A traditional Chinese medicine composition for treating liver stagnation and spleen deficiency syndrome of metabolic-related fatty liver disease

Abstract

The application belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency syndrome, which is composed of the following raw materials by weight: 8-10 parts of ginseng, 10-15 parts of bupleurum, 10-15 parts of curcuma zedoary, 6-9 parts of pinellia, 6-10 parts of amomum, 10-15 parts of atractylodes, 10-15 parts of poria, 10-15 parts of hovenia dulcis, 10-15 parts of rehmannia, 8-10 parts of giant knotweed, and 6-9 parts of olibanum. The traditional Chinese medicine composition treats metabolic-related fatty liver disease from the perspective of liver stagnation and spleen deficiency and phlegm and blood stasis, and starts from the core pathological chain of liver stagnation, spleen deficiency, phlegm and blood stasis, and has the functions of soothing liver and strengthening spleen, removing dampness and fat, and activating blood and dredging collaterals. The traditional Chinese medicine composition is especially suitable for patients with metabolic-related fatty liver disease of liver stagnation and spleen deficiency syndrome. Clinical tests prove that the traditional Chinese medicine composition has good therapeutic effect on patients with metabolic-related fatty liver disease of liver stagnation and spleen deficiency syndrome, and the total effective rate is more than 94%. The traditional Chinese medicine composition has mild medicinal properties, good safety, stable curative effect, and is not easy to relapse, and is suitable for long-term taking.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine compositions, and more particularly relates to a traditional Chinese medicine composition for treating liver stagnation and spleen deficiency syndrome metabolic-related fatty liver disease. BACKGROUND

[0002] Metabolic dysfunction-associated fatty liver disease (MAFLD) refers to a chronic progressive liver disease caused by overnutrition and insulin resistance in genetically susceptible individuals. It is renamed from the original "non-alcoholic fatty liver disease (NAFLD)", aiming to emphasize the direct relationship between metabolic abnormalities (such as obesity, insulin resistance) and fatty liver. MAFLD has now replaced viral hepatitis to become the first chronic liver disease in China. The overall prevalence of MAFLD in Chinese adults over the past 20 years was 29.6%, with males (34.8%) higher than females (23.5%), and continues to grow, is prone to progress to liver fibrosis, and the 5-year fibrosis rate of ordinary patients is 20%-30%, is also associated with multiple diseases, and has a heavy economic burden.

[0003] Metabolic-related fatty liver disease belongs to the category of "hypochondriac pain", "accumulation", "phlegm turbidity", "fatty" and the like in traditional Chinese medicine. Its etiology and pathogenesis is complex, and it is currently believed that improper diet, improper rest, emotional disorders, prolonged illness, and insufficient innate factors are the main predisposing factors for the disease. The disease is located in the liver and involves the spleen, kidney and other organs. Diet depends on the normal operation of the spleen and stomach function for the transformation and distribution of subtle substances in the body. If the spleen and stomach are weak or too much is ingested, the subtle substances cannot be normally operated and distributed, and are transformed into water, phlegm, turbidity, stasis and heat. The accumulation of phlegm, dampness, turbidity, stasis and heat in the liver is the main etiology and pathogenesis of the disease.

[0004] When treating MAFLD by TCM syndrome differentiation, it is often divided into liver stagnation and spleen deficiency, phlegm turbidity obstruction, damp-heat accumulation, and phlegm and blood stasis accumulation, etc. Among them, liver stagnation and spleen deficiency: chest and rib distending and depressed, depressed and not comfortable, lassitude and debilitation, abdominal fullness, abdominal distension and discomfort, decreased appetite, nausea and vomiting, irregular bowel movement, and sometimes sighing; tongue and pulse: pale red tongue, thin white fur, teeth marks, and thin pulse. Phlegm turbidity obstruction: obesity, right costal discomfort or distending and depressed, sticky and sluggish stool, abdominal distension, lassitude and debilitation, decreased appetite, dizziness and nausea; tongue and pulse: pale tongue, white and greasy fur, and slippery pulse. Damp-heat accumulation: right costal rib distending pain, sticky and sluggish stool, abdominal distension or pain, yellowish complexion and eyes, heavy body, sticky mouth, dry mouth, and bitter taste; tongue and pulse: red tongue, yellow and greasy fur, and stringy or slippery and numberous pulse. Phlegm and blood stasis accumulation: costal rib stabbing or dull pain, costal mass, dark complexion, chest and abdominal fullness, expectoration of sputum, poor appetite, obesity, and heavy limbs; tongue and pulse: dark red tongue with blood stasis spots, large tongue, teeth marks on the edge, greasy fur, stringy or slippery pulse, and astringent pulse. Different syndromes have different treatments. There are many disclosed Chinese medicine compositions for MAFLD, but there are few existing Chinese medicine compositions for liver stagnation and spleen deficiency, which leads to poor treatment effect and low total effective rate for patients with liver stagnation and spleen deficiency MAFLD in clinical application.

[0005] Ganoderma lucidum capsule is a commonly used Chinese medicine for MAFLD. The drug has the effects of clearing heat and dampness, tonifying spleen and nourishing blood, and benefiting qi and relieving depression. According to the existing literature (“Effect of Ganoderma lucidum capsule combined with diammonium glycyrrhizinate enteric-coated capsule in the treatment of non-alcoholic fatty liver”, Henan Medical Research, June 2019, 1089-1091), Ganoderma lucidum capsule can improve liver function indicators [aspartate aminotransferase (AST), glutamyltransferase (GGT), alanine aminotransferase (ALT)], and the total effective rate is 88.24%, but it cannot be confirmed which syndrome of MAFLD is treated.

