A traditional Chinese medicine composition for preventing, treating and improving non-alcoholic fatty liver, alcoholic fatty liver and obesity

Abstract

The present application relates to the field of medicine, and particularly relates to a traditional Chinese medicine composition for preventing, treating and improving non-alcoholic fatty liver, alcoholic fatty liver and obesity and application thereof; the composition is composed of chuanqiong, xiangfu, mayi, jineijin, baizhi, baicaoren, aloe or dahuang, cheqiancao, chixiaodou, meigui, yujin, wumei, biejia, zhizi and taizishen, based on the compatibility concept of "warm and hot dissolving, multi-target intervention", a three-dimensional treatment network of soothing liver and regulating qi, regulating qi and eliminating stagnation, moistening the intestines and defecation, promoting blood circulation to soften the liver and clearing heat and invigorating the spleen is constructed; the composition can be made into various oral preparations, and the animal test proves that the composition can effectively reduce liver fat deposition, improve liver function and related metabolic indicators, and has high safety, and is suitable for long-term conditioning.

Description

Technical Field

[0001] This invention relates to the field of medicine, and more specifically, to a composition for the prevention and / or treatment of non-alcoholic fatty liver disease, alcoholic fatty liver disease, and obesity, which can be used as a medicine or health food. Background Technology

[0002] Nonalcoholic fatty liver disease (NAFLD), also known as hepatocellular steatosis, is a clinicopathological syndrome characterized by excessive fat accumulation in hepatocytes due to various causes. With global economic development, improved living standards, and changes in dietary structure, the incidence of NAFLD is rapidly increasing, becoming the second leading cause of liver disease after viral hepatitis, seriously threatening human health. Epidemiological surveys show that the prevalence of NAFLD in the general population continues to rise and is showing a trend towards affecting younger individuals. NAFLD is not a benign or quiescent condition; without effective intervention, some patients may progress from simple NAFLD to steatohepatitis, liver fibrosis, and even cirrhosis and hepatocellular carcinoma, significantly impacting their quality of life and life expectancy.

[0003] Currently, modern medicine has no specific drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). Clinical interventions mainly focus on etiological treatment and lifestyle modifications, such as abstaining from alcohol, controlling diet, and increasing exercise. For patients with metabolic syndrome, lipid-lowering, blood sugar-lowering, and antioxidant drugs are used as adjunctive therapies. However, commonly used chemical lipid-lowering drugs, such as statins and fibrates, although they can improve the lipid profile, may have potential hepatotoxicity. For NAFLD patients whose liver function is already impaired, long-term use may increase the burden on the liver. Other hepatoprotective drugs are mostly adjunctive therapies and are difficult to fundamentally reverse fatty liver disease.

[0004] Alcoholic fatty liver disease is a liver disease caused by long-term excessive drinking. It initially manifests as hepatic steatosis, which can then develop into alcoholic hepatitis, liver fibrosis, and even cirrhosis. Currently, Western medicine treatment mainly focuses on abstinence from alcohol, nutritional support, and liver-protective drugs, but there is a lack of specific drugs, and relapse is common. Traditional Chinese medicine has unique advantages in regulating the liver and spleen, resolving dampness and turbidity, and soothing the liver and regulating qi, making it suitable for long-term management of alcoholic fatty liver disease.

[0005] Traditional Chinese medicine has unique advantages in "preventive treatment" and chronic disease management. In traditional Chinese medicine, non-alcoholic fatty liver disease is mostly classified under the categories of accumulation, hypochondriac pain, phlegm accumulation, and obesity. According to traditional Chinese medicine theory, its core pathogenesis lies in the liver's failure to regulate qi and the spleen's failure to transport and transform qi, leading to qi stagnation, phlegm turbidity, and blood stasis in the hypochondrium. Based on this, soothing the liver and regulating qi, strengthening the spleen and resolving dampness, and promoting blood circulation and removing blood stasis have become the mainstream treatment principles of traditional Chinese medicine for non-alcoholic fatty liver disease.

[0006] In-depth analysis of existing patented technologies reveals that while many currently disclosed traditional Chinese medicine compound formulas follow the aforementioned treatment principles, they exhibit significant limitations in their specific compatibility strategies: Patent CN103933411A discloses a traditional Chinese medicine composition for treating fatty liver, consisting of 17 medicinal materials including Bupleurum, Fructus Aurantii Immaturus, Herba Artemisiae Capillaris, Fructus Gardeniae, Fructus Rhei, and Rhizoma Alisma. Among them, the medicinal materials overlapping with this patent include Ligusticum chuanxiong, Rhizoma Cyperi, Fructus Gardeniae, and Fructus Rhei, totaling 6. This formula uses Bupleurum as the main liver-soothing medicine, which is cold in nature, and is supplemented with a large number of dampness-removing and spleen-strengthening medicines. Its treatment path is significantly different from that of this patent. Patent CN100384467C discloses a traditional Chinese medicine composition for treating hepatitis and fatty liver, consisting of 33 medicinal materials including Evodia rutaecarpa, Artemisia capillaris, Gardenia jasminoides, Scutellaria baicalensis, and Plantago asiatica. Among them, the medicinal materials overlapping with this patent include Cyperus rotundus, Hordeum vulgare, Gallus gallus domesticus gizzard lining, Curcuma longa, Trionyx sinensis, Gardenia jasminoides, and Rheum palmatum, totaling 7 medicinal materials. This formula has many medicinal materials and mainly focuses on clearing heat and dampness, detoxifying and relieving jaundice, emphasizing the clearance of hepatitis virus and the repair of liver cells. Patent CN106806828A discloses a traditional Chinese medicine for treating fatty liver, which is composed of 15 medicinal materials including Bupleurum, Cyperus, Corydalis, and Salvia miltiorrhiza. Among them, the medicinal materials that overlap with this patent include Cyperus, Curcuma longa, and Hordeum vulgare, totaling 5. This formula still takes Bupleurum as the core and combines it with blood-activating and qi-regulating herbs, and the overall nature is cold. Patent CN105381420A discloses a traditional Chinese medicine for treating fatty liver, which is composed of 33 medicinal materials including yam, jujube, hawthorn, and salvia miltiorrhiza. Among them, the medicinal materials that overlap with this patent include turmeric, plantain, and turtle shell, totaling 5. This formula is mainly tonifying, while also taking into account promoting blood circulation and removing dampness, but it contains a large number of medicinal materials.

