Composition of alcohol and cooling agent to regulate sexual functions, protect the cardiovascular and cerebrovascular systems, promote liver cell regeneration, and improve immunity and sleep quality

ES3072893T3Undetermined Publication Date: 2026-07-06

Patent Information

Authority / Receiving Office
ES · ES
Patent Type
Patents
Filing Date
2022-01-27
Publication Date
2026-07-06

AI Technical Summary

Technical Problem

Existing dietary therapies and health supplements are ineffective in providing short-term relief for weakened immunity, decreased sexual functions, and poor sleep, and take a long time to show effects, while excessive alcohol consumption leads to cardiovascular and cerebrovascular diseases, alcoholic liver diseases, and tumors.

Method used

A composition of alcohol, a cooling agent, and organic acid is formulated to activate the parasympathetic nerve signaling pathway, regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting liver cell regeneration, and improving immunity and sleep quality.

Benefits of technology

The composition effectively regulates sexual functions, protects cardiovascular and cerebrovascular systems, promotes liver cell regeneration, prevents and treats tumors, and improves immunity and sleep quality within 5-7 days by activating the parasympathetic nerve signaling pathway.

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Abstract

The use of a composition of alcohol and a cooling agent to regulate sexual function, protect the cardiovascular and cerebrovascular systems, promote hepatocyte regeneration, combat tumors, and improve immunity and sleep quality is explored in the fields of medicine, health care products, and nutrition. The composition consists of alcohol and a cooling agent. It also contains an organic acid. The alcohol content ranges from 1% to 99% vol., and the cooling agent content ranges from 0.05 to 500 ppm. The composition can regulate sexual function, protect the cardiovascular and cerebrovascular systems, promote hepatocyte regeneration, combat tumors, and improve immunity and sleep quality in a short period.
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Description

Technical field

[0001] The present invention belongs to the fields of medicine, health care and food, and specifically relates to a composition of alcohol and a cooling agent in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, and improving immunity and sleep quality.Background

[0002] Most people are busy at work, under great pressure, often drinking too much in social occasions, and lack of exercise. With the increasing pressure of life and work, their bodies are prone to long-term sympathetic nerve hyper tension. Sustained excessive excitement of sympathetic nerve will lead to many diseases, such as autoimmunity decline, sexual dysfunction, and poor sleep or insomnia.

[0003] Long-term excessive drinking will lead to cardiovascular and cerebrovascular diseases, alcoholic liver diseases (ALD) and tumors. In 2021, the International Agency for Research on Cancer (IARC) affiliated to the WHO issued a report on the global burden of alcohol-related cancers in Lancet Oncology. This report shows that in 2020, approximately 740,000 new cancers worldwide will be associated with alcohol drinking, including 76.7% in men and 23.3% in women. China's patients with cardiovascular and cerebrovascular diseases have exceeded 270 million people. Alcoholic liver disease (ALD) is a common clinical form of liver injury. The latest epidemiological surveys have found that ALD continues to be one of the common diseases that seriously jeopardize public health worldwide and is on the rise year after year. More than 90% of alcoholics are susceptible to fatty liver, 10%-35% develop alcoholic hepatitis, and about 8%-20% of chronic alcoholics evolve into cirrhosis of the liver, or even lead to liver cancer. In China, nearly 3 million people die from cardiovascular and cerebrovascular diseases each year, accounting for 51% of the total annual causes of death. However, 75% of survivors lost their ability to work to varying degrees, and 40% were severely disabled.

[0004] 2018 China Sleep Quality Survey Report released by the Sleep and Breathing Center of Beijing Chaoyang Hospital surveyed 100,000 people, covering all provinces in China. Survey results show that 83.81% of respondents were often troubled by sleep problems. The survey shows that China's sleep problems are rising year by year, sleep problems are gradually transformed into a social problem, and people with sleep problems are often accompanied by autoimmunity decline, sexual dysfunction and other symptoms.

[0005] Most of people who have the above health problems such as weakened immunity, decreased sexual functions and poor sleep cannot be detected for actual disease and cannot be effectively treated by drugs for a long time. Generally, they are treated through diets or by administering health supplements, but those ways cannot be effective in short-term relief of weakened immunity, decreased sexual functions, poor sleep and other health problems. In addition, treatment through diets or administering health supplements takes a long time and is slow to take effect, so patients are difficult to persist in such treatment. Ming et al (China Food, 11, 2021, pp.88-93) studied how to control liquor properties to promote the secretion of saliva and to improve human immune indicators, serotonin and sex hormone levels, and sleep; the original hot and dry properties of baijiu are transformed into moderately cool and mild properties, which can promote the secretion of saliva after drinking.

[0006] Kazadi et al. (EXPERIMENTAL PHYSIOLOGY, CAMBRIDGE UNIVERSITY PRESS, CAMBRIDGE, vol. 103, no. 10, 2018, pp. 1302-1308) discloses that gastric cooling stimuli, particular by peppermint oil, cause bradycardia, which appears to be a result of a parasympathetically mediated reflex initiated by cold thermoreceptors.

[0007] CN 109 022 223 discloses alcoholic beverages comprising alcohol, a cooling agent, and an organic acid.Summary

[0008] The present invention is directed to subject matter as defined in the claims.

[0009] It is provided a composition of alcohol and a cooling agent and organic acid for regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, and improving immunity and sleep quality.

[0010] The beneficial effect of the present invention is that the cooling agent is added into a base liquor with a specific alcohol concentration, or cooling agent natural plants (such as peppermint and spearmint ) including menthol are added into to take participate in all fermentation stages of various liquors to obtain the cooling agent, then the cooling agent and the alcohol are controlled through blending or purification to prepare the composition having the ability of regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. The composition of the present invention can play the role of regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality within 5-7 days by activating a parasympathetic nerve signaling pathway, thereby largely resolving the problem that common dietary therapies and health supplements are not able to improve sexual function, immunity and sleep quality within a short period, and enabling the organism to be protected, recuperated and restored. Additional organic acids in the base liquor including the cooling agent have a better effect. The compositions of the present invention can be utilized in the fields of medicine, food and health care products.Detailed Description

[0011] Terminology "liquor" is distilled alcoholic drink, fermented alcoholic drink, alcoholic beverages or integrated alcoholic beverage.

[0012] The human body is a complex system, which maintains the balance of body functions through various adjustments, rather than a single adjustment. The present invention provides use of a composition of alcohol and a cooling agent in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. The alcohol in the composition of the present invention in the composition is 30%vol-60%vol, and the cooling agent therein is 10ppm-100ppm.

[0013] The alcohol of the present invention is selected from at least one of distilled liquor, fermented liquor or edible alcohol.

[0014] The distilled liquor is selected from at least one of liquor, brandy, whiskey, vodka, rum, gin, tequila, or fruit distillate liquor.

[0015] The fermented liquor is selected from at least one of yellow liquor, beer, liquor, fruit liquor, fine rice liquor or milk liquor.

[0016] The cooling agent is a substance having the ability of activate a receptor of a thermoreceptor TRPM8, and includes at least one of menthyl acetate, L-menthyl lactate, or N,2,3-trimethyl-2-isopropylbutamide.

[0017] Further, the applicant has found that the addition of organic acids to the base liquor including the cooling agent has a better effect in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality.

[0018] The organic acid is 1,000ppm-6,000ppm.

[0019] The organic acid is selected from at least one of acetic acid, lactic acid, hexanoic acid, citric acid or malic acid.

[0020] The composition of the present invention also includes water to adjust alcohol concentration.

[0021] A method for preparing the composition of the present invention includes the following steps: dissolving the cooling agent in alcohol; then adding water and mixing the mixture well. Alternatively, dissolving the cooling agent in alcohol; then adding an organic acid; finally adding water and mixing the mixture well.

