Composition for dispelling effects of alcohol and resisting hangover and preparation method thereof

Abstract

The invention belongs to the field of biological pharmacy, and particularly relates to a hangover-alleviating hangover-resisting composition and a preparation method thereof.The preparation method comprises the following steps that 1, a part of yeast extract is added into purified water to obtain a solution A, curcumin is added into absolute ethyl alcohol to obtain a solution B, and the solution A and the solution B are mixed to obtain a mixed solution; 2) adjusting the pH value of the mixed solution to 5-6; 3) placing the mixed solution in a cold trap at-25 DEG C, and standing for 16-32 hours until crystals are separated out; 4) performing suction filtration at 4 DEG C to obtain a filter cake and filtrate; according to the alcohol effect dispelling and hangover alleviating composition and the preparation method thereof, the yeast extract and curcumin are subjected to eutectic precipitation to obtain the composition, the application range of the composition is widened, and the solubility and bioavailability of curcumin are improved.

Description

Technical Field

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

[0002] As the pace of modern social life accelerates, people's social activities are gradually increasing, which inevitably involves drinking culture. However, excessive drinking can affect human health, including damage to the liver. Therefore, studying how to protect the liver and sober up has become an important topic. Existing alcohol sobering and liver protection products usually contain liver protection ingredients, such as puerarin, taurine, curcumin, etc., which aim to reduce the damage of alcohol to the liver and relieve the discomfort symptoms after 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 have many biological activities, such as antioxidant, cardio- and neuroprotective, anti-diabetic, antibacterial, anti-malarial, anti-human immunodeficiency virus (HIV), thrombus inhibition, anti-tumor and chemotherapeutic activities. It can improve alcohol-induced hepatocyte oxidative stress in vitro. Animal experiments showed that curcumin alleviated alcohol-induced liver histopathological changes and reduced the significant release of cellular alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Alcohol promotes the production of reactive oxygen species (ROS), the increase of malondialdehyde (MDA) content, the loss of GSH and the destruction of the antioxidant defense system, and this result is significantly improved under curcumin treatment. In summary, curcumin can prevent chronic alcoholic fatty liver.

[0004] Dihydroquercetin, also known as Taxifolin, is a natural dihydroflavonol compound, mainly extracted from the roots of alpine larch. It belongs to the bioflavonoids and has a variety of biological activities, including antioxidant, antiviral, anti-allergic, anti-atherosclerotic, anti-arrhythmic, and blood pressure regulation. Dihydroquercetin has five phenolic hydroxyl structures and excellent antioxidant capacity, which can be used to improve and protect alcoholic fatty liver.

[0005] Yeast extract is a product obtained by enzymatic autolysis (which can be separated and extracted) with food yeast as the main raw material under the joint action of yeast's own enzymes or external food-grade enzymes, and is rich in soluble components in yeast cells such as amino acids, peptides, and polypeptides. Glutathione in yeast extract can protect the activity of protein sulfhydryl groups in organisms and maintain the normal activity of proteins. It is also a coenzyme and cofactor of many enzymes and has many biological functions. It can not only remove free radicals in the body, but also protect liver cell membranes, promote liver membrane activity, anti-oxidation, detoxify, and maintain the integrity of red blood cell membranes.

[0006] Patent application number: CN201910402078.9, published on November 13, 2020, discloses a composition with alcohol sobering and liver protection functions, its preparation method and application, the composition contains 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, published on September 19, 2023, discloses a yeast complex with alcohol sobering and liver protection effects. The complex provided by the invention uses yeast extract, curcumin, grape seed powder, Hovenia dulcis powder, Rosa roxburghii powder, Pueraria powder and Dandelion powder as the main alcohol sobering and liver protection active substances, contains a variety of biologically active ingredients, on the one hand, can effectively slow down the gastrointestinal absorption of alcohol, and can increase the activity of acetaldehyde dehydrogenase in the body, accelerate the decomposition of alcohol, on the other hand, can effectively improve the liver's antioxidant capacity, remove free radicals in the body, and protect liver cells.

[0007] Yeast extract is rich in free amino acids and oligopeptides. When the purity is high, it has a unique taste of umami and a special odor. Curcumin has a bitter taste. When yeast extract and curcumin are mixed orally, they will not only produce a special odor, bitterness and other unpleasant tastes, but also easily irritate the stomach, causing nausea and vomiting, resulting in bad breath with a strong aftertaste that lasts for a long time. In severe cases, it can also cause nausea and vomiting, affecting the compliance of medication, 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 alcohol-relieving and anti-hangover composition with good compliance and high bioavailability.

