CN117229342A - Glycocholic acid purification method - Google Patents
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- CN117229342A CN117229342A CN202311188292.1A CN202311188292A CN117229342A CN 117229342 A CN117229342 A CN 117229342A CN 202311188292 A CN202311188292 A CN 202311188292A CN 117229342 A CN117229342 A CN 117229342A
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- 108010007979 Glycocholic Acid Proteins 0.000 title claims abstract description 68
- RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 229940099347 glycocholic acid Drugs 0.000 title claims abstract description 68
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 title claims abstract description 67
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000000746 purification Methods 0.000 title claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000012043 crude product Substances 0.000 claims abstract description 19
- 239000012046 mixed solvent Substances 0.000 claims abstract description 13
- 238000001816 cooling Methods 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 12
- 150000001298 alcohols Chemical class 0.000 claims abstract description 4
- 150000002148 esters Chemical class 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 6
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 8
- 239000003960 organic solvent Substances 0.000 abstract description 7
- 239000000047 product Substances 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 3
- 235000019441 ethanol Nutrition 0.000 description 32
- 230000000052 comparative effect Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000003613 bile acid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 2
- 239000004380 Cholic acid Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 2
- 229960002471 cholic acid Drugs 0.000 description 2
- 235000019416 cholic acid Nutrition 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010015031 Glycochenodeoxycholic Acid Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229940008309 acetone / ethanol Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000003858 bile acid conjugate Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- -1 ethanol compound Chemical class 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- GHCZAUBVMUEKKP-GYPHWSFCSA-N glycochenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 GHCZAUBVMUEKKP-GYPHWSFCSA-N 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- GHCZAUBVMUEKKP-UHFFFAOYSA-N ursodeoxycholic acid glycine-conjugate Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)CC2 GHCZAUBVMUEKKP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
The invention belongs to the field of chemical pharmacy, and particularly relates to a method for purifying glycocholic acid. The purification method comprises the following steps: and adding the glycocholic acid crude product into a mixed solvent of esters, alcohols and water, heating, stirring, dissolving, cooling and crystallizing to obtain the glycocholic acid. The purification method has good impurity removing effect on the glycocholic acid crude product, and has low organic solvent residue and high product quality, thereby meeting the medicinal requirements.
Description
Technical Field
The invention belongs to the field of chemical pharmacy, and particularly relates to a method for purifying glycocholic acid.
Background
Glycocholic Acid (GCA) is the main component of bile Acid, belonging to primary conjugated bile Acid. Pharmacological studies in recent years show that glycocholic acid has certain immunoregulatory, anti-inflammatory and antioxidant effects. Meanwhile, glycocholic acid is also a good emulsifier and excipient, and is applied to complex injections such as liposome, lipid microsphere, micelle and the like. Glycocholic acid is chemically named as N- [ (3α,5β,7α,12α) -3,7,12-trihydroxy-24-carbonyl cholan-24-yl ] glycine and has the following structural formula:
glycocholic acid can be directly extracted from oxgall and sheep bile, but the method has limited yield and quality. At present, the production of glycocholic acid mainly adopts a chemical synthesis method, uses cholic acid and glycine ethyl ester as raw materials, and synthesizes the glycocholic acid by an azide method, a mixed anhydride method or a condensing agent method.
The glycocholic acid obtained by the synthesis method also contains more impurities, such as cholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, glycocholic acid ethyl ester and the like, and needs to be further purified so as to meet the medicinal requirements.
Patent CN103012538 reports a method for refining glycocholic acid, which uses alcohol ester solvents such as ethanol/ethyl acetate for recrystallization. The purification with ethanol/ethyl acetate is also reported in document "Synthesis ofConjugated Bile Acids, bile Acids and Steroids" (Acta Chem Scand.1953, 7:1126-1127). Experiments show that under the solvent system, the glycocholic acid obtained by recrystallization is actually a solvate, the residual quantity of an organic solvent is very high, and the quality requirement of the medicine is far exceeded (the residual quantity is not more than 0.5%).
Patent CN102464695 reports a method for purifying glycocholic acid by recrystallization using an ethanol/water or ethanol/acetone system. Experiments show that the ethanol/water system is adopted for recrystallization, and the purification effect is poor; the ethanol/acetone system is adopted for recrystallization, the obtained glycocholic acid is actually an ethanol compound, the ethanol residue is very high, and the medicinal quality requirement can not be met.
Therefore, based on the defects of the prior art, a method for purifying glycocholic acid with good purification effect and low organic solvent residue is needed to be invented.
Disclosure of Invention
1. Problems to be solved
Aims at solving the problems of poor purification effect of glycocholic acid or high organic solvent residue in the prior art. The invention provides a method for purifying glycocholic acid, which uses a mixed solvent of esters, alcohols and water to recrystallize the glycocholic acid. The method has good purification effect, and the obtained glycocholic acid has higher purity and low organic solvent residue.
2. Technical proposal
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the invention provides a method for purifying glycocholic acid, which comprises the following steps:
step 1), adding a glycocholic acid crude product into a mixed solvent of esters, alcohols and water, heating, stirring and dissolving to obtain a solution A;
and 2) cooling and crystallizing the solution A, filtering and drying to obtain glycocholic acid.