[0006] China CN 114522206 A discloses “application of a compound medicine in preparation of a medicine for preventing / treating MAFLD”, which is prepared from ginkgo leaves, salvia miltiorrhiza, breviscapine, gynostemma pentaphyllum, hawthorn, garlic, panax notoginseng, and moxa tablets as raw materials; salvia miltiorrhiza as the monarch drug for activating blood and resolving stasis, ginkgo leaves as the minister drug for protecting liver and reducing lipid, gynostemma pentaphyllum and panax notoginseng as the auxiliary drugs for nourishing heart and tranquilizing mind, and breviscapine, hawthorn, lotus leaf, and moxa tablets as the ministerial drugs for clearing turbidity and detoxification, and promoting intestinal peristalsis. However, it does not mention the clinical application, and the clinical efficacy is unknown.

[0007] Chinese CN 114209749 A discloses "Application of Daliankang preparation in preparation of drugs for preventing / treating MAFLD", which is prepared from raw medicinal materials of Herba Veronicae, Radix Rumicis, Saxifraga stolonifera, Caulis Tsoongiodendri, Pteridium aquilinum, Scutellaria baicalensis, Phellodendron amurense and Andrographis paniculata, and is originally used for acute and chronic cholecystitis, cholangitis, cholelithiasis and post-cholecystectomy syndrome caused by liver and gallbladder dampness and heat accumulation. At present, only by constructing metabolic related fatty liver disease in vivo and in vitro model, screening is found that Daliankang compound preparation effectively inhibits the further occurrence and development of metabolic related fatty liver disease by acting on multiple targets. There is also a lack of clinical application experience. Therefore, it is necessary to develop a traditional Chinese medicine composition specially for MAFLD patients with liver stagnation and spleen deficiency syndrome. SUMMARY

[0008] The pathogenesis of metabolic associated fatty liver disease (MAFLD) is based on liver lipid metabolism disorder, and liver stagnation and spleen deficiency syndrome is an important TCM syndrome type. From the perspective of liver and spleen treatment, the present application provides a traditional Chinese medicine composition for treating liver stagnation and spleen deficiency syndrome of metabolic associated fatty liver disease, which starts from the core pathological chain of "liver stagnation", "spleen deficiency", "phlegm-dampness" and "blood stasis", regulates qi by soothing liver and relieving depression, strengthens the spleen and replenishes qi to eliminate phlegm source, and removes blood stasis to eliminate accumulation and stagnation, which embodies the classic treatment ideas of TCM "knowing liver disease, knowing liver transmission to spleen, and first strengthening the spleen" and "soothing blood and qi to regulate and reach".

[0009] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0010] A traditional Chinese medicine composition for treating liver stagnation and spleen deficiency syndrome of metabolic associated fatty liver disease, which is composed of the following raw materials by weight: Radix et Rhizoma Ginseng 8-10 parts, Radix Bupleuri 10-15 parts, Radix Curcumae 10-15 parts, Rhizoma Pinelliae 6-9 parts, Fructus Amomi Rotundus 6-10 parts, Radix Atractylodis 10-15 parts, Poria cocos 10-15 parts, Hovenia dulcis Thunb. 10-15 parts, Radix Rehmanniae 10-15 parts, Rhizoma Polygoni 8-10 parts, and Lignum 6-9 parts.

[0011] As a preferred embodiment of the present application, the traditional Chinese medicine composition is composed of the following raw materials by weight: Radix et Rhizoma Ginseng 8 parts, Radix Bupleuri 10-15 parts, Radix Curcumae 10-15 parts, Rhizoma Pinelliae 6-9 parts, Fructus Amomi Rotundus 10 parts, Radix Atractylodis 10-15 parts, Poria cocos 10-15 parts, Hovenia dulcis Thunb. 10 parts, Radix Rehmanniae 10 parts, Rhizoma Polygoni 8-10 parts, and Lignum 6-9 parts.

[0012] As a preferred embodiment of the present invention, the traditional Chinese medicine composition comprises the following raw materials by weight: 10 parts ginseng, 10-15 parts bupleurum, 10-15 parts turmeric, 6-9 parts ginger-processed pinellia, 10 parts amomum, 10-15 parts atractylodes, 15 parts poria, 10-15 parts jujube, 10-15 parts rehmannia, 10 parts polygonum cuspidatum, and 6-9 parts dalbergia.

[0013] Clinical trials have verified that the traditional Chinese medicine composition of this invention has a significant therapeutic effect on patients with metabolic-related fatty liver disease due to liver stagnation and spleen deficiency, with a total effective rate of over 94%. Simultaneously, it also shows good therapeutic effects on patients with varying degrees of liver dysfunction and lipid metabolism disorders, effectively reducing liver fat content, improving liver function indicators, regulating lipid metabolism, and exhibiting good safety with no significant adverse reactions. Therefore, it can be used in the preparation of drugs for treating metabolic-related fatty liver disease due to liver stagnation and spleen deficiency.

[0014] The dosage form of the drug for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome according to the present invention is an oral preparation, which is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

[0015] The present invention also provides a traditional Chinese medicine decoction for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome, characterized in that the decoction is composed of the following ingredients by weight: ginseng 8-10 parts, bupleurum 10-15 parts, turmeric 10-15 parts, ginger pinellia 6-9 parts, amomum 6-10 parts, atractylodes 10-15 parts, poria 10-15 parts, jujube fruit 10-15 parts, rehmannia 10-15 parts, polygonum cuspidatum 8-10 parts, and dalbergia odorifera 6-9 parts.

