Preparation process of phlegm-eliminating and blood-activating granules and application of phlegm-eliminating and blood-activating granules in metabolism-related fatty liver diseases

Abstract

The invention belongs to traditional Chinese medicine formula granules, and particularly relates to a preparation process of phlegm-eliminating and blood-activating granules and application of the phlegm-eliminating and blood-activating granules in metabolism-related fatty liver diseases. The granule comprises gynostemma pentaphylla and raw hawthorn which are used as monarch drugs, raw bighead atractylodes rhizome, rhodiola rosea and turmeric which are used as ministerial drugs, and auxiliary materials for preparing the granule. The granules with the formula for eliminating phlegm and activating blood, which are researched and developed by the invention, have the characteristics of stable property, convenience in transportation, carrying, storage and use and the like. The preparation technology is high in production efficiency and has good economic value, and the prepared granules can effectively exert the pesticide effect.

Description

Technical Field

[0001] The present application relates to a Chinese medicine formula granule, specifically to a preparation process of phlegm-removing and blood-activating granules and its application in metabolic-related fatty liver disease. Background Art

[0002] Granules are dry granular preparations with a certain particle size made by mixing raw materials with suitable excipients. They are included in the general rules for preparations of the 2020 edition (Part IV) of the "Chinese Pharmacopoeia". Granules can be divided into soluble granules (commonly known as granules), suspension granules, effervescent granules, enteric-coated granules, and sustained-release granules according to different release characteristics. Traditional Chinese medicine granules are made by decocting Chinese herbal medicine slices into a specified clear paste, drying and making a fine powder using a suitable method, adding suitable excipients or fine powder of the herbal medicine slices, mixing and making granules; the clear paste can also be added with suitable excipients or fine powder of the herbal medicine slices, mixed and made into granules.

[0003] This study developed a formula for expectorant and blood-activating. To maximize its efficacy and extend its shelf life, granules are a promising approach. Granules offer the following advantages: ① Stable properties, making them easy to transport, carry, store, and use; ② Less prone to scattering, adhesion, aggregation, and hygroscopicity than powders; ③ Better flowability, making them easier to divide into doses; and ④ Maintaining the rapid onset of action of liquid formulations.

[0004] However, if inappropriate granule excipients are added, not only will the expectorant and blood-activating formula developed in this study not be able to exert better efficacy, but it may also lead to a decrease in efficacy and bring about a series of drug quality problems.

[0005] Metabolic associated fatty liver disease (MAFLD), with a current national prevalence of approximately 29.2%, has become the most common chronic liver disease in my country. MAFLD-related end-stage liver disease and the resulting disease burden will increase significantly in the future, but there is still a lack of effective therapeutic drugs for its prevention and treatment.

[0006] Therefore, developing granules with the expectorant and blood-activating formula for this study will provide an effective therapeutic drug for MAFLD patients and better benefit MAFLD patients. This has urgent clinical needs, as well as important pharmaceutical significance and social benefits.

[0007] Application Contents

[0008] In order to solve the technical problems in the above background technology, this application provides a preparation process of Qutan Huoxue Fang granules and its application in metabolic-related fatty liver disease

[0009] The technical solutions adopted in this application are as follows:

[0010] On the one hand, the present application provides a granule with a formula for removing phlegm and promoting blood circulation, which comprises Gynostemma pentaphyllum and raw hawthorn as main drugs, raw Atractylodes macrocephala, Rhodiola rosea and turmeric as auxiliary drugs, and auxiliary materials for preparing the granule.

[0011] Based on the above technical solution, this application can also be improved as follows.

[0012] Furthermore, the auxiliary materials for preparing the granules include maltodextrin and magnesium stearate.

[0013] Furthermore, the granules include, by weight, 20 parts of Gynostemma pentaphyllum and 15 parts of Crataegus pinnatifida as main drugs, and 6 parts of Rhodiola rosea, 12 parts of Atractylodes macrocephala and 9 parts of Curcuma longa as auxiliary drugs.

[0014] Furthermore, the amount of magnesium stearate is 1% of the total amount of the granules.

[0015] On the other hand, the present application also provides a preparation process of the above-mentioned granules with the expectorant and blood-activating formula, comprising the following steps:

[0016] S1. Perform water extraction on Gynostemma pentaphyllum, Atractylodes macrocephala, Curcuma longa, Crataegus chinensis and Rhodiola rosea, and obtain a filtrate after filtration;

[0017] S2, concentrating the filtrate in step S1 to obtain an extract;

[0018] S3, adding maltodextrin to the extract in step S2, heating and stirring to dissolve, and then drying to obtain a dry paste powder;

[0019] S4, sieving the dry paste powder in step S3, adding maltodextrin and magnesium stearate, mixing evenly and then performing dry granulation to obtain a finished granule with a formula for removing phlegm and promoting blood circulation.

