A hangover remedy composition, its preparation method and application

Abstract

The present application relates to the technical field of health food, in particular to a kind of alcoholism composition and its preparation method and application.Dosage form is effervescent tablet, according to weight parts, including: tremella polysaccharide 200-2000 parts, small molecule peptide 100-1000 parts, Hericium polysaccharide 100-1000 parts, nutritional sugar substitute 100-2000 parts, compound vitamin B 1-50 parts, wherein the tremella polysaccharide is composed of 60-200 million molecular weight tremella polysaccharide and 1-100 thousand molecular weight tremella polysaccharide.The present application uses macromolecular and low molecular weight tremella polysaccharide, Hericium polysaccharide, small molecule peptide and nutritional sugar substitute as main raw materials to prepare effervescent tablet, which has fast dissolution speed, good taste and flavor, small volume, convenient to carry and use, and can be placed in water container containing water, such as mineral water, water cup, water bottle, etc., and then dissolved, which is interesting to eat, easy to absorb, has little irritation to gastrointestinal tract and has superior effects of alcoholism and intestinal and stomach protection.

Description

Technical Field

[0001] This invention relates to the field of health food technology, specifically to a hangover relief composition, its preparation method, and its application. Background Technology

[0002] In real life, most people cannot avoid drinking alcohol due to social interactions, work-related obligations, etc. Long-term drinking will lead to alcoholic liver damage, which can further develop into alcoholic liver disease.

[0003] Most hangover remedies on the market are currently available in capsule, granule, or liquid form. These products have poor taste and flavor, are inconvenient to carry, and are not easily accepted by people. Furthermore, they contain large amounts of sucrose and glucose, which, when consumed with alcohol, further increase the metabolic burden on the body and produce side effects. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a hangover remedy composition, its preparation method, and its application. The hangover remedy composition uses Tremella fuciformis polysaccharide, Hericium erinaceus polysaccharide, small molecule peptides, nutritional sugar substitutes, and compound vitamin B as main raw materials, supplemented with other excipients, and is prepared using a specific method. It can significantly reduce the concentration of ethanol in the blood, reduce the degree of intoxication, shorten the duration of intoxication, and provide sufficient protection for the gastric mucosa.

[0005] A hangover remedy composition, in effervescent tablet form, comprises, by weight: 200-2000 parts of Tremella fuciformis polysaccharide, 100-1000 parts of small molecule peptides, 100-1000 parts of Hericium erinaceus polysaccharide, 100-2000 parts of nutritional sugar substitute, and 50 parts of compound vitamin B1.

[0006] The aforementioned Tremella polysaccharide is composed of Tremella polysaccharide with a molecular weight of 600,000 to 2,000,000 and Tremella polysaccharide with a molecular weight of 10,000 to 100,000, with a weight ratio of (1-2):1.

[0007] The preparation method of the 600,000-2,000,000 molecular weight Tremella polysaccharide is as follows:

[0008] ① After washing the white fungus (1%-3% of the total volume), place it in an extraction tank and soak it at 80-100℃ for 6 hours;

[0009] ② The filter screen intercepts the solid phase;

[0010] ③ Transfer the liquid phase to a new storage tank, wait for the temperature to drop to about 60°C, add trypsin to degrade for 2 hours to obtain the degradation solution;

[0011] ④ The degradation solution is passed through a plate and frame filter twice (coarse filtration and fine filtration) to obtain the filtrate;

[0012] ⑤ The filtrate is concentrated by volume by 1-2 times using an evaporator to obtain a concentrated solution;

[0013] ⑥ The concentrate is sequentially passed through a plate and frame filter (fine filtration), a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain sterile filtrate, which is then transferred to a sedimentation tank;

[0014] ⑦ Slowly pour 3 times the volume of 95° alcohol into the sedimentation tank and let it stand for 3-6 hours;

[0015] ⑧ After extracting the supernatant, continue to add 95° alcohol to adjust the alcohol in the container to above 90°, and let it stand for 2 hours;

[0016] ⑨ After continuing to extract the supernatant, add an equal volume of 95° alcohol, mix thoroughly, and then transfer to a solid-liquid separator to spin dry the alcohol.

[0017] ⑩ Place the spin-dried material in a 60℃ oven and dry until the moisture content is less than 10% to obtain the finished Tremella polysaccharide with a molecular weight of 600,000-2,000,000 Da.

[0018] The preparation method of the 1-100,000 molecular weight Tremella polysaccharide is as follows:

[0019] ① Inoculate Bifidobacterium (10% inoculation amount) into the fermenter and ferment at 37℃ under anaerobic conditions;

[0020] ②After the strain enters the stable growth period, add 3-5 times the volume of 1% Tremella polysaccharide solution (molecular weight 1 million) and continue anaerobic fermentation until the viscosity drops below 5cp;

[0021] ③ A tube-type centrifuge is used for solid-liquid separation to remove bacterial cells;

[0022] ④ The supernatant is sequentially filtered through a 5-micron filter membrane, a 1-micron filter membrane, and a 0.45-micron filter membrane to obtain the filtrate;

[0023] ⑤ After the filtrate is passed through a 100 kDa ultrafiltration membrane, the permeate is obtained;

[0024] ⑥ The permeate is circulated through a 5 kDa ultrafiltration membrane and concentrated 2-3 times to obtain a concentrated solution;

[0025] ⑦ The concentrate was sequentially filtered through a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain a sterile filtrate;

[0026] ⑧ Add 95° alcohol to the sterile filtrate until the alcohol content reaches 70° or higher, and let it stand for 6 hours;

[0027] ⑨ After removing the supernatant, add 1 volume of purified water to redissolve the solution, thus obtaining the solution;

[0028] ⑩ The solution was spray-dried to obtain Tremella polysaccharides with a molecular weight of 10,000 to 100,000.

[0029] Tremella polysaccharides with a molecular weight of 600,000-2,000,000 exhibit excellent film-forming properties, forming a protective layer on the surface of the human gastric mucosa, effectively preventing the erosion of gastric acid and reducing the irritation of the stomach by alcohol. Tremella polysaccharides with a molecular weight of 10,000-100,000 can penetrate deep into the epidermis and gastric mucosa, effectively scavenging reactive oxygen free radicals and preventing and promoting the repair of damaged mucosal cells.

