Anti-alcoholism and anti-fatigue composition with improved stability as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-alcohol and anti-fatigue composition with improved stability as well as a preparation method and application of the anti-alcohol and anti-fatigue composition. Specifically, on the basis of traditional Chinese medicines, effective components in the traditional Chinese medicines are efficiently and quickly extracted to the maximum extent by adopting an ultrahigh pressure technology under specific conditions, meanwhile, recombinant human collagen micromolecules are added, chitosan is used as a capsule wall material to prepare the microcapsule, and the microcapsule is good in stability and can be used for synergistically dispelling the effects of alcohol and protecting the liver, harmonizing the stomach and resisting fatigue. The concentration of serum ethanol and acetaldehyde can be reduced, and the fatigue feeling after drinking is relieved. An oral preparation prepared from the composition is mainly used for dispelling the effects of alcohol, protecting the liver and harmonizing the stomach, and is used for treating excessive drinking or alcoholic liver injury, so that the composition has a good practical application value.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a hangover-relief and anti-fatigue composition with improved stability, and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] At present, there are many kinds of hangover products. The development of hangover products mainly focuses on inhibiting the absorption of ethanol in the gastrointestinal tract, increasing the activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), accelerating the metabolism of ethanol, reducing the content of acetaldehyde, and promoting sobering up; increasing the activity of natural antioxidant enzymes in the body, protecting the body from free radical damage, and thus protecting the liver. There is little research on the relief of discomfort symptoms after drinking and physical recovery. Gastrointestinal system drug delivery also faces many problems such as degradation and destruction of digestive enzymes and gastric acid.

[0004] At the same time, since the ingredients contained in traditional Chinese medicine are very complex, in order to improve the therapeutic effect of traditional Chinese medicine and reduce adverse reactions, it is very important to choose a reasonable extraction process. Traditional methods for extracting effective ingredients of traditional Chinese medicine include decoction, reflux extraction, ultrasound-assisted extraction technology, supercritical fluid extraction technology, and microwave-assisted extraction technology. However, due to the low content of effective ingredients in most traditional Chinese medicines, difficulty in enrichment, large differences in properties, and many effective ingredients are heat-sensitive and easily hydrolyzed, traditional separation and enrichment technologies have low product yields and poor stability. At the same time, they have the disadvantages of high cost, long time, complex process, high solvent consumption, high energy consumption, and large toxic side effects of some solvents.

[0005] The inventor has found through research that alcohol-detoxifying drugs are mainly divided into chemical drugs, Chinese medicine preparations and protein polypeptides. Chemical drugs are mostly vitamins, stimulants and amino acids, etc. Although they can quickly sober up, they also increase the detoxification burden of the liver and kidneys and produce strong toxic side effects; Chinese medicine preparations are mostly Pueraria root, curcumin, etc. These Chinese medicines have fewer side effects and have certain alcohol-detoxifying and liver-protecting effects, but the effects are relatively slow and cannot meet market needs. Protein polypeptide alcohol-detoxifying products, such as corn peptides and soybean peptides, have small side effects, have a high activation effect on alcohol dehydrogenase, and can accelerate the metabolism of ethanol, but have poor protective effects on the gastrointestinal tract and liver, and have the disadvantages of being expensive and difficult to promote. In addition, the inventor found that alcohol-detoxifying Chinese medicine extracts contain a large amount of polysaccharides, small molecule alkaloids, flavonoids, etc., and often have hygroscopic phenomena such as reduced fluidity, increased viscosity, agglomeration, agglomeration and even liquefaction, which are important influencing factors in the preparation process of Chinese medicine solid preparations. Once moisture is absorbed during storage, it will affect the quality of the drug and reduce stability and safety. Summary of the invention

[0006] In order to overcome the above technical problems, the present invention provides a composition for sobering up and resisting fatigue with improved stability, and a preparation method and application thereof. Specifically, the present invention is based on traditional Chinese medicine, and adopts ultra-high pressure technology under specific conditions to efficiently, quickly and maximally extract the effective ingredients in traditional Chinese medicine, and at the same time, adds recombinant human collagen small molecules, and uses chitosan as a capsule material to make microcapsules, which have good stability, can not only synergistically sober up and protect the liver, but also soothe the stomach and resist fatigue. It can reduce serum ethanol and acetaldehyde concentrations and relieve fatigue after drinking. Based on the above research results, the present invention is completed.

[0007] In order to achieve the above technical objectives, the technical solution adopted by the present invention is as follows:

[0008] In a first aspect of the present invention, there is provided a hangover-relieving and anti-fatigue composition with improved stability, wherein the hangover-relieving and anti-fatigue composition is composed of microcapsules made of a core material and a capsule material, wherein the core material comprises the following raw materials calculated by weight:

[0009] 25-35 parts of Pueraria root, 10-30 parts of Hovenia dulcis, 12-18 parts of Poria, 12-18 parts of Herba Eurycomae Longifoliae, 12-18 parts of Eurycoma longifolia, 5-15 parts of Corn Silk, and 5-15 parts of recombinant human collagen.

