Alcohol-relieving and hangover-resistant composition and preparation method thereof

Abstract

The present invention belongs to the field of biopharmaceuticals and specifically relates to a composition for detoxifying alcohol and preventing hangovers and its preparation method, comprising the following steps: 1) adding a portion of yeast extract to purified water to obtain solution A, adding curcumin to anhydrous ethanol to obtain solution B, and mixing solution A and solution B to obtain a mixed solution; 2) adjusting the pH of the mixed solution to 5-6; 3) placing the mixed solution in a -25°C cold trap and allowing it to stand for 16-32 hours until crystals precipitate; 4) filtering at 4°C to obtain a filter cake and a filtrate; 5) pulverizing the filter cake to obtain a crystalline powder; and 6) uniformly mixing the crystalline powder, another portion of yeast extract, dihydroquercetin, and excipients, and then tableting to obtain the composition for detoxifying alcohol and preventing hangovers. The present invention utilizes a complex formed by precipitating the yeast extract and curcumin cocrystals, which expands the application range of the composition and improves the solubility and bioavailability of curcumin.

Description

Technical Field

[0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to an alcohol-relieving and anti-hangover composition and a preparation method thereof. Background Art

[0002] As the pace of modern life accelerates, social activities are increasingly frequent, inevitably involving drinking. However, excessive drinking can negatively impact human health, including liver damage. Therefore, research on liver protection and hangover relief has become a crucial topic. Existing hangover relief and liver protection products typically contain liver-protecting ingredients such as puerarin, taurine, and curcumin, designed to mitigate alcohol-induced liver damage and alleviate the discomfort associated with drinking.

[0003] Curcumin is a secondary metabolite of the famous Indian spice turmeric, derived from the rhizome of the ginger family. Curcumin has been used in Ayurvedic medicine for thousands of years as a treatment for inflammatory diseases and wounds. Curcumin has been shown to possess numerous biological activities, including antioxidant, cardioprotective, neuroprotective, antidiabetic, antimicrobial, antimalarial, anti-HIV, antithrombotic, antitumor, and chemotherapeutic activities. In vitro, it can ameliorate alcohol-induced oxidative stress in hepatocytes. Animal studies have shown that curcumin alleviates alcohol-induced liver histopathological changes and significantly reduces the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Alcohol promotes the production of reactive oxygen species (ROS), increases malondialdehyde (MDA) levels, depletes glutathione (GSH), and disrupts antioxidant defenses; these effects are significantly ameliorated by curcumin treatment. In summary, curcumin may be a preventive for chronic alcoholic fatty liver disease.

[0004] Dihydroquercetin, also known as Taxifolin, is a natural dihydroflavonol compound extracted primarily from the roots of alpine larch. It belongs to the bioflavonoid class and possesses a variety of biological activities, including antioxidant, antiviral, anti-allergic, anti-atherosclerotic, anti-arrhythmic, and blood pressure regulation. Dihydroquercetin has five phenolic hydroxyl groups and possesses excellent antioxidant properties, making it useful in improving and protecting against alcoholic fatty liver disease.

[0005] Yeast extract is made primarily from food-grade yeast, obtained through enzymatic autolysis (which can then be separated and extracted) using either yeast's own enzymes or added food-grade enzymes. It is rich in soluble components of yeast cells, including amino acids, peptides, and polypeptides. The glutathione in yeast extract protects the sulfhydryl groups of proteins in the body, maintaining their normal activity. It also serves as a coenzyme and prosthetic group for various enzymes, exhibiting numerous biological functions. It not only scavenges free radicals but also protects liver cell membranes, promotes liver membrane activity, acts as an anti-oxidant, detoxifies, and maintains the integrity of red blood cell membranes.

[0006] Patent application number: CN201910402078.9, publication date: 2020.11.13, discloses a composition with alcohol sobering and liver protection functions, its preparation method and application, the composition containing curcumin, yeast powder and yeast extract. The composition is prepared by mixing raw materials containing curcumin, yeast powder and yeast extract. Patent application number: CN20226.50353429.8, publication date: 2023.09.19, discloses a yeast complex with alcohol sobering and liver protection functions. The complex provided by the invention uses yeast extract, curcumin, grape seed powder, Hovenia dulcis powder, Rosa roxburghii powder, Pueraria root powder and Dandelion powder as the main alcohol sobering and liver protection active substances, and contains multiple bioactive ingredients. On the one hand, it can effectively slow down the gastrointestinal absorption of alcohol and increase the activity of acetaldehyde dehydrogenase in the body, accelerating the decomposition of alcohol. On the other hand, it can effectively improve the liver's antioxidant capacity, scavenge free radicals in the body, and protect liver cells.