[0022] Test results show that healthy adults who drink a dose of alcohol, cooling agent or organic acid alone over a short period from 5 to 7 days have no significant effect in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. Drinking a dose of a composition of a cooling agent and an organic acid or a dose of a composition of alcohol and an organic acid in a short period has no significant effect in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. However, drinking a dose of a composition of alcohol and a cooling agent in a short period has an improvement effect in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. Drinking a dose of a composition of alcohol, a cooling agent and an organic acid has a significant improvement effect in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality.

[0023] The composition in this application is used for regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality, which is mainly related to the human body's intake of the alcohol and cooling agent in the composition. In view of the body's adaptation to taste and the body's tolerance to alcohol, the intake of the composition may depend on the content of alcohol and cooling agent in the composition. When the alcohol and the cooling agent in the composition are low, the intake of the composition can be increased to increase the intake of the alcohol and cooling agent, thereby playing the role of regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. When the alcohol and the cooling agent in the composition are high, the composition can be diluted with water to satisfy different body's requirements for the adaptation of taste and the tolerance of alcohol and achieve the effect of regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. Table A shows a recommended intake range. Table A Recommended intake range of compositionAlcohol %volCooling agent ppmOrganic acid ppmComposition intake mLPure alcohol intake mLCooling agent intake mgAcid intake mg1-300.05-10150-100050-10000.5-3002.5 µg-107.5-100030-6010-1001000-600015-5004.5-3000.15-5015-300060-80100-2006000-1000015-2509-2001.5-5090-250080-99200-50010000-3000010-2008-1982-100100-6000

[0024] Clinical studies have shown that long-term excessive intake of alcohol can lead to sleep and sexual dysfunction, and even can lead to the onset of cardiovascular disease and alcoholic liver disease, and even the development of tumors, which has the significant impact on the body's immune system. The inhibitory effect of alcohol on the central nervous system means the excitatory effect from cerebral cortex down through limbic system, cerebellum, reticulate structure and medulla oblongata with the dose increase. This is due to the fact that alcohol acts on the postsynaptic membrane γ-aminobutyric acid (GABA) receptor in the brain, thus inhibiting the inhibitory effect of GABA on the brain. As the concentration of the alcohol increases, it will further bind with other receptors, thereby causing a wide effect. Studies have shown that alcohol reduces immune function, inhibits interferon secretion, and interferes with the responsiveness of original antibodies to newly introduced antigens. Studies have shown that long-term heavy drinking can lead to sexual dysfunction in rats, which arises from the fact that alcohol inhibits the hypothalamic-pituitary-gonadal axes, lowering serum levels and directly inhibiting sexual function in rats. In addition, alcohol inhibition can further lead to penile smooth muscle atrophy, inhibiting the activity of choline acetyltransferase in penile tissues, thus indirectly inhibiting sexual function in rats.

[0025] Studies have shown that menthol derivatives can shorten sleep latency, antagonize the central excitatory effect of thiosemicarbazide, and improve sleep quality; at the same time, L-menthol and its derivatives can significantly inhibit the expression levels of glutamate receptors and acetylcholinesterase in the hippocampal region of the rat, thereby improving the cognitive ability and memory of the rat; in addition, studies also have shown that L-menthol and its derivatives have an antidepressant, anti-convulsion and hypnotic effect on the organism. Researchers have found that several menthol derivatives can activate TRPM8, and have higher efficacy and specificity than menthol, with great development potential. Studies show that TRPM8 activation can improve vascular tension and prevent hypertension. TRPM8 is widely distributed. In addition to TRPM8 expressed in prostate cancer, it is also expressed in some non-prostate primary tumors, and associated with the survival and growth of tumor cells; and it is likely to be a new target for anti-tumor therapy.

[0026] Organic acids can regulate a cellular immune system, induce host cells to produce antimicrobial peptides to achieve indirect bacterial inhibition, thereby providing body immunity. Meanwhile, studies have reported that succinic acid has a regulation effect on both GABA and Glu neurotransmitter systems in the CAI region of rat hippocampus, and it may act on the GABA system through the regulation mechanism that centers on calcium ions.

[0027] The present invention initially investigates the useful effect of the composition of the alcohol and the cooling agent in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality, and especially for the useful effect of the composition of the alcohol, the cooling agent and the organic acid in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality. According to the present invention, 3 items of immunoglobulin (IgA, IgG, IgM), serotonin (5-HT), estradiol (E 2 ), testosterone (T) and nitric oxide (NO) in blood are measured to evaluate the function of the composition in regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality; however, for the male, interferon-γ (IFN-γ) needs to be measured; and for the female, progesterone (P), dopamine (DA), endorphin (β-EP) and the human deep sleep percentage are measured.

[0028] Immunoglobulin is a key substance of anti-infection in the body. It is critical to maintain a good level of immunoglobulin against viral and bacterial infections. Clinically, immunoglobulin IgA, IgG and IgM are often examined. Concentration of IgA, IgG and IgM represents the level of humoral immune function, and large concentration indicates strong humoral immune function.

[0029] Interferon-γ (IFN-γ) is a representative cytokine secreted by T lymphocytes, and has antiviral and immunoregulation effects in immune and inflammatory reaction, tumor prevention and inhibition of cell division. IFN-γ has become a widely concerned anti-tumor drug due to its anti-tumor cell proliferation, inhibition of tumor angiogenesis, and immunoregulation effects. IFN-γ can significantly inhibit the growth of a variety of tumors and has been applied to clinical trials. It helps the body immune system to recognize and kill tumor cells by increasing the expression levels of adhesion molecules and MHC molecules on the surfaces of tumor cells and antigen presenting cells and promotes the recruitment of more immune cells, thereby better exerting its anti-tumor effects. Studies have shown that in tumor microenvironment, IFN-γ not only activates CD4+ Th1 cells to exert their immune function, but also inhibits proliferation of cancer cells, promotes apoptosis of cancerous cells, directly kills cancer cells and promotes the high expression level of major histocompatibility complex class-I molecules in cancer cells, so that they are recognized by specific T cells.

[0030] Serotonin (5-HT) is an important immunoregulation factor, which can promote the lethality of natural killer (NK) cells associated with anti-tumor, anti-virus, etc., enhance phagocytosis of macrophages, and promote the proliferation and activation of T cells. As an amine neurotransmitter, serotonin is a natural mood stabilizer and important for us to gain happiness, emotional calm, and concentrated attention. At the same time, recent studies have found that 5-HT can also promote cell mitosis and participate in tissue remodeling. In recent years, many studies have found that 5-HT plays an important role in regulating the proliferation of hepatocytes during liver regeneration. Platelets are the main carriers of 5-HT in blood and can transport 5-HT to various organs.

[0031] Estradiol is an estrogen, and high estradiol can inhibit the synthesis and secretion of androgens by testis, which leads to sexual dysfunction due to insufficient secretion of androgen. Estrogen maintains thickness and elasticity of vaginal mucosa and vaginal lubrication in the stage of sexual arousal.

[0032] Androgens and estrogens are important for the development, functional maintenance, metabolism, and aging of the male and female reproductive organs. Maintaining a high ratio of testosterone / estradiol (T / E 2 ) in the male body is of great significance for maintaining erectile function, sperm formation, and fertilization ability. Female sexual desire is primarily determined by testosterone (T), and testosterone supplement can increase female sexual desire and good mood. When the testosterone / estradiol (T / E2) ratio is increased, testosterone is a highly effective aphrodisiac for women.

