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

Abstract

The present invention relates to the technical field of traditional Chinese medicine preparation, and specifically relates to a traditional Chinese medicine composition, preparation and preparation method for preventing and treating non-alcoholic fatty liver disease. The traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15-25 parts of Pteris multifida Poir., 15-25 parts of Lysimachia christinae Hance, 15-25 parts of Citrus medica L. var. sarcodactylis Swingle, 10-20 parts of Astragalus membranaceus (Fisch.) Bunge, 10-20 parts of Ammannia arenaria H. B. K., 10-20 parts of Hawthorn Fruit (processed), 5-15 parts of Endothelium Corneum Gigeriae Galli, 5-15 parts of Amomum villosum Lour., 5-15 parts of Polyporus umbellatus (Pers.) Fries, 5-15 parts of Pinellia ternata (Thunb.) Breit. (processed), 2-10 parts of Alisma orientale (Sam.) Juz., 2-10 parts of Gardenia jasminoides Ellis; the preparation method includes: weighing the above traditional Chinese medicine composition according to the formula dosage, then decocting with water 5-20 times the total weight of the above traditional Chinese medicine composition for three times to obtain a traditional Chinese medicine decoction; combining, filtering and concentrating the obtained traditional Chinese medicine decoction to a relative density of 1.05-1.10 to obtain a traditional Chinese medicine extract; adding clinically acceptable excipients to the above traditional Chinese medicine extract and formulating by a conventional formulation method to prepare any one of clinically acceptable granule, tablet, capsule, powder, decoction or pill.

Description

Technical Field:

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition, a preparation and a preparation method for preventing and treating non-alcoholic fatty liver disease. Background Art:

[0002] Non-alcoholic fatty liver disease (NAFLD) is considered a metabolic disease associated with hyperlipidemia, obesity, type 2 diabetes mellitus (T2DM), etc. In recent years, it is considered more appropriate to name it metabolic associated fatty liver disease. Its disease process is divided into non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), liver fibrosis, liver cirrhosis (NAC), etc. Among them, NASH plays an important role in the process of NAFLD developing into hepatocellular carcinoma. NASH is mainly characterized by hepatocyte fatty degeneration and hepatocyte injury accompanied by inflammatory reactions. Regarding its pathogenesis, it has not been clarified yet, and it is generally considered to be closely related to metabolic syndrome (MS) such as diabetes, hyperlipidemia, and obesity. Early detection, diagnosis and treatment of NASH are very beneficial to patients, which can delay the disease development process and even reverse its development trend. In terms of treatment, there is no drug targeting its specific target for the time being. Most treatments are symptomatic treatments, which have certain curative effects in the short term, but the long-term effects are not obvious, and long-term medication is required. It not only has certain toxic and side effects, but also causes great mental and economic pressure to patients.

[0003] In recent years, with the great development of traditional Chinese medicine, good curative effects have been achieved in the treatment of this disease. Traditional Chinese medicine, based on the overall concept and syndrome differentiation and treatment, follows individualized treatment and has unique advantages in the treatment of this disease, especially in improving liver-related indicators and restoring liver function, and is increasingly valued. Summary of the Invention:

[0004] Aiming at the deficiencies in the prior art, the present invention provides a traditional Chinese medicine composition, a preparation and a preparation method for preventing and treating non-alcoholic fatty liver disease.

[0005] Specifically, in the first aspect of the present invention, a traditional Chinese medicine composition for preventing and treating non-alcoholic fatty liver disease is provided. The traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15-25 parts of Pteris multifida Poir., 15-25 parts of Lysimachia christinae Hance, 15-25 parts of Citrus medica L. var. sarcodactylis Swingle, 10-20 parts of Astragalus membranaceus (Fisch.) Bunge, 10-20 parts of Ammannia arenaria H.B.K., 10-20 parts of Hawthorn Fruit (processed), 5-15 parts of Endothelium Corneum Gigeriae Galli, 5-15 parts of Amomum villosum Lour., 5-15 parts of Polyporus umbellatus (Pers.) Fries, 5-15 parts of Pinellia ternata (Thunb.) Breit. (processed), 2-10 parts of Alisma orientale (Sam.) Juz., 2-10 parts of Gardenia jasminoides Ellis.

[0006] As a further illustration of the present invention, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 20 parts of Pteris multifida Poir., 20 parts of Lysimachia christinae Hance, 20 parts of Citrus medica L. var. sarcodactylis Swingle, 15 parts of Astragalus membranaceus (Fisch.) Bunge, 15 parts of Ammannia arenaria H.B.K., 15 parts of Hawthorn Fruit (processed), 10 parts of Endothelium Corneum Gigeriae Galli, 10 parts of Amomum villosum Lour., 10 parts of Polyporus umbellatus (Pers.) Fries, 10 parts of Pinellia ternata (Thunb.) Breit. (processed), 5 parts of Alisma orientale (Sam.) Juz., and 5 parts of Gardenia jasminoides Ellis.

[0007] The second aspect of the present invention provides an application of the above traditional Chinese medicine composition in the preparation of a drug for preventing and treating non-alcoholic fatty liver disease.

[0008] As a further illustration of the present invention, the dosage form of the drug for preventing and treating non-alcoholic fatty liver disease is an oral preparation, and the oral preparation is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

[0009] The third aspect of the present invention provides a preparation method of an oral preparation for preventing and treating non-alcoholic fatty liver disease, comprising the following steps:

[0010] S1. Weigh the traditional Chinese medicine composition provided in Claim 1 or 2 according to the formula dosage, and then decoct it three times with water 5 - 20 times the total weight of the above traditional Chinese medicine composition to obtain a traditional Chinese medicine decoction.