[0009] The technical scheme of the present invention is: a method for preparing a hangover-relieving composition, comprising the following steps: 1) adding 100-140g of yeast extract to 1-1.5L of pure water to obtain solution A, adding 25-30g of curcumin to 2L of anhydrous ethanol to obtain solution B, mixing solution A and solution B and homogenizing them under high pressure twice to obtain 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 at 4°C to obtain filter cake and 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 press into tablets to obtain a hangover-relieving and anti-hangover composition.

[0010] Add 100-140g of yeast extract to 1-1.5L of water to obtain a supersaturated solution. The solution is turbid and yellow with a pH value between 6.5-7.5. The isoelectric point of most amino acids in yeast extract is 5.48-6.02 at 25°C, so when HCl is slowly added to the mixed solution to adjust the pH to 5-6, amino acids or peptides with amino acid residues will be more easily precipitated from the mixed solution. After standing in a -25°C cold trap for 16-32h, the positively charged amino acids and amino acid residues form a conjugation with the phenolic hydroxyl group of curcumin, and a eutectic with hydrogen bonds is formed between the molecules, which precipitates from the solution.

[0011] The crystalline powder obtained in step 5) is a yellow-brown needle-shaped crystalline powder.

[0012] The crystal powder was crushed and passed through an 80-mesh sieve.

[0013] The preparation method of the present invention forms a complex by hydrogen bonding yeast extract and curcumin, and forms a conjugated effect between amino acids and amino acid residues and the phenolic hydroxyl group of curcumin, which changes the molecular interaction and spatial arrangement of curcumin and amino acids at the molecular level, and does not stimulate the gastrointestinal tract after oral administration, thereby avoiding bad breath in the mouth. The application of the alcohol sobering and anti-hangover composition is expanded.

[0014] The researchers of the present invention also unexpectedly found that the quality of the tablets was improved after the yeast extract and curcumin cocrystal were combined, and the water solubility and bioavailability of curcumin were improved. The saturated solubility of curcumin in artificial gastric juice after cocrystal with yeast extract was increased by 5.46-5.49 times compared with curcumin without cocrystal. In the mouse drunk experiment, the highest blood concentration of curcumin after cocrystal with yeast extract was 9.8-9.9 times that of curcumin without cocrystal. The area under the drug-time curve was 9.6 times that of curcumin without cocrystal, indicating that curcumin has better water solubility and bioavailability after cocrystal with yeast extract.

[0015] Dihydroquercetin, yeast extract and curcumin have a synergistic effect, jointly inhibiting the metabolism of ethanol and reducing the formation of free radicals in the liver, reducing the damage of ethanol to the liver and nervous system. Dihydroquercetin can also protect the liver by regulating immune response and promoting liver cell regeneration.

[0016] The auxiliary materials include 226.5 g microcrystalline cellulose, 16.5 g povidone K30, 11 g cross-linked carboxymethyl cellulose sodium, 5.5 g silicon dioxide and 5.5 g magnesium stearate.

[0017] Povidone K30 is a wetting agent, which is dissolved in 95% ethanol solution with a mass concentration of 8%. The wetting agent needs to be added slowly and stirred while spraying to prevent the yeast extract from clumping and affecting the uniformity of the product.

[0018] The stirring rate in step 2) is 150-180 r / min.

[0019] The stirring rate should be chosen to ensure uniform mixing, but the stirring rate should not be too high to avoid foaming.

[0020] Wherein, the pH regulator in step 2) is a 0.1 mol / L HCl solution.

[0021] The HCl solution was added dropwise, and the pH was measured after stirring to mix thoroughly after each addition.

[0022] Preferably, in step 2), the pH is adjusted to 5.4.

[0023] 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.

[0024] Grinding the filter cake promotes the eutectic effect between the amino acids and curcumin, making the amino acids and curcumin more tightly bound.

[0025] The invention also discloses an alcohol sobering and anti-hangover composition, which is prepared by the method described in the invention.

