A traditional Chinese medicine composition, preparation and application for treating liver stagnation and spleen deficiency type metabolic-related fatty liver disease

Abstract

The application discloses a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of the type of liver stagnation and spleen deficiency, a preparation and application. The traditional Chinese medicine composition is composed of the following raw medicinal materials in weight: 15-30g of Huangqi, 15-20g of Baishao, 15-30g of Danshen, 15-20g of Gegen, 10-20g of Shengshanzha, 9-15g of Chuanlianzi, 6-9g of Wuzhuyu and 10-15g of Jianghuang. The application is based on qi and yin inheritance, yin and yang syndrome differentiation, coordination of yin and yang, and the treatment principle of regulating qi and blood, and provides a traditional Chinese medicine composition for treating liver stagnation and spleen deficiency. The traditional Chinese medicine composition can relieve the symptoms of patients with metabolic-related fatty liver disease of the type of liver stagnation and spleen deficiency, improve indexes such as CAP, BMI, liver function and blood fat, improve the life quality of the patients, and the total effective rate of traditional Chinese medicine syndrome reaches 93.94% in the treatment group. The traditional Chinese medicine composition is plain and clear, has high acceptance of patients, no obvious toxic and side effects are found in the application and treatment process, and thus can be selected as clinical medication and has important clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine composition and preparation technology, specifically relating to a traditional Chinese medicine composition, preparation and application for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type. Background Technology

[0002] Metabolic associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a chronic liver disease excluding other causes such as excessive alcohol consumption. It is one of the most common chronic liver diseases worldwide, affecting 25% of the general population and 85%–98% of morbidly obese individuals. With rising obesity rates, the global prevalence of MAFLD reaches 20%–40%, making it a leading cause of chronic liver disease and a serious public health problem. Currently, the pathogenesis of MAFLD is not fully understood, and there is no universally accepted ideal treatment for it. Recent clinical studies have shown that Traditional Chinese Medicine (TCM) has advantages in treating MAFLD, suggesting that analyzing MAFLD from a TCM perspective may be helpful in its treatment and prevention.

[0003] In recent years, many physicians have recognized that the pathogenesis of MAFLD in Traditional Chinese Medicine is related to a variety of factors, including improper diet, emotional imbalance, overwork and lack of rest, and old age and physical weakness. For example, the "Suwen·Bi Lun" states, "If one doubles their food intake, the stomach and intestines will be damaged." Overeating rich and greasy foods can easily lead to dysfunction of the spleen and stomach. Or, emotional distress can damage the internal organs, causing stagnation of Qi, which can lead to liver dysfunction and affect the spleen and stomach's digestive function. Another example is the "Wenre Tiaobian," which states, "Excessive leisure leads to spleen stagnation. When the spleen Qi is stagnant and its function is impaired, fluid retention and dampness will occur." Unhealthy lifestyle habits such as overworking and excessive leisure can also easily lead to weakened spleen and stomach function and the accumulation of dampness. Or, due to old age and physical weakness, the internal organs may weaken, leading to deficiency of spleen and kidney function, and the inability of water to nourish wood and warm earth. All of the above-mentioned causes can lead to damage to the spleen and stomach. When the spleen and stomach are damaged, the essence of food and water cannot be transformed, accumulating into phlegm and dampness. Over time, this transforms into blood stasis, with phlegm and blood stasis mutually binding the liver meridian. Simultaneously, impaired spleen function can also aggravate liver dysfunction, leading to stagnation of earth element and liver qi, resulting in qi stagnation and blood stasis, ultimately causing phlegm and blood stasis to bind together in the liver. The *Synopsis of Prescriptions of the Golden Chamber* states, "When liver disease is seen, it is known that it first affects the spleen, so the spleen should be strengthened first…," meaning the liver governs the free flow of qi, and the spleen governs transformation and transportation. Improper free flow and abnormal transformation and transportation lead to simultaneous liver and spleen disease. The disease is located in the liver but involves the spleen. The liver is "yin in substance but yang in function." Inadequate liver function can cause qi stagnation, anger and resentment injure the liver, forming pathological products such as phlegm, dampness, and blood stasis, leading to disease. Therefore, liver stagnation and spleen deficiency are crucial links in the occurrence and development of this disease in clinical practice.

[0004] The present invention aims to provide a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type. Summary of the Invention

[0005] The first objective of this invention is to provide a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type, and the second objective is to provide the formulation and application of the traditional Chinese medicine composition.

