Compositions containing acetic acid, butyric acid, and quercetin, and their uses

Abstract

This invention relates to compositions containing acetic acid, butyric acid, and quercetin, and to the use thereof. This disclosure relates to a composition comprising, by weight, 50% to 95% (w / w) acetic acid, 0.1% to 5% (w / w) butyric acid or its derivatives, and 0.1% to 5% (w / w) quercetin or its derivatives. Furthermore, methods for use in the treatment and prevention of medical conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof, and for use in subjects in need thereof.

Description

Technical Field

[0001] The present disclosure generally relates to the field of compositions containing acetic acid, butyric acid or their derivatives, and quercetin or its derivatives, and is directed to nutraceutical products and food products containing these.

Background Art

[0002] Vinegar is a term used to represent an acidic and / or slightly bitter liquid mainly composed of acetic acid, which is widely used in home cooking. The preparation of vinegar is one of the oldest food manufacturing methods and involves the oxidative fermentation of ethanol, mainly obtained from plant materials, by acetic acid bacteria (Acetobacter Aceae). The composition of vinegar is very complex and may vary depending on the starting material, and examples include vinegar made from alcohol (e.g., brandy vinegar, spirit vinegar), wine vinegar (made from wine, surplus wine or waste wine), vinegar made from powdered substances (e.g., malt vinegar, beer vinegar, sugarcane vinegar, potato vinegar, rice vinegar) and fruit vinegar (made from fruit juice, e.g., apple vinegar, cherry vinegar, banana vinegar, pomegranate vinegar). In addition to acetic acid, the main components of vinegar include other organic acids (mainly gluconic acid, malic acid, tartaric acid, succinic acid) and sugars (mainly glucose and fructose). The class of trace components includes volatile compounds and antioxidant molecules, mainly polyphenols. Such trace components are important for the flavor and aroma of vinegar.

[0003] Vinegar has historically been recognized as having many health benefits. Vinegar has long been used medicinally for circulation, immune function, fatigue recovery, etc., and is effective in preventing adult diseases such as arteriosclerosis and hypertension, reducing cholesterol, reducing body fat, and recovering from fatigue. It not only stimulates the digestive system, but also aids digestion and enhances appetite. It is also added to various dishes to provide a refreshing feeling and eliminate odors, and is widely used as a natural antibacterial agent.

[0004] US9795682B2 discloses a compound vinegar-infused juice blend containing an effective amount of lemon juice, water, honey, peppermint extract, and a vinegar blend for relieving the symptoms of influenza and / or the common cold.

[0005] Patent JP4907215B2 discloses a vinegar-containing fruit juice beverage and a method for producing the same, which suppresses pungent odors and off-flavors derived from vinegar, preserves the original flavor of the fruit juice, and adds the health benefits of vinegar.

[0006] Thus, considering the above, it can be understood that there is a need for novel and improved compositions that contain usable ingredients such as vinegar and have improved nutritional value and improved biological activity. [Overview of the project]

[0007] One aspect of the present disclosure provides a composition comprising 50% to 95% by weight (w / w) of acetic acid, 0.1% to 5% (w / w) of butyric acid or a derivative thereof, and 0.1% to 5% (w / w) of quercetin or a derivative thereof.

[0008] In further embodiments, the composition further comprises 5% to 40% (w / w) of fruit or vegetable material. These material is selected from extracts, biomass, filtrates, concentrates, wort, must, pomace, juice, any fraction thereof, and any combination thereof.

[0009] In further embodiments, acetic acid is vinegar, vinegar extract, vinegar mother, derivative of vinegar, derivative of vinegar extract, derivative of vinegar mother, or any combination thereof.

[0010] In further embodiments, butyric acid or its derivative is triptyline.

[0011] In further embodiments, the w / w ratio of butyric acid or its derivatives to quercetin or its derivatives is between 1.5:1 and 1:2.

[0012] In another aspect of this disclosure, an edible composition comprising the composition according to this disclosure is provided.

[0013] In another aspect of this disclosure, a food product comprising the composition according to this disclosure is provided.

[0014] In another aspect of this disclosure, a pharmaceutical composition is provided comprising the composition according to this disclosure and an optionally pharmaceutically acceptable carrier.

[0015] In further embodiments, the pharmaceutical compositions are intended for use in subjects who require them in the prevention or treatment of medical conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof.

[0016] In further embodiments, the pharmaceutical composition is for preventing, improving or treating conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof, in a subject in need, thereby preventing, improving or treating the condition in the subject.

[0017] Another aspect of this disclosure provides a nutritional composition comprising the composition according to this disclosure.

[0018] Another aspect of the present disclosure provides a method for obtaining a composition according to the present disclosure, the method comprising contacting 0.1% to 5% (w / w) quercetin or a derivative thereof with an acetic acid solution containing 0.1% to 5% (w / w) butyric acid or a derivative thereof for 1 minute to 2 hours under conditions suitable for dissolving the quercetin and obtaining the composition.

[0019] In further embodiments, contact includes shaking, mixing, high-shear mixing, overhead stirring, homogenization, centrifugation, or any combination thereof.

[0020] In further embodiments, suitable conditions for the dissolution of quercetin include heating the solution to a temperature of 22°C to 45°C.

[0021] Another aspect of the present disclosure provides a composition according to the present disclosure, or a pharmaceutical composition according to the present disclosure, preferably a package including an airtight container.

[0022] In another aspect of this disclosure, the use of the composition according to this disclosure is a food supplement. It will be offered as such.

[0023] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as those generally understood by those skilled in the art to whom this disclosure relates. Similar or equivalent methods and materials described herein may be used in the implementation or testing of embodiments of this disclosure, but exemplary methods and / or materials are described below. In case of any conflict, the patent specification, including the definitions, shall prevail. Furthermore, the materials, methods, and examples are illustrative only and are not necessarily intended to be limiting.

[0024] Further embodiments and scope of the Disclosure will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples are merely illustrative, as while they illustrate preferred embodiments of the Disclosure, various changes and modifications within the spirit and scope of the Disclosure will become apparent to those skilled in the art from this detailed description. [Brief explanation of the drawing]

[0025] [Figure 1] Figure 1 is a graph showing the effects of apple or pomegranate supplementation. Cumulative absolute body weight over time. Data were analyzed using standard two-way analysis of variance (ANOVA) and post-hoc Tukey's multiple comparison test. Values ​​are presented as mean ± standard deviation (SD). Apple supplementation (n=15-12); Pomegranate supplementation (n=15); 0.9% saline solution supplementation (n=15);

[0026] [Figure 2] Figure 2 is a graph showing the effect of apple or pomegranate posca supplementation. Delta difference around the relative waist. Values are represented as median and minimum to maximum. Apple posca (n = 15 - 12); pomegranate (n = 15); 0.9% saline (n = 15). Asterisk (*) indicates statistical significance of comparison (*p < 0.05, **p < 0.005).

