Traditional Chinese medicine composition for treating hepatic fibrosis, traditional Chinese medicine preparation and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating hepatic fibrosis, a traditional Chinese medicine preparation and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 90 to 110 parts of meconopsis, 40 to 60 parts of concretio silicea bambusae, 90 to 110 parts of flos carthami, 90 to 110 parts of fructus chebulae, 40 to 60 parts of radix inulae, 30 to 50 parts of herba taxilli paste, 90 to 110 parts of fructus phyllanthi and 3 to 20 parts of stigma croci. The invention further discloses a traditional Chinese medicine preparation for treating hepatic fibrosis and a preparation method thereof. The traditional Chinese medicine preparation can effectively solve the problems of low application safety and high curative effect heterogeneity of western medicines aiming at hepatic fibrosis in the non-alcoholic fatty liver disease at present.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a traditional Chinese medicine composition, preparation and preparation method for treating liver fibrosis. Background Technology

[0002] Nonalcoholic fatty liver disease (NAFLD), as a pathological entity of metabolic disorders, is characterized by the accumulation of pathological lipid droplets in hepatocytes as its core diagnostic marker. The disease spectrum is not related to ethanol metabolism but is significantly correlated with a network of energy metabolism disorders, including obesity-related inflammation, insulin signaling disorders, and abnormal glucose and lipid metabolism. The Global Burden of Disease study reveals that NAFLD has become the fastest-growing type of chronic liver disease. Currently, a "multi-stage pathogenesis model" is used to explain its pathological progression: the initial stage is characterized by an imbalance in the adipose-pancreatic axis, manifested by enhanced lipolysis in adipose tissue and decreased lipid clearance capacity in hepatocytes; the progressive stage is dominated by redox imbalance caused by mitochondrial dysfunction, driving liver fibrosis by activating the NF-κB signaling pathway and promoting myofibroblast transformation. Risk factor stratification studies show that, in addition to basic biomarkers (sex, age), metabolic disorder clusters (low HDL-C, high VLDL secretion) and behavioral metabolomics characteristics (resting lifestyle, nutrient density imbalance) constitute the main predictive factors.

[0003] Currently, the clinical treatment of non-alcoholic fatty liver disease (NAFLD) faces a dual dilemma. At the drug development level, existing guideline-recommended regimens (such as α-tocopherol and PPARγ agonists) are controversial due to potential carcinogenic risks. While next-generation nuclear receptor modulators (such as FXR ligands) have completed clinical validation, they have failed to reach the market due to heterogeneity in efficacy or pharmacokinetic issues, exposing the systemic flaws of modern medicine's single-dimensional treatment strategies.

[0004] Based on this, developing cost-effective intervention programs has become a priority strategy. Molecular compatibility strategies based on phytochemistry, with their resource accessibility and economic efficiency, provide innovative pathways to overcome existing treatment bottlenecks. Summary of the Invention

[0005] The problem this invention aims to solve is to provide a traditional Chinese medicine composition, a traditional Chinese medicine preparation, and a method for preparing the same for treating liver fibrosis. This traditional Chinese medicine preparation can effectively address the problems of low safety and high heterogeneity in efficacy of current Western medicines for treating liver fibrosis in non-alcoholic fatty liver disease.

[0006] The technical solution adopted to solve the technical problem is to provide a traditional Chinese medicine composition for treating liver fibrosis, comprising the following components in parts by weight: 90-110 parts of Meconopsis, 40-60 parts of Bambusa textilis, 90-110 parts of Carthamus tinctorius, 90-110 parts of Terminalia chebula, 40-60 parts of Aucklandia lappa, 30-50 parts of Zha Xun Gao (a traditional Chinese medicine formula), 90-110 parts of Phyllanthus emblica, and 3-20 parts of Saffron.

[0007] Preferred, the traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 95-105 parts of Meconopsis, 45-55 parts of Bambusa textilis, 95-105 parts of Carthamus tinctorius, 95-105 parts of Terminalia chebula, 45-55 parts of Aucklandia lappa, 35-45 parts of Zha Xun Gao (a traditional Chinese medicine formula), 95-105 parts of Phyllanthus emblica, and 5-15 parts of Saffron.

[0008] More preferably, the traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 100 parts of Meconopsis, 50 parts of Bambusa textilis, 100 parts of Carthamus tinctorius, 100 parts of Terminalia chebula, 50 parts of Aucklandia lappa, 40 parts of Zha Xun Gao (a traditional Chinese medicine formula), 100 parts of Phyllanthus emblica, and 10 parts of Saffron.

[0009] A traditional Chinese medicine preparation for treating liver fibrosis includes the above-mentioned traditional Chinese medicine composition and excipients.

[0010] More preferably, the excipients are starch, microcrystalline cellulose and hydroxypropyl methylcellulose.

[0011] More preferably, the dosage form of the traditional Chinese medicine preparation for treating liver fibrosis is pills or tablets.

