A traditional Chinese medicine composition, preparation, preparation method and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition, preparation, preparation method, and application, relating to the field of traditional Chinese medicine technology. It includes the following steps: pulverizing dried tangerine peel and kudzu root, adding ethanol, warm soaking, and filtering to obtain dregs and an ethanol extract; concentrating the ethanol extract to obtain an ethanol extract component; mixing the dregs, Japanese raisin tree fruit, Poria cocos, wolfberry fruit, and raspberry fruit, adding water, hot soaking, and filtering to obtain an aqueous extract; concentrating the aqueous extract to obtain an aqueous extract component; mixing and drying the ethanol extract component and the aqueous extract component to obtain the aforementioned traditional Chinese medicine composition. This invention is beneficial for reducing liver indices, lowering alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, lowering malondialdehyde (MDA) levels, increasing superoxide dismutase (SOD) levels, and improving liver tissue morphology and structure, achieving a therapeutic effect on alcoholic liver disease, with a therapeutic effect superior to the biphenyl diester tablet positive control.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition, preparation, preparation method and application thereof. Background Technology

[0002] Alcoholic liver disease (ALD) is a common liver disease that seriously endangers health. It is caused by long-term heavy drinking and initially manifests as fatty liver, which can progress to alcoholic hepatitis, liver fibrosis, and cirrhosis. Western medicine's basic treatment for ALD is abstinence from alcohol, supplemented by medication and nutritional support. However, many patients find it difficult to quit drinking, and the treatment is limited by factors such as numerous drug side effects and a heavy financial burden.

[0003] In terms of etiology, pathology, and clinical characteristics, ALD aligns with descriptions of symptoms in classical Chinese medicine texts such as "alcohol-induced jaundice," "alcohol addiction," "alcohol-induced armpit injury," "alcohol-induced pain," "accumulation," and "abdominal distension." Professor Tian Delu divides ALD into early, middle, and late stages. The common pathogenesis in the early stage is liver stagnation and spleen deficiency, with qi stagnation and dampness obstruction, clinically manifesting as mild alcoholic liver injury, alcoholic steatosis, and alcoholic hepatitis, etc. Treatment should focus on soothing the liver and strengthening the spleen, detoxifying and resolving dampness. The middle stage is mainly characterized by phlegm and blood stasis, with qi and blood stagnation, clinically manifesting as alcoholic cirrhosis, etc. Treatment should focus on resolving phlegm, regulating qi, and promoting blood circulation. The late stage involves simultaneous liver, spleen, and kidney disease, clinically manifesting as alcoholic cirrhosis, and treatment should focus on supporting the body's resistance and eliminating pathogenic factors.

[0004] Therefore, there is a widespread demand for drugs that can relieve hangovers and prevent and reduce alcohol-induced liver damage, and many related traditional Chinese medicine products exist in the current technology. Examples include combinations containing Atractylodes macrocephala, lily bulb, Bupleurum chinense, Citrus reticulata peel, rhubarb, jujube, Angelica sinensis, Poria cocos, Rubus idaeus, Pueraria lobata, Lycium barbarum, Cinnamomum cassia, Polygonatum sibiricum, Astragalus membranaceus, Scutellaria baicalensis, Curcuma longa, Nelumbo nucifera, Ephedra sinica, Ophiopogon japonicus, Panax ginseng, Cistanche deserticola, Morus alba, Cimicifuga foetida, ginger, Rehmannia glutinosa, Cynomorium songaricum, Asparagus cochinchinensis, Polygonatum odoratum, Hovenia dulcis, Glycyrrhiza uralensis (processed), Coptis chinensis, Schisandra chinensis (processed with vinegar), Morinda officinalis, Saposhnikovia divaricata, Achyranthes bidentata, stalactite powder, Vitex negundo, Cuscuta chinensis (processed with salt), Plantago asiatica, Dendrobium nobile, Dioscorea opposita, Eucommia ulmoides, Polygala tenuifolia (processed), Aconitum carmichaelii, Cnidium monnieri, Ligusticum chuanxiong, Cornus officinalis, Aconitum carmichaelii, Amethyst, and Acorus tatarinowii. Alternatively, it may be a solid beverage made from kudzu flower extract, licorice extract, Japanese raisin tree fruit extract, or raspberry extract.

