Liuwei Anxiao granules as well as preparation method and quality control method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicinal materials, in particular to Liuwei Anxiao granules as well as a preparation method and a quality control method thereof. According to the Liuwei Anxiao granules provided by the invention, water-insoluble impurities and harmful compound trace elements such as magnesium carbonate, calcium carbonate, iron oxide, chromium and aluminum are removed after the alkaline is further purified, so that side effects such as stomach discomfort are avoided; the processing technology of the milk-quenched red gypsum is optimized, so that the content of acid-insoluble ash in the milk-quenched red gypsum is not more than 5.0%, the content of heavy metal is not more than 10mg / kg, the content of arsenic salt is not more than 2mg / kg, the content of calcium sulfate is not less than 80.0%, and the total content of aspartic acid, valine and methionine is more than 100mg / 100g; meanwhile, the rhubarb is processed, so that the property, flavor and effect of the processed rhubarb are changed. The Liuwei Anxiao granules are more convenient to take and carry, small in irritation and quick to absorb, and the drug effect is remarkably improved.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicinal materials, and in particular to Liuwei Anxiao granules and a preparation method and quality control method thereof. Background Art

[0002] Mongolian medicine posits that indigestion and constipation are caused by gastrointestinal dysfunction, leading to indigestion and reversal of the "Hei" (lower clearing) energy, resulting in stomach pain, bloating, bad breath, hiccups, and difficulty passing stool. The cause is a weakening of the "Hei" energy, an excess of "Xila" (blood), and a loss of intestinal fluids, which prevents the body from moistening the intestines and stomach, leading to intestinal discomfort and dryness of the anus. Blood heat from excessive tobacco and alcohol consumption, excessive exertion, and residual heat from a fever that burns the vital essence can also contribute. Chronic illness, postpartum care, obesity, advanced age, and prolonged sedentary life are all contributing factors. Anxiao Liuwei Granules are based on a classic Mongolian formula (powder) with remarkable efficacy. Traditional Mongolian powders suffer from crude production processes, outdated equipment, a rudimentary production environment, lack of purification, and substandard packaging materials. This often leads to moisture and mold during storage. Heat can also cause the powder to clump and the pills to harden, compromising quality. The finished product has the disadvantage of easily exceeding the bacteria and heavy metal standards. At the same time, because the preparation process of the powder is rough and the effective content is low, the dosage required is large, which in turn leads to poor compliance of patients with medication.

[0003] Mongolian medicine decoctions and powders have long been an important traditional dosage form of Mongolian medicine. Their main advantages are readily available, inexpensive raw materials, simple preparation, large specific surface area, rapid absorption, strong therapeutic efficacy, and ease of exerting their efficacy. However, due to the simple production process, the grinding and mixing of raw materials can result in finished products with bitter, spicy, pungent, and sour tastes. They also suffer from drawbacks such as large dosage, strong irritation to the throat and esophagus, a poor taste, stickiness to the tongue and teeth, and difficulty swallowing. This can lead to a fear of medication for patients, making it particularly difficult for children, significantly reducing medication compliance. The term "unpalatable" has become synonymous with Mongolian medicine, which, to some extent, has hampered its development and application.

[0004] In 2020, the applicant optimized the components and preparation method of the "granule composition for soothing the stomach and strengthening the spleen", but the granule combination still has the problem of inadequate or lacking medicinal materials. After taking it, due to the strong effect of the original medicinal materials, abdominal pain, increased flatus, stomach cramps, and some mild diarrhea and other adverse reactions occurred, which were avoided after authentic processing; in addition, the prescription is a classic prescription, and the classics record that it has a nourishing effect. After taking the granule composition, the "nourishing" effect considered by Mongolian medicine is not significant. The present invention restores the milk foam process, and the trial found that it was replenished, and the patient felt refreshed; at the same time, the preparation and refinement of the prescription medicinal materials of the present invention are relatively thorough, and some impurities and invalid substances are removed, which greatly improves the safety of the medication. Summary of the Invention

[0005] The purpose of the present invention is to provide a Liuwei Anxiao granule and a preparation method and quality control method thereof to solve the problems existing in the above-mentioned prior art.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] The present invention provides a Liuwei Anxiao granule, which comprises the following raw materials in parts by weight:

[0008] 180-240 parts of alkali flower crystals, 150-220 parts of milk-quenched red gypsum, 100-200 parts of wine-fried rhubarb, 80-150 parts of Terminalia chebula, 50-120 parts of Kaempferia galanga, and 20-80 parts of Elecampane;

[0009] The preparation method of the alkali flower crystal comprises the steps of mixing the alkali flower and water, and then filtering, concentrating, crystallizing, recrystallizing and drying in sequence to obtain the alkali flower crystal;

[0010] The preparation method of the milk-quenched red gypsum comprises the steps of calcining the red gypsum until it is red, cooling it to 200-250° C., adding it into raw milk to quench it, and drying it to obtain the milk-quenched red gypsum;

[0011] The method for preparing the wine-fried rhubarb comprises the steps of mixing rhubarb and wine, soaking the mixture and then bathing the mixture in water to obtain the wine-fried rhubarb.

[0012] Preferably, the weight ratio of the alkali flower to water is 1:3;

[0013] The weight ratio of the cooled calcined red gypsum to the raw milk is 4:1; the quenching time is 40 minutes;

[0014] The mass volume ratio of the rhubarb and the wine is 10g:15mL, the wine is 60° white wine; the temperature of the water bath is 80°C, and the time is 3-4 hours.

[0015] Preferably, the Liuwei Anxiao granules include the following raw materials in parts by mass:

[0016] 214.28 parts of alkali flower crystals, 178.57 parts of milk-quenched red gypsum, 142.86 parts of wine-roasted rhubarb, 107.15 parts of Terminalia chebula, 71.43 parts of Kaempferia galanga and 35.71 parts of Elecampane;

[0017] Or, 180 parts of alkali flower crystals, 150 parts of milk-quenched red gypsum, 100 parts of wine-fried rhubarb, 80 parts of Terminalia chebula, 50 parts of Kaempferia galanga and 20 parts of Eupatorium vulgaris;

[0018] Or, 240 parts of alkali flower crystals, 220 parts of milk-quenched red gypsum, 200 parts of wine-fried rhubarb, 150 parts of Terminalia chebula, 120 parts of galangal and 80 parts of inula.

[0019] Preferably, the Liuwei Anxiao granules further include excipients, which include fillers, binders and lubricants;

[0020] The filler includes one or more of sucrose powder, dextrin and lactose powder; the binder includes starch slurry; and the lubricant includes magnesium stearate.

[0021] More preferably, the filler is 235-245 parts by mass.

[0022] The present invention provides a preparation method of the above-mentioned Liuwei Anxiao granules, which comprises the step of mixing the alkali flower crystal, the milk-quenched red gypsum, the wine-roasted rhubarb, the Terminalia chebula, the galangal and the inulin powder to obtain the Liuwei Anxiao granules.

[0023] Preferably, after the alkali flower crystal, the milk-quenched red gypsum, the wine-roasted rhubarb, the terminalia chebula, the galangal and the inulin powder are mixed, the step of adding auxiliary materials is further included; the auxiliary materials include fillers, adhesives and lubricants;

[0024] The filler includes one or more of sucrose powder, dextrin and lactose powder; the binder includes starch slurry; and the lubricant includes magnesium stearate.

[0025] Preferably, the specific step of adding auxiliary materials includes the following steps:

[0026] The step of sequentially adding the filler, the binder and the lubricant to the mixed Chinese medicine obtained by mixing the alkali flower crystal, the milk-quenched red gypsum, the wine-fried rhubarb, the terminalia chebula, the galangal and the inulin powder.

[0027] The present invention provides a quality control method for the above-mentioned Liuwei Anxiao granules, comprising:

[0028] (1) observing the shape of the Liuwei Anxiao granules;

[0029] (2) performing microscopic identification on the Liuwei Anxiao granules;

[0030] (3) performing thin layer chromatography identification on the Liuwei Anxiao granules;

[0031] (4) The contents of rhubarb, free anthraquinone, total alkali and calcium sulfate in the Liuwei Anxiao granules were detected by high performance liquid chromatography; the rhubarb content in the Liuwei Anxiao granules was greater than 1.05 mg / g, the free anthraquinone content was greater than 0.6 mg, the total alkali content was greater than 107 mg / g, and the calcium sulfate content was greater than 151 mg / g.

