CN1563073A - Method for preparing enoxolone - Google Patents
Method for preparing enoxolone Download PDFInfo
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- CN1563073A CN1563073A CN 200410018838 CN200410018838A CN1563073A CN 1563073 A CN1563073 A CN 1563073A CN 200410018838 CN200410018838 CN 200410018838 CN 200410018838 A CN200410018838 A CN 200410018838A CN 1563073 A CN1563073 A CN 1563073A
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Abstract
The invention discloses a method for preparing glycyrrhetinic acid. It adopts the glycyrrhizic acid crude product as raw material, and utiizes the processes of ethyl alcohol extraction, using ammonia water to regulate pH value, concentrating and recovering ethyl alcohol, adding water to make dissolution, using ADS-10 macroporous adsorption resin to remove impurity component so as to purity the glycyrrhizic acid being in effluent of resin column, the making acid hydrolysis to obtain the glycyrrhetinic acid crude product, making further purification so as to obtain high-purity glycyrrhetinic acid. The advantage of said invention lies in that the glycyrrhizic acid with different purities can be used to prepare glycyrrhetinic acid, the purification of glycyrrhetinic acid has no need of column chromatography, and adopts the method for making respective extraction at twice by using organic solvent.
Description
Technical field
The present invention relates to a kind of preparation method of glycyrrhetinic acid.
Background technology
Radix Glycyrrhizae is a conventional Chinese medicine, is widely used in fields such as medicine, tobacco, food.It mainly contains the effective constituent Potenlini and has the effect of thyroliberin sample, can be used for detoxifcation, anti-inflammatory, antibechic, antitumor etc.The glucoside unit of Potenlini is a glycyrrhetinic acid, Potenlini through the hydrochloric acid in gastric juice hydrolysis or in liver GRD beta-glucuronidase be decomposed to form glycyrrhetinic acid, the pharmacological action of Potenlini comes down to the effectiveness of glycyrrhetinic acid; In recent years pharmacological research finds, the effect such as have anti-inflammatory, antiulcer agent, antianaphylaxis, antiviral, reducing blood-fat, antibechic, relieving asthma and eliminate the phlegm of Potenlini and glycyrrhetinic acid class medicine also can be used for preventing and treating diseases such as viral hepatitis, hyperlipidemia and cancer.China is the leading exporter of Radix Glycyrrhizae, carries out deep processing and the comprehensive utilization of Radix Glycyrrhizae, and is significant.
The method that in the past prepared glycyrrhetinic acid is a raw material with Glycyrrhizinic acid monopotassium salt or ammonium salt normally, through adding sulphuric acid hydrolysis, filters, and the glycyrrhetinic acid purity that obtains like this is very poor, and is difficult to purify with common recrystallization method; When Glycyrrhizinic acid monopotassium salt or ammonium salt hydrolysis prepare glycyrrhetinic acid,, be easy to take place isomerization reaction if hydrolysising condition control is bad.For example, detected 18 β-H, 18 α-H glycyrrhetinic acid after the bibliographical information hydrolysis, 18 β-H glycyrrhetinic acid methyl esters, glycyrrhetinic acid dewatered product and methyl esters thereof etc.This not only makes the glycyrrhetinic acid yield reduce, and separation difficulty.
People adopt chloroform to dissolve thick glycyrrhetinic acid more, through equipment and higher aluminum oxide or the polymeric amide adsorption chromatography column chromatography for separation of technical requirements, just can make pure glycyrrhetinic acid, the Technology complexity, and turnout also is restricted.
Developed enzymatic hydrolysis process afterwards, Potenlini can obtain pure glycyrrhetinic acid through enzymic hydrolysis.In addition, also available chemical process purifying liquorice hypo acid.After the Potenlini hydrolysis, first acetylize forms the acetylize glycyrrhetinic acid, and then hydrolysis deacetylate and prepare pure glycyrrhetinic acid, or allows it generate glycyrrhetinic acid methyl esters earlier, thereby and then obtains pure glycyrrhetinic acid through basic hydrolysis, acidifying.Though enzyme hydrolysis method and chemical purification method can obtain pure glycyrrhetinic acid, preparation condition and Technology are difficult for realizing industrialization.