[0007] A comprehensive analysis of the existing technologies reveals a common problem: although these formulas overlap to varying degrees in their selection of medicinal materials, their formulation approaches are mostly limited to the single level of "clearing heat and dampness" and "activating blood circulation and removing blood stasis," failing to systematically address the complete pathological chain of "qi stagnation - retention of waste - obstruction of excretion pathways - malnutrition of the liver" involved in both fatty liver and alcoholic fatty liver; specifically manifested as: The liver-soothing effects are singular, relying mostly on Bupleurum or a single Qi-regulating herb, failing to form a synergistic and complementary system. The unblocking of the gastrointestinal pathway is generally neglected, and there is a lack of targeted combinations of qi-regulating and stagnation-relieving drugs. For example, existing formulas such as CN103933411A, although following the principle of soothing the liver and regulating qi, mostly limit their qi-regulating drugs to Bupleurum and Fructus Aurantii Immaturus, while completely ignoring the intensive qi-regulating and stagnation-relieving drug combination such as "malt-chicken gizzard membrane-angelica dahurica-cardamom", which can systematically loosen the waste in the gastrointestinal tract and open up the downward pathway for liver and gallbladder stagnation. This results in the stagnation being difficult to expel even when it is cleared. The strategy of softening the liver and preventing its deterioration is insufficient, and it fails to proactively intervene in the trend of non-alcoholic fatty liver disease evolving into liver fibrosis; Improper combination of cold and warm herbs, with some prescriptions leaning towards coldness, violates the treatment principle of "relieving" rather than "suppressing" liver disease.

[0008] Based on the aforementioned technological status, there is an urgent need in this field for a novel traditional Chinese medicine composition that can break through existing compatibility patterns; compared with the prior art, the present invention has the following outstanding advantages: The innovativeness of the formulation strategy: This invention abandons the traditional liver-soothing mode with Bupleurum as the core and innovatively adopts the warm liver-soothing combination of "Ligusticum chuanxiong-Cyperus rotundus" to conform to the ascending nature of liver wood; at the same time, it densely deploys the qi-regulating and stagnation-eliminating drug group of "malt-chicken gizzard lining-angelica dahurica-white cardamom" to open up the excretion channel of liver and gallbladder stagnation and waste; and more uniquely introduces the liver-soothing and anti-degeneration combination of "Prunus mume-turtle shell" to proactively inhibit the process of liver fibrosis. Advanced treatment concept: This invention breaks through the limitations of existing technologies that only target clearing heat and dampness or promoting blood circulation and removing blood stasis. It constructs a multi-target, three-dimensional treatment network of "soothing the liver and regulating qi - regulating qi and eliminating stagnation - promoting bowel movement and removing dampness - promoting blood circulation and softening the liver - clearing heat and strengthening the spleen", which realizes full intervention in the pathological process of non-alcoholic fatty liver and alcoholic fatty liver. Practicality in clinical application: Through scientific combination of cold and warm properties and a strategy of both attacking and tonifying, this invention effectively prevents the drawbacks of excessive use of cold and cooling herbs that could damage the spleen yang, while ensuring the clearing and relieving of stagnant heat. It is more suitable for long-term use and embodies the advanced concept of "preventive treatment" in traditional Chinese medicine. Therefore, based on the inheritance of traditional treatment principles, this invention provides a new treatment plan for non-alcoholic fatty liver disease, alcoholic fatty liver disease, and obesity through innovative combination strategies and a three-dimensional treatment network. This plan has a more precise pathogenesis approach, more definite curative effect, and higher safety, and has significant technological progress and clinical application value. Summary of the Invention

[0009] Design concept and purpose of this invention Based on a deep understanding of the shortcomings of existing technologies, this invention aims to overcome the limitations of traditional Chinese medicine formulas for treating non-alcoholic fatty liver disease in terms of compatibility strategies. It is applicable not only to non-alcoholic fatty liver disease but also to alcoholic fatty liver disease. The pathogenesis of alcoholic fatty liver disease is mostly "damp-heat accumulation, liver stagnation and spleen deficiency". This composition can effectively alleviate the damp-heat accumulation and liver damage in alcoholic fatty liver disease through multi-target effects such as soothing the liver and regulating qi, strengthening the spleen and resolving dampness, and promoting blood circulation and softening the liver.

[0010] The core design concept of this invention is: taking "warming and dredging" as the general principle, and through multi-target and three-dimensional combination, systematically solving the complete pathological chain of "qi stagnation - internal retention of waste - obstruction of excretion pathways - malnourishment of the liver"; to achieve this purpose, this invention abandons the popular approach of using the cold and cooling herb Bupleurum as the core, and instead uses a large number of warming and dredging herbs to conform to the ascending nature of liver wood; at the same time, based on the treatment principle of "dredging as the core", this composition does not contain the tonifying herbs commonly found in traditional prescriptions during the resolution stage, aiming to prioritize ensuring the smooth flow of stagnation and waste excretion pathways.