[0011] S2. Combine, filter and concentrate the traditional Chinese medicine decoction obtained from the three decoctions in step S1 to a relative density of 1.05 - 1.10 to obtain a traditional Chinese medicine extract.

[0012] S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and carry out formulation by conventional formulation methods to prepare any one of clinically acceptable granules, tablets, capsules, powders, decoctions or pills.

[0013] As a further illustration of the present invention, when preparing granules, step S3 specifically includes:

[0014] Step S31. Add 3 - 7% of dextrin based on the total weight of the traditional Chinese medicine composition to the traditional Chinese medicine extract obtained in step S2, and spray dry to obtain a spray-dried powder.

[0015] Step S32. Add 18% of dextrin based on the total weight of the granule preparation to be prepared to the dried powder obtained in step S3, and mix evenly to prepare the final granules.

[0016] Non-alcoholic fatty liver disease can be classified into the categories of "accumulation syndrome", "hepatic mass", "hepatic mass due to qi stagnation", "hypochondriac pain" and so on in traditional Chinese medicine. "Accumulation syndrome" was first recorded in "Huangdi Neijing", and "Nan Jing" detailedly distinguished the accumulations in the five zang-organs, pointing out that "the accumulation of the liver is called hepatic mass". Non-alcoholic fatty liver disease is based on insulin resistance and is accompanied by metabolic abnormalities such as blood sugar and blood lipid during the course of the disease.

[0017] The liver is the pivot of the body's qi mechanism and plays a role in regulating the circulation of qi, blood, and body fluids. The spleen and stomach are the sea of water and grains, and bad eating habits first damage the spleen and stomach. In traditional Chinese medicine, the spleen in terms of function is closer to the two organs of the stomach and pancreas in the human body. The location of non-alcoholic fatty liver disease is in the liver, involving the zang-fu organs such as the spleen, stomach, kidney, and intestine. The pathogenesis is mainly liver depression and spleen deficiency, and the evolution of the disease is based on the disorder of qi movement. When qi movement is disordered, the liver is the first to be affected. Factors such as mental tension, emotional anxiety, excessive idleness and lack of exercise often cause liver qi stagnation in patients. "Red Stove Melting Snow" states: "Qi is precious in smoothness rather than reverse. When smooth, all meridians are unobstructed; when reverse, the four limbs are uncomfortable." The liver can regulate the qi movement of the whole body. When there is liver disease, the qi movement is blocked and the meridians are not smooth. The liver belongs to wood and the spleen belongs to earth, and liver wood restricts spleen earth. When pathogenic factors are in the liver, it will inevitably affect the function of the spleen and stomach. In addition, in the circulation of the meridians, the Spleen Meridian of Foot-Taiyin "follows behind the tibia on the medial side of the lower leg and crosses in front of the Jueyin Meridian", and the Liver Meridian of Foot-Jueyin "ascends eight cun above the ankle and crosses behind the Taiyin Meridian". The circulation routes of the two meridians of the Spleen Meridian of Foot-Taiyin and the Liver Meridian of Foot-Jueyin intersect and the qi and blood are connected, strengthening the connection between the two zang-fu organs of the liver and spleen. To sum up, most patients with non-alcoholic fatty liver disease have co-pathology of the liver and spleen.

[0018] Pteris multifida Poir.: Nature and flavor: pungent, slightly bitter, cool and pungent; meridian tropism: liver, large intestine, bladder meridians; functions: clearing heat and promoting diuresis, promoting blood circulation and detumescence; indications: dysentery; diarrhea; edema; hepatitis; cholecystitis; sore throat; urinary tract infection; carbuncles and sores; rheumatic arthralgia; traumatic swelling and pain; fractures, etc.

[0019] Lysimachia christinae Hance: Nature and flavor: sweet and light, cold in nature; meridian tropism: liver, gallbladder, kidney, bladder meridians; functions: clearing away damp-heat, promoting diuresis, detumescence. Anti-inflammatory, acute strangury, sandy strangury, expelling stones; can be used to treat chronic cholecystitis, hepatobiliary inflammation, urinary tract stones, abdominal edema, hernia, traumatic injury, furuncles, fractures, kidney deficiency edema, burns, acute mastitis, common cold cough, rheumatic arthritis, etc.

[0020] Citrus medica L. var. sarcodactylis Swingle: Nature and flavor: pungent, bitter, sour; meridian tropism: liver, spleen, lung meridians. Functions: soothing the liver and regulating qi, strengthening the stomach and widening the middle, promoting qi and resolving phlegm. Commonly used clinically for hypochondriac pain or abdominal distension and pain caused by liver qi stagnation and spleen and stomach disharmony, chest and abdominal fullness and oppression, belching and vomiting, loss of appetite, etc., can be used together with green tangerine peel, fingered citron, dried tangerine peel, etc.

[0021] Astragalus membranaceus (Fisch.) Bunge: Bitter in taste, cold in nature. Meridian tropism: lung, gallbladder, spleen, large intestine, small intestine meridians. Functions: clearing away damp-heat, purging fire and detoxifying, stopping bleeding, etc. Indications: damp-warm syndrome, summer-dampness, chest oppression and nausea, damp-heat and fullness, diarrhea, jaundice, cough due to lung heat, high fever and restlessness, hematemesis due to blood heat, carbuncles and sores, etc.

[0022] Ammannia arenaria H. B. K.: Sweet; light; neutral in nature. Meridian tropism: spleen; bladder meridians. Functions: strengthening the spleen and promoting diuresis, promoting qi and dispersing stasis. Commonly used for anorexia due to spleen deficiency, chest oppression, acute and chronic cystitis, leucorrhea in women, traumatic stasis and swelling pain.

