Use of HMB or a substance containing HMB in the manufacture of a medicament for preventing and / or reducing alcohol hangover and / or alleviating acute alcoholic liver injury

Abstract

The application relates to the technical field of medical preparations, and discloses an application of HMB (beta-hydroxy-beta-methylbutyric acid) or a HMB-containing substance in the preparation of a medicine for preventing and / or reducing alcohol hangover and / or relieving acute alcoholic liver injury; the HMB-containing substance comprises calcium beta-hydroxy-beta-methylbutyrate (CaHMB), the CaHMB can significantly improve the tolerance of acute alcohol exposure, improve impaired motor coordination, the CaHMB can reduce the ethanol content in serum and accelerate the change process of acetaldehyde in serum; meanwhile, the CaHMB can enhance the activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH2) in the liver, and accelerate the alcohol metabolism process; in addition, the CaHMB can reduce the ALT and AST levels in serum, alleviate the liver inflammation caused by alcohol, effectively relieve liver injury, and play the effects of relieving alcohol and protecting the liver.

Description

Technical Field

[0001] This invention relates to the field of medical preparations technology, specifically the application of HMB or HMB-containing substances in the preparation of drugs for the prevention and / or relief of alcohol hangovers and / or acute alcoholic liver injury. Background Technology

[0002] my country has a long and rich drinking culture, with thousands of years of history of alcohol consumption. There's a long-standing tradition of drinking at banquets, parties, and business occasions, where alcohol is often involved. However, with the widespread use of alcohol in modern society, health problems caused by excessive alcohol intake are becoming increasingly prominent. Hangovers are a common physiological reaction after excessive drinking, and their core mechanism is closely related to the accumulation of toxic intermediates in alcohol metabolism and multi-organ dysfunction. After ethanol is metabolized into acetaldehyde by alcohol dehydrogenase (ADH) in the liver, it requires aldehyde dehydrogenase (ALDH2) to further convert it into acetic acid. However, acetaldehyde's strong electrophilicity and oxidative stress induce... Acetaldehyde can cause vasodilatory headaches, gastrointestinal mucosal damage, and mitochondrial dysfunction. If acetaldehyde dehydrogenase activity is insufficient, acetaldehyde will accumulate in the body, directly toxicizing liver cells and causing liver cell damage, inflammatory reactions, and even necrosis. During a hangover, the level of acetaldehyde in the body increases, which may trigger acute liver injury, manifested as abnormal liver function indicators (such as elevated transaminases). In addition, alcohol metabolism consumes a large amount of reduced glutathione (GSH), exacerbating the accumulation of reactive oxygen species (ROS), triggering lipid peroxidation of liver cells and the release of inflammatory factors (such as TNF-α and IL-8), further aggravating hangover symptoms such as fatigue and nausea, leading to liver damage.

[0003] HMB, also known as β-hydroxymethylbutyrate or hydroxymethylbutyrate, is produced in the human body from L-leucine through the dehydrogenation of its metabolite α-ketoisocaproic acid. Studies have shown that HMB can reduce the levels of pro-inflammatory cytokines (IL-6, IL-1β, and chemokine ligand 1 [Cxcl-1]) in the colon and increase the level of the anti-inflammatory cytokine IL-10 (Fachi et al., 2019, Cell Reports 27, 750–761.). In addition, HMB can increase mitochondrial biogenesis (MB) in muscle cells. MB can restore mitochondrial function by replacing damaged mitochondria with new functional mitochondria and plays an important role in mitochondrial quality control.

[0004] There are two common supplemental forms of HMB: one is the free form, and the other is its calcium salt form, namely calcium β-hydroxy-β-methylbutyrate (CaHMB). As early as 2011, CaHMB was approved as a new resource food in China, and its scope of use is sports nutrition food and special medical purpose formula food, with a consumption of ≤3 grams / day. As a dietary supplement, the safety of HMB has received widespread attention, and a large number of experiments have proven that it is safe. In early animal experiments, the dosage of HMB used on pigs weighing 20 kg was 100 grams / day, which is almost 100 times the human dosage. The common human dosage of HMB is 2-3 grams / day. Studies have shown that no adverse reactions occurred in the experimental subjects during the one-year period of use.

[0005] Currently, HMB and its calcium salt (CaHMB) are mainly used to help fitness enthusiasts build muscle and improve sarcopenia in the elderly. There are no reports on their use in preventing and alleviating hangovers or relieving acute alcoholic liver injury. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention discloses the application of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of a drug for preventing alcohol hangovers.

[0007] The present invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of a drug for relieving alcohol hangovers.

[0008] The present invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of a drug for relieving acute alcoholic liver injury.

[0009] The present invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of a drug for preventing and alleviating alcohol hangovers.

[0010] The present invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of drugs for preventing alcohol hangovers and relieving acute alcoholic liver injury.

[0011] The present invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of drugs for relieving alcohol hangovers and alleviating acute alcoholic liver injury.

[0012] This invention also discloses the use of HMB (β-hydroxy-β-methylbutyric acid) in the preparation of drugs for preventing and alleviating alcohol hangovers and relieving acute alcoholic liver injury.

[0013] The present invention also discloses the application of an HMB-containing substance in the preparation of a drug for preventing alcohol hangovers.

[0014] This invention also discloses the application of an HMB-containing substance in the preparation of a drug for relieving alcohol hangovers.

[0015] The present invention also discloses the application of an HMB-containing substance in the preparation of a drug for relieving acute alcoholic liver injury.

