 Pledgee: Changsha Bank Co.,Ltd. Changde Economic Development Zone Branch Pledgor: Changdeyungang Biotechnology Co.,Ltd. Registration number: Y2025980008069 |