Composition and compound preparation for improving alcoholic liver injury as well as preparation method and application of composition and compound preparation

Abstract

The invention belongs to the technical field of food and medicine, and particularly relates to a composition for improving alcoholic liver injury, a compound preparation and a preparation method and application thereof. In order to provide the pharmaceutical composition for improving the alcoholic liver injury, which is better in efficacy and simpler in preparation process, the pharmaceutical composition for improving the alcoholic liver injury is prepared from the following components in parts by weight: 3 to 45 parts of cordycepin, 25 to 85 parts of ganoderic acid, 3 to 45 parts of puerarin, 10 to 65 parts of semen hoveniae and 10 to 65 parts of herba taraxaci. Animal experiment results prove that the pharmaceutical composition prepared by the invention can remarkably improve the body weight and liver index of a mouse with alcoholic liver injury and reduce liver lesion ALT, AST, TBA and TG indexes in serum of the mouse, so that the liver detoxification and metabolism functions are remarkably enhanced, and the symptoms of the liver injury are effectively relieved.

Description

Technical Field

[0001] This invention belongs to the field of food and drug technology, specifically relating to compositions, compound preparations, their preparation methods, and applications for improving alcoholic liver injury. Background Technology

[0002] Alcoholic liver injury (ALI) is a liver disease caused by long-term heavy alcohol consumption. Early symptoms include vomiting, stomach pain, and loss of appetite, initially manifesting as fatty liver. If left uncontrolled, it can progress to alcoholic hepatitis, liver fibrosis, cirrhosis, and even liver failure, directly endangering human life. Its pathogenesis is complex and influenced by multiple factors, such as oxidative stress, fatty acid accumulation, and activation of hepatic macrophages. Currently, the main treatments for ALI include abstinence from alcohol, drug therapy, combination therapy, and surgery. Drug therapy includes Western medicines (such as metadoxine), which, while effective to some extent, lack a highly effective specific drug. Therefore, the search for more effective, multi-targeted drugs with fewer adverse reactions is urgent. In recent years, traditional Chinese medicine (TCM) has received considerable attention. It has a long history of treating alcoholic liver disease, with mild effects and minimal irritation to the liver and kidneys. Increasingly, scholars are exploring its effects and mechanisms on ALI.

[0003] Cordyceps militaris, also known as North Cordyceps, is a fungus belonging to the Ascomycota, Clavicipitales, Cordycepsaceae, and Cordyceps genus. Its medicinal and health-promoting value is similar to that of Cordyceps sinensis, making it a valuable medicinal fungus. While Cordyceps sinensis is only used in medicine, Cordyceps militaris can be used both as medicine and food, and is widely used in health foods. It is extensively applied to treat various diseases of the circulatory, immune, respiratory, and glandular systems, as well as for anti-aging purposes.

[0004] The main active ingredient in Cordyceps militaris is cordycepin, also known as 3-deoxyadenosine, a natural product isolated from the plant. Because its structure is very similar to adenosine, cordycepin is considered a highly effective bioactive component. Modern pharmacological studies have shown that it has broad-based regulatory effects on the immune, nervous, musculoskeletal, and endocrine systems. Existing research indicates that cordycepin can significantly reduce alcohol-induced liver damage in mice, manifested by lowering serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and alleviating hepatic steatosis and inflammatory infiltration. Mechanistic studies have found that cordycepin regulates lipid metabolism disorders by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibiting the expression of sterol regulatory element-binding protein-1c (SREBP-1c). Furthermore, cordycepin also inhibits the activation of the nuclear factor-κB (NF-κB) pathway, reducing the inflammatory response. These studies indicate that cordycepin may exert a protective effect against alcoholic liver injury by regulating lipid metabolism and inflammatory responses, with the mechanism involving the AMPK / SREBP-1c and NF-κB signaling pathways. Therefore, compound preparations using cordycepin or plants containing cordycepin as an active ingredient to improve alcoholic liver injury have become a research hotspot. For example, patent CN109527577A discloses a composition with hangover-relieving and liver-protecting functions, which consists of live silkworm pupae, cordyceps, kudzu root, ginseng, wolfberry, dandelion, Japanese raisin tree fruit, silkworm pupae, poria cocos, and corn peptides. However, it requires the use of fresh, sterilized silkworm pupae as a carrier, making the preparation process complex and demanding high levels of expertise from operators, thus hindering widespread application. Summary of the Invention

[0005] In order to provide a pharmaceutical composition for improving alcoholic liver injury with better efficacy and simpler preparation process, the present invention provides a new composition, compound preparation, preparation method and application for improving alcoholic liver injury.

