CN118121648A - Traditional Chinese medicine composition with liver protecting and alcohol effect dispelling effects and preparation method and application thereof - Google Patents
Traditional Chinese medicine composition with liver protecting and alcohol effect dispelling effects and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a traditional Chinese medicine composition with liver protecting and anti-alcohol effects, which is prepared from the following raw materials in parts by weight: 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of hovenia dulcis thunb, 1-5 parts of fructus Broussonetiae and 1-5 parts of radix puerariae. The traditional Chinese medicine composition can be prepared into decoction, granules, powder, capsules, tablets, mixture or oral liquid by adopting a conventional pharmaceutical method in pharmacy. The compatibility of the traditional Chinese medicine composition is obtained by combining modern medical research results on the basis of the theory of traditional Chinese medicine, has the effects of protecting liver and dispelling alcohol, and experimental research shows that the composition has better prevention and treatment effects on alcoholic liver injury and liver cirrhosis.
Description
Technical Field
The invention belongs to the field of medicines, and in particular relates to a traditional Chinese medicine composition with liver protecting and anti-alcohol effects, which consists of rose, chrysanthemum, raisin tree seed, papermulberry fruit and kudzuvine root.
Background
In recent years, with the improvement of the living standard of people in China, the consumption structure is continuously upgraded, the wine yield in China is continuously increased, and the drinking rate and the incidence rate of alcoholic liver diseases are also in a trend of rising year by year. According to white paper data published by China wine society, the drinking status of proper amount of China drinking crowd is up to 6 hundred million. Wherein, the people in 18 to 35 years old are the main people for drinking, and at least one drinking is carried out every day on average. Up to 76% of men aged 36 to 45 who drink wine at least once a day; 53% of women 26 to 35 years old drink wine once a day.
Despite the lack of epidemiological data about alcoholic liver disease (Alcoholic LIVER DISEASE, ALD) nationwide, partial epidemiological surveys have shown that the prevalence of ALD in China is on the rise. ALD prevalence in China was 2.27% in 2000, and has increased by 8.74% in 2015. Wherein, the number of men with ALD disease increases in proportion to the number of men drinking. In 2005, 23.4% of the death associated with liver cancer in men and 2.2% of the death associated with liver cancer in women in our country were due to ALD. In 1990, the number of liver cancer deaths caused by drinking of various ages in China and the age-standardized mortality rate per 100000 are 45333 (95% UI: 39927-50465) and 6.02 (95% UI: 5.34-6.67), respectively, and 25665 (95% UI: 21358-30338) and 1.87 (95% UI: 1.57-2.20), respectively, in 2013. This reduction in data is based mainly on the improvement of health welfare and medical level in our country. The huge cardinality of ALD patient population in China is still a heavy burden in the public health field. How to enable people to drink wine civilized and healthy, not only meeting the social requirements of people on drinking and consumption, but also performing early intervention on excessive drinking, reducing ALD patients in China, and being a big subject currently facing the sanitary field in China.
The pathogenesis of ALD is due to a variety of factors, with early events such as steatosis, reactive Oxygen Species (ROS) formation, and mitochondrial damage being direct results of ethanol metabolism, a common feature of acute and chronic alcohol exposure. In the metabolism of alcohol in liver, reduced coenzyme I (NADH) and coenzyme I (NAD) are increased, and the increase of NADH/NAD ratio can cause abnormal oxidation-reduction state in liver cells, so that some biochemical reactions depending on NAD are changed, and the deposition of fatty acid and triglyceride in liver is aggravated. Alcohol intake increases the production of reactive oxygen species, causing more peroxidation of lipids, proteins and DNA. Excessive drinking for a long period of time can cause the body to accumulate excessive free radicals, induce activation of phospholipase and lipid peroxidation, and finally cause hepatopathy. Alcohol can also directly damage functions of microtubules and mitochondria in liver cells and fluidity of membranes, influence protein output, fat metabolism and the like, and is an important basis for hepatic cell steatosis and necrosis. Targeting these early lesion mechanisms with appropriate drug control is considered an effective strategy to inhibit ALD progression.