[0033] Nitric oxide (NO) is a serum indicator related to erectile function, which can relax cavernous vascular smooth muscle and cause erection. It is a key substance to ensure male erectile function. Nitric oxide can increase the blood flow of genitals and play an important role in maintaining normal sexual function. It can cause hyperaemia of clitoris and vagina, increase clitoris sensitivity and vagina lubricity. Meanwhile, it is also closely related to the cardiovascular and cerebrovascular systems. Endothelium-derived relaxing factor (EDRF) first discovered in 1980 has now been confirmed to be NO, which has a vasodilation effect and plays a role as a messenger for intracellular and intercellular transmission of biological information in pathological conditions such as ischemia. Studies have shown that nitric oxide contacts and relaxes smooth muscle cells in arteries, dilating the arteries, which results in decreased hypertension and improves blood flow. In addition, nitric oxide prevents blood from clotting in some dangerous areas. If blood coagulates in the heart or brain, the patient suffers from heart disease or stroke. Provided that the body produces a sufficient amount of nitric oxide, the risk of the heart disease is greatly reduced. Therefore nitric oxide can effectively lower blood pressure and prevent the stroke and the heart disease.

[0034] Progesterone increases female sexual desire and dopamine increases sexual desire and arousal.

[0035] Serum endorphin (β-EP) is a very important neuroregulator substance in the body and known as the body's natural opium and the "pleasure hormone". It can help people to maintain a young and happy state. At the same time, it can regulate a female endocrine system, relieve depression and enhance pleasure.

[0036] Sleep is extremely important for the protection of human health and the maintenance of normal physiological and psychological activities, and quality sleep also plays a greater role in protecting the body's immune function.

[0037] A large number of studies have shown that a parasympathetic nervous system plays an important regulation role in nervous, endocrine and immune systems, and its basic functions include: promoting secretion of digestive glands to increase secretions of salivary glands, stomach and intestine, liver and gall and pancreas and enhance gastrointestinal peristalsis; promoting the absorption of nutrients and energy; promoting secretion of insulin by pancreatic islet cells; promoting generation of hepatic glycogens to strengthen energy reserve; narrowing pupils to reduce stimulus; slowing down heartbeats, lowering blood pressure and the like to save the unnecessary consumption; participating in endocrine regulation and assisting in reproductive activities to cause dilation and erection of blood vessels of reproductive organs and increased secretion of sexual organs. Studies have also shown that parasympathetic nerve impulse can directly cause male erection. To sum up, a parasympathetic nerve helps our bodies to relax, allowing us to perceive peace and tranquility, pleasure and relaxation, thus enhancing energy reserves and fatigue recovery to achieve the recuperation, recovery and protection of the body. In addition, this can make a sympathetic nerve continually overexcited restore its normalcy and improve the chronic stress state of the body.

[0038] When the parasympathetic nerve is stimulated, it releases a large amount of acetylcholine (Ach) as a transmitter of nerve signals; and the acetylcholine is transmitted to a target organ through the parasympathetic nerve. An M receptor is short for muscarinicreceptor and widely found on effector cells innervated by parasympathetic postganglionic fibers. The M receptor receives signals (acetylcholine) from the parasympathetic nerve and produces a series of biochemical reactions within the cell, exhibiting the excitatory effect on a sympathetic nerve ending. In contrast, the M receptor achieves the excitatory effects of the parasympathetic nerve through a PLC / PIP2 / IP3 signaling pathway.

[0039] An intracellular M receptor is linked to G protein, and a Gαq protein-linked receptor-mediated phospholipase C (PLC) signaling system is a widespread signal transduction mechanism. After activation of Gαq protein, PLCβ is activated, then phosphatidylinositol-4,5-bisphosphate (PIP2) on cytomembrane is hydrolyzed into two secondary messengers, that is, inositol triphosphate (IP3) and diacylglycerol pyrophosphate (DAG). An M3 receptor is widely found in the endoplasmic reticulum membrane and serves as a channel protein capable of triggering intracellular calcium mobilization. It can bind with IP3 and trigger the intracellular calcium mobilization, leading to an increase in the intracellular calcium level, which initiates an intracellular calcium signaling system; in addition, a series of physiological processes, for example, ion channel function, cell cycle, glandular secretion, smooth muscle contraction, vasodilatation, and genital erection, are regulated through the change of enzymatic activity such as calmodulin of calcium ions. Therefore, the M3 receptor achieves the parasympathetic excitatory effect through the PLC / PIP2 / IP3 signaling pathway.

[0040] Through experiments, it is found that the composition of the present invention can increase the expression level of the muscarinic acetylcholine receptor (M3 receptor) and the content of PLC and IP3 in the PLC / PIP2 / IP3 signaling pathway. This indicates that the functions of the composition to regulate sexual functions, protect cardiovascular and cerebrovascular systems, promote regeneration of liver cells, prevent tumors, and improve immunity and sleep quality are regulated through the parasympathetic nerve signaling pathway.

[0041] The following will further explain embodiments of the present invention through specific embodiments, but does not indicate that the scope of protection of the present invention is limited in the scope described in the embodiments.Example 1 Preparation of composition 1 (not according to the present invention)

[0042] Composition 1 includes ingredients: cooling agent prepared by menthyl acetate, L-menthyl lactate, and monomethyl succinate by a weight ratio of 4:5:1; organic acid prepared by acetic acid, lactic acid, propionic acid, butyric acid, and hexanoic acid by a weight ratio of 14:15:1.5:1:1; and 4.5%vol beer as base liquor.

[0043] Composition 1 of alcohol is 1% vol, cooling agent is 0.05ppm, and organic acid is 150ppm was prepared with above cooling agent, organic acid, base liquor blended with purified water.Example 2 Preparation of composition 2 (not according to the present invention)

[0044] Composition 2 includes ingredients: cooling agent prepared by monomethyl succinate, L-monomenthyl glutarate, and N-ethyl-2-isopropyl-5-methylcyclohexane carboxamide by a weight ratio of 2:5:3; organic acid prepared by acetic acid, lactic acid, propionic acid, butanedioic acid, pentanoic acid, and heptanoic acid by a weight ratio of 7:8:1:2:1:1; and 40%vol whiskey as base liquor.

[0045] Composition 2 of alcohol is 30% vol, cooling agent is 10ppm, and organic acid is 1000ppm was prepared with above cooling agent, organic acid, base liquor blended with purified water.Example 3 Preparation of composition 3 (not according to the present invention)

[0046] Composition 3 includes ingredients: cooling agent prepared by N,2,3-trimethyl-2-isopropylbutamide, L-menthyl lactate, monomethyl succinate, and L-menthol ethylene glycol carbonate by a weight ratio of 2:3:2:3; organic acid prepared by formic acid, acetic acid, lactic acid, propionic acid, octanoic acid, nonanoic acid, and decanoic acid by a weight ratio of 1:8:5:2:1:1:1; and 60%vol Chinese Baijiu as a base liquor.

[0047] Composition 3 of alcohol is 60% vol, cooling agent is 100ppm, and organic acid is 6000ppm was prepared with above cooling agent, organic acid blended with base liquor.Example 4 Preparation of composition 4 (not according to the present invention)

[0048] Composition 4 includes ingredients: cooling agent prepared by monomethyl succinate, L-monomenthyl glutarate and N-ethyl-2-isopropyl-5-methylcyclohexane carboxamide by a weight ratio of 3:4:3; organic acid prepared by acetic acid, lactic acid, propionic acid, citric acid, malic acid and tartaric acid by a weight ratio of 5:5:1:2:1:1; and 12%vol Chinese rice liquor as base liquor.