[0006] To achieve the above-mentioned objectives, the technical solution adopted in this application is as follows: In a first aspect, the present invention provides a pharmaceutical composition for improving alcoholic liver injury, comprising the following components in parts by weight: cordycepin 3-45 parts, ganoderic acid 25-85 parts, puerarin 3-45 parts, Japanese raisin tree fruit 10-65 parts, and dandelion 10-65 parts.

[0007] Furthermore, the pharmaceutical composition for improving alcoholic liver injury comprises the following components in parts by weight: cordycepin 4-40 parts, ganoderic acid 30-80 parts, puerarin 4-40 parts, Japanese raisin tree fruit 13-60 parts, and dandelion 13-60 parts.

[0008] Preferably, the pharmaceutical composition for improving alcoholic liver injury comprises the following components in parts by weight: cordycepin 5-30 parts, ganoderic acid 35-70 parts, puerarin 5-30 parts, Japanese raisin tree fruit 15-50 parts, and dandelion 15-50 parts.

[0009] More preferably, the pharmaceutical composition for improving alcoholic liver injury comprises the following components in parts by weight: 10-20 parts cordycepin, 40-60 parts ganoderic acid, 10-20 parts puerarin, 20-40 parts Japanese raisin tree fruit, and 20-40 parts dandelion.

[0010] Most preferably, the pharmaceutical composition comprises the following components in parts by weight: 20 parts cordycepin, 60 parts ganoderic acid, 20 parts puerarin, 40 parts Japanese raisin tree fruit, and 40 parts dandelion.

[0011] Furthermore, the cordycepin is extracted from wild Cordyceps militaris and / or artificially cultivated Cordyceps sinensis.

[0012] Furthermore, the purity of the cordycepin is 95% or higher. Preferably, the purity of the cordycepin is 98% or higher.

[0013] Furthermore, the purity of the ganoderic acid is 95% or higher. Preferably, the purity of the ganoderic acid is 98% or higher.

[0014] Furthermore, the ganoderic acid is selected from ganoderic acid B and Me.

[0015] Furthermore, the purity of the puerarin is 95% or higher, preferably 98% or higher.

[0016] Furthermore, the purity of the Hovenia dulcis seeds is 95% or higher. Preferably, the purity of the Hovenia dulcis seeds is 98% or higher.

[0017] Furthermore, the Hovenia dulcis seeds are powder with a particle size ≤100μm that has passed through a 150-mesh sieve.

[0018] Furthermore, the purity of the dandelion is 95% or higher. Preferably, the purity of the dandelion is 98% or higher.

[0019] Furthermore, the dandelion is a powder that has passed through a 150-mesh sieve and has a particle size ≤100μm.

[0020] Secondly, the present invention provides a compound preparation for improving alcoholic liver injury, which contains the above-mentioned pharmaceutical composition.

[0021] Furthermore, the compound preparation is an oral preparation, a topical preparation, or an injectable preparation.

[0022] Preferably, the oral preparation is a decoction, powder, granule, tea, tablet, tincture, pill, extract, oral liquid, capsule or granule; the external preparation is a nasal cream, drops, patch or spray.

[0023] Thirdly, the present invention provides a method for preparing the above-mentioned pharmaceutical composition, which includes the following steps: mixing cordycepin, ganoderic acid, puerarin, Japanese raisin tree seed, and dandelion in a solvent according to the weight ratio.

[0024] Fourthly, the present invention provides a method for preparing the above-mentioned compound preparation, which includes the following steps: mixing cordycepin, ganoderic acid, puerarin, Japanese raisin tree fruit and dandelion in proportion by weight, adding at least one pharmaceutically acceptable excipient, and preparing the preparation according to conventional pharmaceutical preparation methods.