[0010] The recombinant human collagen may be the recombinant human collagen disclosed in Chinese Patent CN 118255869A, which is not specifically limited here.

[0011] The capsule material can be chitosan, and the molecular weight of the chitosan is 40-60 kDa, and the degree of deacetylation is greater than 80%.

[0012] The second aspect of the present invention provides a method for preparing the above-mentioned alcohol sobering and anti-fatigue composition, the preparation method comprising:

[0013] S1. Preparation of core material: grinding and sieving other core material raw material components except recombinant human collagen to obtain Chinese medicine powder raw material, mixing and soaking the Chinese medicine powder raw material with ethanol, and then subjecting the Chinese medicine powder raw material to ultrahigh pressure treatment, centrifuging to obtain liquid medicine, concentrating and adding recombinant human collagen, and freeze-drying and grinding to obtain powdered core material;

[0014] S2, preparing microcapsules: dispersing the powdered core material obtained in step S1 in a chitosan solution, and spray drying the solution to obtain microcapsules.

[0015] The third aspect of the present invention provides use of the above composition in preparing products.

[0016] The product has any one or more of the following effects: sobering up, protecting the liver, soothing the stomach, and resisting fatigue, and can be used for excessive drinking or alcoholic liver damage.

[0017] The product can be food or medicine. The food is specifically health food.

[0018] The beneficial technical effects of one or more of the above technical solutions are:

[0019] (1) The formula of the alcohol-detoxifying and anti-fatigue composition described in the above technical scheme is scientific and reasonable. The combined action of various components can synergistically exert the effects of rapid alcohol detoxification and liver protection, and can also relieve fatigue after drinking. The obtained composition has been confirmed by animal experiments to be able to activate alcohol dehydrogenase and acetaldehyde dehydrogenase, reduce serum ethanol and acetaldehyde concentrations, and has a good alcohol-detoxifying effect. It is of great significance in the preparation of alcohol-detoxifying and liver-protecting drugs, foods or health products.

[0020] (2) By establishing a rat model of chronic alcoholic liver injury, it was found that the composition of the above technical solution can inhibit the abnormal increase of alanine aminotransferase and aspartate aminotransferase levels in mouse serum, increase the activity of SOD in the liver, and inhibit the production of malondialdehyde, confirming that the composition of the present invention has a certain protective effect on chronic alcoholic liver injury and can enhance the antioxidant capacity of the liver of mice with chronic alcoholic liver injury.

[0021] (3) The above technical solution adopts ultra-high pressure technology under specific conditions to efficiently, quickly and maximally extract the effective ingredients in traditional Chinese medicine, with low energy consumption, and can avoid the problems of structural changes, losses and reduced physiological activity of effective ingredients caused by thermal effects. At the same time, since ultra-high pressure extraction is carried out in a closed environment, there is no solvent volatilization and no environmental pollution. It can realize large-scale industrial production and has good practical application value.

[0022] (4) The above technical solution uses chitosan as the capsule material, which has excellent mucosal adhesion, can prolong the retention time in the stomach, and synergistically relieve alcohol, protect the liver and stomach; and the spray drying method is used to microencapsulate the mixture powder to give it moisture resistance, maximize the preservation of effective ingredients, and improve stability.

[0023] In summary, the composition provided by the above technical scheme is mainly used for sobering up, protecting the liver, soothing the stomach, and resisting fatigue. It is used for excessive drinking or alcoholic liver damage and has good practical application value. DETAILED DESCRIPTION

[0024] It should be noted that the following detailed descriptions are all illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0025] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof. It should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the embodiments of the present invention are intended to describe specific embodiments, rather than to limit the scope of protection of the present invention.

[0026] In a typical embodiment of the present invention, a hangover-relieving and anti-fatigue composition with improved stability is provided, wherein the hangover-relieving and anti-fatigue composition is composed of microcapsules made of core materials and capsule materials, and the core material, calculated by mass, comprises the following raw materials:

[0027] 25-35 parts of Pueraria root, 10-30 parts of Hovenia dulcis, 12-18 parts of Poria, 12-18 parts of Herba Eurycomae Longifoliae, 12-18 parts of Eurycoma longifolia, 5-15 parts of Corn Silk, and 5-15 parts of recombinant human collagen.