[0006] The first objective of this invention is achieved as follows: a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type, comprising the following raw materials by weight: Astragalus membranaceus 15-30g, Paeonia lactiflora 15-20g, Salvia miltiorrhiza 15-30g, Pueraria lobata 15-20g, Crataegus pinnatifida 10-20g, Melia toosendan 9-15g, Evodia rutaecarpa 6-9g, and Curcuma longa 10-15g.

[0007] The second objective is achieved by preparing a formulation based on the traditional Chinese medicine composition for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type, wherein medically acceptable excipients are added to the formulation of the traditional Chinese medicine composition, and the formulation is prepared into any one of the following: decoction, granules, pills, tablets, capsules, ointments, syrups, powders, and powders.

[0008] The application of the traditional Chinese medicine composition is in the preparation of drugs for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type.

[0009] In this formula, Astragalus membranaceus is the chief herb, slightly warm in nature, sweet in taste, and enters the lung and spleen meridians. It has the characteristics of tonifying qi and raising yang, strengthening the spleen and promoting diuresis. White peony root and Salvia miltiorrhiza are the assistant herbs. White peony root is sour, sweet, and bitter in taste, enters the liver and spleen meridians, and has the effects of "clearing spleen heat, stopping abdominal pain, stopping watery diarrhea, astringing liver qi stagnation and pain, regulating the blood of the heart, liver, and spleen meridians, soothing the liver and lowering qi, and stopping liver qi pain." Salvia miltiorrhiza invigorates blood circulation, unblocks collaterals, and dredges qi and blood, assisting Astragalus membranaceus in achieving the effects of tonifying qi and raising yang, resolving phlegm and removing blood stasis. Kudzu root is added to unblock meridians, raise yang and stop diarrhea. Hawthorn is sour, sweet, and slightly warm in nature, and enters the spleen, stomach, and liver meridians. It has the effects of promoting digestion and strengthening the stomach, promoting qi circulation and dispersing blood stasis, resolving turbidity and lowering lipids. The Ming Dynasty scholar Li Zhongzi recorded in his *Ben Cao Tong Xuan* that "hawthorn has a neutral taste and eliminates the accumulation of oil and grime." The Yuan Dynasty scholar Wei Yilin also recorded in his *Wei Shi De Xiao Fang* that hawthorn "is good at removing fishy, ​​greasy, and oily accumulations." Hawthorn combined with Salvia miltiorrhiza invigorates the spleen, dispels phlegm, eliminates dampness, unblocks the meridians, and promotes blood circulation. Sichuan pepper clears liver fire, eliminates dampness, and regulates qi; Evodia rutaecarpa warms the liver and spleen, dispels cold, and relieves pain; turmeric warms the meridians, promotes qi circulation, unblocks the meridians, and relieves pain.

[0010] The liver, belonging to the wood element, possesses the nature of ascending and regulating. Smooth flow of qi and harmonious blood circulation are signs of normal liver function. If the liver fails to regulate qi, qi stagnates, blood circulation is impaired, and these factors intertwine to cause qi stagnation and blood stasis, obstructing the liver meridian. The spleen governs transformation and transportation, converting food into essential substances and distributing them throughout the body. It is the hub of qi, blood, and body fluid distribution and metabolism. If the spleen fails to function properly, food and water cannot be transformed to nourish the body, instead becoming phlegm, dampness, and stagnation in the middle jiao, leading to the internal generation of viscous substances. Furthermore, dampness, with its heavy, turbid, and sticky characteristics, affects the ascending and descending of qi, thus hindering the liver's function of regulating qi. The liver can assist the spleen in its function of regulating qi; with the liver's regulation, the spleen's ascending and descending functions are coordinated, and its transformation and transportation functions are robust—just as "earth benefits from wood." If liver qi is stagnant and attacks the spleen, hindering its transformation and transportation, phlegm and dampness accumulate internally. Therefore, the liver and spleen are closely related and mutually influential, often resulting in simultaneous liver and spleen disorders. This formula treats metabolic fatty liver disease of the liver-stagnation and spleen-deficiency type by focusing on strengthening the spleen and replenishing qi, warming the liver and regulating qi, and eliminating dampness and turbidity. The medications align with the principles of the Qi-Yin school of thought, harmonizing Yin and Yang and unblocking Qi and blood. Astragalus is the principal ingredient, replenishing qi, warming the middle jiao, and promoting diuresis; Salvia miltiorrhiza invigorates blood and removes blood stasis. Astragalus and Salvia miltiorrhiza are representative qi-tonifying and blood-activating herbs, respectively. Their combination harmonizes qi and blood, preventing various diseases. White peony root replenishes qi, nourishes Yin, and softens the liver. Combined with astragalus, it replenishes qi and blood, harmonizes Yin and Yang, and unblocks the Qi mechanism, achieving the effect of regulating the pivot and balancing Yin and Yang. Salvia miltiorrhiza, combined with white peony root, soothes the liver while strengthening blood activation. For chronic cases with severe blood stasis, white peony root can be replaced with red peony root to invigorate blood, remove blood stasis, and unblock the meridians. The adjuvant herbs in the formula, such as kudzu root, hawthorn, evodia, and turmeric, assist the principal and adjuvant herbs in achieving Yin-Yang harmony, unblocking Qi and blood, and promoting the regulation of the three jiaos, eliminating dampness and turbidity, thus improving patient symptoms and basal metabolic function.