[0025] Furthermore, in the above-mentioned method for the pharmaceutical composition or compound preparation, in order to improve the efficacy, the Hovenia dulcis and Taraxacum mongolicum are added in the form of extracts; the extracts are obtained by extraction with an extraction solvent, and the extract is obtained by vacuum concentration and drying.

[0026] Fifthly, the present invention provides the use of the above-described pharmaceutical composition or compound preparation in the preparation of products for improving, regulating, preventing and / or treating alcoholic liver injury.

[0027] Furthermore, the product is selected from at least one of functional foods, pharmaceuticals, or health products.

[0028] Beneficial Effects: This invention uses cordycepin, ganoderic acid, puerarin, Japanese raisin tree seed, and dandelion to prepare a pharmaceutical composition to improve alcoholic liver injury. Cordycepin regulates lipid metabolism disorders by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibiting the expression of sterol regulatory element-binding protein-1c (SREBP-1c). In addition, cordycepin inhibits the activation of the nuclear factor-κB (NF-κB) pathway, reducing the inflammatory response; while ganoderic acid, by regulating the PPARα / NF-κB signaling pathway, affects lipid metabolism and inflammatory response, thereby playing a protective role against acute alcoholic liver injury; puerarin can improve the antioxidant capacity of patients with acute alcohol poisoning and alleviate liver damage; puerarin has an ameliorative effect on subacute ALD caused by excessive drinking in a short period of time, mainly by reducing the expression levels of inflammatory factors such as TNF-α and IL-6 in serum and inhibiting the inflammatory response, thereby protecting the liver; Hovenia dulcis can reduce alcohol-induced hepatic steatosis and inflammatory cell infiltration, and reduce fibrosis; dandelion can increase the content of superoxide dismutase (SOD) and glutathione (GSH) in drug-damaged liver, and reduce the content of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), effectively protecting the liver. These five raw materials complement each other and work synergistically at different levels to enhance the improvement of alcoholic liver injury. Detailed Implementation

[0029] To make the technical problems, solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with the embodiments. Unless otherwise defined, all technical terms used herein have the same meaning as understood by one of ordinary skill in the art.

[0030] In one embodiment of the present invention, a pharmaceutical composition for improving alcoholic liver injury is provided, comprising the following components in parts by weight: cordycepin 3-45 mg, ganoderic acid 25-85 mg, puerarin 3-45 mg, Japanese raisin tree fruit 10-65 mg, and dandelion 10-65 mg.

[0031] Cordycepin is the main active ingredient in Cordyceps militaris, and it has certain pharmacological effects in immunomodulation, anti-tumor activity, and lipid-lowering. Cordycepin can increase the turnover rate of liver nucleic acids and proteins, stimulate glycolysis, thereby increasing ATP synthesis and enhancing liver function. In this invention, cordycepin regulates lipid metabolism disorders by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibiting the expression of sterol regulatory element-binding protein-1c (SREBP-1c).

[0032] Ganoderic acids are a class of triterpenoid compounds mainly derived from Ganoderma lucidum and its closely related species, and are one of the important active components of Ganoderma lucidum. Currently, more than 100 different ganoderic acids have been identified, such as ganoderic acids A, B, C, D, T, and Me. Different types of ganoderic acids differ in structure, thus their biological activities and effects also vary. For example, ganoderic acid A inhibits tumor cell proliferation and induces apoptosis (e.g., liver cancer and breast cancer cells); it also reduces inflammatory responses by inhibiting the NF-κB pathway; lowers liver damage markers (ALT, AST), and promotes hepatocyte repair; and scavenge free radicals, reducing oxidative stress damage. Ganoderic acid B can reduce β-amyloid protein deposition, improve Alzheimer's disease, and inhibit the growth of lung cancer and colon cancer cells. Ganoderic acid T inhibits tumor cell migration and invasion (e.g., breast cancer and melanoma) and can also alleviate pulmonary fibrosis and liver fibrosis. Ganoderic acids Me and ganoderic acids DM have anti-aging, hypoglycemic, anti-inflammatory, analgesic, and bone-protective effects, respectively. In this invention, ganoderic acid B and Me are mixed to regulate the PPARα / NF-κB signaling pathway, thereby affecting lipid metabolism and inflammatory response and thus exerting a protective effect against acute alcoholic liver injury.