[0005] The aforementioned Chinese medicine products have several shortcomings, including a wide variety of raw materials, unclear effective components, and unknown potential side effects; and the physical mixing of extracts obtained from individual Chinese medicines without a chemical reaction during decoction results in the loss of the traditional efficacy basis of "mutual compatibility and synergy" in decoction. Summary of the Invention

[0006] In view of the shortcomings of the above-mentioned related technologies, the present invention provides a traditional Chinese medicine composition, preparation, preparation method and application thereof.

[0007] The present invention provides a method for preparing a traditional Chinese medicine composition using the following technical solution.

[0008] A method for preparing a traditional Chinese medicine composition includes the following steps: taking dried tangerine peel and kudzu root, crushing them, adding ethanol, soaking them at a warm temperature, filtering to obtain dregs and ethanol extract, concentrating the ethanol extract to obtain an ethanol extract component; taking dregs, Japanese raisin tree fruit, Poria cocos, wolfberry fruit and raspberry fruit, mixing them, adding water, soaking them at a hot temperature, filtering to obtain an aqueous extract, concentrating the aqueous extract to obtain an aqueous extract component; mixing the ethanol extract component and the aqueous extract component and drying to obtain the traditional Chinese medicine composition.

[0009] Preferably, the weight concentration of the ethanol is 50%-60%, and the weight ratio of the total weight of the dried tangerine peel and kudzu root to the weight of the ethanol is 1:5-7.

[0010] Preferably, the ethanol has a weight concentration of 55%, and the ratio of the total weight of the dried tangerine peel and kudzu root to the weight of the ethanol is 1:6.

[0011] Preferably, the temperature of the warm soaking is 40-50°C, the number of soakings is 1-3, and the duration of each soaking is 1-3 hours.

[0012] Preferably, the temperature of the warm soaking is 45°C, the number of soakings is 2, and the duration of each soaking is 1.5 hours.

[0013] Preferably, the total weight ratio of the dregs, Japanese raisin tree fruit, Poria cocos, wolfberry fruit, and raspberry to the weight of the water is 1:7-9.

[0014] Preferably, the total weight ratio of the dregs, Japanese raisin tree fruit, Poria cocos, wolfberry fruit, and raspberry to the weight of the water is 1:8.

[0015] Preferably, the hot immersion temperature is 85-95℃, the number of times is 1-4, and the duration of each time is 0.5-2h.

[0016] Preferably, the hot immersion temperature is 90°C, the number of times is 2, and the duration of each time is 1 hour.

[0017] Preferably, the raw materials used include the following Chinese medicinal herbs in parts by weight: 10-13 parts of kudzu root, 5-7 parts of dried tangerine peel, 12-16 parts of Japanese raisin tree fruit, 12-16 parts of poria cocos, 10-13 parts of wolfberry fruit, and 8-11 parts of raspberry fruit.

[0018] Preferably, the raw materials used include the following Chinese medicinal herbs in parts by weight: 10-12 parts of kudzu root, 5-6 parts of dried tangerine peel, 12-15 parts of Japanese raisin tree fruit, 12-15 parts of poria cocos, 10-12 parts of wolfberry fruit, and 8-10 parts of raspberry fruit.

[0019] Preferably, the raw materials used include the following Chinese medicinal herbs in parts by weight: 12 parts kudzu root, 6 parts dried tangerine peel, 15 parts Japanese raisin tree fruit, 15 parts poria cocos, 12 parts wolfberry fruit, and 10 parts raspberry.

[0020] The present invention provides a traditional Chinese medicine composition using the following technical solution.

[0021] A traditional Chinese medicine composition is prepared using the method described above.

[0022] The present invention provides a traditional Chinese medicine composition preparation using the following technical solution.

[0023] A traditional Chinese medicine composition preparation comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients, wherein the dosage form is tablet, powder, granule, capsule or pill.

[0024] The present invention provides a method for preparing a traditional Chinese medicine composition preparation using the following technical solution.

[0025] A method for preparing the above-mentioned traditional Chinese medicine composition preparation is characterized in that: the traditional Chinese medicine composition, dextrin and lactose are mixed and stirred evenly in a weight ratio of 2.5-3.5:2:1 to form wet granules; the wet granules are dried at a constant temperature and then sieved through a 10-14 mesh sieve to granulate, and qualified granules are screened to obtain the granule dosage form of the traditional Chinese medicine composition preparation.

[0026] Preferably, the weight ratio of the traditional Chinese medicine composition, dextrin, and lactose is 3:2:1.