[0023] Fried Hawthorn Fruit: Sour, sweet, and slightly warm in nature. It belongs to the spleen, stomach, and liver meridians. Its functions include promoting digestion and resolving food stagnation, promoting qi circulation and removing stasis. For food stagnation, being slightly warm and not overly hot, it is good at promoting digestion and resolving food stagnation, and can treat various types of food stagnation. It is particularly the key herb for digesting greasy and meaty food stagnation.

[0024] Galli Gigeriae Endothelium: Sweet and flat in flavor. It belongs to the spleen, stomach, small intestine, and bladder meridians. It can promote digestion and strengthen the stomach, and astringe sperm and stop seminal emission.

[0025] Amomum villosum: Pungent and warm in flavor. It enters the spleen and stomach meridians. It has the effects of awakening the spleen and promoting appetite, and promoting diuresis and stopping vomiting. It is used to treat dampness turbidity obstructing the middle energizer, fullness and discomfort in the epigastric region, lack of appetite, spleen-stomach deficiency-cold, vomiting and diarrhea, morning sickness during pregnancy, and fetal restlessness.

[0026] Polyporus umbellatus: Sweet, light, and flat in flavor. It has the effect of promoting diuresis and percolating dampness. It belongs to the kidney and spleen meridians; it is mainly used to treat edema, dysuria, tumors and other diseases.

[0027] Prepared Pinellia Rhizome: Prepared Pinellia Rhizome, pungent and warm in flavor. It belongs to the spleen, stomach, and lung meridians. It can dry dampness and resolve phlegm. It is used for excessive phlegm with cough and asthma, dizziness and palpitation due to phlegm retention, wind-phlegm dizziness, and headache due to phlegm syncope.

[0028] Alisma orientale: Sweet and cold in flavor. It belongs to the kidney and bladder meridians. It can promote diuresis and percolate dampness, clear heat and reduce turbidity and lipid. It is mostly used for dysuria, edema and distension, dizziness due to phlegm retention, and hyperlipidemia.

[0029] Gardenia jasminoides: Bitter and cold in flavor. It belongs to the heart, lung, and triple energizer meridians. It has the effects of purging fire and relieving vexation, clearing heat and promoting diuresis, cooling blood and detoxifying. Gardenia jasminoides is bitter and cold to clear heat, can clear the fire of the triple energizer and purge the heat of the heart meridian, and can treat restlessness and annoyance due to febrile diseases, high fever, restlessness, delirium and other syndromes caused by the blazing of fire-toxin and the accumulation of heat in the triple energizer.

[0030] Explanation of the formula: This application is based on the basic theory of treating both the liver and spleen, combined with the formula for promoting qi circulation and removing stasis, and adding prescriptions for soothing the liver and reducing swelling, clearing heat and purging fire, and promoting blood circulation. It achieves the effect of jointly preventing and treating fatty liver disease. Specifically, in the formula: Pteris multifida Poir. and Lysimachia christinae Hance are the sovereign drugs, which have the effects of soothing the liver and reducing swelling, promoting blood circulation and removing stasis, promoting diuresis and percolating dampness, clearing heat and purging fire. The two are used together to jointly remove the "garbage" stagnated in the liver, maintain the elasticity of blood vessels and smooth blood circulation; Citrus medica L. var. sarcodactylis Swingle, Astragalus membranaceus (Fisch.) Bunge, and Ammannia arenaria H. B. K. are the ministerial drugs, which have the effects of regulating qi and harmonizing the middle, replenishing middle qi, and invigorating the spleen and nourishing blood. The three are used together to, on the basis of regulating both qi and blood, assist the sovereign drugs to enhance the tonifying effect, treat both the liver and spleen, and match the medicine with the syndrome, better treating the root cause of liver problems; Fried Hawthorn Fruit, Galli Gigeriae Endothelium, and Amomum villosum are the adjuvant drugs, which have the effects of promoting digestion and dispersing accumulation, reducing blood lipid, and promoting dampness and awakening the spleen. The three work together to achieve the effects of strengthening the spleen and promoting digestion, regulating qi and promoting dampness; Polyporus umbellatus, Prepared Pinellia Rhizome, Alisma orientale, and Gardenia jasminoides are the guiding drugs, which have the effects of purging heat and promoting diuresis, moistening the intestines and promoting defecation, and resolving mass and dissipating binds. The four jointly enhance lipid metabolism and timely discharge the "garbage" out of the body.

[0031] Compared with the prior art, the present invention has the following beneficial technical effects:

[0032] In the present invention, Pteris multifida Poir. and Lysimachia christinae Hance are the monarch drugs, which have the effects of soothing the liver and reducing swelling, promoting blood circulation to remove blood stasis, promoting diuresis and percolating dampness, and clearing heat and purging fire. The combination of the two can jointly remove the "garbage" in the liver depression, maintain the elasticity of blood vessels and smooth blood flow; Citrus medica L. var. sarcodactylis Swingle, Astragalus membranaceus (Fisch.) Bunge, and Ammannia arenaria H.B.K. are the ministerial drugs, which have the effects of regulating qi and harmonizing the middle, replenishing qi to the middle energizer, and strengthening the spleen and enriching blood. The combination of the three can, on the basis of regulating qi and blood, assist the monarch drugs to enhance the tonifying effect, treat the liver and spleen simultaneously, and the medicine and syndrome match well, so as to better treat the root cause of liver problems; Adjuvant drugs: Fructus Crataegi Pyrolatus, Endothelium Corneum Gigeriae Galli, and Fructus Amomi have the effects of promoting digestion and dissipating accumulation, reducing blood lipid, and promoting qi movement and awakening the spleen. The three drugs together play the role of strengthening the spleen and promoting digestion, regulating qi and promoting dampness; Guiding drugs: Polyporus umbellatus, Pinellia ternata (Thunb.) Breit., Alisma orientale (Sam.) Juzep., and Gardenia jasminoides Ellis have the effects of purging heat and promoting diuresis, moistening the intestines and relieving constipation, and dissipating masses and relieving distension. The four drugs together enhance lipid metabolism and timely discharge the "garbage" out of the body. By utilizing the synergistic cooperation of the above traditional Chinese medicine composition, the present invention can play a very good role in preventing and treating non-alcoholic fatty liver disease. Description of the Drawings:

