Composition for relieving headache after drinking and preparation method thereof

Abstract

The present invention relates to the field of medical technology, and in particular to a composition for relieving headaches caused by alcohol consumption and a preparation method thereof. The composition comprises the following raw materials in parts by weight: 5-10 parts of curcumin composite particles, 20-30 parts of chitosan stabilized fermentation broth, 10-15 parts of kudzu root extract, 5-10 parts of emblica fruit extract, 10-15 parts of wolfberry fruit, 5-10 parts of cassia seed, 5-10 parts of black plum, 5-10 parts of roselle extract, 10-15 parts of sweetener, and 5-8 parts of stabilizer. The curcumin composite particles are prepared by nanoliposome embedding and tannic acid and polyethylene glycol functionalization treatment, the chitosan stabilized fermentation broth is prepared by combining chitosan and red pitaya fermentation broth, and the composition is prepared by processes such as plant component extraction, mixing and blending, and sterilization treatment. The composition can accelerate ethanol metabolism, enhance liver antioxidant capacity, thereby reducing liver damage caused by alcohol, and effectively relieve headaches caused by alcohol consumption.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to a composition for relieving headache after drinking and a preparation method thereof. Background Art

[0002] Alcohol headaches are a common symptom experienced by many people after drinking alcohol. They are primarily caused by factors such as acetaldehyde accumulation during alcohol metabolism, dehydration, vasodilation, and nervous system stimulation. Studies have shown that acetaldehyde produced during alcohol metabolism is a toxic substance that can damage the central nervous system and liver, leading to symptoms such as headaches, nausea, and fatigue. Furthermore, alcohol can cause vasoconstriction and dilation, leading to insufficient blood supply to the brain and, consequently, headaches. Currently, common methods for relieving alcohol headaches include medications (such as ibuprofen and acetaminophen) or dietary adjustments (such as sobering teas), but these methods often have limited effectiveness and are associated with side effects.

[0003] The Chinese patent application number CN202211063577.8 discloses a hangover-relieving composition, its preparation method and application. The raw materials of the composition include Acanthopanax senticosus saponins, Schisandra chinensis extract, Rhizoma Bombycis extract and Polygala tenuifolia extract. The hangover-relieving composition aims to protect the liver, kidneys and other major organs by inhibiting the gastrointestinal absorption of ethanol and accelerating the metabolism of ethanol, thereby effectively alleviating symptoms such as headaches and stomach acid after drinking. In addition, the composition is made of natural plant extracts and has no toxic side effects. However, the extraction and purification steps of Acanthopanax senticosus total glycosides mentioned in the invention are relatively complicated, and the cost, efficiency and scale issues in industrial production are not considered. Chinese patent application number CN201811640541.5 discloses a hangover-relief and liver-protecting composition, its preparation method, and application. The composition is composed of the following ingredients: 5-20 parts of fresh ginseng extract, 10-30 parts of persimmon extract, 5-25 parts of kudzu root extract, 5-25 parts of Hovenia dulcis extract, 2-15 parts of turmeric extract, 2-10 parts of yeast, 5-25 parts of corn oligopeptides, 2-10 parts of sea buckthorn extract, 2-10 parts of blueberry extract, 2-10 parts of mulberry extract, and 2-10 parts of black plum extract. This invention uses safe and non-toxic natural traditional Chinese medicines extracted through modern technology. It can not only effectively relieve hangover symptoms after drinking, but also prevent discomfort such as dry mouth and headache the next day. At the same time, the composition can shorten the sobering time and has a good alleviating effect on alcohol-induced liver damage. However, ginsenosides in fresh ginseng extract can enhance the excitatory effect of alcohol on the central nervous system, which is contrary to the goal of sobering up, and therefore is not suitable for use in sobering up drugs or foods.

[0004] Therefore, developing a safe, effective and side-effect-free composition for alleviating headache after drinking has important practical significance. Summary of the Invention

[0005] To address the above issues, the present invention provides a composition for relieving post-alcohol headaches and its preparation method. Curcumin composite particles are protected by nanoliposomes and treated with tannic acid and polyethylene glycol, enhancing the stability and bioavailability of curcumin. Chitosan-stabilized fermentation broth further enhances the stability and antioxidant capacity of the composition through its antioxidant properties. Other plant extracts, such as kudzu root extract and emblica fruit extract, further enhance the overall effectiveness of the composition by providing additional antioxidants and alcohol-resolving properties. The synergistic effect of these ingredients not only improves the product's stability and bioavailability, but also reduces adverse reactions, ensuring its safety and effectiveness.

[0006] The technical solutions adopted by the present invention to achieve the above-mentioned purpose are:

[0007] A composition for relieving headaches after drinking alcohol comprises the following raw materials in parts by weight: 5-10 parts of curcumin composite particles, 20-30 parts of chitosan stabilized fermentation liquid, 10-15 parts of kudzu root extract, 5-10 parts of emblica fruit extract, 10-15 parts of wolfberry fruit, 5-10 parts of cassia seed, 5-10 parts of black plum, 5-10 parts of roselle extract, 10-15 parts of sweetener, and 5-8 parts of stabilizer.