[0032] Preferably, the thin layer chromatography identification includes method 1, method 2 and method 3;

[0033] The method 1 comprises the steps of spotting a test solution, a rhubarb reference substance and a galangal reference substance solution onto a silica gel GF254 thin layer plate, developing the plate with a mixed solution of cyclohexane, ethyl acetate and formic acid as a developing agent, and observing the plate under a 365nm ultraviolet lamp; the preparation method of the test solution comprises the steps of mixing a sample powder to be tested with a methanol solution, and sequentially performing ultrasound and filtration to obtain the test solution; the preparation method of the rhubarb reference substance solution comprises the steps of mixing a rhubarb reference medicinal material with methanol, and performing ultrasound to obtain the rhubarb reference substance solution; the preparation method of the galangal reference substance solution comprises the steps of mixing a galangal reference medicinal material with methanol, and performing ultrasound to obtain the galangal reference substance solution;

[0034] The method 2 comprises the steps of spotting a test solution and a Terminalia chebula reference solution onto a silica gel GF254 thin layer plate, developing the plate with a mixed solution of cyclohexane, ethyl acetate and formic acid as a developing agent, and observing the plate under a 254 nm ultraviolet lamp; the method for preparing the test solution comprises the steps of mixing a sample powder to be tested with a methanol solution, and sequentially performing ultrasound and filtration to obtain the test solution; the method for preparing the Terminalia chebula reference solution comprises the steps of mixing a Terminalia chebula reference medicinal material with methanol, and performing ultrasound to obtain the Terminalia chebula reference solution;

[0035] The method 3 includes the steps of spotting a test sample solution and an Inula japonica reference solution on a silica gel G thin layer plate, developing the plate using a mixed solution of petroleum ether and ethyl acetate as a developing agent, spraying anisaldehyde test solution, heating, and observing; the method for preparing the test sample solution includes the steps of mixing the sample powder to be tested with an ethyl acetate solution, sequentially performing reflux extraction, filtering, evaporating to dryness, and redissolving to obtain the test sample solution; the method for preparing the Inula japonica reference solution includes the steps of mixing an Inula japonica reference medicinal material with an ethyl acetate solution, sequentially performing reflux extraction, filtering, evaporating to dryness, and redissolving to obtain the Inula japonica reference solution.

[0036] Preferably, in the method 1, the volume ratio of cyclohexane, ethyl acetate and formic acid in the developing solvent is 12:3:0.1; the mass volume ratio of the test sample powder and the ethanol solution is 1.5 g:4 mL; the mass volume ratio of the rhubarb control medicinal material and methanol is 0.3 g:3 mL; the mass volume ratio of the galangal control medicinal material and methanol is 0.2 g:3 mL;

[0037] In the method 2, the volume ratio of cyclohexane, ethyl acetate and formic acid in the developing solvent is 6:4:0.5; the mass volume ratio of the test sample powder and the ethanol solution is 2 g:20 mL; the mass volume ratio of the Terminalia chebula reference medicinal material and methanol is 0.2 g:3 mL;

[0038] In method 3, the volume ratio of petroleum ether and ethyl acetate in the developing solvent is 10:1.5; the mass volume ratio of the sample powder to be tested and the ethyl acetate solution is 1 g:25 mL; and the mass volume ratio of the Inula japonica reference medicinal material and the ethyl acetate solution is 2 g:20 mL.

[0039] The present invention discloses the following technical effects:

[0040] Natural alkali soil contains complex impurities and ingredients that are not conducive to therapeutic purposes. It is difficult to control the dosage and efficacy in clinical use. In the Liuwei Anxiao granules provided by the present invention, the alkali flower is further purified to remove water-insoluble impurities and harmful compounds and trace elements such as magnesium carbonate, calcium carbonate, iron oxide, chromium (reportedly generally containing more than 2.5ppm), and aluminum to avoid side effects such as stomach discomfort; the processing technology of milk-quenched red gypsum is optimized to ensure that the acid-insoluble ash content in the milk-quenched red gypsum does not exceed 5.0%, the heavy metal content does not exceed 10mg / kg, the arsenic salt content does not exceed 2mg / kg, the calcium sulfate content does not fall below 80.0%, and the total amount of aspartic acid, valine, and methionine (three amino acids with relatively high content, derived from milk) is above 100mg / 100g; at the same time, rhubarb is processed to change the properties, flavor, and efficacy of the processed rhubarb. The present invention leverages the concept of traditional Chinese medicine formula granules and is guided by Mongolian medicine theory, ensuring the principles of traditional Mongolian medicine decoction pieces and preserving the original flavor of Mongolian medicine. Compared to traditional decoctions and powders, it overcomes the inconvenience of taking Mongolian medicine decoctions and powders. It can be taken directly with warm water and rapidly disintegrates or dissolves in the stomach. Its pharmacokinetic parameters are very similar to those of powdered decoctions and powders, but it overcomes the throat and esophageal irritation of decoctions and powders, making it a suitable alternative dosage form for clinical use. Furthermore, due to its larger drug specific surface area, its in vivo disintegration and absorption rates are significantly improved compared to traditional water pills, which not only enhances its efficacy but also improves patient compliance, especially oral compliance in children. Furthermore, the Liuwei Anxiao granules are more convenient to take and carry, have less irritation, are rapidly absorbed, and have significantly increased efficacy. Furthermore, they improve drug stability and quality controllability, further facilitating the digitalization and intelligentization of drug dispensing. Furthermore, the Liuwei Anxiao granules provided by the present invention significantly eliminate bad breath in middle-aged and elderly patients. This shows that the Liuwei Anxiao granules provided by the present invention have better effects.

[0041] The preparation method provided by the present invention utilizes modern pharmaceutical techniques and adopts a raw powder granulation process without heating, concentration, or extraction. This ensures the multi-pharmacological properties of Mongolian medicine formulas and transforms the stomach-tonifying and spleen-strengthening granular composition into a dosage form suitable for modern clinical application. This method not only maintains the characteristics of Mongolian medicine and the beneficial ingredients of the original powder or granule, but also has the characteristic of powder with a fast onset of action and is more conducive to improving patient compliance with medication. Furthermore, the method can be combined with an automatic medicine dispensing machine to increase production capacity.

[0042] The present invention further improves the quality control method of Liuwei Anxiao Granules, determines that the total content of total chrysophanol and total emodin in Liuwei Anxiao Granules is greater than 1.05 mg / g, the content of total alkali is greater than 107 mg / g, and the content of calcium sulfate is greater than 151 mg / g, and reconstructs the quality standard of Liuwei Anxiao Granules, laying the foundation for the industrialization and industrial production of Liuwei Anxiao Granules, and greatly improving the safety of clinical drug use. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0044] Figure 1 HPLC chart of mixed reference substance; wherein 1 is aloe-emodin, 2 is rhein, 3 is emodin, 4 is chrysophanol, and 5 is physophanol methyl ether;

[0045] Figure 2 HPLC chart of total anthraquinone aglycones of rhubarb; wherein 1 is aloe-emodin, 2 is rhein, 3 is emodin, 4 is chrysophanol, and 5 is physophanol methyl ether;

[0046] Figure 3 This is the HPLC chart of free anthraquinones in raw rhubarb; 1 is aloe-emodin, 2 is rhein, 3 is emodin, 4 is chrysophanol, and 5 is physophanol methyl ether;

[0047] Figure 4 This is the HPLC chart of total anthraquinone aglycones of wine-cured rhubarb; among them, 1 is aloe-emodin, 2 is rhein, 3 is emodin, 4 is chrysophanol, and 5 is physophanol methyl ether;

[0048] Figure 5 This is the HPLC chart of free anthraquinones in wine-fried rhubarb; among them, 1 is aloe-emodin, 2 is rhein, 3 is emodin, 4 is chrysophanol, and 5 is physophanol methyl ether;

[0049] Figure 6 This is a thin layer chromatogram of the identification of wine-fried rhubarb in Liuwei Anxiao granules provided in Examples 1-3 of the present invention; wherein 1 is a rhubarb control medicinal material solution, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao granules provided in Examples 1-3, respectively;

[0050] Figure 7This is a thin layer chromatogram of the identification of Kaempferia galanga in Liuwei Anxiao Granules provided in Examples 1-3 of the present invention; wherein 1 is a Kaempferia galanga control medicinal material solution, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao Granules provided in Examples 1-3, respectively;

[0051] Figure 8 This is a thin layer chromatogram of the identification of Terminalia chebula in Liuwei Anxiao Granules provided in Examples 1-3 of the present invention; wherein 1 is a Terminalia chebula control medicinal material solution, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao Granules provided in Examples 1-3, respectively;

[0052] Figure 9 This is a thin layer chromatogram of identification of costus root in Liuwei Anxiao granules provided in Examples 1-3 of the present invention; wherein 1 is a control medicinal material solution of Inula root, and 2-4 correspond to the test sample solutions prepared from Liuwei Anxiao granules provided in Examples 1-3, respectively;

[0053] Figure 10 This is a chromatogram of the reference substances of wine-fried chrysophanol and wine-fried emodin in Liuwei Anxiao Granules provided in Example 1 of Example 6 of the present invention; wherein 1 represents chrysophanol and 2 represents emodin;

[0054] Figure 11 This is a sample chromatogram of the total wine-cured chrysophanol and total wine-cured emodin content in Liuwei Anxiao Granules provided in Example 2 of Example 6 of the present invention; wherein 1 represents chrysophanol and 2 represents emodin;

[0055] Figure 12 This is a sample chromatogram of the free wine-cured chrysophanol and free total wine-cured emodin content in Liuwei Anxiao Granules provided in Example 3 of Example 6 of the present invention; wherein 1 represents chrysophanol and 2 represents emodin;

[0056] Figure 13 This is a process flow chart of Liuwei Anxiao Granules provided in Examples 1-5 of the present invention. DETAILED DESCRIPTION

[0057] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0058] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value within any stated value or stated range, and each smaller range between any other stated value or intermediate value within the stated range, is also encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0059] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0060] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0061] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0062] The process flow chart of Liuwei Anxiao granules provided in Examples 1-5 of the present invention is as follows Figure 13 As shown, the details are as follows:

[0063] Example 1

[0064] The purpose of this embodiment is to provide a Liuwei Anxiao granule (a granule composition for soothing the stomach and strengthening the spleen), which is mainly prepared by the following steps:

[0065] (1) Unique preparation of medicinal materials:

[0066] A. Alkali Flower Crystals: Alkali flower crystals are crude crystals of natural Trona soil alkali. Alkali flower crystals are processed to become alkali flower crystals. Alkali flower crystals are abundant in western Inner Mongolia and are a high-quality natural alkali, marketed as alkali flower crystals. Their chemical composition is complex, primarily sodium carbonate (Na2CO3), with significant amounts of sulfate, magnesium, and aluminum. However, their pharmacological and efficacy responses vary, and their stability is poor. Therefore, based on Mongolian pharmacological theory and the clinical experience of traditional Mongolian doctors, they are carefully processed to remove impurities and insoluble trace elements, improve the precision of their pharmacological and efficacy, and ensure safe and effective clinical use.

