Use of a composition for the manufacture of a medicament for the prevention and / or alleviation of hangover

Abstract

The application relates to the technical field of medical preparations, and discloses application of a composition in preparation of a medicine for preventing and / or reducing hangover, wherein the composition is composed of calcium beta-hydroxy-beta-methylbutyrate (CaHMB), probiotics and prebiotics; the probiotics include at least one of Pediococcus pentosaceus, Lactobacillus rhamnosus, Lactobacillus casei and Bifidobacterium longum; the prebiotics include at least one of fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, inulin, polydextrose and resistant dextrin; the composition with the function of preventing and / or reducing hangover is used in preparation of a preparation for preventing and reducing hangover together with a pharmaceutically acceptable carrier, and the preparation includes an injection, a freeze-dried powder injection, a paste, a spray or an oral preparation; the composition of the application not only has the effect of preventing and reducing hangover, but also can effectively improve alcohol-induced liver injury.

Description

Technical Field

[0001] This invention relates to the field of medical preparations technology, specifically to the use of a composition in the preparation of a medicament for preventing and / or alleviating hangovers. Background Technology

[0002] The number of alcohol consumers in China has increased, exceeding 500 million according to statistics. Among these 500 million drinkers, 60% have a need for hangover relief, and 123 million people have engaged in excessive drinking. Hangover is a series of unpleasant experiences that occur after drinking, such as headache, diarrhea, loss of appetite, nausea, vomiting, chills, and sweating. Objective symptoms of hangover include cognitive and motor impairments, blood changes, and hormonal changes. The causes of hangover are understood to include dehydration, toxicity of alcohol and alcohol metabolites (acetaldehyde, formaldehyde, acetone, etc.), and malnutrition due to malabsorption (insufficient blood sugar, vitamins, and minerals).

[0003] To alleviate hangover symptoms, several commercially available beverages exist, such as: Condition, a hangover remedy made by CJ Corporation in South Korea using extracts from prickly pear, astragalus, lotus seeds, rice germ, and Japanese raisin tree seeds; Morning Care, a hangover remedy made by Dong-A Pharmaceutical Co., Ltd. in South Korea using extracts from fermented rice germ and soybeans, as well as milk thistle extract powder as its main ingredients; and Dawn 808, made by Glami Co., Ltd. using extracts from alder and rowan trees. Various hangover-relieving beverages have been developed using these methods, each with unique properties. However, despite these achievements, there is still a need to develop products that can effectively alleviate hangovers.

[0004] β-hydroxy-β-methyl butyric acid (HMB) is a five-carbon organic acid and an active metabolite of leucine, an essential branched-chain amino acid in the human body. There are two common supplemental forms of HMB: its free form and its calcium salt form, calcium β-hydroxy-β-methyl butyrate (CaHMB). As early as 2011, CaHMB was approved as a new resource food in China, with its use limited to sports nutrition foods and special medical purpose formula foods, with a daily intake of ≤3 grams. Subsequently, in Announcement No. 7 of 2017, the scope of CaHMB's use was further expanded. It can be used in beverages, milk and dairy products, cocoa products, chocolate and chocolate products, confectionery and baked goods. In Announcement No. 1 of 2025, the recommended daily intake was increased to ≤6 grams. After years of experimental and clinical application, the safety and efficacy of HMB have gradually been supported by experimental and clinical data. HMB was initially used in clinical medical fields such as alleviating muscle loss in patients who have been bedridden for a long time, and has gradually expanded to the field of civilian health care. At present, HMB is mainly favored as a sports nutrition supplement and has not been involved in the prevention and relief of hangovers. Summary of the Invention

[0005] To address the aforementioned technical problems, the present invention provides the use of a composition in the preparation of a medicament for preventing and / or alleviating hangovers, the composition comprising calcium β-hydroxy-β-methylbutyrate, probiotics, and prebiotics.

[0006] In this invention, "preventing and / or alleviating hangovers" means preventing and alleviating hangovers, preventing hangovers, or alleviating hangovers. That is, this invention discloses one or more of the following: the use of a composition in the preparation of a medicament with hangover prevention effect, the use of a composition in the preparation of a medicament with hangover relief effect, and the use of a composition in the preparation of a medicament with hangover prevention and alleviation effect.

[0007] The composition includes calcium β-hydroxy-β-methylbutyrate, probiotics, and prebiotics.

[0008] Further, the mass ratio of the calcium β-hydroxy-β-methylbutyrate, probiotics, and prebiotics, by weight, is (0.08-0.66):(0.04-0.12):(0.3-0.8).

[0009] Further, the mass ratio of the calcium β-hydroxy-β-methylbutyrate, probiotics, and prebiotics, by weight, is (0.16-0.58):(0.05-0.11):(0.37-0.73).