[0026] The advantages and positive effects of the present invention are as follows: curcumin and yeast extract form a eutectic complex, thereby improving the compliance of yeast extract and curcumin, avoiding the side effects of nausea and bad breath, increasing the application range of yeast extract and curcumin, increasing the water solubility and bioavailability of curcumin, and improving the quality of tablets. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a bar graph showing the effects of different doses of intragastric drugs on the drunkenness behavior of mice in Experimental Example 4 of the present invention.

[0028] Figure 2 This is the blood drug concentration curve of Experimental Example 3 of the present invention.

[0029] Figure 3 This is the x-ray powder diffraction pattern of the curcumin-yeast extract co-crystal powder of Example 1 of the present invention. DETAILED DESCRIPTION Example 1

[0030] 1) Add 100 g of yeast extract to 1 L of pure water to obtain solution A, add 25 g of curcumin to 2 L of anhydrous ethanol to obtain solution B, mix solution A and solution B, and homogenize twice under high pressure to obtain a mixed solution; 2) Place the mixed solution in a 25°C water bath, slowly add 0.1 mol / L HCl solution while stirring at 150 r / min, and adjust the pH to 5; 3) Place the mixed solution in a -25°C cold trap and let it stand for 16 hours until crystals precipitate; 4) Filter at 4°C to obtain filter cake and filtrate; 5) crushing and drying the filter cake to obtain crystalline powder; 6) The crystal powder is crushed and passed through an 80-mesh sieve, and 150 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of cross-linked sodium carboxymethyl cellulose, and 5.5 g of silicon dioxide are added, and mixed evenly to obtain a mixed powder. 255 mL of a wetting agent is slowly sprayed into the mixed powder. The wetting agent is a povidone K30 solution with a mass concentration of 8%, dissolved in 95% ethanol, and the amount of povidone K30 added is 16.5 g. The mixture is stirred while spraying, and after mixing evenly, it is vacuum dried at low temperature for 10-30 min. After adding 5.5 g of magnesium stearate and mixing evenly, it is tableted to obtain a hangover-relieving and anti-hangover composition. The tablet specification is 0.5 g / tablet.

[0031] A small amount of crystalline powder was vacuum dried and measured with Cu-Kα rays. 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

[0032] 1) Add 140 g of yeast extract to 1.5 L of pure water to obtain solution A, add 30 g of curcumin to 2 L of anhydrous ethanol to obtain solution B, mix solution A and solution B and homogenize them twice under high pressure to obtain 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 6; 3) Place the mixed solution in a -25°C cold trap and let it stand for 32 hours until crystals precipitate; 4) Filter at 4°C to obtain filter cake and filtrate; 5) Place the filter cake in a ball mill, grind for 30 minutes, crush and dry to obtain crystalline powder; 6) The crystal powder is crushed and passed through an 80-mesh sieve, and 110 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of cross-linked sodium carboxymethyl cellulose, and 5.5 g of silicon dioxide are added and mixed to obtain a mixed powder. 255 mL of a wetting agent is slowly sprayed into the mixed powder. The wetting agent is a povidone K30 solution with a mass concentration of 8%, dissolved in 95% ethanol, and the amount of povidone K30 added is 16.5 g. The mixture is stirred while spraying. After mixing evenly, the mixture is vacuum dried at low temperature for 10-30 min. After adding 5.5 g of magnesium stearate and mixing evenly, the mixture is tableted to obtain a hangover-relieving and anti-hangover composition. The tablet specification is 0.5 g / tablet. Example 3

[0033] 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 solution A and solution B, and homogenize them twice under high pressure to obtain 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 5.4; 3) Place the mixed solution in a -25°C cold trap and let it stand for 32 hours until crystals precipitate; 4) Filter at 4°C to obtain filter cake and filtrate; 5) Place the filter cake in a ball mill, grind for 30 minutes, and then crush and dry to obtain crystalline powder; 6) The crystal powder is crushed and passed through an 80-mesh sieve, and 130 g of yeast extract, 5 g of dihydroquercetin, 226.5 g of microcrystalline cellulose, 11 g of cross-linked sodium carboxymethyl cellulose, and 5.5 g of silicon dioxide are added and mixed to obtain a mixed powder. 255 mL of a wetting agent is slowly sprayed into the mixed powder. The wetting agent is a povidone K30 solution with a mass concentration of 8%, dissolved in 95% ethanol, and the amount of povidone K30 added is 16.5 g. The mixture is stirred while spraying, and after mixing evenly, it is vacuum dried at low temperature for 10-30 min. After adding 5.5 g of magnesium stearate and mixing evenly, it is tableted to obtain a hangover-relieving and anti-hangover composition. The tablet specification is 0.5 g / tablet. Comparative Example 1