[0067] Preparation method: Take alkali flower, add 3 times the amount of hot water (75-85℃), stir slowly to dissolve it all, filter it while hot, concentrate the filtrate to about half, let it stand and cool, and precipitate crystals. The mother liquor (the liquid remaining after filtration, concentration and crystallization in the previous step) continues to concentrate and stand for recrystallization, collect the crystals, combine the crystals, mix them, dry them, and grind them into powder to obtain the product. Natural alkali contains complex impurities and ingredients that are not conducive to therapeutic purposes. It is difficult to control the dosage and efficacy in clinical use. After further purification, water-insoluble impurities and harmful compounds and trace elements such as magnesium carbonate, calcium carbonate, iron oxide, chromium (reportedly generally contain more than 2.5ppm), and aluminum are removed to avoid side effects such as stomach discomfort.

[0068] Testing and Effect Evaluation: Impurities must not exceed 1%, heavy metals must not exceed 15mg / kg, and arsenic salts must not exceed 10mg / kg; total alkali content must not be less than 50%. All alkali flower crystals described in the examples of this invention have passed testing and have not been found to have adverse reactions such as gastric discomfort during clinical use.

[0069] B. Milk-Quenched Red Gypsum: Red gypsum (known as Northern Hanshui Stone in Traditional Chinese Medicine) is a processed product of red gypsum (Northern Hanshui Stone), a monoclinic calcium sulfate mineral. It primarily contains hydrated calcium sulfate (CaSO4·2H2O) and is a very commonly used medicinal ingredient in Mongolian medicine.

[0070] Preparation method: calcine the red gypsum in a smokeless open flame until it turns red, take it out and place it in a suitable container to cool to 200℃, slowly add it into raw milk to quench it, take it out and dry it to obtain the milk-quenched red gypsum. 10kg of red gypsum requires about 2.5kg of raw milk.

[0071] Processing control standards: The surface is grayish white or yellowish white block, extremely brittle, and becomes powdery, sticky, and slightly sticky to the hands; it has a slight milky aroma and a light taste.

[0072] Optimization of the processing process for milk-quenched red gypsum: Orthogonal experiments were conducted to optimize the processing parameters. Two veteran Mongolian medicine practitioners, both nationally recognized, were invited to conduct subjective evaluations of the processed products. Texture, hand-twisting sensation, and slice formation were used as observational indicators. An orthogonal experiment was conducted using three factors and three levels for quenching temperature, the ratio of medicinal material to milk (by weight), and drying time. The results are shown in Table 1.

[0073] Table 1 Comparative study results

[0074]

[0075] The results showed that both groups 2 and 3 were suitable. The best process conditions after comprehensive evaluation should be: calcining until red, cooling to 200℃, quenching with 1 / 4 of raw milk, and drying for 40 minutes for the best processing effect.

[0076] The following tests were performed: Acid-insoluble ash must not exceed 5.0%, heavy metals must not exceed 10 mg / kg, arsenic salts must not exceed 2 mg / kg, and the calcium sulfate (CaSO4) content must not be less than 80.0%. Furthermore, the content of amino acids such as aspartic acid was tested and determined using liquid chromatography. The results were as follows: The combined content of aspartic acid, valine, and methionine (three amino acids with relatively high content, derived from milk) was above 100 mg / 100 g, distinguishing it from calcined and processed products of Northern Hanshui Stone (red gypsum) in Traditional Chinese Medicine.

[0077] C. Wine-fried Rhubarb: It is a processed product of the dried roots and rhizomes of Rheum palmatum, Rheum tanguticum or Rhubarb, which are plants of the Polygonaceae family and are listed in the Chinese Pharmacopoeia. It comes from the medicine market.

[0078] a. Preparation Method: Take thick slices of clean rhubarb, crush them into vinegar granules, place them in a suitable container with a stopper, add 60° high-proof edible liquor, and leave overnight to moisten the herbs. Then transfer to a water bath and heat until just below boiling. Keep in the water bath for about 4 hours, remove the herbs and let them dry.

[0079] Processing control standards: The surface of the processed product is brown, with a slight aroma of wine, and a slightly bitter and astringent taste.

[0080] b. Processing Principle: Rhubarb contains anthraquinone derivatives, which are the most studied active ingredients in rhubarb. They are divided into free and bound forms. Free forms include rhein, emodin, rhubarb, aloe-emodin, physcion, isoemodin, chrysophanol, and lacinic acid D. Bound forms include physcion glucoside, aloe-emodin glucoside, and sennosides A, B, C, D, E, and F. Numerous studies have shown that bound anthraquinones, primarily sennosides, are the primary active ingredients in rhubarb for purgative effects. Rhubarb has a strong purgative effect, but the present invention aims to soothe the stomach and strengthen the spleen, and thus avoids purgative effects or diarrhea-induced side effects such as abdominal pain and intestinal colic. This invention utilizes the experience of traditional Mongolian medicine to mitigate its purgative effect and avoid side effects such as pain during the purgative process. This invention achieves this ideal effect through its unique wine-braised preparation method.

[0081] c. Research on optimization of processing technology:

[0082] The rhubarb preparation method employed in this invention is based on the empirical methods of traditional Mongolian medicine. Key parameters include the ratio of medicinal material to liquor (when thick slices of the medicinal material are thoroughly moistened with liquor, the material-liquid ratio is generally fixed at 10:15 (g:mL)), the alcohol content, the heating temperature, and the water bath time. Using changes in free anthraquinones as an observation indicator, this invention employed a three-factor, three-level orthogonal experiment to optimize the preparation process as follows:

[0083] The experimental settings for liquor alcohol content, water bath temperature and time were three levels, see Table 2.

[0084] Table 2 Visual analysis of free anthraquinone content

[0085]

[0086] After analysis, the factors affecting the wine-braised processing indicators are temperature B, water bath time C, and wine alcohol content A; the optimal process conditions are: A2B1C2, that is, moistening with 60° white wine and then bathing in water at 80℃ for 3 hours for the best effect.

[0087] d. Inspection and effect evaluation:

[0088] ① Drugs: Rhubarb (purchased from Inner Mongolia Tiankang Mongolian Traditional Chinese Medicine Co., Ltd., batch number: 20140602), authenticated as authentic by the Inner Mongolia Institute of Drug Control. Aloe-emodin standard (National Institute for the Control of Pharmaceutical and Biological Products, batch number: 110795-201007); rhein standard (National Institute for the Control of Pharmaceutical and Biological Products, batch number: 110757-200206); emodin standard (National Institute for the Control of Pharmaceutical and Biological Products, batch number: 110756-200110); chrysophanol standard (National Institute for the Control of Pharmaceutical and Biological Products, batch number: 110796-201017); and physcion methyl ether standard (National Institute for the Control of Pharmaceutical and Biological Products, batch number: 110758-201013). Methanol was the chromatographic alcohol, and water was Wahaha brand purified water. All other reagents were of analytical grade.

[0089] ② Prepared sample: Wine-roasted rhubarb (homemade: remove impurities, wash, soak thoroughly, cut into slices or blocks about 8-12mm thick, and dry; prepare in the same way as above).

[0090] ③Testing, analysis methods and results

[0091] Chromatographic conditions:

[0092] The chromatographic column was Nuclesil ODS (4 mm×25 cm, 5 μm); the mobile phase was 80% methanol solution containing 0.1% perchloric acid; the flow rate was 0.5 mL / min; and the detection wavelength was 254 nm.

[0093] Preparation of reference solution: Accurately weigh 2 mg each of aloe-emodin, rhein, emodin, chrysophanol, and physophanol methyl ether into five 25 mL brown volumetric flasks. Add 5 mL of methanol to each to dissolve, and then add methanol to the mark to prepare the standard stock solution. Pipette 0.1 mL, 1.0 mL, 1.0 mL, 0.5 mL, and 0.5 mL of the standard stock solution into 5 mL brown volumetric flasks, add methanol to the mark, and mix thoroughly to prepare the mixed reference solution.