[0012] The preparation method of a traditional Chinese medicine preparation for treating liver fibrosis includes the following steps: (1) Pulverize and sieve the following herbs: Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao and Phyllanthus emblica. Add 12 to 16 times the weight of the herbs in water, reflux and extract, repeat 2 to 4 times, combine the filtrates and concentrate under reduced pressure to obtain an extract with a relative density of 1.01 to 1.03. (2) Crush the saffron, sieve it, and then dry it to obtain saffron powder; (3) Mix saffron pollen, cornstarch, microcrystalline cellulose and hydroxypropyl methylcellulose evenly to obtain a mixture; (4) Add the extract in two parts to the mixture and stir to obtain a soft material; (5) Extrude the soft material to form pills or tablets.

[0013] Preferably, in step (1), Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao, and Phyllanthus emblica are pulverized and passed through a No. 2 sieve of the Pharmacopoeia.

[0014] Preferably, in step (1), the reflux extraction temperature is 94~102℃ and the time is 1~3h; the vacuum degree of the reduced pressure concentration is -0.05~-0.08Mpa and the temperature is 70~80℃; in step (2), the drying temperature is 50~70℃ and the time is 1~3h; in step (3), saffron pollen, raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose are mixed in a high-shear wet granulator with a rotation speed of 200~220rpm, a cutting speed of 1800~1900rpm and a mixing time of 4~6min; the mass ratio of raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose to the extract is (15~25):(930~970):(25~35):900.

[0015] More preferably, in step (1), the reflux extraction temperature is 98°C and the time is 2h; the vacuum degree of the reduced pressure concentration is -0.06Mpa and the temperature is 75°C; in step (2), the drying temperature is 60°C and the time is 2h; in step (3), saffron pollen, raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose are mixed in a high-shear wet granulator at a speed of 210rpm, a cutting speed of 1900rpm and a mixing time of 5min; the mass ratio of raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose to the extract is 20:950:30:900.

[0016] More preferably, in step (2), saffron is pulverized through a No. 6 sieve from the pharmacopoeia.

[0017] Preferably, step (4) is carried out in a high-shear wet granulator; during the process of adding the extract in two stages, the high-shear wet granulator speed is 250~300 rpm, the cutter speed is 2000~3000 rpm, 55~65% by weight of extract is added in the first stage, and 35~45% by weight of extract is added in the second stage; the stirring includes the following steps: setting the high-shear wet granulator speed to 320~340 rpm, the cutter speed to 2500~3000 rpm, adding water by spraying, and stirring until well mixed.

[0018] More preferably, the spray pressure is 0.19 MPa.

[0019] More preferably, step (4) is carried out in a high-shear wet granulator; during the process of adding the extract in two stages, the high-shear wet granulator speed is 290 rpm and the cutter speed is 2500 rpm, 60% by weight of the extract is added in the first stage and 40% by weight of the extract is added in the second stage; the stirring includes the following steps: setting the high-shear wet granulator speed to 330 rpm and the cutter speed to 2800 rpm, adding water by spraying, and stirring to mix evenly.

[0020] Preferably, step (5) includes the following steps: feeding the soft material into an extrusion rounding coating machine, with a first extrusion speed of 40-50 rpm and a second extrusion speed of 5-15 rpm; after the soft material is extruded and formed, placing the extruded soft material in a rounding disc, and sequentially setting the rounding speed to 80-120 rpm for 15-25 s, 300-400 rpm for 15-25 s, 450-550 rpm for 15-25 s, 550-650 rpm for 630-690 s and 350-450 rpm for 180-240 s, and setting the fan speed to 800-2000 rpm to obtain wet pills; placing the wet pills in a cool and dry place for 22-26 h, and then drying them at 65-75℃ for 2-4 h to obtain pills.

[0021] More preferably, step (5) includes the following steps: feeding the soft material into an extrusion rounding coating machine, with a first extrusion speed of 45 rpm and a second extrusion speed of 10 rpm; after the soft material is extruded and formed, placing the extruded soft material in a rounding disc, and sequentially setting the rounding speed to 100 rpm for 20 s, 350 rpm for 20 s, 500 rpm for 20 s, 600 rpm for 660 s and 400 rpm for 210 s, and setting the fan speed to 1000 rpm to obtain wet pills; placing the wet pills in a cool and dry place for 24 h, and then drying them at 70°C for 3 h to obtain pills.