[0011] This invention, based on the principles of Qi-Yin inheritance and Yin-Yang differentiation, and the treatment principle of harmonizing Yin and Yang and regulating Qi and Blood, provides a traditional Chinese medicine composition for treating liver stagnation and spleen deficiency type fatty liver disease. This composition can alleviate symptoms in patients with liver stagnation and spleen deficiency type metabolic-related fatty liver disease, improve indicators such as CAP, BMI, liver function, and blood lipids, and improve patients' quality of life. The total effective rate of TCM syndrome differentiation in the treatment group reached 93.94%, which is superior to the control group drug Xiaoyao Wan. The medicine in this invention is mild and easily absorbed by patients, and no significant adverse reactions were observed in either group during treatment. It can be considered as a clinical medication option and has significant clinical application value. Detailed Implementation

[0012] The present invention will be further described below with reference to embodiments, but this is not intended to limit the present invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0013] This invention discloses a traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type, which is composed of the following raw materials by weight: Astragalus membranaceus 15-30g, Paeonia lactiflora 15-20g, Salvia miltiorrhiza 15-30g, Pueraria lobata 15-20g, Crataegus pinnatifida 10-20g, Melia toosendan 9-15g, Evodia rutaecarpa 6-9g, and Curcuma longa 10-15g.

[0014] The present invention also provides a preparation based on the traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type, wherein the traditional Chinese medicine composition is formulated with medically acceptable excipients and prepared into any one of decoction, granules, pills, tablets, capsules, ointments, syrups, powders and powders.

[0015] The decoction is prepared as follows: Place each raw material in a pot, add 6 times the amount of boiling water, and decoct twice, each time for 0.5-1 hour, to obtain the decoction.

[0016] The granules are prepared according to the following method: 1) Decoction: Add water to each herb in the formula at a weight ratio of 1:6 to 12 and decoct 1 to 3 times, each time for 30 to 90 minutes, and combine the decoction liquids; 2) Concentration: The obtained decoction is concentrated into a thick paste at 55-75℃ and a vacuum of -0.02--0.06MPa. The density of the thick paste at 50-60℃ is 1.20-1.35g / ml. 3) Drying: Dry the thick paste at 65-75℃ and under a vacuum of -0.02--0.06MPa to obtain a dry paste for later use; 4) The dry paste is pulverized and passed through a 100-mesh sieve to obtain mixed dry paste powder. 20-40g of granulation excipients are added and mixed evenly. An appropriate amount of 60%-95% ethanol is added, and wet granulation is performed. After drying, granules are obtained.

[0017] The granulation excipient is one or more of dextrin, maltodextrin, or sucrose.

[0018] The pills are prepared according to the following method: 1) Decoction: Weigh all the herbs in the formula except for hawthorn, kudzu root and turmeric according to the formula amount, and add water at a ratio of 1:6 to 12 to decoct 1 to 3 times, each time for 30 to 90 minutes, and combine the decoction liquids. 2) Concentration: The obtained decoction is concentrated into a thick paste at 55-75℃ and a vacuum of -0.02--0.06MPa. The density of the thick paste at 50-60℃ is 1.20-1.35g / ml. 3) Drying: Dry the thick paste at 65-75℃ and a vacuum of -0.02--0.06MPa to obtain a dry paste; 4) Weigh out hawthorn, kudzu root, and turmeric according to the weight in the formula, mix them with the dry extract, and pulverize them through a 100-mesh sieve to obtain mixed dry extract powder. Use water or ethanol of 30% or lower concentration to form pills to obtain pills.