[0011] Technical solution of the present invention To achieve the above-mentioned goals, this invention provides a traditional Chinese medicine composition for the prevention, treatment, and improvement of non-alcoholic fatty liver disease, alcoholic fatty liver disease, and obesity. It comprises herbs that soothe the liver and regulate qi, relieve qi stagnation, moisten the intestines and promote bowel movements, promote diuresis and eliminate dampness, invigorate blood circulation, soothe the liver, clear heat and reduce fire, and strengthen the spleen. The key lies in creating a synergistic and multi-dimensional compatibility network: In terms of soothing the liver and regulating qi: Chuanxiong, a "qi-regulating herb in the blood," is combined with Xiangfu, a "general manager of qi-related diseases," to deeply relieve the deep-seated stagnation in the liver meridian at the intersection of qi and blood. This is the common basis for resolving non-alcoholic fatty liver disease and alcoholic fatty liver disease. In terms of regulating Qi and relieving stagnation: malt, chicken gizzard membrane, angelica dahurica, and white cardamom are densely deployed to systematically loosen the waste retained in the liver, gallbladder, stomach and intestines, and open up the middle Jiao pathway for relieving stagnation. At the level of excretion pathway: use aloe vera (or rhubarb) to lubricate the intestines and promote bowel movements, supplemented by plantain and red beans to promote diuresis and eliminate dampness, together providing a channel for the excretion of loosened waste and stagnant qi. In terms of promoting blood circulation and soothing the liver to prevent deterioration: Rose and turmeric are used to promote blood circulation and regulate qi, while the innovative introduction of dried plum to astringe and soothe the liver and turtle shell to nourish yin and soften hardness takes into account both the current loss of liver suppleness and the prevention and treatment of long-term fibrosis. In terms of clearing heat and strengthening the spleen: a small amount of gardenia is added to clear away stagnant heat, and codonopsis is used to strengthen the spleen and consolidate the foundation, preventing damage to the body's vital energy and ensuring the safety of the whole formula in long-term use.

[0012] Based on the above compatibility philosophy, the specific composition provided by the present invention is as follows: The liver-soothing and qi-regulating herbs are selected from Ligusticum chuanxiong and Cyperus rotundus; The herbs used to regulate qi and relieve stagnation are selected from malt, chicken gizzard lining, angelica dahurica, and cardamom; The laxative herbs are selected from aloe vera or rhubarb, with processed rhubarb being preferred for better application in the health food industry; Diuretic and dampness-removing herbs are selected from plantain and red adzuki bean; Blood-activating herbs are selected from rose petals and turmeric. Liver-soothing medicinal materials are selected from dried plum and turtle shell; The heat-clearing and fire-reducing medicinal materials are selected from gardenia; The spleen-strengthening herbs are selected from Codonopsis pilosula.

[0013] (1) Chuanxiong and Xiangfu: Chuanxiong is a qi-regulating herb in the blood, and is especially good at relieving stagnation in the blood; Xiangfu is very good at soothing the liver and regulating qi, and can guide the medicinal power of Chuanxiong to penetrate deeper into the places where qi and blood intersect and stagnate the most; the combination of the two Chinese herbs can effectively relieve qi stagnation in the liver; qi stagnation is the core cause of various liver diseases such as fat accumulation. Once the qi stagnation is relieved, the liver will no longer have the basis for further disease. (2) Angelica dahurica, white cardamom, malt, and chicken gizzard: These four Chinese medicines regulate qi and relieve stagnation, loosening the stagnant waste in the liver, gallbladder, stomach and intestines; only when the stagnant waste in the entire digestive tract is loosened can the qi stagnation relieved by Ligusticum chuanxiong and Cyperus rotundus be expelled from the body smoothly. (3) Aloe vera, plantain and red bean: Aloe vera moistens the intestines and promotes bowel movement, while plantain and red bean promote diuresis and eliminate dampness. When used together, the three herbs can expel stagnant qi and waste from the body through urination and defecation. (4) Rose and turmeric: The liver stores blood. Without blood circulation, it is not conducive to the release of waste and stagnant qi. In addition to promoting blood circulation, turmeric also has a strong function of regulating qi and relieving depression, which is of great help to relieve the stagnation in the liver. Rose can also work with chuanxiong and cyperus to further soothe the liver. (5) Gardenia: Non-alcoholic fatty liver and alcoholic fatty liver are diseases caused by the stagnation of qi and waste in the human body. When there is stagnation, there will inevitably be heat accumulation. Therefore, adding a small amount of gardenia can clear the heat accumulation. At the same time, it can also be combined with aloe vera, red beans, plantain and other medicines to enhance the efficiency of excretion of urine and feces. (6) Ume and turtle shell: When the liver retains too much waste and stagnation, it will cause the liver to lose its original flexibility, which is not conducive to the treatment of non-alcoholic fatty liver, alcoholic fatty liver and obesity. Therefore, ume can astringe the liver qi and soften the liver, and turtle shell can nourish yin and subdue yang, soften the liver and relieve stagnation, thereby softening the liver and enhancing the efficacy of other drugs in this formula. (7) Codonopsis pilosula: The core of treating non-alcoholic fatty liver, alcoholic fatty liver and obesity is to remove waste from the body. In this process, the spleen and stomach may be damaged. Codonopsis pilosula strengthens the spleen, so there is no worry about damage.

[0014] The composition provided by the present invention comprises Ligusticum chuanxiong, Cyperus rotundus, malt, chicken gizzard lining, Angelica dahurica, white cardamom, aloe vera, Plantago asiatica, red adzuki bean, rose, turmeric, dried plum, turtle shell, gardenia, and codonopsis pilosula; Of which, by weight, One part of Ligusticum chuanxiong; Cyperus rotundus 0.8-1.2 parts; 1.5-1.8 parts malt; Chicken gizzard lining 0.8-1 part; Angelica dahurica 0.8-1.2 parts; 0.7-0.9 parts white cardamom; Aloe vera 1-1.5 parts; Plantain 2-2.5 parts; 3-3.5 servings of red beans; 0.8-1.2 parts rose petals; 1-1.5 parts of turmeric; 1-1.5 servings of dried plums; 1.8-2.3 parts of turtle shell; Gardenia 0.2-0.4 parts; 1.5-1.8 parts of Codonopsis pilosula.