[0028] The specific functions of the raw materials of the above core materials are described as follows:

[0029] Pueraria root, with a sweet and slightly spicy taste and a light fragrance, mainly enters the spleen and stomach meridians, relieves exterior symptoms and fever, detoxifies alcohol, regulates human functions, and strengthens physical fitness. "Compendium of Materia Medica" states: it has the effects of clearing heat, reducing fire, and expelling various toxins; "Qianjin Fang" states: it can treat drunkenness; "Yao Xing Lun" states: "It can treat upper air, vomiting, stimulate appetite, detoxify alcohol, and stop thirst; it can treat stomach deficiency, heat, thirst, and vomiting caused by alcohol poisoning." As one of the most representative alcohol-detoxifying drugs in traditional Chinese medicine, Pueraria root has multiple pharmacological effects such as detoxification and intoxication prevention, improving cardiovascular and cerebrovascular circulation, reducing myocardial oxygen consumption, anti-liver toxicity, anti-inflammatory, expectorant, antipyretic, improving body immunity, antibacterial, and antiviral, and can effectively increase the activity of liver alcohol dehydrogenase and acetaldehyde dehydrogenase. As a safe medicinal and edible herb, Pueraria root has the following active ingredients: flavonoid bioactive ingredients (daidzein, daidzin, puerarin, etc.), Pueraria root polysaccharides, Pueraria root polypeptides, etc., which are beneficial for activating stomach qi, relieving alcohol poisoning and vomiting, decomposing acetaldehyde toxicity, slowing down the central nervous system inhibition of alcohol, inhibiting the absorption of alcohol by the stomach and intestines, and promoting the metabolism and excretion of alcohol in the blood. Among them, daidzin, Pueraria root polysaccharides, Pueraria root polypeptides and other ingredients have been proven to have biological activity of sobering up and protecting the liver.

[0030] Hovenia dulcis is sweet and neutral in nature. It has the effects of detoxifying alcohol, quenching thirst, relieving restlessness, stopping vomiting, and promoting urination and defecation. It is mainly used to treat drunkenness, thirst, vomiting, and constipation. Li Shizhen's Compendium of Materia Medica once recorded that "its branches and leaves can stop vomiting, detoxify alcohol, and prevent insect poisoning." Hovenia dulcis extract contains flavonoid active substances and anthraquinone compound emodin. Studies have shown that it can enhance the activity of glutathione peroxidase, scavenge free radicals, inhibit lipid peroxidation, accelerate the metabolic process of ethanol and metabolites, reduce the concentration of ethanol in the blood, reduce the damage of ethanol to liver tissue, and avoid alcohol poisoning. There is a saying among the people that "Hovenia dulcis will not make you drunk even if you drink a thousand cups." Studies have shown that the combination of Hovenia dulcis extract and Pueraria root can significantly accelerate the removal of ethanol and inhibit the increase of serum alanine aminotransferase and aspartate aminotransferase caused by ethanol.

[0031] The taste of the herb is sweet, light, slightly sour and cool. It enters the liver, gallbladder, heart and small intestine meridians. It contains N-methylisopunicrine, dihydro-N-methylisopunicrine, sedoheptulose, glucose, fructose and sucrose. It has a good effect on lowering serum alanine aminotransferase, has the effects of clearing away heat and detoxification, diuresis and swelling, pus discharge and tissue regeneration, and is mainly used to treat erysipelas ulcers, urinary problems and acute and chronic hepatitis.

[0032] Poria cocos is sweet, light and neutral in nature. It enters the heart, spleen, liver and kidney meridians. It has the functions of nourishing the brain and strengthening the body, promoting diuresis and removing dampness, benefiting the spleen and stomach, and calming the mind. It is known as one of the "eight treasures" of traditional Chinese medicine. Because Poria cocos contains active ingredients such as tuckahoe polysaccharide, tuckahoe acid, polysaccharides, and ergosterol, it has diuretic, sedative, and liver-protecting effects, and can promote the activity of ethanol-degrading enzymes in the liver.

[0033] Tongkat Ali contains a variety of active substances, such as terpenes, alkaloids, volatile oils, phenylpropanoids, polyphenols, flavonoids, etc. It has good anti-cancer, antimalarial, anti-fatigue, and improvement of male sexual dysfunction. The extract also has the effects of improving physical strength, relieving fatigue, anti-ulcer, sterilization, lowering blood pressure and treating diabetes. Studies have shown that it has a similar therapeutic effect as ranitidine on gastric damage caused by alcohol, and can protect liver cells, promote liver detoxification and metabolism, and reduce the retention time of poisons such as ethanol in the body.

[0034] Corn silk is sweet, light, and neutral in nature. It belongs to the bladder and gallbladder meridians. The main active ingredients include flavonoids, polysaccharides, sterols, saponins, alkaloids, organic acids, amino acids, etc. It has the effects of diuresis and swelling, clearing the liver and promoting bile secretion. It can improve the liver's detoxification function by regulating liver-related antioxidant enzymes, and can quickly clean up the alcohol content in our body, decompose alcohol, and quickly decompose the alcohol content in the body to avoid hangover headaches and headaches after drinking.