[0027] [Figure 3] Figure 3 is a graph showing the effect of apple or pomegranate posca supplementation. Delta difference in relative nasoanal length. Values are represented as median and minimum to maximum. Apple posca (n = 15 - 12); pomegranate (n = 15); 0.9% saline (n = 15) P. period;

[0028] [Figure 4] Figures 4A - B are bar graphs showing the effect of apple or pomegranate posca supplementation. Cumulative water consumption (mL) (Figure 4A) and cumulative food consumption (g) (Figure 4B). Values are represented as mean ± standard deviation (SD). Treatment group (black; n = 30); 0.9% saline group (gray; n = 15). Asterisk (*) indicates statistical significance of comparison (*p < 0.05; **p < 0.005). And

[0029] [Figure 5] Figures 5A - B are graphs showing the effect of apple or pomegranate posca supplementation on the liver - to - body weight ratio (Figure 5A) and the mean difference in liver - to - body weight ratio (%) (Figure 5B). Values are shown as median and minimum to maximum. Apple posca (n = 15 - 12); pomegranate (n = 15); 0.9% saline (n = 15) P. period. Asterisk (*) indicates statistical significance of comparison (*p < 0.05; **p < 0.005).

Mode for Carrying Out the Invention

[0030] According to some embodiments, the present disclosure provides compositions comprising acetic acid, butyric acid or derivatives thereof, and quercetin or derivatives thereof.

[0031] In some embodiments, the composition (e.g., a pharmaceutical composition and / or a nutritional supplement composition) is vinegar or contains vinegar. In some embodiments, the composition (e.g., a pharmaceutical composition and / or a nutritional supplement composition) is at least one activator derived from vinegar or contains them. In some embodiments, the composition (e.g., a pharmaceutical composition and / or a nutritional supplement composition) is at least one activator found in vinegar or contains them. In some embodiments, the activator is a synthetic compound or a natural compound. In some embodiments, the activator is an isolated compound (e.g., a purified compound) derived from vinegar. In some embodiments, the activator contains a compound that is composed of, secreted, derived from, isolated or produced by vinegar. In some embodiments, the activator is vinegar. In some embodiments, the compound is a natural compound or a synthetic compound.

[0032] Suitable vinegars as provided in this disclosure include natural vinegars prepared from common agricultural products known in the art.

[0033] As used herein, “vinegar” refers to an aqueous solution of acetic acid and trace compounds (e.g., phenolic compounds) produced by a two-step fermentation process in which yeast is used to convert monosaccharides into ethanol, and then acetic acid bacteria are used to convert ethanol into acetic acid. Vinegar typically contains 5-8% acetic acid by volume. As used herein, acetic acid or ethaneic acid refers to an acidic, colorless liquid and organic compound having the chemical formula CH3COOH. Vinegar is at least 4% acetic acid by volume, and acetic acid is the main component of vinegar, apart from water and other trace elements.

[0034] In some embodiments of this disclosure, the terms “vinegar” and “acetic acid” are synonymous and used interchangeably.

[0035] As used herein, the term “isolated compound” refers to a compound that is essentially free from other contaminants such as impurities. Typically, the activator and / or isolated compound are present in the composition in a highly purified form, i.e., at least about 80% purity, at least about 90% purity, at least about 95% purity, above 95% purity, or above 99% purity. In some embodiments, the activator is or contains a pharmaceutical-grade compound. In some embodiments, the activator is or contains a food-grade compound.

[0036] As used herein, “butyric acid” (BA), also known systematically as butanoic acid, is a linear alkylcarboxylic acid having the chemical formula CH3CH2CH2CO2H and refers to a short-chain fatty acid (SCFA). The compositions according to this disclosure include butyric acid, its derivatives, or its precursors. In some embodiments, butyric acid as used herein refers to triptyline. In some embodiments, the compositions according to this disclosure include triptyline. As used herein, “tributyline” refers to a glyceride of butyric acid containing three butyric acid molecules esterified to a glycerol skeleton. Tributyline has been shown to be an effective source of butyric acid. Tributyline is an alternative source of dietary butyric acid that does not require coating and can pass through the upper gastrointestinal tract to release butyric acid in the small intestine after degradation by pancreatic lipase. In some embodiments of this disclosure, the terms “butyric acid or its derivatives” and “tributyline” are synonymous and used interchangeably.

[0037] As used herein, "quercetin" refers to a polyphenolic flavonoid, more specifically, a pentahydroxyflavone having five hydroxyl groups located at the 3-, 3'-, 4'-, 5-, and 7-positions. Quercetin is one of the most abundant flavonoids found in edible vegetables, fruits, and wine.

[0038] According to some embodiments of this disclosure, the compositions described herein are edible compositions. As used herein, the term “edible composition” typically refers to a composition suitable for oral consumption (however, consumption may occur via parenteral means such as inhalation). Edible compositions may exist in any form, including but not limited to liquids, solids, semi-solids, tablets, lozenges, powders, gels, gums, pastes, flurries, syrups, aerosols, and sprays. As used herein, edible compositions include foods, pharmaceutical compositions, and consumer products. The term edible composition also refers, for example, to dietary supplements and nutritional supplements.

[0039] In some embodiments, the composition and / or food is in the form of gum. In some embodiments, the composition and / or food is in the form of a semi-solid. In some embodiments, the composition and / or food is in the form of a liquid.

[0040] This disclosure is based in part on the finding that compositions comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives, as described herein, in the proportions described herein, are suitable for consumption and mask off-odors derived from acetic acid. This disclosure is based in part on the finding that compositions comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives, as described herein, in the proportions described herein, are suitable for consumption and mask off-odors derived from butyric acid or its derivatives. This disclosure is based in part on the finding that compositions comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives, as described herein, in the proportions described herein, are suitable for consumption and mask off-odors derived from quercetin.

[0041] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit desired stability and improved biological activity compared to formulations comprising only one or two of the same materials.

[0042] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit desired stability and improved biological activity compared to formulations containing the same materials but with different volume or weight ratios.

[0043] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit desired stability and improved biological activity compared to control formulations. In some embodiments, the control is physiological saline.

[0044] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit improved antioxidant and / or anti-inflammatory activity compared to formulations comprising only one or two of the same materials.

[0045] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined ratios, regulate appetite and reduce abdominal fat accumulation in subjects. In some embodiments, compositions (e.g., formulations) according to this disclosure, when administered to a subject, reduce the amount of fat accumulated in the subject's liver.

[0046] This disclosure is based in part on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit improved antioxidant and / or anti-inflammatory activity compared to formulations containing the same materials but with different volume or weight ratios thereof.

[0047] This disclosure is partly based on the finding that compositions (e.g., formulations) according to this disclosure, comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in predetermined proportions, exhibit synergistic effects.

[0048] Throughout this specification, "composition" means a formulation.

[0049] In some embodiments, the Disclosure provides non-toxic formulations. In some embodiments, the Disclosure provides food-grade formulations. As used herein, the term “formulation” means a vehicle composition in the form of a solution, emulsion, lotion, cream, gel, etc., which optionally further comprises a carrier and / or excipient, and optionally other chemical components. The formulation may optionally further contain additional activators and / or additives.

[0050] In some embodiments, the term “by weight” means by the weight of the entire composition.

[0051] As used herein, the term “activator” refers to any small organic molecule that is synthesized or naturally occurring. In some embodiments, the activator includes butyric acid or its derivatives, quercetin or its derivatives, vinegar, or compounds composed of, secreted, induced, isolated, or produced by vinegar, or any combination thereof. As used herein, the term “small organic molecule” refers to a molecule of a size comparable to those organic molecules commonly used in pharmaceuticals. This term excludes naturally occurring biomacromolecules (e.g., proteins, nucleic acids, etc.). In some embodiments, the organic molecule has a size including up to 5000 Da, up to 2000 Da, or up to 1000 Da, or any value in between. Each possibility represents a separate embodiment of the disclosure.