[0007] Yeast extract is rich in free amino acids and oligopeptides. At high purity, it possesses a unique flavor, a blend of umami and a distinctive off-flavor. Curcumin has a bitter taste. When taken orally, a combination of yeast extract and curcumin not only produces a distinctive off-flavor, bitterness, and other unpleasant flavors, but also can easily irritate the stomach, causing nausea and vomiting, resulting in a strong, long-lasting bad breath. In severe cases, it can also cause nausea and vomiting, impacting medication compliance and limiting the application of curcumin and yeast extract liver protection products. Summary of the Invention

[0008] The purpose of the present invention is to overcome the problem of poor compliance of curcumin and yeast extract in the prior art and to provide an anti-hangover composition with good compliance and high bioavailability.

[0009] The technical solution of the present invention is: a method for preparing an alcohol-relieving and anti-hangover composition, comprising the following steps: 1) adding 100-140 g of yeast extract to 1-1.5 L of purified water to obtain solution A, adding 25-30 g of curcumin to 2 L of anhydrous ethanol to obtain solution B, mixing solution A and solution B, and then homogenizing under high pressure twice to obtain a mixed solution;

[0010] 2) Place the mixed solution in a 25°C water bath and slowly add a pH adjuster while stirring to adjust the pH to 5-6;

[0011] 3) Place the mixed solution in a -25°C cold trap and let it stand for 16-32 hours until crystals precipitate;

[0012] 4) Filter at 4°C to obtain filter cake and filtrate;

[0013] 5) crushing and drying the filter cake to obtain crystalline powder;

[0014] 6) Add 110-150 g of yeast extract and 5 g of dihydroquercetin to the crystalline powder, add auxiliary materials, mix well, and then compress into tablets to obtain an alcohol-relieving and anti-hangover composition.

[0015] Add 100-140g of yeast extract to 1-1.5L of water to obtain a supersaturated solution. The solution is turbid with a yellow tint and has a pH between 6.5-7.5. Most amino acids in yeast extract have an isoelectric point of 5.48-6.02 at 25°C. Therefore, when HCl is slowly added to the mixed solution to adjust the pH to 5-6, the amino acids or peptides containing amino acid residues are more easily precipitated from the mixed solution. After standing in a -25°C cold trap for 16-32 hours, the positively charged amino acids and amino acid residues form conjugation with the phenolic hydroxyl groups of curcumin, forming a hydrogen-bonded eutectic between the molecules and precipitating from the solution.

[0016] The crystalline powder obtained in step 5) is a yellow-brown needle-shaped crystalline powder.

[0017] The crystal powder was crushed and passed through an 80-mesh sieve.

[0018] The preparation method of the present invention hydrogen bonds yeast extract with curcumin to form a complex. This creates a conjugated interaction between the amino acids and their residues and the phenolic hydroxyl groups of curcumin. This modifies the molecular interactions and spatial arrangement of curcumin and amino acids at the molecular level. Oral administration reduces gastrointestinal irritation and prevents oral odor. This expands the application of this alcohol-relieving and hangover-relieving composition.

[0019] The researchers also unexpectedly discovered that combining yeast extract and curcumin cocrystals improved tablet quality, enhancing curcumin's water solubility and bioavailability. The saturated solubility of curcumin in artificial gastric fluid after cocrystalization with yeast extract was 5.46-5.49 times higher than that of curcumin without cocrystals. In a mouse intoxication experiment, the peak plasma concentration of curcumin after cocrystalization with yeast extract was 9.8-9.9 times higher than that of curcumin without cocrystals. The area under the drug-time curve was 9.6 times that of curcumin without cocrystals, demonstrating that the cocrystals of curcumin and yeast extract possess superior water solubility and bioavailability.

[0020] Dihydroquercetin, yeast extract, and curcumin work synergistically, inhibiting ethanol metabolism and reducing free radical formation in the liver, thereby alleviating ethanol damage to the liver and nervous system. Dihydroquercetin also protects the liver by modulating immune responses and promoting liver cell regeneration.