[0030] The small molecule peptide is at least one selected from soybean protein peptide, pea protein peptide, corn peptide, sunflower seed peptide, and collagen peptide. More preferably, the molecular weight of the small molecule peptide is ≤3000 Da.

[0031] The preparation method of the Hericium erinaceus polysaccharide is as follows:

[0032] ① After washing the dried monkey head mushrooms, add purified water in a 1:1 ratio and homogenize in a homogenizer or grinder;

[0033] ② Add purified water to make the ratio of Hericium erinaceus to water 1:20-1:30, raise the temperature to 50℃, adjust the pH to 7.5-8, add cellulase and trypsin, turn on the stirrer and maintain 120 rpm, and react for 2 hours.

[0034] ③ Heat to 80℃ for hot extraction, and maintain stirring at 120 rpm for 2 hours;

[0035] ④ Pass the liquid material through a plate and frame filter twice (coarse filtration and fine filtration) to obtain the filtrate;

[0036] ⑤ The filtrate is fed into a vacuum concentration tank and concentrated at 60-80℃ for 1-2 times to obtain a concentrated solution;

[0037] ⑥ The concentrate was sequentially filtered through a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain a sterile filtrate;

[0038] ⑦ Add 95% alcohol to the filtrate to achieve a final alcohol content of 90°-95°, and let it stand for 6 hours;

[0039] ⑧ After removing the supernatant, repeat step ⑦ two to three times for washing and dehydration;

[0040] ⑨ The precipitate was placed in a 60℃ oven and dried until the moisture content was less than 10% to obtain Hericium erinaceus polysaccharide.

[0041] The nutritional sugar substitute is selected from one of tagatose, allulose, or arabinose, all of which are commercially available products.

[0042] The hangover relief composition, by weight, further includes: 0-1000 parts hawthorn powder, 0-1000 parts freeze-dried tomato powder, 0-1000 parts water-soluble cellulose, and 0-1000 parts pectin.

[0043] The hawthorn powder and tomato freeze-dried powder both have the effects of reducing alcohol concentration, sobering up, and promoting digestion; water-soluble cellulose and pectin act as thickeners and stabilizers, and on the other hand, they can create a feeling of fullness, reduce alcohol stimulation, and promote intestinal peristalsis, thus accelerating the decomposition and excretion of alcohol.

[0044] The hangover relief composition, by weight, further includes: 1000-5000 parts of disintegrant, 100-1000 parts of lubricant, 0-100 parts of stevia, 0-10 parts of food coloring, and 0-10 parts of flavoring.

[0045] The disintegrant is an acid and a base in a weight ratio of (1-1.9):1, wherein the acid is selected from one or more of citric acid, malic acid, fumaric acid or tartaric acid, and the base is selected from one or two of sodium bicarbonate or sodium carbonate.

[0046] The lubricant is selected from one or more of magnesium stearate, sodium chloride, or polyethylene glycol (PEG) 6000.

[0047] Preferably, a hangover remedy composition comprises, by weight, the following components: 1000 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 620 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 400 parts of pea protein peptide, 500 parts of Hericium erinaceus polysaccharide, 800 parts of tagatose, 30 parts of compound vitamin B, 300 parts of hawthorn powder, 350 parts of freeze-dried tomato powder, 200 parts of water-soluble cellulose, 300 parts of pectin, 160 parts of PEG6000, 340 parts of sodium chloride, 100 parts of stevia, 0.1 parts of lycopene, 0.5 parts of tomato flavoring, and 4900 parts of disintegrant.

[0048] The disintegrant is citric acid and sodium bicarbonate in a weight ratio of 1.3:1.

[0049] The preparation process of the hangover relief composition is as follows:

[0050] (1) Place 600,000-2,000,000 molecular weight Tremella polysaccharide, 100,000-100,000 molecular weight Tremella polysaccharide, Hericium erinaceus polysaccharide, nutritional sugar substitute, compound vitamin B, water-soluble cellulose and pectin in a mixer and mix evenly.

[0051] (2) Mix pea protein peptides, hawthorn powder, tomato freeze-dried powder, organic acid, and lubricant, then grind them in a grinder and pass them through a 100-200 mesh sieve.

[0052] (3) Place the materials that were mixed evenly in step (1), the materials that were sieved in step (2), lycopene, tomato flavoring, and sodium bicarbonate into a mixer and mix them evenly.

[0053] (4) Place the material that has been mixed evenly in step (3) into a single-punch tablet press and press it into effervescent tablets, then bottle and package them.

[0054] The mixer mentioned in step (1) is manufactured by Changzhou Xiaochang Drying Equipment Co., Ltd., model: SYH-5. The pulverizer mentioned in step (2) is manufactured by Hunan Ruiyi Intelligent Technology Co., Ltd., model: WK-2000. The single-punch tablet press mentioned in step (4) is manufactured by Shanghai Laole Machinery Equipment Co., Ltd., model: TDP-1.5T.

[0055] To avoid the influence of large particles, the pulverization process in step (2) is carried out intermittently, the ambient temperature is kept constant at 26°C, the air humidity is below 45%, and the internal temperature of the pulverizer is below 40°C to avoid high temperature damage to active substances.

[0056] In step (3), the mixing temperature is below 30°C and the air humidity is below 45% to prevent the materials from sticking together due to excessive temperature and humidity, which would affect the quality of the mixing.

[0057] During the tableting process described in step (4), the ambient temperature is maintained at a constant 26°C and the air humidity is below 40% to avoid material adhesion and sticking caused by excessive temperature and humidity.

[0058] The tablets are 1-8g / tablet.

[0059] Preferably, the tablets are 4g / tablet.

[0060] The present invention also provides the application of the above-mentioned hangover relief composition or the hangover relief composition prepared by the above-mentioned preparation method, wherein each hangover relief composition tablet is dissolved in 200±50mL of water and is taken before drinking alcohol.

[0061] Compared with the prior art, the present invention has the following advantages:

[0062] (1) This invention uses macromolecular and low molecular weight Tremella fuciformis polysaccharide, Hericium erinaceus polysaccharide, small molecule peptides and nutritional sugar substitutes as the main raw materials to prepare effervescent tablets. The tablets dissolve quickly, have a good taste and flavor, are small in size, easy to carry, and convenient to use. They can be placed in a water container such as mineral water, water cup, or water bottle and allowed to dissolve. They are fun to eat, easy to take and absorb, have little irritation to the gastrointestinal tract, and have excellent effects in relieving hangovers and protecting the stomach and intestines.

