Traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, traditional Chinese medicine preparation and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, a traditional Chinese medicine preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparations. 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 tabasheer, 90 to 110 parts of flos carthami, 70 to 90 parts of saxifraga stolonifera, 60 to 80 parts of herba aristolochiae, 30 to 50 parts of herba taxilli paste and 20 to 40 parts of semen herpetospermi. The invention further discloses a traditional Chinese medicine preparation for treating the non-alcoholic fatty liver disease and a preparation method of the traditional Chinese medicine preparation. The traditional Chinese medicine preparation can be used for effectively solving the problems of poor reversing effect, poor overall regulation and control capability and insufficient stability of the existing non-alcoholic fatty liver disease treatment medicine on hepatic fibrosis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, a traditional Chinese medicine preparation and a preparation method thereof. BACKGROUND

[0002] Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely related to metabolic disorders, and its core pathological feature is abnormal deposition of lipids in hepatocytes. The disease often coexists with obesity, type 2 diabetes, hypertension and other components of metabolic syndrome, forming a vicious cycle. Its clinical progression is occult, and in the early stage, it can be asymptomatic, but it can gradually develop into non-alcoholic steatohepatitis (NASH), liver fibrosis and even cirrhosis, and in severe cases, it can induce hepatocellular carcinoma. In addition to liver damage itself, the risk of cardiovascular events in patients with NAFLD is significantly increased, which has become an important burden on public health worldwide.

[0003] Currently, the treatment of NAFLD still faces multiple challenges. Although many candidate drugs have been developed in the field of Western medicine, there are obvious limitations: some drugs can improve liver steatosis or inflammation, but the effect of reversing liver fibrosis is limited; the clinical application of some drugs is limited due to side effects (such as dyslipidemia and reduced bone density); and the long-term safety of some drugs is not clear, which makes it difficult to meet the needs of long-term management of chronic liver disease. Although traditional Chinese medicine treatment has the advantages of multi-component and multi-target intervention, existing traditional Chinese medicine preparations mainly focus on protecting the liver and anti-inflammation, and lack of high-quality clinical evidence to support the stability and repeatability of their efficacy.

[0004] Therefore, it is of great significance to develop a traditional Chinese medicine compound preparation with metabolic regulation, anti-inflammatory and anti-fibrosis effects and clear safety for meeting the needs of NAFLD whole course management. SUMMARY

[0005] The present application solves the problem of providing a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, a traditional Chinese medicine preparation and a preparation method thereof, which can effectively solve the problems of poor reversal effect on liver fibrosis, poor overall regulation ability and insufficient stability of current non-alcoholic fatty liver disease treatment drugs.

[0006] To solve the technical problem, a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease is provided, which comprises the following components in parts by weight: green wormwood 90-110 parts, rhizoma anemarrhenae 40-60 parts, safflower 90-110 parts, small umbrella saxifrage 70-90 parts, Bashaga 60-80 parts, Zhaxun paste 30-50 parts and Boenguazi 20-40 parts.

[0007] Preferably, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following components in parts by weight: 95-105 parts of Bunge pricklyash bark, 45-55 parts of Radix Pseudostellariae, 95-105 parts of Safflower, 75-85 parts of Saxifraga stella, 65-75 parts of Radix Bistortae, 35-45 parts of Radix Rubi and 25-35 parts of Fructus Trichosanthis.

[0008] More preferably, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following components in parts by weight: 100 parts of Bunge pricklyash bark, 50 parts of Radix Pseudostellariae, 100 parts of Safflower, 80 parts of Saxifraga stella, 70 parts of Radix Bistortae, 40 parts of Radix Rubi and 30 parts of Fructus Trichosanthis.

[0009] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease comprises the above-mentioned traditional Chinese medicine composition and excipients.

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

[0011] More preferably, the dosage form of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease is a plaster, a pill or a tablet.

[0012] A preparation method of a traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease comprises the following steps: (1) grinding Bunge pricklyash bark, Radix Pseudostellariae, Safflower, Saxifraga stella, Radix Bistortae, Radix Rubi and Fructus Trichosanthis, then adding 9-13 times the weight of the medicinal materials in water, refluxing and extracting, repeating 2-4 times, combining the filtrates and concentrating under reduced pressure to obtain an extract with a relative density of 0.95-0.99, and preparing a plaster; (2) mixing microcrystalline cellulose and hydroxypropyl methyl cellulose uniformly to obtain an excipient mixture; (3) adding the extract to the excipient mixture in two stages, and stirring to obtain a soft material; (4) extruding the soft material to form a pill or a tablet.