[0021] The auxiliary materials include 226.5g microcrystalline cellulose, 16.5g povidone K30, 11g cross-linked carboxymethyl cellulose sodium, 5.5g silicon dioxide and 5.5g magnesium stearate.

[0022] Povidone K30 is a wetting agent, dissolved in 95% ethanol at a concentration of 8%. The wetting agent should be added slowly and stirred while spraying to prevent the yeast extract from clumping and affecting product uniformity.

[0023] The stirring rate in step 2) is 150-180 r / min.

[0024] The stirring rate should be chosen to ensure uniform mixing, but not too high to avoid foaming.

[0025] Wherein, the pH regulator in step 2) is a 0.1 mol / L HCl solution.

[0026] HCl solution was added dropwise, and the pH was measured after stirring and mixing thoroughly after each addition.

[0027] Preferably, in step 2), the pH is adjusted to 5.4.

[0028] In step 5), the filter cake is placed in a ball mill, ground for 20-30 minutes, and then crushed through an 80-mesh sieve to obtain a crystalline powder.

[0029] Grinding the filter cake promotes the eutectic effect between the amino acids and curcumin, making the amino acids and curcumin more tightly bound.

[0030] The invention also discloses an alcohol-relieving and hangover-resistant composition, which is prepared by the method described in the invention.

[0031] The advantages and positive effects of the present invention are as follows: curcumin and yeast extract form a cocrystal complex, thereby improving the compatibility of yeast extract and curcumin, avoiding the side effects of nausea and bad breath, expanding the application range of yeast extract and curcumin, improving the water solubility and bioavailability of curcumin, and improving the quality of tablets. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a bar graph showing the effects of different oral administration drugs at equal doses on the drunken behavior of mice in Experimental Example 4 of the present invention.

[0033] Figure 2 This is the blood drug concentration curve of Experimental Example 3 of the present invention.

[0034] Figure 3 This is the X-ray powder diffraction pattern of the curcumin-yeast extract cocrystal powder of Example 1 of the present invention. DETAILED DESCRIPTION Example 1

[0035] 1) Add 100 g of yeast extract to 1 L of purified water to obtain solution A. Add 25 g of curcumin to 2 L of anhydrous ethanol to obtain solution B. Mix solutions A and B and homogenize them twice under high pressure to obtain a mixed solution.

[0036] 2) Place the mixed solution in a 25°C water bath and slowly add 0.1 mol / L HCl solution while stirring at 150 rpm to adjust the pH to 5.

[0037] 3) Place the mixed solution in a -25°C cold trap and let it stand for 16 hours until crystals precipitate;

[0038] 4) Filter at 4°C to obtain filter cake and filtrate;

[0039] 5) crushing and drying the filter cake to obtain crystalline powder;

[0040] 6) The crystalline powder was pulverized and passed through an 80-mesh sieve. 150 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of croscarmellose sodium, and 5.5 g of silicon dioxide were added and mixed uniformly to obtain a mixed powder. 255 mL of a wetting agent (16.5 g of 8% povidone K30 solution dissolved in 95% ethanol) was slowly sprayed into the mixed powder while stirring. After uniform mixing, the mixture was vacuum-dried at low temperature for 10-30 minutes. 5.5 g of magnesium stearate was added, mixed uniformly, and tablets were pressed to obtain a composition for detoxifying alcohol and preventing hangovers. The tablet size was 0.5 g / tablet.

[0041] A small amount of crystalline powder was vacuum dried and measured using Cu-Kα rays, and the characteristic peaks in the X-ray powder diffraction pattern at 2θ were: 6.3, 13.9, 16.9, 17.3, 17.6, 17.8, 18.6, 19.5, 20.6, 20.9, 22.2, 22.8, 23.7, and 25.1. Example 2

[0042] 1) Add 140 g of yeast extract to 1.5 L of purified water to obtain solution A. Add 30 g of curcumin to 2 L of anhydrous ethanol to obtain solution B. Mix solutions A and B and homogenize them twice under high pressure to obtain a mixed solution.