[0019] The present invention further provides the application of the aforementioned traditional Chinese medicine composition, specifically its application in the preparation of a drug for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type.

[0020] Example 1 Formula: Astragalus membranaceus 20g, Paeonia lactiflora 20g, Salvia miltiorrhiza 20g, Pueraria lobata 15g, Crataegus pinnatifida 15g, Melia toosendan 10g, Evodia rutaecarpa 9g, Curcuma longa 10g. Place all ingredients in a pot according to the formula, add 6 times the amount of boiling water, and decoct twice, 0.5 hours each time, to obtain the decoction.

[0021] Example 2 Formula: Astragalus membranaceus 20g, Paeonia lactiflora 15g, Salvia miltiorrhiza 20g, Pueraria lobata 20g, Crataegus pinnatifida 15g, Melia toosendan 10g, Evodia rutaecarpa 6g, Curcuma longa 10g. According to the formula, add water to each raw material at a weight ratio of 1:6 and decoct three times, 30 minutes each time. Combine the decoctions. Concentrate the resulting decoction at 55℃ under vacuum of -0.02 to -0.06 MPa to form a thick paste. The density of the thick paste at 50℃ is 1.20 g / ml. Dry the thick paste at 65℃ under vacuum of -0.02 to -0.06 MPa to form a dry paste. Grind the dry paste through a 100-mesh sieve to obtain a mixed dry paste powder. Add 20g of sucrose and mix well. Add an appropriate amount of 60% ethanol, granulate by wet granulation, and dry to obtain granules.

[0022] Example 3 Formula: Astragalus membranaceus 25g, Paeonia lactiflora 18g, Salvia miltiorrhiza 15g, Pueraria lobata 15g, Crataegus pinnatifida 10g, Melia toosendan 12g, Evodia rutaecarpa 8g, Curcuma longa 12g. Except for Crataegus pinnatifida, Pueraria lobata, and Curcuma longa, all the herbs in the formula are decocted with water at a weight ratio of 1:9, three times, 60 minutes each time, and the decoctions are combined. The resulting decoction is concentrated into a thick paste at 75℃ and a vacuum degree of -0.02 to -0.06 MPa, with a density of 1.35 g / ml at 60℃. The thick paste is then dried at 75℃ and a vacuum degree of -0.02 to -0.06 MPa to obtain a dry paste. Crataegus pinnatifida, Pueraria lobata, and Curcuma longa are added, mixed, and pulverized through a 100-mesh sieve to obtain a mixed dry paste powder. This powder is then used to form pills with 30% ethanol to obtain pills.

[0023] Example 4 Formula: Astragalus membranaceus 30g, Paeonia lactiflora 20g, Salvia miltiorrhiza 30g, Pueraria lobata 20g, Crataegus pinnatifida 20g, Melia toosendan 15g, Evodia rutaecarpa 9g, Curcuma longa 15g. Place all ingredients in a pot according to the formula, add 6 times the amount of boiling water, and decoct twice, 0.5 hours each time, to obtain the decoction.

[0024] Example 5 Formula: Astragalus membranaceus 20g, Paeonia lactiflora 20g, Salvia miltiorrhiza 15g, Pueraria lobata 15g, Crataegus pinnatifida 10g, Melia toosendan 12g, Evodia rutaecarpa 6g, Curcuma longa 15g. According to the formula, add water to each raw material at a weight ratio of 1:12 and decoct three times, 90 minutes each time. Combine the decoctions. Concentrate the resulting decoction at 65℃ under vacuum of -0.02 to -0.06 MPa to form a thick paste. The density of the thick paste at 50℃ is 1.20 g / ml. Dry the thick paste at 65℃ under vacuum of -0.02 to -0.06 MPa to form a dry paste. Grind the dry paste through a 100-mesh sieve to obtain a mixed dry paste powder. Add 30g of dextrin and mix well. Add an appropriate amount of 95% ethanol, granulate by wet granulation, and dry to obtain granules.