[0063] (2) High molecular weight Tremella fuciformis polysaccharides (600,000-2,000,000 molecular weight) have good film-forming properties and can form a good protective layer to protect the gastric mucosa; low molecular weight Tremella fuciformis polysaccharides (10,000-100,000 molecular weight) can penetrate deep into the epidermis and gastric mucosa, scavenge reactive oxygen free radicals, prevent and promote the repair of damaged mucosal cells, and play a protective role for the gastric mucosa from the inside. Although Tremella fuciformis polysaccharides can form a film, their adhesion to the gastric mucosa is relatively weak, while small molecular weight peptides (soybean protein peptides / pea protein peptides / corn peptides / sunflower disc peptides / collagen peptides) have a superior ability to adhere to the gastric wall. When combined with small molecular weight peptides, the adhesion ability of Tremella fuciformis polysaccharides can be greatly enhanced, thus strengthening the protective effect of the gastric wall. Hericium erinaceus polysaccharides have antioxidant, gastric acid-reducing, and pepsin-inhibiting effects. When combined with Tremella fuciformis polysaccharides and small molecular weight peptides, the decomposition effect of gastric acid and pepsin on Tremella fuciformis polysaccharides and small molecular weight peptides can be reduced, thus greatly prolonging the protective time. Complex B vitamins can accelerate alcohol breakdown. Combined with tremella polysaccharides, small molecule peptides, and hericium erinaceus polysaccharides, they can significantly reduce the duration and severity of alcohol irritation to the stomach. Nutritional sugar substitutes (tagatose / alokulose / arabinose) are isomers of glucose and fructose, are not absorbed by the body, and do not burden the body. When used in hangover remedies, they can satisfy the body's craving for sweetness while ensuring health. Attached Figure Description

[0064] Figure 1 (a) is a diagram of the gastric mucosa in the normal control group. Figure 1 (b) HE slices of the stomach from the normal control group;

[0065] Figure 2 (a) shows the gastric mucosal condition of the control group. Figure 2 (b) HE slices of the stomach of the control group;

[0066] Figure 3 (a) is a diagram of the gastric mucosa in experimental group 1. Figure 3 (b) HE section of the stomach of experimental group 1;

[0067] Figure 4 (a) is a diagram of the gastric mucosa in experimental group 2. Figure 4 (b) HE section of the stomach in experimental group 2;

[0068] Figure 5 (a) is a diagram of the gastric mucosa in experimental group 3. Figure 5 (b) HE section of stomach tissue from experimental group 3;

[0069] Figure 6 (a) is a diagram of the gastric mucosa in experimental group 4. Figure 6 (b) HE section of the stomach of experimental group 4;

[0070] Figure 7 (a) is a diagram of the gastric mucosa in experimental group 5. Figure 7 (b) HE section of the stomach of experimental group 5;

[0071] Figure 8 (a) is a diagram of the gastric mucosa in experimental group 6. Figure 8 (b) HE section of the stomach of experimental group 6;

[0072] Figure 9 (a) is a diagram of the gastric mucosa in experimental group 7. Figure 9 (b) HE section of the stomach of experimental group 7;

[0073] Figure 10 (a) is a diagram of the gastric mucosa in experimental group 8. Figure 10 (b) HE section of the stomach of experimental group 8;

[0074] Figure 11 (a) is a diagram of the gastric mucosa in experimental group 9. Figure 11 (b) is a HE section of the stomach of experimental group 9. Detailed Implementation

[0075] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0076] Pea protein peptides were purchased from Xi'an Green Peptide Biotechnology Co., Ltd.; tagatose from Hebei Kelongduo Biotechnology Co., Ltd.; compound vitamin B from Henan Ruli Biotechnology Co., Ltd.; hawthorn powder from Shaanxi Chengqian Biotechnology Co., Ltd.; freeze-dried tomato powder from Shaanxi Bocuijian Biotechnology Co., Ltd.; water-soluble cellulose from Guangzhou Huamao Biotechnology Co., Ltd.; pectin from Jiangsu Jiujia Biotechnology Co., Ltd.; PEG6000 from Shandong Ruisheng Pharmaceutical Excipients Co., Ltd.; sodium chloride from Sinopharm Group; stevia from Zhengzhou Yuhe Food Additives Co., Ltd.; lycopene from Guangzhou Huayu Biotechnology Co., Ltd.; tomato flavoring from Shandong Jianyou Bioengineering Co., Ltd.; citric acid from Weifang Yingxuan Industry Co., Ltd.; sodium bicarbonate from Shenzhen Jiahe Xuri Trading Co., Ltd.; other reagents can be selected from commercially available products as needed, and will not be described further here.

[0077] Food-grade trypsin was selected from Guangdong Kangda Biotechnology Co., Ltd.; food-grade cellulase was also selected from Guangdong Kangda Biotechnology Co., Ltd.; and Bifidobacterium was a laboratory-isolated strain.

[0078] Example 1

[0079] A hangover remedy composition, by weight, comprises the following components: 1000 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 620 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 400 parts of small molecule peptides (pea protein peptides are used in this embodiment), 500 parts of Hericium erinaceus polysaccharide, 800 parts of tagatose, 30 parts of compound vitamin B, 300 parts of hawthorn powder, 350 parts of freeze-dried tomato powder, 200 parts of water-soluble cellulose, 300 parts of pectin, 160 parts of PEG6000, 340 parts of sodium chloride, 100 parts of stevia, 0.1 parts of lycopene, 0.5 parts of tomato flavoring, and 4900 parts of disintegrant. The disintegrant is citric acid and sodium bicarbonate in a weight ratio of 1.3:1.