[0022] The present invention has the following beneficial effects: The core pathogenesis of liver fibrosis in non-alcoholic fatty liver is as follows: the liver fails to disperse and dredge, the gallbladder is stagnated with heat, and the spleen and stomach have abnormal transportation and transformation functions, resulting in the intermingling of dampness, heat, phlegm, turbidity and stasis of blood, with "blood stasis" and "heat-toxin" as the core. In the traditional Chinese medicine composition of the present invention, saffron and meconopsis are the monarch drugs. Meconopsis has comprehensive effects of clearing heat from the liver and gallbladder, promoting diuresis and subsiding jaundice, and promoting blood circulation to remove blood stasis. Its dosage is the largest, and it acts as the monarch drug in terms of "quantity". At the same time, saffron is an excellent medicinal material for promoting blood circulation to remove blood stasis, with strong power and remarkable effects. It is especially good at cooling blood and detoxifying, and dissipating stasis and resolving masses. It is the first choice for treating liver fibrosis and liver cirrhosis, and it acts as the monarch drug in terms of "quality". Further, safflower and zhaxun paste are the ministerial drugs. Safflower is a classic medicinal herb for promoting blood circulation to dredge the meridian and dispelling stasis to relieve pain. Its dosage is the same as that of meconopsis, and it can greatly enhance the power of saffron and meconopsis in promoting blood circulation to remove blood stasis, jointly dredge the liver collaterals, improve liver microcirculation, and reverse fibrosis. Zhaxun paste is a compound paste prepared by special processing of mineral salts and plant drugs. Its effects are clearing heat and detoxifying, promoting bile flow and removing blood stasis, and regulating the liver and stomach. It can significantly enhance the effects of the monarch drugs in clearing heat and stagnation from the liver and gallbladder and resolving stasis-toxin. At the same time, its cholagogic effect helps to dredge the gallbladder and reduce the burden on the liver from the source. And bamboo shavings and costus root together are the adjuvant drugs. The effect of bamboo shavings is clearing heat and resolving phlegm, removing the pathological products that block qi movement and promote blood stasis. The effect of costus root is strengthening the spleen and stomach, regulating qi and relieving pain. Liver diseases often transmit to the spleen, resulting in stagnation of qi in the spleen and stomach. Costus root can strengthen the spleen and regulate qi, restore the transportation and transformation function of the spleen and stomach, prevent the generation of "phlegm-dampness" from the root, and at the same time prevent the large amount of cold drugs in the formula from damaging the function of the spleen and stomach. Terminalia chebula and Phyllanthus emblica are the envoy drugs. Terminalia chebula is mild in nature, and its effects are coordinating the properties of all drugs in the formula, clearing heat and detoxifying, astringing yin and promoting the production of body fluid. It can integrate the properties of all drugs in the formula, make its effect mild and lasting, and prevent the excessive pungent-dispersing and bitter-purging effects of the monarch, ministerial and adjuvant drugs from consuming yin fluid. Phyllanthus emblica is cool in nature, sweet, sour and astringent in taste, and its effects are clearing heat and cooling blood, promoting the production of body fluid and relieving cough, and regulating qi and blood. Matched with Terminalia chebula, it can enhance the power of "generating yin from sour and sweet", and protect the healthy qi of the human body from being damaged by the attacking drugs. The whole formula regulates through multiple channels and multiple targets, not only improves the abnormal metabolism of fatty liver, but also delays the process of liver fibrosis, and at the same time takes into account the dual effects of protecting the liver and relieving symptoms, treating both the symptoms and the root causes. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a sample diagram of the traditional Chinese medicine preparation for treating liver fibrosis prepared in Example 1 of the present invention; Figure 2 It is a direct-view diagram of the livers of rats in different groups in the test example; among them, (a) is the control group; (b) is the model group; (c) is the positive drug group; (d) is the high-dose concentrated pill group; (e) is the medium-dose concentrated pill group; (f) is the low-dose concentrated pill group; (g) is the crude drug group; Figure 3 It is a result diagram of the liver weight and liver coefficient of rats in different groups in the test example; among them, (a) is the result diagram of the liver weight of rats in different groups; (b) is the result diagram of the liver coefficient of rats in different groups; Figure 4HE-stained sections of rats in different groups in the experimental case are shown; (a) is the control group; (b) is the model group; (c) is the positive drug group; (d) is the high-dose concentrated pill group; (e) is the medium-dose concentrated pill group; (f) is the low-dose concentrated pill group; (g) is the original drug group. Figure 5 The images show the microscopic pathological scoring results of liver tissue from different groups of rats in the experimental cases; (a) is the NAFLD activity score; (b) is the ballooning degeneration score; (c) is the inflammation score; and (d) is the fatty degeneration score. Figure 6 The images show the serum liver function indicators and liver fibrosis levels of rats in different groups in the experimental case; (a) is the laminin level; (b) is the hyaluronic acid level; (c) is the alanine aminotransferase level; (d) is the type IV collagen level; (e) is the type III procollagen level; and (f) is the aspartate aminotransferase level. Figure 7 The images show the levels of inflammatory factors in the liver tissue and serum of rats in different groups in the experimental case; (a) shows the level of IL-1β; (b) shows the level of IL-6; (c) shows the level of TNF-α; (d) shows the level of IL-13; (e) shows the level of IL-18; and (f) shows the level of IL-4. Figure 8 The graph shows the results of hydroxyproline determination in the liver tissue of rats in different groups in the experimental case. Figure 9 The images show the collagen fiber content and Collagen I staining results in the liver tissue of rats from different groups in the experimental case; (a) is the area density map of Masson-stained collagen fibers; (b) is the percentage map of Collagen I positive areas. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0025] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0026] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0027] Example 1 A traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 100 parts of Meconopsis, 50 parts of Bambusa textilis, 100 parts of Carthamus tinctorius, 100 parts of Terminalia chebula, 50 parts of Aucklandia lappa, 40 parts of Zha Xun Gao (a traditional Chinese medicine formula), 100 parts of Phyllanthus emblica, and 10 parts of Saffron.

