CN114073721B - Preparation and application of vinegar-soaked licorice tablets - Google Patents
Preparation and application of vinegar-soaked licorice tablets Download PDFInfo
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- CN114073721B CN114073721B CN202010811868.5A CN202010811868A CN114073721B CN 114073721 B CN114073721 B CN 114073721B CN 202010811868 A CN202010811868 A CN 202010811868A CN 114073721 B CN114073721 B CN 114073721B
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- vinegar
- licorice
- soaked
- liver
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Abstract
The application provides a preparation method and an application method of vinegar-soaked licorice, wherein the preparation method of the vinegar-soaked licorice comprises the following steps: soaking Glycyrrhrizae radix tablet in ammonia water to obtain Glycyrrhrizae radix; soaking Glycyrrhrizae radix in acetic acid solution to obtain vinegar Glycyrrhrizae radix; and (3) steaming and boiling the vinegar licorice under high pressure, and drying to obtain a vinegar-soaked licorice finished product. The vinegar-soaked licorice of the application is used for treating viral hepatitis and liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, liver fibrosis, liver cirrhosis, liver cancer and liver failure. The preparation method of the vinegar-soaked licorice tablet provided by the application has the advantages of short preparation period and high efficiency, and meanwhile, the content of the effective component 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid in the vinegar-soaked licorice is high, so that the vinegar-soaked licorice tablet has a remarkable curative effect on liver diseases.
Description
Technical Field
The application belongs to the technical field of medical medicines, and particularly relates to a vinegar-soaked licorice tablet and application thereof.
Background
According to the ancient medical records, licorice root, radix Glycyrrhizae "is soaked in children's feces and vacuoles for several days, dried in the air, soaked in vinegar, wrapped with several layers of paper, and dried by slow stewing in fire, and soaked for seven times. This is a licorice processing method that has been repeatedly experienced and summarized for liver disease in ancient medical practice. It appears that this is a rational and difficult experience, and it is also difficult to specify a finished product to be roasted. Only has the advantages of complex operation, overlong period and difficult mass production.
Liver injury and liver fibrosis are common clinical diseases. In recent years, the incidence of diseases is on the rise, and lesions are the active matrix proliferation process. On the pathological mechanism, the cytologic basis for elucidating hepatic fibrosis formation is the activation of hepatic stellate cells, the biochemical basis is the imbalance of extracellular matrix (ECM) component metabolism in liver tissue, leading to greater than degradation. Therapeutically, liver fibrosis and a degree of cirrhosis are both confirmed to be reversible, but so far there is a clinical lack of biological or chemical drugs. Traditional national medicine based on theoretical guidance of diagnosis and treatment has unique knowledge on liver fibrosis in long-term practice, and new anti-liver fibrosis traditional Chinese medicine capsules (tablets) for strengthening body resistance and removing blood stasis, turtle shell liver-softening tablets and the like are also appeared in recent years; although no new medicine exists in the traditional Mongolian medicine, the clinical treatment has good effect. It appears in the industry that the study of anti-hepatic fibrosis is an important issue in the future.
Disclosure of Invention
The embodiment of the application aims to provide a preparation method of vinegar-soaked licorice tablets, which aims to solve the technical problems of complex preparation process and long preparation period of vinegar-soaked licorice in the prior art.
In order to achieve the above purpose, the application adopts the following technical scheme: the preparation method of the vinegar-soaked licorice tablets comprises the following steps:
soaking Glycyrrhrizae radix tablet in ammonia water to obtain Glycyrrhrizae radix;
soaking Glycyrrhrizae radix in acetic acid solution to obtain vinegar Glycyrrhrizae radix;
steaming and drying the vinegar-soaked licorice to obtain a vinegar-soaked licorice finished product.
Optionally, the step of soaking the licorice sheet in ammonia water to obtain the urinary licorice comprises the following steps:
heating Glycyrrhrizae radix tablet in ammonia water at 50-60deg.C for two hours;
soaking the heated Glycyrrhrizae radix tablet in a closed environment for 24-72 hr;
and drying the soaked licorice slices to obtain the urinary licorice.