[0052] According to some embodiments, the present disclosure provides compositions comprising, by weight, 50% to 95% (w / w) acetic acid, 0.1% to 5% (w / w) butyric acid or its derivatives, and 0.1% to 5% (w / w) quercetin or its derivatives.

[0053] In some embodiments, the simplest options are 50%~95%(w / w), 55%~95%(w / w), 60%~95%(w / w), 65%~95%(w / w), 70%~95%(w / w), 75%~95%(w / w), 80%~95%(w / w), 85%~95%(w / w), 50%~90%(w / w), 55%~90%(w / w), 60%~90%( This includes acetic acid in the following concentrations: w / w), 65%-90% (w / w), 70%-90% (w / w), 75%-90% (w / w), 80%-90% (w / w), 85%-90% (w / w), 50%-85% (w / w), 55%-85% (w / w), 60%-85% (w / w), 65%-85% (w / w), or 70%-85% (w / w) (including any range in between). Each possibility represents a distinct embodiment of this disclosure.

[0054] In some embodiments, the composition is 0.1%~5% (w / w), 0.2%~5% (w / w), 0.3%~5% (w / w), 0.4%~5% (w / w),

[0055] This includes butyric acid or its derivatives (including any range in between) in concentrations of 0.1% to 2% (w / w), 0.2% to 2% (w·w), 0.3% to 2% (w / w), 0.4% to 2% (w / w), 0.1% to 1% (w / w), 0.2% to 1% (w / w), 0.3% to 1% (w / w), 0.4% to 1% (w / w), 0.1% to 0.8% (w / w), 0.2% to 0.8% (w / w), 0.3% to 0.8% (w / w), or 0.4% to 0.8% (w / w). Each possibility represents a distinct embodiment of the present disclosure.

[0056] In some embodiments, the composition comprises 0.1% to 5% (w / w), 0.2% to 5% (w / w), 0.3% to 5% (w / w), 0.4% to 5% (w / w), 0.1% to 2% (w / w), 0.2% to 2% (w / w), 0.3% to 2% (w / w), 0.4% to 2% (w / w), 0.1% to 1% (w / w), 0.2% to 1% (w / w), 0.3% to 1% (w / w), 0.4% to 1% (w / w), 0.1% to 0.8% (w / w), 0.2% to 0.8% (w / w), 0.3% to 0.8% (w / w), or 0.4% to 0.8% (w / w) of quercetin or its derivatives (including any range in between). Each possibility represents a distinct embodiment of the present disclosure.

[0057] In some embodiments, the composition comprises 5%–40% (w / w), 10%–40% (w / w), 15%–40% (w / w), 20%–40% (w / w), 25%–40% (w / w), 5%–35% (w / w), 10%–35% (w / w), 15%–35% (w / w), 20%–35% (w / w), and 25%–35% of fruit or vegetable material (including any range in between). Each possibility represents a separate embodiment of the present disclosure. In some embodiments, the material is selected from extracts, biomass, filtrates, concentrates, wort, must, pomace, juice, any fraction thereof, and any combination thereof. In some embodiments, the material is fruit juice or fruit concentrate.

[0058] According to this disclosure, fruit “must” refers to the must of fruit concentrate, which is a product made from crushed fruit juice processed to remove some or most of the water, resulting in a thicker, more concentrated juice.

[0059] This disclosure is based in part on the finding that compositions according to this disclosure, comprising acetic acid, butyric acid or its derivatives, quercetin or its derivatives, and fruit or vegetable materials in predetermined ratios and concentrations as disclosed herein, reduce effects derived from the acidity of vinegar (e.g., stomach discomfort).

[0060] This disclosure is, in part, based on the discovery that compositions according to this disclosure, comprising acetic acid, butyric acid or its derivatives, quercetin or its derivatives, and fruit or vegetable material in predetermined ratios and concentrations as disclosed herein, mask the acidic taste of vinegar.

[0061] This disclosure is based in part on the discovery that compositions according to this disclosure, comprising acetic acid, butyric acid or its derivatives, quercetin or its derivatives, and fruit or vegetable material in predetermined ratios and concentrations as disclosed herein, smooth the taste of vinegar. According to this disclosure, "smoothen" and "smooth" are used interchangeably to mean having a good taste, being not bitter, having little bitterness, being not acidic, having little acidity, or any combination thereof.

[0062] In some embodiments, the disclosure provides compositions comprising, by weight, 50% to 95% (w / w) acetic acid and 5% to 40% (w / w) fruit or vegetable material. In some embodiments, a composition comprising, by weight, 50% to 95% (w / w) acetic acid and 5% to 40% (w / w) fruit or vegetable material is further enhanced in nutritional value with 0.1% to 5% (w / w) butyric acid or its derivatives and 0.1% to 5% (w / w) quercetin or its derivatives.

[0063] In some embodiments, acetic acid is vinegar, vinegar extract, vinegar mother, derivative of vinegar, derivative of vinegar extract, derivative of vinegar mother, or any combination thereof. In some embodiments, acetic acid comprises vinegar, vinegar extract, vinegar mother, derivative of vinegar, derivative of vinegar extract, derivative of vinegar mother, or any combination thereof. In some embodiments, acetic acid consists of vinegar, vinegar extract, vinegar mother, derivative of vinegar, derivative of vinegar extract, derivative of vinegar mother, or any combination thereof.

[0064] In some embodiments, acetic acid is vinegar and vinegar mother. In some embodiments, acetic acid consists of vinegar and vinegar mother.

[0065] As used herein, "vinegar mother" refers to a biofilm consisting of cellulose and acetic acid bacteria that develop on the alcoholic liquid during fermentation, which converts the alcohol into acetic acid with the help of oxygen in the air.

[0066] In some embodiments, vinegar, vinegar extract, or vinegar mother is obtained from fruits, vegetables, syrups, wine, or any combination thereof. In some embodiments, vinegar, vinegar extract, or vinegar mother is obtained from grapes, apples, malt, pineapples, pomegranates, or any combination thereof.

[0067] In some embodiments, the w / w ratio of butyric acid or its derivatives to quercetin or its derivatives is between 1.5:1 and 1:2, between 1.3:1 and 1:2, between 1.1:1 and 1:2, between 1.5:1 and 1:1.7, between 1.5:1 and 1:1.6, or between 1.5:1 and 1:1, and includes any range in between. Each possibility represents a separate embodiment of the present disclosure.

[0068] In some embodiments, the composition further comprises a flavoring agent. In some embodiments, the flavoring agent is an extract or concentrate. Flavoring agents are well known to those skilled in the art. Suitable flavoring agents include fruit juices, herbs, spices, and flowers. For example, fruits may be citrus fruits such as oranges, lemons, limes, grapefruits, tangerines, sweet potatoes, and clementines; tropical fruits such as pineapples, mangoes, and passion fruits; berries such as strawberries, raspberries, blueberries, blackberries, and cranberries; superfruits such as acai, goji, maca, mangosteen, noni, and pomegranates; and other fruits such as grapes, apples, pears, tomatoes, and blackcurrants. Spices may be ginger or cinnamon. Flowers may be elderflower. In one embodiment, the flavoring agent comprises fruit juices, extracts, concentrates thereof, or any combination thereof. The fruit juice, or its extract or concentrate, may be selected from oranges, lemons, limes, apples, and / or blackcurrants. In other embodiments, the composition comprises several flavoring agents. In some embodiments, the flavoring agents are naturally occurring flavoring agents suitable for human consumption.