[0043] 2) Place the mixed solution in a 25°C water bath and slowly add a pH adjuster while stirring to adjust the pH to 6;

[0044] 3) Place the mixed solution in a -25°C cold trap and let it stand for 32 hours until crystals precipitate;

[0045] 4) Filter at 4°C to obtain filter cake and filtrate;

[0046] 5) Place the filter cake in a ball mill, grind for 30 minutes, crush and dry to obtain crystalline powder;

[0047] 6) The crystalline powder was pulverized and passed through an 80-mesh sieve. 110 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of croscarmellose sodium, and 5.5 g of silicon dioxide were added and mixed uniformly to obtain a mixed powder. 255 mL of a wetting agent (16.5 g of 8% povidone K30 solution dissolved in 95% ethanol) was slowly sprayed into the mixed powder while stirring. After uniform mixing, the mixture was vacuum-dried at low temperature for 10-30 minutes. 5.5 g of magnesium stearate was added, mixed uniformly, and tablets were pressed to obtain a composition for detoxifying alcohol and preventing hangovers. The tablet size was 0.5 g / tablet. Example 3

[0048] 1) Add 120 g of yeast extract to 1.5 L of purified water to obtain solution A. Add 30 g of curcumin to 2 L of anhydrous ethanol to obtain solution B. Mix solutions A and B and homogenize them twice under high pressure to obtain a mixed solution.

[0049] 2) Place the mixed solution in a 25°C water bath and slowly add a pH adjuster while stirring to adjust the pH to 5.4;

[0050] 3) Place the mixed solution in a -25°C cold trap and let it stand for 32 hours until crystals precipitate;

[0051] 4) Filter at 4°C to obtain filter cake and filtrate;

[0052] 5) Place the filter cake in a ball mill, grind for 30 minutes, and then crush and dry to obtain crystalline powder;

[0053] 6) The crystalline powder was pulverized and passed through an 80-mesh sieve. 130 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of croscarmellose sodium, and 5.5 g of silicon dioxide were added and mixed uniformly to obtain a mixed powder. 255 mL of a wetting agent (16.5 g of 8% povidone K30 solution dissolved in 95% ethanol) was slowly sprayed into the mixed powder while stirring. After uniform mixing, the mixture was vacuum-dried at low temperature for 10-30 minutes. 5.5 g of magnesium stearate was added, mixed uniformly, and tablets were pressed to obtain a composition for detoxifying alcohol and preventing hangovers. The tablet size was 0.5 g / tablet. Comparative Example 1

[0054] 250 g of yeast extract, 30 g of curcumin, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of croscarmellose sodium, and 5.5 g of silicon dioxide were uniformly mixed to obtain a mixed powder. 255 mL of a wetting agent (16.5 g of 8% povidone K30 solution dissolved in 95% ethanol) was slowly sprayed into the mixed powder while stirring. After uniform mixing, the mixture was vacuum-dried at low temperature for 10-30 minutes. 5.5 g of magnesium stearate was added, mixed uniformly, and tableted to obtain the alcohol detoxification and anti-hangover composition of Comparative Example 1. Tablet size: 0.5 g / tablet.

[0055] Experimental Example 1: Product Quality Inspection

[0056] The hardness and friability of the tablets prepared in Examples 1-3 and Comparative Example 1 were tested. The hardness test method was based on the national standard GB / T17659-1999 "Test Method for Hardness of Pharmaceutical Tablets", and the friability test method was based on the "Chinese Pharmacopoeia Part III Tablet Friability Test Method". The test results are shown in Table 1.

[0057] Preparation of curcumin reference solution: Take an appropriate amount of curcumin reference, accurately weigh it, and add methanol to make a solution containing 10 μg per 1 ml.

[0058] Preparation of glutathione reference solution: Accurately weigh an appropriate amount of glutathione reference solution, dissolve it in mobile phase, and quantitatively dilute it to a solution containing approximately 0.2 mg per 1 mL. The mobile phase should be a mixture of sodium dihydrogen phosphate and sodium octane sulfonate (3.0 g sodium dihydrogen phosphate, 1.0 g sodium octane sulfonate, dissolved in water and diluted to 500 mL; adjust the solution to pH 3 with phosphoric acid): acetonitrile = 96:4 (volume ratio).