[0010] Furthermore, the mass ratio of the calcium β-hydroxy-β-methylbutyrate, probiotics, and prebiotics is 46:7:47 by weight.

[0011] Preferably, the probiotics include at least one of Pediococcus pentosaceus, Lactobacillus rhamnosus, Lactobacillus casei, and Bifidobacterium longum.

[0012] Furthermore, the *Pediococcus pentosus* includes *Pediococcus pentosus* PP06, the *Lactobacillus rhamnosus* includes *Lactobacillus rhamnosus* WKA55, the *Lactobacillus casei* includes *Lactobacillus casei* LC89, and the *Bifidobacterium longum* includes *Bifidobacterium longum* BL11.

[0013] Preferably, the prebiotic includes at least one of fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, inulin, polydextrose, and resistant dextrin.

[0014] The use of the composition having the effect of preventing and / or alleviating hangovers in the preparation of a medicament for preventing and / or alleviating hangovers.

[0015] Medications for preventing and / or alleviating hangovers include formulations; said formulations include one or more of the following: hangover prevention formulations, hangover relief formulations, and hangover prevention or relief formulations.

[0016] Preferably, the hangover prevention and relief formulation comprises a composition having a hangover prevention and / or hangover relief effect and a pharmaceutically acceptable carrier, said carrier comprising sugars, lubricants, and flavoring agents; said sugars comprising at least one of lactose, glucose, sucralose, and sorbitol; said lubricants comprising at least one of stearic acid and magnesium stearate; and said flavoring agents comprising at least one of fruit powder, sweet orange powder, blueberry powder, and pomegranate powder.

[0017] Preferably, the dosage form of the preparation includes injections, lyophilized powder injections, ointments, sprays, and oral preparations.

[0018] Preferably, the oral preparation includes at least one of capsules, tablets, and granules.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention provides a composition with the effect of preventing and / or alleviating hangovers, the main components of which are calcium β-hydroxy-β-methylbutyrate (CaHMB), probiotics, and prebiotics, wherein: CaHMB can significantly improve the tolerance of mice to acute alcohol exposure, improve the impaired motor coordination and fine motor control caused by alcohol, and has a certain effect in preventing and alleviating hangovers. Probiotics offer numerous health benefits, including regulating the digestive system, enhancing immunity, and combating allergies. Some probiotics can even increase the activity of acetaldehyde dehydrogenase and alcohol dehydrogenase, aiding in the degradation of ethanol in the blood. Furthermore, probiotics can alleviate intestinal discomfort caused by alcohol consumption by improving the gut microbiota. Additionally, probiotics can utilize their metabolites, such as butyric acid and acetic acid, to regulate the activation and expression of the immune system and reduce oxidative stress. For instance, Lactobacillus and Bifidobacterium do not convert alcohol into the toxic carcinogen acetaldehyde. In simulated intestinal environments, they exhibit a good ability to metabolize and eliminate acetaldehyde. Moreover, Lactobacillus and Bifidobacterium have a strong regulatory effect on endogenous and exogenous acetaldehyde levels in the colon, meaning that probiotics can reduce the incidence of gastrointestinal diseases caused by acetaldehyde production from excessive alcohol intake. Prebiotics such as fructooligosaccharides, galactooligosaccharides, inulin, polydextrose, and resistant dextrin serve as "food" for probiotics, promoting their growth and activity. The combination of probiotics and prebiotics can produce a synergistic effect, enhancing each other's efficacy. Probiotics can directly increase the number of beneficial bacteria in the gut, while prebiotics indirectly improve the gut environment by promoting the growth of beneficial bacteria, thereby alleviating gastrointestinal reactions caused by hangovers. CaHMB can reduce alcohol-induced liver cell damage, while probiotics and prebiotics can reduce endotoxins entering the bloodstream and improve intestinal barrier function by regulating the balance of intestinal flora. The three work together to reduce alcohol toxicity through the gut-liver dual pathway, relieve post-drinking discomfort, protect liver and intestinal health, and improve the efficiency of alcohol detoxification and the body's metabolic repair capabilities. In summary, the synergistic effect of CaHMB, probiotics, and prebiotics can prevent and alleviate inflammatory responses, mitochondrial dysfunction, and gastrointestinal reactions caused by hangovers, demonstrating a good effect in preventing and alleviating hangovers.