[0049] Composition 4 of alcohol is 80% vol, cooling agent is 200ppm, and organic acid is 10000ppm was prepared with above cooling agent, organic acid base liquor blended with edible alcohol.Example 5 Preparation of composition 5 (not according to the present invention)

[0050] Composition 5 includes ingredients: cooling agent prepared by N,2,3-trimethyl-2-isopropylbutamide, L-menthyl lactate, 3-L-menthoxypropane-1,2-diol, L-menthol 1-(or 2-)-propylene glycol carbonate, and L-monomenthyl glutarate by a weight ratio of 4:1:2:3:1; organic acid prepared by lactic acid, propionic acid, hexanoic acid, citric acid and malic acid by a weight ratio of 5:1:1:2:2; and 99%vol dehydrated edible alcohol as a base liquor.

[0051] Composition 5 of alcohol is 99% vol, cooling agent is 500ppm, and organic acid is 30000ppm was prepared with above cooling agent, organic acid blended with base liquor.Example 6 Preparation of composition 6 of the present invention

[0052] Composition 6 includes ingredients: cooling agent prepared by menthyl acetate, L-menthyl lactate, and N,2,3-trimethyl-2-isopropylbutamide by a weight ratio of 2:3:5; organic acid prepared by acetic acid, butanedioic acid, hexanoic acid, citric acid and malic acid by a weight ratio of 3:1:1 :4:2; and 50%vol Chinese Baijiu as a base liquor.

[0053] Composition 6 of alcohol is 50% vol, cooling agent is 50ppm, and organic acid is 3000ppm was prepared with above cooling agent, organic acid blended with base liquor.Example 7 Preparation of composition 7 (not according to the present invention)

[0054] Composition 7 includes ingredients: 150ppm cooling agent prepared by L-menthyl lactate and monomethyl succinate by a weight ratio of 4:6; organic acid prepared by acetic acid, lactic acid, butanedioic acid, hexanoic acid and tartaric acid by a weight ratio of 3:3:1:1:2; and 70%vol edible alcohol as a base liquor.

[0055] Composition 7 of alcohol is 70% vol, cooling agent is 150ppm, and organic acid is 8000ppm was prepared with above cooling agent, organic acid blended with base liquor.Comparative example 1 Preparation of low-alcohol composition 8

[0056] Composition 8 includes ingredients: cooling agent prepared by menthyl acetate, L-menthyl lactate and monomethyl succinate by a weight ratio of 4:5:1; organic acid prepared by acetic acid, lactic acid, propionic acid, butyric acid and hexanoic acid by a weight ratio of 14:15:1.5:1:1; and 15%vol sake as base liquor.

[0057] Composition 8 of alcohol is 0.5% vol, cooling agent is 5ppm, and organic acid is 500ppm was prepared with above cooling agent, organic acid, base liquor blended with purified water.Comparative example 2 Preparation of low-cooling agent composition 9

[0058] Composition 9 includes ingredients: cooling agent prepared by monomethyl succinate, L-monomenthyl glutarate, and N-ethyl-2-isopropyl-5-methylcyclohexane carboxamide by a weight ratio of 2:5:3; organic acid prepared by acetic acid, lactic acid, propionic acid, butanedioic acid, pentanoic acid and heptanoic acid by a weight ratio of 7:8:1:2:1:1; and 53%vol jiangxiangxing baijiu as a base liquor.

[0059] Composition 9 of alcohol is 53% vol, cooling agent is 0.04ppm, and organic acid is 2000ppm was prepared with above cooling agent, organic acid blended with base liquor.Example 8 Preparation of low-acidity composition 10

[0060] Composition 10 includes ingredients: cooling agent prepared by N,2,3-trimethyl-2-isopropylbutamide, L-menthyl lactate, monomethyl succinate and L-menthol ethylene glycol carbonate by a weight ratio of 2:3:2:3; organic acid prepared by formic acid, acetic acid, lactic acid, propionic acid, octanoic acid, nonanoic acid and decanoic acid by a weight ratio of 1:8:5:2:1:1:1; and 50%vol edible alcohol as a base liquor.

[0061] Composition 10 of alcohol is 50% vol, cooling agent is 50ppm, and organic acid is 100ppm was prepared with above cooling agent, organic acid blended with base liquor.Comparative example 3 Preparation of alcohol-free composition 11

[0062] Composition 11 includes ingredients: cooling agent prepared by N,2,3-trimethyl-2-isopropylbutamide, L-monomenthyl glutarate, monomethyl succinate, and L-menthol ethylene glycol carbonate by a weight ratio of 2:3:3:1; organic acid prepared by acetic acid, lactic acid, propionic acid, citric acid, malic acid and tartaric acid by a weight ratio of 5:5:1:2:1:1.

[0063] Composition 11 of cooling agent is 5ppm, and organic acid is 1000ppm was prepared with above cooling agent, organic acid blended with purified water.Comparative example 4 Preparation of cooling agent -free composition 12

[0064] Composition 12 includes ingredients: organic acid prepared by acetic acid, butanedioic acid, hexanoic acid, citric acid and malic acid by a weight ratio of 3:1:1:4:2; and 53%vol jiangxiangxing baijiu as a base liquor.

[0065] Composition 12 of alcohol is 53% vol and organic acid is 2000ppm was prepared with above organic acid blended with base liquor.Example 9 Preparation of composition 13 without organic acid (not according to the invention)

[0066] Composition 13 includes ingredients: cooling agent prepared by N,2,3-trimethyl-2-isopropylbutamide, 3-L-menthoxypropane-1,2-diol, L-menthol 1-(or 2-)-propylene glycol carbonate and L-monomenthyl glutarate by a weight ratio of 4:1:2:3; and 60%vol edible alcohol as a base liquor.

[0067] Composition 13 of alcohol is 60% vol and cooling agent is 100ppm was prepared with above cooling agent blended with base liquor.Example 10 Preparation of composition 14 without organic acid (not according to the invention)

[0068] Composition 14 includes ingredients: cooling agent prepared by menthyl acetate, monomethyl succinate, menthol and menthone by a weight ratio of 10:8:2:1; and 1%vol edible alcohol as a base liquor.

[0069] Composition 14 of alcohol is 1% vol and cooling agent is 0.05ppm was prepared with above cooling agent blended with base liquor.Example 11 Preparation of composition 15 without organic acid (not according to the invention)

[0070] Composition 15 includes ingredients:cooling agent prepared by menthyl acetate, L-menthyl lactate, monomethyl succinate, L-monomenthyl glutarate, and L-menthol ethylene glycol carbonate by a weight ratio of 3:2:1:2:2; and 30%vol edible alcohol as a base liquor.

[0071] Composition 15 of alcohol is 30% vol and cooling agent is 10ppm was prepared with above cooling agent blended with base liquor.Example 12 Preparation of composition 16 without organic acid (not according to the invention)

[0072] Composition 16 includes ingredients: cooling agent prepared by monomethyl succinate, 3-L-menthoxy-2-methylpropane-1,2-diol, N-ethyl-2-isopropyl-5-methylcyclohexane carboxamide and 2-isopropyl-N-2, 3-trimethylbutyramide by a weight ratio of 2:1:3:1; and 99%vol edible alcohol as a base liquor.

[0073] Composition 16 of alcohol is 99% vol and cooling agent is 500ppm was prepared with above cooling agent blended with base liquor.

[0074] Amounts of alcohols, cooling agents and organic acids in the above compositions are shown in Table B. Table B Amounts of alcohols, cooling agents and organic acids in different compositionsCompositionAlcohol / %volCooling agent / ppmOrganic acid / ppm110.0515023010100036010060004802001000059950030000650503000770150800080.555009530.04200010505010011-510001253-20001360100-1410.05-153010-1699500- Effect verification

[0075] Sexual functions, cardiovascular and cerebrovascular systems, regeneration of liver cells, tumor prevention, immune and sleep quality improvement are evaluated for the indicators of the compositions prepared in the examples and comparative examples. Specific methods were as follows: Subjects: 31 healthy males (19-56 years old) and 36 healthy females (25-50 years old). Participants were uniformly admitted to the study after fully understanding study liquor samples and study testing methods and requirements, and signing an informed consent form.