In recent years, research shows that the Chinese herbal medicine has small toxic and side effects and drug dependence, has the characteristic of treating both principal and secondary aspects of disease on the aspect of protecting mechanism, and particularly has great potential in the aspect of improving liver function, so that the Chinese herbal medicine has great potential in the aspect of protecting alcoholic liver injury. The existing researches show that the protection mechanism of the Chinese herbal medicine on alcoholic liver injury is mainly the functions of regulating liver lipid peroxidation, reducing liver tissue pro-inflammatory factors, improving antioxidant enzyme level, inhibiting apoptosis and the like, and the functions are often the integration functions of multiple components, multiple links and multiple targets. However, although many animal experiments show that a large number of Chinese herbal medicines have a certain protection effect on alcoholic liver injury on animal models, the method can truly study the landing and is not applied to the population.
Disclosure of Invention
Therefore, the invention aims to provide a traditional Chinese medicine composition with liver protecting and anti-alcohol effects for treating alcoholic liver disease injury, and a preparation method and application thereof.
On one hand, the invention provides a traditional Chinese medicine composition with liver protecting and anti-alcohol effects, which is prepared from the following raw materials in parts by weight: 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of hovenia dulcis thunb, 1-5 parts of fructus Broussonetiae and 1-5 parts of radix puerariae.
In a preferred embodiment of the invention, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 1-2 parts of rose, 1-2 parts of chrysanthemum, 1-2 parts of hovenia dulcis thunb, 1-2 parts of fructus Broussonetiae, and 1-2 parts of radix puerariae.
In the most preferred embodiment of the invention, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 1 part of rose, 1 part of chrysanthemum, 1 part of semen hoveniae, 1 part of fructus Broussonetiae, and 1 part of radix puerariae.
In some embodiments of the invention, the traditional Chinese medicine composition is concentrated traditional Chinese medicine particles and/or traditional Chinese medicine extracts of the crude drug.
In some embodiments of the present invention, the traditional Chinese medicine composition is prepared into an oral preparation by a conventional pharmaceutical method in pharmacy.
Further, the traditional Chinese medicine composition can be decoction, granules, powder, capsules, tablets, mixture or oral liquid.
On the other hand, the invention also provides a preparation method of the traditional Chinese medicine composition with the liver protecting and anti-alcohol effects, which comprises the following steps:
(1) Weighing 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of hovenia dulcis thunb, 1-5 parts of papermulberry fruit and 1-5 parts of kudzuvine root according to parts by weight, grinding and crushing;
(2) Extracting with 5-15 times of 50-95% ethanol for 0.5-2 hours for 1-3 times;
(3) The extract was filtered, centrifuged and concentrated.
In a preferred embodiment of the invention, the bulk drug in the step (1) is 1-2 parts of rose, 1-2 parts of chrysanthemum, 1-2 parts of hovenia dulcis thunb, 1-2 parts of papermulberry fruit and 1-2 parts of kudzuvine root.
In the most preferred embodiment of the invention, the bulk drugs in the step (1) are 1 part of rose, 1 part of chrysanthemum, 1 part of hovenia dulcis thunb, 1 part of papermulberry fruit and 1 part of kudzuvine root.
In some embodiments of the invention, the temperature of the hot dip extraction in step (2) may be from 60 to 80 ℃, most preferably about 70 ℃.
In some embodiments of the present invention, the step (3) may further comprise freeze-drying and pulverizing the resulting concentrate into fine powder.
In some embodiments of the present invention, the step (3) may further include freeze-drying the obtained concentrated solution, pulverizing into fine powder, then adding an auxiliary material, and encapsulating.
In still another aspect, the invention also provides a medicine or health care product for preventing and/or treating alcoholic liver injury, wherein the medicine or health care product comprises the traditional Chinese medicine composition provided by the invention.
In still another aspect, the invention also provides a medicine or health care product for preventing and/or treating liver cirrhosis, wherein the medicine or health care product comprises the traditional Chinese medicine composition provided by the invention.