[0033] Puerarin is an isoflavone compound extracted from the kudzu root (Pueraria lobata), a legume, and is one of the main active ingredients of kudzu. Its chemical structure is similar to that of soy isoflavones, but it has stronger biological activity and a wide range of pharmacological effects. These include cardiovascular protection, improvement of cerebral blood flow, neuroprotection, lowering blood sugar and improving diabetic complications, antioxidant and anti-aging effects, hangover relief and liver protection, anti-inflammation, and immune regulation. In this invention, puerarin has a mitigating effect on subacute ALD caused by excessive alcohol consumption in a short period, mainly by reducing the expression levels of inflammatory factors such as TNF-α and IL-6 in serum and inhibiting the inflammatory response, thereby protecting the liver.

[0034] The seeds of *Hovenia dulcis*, *Hovenia sinensis*, and *Hovenia pubescens*, all belonging to the genus *Hovenia* in the family Rhamnaceae, are mature and have the effects of relieving alcohol poisoning, quenching thirst and relieving irritability, stopping vomiting, and promoting urination and defecation. They are primarily used to treat drunkenness, thirst, vomiting, and difficulty in urination and defecation. In this invention, *Hovenia dulcis* seeds can reduce alcohol-induced fatty degeneration and inflammatory cell infiltration in the liver, and decrease fibrosis.

[0035] Dandelion is a perennial herbaceous plant belonging to the Asteraceae family and the Taraxacum genus. Raw dandelion is rich in vitamins A and C, as well as potassium, iron, calcium, vitamin B2, vitamin B1, magnesium, vitamin B6, folic acid, and copper. Dandelion has the following health benefits: 1. Clearing heat and detoxifying: Dandelion's medicinal properties are primarily suited for treating various heat-related illnesses. It is very effective in treating many heat-related symptoms or suppurative diseases. Its effect in clearing liver heat is particularly significant in cases of severe redness, swelling, and pain caused by liver heat.

[0036] 2. Beauty and skin care: Dandelion leaves contain a large amount of protein, fat, trace elements, carbohydrates, vitamins, etc. Daily consumption of dandelion water can help improve skin diseases such as dermatitis and eczema.

[0037] 3. Cancer Prevention and Treatment: Modern research has also found that dandelion leaves have anti-tumor effects. Regular consumption can improve the body's immunity.

[0038] 4. Liver and Gallbladder Protection: Dandelion is a natural diuretic and digestive aid; it is rich in minerals, which not only help prevent iron-deficiency anemia, but its high potassium content also works with sodium to regulate the body's water and electrolyte balance and normalize heart rate; it is also rich in lecithin, which can prevent cirrhosis and enhance liver and gallbladder function. In this invention, dandelion can increase the levels of superoxide dismutase (SOD) and glutathione (GSH) in drug-damaged livers, while reducing the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), effectively protecting the liver.

[0039] The following specific embodiments will be provided to explain the solution of the present invention. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0040] In the following examples, the cordycepin and puerarin used had a purity greater than 98%.

[0041] The ganoderic acids used were ganoderic acid B and ganoderic acid Me (mass ratio 1:1), both with a purity greater than 98%.

[0042] The Hovenia dulcis seeds used were powdered Hovenia dulcis seeds that passed through a 150-mesh sieve, with a particle size ≤100 μm and a purity greater than 98%.

[0043] The dandelion used is medicinal dandelion powder that has passed through a 150-mesh sieve and has a particle size ≤100 μm, with a purity greater than 98%.

[0044] Example 1: Preparation of the compound preparation 1 for improving alcoholic liver injury according to the present invention Weigh out 20 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation 1.

[0045] Example 2: Preparation of the compound preparation 2 of the present invention for improving alcoholic liver injury Weigh out 10 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation 2.

[0046] Example 3: Preparation of the compound preparation 3 of the present invention for improving alcoholic liver injury Weigh out 20 mg of cordycepin, 40 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water. Stir thoroughly to dissolve and obtain preparation 3.