[0027] This invention provides the use of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine composition preparation in the preparation of a drug for the prevention and / or treatment of alcoholic liver disease.

[0028] This invention provides the application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine composition preparation in the preparation of a drug for relieving the increase of liver index caused by alcoholic liver disease.

[0029] This invention provides the application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine composition preparation in the preparation of a drug to alleviate the increase of alanine aminotransferase and aspartate aminotransferase caused by alcoholic liver disease.

[0030] This invention provides the application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine composition preparation in the preparation of a drug that improves the increase of malondialdehyde (MDA) and the decrease of superoxide dismutase (SOD) caused by alcoholic liver disease.

[0031] In summary, the present invention has at least one of the following beneficial technical effects: (1) In this invention, kudzu root and Japanese raisin tree fruit are used as the principal herbs to relieve the symptoms of alcohol poisoning; poria cocos and tangerine peel are used as the assistant herbs to strengthen the spleen and regulate qi; and wolfberry and raspberry are used as adjuvant herbs to nourish the liver and kidneys. Compared with the four-herb basic formula without Japanese raisin tree fruit and raspberry, the prepared drug composition can significantly reduce the AST level in model animals (56.7% vs 33.3%), significantly reduce the AST level in model animals (38.5% vs 12.3%), significantly increase the SOD level in model animals (38.1% vs 23.8%), and reduce the degree of fatty infiltration in liver tissue.

[0032] (2) The present invention uses a combination of alcohol extraction and water extraction, and decocts tangerine peel and kudzu root together, and decocts jujube fruit, poria cocos, wolfberry fruit and raspberry together. The resulting drug composition is more effective than the drug composition extracted by decocting all raw materials together, in reducing liver index, reducing alanine aminotransferase and aspartate aminotransferase levels, reducing malondialdehyde level and increasing superoxide dismutase level, and improving liver tissue morphology and structure, thus achieving the effect of treating alcoholic liver disease. Moreover, the therapeutic effect is better than that of biphenyl diester tablets positive control.

[0033] (3) Compared with decoction, the granule dosage form of traditional Chinese medicine composition of the present invention is more convenient to carry, take and store. Attached Figure Description

[0034] Figure 1 These are images showing the state of mice with alcoholic liver disease after modeling. Figure 2 These are the weight change curves of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group over time. Figure 3 This is a comparison chart of the liver coefficients of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group; Figure 4 This is a comparison chart of the levels of aspartate aminotransferase in the blood of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group; Figure 5 This is a comparison chart of the alanine aminotransferase (ALT) levels in the blood of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. Figure 6 This is a comparison chart of malondialdehyde levels in the liver tissues of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. Figure 7This is a comparison chart of superoxide dismutase levels in liver tissues of mice in the blank group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. Figure 8 These are histopathological images of liver tissue from mice in the control group; Figure 9 These are histopathological images of the liver tissue from the model group mice; Figure 10 These are histopathological images of liver tissue from mice in Example 1 group; Figure 11 These are histopathological images of the liver tissue of mice in Example 2. Detailed Implementation

[0035] The present invention will be further described in detail below with reference to the embodiments. The following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the following embodiments were performed under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the methods used are conventional methods known in the art, and the consumables and reagents used are commercially available. Unless otherwise stated, the technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods or materials similar to or equivalent to those described herein may also be applied to the present invention.

[0036] The traditional Chinese medicine composition of this invention has the effects of relieving hangovers and dispelling pathogenic factors, strengthening the spleen and resolving phlegm and dampness, and tonifying the liver and kidneys. This traditional Chinese medicine composition is particularly suitable for mild alcoholic fatty liver, liver protection and prevention in high-risk groups who frequently drink alcohol, and during the recovery period of mild alcoholic hepatitis. The efficacy and indications of each herb in the traditional Chinese medicine composition of this invention are as follows: "Hovenia dulcis fruit" refers to the fruit or seed of *Hovenia dulcis*, a plant belonging to the Rhamnaceae family. It has a sweet and sour taste and is neutral in nature; it enters the spleen meridian. It promotes diuresis, reduces swelling, and detoxifies alcohol. *Hovenia dulcis fruit* has a significant diuretic effect, promoting the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase, accelerating alcohol metabolism, and reducing acetaldehyde accumulation; it also inhibits lipid peroxidation in hepatocytes, reduces triglyceride deposition in the liver, improves alcoholic fatty liver, and alleviates alcohol-induced liver damage.