[0008] The preparation method of the curcumin composite particles is as follows:

[0009] Step S1, dissolving curcumin, soybean lecithin, and cholesterol in anhydrous ethanol at 50-60° C. with stirring, then rotary evaporating at 40-50° C. to form a thin film, then rotary hydrating with citrate buffer containing Tween 80 at 50-60° C. for 40-50 minutes, and high-pressure homogenizing and post-processing to obtain liposome particles;

[0010] Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 25-30° C. for 22-26 hours, and obtaining tannic acid functionalized particles through post-treatment;

[0011] Step S3: dispersing the tannic acid functionalized particles in anhydrous ethanol, adding polyethylene glycol, and reflux reacting at 65-75° C. under inert atmosphere for 11-13 hours, and obtaining curcumin composite particles through post-treatment.

[0012] Furthermore, in step S1, the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:7-8:0.7-1, the amount of curcumin added to anhydrous ethanol is 0.01-0.015 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.05-0.1 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 2-5 mg / mL.

[0013] Furthermore, the solvent used for the tannic acid solution in step S2 is deionized water, the concentration of the tannic acid solution is 4-6 mg / mL, and the mass volume ratio of the liposome particles to the tannic acid solution is 0.04-0.065 g / mL.

[0014] Furthermore, in step S3, the amount of tannic acid functionalized particles added to the anhydrous ethanol is 5-10 mg / mL, and the mass ratio of polyethylene glycol to tannic acid functionalized particles is 0.15-0.2:1.

[0015] Furthermore, the preparation method of the chitosan-stabilized fermentation broth is as follows: adding the chitosan solution to the clarified red pitaya fermentation broth with a pH value of 5.0-6.5 at room temperature and stirring, stirring for 10-15 minutes, and obtaining the chitosan-stabilized fermentation broth through post-treatment.

[0016] The preparation method of clarifying the fermented liquid of red pitaya has been disclosed in the patent document CN108402454B, specifically:

[0017] The first step is aerobic and anaerobic fermentation: by weight, add 4-7 parts of brown sugar to 100 parts of crushed red pitaya pulp. Follow the rule that yeast is the dominant bacteria in the initial fermentation, and timely aerate or no aeration management;

[0018] The second step is complete anaerobic fermentation: when the yeast activity weakens and sporulates, add 4-8 parts of brown sugar and inoculate 0.7-1.5 parts of microbial combination fermentation agent, strictly control the anaerobic fermentation to produce a large amount of short-chain fatty acids;

[0019] The third step is complete aerobic fermentation: when the pH value no longer changes, 0.4-0.7 parts of acetic acid bacteria are inoculated for aerobic fermentation to convert ethanol into acetic acid, and the filtrate is filtered to obtain the filtrate;

[0020] The filtrate is post-ripened, further oxidized, and clarified until the mass fraction of ethanol in the fermentation product is less than 0.2%, thereby obtaining a red pitaya fermentation liquid, wherein the microbial combination fermentation agent is mainly composed of Bifidobacterium, Bacteroides, and Eubacterium. The Bifidobacterium is a Bifidobacterium bifidum species, the brand is Mingzhou Biological, the product number is B86053; the Bacteroides is a Bacteroides thetaiotaomicron species, the brand is Mingzhou Biological, the product number is B81084; the Eubacterium is a Clostridium butyricum species, the brand is Mingzhou Biological, the product number is B90320;

[0021] Furthermore, the chitosan solution uses 1% acetic acid solution as a solvent, the concentration of the chitosan solution is 0.5-1%, and the volume ratio of the chitosan solution to the clarified red pitaya fermentation liquid is 1:9-10.

[0022] Furthermore, the sweetener is maltitol or erythritol.

[0023] Furthermore, the stabilizer is carrageenan or agar.

[0024] The present invention also provides a method for preparing a composition for relieving headache after drinking, comprising the following steps:

[0025] (1) Wash wolfberry, cassia seed and black plum, dry, grind into fine powder, add together with kudzu root extract, emblica fruit extract and roselle extract into deionized water, boil, extract, cool and filter to obtain extract;

[0026] (2) Add the sweetener and stabilizer to the extract obtained in step (1) and mix evenly, then add the chitosan stabilized fermentation liquid and curcumin composite particles, mix evenly, and finally fill, seal and sterilize to obtain the product.