Optionally, the mass fraction of ammonia in the aqueous ammonia is 0.1% -1%.
Optionally, the acetic acid solution is a ninety-aromatic ester vinegar.
Optionally, the concentration of acetic acid in the Jiuqu ester vinegar is at least 10g/100mL.
Optionally, preparation of vinegar licorice is added according to a ratio of 1Kg licorice to 1L acetic acid.
Optionally, the step of soaking the Glycyrrhiza uralensis Fisch in acetic acid solution is performed with sealing.
Optionally, the temperature of the cooking is: 100-140 ℃.
Optionally, in the drying step, the drying temperature is 50-60 ℃ and the drying time is 1-3 hours.
In another aspect, the application provides a method of using the vinegar-soaked licorice tablets for treating viral hepatitis and liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, liver fibrosis, cirrhosis and liver cancer, and liver failure.
The preparation and application methods of the vinegar-soaked licorice provided by the application have the beneficial effects that: compared with the prior art, the vinegar-soaked licorice prepared by the method has the advantages of short preparation period and high efficiency, and meanwhile, the content of the effective component 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid in the vinegar-soaked licorice is high, so that the vinegar-soaked licorice has remarkable curative effect on liver diseases.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the embodiments or the description of the prior art will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic flow chart of a preparation method of vinegar-soaked licorice according to an embodiment of the present application;
FIG. 2 shows the effect of vinegar-soaked licorice on important markers such as serum P III P, LN, HA, etc. of rat liver fibrosis model in the example of the present application.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved more clear, the application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the application.
The embodiment of the application aims to provide a preparation method of vinegar-soaked licorice tablets, which aims to solve the technical problems of complex preparation process and long preparation period of vinegar-soaked licorice in the prior art.
In order to achieve the above purpose, the application adopts the following technical scheme: the preparation method of the vinegar-soaked licorice tablets comprises the following steps:
soaking Glycyrrhrizae radix tablet in ammonia water to obtain Glycyrrhrizae radix;
soaking Glycyrrhrizae radix in acetic acid solution to obtain vinegar Glycyrrhrizae radix;
steaming and drying the vinegar-soaked licorice to obtain a vinegar-soaked licorice finished product. If the liquorice tablets can be soaked in ammonia water, the liquorice tablets can be placed in a closed container with a plug for soaking to obtain the liquorice; the cooking may be performed using an atmospheric cooking device such as a steamer or a high-pressure device such as a pressure cooker. When high pressure equipment is used, as the cooking temperature is increased, the pressure within the equipment increases accordingly. By adopting the technical scheme, the preparation process of the vinegar-soaked licorice can be simplified, the preparation period is shortened, the hydrolysis rate of the glycyrrhizic acid is improved, the content of 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-carboxylic acid in the medicine is improved, and the treatment effect of liver diseases is improved.
Further, the step of soaking the licorice tablet in ammonia water to obtain urinary licorice, wherein the soaking comprises the following steps:
heating Glycyrrhrizae radix tablet in ammonia water at 50-60deg.C for two hours;
soaking the heated Glycyrrhrizae radix tablet in a closed environment for 24-72 hr;
and drying the soaked licorice slices to obtain the urinary licorice.
Through the technical scheme, the liquorice is heated at a proper temperature, and the reaction speed of the liquorice and ammonia water is effectively improved by means of stewing, soaking and the like, so that the production efficiency of the liquorice is improved.
Further, the mass fraction of ammonia in the ammonia water is 0.1% -1%. The ammonia water content of 1% can better promote the absorption of ammonia by the vinegar-soaked licorice tablets.
Further, the step of immersing the liquorice in an acetic acid solution to obtain the liquorice vinegar, wherein the acetic acid solution is the nine-yeast fragrant ester vinegar.
Further, the concentration of acetic acid in the Jiuquxiang ester vinegar is 10g/100mL at minimum. The concentration of the acetic acid is 10g/100mL, so that the reaction efficiency and the reaction speed of the acetic acid and the Glycyrrhiza uralensis can be ensured to be maximized.