[0037] Kudzu root is the dried tuberous root of the legume *Pueraria lobata*. It has a sweet and pungent taste and is cool in nature; it enters the spleen, stomach, and lung meridians. It relieves muscle tension and fever, and promotes the production of body fluids and quenches thirst. Kudzu root contains puerarin, which expands hepatic microcirculation, improves hepatic blood supply, inhibits alcohol-induced hepatocyte inflammation and oxidative stress, alleviates lipid accumulation in the liver after drinking, helps lower transaminase levels, and improves alcohol-induced gastrointestinal damage.

[0038] "Poria" is the dried sclerotium of the fungus Poria cocos, belonging to the Polyporaceae family. It has a sweet and bland taste and is neutral in nature; it enters the heart, lung, spleen, and kidney meridians. Poria contains polysaccharides, which can strengthen the spleen and eliminate dampness, promote diuresis and remove turbidity, and reduce lipid deposition in the liver; it also protects the liver and has anti-inflammatory properties, reduces early indicators of liver fibrosis, and improves symptoms such as abdominal distension and fatigue caused by spleen deficiency due to alcohol.

[0039] "Chenpi" is the dried, mature peel of the citrus fruit, a plant belonging to the Rutaceae family. It has a pungent and bitter taste, and is warm in nature; it enters the spleen and lung meridians. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. Chenpi can regulate qi and strengthen the spleen, dry dampness and resolve phlegm, soothe the liver and gallbladder, relieve abdominal distension, nausea, and liver area distension caused by alcohol; inhibit fatty degeneration of the liver, promote gastrointestinal motility, and reduce the internal generation of dampness from alcohol.

[0040] Goji berries are the dried, ripe fruit of the Ningxia goji berry plant, belonging to the Solanaceae family. They are sweet in taste and neutral in nature; they enter the liver and kidney meridians. They nourish the liver and kidneys, benefit essence and improve eyesight. Goji berry polysaccharides have antioxidant properties, repair damaged liver cells, combat liver fibrosis, regulate blood lipids, and improve oxidative damage to liver tissue caused by alcoholic liver disease.

[0041] "Raspberry" refers to the dried, immature aggregate fruit of *Raspberry arvensis* (a member of the Rosaceae family). It has a sweet and sour taste and is warm in nature; it enters the liver, kidney, and bladder meridians. It has the effects of tonifying the kidneys and strengthening essence, nourishing the liver and improving eyesight. By tonifying the kidneys and strengthening essence, and nourishing the liver, it gently replenishes the liver and kidneys, reducing the continuous damage to the liver and kidneys caused by alcohol. Its medicinal properties are mild and not greasy or irritating to the stomach.

[0042] Example 1 Example 1 of this invention provides a traditional Chinese medicine composition and its granules that have preventive and / or therapeutic effects on alcoholic liver disease. The preparation steps are as follows: (1) Take 6g of dried tangerine peel and 12g of kudzu root powder, add 108g of 55% ethanol, control the temperature at 45℃ and soak for 1.5h, filter and collect the alcohol extract, add 108g of 55% ethanol to the filter residue again, control the temperature at 45℃ and soak for 1.5h, filter again to get the residue, combine the alcohol extracts obtained twice and recover the ethanol under reduced pressure, concentrate the alcohol extract to get the alcohol extract component; (2) Take 15g of Japanese raisin tree fruit, 15g of Poria cocos, 12g of wolfberry fruit and 10g of raspberry and mix with the residue obtained in the above steps. Add 416g of purified water and heat-soak at 90℃ for 1 hour. Filter and collect the water extract. Add 416g of purified water to the filter residue again and heat-soak at 90℃ for 1 hour. Filter again. Combine the two water extracts and evaporate and concentrate the water extract to obtain the water extract component. (3) Mix the alcohol extract and water extract evenly, and freeze dry under vacuum to obtain the traditional Chinese medicine composition.

[0043] (4) The above-obtained Chinese medicine composition is mixed with dextrin and lactose in a weight ratio of 3:2:1, stirred thoroughly, and granulated by wet extrusion to produce uniform wet granules.

[0044] (5) Dry the wet granules at a constant temperature of 60-65℃, and after cooling, granulate them through a 10-14 mesh sieve to remove fine powder and agglomerated granules.