Further, it is characterized in that: the ester solvent comprises any one or more of ethyl acetate, ethyl formate, methyl acetate and propyl acetate.
Further, it is characterized in that: the alcohol solvent comprises any one or more of ethanol, methanol or isopropanol.
Further, it is characterized in that: the volume/mass ratio of the ester solvent to the glycocholic acid crude product is (3-7): 1, wherein the volume unit is milliliter, and the mass unit is g.
Further, it is characterized in that: the volume/mass ratio of the alcohol solvent to the glycocholic acid crude product is (0-2): 1, wherein the volume unit is milliliter, and the mass unit is g.
Further, it is characterized in that: the volume/mass ratio of the water to the glycocholic acid crude product is (2-10): 1, wherein the volume unit is milliliter, and the mass unit is g.
Further, it is characterized in that: the ester solvent is ethyl acetate, and the alcohol solvent is ethanol.
Further, it is characterized in that: the crystallization temperature in the step 2) is 5-40 ℃.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) The glycocholic acid purification method has excellent impurity removal effect on the crude glycocholic acid product, and the purified product has high quality, and is more suitable for industrial production due to good purification effect, no repeated refining, high process yield and low production cost.
(2) The method for purifying the glycocholic acid has the advantages that the obtained glycocholic acid has very low residual quantity of the organic solvent (less than 0.1 percent), and can well meet the requirement of medicinal quality.
Detailed Description
The invention is further described below in connection with specific embodiments.
The terms such as "upper", "lower", "left", "right", "middle" and the like are also used in the present specification for convenience of description, and are not intended to limit the scope of the present invention, but rather to change or adjust the relative relationship thereof, and are also considered to be within the scope of the present invention without substantial change of technical content.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs; the term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
As used herein, the term "about" is used to provide the flexibility and inaccuracy associated with a given term, metric or value. The degree of flexibility of a particular variable can be readily determined by one skilled in the art.
The crude glycocholic acid used in the examples can be prepared by the methods reported in WO2010128472 and 18-20 and according to the literature of improved synthesis process of sodium glycocholate, chemical working hours journal 2013,28 (2), and the purity is 98.43% and the maximum single impurity is 0.56%.
The purity detection method in the examples is as follows:
adopting octadecylsilane chemically bonded silica gel chromatographic column; gradient elution was performed using 0.1% formic acid as mobile phase a and acetonitrile as mobile phase B according to the following table; the flow rate is 1.0ml per minute; the detector is an evaporative light scattering detector; the column temperature was 30 ℃.
TABLE 1 gradient elution procedure
Example 1
Adding 10.00g of glycocholic acid crude product, 50mL of ethyl acetate, 5mL of ethanol and 25mL of water into a reaction bottle, starting stirring, heating to about 65 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 20 ℃. Filtering, washing with ethanol/water mixed solvent (1/3), and drying at 50deg.C to obtain 9.35g of glycocholic acid (white solid with purity of 99.55%, maximum single impurity of 0.12%, ethyl acetate residue of 0.01%, and undetected ethanol).
Example 2
Adding 10.00g of glycocholic acid crude product, 50mL of ethyl acetate, 10mL of ethanol and 50mL of water into a reaction bottle, starting stirring, heating to about 65 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 25 ℃. Filtering, washing with ethanol/water mixed solvent (1/3), and drying at 50deg.C to obtain 8.96g of glycocholic acid (white solid with purity of 99.42%, maximum single impurity of 0.16%, ethyl acetate residue of 0.01%, and undetected ethanol).
Example 3
Adding 10.00g of glycocholic acid crude product, 70mL of ethyl acetate, 5mL of ethanol and 70mL of water into a reaction bottle, starting stirring, heating to about 65 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 30 ℃. Filtering, washing with ethanol/water mixed solvent (1/3), and drying at 50deg.C to obtain 9.12g of glycocholic acid (white solid with purity of 99.52%, maximum single impurity of 0.15%, ethyl acetate residue of 0.01%, and undetected ethanol).
Example 4
Adding 10.00g of glycocholic acid crude product, 50mL of ethyl acetate, 5mL of methanol and 70mL of water into a reaction bottle, starting stirring, heating to about 65 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 20 ℃. Filtering, washing with a methanol/water mixed solvent (1/3), and drying at 50 ℃ to obtain 9.01g of glycocholic acid (the character is white solid, the purity is 99.39%, the maximum single impurity is 0.18%, the ethyl acetate residual quantity is 0.02%, and methanol is not detected).
Example 5
Adding 10.00g of glycocholic acid crude product, 30mL of methyl acetate, 10mL of isopropanol and 70mL of water into a reaction bottle, starting stirring, heating to about 65 ℃, stirring and dissolving; cooling, preserving heat at about 15 ℃ and crystallizing for 2 hours. Filtering, washing with isopropanol/water mixed solvent (1/3), and drying at 50deg.C to obtain 9.32g of glycocholic acid (white solid, purity 99.25%, maximum single impurity 0.20%, methyl acetate residue 0.01%, and undetected isopropanol).