Summary of the invention
Technical problem to be solved by this invention provides a kind of preparation and separation and purification method of high-purity liquorice hypo acid.The molecular formula of glycyrrhetinic acid is: C
30H
46O
4, molecular weight is 470, is prepared by the Potenlini hydrolysis, that is:
Potenlini (Glycyrrhizinic acid) glycyrrhetinic acid (Glycyrrtinic acid)
C
42H
62O
16?FW?822.92 C
30H
46O
4?FW?470.67
The present invention solves this technical problem the technical scheme that is adopted:
Present method is divided into two steps: the first step is removed impurity composition with the ADS-10 absorption with macroporous adsorbent resin and is come the thick Potenlini of purifying, its preparation technology is: with the ethanol heat of solution of Radix Glycyrrhizae crude extract, add ammoniacal liquor and transfer pH8-9, after concentrating recovery ethanol, residuum is dissolved in water, with the impurity composition in this solution usefulness ADS-10 macroporous adsorptive resins adsorbent solution, and water-soluble ammonium glycyrrhizunate is not by resin absorption, to adsorb effluent liquid and transfer pH 1-2 with hydrochloric acid, heating hydrolysis, after the solution cooling, the solids of separating out obtains thick glycyrrhetinic acid after filtering; Second step was the preparation of glycyrrhetinic acid and purifying, and its preparation technology is: with thick glycyrrhetinic acid organic solvent dissolution, leaching insoluble impurities, is the glycyrrhetinic acid sodium salt with buck with the glycyrrhetinic acid alkalization, makes it to separate with non-water-soluble impurity; Make it become the glycyrrhetinic acid that is dissolved in organic solvent with acidifying then, separate with water-soluble impurity, after twice such separation, the purity of glycyrrhetinic acid improves greatly.Behind twice recrystallization, can obtain purity again and be higher than 98% product.
The first step is taked different treatment processs respectively according to the Potenlini raw material of different purity.If adopt the lower glycyrrhizic acid inclusion compound of purity, just remove impurity with the ADS-10 absorption with macroporous adsorbent resin, make water-soluble Monoammonium glycyrrhizinate be able to purifying, promptly carry out acid hydrolysis without concentrating then, because glycyrrhetinic acid is water-soluble very poor, can in water, separate out, filter and obtain the glycyrrhetinic acid crude product.If adopt glycyrrhizic acid content high product such as monoammonium glycyrrhizinate or monopotassium salt, can take direct alcohol-water dissolution, the method for acid hydrolysis obtains thick glycyrrhetinic acid.
The invention has the beneficial effects as follows and can select for use the Potenlini of different purity to prepare glycyrrhetinic acid, the purifying of glycyrrhetinic acid adopts twice difference of organic solvent method of extraction not by column chromatography, and it is good to separate refining effect, and product purity can reach more than 98%.
Description of drawings
Fig. 1 is preparation technology's schematic flow sheet of glycyrrhetinic acid
Embodiment
Embodiment 1
Extracting liquorice acid crude (content about 40%) 40g, with 400ml alcohol heating for dissolving 4 hours, leach insoluble impurities, filtrate is transferred pH7-8 with strong aqua, recovery of alcohol distillation, residuum 300ml water dissolution is crossed ADS-10 macroporous adsorptive resins (50,50,50ml) three posts series connection absorption with this aqueous solution, use the water wash resin column, merge effluent liquid and water lotion, adding concentrated hydrochloric acid to the acid concentration of solution is 3%, and 200ml alcohol, reflux 6 hours, cold putting filtered the solids of separating out, water washing, dry, obtain the glycyrrhetinic acid crude product.Adsorb saturated resin column with ammoniacal liquor-ethanolic soln regeneration, wash the back resin column and can be used for down-circulation absorption.
The glycyrrhetinic acid crude product is further purified, and recrystallization can obtain pure glycyrrhetinic acid product 4.2g, purity 95% (HPLC method).
Embodiment 2
10g monoammonium glycyrrhizinate (content about 70%) adds water 100ml heating for dissolving, drips the 20ml concentrated hydrochloric acid, adds 70ml ethanol, stirring and refluxing reaction 6 hours, and cold putting filtered the solids of separating out, water washing, solids dries, and obtains the glycyrrhetinic acid crude product.Be further purified, and recrystallization can obtain pure glycyrrhetinic acid product 2.3g.Purity 96% (HPLC method).