[0045] (6) Select qualified granules according to the requirements of the 2025 edition of the Chinese Pharmacopoeia to obtain the finished granule product of the traditional Chinese medicine composition.

[0046] Example 2 Example 2 of this invention provides a traditional Chinese medicine composition and its granules that have the effect of preventing and / or treating alcoholic liver disease. The difference between Example 2 and Example 1 is that in the preparation process of Example 2, the amount of dried tangerine peel is 5g, the amount of kudzu root is 10g, the amount of ethanol used in a single hot soak is 90g, the amount of jujube fruit is 12g, the amount of poria cocos is 12g, the amount of wolfberry is 10g, the amount of raspberry is 8g, and the amount of water used in a single hot soak is 336g.

[0047] Comparative Example 1 Comparative Example 1 provides a traditional Chinese medicine composition and its granules. The difference between Comparative Example 1 and Example 2 is that Comparative Example 1 does not add Hovenia dulcis and Rubus idaeus during the preparation process, and the amount of water used for a single hot soak is 180g.

[0048] Comparative Example 2 Comparative Example 2 provides a traditional Chinese medicine composition and its granules, wherein the traditional Chinese medicine composition is prepared by decoction, and the specific steps are as follows: (1) Take 12g of kudzu root, 15g of Japanese raisin tree fruit, 15g of poria cocos, 6g of dried tangerine peel, 12g of wolfberry fruit and 10g of raspberry, crush them and pass them through a 20-mesh sieve, add cold water to cover the surface of the herbs by 2-3cm, and soak at room temperature for 30min.

[0049] (2) Add water (560g) equal to 8 times the total amount of medicine and simmer for 25 minutes. Filter the decoction through gauze and collect the decoction. Add 420g of water to the residue and simmer for 20 minutes. Filter again and combine the two decoctions. Concentrate the decoction under vacuum at 60°C until it becomes a thick paste to obtain the traditional Chinese medicine composition.

[0050] (3) Prepare the Chinese medicine composition into granule product according to steps (4), (5) and (6) of Example 1.

[0051] Comparative Example 3 Comparative Example 3 provides a positive control. The preparation steps are as follows: take biphenyl diester tablets, crush them, use 0.5% sodium carboxymethyl cellulose aqueous solution as the dispersion medium, grind and mix them, and prepare 100 mL of 10 mg / mL biphenyl diester suspension. Shake well before use.

[0052] Testing and Inspection Seventy male Kunming mice (6-8 weeks old, weighing 18-22g) were randomly divided into seven groups of ten each: control group, model group, Example 1 group, Example 2 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group.

[0053] Alcoholic liver disease modeling in mice: After one week of acclimatization, except for the control group mice which had free access to purified water daily, the other groups were administered 10% alcohol (v / v) by gavage once daily during week 1, 20% alcohol (v / v) once daily during week 2, and 42% alcohol (v / v) once daily during weeks 3-6. Two hours after the alcohol administration, the granules from Examples 1-2 and Comparative Examples 1-2 were ground and mixed using 0.5% sodium carboxymethyl cellulose aqueous solution as the dispersion medium to prepare a 10 mg / mL suspension, which was then administered by gavage to the mice in Examples 1-2 and Comparative Examples 1-2 groups, respectively. The suspension from Comparative Example 3 was administered by gavage to the mice in Comparative Example 3 group. The normal group and the model group were administered physiological saline by gavage. The gavage volume for all groups was 0.1 mL / 10 g body weight. The experiment lasted for 6 weeks. After the last gavage, the mice were fasted, and euthanized 12 hours later. Blood was collected from each group of experimental animals using centrifuge tubes containing anticoagulants, and the livers of each group of mice were separated.

[0054] Observations of food intake and mental state in each group of mice revealed that the control group mice maintained a stable food intake, were active, and had good mental state. However, mice in other groups, after receiving alcohol via gavage, showed a decrease in food intake over time, accompanied by symptoms of intoxication such as slow movement, unsteady gait, and general lethargy. The model group mice exhibited the following condition: Figure 1 As shown.

[0055] (1) Measurement of body weight and liver index The experiment was conducted continuously for 6 weeks. After the drug administration was completed, the mice in each group were fasted for 12 hours, and their body weight was recorded. The results are as follows: Figure 2 As shown; then the mice were euthanized by cervical dislocation, and their livers were dissected and weighed. The liver coefficient (%) was calculated by dividing the mouse's liver weight (g) by its body weight (g). The results are shown below. Figure 3 As shown, the liver coefficient is an important indicator reflecting increased liver volume and fat accumulation.