[0015] The composition provided by the present invention comprises Ligusticum chuanxiong, Cyperus rotundus, malt, chicken gizzard lining, Angelica dahurica, white cardamom, prepared rhubarb, Plantago asiatica, red adzuki bean, rose, Curcuma longa, dried plum, turtle shell, gardenia, and Codonopsis pilosula. Of which, by weight; One part of Ligusticum chuanxiong; Cyperus rotundus 0.8-1.2 parts; 1.5-1.8 parts malt; Chicken gizzard lining 0.8-1 part; Angelica dahurica 0.8-1.2 parts; 0.7-0.9 parts white cardamom; Prepared rhubarb, 0.2-0.3 parts; Plantain 2-2.5 parts; 3-3.5 servings of red beans; 0.8-1.2 parts rose petals; 1-1.5 parts of turmeric; 1-1.5 servings of dried plums; 1.8-2.3 parts of turtle shell; Gardenia 0.2-0.4 parts; 1.5-1.8 parts of Codonopsis pilosula.

[0016] The laxative herbs are selected from aloe vera or rhubarb, and the rhubarb is processed rhubarb, preferably prepared rhubarb, including but not limited to wine-processed rhubarb and cooked rhubarb, to mitigate its cold medicinal properties and make it more suitable for the health food industry.

[0017] Animal experiments and market application statistics have confirmed that the composition provided by this invention has good effects in preventing or treating non-alcoholic fatty liver disease, alcoholic fatty liver disease, and improving obesity-related indicators. Adding other types of medicinal materials may improve its efficacy, but not significantly, or even reduce it. Using other similar medicinal materials will reduce its efficacy.

[0018] The composition provided by this invention can be prepared into an oral formulation; the oral formulation may contain a pharmaceutically acceptable carrier; all dosage forms suitable for oral administration are applicable to the composition of this invention, such as pills, tablets, capsules, granules, suspensions, powders, oral liquids, chewable tablets, etc.; when formulated into health food, granules and oral liquids are more suitable.

[0019] This invention provides a method for preparing a composition, wherein all medicinal materials are pulverized to a particle size of less than 80 mesh; and then various preparations are obtained by conventional methods; appropriate excipients can be added to make tablets, granules, etc.; if a coating layer is added to the outside of the preparation to prevent moisture absorption.

[0020] While ensuring that the core therapeutic composition remains unchanged, some medicinal materials, such as wolfberry, osmanthus, chrysanthemum, and licorice, can be added to improve the taste, aroma, and appearance. An appropriate amount of natural honey can also be added for flavoring. In addition, those skilled in the art can also conventionally choose to add pharmaceutically acceptable flavoring agents or coloring agents. These auxiliary additions will not have a substantial impact on the core therapeutic effect of the present invention.

[0021] The present invention also provides the use of the composition in the preparation of articles for treating non-alcoholic fatty liver disease, alcoholic fatty liver disease and obesity; The products mentioned therein can be pharmaceuticals, health foods, functional foods, etc.

[0022] The intended use is to improve the fat accumulation and obesity in hepatocytes caused by non-alcoholic fatty liver disease and alcoholic fatty liver disease, and to prevent them from progressing to more serious liver damage such as steatohepatitis and alcoholic hepatitis.

[0023] The composition of the present invention can be taken orally at a dose of 16-20 grams per day, divided into two doses, one of which is taken 2 hours before bedtime. The dosage can be adjusted according to the severity of non-alcoholic fatty liver disease, alcoholic fatty liver disease, obesity and related indicators, as well as body shape and weight.

[0024] In the composition of the present invention, the Chinese herbs that can be used to treat non-alcoholic fatty liver disease are mainly Cyperus rotundus, Ligusticum chuanxiong, rose, Gardenia jasminoides, and malt. Other Chinese herbs mainly play an auxiliary role in soothing the liver and clearing the body's excretory channels.

[0025] Currently popular medications for treating non-alcoholic fatty liver disease include: Xiaoyao San, Chaihu Shugan San, and Huazhi Rougan Granules. The differences between the composition of this invention and these three traditional Chinese medicines include: (1) Use of Bupleurum: All three of the above-mentioned Chinese patent medicines use Bupleurum as the main medicine for soothing the liver. Bupleurum is slightly cold in nature and is regarded as the first medicine for soothing the liver because it relieves exterior fever, soothes the liver and relieves depression. In the Treatise on Febrile Diseases, Bupleurum is used more to resolve the stagnant heat between the exterior and interior, and there is no record of it being used for soothing the liver. At present, when the use of Bupleurum has become popular, this invention decisively abandons the use of Bupleurum and instead uses a large amount of warm medicines for the treatment of non-alcoholic fatty liver. (2) Use of warm Chinese medicine; Traditional Chinese medicine theory holds that blood congeals when it encounters cold, and body fluids gather when they encounter cold. For the "stagnation" formed by the mutual binding of qi stagnation, phlegm turbidity, and blood stasis, warm and pungent medicines are like the spring sun melting ice, which is more conducive to promoting its dissipation and dissipation. Therefore, the dissipation of all stagnation must be based on the use of warm medicines, just like kitchen grease cannot be dissolved without hot water. The liver belongs to spring, which is the time when all things sprout. Using cold medicines to treat liver disease is like pouring cold water on all things when they sprout. Obviously, it cannot relieve liver stagnation, but will further suppress liver stagnation. Therefore, it is necessary to use a lot of warm medicines that conform to the spring season in order to dissipate the dregs. (3) Use of tonifying Chinese medicines; Among the above-mentioned Chinese patent medicines, such as the prepared licorice root, atractylodes macrocephala, angelica sinensis, and poria cocos in Xiaoyao San, and the atractylodes macrocephala, privet fruit, eclipta prostrata, and wolfberry fruit in Huazhi Rougan Granules, are all tonifying medicines; According to the theoretical system and research of this invention, when targeting the core pathogenesis of stagnation of turbidity, the premature use of tonifying medicines may be detrimental to the clearance of pathological products; Regardless of the specific cause of each non-alcoholic fatty liver disease patient, the use of tonifying medicines has no positive help in the resolution of non-alcoholic fatty liver disease; (4) Cleaning up the waste in the gastrointestinal tract; Compared with the above three Chinese patent medicines, this invention attaches great importance to cleaning up the waste in the gastrointestinal tract, because according to Zhang Zhongjing's theory of six sections of visceral manifestation, if the pathway in front of the liver and gallbladder is not cleaned up, the waste and stagnant qi in the liver and gallbladder will not be able to be expelled from the human body.

