Method and composition for enhancing athletic performance

Abstract

Disclosed in the present invention are a method and a composition for regulating or increasing intestinal microbiota, and the use thereof in the preparation of a drug, nutritional product, health-care product, food product and beverage for regulating intestinal flora. The composition of the present invention can significantly regulate or increase the level of intestinal flora in a subject, and increase dopamine in the brain by means of regulating or increasing the level of intestinal flora in the subject, thereby enhancing the athletic performance.

Description

Methods and compositions for enhancing athletic performance Technical Field

[0001] The present invention belongs to the technical field of health foods and dietary supplements, and specifically relates to compositions and methods for enhancing athletic performance, as well as related applications thereof in medicines, nutritional supplements, health products, foods, animal feeds, and beverages. Background Art

[0002] Currently, supplements that enhance athletic performance are very popular among consumers, but many supplements are not very effective in enhancing athletic performance and have some side effects, such as palpitations, deeper breathing, increased respiratory rate, and worsening symptoms such as nausea and vomiting, loss of appetite, headaches, and dizziness.

[0003] The study showed that giving mice broad-spectrum antibiotics to eliminate their gut bacteria reduced their running performance by about half, suggesting that the difference in running performance was primarily due to the presence of certain gut bacterial species in the better-performing mice. The relationship between the specific gut microbiota and athletic performance is currently unclear.

[0004] Ergothioneine (EGT) is a safe, natural compound with excellent anti-inflammatory and antioxidant properties. Furthermore, EGT has been reported to have a favorable regulatory effect on intestinal microbiota (Matsuda, Ozawa et al. 2020). Anandamide (AEA) is an endogenous cannabinoid that can maintain the homeostasis of the intestinal microbiota and regulate dopamine levels (Solinas, Justinova et al. 2006). Tributyrin (TB) has a certain regulatory effect on the intestinal microbiota (Yang, Lan et al. 2023). Dehydrogingerone (DHZ), also known as feruloyl methane, has a CAS number of 1080-12-2 and is isolated from turmeric. It is a structural analog of curcumin. These raw materials can be widely used in nutritional supplements, foods, beverages, animal feed, etc. Therefore, studying the relationship between the above-mentioned related substances and the intestinal microbiota, as well as their relationship with athletic performance, is crucial for finding appropriate nutritional health strategies. In addition, the inventors have also discovered that the novel composition can significantly enhance athletic performance and can be widely used in nutritional supplements, foods, beverages, animal feed, and the like. Summary of the Invention

[0005] To achieve the above objectives, the present invention provides the following technical solutions:

[0006] One aspect of the present invention relates to a method for regulating or increasing the level of intestinal flora in a subject, the method comprising: administering to the subject a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof; the intestinal flora being Gram-positive bacteria.

[0007] In some embodiments, the Gram-positive bacteria are Eubacterium rectale and / or Coprococcus regulatus.

[0008] In some embodiments, the method increases dopamine in the brain by regulating or increasing the level of gut flora in a subject, thereby enhancing athletic performance. The enhanced athletic performance includes improved endurance, increased heart rate, increased blood flow, increased muscular endurance, and increased muscle strength or power.

[0009] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof, is formulated as a nutritional supplement, food, beverage, or animal feed.

[0010] In some embodiments, the composition containing ergothioneine or a salt, acid, ester or derivative thereof, or the composition containing tributyrin or a derivative thereof is prepared as a solid preparation or a liquid preparation.

[0011] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, elixir, tincture, tonic, liquid suspension, or syrup.

[0012] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester or derivative thereof is administered to the subject at a dose of 1-1500 mg, or the composition comprising tributyrin or a derivative thereof is administered to the subject at a dose of 20-2000 mg.

[0013] In some embodiments, the composition is administered at least once daily for 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, or 4 weeks to 7 weeks.

[0014] In some embodiments, the method includes oral, intravenous, intramuscular, intraperitoneal, local instillation, topical or sublingual administration.

[0015] In some embodiments, the composition is administered to a subject so that the daily intake of the composition is between about 1 mg and about 1500 mg, or between about 5 mg and about 1000 mg, or between about 10 mg and about 800 mg, or between about 10 mg and about 500 mg, or between about 20 mg and about 2000 mg, or between about 40 mg and about 1500 mg, or between about 50 mg and about 1200 mg, or between about 100 mg and about 1000 mg, or between about 1 mg and about 300 mg, or between about 1 mg and about 200 mg, between about 5 mg and about 200 mg, between about 10 mg and about 150 mg, between about 20 mg and about 100 mg.

[0016] Another aspect of the present invention relates to the use of a composition containing ergothioneine or a salt, acid, ester or derivative thereof, or a composition containing tributyrin or a derivative thereof, in the manufacture of a nutritional supplement, food, beverage or animal feed for regulating or increasing the level of intestinal flora in a subject, wherein the intestinal flora is Gram-positive bacteria.

[0017] In some embodiments, the Gram-positive bacteria are Eubacterium rectale and / or Coprococcus regulatus.

[0018] In some embodiments, the composition increases dopamine in the brain by modulating or increasing the level of gut flora in a subject, thereby enhancing athletic performance. Enhanced athletic performance includes improved endurance, increased heart rate, increased blood flow, increased muscular endurance, and increased muscle strength or power.

[0019] In some embodiments, the composition is administered at a dose of 1-1500 mg, or 20-2000 mg.

[0020] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, elixir, tincture, tonic, liquid suspension, or syrup.