[0016] The preparation method of the decoction is as follows: Wash and soak the medicinal materials; First decoction: Except for the cardamom, heat the other soaked medicinal materials over high heat, bring to a boil, then reduce to low heat and simmer for 45-60 minutes. Pour out the first decoction, filter it with a strainer, and store the decoction in a clean container; Second decoction: Add water to the dregs, covering them by 1-2 cm, bring to a boil over high heat, then reduce to low heat and simmer for 30-45 minutes; When 15 minutes have passed, add the reserved cardamom to the pot and continue simmering until the time is up. Mix the filtered decoction with the first decoction and stir well.

[0017] The traditional Chinese medicine composition provided by the present application has the functions of soothing liver and strengthening spleen, resolving dampness and eliminating fat, and activating blood and dredging collaterals. The present application takes Xiaoyao Powder combined with Erchen Decoction (Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae, Rhizoma Pinelliae, Pericarpium Citri Reticulatae, and Radix Zingiberis) as the base formula, and takes the compatibility characteristics of soothing liver and strengthening spleen and regulating liver and spleen. In the formula, Rhizoma Atractylodis Macrocephalae is replaced by Atractylodes Rhizome, which has the characteristics of strong dampness and spleen strengthening, and is more suitable for the syndrome of internal retention of dampness and turbidity. Radix Angelicae Sinensis is replaced by Radix Ginseng, which has the effects of tonifying primordial qi and invigorating spleen and kidney, and enhances the spleen-strengthening effect. In the pharmacological research, Radix Ginseng, Radix Bupleuri, and Poria can improve lipid metabolism and reduce liver fatty degeneration. The present application removes ginger and Radix Paeoniae Alba in Xiaoyao Powder, and Pericarpium Citri Reticulatae and Radix Glycyrrhizae in Erchen Decoction, so as to avoid the dampness and wetness caused by blood-nourishing drugs. The present application newly adds Fructus Hoveniae and Rhizoma Polygoni Cuspidati, and adds Radix Rehmanniae for the scene of internal retention of alcohol toxicity and excessive dampness and heat. In addition, Fructus Hoveniae has the effects of clearing heat and dampness, protecting liver, and modern pharmacological researches have confirmed that it can reduce serum aminotransferase and improve liver function, which is helpful for soothing liver and benefiting gallbladder. In the formula, Radix Curcumae has the effects of activating blood and qi and clearing liver and benefiting gallbladder, and is combined with Radix Bupleuri to enhance the effect of soothing liver and relieving depression. Rhizoma Polygoni Cuspidati and Acronychia Fruit activate blood and resolve stasis and dredge collaterals. Rhizoma Polygoni Cuspidati is good at clearing heat and dampness and reducing jaundice, and Acronychia Fruit is good at regulating qi and relieving pain, and the two drugs can resolve stasis and dredge collaterals, and protect liver cells. Jiang and Rhizoma Pinelliae dry dampness and resolve phlegm, regulate qi and harmonize stomach, Jiang resolves adverse flow and stops vomiting, and Amomum Wakes up the spleen and stimulates the appetite, and the two drugs are combined to invigorate the spleen, so that the spleen is strengthened, dampness is resolved, and the ascending and descending of qi is in order, so that the physiological functions of viscera are normally performed. Radix Rehmanniae nourishes yin and blood, prevents the warm and dry drugs from damaging yin, makes the tonification not stagnated, and the soothing not damaged. Rhizoma Polygoni Cuspidati, Acronychia Fruit, Radix Curcumae, and Fructus Hoveniae are combined to enhance the effects of activating blood and resolving stasis, clearing liver and benefiting gallbladder, and lead the drugs into liver meridians and collaterals, so that the blood-activating and dampness-removing drugs directly reach the disease site, and the effect is doubled with half the effort. The formula dredges liver collaterals from different aspects of phlegm, stasis, and dampness, resolves phlegm, stasis, and dampness, and makes liver collaterals unobstructed, so that it can improve the disorder of liver lipid metabolism and reverse liver cell fatty degeneration.

[0018] From the monarch, minister, assistant, and messenger, in the present formula, Radix Bupleuri is used as the monarch drug to soothe liver and relieve depression as the basis; Radix Ginseng, Poria, and Atractylodes Rhizome are used as the minister drugs to enhance the effects of invigorating spleen and resolving dampness, and at the same time, to achieve the purposes of tonifying qi and supporting the healthy energy, and drying dampness and eliminating fat; Radix Curcumae, Rhizoma Polygoni Cuspidati, Acronychia Fruit, and Fructus Hoveniae are used as the assistant drugs to activate blood and resolve stasis, clear liver and benefit gallbladder, prevent liver depression and heat from damaging liver, and eliminate fat and protect liver and dredge collaterals and relieve pain; Jiang, Rhizoma Pinelliae, and Radix Rehmanniae are used as the messenger drugs to regulate spleen and stomach, nourish yin and blood, and lead the monarch and minister into liver and spleen meridians and collaterals, so as to achieve the effects of soothing liver and strengthening spleen, resolving dampness and dredging collaterals, and regulate the drugs to prevent the warm and dry drugs from damaging yin.

[0019] This formula treats metabolic-related fatty liver disease (MRDL) with liver stagnation and spleen deficiency by addressing both the root cause and symptoms, thus treating both liver and spleen deficiency simultaneously. It improves hepatic lipid metabolism, reduces hepatocyte steatosis, lowers serum transaminase and lipid levels, inhibits the progression of liver fibrosis, reverses liver inflammation and fat deposition, and restores normal liver function, thereby effectively treating MRDL. Clinical trials have demonstrated that this formula has significant therapeutic effects on patients with MRDL of liver stagnation and spleen deficiency type, with a total effective rate exceeding 94%. It also shows good therapeutic effects on patients with varying degrees of liver dysfunction and lipid metabolism disorders. Therefore, this traditional Chinese medicine composition can significantly improve hepatic lipid metabolism and significantly reduce the risk of cirrhosis and liver cancer.