[0080] The preparation method of the 600,000-2,000,000 molecular weight Tremella polysaccharide is as follows:

[0081] ① After washing the white fungus (1%-3% of the total volume), place it in an extraction tank and soak it at 80-100℃ for 6 hours;

[0082] ② The filter screen intercepts the solid phase;

[0083] ③ Transfer the liquid phase to a new storage tank, wait for the temperature to drop to about 60°C, add trypsin to degrade for 2 hours to obtain the degradation solution;

[0084] ④ The degradation solution is passed through a plate and frame filter twice (coarse filtration and fine filtration) to obtain the filtrate;

[0085] ⑤ The filtrate is concentrated by volume by 1-2 times using an evaporator to obtain a concentrated solution;

[0086] ⑥ The concentrate is sequentially passed through a plate and frame filter (fine filtration), a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain sterile filtrate, which is then transferred to a sedimentation tank;

[0087] ⑦ Slowly pour 3 times the volume of 95° alcohol into the sedimentation tank and let it stand for 3-6 hours;

[0088] ⑧ After extracting the supernatant, continue to add 95° alcohol to adjust the alcohol in the container to above 90°, and let it stand for 2 hours;

[0089] ⑨ After continuing to extract the supernatant, add an equal volume of 95° alcohol, mix thoroughly, and then transfer to a solid-liquid separator to spin dry the alcohol.

[0090] ⑩ Place the spin-dried material in a 60℃ oven and dry until the moisture content is less than 10% to obtain the finished Tremella polysaccharide with a molecular weight of 600,000-2,000,000 Da.

[0091] The preparation method of the 1-100,000 molecular weight Tremella polysaccharide is as follows:

[0092] ① Inoculate Bifidobacterium (10% inoculation amount) into the fermenter and ferment at 37℃ under anaerobic conditions;

[0093] ②After the strain enters the stable growth period, add 3-5 times the volume of 1% Tremella polysaccharide solution (molecular weight 1 million) and continue anaerobic fermentation until the viscosity drops below 5cp;

[0094] ③ A tube-type centrifuge is used for solid-liquid separation to remove bacterial cells;

[0095] ④ The supernatant is sequentially filtered through a 5-micron filter membrane, a 1-micron filter membrane, and a 0.45-micron filter membrane to obtain the filtrate;

[0096] ⑤ After the filtrate is passed through a 100 kDa ultrafiltration membrane, the permeate is obtained;

[0097] ⑥ The permeate is circulated through a 5 kDa ultrafiltration membrane and concentrated 2-3 times to obtain a concentrated solution;

[0098] ⑦ The concentrate was sequentially filtered through a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain a sterile filtrate;

[0099] ⑧ Add 95° alcohol to the sterile filtrate until the alcohol content reaches 70° or higher, and let it stand for 6 hours;

[0100] ⑨ After removing the supernatant, add 1 volume of purified water to redissolve the solution, thus obtaining the solution;

[0101] ⑩ The solution was spray-dried to obtain Tremella polysaccharides with a molecular weight of 10,000 to 100,000.

[0102] The preparation method of the Hericium erinaceus polysaccharide is as follows:

[0103] ① After washing the dried monkey head mushrooms, add purified water in a 1:1 ratio and homogenize in a homogenizer or grinder;

[0104] ② Add purified water to make the ratio of Hericium erinaceus to water 1:20-1:30, raise the temperature to 50℃, adjust the pH to 7.5-8, add cellulase and trypsin, turn on the stirrer and maintain 120 rpm, and react for 2 hours.

[0105] ③ Heat to 80℃ for hot extraction, and maintain stirring at 120 rpm for 2 hours;

[0106] ④ Pass the liquid material through a plate and frame filter twice (coarse filtration and fine filtration) to obtain the filtrate;

[0107] ⑤ The filtrate is fed into a vacuum concentration tank and concentrated at 60-80℃ for 1-2 times to obtain a concentrated solution;

[0108] ⑥ The concentrate was sequentially filtered through a 1-micron filter membrane, a 0.45-micron filter membrane, and a 0.22-micron filter membrane to obtain a sterile filtrate;

[0109] ⑦ Add 95% alcohol to the filtrate to achieve a final alcohol content of 90°-95°, and let it stand for 6 hours;

[0110] ⑧ After removing the supernatant, repeat step ⑦ two to three times for washing and dehydration;

[0111] ⑨ The precipitate was placed in a 60℃ oven and dried until the moisture content was less than 10% to obtain Hericium erinaceus polysaccharide.

[0112] The preparation process of the hangover relief composition is as follows:

[0113] (1) Place 600,000-2,000,000 molecular weight Tremella polysaccharide, 100,000-100,000 molecular weight Tremella polysaccharide, Hericium erinaceus polysaccharide, nutritional sugar substitute, compound vitamin B, water-soluble cellulose and pectin in a mixer and mix evenly.

[0114] (2) Mix pea protein peptides, hawthorn powder, tomato freeze-dried powder, PEG6000 and sodium chloride and then grind them in a grinder. Use intermittent grinding, keep the ambient temperature constant at 26℃, control the air humidity to be below 45%, control the internal temperature of the grinder to be below 40℃, and pass through a 100-200 mesh sieve.

[0115] (3) Place the materials that were mixed evenly in step (1), the materials that were sieved in step (2), and the remaining materials, including stevia, lycopene, tomato flavoring, and disintegrant, into a mixer and mix them evenly. The mixing temperature is below 30°C and the air humidity is below 45%.

[0116] (4) Place the material mixed evenly in step (3) into a single punch tablet press and press it into 4g / tablet effervescent tablets. During the tablet pressing process, the ambient temperature is kept constant at 26℃ and the air humidity is below 40%. Finally, it is bottled and packaged.

[0117] Example 2

[0118] A hangover remedy composition, by weight, comprises the following components: 1000 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 1000 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 1000 parts of small molecule peptides (in this embodiment, the small molecule peptides are composed of corn peptides: sunflower disc peptides: soybean protein peptides in a mass ratio of 1:1:1), 100 parts of Hericium erinaceus polysaccharide, 2000 parts of allulose, 1 part of compound vitamin B1, 1000 parts of freeze-dried tomato powder, 1000 parts of water-soluble cellulose, 100 parts of magnesium stearate, and 2799 parts of disintegrant. The disintegrant is malic acid, tartaric acid, and sodium carbonate in a weight ratio of 1:1:2.

[0119] The preparation method of the hangover relief composition is the same as in Example 1, and each tablet weighs 1g.