[0026] In addition to the differences mentioned above compared to currently popular non-alcoholic fatty liver drugs, this invention also has the following unique innovations and features: (1) Multi-line operation with mutual coordination: When people make prescriptions, they tend to focus only on "strengthening the spleen and removing dampness" or "soothing the liver and regulating qi"; but this invention attacks on multiple fronts: regulating qi + strengthening the spleen + promoting blood circulation + clearing heat and removing dampness + astringing and nourishing the liver, with a very three-dimensional structure; (2) The medication approach is highly dynamic and precise: the use of white cardamom is not simply to regulate qi, but to "aromatically resolve dampness" and "warm the middle and regulate the spleen"; the use of turtle shell is to prevent and control the long-term development of non-alcoholic fatty liver disease by recognizing the potential trend of "hardening, degeneration, and fibrosis"; the use of turmeric and rose is common in prescriptions for blood stasis, blood circulation, or liver qi regulation, but is not frequently used in compound prescriptions for treating non-alcoholic fatty liver disease. (3) Protect the body’s vital energy and prevent the spleen from being damaged by bitter and cold herbs: Adding herbs such as dried plum and codonopsis can take care of the patient’s overall condition and prevent the body’s vital energy from being damaged by excessive attack.

[0027] The composition provided by this invention focuses on clearing and draining heat, and long-term use will not cause the accumulation of internal heat and waste, resulting in stable and consolidated therapeutic effects. Furthermore, the composition of this invention can use only ingredients from food-medicine homologous health foods without medicinal herbs, resulting in extremely low side effects and greater safety. Unexpectedly, it was also discovered that the various medicinal herbs have excellent synergistic effects. In addition to being effective in the treatment and management of non-alcoholic fatty liver disease, it can also be used for the treatment and management of alcoholic fatty liver disease and obesity. The composition of this invention can effectively prevent and improve these conditions. Detailed Implementation

[0028] Example 1: Preparation of fine powder Take 10 kg of Ligusticum chuanxiong, 10 kg of Cyperus rotundus, 15 kg of malt, 8 kg of chicken gizzard lining, 10 kg of Angelica dahurica, 6 kg of white cardamom, 3 kg of rhubarb (processed with wine), 23 kg of Plantago asiatica, 31 kg of red adzuki bean, 10 kg of rose, 13 kg of Curcuma longa, 13 kg of dried plum, 19 kg of turtle shell, 4 kg of Gardenia jasminoides, and 15 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0029] Example 2: Preparation of fine powder Take 10 kg of Ligusticum chuanxiong, 8 kg of Cyperus rotundus, 12 kg of malt, 6 kg of chicken gizzard lining, 8 kg of Angelica dahurica, 4 kg of white cardamom, 2 kg of rhubarb (processed with wine), 20 kg of Plantago asiatica, 30 kg of red adzuki bean, 8 kg of rose, 10 kg of Curcuma longa, 10 kg of dried plum, 15 kg of turtle shell, 2 kg of Gardenia jasminoides, and 12 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0030] Example 3: Preparation of fine powder Take 10 kg of Ligusticum chuanxiong, 12 kg of Cyperus rotundus, 18 kg of malt, 10 kg of chicken gizzard lining, 12 kg of Angelica dahurica, 9 kg of white cardamom, 4 kg of rhubarb (processed with wine), 25 kg of Plantago asiatica, 35 kg of red adzuki bean, 12 kg of rose, 15 kg of Curcuma longa, 15 kg of dried plum, 23 kg of turtle shell, 6 kg of Gardenia jasminoides, and 18 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0031] Example 4: Preparation of fine powder Take 10 kg of Ligusticum chuanxiong, 10 kg of Cyperus rotundus, 15 kg of malt, 8 kg of chicken gizzard lining, 10 kg of Angelica dahurica, 6 kg of white cardamom, 12 kg of aloe vera, 23 kg of Plantago asiatica, 31 kg of red adzuki bean, 10 kg of rose, 13 kg of Curcuma longa, 13 kg of dried plum, 19 kg of turtle shell, 4 kg of Gardenia jasminoides, and 15 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0032] Example 5: Preparation of fine powder Take 10 kg of Ligusticum chuanxiong, 10 kg of Cyperus rotundus, 15 kg of malt, 8 kg of chicken gizzard lining, 10 kg of Angelica dahurica, 6 kg of white cardamom, 3 kg of rhubarb (processed with wine), 23 kg of Plantago asiatica, 31 kg of red adzuki bean, 10 kg of rose, 13 kg of Curcuma longa, 13 kg of dried plum, 19 kg of turtle shell, 4 kg of Gardenia jasminoides, and 15 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0033] Comparative Example 1: Preparation of Fine Powder Take 10 kg of Ligusticum chuanxiong, 10 kg of Cyperus rotundus, 15 kg of malt, 8 kg of chicken gizzard lining, 10 kg of Angelica dahurica, 6 kg of white cardamom, 3 kg of rhubarb (processed with wine), 23 kg of Plantago asiatica, 31 kg of red adzuki bean, 5 kg of rose, 7 kg of Curcuma longa, 13 kg of dried plum, 19 kg of turtle shell, 4 kg of gardenia, and 15 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0034] Comparative Example 2: Preparation of Fine Powder Take 10 kg of Ligusticum chuanxiong, 10 kg of Cyperus rotundus, 15 kg of malt, 8 kg of chicken gizzard lining, 10 kg of Angelica dahurica, 6 kg of white cardamom, 3 kg of rhubarb (processed with wine), 23 kg of Plantago asiatica, 31 kg of red adzuki bean, 10 kg of rose, 13 kg of Curcuma longa, 7 kg of dried plum, 10 kg of turtle shell, 4 kg of gardenia, and 15 kg of Codonopsis pilosula. Dry each of the above medicinal materials separately at about 65℃ for 60 hours, then pulverize them with a pulverizer, pass them through an 80-mesh sieve, and mix the powders to obtain a fine powder.