Further, preparation of vinegar licorice was added at a ratio of 1Kg licorice to 1L acetic acid. It is understood that when the mass of the prepared licorice is 100g, the addition amount of acetic acid is 100mL; when the mass of the liquorice is 500g, the adding amount of the acetic acid is 500mL; when the quality of the liquorice is changed, the liquorice is added according to the proportion. The ratio ensures the effective amount of acetic acid in the dosage of the vinegar-soaked licorice, and simultaneously ensures that the pH value of the vinegar-soaked licorice in the processing process maintains a weak acidic environment (pH value of 3+/-0.5) so as to ensure the smooth realization of the processing effect.
Further, the step of soaking the liquorice in acetic acid solution to obtain the liquorice with vinegar, and sealing the soaking process. If the liquorice can be placed in a closed container for soaking, the closed environment can reduce the volatilization of acetic acid, and the reaction efficiency between the liquorice and the acetic acid is improved.
Further, the cooking temperature is: 100-140 ℃. The high-pressure equipment is adopted for the stewing, so that the reaction efficiency of acetic acid and the urinary licorice can be effectively improved.
Further, in the drying step, the drying temperature is 50-60 ℃ and the drying time is 1-3 hours. Through the technical scheme, redundant water in the vinegar-soaked licorice tablets is removed, the content of active ingredients is improved, and meanwhile, the vinegar-soaked licorice tablets are convenient to package and take.
The vinegar-soaked Glycyrrhrizae radix tablet in this embodiment can be used for treating viral hepatitis and its liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, liver fibrosis, liver cirrhosis, liver cancer, and liver failure.
The preparation and application methods of the vinegar-soaked licorice provided by the application have the beneficial effects that: compared with the prior art, the vinegar-soaked licorice prepared by the method has the advantages of short preparation period and high efficiency, and meanwhile, the content of the effective component 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid in the vinegar-soaked licorice is high, so that the vinegar-soaked licorice has remarkable curative effect on liver diseases.
Example 1
First, referring to FIG. 1, the vinegar-soaked licorice tablets of the present application were prepared according to the following steps,
1) Slicing Glycyrrhrizae radix to give slices with thicknessPreparing Glycyrrhrizae radix tablet, removing impurities, cleaning, heating with 1% ammonia water at 55deg.C for 2 hr, soaking for 48 hr, and oven drying at 55-60deg.C to obtain Glycyrrhrizae radix;
2) Taking a urine licorice tablet, placing the urine licorice tablet into a container with a plug, and adding nine-yeast fragrant ester vinegar (obtained from Dade brewing company) according to the dry product; the total acid (calculated by acetic acid)/(g/100 mL) is equal to or more than 10 (weight to volume ratio), and the mixture is plugged and stewed for 24 hours, so that the vinegar liquid is basically absorbed into the medicinal materials, and the vinegar-soaked licorice wet product is prepared;
3) Taking wet product of radix Glycyrrhrizae immersed with vinegar, transferring to a high pressure steaming device while wet, heating at 120deg.C for 20 hr, and drying at below 60deg.C to obtain final product of radix Glycyrrhrizae immersed with vinegar.
The processing of vinegar-soaked licorice tablets in this embodiment has the function and principle of:
the main active ingredient of Glycyrrhrizae radix is glycyrrhizic acid (glycyrrhizin). After oral administration, glycyrrhizic acid is absorbed into blood, discharged from bile into intestinal tract in original form, part of glycyrrhizic acid is excreted (bioavailability is reduced), part of glycyrrhizic acid is hydrolyzed by intestinal bacteria to generate 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid, and the substance enters liver again through intestinal liver circulation to exert drug effect. In view of the fact that intestinal flora of most liver disease patients is disturbed, and glycyrrhizic acid cannot be hydrolyzed normally due to the disorder of intestinal flora, it is generally suggested to use 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid to replace glycyrrhizic acid for treating gastrointestinal diseases, complicated with hepatitis and liver cirrhosis diseases in clinic.