[0025] Example 6 Formula: Astragalus membranaceus 15g, Paeonia lactiflora 15g, Salvia miltiorrhiza 15g, Pueraria lobata 15g, Crataegus pinnatifida 10g, Melia toosendan 9g, Evodia rutaecarpa 6g, Curcuma longa 10g. Except for Crataegus pinnatifida, Pueraria lobata, and Curcuma longa, all the herbs in the formula are decocted with water at a weight ratio of 1:6 for 60 minutes each time. The decoctions are combined. The resulting decoction is concentrated into a thick paste at 55℃ and a vacuum degree of -0.02 to -0.06 MPa. The density of the thick paste at 50℃ is 1.20 g / ml. The thick paste is dried into a dry paste at 65℃ and a vacuum degree of -0.02 to -0.06 MPa. Crataegus pinnatifida, Pueraria lobata, and Curcuma longa are added, mixed, and pulverized through a 100-mesh sieve to obtain a mixed dry paste powder. The powder is then used to form pills with water to obtain pills.

[0026] Example 7 Formula: Astragalus membranaceus 25g, Paeonia lactiflora 20g, Salvia miltiorrhiza 20g, Pueraria lobata 15g, Crataegus pinnatifida 10g, Melia toosendan 12g, Evodia rutaecarpa 12g, Curcuma longa 10g. Place all ingredients in a pot according to the formula, add 6 times the amount of boiling water, and decoct twice, 0.5 hours each time, to obtain the decoction.

[0027] Case 1 Patient Liu XX, male, 42 years old, presented with "discomfort in the right hypochondrium accompanied by abdominal distension for one week." One week prior, the patient developed right hypochondrium discomfort, accompanied by dry mouth, bitter taste, abdominal distension, decreased appetite, occasional foreign body sensation in the throat, poor sleep with frequent dreams, loose stools, and normal urination after work fatigue and emotional fluctuations. Examination revealed: height 173cm, weight 88kg, obese build, soft abdomen, no tenderness, and no percussion tenderness in the liver area. Tongue was pale and swollen with a slightly greasy white coating, and pulse was thready and wiry. Physical and chemical data showed: liver function was normal, liver elasticity test showed a fat attenuation of 291, blood lipids, TG: 1.9mmol / L, CHO: 6.8mmol / L. The patient had a history of fatty liver disease but denied any history of alcohol consumption. The Western medical diagnosis was metabolic-related fatty liver disease.

[0028] The TCM diagnosis was liver stagnation (liver qi stagnation, spleen deficiency, and dampness obstruction). The prescription included: Astragalus membranaceus 20g, Paeonia lactiflora 20g, Salvia miltiorrhiza 20g, Pueraria lobata 15g, Crataegus pinnatifida 15g, Melia toosendan 10g, Evodia rutaecarpa 9g, Curcuma longa 10g, Bupleurum chinense 10g, Poria cocos 15g, Atractylodes macrocephala (fried) 15g, Magnolia officinalis 15g, Perilla frutescens 10g, Pinellia ternata (processed) 15g, and Glycyrrhiza uralensis (processed) 6g. One dose daily. After one week of treatment, the patient's dry mouth and bitter taste significantly improved, and there was no more significant discomfort in the liver area. However, a foreign body sensation in the throat and a feeling of heaviness remained. The tongue was pale and swollen with teeth marks on the edges, and the coating was white and greasy. The pulse was thready and slippery. Bupleurum chinense was reduced, and Citrus reticulata 10g and Codonopsis pilosula 15g were added to strengthen the spleen and eliminate dampness. Three months later, the patient's foreign body sensation in the throat disappeared, and the heaviness disappeared. A follow-up examination showed a weight loss to 80kg, a fat reduction of 268g, and blood lipids: TG: 1.3mmol / L, CHO: 5.4mmol / L.