[0035] Collagen has certain nutritional value, but due to its large molecular weight, it is difficult to be digested and absorbed by the human body. The intermediate peptides produced when animal collagen is enzymatically hydrolyzed into free amino acids during the digestion and absorption process have many special physiological functions, and studies have confirmed that bioactive peptides have higher in vivo absorption efficiency than amino acid monomers. However, the collagen extracted from animals has poor water solubility and weak processability, which directly limits the development of many potential uses. The collagen produced by genetic engineering technology can effectively overcome the above shortcomings. The recombinant human collagen used in the present invention is a recombinant human collagen developed by Shandong Junxiu Biotechnology Co., Ltd., which has been disclosed in the Chinese patent with publication number CN 118255869A. It has small molecules and is easily soluble in water. It contains glycine, alanine, valine, leucine, isoleucine, methionine, proline, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and histidine. It is used to replenish the loss of amino acids during the decomposition of alcohol, assist the body in metabolizing ammonia through the urea cycle, improve nitric oxide metabolism in the blood circulation, relax blood vessels, and repair gastric mucosal damage caused by drinking.

[0036] Furthermore, the core material, calculated by weight, comprises the following raw materials: 30 parts of Pueraria root, 20 parts of Hovenia dulcis, 15 parts of Poria cocos, 15 parts of Creeping Jasmine, 15 parts of Eurycoma longifolia, 10 parts of Corn Silk, and 10 parts of recombinant human collagen freeze-dried powder.

[0037] The capsule material can be chitosan, and the molecular weight of the chitosan is 40-60 kDa, and the degree of deacetylation is greater than 80%.

[0038] Chitosan is the only alkaline aminopolysaccharide with no toxic side effects that exists in large quantities in nature. It is also a natural product with a small number of positive charges. It can combine with a large number of anions in the mucus layer on the mucosa, and has excellent antibacterial ability, inhibits the occurrence of gastric ulcers, and prevents and treats fatty liver. In the present invention, it is used as a microcapsule material to form a protective film on the surface of the Chinese medicine extract, which can significantly reduce the hygroscopicity of the core material within a certain period of time. The capsule material is weakly alkaline and soluble in gastric acid. Combined with the excellent mucosal adhesion of chitosan, the microcapsule can be rapidly swollen in the stomach, which can resist gastric emptying and effectively absorb the drug. The microcapsule has a small particle size and can be embedded in the gastric folds, prolonging the gastric retention time of the drug-loaded microcapsule, and promoting the effects of soothing the stomach, sobering up, and protecting the liver.

[0039] The mass ratio of the core material to the capsule material is 1:1-8.

[0040] In another specific embodiment of the present invention, a method for preparing the above-mentioned alcohol sobering and anti-fatigue composition is provided, and the preparation method comprises:

[0041] S1. Preparation of core material: grinding and sieving other core material raw material components except recombinant human collagen to obtain Chinese medicine powder raw material, mixing and soaking the Chinese medicine powder raw material with ethanol, and then subjecting the Chinese medicine powder raw material to ultrahigh pressure treatment, centrifuging to obtain liquid medicine, concentrating and adding recombinant human collagen, and freeze-drying and grinding to obtain powdered core material;

[0042] S2, preparing microcapsules: dispersing the powdered core material obtained in step S1 in a chitosan solution, and spray drying the solution to obtain microcapsules.

[0043] Wherein, in the step S1, the mesh number of the sieved Chinese medicine powder raw material is 60-100 mesh, preferably 80 mesh; the material-liquid ratio of the Chinese medicine powder raw material to ethanol is 1:5-60 (g / mL); the ethanol concentration is 40-80%; the mixing and soaking time is 1-60min (preferably 30min);

[0044] The specific conditions of the ultra-high pressure treatment are: 150MPa to 500MPa, and then maintaining this pressure for 5 to 15 minutes; in the present invention, the ultra-high pressure treatment can be carried out in a single pressurization and pressure maintenance manner or in a staged pressurization and pressure maintenance manner.

[0045] Specifically, the stepwise pressurization and pressure-maintaining method includes: controlling the material-liquid ratio in the mixture to be 1:5-20 (g / mL);

[0046] The pressure is first increased to 150-300 MPa (preferably 250 MPa), maintained for 1-10 min (preferably 3 min), then the pressure is released, and ethanol is added thereto so that the material-liquid ratio is 1:30-60 (g / mL), and the pressure is secondarily increased to 300-500 MPa (preferably 400 MPa), maintained for 1-10 min (preferably 3 min).

[0047] The specific conditions for obtaining the drug solution by centrifugation are: centrifugation at 2000-5000 r / min for 1-10 min, preferably at 3500 r / min for 5 min.

[0048] In the present invention, the added recombinant human protein can be a recombinant human protein aqueous solution, and its mass fraction is 10-80% (w / v), preferably 50%.

[0049] The specific conditions for freeze-drying are: vacuum gradient freeze-drying, the program is: -50℃: 2h; -20℃: 2h; -5℃: 20h; 10℃: 2h; 20℃: 2h.