[0059] Determination of curcumin content in tablets prepared in Examples 1-3 and Comparative Example 1: Ten tablets prepared in Examples 1-3 and Comparative Example 1 were taken, crushed, and 0.2000 g was accurately weighed. The tablets were placed in a stoppered conical flask, and 10 ml of methanol was accurately added. The weight was weighed, and the mixture was heated under reflux for 30 minutes. The mixture was cooled, and the weight was reweighed. The weight loss was supplemented with methanol, shaken, and centrifuged. 1 ml of the supernatant was accurately measured and placed in a 20 ml volumetric flask. Methanol was added to dilute to the mark, shaken, and 5 μl of each of the reference solution and the test solution were accurately aspirated and injected into the liquid chromatograph. Chromatographic conditions: ODS column (250 mm × 4.6 mm, 5 μm), mobile phase: methanol-5% acetic acid solution (65:35), flow rate: 1.0 ml / min, measurement wavelength: 425 nm, column temperature: 30 ° C, injection volume: 10 μL.

[0060] Determination of Glutathione Content in Tablets Prepared in Examples 1-3 and Comparative Example 1: Ten tablets prepared in Examples 1-3 and Comparative Example 1, respectively, were pulverized and ground, and 0.6000 g was accurately weighed. The mixture was placed in a 100 mL volumetric flask, and an appropriate amount of mobile phase was added. The mixture was sonicated to dissolve the mixture, diluted to the mark with the mobile phase, shaken, and filtered. An appropriate amount of the filtrate was accurately measured and quantitatively diluted with the mobile phase to produce a solution containing approximately 5 mg of sample per 1 mL. Chromatographic conditions: ODS column (250 mm × 4.6 mm, 5 μm), mobile phase: a mixed solution of sodium dihydrogen phosphate and sodium octane sulfonate (3.0 g sodium dihydrogen phosphate, 1.0 g sodium octane sulfonate, dissolved in water and diluted to 500 mL, adjusted to pH 3 with phosphoric acid): acetonitrile = 96:4 (volume ratio), flow rate 0.8 mL / min, detection wavelength: 210 nm, column temperature 30°C, injection volume 10 μL.

[0061] The test results are shown in Table 1.

[0062] Table 1 Tablet hardness, friability and content of each ingredient.

[0063] Group Average hardness (N) Friability(%) Curcumin content (mg / g) Glutathione content (mg / g) Example 1 51.9 0.12 48.57 72.39 Example 2 52.1 0.12 50.28 72.46 Example 3 52. 0.13 50.34 72.31 Comparative Example 1 35.4 1.24 53.24 74.27

[0064] As can be seen from Table 1, the preparation method of the present invention increases tablet hardness, reduces tablet friability, and improves tablet quality. The curcumin and glutathione contents in the tablets meet quality standards. The glutathione content is ≥60 mg / g, and the curcumin content is ≥43 mg / g.

[0065] Example 2 Curcumin in vitro dissolution experiment

[0066] Tablets from Examples 1-3 and Comparative Example 1 were placed in an Erlenmeyer flask. 100 mL of hydrochloric acid solution (pH 1.2) containing 0.5% Tween-80 was added. The mixture was heated in a water bath at 37 ± 0.5°C with stirring at 50 rpm. After stirring for 24 hours, the mixture was allowed to equilibrate. 2 mL of the supernatant was filtered, and the filtrate was filtered through a 0.22 μm microporous membrane. The filtrate was analyzed by HPLC. Chromatographic conditions: ODS column (250 mm × 4.6 mm, 5 μm), mobile phase: methanol-5% acetic acid solution (65:35), flow rate: 1.0 mL / min, measurement wavelength: 425 nm, column temperature: 30°C, injection volume: 10 μL. Each sample was tested five times to calculate the saturated solubility of curcumin in simulated gastric fluid. The results are shown in Table 2.

[0067] Table 2 Saturated solubility of curcumin in simulated gastric fluid of Examples 1-3 and Comparative Example 1.

[0068]

[0069] As shown in the table above, the saturated solubility of curcumin in artificial gastric juice in the composition prepared using the preparation method of the present invention was increased by 5.42-5.46 times compared to that in Comparative Example 1. The cocrystals of curcumin and yeast extract of the present invention increased the water solubility of curcumin in artificial gastric juice. As shown in the table above, the saturated solubility of curcumin in artificial gastric juice in the composition prepared using the preparation method of the present invention was increased by 5.42-5.46 times compared to that in Comparative Example 1. The cocrystals of curcumin and yeast extract of the present invention increased the water solubility of curcumin in artificial gastric juice.