[0029] Note: Metabolic fatty liver disease is a modern medical term; there is no such term as "fatty liver" in traditional Chinese medicine (TCM) texts. The clinical manifestations of MAFLD are often insidious, with initial symptoms including discomfort in the liver area, rib distension, and abdominal fullness. Therefore, MAFLD is often categorized under TCM terms such as "liver obstruction," "hypochondriac pain," "accumulation," "abdominal fullness," and "fat qi." For example, the *Nan Jing* (Classic of Difficult Issues), Chapter 56, states: "The accumulation in the liver is called fat qi, located under the left rib, resembling an overturned cup, with a head and feet." The 2017 *Consensus Opinion on the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease in Traditional Chinese Medicine* officially designated MAFLD as "liver obstruction" in TCM. The patient is obese, emotionally imbalanced, and suffers from qi stagnation, which leads to impaired liver function and affects the spleen and stomach's digestive function. When the spleen and stomach are damaged, the essence of food cannot be transformed and produced, resulting in the accumulation of phlegm and dampness. Over time, this leads to blood stasis, with phlegm and blood stasis mutually binding in the liver meridian. At the same time, impaired spleen function can also aggravate liver dysfunction, causing stagnation of earth and wood, leading to qi stagnation and blood stasis, ultimately resulting in phlegm and blood stasis mutually binding in the liver. The treatment focused on strengthening the spleen and soothing the liver, using the "Qi-regulating and Blood-activating Formula." Astragalus membranaceus (Huang Qi) was the chief ingredient, tonifying Qi and raising Yang, strengthening the spleen and promoting diuresis. White peony root (Bai Shao) was sour, sweet, and bitter, entering the liver and spleen meridians, and had the effects of "clearing spleen heat, stopping abdominal pain, stopping watery diarrhea, astringing liver Qi stagnation and pain, regulating the blood of the heart, liver, and spleen meridians, soothing the liver and lowering Qi, and stopping liver Qi pain." Salvia miltiorrhiza (Dan Shen) activated blood circulation and unblocked the meridians, clearing Qi and blood. Pueraria lobata (Ge Gen) unblocked the meridians, raised Yang and stopped diarrhea. Hawthorn (Shan Zha) cleared turbidity, lowered lipids, broke up blood stasis and resolved phlegm. Sichuan pepper (Chuan Lian Zi) cleared liver fire, dispelled dampness and regulated Qi. Evodia rutaecarpa (Wu Zhu Yu) warmed the liver and spleen, dispelled cold and relieved pain. Curcuma longa (Jiang Huang) warmed the meridians, promoted Qi circulation, unblocked the meridians and relieved pain. Bupleurum chinense (Chai Hu) was added to soothe the liver, Poria cocos (Fu Shen) to calm the mind, and stir-fried Atractylodes macrocephala (Chao Bai Zhu) to strengthen the spleen. A modified Banxia Houpu Decoction was used to resolve phlegm and dissipate nodules, and roasted licorice root (Zhi Gan Cao) harmonized the effects of the other herbs. After taking the medicine, the symptoms improved, and Liu Jun Zi Tang (Liu Jun Zi Tang) was added to enhance the effects of strengthening the spleen, dispelling dampness and resolving phlegm.

[0030] The clinical efficacy trials of the present invention are described in detail below: 1. Materials and Methods 1.1 General Information: This study selected 72 patients with metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type, who were treated at the renowned TCM doctors' studio and the outpatient and inpatient departments of the Department of Spleen, Stomach and Liver Diseases at Kunming Municipal Hospital of Traditional Chinese Medicine from March 2023 to March 2024. Western medicine diagnosis was based on the "Guidelines for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (2018 Updated Edition)" published in 2018 by the Fatty Liver and Alcoholic Liver Disease Group of the Chinese Medical Association's Hepatology Branch and the Expert Committee on Fatty Liver Disease of the Chinese Medical Doctor Association. TCM diagnosis was based on the 2017 "Expert Consensus on the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease with Traditional Chinese Medicine" and the diagnostic criteria for liver-stagnation and spleen-deficiency syndrome in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs (Trial)" (published by China Medical Science and Technology Press in 2002).

[0031] The 72 patients participating in the observation were randomly assigned to a treatment group and a control group using a randomized controlled trial method. The treatment group consisted of 36 patients, and the control group consisted of 36 patients. During the study, 3 patients dropped out in both the treatment and control groups, resulting in 66 patients completing the study. The treatment group consisted of 33 patients (11 males and 15 females, with a disease duration of 65.31 ± 20.71 months and an age of 52.08 ± 12.30 years), while the control group consisted of 33 patients (9 males and 15 females, with a disease duration of 72.04 ± 23.44 months and an age of 51.13 ± 12.37 years).

[0032] 1.2 Inclusion criteria: ① Meets the diagnostic criteria of both traditional Chinese medicine and Western medicine; ② Age between 18 and 70 years; ③ Has not taken any related medications for at least one week prior to the start of the study; ④ Has not participated in other clinical trials; ⑤ Has signed an informed consent form.

[0033] 1.3 Exclusion criteria: ① Those who do not meet the inclusion criteria; ② Those with severe liver dysfunction; ③ Those with hepatitis B, drug-induced hepatitis, or autoimmune liver disease, or a history of mental illness; ④ Those currently using thyroxine, heparin, or other drugs that affect lipid metabolism; ⑤ Those participating in other clinical trials.