[0076] Drinking amount and time: 50mL / person / day, with unified drinking at dinner for 7 consecutive days. Other alcoholic and functional beverages and health supplements are stopped drinking from first 7 days before drinking until various indicators are tested at the end of drinking. A before-and-after control comparison method was used.Study indicators

[0077] Serological indicators: blood was collected before drinking and 7 days after drinking, and 3 items of immunoglobulin (IgA, IgG, IgM), interferon-γ (IFN-γ), serotonin (5-HT), estradiol (E 2 ), testosterone (T), and nitric oxide (NO) were tested for the male. 3 items of serum immunoglobulin (IgA, IgG, IgM), serotonin (5-HT), estradiol (E 2 ), testosterone (T), progesterone (P), nitric oxide (NO), dopamine (DA), and endorphin (β-EP) were tested for the female.

[0078] Blood sample test organization: Chengdu Lilai Biotechnology Co., Ltd.

[0079] Sleep bracelet and scale assessment: a sleep monitoring bracelet (Huawei Bracelet 4) monitored daily sleep data from two days before drinking to two days after drinking. The purpose of monitoring two days before drinking was to obtain the average data of 2 days and avoid abnormal data or incomplete records of the bracelet.

[0080] Statistical methods: software SPSS 22.0, paired-samples T test.

[0081] Serum immunoglobulin indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 1 below were obtained. Table 1 Changes in immunoglobulin before and after men drink the compositionsComposition sampleImmunoglobulin indicatorsBefore drinkingAfter drinkingIncrease / decrease %Composition 1IgM (pg / mL)114.02±38.52134.22±106.1517.72IgG (pg / mL)1.77±0.671.96±0.8811.19IgA (µg / mL)243.95±76.24264.47±62.648.41Composition 2IgM (pg / mL)113.35±35.62135.72±66.1519.73IgG (pg / mL)1.71±0.541.94±0.8213.45IgA (µg / mL)241.15±66.24265.97±52.1410.29Composition 3IgM (pg / mL)115.22±34.26136.02±86.6318.05IgG (pg / mL)1.67±0.811.91±0.5714.37IgA (µg / mL)242.58±56.85266.74±47.499.96Composition 4IgM (pg / mL)113.74±36.32134.22±76.6218.01IgG (pg / mL)1.69±0.681.95±0.6715.38IgA (µg / mL)242.18±64.27265.97±61.259.82Composition 5IgM (pg / mL)113.52±35.28133.82±82.5517.88IgG (pg / mL)1.70±0.691.91±0.6212.35IgA (µg / mL)241.50±67.04265.19±52.589.81Composition 6IgM (pg / mL)114.55±35.12135.17±76.8418.00IgG (pg / mL)1.68±0.731.97±0.7817.26IgA (µg / mL)242.58±70.29265.29±55.049.36Composition 7IgM (pg / mL)112.02±31.53133.96±86.3419.59IgG (pg / mL)1.79±0.751.99±0.8111.73IgA (µg / mL)243.01±70.11266.38±49.639.62Composition 8IgM (pg / mL)113.98±38.52114.12±46.150.12IgG (pg / mL)1.67±0.821.65±0.80-1.19IgA (µg / mL)235.95±76.74240.47±77.16-0.09Composition 9IgM (pg / mL)109.02±38.52109.92±36.150.08IgG (pg / mL)1.85±0.911.87±0.681.08IgA (µg / mL)223.95±76.34224.47±62.640.23Composition 10IgM (pg / mL)110.02±38.52122.27±56.1511.13IgG (pg / mL)1.82±0.581.94±0.786.59IgA (µg / mL)253.95±92.54269.47±93.046.11Composition 11IgM (pg / mL)171.38±58.12173.64±65.541.32IgG (pg / mL)1.87±0.921.86±0.95-0.53IgA (µg / mL)218.25±98.18217.93±107.91-0.15Composition 12IgM (pg / mL)103.22±29.48102.92±38.59-0.29IgG (pg / mL)1.84±0.811.86±0.721.09IgA (µg / mL)241.59±80.45242.74±90.480.48Composition 13IgM (pg / mL)180.53±50.12192.26±69.186.50IgG (pg / mL)1.77±0.671.86±0.705.08IgA (µg / mL)243.55±81.45255.42±89.404.87Composition 14IgM (pg / mL)128.21±41.37133.59±53.804.20IgG (pg / mL)1.69±0.611.76±0.694.14IgA (µg / mL)221.85±60.24230.23±76.033.78Composition 15IgM (pg / mL)145.71±46.11159.29±59.609.32IgG (pg / mL)1.75±0.521.85±0.615.71IgA (µg / mL)250.01±72.06264.18±76.045.67Composition 16IgM (pg / mL)130.09±50.18147.24±59.6413.18IgG (pg / mL)1.70±0.491.83±0.617.65IgA (µg / mL)230.08±75.14246.41±99.017.10

[0082] According to the above study results, it is found that for test groups drinking the compositions in the examples, their immunoglobulin levels increased to a varying extent, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there were no significant differences in immunoglobulin levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the male immunoglobulin level, thereby indicating that the compositions can enhance the immunity by increasing the male immunoglobulin level.

[0083] Serum immunoglobulin indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 2 below were obtained. Table 2 Changes in immunoglobulin before and after women drink the compositionsComposition sampleImmunoglobulin indicatorsBefore drinkingAfter drinkingIncrease / decrease %Composition 1IgM (pg / mL)104.02±32.52123.12±83.4518.36IgG (pg / mL)1.66±0.641.85±0.6511.45IgA (µg / mL)233.15±56.74251.17±52.617.73Composition 2IgM (pg / mL)110.51±31.64130.15±16.4517.77IgG (pg / mL)1.72±0.241.93±0.6712.21IgA (µg / mL)240.95±62.74264.14±50.369.62Composition 3IgM (pg / mL)112.42±37.16135.82±75.1320.81IgG (pg / mL)1.69±0.691.90±0.5212.43IgA (µg / mL)241.88±57.75265.94±49.389.95Composition 4IgM (pg / mL)111.94±39.24133.58±66.6119.33IgG (pg / mL)1.65±0.681.91±0.5715.76IgA (µg / mL)241.18±64.27264.47±60.159.66Composition 5IgM (pg / mL)112.51±38.18134.12±71.2619.21IgG (pg / mL)1.79±0.611.98±0.6910.61IgA (µg / mL)240.21±69.38266.09±51.5210.77Composition 6IgM (pg / mL)117.26±31.62138.13±70.2417.80IgG (pg / mL)1.69±0.701.89±0.6111.83IgA (µg / mL)240.98±71.09264.74±65.749.86Composition 7IgM (pg / mL)111.95±36.38134.62±76.1520.25IgG (pg / mL)1.70±0.661.92±0.7212.94IgA (µg / mL)242.38±68.82265.18±79.469.41Composition 8IgM (pg / mL)111.98±31.25112.92±41.750.84IgG (pg / mL)1.69±0.621.67±0.78-1.18IgA (µg / mL)229.25±86.36231.74±68.451.09Composition 9IgM (pg / mL)110.20±39.85111.52±38.541.20IgG (pg / mL)1.75±0.651.77±0.851.14IgA (µg / mL)222.45±71.48223.97±61.340.68Composition 10IgM (pg / mL)116.52±48.73128.93±56.2510.65IgG (pg / mL)1.79±0.741.88±0.865.03IgA (µg / mL)243.65±67.54255.17±67.044.73Composition 11IgM (pg / mL)170.82±65.21172.46±75.460.96IgG (pg / mL)1.67±0.811.66±0.79-0.60IgA (µg / mL)213.95±89.58214.33±99.010.18Composition 12IgM (pg / mL)115.22±49.84116.92±42.981.47IgG (pg / mL)1.74±0.741.75±0.690.57IgA (µg / mL)250.84±79.47249.14±90.88-0.68Composition 13IgM (pg / mL)111.03±30.52122.27±59.0510.12IgG (pg / mL)1.87±0.711.98±0.795.88IgA (µg / mL)230.11±63.82243.24±78.055.71Composition 14IgM (pg / mL)119.35±48.21127.71±51.507.00IgG (pg / mL)1.78±0.631.86±0.684.49IgA (µg / mL)241.52±59.37250.41±81.533.68Composition 15IgM (pg / mL)129.30±51.16141.36±62.549.33IgG (pg / mL)1.80±0.611.91±0.706.11IgA (µg / mL)223.46±71.28238.44±80.246.70Composition 16IgM (pg / mL)134.32±60.21148.90±65.1510.85IgG (pg / mL)1.83±0.661.99±0.818.74IgA (µg / mL)209.45±72.17225.48±80.317.65