[0035] Example 6: Preparation of capsules (0.5 g / capsule) Prescription information

[0036]

[0037] Preparation method: Weigh out the fine powder, microcrystalline cellulose, and silicon dioxide according to the table above, and disperse them through a 60-mesh sieve. Mix the dispersed materials and magnesium stearate in a mixer for 5-10 minutes. Fill 10,000 No. 0 gelatin capsules using a capsule filling machine. Each capsule contains approximately 0.5 grams of contents.

[0038] Experiment 1: An animal study that helped alleviate hepatic steatosis and promote weight loss. 1. Animal experiments a) Laboratory animals and modeling methods Thirty-five healthy male C57BL / 6 mice, 5 weeks old and weighing 18-22g, were purchased from Shanghai Slack Laboratory Animal Co., Ltd. The mice were fed a high-fat diet (D12450B, Research diets) for 20 weeks before the experiment began. b) Test environment Temperature 22~25℃, humidity 45%~65%, lighting time 12 hours / day; c) Random grouping Thirty-five mice were randomly divided into seven groups: the high (HD), medium (MD), and low (LD) dose groups of Example 1, the comparative example group 1, the comparative example group 2, the positive control group, and the blank group; five mice were in each group, with an average weight of 48.6 g. d) Preparation of test drug After the fine powder of each group of test samples was accurately weighed, it was added to distilled water and dissolved by sonication for 30 minutes to prepare a suspension of the target concentration. According to the clinically intended dose in Example 1, the dosage was converted according to the "equivalent dose coefficient conversion method based on human and animal body surface area" and the dosage was 3 g / kg, which was set as the medium dose group. The high and low doses were 2 and 0.5 times the clinically intended dose, respectively. e) Preparation of positive reference material The positive control drug was selected from Huazhi Rougan Granules (Shandong New Era Pharmaceutical Co., Ltd.), purchased from Laobaixing Health Pharmacy, with production batch number 0052409005. Huazhi Rougan Granules are made from 16 kinds of Chinese medicinal materials, including Artemisia capillaris, Cassia tora (stir-fried), Rheum palmatum (stewed with wine), Alisma plantago-aquatica, Polyporus umbellatus, Crataegus pinnatifida, Atractylodes lancea (stir-fried with wheat bran), Atractylodes macrocephala (stir-fried with wheat bran), and Citrus reticulata. Huazhi Rougan Granules are widely used in clinical practice for non-alcoholic simple fatty liver. The dosage of Huazhi Rougan Granules was set at 3 g / kg, consistent with the medium dose group of the test sample. f) Test methods Mice were administered the drug via gavage (PO), while the blank control group was given distilled water. The drug volume was 10 mL / kg, administered once daily for 35 consecutive days. During the experimental drug administration period, mice were also fed a high-fat diet.

[0039] 2. Experimental Procedure: a) Sample collection After the last administration on day 35, mice in each group were weighed, blood was collected from the heart, liver tissue was separated, washed with physiological saline, the surface moisture was blotted dry with filter paper and weighed, and the liver index was calculated (liver index (%) = liver mass (g) / mouse body mass (g) × 100%). The livers were then frozen at -80℃. b) Sample testing Serum biochemical assay: Blood samples were left to stand at room temperature for 30 minutes, then centrifuged at 3500 rpm for 15 minutes at 4°C to separate serum. AST, ALT, triglycerides (TG), cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) in mouse serum were detected using a fully automated biochemical analyzer. Determination of TG and TC content in liver: 50 mg of liver tissue was taken, and the TG content in the liver was detected by Folch method; the TC content in the liver was detected by ELISA method using TC content detection kit (Solepro: BC1985).

[0040] Test results Table 1. Mean results of body weight and serum biochemical parameters

[0041]

[0042] Table 2. Liver index and mean results of liver TG and TC.