[0034] 1.4 Treatment methods: Treatment group: Administered granules of the traditional Chinese medicine composition prepared in Example 2 of this invention, dissolved in boiling water, taken in 3 divided doses, 1 dose per day.

[0035] Control group: Xiaoyao Pills (National Drug Approval Number Z41021831, Zhongjing Wanxi Pharmaceutical Co., Ltd.) were administered orally, 8 pills each time, 3 times a day. The total treatment course for both groups was 3 months.

[0036] 1.5 Observation indicators and efficacy evaluation; (1) Efficacy observation indicators: The changes in TCM symptom scores before and after treatment were observed in both the treatment group and the control group. The TCM symptom scores were based on the "Principles of Clinical Research of New Chinese Medicines" published by the National Press of Traditional Chinese Medicine Science and Technology in 2002. The main symptoms were: distension or wandering pain in the right hypochondrium, which was often triggered by worries and anger; secondary symptoms were: abdominal distension; loose stools; abdominal pain with diarrhea; fatigue; chest tightness; frequent sighing; pale tongue with teeth marks on the sides, thin white or greasy coating; and wiry or thready pulse. The main symptoms were scored as 0, 2, 4, and 6 points respectively for mild, moderate, and severe symptoms, and 0, 1, 2, and 3 points respectively for secondary symptoms. The tongue and pulse were each scored as 1 point.

[0037] (2) Observe the controlled liver decay parameter (CAP) detected by Fibroscan; calculate the changes in body mass index (BMI), liver function and blood lipid index.

[0038] (3) Clinical efficacy evaluation criteria: A. Clinical cure: TCM clinical symptoms and signs disappear or basically disappear, and the syndrome score decreases by ≥95%. B. Significant effect: TCM clinical symptoms and signs improve significantly, and the syndrome score decreases by ≥70%. C. Effective: TCM clinical symptoms and signs improve, and the syndrome score decreases by ≥30%. D. Ineffective: TCM clinical symptoms and signs do not improve significantly, or even worsen, and the syndrome score decreases by less than 30%. Note: The calculation formula (nimodipine method) is: [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%.

[0039] 1.6 Statistical Methods: The SPSS 28.0 statistical analysis software package was used to establish the database and perform statistical analysis on the data. The t-test was used for continuous data, the chi-square test was used for categorical data, and the rank-sum test was used for ordinal data.

[0040] 2. Results 2.1 The general characteristics of the two groups are compared as shown in Table 1. The age was compared using a t-test, and there was no statistically significant difference (P>0.05).

[0041] Table 1 Comparison of gender, age, and disease duration among patients in the control group and treatment group 2.2 Results of therapeutic efficacy indicators: (1) Comparison of TCM symptom scores between the two groups: There were no statistically significant differences in symptom scores between the two groups before treatment. Both groups showed improvement in major symptom scores and total symptom scores before treatment, with the treatment group showing greater improvement than the control group. (See Table 2) Table 2 Comparison of total symptom scores between the two groups before and after treatment ( ±S) Note: Comparison before and after treatment in the two groups. ※ P<0.05, comparison between the two groups after treatment △ P <0.05.

[0042] (2) Comparison of the therapeutic effects of TCM syndromes in the two groups: The treatment group showed better results than the control group in improving patients' TCM syndromes. A comparison of the clinical treatment effectiveness rates between the two groups is shown in Table 3.

[0043] Table 3 Comparison of symptom-treatment efficacy between the two groups (3) Comparison of CAP and BMI before and after treatment in the two groups: There were no statistically significant differences in CAP and BMI values ​​between the two groups before treatment (P > 0.05), indicating comparability. Before and after treatment, CAP and BMI were significantly different in both the treatment and control groups (P < 0.05). After treatment, CAP was significantly different in both groups (P < 0.05), but BMI was not significantly different between the two groups (P > 0.05). See Table 4.

[0044] Table 4 Comparison of CAP and BMI between the two groups before and after treatment ( ±S) Note: Comparison between the two groups before treatment. P >0.05, comparing pre- and post-treatment values ​​within both groups. ※ P <0.05, comparison between the two groups after treatment △ P <0.05.