[0013] Preferably, 11 times the weight of the medicinal materials in water is added in step (1).

[0014] Preferably, the refluxing and extracting temperature in step (1) is 94-102℃, the time is 1.5-2.5h; the vacuum degree for concentration under reduced pressure is -0.05 to -0.08 Mpa, and the temperature is 60-70℃; in step (2), the microcrystalline cellulose and hydroxypropyl methyl cellulose are mixed in a high-shear wet granulator at a rotation speed of 180-200 rpm and a cutter speed of 1500-1900 rpm for 4-6 min; the mass ratio of microcrystalline cellulose, hydroxypropyl methyl cellulose and the extract is (950-1000):(25-35):900.

[0015] More preferably, the reflux extraction temperature in step (1) is 98℃, and the time is 2h; the vacuum concentration degree is -0.06Mpa, and the temperature is 65℃; in step (2), the microcrystalline cellulose and hydroxypropyl methyl cellulose are mixed in a high-shear wet granulator, the rotating speed is 190rpm, the cutter speed is 1700rpm, and the mixing time is 5min; the mass ratio of the microcrystalline cellulose, the hydroxypropyl methyl cellulose and the extract is 970:30:900.

[0016] Preferably, step (3) is carried out in a high-shear wet granulator; during the process of adding the extract in two stages, the rotating speed of the high-shear wet granulator is 240~280rpm, the cutter speed is 2200~2600rpm, 35~45% by weight of the extract is added in the first stage, and 55~65% by weight of the extract is added in the second stage; the stirring includes the following steps: setting the rotating speed of the high-shear wet granulator to 290~330rpm, the cutter rotating speed to 2500~3000rpm, and adding water in a spraying manner, and stirring uniformly.

[0017] More preferably, the spraying pressure is 0.19Mpa.

[0018] More preferably, step (3) is carried out in a high-shear wet granulator; during the process of adding the extract in two stages, the rotating speed of the high-shear wet granulator is 260rpm, the cutter speed is 2400rpm, 40% by weight of the extract is added in the first stage, and 60% by weight of the extract is added in the second stage; the stirring includes the following steps: setting the rotating speed of the high-shear wet granulator to 310rpm, the cutter rotating speed to 2700rpm, and adding water in a spraying manner, and stirring uniformly.

[0019] Preferably, step (4) includes the following steps: putting the soft material into an extrusion rounding coating machine, the first extrusion speed is 20~30rpm, and the second extrusion speed is 5~15rpm; after the soft material is extruded and formed, the extruded and formed soft material is placed in a rounding disc, the rounding speeds are set as 80~120rpm for 15~25s, 400~500rpm for 15~25s, 450~550rpm for 15~25s, 550~650rpm for 660~720s, and 300~400rpm for 150~210s, and the fan speed is set to 800~2000rpm, to obtain wet pellets; after the wet pellets are placed in a cool and dry place for 10~14h, and dried at 70~90℃ for 0.5~1.5h, the pellets are prepared.

[0020] More preferably, the step (4) comprises the following steps: the soft material is put into an extrusion rounding coating machine, the first extrusion speed is 25 rpm, and the second extrusion speed is 10 rpm; after the soft material is extruded and formed, the extruded and formed soft material is placed in a rounding disc, the rounding speeds are set as 100 rpm for 20 s, 450 rpm for 20 s, 500 rpm for 20 s, 600 rpm for 690 s and 350 rpm for 180 s in sequence, and the fan speed is set as 1000 rpm, so that wet pellets are obtained; the wet pellets are placed in a cool and dry place for 12 h, and then dried at 80 ℃ for 1 h, so that the pellets are prepared.