[0034] 250g of yeast extract, 30g of curcumin, 5g of dihydroquercetin, 226.5g of microcrystalline cellulose, 11g of cross-linked sodium carboxymethyl cellulose and 5.5g of silicon dioxide were mixed to obtain a mixed powder, 255mL of a wetting agent was slowly sprayed into the mixed powder, the wetting agent was a povidone K30 solution with a mass concentration of 8%, dissolved in 95% ethanol, and the amount of povidone K30 added was 16.5g, and the mixture was stirred while spraying, and after mixing evenly, it was vacuum dried at low temperature for 10-30min, and 5.5g of magnesium stearate was added and mixed evenly, and then tableted to obtain the alcohol-relieving and anti-hangover composition of comparative example 1. The tablet specification is 0.5g / tablet. Experimental Example 1: Product Quality Inspection

[0035] The hardness and friability of the tablets prepared in Examples 1-3 and Comparative Example 1 were tested. The hardness test method referred to the national standard GB / T17659-1999 "Test Method for Hardness of Pharmaceutical Tablets", and the friability test method referred to the friability test method for tablets in Part III of the "Chinese Pharmacopoeia". The test results are shown in Table 1.

[0036] 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.

[0037] Preparation of glutathione reference solution: Take an appropriate amount of glutathione reference, weigh accurately, dissolve in mobile phase and quantitatively dilute to make a solution containing about 0.2 mg per 1 ml. The mobile phase is a mixed solution of sodium dihydrogen phosphate and sodium octane sulfonate (3.0 g sodium dihydrogen phosphate, 1.0 g sodium octane sulfonate, dissolve in water and make up to 500 mL, adjust the solution pH to 3 with phosphoric acid): acetonitrile = 96:4 (volume ratio).

[0038] Determination of curcumin content in the tablets prepared in Example 1-3 and Comparative Example 1: Take 10 tablets prepared in Examples 1-3 and Comparative Example 1 of the present invention, crush and grind them, accurately weigh 0.2000g, place them in a stoppered conical flask, accurately add 10ml of methanol, weigh the weight, heat and reflux for 30 minutes, cool, weigh again, make up the lost weight with methanol, shake well, centrifuge, accurately measure 1ml of supernatant, place it in a 20ml volumetric flask, dilute to the scale with methanol, shake well, accurately draw 5μl of reference solution and test solution respectively, and inject them into the liquid chromatograph. Chromatographic conditions: chromatographic column ODS chromatographic column (250mm×4.6mm, 5μm), mobile phase: methanol-5% acetic acid solution (65:35), flow rate: 1.0ml / min, measurement wavelength: 425nm, column temperature: 30℃, injection volume 10μL.

[0039] Determination of glutathione content in the tablets prepared in Example 1-3 and Comparative Example 1: Take 10 tablets prepared in Examples 1-3 and Comparative Example 1 of the present invention, crush and grind them, accurately weigh 0.6000g, put them in a 100ml volumetric flask, add an appropriate amount of mobile phase, dissolve them by ultrasound, dilute them to the mark with the mobile phase, shake them well, filter them, accurately measure an appropriate amount of the filtrate, and quantitatively dilute them with the mobile phase to make a solution containing about 5mg of the sample per 1ml. Chromatographic conditions: Chromatographic column ODS chromatographic column (250mm×4.6mm, 5μm), mobile phase: mixed solution of sodium dihydrogen phosphate and sodium octane sulfonate (3.0 g of sodium dihydrogen phosphate, 1.0 g of sodium octane sulfonate, dissolve them in water and make them dilute to 500 mL, adjust the solution pH to 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.

[0040] The test results are shown in Table 1.

[0041] Table 1 Hardness, friability and content of each ingredient of the tablets.