[0020] 2. The composition of this invention can significantly reduce the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the liver of mice. These two enzymes are core markers of liver damage and are mainly present in hepatocytes under normal conditions. When alcohol induces liver damage, hepatocytes rupture, releasing the enzymes into the blood, resulting in an abnormally low level in the liver and an increased level in the plasma. The composition of this invention protects the integrity of hepatocytes and reduces enzyme loss, thereby restoring the normal levels of ALT and AST in the liver and reducing the concentration of ALT and AST in the plasma. At the same time, the composition of this invention can significantly increase the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) in the liver. ADH can efficiently catalyze the conversion of alcohol into acetaldehyde, and ALDH2 further decomposes the more toxic acetaldehyde into non-toxic acetic acid, accelerating the metabolism and clearance of alcohol in the body and reducing the direct damage of alcohol and its intermediate product acetaldehyde to the liver. In addition, the composition of this invention reduces alcohol-induced inflammatory infiltration and tissue damage in the liver, playing a multi-dimensional role in protecting hepatocyte structure, accelerating alcohol metabolism, and alleviating liver inflammation, effectively improving alcohol-induced liver damage and achieving significant effects in detoxifying and protecting the liver. Attached Figure Description

[0021] Figure 1 This is a comparative graph showing the average time mice spent on the rotarod in Experiment 1 of the present invention, including the normal group, control group, 0.5CaHMB pretreatment group, 1CaHMB pretreatment group, 4CaHMB pretreatment group, and 7CaHMB pretreatment group. Figure 1 In the figure, A is a comparison chart of the rotarod behavioral test 30 minutes after acute alcohol administration in Experiment Example 1; Figure 1 B in the figure is a comparison chart of the rotarod behavioral test 60 minutes after acute alcohol administration in Experiment Example 1; Figure 1 C in the figure is a comparison chart of the rotarod behavioral test 90 minutes after acute alcohol administration in Experiment Example 1; Figure 1 D in the figure is a comparison chart of the rotarod behavioral test 120 minutes after acute alcohol administration in Experiment Example 1; Figure 2 This is a comparative graph showing the average time mice spent on the rotarod in Experimental Example 2 of the present invention, including the normal group, control group, treatment group A, treatment group B, treatment group C, treatment group D, and treatment group E. Figure 2 In the figure, A is a comparison chart of the rotarod behavioral test 30 minutes after acute alcohol administration in Experiment Example 2; Figure 2 B in the figure is a comparison chart of the rotarod behavioral test 60 minutes after acute alcohol administration in Experiment Example 2; Figure 2 C in the figure is a comparison chart of the rotarod behavioral test 90 minutes after acute alcohol administration in Experiment Example 2; Figure 2 D in the figure is a comparison chart of the rotarod behavioral test 120 minutes after acute alcohol administration in Experiment Example 2; Figure 3 This is a comparison chart of the ethanol and acetaldehyde content in the blood of mice in the control group and the CaHMB treatment group in Experiment Example 3 of this invention; Figure 3 In the figure, A is a bar chart of blood ethanol concentration in the CaHMB treatment group and the control group 3 hours after acute alcohol administration; Figure 3 B in the figure represents the blood acetaldehyde concentration changes in the CaHMB treatment group and the control group during the acute alcohol administration period of 1-6 hours. Figure 3 The left graph of C in the figure is a bar chart of blood acetaldehyde concentration in the CaHMB treatment group and the control group 1.5 hours after acute alcohol administration. Figure 3 The middle graph of C in the figure is a bar chart of blood acetaldehyde concentration in the CaHMB treatment group and the control group 3 hours after acute alcohol administration. Figure 3 The right figure of C in the figure is a bar chart of blood acetaldehyde concentration in the CaHMB treatment group and the control group within 6 hours after acute alcohol administration; Figure 4 This is a comparison chart of the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the plasma of mice in the normal group, control group, and CaHMB treatment group in Experiment Example 4 of the present invention. Figure 5 These are HE-stained sections of mouse livers from the normal group, control group, and CaHMB treatment group in Experiment Example 4 of this invention; Figure 6 This is a comparative graph showing the levels of ADH and ALDH2 in the livers of mice in the normal group and the CaHMB treatment group in Experiment Example 5 of this invention. Detailed Implementation

[0022] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0023] Example 1 This embodiment discloses a method for preparing a composition tablet with the effect of preventing and / or alleviating hangovers, comprising the following steps: Step 1: Disinfect the workshop environment, turn on the dehumidifier, and control the humidity to 45%. Take CaHMB, probiotics, fructooligosaccharides, sorbitol, sweet orange fruit powder, magnesium stearate, and sucralose raw materials respectively. Pass each of the above raw materials through a 40-mesh sieve to remove uneven raw materials. Then weigh and label each raw material separately for later use. Among them, the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:1. Step 2: Clean and disinfect the environment and necessary equipment and instruments, turn on the dehumidifier and control the humidity to 45%; weigh out 56 g of CaHMB, 76 g of probiotics, 520 g of fructooligosaccharides, 896 g of sorbitol, 423 g of sweet orange fruit powder, 24 g of magnesium stearate, and 5 g of sucralose, mix them at 15 rpm for 15 minutes, seal and store, and label. Step 3: Disinfect the environment and equipment, control the humidity at 45%, compress the tablets, check the tablet weight and hardness every 30 minutes, control the tablet weight at the outlet to 2000 mg and the hardness at the outlet to 80 N, and obtain a composition tablet with the effect of preventing and / or reducing hangovers.