[0028] A traditional Chinese medicine preparation for treating liver fibrosis, in pill form, is prepared by means of the following steps: (1) Pulverize Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao and Phyllanthus emblica through a No. 2 sieve of the pharmacopoeia and add them into an extraction tank. Add 14 times the weight of the medicinal materials of water and reflux extract at 98°C for 2 hours. Repeat 3 times. Combine the filtrates and concentrate under reduced pressure at -0.06 MPa and 75°C. Pass the concentrate through a 100-mesh sieve and collect the filtrate to obtain an extract with a relative density of 1.02. (2) Crush saffron and pass it through a No. 6 sieve of the pharmacopoeia, and then dry it in an oven at 60°C for 2 hours to obtain saffron powder; (3) Take saffron powder, 20 parts by weight of raw starch, 950 parts by weight of microcrystalline cellulose and 30 parts by weight of hydroxypropyl methylcellulose and put them into a high-shear wet granulation machine. Set the rotation speed to 210 rpm and the cutter speed to 1900 rpm and mix for 5 min to obtain a mixture. (4) Adjust the parameters of the high shear wet granulator to a rotation speed of 290 rpm and a cutter speed of 2500 rpm. Take 900 parts of extract and add them to the excipient mixture in two stages. Add 60% of the extract by weight in the first stage and 40% of the extract by weight in the second stage. After the addition is completed, set the rotation speed of the high shear wet granulator to 330 rpm and the cutter speed to 2800 rpm. Add water by spraying at a pressure of 0.19 MPa. Stir and mix well to obtain a soft material. (5) The soft material is put into the extrusion rolling coating machine. The first extrusion speed is 45 rpm and the second extrusion speed is 10 rpm. After the soft material is extruded, the extruded soft material is placed in the rolling disc. The rolling speed is set sequentially to 100 rpm for 20 s, 350 rpm for 20 s, 500 rpm for 20 s, 600 rpm for 660 s and 400 rpm for 210 s. The fan speed is set to 1000 rpm to obtain wet pills. The wet pills are placed in a cool and dry place for 24 h and then dried at 70 ℃ for 3 h to obtain pills.

[0029] The prepared traditional Chinese medicine preparation for treating liver fibrosis has the following appearance: Figure 1 As shown.

[0030] Example 2 A traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 95 parts of Meconopsis, 45 parts of Bambusa textilis, 95 parts of Carthamus tinctorius, 95 parts of Terminalia chebula, 45 parts of Aucklandia lappa, 35 parts of Zha Xun Gao (a traditional Chinese medicine formula), 95 parts of Phyllanthus emblica, and 5 parts of Saffron.

[0031] A traditional Chinese medicine preparation for treating liver fibrosis, in pill form, is prepared by means of the following steps: (1) Pulverize Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao and Phyllanthus emblica through a No. 2 sieve of the pharmacopoeia and add them into an extraction tank. Add 12 times the weight of the medicinal materials of water and reflux extract at 94°C for 3 hours. Repeat 3 times. Combine the filtrates and concentrate under reduced pressure at -0.05 MPa and 80°C. Pass the concentrate through a 100-mesh sieve and collect the filtrate to obtain an extract with a relative density of 1.03. (2) Crush saffron and pass it through a No. 6 sieve of the pharmacopoeia, and then dry it in an oven at 50°C for 3 hours to obtain saffron powder. (3) Take saffron powder, 15 parts by weight of raw starch, 970 parts by weight of microcrystalline cellulose and 25 parts by weight of hydroxypropyl methylcellulose and put them into a high-shear wet granulation machine. Set the rotation speed to 200 rpm and the cutter speed to 1800 rpm and mix for 6 minutes to obtain a mixture. (4) Adjust the parameters of the high shear wet granulator to a rotation speed of 250 rpm and a cutter speed of 2000 rpm. Take 900 parts of extract and add them to the excipient mixture in two stages. Add 55% by weight of extract in the first stage and 45% by weight of extract in the second stage. After the addition is completed, set the rotation speed of the high shear wet granulator to 320 rpm and the cutter speed to 2500 rpm. Add water by spraying at a pressure of 0.19 MPa. Stir and mix well to obtain a soft material. (5) The soft material is put into the extrusion rounding coating machine. The first extrusion speed is 40 rpm and the second extrusion speed is 5 rpm. After the soft material is extruded, the extruded soft material is placed in the rounding disc. The rounding speed is set sequentially to 80 rpm for 25 s, 300 rpm for 25 s, 450 rpm for 25 s, 550 rpm for 690 s and 350 rpm for 240 s, and the fan speed is set to 800 rpm to obtain wet pills. The wet pills are placed in a cool and dry place for 22 h and then dried at 75 ℃ for 2 h to obtain pills.