[0070] Experimental Example 3: Mouse drunken behavior experiment

[0071] Experimental Grouping: 48 SPF male C57 mice aged 6-8 weeks, weighing 25±2g, were randomly divided into 6 groups of 8 mice each after 3 days of adaptive feeding, namely blank control group, model group, experimental group 1-3, and comparative group 1.

[0072] Pre-intoxication experiment: Before the experiment began, mice in each group were gavaged with 14 ml / kg of 56% alcohol (Beijing Erguotou) at an intoxicating dose. The blank control group was gavaged with normal saline. The duration of intoxication and sobriety before dosing were recorded for each mouse in each group. Intoxication duration was measured from gavage administration to loss of righting reflex. Sobriety duration was measured from onset of intoxication to recovery of righting reflex after sobriety.

[0073] Among them, the standard for judging the drunken state is: after drinking, the mouse is placed with its back facing down and its limbs facing up to observe whether the righting reflex disappears. If it disappears and lasts for 30 seconds, it can be judged as a drunken state.

[0074] Criteria for determining the sober state: After the mouse enters the drunken state, the righting reflex is observed to be restored during the observation period. If the turning time is less than 30 seconds, it can be determined to be in the sober state.

[0075] Mice in each group were gavaged daily with 10 ml / kg of 56% alcohol (Beijing Erguotou) at a dose consistent with mouse intoxication. A blank control group was gavaged with the same volume of saline. Thirty minutes after the alcohol infusion, groups 1-3 were gavaged with the compositions of Examples 1-3 of the present invention, respectively, and group 1 of Comparative Example 1 was gavaged with the composition of Comparative Example 1 of the present invention. The blank control group and the model group were gavaged with saline.

[0076] The conversion method for the oral dose of mice is: the daily dose for humans (60kg) is 13.3mg / kg, and the dose for mice should be 80mg / kg, that is, the daily oral dose for each mouse is 2mg; the samples in the experimental group were diluted with normal saline for oral administration.

[0077] After 30 days of continuous gavage treatment, on day 31 of the experiment, mice in each group were once again gavaged with 14 ml / kg of 56% alcohol (Beijing Erguotou) at an intoxicating dose. The duration of intoxication and sobriety after administration was recorded for each mouse. Experimental Grouping: 48 SPF-grade male C57 mice aged 6-8 weeks, weighing 25 ± 2 g, were acclimated for 3 days and then randomly divided into 6 groups of 8 mice each: a blank control group, a model group, experimental groups 1-3, and a comparative group 1.

[0078] Pre-intoxication experiment: Before the experiment began, mice in each group were gavaged with 14 ml / kg of 56% alcohol (Beijing Erguotou) at an intoxicating dose. The blank control group was gavaged with normal saline. The duration of intoxication and sobriety before dosing were recorded for each mouse in each group. Intoxication duration was measured from gavage administration to loss of righting reflex. Sobriety duration was measured from onset of intoxication to recovery of righting reflex after sobriety.

[0079] Among them, the standard for judging the drunken state is: after drinking, the mouse is placed with its back facing down and its limbs facing up to observe whether the righting reflex disappears. If it disappears and lasts for 30 seconds, it can be judged as a drunken state.

[0080] Criteria for determining the sober state: After the mouse enters the drunken state, the righting reflex is observed to be restored during the observation period. If the turning time is less than 30 seconds, it can be determined to be in the sober state.

[0081] Mice in each group were gavaged daily with 10 ml / kg of 56% alcohol (Beijing Erguotou) at a dose consistent with mouse intoxication. A blank control group was gavaged with the same volume of saline. Thirty minutes after the alcohol infusion, groups 1-3 were gavaged with the compositions of Examples 1-3 of the present invention, respectively, and group 1 of Comparative Example 1 was gavaged with the composition of Comparative Example 1 of the present invention. The blank control group and the model group were gavaged with saline.

[0082] The conversion method for the oral dose of mice is: the daily dose for humans (60kg) is 13.3mg / kg, and the dose for mice should be 80mg / kg, that is, the daily oral dose for each mouse is 2mg; the samples in the experimental group were diluted with normal saline for oral administration.

[0083] After 30 days of continuous gavage treatment, on the 31st day of the experiment, each group of mice was once again gavaged with 14 ml / kg of 56-proof liquor (Beijing Erguotou) according to the intoxicating dose. The intoxication time and soberness time of each mouse after administration were recorded in each group.