[0021] In some embodiments, the composition containing ergothioneine or a salt, acid, ester or derivative thereof, or the composition containing tributyrin or a derivative thereof is prepared as a solid preparation or a liquid preparation.

[0022] Another aspect of the present invention relates to a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof, for use in regulating or increasing the level of intestinal flora in a subject, wherein the intestinal flora is Gram-positive bacteria.

[0023] In some embodiments, the Gram-positive bacteria are Eubacterium rectale and / or Coprococcus regulatus.

[0024] In some embodiments, the composition increases dopamine in the brain by modulating or increasing the level of gut flora in a subject, thereby enhancing athletic performance. Enhanced athletic performance includes improved endurance, increased heart rate, increased blood flow, increased muscular endurance, and increased muscle strength or power.

[0025] In some embodiments, the composition is administered at a dose of 1-1500 mg, or 20-2000 mg.

[0026] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof is formulated as a nutritional supplement, food, beverage, animal feed, or pharmaceutical.

[0027] Another aspect of the present invention relates to a method of enhancing athletic performance in a subject, comprising administering to the subject a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof, or a composition comprising anandamide or a salt, acid, ester or derivative thereof.

[0028] In some embodiments, the method enhances the subject's athletic performance by increasing dopamine in the brain or by stimulating the CB1 receptor in the nerve.

[0029] In some embodiments, enhanced athletic performance includes increased endurance, increased heart rate, increased blood flow, enhanced muscular endurance, and increased muscle strength or power.

[0030] In some embodiments, the composition containing ergothioneine or a salt, acid, ester, or derivative thereof, or the composition containing tributyrin or a derivative thereof, or the composition containing anandamide or a salt, acid, ester, or derivative thereof is formulated as a nutritional supplement, food, beverage, or animal feed.

[0031] In some embodiments, the composition containing ergothioneine or a salt, acid, ester or derivative thereof, or the composition containing tributyrin or a derivative thereof, or the composition containing anandamide or a salt, acid, ester or derivative thereof is prepared as a solid preparation or a liquid preparation.

[0032] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising anandamide or a salt, acid, ester or derivative thereof is administered in a form selected from suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, spirits, tinctures, tonics, liquid suspensions, syrups, functionalized foods, beverages, or sublingual preparations.

[0033] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester or derivative thereof is administered to the subject at a dose of 1-1500 mg, or the composition comprising tributyrin or a derivative thereof is administered to the subject at a dose of 20-2000 mg, or the composition comprising anandamide or a salt, acid, ester or derivative thereof is administered to the subject at a dose of 15-2000 mg.

[0034] In some embodiments, the composition is administered at least once daily for 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, or 4 weeks to 7 weeks.

[0035] In some embodiments, the method includes oral, intravenous, intramuscular, intraperitoneal, local instillation, topical or sublingual administration.

[0036] In some embodiments, the composition is administered to a subject so that the daily intake of the composition is between about 1 mg and about 1500 mg, or between about 5 mg and about 1000 mg, or between about 10 mg and about 800 mg, or between about 10 mg and about 500 mg, or between about 20 mg and about 2000 mg, or between about 40 mg and about 1500 mg, or between about 50 mg and about 1200 mg, or between about 100 mg and about 1000 mg, or between 1 mg and about 300 mg, or between about 1 mg and about 200 mg, between about 5 mg and about 200 mg, between about 10 mg and about 150 mg, between about 20 mg and about 100 mg.

[0037] Another aspect of the present invention relates to the use of a composition containing ergothioneine or a salt, acid, ester or derivative thereof, or a composition containing tributyrin or a derivative thereof, or a composition containing anandamide or a salt, acid, ester or derivative thereof in the manufacture of a nutritional supplement, food, beverage or animal feed for enhancing the athletic performance of a subject.

[0038] In some embodiments, the composition enhances a subject's athletic performance by increasing dopamine in the brain or stimulating a CB1 receptor in the nerve, thereby enhancing the subject's athletic performance. Enhanced athletic performance includes increased endurance, increased heart rate, increased blood flow, increased muscular endurance, and increased muscle strength or power.

[0039] In some embodiments, the composition is administered at a dose of 1-1500 mg, 20-2000 mg, or 15-2000 mg.

[0040] In some embodiments, the composition containing ergothioneine or a salt, acid, ester or derivative thereof, or the composition containing tributyrin or a derivative thereof, or the composition containing anandamide or a salt, acid, ester or derivative thereof is prepared as a solid preparation or a liquid preparation.

[0041] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising anandamide or a salt, acid, ester, or derivative thereof is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, elixir, tincture, tonic, liquid suspension, or syrup.

[0042] Another aspect of the present invention relates to a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof, or a composition comprising anandamide or a salt, acid, ester or derivative thereof, for use in enhancing athletic performance in a subject.

[0043] In some embodiments, the composition enhances a subject's athletic performance by increasing dopamine in the brain or stimulating a CB1 receptor in the nerve, thereby enhancing the subject's athletic performance. Enhanced athletic performance includes increased endurance, increased heart rate, increased blood flow, increased muscular endurance, and increased muscle strength or power.

[0044] In some embodiments, the composition is administered at a dose of 1-1500 mg, 20-2000 mg, or 15-2000 mg.

[0045] In some embodiments, the composition containing ergothioneine or a salt, acid, ester, or derivative thereof, or the composition containing tributyrin or a derivative thereof, or the composition containing anandamide or a salt, acid, ester, or derivative thereof is formulated as a nutritional supplement, food, beverage, animal feed, or pharmaceutical.