[0020] Based on the above technical solution, this application can also be improved as follows.

[0021] Further, in step S1, the water extraction process is to add 8 times the amount of water, soak for 30 minutes, heat to boiling and decoct for 60 minutes, filter, add 8 times the amount of water to the residue, heat and keep it slightly boiling for 60 minutes, filter, and combine the two filtrates.

[0022] Furthermore, in step S2, the concentration is carried out by reduced pressure concentration, the concentration temperature is controlled at 50° C. to 70° C., and the drug solution is concentrated to a relative density of 1.05 to 1.10.

[0023] Furthermore, in step S3, the amount of magnesium stearate added is 1% of the total amount of the granules.

[0024] On the other hand, the present application also provides the use of the above-mentioned granules with the expectorant and blood-activating formula in the preparation of drugs for treating metabolic-related fatty liver disease and liver fibrosis thereof.

[0025] The beneficial effects of the present application are that the granules of the expectorant and blood-activating formula developed in this study have stable properties and are easy to transport, carry, store, and use; have less scattering, adhesion, aggregation, and hygroscopicity than powders; have good fluidity and are easy to divide into doses; and maintain the rapid onset of action of liquid preparations. The preparation method of the granules of the expectorant and blood-activating formula developed in this study can well complete the preparation of the granules, has high production efficiency, has good economic value, and the prepared granules can effectively exert their medicinal effects, have a long shelf life, are convenient for patients to take, and improve patient dependence. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 A schematic diagram of the preparation process of the granules of the present invention for removing phlegm and promoting blood circulation is shown;

[0027] Figure 2 The liver weight and liver-to-body weight ratio of each group of mice in this application are shown. Figure 2 A neutralization Figure 2 In panel B, CON represents the control group, CDAHFD represents the model group, PIO represents the pioglitazone group, ZY represents the Qutan Huoxue Fang group 1, QTHXF-L represents the Qutan Huoxue Fang group 2, which is low-dose, and QTHXF-H represents the Qutan Huoxue Fang group 2, which is high-dose. Compared with the CON group, aP < 0.05; compared with the CDAHFD group, bP < 0.05; and compared with the ZY group, cP < 0.05.

[0028] Figure 3 The HE staining diagram and NAS score of each group of mice in this application are shown. Figure 3 A shows the schematic diagram of HE staining of liver tissue (Bar: 100 μm). Figure 3 B shows the NAS score of liver tissue; CON represents the control group, CDAHFD represents the model group, PIO represents the pioglitazone group, ZY represents the Qutan Huoxue Fang group 1, QTHXF-L represents the Qutan Huoxue Fang group 2 low-dose group, and QTHXF-H represents the Qutan Huoxue Fang group 2 high-dose group. Compared with the CON group, aP < 0.05; compared with the CDAHFD group, bP < 0.05; compared with the ZY group, cP < 0.05.

[0029] Figure 4 The serum ALT and AST activities of each group of mice in this application are shown. Figure 4 A shows the serum ALT activity, Figure 4B shows serum AST activity; CON represents the control group, CDAHFD represents the model group, PIO represents the pioglitazone group, ZY represents the Qutan Huoxue Fang group 1, QTHXF-L represents the Qutan Huoxue Fang group 2, which is low-dose, and QTHXF-H represents the Qutan Huoxue Fang group 2, which is high-dose. Compared with the CON group, aP < 0.05; compared with the CDAHFD group, bP < 0.05; compared with the ZY group, cP < 0.05.

[0030] Figure 5 The TG and HYP contents in the liver tissues of mice in each group of this application are shown. Figure 5 A shows the TG content in liver tissue, Figure 5 B shows the HYP content in liver tissue; CON represents the control group, CDAHFD represents the model group, PIO represents the pioglitazone group, ZY represents the Qutan Huoxue Prescription I group, QTHXF-L represents the Qutan Huoxue Prescription II low-dose group, and QTHXF-H represents the Qutan Huoxue Prescription II high-dose group. Compared with the CON group, aP < 0.05; compared with the CDAHFD group, bP < 0.05; compared with the ZY group, cP < 0.05. DETAILED DESCRIPTION

[0031] The principles and features of the present application are described below in conjunction with the accompanying drawings. The examples given are only used to explain the present application and are not used to limit the scope of the present application.