[0016] The present invention also discloses the application of an HMB-containing substance in the preparation of a drug for preventing and alleviating alcohol hangovers.

[0017] The present invention also discloses the application of an HMB-containing substance in the preparation of a drug for preventing alcohol hangovers and relieving acute alcoholic liver injury.

[0018] This invention also discloses the application of an HMB-containing substance in the preparation of a drug for relieving alcohol hangovers and alleviating acute alcoholic liver injury.

[0019] This invention also discloses the application of an HMB-containing substance in the preparation of a drug for preventing and alleviating alcohol hangovers and relieving acute alcoholic liver injury.

[0020] Preferably, the HMB-containing substance includes valerate.

[0021] Preferably, the valerate comprises a salt of β-hydroxy-β-methylbutyric acid.

[0022] Preferably, the salt of β-hydroxy-β-methylbutyric acid includes calcium β-hydroxy-β-methylbutyrate.

[0023] Preferably, the effective dose of the calcium β-hydroxy-β-methylbutyrate is 3.22-45.06 mg / Kg / d.

[0024] Preferably, the effective dose of the calcium β-hydroxy-β-methylbutyrate is 6.44-25.75 mg / Kg / d.

[0025] Preferably, the medicament for preventing and / or alleviating alcohol hangovers and / or relieving acute alcoholic liver injury comprises a formulation made of calcium β-hydroxy-β-methylbutyrate with a pharmaceutically acceptable carrier or additive.

[0026] Preferably, the formulation includes at least one of injections, lyophilized powder injections, ointments, sprays, and oral formulations.

[0027] Preferably, the oral preparation includes at least one of capsules, tablets, and granules.

[0028] Preferably, the preparation is taken before or after drinking or consuming alcohol.

[0029] The range of human doses (i.e., effective doses) involved in this invention is derived from the animal experimental doses in the embodiments using a scientific method of converting body surface area. The conversion formula is as follows: .

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention discloses the application of calcium β-hydroxy-β-methylbutyrate (CaHMB), a substance containing HMB, in the prevention or relief of alcohol hangovers. CaHMB can significantly improve the tolerance of mice to acute alcohol exposure and improve their impaired motor coordination. Furthermore, CaHMB can reduce the ethanol content in the blood of mice that have consumed alcohol and accelerate the change of acetaldehyde in the blood, thus accelerating the detoxification process. Therefore, it has the effect of preventing and relieving alcohol hangovers. In addition, CaHMB has a better effect when used in combination with probiotics and prebiotics.

[0031] 2. This invention also discloses the application of calcium β-hydroxy-β-methylbutyrate (CaHMB) valerate in drugs for relieving acute alcoholic liver injury; CaHMB can also significantly reduce ALT and AST levels in mouse liver, increase the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) in liver, and reduce alcohol-induced liver inflammation, effectively relieving liver damage and having the effect of detoxifying alcohol and protecting the liver. Attached Figure Description

[0032] 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

[0033] 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.

[0034] Example 1 This embodiment discloses a method for preparing tablets containing CaHMB, including 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 tablets containing CaHMB.

[0035] Example 2 This embodiment discloses a method for preparing tablets containing CaHMB, including 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 tablets containing CaHMB.

[0036] Example 3 This embodiment discloses a method for preparing tablets containing CaHMB, including 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, and 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 to obtain tablets containing CaHMB.

[0037] Example 4 This embodiment discloses a method for preparing tablets containing CaHMB, including 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 tablets, and check the tablet weight and hardness every 30 minutes. Control the tablet weight at the outlet to 2000mg and the hardness at the outlet to 100N to obtain tablets containing CaHMB.

[0038] Example 5 This embodiment discloses a method for preparing tablets containing CaHMB, including 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, and 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 to obtain tablets containing CaHMB.

[0039] 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).

[0040] The test results are shown in Table 1 and Figure 1 As shown: Table 1

[0041] 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.

[0042] Experimental 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 tablets containing CaHMB prepared in Examples 1, 2, 3, 4, and 5 were 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.

[0043] The test results are shown in Table 2 and Figure 2 As shown: Table 2

[0044] 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 can significantly improve the tolerance of mice to acute alcohol exposure. Experiment 2, based on CaHMB, further added probiotics and prebiotics. Probiotics and prebiotics reduce endotoxin entry into the bloodstream and improve intestinal barrier function by regulating the balance of intestinal flora. Therefore, the CaHMB-containing tablets A, B, C, D, and E of this invention 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 in preventing and alleviating hangovers.

[0045] 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.

[0046] The test results are shown in Table 3 and Figure 3 As shown: Table 3

[0047] 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.

[0048] 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.

[0049] The test results are shown in Table 4. Figure 4 and Figure 5 As shown: Table 4

[0050] 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.

[0051] 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.

[0052] The test results are shown in Table 5 and Figure 6 As shown: Table 5

[0053] 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.

[0054] 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 an HMB-containing substance in the preparation of a drug for preventing and / or alleviating alcohol hangovers and / or relieving acute alcoholic liver injury, characterized in that, The HMB-containing substance is calcium β-hydroxy-β-methylbutyrate.

2. The application according to claim 1, characterized in that, The drug used to prevent and / or alleviate alcohol hangovers and / or relieve acute alcoholic liver injury is a formulation made of calcium β-hydroxy-β-methylbutyrate and a pharmaceutically acceptable carrier.

3. The application according to claim 2, characterized in that, The formulation is selected from at least one of injections, ointments, sprays, and oral formulations.

4. The application according to claim 3, characterized in that, The oral preparation is selected from at least one of capsules, tablets, and granules.

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