[0050] The powdered core material has a sieve mesh number of 60-100 meshes, preferably 80 meshes.

[0051] In the step S2, the concentration of the chitosan solution is 0.5-5% (w / v), preferably 2%; the solvent is 0.5-5% (v / v, preferably 2%) acetic acid solution.

[0052] The specific conditions of the spray drying are: injection speed of 2 to 18 mL / min, and air inlet temperature of 120 to 200°C.

[0053] In the present invention, the preparation method further comprises the steps of packaging the obtained composition and irradiating and sterilizing it, which is not specifically limited here.

[0054] Another specific embodiment of the present invention provides use of the above composition in preparing a product.

[0055] The product has any one or more of the following effects: sobering up, protecting the liver, soothing the stomach, and resisting fatigue, and can be used for excessive drinking or alcoholic liver damage.

[0056] The product can be food or medicine. The food is specifically health food.

[0057] The technical scheme of the present invention is described below by means of specific examples. The raw materials used in the following examples can be obtained commercially, and the equipment used are all existing equipment. The recombinant human collagen used in the examples and comparative examples is the recombinant human collagen prepared in Example 1 of CN 118255869A.

[0058] Example 1

[0059] 1. Core material preparation

[0060] 30 parts of Pueraria root, 20 parts of Hovenia dulcis, 15 parts of Poria, 15 parts of Herba Eurycomae Longifoliae, 15 parts of Eurycoma longifolia, 20 parts of 50% (w / v) aqueous solution of recombinant human collagen, and 10 parts of Corn Silk.

[0061] The present invention mixes the Chinese medicine components except recombinant human collagen according to the above formula and then crushes them through an 80-mesh sieve, mixes the powdered Chinese medicine with 50% (v / v) ethanol, and soaks them for 30 minutes at room temperature, wherein the solid-liquid ratio of the Chinese medicine mass to the added ethanol is 1:10 (g / mL). The above mixture is poured into a pressure-resistant bag, put into a high-pressure container in an ultra-high pressure extraction device, the pressure pump is started, and then the pressure is rapidly increased to 200MPa within 3 minutes, then maintained at this pressure for 3 minutes, and then the valve controlling the high-pressure circuit is quickly opened, and the pressure is relieved within 2 seconds. A certain amount of ethanol is added to the feed liquid after high-pressure treatment to make the feed-liquid ratio reach 1:40 (g / mL), the above mixture is poured into a pressure-resistant bag again, put into a high-pressure container in an ultra-high pressure extraction device, the pressure pump is started, and then the pressure is rapidly increased to 400MPa within 3 minutes, then maintained at this pressure for 4 minutes, and then the valve controlling the high-pressure circuit is quickly opened, and the pressure is relieved within 2 seconds. The high pressure treated liquid was taken out and centrifuged at 3500r / min for 5 minutes to obtain the treated Chinese medicine liquid. Both pressure increasing and pressure maintaining processes were carried out at room temperature.

[0062] After the above Chinese medicine liquid is concentrated to one third of the volume of the ethanol initially added, 20 parts of 50% (w / v) recombinant human collagen aqueous solution are added, gently stirred and mixed for 15 minutes, and vacuum gradient freeze-dried: -50°C: 2h; -20°C: 2h; -5°C: 20h; 10°C: 2h; 20°C: 2h. Then, the powdered core material 1 is obtained by crushing and passing through an 80-mesh sieve.

[0063] 2. Preparation of microcapsules: Accurately weigh an appropriate amount of chitosan (molecular weight 50kDa, deacetylation degree 85%), dissolve it in 1% (v / v) acetic acid solution and prepare it into 2% (w / v) chitosan solution for use. Disperse the core material evenly in the above chitosan solution, prepare the solution to be sprayed according to the mass ratio of core material to chitosan of 1:4, place it on a magnetic stirrer and stir it evenly, let it stand to remove bubbles and then spray dry, with an injection speed of 8mL / min and an inlet air temperature of 160°C. Then encapsulate, irradiate and sterilize, seal and store in a dark and dry place. The average drug loading is 18.51% and the average yield is 59.08%, indicating that the process has good repeatability. The average particle size of the obtained microcapsules is 103.78μm, the particle size distribution is relatively uniform, and the encapsulation rate is 84.95%.

[0064] Example 2

[0065] 1. Core material preparation

[0066] 30 parts of Pueraria root, 20 parts of Hovenia dulcis, 15 parts of Poria, 15 parts of Herba Eurycomae Longifoliae, 15 parts of Eurycoma longifolia, 20 parts of 50% (w / v) aqueous solution of recombinant human collagen, and 10 parts of Corn Silk.