[0069] In some embodiments, the composition may be in the form of a powder, capsule, tablet, lotion, gel, gummy composition, liquid solution, or liquid suspension.

[0070] In some embodiments, the composition is an edible composition. In some embodiments, the composition is a pharmaceutical composition or a dietary supplement composition. As used herein, the term “dietary supplement composition” refers to a composition comprising bioactive compounds, vitamins, minerals, herbal extracts, or other dietary ingredients having potential health-promoting properties. According to this disclosure, a dietary supplement composition refers to a dietary supplement or functional food formulated to provide health benefits beyond basic nutrition.

[0071] In some embodiments, the composition is a dietary supplement or nutritional supplement.

[0072] In some embodiments, the composition is a probiotic composition, a prebiotic composition, or both.

[0073] In some embodiments, the composition is a vegan composition.

[0074] In some embodiments, this disclosure provides the use of the compositions described herein as dietary supplements.

[0075] In some embodiments, the present disclosure provides a food product comprising the above-described composition.

[0076] As used herein, the term “food” refers to any material, substance, or additive that can be used as food or added to food. Typically, food is any composition that can be consumed as part of the diet of an animal, preferably a mammal such as a human. In some embodiments, as used herein, the term “food” refers to dietary supplements, dietary supplements, and nutritional supplements.

[0077] According to this disclosure, the dietary supplements disclosed herein are suitable for oral intake and are administered orally. In some embodiments, the dietary supplements are in the form of capsules (e.g., intended to be swallowed or chewed), tablets (e.g., intended to be swallowed or chewed), powders (e.g., powders that can be added to water, milk, or another liquid), liquids (e.g., ready-to-drink form or suitable for dilution with another beverage), or nutritional foodstuffs. For example, the dietary supplements may be in the form of nutrition bars (e.g., meal bars or snack bars), cookies, candies (e.g., chewable items such as toffee, caramel, jelly, chocolate meltaway, fruit chews, or gum), syrups, or beverages (e.g., ready-to-drink form or in the form of concentrates or powders).

[0078] According to this disclosure, the nutritional supplements disclosed herein are suitable for oral intake and are administered orally. In some embodiments, the nutritional supplements are in the form of capsules (e.g., intended to be swallowed or chewed), tablets (e.g., intended to be swallowed or chewed), powders (e.g., powders that can be added to water, milk, or another liquid), liquids (e.g., ready to drink or suitable for dilution with another beverage), or nutritional foods. For example, the nutritional supplements may be in the form of nutrition bars (e.g., meal bars or snack bars), cookies, candies (e.g., chews such as toffee, caramel, jelly, chocolate meltaway, fruit chew, or gum), syrups, or beverages (e.g., ready to drink or in the form of concentrates or powders).

[0079] In some embodiments, the dietary supplements disclosed herein are intended for use in subjects who require them in the prevention or treatment of medical conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof.

[0080] In some embodiments, the dietary supplements disclosed herein are for the prevention, improvement, or treatment of conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof in subjects requiring such supplementation, thereby preventing, improving, or treating the conditions in subjects.

[0081] In some embodiments, the dietary supplement is or comprises Posca. In some embodiments, the dietary supplement is or comprises vinegar, butyric acid or its derivatives, and quercetin or its derivatives. In some embodiments, the dietary supplement is a vegan dietary supplement. In some embodiments, the dietary supplement consists of the compositions described herein.

[0082] In some embodiments, the dietary supplement is intended to regulate the subject's appetite and reduce the accumulation of abdominal fat. In some embodiments, the dietary supplement is intended to reduce the amount of fat accumulated in the liver.

[0083] In some embodiments, the food is vinegar or contains vinegar. In some embodiments, the food is Posca or contains Posca. In some embodiments, the food is vinegar, butyric acid or derivatives thereof, and quercetin or derivatives thereof or contains them. In some embodiments, the food is a vegan food. In some embodiments, the food consists of a composition as described herein.

[0084] As used herein, the term "posca" refers to a composition comprising wine vinegar and water. According to this disclosure, the term posca is used to describe a composition comprising acetic acid, butyric acid or its derivatives, and quercetin or its derivatives in the proportions disclosed herein.

[0085] In this specification, the term "vegan" refers to the characteristics of an ingredient, indicating that the ingredient does not originate from animals or animal products. Therefore, "vegan" ingredients do not contain any animal products or animal by-products. The components of animal products and animal by-products are well known in this field and to people who follow vegetarian or vegan diets. In particular, the term "animal product" refers to parts of animals, animal by-products, or products produced by animals. Examples of materials considered "animal products" include parts of animals that are edible by humans or that are commonly cooked for human consumption (e.g., fat, meat, blood, etc.). Products produced by animals are also considered "animal products" in this specification, and refer to products produced by animals without the slaughter of the animals (e.g., milk, eggs, honey, etc.). "Animal by-products" refer to by-products (e.g., bones, carcasses, etc.) that are not usually consumed on their own but are produced when animals are slaughtered for food. However, animal by-products are often processed into human-consumable foods, with well-known examples including gelatin, casein, whey, and rennet. In this specification, these processed animal by-products (e.g., gelatin, casein, whey, rennet, etc.) are encompassed by the term “animal by-products.” The “vegan” and “plant-based” ingredients or raw materials described herein are substantially free (or, in some embodiments, completely free) of such animal products and by-products.

[0086] In some embodiments, the compositions and foods described herein are suitable for vegan and / or vegetarian diets. For example, in embodiments in which a composition is suitable for a vegetarian diet, the composition comprises mainly plant-derived ingredients, and as a result, the composition is substantially free of animal products, animal by-products, or ingredients derived from these animal sources.

[0087] In some embodiments, the foods or compositions described herein include one or more flavoring agents. In some embodiments, the foods or compositions described herein include yeast, sugars, salts, and any combination thereof. Various natural or artificial flavoring agents are known to those skilled in the art and may include, for example, salts, spices, sugars, sweeteners, sulfuric acid flavoring agents such as monosodium glutamate and black salt, or other flavoring agents.

[0088] In some embodiments, the foods or compositions described herein include one or more colorants. Various natural or artificial colorants are known to those skilled in the art and may include, for example, carotenoids such as beta-carotene, turmeric, annatto, mango yellow, or palm-based oil.

[0089] In some embodiments, the food or composition described herein further includes emulsifiers, thickeners, oils, or any combination thereof.

[0090] In some embodiments, the oil is a plant-based oil. Examples of plant oils that may be used in accordance with this disclosure include, but are not limited to, soybean oil, safflower oil, linseed oil, corn oil, sunflower oil, olive oil, canola oil, sesame oil, cottonseed oil, palm oil, rapeseed oil, tung oil, or mixtures thereof. Alternatively, any partially hydrogenated or genetically modified plant oil may be used. Examples of partially hydrogenated or genetically modified plant oils include, but are not limited to, high-oleic safflower oil, high-oleic soybean oil, high-oleic peanut oil, high-oleic sunflower oil, and high-erucic rapeseed oil (crambeseed oil).

[0091] According to some embodiments, the disclosure provides a pharmaceutical composition comprising the above-described composition and an optionally pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises the above-described composition.