[0046] In some embodiments, the composition containing ergothioneine or a salt, acid, ester or derivative thereof, or the composition containing tributyrin or a derivative thereof, or the composition containing anandamide or a salt, acid, ester or derivative thereof is prepared as a solid preparation or a liquid preparation.

[0047] In some embodiments, the composition comprising ergothioneine or a salt, acid, ester, or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising anandamide or a salt, acid, ester, or derivative thereof is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, elixir, tincture, tonic, liquid suspension, or syrup.

[0048] The method of applying the composition of the present invention can significantly regulate or increase the level of intestinal flora in the subject, increase dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, and thus enhance athletic performance; or stimulate the nerve receptor CB1, and thus enhance the athletic performance of the subject. Administering a composition of ergothioneine or its salt, acid, ester or derivative, or a composition containing tributyrin or its derivative, or a composition containing anandamide or its salt, acid, ester or derivative can significantly enhance athletic performance, including improving endurance, increasing heart rate, increasing blood flow, enhancing muscle endurance and muscle strength or power, etc.

[0049] In another aspect, the present invention provides a composition comprising two or more components selected from the group consisting of: ergothioneine or a physiologically acceptable salt, acid, ester, analog or derivative thereof and dehydrogingerone or a salt, acid, ester or derivative thereof, tributyrin or a derivative thereof, and anandamide or a salt, acid, ester or derivative thereof.

[0050] In some embodiments, the amount of the component is 1-2000 mg or 0.1 μM to 1 M or 0.001 to 50.0 weight % (w / w).

[0051] In some embodiments, the composition is administered at least once daily for 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, or 4 weeks to 7 weeks.

[0052] In some embodiments, the composition can be administered orally, intravenously, intramuscularly, intraperitoneally, topically or sublingually. For example, the composition can be administered in a single dose or multiple divided doses, and the daily dose range of the composition is 1 mg to 2000 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, or 40 mg to 300 mg. In some embodiments, the daily dose range is 0.005% to 45%, 0.005% to 40%, 0.005% to 30%, 0.005% to 25%, 0.01% to 40%, 0.01% to 30%, 0.01% to 25%, 0.01% to 15%, 0.05% to 30%, 0.05% to 20%, 0.05% to 10%, 0.1% to 35%, 0.1% to 25%, 0.1% to 10%, 0.2% to 25%, 0.2% to 10%, 0.5% to 9%, 1% to 7%, 2% to 7%, 0.005% to 7%, 0.005% to 9% by weight (w / w). In some embodiments, the daily dose range is 0.1 μM to 1 M (e.g., 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5 mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5 mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM).

[0053] In some embodiments, the composition is used to regulate or increase the level of intestinal flora, wherein the intestinal flora is Gram-positive bacteria. Further, the Gram-positive bacteria are Eubacterium rectum and / or Coprococcus regulatus.

[0054] In some embodiments, the composition is used to enhance or improve athletic performance. Further, the composition increases dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing athletic performance, or by stimulating the CB1 receptor of the nerve, thereby enhancing the athletic performance of the subject.

[0055] In some embodiments, the composition is prepared as a solid preparation or a liquid preparation.

[0056] In another aspect, the present invention provides a nutritional supplement, food, or beverage comprising the composition of the present invention as described above.

[0057] In some embodiments, the nutritional supplement, food, or beverage is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, elixir, tincture, tonic, liquid suspension, or syrup.

[0058] In some embodiments, the weight ratio of the composition of the present invention in nutritional supplements, foods, and beverages is 0.1-95%.

[0059] In some embodiments, the weight ratio of the composition of the present invention in nutritional supplements, foods, and beverages is 1-50%.

[0060] In another aspect, the present invention provides a use of the composition of the present invention as described above in the preparation of nutritional supplements, foods, and beverages.

[0061] In some embodiments, the composition is used to regulate or increase the level of intestinal flora, wherein the intestinal flora is Gram-positive bacteria. Further, the Gram-positive bacteria are Eubacterium rectum and / or Coprococcus regulatus.

[0062] In some embodiments, the composition is used to enhance or improve athletic performance. Further, the composition increases dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing athletic performance, or by stimulating the CB1 receptor of the nerve, thereby enhancing the athletic performance of the subject.

[0063] The composition of the present invention can enable the effective ingredients to cooperate with each other and synergistically exert a greater effect. It is widely used in nutritional supplements, foods, and beverages, and can significantly enhance or improve the exercise performance of subjects. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] FIG1 shows the brain dopamine levels of mice in Groups 1 to 4.

[0065] FIG2 shows the running distances of mice in Groups 1 to 4. ...

[0066] FIG3 shows the copy numbers of Eubacterium rectale from Groups 1 to 4 in the cecal feces of mice.

[0067] FIG4 shows the copy numbers of regular Coprococcus from Groups 1 to 4 in the cecal feces of mice.

[0068] FIG5 shows the brain dopamine levels of mice in Groups 5 to 10.

[0069] FIG6 shows the running distances of mice in groups 5 to 10. FIG6 shows the running distances of mice in groups 5

[0070] FIG. 7 shows the copy numbers of Eubacterium rectale of Groups 5 to 10 in the cecal feces of mice.