[0020] Advantages and beneficial effects of the present invention:

[0021] (1) The traditional Chinese medicine composition provided by the present invention has a significant therapeutic effect on metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome. Clinical trials have shown that the composition has a significant therapeutic effect on patients with metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome, and can effectively improve the clinical symptoms of patients, including hypochondriac pain, epigastric fullness, poor appetite and weakness, loose stools, etc., with a total effective rate of over 94%.

[0022] (2) The traditional Chinese medicine composition provided by the present invention involves multiple aspects of the treatment of metabolic-related fatty liver disease. It has the effects of protecting the liver, regulating lipids and lowering enzymes. It is especially suitable for patients with metabolic-related fatty liver disease accompanied by abnormal liver function and lipid metabolism disorder. It can significantly reduce serum transaminase (ALT, AST) levels, improve liver function indicators, regulate lipid metabolism (reduce TC, TG, LDL-C, and increase HDL-C), reduce liver fat content, and reduce the risk of cirrhosis and liver cancer. In addition, it can also restore the spleen and stomach's digestive function.

[0023] (3) The traditional Chinese medicine composition provided by the present invention has a reasonable formulation and scientific compatibility. It combines multiple methods such as soothing the liver and strengthening the spleen, eliminating dampness and fat, and promoting blood circulation and unblocking collaterals. It treats both the root cause and the symptoms. It can soothe the liver and relieve depression, strengthen the spleen and eliminate dampness, promote blood circulation and remove blood stasis, and unblock collaterals and protect the liver. It comprehensively regulates the function of the internal organs from the perspective of treating both the liver and the spleen. Moreover, the medicine is mild, safe, has no obvious adverse reactions, has stable efficacy, is not easy to relapse, and is suitable for long-term use. Detailed Implementation

[0024] This invention discloses a traditional Chinese medicine composition for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome. Those skilled in the art can refer to the content of this document and make appropriate adjustments and optimizations to the component ratios or preparation processes according to actual circumstances. It should be particularly noted that all equivalent substitutions and modifications based on this invention are obvious to those skilled in the art and should be considered to be included within the scope of protection of this invention.

[0025] Example 1:

[0026] The embodiment provides a traditional Chinese medicine composition for treating liver stagnation and spleen deficiency syndrome metabolic-related fatty liver disease, which is composed of the following raw materials in parts by weight: 10 g of ginseng, 15 g of bupleurum, 10 g of curcuma zedoary, 9 g of pinellia ternate, 10 g of amomum villosum, 10 g of atractylodes, 15 g of poria cocos, 10 g of hovenia dulcis thunb, 10 g of rehmannia glutinosa, 10 g of giant knotweed, and 9 g of dalbergcon odorifera.

[0027] The present prescription is made by adding and subtracting the modified Xiaoyao Powder and Erchen Decoction. In the prescription, bupleurum soothes the liver and relieves depression, and is the monarch drug. Ginseng greatly supplements primordial qi, invigorates the spleen and lung, poria cocos invigorates the spleen, dries dampness, calms the heart and tranquilizes the mind, atractylodes dries dampness, invigorates the spleen, dispels wind and cold, and the three drugs are used together as the minister drugs to enhance the effect of invigorating the spleen and resolving dampness. Modern pharmacological research shows that ginseng and poria cocos have the effects of regulating lipid metabolism and protecting liver cells. Curcuma zedoary promotes qi and relieves depression, promotes blood circulation and relieves pain, and clears the heart and cools blood, and is combined with bupleurum to enhance the function of soothing the liver and regulating qi. Giant knotweed and dalbergcon odorifera promote blood circulation and remove blood stasis and dredge collaterals, giant knotweed can also clear heat, drain dampness and relieve jaundice, dalbergcon odorifera can also regulate qi and relieve pain, and the two drugs are used together to remove blood stasis and dredge collaterals and protect the liver and reduce enzymes. Hovenia dulcis thunb clears heat and drains dampness, relieves alcohol and protects the liver, and pharmacological research has confirmed that it can reduce serum aminotransferase and improve liver function. Pinellia ternate dries dampness, resolves phlegm, reduces adverse and stops vomiting, and amomum villosum resolves dampness and regulates qi, warms the middle and stops diarrhea, and the two drugs are combined to regulate the spleen and stomach, so that the spleen is invigorated and dampness is resolved, and the qi movement is smooth. Rehmannia glutinosa nourishes yin and blood, clears heat and cools blood, and prevents the warm and dry drugs from damaging yin, so that the whole prescription is supplemented without stagnation and dredged without damage. The combined use of the drugs combines soothing the liver and invigorating the spleen, resolves dampness and promotes blood circulation, and treats the symptoms and the root cause, and treats the liver and the spleen together, and has the functions of soothing the liver, invigorating the spleen, resolving dampness, reducing fat, promoting blood circulation and dredging collaterals, and is particularly suitable for patients with liver stagnation and spleen deficiency syndrome metabolic-related fatty liver disease.

[0028] The traditional Chinese medicine composition provided in the embodiment can be any one of granules, tablets, capsules, powders, decoctions or pills when actually taken. Among the above-mentioned dosage forms, the decoction has the advantages of simple preparation, rapid absorption and rapid drug efficacy, and is therefore preferred. The decoction is prepared by water decoction, residue removal and juice extraction.