[0021] The present application has the following beneficial effects: The core pathogenesis of NAFLD can be summarized as follows: liver losing the function of dredging, gall bladder dysfunction, spleen losing the function of transportation, leading to internal retention of damp-heat, phlegm and blood stasis, and accumulation in the hypochondrium. In the treatment of this disease, the principles of "dispelling the solid", "dispersing the accumulated", "clearing the damp", and "cooling the heat" should be followed. Deficiency should be tonified and excess should be purged. The pathogenic factors should be removed without damaging the normal body functions. The basic treatment principles for this disease are clearing heat and removing dampness, soothing the liver and strengthening the spleen, promoting blood circulation and removing blood stasis, and tonifying the liver and kidney. These principles should be flexibly used based on the syndrome differentiation and specific conditions, so as to achieve good curative effects. The composition of the traditional Chinese medicine composition is rigorous and follows the compatibility principle of "monarch, minister, assistant and courier". The core of NAFLD is lipid metabolism disorder and inflammatory damage. Green fennel is the monarch drug, which has the effects of clearing liver and gallbladder heat, removing dampness and reducing yellow, and promoting blood circulation and removing blood stasis. The minister drugs are safflower and fructus benincasae. Safflower can assist the monarch drug green fennel in promoting blood circulation, dredging liver collaterals, improving liver microcirculation, and preventing and reversing liver fibrosis. Fructus benincasae is the first drug for clearing liver and gallbladder heat in Tibetan medicine, and it is especially good at removing gallbladder heat. It has strong heat-removing and damp-removing effects, and can significantly enhance the effect of the monarch drug green fennel in clearing liver and gallbladder damp-heat. The assistant drugs are saxifraga stolonifera, baxaga, curcuma zedoaria, and rhizoma coptidis. Saxifraga stolonifera has the effects of removing dampness and reducing yellow, and clearing heat and detoxifying. It has significant diuretic effect and can remove damp-heat through urine. Baxaga has the effects of removing yellow water, clearing heat, relieving inflammation and relieving pain. In Tibetan medicine, "yellow water" is similar to inflammatory exudate and allergic mediators. Baxaga can remove liver and gallbladder inflammation and assist the monarch and minister drugs in resisting liver inflammatory damage. Curcuma zedoaria has the effects of clearing heat and reducing phlegm. NAFLD is prone to "phlegm turbidity" due to spleen deficiency and transportation failure. Curcuma zedoaria can clear heat and reduce phlegm and remove pathological products that block the qi mechanism. Rhizoma coptidis is a compound paste prepared from mineral salts and plant drugs through special processing. It has the effects of clearing heat and detoxifying, and regulating liver and stomach. It can assist in clearing heat and protect the gastric mucosa from damage by a large amount of bitter and cold drugs in the prescription due to its acid-removing effect. At the same time, rhizoma coptidis is the courier drug. Rhizoma coptidis is made of multiple components and has the property of regulating and integrating the effects of other drugs, so that the overall effect of the prescription is more harmonious. Rhizoma coptidis enters the liver and stomach meridians and can guide the effects of other drugs in the prescription to act on the liver, gallbladder, spleen and stomach. In Tibetan medicine, rhizoma coptidis often plays the role of a "courier drug", but its role is beyond that of a regular courier drug, so it is often called a "regulating drug". The monarch, minister, assistant and courier drugs in the prescription are in order, which can clear heat and reduce phlegm to eliminate liver lipid accumulation, and promote blood circulation and protect the liver to block the progression of the disease. It has a positive significance for improving liver cell steatosis and restoring normal liver function. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 A sample chart of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease prepared in Example 1 of the present application; Figure 2 A chart of body weight changes of rats in different groups in the test example; Figure 3Figures for changes in liver weight, liver coefficient, epididymal fat weight and epididymal fat coefficient of rats in different groups in the test example; wherein, (a) is a figure for liver weight of rats in different groups; (b) is a figure for liver coefficient of rats in different groups; (c) is a figure for epididymal fat weight of rats in different groups; (d) is a figure for epididymal fat coefficient of rats in different groups; Figure 4 Figures for HE staining sections of rats in different groups in the test example; wherein, (a) is a control group; (b) is a model group; (c) is a positive drug group; (d) is a high-dose concentrated pill group; (e) is a medium-dose concentrated pill group; (f) is a low-dose concentrated pill group; (g) is a raw drug group; Figure 5 Figures for microscopic pathological observation and scoring results of rats in different groups in the test example; wherein, (a) is a figure for steatosis scoring; (b) is a figure for inflammation scoring; (c) is a figure for ballooning scoring; (d) is a figure for NAFLD activity scoring; Figure 6 Figures for serum liver function index and blood lipid four-item level results of rats in different groups in the test example; wherein, (a) is a figure for aspartate aminotransferase level; (b) is a figure for alanine aminotransferase level; (c) is a figure for high-density lipoprotein cholesterol level; (d) is a figure for triglyceride level; (e) is a figure for total cholesterol level; (f) is a figure for low-density lipoprotein cholesterol level; Figure 7 Figures for serum inflammatory factor levels of rats in different groups in the test example; wherein, (a) is a figure for IL-4 level; (b) is a figure for IL-6 level; (c) is a figure for IL-13 level; (d) is a figure for IL-1β level; (e) is a figure for TNF-α level; (f) is a figure for IL-18 level. DETAILED DESCRIPTION