[0094] Preparation of test solution: Accurately weigh 0.1 g of sample powder (No. 4 sieve) and place it in a 50 mL ground-mouth stoppered conical flask. Accurately add 20 mL of methanol and soak at room temperature for 15 hours. Filter through dry filter paper, discard the initial filtrate, and take the subsequent filtrate for later use.

[0095] Extraction of free anthraquinone: Accurately draw 5 mL of the above filtrate into a 20 mL stoppered test tube, evaporate the methanol on a water bath, add 2 mL of water, shake to dissolve the residue, place in an ice bath to cool, then accurately add 10 mL of ether and 0.2 mL of hydrochloric acid, immediately seal and shake vigorously for 3 minutes. After stratification, accurately measure 5 mL of ether solution and place in another stoppered test tube, evaporate the ether under air flow, then accurately add 2 mL of methanol to dissolve the residue, filter with a filter membrane to obtain test solution I.

[0096] Extraction of total anthraquinone aglycones: Accurately draw 2.5 mL of the above filtrate into a 20 mL stoppered test tube, evaporate the methanol on a water bath, add 2 mL of water and 0.2 mL of hydrochloric acid, place in a boiling water bath for hydrolysis for 30 minutes, remove, place in an ice bath for cooling, then accurately add 10 mL of ether, and perform the same operation as in the step "immediately seal and shake vigorously for 3 minutes" in "Test Solution I" to obtain test solution II.

[0097] Linearity Assessment: Accurately pipette 2 μL, 4 μL, 6 μL, 8 μL, and 10 μL of the mixed standard solution for analysis. Standard curves were plotted with injection volume (μg) as the abscissa (X) and peak area as the ordinate (Y). Linear regression equations and linear ranges were obtained for the five components. The results showed good linearity for aloe-emodin within the 0.0032-0.0160 μg range; for rhein, for 0.0320-0.160 μg; for emodin, for 0.0160-0.160 μg; and for chrysophanol and physophanol methyl ether, for 0.0160-0.0800 μg. See Table 3.

[0098] Table 3 Linear range of mixed reference substances

[0099]

[0100] Content determination: Under the chromatographic conditions set above, 4 μL of each of test sample I and test sample II was injected, and the content of total anthraquinone and free anthraquinone in each sample was calculated according to the standard curve equation. The content of bound anthraquinone in rhubarb and wine-fried rhubarb was calculated using the formula "total amount of bound anthraquinone = total amount of anthraquinone - total amount of free anthraquinone". Total amount of bound anthraquinone = total amount of anthraquinone - total amount of free anthraquinone. See Table 4 and HPLC chromatogram as shown below. Figure 1-Figure 5 shown.

[0101] Table 4 Anthraquinone content determination results of rhubarb and wine-fried rhubarb

[0102]

[0103] Note: Rhubarb cooked in wine is called wine-roasted rhubarb.

[0104] ④ Analysis and Discussion: This experiment showed that the contents of total anthraquinones, free anthraquinones, and bound anthraquinones changed significantly before and after processing rhubarb. The bound anthraquinone contents in rhubarb and wine-fried rhubarb were 0.384% and 0.056%, respectively; the bound anthraquinone content in the latter was significantly lower than that in the former. The total anthraquinone content decreased slightly from 1.232% to 0.772%, and the free anthraquinone content decreased slightly from 0.848% to 0.716%, indicating a relatively small loss. Therefore, processing rhubarb alleviates its laxative effect and avoids pain during the catharsis process. This experiment demonstrates that the changes in the properties, flavor, and efficacy of rhubarb after processing are due to the transformation of its chemical components, and that changes in chemical components cause changes in its pharmacological effects. This is consistent with the purpose of Mongolian medicine processing (changing efficacy) in Mongolian medicine theory and is also one of the inventive points of the present invention.

[0105] (2) Crushing into coarse powder: Weigh six Mongolian medicinal pieces, specifically 214.28 g of alkali flower crystal, 178.57 g of milk-quenched red gypsum, 142.86 g of wine-fried rhubarb, 107.15 g of Terminalia chebula, 71.43 g of Kaempferia galanga, and 35.71 g of Inula officinalis, and crush them into coarse powder;

[0106] (3) Sterilization: Spread the coarse powder of medicinal materials in step (2) on a tray with holes all over the body, make the material temperature 50-60°C, and keep it warm for 2-3 hours for sterilization;

[0107] (4) Grinding and sieving: Grind the sterilized medicinal material coarse powder in step (3) into fine powder, pass through an 80-100 mesh sieve, and obtain medicinal material fine powder; all of the powder passes through a No. 5 sieve, and no less than 95% passes through a No. 6 sieve;

[0108] (5) Mixing: Weigh 240 g of filler (sucrose powder), add the filler and the medicinal material powder in step (4) to a granulation wet mixing granulator (prepared by wet mixing), and mix for 30 minutes to obtain a mixed powder;

[0109] (6) Preparation of soft material: Adding a binder to the mixed powder obtained in step (5) to prepare a soft material. When the soft material can be held in a ball by hand and then falls apart, the soft material is taken out for later use. The amount of binder used is about 1% of the total mass of the mixed powder and the binder (calculated on a dry basis). Effect experiments were conducted using various types of binders. After parallel comparative experiments, the binder was preferably starch slurry.

[0110] (7) Granulation: The soft material in step (6) is sieved through a 12-14 mesh sieve to granulate the wet granules. The resulting wet granules should be complete and uniform in size.

[0111] (8) Drying: The wet granules prepared in step (7) are evenly spread on a plate with a thickness of 3-5 cm, placed on a feed cart, and pushed into a hot air circulation oven. The temperature is adjusted to 60-70° C. and dried for 2-3 hours to control the moisture content of the granules to less than 8%, thereby obtaining dry granules.

[0112] (9) Granulation: Place the dried granules in step (8) in a YK160 swing granulator and sieve them with a 14-16 mesh screen. Place the granules after granulation in a clean container lined with a plastic bag. Observe the granules to see if there are any black spots or foreign matter. If the screen is damaged, replace it in time. Weigh the granules after granulation.

[0113] (10) Sieving: The granules prepared in step (9) are placed in a rotary vibrating sieve for granulation. The upper layer is sieved with a 10-mesh sieve to remove large pieces, and the lower layer is sieved with a 60-mesh sieve to remove fine powder. The intermediate granules are collected and placed in a clean container for later use. The part that passes through the 10-mesh sieve and does not pass through the 60-mesh sieve is qualified granules (qualified rate>95%);

[0114] (11) Mixing: The qualified granules prepared in step (10) are placed in a mixer, lubricant (magnesium stearate, the amount of magnesium stearate is 0.5% of the total mass of the qualified granules and magnesium stearate) is added, and mixed for 15 minutes to obtain Liuwei Anxiao granules;

[0115] (12) Packaging: Adjust the filling volume according to the weight of each bag and operate according to the "granule filling SOP" and granule filling post operating procedures. During the packaging process, take a sample of the filling volume every 10 minutes and record the sampling results to ensure that the filling volume of each bag is within the control range; the bagged granules are placed in a special container, with 2g or 4g per bag, which is equivalent to about 1.5g or 3g of the original medicinal material;

[0116] (13) Outer packaging: In accordance with the standard operating procedures for outer packaging, pack small boxes, pack large boxes, affix anti-counterfeiting trademarks, stamp batch numbers, and pack into outer boxes during the packaging process; place a product certificate in the outer box, seal it tightly with sealing tape, and tie it securely.

[0117] Example 2

[0118] The purpose of this embodiment is to provide a Liuwei Anxiao granule, which is mainly prepared by the following steps:

[0119] (1) Unique preparation of medicinal materials: same as in Example 1;

[0120] (2) Grinding into coarse powder: Weigh six Mongolian medicinal pieces, specifically including 214.28 g of alkali flower crystal, 178.57 g of milk-quenched red gypsum, 142.86 g of wine-fried rhubarb, 107.15 g of Terminalia chebula, 71.43 g of Kaempferia galanga, and 35.71 g of Inula officinalis, and grind them into coarse powder;

[0121] (3) Sterilization: Spread the coarse powder of medicinal materials in step (2) on a tray with holes all over the body, make the material temperature 50-60°C, and keep it warm for 2-3 hours for sterilization;

[0122] (4) Grinding and sieving: Grind the sterilized medicinal material coarse powder in step (3) into fine powder, pass through an 80-100 mesh sieve, and obtain medicinal material fine powder; all of the powder passes through a No. 5 sieve, and no less than 95% passes through a No. 6 sieve;

[0123] (5) Mixing: Weigh 240 g of filler (dextrin), add the filler and the medicinal material powder prepared in step (4) into a wet granulator, and mix for 30 minutes to obtain a mixed medicinal powder;

[0124] (6) Preparing a soft material: Adding a binder (starch slurry) to the mixed powder obtained in step (5) to prepare a soft material. When the soft material can be held in a ball by hand and falls apart when released, remove the soft material and set aside. The amount of binder used is about 1% of the total mass of the mixed powder and the binder.

[0125] (7) Granulation: The soft material in step (6) is sieved through a 12-14 mesh sieve to granulate the wet granules. The resulting wet granules should be complete and uniform in size.