[0067] The present invention mixes the Chinese medicine components except recombinant human collagen according to the above formula and then crushes them through an 80-mesh sieve, mixes the powdered Chinese medicine with 50% (v / v) ethanol, and soaks them at room temperature for 30 minutes. The material-liquid ratio of the Chinese medicine mass to the added ethanol is 1:40 (g / mL). The above mixture is poured into a pressure-resistant bag, put into a high-pressure container in an ultra-high pressure extraction device, and the pressure pump is started. Then, the pressure is rapidly increased to 400MPa for 3 minutes, and then maintained at this pressure for 7 minutes, and then the valve controlling the high-pressure circuit is quickly opened, and the pressure is relieved within 2 seconds. The feed liquid after high-pressure treatment is taken out, centrifuged at 3500r / min for 5 minutes, and the treated Chinese medicine liquid is obtained. The pressure-raising and pressure-maintaining process is carried out at room temperature.

[0068] After the above Chinese medicine liquid is concentrated to one third of the volume of the ethanol initially added, 20 parts of 50% (w / v) recombinant human collagen aqueous solution are added, gently stirred and mixed for 15 minutes, and vacuum gradient freeze-dried: -50°C: 2h; -20°C: 2h; -5°C: 20h; 10°C: 2h; 20°C: 2h. Then, the powdered core material 2 is crushed and passed through an 80-mesh sieve.

[0069] The microcapsule was prepared in the same manner as in Example 1 to obtain microcapsule 2.

[0070] Comparative Example 1

[0071] The core material is prepared in the same manner as in Example 2, and modified with auxiliary calcium hydrogen phosphate to prepare particles. The wetting agent is an ethanol solution with a volume fraction of 60%.

[0072] Select core material 1 and mix it evenly with calcium hydrogen phosphate in a ratio of 1:1, slowly add 60% ethanol solution by volume, and the material-liquid ratio is 5:1 (g / mL) to prepare soft material, press wet granules through a 10-mesh sieve, place in a 50°C oven to dry for 2 hours, then package, and then irradiate to sterilize, to obtain granules 3, and seal and store in a dark and dry place.

[0073] Comparative Example 2

[0074] The difference between this comparative example and Example 2 is that 30 parts of Pueraria root, 20 parts of Hovenia dulcis, 15 parts of Poria cocos, 15 parts of Creeping Jasmine, 20 parts of 50% (w / v) recombinant human collagen aqueous solution, and 10 parts of Corn Silk are used to obtain core material 3 and microcapsule 3.

[0075] Comparative Example 3

[0076] The difference between this comparative example and Example 2 is that the raw material does not contain the recombinant human collagen in Example 1, and a core material 4 and a microcapsule 4 are obtained.

[0077] Comparative Examples 4 to 7

[0078] The difference between Comparative Examples 4 to 7 and Example 2 is that the Chinese medicine extraction process parameters are different. The changes of each parameter are shown in Table 1, and microcapsules 5, 6, 7, and 8 are prepared respectively.

[0079] Table 1 Process parameters of each comparative example

[0080]

[0081]

[0082] The preparation methods of the microcapsules in each comparative example are the same as those in Example 1.

[0083] (1) Alcohol sobering performance test experiment

[0084] 1) Alcohol dehydrogenase (ADH) activation ability test

[0085] Waller-Hoch assay for alcohol dehydrogenase activity: Given that NADH and NAD+ have their own maximum absorption peaks at 340nm and 260nm, when NAD+ is converted to NADH, the absorbance changes, and the change value is proportional to the enzyme reaction rate. Therefore, ADH with NAD+ as a coenzyme can be measured by the change in absorbance at 340nm.

[0086] The specific operation is as follows: the base solution uses 1.5 mL of pyrophosphate buffer with a pH value of 9.0, 1 mL of 30 mmol / L NAD+, and 0.5 mL of 11.5% (V:V) ethanol solution. The positive drug group and the example group (adult dose) each take 0.1 mL (the blank group is replaced with distilled water), mix them, and put them in a 25°C water bath for 10 minutes. After the insulation, add 0.1 mL of ADH (0.25 U / mL), shake well, and immediately measure the absorbance value at a wavelength of 340 nm, record it every 15 seconds, and measure it continuously for 5 minutes.

[0087] The activation rate was calculated as follows: Activation rate = (enzyme activity test group - enzyme activity blank group) / enzyme activity blank group × 100%

[0088] The experimental results are shown in Table 2.

[0089] Table 2 Enzyme activation rate results

[0090]

[0091] Note: Comparison between the example group and the positive drug group *p<0.05

[0092] Alcohol dehydrogenase is a key enzyme involved in ethanol metabolism in the body. It inhibits the absorption of ethanol in the body and strengthens the first-pass effect of ethanol in the gastrointestinal tract, thereby reducing the damage of ethanol to the digestive system, liver system and nervous system, and achieving the effect of sobering up and protecting the liver. The experimental results show that the composition of the present invention can synergistically activate the effect of alcohol dehydrogenase, thereby playing a good sobering up effect. As can be seen from Table 2, the ADH of the positive drug group, the embodiment group and each comparative example group has different degrees of activation, and the activation effect of the embodiment group is significantly higher than that of the positive drug group (p <0.05), and the effect of each comparative example group is worse than that of the embodiment group. It shows that the synergistic effect between the various components enhances the sobering up effect, and the ultra-high pressure extraction process conditions of traditional Chinese medicine will also affect the extraction effect of the effective ingredients, thereby affecting the sobering up effect.