[0032] Definition of terms:

[0033] As used herein, the term "treat" means to alleviate or alleviate at least one symptom of a disease in a subject. Within the meaning of the present disclosure, the term "treat" also refers to inhibiting, delaying the onset (i.e., the pre-clinical manifestation of the disease) and / or reducing the risk of developing or worsening the disease.

[0034] As used herein, the term "recovery" means that under the influence of certain endogenous or exogenous stimuli, such as endotoxins, cell function and / or structure may change, resulting in structural and / or functional abnormalities. "Recovery" refers to returning this abnormal state to normal. "Protection" means reducing or preventing further changes or damage to cell structure and / or function caused by these endogenous or exogenous stimuli.

[0035] The medicaments or pharmaceutical compositions of the present disclosure can be administered orally, topically, parenterally or mucosally (e.g., buccally, by inhalation or rectally) in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers. The oral route is generally desired.

[0036] Example 1: Development of a preparation process for a granule formulation for removing phlegm and promoting blood circulation

[0037] like Figure 1As shown, the preparation process of the granules with the expectorant and blood-activating formula developed in this study includes: 800g of Gynostemma pentaphyllum, 480g of Atractylodes macrocephala, 360g of Curcuma longa, 600g of Raw Crataegus pinnatifida, and 240g of Rhodiola rosea. The above 5 pieces of medicinal materials are weighed, decocted twice with water, 8 times the amount of water is added for the first time, soaked for 30 minutes, and decocted for 1 hour. The second time, 8 times the amount of water is added for the second time, decocted for 1 hour, filtered, the filtrate is combined, concentrated, an appropriate amount of maltodextrin is added, dried, and an appropriate amount of maltodextrin and magnesium stearate are added. The mixture is mixed, granulated, made into 1000 grams, and packaged.

[0038] The specific process development process is as follows:

[0039] 1.1 Extraction process research

[0040] 1.1.1 Test method

[0041] The heating reflux extraction method was used to investigate the amount of water added (A), extraction time (B), and number of extractions (C). The levels of each factor are shown in Table 1. The design L9 (3 4 The orthogonal table is shown in Table 2. Nine portions of the daily prescription were weighed according to the prescription ratio and an orthogonal design was performed according to the orthogonal design table (each portion was soaked at room temperature for 30 minutes before the first reflux extraction). The extract was filtered through a 200-mesh filter cloth and concentrated under reduced pressure to 100 ml (50-80°C). This yielded the Qutan Huoxue Recipe extract. The dry extract yield and protocatechuic acid content (mg / ml extract) were used as evaluation criteria, and the optimal decoction process was determined through data analysis.

[0042] Table 1: Factors affecting extraction process

[0043]

[0044] 1.1.2 Determination method

[0045] (1) Dry extract yield determination method

[0046] According to the loss on drying method, accurately transfer 5 ml of the extract obtained in the orthogonal experiment, place it in an evaporating dish that has been dried to constant weight, evaporate it in a water bath until it has no fluidity, place it in a constant temperature oven at 105°C and dry it for 3 hours, then take it out and transfer it to a desiccator to cool for 30 minutes. Accurately weigh the weight and calculate the yield of dry extract.

[0047] (2) Determination of protocatechuic acid content

[0048] Determined according to high performance liquid chromatography (General Rule 0512).

[0049] The chromatographic conditions were octadecylsilane bonded silica gel as the filler, acetonitrile-0.1% phosphoric acid solution (10:90) as the mobile phase, and a detection wavelength of 260 nm. The theoretical plate number calculated based on protocatechuic acid should be no less than 3000.

[0050] Preparation of reference solution: Take an appropriate amount of protocatechuic acid reference substance, accurately weigh it, and add 25% methanol to make a solution containing 0.1 mg per 1 ml.

[0051] Preparation of the test solution: Accurately pipette 1 ml of the extract obtained from the orthogonal experiment, dilute it with 25% methanol solution and make up to 25 ml. After thorough mixing, centrifuge at 4000 r / min for 5 min, take the supernatant, and filter it with a 0.45 μm microporous membrane.

[0052] Determination method: Accurately aspirate 10μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0053] 1.1.3 Analysis of orthogonal test results

[0054] Orthogonal test was carried out according to the above method and conditions. The results are shown in Table 2 and Table 3.