[0027] The present invention has the following beneficial effects:

[0028] The present invention first uses nanoliposome encapsulation technology to encapsulate fat-soluble curcumin into nano-scale particles, significantly improving its water solubility and bioavailability, avoiding gastric acid degradation, and enabling efficient absorption in the intestine. Tannic acid and polyethylene glycol are then introduced to further enhance the antioxidant effect of the curcumin composite particles, thereby relieving vasodilatory headaches caused by acetaldehyde, a product of alcohol metabolism, from the root. Furthermore, the curcumin composite particles synergize with kudzu root extract to accelerate the decomposition of acetaldehyde, reduce the accumulation of toxic substances, and help alleviate post-alcohol discomfort. After chitosan is compounded with red pitaya fermentation broth, polyphenols such as anthocyanins and betaine in the fermentation broth work synergistically with the emblica extract rich in vitamin C and polyphenols to enhance the body's antioxidant capacity, scavenge free radicals generated by alcohol metabolism, and reduce liver oxidative damage. The cationic properties of chitosan form a complex with negatively charged components such as pectin and organic acids in the red pitaya fermentation broth through electrostatic interaction, improving the dispersion stability of the composite system and avoiding particle aggregation. In addition, natural ingredients such as Pueraria root extract, Emblica fruit extract, Lycium barbarum, Cassia seed, Black plum and Hibiscus sabdariffa extract together constitute the natural plant part of the composition. These ingredients have antioxidant and alcohol-relieving effects, can work synergistically to enhance the therapeutic effect of curcumin, and help to restore discomfort such as headaches caused by drinking.

[0029] The composition provided by the present invention is compounded with raw materials such as curcumin composite particles, chitosan stabilized fermentation liquid, kudzu root extract, emblica fruit extract, wolfberry fruit, cassia seed, black plum, and roselle extract, thereby increasing the ADH and ALDH enzyme activities in liver tissue, accelerating ethanol metabolism and reducing ethanol accumulation in the body, thereby alleviating the burden on the liver; lowering serum AST and ALT levels, directly improving the degree of liver damage; and simultaneously enhancing the antioxidant capacity of SOD, effectively reducing MDA content, and reducing oxidative damage to liver cell membranes and organelles by free radicals, thereby significantly improving the effects of the composition in sobering up, protecting the liver, and relieving headaches in many aspects. DETAILED DESCRIPTION

[0030] The following will be combined with the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the embodiments described are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments of the present application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0031] The raw materials used in the following examples are all common commercially available products. Soybean lecithin has a drying loss of 0.87%, purchased from Guangzhou Huayu Biotechnology Co., Ltd.; ammonia water has an ammonia content of 25%, purchased from Boxuan Chemical; polyethylene glycol is PEG6000, with an effective ingredient content of 99%, purchased from Xi'an Hongyao Pharmaceutical Excipients Co., Ltd.; chitosan has an effective ingredient content of 99%, purchased from Sichuan Huatang Jurui Biotechnology Co., Ltd.; the ethanol mass fraction in the red pitaya fermentation liquid is ≤0.2%, and the pH value is 5.0-6.5. It is obtained by aerobic and anaerobic fermentation, complete anaerobic fermentation, and complete aerobic fermentation in sequence. The microbial strains used in the fermentation are composed of Bifidobacterium, Bacteroides, and Eubacterium, and the total number of microorganisms is ≥8×1015 cfu / g; the effective ingredient content of carrageenan is 99.9%, the pH value is 8-11, and the total ash content is 15-40%. Purchased from Qingdao Dehui Marine Biotechnology Co., Ltd.; agar with an active ingredient content of 99% and a melting point of 85-95°C was purchased from Shanghai Zhongfeng Biotechnology Co., Ltd.; wolfberry fruit with a specification of 250g was purchased from Zhongning Qifuyuan Trading Co., Ltd.; cassia seed with a moisture content of 10% was purchased from Bozhou Ruantang Pharmaceutical Co., Ltd.; black plum with a packaging specification of 500g was purchased from Bozhou Huozhengtang Pharmaceutical Co., Ltd.; kudzu root extract with an active ingredient content of 99% and a moisture content of 9.3% was purchased from Sichuan Chengzhu Biotechnology Co., Ltd.; emblica bud extract with a mesh size of 80-100 was purchased from Shanyang Lianfeng Biotechnology Co., Ltd.; roselle extract with a mesh size of 80 was purchased from Xi'an Ruierli Bioengineering Co., Ltd.; Neptune Gold Bottle was purchased from Nanning Neptune Health Biotechnology Co., Ltd., with a specification of 50mL 8 bottles; Citrate buffer pH 4.5-8.0, purchased from Yisejiu (Lianyungang, Jiangsu) Biotechnology Co., Ltd.

[0032] Example 1

[0033] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 5 parts of curcumin composite particles, 20 parts of chitosan stabilized fermentation broth, 10 parts of kudzu root extract, 5 parts of emblica fruit extract, 10 parts of wolfberry fruit, 5 parts of cassia seed, 5 parts of black plum, 5 parts of roselle extract, 10 parts of sweetener, and 5 parts of stabilizer;

[0034] The sweetener is maltitol and the stabilizer is carrageenan;

[0035] The preparation method of the curcumin composite particles is as follows:

[0036] Step S1, at 55 ° C, under stirring conditions, curcumin, soybean lecithin, and cholesterol were dissolved in anhydrous ethanol, and then rotary evaporated at 45 ° C, 120 rpm to form a film, and then rotary hydrated with citrate buffer containing Tween 80 at 55 ° C for 45 minutes, homogenized under 120 MPa high pressure under ice bath conditions, homogenized three times to obtain nanoliposomes, and the nanoliposomes were centrifuged at 12000 rpm for 15 minutes, and then washed three times with a mixed solution of anhydrous ethanol and water in a volume ratio of 1:1, and then vacuum dried at 40 ° C to constant weight to obtain liposome particles, wherein the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:7.5:0.8, the amount of curcumin added to the anhydrous ethanol is 0.013 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.07 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 4 mg / mL;

