A traditional Chinese medicine composition with hepatoprotective and alcoholism-relieving effects, and a preparation method and application thereof

Abstract

This invention provides a traditional Chinese medicine composition with hepatoprotective and alcohol-relieving effects, made from the following raw materials in parts by weight: 1-5 parts rose petals, 1-5 parts chrysanthemum, 1-5 parts Japanese raisin tree fruit, 1-5 parts paper mulberry fruit, and 1-5 parts kudzu root. The traditional Chinese medicine composition of this invention can be prepared into decoctions, granules, powders, capsules, tablets, mixtures, or oral liquids using conventional pharmaceutical methods. The formulation of the traditional Chinese medicine composition of this invention is based on traditional Chinese medicine theory combined with modern medical research findings, and has hepatoprotective and alcohol-relieving effects. Experimental studies have shown that this composition has good preventive and therapeutic effects on alcoholic liver damage and cirrhosis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medicine, and particularly relates to a traditional Chinese medicine composition with the functions of protecting liver and relieving alcoholism, which is composed of rose, chrysanthemum, jujube seed, hackberry and kudzu root. BACKGROUND

[0002] In recent years, with the improvement of people's living standards in China, the consumption structure is continuously upgraded, the output of wine in China is continuously increased, and the incidence of alcohol consumption and alcoholic liver disease is also increasing year by year. According to the white paper data of "China Drinking Population Moderate Drinking Status" released by China Wine Industry Association, the drinking population in China is as high as 600 million. Among them, the 18 to 35 age group is the main drinking population, and at least once a day on average. As high as 76% of 36 to 45 year old men drink at least once a day; 53% of 26 to 35 year old women drink once a day.

[0003] Although there is a lack of nationwide epidemiological data on alcoholic liver disease (ALD), some epidemiological surveys show that the prevalence of ALD in China is on the rise. In 2000, the prevalence of ALD in China was 2.27%, and in 2015 it had increased to 8.74%. Among them, the number of male ALD patients and the number of male drinkers increased proportionally. In 2005, 23.4% of male liver cancer-related deaths and 2.2% of female liver cancer-related deaths in China were due to ALD. In 1990, the number of liver cancer deaths caused by drinking in China and the age-standardized mortality rate per 100,000 people were 45333 (95% UI: 39927-50465) and 6.02 (95% UI: 5.34-6.67), respectively, while in 2013 they were 25665 (95% UI: 21358-30338) and 1.87 (95% UI: 1.57-2.20), respectively. The decrease in this data is mainly based on the improvement of health and medical level in China. The huge base of ALD patients in China is still a heavy burden in the field of public health. How to let people drink in a civilized and healthy way, both to meet people's social requirements for drinking consumption and to carry out early intervention on excessive drinking to reduce ALD patients in China, is a major issue currently faced by the health field in China.

[0004] The pathogenesis of acute liver disease (ALD) is caused by multiple factors. Early events such as steatosis, reactive oxygen species (ROS) generation, and mitochondrial damage are direct results of ethanol metabolism and are common characteristics of both acute and chronic alcohol exposure. During alcohol metabolism in the liver, the levels of reduced coenzyme I (NADH) and coenzyme I (NAD) increase. An elevated NADH / NAD ratio leads to abnormal redox states in hepatocytes, altering some NAD-dependent biochemical reactions and exacerbating the deposition of fatty acids and triglycerides in the liver. Alcohol intake increases the generation of reactive oxygen species, causing more lipid, protein, and DNA peroxidation. Long-term excessive alcohol consumption leads to the accumulation of excessive free radicals in the body, inducing phospholipase activation and lipid peroxidation, ultimately resulting in hepatocyte lesions. Alcohol can also directly damage the function and membrane fluidity of microtubules and mitochondria in hepatocytes, affecting protein output and lipid metabolism, and is an important basis for hepatocyte steatosis and necrosis. Targeting these early pathological mechanisms with appropriate drugs is considered an effective strategy to inhibit the progression of ALD.