[0084] The experimental results are shown in Table 3 and Figure 1 shown.

[0085] Table 3 Effects of different oral administration of equal doses of drugs on the drunken behavior of mice.

[0086] Group Time of intoxication before drug administration (min) Sobering time before administration (min) Time to intoxication after drug administration (min) Sobering time after drug administration (min) Blank control group —— —— —— —— Model Group 36.74±3.99 141.97±6.26 34.98±3.25 142.50±6.66 Example 1 group 37.60±5.11 147.48±6.96 57.83±3.39** 92.15±6.09** Example 2 group 37.67±4.34 144.15±8.33 58.50±3.48** 90.75±4.82** Example 3 group 36.55±5.71 145.64±8.71 58.11±3.65** 91.95±5.41** Comparative Example 1 39.28±5.88 147.67±9.84 46.94±2.64** 114.30±9.78**

[0087] Remark: * Compared with the model group, there was a statistically significant difference (P<0.05); ** Compared with the model group, there was a significant difference (P<0.01).

[0088] From Table 3 and Figure 1 As can be seen, there was no statistical difference in the time of drunkenness before and after administration in the model group, and no statistical difference in the time of sobering up before and after administration. The time of drunkenness after administration in the Example 1-3 group was extended by 22.85-23.82 minutes compared with the model group, and the time of drunkenness after administration in the Comparative Example 1 group was extended by 11.96 minutes compared with the model group. The time of sobering up after administration in the Example 1-3 group was shortened by 50.35-51.75 minutes compared with the model group, and the time of sobering up after administration in the Comparative Example 1 group was shortened by 28.2 minutes compared with the model group. Compared with the Comparative Example 1, the Examples 1-3 of the present invention have excellent anti-hangover effects.

[0089] Experimental Example 4: Bioavailability Experiment in Mice

[0090] 0.2 mL of blood was collected from the orbital venous plexus of mice in Example 1-3 and Comparative Example 1 groups at 15 min, 30 min, 1 h, 1.5 h, 2.5 h, 4 h, 6 h, and 8 h after the first oral administration. After blood collection, plasma was separated, methanol-5% acetic acid solution was added, extracted and centrifuged, and the supernatant was filtered through a 0.22 μm microporous filter membrane and then analyzed by HPLC. The blood concentration of curcumin in the mouse blood was detected. The results are shown in Table 4. The blood concentration curve is shown in Figure 2 The pharmacokinetic parameters of curcumin in the compositions of Examples 1-3 and Comparative Example 1 are shown in Table 5.

[0091] Table 4 Blood drug concentrations (ng / mL) in mice at different times.

[0092] Sampling time Example 1 Example 2 Example 3 Comparative Example 1 0.25h 590.45±28.00 588.36±31.51 584.34±27.71 18.27±1.36 0.5h 892.23±39.18 889.11±56.36 888.54±44.50 33.32±1.87 1h 371.74±17.81 373.48±26.70 373.20±20.73 44.46±1.90 1.5h 101.88±18.34 103.23±20.50 100.24±24.02 90.43±5.62 2h 71.57±7.10 72.31±8.33 71.53±6.54 18.41±2.24 2.5h 51.39±8.00 52.80±7.43 52.70±4.94 6.86±1.65 4h 46.80±4.81 47.91±6.16 49.07±4.91 1.02±0.20 6h 44.12±5.81 44.79±9.23 44.55±6.51 0.63±0.28 8h 20.21±4.06 19.71±4.18 19.39±4.23 0.20±0.12

[0093] Table 5 Pharmacokinetic parameters of curcumin in the compositions of Examples 1-3 and Comparative Example 1 of the present invention.