[0024] Example 2 This embodiment discloses a method for preparing a composition tablet with the effect of preventing and / or alleviating hangovers, comprising the following steps: Step 1: Disinfect the workshop environment, turn on the dehumidifier, and control the humidity to 45%. Take CaHMB, probiotics, fructooligosaccharides, sorbitol, sweet orange fruit powder, magnesium stearate, and sucralose raw materials respectively. Pass each of the above raw materials through a 40-mesh sieve to remove uneven raw materials. Then weigh and label each raw material separately for later use. Among them, the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:1. Step 2: Clean and disinfect the environment and necessary equipment and instruments, turn on the dehumidifier and control the humidity to 45%; weigh out 112 g of CaHMB, 72 g of probiotics, 500 g of fructooligosaccharides, 886 g of sorbitol, 401 g of sweet orange fruit powder, 24 g of magnesium stearate, and 5 g of sucralose, mix them at 15 rpm for 15 min, seal and store, and label. Step 3: Disinfect the environment and equipment, control the humidity at 45%, compress the tablets, check the tablet weight and hardness every 30 minutes, control the tablet weight at the outlet to 2000 mg and the hardness at the outlet to 80 N, and obtain a composition tablet with the effect of preventing and / or reducing hangovers.

[0025] Example 3 This embodiment discloses a method for preparing a composition tablet with the effect of preventing and / or alleviating hangovers, comprising the following steps: Step 1: Disinfect the workshop environment, turn on the dehumidifier, and control the humidity to 45%. Take CaHMB, probiotics, fructooligosaccharides, sorbitol, sweet orange fruit powder, magnesium stearate, and sucralose raw materials respectively. Pass each of the above raw materials through a 40-mesh sieve to remove uneven raw materials. Then weigh and label each raw material separately for later use. Among them, the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:1. Step 2: Clean and disinfect the environment and necessary equipment and instruments, turn on the dehumidifier and control the humidity to 45%; weigh out 450 g of CaHMB, 67 g of probiotics, 464 g of fructooligosaccharides, 685 g of sorbitol, 305 g of sweet orange fruit powder, 24 g of magnesium stearate, and 5 g of sucralose, mix them at 15 rpm for 15 min, seal and store, and label. Step 3: Disinfect the environment and equipment, control the humidity at 45%, compress the tablets, check the tablet weight and hardness every 30 minutes, control the tablet weight at the outlet to 2000 mg and the hardness at the outlet to 90 N, and obtain a composition tablet with the effect of preventing and / or reducing hangovers.

[0026] Example 4 This embodiment discloses a method for preparing a composition tablet with the effect of preventing and / or alleviating hangovers, comprising the following steps: Step 1: Disinfect the workshop environment, turn on the dehumidifier, and control the humidity to 45%. Take CaHMB, probiotics, fructooligosaccharides, sorbitol, sweet orange fruit powder, magnesium stearate, and sucralose raw materials respectively. Pass each of the above raw materials through a 40-mesh sieve to remove uneven raw materials. Then weigh and label each raw material separately for later use. Among them, the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:1. Step 2: Clean and disinfect the environment and necessary equipment and instruments, turn on the dehumidifier and control the humidity to 45%; weigh out 675 g of CaHMB, 64 g of probiotics, 440 g of fructooligosaccharides, 535 g of sorbitol, 257 g of sweet orange fruit powder, 24 g of magnesium stearate, and 5 g of sucralose, mix them at 15 rpm for 15 minutes, seal and store, and label. Step 3: Disinfect the environment and equipment, control the humidity at 45%, compress the tablets, check the tablet weight and hardness every 30 minutes, control the tablet weight at the discharge port to 2000 mg and the hardness at the discharge port to 100 N, and obtain a composition tablet with the effect of preventing and / or reducing hangovers.