[0023] In order to make the objectives, technical solutions, and advantages of the present application clearer, the following further describes the present application in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely intended to explain the present application, and are not intended to limit the present application, i.e., the described embodiments are only a part of the embodiments of the present application, but not all of the embodiments.

[0024] Therefore, the following detailed description of the embodiments of the present application provided herein is not intended to limit the scope of the claimed present application, but merely represents selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative efforts fall within the scope of the present application.

[0025] The features and performances of the present application are further described in detail in conjunction with the embodiments below.

[0026] Embodiment 1 A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, comprising the following components in parts by weight: Herba Bungeanae 100 parts, Radix Curcumae 50 parts, Flos Carthami 100 parts, Saxifraga stella 80 parts, Radix Bistortae 70 parts, Radix Rubi 40 parts, and Fructus Trichosanthis 30 parts.

[0027] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease, in the form of a pill, prepared by the following steps: (1) Herba Bungeanae, Radix Curcumae, Flos Carthami, Saxifraga stella, Radix Bistortae, Radix Rubi, and Fructus Trichosanthis are ground through a No. 2 pharmacopoeia sieve and added to an extraction tank, 11 times the weight of the medicinal materials in water is added, and reflux extraction is carried out at 98°C for 2 hours, repeated 3 times. The filtrate is combined and concentrated under reduced pressure at a pressure of -0.06 Mpa and a temperature of 65°C. The concentrated liquid is sieved through a 100-mesh sieve, and the filtrate is collected to obtain an extract with a relative density of 0.97; (2) 970 parts by weight of microcrystalline cellulose and 30 parts by weight of hydroxypropyl methylcellulose are added to a high-shear wet granulator, the rotation speed is set to 190 rpm, and the cutter speed is set to 1700 rpm, and mixing is carried out for 5 minutes to obtain a mixture of auxiliary materials; (3) The parameters of the high-shear wet granulator are adjusted to a rotation speed of 260 rpm and a cutter speed of 2400 rpm, 900 parts of the extract are added to the mixture of auxiliary materials in two stages, 40% by weight of the extract is added in the first stage, and 60% by weight of the extract is added in the second stage. After the addition is complete, the rotation speed of the high-shear wet granulator is set to 310 rpm, the cutter rotation speed is set to 2700 rpm, water is added in a spraying manner, the spraying pressure is 0.19 Mpa, and the mixture is stirred and mixed uniformly to obtain soft material; (4) The soft material is placed in an extrusion rounding and coating machine, the first extrusion speed is 25 rpm, and the second extrusion speed is 10 rpm. After the soft material is extruded and formed, the extruded and formed soft material is placed in a rounding disc, the rounding speeds are set in sequence as 100 rpm for 20 s, 450 rpm for 20 s, 500 rpm for 20 s, 600 rpm for 690 s, and 350 rpm for 180 s, and the fan speed is set to 1000 rpm to obtain wet pills. The wet pills are placed in a cool and dry place for 12 hours, and then dried at 80°C for 1 hour to obtain pills.

[0028] The appearance of the prepared traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease is as shown in Figure 1 .

[0029] Example 2 A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, comprising the following components in parts by weight: Herba Bungeanae 100 parts, Radix Curcumae 50 parts, Flos Carthami 100 parts, Saxifraga stella 80 parts, Radix Bistortae 70 parts, Radix Rubi 40 parts, and Fructus Trichosanthis 30 parts.