[0029] Specifically, the preparation method of the decoction is as follows:

[0030] Wash the medicinal materials, soak for 1 hour; first decoction: the soaked medicinal materials (except for amomum villosum) are heated with a large fire, and after boiling, the fire is turned to small to keep a state of slight boiling, and the medicinal materials are decocted for 45-60 minutes, the first decoction liquid is poured out, filtered with a filter screen, and the filtered decoction liquid is stored in a clean container, about 150-200 ml; second decoction: the medicinal dregs are added with clean water, and the water level is 1-2 cm higher than the medicinal dregs, and after boiling with a large fire, the fire is turned to small to keep a state of slight boiling, and the medicinal dregs are decocted for 30-45 minutes; when the decoction time is 15 minutes, the reserved amomum villosum is poured into the pot, and the decoction is continued until the end of the decoction time, and the filtered medicinal liquid is mixed with the first decoction liquid, and the total medicinal liquid is about 300-400 ml, and the medicinal liquid is stirred uniformly. When taken, 150-200 ml is taken twice a day, in the morning and evening after meals.

[0031] Example 2

[0032] The traditional Chinese medicine composition described in this example is composed of the following raw materials by weight: 8 g of ginseng, 15 g of bupleurum, 15 g of curcuma, 9 g of pinellia, 10 g of amomum villosum, 15 g of atractylodes, 15 g of poria, 10 g of hovenia dulcis, 10 g of rehmannia, 8 g of giant knotweed, and 9 g of olibanum.

[0033] The difference from example 1 is that 15 g of bupleurum, 15 g of curcuma, 15 g of atractylodes, 10 g of amomum villosum, 9 g of pinellia, and 9 g of olibanum are all taken at the upper limit, and the core is strengthened to "soothe the liver, dry dampness, and harmonize the stomach", directly attacking the core of liver depression and dampness stagnation. 8 g of ginseng, 10 g of rehmannia, 10 g of hovenia dulcis, and 8 g of giant knotweed are taken at the lower limit, reducing the tonifying qi and greasy, and avoiding affecting the dampness, while the basic protection of dryness and dampness is avoided. This example is more suitable for liver depression with spleen and stomach dampness, without obvious dry mouth and yin deficiency.

[0034] Example 3

[0035] The traditional Chinese medicine composition described in this example is composed of the following raw materials by weight: 10 g of ginseng, 10 g of bupleurum, 10 g of curcuma, 6 g of pinellia, 10 g of amomum villosum, 10 g of atractylodes, 15 g of poria, 15 g of hovenia dulcis, 15 g of rehmannia, 10 g of giant knotweed, and 6 g of olibanum.

[0036] The difference from example 1 is that 10 g of ginseng, 15 g of hovenia dulcis, 10 g of giant knotweed, 15 g of rehmannia, 15 g of poria, and 10 g of amomum villosum are taken at the upper limit, and the core is strengthened to "alcohol toxicity, clearing dampness and heat, and nourishing yin", aiming at the key problem of alcohol toxicity and dampness and heat coexisting with yin deficiency. 10 g of atractylodes, 6 g of pinellia, 6 g of olibanum, 10 g of bupleurum, and 10 g of curcuma are taken at the lower limit, reducing the consumption of yin liquid by dampness and qi regulating drugs, and taking into account the liver without yin. This example is more suitable for those with obvious alcohol toxicity and dampness and heat, and relatively mild liver depression.

[0037] It should be noted that the traditional Chinese medicine composition provided by the present application can be appropriately added or subtracted according to the severity of the patient's symptoms and the length of the course of treatment.

[0038] The liver-spleen regulating traditional Chinese medicine composition provided by the application is used for treating metabolic related fatty liver disease from the aspects of phlegm, dampness, blood stasis and deficiency and the liver-spleen regulating theory, through the combination of soothing the liver and relieving depression, invigorating the spleen and replenishing qi, reducing turbidity and eliminating phlegm, and removing blood stasis and dredging collaterals. The traditional Chinese medicine decoction has been used in the Affiliated Hospital of Changchun University of Chinese Medicine for many years, and has good therapeutic effect on patients with liver depression and spleen deficiency syndrome MAFLD. The following will illustrate the therapeutic effect of the traditional Chinese medicine decoction of the application through clinical data, and the specific conditions are as follows:

[0039] 1. General information:

[0040] Seventy-two patients with liver depression and spleen deficiency syndrome MAFLD in the outpatient department of the Department of Gastroenterology of the Affiliated Hospital of Changchun University of Chinese Medicine from July 2024 to May 2025 were selected and randomly divided into two groups, 36 cases in each group; the treatment group: 21 males and 15 females, with an average age of 30-75 years old, and a disease course of 3-8 years; the control group: 19 males and 17 females, with an average age of 28-74 years old, and a disease course of 2-9 years; the gender, age, disease course and disease condition of the patients in the two groups were compared, and the differences were not significant, and they were comparable.

[0041] 2. Diagnostic criteria:

[0042] 2.1 Western medicine diagnostic criteria:

[0043] Refer to the Metabolic Related (Non-alcoholic) Fatty Liver Disease Prevention and Treatment Guidelines (2024 Edition) and the Non-alcoholic Fatty Liver Disease Diagnosis and Treatment Guidelines (2018 Updated Edition).

[0044] 1) Clinical manifestations: liver region pain, rib side distension, general weakness, loss of appetite, etc.

[0045] 2) Signs: the common signs of NAELD are liver enlargement, and a small number of patients may be accompanied by mild jaundice; the signs of liver cirrhosis include liver disease face, jaundice, splenomegaly, liver palms, spider nevi, ascites and lower extremity edema, abdominal wall venous exposure, male breast development, skin pigmentation, etc.

[0046] 2.2 TCM syndrome differentiation criteria:

[0047] Refer to the syndrome differentiation criteria of liver depression and spleen deficiency in the Non-alcoholic Fatty Liver Disease Diagnosis and Treatment Consensus Opinion (2017).