[0032] Example 3 A traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 105 parts of Meconopsis, 55 parts of Bambusa textilis, 105 parts of Carthamus tinctorius, 105 parts of Terminalia chebula, 55 parts of Aucklandia lappa, 45 parts of Zha Xun Gao (a traditional Chinese medicine formula), 105 parts of Phyllanthus emblica, and 15 parts of Saffron.

[0033] A traditional Chinese medicine preparation for treating liver fibrosis, in pill form, is prepared by means of the following steps: (1) Pulverize Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao and Phyllanthus emblica through a No. 2 sieve of the pharmacopoeia and add them into an extraction tank. Add 16 times the weight of the medicinal materials of water and reflux extract at 102℃ for 1.5h. Repeat 3 times. Combine the filtrates and concentrate under reduced pressure at -0.08Mpa and 70℃. Pass the concentrate through a 100-mesh sieve and collect the filtrate to obtain an extract with a relative density of 1.01. (2) Crush saffron and pass it through a No. 6 sieve of the pharmacopoeia, and then dry it in an oven at 70°C for 1 hour to obtain saffron powder. (3) Take saffron powder, 25 parts by weight of raw starch, 930 parts by weight of microcrystalline cellulose and 35 parts by weight of hydroxypropyl methylcellulose and put them into a high-shear wet granulation machine. Set the rotation speed to 220 rpm and the cutter speed to 1900 rpm and mix for 4 min to obtain a mixture. (4) Adjust the parameters of the high shear wet granulator to a rotation speed of 300 rpm and a cutter speed of 3000 rpm. Take 900 parts of extract and add them to the excipient mixture in two stages. Add 65% by weight of extract in the first stage and 35% by weight of extract in the second stage. After the addition is completed, set the rotation speed of the high shear wet granulator to 340 rpm and the cutter speed to 3000 rpm. Add water by spraying at a pressure of 0.19 MPa. Stir and mix well to obtain a soft material. (5) The soft material is put into the extrusion rolling coating machine. The first extrusion speed is 50 rpm and the second extrusion speed is 15 rpm. After the soft material is extruded, the extruded soft material is placed in the rolling disc. The rolling speed is set sequentially to 120 rpm for 15 s, 400 rpm for 15 s, 550 rpm for 15 s, 650 rpm for 630 s and 450 rpm for 180 s. The fan speed is set to 2000 rpm to obtain wet pills. The wet pills are placed in a cool and dry place for 26 h and then dried at 65 ℃ for 4 h to obtain pills.

[0034] Example 4 A traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 90 parts of Meconopsis, 40 parts of Bambusa textilis, 90 parts of Carthamus tinctorius, 90 parts of Terminalia chebula, 40 parts of Aucklandia lappa, 30 parts of Zha Xun Gao (a traditional Chinese medicine formula), 90 parts of Phyllanthus emblica, and 3 parts of Saffron.

[0035] A traditional Chinese medicine preparation for treating liver fibrosis, in pill form, is prepared using the same method as in Example 1.

[0036] Example 5 A traditional Chinese medicine composition for treating liver fibrosis comprises the following components in parts by weight: 110 parts of Meconopsis, 60 parts of Bambusa textilis, 110 parts of Carthamus tinctorius, 110 parts of Terminalia chebula, 60 parts of Aucklandia lappa, 50 parts of Zha Xun Gao (a traditional Chinese medicine formula), 110 parts of Phyllanthus emblica, and 20 parts of Saffron.

[0037] A traditional Chinese medicine preparation for treating liver fibrosis, in pill form, is prepared using the same method as in Example 1.