[0005] Recent studies have shown that traditional Chinese medicine (TCM) has great potential in protecting against alcoholic liver injury due to its low toxicity and drug dependence, and its ability to address both the symptoms and root cause of the problem, particularly in improving liver function. Existing research indicates that the protective mechanisms of TCM against alcoholic liver injury mainly involve regulating hepatic lipid peroxidation, reducing the production of pro-inflammatory factors in liver tissue, increasing antioxidant enzyme levels, and inhibiting apoptosis. These effects are often multi-component, multi-process, and multi-target integrated. However, although many animal experiments have shown that a large number of TCM herbs have a certain protective effect against alcoholic liver injury in animal models, few studies have been successfully applied to human populations. Summary of the Invention

[0006] Therefore, the purpose of this invention is to provide a traditional Chinese medicine composition with liver-protecting and alcohol-relieving effects, as well as its preparation method and application, for alcoholic liver disease.

[0007] On the one hand, the present invention provides a traditional Chinese medicine composition with liver-protecting and hangover-relieving effects, which is made from the following raw materials in parts by weight: 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of Japanese raisin tree fruit, 1-5 parts of paper mulberry fruit, and 1-5 parts of kudzu root.

[0008] In a preferred embodiment of the present invention, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 1-2 parts rose, 1-2 parts chrysanthemum, 1-2 parts Japanese raisin tree fruit, 1-2 parts paper mulberry fruit, and 1-2 parts kudzu root.

[0009] In the most preferred embodiment of the present invention, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 1 part rose, 1 part chrysanthemum, 1 part Japanese raisin tree fruit, 1 part paper mulberry fruit, and 1 part kudzu root.

[0010] In some embodiments of the present application, the traditional Chinese medicine composition is concentrated traditional Chinese medicine granules and / or traditional Chinese medicine extract of the raw material medicine.

[0011] In some embodiments of the present application, the traditional Chinese medicine composition is prepared into oral preparations by using conventional pharmaceutical methods in pharmacy.

[0012] Further, the above-mentioned traditional Chinese medicine composition can be decoction, granules, powder, capsules, tablets, mixture or oral liquid.

[0013] In another aspect, the present application also provides a preparation method of a traditional Chinese medicine composition with the effects of protecting liver and relieving alcoholism, comprising the following steps:

[0014] (1) 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of jujube fruit, 1-5 parts of horse chestnut and 1-5 parts of radix puerariae are weighed by weight parts and ground;

[0015] (2) hot extraction is performed with 5-15 times weight of 50-95% ethanol for 0.5-2 hours, and extraction is performed for 1-3 times;

[0016] (3) the extract is filtered, centrifuged and concentrated.

[0017] In a preferred embodiment of the present application, the raw material medicine in step (1) is 1-2 parts of rose, 1-2 parts of chrysanthemum, 1-2 parts of jujube fruit, 1-2 parts of horse chestnut and 1-2 parts of radix puerariae.

[0018] In a most preferred embodiment of the present application, the raw material medicine in step (1) is 1 part of rose, 1 part of chrysanthemum, 1 part of jujube fruit, 1 part of horse chestnut and 1 part of radix puerariae.

[0019] In some embodiments of the present application, the temperature of the hot extraction in step (2) can be 60-80°C, and most preferably about 70°C.

[0020] In some embodiments of the present application, step (3) can further comprise freeze-drying the obtained concentrated solution and grinding into fine powder.

[0021] In some embodiments of the present application, step (3) can further comprise freeze-drying the obtained concentrated solution, grinding into fine powder, then adding excipients and loading into hard capsules.

[0022] In another aspect, the present application also provides a medicine or health product for preventing and / or treating alcoholic liver injury, wherein the medicine or health product comprises the traditional Chinese medicine composition provided by the present application.

[0023] In another aspect, the present application also provides a medicine or health product for preventing and / or treating liver cirrhosis, which comprises the traditional Chinese medicine composition provided by the present application.