Embodiment 3
100g Glycyrrhizinic acid monopotassium salt (content about 80%) after 500ml water heating for dissolving, adds 300ml alcohol, stir and drip 100ml concentrated hydrochloric acid, back flow reaction 6 hours, cold putting down, the solids that filtration is separated out, water washing, solids dissolves with the 400ml chloroform, and insoluble solids leaches, NaOH aqueous solution extraction secondary with 1mol/L, merge water, be neutralized to pH2-3, use chloroform extraction water secondary again with hydrochloric acid.Chloroform is washed mutually, concentrates, and the excess ethyl alcohol recrystallization obtains glycyrrhetinic acid product 22.3g purity 96%, behind the secondary recrystallization, obtains the 18.2g product.Purity 〉=98%.
Claims (4)
1. the preparation method of a glycyrrhetinic acid, this method is divided into two steps: the first step is removed impurity composition with the ADS-10 absorption with macroporous adsorbent resin and is come the thick Potenlini of purifying, its preparation technology is: with the ethanol heat of solution of Radix Glycyrrhizae crude extract, add ammoniacal liquor and transfer pH8-9, after concentrating recovery ethanol, residuum is dissolved in water, with the impurity composition in this solution usefulness ADS-10 macroporous adsorptive resins adsorbent solution, and water-soluble ammonium glycyrrhizunate is not by resin absorption, to adsorb effluent liquid and transfer pH1-2 with hydrochloric acid, heating hydrolysis, after the solution cooling, the solids of separating out obtains thick glycyrrhetinic acid after filtering; Second step was the preparation of glycyrrhetinic acid and purifying, and its preparation technology is: with thick glycyrrhetinic acid organic solvent dissolution, leaching insoluble impurities, is the glycyrrhetinic acid sodium salt with buck with the glycyrrhetinic acid alkalization, makes it to separate with non-water-soluble impurity; Make it become the glycyrrhetinic acid that is dissolved in organic solvent with acidifying then, separate with water-soluble impurity again,, behind twice recrystallization, can obtain purity again and be higher than 98% product by twice such separation.
2. the preparation method of a kind of glycyrrhetinic acid as claimed in claim 1, it is characterized in that: the first step is taked different treatment processs respectively according to the Potenlini raw material of different purity.
(1) with the lower glycyrrhizic acid inclusion compound of purity, just remove impurity with the ADS-10 absorption with macroporous adsorbent resin, make water-soluble Monoammonium glycyrrhizinate be able to purifying, promptly carry out acid hydrolysis without concentrating then, the glycyrrhetinic acid of separating out is filtered obtain the glycyrrhetinic acid crude product.
(2) if adopt glycyrrhizic acid content high product such as monoammonium glycyrrhizinate or monopotassium salt, can take a directly pure water dissolution, the method for acid hydrolysis obtains thick glycyrrhetinic acid.
3. the preparation method of a kind of glycyrrhetinic acid as claimed in claim 1 is characterized in that: twice difference of second step employing organic solvent method of extraction purifying liquorice hypo acid.
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| CN 200410018838 CN1257182C (en) | 2004-04-06 | 2004-04-06 | Method for preparing enoxolone |
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| CN 200410018838 CN1257182C (en) | 2004-04-06 | 2004-04-06 | Method for preparing enoxolone |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007041969A1 (en) * | 2005-10-14 | 2007-04-19 | Tianjin Institute Of Pharmaceutical Research | Glycyrrhetinic acid-30-amide derivatives and the uses thereof |
| CN100415766C (en) * | 2006-06-06 | 2008-09-03 | 南京工业大学 | Method for purifying glycyrrhetinic glycoside |
| CN101817867A (en) * | 2010-05-27 | 2010-09-01 | 高颖 | Method for preparing glycyrrhetinic acid |
| CN101838303A (en) * | 2010-06-07 | 2010-09-22 | 昆明理工大学 | Preparation method of glycyrrhetinic acid |
| CN102653550A (en) * | 2011-03-01 | 2012-09-05 | 广西壮族自治区药用植物园 | Preparation and application of glycyrrhetinic acid |