[0037] Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 28° C. for 24 h, centrifuging at 10,000 rpm for 10 min, then washing three times with deionized water, and freeze-drying at −50° C. for 48 h to obtain tannic acid-functionalized particles, wherein the solvent used for the tannic acid solution is deionized water, the concentration of the tannic acid solution is 5 mg / mL, and the mass-to-volume ratio of the liposome particles to the tannic acid solution is 0.05 g / mL;

[0038] Step S3, dispersing the tannic acid functionalized particles in anhydrous ethanol, then adding polyethylene glycol, reflux reacting at 70°C under nitrogen atmosphere for 12 hours, centrifuging at 10,000 rpm for 10 minutes, then washing with anhydrous ethanol and deionized water in sequence, and then freeze-drying at -50°C for 48 hours to obtain curcumin composite particles, wherein the amount of tannic acid functionalized particles added to the anhydrous ethanol is 8 mg / mL, and the mass ratio of polyethylene glycol to tannic acid functionalized particles is 0.18:1.

[0039] The preparation method of the chitosan-stabilized fermentation broth is as follows: under room temperature and stirring conditions, a chitosan solution is added to a clarified red pitaya fermentation broth with a pH value of 5.0-6.5, stirred for 13 minutes, centrifuged at 4000 rpm for 15 minutes, and the supernatant is taken as the chitosan-stabilized fermentation broth, wherein the chitosan solution is prepared by using 1% acetic acid solution as a solvent and stirring and dissolving at 40° C., the concentration of the chitosan solution is 0.8%, and the volume ratio of the chitosan solution to the clarified red pitaya fermentation broth is 1:9.5;

[0040] The preparation method of clarifying the fermented liquid of red pitaya has been disclosed in the patent document CN108402454B, specifically:

[0041] The first step is aerobic and anaerobic fermentation: take the raw materials including 100 parts of red pitaya pulp and 5 parts of brown sugar by weight, control the temperature at 28℃, and ventilate 1m3 per 2.5 tons of material every day. 3 Mixed fermentation for 25 days.

[0042] The second step is complete anaerobic fermentation: add 5 parts of brown sugar and inoculate 1.0 part of microbial combination fermentation agent, control the temperature at 33°C, and perform complete anaerobic fermentation until the 40th day.

[0043] The third step is complete aerobic fermentation: inoculate 0.5 parts of commercial acetic acid bacteria, control the temperature at 33 ° C, ventilate 3 times a day, and ventilate 1m for every 2.5 tons of material each time. 3 , completely aerobic fermentation until the pomace is completely precipitated, and filtration is performed to obtain the filtrate.

[0044] The filtrate is post-ripened, further oxidized and clarified until the mass fraction of ethanol in the fermentation product is lower than 0.2%, thereby obtaining a clarified red-heart pitaya fermentation liquid, wherein the microbial combination fermentation agent is mainly composed of Bifidobacterium, Bacteroides and Eubacterium. The Bifidobacterium is a Bifidobacterium bifidum species, the brand is Mingzhou Biological, and the product number is B86053; the Bacteroides is a Bacteroides thetaiotaomicron species, the brand is Mingzhou Biological, and the product number is B81084; the Eubacterium is a Clostridium butyricum species, the brand is Mingzhou Biological, and the product number is B90320.

[0045] A method for preparing a composition for relieving headache after drinking, comprising the following steps:

[0046] (1) Wash wolfberry, cassia seed and black plum, dry, and grind into 100 mesh fine powder, then add kudzu root extract, emblica fruit extract and roselle extract into 12 times volume of deionized water, boil, concentrate to 1 / 5 of the original volume, extract the active ingredients, cool naturally to room temperature, and filter to obtain the extract;

[0047] (2) Add the sweetener and stabilizer to the extract obtained in step (1) and mix evenly, then add the chitosan stabilized fermentation liquid and curcumin composite particles, mix evenly, and finally fill, seal and sterilize the mixed liquid.

[0048] Example 2

[0049] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 10 parts of curcumin composite particles, 30 parts of chitosan stabilized fermentation liquid, 15 parts of kudzu root extract, 10 parts of emblica fruit extract, 15 parts of wolfberry fruit, 10 parts of cassia seed, 10 parts of black plum, 10 parts of roselle extract, 15 parts of sweetener, and 8 parts of stabilizer;

[0050] The sweetener is erythritol and the stabilizer is agar;

[0051] The preparation methods of the curcumin composite particles, the preparation method of the chitosan-stabilized fermentation broth, and the preparation method of the composition for relieving headache after drinking are the same as those in Example 1, and the preparation method of the clarified red pitaya fermentation broth is also the same as that in Example 1.