[0094] Group <![CDATA[T max (min)]]> <![CDATA[C max (ng / mL)]]> <![CDATA[AUC 0-8h (ng / mL h)]]> Example 1 group 30 892.23 996.54 Example 2 group 30 889.11 1000.95 Example 3 group 30 888.54 998.84 Comparative Example 1 30 90.43 103.82

[0095] Depend on Figure 2 It can be seen that the blood drug concentration curves of Example 1-3 groups are almost identical, which is very different from that of Comparative Example 1. The time for Example 1-3 groups to reach the maximum blood drug concentration is 30 minutes, and the time for Comparative Example 1 group to reach the maximum blood drug concentration is 90 minutes. The maximum blood drug concentration of Example 1-3 groups is 9.83-9.87 times that of Comparative Example 1 group. The area under the drug-time curve (AUC) reflects the bioavailability of the drug under oral administration. The larger the area under the drug-time curve, the higher the bioavailability. The area under the drug-time curve (AUC) of Example 1-3 groups of the present invention 0-8h ) is 9.60-9.64 times that of the comparative example 1. This indicates that the bioavailability of curcumin by the preparation method of the present invention is much higher than that of the comparative example 1 without eutectic bonding.

[0096] Experimental Example 5 Oral Compliance and Side Effect Evaluation of Composition

[0097] Twenty healthy volunteers aged 24-40 (half male and half female) were asked to rate the oral compliance and side effects of the compositions prepared in Examples 1-3 and Comparative Example 1 on a scale of 1-5. Each dose was taken at least 4 hours apart. A score of 1 indicated side effects such as nausea, vomiting, bad breath, and vomiting; 2 indicated three of these side effects; 3 indicated two of these side effects; 4 indicated one of these side effects; and 5 indicated good compliance with no side effects. The higher the score, the better the product's compliance. The total score is shown in Table 6.

[0098] Table 6 Composition compliance evaluation scores.

[0099] Serial number Example 1 Example 2 Example 3 Comparative Example 1 1 5 5 5 2 2 5 5 5 2 3 5 5 5 1 4 5 5 5 1 5 5 5 5 2 6 5 5 5 1 7 5 5 5 1 8 4 4 4 1 9 4 4 4 1 10 4 4 4 1 11 4 4 4 1 12 5 5 5 2 13 4 4 4 1 14 4 4 4 1 15 5 5 5 1 16 5 5 5 2 17 4 5 5 1 18 4 4 5 1 19 4 4 4 1 20 1 5 5 1 total 89 92 93 25

[0100] As can be seen from Table 6, the compositions prepared in Examples 1-3 of the present invention improved the side effects of yeast extract such as nausea, bad breath, and vomiting, compared with Comparative Example 1, thereby improving medication compliance and expanding the application range of the products.

[0101] The embodiments of the present invention are described in detail above, but the contents described are only preferred embodiments of the present invention and should not be considered to limit the scope of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.

Claims

1. A method for preparing a composition for sobering up and resisting hangover, characterized in that: The steps include: 1) Add 100-140g of yeast extract to 1-1.5L of purified water and mix well to obtain solution A. Add 25-30g of curcumin to 2L of anhydrous ethanol to obtain solution B. Mix solution A and solution B and homogenize under high pressure twice. obtaining a mixed solution; 2) Place the mixed solution in a 25°C water bath and slowly add a pH adjuster while stirring to adjust the pH to 5-6; 3) Place the mixed solution in a -25°C cold trap and let it stand for 16-32 hours until crystals precipitate; 4) Filter under suction at 4°C to obtain a filter cake and a filtrate; 5) crushing and drying the filter cake to obtain crystalline powder; 6) Add 110-150 g of yeast extract and 5 g of dihydroquercetin to the crystal powder, add auxiliary materials, mix well, and then compress into tablets to obtain an alcohol-relieving and anti-hangover composition.

2. The method for preparing the anti-hangover composition according to claim 1, wherein: In the step 5), the crystal powder is crushed and passed through an 80-mesh sieve.

3. The method for preparing the anti-hangover composition according to claim 1, wherein: The stirring rate in step 2) is 150-180 r / min.

4. The method for preparing the anti-hangover composition according to claim 1, wherein: Step 2) The pH regulator is a 0.1 mol / L HCl solution.

5. The method for preparing the anti-hangover composition according to any one of claims 1 to 4, characterized in that: In the step 2), the pH is adjusted to 5.

4.

6. The method for preparing the anti-hangover composition according to claim 5, characterized in that: The auxiliary materials include 226.5g microcrystalline cellulose, 16.5g povidone K30, 11g cross-linked carboxymethyl cellulose sodium, 5.5g silicon dioxide and 5.5g magnesium stearate.

7. A composition for relieving alcohol and preventing hangover, characterized in that: Prepared by the method according to any one of claims 1 to 6.

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