[0084] According to the above study results, it is found that for test groups drinking the compositions in the examples, their immunoglobulin levels increased to a varying extent, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there were no significant differences in immunoglobulin levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the female immunoglobulin level, thereby indicating that the compositions can enhance the immunity by increasing the female immunoglobulin level.

[0085] Interferon-γ (IFN-γ) indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 3 below were obtained. Table 3 Changes in interferon-y (IFN-y) before and after men drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 137.49±12.3641.77±23.1111.41Composition 234.44±10.3739.47±13.0114.61Composition 335.59±12.5640.17±16.2112.87Composition 435.81±10.1638.72±18.458.13Composition 536.42±10.8640.92±17.3512.36Composition 638.09±11.9742.37±15.7411.24Composition 738.74±12.9442.57±16.639.88Composition 836.82±11.4636.97±14.180.41Composition 936.14±15.3636.43±15.640.80Composition 1036.59±14.7539.12±16.116.91Composition 1139.82±9.6839.17±11.77-1.63Composition 1233.41±10.6333.43±11.460.06Composition 1337.25±13.0539.81±12.896.87Composition 1435.60±10.2137.59±11.355.59Composition 1538.42±11.0740.93±12.016.53Composition 1636.31±10.9238.94±11.917.24

[0086] According to the above study results, it is found that for test groups drinking the compositions in the examples, their IFN-γ levels increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that| of the compositions 1-7. However, there were no significant differences in IFN-γ levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the male IFN-γ level, thereby indicating that the compositions can prevent tumors and enhance the immunity by increasing the male IFN-γ level.

[0087] Serotonin (5-HT) indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 4 below were obtained. Table 4 Changes in serotonin (5-HT) (pg / mL) before and after men drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 11.07±0.551.31±0.6622.43Composition 21.01±0.451.25±0.7623.76Composition 31.03±0.511.27±0.4823.30Composition 41.06±0.471.34±0.6926.42Composition 51.08±0.351.30±0.7120.37Composition 61.07±0.421.35±0.7426.17Composition 71.05±0.581.33±0.7226.67Composition 81.01±0.411.00±0.61-1.00Composition 91.09±0.571.10±0.570.92Composition 101.04±0.521.18±0.6713.46Composition 111.10±0.391.11±0.501.00Composition 121.09±0.621.08±0.69-0.9Composition 131.08±0.511.19±0.5910.19Composition 141.06±0.601.14±0.547.55Composition 151.01±0.491.11±0.519.91Composition 161.04±0.531.17±0.5912.5

[0088] According to the above study results, it is found that for test groups drinking the compositions in the examples, their serotonin levels (5-HT) significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there were no significant differences in serotonin (5-HT) levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low- cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the male serotonin (5-HT) level, thereby indicating that the compositions can promote the regeneration of liver cells and enhance the immunity by increasing the male 5-HT level.

[0089] Serotonin (5-HT) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 5 below were obtained. Table 5 Changes in serotonin (5-HT) (pg / mL) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 11.04±0.451.23±0.5618.27Composition 21.02±0.411.23±0.5920.59Composition 31.03±0.481.25±0.5321.36Composition 41.05±0.471.29±0.5722.86Composition 51.08±0.421.34±0.6124.07Composition 61.06±0.531.34±0.6426.41Composition 71.04±0.541.32±0.7126.92Composition 81.03±0.511.04±0.650.97Composition 91.11±0.611.10±0.66-0.90Composition 101.04±0.521.16±0.5811.54Composition 111.08±0.521.09±0.620.93Composition 121.01±0.491.00±0.46-0.99Composition 131.05±0.441.18±0.6812.38Composition 141.04±0.471.11±0.536.73Composition 151.07±0.501.19±0.6111.21Composition 161.09±0.541.20±0.6611.93

[0090] According to the above study results, it is found that for test groups drinking the compositions in the examples, their serotonin levels (5-HT) significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also had slight increase, but their percentage increase was inferior to that of the compositions1-7. However, there were no significant differences in serotonin (5-HT) levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the female serotonin (5-HT) level, thereby indicating that the compositions can prompt the regeneration of liver cells and enhance the immunity by increasing the female 5-HT level.

[0091] Estradiol (E 2 ) indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 6 below were obtained. Table 6 Changes in estradiol (E 2 ) (pg / mL) before and after men drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 142.99±31.2138.68±29.83-10.03Composition 241.39±21.6337.21±25.37-10.10Composition 341.99±26.6137.18±22.82-11.46Composition 440.54±25.7436.18±23.74-10.75Composition 541.94±26.3637.88±21.36-9.68Composition 642.19±29.6638.36±29.83-9.08Composition 742.36±28.4737.98±25.73-10.34Composition 840.19±29.2139.88±26.97-0.77Composition 940.54±24.6540.78±26.130.59Composition 1041.37±30.3738.83±28.43-6.14Composition 1143.59±19.1244.01±16.690.96Composition 1241.24±20.5640.98±22.31-0.63Composition 1344.38±20.1842.23±24.52-4.84Composition 1440.12±19.8537.58±20.01-6.33Composition 1544.92±21.7241.23±21.24-8.21Composition 1642.21±22.0338.90±20.02-7.84

[0092] According to the above study results, it is found that for test groups drinking the compositions in the examples, their estradiol (E 2 ) levels decreased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly decreased, but their percentage decrease was inferior to that of the compositions 1-7. However, there were no significant differences in estradiol (E 2 ) levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can decrease the male estradiol (E 2 ) levels, thereby indicating that the compositions can regulate the sexual functions by decreasing the male E 2 levels.

[0093] Estradiol (E 2 ) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 7 below were obtained. Table 7 Changes in estradiol (E 2 ) (pg / mL) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 1156.69±38.87175.23±34.3511.83Composition 2130.48±30.31147.19±33.9312.81Composition 3221.58±55.02252.49±76.6113.95Composition 4182.18±61.74210.57±56.2415.58Composition 5386.28±81.38442.81±90.9614.63Composition 6218.36±76.83252.63±88.6215.69Composition 7129.98±65.13149.36±76.1914.91Composition 8254.28±96.47258.19±87.211.54Composition 9361.78±126.13356.54±105.35-1.45Composition 10270.23±88.43289.37±91.517.83Composition 11244.82±101.45245.91±97.680.45Composition 12361.78±106.21360.10±101.55-0.46Composition 13301.58±81.49322.03±94.276.78Composition 14261.35±98.34272.30±81.154.19Composition 15314.15±91.58339.18±99.507.97Composition 16297.82±94.80325.85±97.339.41

[0094] According to the above study results, it is found that for test groups drinking the compositions in the examples, their estradiol (E 2 ) levels increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage decrease was inferior to that| of the compositions 1-7. However, there were no significant differences in estradiol (E 2 ) levels before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the female estradiol (E 2 ) levels, thereby indicating that the compositions can regulate the sexual functions by increasing the female E 2 levels.