[0120] Example 3

[0121] A hangover remedy composition, by weight, comprises the following components: 1300 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 650 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 100 parts of small molecule peptides (collagen peptides are used in this embodiment), 1000 parts of Hericium erinaceus polysaccharide, 100 parts of arabinose, 50 parts of compound vitamin B, 1000 parts of hawthorn powder, 1000 parts of pectin, 100 parts of magnesium stearate, 540 parts of sodium chloride, 360 parts of PEG6000, 100 parts of stevia, 10 parts of lycopene, 10 parts of tomato flavoring, and 3680 parts of disintegrant. The disintegrant is fumaric acid and sodium carbonate in a weight ratio of 1.9:1.

[0122] The preparation method of the hangover relief composition is the same as in Example 1, and each tablet weighs 8g.

[0123] Example 4

[0124] A hangover remedy composition, by weight, comprises the following components: 1333 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 667 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 1000 parts of small molecule peptides (collagen peptides are used in this embodiment), 1000 parts of Hericium erinaceus polysaccharide, 2000 parts of tagatose, 25 parts of compound vitamin B, 600 parts of hawthorn powder, 600 parts of freeze-dried tomato powder, 600 parts of water-soluble cellulose, 600 parts of pectin, 615 parts of sodium chloride, 50 parts of stevia, 5 parts of lycopene, 5 parts of tomato flavoring, and 1000 parts of disintegrant. The disintegrant is citric acid, fumaric acid, and sodium carbonate in a weight ratio of 1:0.5:1.

[0125] The preparation method of the hangover relief composition is the same as in Example 1, and each tablet weighs 6g.

[0126] Example 5

[0127] A hangover remedy composition, by weight, comprises the following components: 100 parts of Tremella fuciformis polysaccharide with a molecular weight of 600,000-2,000,000, 100 parts of Tremella fuciformis polysaccharide with a molecular weight of 10,000-100,000, 100 parts of small molecule peptides (corn peptides are used in this embodiment), 100 parts of Hericium erinaceus polysaccharide, 100 parts of arabinose, 1 part of compound vitamin B1, 1000 parts of hawthorn powder, 1000 parts of freeze-dried tomato powder, 1000 parts of water-soluble cellulose, 379 parts of pectin, 1000 parts of lubricant (magnesium stearate: sodium chloride: PEG6000 in a ratio of 1:3:2), 1000 parts of stevia, 10 parts of lycopene, 10 parts of tomato flavoring, and 5000 parts of disintegrant. The disintegrant is citric acid, malic acid, tartaric acid, and sodium bicarbonate in a weight ratio of 0.5:0.5:0.5:1.

[0128] The preparation method of the hangover relief composition is the same as in Example 1, and each tablet weighs 3g.

[0129] Experimental Example 1

[0130] Effervescent tablet performance test

[0131] Experimental equipment: pH meter (a-AB33PHZH, Shanghai Youke Instrument Co., Ltd.); hardness tester (YD-200A, Shanghai Mingxiang Pharmaceutical Testing Instrument Co., Ltd.), timer, small single-punch tablet press (TDP-1.5T, Shanghai Laole Machinery Equipment Co., Ltd.), electronic balance (ME1002E / 02, Mettler Toledo Instruments (Shanghai) Co., Ltd.).

[0132] The hangover relief compositions prepared in Examples 1-5 were subjected to four process verifications: pH, hardness, stability (hardness after 30 days at room temperature), and disintegration time. The experimental methods were referenced in: Orthogonal design optimization of the types and amounts of excipients for inulin compound effervescent tablets [J] (Zhu Xiaozhen, Liu Yunchao, Jia Chenchen, Yi Yuetao. Food Industry, 2018, 39(09):68-72.). Each process was measured three times and the average value was taken. The specific results are shown in Table 1.

[0133] Table 1 Four Process Data

[0134]

[0135] Table 1 shows that pH, hardness, stability, and disintegration time were measured in the experimental groups. Different groups showed variations in pH due to variations in the proportion of disintegrant added and the acid-base ratio. The hardness test results indicate that Examples 1, 3, and 5 showed minimal hardness change after 30 days, demonstrating stronger stability. The disintegration test results show that the disintegration time for all five groups was approximately 120 seconds, with Example 3 having the shortest disintegration time at 103.51 seconds and Example 5 having the longest at 130.17 seconds. All indicators comply with the relevant provisions of the Pharmacopoeia of the People's Republic of China.

[0136] The pH value is related to the acid-base ratio in the disintegrant; the higher the acid-base ratio, the greater the acidity and the lower the pH value.

[0137] The disintegration time is related to the content of disintegrant. Analysis of experimental data shows that the higher the proportion of disintegrant in the formulation, the longer the disintegration time.

[0138] The hardness on day 30 is mainly related to the content of polysaccharides (silver ear fungus polysaccharide and lion's mane mushroom polysaccharide). Because polysaccharides have a certain degree of hygroscopicity, a high polysaccharide content makes it easier to absorb moisture in the air, resulting in a decrease in hardness.

[0139] Experiment Example 2

[0140] Effervescent tablet taste acceptance test

[0141] The taste of the hangover relief compositions prepared in Examples 1-5 was evaluated. Fifty people were randomly selected to taste the prepared hangover relief compositions, and scores were given according to sensory evaluation criteria. The specific scoring criteria are shown in Table 2.

[0142] Table 2 Taste Rating

[0143]

[0144]

[0145] Note: Sample size n = 50 (where (S represents the average score, and S represents the error).

[0146] As shown in Table 2, a survey of 50 people was conducted on aspects such as appearance, color, unpleasant odor, aroma, bitterness, sweetness and sourness, solubility, and taste. The data results show that among the five groups, the groups with higher scores were Example 1, Example 4, and Example 5. Among them, Example 4 had relatively poor solubility, and Example 5 had a certain bitter taste. From the overall scoring results, Example 1 had the highest score, and the average scores in all aspects were also high, indicating that people generally had a high degree of acceptance of Example 1 and were quite satisfied with the effervescent tablets prepared by Example 1.