[0048] Main symptoms: ① rib side distension; ② depression and discomfort; ③ lassitude and weakness; ④ abdominal fullness.

[0049] Secondary symptoms: ① abdominal distension; ② loss of appetite; ③ nausea and vomiting; ④ irregular bowel movements; ⑤ sighing.

[0050] Tongue and pulse: pale red tongue, thin white or white fur, tooth marks, and thin pulse.

[0051] With the above main symptoms 2 and secondary symptoms 1 or 2, reference to the tongue pulse, that is, the syndrome can be clearly identified.

[0052] 3. Inclusion criteria:

[0053] 1) In line with the Western medical diagnostic criteria for MAFLD;

[0054] 2) In line with the TCM syndrome differentiation criteria for liver stagnation and spleen deficiency;

[0055] 3) Age between 18 and 75 years old;

[0056] 4) Liver function indicators show alanine aminotransferase (ALT) and aspartate aminotransferase (AST) persistently elevated for more than 4 weeks;

[0057] 5) Patient's informed consent.

[0058] 4. Exclusion criteria:

[0059] 1) Combined with severe diseases of heart, brain, lung, kidney and hematopoietic system, etc;

[0060] 2) With mental illness or communication and consciousness disorders;

[0061] 3) Combined with liver failure;

[0062] 4) Combined with connective tissue disease, anxiety and depression, and other conditions not suitable for inclusion;

[0063] 5) Allergic to drugs used in this study, voluntarily terminate treatment;

[0064] 6) With alcoholic liver disease, drug-induced liver disease, chronic viral hepatitis, autoimmune liver disease, liver degeneration, liver cancer, and combined with cardiac and renal insufficiency and other malignancies.

[0065] 5. Treatment method:

[0066] 5.1 Basic treatment includes establishing correct lifestyle habits and healthy diet, low-fat and low-sugar diet, reducing high-calorie food intake, avoiding alcohol, moderate exercise, and controlling body mass.

[0067] 5.2 Treatment group is given liver and spleen regulating decoction on the basis of basic treatment. The composition of the decoction is: 10g of ginseng, 15g of bupleurum, 10g of curcuma, 9g of pinellia, 10g of amomum, 10g of atractylodes, 15g of poria, 10g of hovenia dulcis, 10g of rehmannia, 10g of giant knotweed, and 9g of acorus. One dose (300-400ml of water decoction) is taken every day, 2 times a day (150-200ml each time), taken in the morning and evening after meals.

[0068] 5.3 The control group was given Shugankang Capsule (Lanzhou Heshengtang Pharmaceutical Co., Ltd., specification 0.4 g*12 tablets / box, State Drug Standard Z20026871) on the basis of treatment, 3 tablets at a time, 3 times a day. Warm water for service.

[0069] 2 Both groups were treated for 8 weeks.

[0070] 6. Efficacy observation

[0071] 6.1 Observation index:

[0072] 1) TCM syndrome score. The main symptoms of patients were scored 0, 2, 4, and 6 points according to no, mild, moderate, and severe degrees, respectively, and the syndrome scores were compared after treatment.

[0073] 2) Laboratory index. Liver function, cholinesterase, and blood lipid indexes were detected in both groups before and after treatment, mainly including alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), triglyceride (TC), and total cholesterol (TC).

[0074] 6.2 Efficacy criteria:

[0075] Refer to the relevant standards in the Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine.

[0076] Cure: symptoms and signs completely disappeared, liver ultrasound showed normal liver parenchyma and morphology, laboratory tests showed normal liver function and indicators;

[0077] Marked effect: symptoms disappeared, positive signs significantly decreased, liver ultrasound showed a decrease of 1-2 degrees in fatty liver, laboratory tests showed normal liver function, TC decreased by >20% or TG decreased by >40%;

[0078] Effective: symptoms were relieved, positive signs were reduced, liver ultrasound showed a decrease of 1 degree in fatty liver, laboratory tests showed improvement in liver function but not completely normal, TC decreased by >10% and ≤20%, or TG decreased by >70% and ≤40%;

[0079] No effect: symptoms and signs had no obvious changes or were aggravated, liver ultrasound showed no obvious changes in fatty liver, liver function indicators were not significantly improved or were even aggravated, and the decrease in blood lipid indicators was not as good as the above criteria or was even aggravated.

[0080] 6.3 Statistical method:

[0081] All data were analyzed by SPSS 23.0 statistical software. Measurement data were expressed as mean ± standard deviation (±s), and t test was used for normal distribution, rank sum test was used for non-normal distribution; count data were expressed as rate (%), and chi-square test was used; P<0.05 was considered statistically significant.

[0082] 7. Treatment results:

[0083] 7.1 The total effective rate of the treatment group was 94.44%, which was significantly higher than that of the control group (75.00%), and the difference was statistically significant (P<0.05), as shown in Table 1.

[0084] Table 1 Comparison of comprehensive efficacy between treatment group and control group [cases (%)]

[0085] Group Cases Cured Markedly effective Effective Ineffective Total effective Treatment group 36 10（27.76） 17（47.22） 7（19.44） 2（5.56） 34 (94.44) a ]] Control group 36 6（16.67） 10（27.77） 11（30.56） 9（25.00） 33（75.00）

[0086] Note: Compared with the control group, a P<0.05.

[0087] 7.2 Comparison of TCM syndrome scores between treatment group and control group after treatment, the TCM syndrome scores (chest and rib distending and stuffiness; depression and discomfort; fatigue and weakness; abdominal fullness; and frequent sighing) of the treatment group were lower than those of the control group after treatment, and the difference was statistically significant (P<0.01), as shown in Table 2.

