CN113004366A - Novel method for producing diammonium glycyrrhizinate - Google Patents
Novel method for producing diammonium glycyrrhizinate Download PDFInfo
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- CN113004366A CN113004366A CN202110246748.XA CN202110246748A CN113004366A CN 113004366 A CN113004366 A CN 113004366A CN 202110246748 A CN202110246748 A CN 202110246748A CN 113004366 A CN113004366 A CN 113004366A
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- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
Abstract
The invention discloses a new method for producing diammonium glycyrrhizinate, which comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization; wherein in the first step, glycyrrhizic acid A is used as a preparation raw material, and is mixed with sodium hydroxide for heating reflux reaction, the heating temperature is controlled to be 90 ℃, and the reflux reaction is carried out for 12 hours; in the second step, the solution after the reflux reaction is cooled to 0 ℃, hydrochloric acid solution is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled to be not more than 4 ℃ in the dripping process of hydrochloric acid, and when white crystals are separated out, the solution is subjected to heat preservation for 1h and is filtered to obtain white solid; the new method for producing diammonium glycyrrhizinate has the advantages of simple preparation process, easy operation, suitability for industrial production, mild reaction conditions, high conversion rate, easy quality control, good color and shape of products, high yield, high purity, energy conservation and environmental protection in the preparation process.
Description
Technical Field
The invention relates to the technical field of compound preparation, in particular to a novel method for producing diammonium glycyrrhizinate.
Background
Diammonium glycyrrhizinate, white crystalline powder. No odor, sweet taste, and has strong antiinflammatory, liver cell membrane protecting and liver function improving effects. Prevent serum ALT increase caused by ammonium galactoside and carbon tetrachloride, and improve liver tissue damage. Has become a novel medicine for protecting the liver. The glycyrrhizic acid exists in two configurations of 18 alpha-H body and 18 beta-H body, the alpha body has stronger anti-inflammatory action than the beta body, the liver targeting property is high, the adverse reaction is small, the safety is strong, and the glycyrrhizic acid is more suitable for treating clinical liver diseases.
The existing synthesis method of diammonium glycyrrhizinate generally extracts glycyrrhizic acid from liquorice by using a solvent and then synthesizes the glycyrrhizic acid, and the method has the advantages of longer synthesis step, higher cost, need of using a large amount of solvent, no environmental pollution caused by the used solvent and lower content of the obtained product. In addition, the synthesis of diammonium glycyrrhizinate by using monoammonium glycyrrhizinate as a raw material is reported in documents, but the defects of high loss rate, low yield and n-butanol solvent residue caused by extracting effective components by n-butanol exist.
Disclosure of Invention
The invention aims to provide a new method for producing diammonium glycyrrhizinate, which aims to solve the problems in the background technology.
In order to solve the technical problems, the invention provides the following technical scheme: a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
wherein in the first step, glycyrrhizic acid A is used as a preparation raw material, and is mixed with sodium hydroxide for heating reflux reaction, the heating temperature is controlled to be 90 ℃, and the reflux reaction is carried out for 12 hours;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, hydrochloric acid solution is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled to be not more than 4 ℃ in the dripping process of hydrochloric acid, and when white crystals are separated out, the solution is subjected to heat preservation for 1h and is filtered to obtain white solid;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method is to recrystallize the obtained product by acid or alcohol.
According to the technical scheme, in the second step, after filtration, the obtained white solid is washed more than once by hydrochloric acid aqueous solution with the pH value of 1-2.
According to the technical scheme, in the fourth step, the recrystallization method comprises the steps of heating the acid or the alcohol, adding the substances obtained in the third step, heating and refluxing, adding activated carbon for decoloring, filtering, standing and crystallizing filtrate after the solution is clear, and recrystallizing for multiple times.
According to the technical scheme, in the fourth step, the acid used for recrystallizing the acid or the alcohol is acetic acid, and the concentration of the acetic acid is 80-85%; the alcohol is ethanol with the concentration of 75-80%.
Compared with the prior art, the invention has the following beneficial effects: the novel method for producing diammonium glycyrrhizinate has the advantages of novel preparation process, simple and convenient operation, energy conservation, environmental protection and strong practicability; meanwhile, in the preparation process, the reaction condition is mild, the conversion rate is high, and the quality is easy to control; the method has the advantages of reducing the use of other solvents, reducing the introduction of impurities, better color, convenient operation process, low equipment and material cost, high processing capacity, good product chromaticity, high yield and content, suitability for industrial mass production, good product color, uniform crystal and good quality.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:
FIG. 1 is a flow chart of the method of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, 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.
Referring to fig. 1, the present invention provides a technical solution:
example 1:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 25%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, hydrochloric acid solution with the concentration of 40% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid aqueous solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the step of carrying out acid recrystallization on the obtained product, wherein the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into acetic acid with the concentration of 85%, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and carrying out recrystallization for multiple times.
Example 2:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 25%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, hydrochloric acid solution with the concentration of 40% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid aqueous solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the steps of carrying out alcohol recrystallization on the obtained product, and the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into 80% ethanol, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing and crystallizing the filtrate, and carrying out recrystallization for multiple times.
Example 3:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 30%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, a hydrochloric acid solution with the concentration of 30% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the step of carrying out acid recrystallization on the obtained product, wherein the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into acetic acid with the concentration of 80%, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and carrying out recrystallization for multiple times.
Example 4:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 30%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, a hydrochloric acid solution with the concentration of 30% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the steps of carrying out alcohol recrystallization on the obtained product, and the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into 75% ethanol, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and carrying out recrystallization for multiple times.