[0038] A pharmacodynamic study of traditional Chinese medicine preparations for treating liver fibrosis and improving non-alcoholic fatty liver disease in experimental cases. Eighty-four male SD rats (100-110g) were randomly divided into seven groups (n=12) after a one-week acclimatization period: Control, Model, Positive Agent (silymarin, 29mg / kg), Low-dose Concentrated Pill (150mg / kg), Middle-dose Concentrated Pill (300mg / kg), High-dose Concentrated Pill (600mg / kg), and Original Drug (ESWWLRHW, 400mg / kg). The Low-dose, Middle-dose, and High-dose Concentrated Pill groups used the traditional Chinese medicine preparation prepared in Example 1; the Original Drug group used the Twenty-Five Flavor Meconopsis Pill produced by Qinghai Chaidamu High-Tech Pharmaceutical Co., Ltd. Except for the Control group, rat liver fibrosis models were established by intraperitoneal injection of carbon tetrachloride (CCl4). The model and drug-treated groups received an initial intraperitoneal injection of 40% carbon tetrachloride olive oil solution at a dose of 5 mL / kg. Three days later, the dose was adjusted to 3 mL / kg for model initiation. The blank control group received an intraperitoneal injection of olive oil at a dose of 5 mL / kg, twice weekly for six weeks (12 weeks total). Simultaneously with model initiation, the control and model groups were administered 1 mL / 100g of distilled water daily via gavage, while the other five groups received 1 mL / 100g of the corresponding drug once daily via gavage. After eight weeks of treatment, the rats were fasted and deprived of water for 24 hours. They were then anesthetized with glutaraldehyde solution, and blood and liver tissue were collected for subsequent experiments.

[0039] 1.1 Observation of rat liver and tissue sections First, the rat liver was observed directly, and the results were as follows: Figure 2 As shown. From Figure 2 As can be seen, the livers in the Control group were bright red in color and soft in texture. The livers in the Model group were slightly paler in color than those in the Control group, with rounded edges, dull surface, uneven texture, and even visible granular nodules.

[0040] The liver weight and liver coefficient of rats in each group were analyzed. The formula for calculating the liver coefficient is shown in equation (1) below. The results are as follows: Figure 3 As shown; Figure 3 In the middle ns group: no significant difference; compared with the control group: #### P <0.001; compared to the Model group: * P <0.05, ** P <0.01, *** P <0.005, **** P <0.001.

[0041] Liver coefficient = liver weight / rat body weight (1) In the formula, the liver weight is in mg; the rat's weight is in 100g.

[0042] from Figure 3 As can be seen from the results, the liver volume and liver coefficient of rats in the concentrated pill administration group of the present invention decreased significantly with the increase of drug dosage, especially in the medium and high dose administration groups, where the improvement was very obvious compared with the original drug group.

[0043] The liver sections of rats in each group were then observed using an optical microscope after HE staining, and the liver tissue micropathology of each group was scored. The average score was used to represent the sample. The specific scoring criteria are shown in Table 1 below. The results are as follows: Figures 4-5 As shown; Figure 5 In the middle ns: no significant difference; compared with the control group: #### P<0.001; compared with the model group: * P<0.05, ** P<0.01, *** P<0.005, **** P<0.001.

[0044] Table 1 NAFLD Activity Scoring Criteria

[0045] from Figure 4 As can be seen from the 40x objective lens, the pathological changes in the Control group were not obvious, the hepatic sinusoids were clear and there were no obvious abnormalities; the Model group showed disordered arrangement of hepatic cords, confluent focal necrosis around the central vein, a large number of inflammatory cell infiltrations in the hepatic sinusoids and portal areas, and fatty degeneration in some hepatocytes; combined with Figure 5 It can be seen that the low-dose administration group showed less improvement, while the concentrated pill administration group and the silymarin group showed more intact liver lobule structure and a small amount of inflammatory infiltration. The lesions showed a higher degree of improvement than the model group, indicating that the efficacy of the drug is dose-dependent, and that high-dose administration tends to be superior to the positive control drug.

[0046] 1.2 Changes in liver function and four liver fibrosis markers in rats The liver function indicators of the rat serum in each group were measured. The specific method was as follows: the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of each group of rats were measured by microplate method. The OD value was substituted into the standard curve for calculation according to the kit instructions. The AST and ALT activities in the serum of each group of rats were then obtained by the formulas for AST activity and ALT activity. The formula for calculating AST activity is shown in formula (2) below, and the formula for calculating ALT activity is shown in formula (3) below. AST activity (U / L) = Substituting into the standard curve, we get AST activity × 0.48 × N (2) ALT activity (U / L) = ALT activity × 0.48 × N (3) (Substitute into the standard curve) In equations (2) and (3) above, the AST activity unit is obtained by substituting into the standard curve and the ALT activity unit is obtained by substituting into the standard curve; 0.48 are the conversion factor from Kamen's units to U / L; N are the dilution factor of the sample before testing.

[0047] The four liver fibrosis markers are commonly used serological indicators for assessing the degree of liver fibrosis, including type III procollagen (PCIII), type IV collagen (C-IV), laminin (LN), and hyaluronic acid (HA). Blood tests can indirectly reflect the metabolic status of the extracellular matrix in the liver, the progression of fibrosis, and the degree of inflammatory activity. The specific detection method for the four liver fibrosis markers is as follows: using a commercial ELISA kit, the procedure is performed accurately according to the kit instructions to measure the levels of PCIII, C-IV, LN, and HA in the serum of rats in each group. Results are as follows... Figure 6 As shown, Figure 6 In the middle ns group: no significant difference; compared with the control group: #### P <0.001; compared to the Model group: * P <0.05, ** P <0.01, *** P <0.005, **** P <0.001.