| CN102786573A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal B substance, its preparation method, and its applications in medicines and healthcare products |
| CN102786574A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal A substance, its preparation method, and its applications in medicines and healthcare products |
| CN103588849A (en) * | 2012-08-14 | 2014-02-19 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid |
| CN103788167A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid monoglucuronide (GAMG) |
| CN104829681A (en) * | 2015-05-08 | 2015-08-12 | 江苏天晟药业有限公司 | Method for purifying glycyrrhetinic acid |
| CN105693813A (en) * | 2016-03-15 | 2016-06-22 | 合肥华方医药科技有限公司 | Preparation and medical application of glycyrrhizic acid berberine coupling compound |
| CN107412319A (en) * | 2017-06-02 | 2017-12-01 | 新疆全泰兴药业科技有限公司 | A kind of efficiency reduces the method for glycyrrhizic acid and enoxolone in liquorice flavonoids compound |
| CN107531745A (en) * | 2015-05-19 | 2018-01-02 | 正大天晴药业集团股份有限公司 | A kind of new 18 α Enoxolone derivatives and its medical usage |
| CN110283225A (en) * | 2019-07-29 | 2019-09-27 | 洛阳蓝斯利科技有限公司 | A kind of preparation method of 24- hydroxyl-enoxolone |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106565817A (en) * | 2016-11-09 | 2017-04-19 | 深圳市新阳唯康科技有限公司 | Amorphous glycyrrhetinic acid and preparation method thereof |
| CN111171106A (en) * | 2020-02-19 | 2020-05-19 | 洛阳蓝斯利科技有限公司 | Preparation method of 24-hydroxystearyl glycyrrhetinate |
-
2004
- 2004-04-06 CN CN 200410018838 patent/CN1257182C/en not_active Expired - Fee Related
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7790759B2 (en) | 2005-10-14 | 2010-09-07 | Tianjin Institute Of Pharmaceutical Research | Glycyrrhetinic acid-30-amide derivatives and their use |
| WO2007041969A1 (en) * | 2005-10-14 | 2007-04-19 | Tianjin Institute Of Pharmaceutical Research | Glycyrrhetinic acid-30-amide derivatives and the uses thereof |
| CN100415766C (en) * | 2006-06-06 | 2008-09-03 | 南京工业大学 | Method for purifying glycyrrhetinic glycoside |
| CN101817867B (en) * | 2010-05-27 | 2012-12-05 | 高颖 | Method for preparing glycyrrhetinic acid |
| CN101817867A (en) * | 2010-05-27 | 2010-09-01 | 高颖 | Method for preparing glycyrrhetinic acid |
| CN101838303A (en) * | 2010-06-07 | 2010-09-22 | 昆明理工大学 | Preparation method of glycyrrhetinic acid |
| CN102653550A (en) * | 2011-03-01 | 2012-09-05 | 广西壮族自治区药用植物园 | Preparation and application of glycyrrhetinic acid |
| CN102786573B (en) * | 2011-05-17 | 2016-01-13 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal B-type material and preparation method and apply in medicine and healthcare products |
| CN102786574A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal A substance, its preparation method, and its applications in medicines and healthcare products |
| CN102786573A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal B substance, its preparation method, and its applications in medicines and healthcare products |
| CN103588849A (en) * | 2012-08-14 | 2014-02-19 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid |
| CN103788167A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid monoglucuronide (GAMG) |
| CN103788167B (en) * | 2012-10-31 | 2015-06-03 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid monoglucuronide (GAMG) |
| CN104829681A (en) * | 2015-05-08 | 2015-08-12 | 江苏天晟药业有限公司 | Method for purifying glycyrrhetinic acid |
| CN107531745A (en) * | 2015-05-19 | 2018-01-02 | 正大天晴药业集团股份有限公司 | A kind of new 18 α Enoxolone derivatives and its medical usage |
| CN105693813A (en) * | 2016-03-15 | 2016-06-22 | 合肥华方医药科技有限公司 | Preparation and medical application of glycyrrhizic acid berberine coupling compound |
| CN107412319A (en) * | 2017-06-02 | 2017-12-01 | 新疆全泰兴药业科技有限公司 | A kind of efficiency reduces the method for glycyrrhizic acid and enoxolone in liquorice flavonoids compound |
| CN110283225A (en) * | 2019-07-29 | 2019-09-27 | 洛阳蓝斯利科技有限公司 | A kind of preparation method of 24- hydroxyl-enoxolone |
| CN110283225B (en) * | 2019-07-29 | 2021-02-02 | 洛阳蓝斯利科技有限公司 | Preparation method of 24-hydroxy-glycyrrhetinic acid |
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|---|---|
| CN1257182C (en) | 2006-05-24 |
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