[0055] Table 2: Orthogonal experimental design and results of extraction process

[0056]

[0057]

[0058] Note: Comprehensive score = (protocatechuic acid content / maximum protocatechuic acid content) * 50% + (dry paste yield / maximum dry paste yield) * 50%

[0059] Table 3: Analysis of variance of extraction process

[0060] Sources of variance Sum of Squares of Deviations mean square F-number P-value Significance A 281.58 140.79 4.257 0.19 >0.05 B 323.82 161.91 4.896 0.17 >0.05 C 1694.96 847.48 25.626 0.04 <0.05 D(error) 66.14 33.07 - - -

[0061] As shown in Table 2, the primary and secondary factors influencing extraction efficiency are: number of extractions (C) > extraction time (B) > amount of water added (A). Table 3 shows that there is a significant difference in the number of extractions (C), while there are no significant differences in extraction time (B) and amount of water added (A). Comprehensive analysis determined that the optimal extraction process is A3B3C3. Based on the actual production conditions and economic factors such as production costs, the optimal extraction process was adjusted to: add 8 times the amount of water, decoct twice, decoct for 1 hour the first time, and 1 hour the second time.

[0062] 1.2 Verification of the optimal extraction process

[0063] The daily dose of slices was weighed according to the prescribed ratio. The optimal decoction process was followed: adding 8 times the amount of water, allowing the mixture to stand for 30 minutes, and performing two cycles of reflux extraction, each lasting 1 hour. The filtrates were combined, concentrated, and the volume was adjusted to 100 ml. The protocatechuic acid content and dry extract yield were determined, as shown in Table 4. These results demonstrate that the optimal extraction process is stable and feasible.

[0064] Table 4: Verification test results

[0065] Experiment number Protocatechuic acid content (mg / ml) Dry extract yield (%) 1 0.0831 30.82 2 0.0817 30.98 3 0.0811 30.93

[0066] 1.3 Pilot process study to determine the final process

[0067] 1.3.1 Key steps, key process parameters and process results

[0068] The final granule preparation process was determined through Chinese process research, and the developed process is as follows: The key steps and process parameters of the development are shown in Table 5.

[0069] Table 5 Process parameter list

[0070]

[0071] The process results were tested according to Table 5, and the test results are shown in Table 6.

[0072] Table 6 Summary of batch analysis results

[0073]

[0074] 1.3.2 The final developed process is described as follows:

[0075] Based on the results in Table 6, the final developed process is described as follows:

[0076] Extraction: Weigh the five medicinal pieces according to the formula in Table 7 and place them in an extraction tank. Add 8 times the amount of water and soak for 30 minutes. Heat to a boil and simmer for 60 minutes. Filter. Add 8 times the amount of water to the residue and heat to a gentle boil for 60 minutes. Filter. Combine the two filtrates and record the total amount of the extract. The volume of the extract (L) should be: Total amount of medicinal pieces * 16 * 0.70 ~ Total amount of medicinal pieces * 16 * 0.90.

[0077] Concentration: Concentrate under reduced pressure. Based on actual production conditions, control the concentration temperature to around 50°C to 70°C. Concentrate the liquid to a relative density of 1.05 to 1.10 (measured at 60±5°C) and a paste yield of 24% to 32%. Record the weight and relative density of the concentrate.

[0078] Spray Drying: Add the maltodextrin listed in Table 7, heat and stir until completely dissolved, and spray dry to obtain a dry paste powder. Adjust the inlet air temperature to 175°C to 190°C and the outlet air temperature to 85°C to 95°C. The moisture content of the dry paste powder should not exceed 5%.

[0079] Sieve: Pass the dry paste powder through an 80-mesh sieve and set aside.

[0080] Mixing: Take the dry paste powder, add the maltodextrin and magnesium stearate listed in Table 7, mix well, and set aside. Record the mixing time.

[0081] Dry granulation: During granulation, the feed speed is controlled at 60-150 r / min, the roller pressure is controlled at 2-20 MPa, the roller speed is controlled at 20-40 r / min, and 12-mesh and 40-mesh sieves are used. After granulation, the moisture content of the granules is no more than 6.0%.

[0082] Packaging: Particles with a mesh size of 12-40 are packaged into 12.5g bags. During the packaging process, regular checks are performed on the difference in packing volume and the airtightness of the bags.