[0033] Figure 1 This is the IHC scoring of the expression of SREBP-1 in the liver tissue of mice provided by the present invention. Note that in the figure, compared with the blank group, # P < 0.05, ## P < 0.01 and ### P < 0.001; compared with the model group, * P < 0.05, ** P < 0.01 and *** P < 0.001; compared with the high-dose group of Example 1, △ P < 0.05, △△ P < 0.01 and △△△ P < 0.001 (n = 10). Detailed Embodiments:

[0034] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0035] Example 1

[0036] A traditional Chinese medicine composition, which is composed of the following raw medicinal materials in parts by weight: 20 parts of Pteris multifida Poir., 20 parts of Lysimachia christinae Hance, 20 parts of Citrus medica L. var. sarcodactylis Swingle, 15 parts of Astragalus membranaceus (Fisch.) Bunge, 15 parts of Ammannia arenaria H.B.K., 15 parts of Fructus Crataegi Pyrolatus, 10 parts of Endothelium Corneum Gigeriae Galli, 10 parts of Fructus Amomi, 10 parts of Polyporus umbellatus, 10 parts of Pinellia ternata (Thunb.) Breit., 5 parts of Alisma orientale (Sam.) Juzep., and 5 parts of Gardenia jasminoides Ellis.

[0037] Example 2

[0038] A traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15 parts of Pteris multifida Poir., 15 parts of Lysimachia christinae Hance, 15 parts of Citrus medica L. var. sarcodactylis Swingle, 10 parts of Astragalus membranaceus (Fisch.) Bunge, 10 parts of Ammannia arenaria H.B.K., 10 parts of Hawthorn Fruit (parched), 5 parts of Endothelium Corneum Gigeriae Galli, 5 parts of Amomum villosum Lour., 5 parts of Polyporus umbellatus (Pers.) Fries, 5 parts of Pinellia ternata (Thunb.) Breit. prepared with Rhizoma Zingiberis Recens, 2 parts of Alisma orientale (Sam.) Juzep., 2 parts of Gardenia jasminoides Ellis.

[0039] Example 3

[0040] A traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 25 parts of Pteris multifida Poir., 25 parts of Lysimachia christinae Hance, 25 parts of Citrus medica L. var. sarcodactylis Swingle, 20 parts of Astragalus membranaceus (Fisch.) Bunge, 20 parts of Ammannia arenaria H.B.K., 20 parts of Hawthorn Fruit (parched), 15 parts of Endothelium Corneum Gigeriae Galli, 15 parts of Amomum villosum Lour., 15 parts of Polyporus umbellatus (Pers.) Fries, 15 parts of Pinellia ternata (Thunb.) Breit. prepared with Rhizoma Zingiberis Recens, 10 parts of Alisma orientale (Sam.) Juzep., 10 parts of Gardenia jasminoides Ellis.

[0041] Comparative Examples 1 - 7 all provide a traditional Chinese medicine composition, and the specific raw medicinal materials and their dosages of the traditional Chinese medicine compositions in Comparative Examples 1 - 7 are shown in Table 1 below.

[0042] Table 1 Raw Medicinal Materials and Their Dosage Table

[0043] Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Pteris multifida Poir. / parts 20 — — 20* 20 20 20 20 Desmodium styracifolium (Osbeck) Merr. / parts 20 — 20 20* 20 20 20 20 Citrus medica L. var. sarcodactylis Swingle / parts 20 20 20 20 — 20 20 20 Astragalus membranaceus (Fisch.) Bunge / parts 15 15 15 15 — — 15 15 Ammannia arenaria H. B. K. / parts 15 15 15 15 — — 15 15 Fried Fructus Crataegi 15 15 15 15 15 15 — 15 Endothelium Corneum Gigeriae Galli / parts 10 10 10 10 10 10 — 10 Amomum villosum Lour. / parts 10 10 10 10 10 10 — 10 Polyporus umbellatus (Pers.) Fries / parts 10 10 10 10 10 10 10 — Pinellia ternata (Thunb.) Breit. processed with Rhizoma Zingiberis Recens / parts 10 10 10 10 10 10 10 — Alisma orientale (Sam.) Juzep. / parts 5 5 5 5 5 5 5 — Gardenia jasminoides Ellis / parts 5 5 5 5 5 5 5 —

[0044] In the table, the two 20* in Comparative Example 3 respectively indicate that 20 parts of Pteris multifida Poir. are replaced with 20 parts of Bupleurum chinense DC., and 20 parts of Lysimachia christinae Hance are replaced with 20 parts of Atractylodes macrocephala Koidz. “—” indicates that the corresponding raw medicinal material is not added to the traditional Chinese medicine composition.

[0045] The raw medicinal materials in the above examples and comparative examples are all commercially available traditional Chinese medicine cut pieces.

[0046] The traditional Chinese medicine compositions provided in the above examples and comparative examples are made into granule preparations for preventing and treating non - alcoholic fatty liver disease, and the specific preparation process is as follows:

[0047] S1. Weigh the traditional Chinese medicine compositions provided in the above examples and comparative examples according to the formula dosages, and then decoct them three times with 10 times the total weight of the above traditional Chinese medicine compositions in water to obtain a traditional Chinese medicine decoction.