[0047] Example 4: Preparation of the compound preparation 4 of the present invention for improving alcoholic liver injury Weigh out 20 mg of cordycepin, 60 mg of ganoderic acid, 10 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation 4.

[0048] Example 5: Preparation of the compound preparation 5 of the present invention for improving alcoholic liver injury Weigh out 20 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of puerarin, 20 mg of Japanese raisin tree fruit, and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation 5.

[0049] Example 6: Preparation of the compound preparation 6 of the present invention for improving alcoholic liver injury Weigh out 20 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 20 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation 6.

[0050] Comparative Example 1: Preparation of Compound Preparation A Weigh out 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation A.

[0051] Comparative Example 2: Preparation of Compound Formulation B Weigh out 20 mg of cordycepin, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation B.

[0052] Comparative Example 3: Preparation of Compound Preparation C Weigh out 20 mg of cordycepin, 60 mg of ganoderic acid, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation C.

[0053] Comparative Example 4: Preparation of Compound Preparation D Weigh 20 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit, and 40 mg of sialic acid, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve, and preparation D is obtained.

[0054] Comparative Example 5: Preparation of Compound Formulation E 20 mg of cordycepin, 60 mg of ganoderic acid, 20 mg of ginsenosides, 40 mg of Japanese raisin tree fruit, and 40 mg of dandelion are dissolved together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. The mixture is stirred thoroughly to dissolve, thus obtaining preparation E.

[0055] Comparative Example 6: Preparation of Compound Preparation F Weigh out 20 mg of cordycepic acid, 60 mg of ganoderic acid, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation F.

[0056] Comparative Example 7: Preparation of Compound Preparation G Weigh out 20 mg of cordycepin, 60 mg of wolfberry, 20 mg of puerarin, 40 mg of Japanese raisin tree fruit and 40 mg of dandelion, and dissolve them together in 10 mL of sterile water + 0.1% (i.e., 10 mg / 10 mL solution) Tween-80. Stir thoroughly to dissolve and obtain preparation G.

[0057] Table 1. Components and content of different formulations

[0058] Note: In Table 1, "--" means not to be added, and "R" means to be replaced with the corresponding ingredient.

[0059] Experimental Example 1: Effects of different formulations on mouse body weight, organ indices, and peripheral blood routine tests 1. Experimental Methods (1) Grouping and administration of experimental animals Male C57 mice, aged 6-8 weeks and weighing (18±2) g, were purchased from Nanjing Qinglongshan Animal Breeding Farm and housed at the Animal Center of Nanjing University of Technology. The mice were placed in a sterile environment with free access to food and water at 22-26 ℃ and 45-55% humidity, and underwent a 12 / 12-hour light / dark cycle. They were acclimatized for one week prior to the experiment and fed a Lieber-DeCarli diet.

[0060] Mice were randomly divided into 15 groups of 8 mice each, as follows: Group 1 was the blank control group, Group 2 was the pathological model group, Groups 3-8 were Examples 1-6, and Groups 9-15 were Comparative Examples 1-7.

[0061] The treatment methods for each group of mice are as follows: Normal control (Contorl) group: Free access to ethanol-free Lieber-DeCarli feed for 1-10 days of the experiment; 20 mL / kg of 45 wt% maltodextrin solution was given at 8:00 am on the 11th day, and the samples were dissected and collected at 5:00 pm on the same day.

[0062] Pathological model (Model) group: From day 1 to 10, the animals were allowed free access to Lieber-DeCarli feed containing 5 vt% ethanol. On day 11, at 8:00 AM, the animals were given 20 mL / kg of 31.5 vt% ethanol solution, and the animals were dissected and smeared at 5:00 PM on the same day.

[0063] Examples 1-6: The feeding environment and modeling method were the same as those of the pathological model group. From day 1 to day 11 of the experiment, each mouse was administered the drug by gavage at a dose of 100 mg / kg, which were preparations 1-6 prepared in Examples 1-6, respectively. The drug was administered at 7:00 AM on day 11.