[0126] (8) Drying: The wet granules prepared in step (7) are evenly spread on a plate with a thickness of 3-5 cm, placed on a feed cart, and pushed into a hot air circulation oven. The temperature is adjusted to 60-70° C. and dried for 2-3 hours to control the moisture content of the granules to less than 8%, thereby obtaining dry granules.

[0127] (9) Granulation: Place the dried granules in step (8) in a YK160 swing granulator and sieve them with a 14-16 mesh screen. Place the granules after granulation in a clean container lined with a plastic bag. Observe the granules to see if there are any black spots or foreign matter. If the screen is damaged, replace it in time. Weigh the granules after granulation.

[0128] (10) Sieving: The granules prepared in step (9) are placed in a rotary vibrating sieve for granulation. The upper layer is sieved with a 10-mesh sieve to remove large pieces, and the lower layer is sieved with a 60-mesh sieve to remove fine powder. The intermediate granules are collected and placed in a clean container for later use. The part that passes through the 10-mesh sieve and does not pass through the 60-mesh sieve is qualified granules (qualified rate>95%);

[0129] (11) Mixing: The qualified granules prepared in step (10) are placed in a mixer, lubricant (magnesium stearate, the amount of magnesium stearate is 0.5% of the total mass of the qualified granules and magnesium stearate) is added, and mixed for 15 minutes to obtain Liuwei Anxiao granules;

[0130] (12) Packaging: Adjust the filling volume according to the weight of each bag and operate according to the "granule filling SOP" and granule filling post operating procedures. During the packaging process, take a sample of the filling volume every 10 minutes and record the sampling results to ensure that the filling volume of each bag is within the control range; the bagged granules are placed in a special container, with 2g or 4g per bag, which is equivalent to about 1.5g or 3g of the original medicinal material;

[0131] (13) Outer packaging: In accordance with the standard operating procedures for outer packaging, pack small boxes, pack large boxes, affix anti-counterfeiting trademarks, stamp batch numbers, and pack into outer boxes during the packaging process; place a product certificate in the outer box, seal it tightly with sealing tape, and tie it securely.

[0132] Example 3

[0133] The purpose of this embodiment is to provide a Liuwei Anxiao granule, which is mainly prepared by the following steps:

[0134] (1) Unique preparation of medicinal materials: same as in Example 1;

[0135] (2) Crushing into coarse powder: Weigh six Mongolian medicinal pieces, specifically including 214.28 g of alkali flower crystal, 178.57 g of milk-quenched red gypsum, 142.86 g of wine-fried rhubarb, 107.15 g of Terminalia chebula, 71.43 g of Kaempferia galanga, and 35.71 g of costus root, and crush them into coarse powder;

[0136] (3) Sterilization: Spread the coarse powder of medicinal materials in step (2) on a tray with holes all over the body, make the material temperature 50-60°C, and keep it warm for 2-3 hours for sterilization;

[0137] (4) Grinding and sieving: Grind the sterilized medicinal material coarse powder in step (3) into fine powder, pass through an 80-100 mesh sieve, and obtain medicinal material fine powder; all of the powder passes through a No. 5 sieve, and no less than 95% passes through a No. 6 sieve;

[0138] (5) Mixing: Weigh 240 g of filler (lactose), add the filler and the medicinal material powder prepared in step (4) into a wet granulator, and mix for 30 minutes to obtain a mixed powder;

[0139] (6) Preparing a soft material: Adding a binder (starch slurry) to the mixed powder obtained in step (5) to prepare a soft material. When the soft material can be held in a ball by hand and falls apart when released, remove the soft material and set aside. The amount used is about 1% of the total mass of the mixed powder and the binder.

[0140] (7) Granulation: The soft material in step (6) is sieved through a 12-14 mesh sieve to granulate the wet granules. The resulting wet granules should be complete and uniform in size.

[0141] (8) Drying: The wet granules prepared in step (7) are evenly spread on a plate with a thickness of 3-5 cm, placed on a feed cart, and pushed into a hot air circulation oven. The temperature is adjusted to 60-70° C. and dried for 2-3 hours to control the moisture content of the granules to less than 8%, thereby obtaining dry granules.

[0142] (9) Granulation: Place the dried granules in step (8) in a YK160 swing granulator and sieve them with a 14-16 mesh screen. Place the granules after granulation in a clean container lined with a plastic bag. Observe the granules to see if there are any black spots or foreign matter. If the screen is damaged, replace it in time. Weigh the granules after granulation.

[0143] (10) Sieving: The granules prepared in step (9) are placed in a rotary vibrating sieve for granulation. The upper layer is sieved with a 10-mesh sieve to remove large pieces, and the lower layer is sieved with a 60-mesh sieve to remove fine powder. The intermediate granules are collected and placed in a clean container for later use. The part that passes through the 10-mesh sieve and does not pass through the 60-mesh sieve is qualified granules (qualified rate>95%);

[0144] (11) Mixing: The qualified granules prepared in step (10) are placed in a mixer, lubricant (magnesium stearate, the amount of magnesium stearate is 0.5% of the total mass of the qualified granules and magnesium stearate) is added, and mixed for 15 minutes to obtain Liuwei Anxiao granules;

[0145] (12) Packaging: Adjust the filling volume according to the weight of each bag and operate according to the "granule filling SOP" and granule filling post operating procedures. During the packaging process, take a sample of the filling volume every 10 minutes and record the sampling results to ensure that the filling volume of each bag is within the control range; the bagged granules are placed in a special container, with 2g or 4g per bag, which is equivalent to about 1.5g or 3g of the original medicinal material;

[0146] (13) Outer packaging: In accordance with the standard operating procedures for outer packaging, pack small boxes, pack large boxes, affix anti-counterfeiting trademarks, stamp batch numbers, and pack into outer boxes during the packaging process; place a product certificate in the outer box, seal it tightly with sealing tape, and tie it securely.

[0147] Examples 1-3 primarily examined the effects of commonly used fillers such as sucrose, dextrin, and lactose on granule formation. The results demonstrated no significant effect. Based on the properties of the medicinal ingredients in this formulation, it is theoretically possible to surmise that sucrose, due to its relatively high viscosity, is an appropriate choice. In future production, variations in medicinal preparation conditions can be tolerated or mitigated.

[0148] Example 4

[0149] The purpose of this embodiment is to provide a Liuwei Anxiao granule, which is mainly prepared by the following steps:

[0150] (1) Unique preparation of medicinal materials: same as in Example 1;

[0151] (2) Crushing into coarse powder: Weigh six Mongolian medicinal pieces separately, specifically 180 g of alkali flower crystal, 150 g of milk-quenched red gypsum, 100 g of wine-fried rhubarb, 80 g of Terminalia chebula, 50 g of Kaempferia galanga, and 20 g of Inula officinalis, and crush them into coarse powder;

[0152] (3) Sterilization: Spread the coarse powder of medicinal materials in step (2) on a tray with holes all over the body, make the material temperature 50-60°C, and keep it warm for 2-3 hours for sterilization;

[0153] (4) Grinding and sieving: Grind the sterilized medicinal material coarse powder in step (3) into fine powder, pass through an 80-100 mesh sieve, and obtain medicinal material fine powder; all of the powder passes through a No. 5 sieve, and no less than 95% passes through a No. 6 sieve;

[0154] (5) Mixing: Weigh 240 g of filler (dextrin), add the filler and the medicinal material powder prepared in step (4) into a wet granulator, and mix for 30 minutes to obtain a mixed medicinal powder;

[0155] (6) Preparing a soft material: Adding a binder (starch slurry) to the mixed powder obtained in step (5) to prepare a soft material. When the soft material can be held in a ball by hand and falls apart when released, remove the soft material and set aside. The amount of binder used is about 1% of the total mass of the mixed powder and the binder.

[0156] (7) Granulation: The soft material in step (6) is sieved through a 12-14 mesh sieve to granulate the wet granules. The resulting wet granules should be complete and uniform in size.

[0157] (8) Drying: The wet granules prepared in step (7) are evenly spread on a plate with a thickness of 3-5 cm, placed on a feed cart, and pushed into a hot air circulation oven. The temperature is adjusted to 60-70° C. and dried for 2-3 hours to control the moisture content of the granules to less than 8%, thereby obtaining dry granules.

[0158] (9) Granulation: Place the dried granules in step (8) in a YK160 swing granulator and sieve them with a 14-16 mesh screen. Place the granules after granulation in a clean container lined with a plastic bag. Observe the granules to see if there are any black spots or foreign matter. If the screen is damaged, replace it in time. Weigh the granules after granulation.

[0159] (10) Sieving: The granules prepared in step (9) are placed in a rotary vibrating sieve for granulation. The upper layer is sieved with a 10-mesh sieve to remove large pieces, and the lower layer is sieved with a 60-mesh sieve to remove fine powder. The intermediate granules are collected and placed in a clean container for later use. The part that passes through the 10-mesh sieve and does not pass through the 60-mesh sieve is qualified granules (qualified rate>95%);

[0160] (11) Mixing: The qualified granules prepared in step (10) are placed in a mixer, lubricant (magnesium stearate, the amount of magnesium stearate is 0.5% of the total mass of the qualified granules and magnesium stearate) is added, and mixed for 15 minutes to obtain Liuwei Anxiao granules;

[0161] (12) Packaging: Adjust the filling volume according to the weight of each bag and operate according to the "granule filling SOP" and granule filling post operating procedures. During the packaging process, take a sample of the filling volume every 10 minutes and record the sampling results to ensure that the filling volume of each bag is within the control range; the bagged granules are placed in a special container, with 2g or 4g per bag, which is equivalent to about 1.5g or 3g of the original medicinal material;

[0162] (13) Outer packaging: In accordance with the standard operating procedures for outer packaging, pack small boxes, pack large boxes, affix anti-counterfeiting trademarks, stamp batch numbers, and pack into outer boxes during the packaging process; place a product certificate in the outer box, seal it tightly with sealing tape, and tie it securely.