[0095] Testosterone / estradiol (T / E 2 ) indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 8 below were obtained. Table 8 Changes in testosterone / estradiol (T / E 2 ) before and after men drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 10.025±0.0100.027±0.01312.00Composition 20.021±0.0110.023±0.0119.52Composition 30.023±0.0100.025±0.0128.69Composition 40.022±0.0110.024±0.0119.10Composition 50.025±0.0140.028±0.01112.00Composition 60.023±0.0130.025±0.0138.69Composition 70.026±0.0110.029±0.01211.54Composition 80.021±0.0120.021±0.0130.00Composition 90.028±0.0130.027±0.011-3.57Composition 100.022±0.0110.023±0.0124.35Composition 110.029±0.0150.028±0.014-3.45Composition 120.026±0.0130.026±0.0150.00Composition 130.026±0.0140.028±0.0167.69Composition 140.025±0.0120.026±0.0144.00Composition 150.031±0.0150.033±0.0186.45Composition 160.027±0.0130.029±0.0157.41

[0096] According to the above study results, it is found that for test groups drinking the compositions in the examples, the ratio of testosterone / estradiol (T / E 2 ) increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there was almost no increase in the ratio of testosterone / estradiol (T / E 2 ) before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can somewhat increase the ratio of testosterone / estradiol (T / E 2 ) for the male, thereby indicating that the compositions can regulate the sexual functions by increasing the ratio of testosterone / estradiol (T / E 2 ) for the male.

[0097] Testosterone / estradiol (T / E 2 ) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 9 below were obtained. Table 9 Changes in testosterone / estradiol (T / E 2 ) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 10.535±0.1790.587±0.2139.72Composition 20.421±0.1940.463±0.20812.59Composition 30.513±0.2100.572±0.27311.50Composition 40.322±0.1040.359±0.17511.49Composition 50.520±0.2140.589±0.24113.27Composition 60.603±0.3160.678±0.36412.44Composition 70.426±0.2010.482±0.21513.15Composition 80.521±0.3120.523±0.3410.38Composition 90.619±0.4150.617±0.372-0.32Composition 100.622±0.4260.643±0.3583.38Composition 110.415±0.2010.420±0.1811.20Composition 120.619±0.2150.620±0.2710.16Composition 130.548±0.2470.569±0.2213.83Composition 140.574±0.2910.590±0.2852.79Composition 150.481±0.2140.499±0.2183.74Composition 160.632±0.2460.654±0.3013.48

[0098] According to the above study results, it is found that for test groups drinking the compositions in the examples, the ratio of testosterone / estradiol (T / E 2 ) increased, and low-acidity compositions 10 and compositions 13-16 without organic acids showed no slight increase. However, there was almost no increase in the ratio of testosterone / estradiol (T / E 2 ) before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can somewhat increase the ratio of testosterone / estradiol (T / E 2 ) for the female, thereby indicating that the compositions can regulate the sexual functions by increasing the ratio of testosterone / estradiol (T / E 2 ) for the female.

[0099] Nitric oxide (NO) indicators of men who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 10 below were obtained. Table 10 Changes in nitric oxide (NO) (mIU / mL) before and after men drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 111.17±3.7817.75±3.7258.91Composition 210.75±2.4518.18±4.0269.11Composition 310.36±2.7316.95±3.6463.61Composition 410.97±2.8517.23±4.7557.06Composition 510.35±2.5716.98±4.1264.06Composition 611.36±2.5818.85±3.6365.93Composition 710.77±3.0217.34±5.7261.00Composition 810.37±2.6810.45±3.720.77Composition 911.18±3.7811.25±3.230.63Composition 1010.87±3.3814.45±6.0232.93Composition 1111.30±4.6811.51±4.121.86Composition 1212.62±4.7812.52±5.39-0.60Composition 1312.45±5.5916.18±6.0229.96Composition 1411.78±4.8514.45±5.2422.67Composition 1513.01±5.9116.92±7.0530.06Composition 1612.88±6.1517.02±7.1132.14

[0100] According to the above study results, it is found that for test groups drinking the compositions in the examples, their nitric oxide levels significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there was almost no increase in nitric oxide level before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can effectively increase the male nitric oxide level, thereby indicating that the compositions can regulate the sexual functions and protect the cardiovascular and cerebrovascular systems by increasing the male nitric oxide level.

[0101] Nitric oxide (NO) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 11 below were obtained. Table 11 Changes in nitric oxide (NO) (mIU / mL) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 119.23±16.1427.63±16.9843.68Composition 217.75±6.7523.18±5.9230.59Composition 318.36±6.2326.95±7.2746.79Composition 416.37±5.1522.53±8.7537.63Composition 513.28±6.7319.48±7.0246.69Composition 612.16±6.1818.85±5.8355.02Composition 714.15±8.0719.84±5.1240.21Composition 811.37±5.6811.45±5.250.70Composition 912.48±6.0812.55±7.130.56Composition 1013.27±5.3114.00±4.185.50Composition 1116.75±6.0816.52±5.91-1.37Composition 1215.48±6.0815.55±6.700.45Composition 1314.82±5.6815.40±6.083.91Composition 1418.70±7.2119.10±8.852.14Composition 1515.25±6.0316.09±5.995.51Composition 1616.56±6.2918.02±7.548.81

[0102] According to the above study results, it is found that for test groups drinking the compositions in the examples, their nitric oxide levels significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids showed no significant increase. However, there was almost no increase in nitric oxide level before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can effectively increase the female nitric oxide level, thereby indicating that the compositions can regulate the sexual functions and protect the cardiovascular and cerebrovascular systems by increasing the female nitric oxide level.

[0103] Progesterone (P) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 12 below were obtained. Table 12 Changes in progesterone (P) (ng / mL) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 10.75±0.350.94±0.4625.33Composition 21.20±0.711.54±0.8428.33Composition 31.82±0.852.35±1.1429.12Composition 40.95±0.481.19±0.6525.26Composition 50.48±0.210.63±0.2831.25Composition 61.30±0.761.71±0.9231.54Composition 70.63±0.360.85±0.3234.92Composition 81.44±0.621.46±0.771.39Composition 91.78±0.641.77±0.92-0.56Composition 100.85±0.420.98±0.5515.29Composition 111.64±0.711.66±0.901.22Composition 121.58±0.641.57±0.92-0.63Composition 130.59±0.290.68±0.3115.25Composition 140.55±0.210.61±0.2810.91Composition 151.12±0.431.28±0.3614.29Composition 161.48±0.641.69±0.4914.19

[0104] According to the above study results, it is found that for test groups drinking the compositions in the examples, their progesterone (P) levels significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also slightly increased, but their percentage increase was inferior to that of the compositions 1-7. However, there was almost no increase in progesterone (P) level before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can effectively increase the female progesterone (P) level, thereby indicating that the compositions can regulate the sexual functions by increasing the female progesterone (P) level.