[0048] from Figure 6As can be seen, compared with the Control group, the Model group showed a significant increase in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating liver damage in rats. After treatment with medium and high doses of concentrated pills, the levels of AST and ALT decreased significantly, showing a certain dose-dependent effect, and the effect was more significant than that of the original drug group, suggesting that the traditional Chinese medicine preparation for treating liver fibrosis prepared in this invention has a good therapeutic effect on liver fibrosis in non-alcoholic fatty liver disease. Figure 6 The changes in the levels of the four liver fibrosis markers showed that after drug treatment, the expression levels of each marker were significantly reduced in the medium and high dose groups, further demonstrating that the formula has a good anti-liver fibrosis effect, and the high dose showed a trend of being superior to the positive control drug.

[0049] 1.3 Changes in the levels of inflammatory factors in rat liver tissue and serum The changes in serum inflammatory factor levels were detected using an ELISA kit. Standard wells, blank wells, and sample wells were sequentially set up on the ELISA plate according to the kit instructions. The plate was then placed in an ELISA reader, and the wavelength was set to 450 nm to measure the absorbance (OD) value of each sample well. The expression levels of inflammatory factors in each group of serum samples were calculated based on a standard curve. Results are as follows: Figure 7 As shown, Figure 7 In the middle ns group: no significant difference; compared with the control group: #### P <0.001; compared to the Model group: * P <0.05, ** P <0.01, *** P <0.005, **** P <0.001.

[0050] from Figure 7 As can be seen, compared with the Control group, the serum IL-13 and IL-4 levels in the Model group were significantly decreased, while the levels of pro-inflammatory factors IL-18, IL-1β, IL-6, and TNF-α were significantly increased, indicating that there was a significant inflammatory response in the Model group rats. After treatment with various doses of drugs, the serum IL-13 and IL-4 levels in the medium and high dose groups of rats were significantly restored, while the levels of pro-inflammatory factors IL-18, IL-1β, IL-6, and TNF-α showed a decreasing trend. However, the effect of low-dose concentrated pills was not obvious, indicating that the formula may have inhibited the inflammatory response, promoted the resolution of fibrosis, and played an anti-liver fibrosis role. Moreover, the effect of medium and high doses of concentrated pills in improving rat inflammation was significantly better than that of the prepared drug.

[0051] 1.4 HYP assay in rat liver tissue Changes in hydroxyproline (HYP) levels reflect the degree of liver fibrosis in the disease. Using an ELISA kit, standard wells, blank wells, and sample wells were sequentially set up on a microplate according to the kit instructions. The plate was then placed in a microplate reader, and the absorbance (OD) value of each sample well was measured. The expression level of HYP in liver tissue of each group was calculated based on a standard curve. Results are as follows: Figure 8 As shown, Figure 8 In the middle ns group: no significant difference; compared with the control group: #### P <0.001; compared to the Model group: * P <0.05, ** P <0.01, *** P <0.005, **** P <0.001.

[0052] from Figure 8 The results showed that the HYP content in the treatment group decreased significantly and in a dose-dependent manner, indicating that the treatment effect of this formula was very significant. Moreover, the effect of medium and high doses of concentrated pills in improving liver fibrosis in rats was significantly better than that of the prepared medicine.

[0053] 1.5 Masson staining and immunohistochemical staining of rat liver tissue The collagen fiber content and Collagen I staining in rat liver tissue were analyzed using ImageJ image analysis software. The results are as follows: Figure 9 As shown, Figure 9 In the middle ns group: no significant difference; compared with the control group: #### P <0.001; compared to the Model group: * P <0.05, ** P <0.01, *** P <0.005, **** P <0.001.

[0054] from Figure 9Masson staining revealed that the hepatocytes in the Control group rats had normal morphology and no collagen fiber hyperplasia; the Model group rats showed abundant collagen fibers accompanied by pseudolobule formation; compared with the Model group, the collagen fiber content in the medium- and high-dose treatment groups gradually decreased with increasing drug concentration. Statistical analysis showed that compared with the Control group, the collagen content in the liver of the Model group rats was significantly increased; compared with the Model group, the collagen content in the liver of the medium- and high-dose treatment groups was significantly decreased. Immunohistochemical detection of Collagen I expression in rat liver tissue showed that compared with the Control group, the positive expression of Collagen I in the Model group was significantly increased, and its expression was significantly reduced after medium- and high-dose administration, indicating that this formula has a certain therapeutic effect on liver fibrosis, and the effect of medium- and high-dose concentrated pills in improving rat liver fibrosis is significantly better than that of the prepared medicine.