[0163] Example 5

[0164] The purpose of this embodiment is to provide a Liuwei Anxiao granule, which is mainly prepared by the following steps:

[0165] (1) Unique preparation of medicinal materials: same as in Example 1;

[0166] (2) Crushing into coarse powder: Weigh six Mongolian medicinal pieces separately, specifically 240 g of alkali flower crystal, 220 g of milk-quenched red gypsum, 200 g of wine-fried rhubarb, 150 g of Terminalia chebula, 120 g of Kaempferia galanga, and 80 g of Inula officinalis, and crush them into coarse powder;

[0167] (3) Sterilization: Spread the coarse powder of medicinal materials in step (2) on a tray with holes all over the body, make the material temperature 50-60°C, and keep it warm for 2-3 hours for sterilization;

[0168] (4) Grinding and sieving: Grind the sterilized medicinal material coarse powder in step (3) into fine powder, pass through an 80-100 mesh sieve, and obtain medicinal material fine powder; all of the powder passes through a No. 5 sieve, and no less than 95% passes through a No. 6 sieve;

[0169] (5) Mixing: Weigh 240 g of a filler (dextrin), preferably dextrin, and add the filler and the medicinal material powder prepared in step (4) to a wet granulator for mixing for 30 minutes to obtain a mixed medicinal powder;

[0170] (6) Preparing a soft material: Adding a binder (starch slurry) to the mixed powder obtained in step (5) to prepare a soft material. When the soft material can be held in a ball by hand and falls apart when released, remove the soft material and set aside. The amount of binder used is about 1% of the total mass of the mixed powder and the binder.

[0171] (7) Granulation: The soft material in step (6) is sieved through a 12-14 mesh sieve to granulate the wet granules. The resulting wet granules should be complete and uniform in size.

[0172] (8) Drying: The wet granules prepared in step (7) are evenly spread on a plate with a thickness of 3-5 cm, placed on a feed cart, and pushed into a hot air circulation oven. The temperature is adjusted to 60-70° C. and dried for 2-3 hours to control the moisture content of the granules to less than 8%, thereby obtaining dry granules.

[0173] (9) Granulation: Place the dried granules in step (8) in a YK160 swing granulator and sieve them with a 14-16 mesh screen. Place the granules after granulation in a clean container lined with a plastic bag. Observe the granules to see if there are any black spots or foreign matter. If the screen is damaged, replace it in time. Weigh the granules after granulation.

[0174] (10) Sieving: The granules prepared in step (9) are placed in a rotary vibrating sieve for granulation. The upper layer is sieved with a 10-mesh sieve to remove large pieces, and the lower layer is sieved with a 60-mesh sieve to remove fine powder. The intermediate granules are collected and placed in a clean container for later use. The part that passes through the 10-mesh sieve and does not pass through the 60-mesh sieve is qualified granules (qualified rate>95%);

[0175] (11) Mixing: The qualified granules prepared in step (10) are placed in a mixer, lubricant (magnesium stearate, the amount of magnesium stearate is 0.5% of the total mass of the qualified granules and magnesium stearate) is added, and mixed for 15 minutes to obtain Liuwei Anxiao granules;

[0176] (12) Packaging: Adjust the filling volume according to the weight of each bag and operate according to the "granule filling SOP" and granule filling post operating procedures. During the packaging process, take a sample of the filling volume every 10 minutes and record the sampling results to ensure that the filling volume of each bag is within the control range; the bagged granules are placed in a special container, with 2g or 4g per bag, which is equivalent to about 1.5g or 3g of the original medicinal material;

[0177] (13) Outer packaging: In accordance with the standard operating procedures for outer packaging, pack small boxes, pack large boxes, affix anti-counterfeiting trademarks, stamp batch numbers, and pack into outer boxes during the packaging process; place a product certificate in the outer box, seal it tightly with sealing tape, and tie it securely.

[0178] In Examples 4-5, the effects of changes in the ratio of the prescribed medicinal materials on the molding process were investigated. The results confirmed that changes in the ratio of the prescribed medicinal materials within a reasonable range did not affect the molding process, indicating that the process parameters were reasonable and the process was stable.

[0179] Example 6

[0180] The purpose of this embodiment is to provide a quality control method for Liuwei Anxiao granules.

[0181] 1. Trait detection

[0182] The properties of the Liuwei Anxiao granules obtained in Examples 1-5 of the present invention were detected by visual inspection, olfactory smell and oral tasting. The test results showed that the Liuwei Anxiao granules provided by the examples of the present invention were yellow-brown to brown-brown granules; they had a slightly fragrant smell and a salty and slightly bitter taste.

[0183] 2. Microscopic identification

[0184] Take the Liuwei Anxiao Granules obtained in Examples 1-5 and observe them under a microscope. The Liuwei Anxiao Granules obtained in Examples 1-5 of the present invention were placed under a microscope and observed: the starch granules were round, oval or triangular, with a diameter of 10-30 μm, and the hilum and layer patterns were not obvious (Kaempferia galanga). The calcium oxalate clusters were large, with a diameter of 60-140 μm (rhubarb). Inulin was colorless and in the form of fan-shaped or irregular fragments (Inula). The results showed that the Liuwei Anxiao Granules obtained in Examples 1-5 all had the significant characteristics of Kaempferia galanga, rhubarb and Inula.

[0185] 3. Thin layer chromatography identification

[0186] The instruments used in this experiment include mortar, measuring cylinder, round-bottom flask, straight condenser, electric heating mantle, filter, tray balance, evaporating dish, spotter, GF254 thin layer plate, silica gel G thin layer plate, UV spot analyzer, chromatography cylinder and drying oven; the required control herbs include rhubarb control herbs, galangal control herbs, terminalia chebula control herbs and elecampane control herbs; the required reagents include methanol, cyclohexane, ethyl acetate, formic acid, petroleum ether (30-60℃), chloroform, sulfuric acid and ethanol.

[0187] Identification was performed using thin layer chromatography, as follows:

[0188] Test method 1: Take 1.5g of Liuwei Anxiao granules provided in Examples 1-3, add 4mL of methanol, and ultrasonically treat for 10 minutes (power 160W, rate 50kH Z , the same below), filtered, and the filtrate was used as the test solution. Separately, 0.3 g of rhubarb control medicinal material and 0.2 g of galangal control medicinal material were taken, 3 mL of methanol was added to the rhubarb control medicinal material and galangal control medicinal material respectively, ultrasonically treated for 10 minutes, and the supernatant was taken to obtain rhubarb control medicinal material solution and galangal control medicinal material solution. According to the thin layer chromatography method (General Rule 0502), 3-6 μL of each of the above solutions were taken and spotted on the same silica gel GF254 thin layer plate, and cyclohexane-ethyl acetate-formic acid (the volume ratio of cyclohexane, ethyl acetate and -formic acid is 12:3:0.1) was used as the developing agent. The plate was developed, taken out, dried, and inspected under ultraviolet light (365 nm). The results are as follows. Figure 6 As shown, in the chromatogram of the test sample, at the corresponding position of the chromatogram of the rhubarb control medicinal material, a fluorescent spot of the same color is shown. 1 is the rhubarb control medicinal material solution, and 2-4 correspond to the test solution prepared from the Liuwei Anxiao granules provided in Examples 1-3. Then, the solution is examined under ultraviolet light (254nm). The results are as follows. Figure 7 As shown, in the test sample chromatogram, a main spot of the same color appears at the corresponding position in the chromatogram of the kaempferia galanga control medicinal material. 1 is the kaempferia galanga control medicinal material solution, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao granules provided in Examples 1-3, respectively.

[0189] Test method 2: Take 1.5 g of Liuwei Anxiao Granules provided in Examples 1-3 respectively, add 4 mL of methanol, ultrasonically treat for 10 minutes, filter, and use the filtrate as the test solution. Take 0.2 g of Terminalia chebula control medicinal material, add 3 mL of methanol, ultrasonically treat for 10 minutes, take the supernatant, and obtain Terminalia chebula control medicinal material solution. According to the thin layer chromatography method (General Rule 0502), 3-6 μL of the test solution and the control medicinal material solution were taken, and spotted on the same silica gel GF254 thin layer plate, respectively, and cyclohexane-ethyl acetate-formic acid (the volume ratio of cyclohexane, ethyl acetate and formic acid is 6:4:0.5) was used as the developing agent. Develop, take out, dry, and inspect under ultraviolet light (254 nm). The results are as follows. Figure 8 As shown, in the test sample chromatogram, spots of the same color appear at the corresponding positions in the control medicinal material chromatogram. 1 is the Terminalia chebula control medicinal material solution, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao granules provided in Examples 1-3, respectively.