[0071] FIG8 shows the copy numbers of regular Coprococcus from Groups 5 to 10 in mouse cecal feces. DETAILED DESCRIPTION

[0072] Reference will now be made in detail to the preferred embodiments of the present invention to further illustrate examples thereof. Although the present invention will be described in conjunction with the preferred embodiments, it should be understood that they are not intended to limit the present invention to these embodiments. On the contrary, the present invention is intended to encompass alternatives, modifications, and equivalents, which may be included within the spirit and scope of the present invention as defined in the claims. In addition, in the detailed description of the present invention, many specific details are set forth to provide a thorough understanding of the present invention. However, it will be apparent to one of ordinary skill in the art that the present invention can be implemented without these specific details. In other cases, well-known methods, procedures, components, and other features are not described in detail to avoid unnecessarily obscuring aspects of the present invention.

[0073] As used herein, the term "or" is intended to include both "and" and "or." In other words, the term "or" can also be replaced by "and / or."

[0074] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0075] As used herein, the terms "subject" or "individual" are used interchangeably to refer to any subject to which the methods and compositions of the present disclosure can be applied or administered. The subject may have a disease or condition, but the subject does not need to be sick to benefit from the methods and compositions of the present disclosure. The subject may need to regulate his or her intestinal tract and / or overall health, but the subject may also have a generally healthy intestinal tract and wish to maintain or further regulate his or her intestinal tract and / or overall health. Therefore, any subject can take the disclosed compositions or become a recipient of the disclosed methods. Herein, the term "subject" refers to an animal (e.g., birds, reptiles, and mammals). In certain embodiments, the subject can be a mammal including non-primates (e.g., camels, donkeys, zebras, cows, horses, cats, dogs, rats, and mice) and primates (e.g., monkeys, chimpanzees, humans). In certain embodiments, the subject can be a non-human mammal. In other embodiments, the subject can be a human.

[0076] As used herein, the term "administering" refers to directly administering a compound or a pharmaceutically acceptable salt or composition of a compound to a subject, or administering a prodrug derivative or analog of a compound or a pharmaceutically acceptable salt or composition of a compound to a subject, which can form an equivalent amount of an active compound in the subject's body.

[0077] The present invention relates to a method of increasing dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing athletic performance, or enhancing athletic performance in the subject by stimulating a nerve receptor CB1, by administering a composition containing ergothioneine or its salt, acid, ester or derivative, or a composition containing tributyrin or its derivative, or a composition containing anandamide or its salt, acid, ester or derivative to a subject at a certain dose.

[0078] The method of expectation comprises the ergothioneine or ergothioneine substitute of at least 1mg, or 20mg tributyrin or its substitute, or 15mg anandamide or its substitute, and this depends on specific preparation and form.This amount every day can be used once or repeatedly.Typically, the effective amount of ergothioneine or ergothioneine derivative in the composition containing ergothioneine used once or repeatedly every day is 1 milligram (mg) to 1500mg or between 1 milligram (mg) to 1500mg; The effective amount of tributyrin or tributyrin derivative in the tributyrin composition used once or repeatedly every day is 20 milligrams (mg) to 2000mg or between 20 milligrams (mg) to 2000mg; The effective amount of anandamide or anandamide derivative in the anandamide composition used once or repeatedly every day is 15 milligrams (mg) to 2000mg or between 15 milligrams (mg) to 2000mg. One or more dosages can be used once a day in any time period.For example, effective dose can be used every day, continue one day, several days, many days or indefinitely use every day, compositions of the present invention can take 7 days and more in one cycle, depending on the effect of hope.More typically, the amount of thioneine used every day or thioneine derivative is 2mg, 5mg, 10mg, 25mg, 250mg, 100mg, 200mg, 300mg, 400mg, 500mg, 600mg, 700mg, 800mg, 900mg, 1000mg, 1100mg, 1200mg, 1300mg, 1400mg, 1500mg.More typically, the amount of thioneine used every day or thioneine derivative is 1mg to 1000mg.Most typically, the amount of thioneine used every day or thioneine derivative is 50mg. The amount of tributyrin or a tributyrin derivative administered per day is 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg or 2000 mg. More typically, the amount of tributyrin or a tributyrin derivative administered per day is 20 mg to 1000 mg. Most typically, the amount of tributyrin or a tributyrin derivative administered per day is 200 mg.The amount of anandamide or anandamide derivative administered daily is 20 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg. More typically, the amount of anandamide or anandamide derivative administered daily is 15 mg to 2000 mg. Most typically, the amount of anandamide or anandamide derivative administered daily is 200 mg. In certain embodiments, the amount of anandamide administered per day can be about 1-30 mg / kg, about 1-25 mg / kg, about 1-20 mg / kg, about 1-15 mg / kg, about 1-10 mg / kg, about 1-5 mg / kg, or about 3-4 mg / kg of body weight.

[0079] The various forms and preparations containing the compositions of the present invention are considered to be used for regulating or increasing the level of intestinal flora in the subject. The compositions will be formulated into nutritional supplements or dietary supplements, (medical) food, animal feed, in liquid or solid form, and can also optionally include a nutrient or pharmaceutically acceptable carrier. For example, when the composition is in solid form, the composition can be formulated into snack bars, yogurt, lozenges, tablets or capsules, or can be applied to cereal products, included in baked goods. On the other hand, when the supplement is in liquid form, the composition can be formulated into tinctures, soft gel capsules, liquid capsules, syrups, carbonated beverages, brewed beverages (such as coffee or tea), fruit juices, energy drinks, sports drinks or flavored waters. While nutritional and pharmaceutical compositions for human use are particularly contemplated, it will be appreciated that the compositions and formulations containing the compositions may also be used for veterinary purposes (e.g., in animal feed for domestic companion animals ("pets") or animal feed for farm animals. In other contemplated aspects, the compositions containing the compositions may also be provided as bulk products (e.g., in amounts equal to or greater than 100 g, equal to or greater than 1000 g, or equal to or greater than 10 kg) for the production of nutritional supplements, (medical) foods, animal feeds.