[0027] Example 5 This embodiment discloses a method for preparing a composition tablet with the effect of preventing and / or alleviating hangovers, comprising the following steps: Step 1: Disinfect the workshop environment, turn on the dehumidifier, and control the humidity to 45%. Take CaHMB, probiotics, fructooligosaccharides, sorbitol, sweet orange fruit powder, magnesium stearate, and sucralose raw materials respectively. Pass each of the above raw materials through a 40-mesh sieve to remove uneven raw materials. Then weigh and label each raw material separately for later use. Among them, the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:1. Step 2: Clean and disinfect the environment and necessary equipment and instruments, turn on the dehumidifier and control the humidity to 45%; weigh out 900 g of CaHMB, 60 g of probiotics, 420 g of fructooligosaccharides, 385 g of sorbitol, 206 g of sweet orange fruit powder, 24 g of magnesium stearate, and 5 g of sucralose, mix them at 15 rpm for 15 min, seal and store, and label. Step 3: Disinfect the environment and equipment, control the humidity at 45%, compress the tablets, check the tablet weight and hardness every 30 minutes, control the tablet weight at the outlet to 2000 mg and the hardness at the outlet to 110 N, and obtain a composition tablet with the effect of preventing and / or alleviating hangovers.

[0028] Experimental Example 1 Alcohol acts on the central nervous system, causing various behavioral problems, such as impaired motor coordination. The rotarod test is used to record the time it takes for mice to maintain balance on a rotating rod to assess the motor imbalance of mice in response to alcohol. Nathan R. Rustay et al., “Evaluation of genetic susceptibility to ethanol poisoning in mice” (PNAS 2003, 100(5): 2917-2922), defined the time it takes for mice to maintain balance on a rotating rod as the time they stay on the rotating rod. Male C57BL / 6J mice were used in the animal experiments and housed under standard laboratory conditions: temperature 22±1℃, dark / light cycle 12 / 12 h, and relative humidity 55±5%. Mice were randomly divided into four groups: normal group, control group, 0.5 CaHMB pretreatment group, 1 CaHMB pretreatment group, 4 CaHMB pretreatment group, and 7 CaHMB pretreatment group, with seven mice in each group. Mice in each group were fasted for 12 hours. One hour before ingestion of 3 g / kg ethanol (38% w / v, double-distilled water), the normal group received only the corresponding amount of double-distilled water, while the treatment groups were pretreated by gavage with different doses of CaHMB (0.5 CaHMB: 29.0 mg / kg; 1 CaHMB: 58.0 mg / kg; 4 CaHMB: 232.0 mg / kg; 7 CaHMB: 406.0 mg / kg). The control group received no treatment before ingestion of 3 g / kg ethanol (38% w / v, double-distilled water). Rotational behavior tests were performed on mice at four time points: 30, 60, 90, and 120 minutes after alcohol exposure to determine the effect of different concentrations of CaHMB on acute alcohol exposure tolerance (Note: 3). g / Kg is the mass ratio of ethanol to mouse body weight, and 29.0 mg / Kg is the mass ratio of CaHMB to mouse body weight, the same below).

[0029] The test results are shown in Table 1 and Figure 1 As shown: Table 1

[0030] From Table 1 and Figure 1It can be seen that acute alcohol intake in the control group (alcohol intake alone) caused motor imbalance in mice: 30 minutes after intake, the average time the mice stayed on the rotundus was about 105.8 seconds; 60 minutes after intake, the average time was about 108.1 seconds; 90 minutes after intake, the average time was about 156.57 seconds; 120 minutes after intake, the average time was about 177.41 seconds; while the average time of mice pretreated with different doses of CaHMB was prolonged. It is gratifying that: (1) at 29.0 mg / Kg In the CaHMB (0.5CaHMB) pretreatment group, the average time of alcohol residence 30 minutes after ingestion was extended to 140.7 seconds, which was 1.33 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 151.5 seconds, which was 1.40 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 192.76 seconds, which was 1.23 times that of the control group; and the average time of alcohol residence 120 minutes after ingestion was extended to 232.21 seconds, which was 1.31 times that of the control group; (2) at 58.0 mg / Kg In the CaHMB (1CaHMB) pretreatment group, the average time of alcohol residence 30 minutes after ingestion was extended to 141.66 seconds, which was 1.34 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 159.5 seconds, which was 1.48 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 236.9 seconds, which was 1.51 times that of the control group; the average time of alcohol residence 120 minutes after ingestion was extended to 280.69 seconds, which was consistent with the normal group; (3) at 232.0 mg / Kg In the CaHMB (4CaHMB) pretreatment group, the average time of alcohol residence 30 minutes after ingestion was extended to 160.8 seconds, which was 1.52 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 178.7 seconds, which was 1.65 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 242.8 seconds, which was 1.55 times that of the control group; the average time of alcohol residence 120 minutes after ingestion was extended to 287.99 seconds, which was consistent with the normal group; (4) at 406.0 mg / Kg In the CaHMB (7CaHMB) pretreatment group, the average time of alcohol exposure 30 minutes after ingestion was extended to 177.69 seconds, which was 1.68 times that of the control group; the average time of alcohol exposure 60 minutes after ingestion was extended to 192.36 seconds, which was 1.78 times that of the control group; the average time of alcohol exposure 90 minutes after ingestion was extended to 222.5 seconds, which was 1.42 times that of the control group; and the average time of alcohol exposure 120 minutes after ingestion was extended to 283.01 seconds, which was consistent with the normal group. Acute alcohol exposure in mice leads to various behavioral problems, such as impaired motor coordination, due to the effects of alcohol on the central nervous system. CaHMB treatment significantly improves these alcohol-induced behavioral problems, as evidenced by prolonged time mice spend on the rotating rod. Therefore, these results indicate that CaHMB can significantly improve the tolerance of mice to acute alcohol exposure.