[0088] Table 2 Comparison of TCM syndrome scores between treatment group and control group after treatment , points

[0089] Group Cases Chest and rib distending oppression Depression and discomfort Chest oppression and abdominal distention Lassitude and debilitation Occasional desire for large breath Treatment group 36 3.05±1.01* 2.94±1.11* 3.16±1.11* 3.33±1.17* 2.88±1.21* Control group 36 4.38±1.33 4.66±1.06 4.44±1.27 4.33±1.31 4.38±1.15

[0090] Note: Compared with the control group, * P<0.01.

[0091] 7.3 Comparison of liver function indicators between treatment group and control group before and after treatment, there was no statistically significant difference in ALT, AST, and GGT indicators between the two groups before treatment (P>0.05); after treatment, the ALT, AST, and GGT indicators of the two groups were improved compared with before treatment, and the improvement in the treatment group was greater than that in the control group, and the difference was statistically significant (P<0.05).

[0092] Table 3 Comparison of liver function indicators between treatment group and control group before and after treatment , U / L

[0093]

[0094] Note: Compared with before treatment in the group, a p<0.05; compared with the control group after treatment, b p<0.05.

[0095] 7.4 Comparison of blood lipid indicators between treatment group and control group before and after treatment, TG and TC indicators of 2 groups before treatment had no statistically significant difference (P>0.05); after treatment, TG and TC indicators of 2 groups were improved compared with before treatment, and the improvement range of treatment group was greater than that of control group, and the difference was statistically significant (P<0.05), see Table 4 for details.

[0096] Table 4 Comparison of blood lipid indicators between treatment group and control group before and after treatment , mmol / L)

[0097]

[0098] Note: compared with this group before treatment, a p<0.05; compared with control group after treatment, b p<0.05.

[0099] 7.5 Follow-up of treatment group and control group:

[0100] The treatment group and the control group were followed up 3 months and 6 months after treatment respectively. Among them, the patients in the treatment group had no abnormality or aggravation in the review of blood lipid, liver function and other indicators; 2 patients in the control group had mild increase in liver function after review, and 4 patients had increased blood lipid after review, and were given symptomatic treatment. The results showed that the long-term effect of the treatment group was better.

[0101] Typical cases:

[0102] Zhang, male, 42 years old, November 16, 2024, initial diagnosis. Onset of symptoms: chest rib distending and stuffy repeated for 1 year, aggravated for 1 month, low mood, depression, sighing, obvious fatigue and weakness at work, aggravated after activity, abdominal fullness, more after eating. Daily abdominal distension, loss of appetite, 1 / 3 less than before, occasional nausea and vomiting (especially after drinking), irregular bowel movements (loose and soft, 1-2 times a day). Pale red tongue, white and slightly greasy fur, tooth marks on the edge of the tongue, thin pulse. Past medical history: physical examination found “fatty liver” for 1 year, no regular treatment; no history of hepatitis, diabetes, hypertension. Personal history: more social occasions, 3-4 times a week, diet is slightly greasy. Related examination: liver function: alanine aminotransferase (ALT) 68 U / L, aspartate aminotransferase (AST) 45 U / L, gamma glutamyl transpeptidase (GGT) 92 U / L. Abdominal ultrasound: liver shape is full, parenchymal echo is diffusely enhanced, suggesting “moderate fatty liver disease”. Blood lipids: triglycerides (TG) 2.8 mmol / L, total cholesterol (TC) 5.9 mmol / L. TCM diagnosis: liver accumulation (liver stagnation and spleen deficiency); Western medicine diagnosis: metabolic-related fatty liver disease. Treatment: mainly for soothing liver and invigorating spleen, reducing fat and resolving turbidity, removing blood stasis and dredging collaterals, taking liver and spleen regulating formula: 10g of ginseng, 15g of bupleurum, 10g of curcuma, 9g of pinellia, 10g of amomum, 10g of atractylodes, 15g of poria, 10g of hovenia dulcis, 10g of rehmannia, 10g of giant knotweed, 9g of dalbergia hupeana, 1 dose per day, decocted by pharmacy of our hospital (Changchun University of Chinese Medicine Affiliated Hospital), water decoction 300-400ml, 150-200ml each time, 2 times a day, morning and evening after meals, 10 doses.

[0103] Second visit: chest rib distending and stuffy significantly reduced (frequency of attack from 3-4 times a day to 1 time), depression slightly relieved, fatigue and weakness improved (no obvious fatigue after working for half a day), abdominal fullness relieved (only mild distension after eating). Still sighing, irregular bowel movements, tongue and pulse: pale red tongue, thin white fur, tooth marks shallower than before, thin and slightly fine pulse. Adjust the prescription: the patient still sighs, has irregular bowel movements, and has thin and slightly fine pulse, so increase the dosage of curcuma to 15g to enhance the function of promoting qi and resolving depression; increase the dosage of atractylodes to 15g to enhance the function of drying dampness and invigorating spleen, the rest of the drug dosage remains the same, continue to take 14 doses, the same as before.