[0024] The traditional Chinese medicine composition of the present application is screened on the basis of traditional Chinese medicine theory combined with modern medical research results, and has the effects of protecting liver and relieving alcoholism. Experimental research shows that the composition has good preventive and therapeutic effects on alcoholic liver injury and liver cirrhosis. BRIEF DESCRIPTION OF DRAWINGS

[0025] Hereinafter, the embodiments of the present application will be described in detail with reference to the accompanying drawings, in which:

[0026] Figure 1 HPLC chromatographic analysis results of Example 1 of the present application;

[0027] Figure 2 Experimental results of the effects of the traditional Chinese medicine composition in each group on the mouse model of acute alcoholic liver injury in Example 6;

[0028] Figure 3 Experimental results of the effects of the traditional Chinese medicine composition in each group on the mouse model of chronic alcoholic liver injury in Example 7. DETAILED DESCRIPTION

[0029] The present application will be further described in detail below with reference to the specific embodiments, and the given examples are only for illustrating the present application, but not for limiting the scope of the present application.

[0030] Example 1

[0031] Preparation of the traditional Chinese medicine composition and detection of the chemical fingerprint

[0032] 1. Experimental materials

[0033] 1.1 Reagents: acetonitrile is chromatographically pure, and water is deionized water

[0034] 1.2 Test drug: equal weights of rose, chrysanthemum, jujube, Chinese hackberry and kudzu root were weighed, ground and crushed, then hot-extracted with 10 times the amount of 75% ethanol for 2h, the extract was filtered and centrifuged, and then the extract was freeze-dried and crushed into fine powder. The above powder was prepared into 50mg / ml with methanol, filtered through a 0.22μm filter membrane, and then tested on the machine.

[0035] 2. HPLC analysis: the chromatographic conditions are shown in Table 1.

[0036] Octadecylsilane-bonded silica gel was used as the filler, the detection wavelength was 254nm, the injection amount was 5μl, and finally the detector was used for detection and analysis.

[0037] Table 1. HPLC chromatographic conditions

[0038] mobile phase acetonitrile water 0 5 95 75 100 0

[0039] 2. Experimental results

[0040] Experimental results please see Figure 1 By ultraviolet spectrum and retention time comparison, it can be known that the main component in the traditional Chinese medicine extract is puerarin.

[0041] Example 2

[0042] Prescription: rose 500g, chrysanthemum 500g, jujube 500g, Chinese ash 500g, pueraria 500g

[0043] Method: take dry rose 500g, chrysanthemum 500g, jujube 500g, Chinese ash 500g, pueraria 500g, add 25 liters of 75% alcohol hot dip twice, each time 2 hours, combine the filtrate, concentrate, freeze-drying, get the traditional Chinese medicine composition of the invention.

[0044] Example 3

[0045] Prescription: rose 500g, chrysanthemum 500g, jujube 500g, Chinese ash 500g, pueraria 500g

[0046] Method: take dry rose 500g, chrysanthemum 500g, jujube 500g, Chinese ash 500g, pueraria 500g, add 20 liters of 50% alcohol hot dip three times, each time 1 hour, combine the filtrate, concentrate, add appropriate amount of starch, magnesium stearate, mix evenly, made into granules, dry, press into tablets, coating, made into 1000 tablets.

[0047] Example 4

[0048] Prescription: rose 200g, chrysanthemum 100g, jujube 200g, Chinese ash 500g, pueraria 500g

[0049] Method: take dry rose 200g, chrysanthemum 100g, jujube 200g, Chinese ash 500g, pueraria 500g, add 50 liters of 90% alcohol hot dip once, a total of 2 hours, concentrate the filtrate, add appropriate amount of dextrin, mix evenly, made into granules, loaded into capsules, made into hard capsule 1000.

[0050] Example 5

[0051] Prescription: rose 300g, chrysanthemum 200g, jujube 200g, Chinese ash 400g, pueraria 100g

[0052] Preparation: rose 200g, chrysanthemum 200g, jujube 200g, paper mulberry fruit 300g, kudzu root 100g, hot soak in 12.5L 75% alcohol for three times, 0.5h each time, combine the filtrate, concentrate to no alcohol, filter, add water to adjust the total volume to 5000mL, fill in bottles, 5mL per bottle, sterilize, make into oral liquid 1000 bottles.

[0053] Example 6

[0054] Effect of the traditional Chinese medicine composition on the acute alcoholic liver injury model of mice

[0055] In this experiment, the acute alcoholic liver injury model of mice close to the clinic was used to observe the effect of the traditional Chinese medicine composition on the sober-up time and liver function indexes of the mice.