[0048] S2. Combine, filter and concentrate the traditional Chinese medicine decoction obtained from the three decoctions in step S1 to a relative density of 1.05 - 1.10 (60 °C) to obtain a traditional Chinese medicine extract.

[0049] S3. Add 5% of dextrin based on the total weight of the traditional Chinese medicine composition to the traditional Chinese medicine extract obtained in step S2, and spray - dry to obtain a spray - dried powder.

[0050] S4. Add 18% of dextrin based on the total weight of the granule preparation to be prepared to the dried powder obtained in step S3 and mix evenly to make the final granule preparation.

[0051] 1. Animal experiment:

[0052] 1.1 Experimental agents: Sunflower Liver Protecting Tablets, Heilongjiang Sunflower Pharmaceutical Co., Ltd., approval number of national drug standard: Z2003336; Granule preparations prepared from the traditional Chinese medicine formulas provided in Example 1 and Comparative Examples 1-7 above.

[0053] 1.2 Experimental animals: 150 SPF-grade male Wistar mice (body weight: 25±3 g) were purchased from the Experimental Animal Center of Heilongjiang University of Chinese Medicine. After being bought, the mice were placed under SPF-grade conditions and adaptively raised for 3 days before the experiment.

[0054] 1.3 Process of animal experiment: The mice were randomly divided into a blank group and a fructose-fed group. Among them, there were 20 mice in the blank group and 130 mice in the fructose-fed group.

[0055] The 150 mice in the above blank group and fructose-fed group were given 80 g of standard food every day. The food intake of the mice in each group was recorded every day, and the body weight of the mice in each group was recorded every 3 days. The total feeding period of the experiment was 12 weeks. From the 1st week to the 12th week, except for the mice in the blank group drinking fructose-free drinking water, the rest of the mice drank drinking water containing 10% fructose. After the end of the 8th week, 10 mice were randomly selected from the blank group and the fructose-fed group respectively to measure the body weight of the mice and the indexes of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the serum. The results showed that the body weight of the fructose-fed group exceeded that of the blank group by more than 20%, and compared with the blank group, the levels of TG, TC and LDL-C in the fructose-fed group increased, while the level of HDL-C decreased, indicating that the model was successfully established. Then, for the remaining mice, after the end of the 8th week, except for 10 mice in the blank group, the remaining 120 mice in the fructose-fed group were randomly divided into 12 groups, with 10 mice in each group. The specific grouping of the remaining 120 mice in the fructose-fed group was as follows: model group, positive control group: Sunflower Liver Protecting Tablets 80 mg / kg, low-dose group of Example 1: 20 mg / kg, medium-dose group of Example 1: 40 mg / kg, high-dose group of Example 1: 80 mg / kg, high-dose groups of Comparative Examples 1-7: 80 mg / kg.

[0056] The drugs used in the three dose groups of Example 1 above were granule preparations for preventing and treating non-alcoholic fatty liver disease obtained by using the granule preparation method for the traditional Chinese medicine formula provided in Example 1. The drugs used in the medium-dose groups of Comparative Examples 1-7 above were granule preparations obtained by using the granule preparation method for the traditional Chinese medicine formulas provided in Comparative Examples 1-7.

[0057] From the 9th week to the end of the 12th week, mice in the positive drug group and the traditional Chinese medicine intervention groups of Example 1 at three different doses and Comparative Examples 1-7 were intragastrically administered with Sunflower Liver Protecting Tablets and traditional Chinese medicine granule preparations of the corresponding formulations at the above-mentioned doses and dosages every day, once a day for 4 consecutive weeks.

[0058] 1.4 Detection indicators:

[0059] After the end of the 12th week, all mice were fasted for 12 hours, anesthetized with 10% urethane at a dose of 1 mL / 100 g, liver tissues and blood samples were collected, and the supernatant was taken after centrifugation. The levels of blood lipid indicators TG, TC, LDL-C, HDL-C and liver function indicators ALT, AST were detected using an automatic biochemical analyzer. The expression of SREBP-1 (AF6283) in liver tissues was detected by immunohistochemical analysis method respectively, and then the IHC score was calculated. The IHC score was evaluated according to the staining intensity of positive reaction and the percentage of positive cells, that is, the IHC score was the sum of the staining intensity score and the positive cell ratio score.

[0060] 1.5 Statistical methods:

[0061] Measurement data were analyzed by t-test, and count data were analyzed by χ 2 test. All measurement data were expressed as ( ), and the statistical software SPSS 17.0 was used for data processing.

[0062] 1.6 Experimental results:

[0063] 1.61 Changes in blood lipids are shown in Table 2.

[0064] Table 2 Changes in blood lipids of mice in each group

[0065]

[0066] Note: Compared with the blank group, # P<0.05, ## P<0.01 and ### P<0.001; compared with the model group, * P<0.05, ** P<0.01 and *** P<0.001; compared with the high-dose group of Example 1, △ P<0.05, △△ P<0.01 and △△△ P<0.001 (n = 10).

[0067] As shown in Table 2, after 12 weeks of fructose feeding, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the serum of the mice in the model group were significantly increased, while the level of high-density lipoprotein cholesterol (HDL-C) was significantly decreased.

[0068] 1.62 The changes in liver function are shown in Table 3.

[0069] Table 3 Changes in liver function of mice in each group

[0070]

[0071] Note: Compared with the blank group, # P < 0.05, ## P < 0.01 and ### P < 0.001; compared with the model group, * P < 0.05, ** P < 0.01 and *** P < 0.001; compared with the high-dose group of Example 1, △ P < 0.05, △△ P < 0.01 and △△△ P < 0.001 (n = 10).