[0092] In some embodiments, the pharmaceutical composition of the Disclosure comprises a therapeutically effective amount of the composition of the Disclosure and / or any pharmaceutically acceptable salt and / or derivative thereof. In some embodiments, the therapeutically effective amount is sufficient to alleviate or substantially reduce the severity of at least one symptom of the disease, disorder, or condition described herein, and / or inhibit its progression. In some embodiments, the therapeutically effective amount may be determined as described herein.

[0093] Another aspect of the disclosure disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of an activator described herein and an optionally pharmaceutically acceptable carrier.

[0094] In some embodiments, the pharmaceutical composition is in the form of a powder, capsule, tablet, lotion, gel, liquid solution, or liquid suspension.

[0095] In some embodiments, the compositions and / or pharmaceutical compositions are intended for use in subjects who require them in the prevention or treatment of medical conditions associated with cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof.

[0096] In some embodiments, the prevention or treatment of a condition associated with an inflammatory disease or disorder includes reducing or inhibiting the expression of NO, PGE, TNF-α, IL-6, IL-10, IL-1, PGE2, or any combination thereof in the subject.

[0097] In some embodiments, the composition and / or pharmaceutical composition is for the prevention or treatment of inflammation-related diseases or disorders in a subject requiring it. In some embodiments, prevention or treatment involves inhibiting the production, expression, secretion, or any combination thereof of interleukins (IL-6, IL-10, IL-1, or any combination thereof) in a subject. In some embodiments, prevention or treatment involves inhibiting the production, expression, and secretion of IL-6, IL-10, IL-1, or any combination thereof in myeloid cells, monocytes, macrophages, or any combination thereof. In some embodiments, inflammation-related diseases include inflammation-based diseases. As used herein, the term “inflammation-related / related disease” includes any disease or disorder that is involved in, promoted by, induced by, or results from inflammation. In some embodiments, inflammation-related diseases are characterized by or include IL-6, IL-10, IL-1, or any combination thereof, being increased in production, expression, secretion, or any combination thereof from cells such as those disclosed herein in a subject.

[0098] In some embodiments, the composition and / or pharmaceutical composition is intended for use in activating the innate immune response in a subject that requires it. In some embodiments, the pharmaceutical composition is intended for use in preventing or treating an inflammatory disease or disorder in a subject that requires it. In some embodiments, prevention or treatment includes inhibiting one of the production, expression, and secretion of TNF-α in the subject. In some embodiments, prevention or treatment includes, but is not limited to, inhibiting one of the production, expression, and secretion of TNF-α in bone marrow cells such as monocytes or macrophages.

[0099] As used herein, the term "monocyte" refers to immune cells that circulate in the blood and infiltrate damaged or infected organs to participate in inflammatory processes. As macrophages, monocytes are the first line of defense of the immune system and play a major role in inflammation as part of the innate immune system. Inflammatory monocytes are selectively transported to the site of inflammation, produce inflammatory cytokines, and contribute to local and systemic inflammation. They are highly invasive and can differentiate into inflammatory macrophages. One of the main differences between monocytes and macrophages is that monocytes are precursors to some macrophages, while macrophages are specialized phagocytic cells that engulf pathogens that invade the body. Monocytes are small, bean-shaped cells, while macrophages are large, irregularly shaped cells.

[0100] In some embodiments, the composition and / or pharmaceutical composition is intended for use in reducing the levels of cytokine production, cytokine secretion, or both in a subject. Methods for determining the levels of cytokine production, secretion, or both are common and will be apparent to those skilled in the art. Non-limiting examples of such measurement methods include, but are not limited to, immunoassays, e.g., enzyme-linked immunosorbent assay (ELISA), Western blotting, dot blotting, MS-MS, or any combination thereof.

[0101] In some embodiments, the compositions and / or pharmaceutical compositions are intended for use in reducing the amount of fat in tissues, improving body composition, reducing fat infiltrating muscle fibers, reducing fat in the liver (fatty liver), increasing contractile proteins in muscles, or any combination thereof.

[0102] In some embodiments, the composition and / or pharmaceutical composition is intended to regulate the appetite of the subject and reduce the accumulation of abdominal fat. In some embodiments, the dietary supplement is intended to reduce the amount of fat accumulated in the liver.

[0103] In some embodiments, the compositions and / or pharmaceutical compositions are intended for use in reducing the risk of diabetes, hypertension, vascular disease, inflammation, chronic disease, or any combination thereof.

[0104] In some embodiments, the compositions and / or pharmaceutical compositions are intended for use in reducing released insulin (improving the glycemic index - reducing the risk of diabetes), reducing blood sugar levels (reducing the risk of metabolic syndrome), regulating appetite, regulating immune system activity, reducing inflammation, or any combination thereof.

[0105] Non-limiting examples of pharmaceutically acceptable salts include, but are not limited to, acetates, aspartates, benzenesulfons, benzoates, bicarbonates, carbonates, halides (such as bromides, chlorides, iodides, and fluorides), tartrates, citrates, salicylates, stearates, succinates, sulfates, tartrates, decanoates, edetates, fumarates, glucons, and lactates, or any combination thereof.

[0106] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the activator of the present disclosure and a pharmaceutically acceptable carrier.

[0107] In some embodiments, the pharmaceutical composition is in the form of a combination or a kit of components. In some embodiments, the pharmaceutical composition of this disclosure is intended for use as a pharmaceutical.

[0108] For example, the term “medically acceptable” may mean that its use in animals, particularly humans, has been approved by a federal or state regulatory authority, or is listed in the United States Pharmacopeia or other generally accepted pharmacopoeias. In some embodiments, the compounds of this disclosure are referred to herein as the active ingredient of a pharmaceutical composition.

[0109] In some embodiments, the pharmaceutical compositions described herein are topical compositions. In some embodiments, the compositions and / or pharmaceutical compositions are oral compositions. In some embodiments, the pharmaceutical compositions are injectable compositions. In some embodiments, the pharmaceutical compositions are for systemic use.

[0110] As used herein, the term “carrier” refers to a diluent, adjuvant, excipient, or vehicle to which the active ingredient is administered. Such carriers may be sterile liquids such as water-based liquids, and oils including petroleum, animal, plant, or synthetic origins such as peanut oil, soybean oil, mineral oil, sesame oil, polyethylene glycol, glycerin, propylene glycol, or other synthetic solvents.

[0111] Other non-limiting examples of carriers include terpenes derived from cannabis, or total terpene extracts from cannabis plants, terpenes from coffee or cocoa, mint extracts, eucalyptus extracts, citrus extracts, tobacco extracts, anise extracts, any vegetable oil, peppermint oil, d-limonene, β-myrcene, α-pinene, linalool, anethole, α-bisabolol, camphor, β-caryophyllene and caryophyllene oxide, 1,8-cineole, citral, citronella, delta-3-carene, farnesol, geraniol, indomethacin, Examples of such carriers include, but are not limited to, isopulegol, linalool, unalyl acetate, β-myrcene, myrcenol, L-menthol, menthone, menthol and neomenthol, oridonine, α-pinene, diclofenac, nepafenac, bromfenac, phytol, terpineol, terpinen-4-ol, thymol, and thymoquinone. Those skilled in the art will understand that the specific carriers used in the pharmaceutical compositions of this disclosure may vary depending on the route of administration.

[0112] In some embodiments, the carrier improves the stability of the active ingredient in a living organism. In some embodiments, the carrier improves the stability of the active ingredient in a pharmaceutical composition. In some embodiments, the carrier enhances the bioavailability of the active ingredient.