[0043]

[0044] Experimental conclusions a) Weight Mice were administered gavage for 35 consecutive days, and the body weight of the control group increased with time. Compared with the blank group, the high, medium and low dose groups in Example 1 all significantly reduced the weight of mice; the high dose group had the largest weight reduction, with an average weight reduction of 36.0 g, and the weight reduction of each group in Example 1 showed a dose-response relationship. Compared with the control group, the same dose (3 g / kg) of Example 1, Comparative Example 1, Comparative Example 2, and positive control significantly reduced the weight of mice; the weight reduction was the largest in the Example 1 group, with an average weight reduction of 38.2 g. b) Serum biochemistry Compared with the blank group, the high, medium and low dose groups of Example 1 significantly reduced the levels of AST, ALT, TG, TC, HDL and LDL in mouse serum. The high dose group showed the greatest reduction, with average levels decreasing to 173.3 U / L (AST), 65.2 U / L (ALT), 123.6 mg / dl (TG), 162.1 mg / dl (TC), 111.3 mg / dl (HDL) and 15.1 mg / dl (LDL), respectively. Furthermore, the reduction in levels in each group of Example 1 showed a dose-response relationship. Compared with the control group, the same dose (3 g / kg) of Example 1, Comparative Example 1, Comparative Example 2, and positive control significantly reduced AST, ALT, TG, TC, HDL, and LDL in mouse serum. The Example 1 group showed the greatest reduction, with average values ​​decreasing to 197.5 U / L (AST), 62.7 U / L (ALT), 126.1 mg / dl (TG), 171.4 mg / dl (TC), 121.4 mg / dl (HDL), and 17.7 mg / dl (LDL), respectively. c) Liver indices and liver TG and TC Compared with the blank group, the high, medium and low dose groups of Example 1 can significantly reduce the liver index and TG and TC in the liver of mice; the high dose group has the largest reduction, with the average data of each reduced to 4.5% (liver index), 28.3 mg / g (TG) and 6.2 mg / g (TC), respectively. Moreover, the reduction of data in each group of Example 1 is dose-dependent. Compared with the blank group, the same dose (3 g / kg) of Example 1, Comparative Example 1, Comparative Example 2 and positive reference significantly reduced the liver index and TG and TC in the liver of mice; the reduction was the largest in Example 1 group, with the average data reduced to 4.7% (liver index), 35.4 mg / g (TG) and 8.1 mg / g (TC).

[0045] The results of this study show that all formulations in the experiment (Example 1, Comparative Example 1, Comparative Example 2, and positive reference) can effectively reduce excessive fat deposition in liver tissue, restore liver function, and reduce fat synthesis and promote fat metabolism. They can be applied to the treatment of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, liver fibrosis and cirrhosis induced by hepatic steatosis, as well as obesity and metabolic syndrome caused by obesity. The formulations can alleviate hepatic steatosis and reduce weight in obese mice to varying degrees, with the formulation in Example 1 showing the best efficacy.

[0046] Experimental Example 2: An animal study experiment that helps prevent and treat alcoholic fatty liver and alcoholic liver injury. 1. Animal experiments a) Experimental animals and modeling methods Thirty-five healthy male C57BL / 6J mice, aged 8-10 weeks and weighing 22-25 g, were purchased from Shanghai Slack Laboratory Animal Co., Ltd.; the chronic liquid diet plus acute gavage model recommended by NIAAA (National Institute on Alcohol Abuse and Alcoholism) was used to establish the model. b) Test environment Temperature 22~25°C, humidity 45%~65%, lighting time 12 hours / day; c) Random grouping After 5 days of adaptive feeding, 35 mice were randomly divided into 7 groups: the high (HD), medium (MD), and low (LD) dose groups of Example 1, the comparative example 1 group, the comparative example 2 group, the positive control group, and the blank group; 5 mice in each group. d) Preparation of test drug After the fine powder of each group of test samples (Example 1, Comparative Example 1, Comparative Example 2) was accurately weighed, it was added to distilled water, and after being sonicated for 30 minutes, a suspension of the target concentration was prepared. Based on the clinically intended dose (18 g / day) in Example 1, the dosage was converted using the "equivalent dose conversion method based on human and animal body surface area" to obtain a dosage of 3 g / kg, which was designated as the medium-dose group. The high and low doses were 2 and 0.5 times the clinically intended dose, respectively (i.e., 6 g / kg and 1.5 g / kg). The dosages for Comparative Example 1 and Comparative Example 2 were set to be consistent with the dosage group in Example 1 (3 g / kg). e) Preparation of positive reference Silybin was selected as a positive reference. Silybin standard (≥98% (HPLC), Sigma-Aldrich, SO417-10g) was weighed and dissolved in 0.5% sodium carboxymethyl cellulose (CMC-Na) solution to prepare a suspension with a concentration of 10 mg / mL. The dosage was set at 100 mg / kg (i.e. 0.1 g / kg). f) Test methods All mice (including the control group) were fed with Lieber-DeCarli liquid diet containing 5% ethanol for 10 days, and on day 11, they were given a single gavage of 31.5% ethanol (5 g / kg, simulating acute binge drinking). During the modeling period (day 1 to day 10), each drug group was given the corresponding dose of drug suspension or silymarin CMC-Na suspension by gavage at 9:00 am every day, while the control group was given an equal volume of distilled water by gavage. The drug volume was 10 mL / kg, once a day.

[0047] 2. Experimental process a) Sample collection Nine hours after acute ethanol gavage on day 11, mice were anesthetized; blood was collected from the eyeballs, and serum was separated by centrifugation after standing at room temperature (blood samples were allowed to stand at room temperature for 30 minutes, then centrifuged at 3500 rpm for 15 minutes at 4°C); the liver was dissected, washed with physiological saline, blotted dry with filter paper, and weighed, and the liver index was calculated (liver index (%) = liver mass (g) / mouse body mass (g) × 100%); the liver tissue was aliquoted and stored at -80°C for later use; b) Sample testing Serum biochemistry and endotoxin assays: Serum was collected and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were detected using a fully automated biochemical analyzer; serum endotoxin (LPS) levels were determined using the Limulus Amebocyte Lysate (LAL) reagent method. Liver metabolic enzyme and lipid assays: A portion of liver tissue was homogenized and the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were detected by enzyme-linked immunosorbent assay (ELISA) or colorimetric method; the liver triglyceride (TG) content was determined by enzymatic method.