Example 5:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 30%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, a hydrochloric acid solution with the concentration of 30% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the step of carrying out acid recrystallization on the obtained product, wherein the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into acetic acid with the concentration of 80%, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and carrying out recrystallization for multiple times.
Example 6:
a new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization;
in the first step, the glycyrrhizic acid A is used as a preparation raw material, 300 parts by weight of glycyrrhizic acid A and 1500 parts by weight of sodium hydroxide are selected to be mixed, heated and subjected to reflux reaction, the heating temperature is controlled to be 90 ℃, the reflux reaction is carried out for 12 hours, and the concentration of the sodium hydroxide is 30%;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, a hydrochloric acid solution with the concentration of 30% is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled not to exceed 4 ℃ in the dripping process of hydrochloric acid, when white crystals are separated out, the temperature is kept for 1h, filtration is carried out to obtain white solids, and after filtration, the obtained white solids are washed twice by the hydrochloric acid solution with the pH value of 1-2;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method comprises the steps of carrying out alcohol recrystallization on the obtained product, and the recrystallization method comprises the steps of adding diammonium glycyrrhizinate into 75% ethanol, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and carrying out recrystallization for multiple times.
The diammonium glycyrrhizinate refined salts obtained in the above embodiments are respectively detected, and the obtained results are as follows:
precision of diammonium glycyrrhizinate refined salt | |
Example 1 | 98.5% |
Example 2 | 99.4% |
Example 3 | 98.5% |
Example 4 | 99.4% |
Example 5 | 98.8% |
Example 6 | 99.6% |
Based on the above, the invention has the advantages of novel preparation process, simple and convenient operation, energy saving, environmental protection and strong practicability; meanwhile, in the preparation process, the reaction condition is mild, the conversion rate is high, and the quality is easy to control; the method has the advantages of reducing the use of other solvents, reducing the introduction of impurities, improving the precision of the diammonium glycyrrhizinate refined salt, along with convenient working procedures, low equipment and material cost, high treatment capacity, good product chromaticity, high yield and content, contribution to industrial mass production, excellent product color and luster, uniform crystals and good quality.
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (4)
1. A new method for producing diammonium glycyrrhizinate comprises the following steps: step one, heating and refluxing; step two, stirring and filtering; step three, adding and dissolving; step four, recrystallization; the method is characterized in that:
wherein in the first step, glycyrrhizic acid A is used as a preparation raw material, and is mixed with sodium hydroxide for heating reflux reaction, the heating temperature is controlled to be 90 ℃, and the reflux reaction is carried out for 12 hours;
in the second step, the solution after the reflux reaction is cooled to 0 ℃, hydrochloric acid solution is added while slowly stirring to adjust the pH value to 1-2, the temperature is controlled to be not more than 4 ℃ in the dripping process of hydrochloric acid, and when white crystals are separated out, the solution is subjected to heat preservation for 1h and is filtered to obtain white solid;
dissolving the white solid obtained in the step two in absolute ethyl alcohol, adding ammonia water, adjusting the pH value to 7.0-8.0 to generate diammonium glycyrrhizinate, stirring the ammonia water and ammonium chloride at 50 ℃ for 30min, and cooling to 10-15 ℃;
in the fourth step, diammonium glycyrrhizinate refined salt is obtained by separating the substances obtained in the third step; and the separation method is to recrystallize the obtained product by acid or alcohol.
2. The novel method for producing diammonium glycyrrhizinate according to claim 1, wherein: in the second step, after filtration, the obtained white solid is washed more than once with an aqueous hydrochloric acid solution having a pH of 1 to 2.
3. The novel method for producing diammonium glycyrrhizinate according to claim 1, wherein: in the fourth step, the recrystallization method comprises the steps of heating the acid or the alcohol, adding the substances obtained in the third step, heating and refluxing, adding activated carbon for decolorization after the solution is clear, filtering, standing the filtrate for crystallization, and recrystallizing for multiple times.
4. The novel method for producing diammonium glycyrrhizinate according to claim 1, wherein: in the fourth step, the acid used for recrystallizing the acid or the alcohol is acetic acid, and the concentration of the acetic acid is 80-85 percent; the alcohol is ethanol with the concentration of 75-80%.
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CN114409720A (en) * | 2021-12-31 | 2022-04-29 | 江苏天晟药业股份有限公司 | Method for improving large production content of diammonium glycyrrhizinate |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104861029A (en) * | 2015-01-30 | 2015-08-26 | 李玉山 | Preparation method of ammonium 18alpha,beta-H-glycyrrhetate and hydrate thereof |
CN106478762A (en) * | 2016-08-29 | 2017-03-08 | 江苏天晟药业股份有限公司 | A kind of preparation method of diammonium glycyrhetate |
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CN104861029A (en) * | 2015-01-30 | 2015-08-26 | 李玉山 | Preparation method of ammonium 18alpha,beta-H-glycyrrhetate and hydrate thereof |
CN106478762A (en) * | 2016-08-29 | 2017-03-08 | 江苏天晟药业股份有限公司 | A kind of preparation method of diammonium glycyrhetate |
Cited By (2)
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CN114409720A (en) * | 2021-12-31 | 2022-04-29 | 江苏天晟药业股份有限公司 | Method for improving large production content of diammonium glycyrrhizinate |
CN114409720B (en) * | 2021-12-31 | 2023-12-29 | 江苏天晟药业股份有限公司 | Method for improving large-scale production content of diammonium glycyrrhizinate |
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