[0030] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease, the dosage form is pill, the preparation method comprises the following steps: (1) The Artemisia rupestris, Radix Curcumae, Crocus sativus, Saxifraga stella, Basha Ga, Zhaxin Gao and Powdery Benincasa cerifera are crushed to pass through the No. 2 pharmacopoeia sieve and are added into an extraction tank, 9 times the weight of water of the medicinal materials is added, reflux extraction is carried out at 94 DEG C for 1.5 h, the operation is repeated for 3 times, the filtrates are combined and concentrated under reduced pressure at a pressure of-0.05 Mpa and a temperature of 60 DEG C, the concentrated liquid obtained is sieved through a 100-mesh sieve, and the filtrate is collected, so that the extract with a relative density of 0.95 is obtained; (2) 950 parts by weight of microcrystalline cellulose and 35 parts by weight of hydroxypropyl methyl cellulose are put into a high-shear wet granulator, the rotation speed is set to 180 rpm, the cutter speed is set to 1500 rpm, and mixing is carried out for 6 min, so that a mixture of auxiliary materials is obtained; (3) The parameters of the high-shear wet granulator are adjusted to a rotation speed of 240 rpm and a cutter speed of 2200 rpm, 900 parts of the extract are added into the mixture of auxiliary materials in two stages, 35% of the extract is added in the first stage, and 65% of the extract is added in the second stage, after the addition is completed, the rotation speed of the high-shear wet granulator is set to 290 rpm, the cutter rotation speed is set to 2500 rpm, water is added in a spraying manner, the spraying pressure is 0.19 Mpa, and stirring and mixing are carried out, so that soft materials are obtained; (4) The soft materials are put into an extrusion rounding and coating machine, the first extrusion speed is 20 rpm, and the second extrusion speed is 5 rpm; after the soft materials are extruded and formed, the extruded and formed soft materials are placed in a rounding disc, the rounding speeds are set to 80 rpm for 25 s, 400 rpm for 25 s, 450 rpm for 25 s, 550 rpm for 720 s and 300 rpm for 210 s in sequence, and the fan speed is set to 800 rpm, so that wet pills are obtained; the wet pills are placed in a cool and dry place for 14 h, and then are dried at 90 DEG C for 1.5 h, so that the pill is prepared.

[0031] Example 3 A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, comprising the following components in parts by weight: Artemisia rupestris 105 parts, Radix Curcumae 55 parts, Crocus sativus 105 parts, Saxifraga stella 85 parts, Basha Ga 75 parts, Zhaxin Gao 45 parts and Powdery Benincasa cerifera 35 parts.

[0032] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease, the dosage form is pill, the preparation method comprises the following steps: (1) Green, rhizoma curculiginis, safflower, Saxifraga stellariifolia, Bashaga, Zhaxin paste and Trichosanthes kirilowii Maxim. are crushed to pass through the No. 2 pharmacopoeia sieve and are added into the extraction tank. Then, 13 times the weight of water of the medicinal materials is added. The extraction is carried out at 102℃ for 2.5h, and the operation is repeated for 3 times. The filtrate is combined and concentrated under reduced pressure at the pressure of-0.08Mpa and the temperature of 70℃. The concentrated solution is sieved through a 100 mesh sieve. The filtrate is collected to obtain the extract with the relative density of 0.99; (2) 1000 parts by weight of microcrystalline cellulose and 25 parts by weight of hydroxypropyl methylcellulose are put into a high-shear wet granulator. The rotation speed is set to 200rpm, and the cutter speed is set to 1900rpm. The mixing is carried out for 4min to obtain a mixture of excipients. (3) The parameters of the high-shear wet granulator are adjusted to the rotation speed of 280rpm and the cutter speed of 2600rpm. 900 parts of the extract are added into the mixture of excipients in two stages. In the first stage, 45% of the extract by weight is added. In the second stage, 55% of the extract by weight is added. After the addition is completed, the rotation speed of the high-shear wet granulator is set to 330rpm, and the cutter rotation speed is set to 3000rpm. Water is added in a spraying manner. The spraying pressure is 0.19Mpa. The mixture is stirred and mixed uniformly to obtain soft materials. (4) The soft materials are put into an extrusion rounding and coating machine. The first extrusion speed is 30rpm, and the second extrusion speed is 15rpm. After the soft materials are extruded and formed, the extruded and formed soft materials are placed in a rounding disc. The rounding speeds are set to 120rpm for 15s, 500rpm for 15s, 550rpm for 15s, 650rpm for 660s, and 400rpm for 150s, respectively. The fan speed is set to 2000rpm. The wet pellets are obtained. After the wet pellets are placed in a cool and dry place for 10h, they are dried at 70℃ for 0.5h to obtain pellets.