[0064] Comparative groups 1-7: The feeding environment and modeling method were the same as those of the pathological model group. From day 1 to day 11, each mouse was administered the drug by gavage at a dose of 100 mg / kg, which were preparations A-G prepared in comparative groups 1-7, respectively. The drug was administered at 7:00 AM on day 11.

[0065] (2) Body weight and organ index At the end of the experiment, the mice were euthanized, their weight was measured, their livers were removed, washed with physiological saline, dried with filter paper, weighed, and the liver index was calculated.

[0066] Liver index = Liver weight (mg) / Body weight (g) (3) Detection of serum biochemical indicators in mice When the liver is damaged, it releases large amounts of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) into the bloodstream. As the primary site of bile acid metabolism, liver disease also leads to an increase in total bile acid (TBA) levels in the blood. Furthermore, fatty liver disease also increases triglyceride (TG) levels in the blood. Therefore, a kit was used to analyze ALT, AST, TBA, and TG levels in mouse serum to assess the degree of liver damage.

[0067] 2. Effects of different formulations on body weight and organ indices in mice with alcoholic liver injury (1) Effects of different formulations on body weight and liver index in mice with alcoholic liver injury The body weight and liver index results of mice in each experimental group are shown in Table 2. The results showed that compared with the blank control group, the body weight of mice in the pathological model group was significantly reduced (16.8 g vs 21.5 g) and the liver index was significantly decreased (4.1 g / 100g BW vs 7.6 g / 100g BW), indicating that the mouse model of liver injury was successfully established. Compared with the pathological model group, the body weight and liver index of all drug-treated groups were improved to varying degrees. Among them, the effect of the Example 1 group (formulation 1) was the most outstanding, with its body weight (20.4 g) and liver index (6.9 g / 100g BW) being closest to the normal level, which was significantly better than other drug-treated groups.

[0068] In the example groups, the improvement effects of each formulation on body weight and liver index were ranked as follows: Example 1 group > Example 3 group > Example 6 group > Example 4 group > Example 5 group > Example 2 group; and the improvement effects of all example groups (1-6) were significantly better than those of the comparative groups (A-G). Among them, the comparative group 1 (formulation A, without cordycepin) had the worst effect (body weight 17.5g, liver index 5.2 g / 100g BW), while the comparative group 6 (formulation F, cordycepin replaced with cordycepic acid) had the best effect (body weight 18.4g, liver index 6.1 g / 100g BW), but it was still not as good as the example groups.

[0069] This result fully demonstrates that the formulations of Examples 1-6 of this invention have a more significant hepatoprotective effect compared to Comparative Examples A-G, and can effectively improve weight loss and liver index reduction caused by liver injury. In particular, the excellent recovery effect of Example 1 group indicates that the active ingredients cordycepin, ganoderic acid, puerarin, Hovenia dulcis, and dandelion in this formulation significantly enhance liver repair and metabolic regulation functions through synergistic effects, thereby more effectively alleviating liver injury symptoms.

[0070] Table 2. Body weight and liver index of mice in each experimental group

[0071] Note: The data in the table are averages.

[0072] (2) Effects of different formulations on serum biochemical indicators in mice with alcoholic liver injury The serum biochemical parameters of mice in each experimental group are shown in Table 3. The results showed that, compared with the blank control group, the serum ALT activity (78 U / L vs 21 U / L), AST activity (151 U / L vs 62 U / L), TBA concentration (80 μmol / L vs 42 μmol / L), and TG concentration (8.1 mmol / L vs 3.8 mmol / L) of mice in the pathological model group were significantly increased, indicating that the mouse model of liver injury was successfully established.

[0073] Compared with the pathological model group, all treatment groups showed varying degrees of improvement in liver function indicators. The most significant effect was observed in Example 1 (Formulation 1), with ALT activity (28 U / L), AST activity (85 U / L), TBA concentration (41 μmol / L), and TG concentration (4.2 mmol / L) all closest to normal levels. The improvement effect of each example group was ranked as follows: Example 1 > Example 5 > Example 3 > Example 6 > Example 4 > Example 2.