[0031] Experiment Example 2 Male C57BL / 6J mice were used in the animal experiments and housed under standard laboratory conditions: temperature 22±1℃, dark / light cycle 12 / 12 h, and relative humidity 55±5%. The tablet compositions prepared in Examples 1, 2, 3, 4, and 5, which have the effect of preventing and / or alleviating hangovers, are designated as A, B, C, D, and E, respectively. Mice were randomly divided into a normal group, a control group, and treatment groups A, B, C, D, and E, with 7 mice in each group. The mice in each group were fasted for 12 hours. One hour before ingesting 3 g / Kg ethanol (38% w / v, double-distilled water), the normal group was given only the corresponding double-distilled water, and the treatment groups A and E were administered 257.4 mg / Kg A, B, C, D, and E by gavage, respectively. The control group was not treated before ingesting 3 g / Kg ethanol (38% w / v, double-distilled water). The rotarod behavior of mice in each group was tested at four time points: 30 minutes, 60 minutes, 90 minutes, and 120 minutes after alcohol treatment to determine the effect of each composition on acute alcohol exposure tolerance. The Unpaired t-test was used to analyze the difference in the time mice spent on the rotarod and to assess the motor imbalance of the mice.

[0032] The test results are shown in Table 2 and Figure 2 As shown: Table 2

[0033] From Table 2 and Figure 2It can be seen that acute alcohol intake in the control group (simple alcohol intake) caused motor imbalance in mice: 30 minutes after intake, the average time the mice stayed on the rotundus was about 105.8 seconds; 60 minutes after intake, the average time was about 108.1 seconds; 90 minutes after intake, the average time was about 156.57 seconds; 120 minutes after intake, the average time was about 177.41 seconds; while the mice pretreated with tablets of combinations A, B, C, D, and E had a longer time on the rotundus, specifically, (1) at 257.4 mg / Kg In the pretreatment group A, the average time of alcohol residence 30 minutes after ingestion was extended to 140.7 seconds, which was 1.33 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 151.5 seconds, which was 1.40 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 192.76 seconds, which was 1.23 times that of the control group; and the average time of alcohol residence 120 minutes after ingestion was extended to 232.21 seconds, which was 1.31 times that of the control group; (2) at 257.4 mg / Kg In the B pretreatment group, the average time of alcohol residence 30 minutes after ingestion was extended to 156.7 seconds, which was 1.48 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 166.5 seconds, which was 1.54 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 240.6 seconds, which was 1.54 times that of the control group; the average time of alcohol residence 120 minutes after ingestion was extended to 266.5 seconds, which was 1.50 times that of the control group; (3) at 257.4 mg / Kg In the C pretreatment group, the average time of alcohol residence 30 minutes after ingestion was extended to 166.7 seconds, which was 1.58 times that of the control group; the average time of alcohol residence 60 minutes after ingestion was extended to 183.0 seconds, which was 1.69 times that of the control group; the average time of alcohol residence 90 minutes after ingestion was extended to 252.2 seconds, which was 1.61 times that of the control group; the average time of alcohol residence 120 minutes after ingestion was extended to 287.6 seconds, which was 1.62 times that of the control group, consistent with the normal group; (4) at 257.4 mg / Kg In the D pretreatment group, the average time of alcohol intake 30 minutes after ingestion was extended to 168.7 seconds, which was 1.59 times that of the control group; the average time of alcohol intake 60 minutes after ingestion was extended to 190.2 seconds, which was 1.76 times that of the control group; the average time of alcohol intake 90 minutes after ingestion was extended to 236.0 seconds, which was 1.51 times that of the control group; the average time of alcohol intake 120 minutes after ingestion was extended to 284.8 seconds, which was 1.61 times that of the control group, consistent with the normal group; (5) In the 257.4 mg / Kg E pretreatment group, the average time of alcohol intake 30 minutes after ingestion was extended to 174.2 seconds, which was 1.65 times that of the control group; the average time of alcohol intake 60 minutes after ingestion was extended to 197.7 seconds, which was 1.83 times that of the control group; the average time of alcohol intake 90 minutes after ingestion was extended to 231.The average time spent in the control group was 8 seconds, which is 1.48 times that of the control group; the average time spent in the control group 120 minutes after alcohol ingestion was extended to 282.5 seconds, which is 1.59 times that of the control group, and consistent with the normal group. Experiment 1 demonstrated that CaHMB significantly improved the tolerance of mice to acute alcohol exposure. Experiment 2, based on CaHMB, added probiotics and prebiotics. Probiotics and prebiotics reduced endotoxin entry into the bloodstream and improved intestinal barrier function by regulating the balance of intestinal flora. Therefore, the composition tablets A, B, C, D, and E of this invention, which have the effect of preventing and / or alleviating hangovers, can further improve the tolerance of mice to acute alcohol exposure, as evidenced by the prolonged time mice spend on the rotating rod. This indicates that the addition of probiotics and prebiotics has a synergistic effect with CaHMB, improving the tolerance of mice to acute alcohol exposure and having a certain effect of preventing and alleviating hangovers.