[0042] 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 As can be seen from Table 1, the preparation method of the present invention improves the hardness of the tablets, reduces the friability of the tablets, and improves the quality of the tablets. The curcumin content and glutathione content in the tablets meet the quality standard requirements. The glutathione content is ≥60 mg / g, and the curcumin content is ≥43 mg / g. Example 2 Curcumin in vitro dissolution experiment

[0043] The tablets of Examples 1-3 and Comparative Example 1 were placed in a conical flask, and 100 mL of hydrochloric acid solution (pH 1.2) containing 0.5% Tween-80 was added, respectively, and heated in a water bath at 37±0.5°C, with a stirring speed of 50 r / min. After stirring for 24 hours, the supernatant was filtered with 2 mL, and the filtrate was filtered with a 0.22 μm microporous filter membrane, and the subsequent filtrate was analyzed by HPLC. Chromatographic conditions: chromatographic column ODS chromatographic 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 5 times to calculate the saturated solubility of curcumin in simulated gastric fluid. The results are shown in Table 2.

[0044] Table 2 Saturated solubility of curcumin in simulated gastric fluid of Examples 1-3 and Comparative Example 1.

[0045]

[0046] As can be seen from the above table, in the composition prepared by the preparation method of the present invention, the saturated solubility of curcumin in artificial gastric juice is increased by 5.42-5.46 times compared with the group 1 of comparative example. The cocrystal of curcumin and yeast extract of the present invention improves the water solubility of curcumin in artificial gastric juice. As can be seen from the above table, in the composition prepared by the preparation method of the present invention, the saturated solubility of curcumin in artificial gastric juice is increased by 5.42-5.46 times compared with the group 1 of comparative example. The cocrystal of curcumin and yeast extract of the present invention improves the water solubility of curcumin in artificial gastric juice. Experimental Example 3: Mouse drunkenness behavior experiment

[0047] Experimental groups: 48 SPF male C57 mice aged 6-8 weeks, weighing 25±2g, were randomly divided into 6 groups after 3 days of adaptive feeding, including blank control group, model group, experimental example 1-3 groups and comparative example 1 group.

[0048] Pre-drunkenness experiment: Before the experiment, mice in each group were gavaged with 14 ml / kg of 56% liquor (Beijing Erguotou) according to the intoxicating dose, and the blank control group was gavaged with saline. The drunkenness time and sobering time before administration were recorded for each mouse in each group. The drunkenness time is the time from gavage to the disappearance of the righting reflex. The sobering time is the time from entering the drunken state to the recovery of the righting reflex after sobering.

[0049] Among them, the standard for judging the drunken state is: after drinking, the mouse is placed with its back facing downward and its limbs facing upward to observe whether the righting reflex disappears. If it disappears and lasts for 30 seconds, it can be judged as a drunken state.

[0050] Criteria for determining the sober state: After the mouse enters the drunken state, observe whether the righting reflex is restored during the observation period. If the turning over time is shorter than 30s, it can be determined to be in the sober state.

[0051] Each group was gavaged with 10 ml / kg of 56% liquor (Beijing Erguotou) daily according to the intoxicating dose for mice, and the blank control group was gavaged with the same volume of saline. 30 minutes after gavage, the Example 1-3 groups were gavaged with the compositions of the Examples 1-3 of the present invention, and the Comparative Example 1 group was gavaged with the composition of the Comparative Example 1 of the present invention. The blank control group and the model group were gavaged with saline.

[0052] The conversion method for the oral gavage dose for 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 gavage dose for each mouse is 2mg; the samples in the experimental group were diluted with normal saline for oral gavage.

[0053] After 30 days of continuous gavage treatment, on the 31st day of the experiment, mice in each group were gavaged with 14 ml / kg of 56-degree liquor (Beijing Erguotou) according to the intoxicating dose. The intoxication time and sobering time of each mouse after administration were recorded in each group. Experimental grouping: 48 SPF male C57 mice aged 6-8 weeks, weighing 25±2g, were randomly divided into 6 groups after 3 days of adaptive feeding, with 8 mice in each group. They were blank control group, model group, experimental group 1-3 and comparative group 1.

[0054] Pre-drunkenness experiment: Before the experiment, mice in each group were gavaged with 14 ml / kg of 56% liquor (Beijing Erguotou) according to the intoxicating dose, and the blank control group was gavaged with saline. The drunkenness time and sobering time before administration were recorded for each mouse in each group. The drunkenness time is the time from gavage to the disappearance of the righting reflex. The sobering time is the time from entering the drunken state to the recovery of the righting reflex after sobering.

[0055] Among them, the standard for judging the drunken state is: after drinking, the mouse is placed with its back facing downward and its limbs facing upward to observe whether the righting reflex disappears. If it disappears and lasts for 30 seconds, it can be judged as a drunken state.