[0093] 2) Determination of ethanol content in mouse serum, ADH and ALDH content in liver

[0094] 36 mice were randomly divided into a blank group, a model group, a positive drug group, an embodiment group and a comparative group. After the mice were fasted for 12 hours, the blank group was given 12mL / kg of distilled water, and the other groups were given 12mL / kg of 50% alcohol; 30 minutes later, the mice in the embodiment group and the comparative group were respectively gavaged with distilled water to dilute the preparation, so that the dosage of the preparation in the mice was 35mg / kg, the blank group and the model group were given an equal volume of distilled water, and the mice in the positive drug group were gavaged with distilled water to dissolve the positive drug group, so that the dosage of the positive drug group was 50mg / kg; 60 minutes later, the ethanol content in the serum was measured. The animals were then killed, the liver was immediately removed aseptically, 10% liver homogenate was prepared, and the supernatant alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were measured, and the test results are shown in Table 3.

[0095] Table 3 Effects on ethanol content in mouse serum, ADH and ALDH content in liver

[0096]

[0097]

[0098] Note: Compared with the model group, *p<0.05, compared with the example group and the positive drug group # p<0.05

[0099] As shown in Table 3, the embodiment group, the comparative example group and the positive drug group can significantly reduce the ethanol content in the mouse serum and increase the ADH and ALDH activities. The products obtained in the Example 1 and 2 groups are superior to the other groups in reducing the ethanol content in the mouse serum and promoting the ADH and ALDH activities in the mouse liver, and are also significantly superior to the positive drug group. This shows that the combination provided by the present invention can synergistically reduce the serum ethanol concentration, increase the ADH and ALDH activities in the liver, and the alcohol sobering effect is better than the commonly used drugs on the market.

[0100] (2) Liver protection test

[0101] Take 36 mice and randomly divide them into blank group, model group, positive drug group, embodiment group and comparative group. After fasting for 12h, mice were gavaged with embodiment group and comparative group (microcapsule or granule was made into suspension, equivalent to 2.1g / day, 35mg / kg for 60kg adult after drunkenness), positive drug group (positive drug group tablet was ground into powder, made into suspension. Equivalent to 3 tablets, 50mg / kg for 60kg adult after drunkenness), blank group and model group were given the same volume of distilled water. After 30min, mice in each group were gavaged with 12mL / kg, 50% alcohol, and the blank group was gavaged with the same volume of distilled water. After continuous gavage for 4 weeks, mice were fasted for 12h, tails were cut off to take blood and liver was taken, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, liver SOD activity and malondialdehyde (MDA) content were measured, and the data were recorded in Table 3.

[0102] Table 3 Results of biochemical index detection in mice

[0103]

[0104]

[0105] Note: Compared with the model group, *p<0.05, compared with the example group and the positive drug group # p<0.05

[0106] ALT and AST have always been used as the standard of liver cell damage, and the degree of their increase can be used as a manifestation of liver damage. MDA can reflect the degree of lipid peroxidation of liver cell membranes. SOD is a natural substance that removes free radicals in the body. This test example uses these four indicators to measure the liver protection effect. The data in Table 3 show that the ALT, AST, and MDA activities of the model group are higher than those of the blank group, and the example group and the comparative example group are lower than the model group; the SOD activity of the model group is the lowest, and the effect of the example group is stronger than that of each comparative example group and the positive drug group, indicating that the composition of the present invention has a certain protective effect on chronic alcoholic liver damage, and can enhance the antioxidant capacity of the liver of mice with chronic alcoholic liver damage, and there is a synergistic effect between the components. Comparative Examples 4 to 7 reflect that the process conditions do not meet the requirements of this application, the effective ingredients are not fully extracted, and the effect is affected.

[0107] (3) Fatigue resistance test

[0108] The samples prepared in the Example group and the Comparative Example were subjected to a mouse weight-bearing swimming anti-fatigue test. After gavage treatment using the method of Test (2), the mice in each group swam with a weight of 5%. The swimming time is shown in Table 4. The Comparative Example 2 group did not contain Tongkat Ali, and the Comparative Example 3 did not contain recombinant humanized collagen. The anti-fatigue degree was significantly lower than that of the other Example groups and the Comparative Example groups.

[0109] Table 4 Weighted swimming status of mice in each group

[0110]

[0111] The results of the above tests (1), (2), and (3) show that the hangover-relief, liver-protection, and anti-fatigue effects of the sample in Example 1 are better than those of the sample in Example 2. It is speculated that the content of active ingredients after gradient ultrahigh pressure extraction is higher than that after single ultrahigh pressure extraction. Comparative Example 1 does not contain chitosan because it lacks the adhesion of chitosan and the absorption of active ingredients in the stomach is less than that of the two groups in Examples 1 and 2.