The key principle of the processing method is that glycyrrhizic acid in liquorice is hydrolyzed into 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid. Through measurement, if the processing process is strictly standardized, the hydrolysis rate of glycyrrhizic acid in liquorice can reach more than 50%. Therefore, the quality control content measurement of the vinegar-soaked liquorice takes 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid as an index. This is where the Mongolian medicine is to prepare the mysterious licorice root.
The clinical application method of the vinegar-soaked licorice adopts a single decoction piece to prepare a solid preparation for taking, or the solid preparation is prepared by preparing a prescription with other medicines, or the solid preparation can be prepared by adding a proper amount of the prescription into the prescription in a mode of adding the medicines.
The vinegar-soaked licorice decoction pieces are applied to clinic for decades, treat hundreds of hepatopathy and liver cirrhosis patients, have satisfactory curative effects, and exert considerable social and economic benefits. Is an extremely important agent in Mongolian medicine decoction pieces for treating liver diseases, and is always inherited by teachers and students.
Pharmacological experiments are carried out by using the vinegar-soaked licorice in the embodiment, and the specific experimental process is as follows:
1. modeling (carbon tetrachloride-induced liver fibrosis model): male SD rat (180-220 g) is subcutaneously injected with 40-60% CCl 4 Olive oil solution 1ml kg -1 0.3ml/100g body weight, doubling the initial dose, molding for 4 weeks 2 times per week,
2. the experimental method comprises the following steps: the experimental animals are divided into a blank group, a model group, a positive group (colchicine 1.5 mg/kg) and a dosing group (low dose 0.6g/kg and high dose 1.2 g/kg), 10 mice are continuously fed by stomach for 4 weeks, SPF feed is fed by free diet and drinking water, the feeding humidity is 45% -70%, the temperature is 18-26 ℃, and the feeding is carried out for 12 hours each day by stomach feeding for 1 time each day.
3. Detecting the index: alanine transferase (ALT), glutamic-oxaloacetic transaminase (AST), type III procollagen peptide (PILP), hyaluronic Acid (HA), laminin (LN) in rat serum, pathological tissue HE staining to evaluate the effectiveness of vinegar-soaked licorice pieces against liver fibrosis.
The test results are shown in Table 1, table 2 and FIG. 2, and Table 1 shows the pair CCl of vinegar-soaked licorice 4 Effects of liver fibrosis on serum ALT and AST activity (x+ -s).
TABLE 1
| Group of | Dosage (x/kg) | Animals (only) | ALT/(U·L -1 ) | AST/(U·L -1 ) |
| Blank space | - | 10 | 80.54±4.46 | 98.83±9.56 |
| Model | - | 10 | 170.12±11.6* | 175.26±10.8* |
| Positive and negative | 1.5mg | 11 | 90.91±18.55 ▲ | 101.05±17.3 ▲ |
| Low agent | 0.6g | 10 | 130.01±24.48 ▲ | 132.65±21.5 ▲ |
| High agent | 1.2g | 10 | 155.97±15.69 ▲## | 151.06±13.5 ▲ |
Referring to Table 2 in combination, the effect of vinegar-soaked licorice on CCl 4-induced liver fibrosis rat serum PIIIP, LN, HA (x.+ -.s).
TABLE 2
As can be seen from tables 1 and 2, there was a significant difference compared to the blank group; is significantly different from the model set. The vinegar-soaked licorice in the embodiment has obvious curative effect on liver fibrosis of mice.