[0055] The present invention has been described according to the above embodiments. It should be understood that the above embodiments do not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent transformation fall within the scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating liver fibrosis, characterized in that, The ingredients include the following components by weight: 90-110 parts of Meconopsis, 40-60 parts of Bambusa textilis, 90-110 parts of Carthamus tinctorius, 90-110 parts of Terminalia chebula, 40-60 parts of Aucklandia lappa, 30-50 parts of Zha Xun Gao (a type of herbal extract), 90-110 parts of Phyllanthus emblica, and 3-20 parts of Saffron.

2. The traditional Chinese medicine composition for treating liver fibrosis as described in claim 1, characterized in that, The ingredients include the following components by weight: 95-105 parts of Meconopsis, 45-55 parts of Bambusa textilis, 95-105 parts of Carthamus tinctorius, 95-105 parts of Terminalia chebula, 45-55 parts of Aucklandia lappa, 35-45 parts of Zha Xun Gao (a type of herbal extract), 95-105 parts of Phyllanthus emblica, and 5-15 parts of Saffron.

3. The traditional Chinese medicine composition for treating liver fibrosis as described in claim 1 or 2, characterized in that, The ingredients include the following components by weight: 100 parts Meconopsis, 50 parts Bambusa textilis, 100 parts Carthamus tinctorius, 100 parts Terminalia chebula, 50 parts Aucklandia lappa, 40 parts Zha Xun Gao (a type of herbal extract), 100 parts Phyllanthus emblica, and 10 parts Saffron.

4. A traditional Chinese medicine preparation for treating liver fibrosis, characterized in that, It includes the traditional Chinese medicine composition and excipients as described in any one of claims 1 to 2.

5. The traditional Chinese medicine preparation for treating liver fibrosis as described in claim 4, characterized in that, The excipients are starch, microcrystalline cellulose and hydroxypropyl methylcellulose.

6. The traditional Chinese medicine preparation for treating liver fibrosis as described in claim 5, characterized in that, The dosage form of the traditional Chinese medicine preparation is pills or tablets.

7. The method for preparing the traditional Chinese medicine preparation for treating liver fibrosis according to claim 6, characterized in that, Includes the following steps: (1) Pulverize and sieve the following herbs: Meconopsis, Bambusa textilis, Carthamus tinctorius, Terminalia chebula, Aucklandia lappa, Zha Xun Gao and Phyllanthus emblica. Add 12 to 16 times the weight of the herbs in water, reflux and extract, repeat 2 to 4 times, combine the filtrates and concentrate under reduced pressure to obtain an extract with a relative density of 1.01 to 1.

03. (2) Crush the saffron, sieve it, and then dry it to obtain saffron powder; (3) Mix saffron powder, cornstarch, microcrystalline cellulose and hydroxypropyl methylcellulose evenly to obtain a mixture; (4) Add the extract to the mixture in two parts and stir to obtain a soft material; (5) Extrude the soft material to form pills or tablets.

8. The method for preparing the traditional Chinese medicine preparation for treating liver fibrosis as described in claim 7, characterized in that, In step (1), the reflux extraction temperature is 94~102℃ and the time is 1~3h; the vacuum degree of the reduced pressure concentration is -0.05~-0.08Mpa and the temperature is 70~80℃; in step (2), the drying temperature is 50~70℃ and the time is 1~3h; in step (3), saffron powder, raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose are mixed in a high shear wet granulator with a rotation speed of 200~220rpm, a cutting speed of 1800~1900rpm and a mixing time of 4~6min; the mass ratio of raw starch, microcrystalline cellulose and hydroxypropyl methylcellulose to extract is (15~25):(930~970):(25~35):

900.

9. The method for preparing the traditional Chinese medicine preparation for treating liver fibrosis as described in claim 7, characterized in that, Step (4) is carried out in a high-shear wet granulation machine; during the process of adding the extract in two stages, the high-shear wet granulation machine rotates at 250~300 rpm and the cutter speed is 2000~3000 rpm. 55~65% by weight of the extract is added in the first stage and 35~45% by weight of the extract is added in the second stage; the stirring includes the following steps: setting the high-shear wet granulation machine to 320~340 rpm and the cutter speed to 2500~3000 rpm, adding water by spraying, and stirring until well mixed.

10. The method for preparing the traditional Chinese medicine preparation for treating liver fibrosis as described in claim 7, characterized in that, Step (5) includes the following steps: the soft material is fed into an extrusion rolling coating machine, the first extrusion speed is 40-50 rpm, and the second extrusion speed is 5-15 rpm; after the soft material is extruded and formed, the extruded soft material is placed in a rolling disc, and the rolling speed is set sequentially to 80-120 rpm for 15-25 s, 300-400 rpm for 15-25 s, 450-550 rpm for 15-25 s, 550-650 rpm for 630-690 s and 350-450 rpm for 180-240 s, and the fan speed is set to 800-2000 rpm to obtain wet pills; the wet pills are placed in a cool and dry place for 22-26 h, and then dried at 65-75℃ for 2-4 h to obtain pills.

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