[0033] Example 4 A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following components in parts by weight: Green 90 parts, rhizoma curculiginis 40 parts, safflower 90 parts, Saxifraga stellariifolia 70 parts, Bashaga 60 parts, Zhaxin paste 30 parts and Trichosanthes kirilowii Maxim. 20 parts.

[0034] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease has a dosage form of pellets. The preparation method is the same as that of Example 1.

[0035] Example 5 A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following components in parts by weight: Green 110 parts, rhizoma curculiginis 60 parts, safflower 110 parts, Saxifraga stellariifolia 90 parts, Bashaga 80 parts, Zhaxin paste 50 parts and Trichosanthes kirilowii Maxim. 40 parts.

[0036] A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease has a dosage form of pellets. The preparation method is the same as that of Example 1.

[0037] Test Example Pharmacodynamic study of Chinese medicine preparation for treating non-alcoholic fatty liver disease to improve non-alcoholic fatty liver After 1 week of adaptive feeding, 84 male SD rats (100-110 g) were randomly divided into 7 groups (n=12), control group (Control), model group (Model), positive drug group (Positive, obeticholic acid: 25 mg / kg), concentrated pill low-dose group (Low, 150 mg / kg), concentrated pill middle-dose group (Middle, 300 mg / kg), concentrated pill high-dose group (High, 600 mg / kg) and raw medicine group (ESWWLRHW, 400 mg / kg); among them, the concentrated pill low-dose group, the concentrated pill middle-dose group and the concentrated pill high-dose group all used the Chinese medicine preparation prepared in Example 1; the raw medicine group used the twenty-five green wormwood pills produced by Qinghai Chaidamu High-tech Pharmaceutical Co., Ltd. The Control group was fed with ordinary maintenance feed, and the other groups were fed with high-fat feed (60% fat) to establish a non-alcoholic fatty liver disease (NAFLD) model, and each group was given enough drinking water. After 4 weeks of feeding, the Control group and the Model group were given 0.5% CMC-Na by gavage, and each drug group of rats was given corresponding drugs by gavage for intervention treatment, once a day for 6 weeks.

[0038] 1.1 Changes in body weight of rats During the experiment, the mental state, changes in fur, drinking and eating of rats in each group were observed, body weight was monitored every week, and body weight changes were recorded, as shown in Figure 2 .

[0039] As can be seen from Figure 2 , during the 10-week experiment, the body weight of rats in each group showed different trends of increase. Compared with the Control group of rats, the body weight of rats fed with high-fat feed showed a more obvious trend of increase, and the fur was more shiny and smooth. After drug intervention treatment at the 5th week, the body weight of the drug groups showed a slower trend of increase, and with the progress of drug administration, the body weight of rats in each drug group gradually decreased to close to the level of the Control group of rats, and showed a certain dose-dependent effect.

[0040] 1.2 Observation of rat liver tissue sections The changes of liver weight, liver coefficient, epididymal fat weight and epididymal fat coefficient of rats in each group were analyzed. The specific test method of epididymal fat weight was as follows: a large white and soft fat tissue attached to the testis of each group of rats was found, which was epididymal fat, and it was separated from the surrounding connective tissue and blood vessels with an ophthalmic forceps, and then peeled off completely. The removed epididymal fat was quickly put into pre-cooled physiological saline to remove the surface blood and impurities; after being taken out, it was placed on a clean filter paper, and the excess liquid on the surface was absorbed, and then weighed. The liver coefficient was calculated according to the formula (1) as shown below, and the epididymal fat coefficient was calculated according to the formula (2) as shown below, and the results are shown in Figure 3 ; Figure 3 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; ns: no significant difference.

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

[0042] Epididymal fat coefficient = epididymal fat weight / rat weight (2) In the formula, the epididymal fat weight is in mg; and the rat weight is in 100 g.