[0056] Criteria for determining the sober state: After the mouse enters the drunken state, observe whether the righting reflex is restored during the observation period. If the turning over time is shorter than 30s, it can be determined to be in the sober state.

[0057] Each group was gavaged with 10 ml / kg of 56% liquor (Beijing Erguotou) daily according to the intoxicating dose for mice, and the blank control group was gavaged with the same volume of saline. 30 minutes after gavage, the Example 1-3 groups were gavaged with the compositions of the Examples 1-3 of the present invention, and the Comparative Example 1 group was gavaged with the composition of the Comparative Example 1 of the present invention. The blank control group and the model group were gavaged with saline.

[0058] The conversion method for the oral gavage dose for 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 gavage dose for each mouse is 2mg; the samples in the experimental group were diluted with normal saline for oral gavage.

[0059] 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 sobering time of each mouse after administration were recorded in each group.

[0060] The experimental results are shown in Table 3 and Figure 1 shown.

[0061] Table 3 Effects of different oral gavage drugs at equal doses on the drunken behavior of mice.

[0062] Group Intoxication time before drug administration (min) Sobering up time before medication (min) Time to intoxication after drug administration (min) Sobering up time after 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** 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).

[0063] From Table 3 and Figure 1 It can be seen that there is no statistical difference in the drunkenness time before and after administration in the model group, and there is no statistical difference in the sobering time before and after administration. The drunkenness time after administration in the Example 1-3 group was extended by 22.85-23.82min compared with the model group, and the drunkenness time after administration in the Comparative Example 1 group was extended by 11.96min compared with the model group. The sobering time after administration in the Example 1-3 group was shortened by 50.35-51.75min compared with the model group, and the sobering time after administration in the Comparative Example 1 group was shortened by 28.2min compared with the model group. Compared with the Comparative Example 1, the Examples 1-3 of the present invention have excellent sobering and anti-hangover effects. Experimental Example 4: Bioavailability experiment in mice

[0064] 0.2 mL of blood was collected from the mice in Example 1-3 and Comparative Example 1 groups through the orbital venous plexus 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 analyzed by HPLC. The blood concentration of curcumin in the blood of mice was detected, and 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.

[0065] Table 4 Blood drug concentrations (ng / mL) of mice at different times.

[0066] 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 Table 5 Pharmacokinetic parameters of curcumin in the compositions of Examples 1-3 and Comparative Example 1 of the present invention.

[0067] 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 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 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. Experimental Example 5 Evaluation of oral compliance and side effects of the composition

[0068] 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 from 1 to 5 points, with at least 4 hours between each dose. 1 point represents side effects such as nausea, nausea, bad breath, and vomiting; 2 points represent 3 of the side effects; 3 points represent 2 of the side effects; 4 points represent 1 of the side effects; 5 points represent good compliance and no side effects. The higher the score, the better the compliance of the product. The total score is shown in Table 6.

[0069] Table 6 Composition compliance evaluation scores.

[0070] 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 As can be seen from Table 6, the compositions prepared in Examples 1-3 of the present invention improve the side effects of yeast extract that easily cause nausea, bad breath, and vomiting, improve medication compliance, and expand the application range of the product compared with Comparative Example 1.

[0071] The embodiments of the present invention are described in detail above, but the contents described are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made according to the scope of application 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 method comprises the following steps: 1) adding 100-140 g of yeast extract into 1-1.5 L of pure water, mixing uniformly to obtain solution A, adding 25-30 g of curcumin into 2 L of anhydrous ethanol to obtain solution B, mixing solution A and solution B and homogenizing them under high pressure twice to obtain 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 4°C to obtain filter cake and 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 press into tablets to obtain a hangover-relieving and anti-hangover composition.

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

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

5. The method for preparing the alcohol-relieving and 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 226.5 g microcrystalline cellulose, 16.5 g povidone K30, 11 g cross-linked carboxymethyl cellulose sodium, 5.5 g silicon dioxide and 5.5 g magnesium stearate.

7. A composition for sobering up and resisting hangover, characterized in that: In the step 5), the filter cake is placed in a ball mill, ground for 20-30 minutes, and then crushed to obtain crystalline powder.

8. A composition for sobering up and resisting hangover, characterized in that: Prepared by the method according to any one of claims 1 to 7.

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