[0052] Example 3

[0053] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 8 parts of curcumin composite particles, 25 parts of chitosan stabilized fermentation broth, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry fruit, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0054] The sweetener is erythritol and the stabilizer is agar;

[0055] The preparation methods of the curcumin composite particles, the preparation method of the chitosan-stabilized fermentation broth, and the preparation method of the composition for relieving headache after drinking are the same as those in Example 1, and the preparation method of the clarified red pitaya fermentation broth is also the same as that in Example 1.

[0056] Example 4

[0057] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 8 parts of curcumin composite particles, 25 parts of chitosan stabilized fermentation broth, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry fruit, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0058] The sweetener is maltitol and the stabilizer is carrageenan;

[0059] The preparation method of the curcumin composite particles is as follows:

[0060] Step S1, at 60 ° C, under stirring conditions, curcumin, soybean lecithin, and cholesterol were dissolved in anhydrous ethanol, and then rotary evaporated at 50 ° C, a speed of 120 rpm to form a film, and then rotary hydrated with a citrate buffer containing Tween 80 at 60 ° C for 50 min, homogenized under 120 MPa high pressure under ice bath conditions, homogenized three times to obtain nanoliposomes, and the nanoliposomes were centrifuged at 12000 rpm for 15 min, and then washed three times with a mixed solution of anhydrous ethanol and water with a volume ratio of 1:1, and then vacuum dried at 40 ° C to constant weight to obtain liposome particles, wherein the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:8:1, the amount of curcumin added to the anhydrous ethanol is 0.015 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.1 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 5 mg / mL;

[0061] Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 30° C. for 26 hours, centrifuging at 10,000 rpm for 10 minutes, then washing three times with deionized water, and freeze-drying at -50° C. for 48 hours to obtain tannic acid-functionalized particles, wherein the solvent used for the tannic acid solution is deionized water, the concentration of the tannic acid solution is 6 mg / mL, and the mass-to-volume ratio of the liposome particles to the tannic acid solution is 0.065 g / mL;

[0062] Step S3, dispersing the tannic acid functionalized particles in anhydrous ethanol, then adding polyethylene glycol, reflux reacting at 75°C under nitrogen atmosphere for 13 hours, centrifuging at 10,000 rpm for 10 minutes, then washing with anhydrous ethanol and deionized water in sequence, and then freeze-drying at -50°C for 48 hours to obtain curcumin composite particles, wherein the amount of tannic acid functionalized particles added to the anhydrous ethanol is 10 mg / mL, and the mass ratio of polyethylene glycol to tannic acid functionalized particles is 0.2:1.

[0063] The preparation method of the chitosan-stabilized fermentation broth is as follows: under room temperature and stirring conditions, a chitosan solution is added to a clarified red pitaya fermentation broth with a pH value of 5.0-6.5, stirred for 15 minutes, centrifuged at 4000 rpm for 15 minutes, and the supernatant is taken as the chitosan-stabilized fermentation broth, wherein the chitosan solution is prepared by using 1% acetic acid solution as a solvent and stirring and dissolving at 40° C., the concentration of the chitosan solution is 1%, and the volume ratio of the chitosan solution to the clarified red pitaya fermentation broth is 1:10;

[0064] The preparation method of the clarified red pitaya fermented liquid is the same as that in Example 1.

[0065] The preparation method of the composition for relieving headache after drinking is the same as that in Example 1;

[0066] Comparative Example 1

[0067] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 2 parts of curcumin composite particles, 10 parts of chitosan stabilized fermentation broth, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry fruit, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0068] The sweetener is maltitol and the stabilizer is carrageenan;

[0069] The preparation method of the curcumin composite particles is as follows:

[0070] Step S1, at room temperature and under stirring conditions, curcumin, soybean lecithin, and cholesterol were dissolved in anhydrous ethanol, and then rotary evaporated at 45° C. and a speed of 120 rpm to form a film, and then rotary hydrated with a citrate buffer containing Tween 80 at room temperature for 45 minutes, and homogenized under a high pressure of 120 MPa under ice bath conditions for 3 times to obtain nanoliposomes, and the nanoliposomes were centrifuged at 12000 rpm for 15 minutes, and then washed 3 times with a mixed solution of anhydrous ethanol and water in a volume ratio of 1:1, and then vacuum dried at 40° C. to constant weight to obtain liposome particles, wherein the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:7.5:0.1, the amount of curcumin added to the anhydrous ethanol is 0.013 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.07 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 1 mg / mL;

[0071] Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 28° C. for 24 h, centrifuging at 10,000 rpm for 10 min, washing three times with deionized water, and freeze-drying at −50° C. for 48 h to obtain tannic acid-functionalized particles, wherein the solvent used for the tannic acid solution is deionized water, the concentration of the tannic acid solution is 10 mg / mL, and the mass-to-volume ratio of the liposome particles to the tannic acid solution is 0.01 g / mL;

[0072] Step S3, dispersing the tannic acid functionalized particles in anhydrous ethanol, then adding polyethylene glycol, reflux reacting at 70° C. for 12 hours, centrifuging at 10,000 rpm for 10 minutes, then washing with anhydrous ethanol and deionized water in sequence, and then freeze-drying at -50° C. for 48 hours to obtain curcumin composite particles, wherein the amount of tannic acid functionalized particles added to the anhydrous ethanol is 20 mg / mL, and the mass ratio of polyethylene glycol to tannic acid functionalized particles is 0.18:1.