The main pharmacodynamic experiments prove that: (1) the vinegar-soaked licorice (prepared into capsules-the same applies below) has a preventive effect on acute liver injury. Can resist CCl after being administered by stomach (2.5 g/kg.d) for one week 4 The liver injury of mice caused by the method can obviously reduce serum ALT and AST levels (P<0.05～P<0.01 A) is provided; (2) the MDA content of liver tissues is obviously increased, the activities of CAT and SOD of the liver tissues are improved, and the aging necrosis of liver cells is effectively protected; (3) causing acute CCl 4 Liver injury model mice had liver lobular structures that were mostly restored to integrity compared to the placebo group. The HE-stained liver tissue is analyzed under a microscope, the liver lobule structure is complete and clear, the liver lobule structure is arranged in a radial way from the strip shape to the periphery, no steatosis and necrosis exist, no obvious inflammatory cell infiltration exists in a manifold area, and the nuclear cytoplasm is uniformly distributed; (4) serum important marker P III P content elevation (P) of significant resistance SD rat liver fibrosis model<0.05 A) is provided; resistance to synthesis or elevation of LN (laminin); reducing the elevation of HA, thereby effectively preventing or reversing the fibrotic progression of liver tissue; (5) the acute toxicity experiment shows that the daily oral maximum tolerance of the mice is 60g/kg body weight, which is 600 times of the daily dosage of the clinical adults, and the administration is quite safe.
Furthermore, we firstly carry out control observation of vinegar-soaked licorice capsules (vinegar-soaked licorice powder is filled into hollow capsules, and the dosage of the vinegar-soaked licorice powder is 0.5g per 1 capsule, 4 capsules are taken once, 3 times a day and before meals) for treating liver cirrhosis after hepatitis, and find that the vinegar-soaked licorice capsule can improve liver functions of patients, regulate abnormal immune functions, reduce serum liver fibrosis marker levels and the like, and has good comprehensive curative effects. Then we developed a 6 month treatment clinical observation of a total of 61 cases (in treatment group 33, control group 28) by using a method of randomized, drug (and luo shu gan capsule) parallel control. The curative effect and safety of the vinegar-soaked licorice on resisting liver fibrosis are comprehensively evaluated by using serum liver fibrosis chemical indexes and liver functions.
The pharmacodynamic experimental research results strongly support the treatment of liver diseases, hepatic fibrosis and liver cirrhosis diseases, and also verify the scientificity and processing effectiveness of the method and the medication safety.
Example 2
Preferably, in the embodiment, a proper amount of liquorice is taken, ammonia water with the mass fraction of 1.2% is added, and the mixture is placed into a closed container for soaking for 48 hours, so as to obtain the urinary liquorice. Slicing Glycyrrhrizae radix, and drying at 55deg.C to obtain Glycyrrhrizae radix tablet. Adding vinegar for stewing, wherein the vinegar is selected from Jiuqu ester vinegar produced by Dade brewing company, the pH is 2.5, and the stewing time is 24 hours, so as to obtain wet product of vinegar-soaked Glycyrrhrizae radix. Adding wet vinegar-soaked Glycyrrhrizae radix into a digester, steaming at 120deg.C for 20 hr to obtain final product.
Directly crushing the prepared vinegar-soaked licorice finished product to obtain vinegar-soaked licorice granules, crushing the vinegar-soaked licorice finished product to obtain vinegar-soaked licorice coarse powder, and crushing the vinegar-soaked licorice finished product to obtain vinegar-soaked licorice powder. In daily treatment, vinegar-soaked licorice with different particle sizes is selected for treatment according to different conditions of patients.
Example 3
The embodiment adopts the external liquorice as the raw material for preparation, the external liquorice is provided by Humulus brocade medicinal material company of Erdos, and is identified by Mongolian medicine inspection institute, belonging to the dry root and rhizome of the leguminous plant Glycyrrhiza uralensis Fisch carried in 2015 of the pharmacopoeia of the people's republic of China. Glycyrrhetinic acid reference, lot No. 110723-201615, national institute of pharmaceutical and biological products; ammonium glycyrrhizate reference substance, lot number 18053006; glycyrrhizin control lot 111610-201908; glycyrrhrizae radix control materials, batch No. 120904-201620, are provided by China medicine biological product inspection institute.