[0056] 1. Experimental method

[0057] The alcoholic liver injury model of mice was established by ethanol (6g / kg, gavage) or maltodextrin solution (control group). Under this dose of alcohol, the mice were sluggish, but their consciousness was clear, and they returned to normal behavior within 6 hours after drinking.

[0058] 6-8 weeks old C57 male mice were divided into model group, control group and traditional Chinese medicine composition experimental group (the experimental group used the prescription of the traditional Chinese medicine composition of Example 1, marked as composition 1), wherein the traditional Chinese medicine composition experimental group was further divided into low, medium and high dose groups (1.8, 3.6, 7.2g / kg), and composition minus jujube group (except that it did not contain jujube, the other ingredients were the same as composition 1), composition minus kudzu root group (except that it did not contain kudzu root, the other ingredients were the same as composition 1), composition minus chrysanthemum group (except that it did not contain chrysanthemum, the other ingredients were the same as composition 1), each group of mice had 6 mice. The mice in the model group and the control group were given 0.2mL of distilled water by gavage once a day, and the mice in all experimental groups were given the corresponding dose of traditional Chinese medicine composition by gavage, for 10 consecutive days. On the last day, one hour after gavage, the mice in the model group and the experimental group were given ethanol gavage (6g / kg), and the mice in the control group were given the same volume of distilled water by gavage. After the ethanol gavage, the mice were strictly monitored, and the time of mouse activity retardation was recorded. This would help to observe whether the traditional Chinese medicine composition could alleviate the fatigue caused by alcohol. After 12 hours, the mice were anesthetized and sacrificed, and liver tissue samples were collected.

[0059] 2. Experimental results

[0060] The experimental results are shown in Figure 2 , which show that the traditional Chinese medicine composition of the present application can effectively accelerate the time of mice returning to normal activity, indicating that it has good alcoholism-relieving function Figure 2 , and the traditional Chinese medicine extract has significant improvement effect on liver cell fat deposition and inflammatory infiltrationFigure 2 (See Figure b). This suggests that the herbal extract has a significant preventive effect on acute liver injury caused by alcohol. Furthermore, comparative experiments showed that removing Hovenia dulcis, Pueraria lobata, or Chrysanthemum from the herbal composition all affected its hangover-relieving effect.

[0061] Example 7

[0062] Effects of the herbal composition of this invention on a mouse model of chronic alcoholic liver injury

[0063] Since the vast majority of alcohol poisoning patients have a recent history of excessive drinking and a long history of chronic drinking, the acute-chronic drinking pattern (NIAAA model) is similar to the drinking pattern of ALD patients and can better simulate the pathological changes of alcoholic liver disease patients.

[0064] 1. Experimental Methods

[0065] All 6-8 week old male C57 mice were fed a control liquid diet (BioServ, Frenchtown, NJ) for 5 days to acclimatize them to the liquid diet. Subsequently, the mice were randomly assigned to three groups: a model group, a blank control group, and three experimental groups using traditional Chinese medicine compositions (the experimental groups used the traditional Chinese medicine composition prescriptions from Examples 1, 3, and 5, respectively, and were designated as Composition 1, Composition 2, and Composition 3), with 5 mice in each group.

[0066] The model group and experimental group received an ethanol liquid diet (Bio Serv, Frenchtown, NJ) for 11 days, while the control group received a control liquid diet. During the experiment, the experimental group mice were administered 3.6 g / kg of the herbal extract via gavage daily, while the model group and control group mice received the same volume of distilled water via gavage. On day 11, the model group and all herbal extract experimental group mice were administered ethanol (5 g / kg) via gavage, while the control group received the same volume of distilled water via gavage. Similarly, 9 hours after ethanol gavage, the mice were sacrificed, and serum and liver tissues were collected. Serum AST and ALT activities and liver histological changes (H&E staining) were measured.