[0190] Test method 3: Take 2g of Liuwei Anxiao Granules provided in Examples 1-3 respectively, grind them into powder, add 20mL of ethyl acetate, reflux and extract for 30 minutes, filter, evaporate the filtrate in a water bath, and dissolve the residue in 2ml of ethyl acetate to prepare the test solution. Take another 2g of Radix Inulae as a control medicinal material to make a Radix Inulae as a control medicinal material solution, and the preparation method is the same as above. According to the thin layer chromatography method (General Rules 0502 of the 2015 edition of the Chinese Pharmacopoeia), 10μL of each of the above two solutions were taken and spotted on the same silica gel G thin layer plate, and petroleum ether (60-90℃)-ethyl acetate (the volume ratio of petroleum ether (60-90℃) and ethyl acetate is 10:1.5) as the developing agent. Develop, take out, dry, spray with 5% anisaldehyde sulfuric acid solution, bake at 105℃ for 10 minutes, and inspect under sunlight. The results are as follows Figure 9 As shown, in the test sample chromatogram, spots of the same color appear at the corresponding positions in the control medicinal material chromatogram. 1 is the control medicinal material solution of Inula officinalis, and 2-4 correspond to the test sample solutions prepared from the Liuwei Anxiao Granules provided in Examples 1-3, respectively.

[0191] 4. Determination of the content of various active ingredients

[0192] Test method 1: High performance liquid chromatography was used to measure the total chrysophanol (C 15 H0O4) and total emodin (C 15 H 10 O5) and the total chrysophanol in the combined anthraquinone (C 15 H0O4) and total emodin (C 15 H 10 The content of chrysophanol (05) was detected, and the difference between the total amount of total chrysophanol and total emodin and the total amount of free chrysophanol and emodin was obtained by combining chrysophanol and emodin in anthraquinone.

[0193] The instruments used in this test include a high-performance liquid chromatograph, an analytical balance, a pipette, an ultrasonic cleaner, a stoppered conical flask, a brown volumetric flask, and a microporous filter membrane (0.45 μm); the reagents include methanol (chromatographic grade), phosphoric acid solution, and water (double-distilled water); and the reference substances include chrysophanol reference substance and rhamnolide reference substance.

[0194] Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as the filler, acetonitrile-methanol-0.1% phosphoric acid solution (volume ratio of 42:23:35) was used as the mobile phase, and the detection wavelength was 254 nm. The theoretical plate number calculated based on the chrysophanol peak should be no less than 3000.

[0195] Preparation of reference solution: Take appropriate amount of chrysophanol reference substance and emodin reference substance, weigh accurately, add methanol to make a mixed solution containing 18 μg of chrysophanol and 8 μg of emodin per 1 mL.

[0196] Preparation of the test solution: Take 1.0 g of the sample (Liuwei Anxiao Granules provided in Examples 1-3, numbered 1, 2, and 3, respectively), accurately weigh it, place it in a stoppered conical flask, accurately add 25 mL of a mixed solution of methanol and hydrochloric acid (the volume mass ratio of the granule composition and methanol and hydrochloric acid is 10 mL: 1 g), weigh the weight, and heat it under reflux in a 70°C water bath for 30 minutes. If there is adhesion on the wall of the bottle, it must be removed by ultrasonic treatment, and then weigh the weight. Make up the lost weight with methanol, shake well, filter, accurately measure 2 mL of the filtrate, place it in a 5 mL volumetric flask, add 1 mL of 2% sodium hydroxide solution, add methanol to the scale, shake well, filter, and take the filtrate.

[0197] For the determination of free chrysophanol and free emodin content, 0.7 g of the sample (Liuwei Anxiao Granules provided in Examples 1-3, numbered 1, 2, and 3) was accurately weighed and placed in a stoppered conical flask. 25 ml of methanol was accurately added and weighed. The solution was ultrasonically treated for 30 minutes (power 160 W, rate 50 kHz). Z ), let cool, weigh again, make up the lost weight with methanol, mix well, filter, and take the filtrate for the determination of free chrysophanol and free emodin content.

[0198] The specific operation is as follows: 10-20 μL of the reference solution and the two test solutions are accurately drawn, injected into the liquid chromatograph, and measured. The results of chrysophanol and emodin, total chrysophanol and emodin, and free chrysophanol and emodin in the Liuwei Anxiao granules provided in Examples 1-3 are as follows: Figure 10-12 As shown in the three figures, 1 represents chrysophanol and 2 represents emodin.

[0199] Three batches of products were produced according to the method described in Examples 1-3. Each 1g of this product contained chrysophanol (C 15 H 10O4) and total emodin (C 15 H 10 O5), were 1.36mg, 1.38mg, 1.40mg, all greater than 1.05mg; chrysophanol (C 15 H 10 O4) and emodin (C 15 H 10 O5) were 0.80 mg, 0.82 mg, and 0.84 mg, respectively, all greater than 0.6 mg.

[0200] Test method 2: Determine the total alkali content in this product by titration.

[0201] The instruments used in this test include an acid burette, an analytical balance, a pipette, an ultrasonic cleaner, and a stoppered conical flask; the reagents used include methyl red, bromocresol green, and hydrochloric acid.

[0202] The specific operation is as follows: take about 1.5g of the Liuwei Anxiao granules provided in Examples 1-3, which are heated to constant weight at 250-270°C, accurately weighed, and dissolved in 50mL of water. 10 drops of a mixed indicator solution of methyl red and bromocresol green are added, and titrated with a hydrochloric acid titrant (0.5mol / L) until the solution changes from green to dark red. Boil for 2 minutes, cool to room temperature, and continue titrating until the solution changes from green to purple-red. Each 1mL of hydrochloric acid titrant (0.5mol / L) is equivalent to 26.50mg of sodium carbonate (Na2CO3). Three batches of products were produced according to the method described in Examples 1-3. The total alkali content per 1g of sodium carbonate (Na2CO3) was 125mg, 127mg, and 130mg, respectively, all greater than 107mg.

[0203] Test method 3: Determine the content of calcium sulfate (CaSO4) in this product by complexometric titration.

[0204] The instruments used in this test include an acid burette, an analytical balance, a pipette, an ultrasonic cleaner, and a stoppered conical flask; the reagents include methyl red, potassium hydroxide, calcein, and disodium ethylenediaminetetraacetic acid.

[0205] The specific procedure is as follows: Take approximately 0.2g of this product, accurately weigh it, place it in a conical flask, add 10mL of dilute hydrochloric acid, heat to dissolve, add 100mL of water and 2 drops of methyl red indicator solution, add potassium hydroxide test solution dropwise until the solution turns yellow, then add 5mL more, add a small amount of calcein, and titrate with disodium ethylenediaminetetraacetic acid titrant (0.05mol / L) until the yellow-green fluorescence of the solution disappears and an orange color appears. Each 1mL of disodium ethylenediaminetetraacetic acid titrant (0.05mol / L) is equivalent to 6.807g of calcium sulfate (CaSO4).

[0206] Three batches of products were produced according to the method described in Examples 1-3, and each 1g contained 185mg, 187mg, and 190mg of calcium sulfate (CaSO4), respectively, all greater than 151mg.

[0207] In summary, the alkaline flower crystals in the Liuwei Anxiao Granules provided by the embodiments of the present invention are salty and flat, can help digestion, relieve constipation, and dissolve blood stasis, and treat indigestion and constipation, and are the main medicine. The wine-roasted rhubarb is bitter, sour and cool, good at digestion and laxative, and treats indigestion and constipation, and is the ministerial medicine. The milk-quenched red gypsum is pungent and warm, dispels the "badagan" heat in the stomach, helps digestion, and treats epigastric pain; the galangal is bitter and hot, warms the middle and dissolves blood stasis, and treats indigestion, blood stasis in women, and dysmenorrhea. The two medicines are adjuvants. The kelp dispels the "badagan" heat and helps digestion; the terminalia chebula regulates the body's constitution, and are both guiding medicines. The combination of these herbs can strengthen the stomach, aid digestion, reduce acidity and promote bowel movements. It is therefore good at treating indigestion, weakened stomach fire, indigestion, stomach "Bada Gan" heat, epigastric distension and pain, heartburn, belching, Bada Gan He Yi asthma, downward clearing "He Yi" reversal, abdominal distension, constipation, and menstrual blood flow. It has the effects of strengthening the stomach, aiding digestion, reducing acidity and promoting bowel movements. It can be used for indigestion, weakened stomach fire, indigestion, sha syndrome, stomachache, heartburn, belching, "Bada Gan He Yi" asthma, downward clearing "He Yi" reversal, abdominal distension, constipation, and menstrual blood flow. The Liuwei Anxiao Granules draw on the concept of traditional Chinese medicine formula granules and are guided by Mongolian medicine theory. They adhere to the principle of using traditional Mongolian medicinal materials raw and retain the original flavor of Mongolian medicine. On the basis of traditional decoctions and powders, they overcome the disadvantages of Mongolian decoctions and powders that are inconvenient to take. They can be taken directly with warm water and quickly disintegrate or dissolve in the stomach. Their pharmacokinetic parameters are extremely similar to those of powdered decoctions and powders, but they overcome the throat and esophageal irritation of decoctions and powders. They can be used as an alternative dosage form to decoctions and powders in clinical use. Moreover, due to its larger drug specific surface area, its in vivo disintegration rate and absorption rate are greatly improved compared to traditional water pills, which not only enhances the efficacy but also improves children's oral compliance. In addition, the Liuwei Anxiao Granules are more convenient to take and carry, have less irritation, are absorbed quickly, and have significantly increased efficacy.