[0113] When the active ingredient has sufficient water solubility, it can be administered intravenously using water as a carrier. Physiological saline, aqueous dextrose solution, and glycerol solution can also be used as liquid carriers, especially for injection solutions.

[0114] In some embodiments, the carrier is a liquid carrier. In some embodiments, the carrier is an aqueous carrier.

[0115] Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, wheat flour, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, and ethanol. The composition may also optionally contain small amounts of wetting agents or emulsifiers, or pH buffers such as acetates, citrates, or phosphates. Antimicrobial agents such as benzyl alcohol and methylparaben are also possible. Antioxidants such as ascorbic acid and sodium sulfite, as well as tonicity modifiers such as sodium chloride and dextrose, are also conceivable. The carrier may constitute a total of 0.1% to 99.99999% by weight of the composition or pharmaceutical composition presented herein.

[0116] In some embodiments, the pharmaceutical composition involves incorporating one of the active ingredients in or on particulate formulations of polymer compounds such as polylactic acid, polyglycolic acid, and hydrogels, or on liposomes, microemulsions, micelles, monolayers or multilayer vesicles, erythrocyte ghosts, or spheroplasts. Such compositions may have limitations in terms of physical state, solubility, stability, in vivo release rate, and in vivo clearance rate.

[0117] In some embodiments, the pharmaceutical composition comprising the activator of the present disclosure is in unit dose form. In some embodiments, the pharmaceutical composition is prepared by any method known in the pharmaceutical art. In some embodiments, the unit dose form is in the form of a tablet, capsule, lozenge, wafer, patch, ampoule, vial or pre-filled syringe.

[0118] Furthermore, in vitro assays may optionally be employed to determine the optimal dosage range. The precise dose used in the prescription will also vary depending on the route of administration and the nature of the disease or disorder, and should be determined according to the physician's judgment and the individual patient's condition. The effective dose may be estimated from dose-response curves derived from in vitro or in-vivo animal model bioassays or systems. In some embodiments, the effective dose is determined as described herein.

[0119] In another embodiment, the pharmaceutical compositions of the present disclosure are administered by any conventional oral, parenteral or transdermal administration method.

[0120] As used herein, terms such as “administer” and “dosage” refer to any method of delivering a composition containing an activator to a target in a manner that provides a therapeutic effect in sound medical practice. In some embodiments, administration is carried out by oral administration, systemic administration, or a combination thereof.

[0121] In some embodiments, for oral administration, the composition and / or pharmaceutical composition is in the form of a tablet or capsule, which may contain any of the following components or compounds of similar nature: binders such as microcrystalline cellulose, tragacanth gum, or gelatin; excipients such as starch or lactose; disintegrants such as alginic acid, Primogel, or corn starch; lubricants such as magnesium stearate; or flow enhancers such as colloidal silicon dioxide. When the dosage unit form is a capsule, in addition to the above types of materials, it may contain a liquid carrier such as fatty oil. Furthermore, the dosage unit form may include a coating of various other materials that modify the physical form of the dosage unit, such as sugar, shellac, or other enteric coatings. In some embodiments, the tablets of this disclosure are further film-coated. In some embodiments, the oral administration of the pharmaceutical composition or kit is in the form of a drinkable liquid. In some embodiments, the oral administration of the pharmaceutical composition or kit is in the form of an edible product.

[0122] In another aspect of this disclosure, a method for preventing, improving or treating a medical condition associated with cancer, inflammatory disease or disorder, metabolic disorder, obesity, diabetes, hypertension, vascular disease, viral infection, and any combination thereof, comprising administering a therapeutically effective amount of the pharmaceutical compositions described herein to a subject in need thereof, thereby preventing, improving or treating the medical condition of the subject.

[0123] Another aspect of the disclosures disclosed herein involves methods for preventing, improving or treating inflammatory diseases or disorders in subjects requiring such treatment. In some embodiments, the method comprises administering a therapeutically effective amount of the pharmaceutical composition described herein to a subject, thereby preventing, improving or treating inflammatory diseases or disorders in the subject.

[0124] Another aspect of the disclosure disclosed herein is a method for preventing, improving or treating a subject suffering from cytokine release syndrome, comprising administering a therapeutically effective amount of the pharmaceutical composition to the subject, thereby preventing, improving or treating the subject suffering from cytokine release syndrome.

[0125] In some embodiments, cytokine release syndrome includes infectious diseases. In some embodiments, infectious diseases include viral diseases. In some embodiments, cytokine release syndrome includes virus-induced cytokine release syndrome.

[0126] Another aspect of the disclosures disclosed herein is the use of the compositions and / or pharmaceutical compositions disclosed herein to modulate, prevent or treat an immune response in a subject where such treatment is necessary.

[0127] Another aspect of the disclosure disclosed herein is a method for modulating the immune response in a subject requiring such modification, comprising administering the subject a therapeutically effective amount of the pharmaceutical composition described herein, thereby modulating the immune response in the subject.

[0128] In some embodiments, regulation, prevention, or treatment involves reducing the level of intracellular cytokine concentration, cytokine production, cytokine secretion, or both in the subject. In some embodiments, the pharmaceutical composition is selective for at least one cytokine.

[0129] In some embodiments, regulation, prevention, or treatment involves maintaining levels of intracellular cytokine concentration, cytokine production, cytokine secretion, or both in the subject. In some embodiments, the pharmaceutical composition is selective for at least one cytokine.

[0130] In some embodiments, the cytokine is selected from interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor alpha (TNFα), IL-8, IL-10, IL-1β, IL-17, CC motif chemokine ligand 2 (CCL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein-1α and / or beta (MIP-1α / β), monocyte chemoattractant protein-1 (MCP-1), chemokine (CXC motif) ligand 9 (CXCL9), CXCL10 (also known as interferon-gamma-inducible protein 10 (IP-10), or small inducible cytokine B10), or any combination thereof. In some embodiments, the cytokine is TNFα. In some embodiments, the cytokine comprises multiple cytokines including IL-6, IL-1β, TNFα, or any combination thereof. In some embodiments, the cytokine is IL-1β.

[0131] In some embodiments, administration includes systemic administration, oral administration, topical administration, or any combination thereof.

[0132] According to some embodiments, the present disclosure provides a method for obtaining the compositions described herein, the method comprising contacting 0.1% to 5% (w / w) of quercetin or a derivative thereof with an acetic acid solution containing 0.1% to 5% (w / w) of butyric acid or a derivative thereof for a certain period of time under conditions suitable for the dissolution of quercetin, thereby obtaining the composition.

[0133] In some embodiments, contact includes shaking, mixing, high-shear mixing, overhead stirring, homogenization, centrifugation, or any combination thereof.

[0134] In some embodiments, the time period is between 1 minute and 2 hours, between 5 minutes and 2 hours, between 10 minutes and 2 hours, between 30 minutes and 2 hours, between 40 minutes and 2 hours, between 1 hour and 2 hours, between 1 minute and 1 hour, between 5 minutes and 1 hour, between 10 minutes and 1 hour, between 30 minutes and 1 hour, or between 40 minutes and 1 hour (including any range within that period). Each possibility represents a separate embodiment of the present disclosure.

[0135] In some embodiments, suitable conditions for the dissolution of quercetin include heating the solution to a temperature of 22°C to 45°C.

[0136] In some embodiments, the method further includes the step of evaporating the solution.