[0043] From Figure 3 it can be seen that the epididymal fat weight is significantly increased, the liver coefficient and the epididymal fat coefficient are increased, and the liver volume, liver coefficient and epididymal fat coefficient of rats in each drug group are obviously improved with the increase of the drug dose.

[0044] Then, the HE staining sections of liver of rats in each group were observed by optical microscope, and the microscopic pathology of liver tissue of rats in each group was scored, and the average value after scoring represented the sample, and the specific scoring standard is shown in Table 1; the results are shown in Figures 4-5 ; Figure 5 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; ns: no significant difference.

[0045] Table 1 NAFLD Activity Scoring Criteria

[0046] Hematoxylin and eosin (HE) stained sections of rat livers from each group were observed using an optical microscope, such as... Figure 4 As shown, under a 40x objective lens, the hepatocytes in the livers of rats in the Control group were neatly arranged, the liver lobules were normal, and no obvious inflammatory cell aggregation or infiltration was observed; the livers of rats in the Model group, fed a high-fat diet, showed obvious steatosis, with fat vacuoles and inflammatory cell infiltration, indicating significant NAFLD lesions. Simultaneously, combined with... Figure 5 It can be seen that, compared with the Control group, the index values ​​of rats in other groups were significantly increased; after treatment with various doses, the indicators of inflammatory infiltration and fatty degeneration in rats in each treatment group were significantly improved, and the improvement was dose-dependent, which was significantly better than that of the original drug group. The high-dose administration tended to be superior to the positive control drug.

[0047] 1.3 Changes in liver function and four blood lipid parameters in rats The serum liver function indicators and four lipid parameters of rats in each group were measured. The specific methods were as follows: Liver function indicators: The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of rats in each group were measured by microplate method. The OD values ​​were substituted into the standard curve for calculation according to the kit instructions. The activities of AST and ALT in the serum of rats in each group were obtained by the formulas for AST and ALT activities. The formula for calculating AST activity is shown in formula (3) below, and the formula for calculating ALT activity is shown in formula (4) below. AST activity (U / L) = Substituting into the standard curve, we get AST activity × 0.48 × N (3) ALT activity (U / L) = ALT activity × 0.48 × N (4) (Substitute into the standard curve) In equations (3) and (4) 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.

[0048] Four lipid tests: Following the instructions of the kit, the levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (T-CHO), and triglycerides (TG) in the serum of rats in each group were measured.

[0049] The results of serum liver function indicators and four lipid levels in each group of rats 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.

[0050] from Figure 6 As can be seen, compared with the Control group fed with ordinary maintenance diet, the Model group fed with high-fat diet showed significantly increased AST and ALT levels, indicating liver damage in rats. After treatment with various doses of concentrated pills, AST and ALT levels decreased significantly and showed a certain dose-dependent effect, suggesting that our drug has a good therapeutic effect on non-alcoholic fatty liver disease.

[0051] The formation of NAFLD is closely related to abnormal lipid metabolism, the most direct manifestation of which is an increase in T-CHO (total cholesterol), TG (triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels or a decrease in HDL-C (high-density lipoprotein cholesterol) levels. Compared with the control group, the Model group showed significantly increased LDL-C, TG, and T-CHO levels and a significantly decreased HDL-C level after being fed a high-fat diet. This trend was reversed after treatment with various doses of concentrated pills, positive control, and the original drug, showing a certain dose-dependent effect, and the treatment effect was better than that of the original drug. Medium and high doses of concentrated pills significantly improved liver function and blood lipid levels in rats.

[0052] 1.4 Serum inflammatory factor levels in rats The changes in serum inflammatory factor levels in rats of each group were detected using an ELISA kit. The results are as follows: Figure 7Shown, Figure 7 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; ns: no significant difference.

[0053] From Figure 7 It can be seen from the above that compared with the Control group, the serum IL-13 and IL-4 levels of the Model group are significantly reduced, and the pro-inflammatory factors IL-18 and IL-1 beta levels are significantly increased, indicating that the Model group rats have obvious inflammatory reaction, after the treatment of each dose of drug, the serum IL-13 and IL-4 levels of each administration group of rats are significantly increased, and the pro-inflammatory factors IL-18 and IL-1 beta levels are significantly reduced, showing a certain dose-dependent.

[0054] The application is illustrated according to the above examples, and it should be understood that the above examples do not limit the application in any form, and any technical solution obtained by equivalent replacement or equivalent transformation falls within the scope of the application.