[0072] It can be seen from Table 2 and Table 3 that, compared with the blank group, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the serum of the model group decreased significantly, while the level of high-density lipoprotein cholesterol (HDL-C) increased significantly, indicating that the animal model was successfully established and the mice in the model group had obvious symptoms of fatty liver disease. Compared with the model group, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the serum of the high-dose group of the positive group, the low-, medium-, and high-dose groups of Example 1, and the high-dose groups of Comparative Examples 1-7 decreased significantly, while the level of high-density lipoprotein cholesterol (HDL-C) increased significantly, and the liver function indicators AST and ALT also decreased significantly, indicating that the traditional Chinese medicine preparations provided by the positive group, Example 1, and Comparative Examples 1-7 all had an improving effect on fatty liver disease. In addition, compared with the high-dose groups of Comparative Examples 1-7, the improvement effect of the high-dose group of Example 1 of the present application on blood lipid and liver function indicators was more obvious, indicating that the curative effect of the traditional Chinese medicine composition provided by the present application was better than that of the traditional Chinese medicine preparations provided by Comparative Examples 1-7. Specifically, compared with Comparative Examples 1-3, it can be seen that there is a synergistic effect between the monarch drugs Pteris multifida Poir. and Lysimachia christinae Hance in the present application, and the two complement each other and are indispensable. Whether one of them is replaced or removed, the optimal curative effect cannot be achieved. Compared with Comparative Examples 4-5, it can be seen that the ministerial drugs Citrus medica L. var. sarcodactylis Swingle, Astragalus membranaceus (Fisch.) Bunge, and Ammannia arenaria H.B.K. in the present application complement the monarch drug, and without the assistance of the ministerial drugs, the optimal curative effect still cannot be achieved. Compared with Comparative Examples 6-7, it can be seen that the adjuvant drugs and guiding drugs in the present application are also an indispensable part of this traditional Chinese medicine formula, and without any one of them, the best curative effect cannot be achieved.

[0073] 1.63 The expression of SREBP-1 in the liver is shown in Figure 1 .

[0074] Figure 1 In the abscissa are the blank group, the model group, the positive drug group, the high-dose group of Example 1, and the high-dose groups of Comparative Examples 1-7, and the ordinate is the IHC score of the expression of SREBP-1 in the liver tissue of mice in the corresponding groups. It can be seen from Figure 1 that: compared with the blank group, the IHC score of SREBP-1 in the liver of the model group mice increased significantly; compared with the model group mice, the IHC scores of SREBP-1 in the livers of the high-dose group of Example 1 and the high-dose groups of Comparative Examples 1-7 decreased significantly. Compared with the high-dose group of Example 1, the IHC scores of SREBP-1 in the livers of the high-dose groups of Comparative Examples 1-7 increased significantly.

[0075] Studies have shown that SREBP-1 is a regulatory nuclear transcription factor for de novo lipogenesis. It is involved in the metabolism of fatty acids and sugars in the body, regulates the transcriptional activation of liver fatty acid synthesis genes, promotes the synthesis of liver triglycerides, and inhibits triglyceride transport, thereby causing the accumulation of triglycerides in hepatocytes and leading to hepatocyte damage. Through the above Figure 1 results shown, it can be seen that the traditional Chinese medicine composition provided by this application has an obvious regulatory effect on the expression of SREBP-1 in the liver, and thus can effectively inhibit hepatocyte damage. In addition, compared with the traditional Chinese medicine preparations provided in Comparative Examples 1-7, the optimized traditional Chinese medicine composition of this application has a more obvious regulatory effect on the expression of SREBP-1. Therefore, its effect of inhibiting hepatocyte damage is significantly better than that of the traditional Chinese medicine compositions provided in Comparative Examples 1-7.

[0076] Clinical trials

[0077] 2.1 General information

[0078] 80 outpatients and inpatients in the Department of Gastroenterology of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine were selected. Using the stratified randomization method, a suitable section length was selected and divided into a treatment group and a control group at a ratio of 1:1. With the help of the SAS statistical software to give a seed number, the random arrangements of the treatments (treatment drugs and control drugs) received by 80 subjects were generated respectively, that is, the treatment allocations corresponding to the serial numbers 01-80 were listed. There were 40 cases in the treatment group, including 27 males and 13 females, with an average age of (47.2±6.4) years and an average course of disease of (6.9±3.4) years. There were 40 cases in the control group, including 25 males and 15 females, with an average age of (46.7±7.1) years and an average course of disease of (7.2±3.6) years. All 80 patients underwent ultrasound examination and showed fatty liver images, including 26 cases of severe fatty liver, 38 cases of moderate fatty liver, and 16 cases of mild fatty liver. The main symptoms of the patients included dull pain in the liver area, abdominal distension, nausea, loss of appetite, and belching. The symptomatic patients had one or several of these symptoms. And the liver function tests were abnormal, manifested as increased AST and ALT. Dyslipidemia was manifested as elevated serum triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). The distribution of the general information of the two groups of patients had no significant difference after statistical test (P>0.05), and they were comparable.

[0079] 2.2 Diagnostic criteria

[0080] According to the Diagnostic Criteria for Non-alcoholic Fatty Liver Disease (2018 Updated Edition), the diagnostic criteria are as follows:

[0081] Inclusion criteria for cases: Blood lipids (total cholesterol and triglyceride), either double or single increase, clearly diagnosed as fatty liver by ultrasound, abnormal liver function, and one or both of AST or ALT increased.