[0137] In some embodiments, the method is carried out in a sealed container, away from light exposure.

[0138] According to some embodiments, the disclosure provides a package containing the compositions described above, or the pharmaceutical compositions described above. In some embodiments, the package is an airtight container.

[0139] In some embodiments, the package is a blow-filled airtight container. In some embodiments, the package has a twisted opening, a puncture opening, or both a twisted and puncture opening.

[0140] According to some embodiments, the Disclosure provides a kit comprising a composition or pharmaceutical composition described herein, wherein the composition or pharmaceutical composition is stored in a single-use airtight container.

[0141] In some embodiments, the contents of the kit are packaged in a way that allows the ingredients to be stored until they are needed, as described below.

[0142] In some embodiments, some or all components of the kit may be packaged in appropriate packaging to maintain sterility.

[0143] In some embodiments, the composition or pharmaceutical composition may be stored in separate containers within the main kit containment element, such as a box or similar structure, which may or may not be airtight, in order to further maintain the sterility of some or all of the components of the kit.

[0144] In some embodiments, the dosage of the composition or pharmaceutical composition provided in the kit may be sufficient for a single application or for multiple applications.

[0145] In these embodiments, the kit may have multiple doses of a composition or pharmaceutical composition packaged in a single container, such as a single tube, bottle, vial, airtight container, Eppendorf, etc.

[0146] In some embodiments, the kit contains multiple doses of the composition or pharmaceutical composition individually packaged, and a particular kit may contain multiple containers of the composition or pharmaceutical composition.

[0147] In some embodiments, multiple doses of the composition or pharmaceutical composition may be packaged in a single, separate container.

[0148] As used in this specification, the term "approximately" refers to ±10%.

[0149] The terms "comprises, comprising, includes, including," and "having," and their conjugations, all mean "to include but not limit."

[0150] The term “exemplary” is used herein to mean “serving as an example, illustration, or illustration.” Any embodiment described as “exemplary” should not necessarily be construed as being preferable or advantageous to other embodiments, and / or preclude the incorporation of features from other embodiments.

[0151] The term “optional” is used herein to mean “provided in some embodiments and not in other embodiments.” Any particular embodiment of this disclosure may include more than one “optional” feature, provided that such feature does not conflict with each other.

[0152] As used herein, the singular forms "a," "an," and "the" include plural references unless the context explicitly indicates otherwise. For example, the terms "compound" or "at least one compound" may include multiple compounds, including mixtures thereof.

[0153] Throughout this application, various embodiments of the disclosure may be presented in scope form. It should be understood that scope form descriptions are merely for convenience and brevity and should not be interpreted as inflexible limitations on the scope of the disclosure. Therefore, scope descriptions should be considered to specifically disclose not only the individual numbers within that range, but also all possible subranges. For example, a description of the range from 1 to 6 should be considered to specifically disclose subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and the individual numbers within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the range.

[0154] Wherever a numerical range is given herein, it is understood that the cited number (fraction or integer) must fall within that range. The expressions "between" the first and second numbers, and "from" the first to the second number, as used herein, are interchangeable and intended to include the first and second numbers, and all fractions and integers between them.

[0155] As used herein, the term “method” refers to methods, means, techniques and procedures for accomplishing a particular task, including, but not limited to, methods, means, techniques and procedures known by experts in chemistry, pharmacology, biology, biochemistry and medical technology, or readily developed from known methods, means, techniques and procedures.

[0156] As used herein, the term “treat” includes stopping, substantially inhibiting, slowing or reversing the progression of a condition, substantially improving the clinical or aesthetic symptoms of a condition, or substantially preventing or reducing susceptibility to the appearance of clinical or aesthetic symptoms of a condition.

[0157] To clarify certain features of this disclosure, those described in the context of separate embodiments are understood to be provided in combination in a single embodiment. Conversely, various features of this disclosure may, for the sake of brevity, be described in the context of a single embodiment and may also be provided separately, in any suitable subcombination, or as appropriate in any other described embodiments of this disclosure. Certain features described in the context of various embodiments are not considered essential features of those embodiments unless the embodiment would not function without those elements.

[0158] Various embodiments and aspects of this disclosure are shown above and are claimed in the following sections of the claims, finding experimental support in the following examples. [Examples]

[0159] The following embodiments are referenced here, and these embodiments illustrate some embodiments of the present disclosure in a non-limiting manner, in conjunction with the above description.

[0160] An exemplary composition as disclosed herein comprises about 70% (w / w) vinegar and about 30% (w / w) fruit must (apple, pomegranate, or both). This mixture is rich in triptyline and quercetin. To about 1000 mL of the vinegar and must mixture, about 5 g of triptyline and about 6 g of quercetin aglycone are added. The final composition as disclosed herein comprises about 0.5% (w / w) triptyline and about 0.6% (w / w) quercetin aglycone. Example 1

[0161] Composition specifications The content and properties of exemplary compositions were studied.

[0162] Composition 1, comprising organic cider vinegar, organic apple concentrate (must) or juice (approximately 20% V / V), organic pomegranate concentrate (must) or juice (approximately 10% V / V), quercetin, triptyline, and natural flavors, was studied.

[0163] The referenced composition 1 is also referred to herein as “Zakuroposca” (Tables 1 and 2).

[0164] [Table 1]

[0165] [Table 2]

[0166] Composition 2, comprising organic cider vinegar, organic apple concentrate (must) or juice (30% V / V), quercetin, triptyline, and natural flavors, was studied (composition 2 referred to herein is also called “Apple Posca”) (Tables 3 and 4).

[0167] [Table 3]

[0168] [Table 4] Example 2 Studies on the metabolic and anti-inflammatory effects of formulations based on apple and pomegranate extracts.

[0169] In the presented study, male Wistar rats were divided into three research groups, each receiving either 0.9% saline, apple posca (composition 2), or pomegranate posca (composition 1). Dosage: 1 mL / day; Control: Forced; Supplementation period: 6 weeks

[0170] We evaluated various parameters, including effects on organs and mass (murinometry and tissue weight), effects on metabolism (hormones - insulin, leptin, adiponectin, corticosterone, glucose, lactate, plasma lipids - triacylglycerol, cholesterol, HOMA index), inflammatory markers (TNF-α, IL10, IL6, IL1B, PGE2), and toxicological analysis (histology and marker enzymes).

[0171] Figure 1 shows the effects of apple or pomegranate posca supplements. Both the control group and the posca supplement group showed normal weight gain with a normal trend. The groups gained weight as expected (physiologically), and there was no clear difference between the groups (no statistical difference). This benefit becomes even greater as the administered food becomes higher in calories.

[0172] Figure 2 shows the effect of apple or pomegranate posca supplements on waist circumference. According to Figure 2, the change in waist circumference was smaller in animals supplemented with posca than in the control group.

[0173] Figure 3 shows the effect of apple or pomegranate posca supplements on relative nasal cavity length. According to Figure 3, the variation in nasal cavity length was greater in animals supplemented with posca than in the control group.

[0174] Figures 4A and 4B show the effects of apple or pomegranate supplementation on cumulative water consumption (Figure 4A) and cumulative food consumption (Figure 4B). According to Figures 4A and 4B, animals supplemented with POSCA consumed less food than the control group. This result, combined with significant growth in body length but less weight gain and a smaller abdominal circumference, suggests that POSCA effectively controls appetite and prevents the production of excessive fat.