According to the records of medical books, liquorice is soaked in the urina hominis. It is often the case that urina hominis liquid is used as an adjuvant in the preparation of Mongolian medicinal materials. The main reason is that fresh urinate liquid is slightly alkaline initially, and alkaline solution can be used for replacing urinate in modern mass production. For scale development, the children's excrement liquid is replaced by dilute ammonia water. The repeated test determines the proper concentration, soaking mode, time and other factors of the dilute ammonia water, and the original traditional processing purpose can be completely achieved after test substitution.
The medical book further describes that the infiltrated licorice root medicinal material is roasted and dried slowly in fire. Such conventional processes are difficult to implement in modern production and life. The basic principle is as follows: slowly heating to a high temperature and the materials cannot be burnt. In the development process of the application, various methods such as baking, steaming and boiling are adopted for test comparison, and finally, the steaming and boiling method is selected. And simultaneously, the proper temperature, pressure and cooking mode and time are found out through parallel comparison research. The modern improved processing method is tested to shorten the 21-day period of the traditional method to 5 days, and the method can be used for large-scale production, the processing principle is not changed, and the drug effect is further improved.
Taking the content of 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid as a investigation index, and selecting the soaking time of ammonia water, the vinegar soaking time, the steaming time and the temperature as investigation factors to carry out L 9 (3 4 ) Four factors three horizontal orthogonal preference.
Table 3 is a factor level design table, which shows the factors that have a major effect on the efficacy of the present application during development. Table 4 is an analysis table of orthogonal experimental designs and their results.
TABLE 3 Table 3
TABLE 4 Table 4
The test results show that: the order of influencing the content of 12-ene-3 beta-hydroxy-11-one-oleanane-20 beta-carboxylic acid in four factors is the steaming time (B)>Heating temperature (A)>Time of soaking in dilute ammonia (C)>Vinegar immersion time (D). Optimum condition is A 3 B 2 C 3 D 2 Soaking in dilute ammonia water for 48 hours, drying, soaking in edible vinegar for 24 hours, and steaming at 120 ℃ for 20 hours when the edible vinegar is wet.
Proved by verification tests, the average content of 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid can reach 2.449 percent, which is close to 2.5 percent.
The medicine establishes a relatively advanced quality standard in the research process of the application. In the identification item, the new 18-methyl-12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid and the original glycyrrhizic acid which are generated by processing the liquorice, and the liquorice is used for controlling medicinal materials to establish a thin-layer chromatography identification method, so that the identification method has the advantages of extremely high specificity, simplicity, practicability and easiness. The inspection items define the items moisture, total ash, etc. The content measurement item is characterized in that 18-methyl-12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid is singly measured by a high performance liquid phase measurement method, and the sum of the glycyrrhizic acid and the 18-methyl-12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid is measured and limited. Thus, not only ensuring excellent quality control of licorice and limiting the minimum processing effect, but also encouraging more conversion of glycyrrhizic acid into 18-methyl-12-ene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid. The standard rechecks the development requirement of science and technology, and has high precision and good accuracy. The quality of the medicine is controllable, the property is stable, the medicine is safe to take, and the curative effect is reliable; so as to improve the innovation and high-tech content.
Example 4
In this example, the preparation method of the present application was used to prepare vinegar-soaked licorice, and the content of the active ingredient 18-methyl-12-en-3 beta-hydroxy-11-one-oleanane-20 beta-carboxylic acid in the final product was measured.
The licorice used in this example is prepared from dry root and rhizome of Glycyrrhiza uralensis Glycyrrhiza uralensis Fisch. Glycyrrhiza uralensis Glycyrrhiza inflata bat. Or Glycyrrhiza glabra Glycyrrhiza glabra L. Belonging to the family Leguminosae.
The preparation method comprises soaking Glycyrrhrizae radix in dilute ammonia water for 2 days, slicing, drying, soaking in edible vinegar for 1 day to thoroughly soak, steaming under high pressure for 20 hr, and drying; the powder is pulverized into granule when in use. Grinding and sieving vinegar-soaked Glycyrrhrizae radix to obtain the final product.