[0080] The composition of the present invention uses a variety of ingredients that can work together. The composition of the present invention is simple and convenient to prepare and can be prepared by uniformly mixing the raw materials. In some embodiments, the preparation method of the composition of the present invention comprises the following steps: first, after uniformly mixing some of the raw materials in the composition, mixing them with other raw materials; more preferably, the raw materials are mixed in a three-dimensional mixing manner. In some embodiments, the components in the composition of the present invention can be dissolved in a suitable solvent to form a corresponding solution and / or suspension, and then the solutions and / or suspensions of the components are mixed to form a mixed form of the composition of the present invention dissolved in a solvent. In the preparation method of the composition, the components can be reasonably added using a mixing method well known in the art depending on the properties of the raw materials.

[0081] In the composition of the present invention, the composition can be prepared by selecting appropriate content as needed.

[0082] The technical features, implementation methods and beneficial effects of the present invention are further described in detail below with reference to specific implementation cases. The following embodiments are only a part of the embodiments of the present invention, not all of the embodiments. Unless otherwise specified, the materials and reagents described in the following embodiments are all common commercial products and can be purchased on the market.

[0083] Composition formula: 25 mg of ergothioneine, 400 mg of dehydrogingerone; or 25 parts of ergothioneine, 400 parts of dehydrogingerone. Example 2

[0084] Composition formula: 5 mg of ergothioneine, 800 mg of dehydrogingerone; or 5 parts of ergothioneine; 800 parts of dehydrogingerone. Example 3

[0085] Composition formula: 10 mg of ergothioneine, 1000 mg of tributyrin; or 10 parts of ergothioneine, 1000 parts of tributyrin. Example 4

[0086] Composition formula: 25 mg of ergothioneine, 1500 mg of tributyrin; or 25 parts of ergothioneine, 1500 parts of tributyrin. Example 5

[0087] Composition formula: 20 mg of ergothioneine, 300 mg of anandamide; or 20 parts of ergothioneine, 300 parts of anandamide. Example 6

[0088] Composition formula: 30 mg of ergothioneine, 500 mg of anandamide; or 30 parts of ergothioneine, 500 parts of anandamide. Example 7

[0089] Composition formula: 500 mg of dehydrogingerone, 2000 mg of tributyrin; or 500 parts of dehydrogingerone, 2000 parts of tributyrin. Example 8

[0090] Composition formula: 700 mg of dehydrogingerone, 900 mg of tributyrin; or 700 parts of dehydrogingerone, 900 parts of tributyrin. Example 9

[0091] Composition formula: 1000 mg of dehydrogingerone, 1000 mg of anandamide; or 1000 parts of dehydrogingerone, 1000 parts of anandamide. Example 10

[0092] Composition formula: 800 mg of dehydrogingerone, 700 mg of anandamide; or 800 parts of dehydrogingerone, 700 parts of anandamide. Example 11

[0093] Composition formula: 1500 mg of tributyrin, 900 mg of anandamide; or 1500 parts of tributyrin, 900 parts of anandamide. Example 12

[0094] Composition formula: 2000 mg of tributyrin, 800 mg of anandamide; or 2000 parts of tributyrin, 800 parts of anandamide. Example 13

[0095] Composition formula: 5 mg of ergothioneine, 800 mg of dehydrogingerone, 2000 mg of tributyrin; or 5 parts of ergothioneine, 800 parts of dehydrogingerone, and 2000 parts of tributyrin. Example 14

[0096] Composition formula: 5 mg of ergothioneine, 300 mg of dehydrogingerone, 1000 mg of tributyrin; or 5 parts of ergothioneine, 300 parts of dehydrogingerone, and 1000 parts of tributyrin. Example 15

[0097] Composition formula: 25 mg of ergothioneine, 400 mg of dehydrogingerone, and 400 mg of anandamide; or 25 parts of ergothioneine, 400 parts of dehydrogingerone, and 400 parts of anandamide. Example 16

[0098] Composition formula: 30 mg of ergothioneine, 500 mg of dehydrogingerone, and 900 mg of anandamide; or 30 parts of ergothioneine, 500 parts of dehydrogingerone, and 900 parts of anandamide. Example 17

[0099] Composition formula: 5 mg of ergothioneine, 1700 mg of tributyrin, and 400 mg of anandamide; or 5 parts of ergothioneine, 1700 parts of tributyrin, and 400 parts of anandamide. Example 18

[0100] Composition formula: 15 mg of ergothioneine, 2000 mg of tributyrin, and 700 mg of anandamide; or 15 parts of ergothioneine, 2000 parts of tributyrin, and 700 parts of anandamide. Example 19

[0101] Composition formula: 400 mg of dehydrogingerone, 1600 mg of tributyrin, and 500 mg of anandamide; or 400 parts of dehydrogingerone, 1600 parts of tributyrin, and 500 parts of anandamide. Example 20

[0102] Composition formula: 600 mg of dehydrogingerone, 1800 mg of tributyrin, and 900 mg of anandamide; or 600 parts of dehydrogingerone, 1800 parts of tributyrin, and 900 parts of anandamide. Example 21

[0103] Thirty-two purebred Swiss male mice were randomly divided into groups of 8 and placed under a 12:12 hour light and dark cycle with free access to food and water. The first group was the control group (Group 1, no sample), the second group was gavaged with 35 mg / kg EGT (Group 2), the third group was gavaged with 20 mg / kg AEA (Group 3), and the fourth group was gavaged with 300 mg / kg TB (Group 4). Raw material solutions were prepared, and all raw materials were administered at a dose of 10 mL / kg body weight for 4 weeks. After 4 weeks, the mice were subjected to exercise analysis by voluntarily running on a treadmill, and the running distance of the mice when they were exhausted was recorded. All mice were untrained before exercise. The brain tissue was taken and quickly frozen in liquid nitrogen for subsequent dopamine testing. The cecal feces of the mice were collected and frozen for DNA extraction.