[0045] (4) Comparison of liver function and blood lipids before and after treatment in the two groups There were no statistically significant differences in liver function and blood lipid test results between the two groups before treatment (P > 0.05), making them comparable. The treatment group showed statistically significant improvements in liver function and blood lipid test results before and after treatment (P < 0.05). The control group showed statistically significant improvements in ALT and blood lipids before and after treatment (P < 0.05), but no statistically significant improvement in AST (P > 0.05). Both groups showed statistically significant improvements in liver function and blood lipids after treatment (P < 0.05). After 3 months of treatment, the treatment group showed better changes in liver function and blood lipids than the control group (see Table 5).

[0046] Table 5 Comparison of liver function and blood lipid levels between the two groups before and after treatment ( ±S) Note: Comparison between the two groups before treatment. P >0.05, comparing pre- and post-treatment values ​​within both groups. ※ P<0.05, ※※ P >0.05, comparison between the two groups after treatment △ P <0.05.

[0047] In summary, both the treatment and control groups showed improvement in patients with liver stagnation and spleen deficiency type metabolic-related fatty liver disease. The TCM symptom scores for this type of disease were significantly better in the treatment group than in the control group. A statistically significant comparison of symptom scores after treatment showed that the treatment group was significantly better than the control group (P<0.05). Both groups showed improvement in CAP, BMI, liver function, and blood lipids before and after treatment, with the treatment group showing greater improvement in CAP, ALT, and blood lipids than the control group. The total effective rate of TCM syndrome differentiation was 93.94% in the treatment group and 87.88% in the control group, further confirming that the TCM composition of this invention is superior to the control drug Xiaoyao Wan in terms of TCM syndrome differentiation efficacy in treating liver stagnation and spleen deficiency type metabolic-related fatty liver disease.

Claims

1. A traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type, characterized in that, The raw materials are composed of the following ingredients by weight: Astragalus membranaceus 15-30g, Paeonia lactiflora 15-20g, Salvia miltiorrhiza 15-30g, Pueraria lobata 15-20g, Crataegus pinnatifida 10-20g, Melia toosendan 9-15g, Evodia rutaecarpa 6-9g, and Curcuma longa 10-15g.

2. A formulation based on the traditional Chinese medicine composition for treating metabolic-related fatty liver disease of liver stagnation and spleen deficiency type as described in claim 1, characterized in that, The traditional Chinese medicine composition is formulated with medically acceptable excipients and prepared into any one of the following: decoction, granules, pills, tablets, capsules, ointment, syrup, or powder.

3. The formulation of the traditional Chinese medicine composition according to claim 2, characterized in that, The decoction is prepared as follows: Place each raw material in a pot, add 6 times the amount of boiling water, and decoct twice, each time for 0.5-1 hour, to obtain the decoction.

4. The formulation of the traditional Chinese medicine composition according to claim 2, characterized in that, The granules are prepared according to the following method: 1) Decoction: Add water to each herb in the formula at a weight ratio of 1:6~12 and decoct 1~3 times, 30min~90min each time, and combine the decoction liquids; 2) Concentration: The obtained decoction is concentrated into a thick paste at 55~75℃ and -0.02~-0.06MPa vacuum. The density of the thick paste at 50~60℃ is 1.20~1.35g / ml. 3) Drying: Dry the thick paste at 65~75℃ and -0.02~-0.06MPa vacuum to form a dry paste for later use; 4) The dry paste is pulverized and passed through a 100-mesh sieve to obtain mixed dry paste powder. 20-40g of granulation excipients are added and mixed evenly. An appropriate amount of 60%-95% ethanol is added, and wet granulation is performed. After drying, granules are obtained.

5. The formulation of the traditional Chinese medicine composition according to claim 2, characterized in that, The pills are prepared according to the following method: 1) Decoction: Weigh all the herbs in the formula except for hawthorn, kudzu root and turmeric according to the formula amount, and add water at a ratio of 1:6~12 to decoct 1~3 times, each time for 30min~90min, and combine the decoction liquids. 2) Concentration: The obtained decoction is concentrated into a thick paste at 55~75℃ and -0.02~-0.06MPa vacuum. The density of the thick paste at 50~60℃ is 1.20~1.35g / ml. 3) Drying: Dry the thick paste at 65~75℃ and under a vacuum of -0.02~-0.06MPa to obtain a dry paste; 4) Weigh out hawthorn, kudzu root, and turmeric according to the weight in the formula, mix them with the dry extract, and pulverize them through a 100-mesh sieve to obtain mixed dry extract powder. Use water or ethanol of 30% or lower concentration to form pills to obtain pills.

6. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a drug for treating metabolic-related fatty liver disease of the liver-stagnation and spleen-deficiency type.

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