Unground vinegar-soaked licorice was cut into round or round pieces. The outer skin is black brown, has longitudinal wrinkles and has luster. The section is black brown or grey black, is slightly glossy, forms a layer ring obviously, is radial, and has a concave medulla. Hard and sticky. Has acetic acid smell, sour taste and sweet taste. The vinegar-soaked licorice powder is brown to dark brown powder. Has acetic acid smell, sour taste and sweet taste.
The method for measuring the content of the active ingredient 18-methyl-12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid is described below.
Firstly, taking the licorice powder lg of the vinegar-soaked product, adding 40ml of diethyl ether, heating and refluxing for 1 hour, filtering, removing ether liquid, adding 30ml of methanol into dregs, heating and refluxing for 1 hour, filtering, evaporating filtrate to dryness, adding 40ml of water into residues to dissolve, extracting with n-butanol for 3 times, 20ml each time, combining n-butanol liquid, washing with water for 3 times, removing water liquid, evaporating n-Ding Jiaoye to dryness, adding 5ml of methanol into residues to dissolve, and taking the residues as a sample solution. And preparing a reference medicinal material lg of liquorice by the same method. And adding methanol into the monoammonium glycyrrhizinate reference substance to prepare a solution containing 2mg per lml as a reference substance solution. According to a thin layer chromatography (general rule 0502) test, sucking 1-2 μl of each of the above three solutions, respectively spotting on the same silica gel G thin layer plate prepared from 1% sodium hydroxide solution, spreading with ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) as developing agent, taking out, air drying, spraying 10% sulfuric acid ethanol solution, heating at 105deg.C until the spots are clear, and placing under ultraviolet lamp (365 nm) for inspection. In the chromatogram of the test sample, fluorescent spots with the same color appear at the positions corresponding to the chromatogram of the reference medicinal material; the same orange-yellow fluorescent spots were shown at the positions corresponding to the control chromatograms.
In the second method, 5g of the product powder is taken, and 5g of hydrochloric acid lmL and 15mL of three-gas are added, heated and refluxed for 1 hour, cooled and filtered. The filtrate was evaporated to dryness, and the residue was dissolved in 2ml of absolute ethanol to give a sample solution. And adding anhydrous ethanol into a proper amount of 18-methyl-12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid reference substance to prepare a solution containing lmg per lml as a reference substance solution. According to a thin layer chromatography (general rule 0502) test, 5 μl of each of the above two solutions is sucked and respectively spotted on the same silica gel G thin layer plate, and n-hexane-ethyl acetate-acetone-formic acid (10:2:4:0.1) is used as developing agent to develop, taken out, dried, sprayed with 10% phosphomolybdic acid ethanol solution, and heated at 105deg.C until the spots develop clearly. Spots of the same color appear in the sample chromatogram at positions corresponding to those of the control chromatogram.
Preparing reference substance solution, namely taking a proper amount of 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid reference substance, precisely weighing, placing into a conical flask with a plug, precisely adding absolute ethyl alcohol to prepare a solution containing 0.1mg per 1ml, sealing, performing ultrasonic treatment for 10 minutes (power 100W and frequency 40 kHz), cooling, filtering, and taking a subsequent filtrate.
Preparation of sample solution 1.0g of the sample powder (sieving with No. 2 sieve), precisely weighing, placing in a conical flask with a plug of 100ml, precisely adding 50ml of 70% ethanol, sealing, weighing, extracting with ultrasound (power 100W, frequency 40 kHz) for 30 min, cooling, weighing again, supplementing the weight loss with 70% ethanol, shaking, and filtering.
And precisely sucking 10 mu l of each of the two solutions by using a measuring method, and injecting the solution into a liquid chromatograph for measurement to obtain the nano-meter.
The product contains 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid (C) 30 H 46 O 4 ) Not less than 0.40%.
High performance liquid chromatography (general rule 0512) is used for measuring glycyrrhizic acid.