The compatibility of the traditional Chinese medicine composition is obtained by combining modern medical research results on the basis of the theory of traditional Chinese medicine, has the effects of protecting liver and dispelling alcohol, and experimental research shows that the composition has better prevention and treatment effects on alcoholic liver injury and liver cirrhosis.
Drawings
Embodiments of the present invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1 shows the results of HPLC chromatography in example 1 of the present invention;
FIG. 2 is a graph showing experimental results of the effect of each group of the Chinese medicinal composition in example 6 on the acute alcoholic liver injury model of mice;
FIG. 3 is an experimental result of the effect of the chronic alcoholic liver injury model of each group of mice with the Chinese medicinal composition in example 7.
Detailed Description
The following detailed description of the invention is provided in connection with the accompanying drawings that are presented to illustrate the invention and not to limit the scope thereof.
Example 1
Preparation of traditional Chinese medicine composition and detection of chemical fingerprint
1. Experimental materials
1.1 Reagent: acetonitrile is chromatographic pure, water is deionized water
1.2 Test agent: weighing equal weight of flos Rosae Rugosae, flos Chrysanthemi, semen Hoveniae, fructus Broussonetiae and radix Puerariae, grinding, pulverizing, hot-soaking with 10 times of 75% ethanol for 2 hr, filtering the extractive solution, centrifuging, lyophilizing the extractive solution, and pulverizing into fine powder. 50mg/ml of the above powder was prepared with methanol, and the powder was subjected to an on-machine test after passing through a 0.22 μm filter.
Hplc analysis: the chromatographic conditions are shown in Table 1 below.
Octadecylsilane chemically bonded silica is used as a filler, the detection wavelength is 254nm, the sample injection amount is 5 μl, and finally a sample detector is used for detection and analysis.
TABLE 1 HPLC chromatographic conditions
Mobile phase | Acetonitrile | Water and its preparation method |
0 | 5 | 95 |
75 | 100 | 0 |
2. Experimental results
The experimental results are shown in FIG. 1. Comparing the ultraviolet spectrum and retention time, the main component of the extract is puerarin.
Example 2
Prescription: 500g of rose, 500g of chrysanthemum, 500g of semen hoveniae, 500g of fructus Broussonetiae, and 500g of radix puerariae
The preparation method comprises the following steps: taking 500g of dried rose, 500g of chrysanthemum, 500g of semen hoveniae, 500g of fructus Broussonetiae and 500g of radix puerariae, adding 25 liters of 75% alcohol, hot dipping twice, each time for 2 hours, combining the filtrates, concentrating, and freeze-drying to obtain the traditional Chinese medicine composition.
Example 3
Prescription: 500g of rose, 500g of chrysanthemum, 500g of semen hoveniae, 500g of fructus Broussonetiae, and 500g of radix puerariae
The preparation method comprises the following steps: taking 500g of dried rose, 500g of chrysanthemum, 500g of semen hoveniae, 500g of fructus Broussonetiae and 500g of radix puerariae, adding 20 liters of 50% alcohol, hot dipping for three times each time for 1 hour, combining the filtrates, concentrating, adding a proper amount of starch and magnesium stearate, uniformly mixing, granulating, drying, pressing into tablets, coating and preparing 1000 tablets.
Example 4
Prescription: 200g of rose, 100g of chrysanthemum, 200g of semen hoveniae, 500g of fructus Broussonetiae and 500g of radix puerariae
The preparation method comprises the following steps: taking 200g of dried rose, 100g of chrysanthemum, 200g of semen hoveniae, 500g of fructus Broussonetiae and 500g of radix puerariae, adding 50 liters of 90% alcohol, hot dipping once for 2 hours, concentrating filtrate, adding a proper amount of dextrin, uniformly mixing, granulating, and encapsulating to obtain 1000 hard capsules.