[0074] It is noteworthy that the improvement effects of the Example Groups (1-6) were significantly better than those of the Comparative Groups (A-G). Among them, Comparative Group 1 (Formulation A, without cordycepin) showed the worst effect (ALT 61 U / L, AST 135 U / L), while Comparative Group 6 (Formulation F, cordycepin replaced with cordycepic acid) showed the best effect (ALT 50 U / L, AST 115 U / L), but it was still inferior to the Example Groups. This result fully demonstrates that the formulations of Examples 1-6 of the present invention have a more significant liver-protective effect compared with Comparative Groups A-G, effectively reducing serum ALT and AST activities and improving bile acid metabolism and blood lipid levels. In particular, the excellent liver-protective effect of Example Group 1 indicates that the active ingredients cordycepin, ganoderic acid, puerarin, Hovenia dulcis, and dandelion in this formulation significantly enhance liver detoxification and metabolic functions through synergistic effects, thereby more effectively alleviating liver damage symptoms.

[0075] Table 3. Serum biochemical data of mice in each experimental group

[0076] Note: The data in the table are averages.

Claims

1. A pharmaceutical composition for improving alcoholic liver injury, characterized in that, It includes the following components in parts by weight: cordycepin 3-45 parts, ganoderic acid 25-85 parts, puerarin 3-45 parts, Japanese raisin tree fruit 10-65 parts, and dandelion 10-65 parts.

2. The pharmaceutical composition for improving alcoholic liver injury according to claim 1, characterized in that, It includes the following components in parts by weight: cordycepin 4-40 parts, ganoderic acid 30-80 parts, puerarin 4-40 parts, Japanese raisin tree fruit 13-60 parts and dandelion 13-60 parts; Preferably, the pharmaceutical composition for improving alcoholic liver injury comprises the following components in parts by weight: cordycepin 5-30 parts, ganoderic acid 35-70 parts, puerarin 5-30 parts, Japanese raisin tree fruit 15-50 parts, and dandelion 15-50 parts. More preferably, the pharmaceutical composition for improving alcoholic liver injury comprises the following components in parts by weight: 10-20 parts cordycepin, 40-60 parts ganoderic acid, 10-20 parts puerarin, 20-40 parts Japanese raisin tree fruit, and 20-40 parts dandelion.

3. The pharmaceutical composition for improving alcoholic liver injury according to claim 2, characterized in that, The pharmaceutical composition comprises the following components in parts by weight: 20 parts cordycepin, 60 parts ganoderic acid, 20 parts puerarin, 40 parts Japanese raisin tree fruit, and 40 parts dandelion.

4. The pharmaceutical composition for improving alcoholic liver injury according to any one of claims 1 to 3, characterized in that: The purity of cordycepin, ganoderic acid, puerarin, Japanese raisin tree seed, and dandelion is all above 95%.

5. The pharmaceutical composition for improving alcoholic liver injury according to any one of claims 1 to 4, characterized in that: The ganoderic acid is selected from at least one of ganoderic acid B and Me.

6. A compound preparation for improving alcoholic liver injury, characterized in that: The pharmaceutical composition comprising any one of claims 1 to 5.

7. The compound preparation according to claim 6, characterized in that: The compound preparation is an oral preparation, a topical preparation, or an injectable preparation; preferably, the oral preparation is a decoction, powder, granule, tea, tablet, tincture, pill, extract, oral liquid, capsule, or granule; the topical preparation is a nasal cream, drops, patch, or spray.

8. A method for preparing the pharmaceutical composition according to any one of claims 1 to 5, characterized in that, Includes the following steps: The cordycepin, ganoderic acid, puerarin, Japanese raisin tree seed, and dandelion are mixed in a solvent according to the specified weight ratio.

9. The method for preparing the compound preparation according to claim 6 or 7, characterized in that, The process includes the following steps: mixing cordycepin, ganoderic acid, puerarin, Japanese raisin tree fruit, and dandelion in proportion by weight, adding at least one pharmaceutically acceptable excipient, and preparing the drug according to conventional pharmaceutical preparation methods.

10. The use of the pharmaceutical composition according to any one of claims 1 to 5 or the compound preparation according to any one of claims 6 to 7 in the preparation of products for improving, regulating, preventing and / or treating alcoholic liver injury.

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