[0034] Experimental Example 3 After drinking, alcohol mainly enters the bloodstream from the stomach and intestines through passive diffusion. Only 10% of alcohol is excreted through respiration, sweat, and urine. More than 90% of alcohol is absorbed and circulated in the body, eventually transported to the liver via the portal vein for metabolism. Alcohol is primarily metabolized through the oxidative pathway, where alcohol dehydrogenase (ADH) converts alcohol into acetaldehyde, a substance harmful to human health. Aldehyde dehydrogenase (ALDH) then converts acetaldehyde into acetic acid, which is ultimately metabolized into carbon dioxide, fatty acids, and water in peripheral tissues. Therefore, measuring the levels of ethanol and acetaldehyde in the blood can better assess the rate of alcohol metabolism in the body. To assess the effects of CaHMB on blood ethanol and acetaldehyde levels, mice were randomly divided into a control group and a CaHMB treatment group, with seven mice in each group. The mice in the treatment group were fasted for 12 h and were given 58.05 mg / kg CaHMB by gavage 30 min before ingesting 5 g / kg ethanol. The control group was given only double-distilled water. After 3 h of alcohol treatment, serum samples were collected from the mice, and the ethanol content in the serum was detected using a kit. After 1.5 h, 3 h, and 6 h of alcohol treatment, serum samples were collected from the mice, and the acetaldehyde content in the serum was detected using a kit.

[0035] The test results are shown in Table 3 and Figure 3 As shown: Table 3

[0036] From Table 3, Figure 3 As shown in A, CaHMB pretreatment can effectively reduce the ethanol content in mouse blood; as shown in Table 3, Figure 3 As shown in B, CaHMB pretreatment can effectively alter the acetaldehyde change curve in mouse blood; as shown in Table 3, Figure 3As shown in C, CaHMB can accelerate the conversion of ethanol to acetaldehyde and the acetaldehyde metabolism process, thus speeding up the detoxification process. The above results show that CaHMB can reduce the ethanol content in the blood of mice that have consumed alcohol and accelerate the change of acetaldehyde in the blood, thereby accelerating the detoxification process.

[0037] Experiment Example 4 Hepatic marker enzymes in plasma, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are considered sensitive biochemical markers of early liver injury. Hematoxylin-eosin staining (HE staining) is one of the most widely used techniques in pathology, histology, embryology, and scientific research. HE staining can clearly show the morphology of hepatocytes, the type and distribution of inflammatory cell infiltration. Based on this, this study investigated the therapeutic effect of CaHMB on acute alcoholic liver injury by measuring the levels of AST and ALT in plasma after alcohol intake, and observed the effect of CaHMB on the pathological state of the liver in mice that consumed alcohol. Therefore, to evaluate the preventive effect of CaHMB administration, male C57BL / 6J mice were randomly divided into a normal group, a control group, and a CaHMB treatment group, with 7 mice in each group. The mice in each group were fasted for 12 h. The treatment group was given 58.05 mg / Kg CaHMB by gavage 30 min before ingesting 5 g / Kg ethanol, the control group was given the same dose of double-distilled water, and the normal group was not treated. Nine h after alcohol treatment, mouse serum samples were collected, and the changes in the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum were detected by a kit. Nine h after alcohol treatment, mouse liver samples were collected for section preparation and HE staining to detect the effect of CaHMB on the pathological state of the liver of mice that drank alcohol.