Claims

1. A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, characterized in that, It comprises the following components in parts by weight: 90-110 parts of Bunge artemisia, 40-60 parts of Curcuma longa, 90-110 parts of safflower, 70-90 parts of Saxifraga stella, 60-80 parts of Buxaggera, 30-50 parts of Radix Rubi and 20-40 parts of Trichosanthes kirilowii Maxim. 2.The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease according to claim 1, wherein, It comprises the following components in parts by weight: 95-105 parts of Bunge artemisia, 45-55 parts of Curcuma longa, 95-105 parts of safflower, 75-85 parts of Saxifraga stella, 65-75 parts of Buxaggera, 35-45 parts of Radix Rubi and 25-35 parts of Trichosanthes kirilowii Maxim. 3.The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease according to claim 1 or 2, characterized in that, It comprises the following components in parts by weight: 100 parts of Bunge artemisia, 50 parts of Curcuma longa, 100 parts of safflower, 80 parts of Saxifraga stella, 70 parts of Buxaggera, 40 parts of Radix Rubi and 30 parts of Trichosanthes kirilowii Maxim.

4. A traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease, characterized in that, It comprises the Chinese medicine composition of any one of claims 1-2 and excipients.

5. The traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 4, characterized in that, The excipients are microcrystalline cellulose and hydroxypropyl methyl cellulose.

6. The Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 5, characterized in that, The dosage form of the Chinese medicine preparation is a plaster, a pill or a tablet.

7. The preparation method of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 6, characterized in that, It comprises the following steps: (1) grinding and sieving Bunge artemisia, Curcuma longa, safflower, Saxifraga stella, Buxaggera, Radix Rubi and Trichosanthes kirilowii Maxim, then adding 9-13 times the weight of water of the medicinal materials, refluxing and extracting, repeating 2-4 times, combining the filtrates and reducing pressure to concentrate, obtaining an extract with a relative density of 0.95-0.99 to prepare a plaster; (2) mixing microcrystalline cellulose and hydroxypropyl methyl cellulose uniformly to obtain an excipient mixture; (3) adding the extract in two stages to the excipient mixture and stirring to obtain soft material; (4) extruding the soft material into a pill or a tablet.

8. The preparation method of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 7, characterized in that, In step (1), the reflux extraction temperature is 94-102℃ and the time is 1.5-2.5h; the vacuum degree of the reduced pressure concentration is -0.05--0.08Mpa and the temperature is 60-70℃; in step (2), the microcrystalline cellulose and hydroxypropyl methyl cellulose are mixed in a high-shear wet granulator at a rotation speed of 180-200rpm, a cutter speed of 1500-1900rpm and a mixing time of 4-6min; the mass ratio of the microcrystalline cellulose, hydroxypropyl methyl cellulose and the extract is (950-1000):(25-35):

900.

9. The preparation method of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 7, characterized in that, In step (3), the process is carried out in a high-shear wet granulator; during the process of adding the extract in two stages, the rotation speed of the high-shear wet granulator is 240-280rpm, the cutter speed is 2200-2600rpm, 35-45% of the extract by weight is added in the first stage and 55-65% of the extract by weight is added in the second stage; the stirring comprises the following steps: setting the rotation speed of the high-shear wet granulator to 290-330rpm, the cutter rotation speed to 2500-3000rpm, adding water in a spraying manner and stirring uniformly.

10. The preparation method of the traditional Chinese medicine preparation for treating non-alcoholic fatty liver disease according to claim 7, characterized in that, The step (4) comprises the following steps: putting the soft material into an extrusion rounding coating machine, the first extrusion speed is 20-30 rpm, and the second extrusion speed is 5-15 rpm; after the soft material is extruded and formed, the extruded and formed soft material is placed in a rounding disc, the rounding speeds are sequentially set as 80-120 rpm for 15-25 s, 400-500 rpm for 15-25 s, 450-550 rpm for 15-25 s, 550-650 rpm for 660-720 s and 300-400 rpm for 150-210 s, and the fan speed is set as 800-2000 rpm, so that wet pellets are obtained; after the wet pellets are placed in a cool and dry place for 10-14 h, the pellets are dried at 70-90 ℃ for 0.5-1.5 h, so that the pellets are prepared.

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