[0112] (4) Stability test

[0113] Accelerated tests were conducted on samples of Example and Comparative Example 1, respectively, under the conditions of a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5% for three months, and samples were taken at the end of the first, second and third months of the test period, and tested according to the inspection items. The results showed that after the microcapsules 1 and 2 prepared in Example and the particles 3 prepared in Comparative Example 1 were stored for three months, the particles 3 were easy to absorb moisture, and the moisture content was significantly higher than that of microcapsules 1 and 2, and the polysaccharide retention rate was significantly lower than that of microcapsules 1 and 2, indicating that the microcapsules prepared by chitosan encapsulation had better stability.

[0114] Table 5 Accelerated test results of various embodiments

[0115]

[0116] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to perform equivalent replacements on parts thereof. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention. Although the above describes the specific implementation methods of the present invention, it is not intended to limit the protection scope of the present invention. Those skilled in the art should understand that, based on the technical solution of the present invention, various modifications or deformations that can be made by those skilled in the art without creative labor are still within the protection scope of the present invention.

Claims

1. A hangover-relief and anti-fatigue composition with improved stability, characterized in that: The alcohol sobering and anti-fatigue composition is composed of microcapsules made of core materials and capsule materials. The core material, calculated by mass, comprises the following raw materials: 25-35 parts of Pueraria root, 10-30 parts of Hovenia dulcis, 12-18 parts of Poria, 12-18 parts of Herba Eurycomae Longifoliae, 12-18 parts of Eurycoma longifolia, 5-15 parts of Corn Silk, and 5-15 parts of recombinant human collagen; The capsule material is chitosan.

2. The alcohol-relieving and anti-fatigue composition according to claim 1, characterized in that: The molecular weight of the chitosan is 40-60 kDa, and the degree of deacetylation is >80%; The mass ratio of the core material to the capsule material is 1:1-8.

3. The method for preparing the alcohol-relieving and anti-fatigue composition according to claim 1 or 2, characterized in that: The preparation method comprises: S1. Preparation of core material: grinding and sieving other core material raw material components except recombinant human collagen to obtain Chinese medicine powder raw material, mixing and soaking the Chinese medicine powder raw material with ethanol, and then subjecting the Chinese medicine powder raw material to ultrahigh pressure treatment, centrifuging to obtain liquid medicine, concentrating and adding recombinant human collagen, and freeze-drying and grinding to obtain powdered core material; S2, preparing microcapsules: dispersing the powdered core material obtained in step S1 in a chitosan solution, and spray drying the solution to obtain microcapsules.

4. The preparation method according to claim 3, characterized in that: In the step S1, the mesh number of the Chinese medicine powder raw material is 60-100 mesh; the material-liquid ratio of the Chinese medicine powder raw material to ethanol is 1:5-60 (g / mL); the ethanol concentration is 40-80%; and the mixing and soaking time is 1-60 min.

5. The preparation method according to claim 3, characterized in that: In the step S1, the specific conditions of the ultra-high pressure treatment are: 150MPa to 500MPa, and then the pressure is maintained for 5 to 15 minutes.

6. The preparation method according to claim 5, characterized in that: The ultra-high pressure treatment is carried out by a single pressurization and pressure maintenance method or a staged pressurization and pressure maintenance method; Specifically, the method of graded pressurization and pressure maintenance includes: controlling the solid-liquid ratio in the mixture to 1:5-20 (g / mL), increasing the pressure to 150-300 MPa for the first time, maintaining for 1-10 minutes, then releasing the pressure, adding ethanol thereto so that the solid-liquid ratio is 1:30-60 (g / mL), increasing the pressure to 300-500 MPa for the second time, and maintaining for 1-10 minutes.

7. The preparation method according to claim 3, characterized in that: In step S1, the specific conditions for obtaining the drug solution by centrifugation are: centrifugation at 2000-5000 r / min for 1-10 min; The powdery core material has a sieve mesh number of 60-100 meshes.

8. The preparation method according to claim 3, characterized in that: In step S2, the concentration of the chitosan solution is 0.5-5% (w / v); the solvent is 0.5-5% (v / v) acetic acid solution; The specific conditions of the spray drying are: injection speed of 2 to 18 mL / min, and air inlet temperature of 120 to 200°C.

9. Use of the composition according to any one of claims 1 to 2 or the composition prepared by the preparation method according to any one of claims 3 to 8 in preparing a product; The product has any one or more of the following effects: sobering up, protecting the liver, soothing the stomach, and resisting fatigue, and is used for drinking too much or alcoholic liver damage.

10. The use according to claim 9, characterized in that: The product is food or medicine; the food is specifically health food.

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