[0175] Without being bound by any particular theory, we can assume that Posca can regulate appetite and reduce the accumulation of abdominal fat.

[0176] Figures 5A and 5B show the effects of apple or pomegranate posca supplements on the liver-to-body weight ratio (Figure 5A) and the mean difference (%) between the liver-to-body weight ratio and the relative liver-to-body weight ratio (Figure 5B). According to Figures 5A and 5B, the group supplemented with posca not only had normal liver weight, but posca supplementation also helped reduce the amount of fat accumulated in the liver, resulting in clear benefits to liver function and overall health. Liver weight relative to body weight was the same across the groups ("normal"), indicating no liver damage in the posca groups (i.e., no liver problems).

[0177] Further testing has shown no significant effect of supplementation with the formulation on the expected weight gain pattern. It is presumed that there are no adverse effects from chronic supplementation with the formulation (composition 1 or composition 2) over the days shown in the animals' growth patterns. Furthermore, there is little additional weight gain or water retention ("bloating") compared to supplement intake.

[0178] Nasal cavity length is equivalent to measuring human height. None of the supplements provided will impair the growth of the animals.

[0179] Waist circumference, an indirect measure of visceral fat accumulation (whose enlargement is associated with the progressive development of metabolic problems such as insulin resistance), was smaller in the group that consumed the apple-flavored formulation (composition 2). This result may indicate a beneficial effect of chronic intake, even indirectly, which may lead to a reduction in fat accumulation in that area.

[0180] An increase in human liver volume is undesirable because it may be related to the lipid infiltration or hepatotoxic aspects of the formulation. The results show no change in this parameter, indicating that this potentially destructive effect is not associated with chronic consumption of either composition 1 or 2 of the formulation.

[0181] Chronic intake of the formulation did not cause an increase in obesity in the animals (unlike the control group, there was no weight gain due to the supplement). Therefore, it can be said that consumption of the formulations in both presentations (Composition 1 and Composition 2) did not cause an increase in total body fat in the animals.

[0182] The Lee index is approximately equivalent to the human body mass index (BMI). Animals that ingested the apple-flavored formulation (composition 2) tended to show a decrease in the index (corresponding to a decrease in human BMI).

[0183] This treatment had no effect on food intake, demonstrating that this formulation is not an appetite suppressant.

[0184] Since supplementation with composition 1 or composition 2 did not induce an increase in interleukin-1β, a potent inflammatory factor, it is suggested that these compositions are non-toxic to tissues and the immune system and do not cause inflammation.

[0185] Supplementation with an apple-flavored formulation reduced the presence of interleukin-6 in circulation, suggesting the potential anti-inflammatory effects of the supplement.

[0186] Pomegranate preparations can induce a reduction in the presence of the circulating inflammatory cytokine tumor necrosis factor alpha (TNFα), suggesting an anti-inflammatory effect.

[0187] Supplementation with apple-flavored formulations can reduce circulating insulin, which has a highly desirable metabolic effect: better blood glucose control.

[0188] There were no significant differences in the circulation of two factors secreted from adipose tissue due to the supplements. However, a trend toward improved metabolism / inflammation was observed in the group supplemented with the apple-flavored formulation.

[0189] There was no increase in liver protein content. An increase in this parameter may be associated with metabolic problems, inflammation, and increased synthesis of acute-phase proteins that exhibit toxicity. Chronic intake of the formulation did not cause this adverse effect. Chronic intake of the supplement did not cause steatosis (fatty liver deposits), which is associated with supplement toxicity and adverse effects.

[0190] Lactates in circulation cause acidity and therefore need to be removed quickly. Supplements produced a more efficient or effective process in this area, reducing the glycolytic metabolism that produces lactates. Therefore, supplements had a beneficial metabolic effect.

[0191] Regarding liver toxicity, the supplement did not cause any signs of toxicity, but it did show improved results, suggesting a protective effect on the liver.

[0192] Supplementation with an apple-flavored formulation has been shown to reduce circulating glucose, resulting in better blood glucose control and thus desirable metabolic effects.

[0193] This supplement protocol was able to induce a highly desirable metabolic effect: an increase in HDL (high-density lipoprotein), which reduced the likelihood of developing cardiovascular disease and diabetes. In summary, the presented formulation was found to be non-toxic and to produce desirable, consistent metabolic and anti-inflammatory effects.

[0194] While this disclosure is described in conjunction with its specific embodiments, it will be apparent to those skilled in the art that many alternatives, modifications, and variations are evident. Therefore, it is intended to encompass all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims. All publications, patents, and patent applications described herein are incorporated herein by reference in whole, to the same extent as individual publications, patents, or patent applications are specifically and individually indicated. Furthermore, any citation or specification of reference in this application should not be construed as an admission that such reference is available as prior art of this disclosure. Paragraph headings, to the extent they are used, should not necessarily be construed as limiting.

Claims

1. A composition comprising 50% to 95% (w / w) acetic acid, 0.1% to 5% (w / w) butyric acid or its derivative, and 0.1% to 5% (w / w) quercetin or its derivative.

2. It further contains 5% to 40% (w / w) of fruit or vegetable ingredients. The composition according to claim 1, wherein the material is selected from extracts, biomass, filtrates, concentrates, wort, must, pomace, juice, any fraction thereof, and any combination thereof.

3. The composition according to claim 1 or 2, wherein the acetic acid is vinegar, vinegar extract, vinegar mother, a derivative of vinegar, a derivative of vinegar extract, a derivative of vinegar mother, or any combination thereof.

4. The composition according to any one of claims 1 to 3, wherein the butyric acid or a derivative thereof is triptyline.

5. The composition according to any one of claims 1 to 4, wherein the w / w ratio of butyric acid or its derivative to quercetin or its derivative is 1.5:1 to 1:

2.

6. A food product comprising the composition according to any one of claims 1 to 5.

7. A pharmaceutical composition comprising the composition according to any one of claims 1 to 5, and optionally a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, for use in subjects requiring the prevention or treatment of medical conditions related to cancer, inflammatory diseases or disorders, metabolic disorders, obesity, diabetes, hypertension, vascular diseases, viral infections, and any combination thereof.

9. A pharmaceutical composition according to claim 7 or 8 for preventing, improving or treating a medical condition in a subject who requires prevention, improvement or treatment of a medical condition associated with cancer, inflammatory disease or disorder, metabolic disorder, obesity, diabetes, hypertension, vascular disease, viral infection, and any combination thereof.

10. A nutritional supplement composition comprising the composition according to any one of claims 1 to 5.

11. A method for obtaining the composition according to any one of claims 1 to 5, comprising the step of contacting 0.1% to 5% (w / w) quercetin or a derivative thereof with an acetic acid solution containing 0.1% to 5% (w / w) butyric acid or a derivative thereof for 1 minute to 2 hours under conditions suitable for the quercetin to dissolve and obtain the composition.

12. The method according to claim 11, wherein the contact includes shaking, mixing, high-shear mixing, overhead stirring, homogenization, centrifugal separation, or any combination thereof.

13. The method according to claim 11 or 12, wherein the conditions suitable for the dissolution of the quercetin include heating the solution to a temperature of 22°C to 45°C.

14. A package comprising the composition according to any one of claims 1 to 5, or the pharmaceutical composition according to any one of claims 7 to 9, preferably an airtight container.

15. Use of the composition according to any one of claims 1 to 5 as a nutritional supplement.

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