[0147] The taste is mainly affected by the following factors: ① The acid-base ratio, dosage, and type of disintegrant: a higher acid-base ratio results in greater acidity; more disintegrant leads to a more acidic taste; the type of acid has a significant impact on the taste, with excessive addition of malic acid, fumaric acid, and tartaric acid greatly increasing the bitterness. ② The aroma is mainly affected by flavorings, freeze-dried tomato powder, and hawthorn powder. ③ The taste is greatly affected by macromolecular polysaccharides; excessive addition results in slow dissolution and a jelly-like consistency, which, when combined with insoluble substances in freeze-dried tomato powder and hawthorn powder, negatively impacts the taste. ④ Sweetness is affected by the dosage of arabinose / tagatose / alulose, sodium chloride, and stevia; more arabinose / tagatose / alulose and stevia results in a sweeter taste; sodium chloride, at an appropriate concentration, can enhance sweetness; however, excessive stevia can also lead to a bitter taste in the effervescent tablet solution.

[0148] Experimental Example 3

[0149] Experiment on the efficacy of effervescent tablets prepared from the hangover relief composition in mice

[0150] Experimental objective: To verify the hangover-relieving effect of effervescent tablets through mouse experiments.

[0151] Experimental equipment and materials:

[0152] Experimental materials: 56° Red Star Erguotou (a type of Chinese liquor), physiological saline, effervescent tablets of Example 1, Example 2, Example 3, Example 4, and Example 5;

[0153] Laboratory animals: Mice weighing 20-25g. Naturally fed for 3 days at 22℃ with 12h light, mice of similar weight and condition were selected for use.

[0154] Experimental equipment: gavage syringe, forceps, small glass vial with rubber stopper, blood ethanol test kit;

[0155] Group processing:

[0156] (1) Grouping:

[0157] ① Control group: saline group;

[0158] ② Experimental Groups: Experimental Group 1 (Example 1 effervescent tablet), Experimental Group 2 (Example 2 effervescent tablet), Experimental Group 3 (Example 3 effervescent tablet), Experimental Group 4 (Example 4 effervescent tablet), Experimental Group 5 (Example 5 effervescent tablet), Experimental Group 6 (Other components are the same as in Example 1 effervescent tablet, but low molecular weight Tremella polysaccharide is used instead of high molecular weight Tremella polysaccharide), Experimental Group 7 (Other components are the same as in Example 1 effervescent tablet, but low molecular weight Tremella polysaccharide is used instead of high molecular weight Tremella polysaccharide), Experimental Group 8 (Other components are the same as in Example 1 effervescent tablet, but Hericium erinaceus polysaccharide is not added), Experimental Group 9 (Other components are the same as in Example 1 effervescent tablet, but small molecule peptides are not added);

[0159] (2) Drunkenness experiment:

[0160] One hundred mice were randomly selected, marked, and divided into 10 groups of 10 mice each, following the grouping rules outlined above. Mice were fasted for 12 hours but allowed free access to water before the experiment. Before intoxication, mice were administered physiological saline or an effervescent tablet solution (2g / 100ml) to the experimental group via gavage at a dose of 20ml / kg. Twenty minutes after gavage, each group was administered 56° Erguotou (a type of Chinese liquor) via gavage at a dose of 25ml / kg. The mice's behavior was observed, with the disappearance of the righting reflex as the standard: a mouse was considered intoxicated if it remained in a back-down position for 30 seconds without being able to roll over. The time from intoxication to sobering up was recorded.

[0161] (3) Measurement of blood ethanol content:

[0162] Repeat the experiment as in (2). After 1.5 hours, blood was collected from the heart of the mouse. After standing at room temperature for 30 minutes, the mixture was centrifuged at 5000 r / min and 4℃ for 10 minutes. The supernatant was collected, and the reaction system was prepared according to the instructions of the blood ethanol kit. The absorbance was recorded at a wavelength of 340 nm according to the reaction time requirements, and the ethanol content was calculated.

[0163] Experimental results:

[0164] Table 3. Data from the intoxication experiment

[0165]

[0166]

[0167] Note: Sample size n = 10 (where (S represents the average value, and S represents the error)

[0168] Table 4. Blood Ethanol Content

[0169]

[0170] Note: Sample size n = 10; **p < 0.1 (where X represents the mean, S represents the error, and **p represents the significance of the difference)

[0171] Experimental Analysis:

[0172] As shown in Table 3, the data from the alcohol intoxication experiment revealed that, compared with the control group, all experimental groups exhibited a certain degree of alcohol detoxification effect and significantly reduced the mortality rate and intoxication rate of mice. Experimental groups 1 and 4 demonstrated more pronounced alcohol detoxification advantages, with both groups showing a mortality rate of zero, a 70% reduction in intoxication rate, and the shortest intoxication time among all experimental groups, at 248.62 min and 249.76 min respectively, indicating that these two experimental groups had good alcohol detoxification effects.

[0173] Experimental groups 6-9 are comparative examples. The experimental data show that compared with experimental groups 1-5, the four experimental groups had significantly higher rates of intoxication, significantly higher blood ethanol concentrations, and significantly worse hangover relief effects. This indicates that macromolecular Tremella polysaccharide, small molecule Tremella polysaccharide, Hericium erinaceus polysaccharide, and small molecule peptides are all indispensable.

[0174] A horizontal comparison of experimental groups 1, 2, 3, 4, and 5 revealed that the better the hangover relief effect was when the amounts of macromolecular Tremella polysaccharide, small molecule Tremella polysaccharide, Hericium erinaceus polysaccharide, and small molecule peptides were increased simultaneously.

[0175] Table 4 shows that, compared with the control group, experimental groups 1 and 4 had the lowest blood ethanol concentrations, with decreases of 45.32% and 46.49% in blood ethanol levels, respectively. These results indicate that the effervescent tablets in experimental groups 1 and 4 significantly reduced the concentration of ethanol in the blood of mice, demonstrating a good effect in relieving hangovers.

[0176] The data from Experiments 1, 6, and 7 show that the coexistence of large-molecule and small-molecule Tremella fuciformis polysaccharides results in a more significant hangover-relieving effect. The data from Experiments 1, 8, and 9 indicate that Hericium erinaceus polysaccharides and small-molecule peptides are essential components of the compound hangover-relieving effervescent tablets; their absence leads to a decreased hangover-relieving effect. This is because Hericium erinaceus polysaccharides have antioxidant, gastric acid-reducing, and pepsin-inhibiting effects. Combined with Tremella fuciformis polysaccharides and small-molecule peptides, they can reduce the decomposition of Tremella fuciformis polysaccharides and small-molecule peptides by gastric acid and pepsin, significantly extending the protective time. Small-molecule peptides (soybean protein peptides / pea protein peptides / corn peptides / sunflower disc peptides / collagen peptides) have excellent adhesion to the stomach wall; combined with small-molecule peptides, they greatly enhance the adhesion ability of Tremella fuciformis polysaccharides, strengthening the protective effect of the stomach wall.