[0083] Table 7 Batch prescription composition

[0084] Element Dosage Implementation standards Gynostemma pentaphyllum 12.0kg Zhejiang Province Traditional Chinese Medicine Processing Specifications 2015 Edition Atractylodes macrocephala 7.2kg Chinese Pharmacopoeia 2020 Edition turmeric 5.4kg Chinese Pharmacopoeia 2020 Edition Raw hawthorn 9.0kg Chinese Pharmacopoeia 2020 Edition Rhodiola rosea 3.6kg Chinese Pharmacopoeia 2020 Edition maltodextrin Make up to 15kg Chinese Pharmacopoeia 2020 Edition magnesium stearate Total particles 1% Chinese Pharmacopoeia 2020 Edition

[0085] Example 2: Application of phlegm-removing and blood-activating granules in metabolic-related fatty liver disease

[0086] 2.1 Animal grouping

[0087] Forty-eight 5-week-old SPF male C57BL / 6J mice, weighing 16-20 g, were purchased from Shanghai Slake Laboratory Animal Co., Ltd. (animal production license number SCXK(Shanghai)2022-0004). They were maintained at the Experimental Animal Center of the National Science and Technology Ningbo Institute of Life and Health Industry, with a 12-h light-dark cycle and free access to food and water. Adaptive feeding was performed for one week. The mice were randomly divided into a normal group (CON), a low-methionine and choline-deficient high-fat diet (CDAHFD) group, a CDAHFD plus pioglitazone group (PIO), a CDAHFD plus Qutan Huoxue Recipe 1 (ZY), a CDAHFD plus Qutan Huoxue Recipe 2 low-dose group (QTHXF-L), and a CDAHFD plus Qutan Huoxue Recipe 2 high-dose group (QTHXF-H), with 8 mice in each group.

[0088] The ingredients of the Expectorant and Blood Activating Recipe 1 (ZY) include: Gynostemma pentaphyllum 20g, Rhodiola rosea 6g, Raw Atractylodes macrocephala 12g, and Curcuma longa 9g.

[0089] The ingredients of the second phlegm-removing and blood-activating prescription (QTHXF) include: Gynostemma pentaphyllum 20g, Rhodiola rosea 6g, raw Atractylodes macrocephala 12g, turmeric 9g and raw hawthorn 15g.

[0090] 2.2 Model establishment and oral administration

[0091] The CON group was fed with a control diet (XTMRCD10-C, 10% energy supply from fat, normal methionine and choline content, Jiangsu Collaborative Pharmaceutical Bioengineering Co., Ltd.), and the other five groups were fed with a CDAHFD diet (CDAHF60, 60% energy supply from fat, 0.17% methionine, choline deficient, Wuxi Deci Biotechnology Co., Ltd.). Two weeks later, the PIO group was given pioglitazone (10 mg·kg-1·d-1) by gavage; the ZY group was given Chinese medicine (2275 mg·kg-1·d-1 of XX raw Atractylodes macrocephala, 1820 mg·kg-1·d-1 of Gynostemma pentaphyllum, 910 mg·kg-1·d-1 of Rhodiola rosea, and 1365 mg·kg-1·d-1 of Curcuma longa) by gavage; the QTHXF-L group was given Qutan Huoxue Fang (1895.83 mg·kg-1·d-1) by gavage; the QTHXF-H group was given Qutan Huoxue Fang (3791.66 mg·kg-1·d-1) by gavage; the other groups were given an equal amount of normal saline by gavage. The intervention period was 4 weeks.

[0092] 2.3 Experimental Results

[0093] 1.3.1 Effects on liver mass and liver index in MAFLD mice

[0094] like Figure 2 As shown, compared with those of the CON group, the liver weight and liver-to-body ratio of the mice in the CDAHFD group were significantly increased (P<0.05); compared with those of the CDAHFD group, the liver weight and liver-to-body ratio of the mice in the PIO, ZY, QTHXF-L, and QTHXF-H groups were significantly decreased (P<0.05); compared with those of the ZY group, the liver weight and liver-to-body ratio of the mice in the QTHXF-H group were significantly decreased (P<0.05).

[0095] 2.3.2 Effects on liver pathological changes in MAFLD mice

[0096] like Figure 3 As shown in Figure A, HE staining revealed that the liver tissue of mice in the CON group was normal in structure, with no hepatocyte steatosis or inflammatory cell infiltration. However, the liver tissue of mice in the CDAHFD group showed significant steatosis, with numerous intracytoplasmic fat droplets, scattered inflammatory cell infiltration, and ballooning degeneration. However, these pathological changes were significantly alleviated in the QTHXF-L, QTHXF-H, and PIO groups. Compared with the ZY group, the liver tissue steatosis, inflammatory cell infiltration, and ballooning degeneration were reduced in the QTHXF-H group.