[0104] Three diagnosis: the full disappearance of the chest and rib distending and oppression, stable mood, no depression, basically ease of fatigue and weakness (daily activities without discomfort), the full disappearance of the abdominal distention, basically normal diet and stool. Tongue and pulse: pale red tongue, thin white fur, shallow tooth marks, stringy pulse. Recheck related examination: alanine aminotransferase (ALT) 35 U / L, aspartate aminotransferase (AST) 32 U / L, γ-glutamyl transpeptidase (GGT) 48 U / L, triglyceride (TG) 1.8 mmol / L, total cholesterol (TC) 5.2 mmol / L. The patient's symptoms are cured, liver function and blood lipid indicators return to normal, but the patient's tongue fur and pulse suggest that the liver depression gradually relaxes and the spleen deficiency gradually recovers, further adjustment is still needed to consolidate the curative effect, so the prescription is adjusted: 8g of ginseng, 10g of bupleurum, 10g of curcuma, 6g of pinellia, 10g of amomum, 10g of atractylodes, 10g of poria, 10g of hovenia dulcis, 10g of rehmannia, 10g of giant knotweed, 6g of olibanum, focusing on soothing the liver and invigorating the spleen, while preventing disease recurrence, and advising the patient to adhere to a healthy diet, moderate exercise (30 minutes of brisk walking per day), and avoid alcohol rebound. After 6 months of follow-up, the patient's tongue and pulse are normal, the mood is stable, and the disease has not recurred.

[0105] The patient in this case had long-term work pressure and emotional depression, leading to liver failure and stagnation of qi. Long-term drinking and eating greasy food directly damaged the liver and spleen, and the heavy and greasy taste increased the burden of spleen and stomach transportation, leading to internal wetness. Prolonged sitting, irregular work and rest, affected the function of spleen and stomach, and led to poor qi movement, further aggravating liver depression and dampness. Thus, there were a series of symptoms of liver depression and spleen deficiency, such as chest and rib distending and oppression, depression, fatigue and weakness, abdominal distention, irregular bowel movements, and a desire to sigh. Therefore, when treating, liver and qi should be relieved to relieve depression: aiming at the pathogenesis of liver depression, bupleurum and curcuma were selected as the core to relieve liver depression and regulate qi movement, relieving chest and rib distending and oppression and depression. Combined with olibanum to regulate qi and promote blood circulation, to enhance the flow of qi and avoid liver depression for a long time. Invigorating the spleen and tonifying qi to consolidate the foundation: aiming at the pathogenesis of spleen deficiency, ginseng, atractylodes and poria were used together, ginseng tonifying qi and invigorating the spleen, atractylodes drying dampness and invigorating the spleen, and poria invigorating the spleen and promoting water metabolism, the three of them working together to restore the function of spleen and stomach, improve fatigue and weakness, and improve tongue with tooth marks. Lipid-lowering and turbidity-removing to clear the middle: aiming at internal wetness, pinellia and amomum were used to dry dampness, remove phlegm, and harmonize the stomach and reverse, relieving abdominal distention, nausea and vomiting, and loss of appetite, and amomum retained the aroma after the lower abdomen, enhancing the effect of waking up the spleen. At the same time, pay attention to the key points, remove turbidity and lower lipid, nourish yin and prevent dryness, adapt to pathological evolution. In addition, the prescription has a definite effect on improving liver function indicators and regulating blood lipid metabolism, and the follow-up suggests that the long-term effect is good and the disease does not recur.

[0106] The above is the preferred embodiment of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome, characterized in that, The traditional Chinese medicine composition consists of the following raw materials by weight: ginseng 8-10 parts, bupleurum 10-15 parts, turmeric 10-15 parts, ginger-processed pinellia 6-9 parts, amomum 6-10 parts, atractylodes 10-15 parts, poria 10-15 parts, jujube fruit 10-15 parts, rehmannia root 10-15 parts, polygonum cuspidatum 8-10 parts, and dalbergia odorifera 6-9 parts.

2. The traditional Chinese medicine composition for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw materials by weight: 8 parts ginseng, 10-15 parts bupleurum, 10-15 parts turmeric, 6-9 parts ginger-processed pinellia, 10 parts amomum, 10-15 parts atractylodes, 10-15 parts poria, 10 parts jujube, 10 parts rehmannia, 8-10 parts polygonum cuspidatum, and 6-9 parts dalbergia odorifera.

3. The traditional Chinese medicine composition for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw materials by weight: 10 parts ginseng, 10-15 parts bupleurum, 10-15 parts turmeric, 6-9 parts ginger-processed pinellia, 10 parts amomum, 10-15 parts atractylodes, 15 parts poria, 10-15 parts jujube, 10-15 parts rehmannia, 10 parts polygonum cuspidatum, and 6-9 parts dalbergia.

4. The use of the traditional Chinese medicine composition for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome as described in any one of claims 1 to 3 in the preparation of a medicament for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome.

5. The application according to claim 4, characterized in that, The dosage form of the drug for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency is an oral preparation, which is selected from any one of granules, tablets, capsules, powders, decoctions or pills.

6. A traditional Chinese medicine decoction for treating metabolic-related fatty liver disease with liver stagnation and spleen deficiency syndrome, characterized in that... The decoction is composed of the following ingredients by weight: ginseng 8-10 parts, bupleurum 10-15 parts, turmeric 10-15 parts, ginger pinellia 6-9 parts, amomum 6-10 parts, atractylodes 10-15 parts, poria 10-15 parts, jujube fruit 10-15 parts, rehmannia 10-15 parts, polygonum cuspidatum 8-10 parts, and dalbergia odorifera 6-9 parts. The preparation method of the decoction is as follows: Wash and soak the medicinal materials; First decoction: Except for the cardamom, heat the other soaked medicinal materials over high heat, bring to a boil, then reduce to low heat and simmer for 45-60 minutes. Pour out the first decoction, filter it with a strainer, and store the decoction in a clean container; Second decoction: Add water to the dregs, covering them by 1-2 cm, bring to a boil over high heat, then reduce to low heat and simmer for 30-45 minutes; When 15 minutes have passed, add the reserved cardamom to the pot and continue simmering until the time is up. Mix the filtered decoction with the first decoction and stir well.

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