[0105] Dopamine (DA) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 13 below were obtained. Table 13 Changes in dopamine (DA) (µmol / L) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 10.61±0.320.74±0.4121.31Composition 20.41±0.200.51±0.2424.39Composition 30.70±0.350.85±0.4421.43Composition 40.55±0.380.69±0.4524.45Composition 50.48±0.210.58±0.2620.83Composition 60.32±0.160.41±0.2128.12Composition 70.63±0.310.75±0.4219.05Composition 80.44±0.220.43±0.27-2.27Composition 90.74±0.460.75±0.521.35Composition 100.57±0.260.65±0.3514.03Composition 110.51±0.250.50±0.20-1.96Composition 120.61±0.280.62±0.211.64Composition 130.59±0.300.68±0.4115.25Composition 140.49±0.220.54±0.2510.20Composition 150.61±0.290.68±0.3811.47Composition 160.54±0.250.59±0.279.26

[0106] According to the above study results, it is found that for test groups drinking the compositions in the examples, their dopamine (DA) levels significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also increased, but their percentage increase was inferior to that of the compositions 1-7. However, there was almost no increase in dopamine (DA) level before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can effectively increase the female dopamine (DA) level, thereby indicating that the compositions can regulate the sexual functions by increasing the female dopamine (DA) level.

[0107] Endorphin (β-EP) indicators of women who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 14 below were obtained. Table 14 Changes in endorphin (β-EP) (pg / mL) before and after women drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 1166.61±57.32201.74±76.4121.08Composition 2181.18±67.12221.25±81.7421.84Composition 3202.26±57.12246.65±78.8221.94Composition 4170.41±61.62214.63±70.1425.95Composition 5160.64±41.62208.13±45.1829.56Composition 6204.26±57.12258.47±78.8226.54Composition 7192.74±68.37237.75±46.3123.35Composition 8191.62±68.37190.75±56.63-0.45Composition 9174.47±43.16176.23±47.861.01Composition 10171.85±50.46196.38±61.0214.27Composition 11195.37±68.56196.59±72.660.62Composition 12180.56±53.75179.32±67.43-0.69Composition 13169.61±49.21188.45±60.2011.11Composition 14161.26±30.64176.27±41.269.31Composition 15185.19±51.07208.55±57.2112.61Composition 16190.10±70.24216.81±61.5014.05

[0108] According to the above study results, it is found that for test groups drinking the compositions in the examples, their endorphin (β-EP) levels significantly increased, and low-acidity compositions 10 and compositions 13-16 without organic acids also increased, but their percentage increase was inferior to that of the compositions 1-7. However, there was almost no increase in endorphin (β-EP) level before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can effectively increase the female endorphin (β-EP) level, thereby indicating that the compositions can regulate the sexual functions by increasing the female β-EP level.

[0109] The deep sleep percentages of persons who drank the compositions prepared in the examples and the comparative examples were tested according to the above test methods, and results shown in Table 15 below were obtained. Table 15 Changes in deep sleep percentage before and after persons drink the compositionsComposition sampleBefore drinkingAfter drinkingIncrease / decrease %Composition 118.03±3.4821.70±4.6220.34Composition 218.57±3.8522.26±3.9119.87Composition 317.63±3.3621.16±3.8220.02Composition 418.23±2.9721.90±4.2520.13Composition 517.83±2.8620.99±3.8417.72Composition 617.68±3.4021.25±3.8020.19Composition 717.51±3.1821.18±4.0120.96Composition 817.36±3.2517.70±4.421.96Composition 918.15±3.1218.01±4.26-0.77Composition 1017.57±3.1819.79±3.6312.64Composition 1119.63±5.5119.57±6.02-0.31Composition 1216.99±6.2017.08±5.370.53Composition 1318.96±6.7321.59±8.9813.87Composition 1417.00±5.4818.79±6.0310.53Composition 1519.02±8.0521.27±7.8211.83Composition 1618.25±8.2820.56±9.4312.66

[0110] According to the above study results, it is found that for test groups drinking the compositions in the examples, their deep sleep percentages increased to a varying extend, and low-acidity compositions 10 and compositions 13-16 without organic acids also increased, but their percentage increase was inferior to that of the compositions 1- 7. However, there were no significant differences in deep sleep percentages before and after the alcohol-free composition, the low-alcohol composition, the cooling agent-free composition and the low-cooling agent composition in the comparative examples were drunk. It is proved that the compositions of the present invention can increase the human deep sleep percentage, thereby indicating that the compositions may improve the sleep quality by increasing the human deep sleep percentage.

[0111] It can be learned from the above data that the compositions of the present invention have the functions of regulating sexual functions, protecting cardiovascular and cerebrovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality, with the increased and lasting salivary secretion. Analysis on this phenomenon shows that the functions of the composition to regulate sexual functions, protect cardiovascular and cerebrovascular systems, promote regeneration of liver cells, prevent tumors, and improve immunity and sleep quality are regulated by activating the parasympathetic nerve signaling pathway. Therefore, the expression level of the M3 receptor and the content of the PLC and IP3 in the signaling pathway being tested can embody the activation of the parasympathetic nerve signaling pathway. The test method is as follows: SPF male mice, after 7 days of acclimatization feeding, were randomized into groups of 10 mice each according to the randomized numerical expression. Blank control group: normal saline group; test group 1: composition 6; test group 2: 50% vol pure edible alcohol; test group 3: aqueous solution including 50ppm cooling agent; test group 4: aqueous solution including 3000ppm organic acid.

[0112] Administration method: a syringe sucked up the normal saline and the samples of each test group respectively at a dose of 15mL / kg, and slowly dripped them into the oral cavity of the mice in small portions. The mice were administrated once a day for three consecutive days.

[0113] 30 minutes after drug administration on the third day, mice were executed by spinal dislocation, and their submandibular gland tissues were homogenized in a homogenizer and centrifuged at 7000r / min for 5 min, and the supernatant was taken. Enzyme-linked immunosorbent (ELISA) assay was used to determine M3, PLC and IP3. Results shown in Table 16 are obtained. Table 16 M3, PLC and IP3 of submandibular gland tissue homogenatesTest groupsM3 (pg / mL)PLC (ng / mL)IP3 (ng / mL)Blank control group9.720 ± 0.5797.020 ± 1.0695.080 ± 0.530Test group 112.009 ± 0.65112.975 ± 1.13812.720 ± 1.320Test group 29.418± 0.6746.498 ±0.8196.590 ± 0.946Test group 310.005± 0.5487.273 ± 0.9975.153 ± 1.103Test group 49.192± 0.5237.938 ± 1.0316.105 ± 0.862

[0114] According to the above study results, it is found that the test group 1 drinking the composition 6 had the expression level of M3, PLC and IP3 higher than the control group (P< 0.05); there was no significant difference between test groups 2, 3, 4 only including alcohol, cooling agent or organic acid and the control group, indicating that the composition of the present invention can increase the expression level of the M3 receptor and activate the PLC / IP3 pathway of the parasympathetic nerve.

[0115] Through the above test results, it can be verified that the compositions of the present invention can play the role of regulating sexual functions, protecting cardiovascular systems, promoting regeneration of liver cells, preventing and / or treating tumors, and improving immunity and sleep quality by activating the parasympathetic nerve signaling pathway, and can be widely utilized in the fields of medicine, food and health care products.

Claims

1. A composition of alcohol, a cooling agent, and organic acid, wherein the alcohol in the composition is 50%vol and is Chinese Baijiu, the cooling agent therein is 50ppm, and the organic acid therein is 3000ppmppm; wherein the cooling agent is a substance having the ability to activate a receptor of a thermoreceptor TRPM8, and consists of menthyl acetate, L-menthyl lactate, and N,2,3-trimethyl-2-isopropylbutamide in a weight ratio of 2:3:5, and wherein the organic acid is acetic acid, butanedioic acid, hexanoic acid, citric acid and malic acid in a weight ratio of 3:1: 1:4:2.