The chromatographic condition and system applicability test uses octadecylsilane chemically bonded silica as filler; gradient elution was performed using acetonitrile as mobile phase a and 0.05% phosphoric acid solution as mobile phase B, as specified in table 5 below; the detection wavelength was 237nm. The number of theoretical plates should be not less than 5000 calculated according to the glycyrrhizin peak.
TABLE 5
| Time (minutes) | Mobile phase a (%) | Mobile phase B (%) |
| 0～8 | 19 | 81 |
| 8～35 | 19→50 | 81→50 |
| 35～36 | 50→100 | 50→0 |
| 36～40 | 100→9 | 0→81 |
Preparation of control solution A proper amount of ammonium glycyrrhizate control solution is prepared, precisely weighed, and 70% ethanol is added to prepare 0.2mg of ammonium glycyrrhizate solution per lmL, respectively (glycyrrhizic acid weight=ammonium glycyrrhizate weight/1.0207).
Preparation of sample solution about 0.2g of the sample powder (sieving with a third sieve), precisely weighing, placing into a conical flask with a plug, precisely adding 100mL of 70% ethanol, sealing, weighing, performing ultrasonic treatment (power 250W, frequency 40 kHz) for 30 minutes, cooling, weighing again, supplementing the lost weight with 70% ethanol, shaking, filtering, and collecting the subsequent filtrate.
The measurement method comprises precisely sucking lO μl of each of the reference solution and the sample solution, injecting into a liquid chromatograph, measuring, and calculating.
The product is calculated as dry product, glycyrrhizic acid (C) 12 H 62 O 16 ) With 12-ene-3 beta-hydroxy-11-one-oleanane-20 beta-carboxylic acid (C 30 H 46 O 4 ) The sum of (2) is not less than 1.30%.
The vinegar-soaked licorice provided by the application has the beneficial effects that: compared with the prior art, the preparation method has the advantages of short preparation period and high efficiency, and meanwhile, the content of the effective component 12-alkene-3 beta-hydroxy-11-ketone-oleanane-20 beta-formic acid in the vinegar soaked liquorice is high, so that the preparation method has remarkable curative effect on liver diseases.
The foregoing description of the preferred embodiments of the application is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the application.
Claims (6)
1. The preparation method of the vinegar-soaked licorice is characterized by comprising the following steps of:
soaking the licorice slices in dilute ammonia water for 48 hours to obtain urinary licorice, wherein the mass fraction of ammonia in the dilute ammonia water is 0.1% -1%;
soaking the liquorice in acetic acid solution for 24 hours to obtain vinegar liquorice, wherein the acetic acid solution is table vinegar;
and (3) steaming the wet vinegar licorice at 120 ℃ for 20 hours, and drying to obtain a vinegar-soaked licorice finished product.
2. The method for preparing vinegar-soaked licorice according to claim 1, wherein said acetic acid solution is a ninety-ester vinegar.
3. The method for preparing licorice soaked in vinegar according to claim 2, wherein the concentration of acetic acid in said Jiuquxiang ester vinegar is 10g/100mL at the minimum.
4. The method for preparing vinegar-soaked licorice according to claim 2, wherein the urinary licorice is sealed and soaked in acetic acid solution.
5. The method for preparing vinegar-soaked licorice according to claim 1, wherein in the drying step, the drying temperature is 50-60 ℃ and the drying time is 1-3 hours.
6. Use of the vinegar-soaked licorice of any one of claims 1-5 in the preparation of a medicament for treating liver fibrosis.
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| Title |
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| 刘惠杰等.甘草.《参苓白术散》.2009,(第1版),第343-344页，尤其是第344页第4段. * |
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Effective date of registration: 20240717 Address after: No. 4, Unit 5, Building 5, Department of Traditional Chinese Medicine, No. 41 Xilingol South Road, Saihan District, Hohhot City, Inner Mongolia Autonomous Region 010000 Patentee after: Na Shengsang Country or region after: China Address before: 427000 Economic Development Zone C, Zhangjiajie City, Hunan Province Patentee before: Hunan Dade Future Science and Technology Industry Group Co.,Ltd. Country or region before: China |