[0104] Brain tissue was homogenized in PBS and centrifuged at 5000 g for 10 min at 4°C, and 50 μL of the supernatant was used to quantify dopamine in the brain tissue according to the manufacturer's instructions.

[0105] Total DNA was extracted from mouse cecal feces using a DNA isolation kit according to the manufacturer's instructions. DNA quantity and quality were assessed using a Nanodrop 1000. Specific primers were purchased from Sangon Biotechnology (Table 1). Real-time quantitative PCR (qRT-PCR) analysis of Eubacterium rectale and Coprococcus eutactus was performed on a Light Cycler 480 instrument.

[0106] To observe the effects of EGT, AEA, and TB on exercise performance, running endurance and brain dopamine content were measured after 4 weeks of administration to determine whether the improved exercise performance was due to dopamine secretion. Figure 1 shows the brain dopamine levels of mice in all groups after 4 weeks. In Figure 1, with respect to brain dopamine levels, groups 2-4 showed effective regulation of dopamine levels, with group 2 at 17285 ng / g brain, group 3 at 17620 ng / g brain, and group 4 at 15000 ng / g brain, which were significantly higher than the control group 1 (3292 ng / g brain) by approximately 5.25, 5.35, and 4.56 times, respectively. Figure 2 shows the running distance of mice in all groups after 4 weeks. In terms of exercise performance, compared with the control group 1 (954 m), group 2 (1129 m), group 3 (1137 m), and group 4 (1079 m) all showed improved exercise performance. Therefore, it can be concluded that EGT, AEA, and TB supplementation improved exercise performance by increasing brain dopamine levels after 4 weeks.

[0107] Figure 3 shows the copy number of Eubacterium rectum in cecal feces. Figure 4 shows the copy number of Coprococcus regulatus in cecal feces. The results in Figures 3 and 4 show that, compared with the control group, after four weeks of EGT / AEA / TB supplementation, the copy number of Eubacterium rectum increased by approximately 187%, 199%, and 188%, respectively, and the copy number of Coprococcus regulatus increased by approximately 577%, 675%, and 661%, respectively, in Groups 2-4.

[0108] In summary, all sample groups (Groups 2-4) improved the intestinal flora, especially the exercise-related bacteria (Eubacterium rectum and Coprococcus rudimentus), thereby increasing dopamine levels and ultimately enhancing exercise performance. Example 22

[0109] Thirty-two purebred Swiss male mice were randomly divided into groups of eight and housed under a 12:12 hour light-dark cycle with free access to food and water. The fifth group served as the control group (Group 5, no feed), the sixth group received oral administration of 35 mg / kg EGT + 50 mg / kg DHZ + 300 mg / kg TB + 20 mg / kg AEA (Group 6, EGT + DHZ + TB + AEA), the seventh group received oral administration of 35 mg / kg EGT + 20 mg / kg AEA (Group 7, EGT + AEA), the eighth group received oral administration of 35 mg / kg EGT + 300 mg / kg TB (Group 8, EGT + TB), the ninth group received oral administration of 300 mg / kg TB + 20 mg / kg AEA (Group 9, TB + AEA), and the tenth group received oral administration of 35 mg / kg EGT + 300 mg / kg TB + 20 mg / kg AEA (Group 10, EGT + TB + AEA). Sample solutions were prepared, and all ingredients were administered at a dose of 10 mL / kg body weight for four weeks. After four weeks, the mice underwent voluntary treadmill running for exercise analysis, with the distance reached to exhaustion recorded. All mice were untrained prior to the exercise. Brain tissue was harvested and snap-frozen in liquid nitrogen for subsequent dopamine analysis. Cecal feces were collected from the mice and frozen for DNA extraction.

[0110] Brain tissue was homogenized in PBS and centrifuged at 5000 g for 10 min at 4°C, and 50 μL of the supernatant was used to quantify dopamine in the brain tissue according to the manufacturer's instructions.

[0111] Total DNA was extracted from mouse cecal feces using a DNA isolation kit according to the manufacturer's instructions. DNA quantity and quality were assessed using a Nanodrop 1000. Specific primers were purchased from Sangon Biotechnology (Table 1). Real-time quantitative PCR (qRT-PCR) analysis of Eubacterium rectum and Coprococcus rudimentus was performed on a Light Cycler 480 instrument.