Comparative example 1
Adding 10.00g of glycocholic acid crude product, 40mL of absolute ethyl alcohol and 20mL of ethyl acetate into a reaction bottle, starting stirring, heating to about 75 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 25 ℃. Filtering, washing with ethanol/ethyl acetate mixed solvent (1/1), and drying at 50deg.C to obtain glycocholic acid 9.51g (white solid with purity 98.97%, maximum single impurity 0.28%, and ethanol residue 9.91%).
Comparative example 2
Adding 10.00g of glycocholic acid crude product and 20mL of absolute ethyl alcohol into a reaction bottle, starting stirring, heating to about 75 ℃, and stirring for dissolution; 100mL of ethyl acetate was added; cooling, and preserving heat and crystallizing for 2 hours at about 25 ℃. Filtering, washing with ethanol/ethyl acetate mixed solvent (1/1), and drying at 50deg.C to obtain glycocholic acid 8.92g (white solid with purity 98.88%, maximum single impurity 0.30%, ethyl acetate residue 1.85%, and ethanol residue 0.66%).
Comparative example 3
Adding 10.00g of glycocholic acid crude product, 30mL of ethanol and 50mL of water into a reaction bottle, starting stirring, heating to about 75 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 25 ℃. Filtering, washing with ethanol/water mixed solvent (1/3), and drying at 50deg.C to obtain 9.06g of glycocholic acid (white solid with purity of 98.85%, maximum single impurity of 0.47%, and ethanol residue of 0.02%).
Comparative example 4
Adding 10.00g of glycocholic acid crude product, 50mL of acetone and 17mL of absolute ethyl alcohol into a reaction bottle, starting stirring, heating to about 60 ℃, stirring and dissolving; cooling, and preserving heat and crystallizing for 2 hours at about 25 ℃. Filtering, washing with acetone/ethanol mixed solvent (3/1), and drying at 50deg.C to obtain 6.73g of glycocholic acid (white solid with purity of 99.11%, maximum single impurity of 0.24%, and ethanol residue of 6.92%).
The product quality of the examples and comparative examples is shown in table 2.
Table 2 product quality of examples and comparative examples
| Sample source | Purity of | Maximum single impurity | Residual organic solvent | Yield is good |
| Example 1 | 99.55％ | 0.12％ | Ethyl acetate 0.01% | 93.5％ |
| Example 2 | 99.42％ | 0.16％ | Ethyl acetate 0.01% | 89.6％ |
| Example 3 | 99.52％ | 0.15％ | Ethyl acetate 0.01% | 91.2％ |
| Example 4 | 99.39％ | 0.18％ | Ethyl acetate 0.02% | 90.1％ |
| Example 5 | 99.25％ | 0.20％ | Methyl acetate 0.01% | 93.2％ |
| Comparative example 1 | 98.97％ | 0.28％ | Ethanol 9.91% | 95.1％ |
| Comparative example 2 | 98.88％ | 0.30％ | Ethyl acetate 1.85%, ethanol 0.66% | 89.2％ |
| Comparative example 3 | 98.85％ | 0.47％ | Ethanol 0.02% | 90.6％ |
| Comparative example 4 | 99.11％ | 0.24％ | Ethanol 6.92% | 67.3％ |
The above-described embodiments are provided to illustrate the gist of the present invention, but are not intended to limit the scope of the present invention. It will be understood by those skilled in the art that various modifications and equivalent substitutions may be made to the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention.
Claims (8)
1. A method for purifying glycocholic acid, which is characterized in that: the method comprises the following steps:
step 1), adding a glycocholic acid crude product into a mixed solvent of esters, alcohols and water, heating, stirring and dissolving to obtain a solution A;
and 2) cooling and crystallizing the solution A, filtering and drying to obtain glycocholic acid.
2. The method for purifying glycocholic acid according to claim 1, wherein: the ester solvent comprises any one or more of ethyl acetate, ethyl formate, methyl acetate and propyl acetate.
3. The method for purifying glycocholic acid according to claim 1, wherein: the alcohol solvent comprises any one or more of ethanol, methanol or isopropanol.
4. A process for the purification of glycocholic acid according to claims 1-3, characterized in that: the volume/mass ratio of the ester solvent to the glycocholic acid crude product is (3-7): 1, wherein the volume unit is milliliter, and the mass unit is g.
5. A process for the purification of glycocholic acid according to claims 1-3, characterized in that: the volume/mass ratio of the alcohol solvent to the glycocholic acid crude product is (0-2): 1, wherein the volume unit is milliliter, and the mass unit is g.
6. A process for the purification of glycocholic acid according to claims 1-3, characterized in that: the volume/mass ratio of the water to the glycocholic acid crude product is (2-10): 1, wherein the volume unit is milliliter, and the mass unit is g.
7. The method for purifying glycocholic acid according to claim 1, wherein: the ester solvent is ethyl acetate, and the alcohol solvent is ethanol.
8. The method for purifying glycocholic acid according to claim 1, wherein: the crystallization temperature in the step 2) is 5-40 ℃.
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