[0056] (2) Measurement of serum biochemical indicators Blood samples from each group of mice were centrifuged at 3000 rpm and 4°C for 15 minutes. The supernatant was then collected, and plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured using a kit. The results are as follows: Figure 4 and Figure 5 As shown.

[0057] (3) Measurement of liver injury-related indicators The isolated liver tissue was minced, washed 2-3 times with PBS buffer, homogenized, and then centrifuged at 12000 rpm for 10 min at 4°C. The supernatant was collected, and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in mouse liver tissue were measured using a kit. The results are as follows: Figure 6 and Figure 7 As shown.

[0058] (4) Histological analysis of hematoxylin and eosin (HE) staining Liver tissue samples from mice in the blank group, model group, Example 1 group, and Example 2 group were fixed in 4% paraformaldehyde for 24 h, then dehydrated in ethanol, embedded in paraffin, and prepared into 5 μm thick sections. The sections were stained with hematoxylin and eosin, and histopathological images of the liver tissue were obtained using an optical microscope. The results are as follows: Figure 8 , Figure 9 , Figure 10 and Figure 11 As shown.

[0059] (5) Statistical methods The results were analyzed using SPSS 27.0 statistical software. One-way ANOVA was used for comparisons among multiple groups, and t-test was used for comparisons between two groups. p<0.05 was considered statistically significant.

[0060] Results Analysis The experimental results provided in the testing and detection section are analyzed as follows.

[0061] Figure 2 The results showed that the body weight of mice in each group gradually increased over time, and no significant adverse reactions were observed. Figure 3 The results showed that the liver coefficient of the model group mice was significantly increased (#p<0.05), combined with Figure 1 The results indicate that the model of chronic alcoholic liver disease was successfully established; the traditional Chinese medicine compositions of Examples 1 and 2 have a significant reducing effect on liver indices caused by chronic alcohol use. (p<0.05) indicates that the herbal composition of the present invention is beneficial in inhibiting hepatomegaly induced by chronic alcoholic liver disease, and its effect is superior to that of the positive control drug biphenyl diester (comparative Example 3). The results also show that when the medicinal ingredients (Hovenia dulcis and Rubus idaeus) in the herbal composition of the present invention are removed (comparative Example 1), or the extraction method of the herbal composition of the present invention is changed (comparative Example 2), the inhibitory effect of the herbal composition on hepatomegaly caused by chronic alcoholic liver disease is significantly weakened. This suggests that the specific formula of the herbal composition extracted by the preparation method of the herbal composition of the present invention is beneficial in inhibiting hepatomegaly caused by chronic alcoholic liver disease and improving the efficacy of treatment for chronic alcoholic liver disease.

[0062] Reference Figure 4 and Figure 5 The results showed that, compared with the control group, the levels of AST and ALT in the model group were significantly increased (#p<0.05), indicating that the modeling was successful. The traditional Chinese medicine compositions of Examples 1 and 2 both had a very significant effect on reducing the increase in ALT and AST caused by chronic alcohol use. (p<0.05) indicates that the herbal composition of the present invention is beneficial in inhibiting hepatocellular damage caused by chronic alcoholic liver disease, and its effect is superior to that of the positive control drug biphenyl diester (comparative Example 3). The results also show that when the medicinal ingredients (Hovenia dulcis and Rubus idaeus) in the herbal composition of the present invention are removed (comparative Example 1), or the extraction method of the herbal composition of the present invention is changed (comparative Example 2), the inhibitory effect of the herbal composition on the increase of ALT and AST caused by chronic alcoholic liver disease is significantly weakened. This suggests that the herbal composition with a specific formula extracted by the preparation method of the herbal composition of the present invention is beneficial in inhibiting the increase of ALT and AST caused by chronic alcoholic liver disease, alleviating hepatocellular damage, and improving the efficacy of treatment for chronic alcoholic liver disease.