[0177] Experiment Example 4

[0178] Experiment on the protective effect of effervescent tablets prepared from the hangover relief composition on the gastric mucosa of mice

[0179] Experimental objective: To verify, through mouse experiments, that effervescent tablets have the effect of protecting the gastric mucosa and reducing the damage of alcohol to the gastric mucosa.

[0180] Experimental equipment and materials:

[0181] Experimental materials: 56° Red Star Erguotou liquor, physiological saline, experimental group.

[0182] Experimental animals: Mice weighing 20-25g. They were naturally fed for 3 days at 22℃ with 12h light, and mice of similar weight and condition were selected for use.

[0183] Group processing:

[0184] (1) Grouping:

[0185] ① Normal control group: pure water group

[0186] ② Control group: saline group

[0187] ③ Experimental Groups: Experimental Group 1 (Example 1 effervescent tablet), Experimental Group 2 (Example 2 effervescent tablet), Experimental Group 3 (Example 3 effervescent tablet), Experimental Group 4 (Example 4 effervescent tablet), Experimental Group 5 (Example 5 effervescent tablet), Experimental Group 6 (Other components are the same as in Example 1 effervescent tablet, but low molecular weight Tremella polysaccharide is used instead of high molecular weight Tremella polysaccharide), Experimental Group 7 (Other components are the same as in Example 1 effervescent tablet, but low molecular weight Tremella polysaccharide is used instead of high molecular weight Tremella polysaccharide), Experimental Group 8 (Other components are the same as in Example 1 effervescent tablet, but Hericium erinaceus polysaccharide is not added), Experimental Group 9 (Other components are the same as in Example 1 effervescent tablet, but small molecule peptides are not added);

[0188] (2) Drunkenness experiment:

[0189] 110 mice were randomly selected, marked, and divided into groups of 10 mice each. Before the experiment, the mice were fasted for 12 hours but allowed free access to water. Before intoxication, they were administered pure water, physiological saline, or an effervescent tablet solution (2g / 100ml) by gavage at a volume of 20ml / kg. Twenty minutes after gavage, each group of mice was administered pure water (normal control group) or 56° Erguotou (control group and experimental group) by gavage at a volume of 25ml / kg. One hour later, all animals were anesthetized and euthanized, exposing the intact stomach. The pylorus was ligated, and the stomach was fixed in 10% formaldehyde solution for 20 minutes. The gastric mucosa was then spread, and the length and width of bleeding points or bleeding bands were measured visually using calipers. Histopathological examination was performed.

[0190] Evaluation criteria: Visual inspection and scoring, as follows:

[0191] The length and width of the bleeding point or bleeding band are measured visually using calipers. Since the width represents a much greater degree of injury severity than the length, it is scored twice. The scoring criteria are shown in the table below.

[0192] Table 5. Gross Visual Assessment Criteria for Acute Ethanol Injury

[0193]

[0194] Observation indicators: The degree of gastric mucosal damage in each experimental group was expressed as the damage incidence rate (%), damage score index and damage inhibition rate.

[0195] Incidence of injury (%) = Number of rats in a group that developed hemorrhage or ulceration / Number of mice in that group × 100%

[0196] Injury Score Index = Sum of group injury scores / Number of animals in a group

[0197] Damage inhibition rate (%) = (AB) / A × 100% (A and B are the damage scores of the model group and the experimental group, respectively)

[0198] Toxicity pathology examination

[0199] Pathological histological observation and scoring: Tissue fixed in 10% formaldehyde solution was routinely prepared, stained with hematoxylin and eosin (HE), and observed under a microscope. Note that a transverse section of the gastric mucosa, including the entire mucosal layer, should be selected for observation.

[0200] Scoring method: The severity of congestion, hemorrhage, and mucosal cell degeneration and necrosis is classified into 5 grades based on the extent of involvement of the entire mucosal epithelium. Congestion has a weight of 1, hemorrhage has a weight of 2, and epithelial cell degeneration and necrosis has a weight of 3. The scoring criteria and the formula for the total score of the lesion are shown in the table below.

[0201] Table 6. Endoscopic scoring criteria for acute gastric mucosal injury.

[0202]

[0203] Experimental results

[0204] (1) Visual observation and scoring:

[0205] Normal control group: The gastric mucosa of the animals was normal in color, smooth in surface, without bleeding points or bleeding bands, and the incidence of gastric mucosal injury was 0%.

[0206] In both the control and experimental groups, the gastric mucosa was congested, and petechiae and cord-like hemorrhages were visible in the glandular area. The incidence of gastric mucosal injury was 100% in both groups.

[0207] Table 7 Animal Injury Score Index

[0208]

[0209]

[0210] Note: *P<0.05, comparison between each group and the normal control group; #P<0.05, comparison between each group and the control group; Injury score index = sum of group injury scores / number of animals in the group.

[0211] (2) Damage inhibition rate

[0212] Table 8 Animal Injury Inhibition Rate

[0213]

[0214] Note: Damage inhibition rate (%) = (damage score of control group - damage score of experimental group) / damage score of control group × 100%.

[0215] (3) Histopathological examination results

[0216] Table 9 Total Score of Lesions in Animal Histopathological Examination

[0217]

[0218] Note: *P<0.05, comparison between each group and the normal control group; #P<0.05, comparison between each group and the control group; Total lesion score = congestion score + hemorrhage score × 2 + epithelial cell degeneration and necrosis score × 3.

[0219] Experimental results

[0220] The results above show that, compared to normal mice, alcohol causes severe damage to the gastric mucosa of mice. Figure 1 As shown, visual observation revealed that the gastric mucosa of both the control group and the experimental groups was congested, with bleeding points and linear bleeding bands visible in the glandular area, resulting in a 100% injury rate. Compared with the control group, the injury score index of each experimental group decreased and the injury inhibition rate increased. Among them, experimental groups 1 and 4 had the highest injury inhibition rates, at 43.7% and 41.8%, respectively.