[0082] Exclusion criteria for cases: Pregnant or lactating women; Viral hepatitis (hepatitis B, hepatitis C or others), drug-induced hepatitis; Co-existing or combined with other diseases that affect the research results of this application, such as patients with severe cardiovascular and cerebrovascular diseases, malignant tumors, mental disorders, etc.

[0083] 2.3 Treatment method

[0084] Take the traditional Chinese medicine composition formula provided in Example 1 above, and refer to the preparation method of traditional Chinese medicine granules in the Chinese Pharmacopoeia (2020 Edition). The traditional Chinese medicine bagged granules are prepared by the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Each bag contains 10 g of crude drug, constituting the traditional Chinese medicine granules for treatment group to take.

[0085] The dosage for the treatment group is 3 times a day, taken before meals, 1 bag each time (containing 10 g of crude drug), and 6 weeks is one course of treatment.

[0086] The control group takes Kuihua Hugan Tablets (Heilongjiang Kuihua Pharmaceutical Co., Ltd., approval number: Z2003336), 4 tablets each time, 3 times a day, and the course of treatment is 6 weeks, and then various indicators are detected.

[0087] 2.4 Observation indicators

[0088] Observe and compare the changes in the clinical efficacy, liver function, and blood lipids of the two groups of patients before and after treatment.

[0089] 2.5 Efficacy evaluation criteria

[0090] Refer to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial)". Cure: The reduction rate of symptom integral score is ≥90%, ultrasound shows no fatty liver, blood lipids and serum transaminases are normal; Marked effect: The reduction rate of symptom integral score is ≥70% and <90%, ultrasound improves by more than one grade, blood lipids decrease, and serum transaminases are normal; Effective: The reduction rate of symptom integral score is ≥30% and <70%, ultrasound shows improvement or no change, blood lipids decrease, and serum transaminases decrease by more than 50%; Ineffective: The reduction rate of symptom integral score is ≤30%, ultrasound shows no change, and blood lipids and serum transaminases show no obvious improvement.

[0091] 2.6 Statistical method

[0092] Measurement data are analyzed by t-test, and count data are analyzed by χ 2 test. All measurement data are expressed in ( ), and the statistical software SPSS 17.0 is used for data processing.

[0093] 2.7 Experimental results

[0094] 2.1 Comparison of the clinical efficacy results of the two groups of patients, as shown in Table 4.

[0095] Table 4 Comparison of the clinical efficacy of the two groups of patients

[0096]

[0097] Note: Compared with the control group, * P < 0.05.

[0098] As can be seen from Table 4, the total effective rate of the treatment group was 87.5%, and that of the control group was 67.5%. Moreover, the clinical efficacy of the treatment group was significantly better than that of the control group ( * P < 0.05), indicating that the efficacy of the traditional Chinese medicine composition provided by this application is better than that of the traditional Chinese medicine preparations for improving fatty liver disease, and it has obvious clinical advantages.

[0099] 2.2 Changes in blood lipids are shown in Table 5.

[0100] Table 5 Changes in blood lipids in the treatment group and the control group

[0101]

[0102] Note: Compared with before treatment, # P < 0.05, ## P < 0.01 and ### P < 0.001; compared with the control group, * P < 0.05, ** P < 0.01 and *** P < 0.001 (n = 40).

[0103] 2.3 Changes in liver function are shown in Table 6.

[0104] Table 6 Changes in liver function in the treatment group and the control group

[0105]

[0106] Note: Compared with before treatment, ＃＃＃ P < 0.001; compared with the control group, *** P < 0.001 (n = 40).

[0107] As can be seen from Tables 5 and 6, compared with before treatment, after the patients took the traditional Chinese medicine preparations of the treatment group and the control group, the indicators of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the serum decreased significantly, the indicator of high-density lipoprotein cholesterol (HDL-C) increased significantly, and the liver function indicators AST and ALT both decreased significantly, indicating that the traditional Chinese medicine composition provided by this application has an obvious improvement effect on fatty liver disease. In addition, compared with the control group, after the patients took the traditional Chinese medicine preparation of the treatment group of this application, the improvement effect of blood lipids and liver function indicators was more obvious, indicating that the curative effect of the traditional Chinese medicine composition provided by this application is better than that of the traditional Chinese medicine preparations for improving fatty liver disease, and it has obvious clinical advantages.

[0108] Typical case ①:

[0109] Liu XX, male, 47 years old. First diagnosis on April 23, 2023. Chief complaint: Pain and distension in both flanks for 3 - 4 months, accompanied by nausea and loss of appetite in the recent month. Bowel movement once every 3 - 4 days. Due to difficult defecation, cisapride capsules were taken, which were effective in the short term but could not be maintained for a long time. The tongue was dull red, with tooth marks on the sides and yellow greasy coating. There was no history of alcohol consumption or viral hepatitis.

[0110] Physical examination: Blood pressure 145 / 85 mmHg, pulse rate 75 beats / min. Digestive system color Doppler ultrasound showed: Moderate fatty liver, low echo area in the liver (considering uneven fat deposition); Blood biochemistry: Glucose 6.7 mmol / L, glutamyl transferase 51 U / L, total serum protein 63 g / L, total bilirubin 13.5 μmol / L, direct bilirubin 4.5 μmol / L. Western medicine diagnosis: Non-alcoholic fatty liver disease; Traditional Chinese medicine diagnosis: Hypochondriac pain, abdominal distension, nausea, loss of appetite.