[0063] Reference Figure 6 and Figure 7 The results showed that MDA was significantly increased and SOD was significantly decreased in the model group compared with the control group (#p<0.05), indicating successful modeling. Both Example 1 and Example 2 groups showed significant improvement in MDA elevation and SOD reduction caused by chronic alcohol use. (p<0.05) indicates that the herbal composition of the present invention is beneficial in inhibiting oxidative stress caused by chronic alcoholic liver disease, and its effect is superior to that of the positive control drug biphenyl diester (comparative Example 3). The results also show that when the medicinal ingredients (Hovenia dulcis and Rubus idaeus) in the herbal composition of the present invention are removed (comparative Example 1), or the extraction method of the herbal composition of the present invention is changed (comparative Example 2), the inhibitory effect of the herbal composition on oxidative stress caused by chronic alcoholic liver disease is significantly weakened. This suggests that the herbal composition with a specific formula extracted by the preparation method of the herbal composition of the present invention is beneficial in improving the increase of MDA and the decrease of SOD caused by chronic alcoholic liver disease, alleviating oxidative stress, and improving the efficacy of treatment for chronic alcoholic liver disease.

[0064] Reference Figure 8-11The results showed that, compared with the normal group, the model group exhibited central venous congestion of varying sizes in the liver tissue, widespread fatty vacuolation of hepatocytes, disordered hepatocyte arrangement, significantly widened sinusoids, disappearance of cell nuclei, and necrosis and inflammatory cell infiltration, indicating that the liver tissue structure was damaged, and the model was successful. The liver tissue morphology and structure of the Example 1 and Example 2 groups were more intact, with most hepatocytes showing a tight arrangement, significantly reduced hepatocyte fatty degeneration, reduced central venous congestion, and significantly narrowed sinusoids. This indicates that the traditional Chinese medicine composition of Example 1 and Example 2 of this invention is beneficial for restoring the deterioration of liver tissue morphology and structure caused by chronic alcoholic liver disease, improving the integrity of liver tissue morphology and structure, and enhancing the therapeutic effect on chronic alcoholic liver disease.

[0065] Finally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0066] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0067] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for preparing a traditional Chinese medicine composition, characterized in that: Includes the following steps: Take dried tangerine peel and kudzu root, crush them, add ethanol, soak them at a warm temperature, filter them to obtain the residue and ethanol extract, concentrate the ethanol extract to obtain the ethanol extract component; take the residue, Japanese raisin tree fruit, poria cocos, wolfberry fruit and raspberry, mix them, add water, soak them at a hot temperature, filter them to obtain the water extract, concentrate the water extract to obtain the water extract component; mix the ethanol extract component and the water extract component and dry them to obtain the traditional Chinese medicine composition.

2. The preparation method of the traditional Chinese medicine composition according to claim 1, characterized in that: The ethanol has a weight concentration of 50%-60%, and the ratio of the total weight of the dried tangerine peel and kudzu root to the weight of the ethanol is 1:5-7.

3. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that: The temperature of the warm soaking is 40-50℃, the number of times is 1-3, and the duration of each soaking is 1-3 hours.

4. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that: The total weight ratio of the jujube fruit, poria cocos, wolfberry fruit, and raspberry to the weight of the water is 1:7-9.

5. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that: The hot immersion temperature is 85-95℃, the number of times is 1-4, and the duration of each time is 0.5-2 hours.

6. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that: The raw materials used include the following Chinese medicinal herbs in parts by weight: 10-13 parts of kudzu root, 5-7 parts of dried tangerine peel, 12-16 parts of Japanese raisin tree fruit, 12-16 parts of poria cocos, 10-13 parts of wolfberry fruit, and 8-11 parts of raspberry fruit.

7. A traditional Chinese medicine composition, characterized in that: It is prepared by the method of any one of claims 1-6 for the preparation of traditional Chinese medicine composition.

8. A traditional Chinese medicine composition preparation, characterized in that: It includes the traditional Chinese medicine composition as described in claim 7 and pharmaceutically acceptable excipients, and the dosage form is tablets, powders, granules, capsules or pills.

9. A method for preparing a traditional Chinese medicine composition formulation as described in claim 8, characterized in that: The traditional Chinese medicine composition, dextrin, and lactose are mixed and stirred evenly in a weight ratio of 2.5-3.5:2:1 to form wet granules. The wet granules are dried at a constant temperature and then sieved through a 10-14 mesh sieve to form granules. Qualified granules are screened to obtain a granule dosage form of traditional Chinese medicine composition preparation.

10. The use of a traditional Chinese medicine composition as described in claim 7 or a traditional Chinese medicine composition preparation as described in any one of claims 8-9 in the preparation of a medicament for the prevention and / or treatment of alcoholic liver disease.

Images