[0208] The preparation method provided by the embodiment of the present invention applies the technical methods of modern pharmaceutics and adopts a raw powder granulation process without heating, concentration, or extraction. This ensures the multi-pharmacological effects of the Mongolian medicine formula and makes the Liuwei Anxiao granules into a dosage form suitable for modern clinical application. It not only maintains the characteristics of Mongolian medicine and the beneficial ingredients of the original powder or powder, but also has the specificity of the powder for rapid onset of action and is more conducive to improving patient compliance with medication. In addition, it can be combined with an automatic medicine dispensing machine to increase production capacity.

[0209] The quality control method of Liuwei Anxiao Granules provided by the embodiment of the present invention has the following effects: the quality control method provided by the present invention has been subjected to multiple tests, and microscopic identification, thin layer identification and content determination items have been formulated in the quality standard of the Liuwei Anxiao Granules, and specific indicators and parameters of the quality inspection method and standard of the Liuwei Anxiao Granules have been formulated. The use of this quality control method can effectively control the quality of the Liuwei Anxiao Granules, so that the quality of the Liuwei Anxiao Granules can be stable, controllable, efficient and safe.

[0210] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A Liuwei Anxiao granule, characterized in that: The Liuwei Anxiao granules include the following raw materials in parts by mass: 180-240 parts of alkali flower crystals, 150-220 parts of milk-quenched red gypsum, 100-200 parts of wine-fried rhubarb, 80-150 parts of Terminalia chebula, 50-120 parts of Kaempferia galanga, and 20-80 parts of Elecampane; The preparation method of the alkali flower crystal comprises the steps of mixing the alkali flower and water, and then filtering, concentrating, crystallizing, recrystallizing and drying in sequence to obtain the alkali flower crystal; The preparation method of the milk-quenched red gypsum comprises the steps of calcining the red gypsum until it is red, cooling it to 200-250° C., adding it into raw milk to quench it, and drying it to obtain the milk-quenched red gypsum; The method for preparing the wine-fried rhubarb comprises the steps of mixing rhubarb and wine, soaking the mixture and then bathing the mixture in water to obtain the wine-fried rhubarb.

2. The Liuwei Anxiao granules according to claim 1, characterized in that The weight ratio of the alkali flower to water is 1:3; The weight ratio of the cooled calcined red gypsum to the raw milk is 4:1; the quenching time is 40 minutes; The mass volume ratio of the rhubarb to the wine is 10 g:15 mL, the wine is 60°C white wine; the temperature of the water bath is 80°C, and the time is 3-4 hours.

3. The Liuwei Anxiao granules according to claim 1, characterized in that The Liuwei Anxiao granules include the following raw materials in parts by weight: 214.28 parts of alkali flower crystals, 178.57 parts of milk-quenched red gypsum, 142.86 parts of wine-roasted rhubarb, 107.15 parts of Terminalia chebula, 71.43 parts of Kaempferia galanga and 35.71 parts of Elecampane; Or, 180 parts of alkali flower crystals, 150 parts of milk-quenched red gypsum, 100 parts of wine-fried rhubarb, 80 parts of Terminalia chebula, 50 parts of Kaempferia galanga and 20 parts of Eupatorium vulgaris; Or, 240 parts of alkali flower crystals, 220 parts of milk-quenched red gypsum, 200 parts of wine-fried rhubarb, 150 parts of Terminalia chebula, 120 parts of galangal and 80 parts of inula.

4. The Liuwei Anxiao granules according to claim 1, characterized in that The Liuwei Anxiao granules further include excipients, which include fillers, binders and lubricants; The filler includes one or more of sucrose powder, dextrin and lactose powder; the binder includes starch slurry; and the lubricant includes magnesium stearate.

5. The preparation method of Liuwei Anxiao granules according to claim 1, characterized in that: The preparation method comprises the steps of mixing the alkali flower crystal, the milk-quenched red gypsum, the wine-roasted rhubarb, the terminalia chebula, the galangal and the inulin powder to obtain the Liuwei Anxiao granules.

6. The preparation method according to claim 5, characterized in that After the alkali flower crystal, the milk-quenched red gypsum, the wine-roasted rhubarb, the terminalia chebula, the galangal and the inulin powder are mixed, the step of adding auxiliary materials is also included; the auxiliary materials include fillers, adhesives and lubricants; The filler includes one or more of sucrose powder, dextrin and lactose powder; the binder includes starch slurry; and the lubricant includes magnesium stearate.

7. The preparation method according to claim 6, characterized in that The specific steps of adding auxiliary materials include the following steps: The step of sequentially adding the filler, the binder and the lubricant to the mixed Chinese medicine obtained by mixing the alkali flower crystal, the milk-quenched red gypsum, the wine-fried rhubarb, the terminalia chebula, the galangal and the inulin powder.

8. A quality control method for the Liuwei Anxiao granules according to claim 1, characterized in that: include: (1) Observing the shape of the Liuwei Anxiao granules; (2) performing microscopic identification on the Liuwei Anxiao granules; (3) performing thin layer chromatography identification on the Liuwei Anxiao granules; (4) The contents of rhubarb, free anthraquinone, total alkali and calcium sulfate in the Liuwei Anxiao granules were detected by high performance liquid chromatography; the rhubarb content in the Liuwei Anxiao granules was greater than 1.05 mg / g, the free anthraquinone content was greater than 0.6 mg, the total alkali content was greater than 107 mg / g, and the calcium sulfate content was greater than 151 mg / g.

9. The quality control method according to claim 8, characterized in that: The thin layer chromatography identification includes method 1, method 2 and method 3; The method 1 comprises the steps of spotting a test solution, a rhubarb reference substance and a galangal reference substance solution onto a silica gel GF254 thin layer plate, developing the plate with a mixed solution of cyclohexane, ethyl acetate and formic acid as a developing agent, and observing the plate under a 365nm ultraviolet lamp; the preparation method of the test solution comprises the steps of mixing a sample powder to be tested with a methanol solution, and sequentially performing ultrasound and filtration to obtain the test solution; the preparation method of the rhubarb reference substance solution comprises the steps of mixing a rhubarb reference medicinal material with methanol, and performing ultrasound to obtain the rhubarb reference substance solution; the preparation method of the galangal reference substance solution comprises the steps of mixing a galangal reference medicinal material with methanol, and performing ultrasound to obtain the galangal reference substance solution; The method 2 comprises the steps of spotting a test solution and a Terminalia chebula reference solution onto a silica gel GF254 thin layer plate, developing the plate with a mixed solution of cyclohexane, ethyl acetate and formic acid as a developing agent, and observing the plate under a 254 nm ultraviolet lamp; the method for preparing the test solution comprises the steps of mixing a sample powder to be tested with a methanol solution, and sequentially performing ultrasound and filtration to obtain the test solution; the method for preparing the Terminalia chebula reference solution comprises the steps of mixing a Terminalia chebula reference medicinal material with methanol, and performing ultrasound to obtain the Terminalia chebula reference solution; The method 3 includes the steps of spotting a test sample solution and an Inula japonica reference solution on a silica gel G thin layer plate, developing the plate using a mixed solution of petroleum ether and ethyl acetate as a developing agent, spraying anisaldehyde test solution, heating, and observing; the method for preparing the test sample solution includes the steps of mixing the sample powder to be tested with an ethyl acetate solution, sequentially performing reflux extraction, filtering, evaporating to dryness, and redissolving to obtain the test sample solution; the method for preparing the Inula japonica reference solution includes the steps of mixing an Inula japonica reference medicinal material with an ethyl acetate solution, sequentially performing reflux extraction, filtering, evaporating to dryness, and redissolving to obtain the Inula japonica reference solution.

10. The quality control method according to claim 9, characterized in that: In the method 1, the volume ratio of cyclohexane, ethyl acetate and formic acid in the developing solvent is 12:3:0.1; the mass volume ratio of the test sample powder and the ethanol solution is 1.5 g:4 mL; the mass volume ratio of the rhubarb control medicinal material and methanol is 0.3 g:3 mL; the mass volume ratio of the galangal control medicinal material and methanol is 0.2 g:3 mL; In the method 2, the volume ratio of cyclohexane, ethyl acetate and formic acid in the developing solvent is 6:4:0.5; the mass volume ratio of the test sample powder and the ethanol solution is 2 g:20 mL; the mass volume ratio of the Terminalia chebula reference medicinal material and methanol is 0.2 g:3 mL; In method 3, the volume ratio of petroleum ether and ethyl acetate in the developing solvent is 10:1.5; the mass volume ratio of the sample powder to be tested and the ethyl acetate solution is 1 g:25 mL; and the mass volume ratio of the Inula japonica reference medicinal material and the ethyl acetate solution is 2 g:20 mL.

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