[0221] Histopathological examination revealed that, compared with the normal control group, the total score of gastric mucosal lesions in SD rats in all other groups was significantly increased; compared with the control group, the total score of gastric mucosal lesions in SD mice in each experimental group was significantly decreased, with experimental groups 1 and 4 showing the greatest decrease, decreasing by 43 points and 41 points respectively.

[0222] The data from experimental groups 1, 6, and 7 show that experimental group 1 is superior. This is because the presence of both macromolecular and small molecule Tremella fuciformis polysaccharides has a more significant inhibitory effect on damage. The data from experimental groups 1, 8, and 9 show that experimental group 1 is superior. This is because Hericium erinaceus polysaccharides and small molecule peptides are essential components of the compound hangover relief effervescent tablets, and their absence would lead to a poorer effect of the effervescent tablets in inhibiting gastric mucosal damage.

[0223] As can be seen from the above, under these experimental conditions, experimental groups 1 and 4 have a significant ability to reduce alcohol-induced gastric mucosal damage and have a significant protective effect on the gastric mucosa.

[0224] In summary, the experiments above show that experimental groups 1 and 4 have more significant advantages in relieving hangovers: both groups had a mortality rate of zero, a 70% reduction in intoxication rate, and the shortest duration of intoxication; they also had the lowest relative blood ethanol concentrations, with blood ethanol levels decreasing by 45.32% and 46.49% in the two groups of mice, respectively; they had the highest damage inhibition rates, at 43.7% and 41.8%, respectively; and the two experimental groups of SD mice showed the greatest reduction in the total score of gastric mucosal lesions, decreasing by 43 and 41 points respectively compared to the control group. This indicates that these two experimental groups have significant hangover-relieving and stomach-protecting effects.

[0225] However, the results of Experiment 1 and Experiment 2 show that Experiment 1 has better stability and solubility than Experiment 4, and its taste acceptance test score is higher.

[0226] In summary, the formula in experimental group 1 showed the best performance in effervescent tablet performance tests, taste acceptance surveys, mouse intoxication experiments, and gastric mucosal damage experiments, making it the optimal formula with significant hangover relief and stomach protection effects.

Claims

1. An alcoholism relief composition, characterized by comprising: The dosage form is effervescent tablets, which comprises, by weight fraction, 200-2000 parts of tremella polysaccharide, 100-1000 parts of small molecule peptide, 100-1000 parts of hericium polysaccharide, 100-2000 parts of nutritional sugar substitute, 1-50 parts of compound vitamin B, The tremella polysaccharide is composed of 0.6-2 million molecular weight tremella polysaccharide and 1-10 thousand molecular weight tremella polysaccharide, and the weight ratio of the 0.6-2 million molecular weight tremella polysaccharide to the 1-10 thousand molecular weight tremella polysaccharide is (1-2):

1. The small molecule peptide is at least one of soybean protein peptide, pea protein peptide, corn peptide, sunflower disc peptide or collagen peptide.

2. The hangover-alleviating composition of claim 1, wherein The nutritional sugar substitute is selected from one of tagatose, allulose or arabinose.

3. The hangover-alleviating composition of claim 1, wherein It further comprises, by weight fraction, 0-1000 parts of hawthorn powder, 0-1000 parts of tomato freeze-dried powder, 0-1000 parts of water-soluble cellulose and 0-1000 parts of pectin.

4. The hangover-alleviating composition of claim 3, wherein It further comprises, by weight fraction, 1000-5000 parts of disintegrant, 100-1000 parts of lubricant, 0-100 parts of stevia, 0-10 parts of food colorant and 0-10 parts of essence.

5. The alcoholism-relieving composition of claim 4, wherein The disintegrant is an acid and a base in a weight ratio of (1-1.9):1, the acid is selected from one or more of citric acid, malic acid, fumaric acid or tartaric acid, and the base is selected from one or both of sodium bicarbonate and sodium carbonate; The lubricant is selected from one or more of magnesium stearate, sodium chloride or polyethylene glycol (PEG) 6000.

6. The hangover-alleviating composition of claim 5, wherein It is composed of, by weight fraction, 1000 parts of 0.6-2 million molecular weight tremella polysaccharide, 620 parts of 1-10 thousand molecular weight tremella polysaccharide, 400 parts of pea protein peptide, 500 parts of hericium polysaccharide, 800 parts of tagatose, 30 parts of compound vitamin B, 300 parts of hawthorn powder, 350 parts of tomato freeze-dried powder, 200 parts of water-soluble cellulose, 300 parts of pectin, 160 parts of PEG6000, 340 parts of sodium chloride, 100 parts of stevia, 0.1 part of tomato red pigment, 0.5 part of tomato essence and 4900 parts of disintegrant, The disintegrant is citric acid and sodium bicarbonate in a weight ratio of 1.3:

1.

7. A method of preparing the hangover composition according to claim 5 or 6, characterized in that, The method comprises the following steps: (1) mixing 0.6-2 million molecular weight tremella polysaccharide, 1-10 thousand molecular weight tremella polysaccharide, hericium polysaccharide, nutritional sugar substitute, compound vitamin B, water-soluble cellulose and pectin in a mixer to mix uniformly; (2) mixing pea protein peptide, hawthorn powder, tomato freeze-dried powder, organic acid and lubricant, crushing in a crusher and sieving through a 100-200 mesh sieve; (3) mixing the uniformly mixed material of step (1), the sieved material of step (2) and tomato red pigment, tomato essence and sodium bicarbonate in a mixer to mix uniformly; (4) pressing the uniformly mixed material of step (3) into effervescent tablets in a single punch tablet press and packaging in bottles.

8. The preparation method of claim 7, wherein In the crushing process of step (2), intermittent crushing is adopted, the ambient temperature is maintained at 26℃, the air humidity is less than 45%, and the internal temperature of the crusher is less than 40℃. The mixing temperature in step (3) is lower than 30°C, and the air humidity is lower than 45%. During the tabletting process in step (4), the ambient temperature is maintained at 26°C, and the air humidity is lower than 40%. The size of the tablet is 1-8g / tablet.

9. The production method according to claim 8, wherein The size of the tablet is 4g / tablet.

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