[0097] like Figure 3As shown in B, compared with those in the CON group, the NAS score of liver tissue of the mice in the CDAHFD group was significantly increased (P<0.05); compared with those in the CDAHFD group, the NAS score of liver tissue of the mice in the PIO, ZY, QTHXF-L, and QTHXF-H groups was significantly decreased (P<0.05); compared with those in the ZY group, the NAS score of liver tissue of the mice in the QTHXF-H group was significantly decreased (P<0.05).

[0098] 2.3.3 Effects on serum transaminases in MAFLD mice

[0099] like Figure 4 As shown in the data, compared with those of the CON group, the serum ALT and AST activities of the mice in the CDAHFD group were significantly increased (P<0.05); compared with those of the mice in the CDAHFD group, the serum ALT and AST activities of the mice in the PIO, ZY, QTHXF-L, and QTHXF-H groups were significantly decreased (P<0.05); compared with those of the mice in the ZY group, the serum ALT activity of the mice in the QTHXF-H group was significantly decreased (P<0.05).

[0100] 2.3.4 Effects on TG and HYP in liver tissue of MAFLD mice

[0101] like Figure 5 As shown, compared with those of the CON group, the TG and HYP contents in the liver tissue of the mice in the CDAHFD group were significantly increased (P<0.05); compared with those of the CDAHFD group, the TG and HYP contents in the liver tissue of the mice in the PIO, ZY, QTHXF-L and QTHXF-H groups were significantly decreased (P<0.05); compared with those of the ZY group, the TG and HYP contents in the liver tissue of the mice in the QTHXF-H group were significantly decreased (P<0.05).

[0102] Throughout this specification, terms such as "one embodiment," "some embodiments," and "specific embodiments" mean that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0103] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application should be included in the scope of protection of the present application.

Claims

1. A granule for removing phlegm and promoting blood circulation, characterized in that: The granules comprise gynostemma pentaphyllum and raw hawthorn as main drugs, raw atractylodes macrocephala, rhodiola rosea and turmeric as auxiliary drugs, and auxiliary materials for preparing the granules.

2. The granules of the expectorant and blood-activating formula according to claim 1, characterized in that: The auxiliary materials for preparing the granules include maltodextrin and magnesium stearate.

3. The granules of the expectorant and blood-activating formula according to claim 2, characterized in that: In parts by weight, the granules include 20 parts of Gynostemma pentaphyllum and 15 parts of Crataegus pinnatifida as main drugs, and 6 parts of Rhodiola rosea, 12 parts of Atractylodes macrocephala and 9 parts of Curcuma longa as auxiliary drugs.

4. The granules of the expectorant and blood-activating formula according to any one of claims 2 or 3, characterized in that: The amount of magnesium stearate used is 1% of the total amount of the granules.

5. A process for preparing the granules of the expectorant and blood-activating formula according to any one of claims 1 to 4, characterized in that: The steps include: S1. Perform water extraction on Gynostemma pentaphyllum, Atractylodes macrocephala, Curcuma longa, Crataegus chinensis and Rhodiola rosea, and obtain a filtrate after filtration; S2, concentrating the filtrate in step S1 to obtain an extract; S3, adding maltodextrin to the extract in step S2, heating and stirring to dissolve, and then drying to obtain a dry paste powder; S4, sieving the dry paste powder in step S3, adding maltodextrin and magnesium stearate, mixing evenly and then performing dry granulation to obtain a finished granule with a formula for removing phlegm and promoting blood circulation.

6. The preparation process of the granules of the expectorant and blood-activating formula according to claim 5, characterized in that: In step S1, the water extraction process is to add 8 times the amount of water, soak for 30 minutes, heat to boiling and decoct for 60 minutes, filter, add 8 times the amount of water to the residue, heat and keep it slightly boiling for 60 minutes, filter, and combine the two filtrates.

7. The preparation process of the granules of the expectorant and blood-activating formula according to claim 5, characterized in that: In step S2, the concentration is carried out by vacuum concentration, the concentration temperature is controlled at 50° C. to 70° C., and the drug solution is concentrated to a relative density of 1.05 to 1.

10.

8. The preparation process of the granules of the expectorant and blood-activating formula according to claim 5, characterized in that: In step S3, the amount of magnesium stearate added is 1% of the total amount of the granules.

9. Use of the granules of the expectorant and blood-activating formula according to any one of claims 1 to 4 in the preparation of a medicament for treating metabolic-related fatty liver disease and liver fibrosis thereof.

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