[0073] The preparation method of the chitosan-stabilized fermentation broth is as follows: under room temperature and stirring conditions, a chitosan solution is added to a clarified red pitaya fermentation broth with a pH value of 5.0-6.5, stirred for 13 minutes, centrifuged at 4000 rpm for 15 minutes, and the supernatant is taken as the chitosan-stabilized fermentation broth, wherein the chitosan solution is prepared by using 1% acetic acid solution as a solvent and stirring and dissolving at 40° C., the concentration of the chitosan solution is 0.1%, and the volume ratio of the chitosan solution to the clarified red pitaya fermentation broth is 1:1;

[0074] The preparation method of the clarified red pitaya fermented liquid is the same as that in Example 1.

[0075] A method for preparing a composition for relieving headache after drinking, comprising the following steps:

[0076] (1) Wash wolfberry, cassia seed and black plum, dry, and grind into 300 mesh fine powder, then add kudzu root extract, emblica fruit extract and roselle extract into 12 times volume of deionized water, boil, concentrate to 1 / 5 of the original volume, extract the active ingredients, cool naturally to room temperature, and filter to obtain the extract;

[0077] (2) Add the sweetener and stabilizer to the extract obtained in step (1) and mix evenly, then add the chitosan stabilized fermentation liquid and curcumin composite particles, mix evenly, and finally fill, seal and sterilize the mixed liquid.

[0078] Comparative Example 2

[0079] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 8 parts of curcumin composite particles, 25 parts of chitosan stabilized fermentation broth, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry fruit, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0080] The sweetener is maltitol and the stabilizer is carrageenan;

[0081] The preparation method of the curcumin composite particles is as follows:

[0082] Step S1, at 55 ° C, under stirring conditions, curcumin, soybean lecithin, and cholesterol were dissolved in anhydrous ethanol, and then rotary evaporated at 45 ° C, 120 rpm to form a film, and then rotary hydrated with citrate buffer containing Tween 80 at 55 ° C for 45 minutes, homogenized under 120 MPa high pressure under ice bath conditions, homogenized three times to obtain nanoliposomes, and the nanoliposomes were centrifuged at 12000 rpm for 15 minutes, and then washed three times with a mixed solution of anhydrous ethanol and water in a volume ratio of 1:1, and then vacuum dried at 40 ° C to constant weight to obtain liposome particles, wherein the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:7.5:0.8, the amount of curcumin added to the anhydrous ethanol is 0.013 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.07 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 4 mg / mL;

[0083] Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 28° C. for 24 h, centrifuging at 10,000 rpm for 10 min, then washing three times with deionized water, and then freeze-drying at -50° C. for 48 h to obtain curcumin composite particles, wherein the solvent used for the tannic acid solution is deionized water, the concentration of the tannic acid solution is 5 mg / mL, and the mass volume ratio of the liposome particles to the tannic acid solution is 0.05 g / mL;

[0084] The preparation methods of the chitosan-stabilized fermentation broth and the composition for relieving headache after drinking are the same as those in Example 1, and the preparation method of the clarified red pitaya fermentation broth is also the same as that in Example 1.

[0085] Comparative Example 3

[0086] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 8 parts of curcumin composite particles, 25 parts of chitosan stabilized fermentation broth, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry fruit, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0087] The sweetener is maltitol and the stabilizer is carrageenan;

[0088] The preparation method of the curcumin composite particles is as follows: curcumin, soybean lecithin, and cholesterol are dissolved in anhydrous ethanol at 55° C. under stirring conditions, and then rotary evaporated at 45° C. and a rotation speed of 120 rpm to form a thin film, and then rotary hydrated with a citrate buffer containing Tween 80 at 55° C. for 45 minutes, and homogenized under a high pressure of 120 MPa under an ice bath for 3 times to obtain nanoliposomes, and the nanoliposomes are centrifuged at 12000 rpm for 15 minutes, and then washed 3 times with a mixed solution of anhydrous ethanol and water with a volume ratio of 1:1, and then vacuum dried at 40° C. to constant weight to obtain curcumin composite particles, wherein the mass ratio of curcumin, soybean lecithin, and cholesterol is 1:7.5:0.8, the amount of curcumin added to the anhydrous ethanol is 0.013 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.07 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 4 mg / mL;

[0089] The preparation methods of the chitosan-stabilized fermentation broth and the composition for relieving headache after drinking are the same as those in Example 1, and the preparation method of the clarified red pitaya fermentation broth is also the same as that in Example 1.