[0111] Prescription: 20 parts of Pteris multifida Poir., 20 parts of Lysimachia christinae Hance, 20 parts of Citrus medica L. var. sarcodactylis Swingle, 15 parts of Astragalus membranaceus (Fisch.) Bunge, 15 parts of Ammannia arenaria H.B.K., 15 parts of Crataegus pinnatifida Bge. var. major N.E.Br., 10 parts of Endothelium corneum gigeriae galli, 10 parts of Amomum villosum Lour., 10 parts of Polyporus umbellatus (Pers.) Fries, 10 parts of Pinellia ternata (Thunb.) Breit., 5 parts of Alisma orientale (Sam.) Juz., 5 parts of Gardenia jasminoides Ellis. 15 doses. Decoct with water to 300 mL and take warm twice a day. At the same time, the patient was instructed to control diet, avoid greasy and spicy foods, and exercise moderately.

[0112] Follow-up visit on May 15, 2023: After taking the medicine, the pain in the patient's hypochondrium was relieved, the appetite increased, the nausea was reduced, the bowel movement was improved, once every 1 - 2 days, and the other symptoms were all improved. Therefore, the above prescription was continued for consolidation.

[0113] During the physical examination half a year later, the ultrasound examination showed mild fatty liver, and the liver function, blood glucose, and blood lipid levels were normal.

[0114] Typical case ②:

[0115] Mr. Xie, male, 45 years old. Initial diagnosis on July 16, 2023. Chief complaint: Abdominal distension, loss of appetite, and belching in the recent month. The tongue is dull red with yellow and greasy coating. He has no history of alcohol consumption or viral hepatitis.

[0116] Physical examination: Blood pressure 133 / 82 mmHg, pulse rate 75 beats / min. Digestive system color ultrasound shows moderate fatty liver and hypoechoic area in the liver; Blood biochemistry: Glucose 5.9 mmol / L, glutamyl transferase 48 U / L, total serum protein 58 g / L, total bilirubin 13.5 μmol / L, direct bilirubin 4.2 μmol / L. Western medicine diagnosis: Non-alcoholic fatty liver disease; Traditional Chinese medicine diagnosis: Abdominal distension, loss of appetite, and belching.

[0117] Prescription: 20 parts of Pteris multifida, 20 parts of Lysimachia christinae, 20 parts of Citrus medica var. sarcodactylis, 15 parts of Astragalus membranaceus, 15 parts of Ammannia arenaria, 15 parts of Hawthorn Fruit (processed), 10 parts of Endothelium Corneum Gigeriae Galli, 10 parts of Amomum villosum, 10 parts of Polyporus umbellatus, 10 parts of Pinellia ternata (processed), 5 parts of Alisma orientale, 5 parts of Gardenia jasminoides. 13 doses. Decoct with water to 300 mL and take warm orally in the morning and evening. At the same time, the patient is advised to control diet, avoid greasy and spicy foods, and exercise moderately.

[0118] Follow-up visit on August 10, 2023: After taking the medicine, the patient's abdominal distension was relieved, appetite increased, and the tongue basically returned to normal. The above prescription was continued for 10 doses for consolidation.

[0119] During the physical examination half a year later, the ultrasound examination showed no fatty liver, and the liver function, blood glucose, blood lipid levels were normal.

[0120] It should be noted that in this article, terms such as "including", "comprising" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not expressly listed, or also includes elements inherent to such process, method, article or device.

[0121] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicine composition for preventing and treating non-alcoholic fatty liver disease, characterized in that: The Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 15-25 parts of herba schizonepetae, 15-25 parts of herba schizonepetae, 15-25 parts of citron, 10-20 parts of astragalus, 10-20 parts of amaranth, 10-20 parts of charred hawthorn, 5-15 parts of chicken gizzard lining, 5-15 parts of amomum villosum, 5-15 parts of umbellatus, 5-15 parts of pinellia, 2-10 parts of oriental orientalis, and 2-10 parts of gardenia.

2. The Chinese medicine composition for preventing and treating non-alcoholic fatty liver disease according to claim 1, characterized in that: The Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 20 parts of herba jingbiancao, 20 parts of herba lycopersicum, 20 parts of citron, 15 parts of astragalus, 15 parts of amaranth, 15 parts of charred hawthorn, 10 parts of chicken gizzard lining, 10 parts of amomum, 10 parts of umbellate, 10 parts of pinellia, 5 parts of oriental water plantain, and 5 parts of gardenia.

3. Use of the Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a medicament for preventing and treating non-alcoholic fatty liver disease.

4. The use according to claim 3, characterized in that: The dosage form of the drug for preventing and treating non-alcoholic fatty liver disease is an oral preparation, which is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

5. A method for preparing an oral preparation for preventing and treating non-alcoholic fatty liver disease, characterized in that: The following steps are involved: S1. Weigh the Chinese medicine composition provided by claim 1 or 2 according to the dosage of the formula, then add 5-20 times the total weight of the Chinese medicine composition of water and boil three times to obtain a Chinese medicine decoction; S2, combining the Chinese medicine decoctions obtained by decocting three times in step S1, filtering and concentrating to a relative density of 1.05-1.10 to obtain a Chinese medicine extract; S3. Add clinically acceptable excipients to the traditional Chinese medicine extract obtained in step S2, and prepare it in a conventional preparation method to prepare any one of clinically acceptable granules, tablets, capsules, powders, decoctions or pills.

6. The method for preparing the oral preparation for preventing and treating non-alcoholic fatty liver disease according to claim 5, characterized in that: When preparing granules, step S3 specifically includes: Step S31, adding dextrin in an amount of 3-7% by weight of the total weight of the Chinese medicine composition to the Chinese medicine extract obtained in step S2, and spray drying to obtain a spray-dried powder; Step S32: Add dextrin (18% by weight of the total weight of the granule preparation to be prepared) to the dry powder obtained in step S3 and mix well to prepare the final granule preparation.

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