[0112] In order to observe the effect of EGT+DHZ+TB+AEA on exercise performance, running endurance and the content of dopamine in the brain were measured after 4 weeks of administration to ensure whether the secretion of dopamine promoted the improvement of exercise performance. Figure 5 shows the brain dopamine levels of mice in all groups after 4 weeks. In Figure 5, for the dopamine level in the brain, the EGT+DHZ+TB+AEA supplement (Group 6) showed an effective regulation of dopamine levels, which was 29820ng / g brain, 8.25 times higher than the control group (3615ng / g brain). In addition, relative to the control group 1, the other groups all improved brain dopamine levels, of which Group 10 (26201ng / g) was 7.25 times higher than the control group. Figure 6 shows the running distance of mice in all groups after 4 weeks. In terms of exercise performance, compared with control group 5 (930m), groups 6 (1246m), 7 (1148m), 8 (1139m), 9 (1141m), and 10 (1190m) all showed improved exercise performance. Therefore, it can be concluded that supplementation for groups 6-10 for 4 weeks improved exercise performance by increasing brain dopamine levels.

[0113] Figure 7 shows the copy number of Eubacterium rectum in cecal feces. Figure 8 shows the copy number of Coprococcus regulatus in cecal feces. The results in Figures 7 and 8 show that compared with the control group, Groups 6-10 all improved the Eubacterium rectum and Coprococcus regulatus flora. Specifically, after four weeks of supplementation, the copy number of Eubacterium rectum in Groups 6-10 increased by approximately 281%, 90%, 126%, 74%, and 145%, respectively, and the copy number of Coprococcus regulatus increased by approximately 927%, 320%, 382%, 325%, and 681%, respectively.

[0114] In summary, groups 6-10 increased dopamine levels and improved intestinal flora, especially exercise-related bacteria (Eubacterium rectum and Coprococcus rudimentosus), thereby increasing dopamine levels and ultimately enhancing exercise performance.

Claims

1. A method for modulating or increasing the level of gut microbiota in a subject, characterized in that, The method comprises: administering to the subject a composition containing ergothioneine or its salt, acid, ester or derivative, or a composition containing tributyrin or its derivative; the intestinal flora being Gram-positive bacteria.

2. The method according to claim 1, wherein The Gram-positive bacteria are Eubacterium rectale and / or Faecalibacterium prausnitzii.

3. The method according to claim 1 or 2, characterized in that, The method increases dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing exercise performance.

4. The method according to claim 3, wherein The enhanced exercise performance includes increased endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

5. The method according to any one of claims 1-4, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is formulated as a nutritional supplement, food, beverage or animal feed.

6. The method according to any one of claims 1-5, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is prepared as a solid preparation or a liquid preparation.

7. The method according to any one of claims 1-6, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, spirit, tincture, tonic, liquid suspension or syrup.

8. The method according to any one of claims 1 to 7, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative is administered to the subject in a dose of 1 - 1500 mg, or the composition containing tributyrin or its derivative is administered to the subject in a dose of 20 - 2000 mg.

9. Use of a composition containing ergothioneine or its salt, acid, ester or derivative or a composition containing tributyrin or its derivative in the manufacture of a nutritional supplement, food, beverage or animal feed for regulating or increasing the level of gut microbiota in a subject, characterized in that, The intestinal flora are Gram-positive bacteria.

10. The use according to claim 9, characterized in that, The Gram-positive bacteria are Eubacterium rectale and / or Faecalibacterium prausnitzii.

11. The use according to claim 9 or 10, characterized in that, The composition increases dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing exercise performance.

12. The use according to any one of claims 9-11, characterized in that, The administration dose of the composition is 1 - 1500 mg or 20 - 2000 mg.

13. The use according to any one of claims 9-12, characterized in that, The enhanced exercise performance includes increased endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

14. Use according to any one of claims 9 - 13, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is in the form of a suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, spirit, tincture, tonic, liquid suspension or syrup.

15. Use according to any one of claims 1 - 14, wherein the composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is prepared as a solid preparation or a liquid preparation.

16. A composition containing ergothioneine or its salt, acid, ester or derivative, or a composition containing tributyrin or its derivative, characterized in that, The composition is used for regulating or increasing the level of intestinal flora in the subject, and the intestinal flora are Gram-positive bacteria.

17. The composition according to claim 16, wherein The Gram-positive bacteria are Eubacterium rectale and / or Faecalibacterium prausnitzii.

18. The composition according to claim 16 or 17, characterized in that, The composition increases dopamine in the brain by regulating or increasing the level of intestinal flora in the subject, thereby enhancing exercise performance.

19. The composition according to any one of claims 16 - 18, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative is formulated as a nutritional supplement, food, beverage, animal feed or drug.

20. The composition according to any one of claims 16-19, characterized in that, The enhanced exercise performance includes increased endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

21. A method for enhancing the athletic performance of a subject, characterized in that, The method comprises administering to the subject a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof, or a composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof.

22. The method according to claim 21, wherein The method enhances the motor performance of the subject by increasing dopamine in the brain, or stimulates the CB1 receptor of the nerve, thereby enhancing the motor performance of the subject.

23. The method according to claim 21 or 22, characterized in that, The enhanced motor performance includes improved endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

24. The method according to any one of claims 21-23, characterized in that, The composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof is formulated as a nutritional supplement, food, beverage or animal feed.

25. The method according to any one of claims 21 - 24, characterized in that, The composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof is prepared as a solid preparation or a liquid preparation.

26. The method according to any one of claims 21-25, characterized in that, The composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof is administered in a form selected from suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, spirits, tinctures, tonics, liquid suspensions, syrups, functional foods, beverages or sublingual products.

27. The method according to any one of claims 21-26, characterized in that, The composition comprising ergothioneine or a salt, acid, ester or derivative thereof is administered to the subject in a dose of 1 - 1500 mg, or the composition comprising tributyrin or a derivative thereof is administered to the subject in a dose of 20 - 2000 mg, or the composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof is administered to the subject in a dose of 15 - 2000 mg. Use of a composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or a composition comprising tributyrin or a derivative thereof, or a composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof in the manufacture of a nutritional supplement, food, beverage or animal feed for enhancing the motor performance of a subject.