[0067] 2. Experimental Results

[0068] Experimental results are as follows Figure 3 As shown, the results indicate that the traditional Chinese medicine composition of the present invention has a significant inhibitory effect on liver enzyme activity. Figure 3 Figure a) shows a significant improvement in hepatocyte fat deposition and inflammatory infiltration. Figure 3 (See Figure b). This suggests that the extract of this traditional Chinese medicine has a significant therapeutic effect on chronic liver damage caused by alcohol.

[0069] The above embodiments are only preferred embodiments of the present application, and do not limit the present application in any way. Any person skilled in the art can make any equivalent replacement or modification to the technical solutions and technical contents disclosed by the present application without departing from the technical solutions of the present application, and still falls within the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition having a hepatoprotective and alcohol-eliminating effect, the hepatoprotective and alcohol-eliminating effect being treatment of alcoholic liver injury. It is made of raw medicinal materials in the following weight parts: rose 1-5 parts, chrysanthemum 1-5 parts, jujube 1-5 parts, Chinese hackberry 1-5 parts and kudzu root 1-5 parts, and its preparation method comprises the following steps: (1) the raw medicinal materials are weighed according to weight parts and are ground and crushed; (2) hot extraction is carried out with 5-15 times weight of 50-95% ethanol for 0.5-2 hours, and extraction is carried out 1-3 times; (3) the extraction liquid is filtered, centrifuged and concentrated.

2. The traditional Chinese medicine composition for protecting liver and alleviating alcoholism according to claim 1, wherein, The traditional Chinese medicine composition is made of raw medicinal materials in the following weight parts: rose 1-2 parts, chrysanthemum 1-2 parts, jujube 1-2 parts, Chinese hackberry 1-2 parts and kudzu root 1-2 parts.

3. The traditional Chinese medicine composition for protecting liver and alleviating alcoholism according to claim 1, wherein, The traditional Chinese medicine composition is made of raw medicinal materials in the following weight parts: rose 1 part, chrysanthemum 1 part, jujube 1 part, Chinese hackberry 1 part and kudzu root 1 part.

4. The traditional Chinese medicine composition for hepatoprotective and alcoholism-alleviating effects according to any one of claims 1 to 3, wherein, The traditional Chinese medicine composition is concentrated traditional Chinese medicine granules and / or traditional Chinese medicine extract of the raw medicinal materials.

5. The traditional Chinese medicine composition for protecting liver and alleviating alcoholism according to claim 1, wherein, The traditional Chinese medicine composition is a decoction, granules, powder, capsule, tablet, mixture or oral liquid.

6. A preparation method of a traditional Chinese medicine composition with the functions of protecting liver and relieving alcohol, the function of protecting liver and relieving alcohol being the treatment of alcoholic liver injury, the preparation method comprising the following steps: (1) rose 1-5 parts, chrysanthemum 1-5 parts, jujube 1-5 parts, Chinese hackberry 1-5 parts and kudzu root 1-5 parts are weighed according to weight parts, and are ground and crushed; (2) hot extraction is carried out with 5-15 times weight of 50-95% ethanol for 0.5-2 hours, and extraction is carried out 1-3 times; (3) the extraction liquid is filtered, centrifuged and concentrated.

7. The production method according to claim 6, wherein The raw medicinal materials in step (1) are: rose 1-2 parts, chrysanthemum 1-2 parts, jujube 1-2 parts, Chinese hackberry 1-2 parts and kudzu root 1-2 parts.

8. The production method according to claim 6, wherein The raw medicinal materials in step (1) are: rose 1 part, chrysanthemum 1 part, jujube 1 part, Chinese hackberry 1 part and kudzu root 1 part.

9. The production method according to claim 6, wherein The temperature of the hot extraction in step (2) is 60-80 ℃.

10. The production method according to claim 9, wherein The temperature of the hot extraction is 70 ℃.

11. The production method according to claim 6, wherein The step (3) further comprises freeze-drying the obtained concentrated liquid and crushing it into fine powder.

12. The method of making according to claim 6, wherein, The step (3) further comprises freeze-drying the obtained concentrated liquid, crushing it into fine powder, then adding excipients and loading into hard capsules.

13. A medicine for preventing and / or treating alcoholic liver injury, the medicine being made of the traditional Chinese medicine composition according to any one of claims 1 to 5.

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