[0048] Test results Table 3. Average results of mouse body weight, liver index, and serum transaminase levels in each group.

[0049]

[0050] Table 4. Mean results of liver metabolic enzyme activity, serum endotoxin, and liver TG.

[0051]

[0052] Experimental conclusions a) Body weight and liver index Compared with the blank group, the high, medium and low dose groups of Example 1 and the positive control group all improved the weight loss of mice caused by alcohol intake and significantly reduced the liver index; the high dose group of Example 1 showed the most significant improvement, with the average weight restored to 24.9g and the liver index reduced to 4.1%, showing a dose-response relationship. At the same dose (3 g / kg), the liver index of the MD group in Example 1 (4.5%) was significantly lower than that in Comparative Example 1 (5.0%) and Comparative Example 2 (5.2%), indicating that Example 1 was superior to the Comparative Example in inhibiting alcoholic hepatomegaly. b) Serum biochemistry and endotoxin (LPS) The serum ALT, AST, GGT and LPS levels of mice in the blank control group were significantly elevated, indicating severe hepatocellular damage and enterogenic endotoxemia; Compared with the blank group, all dose groups and the positive control group in Example 1 significantly reduced the above biochemical indicators; the high dose group in Example 1 showed the largest reduction, with the average indicators decreasing to 55.4 U / L (ALT), 78.3 U / L (AST), 29.1 U / L (GGT) and 0.65 EU / mL (serum LPS), respectively. At the same dose (3 g / kg), although Comparative Example 1 and Comparative Example 2 could also reduce the above biochemical indicators, their effects were not as good as those of the MD group in Example 1. c) Liver metabolic enzymes (ADH, ALDH) and lipids (TG) Compared with the blank group, all dose groups and the positive control group in Example 1 significantly upregulated the activity of liver metabolic enzymes (ADH, ALDH) and reduced the content of liver triglycerides (TG). The high-dose group in Example 1 showed the greatest change, with the average activity of ADH and ALDH increasing to 22.4 U / mg Prot and 11.5 U / mg Prot, respectively, and the liver TG index decreasing to 25.1 mg / g. At the same dose (3 g / kg), the ADH activity (20.1 U / mg prot) and ALDH activity (9.2 U / mg prot) of the MD group in Example 1 were higher than those of Comparative Example 1 and Comparative Example 2.

[0053] The results of this study show that the formulation in Example 1 can effectively combat alcoholic liver injury by exerting its effects through multiple mechanisms, such as increasing the activity of alcohol-degrading enzymes, reducing endotoxin levels, and protecting hepatocytes. Moreover, its overall efficacy is superior to that of the formulations in the comparison ratios.

Claims

1. A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, alcoholic fatty liver disease, and obesity, characterized in that, It is composed of the following raw materials: Ligusticum chuanxiong, Cyperus rotundus, malt, chicken gizzard lining, Angelica dahurica, white cardamom, aloe vera or processed rhubarb, Plantago asiatica, red adzuki bean, rose, turmeric, dried plum, turtle shell, gardenia, and codonopsis pilosula.

2. The composition according to claim 1, characterized in that, The laxative herb mentioned is aloe vera.

3. The composition according to claim 2, characterized in that, By weight, it includes: 1 part of Ligusticum chuanxiong, 0.8-1.2 parts of Cyperus rotundus, 1.5-1.8 parts of malt, 0.8-1 part of chicken gizzard lining, 0.8-1.2 parts of Angelica dahurica, 0.7-0.9 parts of Amomum villosum, 1-1.5 parts of aloe vera, 2-2.5 parts of Plantago asiatica, 3-3.5 parts of red adzuki bean, 0.8-1.2 parts of rose, 1-1.5 parts of Curcuma longa, 1-1.5 parts of Prunus mume, 1.8-2.3 parts of turtle shell, 0.2-0.4 parts of Gardenia jasminoides, and 1.5-1.8 parts of Codonopsis pilosula.

4. The composition according to claim 1, characterized in that, The laxative herb mentioned is processed rhubarb.

5. The composition according to claim 4, characterized in that, By weight, it includes: 1 part of Ligusticum chuanxiong, 0.8-1.2 parts of Cyperus rotundus, 1.5-1.8 parts of malt, 0.8-1 part of chicken gizzard lining, 0.8-1.2 parts of Angelica dahurica, 0.7-0.9 parts of white cardamom, 0.2-0.3 parts of prepared rhubarb, 2-2.5 parts of Plantago asiatica, 3-3.5 parts of red adzuki bean, 0.8-1.2 parts of rose, 1-1.5 parts of Curcuma longa, 1-1.5 parts of dried plum, 1.8-2.3 parts of turtle shell, 0.2-0.4 parts of Gardenia jasminoides, and 1.5-1.8 parts of Codonopsis pilosula.

6. An oral preparation, characterized in that, Includes the traditional Chinese medicine composition according to any one of claims 1-5.

7. The oral formulation according to claim 6, characterized in that, It also includes a pharmaceutically acceptable carrier, and the oral formulation is a pill, tablet, capsule, granule, suspension, powder, or oral liquid.

8. A method for preparing the oral formulation of claim 6, characterized in that, The process includes the following steps: pulverizing the medicinal materials in the traditional Chinese medicine composition according to any one of claims 1-5, passing them through an 80-mesh sieve to obtain fine powder; Furthermore, the fine powder is mixed with a pharmaceutically acceptable carrier and formulated into pills, tablets, capsules, granules, suspensions, powders, or oral liquids.

9. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a medicament for treating non-alcoholic fatty liver, alcoholic fatty liver and obesity.

10. The application according to claim 9, characterized in that, Nonalcoholic fatty liver disease, alcoholic fatty liver disease, and obesity are all related to the common pathogenesis of "liver qi stagnation, internal damp-heat accumulation, and turbid blood stasis".

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