Example 5
Prescription: 300g of rose, 200g of chrysanthemum, 200g of semen hoveniae, 400g of fructus broussonetiae and 100g of radix puerariae
The preparation method comprises the following steps: 200g of rose, 200g of chrysanthemum, 200g of semen hoveniae, 300g of fructus Broussonetiae and 100g of radix puerariae, adding 12.5 liters of 75% alcohol, hot dipping for three times for 0.5 hour, combining filtrates, concentrating until no alcohol exists, filtering, adding water into the filtrate to adjust the total amount to 5000mL, filling, 5mL each branch, sterilizing, and preparing 1000 branches of oral liquid.
Example 6
Influence of the Chinese medicinal composition on the acute alcoholic liver injury model of mice
The experiment adopts a mouse acute alcoholic liver injury model which is relatively similar to clinic, and the influence of the traditional Chinese medicine composition on sober-up time and liver function indexes of the traditional Chinese medicine composition is observed.
1. Experimental method
The alcoholic liver injury model of mice was established with ethanol (6 g/kg lavage) or maltodextrin solution (control). At this dose of alcohol, the mice were unresponsive, but conscious, and recovered from normal behavior within 6 hours after drinking.
The C57 male mice of 6-8 weeks were divided into a model group, a control group and a traditional Chinese medicine composition experimental group (the experimental group adopts the traditional Chinese medicine composition prescription of example 1 and is marked as composition 1), wherein the traditional Chinese medicine composition experimental group comprises three groups (1.8, 3.6 and 7.2 g/kg) of low, medium and high dosages, a composition reduced hovenia dulcis subgroup (except for the hovenia dulcis, the other components are the same as composition 1), a composition reduced kudzuvine root group (except for the kudzuvine root, the other components are the same as composition 1), a composition reduced chrysanthemum group (except for the chrysanthemum, the other components are the same as composition 1), and 6 mice of each group are respectively. Model and control mice will be filled with 0.2mL of distilled water once daily, and all experimental mice will be filled with the corresponding doses of the Chinese medicinal composition for 10 consecutive days. On the last day, after one hour of gavage, the model and experimental mice were subjected to ethanol gavage (6 g/kg), and the control group was subjected to an equal volume of distilled water gavage. After the ethanol gastric lavage treatment, mice were monitored strictly and the time of bradykinesia was recorded. This will help to see if the Chinese medicinal composition can alleviate alcohol induced fatigue. After 12 hours, mice were sacrificed under anesthesia and liver tissue samples were collected.
2. Experimental results
The experimental result is shown in figure 2, and the result shows that the traditional Chinese medicine composition can effectively accelerate the time for the mice to recover normal activities, which indicates that the traditional Chinese medicine composition has a better anti-alcohol function (a graph of figure 2); the Chinese medicinal extract has remarkable improving effect on hepatic cell fat deposition and inflammatory infiltration (b diagram of FIG. 2). The traditional Chinese medicine extract is suggested to have remarkable prevention effect on acute liver injury caused by alcohol. In addition, the comparison experiment shows that the Chinese medicinal composition minus semen Hoveniae, radix puerariae or chrysanthemum all have influence on the anti-alcohol effect.
Example 7
Influence of the Chinese medicinal composition on the chronic alcoholic liver injury model of mice
Because most alcoholism patients have a history of recent excessive drinking and a history of years of chronic drinking, the acute-chronic drinking mode (NIAAA model) is similar to the ALD patient drinking mode, and can better simulate pathological changes of alcoholic liver disease patients.
1. Experimental method
All 6-8 week C57 male mice will be fed control liquid diet (Control liquid diet, bio Serv, frenchtown, NJ) for 5 days to adapt to the liquid diet. Subsequently, mice were randomly grouped into a model group, a blank group and three experimental groups of the Chinese medicinal composition (experimental groups were respectively prescribed with the Chinese medicinal compositions of examples 1, 3 and 5, which were sequentially designated as composition 1, composition 2 and composition 3), each group of 5 mice.