29. The use according to claim 28, characterized in that, The composition enhances the motor performance of the subject by increasing dopamine in the brain, or stimulates the CB1 receptor of the nerve, thereby enhancing the motor performance of the subject.

30. The use according to claim 28 or 29, characterized in that, The enhanced motor performance includes improved endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

31. The use according to any one of claims 28 - 30, characterized in that, The dosage of the composition is 1 - 1500 mg, 20 - 2000 mg, or 15 - 2000 mg.

32. The use according to any one of claims 28 to 31, characterized in that, The composition comprising ergothioneine or a salt, acid, ester or derivative thereof, or the composition comprising tributyrin or a derivative thereof, or the composition comprising arachidonoylethanolamide or a salt, acid, ester or derivative thereof is prepared as a solid preparation or a liquid preparation.

33. The use according to any one of claims 28 - 32, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative, or the composition containing arachidonoylethanolamide or its salt, acid, ester or derivative is in the form of suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, spirit, tincture, tonic, liquid suspension or syrup.

34. The use according to any one of claims 28 - 33, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative, or the composition containing arachidonoylethanolamide or its salt, acid, ester or derivative is prepared into a solid preparation or a liquid preparation.

35. A composition containing ergothioneine or its salt, acid, ester or derivative, or a composition containing tributyrin or its derivative, or a composition containing arachidonoylethanolamine or its salt, acid, ester or derivative, characterized in that, The composition is used to enhance the exercise performance of a subject.

36. The composition according to claim 35, characterized in that, The composition enhances the exercise performance of a subject by increasing dopamine in the brain, or stimulates the CB1 receptor of the nerve, thereby enhancing the exercise performance of the subject.

37. The composition according to claim 35 or 36, characterized in that, The enhanced exercise performance includes increased endurance, increased heart rate, increased blood flow, enhanced muscle endurance and muscle strength or increased power.

38. The composition according to any one of claims 35-37, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative, or the composition containing arachidonoylethanolamide or its salt, acid, ester or derivative is formulated into a nutritional supplement, food, beverage, animal feed or drug.

39. The composition according to any one of claims 35 - 38, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative, or the composition containing arachidonoylethanolamide or its salt, acid, ester or derivative is prepared into a solid preparation or a liquid preparation.

40. The composition according to any one of claims 35-39, characterized in that, The composition containing ergothioneine or its salt, acid, ester or derivative, or the composition containing tributyrin or its derivative, or the composition containing arachidonoylethanolamide or its salt, acid, ester or derivative is in the form of suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, spirit, tincture, tonic, liquid suspension or syrup.

41. A composition, characterized in that, Comprising two or more components selected from: ergothioneine or its physiologically acceptable salt, acid, ester, analogue or derivative, dehydrogingerdione or its salt, acid, ester or derivative, tributyrin or its derivative, arachidonoylethanolamide or its salt, acid, ester or derivative.

42. The composition according to claim 41, wherein, The amount of the component is 1 - 2000 mg or 0.1 μM to 1 M or 0.001 to 50.0 wt% (w / w).

43. The composition according to claim 41 or 42, characterized in that, The composition is used to regulate or increase the level of intestinal flora.

44. The composition according to claim 43, characterized in that, The intestinal flora is Gram-positive bacteria.

45. The composition according to claim 44, characterized in that, The Gram-positive bacteria are Eubacterium rectale and / or Faecalibacterium prausnitzii.

46. The composition according to claim 41 or 42, characterized in that, The composition is used to enhance or improve exercise performance.

47. The composition according to claim 46, characterized in that, The composition increases dopamine in the brain by regulating or increasing the level of intestinal flora in a subject, thereby enhancing exercise performance, or enhances the exercise performance of the subject by stimulating the CB1 receptor of the nerve.

48. The composition according to any one of claims 41-47, characterized in that, The composition is prepared into a solid preparation or a liquid preparation.

49. A nutritional supplement, food, beverage, or animal feed, characterized in that, Comprising the composition according to any one of claims 1 - 8.

50. The nutritional supplement, food, beverage, or animal feed according to claim 49, characterized in that, It is in the form of suppository, tablet, pill, granule, powder, film, capsule, beverage, aerosol, spirit, tincture, tonic, liquid suspension, syrup.

51. In the nutritional supplement, food, beverage, or animal feed according to claim 49 or 50, wherein The weight ratio of the composition is 0.1 - 95%.

52. The nutritional supplement, food, beverage, or animal feed according to any one of claims 49-51, characterized in that, The weight ratio of the composition is 1-50%.

53. Use of a composition according to any one of claims 41-48 in the preparation of a nutritional supplement, food, beverage, or animal feed.

54. The use according to claim 53, wherein it is used to regulate or increase the level of the intestinal flora, and the intestinal flora is Gram-positive bacteria.

55. The use according to claim 54, wherein the Gram-positive bacteria are Eubacterium rectale and / or Faecalibacterium prausnitzii.

56. The application according to any one of claims 53 - 55, characterized in that, The composition is used to enhance or improve athletic performance.

57. The application according to claim 56, characterized in that, The composition increases dopamine in the brain by regulating or increasing the level of the intestinal flora in a subject, thereby enhancing athletic performance, or enhances the athletic performance of the subject by stimulating the CB1 receptor of the nerve.

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