[0038] The test results are shown in Table 4. Figure 4 and Figure 5 As shown: Table 4

[0039] From Table 4 and Figure 4 It is known that acute alcohol exposure significantly increases plasma ALT and AST levels. ALT and AST levels are considered core markers of liver injury. Under normal conditions, they are mainly present in hepatocytes. When alcohol induces liver injury, hepatocytes rupture, and enzymes are released into the blood, resulting in an abnormal decrease in their content in the liver and an increase in their content in the plasma. Compared with the control group, the plasma ALT and AST levels in the treatment group pretreated with CaHMB were significantly reduced, indicating that CaHMB has a certain therapeutic effect on alcoholic hepatotoxicity. like Figure 5As shown, in the normal group, liver cells were tightly packed, uniform in size, and evenly surrounded the large blood vessels with clear cell membrane boundaries, showing no signs of inflammation. In contrast, the control group showed a large number of cell nuclei clustered near the large blood vessels, indicating inflammatory cell infiltration. After CaHMB pretreatment, the alcohol group showed reduced inflammation under the action of CaHMB, with cells around the blood vessels arranged more evenly and distributed uniformly, showing no obvious inflammatory infiltration. This indicates that CaHMB improved the inflammatory damage to the liver of mice caused by acute alcohol. The above results indicate that CaHMB can significantly reduce ALT and AST levels in mouse livers, alleviate alcohol-induced liver inflammation, effectively relieve liver damage, and has the effect of relieving alcohol poisoning and protecting the liver.

[0040] Experimental Example 5 Alcohol is mainly metabolized in the liver by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2). Detecting the activity of these enzymes can provide a direct understanding of an individual's alcohol metabolism rate and efficiency. To assess the effects of CaHMB administration on hepatic alcohol metabolism, male C57BL / 6J mice were randomly divided into a normal control group and a CaHMB treatment group, with 7 mice in each group. The mice in each group were fasted for 12 h. The normal control group was given 5 μL / g purified water, while the CaHMB treatment group was given 5 μL / g CaHMB (48.88 mg / mL). One h after gavage administration, PBS perfusion was performed to collect samples and detect changes in the activity of ADH and ALDH2 in the liver caused by CaHMB.

[0041] The test results are shown in Table 5 and Figure 6 As shown: Table 5

[0042] From Table 5 and Figure 6 It was found that the activities of ADH and ALDH2 in the liver of mice treated with CaHMB were significantly higher than those in the normal group, and the difference was statistically significant. ADH can efficiently catalyze the conversion of alcohol into acetaldehyde, and ALDH2 further decomposes the more toxic acetaldehyde into non-toxic acetic acid, accelerating the metabolism and clearance of alcohol in the body and reducing the direct damage of alcohol and intermediate product acetaldehyde to the liver. This indicates that CaHMB can effectively enhance the liver's ability to metabolize alcohol, promote the conversion of ethanol to acetic acid, and reduce the accumulation of the toxic intermediate product acetaldehyde, thereby reducing the risk of alcoholic liver injury. This mechanism of action further supports the application value of CaHMB in detoxification and liver protection.

[0043] The human dosage range involved in this invention is derived from the animal experimental dosages in the embodiments using a scientific method of converting body surface area. The conversion formula is as follows: .

[0044] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. The use of a composition in the preparation of a medicament for preventing and / or alleviating hangovers, characterized in that, The composition comprises calcium β-hydroxy-β-methylbutyrate, probiotics, and fructooligosaccharides, wherein the mass ratio of calcium β-hydroxy-β-methylbutyrate, probiotics, and fructooligosaccharides is (0.08-0.66):(0.04-0.12):(0.3-0.8); the probiotics are obtained by mixing Pediococcus pentosaceus PP06, Lactobacillus rhamnosus WKA55, Lactobacillus casei LC89, and Bifidobacterium longum BL11 in a mass ratio of 1:1:1:

1.

2. The application according to claim 1, characterized in that, The mass ratio of the calcium β-hydroxy-β-methylbutyrate, probiotics, and fructooligosaccharides, by weight, is (0.16-0.58):(0.05-0.11):(0.37-0.73).

3. The application according to claim 1, characterized in that, The mass ratio of the calcium β-hydroxy-β-methylbutyrate, probiotics, and fructooligosaccharides is 46:7:47 by weight.

4. The application according to claim 1, characterized in that, The medicament for preventing and / or alleviating hangovers includes a formulation; the formulation comprises a composition having a hangover-preventing and / or hangover-alleviating effect and a pharmaceutically acceptable carrier; the carrier comprises sugars, lubricants, and flavoring agents; the sugars include at least one of lactose, glucose, sucralose, and sorbitol; the lubricants include at least one of stearic acid and magnesium stearate; and the flavoring agents include at least one of fruit powder, sweet orange powder, blueberry powder, and pomegranate powder.

5. The application according to claim 4, characterized in that, The dosage form of the preparation includes at least one of the following: injection, lyophilized powder for injection, ointment, spray, and oral preparation.

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