Model and experimental groups received liquid alcohol diet (Ethanol liquid diet, bio Serv, frenchtown, NJ) for 11 days, and control group received control liquid diet. During the experiment, the mice of the experimental group were given 3.6g/kg of the traditional Chinese medicine extract for the stomach-filling treatment every day, and correspondingly, the mice of the model group and the control group were subjected to the same volume of distilled water for the stomach-filling treatment. On day 11, mice from the model group and all the experimental groups of the extract of traditional Chinese medicine were treated with ethanol (5 g/kg) by gavage, and the control group was gavaged with an equal volume of distilled water. Similarly, after 9 hours of ethanol gavage, mice were sacrificed and tissues such as serum and liver were collected. Serum AST, ALT activity and liver histological changes (H & E staining) were examined.
2. Experimental results
The experimental results are shown in figure 3, and the results show that the traditional Chinese medicine composition has obvious inhibition effect on liver enzyme activity (a graph of figure 3) and obvious improvement effect on hepatocyte fat deposition and inflammatory infiltration (b graph of figure 3). The traditional Chinese medicine extract is suggested to have remarkable treatment effect on chronic liver injury caused by alcohol.
The above-described embodiments are only preferred embodiments of the present invention and do not limit the present invention in any way. Any person skilled in the art may make any equivalent substitution or modification to the technical solution and technical content disclosed in the invention without departing from the technical solution of the invention, and still fall within the protection scope of the invention.
Claims (10)
1. A traditional Chinese medicine composition with liver protecting and anti-alcohol effects is prepared from the following raw materials in parts by weight: 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of hovenia dulcis thunb, 1-5 parts of fructus Broussonetiae and 1-5 parts of radix puerariae.
2. The traditional Chinese medicine composition with liver protection and anti-alcohol effect according to claim 1, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 1-2 parts of rose, 1-2 parts of chrysanthemum, 1-2 parts of hovenia dulcis thunb, 1-2 parts of fructus Broussonetiae, and 1-2 parts of radix puerariae.
3. The traditional Chinese medicine composition with liver protection and anti-alcohol effect according to claim 1 or 2, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 1 part of rose, 1 part of chrysanthemum, 1 part of semen hoveniae, 1 part of fructus Broussonetiae, and 1 part of radix puerariae.
4. The traditional Chinese medicine composition with liver protecting and anti-alcohol effects according to any one of claims 1 to 3, wherein the traditional Chinese medicine composition is concentrated traditional Chinese medicine particles and/or traditional Chinese medicine extract of the raw materials.
5. The traditional Chinese medicine composition with liver protecting and anti-alcohol effects according to any one of claims 1 to 4, wherein the traditional Chinese medicine composition is decoction, granule, powder, capsule, tablet, mixture or oral liquid.
6. A preparation method of a traditional Chinese medicine composition with liver protecting and anti-alcohol effects comprises the following steps:
(1) Weighing 1-5 parts of rose, 1-5 parts of chrysanthemum, 1-5 parts of hovenia dulcis thunb, 1-5 parts of papermulberry fruit and 1-5 parts of kudzuvine root according to parts by weight, grinding and crushing;
(2) Extracting with 5-15 times of 50-95% ethanol for 0.5-2 hours for 1-3 times;
(3) The extract was filtered, centrifuged and concentrated.
7. The preparation method of claim 6, wherein the bulk drugs in step (1) are: 1-2 parts of rose, 1-2 parts of chrysanthemum, 1-2 parts of hovenia dulcis thunb, 1-2 parts of fructus Broussonetiae, and 1-2 parts of radix puerariae; preferably, it is: 1 part of rose, 1 part of chrysanthemum, 1 part of semen hoveniae, 1 part of fructus Broussonetiae, and 1 part of radix puerariae.
8. The process according to claim 6, wherein the temperature of the hot-dip extraction in step (2) is 60 to 80 ℃, most preferably 70 DEG C
Preferably, the step (3) further comprises freeze-drying the obtained concentrated solution and pulverizing into fine powder;
Preferably, the step (3) further comprises freeze-drying the obtained concentrated solution, pulverizing into fine powder, adding adjuvants, and encapsulating.
9. A medicament or health product for preventing and/or treating alcoholic liver injury, comprising the traditional Chinese medicine composition of any one of claims 1 to 5.
10. A medicament or health product for preventing and/or treating liver cirrhosis, comprising the Chinese medicinal composition of any one of claims 1-5.
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