[0090] Comparative Example 4

[0091] A composition for relieving headaches after drinking alcohol, comprising the following raw materials in parts by weight: 8 parts of curcumin, 25 parts of red pitaya fermentation liquid, 13 parts of kudzu root extract, 7 parts of emblica fruit extract, 12 parts of wolfberry, 8 parts of cassia seed, 7 parts of black plum, 8 parts of roselle extract, 12 parts of sweetener, and 6 parts of stabilizer;

[0092] The sweetener is maltitol and the stabilizer is carrageenan;

[0093] The preparation method of the composition for relieving headache after drinking is the same as that in Example 1, wherein the preparation method of the clarified red pitaya fermented liquid is also the same as that in Example 1.

[0094] Antioxidant capacity, alcohol sobering and liver-protecting effects, and alcohol metabolism-related enzyme activity assays:

[0095] Distilled water was used as a blank control and model group, the commercially available Neptune Gold Bottle was used as a positive control, and the compositions of Examples 1-4 and Comparative Examples 1-4 were used as test samples. The experiment used clean-grade NIH healthy adult mice, half male and half female, weighing 24-28g, and were randomly divided into 10 groups (n=10 / group, half male and half female in each group). The blank control group was gavaged with distilled water, and the remaining groups were gavaged with 52-proof liquor at 16mL / kg daily, 1 hour after gavage, once a day for 7 consecutive days. The blank control group and the model group were gavaged with 0.1mL / 10g of distilled water, and the positive control group was gavaged with 0.1mL / 10g of 0.2g / mL alcohol detoxification solution. The compositions of Examples 1-4 and Comparative Examples 1-4 were gavaged with 0.1mL / 10g of the test sample. After the last oral gavage, the mice were fasted but not watered. Twelve hours later, the eyeballs were removed and blood was collected. After standing at room temperature, the blood was centrifuged at 2000 rpm, and the supernatant was stored at -20°C for later use. The AST and ALT levels in the mouse serum were measured. After the mice were killed, the livers were quickly removed and stored in a -80°C ultra-low temperature refrigerator for later use. After thawing, the tissues were weighed and prepared into a 10% homogenate. The ADH, ALDH, and SOD activities and MDA content were detected by refrigerated centrifugation at 3000 rpm. The results are shown in Table 1.

[0096] Table 1 Results of serum AST, ALT levels, liver homogenate ADH, ALDH, SOD activities, and MDA content ( ,Only)

[0097]

[0098] Note: Indicates P < 0.05 compared with the model group.

[0099] Measurement data are presented as mean ± standard deviation (x ± S). Intergroup comparisons were performed using the homogeneity of variance test and one-way ANOVA test. Repeated measures data were analyzed using repeated measures analysis of variance, and multiple comparisons were handled using the least significant difference (LSD) method. All statistical analyses and graphics were performed in SPSS 19.0. P values ​​< 0.05 were considered statistically significant.

[0100] The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were tested to assess the degree of liver damage and verify the composition's effect in alleviating alcohol headaches, drunkenness and liver damage; the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the blood were measured to verify the composition's activation of key enzymes in alcohol metabolism and accelerate the decomposition of alcohol; the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in mouse liver tissue were tested to verify the composition's ability to scavenge free radicals produced by alcohol metabolism, such as hydroxyl radicals and superoxide anions, and reduce oxidative stress damage.

[0101] As shown in Table 1, the compositions prepared in Examples 1-4 significantly reduced serum AST and ALT levels, while increasing the activities of ADH and ALDH enzymes in liver tissue, which are associated with the rate of ethanol metabolism, and enhancing SOD enzyme activity, thereby reducing MDA content. In mouse experiments, compared with Examples 1-4, the composition prepared in Comparative Example 1 increased serum AST and ALT levels, decreased ADH, ALDH, SOD, and GSH activities, and increased MDA content. This indicates that the composition prepared in Comparative Example 1 had reduced effects on relieving alcohol-induced headaches and liver damage, as well as its ethanol decomposition and antioxidant properties. Therefore, the composition ratio proposed in the present invention for preparing a composition for relieving alcohol-induced headaches is optimal. Comparative Example 2 lacks the effect of polyethylene glycol. Compared with the composition prepared in Example 2, the composition prepared in Comparative Example 2 has further increased AST and ALT levels, further decreased ADH, ALDH, SOD and GSH activities, and further increased MDA content. The reason for this result is that the hydrophilic chain segment of polyethylene glycol can improve the solubility of the curcumin composite particles in aqueous solution and prevent agglomeration. This feature not only enables the antioxidant capacity of the curcumin composite particles to be effectively exerted, but also improves the stability of the oral solution. In addition, it can significantly improve the bioavailability of the curcumin composite particles, making them more efficient in absorption in the human body, thereby enhancing their effect in relieving alcohol-induced headaches. As can be seen from Table 1, the composition prepared in Comparative Example 3 has increased AST and ALT levels, decreased ADH, ALDH, SOD, and GSH activities, and increased MDA content. Therefore, the composition has reduced effects in relieving alcohol-induced headaches and sobering up. This is because Comparative Example 3 lacks the introduction of both polyethylene glycol and tannic acid. Tannic acid is a polyphenol structure with strong antioxidant capacity. When tannic acid is combined with liposome particles, it can enhance the surface stability of the liposomes and prevent aggregation or precipitation, thereby further enhancing the stability of the curcumin composite particles in the aqueous phase and helping to maintain the uniformity of the composition. On the other hand, curcumin itself has antioxidant properties. The combination of the two, tannic acid and curcumin, can significantly enhance the antioxidant properties of the composition through synergistic action, making it more effective in relieving alcohol-induced headaches.As can be seen from Table 1, the composition prepared in Comparative Example 4 has the highest AST and ALT levels, the lowest ADH, ALDH, SOD and GSH activities, and the highest MDA content. Therefore, the comprehensive performance of the prepared composition is the worst. This is because the curcumin composite particles of the composition are replaced by curcumin, and the chitosan-stabilized fermentation broth is replaced by red pitaya fermentation broth. The preparation of the curcumin composite particles first uses nanotechnology to encapsulate curcumin in liposomes to improve the stability and bioavailability of curcumin, and further reacts with tannic acid and polyethylene glycol to convert the nanoliposomes into curcumin composite particles. This process not only enhances the stability of curcumin, but also improves the antioxidant properties of the composition by introducing functional substances such as tannic acid; on the other hand, the positively charged chitosan forms a complex with the negatively charged components such as pectin and organic acid in the red pitaya fermentation broth through electrostatic action, thereby inhibiting particle aggregation and improving the clarity and storage stability of the composition solution. The synergistic effect of the chitosan-stabilized fermentation broth and the curcumin composite particles jointly improves the antioxidant, alcohol decomposition and alcohol headache relief effects of the composition.

[0102] Although the embodiments of the present application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations may be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A composition for relieving headache after drinking, characterized in that: The invention is composed of the following raw materials in parts by weight: 5-10 parts of curcumin composite particles, 20-30 parts of chitosan stabilized fermentation liquid, 10-15 parts of kudzu root extract, 5-10 parts of emblica fruit extract, 10-15 parts of wolfberry fruit, 5-10 parts of cassia seed, 5-10 parts of black plum, 5-10 parts of roselle extract, 10-15 parts of sweetener, and 5-8 parts of stabilizer. The preparation method of the curcumin composite particles is as follows: Step S1, dissolving curcumin, soybean lecithin, and cholesterol in anhydrous ethanol at 50-60° C. with stirring, then rotary evaporating at 40-50° C. to form a thin film, then rotary hydrating with citrate buffer containing Tween 80 at 50-60° C. for 40-50 minutes, and high-pressure homogenizing and post-processing to obtain liposome particles; Step S2, dispersing the liposome particles in a tannic acid solution, incubating with shaking at 25-30° C. for 22-26 hours, and obtaining tannic acid functionalized particles through post-treatment; Step S3, dispersing the tannic acid functionalized particles in anhydrous ethanol, adding polyethylene glycol, and reflux reacting at 65-75° C. under inert atmosphere for 11-13 hours, and obtaining curcumin composite particles through post-treatment; The preparation method of the chitosan-stabilized fermentation broth is as follows: under room temperature and stirring conditions, a chitosan solution is added to a clarified red pitaya fermentation broth with a pH value of 5.0-6.5, stirred for 10-15 minutes, and post-treated to obtain the chitosan-stabilized fermentation broth, wherein the chitosan solution uses a 1% acetic acid solution as a solvent, the concentration of the chitosan solution is 0.5-1%, and the volume ratio of the chitosan solution to the clarified red pitaya fermentation broth is 1:9-10.

2. The composition for relieving headache after drinking according to claim 1, characterized in that The mass ratio of curcumin, soybean lecithin, and cholesterol in step S1 is 1:7-8:0.7-1, the amount of curcumin added to anhydrous ethanol is 0.01-0.015 g / mL, the mass volume ratio of the film to the citrate buffer containing Tween 80 is 0.05-0.1 g / mL, and the mass volume ratio of Tween 80 to the citrate buffer is 2-5 mg / mL.

3. The composition for relieving headache after drinking according to claim 1, characterized in that The solvent used for the tannic acid solution in step S2 is deionized water, the concentration of the tannic acid solution is 4-6 mg / mL, and the mass volume ratio of the liposome particles to the tannic acid solution is 0.04-0.065 g / mL.

4. The composition for relieving headache after drinking according to claim 1, characterized in that In step S3, the amount of tannic acid functionalized particles added to the anhydrous ethanol is 5-10 mg / mL, and the mass ratio of polyethylene glycol to tannic acid functionalized particles is 0.15-0.2:

1.

5. The composition for relieving headache after drinking according to claim 1, characterized in that The sweetener is maltitol or erythritol.

6. The composition for relieving headache after drinking according to claim 1, characterized in that The stabilizer is carrageenan or agar.

7. The method for preparing the composition for relieving headache after drinking according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) Wash wolfberry, cassia seed and black plum, dry, grind into fine powder, add together with kudzu root extract, emblica fruit extract and roselle extract into deionized water, boil, extract, cool and filter to obtain extract; (2) Add the sweetener and stabilizer to the extract obtained in step (1) and mix evenly, then add the chitosan stabilized fermentation liquid and curcumin composite particles, mix evenly, and finally fill, seal and sterilize to obtain the product.

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